WO2007111801A2 - Medical devices having nanoporous coatings for controlled therapeutic agent delivery - Google Patents
Medical devices having nanoporous coatings for controlled therapeutic agent delivery Download PDFInfo
- Publication number
- WO2007111801A2 WO2007111801A2 PCT/US2007/004704 US2007004704W WO2007111801A2 WO 2007111801 A2 WO2007111801 A2 WO 2007111801A2 US 2007004704 W US2007004704 W US 2007004704W WO 2007111801 A2 WO2007111801 A2 WO 2007111801A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- medical device
- implantable
- region
- nanoporous
- insertable medical
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
- A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
- A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
- A61L29/146—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
- A61L29/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/146—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30667—Features concerning an interaction with the environment or a particular use of the prosthesis
- A61F2002/30677—Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30667—Features concerning an interaction with the environment or a particular use of the prosthesis
- A61F2002/30677—Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
- A61F2002/3068—Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body the pharmaceutical product being in a reservoir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
- A61F2/30771—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth applied in original prostheses, e.g. holes or grooves
- A61F2002/3084—Nanostructures
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2210/0076—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof multilayered, e.g. laminated structures
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
- A61F2250/0067—Means for introducing or releasing pharmaceutical products into the body
- A61F2250/0068—Means for introducing or releasing pharmaceutical products into the body the pharmaceutical product being in a reservoir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/372—Arrangements in connection with the implantation of stimulators
- A61N1/375—Constructional arrangements, e.g. casings
- A61N1/37512—Pacemakers
Definitions
- This invention relates to therapeutic-agent containing medical devices, and more particularly, to medical devices having porous coatings which control therapeutic agent release.
- In-situ delivery of therapeutic agents within the body of a patient is common in the practice of modern medicine. In-situ delivery of therapeutic agents is often implemented using medical devices that may be temporarily or permanently placed at a target site within the body. These medical devices can be maintained, as required, at their target sites for short or prolonged periods of time, in order to deliver therapeutic agents to the target site.
- Nanoporous materials have the potential to revolutionize drug delivery. For example,
- iMEDD, Inc. has created silicon membranes with parallel channels ranging from 4 to 50 nm. Diffusion rates of various solutes through such membranes have been measured and conform to zero-order kinetics in some instances (i.e., release is constant with time). This is in contrast with typical situations in which drug diffusion rates decay with time, because the concentration gradient, and thus the driving force for diffusion, is also decaying with time.
- zero order behavior is that, by making the diameter of the nanopores only slightly larger than that of the drug, the nanopores act as bottlenecks, forcing the drugs to proceed in a substantially single-file fashion through the membrane, iMedd claims that the membranes can be engineered to control rates of diffusion by adjusting channel width in relation to the size of solutes.
- iMedd has produced a drug delivery device which consists of a drug-filled enclosure which is fitted with a nanoporous membrane as the only connection between the internal reservoir of the device and the external medium. These devices, however, do not have any function beyond drug delivery.
- H. Wieneke, et al. "Synergistic effects of a novel nanoporous stent coating and tacrolimus on intima proliferation in rabbits," Catheterization and Cardiovascular Interventions, Volume 60, Issue 3, pp.
- implantable or insertable medical devices which contain the following (a) one or more depressions that contain at least one therapeutic agent, and
- implantable or insertable devices are configured to perform a role beyond regulating transport, for example, providing mechanical, thermal, magnetic and/or electrical functions within the body, among other functions.
- An advantage of the present invention is that medical devices may be provided, in which the transport of species into the medical device, out of the medical device, or both are tightly controlled, potentially displaying zero order kinetics.
- Another advantage of the present invention is that medical devices may be provided, which hold quantities of therapeutic agents far exceeding the void volume within the nanoporous coatings, while at the same time providing functionality that extends beyond regulating species transport.
- Fig. 1 is a schematic cross-sectional view of two drug-filled depressions, which are capped with nanoporous region, in accordance with an embodiment of the invention.
- FIGs. 2A-2G and 3A-3E are schematic top views illustrating various depression configurations and arrays of the same, in accordance with various embodiments of the invention.
- FIGs. 4A-4E and 5A-5C are schematic cross-sectional views illustrating various depression configurations, in accordance with various embodiments of the invention.
- Fig. 6 is a schematic illustration of an idealized pore.
- FIG.7A is a schematic top view of a strut portion of a vascular stent, in accordance with an embodiment of the invention.
- Fig. 7B is a schematic cross-sectional view of the strut portion of Fig. 7A, taken along line A-A.
- Fig. 8 is a schematic diagram illustrating examples of ways by which a depression within a medical device surface may be loaded with a therapeutic agent and provided with a nanoporous coating.
- FIGs. 9A-B and 10A-B are schematic diagrams illustrating two ways by which an empty depression within a medical device surface may be capped with a nanoporous layer, without filling the depression.
- Fig. 11 is a schematic diagram illustrating examples of ways by which a depression within a medical device surface may be loaded with a therapeutic agent and provided with a nanoporous coating.
- medical devices which contain (a) one or more depressions that contain at least one therapeutic agent, and (b) one or more nanoporous regions, disposed over the therapeutic-agent-containing depressions, which regulate transport of species between the therapeutic-agent-containing depressions and the exterior of the device.
- a therapeutic agent may be transported from the therapeutic-agent- containing depressions such that it is released in vivo, an in vivo species may be transported into the therapeutic-agent-containing depressions where it reacts with the therapeutic agent to form another species (e.g., a less detrimental or more beneficial species) which is then transported from the depressions, and so forth.
- the implantable or insertable medical devices of the invention are also configured to provide a therapeutic function beyond species transport, for instance, providing mechanical, thermal, magnetic and/or electrical functions within the body, among other possible functions.
- medical devices in accordance with the present invention vary widely and include numerous implantable or insertable medical devices, for example, catheters (e.g., renal or vascular catheters such as balloon catheters and various central venous catheters), guide wires, balloons, filters (e.g., vena cava filters), stents (including coronary vascular stents, peripheral vascular stents, cerebral, urethral, ureteral, biliary, tracheal, gastrointestinal and esophageal stents), stent grafts, vascular grafts, vascular access ports, embolization devices including cerebral aneurysm filler coils (including Guglilmi detachable coils and metal coils), myocardial plugs, patches, pacemakers and pacemaker leads, left ventricular assist hearts and pumps, total artificial hearts, heart valves, vascular valves, anastomosis clips and rings, and other prostheses, including tissue engineering scaffolds for cartilage, bone, skin, skin
- the medical devices of the present invention may be implanted or inserted within a variety of tissues or organs of a subject, including tumors; organs and organ systems including but not limited to the heart, coronary and peripheral vascular system (referred to overall as “the vasculature”), lungs, trachea, esophagus, brain, liver, kidney, urogenital system (including, vagina, uterus, ovaries, prostate, bladder, urethra and ureters), eye, intestines, stomach, and pancreas; skeletal muscle; smooth muscle; breast; cartilage; and bone.
- Preferred subjects are vertebrate subjects, more preferably mammalian subjects and more preferably human subjects.
- Fig. 1 is a schematic cross-section illustrating two therapeutic-agent-containing depressions 12Ot within a portion 110 of a medical device 100 such as those described above.
- the therapeutic-agent-containing depressions are capped by a transport-regulating nanoporous region 140.
- Therapeutic-agent-containing depression(s) 120t with associated porous region(s) 140 may be provided over the entire device or only over one or more distinct portions of the device.
- therapeutic-agent-filled depression(s) 12Ot with associated porous region(s) 140 may be provided on the luminal device surfaces, on the abluminal device surfaces, and/or on the lateral device surfaces between the luminal and abluminal surfaces.
- first depressions filled with a first therapeutic agent e.g., an antithrombotic agent
- second depressions filled with a second therapeutic agent that differs from the first therapeutic agent (e.g., an antiproliferative agent) at the outer, abluminal surface.
- first therapeutic agent e.g., an antithrombotic agent
- second depressions filled with a second therapeutic agent that differs from the first therapeutic agent (e.g., an antiproliferative agent) at the outer, abluminal surface.
- One may also provide more than one therapeutic agent in separate depressions on the luminal surface or the abluminal surface.
- the depressions which contain the therapeutic agents may come in various shapes and sizes and can extend partially or completely through the substrate. Examples include depressions whose lateral dimensions are circular (see, e.g., the circular hole of Fig. 2A, in which the depressed area 12Od within the medical device portion 110 is designated with a darker shade of grey), oval (see Fig. 2B), polygonal, for instance triangular (see Fig. 2C), rectangular (see Fig. 2D), pentagonal (see Fig. 2E), as well as holes of various other regular and irregular shapes and sizes. Multiple holes 12Od can be provided in a near infinite variety of arrays. See, e.g., Figs.2F and 2G (one hole numbered in each).
- trenches such as simple linear trenches (see Fig. 3A, one trench numbered), trenches formed from linear segments whose direction undergoes an angular change (see Fig. 3B, one trench numbered), wavy trenches (see Fig. 3C, one trench numbered), trenches intersecting at right angles (see Fig. 3D) as well as other angles (see Fig. 3E), as well as other regular and irregular trench configurations.
- the medical devices of the invention contain drug-containing depressions whose smallest lateral dimension (e.g., the diameter for a cylindrical depression, the width for an elongated depression such a trench, etc.) is less than 1 mm (1000 ⁇ m), for example, ranging from 1000 ⁇ m to 500 ⁇ m to 250 ⁇ m to 100 ⁇ m to 50 ⁇ m to 10 ⁇ m to 5 ⁇ m to 2.5 ⁇ m to 1 ⁇ m or less.
- smallest lateral dimension e.g., the diameter for a cylindrical depression, the width for an elongated depression such a trench, etc.
- 1 mm 1000 ⁇ m
- the depressions 12Od extend only partially into the medical device portion 110, for example, being in the form of blind holes, trenches, etc.
- Such depressions may have a variety of cross-sections, such as polygonal cross-sections, including triangular (see, e.g., Fig. 4A), quadrilateral (see, e.g., Figs. 4B and 4C) and pentalateral (see, e.g., Fig.4D) cross-sections, and semicircular cross-sections (see, e.g., Fig. 4E), as well as other regular and irregular cross-sections.
- the depressions are high aspect ratio depressions, meaning that the depth of the depression is greater than or equal to the smallest lateral dimension of the depression, for example, ranging from 1 to 1.5 to 2 to 2.5 to 5 to 10 to 25 or more times the smallest lateral dimension (e.g., the depth for a cylindrical depression is greater than or equal to its diameter, the depth for an elongated depression such as a trench is greater than or equal to its width, etc.).
- Fig.4B illustrates two high aspect depressions 12Od in cross-section.
- the depressions 12Od may extend through the medical device portion 110, for example, being in the form of through-holes, slots, etc. See, e.g., the cross- sections of Figs. 5A-5D.
- Examples of techniques for forming depressions include molding techniques, direct-write techniques, and mask-based techniques, in which masking is used to protect material that is not to be removed .
- a mold may be provided with various protrusions, which after casting the medical article of interest, create depressions for use in the invention.
- Direct write techniques include those in which depressions are created through contact with solid tools (e.g., microdrilling, micromachining, etc., using high precision equipment such as high precision milling machines and lathes) and those that form depressions without the need for sotid tools (e.g., those based on directed energetic beams such as laser, electron, and ion beams).
- solid tools e.g., microdrilling, micromachining, etc., using high precision equipment such as high precision milling machines and lathes
- sotid tools e.g., those based on directed energetic beams such as laser, electron, and ion beams.
- DOEs diffractive optical elements
- holographic diffraction holographic diffraction
- polarization trepanning among other beam manipulation methods
- Mask-based techniques include those in which the masking material contacts the layer to be machined (e.g., where masks that are formed using known lithographic "techniques, including optical, ultraviolet, deep ultraviolet, electron beam, and x-ray lithography) and techniques in which the masking material does not contact the layer to be machined, but which is provided between a directed source of excavating energy and the material to be machined (e.g., opaque masks having apertures formed therein, as well as semi-transparent masks such as gray-scale masks which provide variable beam intensity and thus variable machining rates).
- One process known as columnated plasma lithography, is capable of producing X-rays for lithography having wavelengths on the order of 10 nm.
- Material is removed in regions not protected by the above masks using any of a range of processes including physical processes (e.g., thermal sublimation and/or vaporization of the material that is removed), chemical processes (e.g., chemical breakdown and/or reaction of the material that is removed), or a combination of both.
- physical processes e.g., thermal sublimation and/or vaporization of the material that is removed
- chemical processes e.g., chemical breakdown and/or reaction of the material that is removed
- Specific examples of removal processes include wet and dry (plasma) etching techniques, and ablation techniques based on directed energetic beams such as electron, ion and laser beams.
- shorter wavelength light is often preferred.
- shorter wavelength iight such as UV and deep-UV light can be imaged to a smaller spot size than light of longer wavelengths (e.g., because the minimum feature size is limited by diffraction, which increases with wavelength).
- Such shorter wavelength light is also typically relatively photolytic, displaying less thermal influence on surrounding material.
- many materials have high absorption coefficients in the ultraviolet region. This means that the penetration depth is small, with each pulse removing only a thin layer of material, thereby allowing precise control of the drilling depth.
- lasers are available for laser ablation, including excimer lasers, solid state lasers such as those based on Nd: YAG and Nd: vanadate, among other crystals, metal vapor lasers, such as copper vapor lasers, and femtosecond lasers. Further information on lasers and laser ablation may be found in Lippert T, and Dickinson JT, "Chemical and spectroscopic aspects of polymer ablation: Special features and novel directions," Chem. Rev., 103(2): 453-485 Feb.
- depressions for use in the present invention are formed in materials for which processing is routine in the semiconducting industry including semiconducting materials such as silicon, insulating materials such as silicon oxide, silicon nitride, and various metal oxides, and conductive materials, including a variety of metals and metal alloys.
- a layer of such a material is provided over another material that, for example, provides the device with desired mechanical characteristics.
- a silicon layer may be grown on a stainless steel or nitinol substrate and further processed to form depressions using known techniques.
- depressions of almost any desired shape and depth may be formed in a wide variety of materials including (a) organic materials (e.g., materials containing 50 wt% or more organic species) such as polymeric materials and biologies (b) inorganic materials (e.g., materials containing 50 wt% or more inorganic species), such as metallic materials (e.g., metals and metal alloys) and non- metallic materials (e.g., including carbon, semiconductors, glasses and ceramics, which may contain various metal- and non-metal-oxides, various metal- and non-metal-nitrides, various metal- and non-metal-carbides, various metal- and non-metal-borides, various metal- and non-metal-phosphates, and various metal- and non-metal-sul fides, among others).
- organic materials e.g., materials containing 50 wt% or more organic species
- inorganic materials e.g., materials containing 50 wt% or more inorganic
- non-metallic inorganic materials may be selected, for example, from materials containing one or more of the following: metal oxides, including aluminum oxides and transition metal oxides (e.g., oxides of titanium, zirconium, hafnium, tantalum, molybdenum, tungsten, rhenium, iron, niobium, and iridium); silicon; silicon-based ceramics, such as those containing silicon nitrides, silicon carbides and silicon oxides (sometimes referred to as glass ceramics); calcium phosphate ceramics (e.g., hydroxyapatite); carbon; and carbon-based, ceramic-like materials such as carbon nitrides.
- metal oxides including aluminum oxides and transition metal oxides (e.g., oxides of titanium, zirconium, hafnium, tantalum, molybdenum, tungsten, rhenium, iron, niobium, and iridium); silicon; silicon-based ceramics, such as those containing silicon ni
- metallic inorganic materials may be selected, for example, from metals (e.g., metals such as gold, iron, niobium, platinum, palladium, iridium, osmium, rhodium, titanium, tantalum, tungsten, ruthenium, and magnesium), metal alloys comprising iron and chromium (e.g., stainless steels, including platinum-enriched radiopaque stainless steel), alloys comprising nickel and titanium (e.g., Nitinol), alloys comprising cobalt and chromium, including alloys that comprise cobalt, chromium and iron (e.g., elgiloy alloys), alloys comprising nickel, cobalt and chromium (e.g., MP 35N) and alloys comprising cobalt, chromium, tungsten and nickel (e.g., L605), alloys comprising nickel and chromium (e.g., inconel alloys), and
- metals e
- organic materials include polymers (biostable or biodegradable) and other high molecular weight organic materials, and may be selected, for example, from suitable materials containing one or more of the following: polycarboxylic acid polymers and copolymers including polyacrylic acids; acetal polymers and copolymers; acrylate and methacrylate polymers and copolymers (e.g., n- butyl methacrylate); cellulosic polymers and copolymers, including cellulose acetates, cellulose nitrates, cellulose propionates, cellulose acetate butyrates, cellophanes, rayons, rayon triacetates, and cellulose ethers such as carboxymethyl celluloses and hydroxyalkyl celluloses; polyoxymethylene polymers and copolymers; polyimide polymers and copolymers such as polyether block imides, polyamidimides, polyesterimides, and polyetherimides; polysulfone polymers and copoly
- the medical devices of the present invention contain depressions, which further contain (i.e., they are at least partially filled with) one or more therapeutic agents (i.e., they may be used singly or in combination).
- the therapeutic agents may be present in pure form or admixed with another material, for example, a diluent, filter, matrix material, etc. Suitable materials for these purposes may be selected, for example, from suitable members of the polymers listed above, among many other possible materials. Where therapeutic agents are used in combination, one therapeutic agent may provide a matrix for another therapeutic agent.
- a range of therapeutic agent loading levels can be achieved.
- the amount of loading may be determined by those of ordinary skill in the art and will ultimately depend, for example, upon the disease or condition being treated, the age, sex and health of the subject, the nature of the therapeutic agent, and so forth.
- Bioly active agents include genetic therapeutic agents, non-genetic therapeutic agents and cells.
- therapeutic agents include genetic therapeutic agents, non-genetic therapeutic agents and cells.
- Numerous therapeutic agents are described here.
- Suitable non-genetic therapeutic agents for use in connection with the present invention may be selected, for example, from one or more of the following', (a) antithrombotic agents such as heparin, heparin derivatives, urokinase, and PPack (dextrophenylalanine proline arginine chloromethylketone); (b) anti-inflammatory agents such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine and mesalamine; (c) antineoplastic/antipr ⁇ liferative/anti-miotic agents such as paclitaxel, 5-fluorouracil, cisplatin, "vinblastine, vincristine, epothilones, endostatin, angiostatin, angiopeptin, monoclonal antibodies capable of blocking smooth muscle cell proliferation, and thymidine kinase inhibitors; (d) anesthetic agents
- Preferred non-genetic therapeutic agents include paclitaxel (including particulate forms thereof, for instance, protein-bound paclitaxel particles such as albumin-bound paclitaxel nanoparticles, e.g., ABRAXANE), sirolimus, everolimus, tacrolimus, Epo D, dexamethasone, estradiol, halofuginone, cilostazole, geldanamycin, ABT-578 (Abbott Laboratories), trapidtl, liprosti ⁇ , Actinomcin D, Resten-NG, Ap- 17, abciximab, clopidogrel, Ridogrel, beta-blockers, bARKct inhibitors, phospholamban inhibitors, Serca 2 gene/protein, imiquimod, human apolioproteins (e.g., AI-AV), growth factors (e.g., VEGF -2) , as well a derivatives of the forgoing, among others.
- Exemplary genetic therapeutic agents for use in connection with the present invention include anti-sense DNA and RNA as well as DNA coding for: (a) anti-sense RNA, (b) tRNA or rRNA to replace defective or deficient endogenous molecules, (c) angiogenic factors including growth factors such as acidic and basic fibroblast growth factors, vascular endothelial growth factor, epidermal growth factor, transforming growth factor ⁇ and ⁇ , platelet-derived endothelial growth factor, platelet-derived growth factor, tumor necrosis factor ⁇ , hepatocyte growth factor and insulin-like growth factor, (d) cell cycle inhibitors including CD inhibitors, and (e) thymidine kinase ("TK”) and other agents useful for interfering with cell proliferation.
- angiogenic factors including growth factors such as acidic and basic fibroblast growth factors, vascular endothelial growth factor, epidermal growth factor, transforming growth factor ⁇ and ⁇ , platelet-derived endothelial growth factor, platelet-
- BMP's bone morphogen ⁇ c proteins
- BMP-3, BMP-4, BMP-5, BMP-6 and BMP-7 are preferred.
- dimeric proteins can be provided as homodimers, heterodimers, or combinations thereof, alone or together with other molecules.
- molecules capable of inducing an upstream or downstream effect of a BMP can be provided.
- Such molecules include any of the "hedgehog" proteins, or the DNA's encoding them.
- Vectors for delivery of genetic therapeutic agents include viral vectors such as adenoviruses, gutted adenoviruses, adeno-associated virus, retroviruses, alpha virus (Semliki Forest, Sindbis, etc.), Antiviruses, herpes simplex virus, replication competent viruses (e.g., ONYX-015) and hybrid vectors; and non-viral vectors such as artificial chromosomes and mini-chromosomes, plasmid DNA vectors (e.g., pCOR), cationic polymers (e.g., polyethyleneimine, polyethyleneimine (PEI)), graft copolymers (e.g., polyether-PEI and polyethylene oxide-PEI), neutral polymers PVP, SP 1017 (SUPRATEK), lipids such as cationic lipids, liposomes, lipoplexes, nanoparticles, or microparticles, with and without targeting sequences such as the protein transduction domain (PTD).
- Cells for use in connection with the present invention include cells of human origin (autologous or allogeneic), including whole bone marrow, bone marrow derived mono-nuclear cells, progenitor cells (e.g., endothelial progenitor cells), stem cells (e.g., mesenchymal, hematopoietic, neuronal), pluripotent stem cells, fibroblasts, myoblasts, satellite cells, pericytes, cardiomyocytes, skeletal myocytes or macrophage, or from an animal, bacterial or fungal source (xenogeneic), which can be genetically engineered, if desired, to deliver proteins of interest.
- progenitor cells e.g., endothelial progenitor cells
- stem cells e.g., mesenchymal, hematopoietic, neuronal
- pluripotent stem cells fibroblasts, myoblasts, satellite cells, pericytes, cardiomyocytes, skeletal myocytes
- agents are useful for the practice of the present invention and suitable examples may be selected from one or more of the following: (a) Ca-channel blockers including benzothiazapines such as diltiazem and clentiazem, dihydropyridines such as nifedipine, amlodipine and nicardapine, and phenylalkylamines such as verapamil, (b) serotonin pathway modulators including: 5-HT antagonists such as ketanserin and naftidrofuryl, as well as 5-HT uptake inhibitors such as fluoxetine, (c) cyclic nucleotide pathway agents including phosphodiesterase inhibitors such as cilostazole and dipyridamole, adenylate/Guanylate cyclase stimulants such as forskolin, as well as
- Nanoporous regions for use in the present invention are not limited to any particular material and can be selected from a range of materials, including suitable members of the organic and inorganic materials listed above.
- a “nanoporous" region is one that contains nanopores.
- a “nanopore” is a void having at least one dimension (e.g., pore width) that does not exceed 100 nm in length.
- nanopores have at least two orthogonal (i.e., perpendicular) dimensions that do not exceed 100 nm and a third orthogonal dimension, which can be greater than 100 nm.
- an idealized cylindrical nanopore is illustrated in Fig. 6.
- the cylindrical pore of Fig. 6 has at least one dimension (in this instance, the orthogonal dimensions "x" and "y,” each of which correspond to the width of the nanopore) that does not exceed 100 nm in length.
- the third orthogonal dimension "z" of the cylindrical pore of Fig. 4 can be greater than 100 nm in length.
- Nanoporous coatings may further comprise pores that are not nanopores. [0052] Depending on the pore size, it is known that nanoporous regions having parallel or near parallel pore structures can release species such as therapeutic agents in accordance with zero order kinetics.
- the species may travel through the region via interconnected networks of pores.
- the lateral dimensions (e.g., the radii) of the interconnected pores approach the lateral dimensions (e.g., the hydrated radius) of the species that is being transported. Consequently, the species may move within, and ultimately be released from, pores of these diameters (as opposed to being trapped by pores having smaller radii).
- the interactions between the species and the walls of the nanopores will have a significant effect upon the transport that is observed. Indeed, as the diameter of the pore approaches the diameter of the species that is being transported, the surface interactions begin to dominate transport. See, e.g., Tejal A.
- the interconnected pore structures are capable of transporting species in a highly controlled manner, and they have the potential to approach zero order transport kinetics where pore diameters approach the size of the species that is being transported.
- the transport rate may also be affected by the depth and tortuousity of the pores within the interconnected porous network.
- nanoporous regions in which pores form an interconnected network may allow species to diffuse laterally, for example, allowing a therapeutic agent to be released laterally beyond the boundaries of an underlying therapeuticagent-containing depression. Pores that are positioned too far laterally from the therapeutic-agent-containing depression to participate in species transport may, nonetheless, promote cell adhesion. See, e.g., E.E.L. Swan, K.C. Popat, CA. Grimes, T.A.
- a precursor region is formed, which is subsequently converted into a nanoporous region.
- a mask with nano-scale apertures may be formed on a precursor region using known lithographic techniques, including optical, ultraviolet, deep ultraviolet, electron beam, and x-ray lithography, and subjected to further processing.
- lithographic techniques including optical, ultraviolet, deep ultraviolet, electron beam, and x-ray lithography
- a process for forming nanoporous silicon is described in L. Leoni, D. Attiah and T.A. Desai, "Nanoporous Platforms for Cellular Sensing and Delivery," Sensors 2002, 2, 111-120.
- a precursor region is formed which comprises first and second materials. Subsequently, the precursor region is subjected to conditions where the first material is either reduced in volume or eliminated from the precursor region.
- a nanoporous region may be formed-
- Materials for forming such removable or size-reducible nanodomains include (a) materials that are converted into gaseous species upon heating, for example, materials that sublime, materials that melt and then evaporate, and materials that form gaseous reaction products such as combustible materials, (b) metal oxides which may be reduced to their corresponding metal, resulting in a loss in volume, (c) materials which are dissolved or otherwise removed in a solution, and so forth.
- nanoporous regions may be produced from a metal alloy that contains two or more metals of differing nobility and at least one of the less noble metals is oxidized and remove from the alloy, thereby forming a nanoporo ⁇ s region.
- the at least one less noble metal corresponds to the nanodomains described above.
- oxidizing and removing the less noble metal(s) from the metal mixture including (i) contact with an appropriate acid (e.g., nitric acid), (ii) application of a voltage of sufficient magnitude and bias during immersion in a suitable electrolyte, and (iii) heating in the presence of oxygen, followed by dissolution of the resultant oxide.
- an appropriate acid e.g., nitric acid
- a voltage of sufficient magnitude and bias during immersion in a suitable electrolyte e.g., nitric acid
- heating in the presence of oxygen e.g., oxygen, followed by dissolution of the resultant oxide.
- Examples include alloys of essentially any substantially non-oxidizing noble metal (e.g., gold, platinum, etc.) having nanodomains of essentially any metal that can be removed (e.g. Zn, Fe, Cu, Ag, etc.).
- suitable alloys include alloys comprising gold and silver (in which the silver is oxidized and removed), alloys comprising gold and copper (in which the copper is oxidized and removed), and so forth. Further details concerning de-alloying can be found, for example, in J. Erlebacher et al. s "Evolution of nanoporosity in de-alloying," Nature, Vo.410, 22 March 2001, 450-453; AJ. Forty, “Corrosion micromorphology of noble metal alloys and depletion gilding," Nature, Vol. 282, 6 December 1979, 597-598; RX. Newman et al., “Alloy Corrosion,” MRS Bulletin, July 1999, 24-28; and U.S. Patent Appln. Pub. No. 2004/0148015 assigned to Setagon.
- High-density arrays of nanopores with high aspect ratios may also be formed based on the self-assembly of incompatible nanodomains using block copolymers.
- Cylindrical nanopores may be formed, for example, using diblock copolymers composed of polymethylmethacrylate (PMMA) and polystyrene (PS).
- PMMA polymethylmethacrylate
- PS polystyrene
- the molecular weight and volume fraction of styrene may be selected such that the copolymer self-assembles into arrays of PMMA cylinders hexagonally packed in a PS matrix.
- the PMMA cylinders may be oriented parallel to each other by applying an electric field, while the copolymer film is heated above the glass transition temperature.
- Deep ultraviolet exposure may be used to degrade the PMMA domains and simultaneously crosslink the PS matrix.
- the PMMA domains may be selectively removed by rinsing the film with acetic acid, yielding a PS film with ordered nanopores.
- nanoporous regions are formed using physical vapor deposition (PVD) techniques.
- PVD physical vapor deposition
- films grown by PVD techniques at lower temperatures e.g., where the ratio of the temperature of the substrate, T s , relative to the melting point of the deposited of the film, T 1n , is less than 0.3
- PVD techniques can also be used to deposit two or more materials, followed by removal of one or more of the materials to produce a nanoporous region.
- two or more metals may be simultaneously deposited via PVD (e.g., by sputtering separate targets of a single metal or by sputtering a single target containing multiple metals), followed by annealing if necessary to cause phase separation, which is followed by de-alloying, for example, using techniques such as those described above.
- CVD chemical vapor deposition
- LPCVD low-pressure chemical vapor deposition
- PECVD plasma-enhanced chemical vapor deposition
- nanoporous silicon dielectric films e.g., silicon oxide films such as silicon dioxide
- organosol icate precursor compounds such as tetraethylorthosilicate (TEOS)
- TEOS tetraethylorthosilicate
- nanoporous silicon oxycarbide films specifically SiOCH, also known as hydrogenated silicon oxycarbide
- PECVD oxidation of (CH 3 ) 3 SiH in the presence of an oxidant i.e., N 2 O.
- an oxidant i.e., N 2 O
- an aerosol of particles is first formed by a gas phase reaction at elevated temperature.
- the particles are then deposited on a substrate, for example, due to the forces of electrophoresis, therm ophoresis, or forced flow.
- a heterogeneous reaction occurs simultaneously with deposition to interconnect the particles and form a nanoporous layer, or the deposited particles are sintered to form a nanoporous layer, or both.
- a CO 2 laser may be used to heat metallorganic precursor compounds in the gas phase, resulting in decomposition of the precursor with concomitant formation of an aerosol of ceramic nanodomains.
- the particles are then deposited on a substrate as a result of a thermal gradient that naturally exists between the heated reaction zone created by the laser and the cooler substrate.
- heterogeneous reactions at the substrate surface can be controlled independently of the gas phase reactions. Further information can be found in Handbook ofNcmophase and Nanostructured Materials. Vol. 1. Synthesis, Zhong Lin Wang, Yi Liu, and Ze Zhang, Editors; Kluwer Academic/Plenum Publishers, Chapter 5, "Chemical Vapor Deposition".
- HFCVD hot-filament CVD
- a precursor gas is thermally decomposed by a resistively heated filament.
- the resulting pyrolysis products then adsorb onto a substrate maintained at a lower temperature (typically around room temperature) and react to form a film.
- a lower temperature typically around room temperature
- One advantage associated with pyrolytic CVD is that the underlying substrate can be maintained at or near room temperature.
- films can be deposited over underlying regions that comprise a wide range of therapeutic agents, including many therapeutic agents that cannot survive other higher-temperature processes due to their thermal sensitivities.
- a fluorocarbon polymer film is prepared by exposing a fluorocarbon monomer (e.g., hexafluoropropylene oxide, among others) to a source of heat having a temperature sufficient to pyrolyze the monomer and produce a reactive species that promotes polymerization.
- a fluorocarbon monomer e.g., hexafluoropropylene oxide, among others
- a source of heat having a temperature sufficient to pyrolyze the monomer and produce a reactive species that promotes polymerization.
- fluorocarbon- organosilicon copolymer films are prepared by exposing a fluorocarbon monomer (e.g., hexafluoropropylene oxide, among others) and an organosol icon monomer (e.g., hexamethylcyclotrisiloxane or octamethylcyclotetrasiloxane, among others) to the heat source. Due to the nucleation and growth mechanisms in the HFCVD processes, nanoporous films can be made using HFCVD. For further information, see, e.g., United States Patent Application No. 2003/013S645 to Gleason et al., U.S. Patent No.
- HWCVD Hot-wire chemical vapor deposition
- Nanoporous regions may be formed by selectively removing the polymer or the metal phase from the mixed film.
- nanoporous regions are formed by processes that comprise a technique commonly referred to as "kinetic metallization.”
- kinetic metallization metal particles (e.g., metal nanoparticles) are impacted with a substrate at high speed (e.g., at supersonic or near supersonic velocities) and at a temperature that is well below the melting point(s) of the metal particles (e.g., at a low temperature, such as ambient temperature).
- the metal particles are mixed with a relatively inert gas such as helium and/or nitrogen in a powder fluidizing unit, and the resulting fluidized powder is sprayed at high velocity onto the substrate.
- the metal particles in this technique may be, for example, particles of metal alloy, a mixture of pure metal particles, a mixture alloy particles, and so forth.
- particles for use in these methods include particles of the various metals described herein, including particles of gold, platinum, aluminum, cobalt, titanium, niobium, zinc, iron, copper, silver, tungsten, nickel, chromium, as well as alloys based on these and other metals.
- nanoporous regions are formed using electrochemical methods. For example, materials with nanodomains may be formed by first incorporating suspended nanoparticles into a matrix that is formed by electrodeposition and/or electroless deposition.
- nanoparticles that are dispersed by adsorbing cations on their surfaces are known to travel to the cathode where electrodeposition takes place, such that the nanoparticles are incorporated into the deposited layer.).
- nanodomains are subsequently reduced in size as discuss above (e.g., by sublimation, evaporation, combustion, dissolution, etc.).
- Another example of an electrochemical technique is the anodization of aluminum to form nanoporous alumina.
- the individual nanopores that are formed in the alumina upon anodization may be ordered into a hexagonally packed structure, with the diameter of each pore and the separation between two adjacent pores being controlled by changing the anodization conditions.
- Pore ordering has been shown to be improved using high- purity aluminum films, which are preannealed and electropolished Pore ordering also depends on anodization conditions, such as anodization voltage and the electrolyte. Pore ordering may be promoted through the use of a pre-texturing process in which an array of shallow concave features is initially formed on aluminum by indentation.
- Pore ordering may also be promoted by employing a two-step anodization method.
- the first step involves anodization of high purity aluminum to form a porous alumina layer. This layer is then dissolved, yielding a patterned aluminum substrate with an ordered array of concave features formed during the First anodization step. The ordered concave features then serve as the initial sites to form a highly ordered nanopore array in a second anodization step.
- Aluminum anodization normally results in a porous alumina structure which is separated from the aluminum substrate by a layer of AI 2 O 3 . The AI2O3 layer and aluminum substrate may then be removed to form a free-standing porous alumina membrane.
- AI 2 O 3 The AI2O3 layer and aluminum substrate may then be removed to form a free-standing porous alumina membrane.
- nanoporous regions are formed using sol- gel techniques.
- the starting materials that are used in the preparation of sol-gel regions are frequently inorganic metal salts, metallic complexes (e.g., metal acetylacetonate complexes), or organometallic compounds (e.g., metal alkoxides).
- the starting material is subjected to hydrolysis and polymerization (sometimes referred to as a condensation) reactions to form a colloidal suspension, or "sol". Further processing of the sol enables ceramic materials to be made in a variety of different forms.
- thin films can be produced on a substrate, for example, by spray coating, coating with an applicator (e.g., by roller or brush), spin-coating, or dip-coating of the sol onto the substrate, whereby a wet gel is formed.
- an applicator e.g., by roller or brush
- the rate of withdrawal from the sol can be varied to influence the properties of the film.
- the wet gel is then dried.
- the porosity of the gel can be regulated in a number of ways, including, for example, varying the solvent/water content, varying the aging time, varying the drying method and rate, and so forth.
- sol-gel processing is carried out at low temperatures (e.g., temperatures of 15-35 0 C).
- the sol-gel is subjected to high temperatures, for example, temperatures of 100 0 C, 200 0 C, 300 0 C, 400 0 C, 500 0 C, or more.
- high temperatures commonly reduce the porosity of the sol-gel, while at the same time increasing its mechanical strength.
- the biologically active agent is present at high temperatures, care should be taken to avoid thermal damage to the same. Further information concerning sol-gel materials can be found, for example, in Viitala R. et ah, "Surface properties of in vitro bioactive and non-bioactive sol-gel derived materials," Biomaterials.2002 Aug; 23 (15):3073-86; Radin, S.
- High porosity, uniform-pore-size mesoporous silicon oxide and aluminum oxide films may also be prepared by sol-gel methods using block copolymers as the structure- directing agents.
- block copolymers as the structure- directing agents.
- J.-A. Paik et al. “Micromachining of mesoporous oxide films for microelectromechanical system structures," J. Mater. Res., Vol. 17, No. 8, Aug 2002, 2121 has reported the formation of films that are over 50% porous with uniform pores of 8-nm average diameter.
- nanoporous regions and methods for making them can be found, for example, in U.S. Patent Serial No. 11/007,867 entitled “Medical Devices Having Nanostructured Regions For Controlled Tissue Biocompatibility And Drug Delivery” and U.S. Patent Serial No. 11/007,877 entitled “Medical Devices Having Vapor Deposited Nanoporous Coatings For Controlled Therapeutic Agent Delivery,” each filed 9 December 2004 and each of which is hereby incorporated by reference in its entirety.
- nanoporous region may be formed on, or formed and then attached to, a wide range of substrates.
- the depressions within the substrates may or may not contain a therapeutic agent at the time the nanoporous region is introduced to the substrate.
- a strut 110 of a stent 100 which may be formed from an organic or inorganic material (e.g., a metallic material such as stainless steel or nitinol, or a polymeric material such as a biodegradable polyester, among many other possibilities).
- Depressions specifically an interconnecting network of trenches 12Ow, 12Ox, 12Oy, 12Oz, in the embodiment shown, are formed within the strut 110, which subsequently act as therapeutic agent reservoirs as discussed above.
- a cross section of the strut 110 and trench 12Ow is illustrated in Fig. 7B, which is take along line A-A of Fig. 7A .
- Fig 8 schematically illustrates a few processes whereby a depression 12Od within a medical device portion 110 may be loaded with a therapeutic agent 12Ot and whereby a porous transport-controlling layer 140 may be established between the therapeutic agent 12Ot and outside environment O.
- the depression 12Od is first loaded with one or multiple therapeutic agents using any of a number of processes, including, for example, dipping, spraying, extrusion, coating with an applicator (e.g., by roller or brush), spin- coating, web coating, techniques involving coating via mechanical suspension including air suspension, ink jet techniques, and combinations of these processes, among other techniques.
- the therapeutic agent(s) may be supplied in pure form or in combination with a supplemental material, such as a polymer matrix.
- the therapeutic agent(s) and any supplemental material may be supplied, for example, in particle form, in the form of a melt, in the form of a solution, etc.
- a porous transport-controlling layer 140 is then provided over the therapeutic agent 12Ot as illustrated in step A2.
- the porous transport-controlling layer 140 may be formed over the therapeutic agent 12Ot, or it may be first formed and then adhered over the therapeutic agent 12Ot.
- a porous transport-controlling layer 140 is first provided over the depression 120d, forming a cavity 120c as illustrated in step Cl.
- the porous transport-controlling layer 140 may first be formed and then adhered over the depression 12Od or it may be formed over the depression 120d. Processes for conducting the latter procedure will now described in conjunction with Figs. 9A, 9B, 1OA and 1OB.
- a PVD material source such as a magnetron sputtering source, is positioned over a depression 12Od within medical device portion 110. Due to the size and relative proximity of the source as well as the line of sight nature of the PVD deposition process, deposition initially proceeds as depicted in Fig.
- the PVD material source is positioned to the left of the depression 12Od within medical device portion 110. Again, based to the size and location of the source, as well as the line of sight nature of the PVD deposition process, deposition initially proceeds as depicted in Fig. 1OA until the PVD deposited material 140 creates cavity 120c as illustrated in Fig. 1OB. To the extent that the PVD deposited material 140 is not nanoporous as desposited, it may be rendered nanoporous using techniques such as those discussed above.
- an aluminum or titanium layer may be deposited, followed by processing which renders the metal nanoporous, for example, using anodic processing as described above.
- pore size may be controlled.
- the pore size may be tailored to approach the diameter of the hydrated therapeutic agent so as to achieve zero-order or near-zero-order release.
- other techniques may be used in addition to those illustrated in Figs. 9 A, 9B, 1OA and 1OB to create cavity 120c, including further line of sight techniques such as kinetic metallization, among others.
- [00791 PVD processes may also be employed in order to increase resistance to species transport to and from the depression 12Od, for example, by proceeding as illustrated in Fig.
- a layer of PVD deposited material 140 with an aperture that is narrowed to nanopore dimensions, but stopping short of completely closing aperture in the PVD deposited material 140 as illustrated in Fig. 9B or 1OB.
- a similar effect may also be achieved by off-angle sputtering as in Fig. I OA, but with a heavy, non-layer-forming species such as Argon. Where a malleable material such as a metal is employed for the medical device portion 110, the sputtered species may act to "hammer" the aperture in the device portion 110 to the dimensions of a nanopore.
- a fluid containing dissolved or dispersed therapeutic agent may be contacted with the porous region 140, for instance, by dipping, spraying, extrusion, coating with an applicator (e.g., by roller or brush), spin-coating, web coating, techniques involving coating via mechanical suspension including air suspension, ink jet techniques, and combinations of these processes, among other techniques.
- an applicator e.g., by roller or brush
- spin-coating web coating
- techniques involving coating via mechanical suspension including air suspension, ink jet techniques, and combinations of these processes among other techniques.
- Water, organic solvents, subcritical fluids, critical point fluids, supercritical fluids, and so forth can be used as carriers for the therapeutic agent.
- the solvent is a supercritical solvent. Further information on supercritical solvent loading may be found in Serial No. 11/007,866, filed 9 December 2004 and entitled "Use of Supercritical Fluids to Incorporate Biologically Active Agents into Nanoporous Medical Articles.” [0082] In a further variation shown in Fig. 8, depression 12Od is first filled with a material 120m that can subsequently uptake significant amounts of drug (e.g., a sponge- like material), as illustrated in step Bl. Subsequently, as illustrated in step B2, the material 120m is loaded with a therapeutic agent 12Ot and a porous region 140 is provided over the medical device portion 110 (or vice versa).
- drug e.g., a sponge- like material
- step Bl of Fig. 8 the depression 120d is filled with a removable material 120m. Then a porous transport-controlling layer 140 is formed over the removable-material-filled depression 120m which removable material 120m is subsequently removed through the porous region 140 producing a cavity 120c as illustrated in step B3.
- Removable material 120m may be removed by various processes, including melting, sublimation, combustion, dissolution, supercritical extraction, or other process.
- the cavity 120c is then loaded with a therapeutic agent 12Ot by conveying the therapeutic agent through the porous region 140, as illustrated in step C2 (discussed above).
- depressions 120 that extend entirely through the device affords the opportunity to first form the nanoporous region 140 over the depression, and then load the depression with therapeutic agent 12Ot, without having to pass the therapeutic agent through the nanoporous region 140.
- a porous transport-controlling layer 140 may be established over one surface of the device portion 110. This can be done directly as shown in step Al (e.g., using techniques such as those described in conjunction with step Cl of Fig. 8 above).
- step Bl This can also be done indirectly, for example by first filling the depression 120 with a removable material 120m such as those described above, followed by the formation of a porous transport- controlling layer 140 over the device portion 110 and removable material 120m as shown in Fig. 11, step Bl. The removable material 120m is then removed as illustrated in step
- the depression 12Od (now capped on one end by porous transport-controlling layer 140) is then filled with a therapeutic agent 12Ot as shown in step A2 (e.g., using techniques such as those described above in conjunction with Fig. 8, step Al).
- a therapeutic agent 12Ot as shown in step A2 (e.g., using techniques such as those described above in conjunction with Fig. 8, step Al).
- an additional layer 150 which may or may not be a nanoporous layer, is provided over the therapeutic-agent-loaded depression 12Ot and the medical device portion 110 as illustrated in Fig. 11, step A3.
- Non nanoporous materials for this purpose may be selected from suitable members of the numerous organic and inorganic materials described above.
- trenches that are all found at a single depth within the substrate, one may also provide trenches that form crisscrossing grids at different depths within the substrate (including submerged trenches, or "veins"), thereby creating interconnected paths for loading and release of drug.
Abstract
According to an aspect of the present invention, implantable or insertable medical devices are provided which contain (a) one or more depressions that contain at least one therapeutic agent, and (b) a nanoporous coating, disposed over the therapeutic-agent-containing depressions, which regulate transport of species between the therapeutic-agent-containing depressions and the exterior of the device. The implantable or insertable devices are configured to perform a role beyond mere drug delivery, for example, providing mechanical and/or electrical functions within the body, among other functions. An advantage of the present invention is that medical devices may be provided, which release therapeutic agents in quantities far exceeding the void volume within the nanoporous coating, while at the same time providing functionality that extends beyond drug delivery. Such release may further approach or achieve a zero order kinetic drug release profile.
Description
MEDICAL DEVICES HAVING NANOPOROUS COATINGS FOR CONTROLLED
THERAPEUTIC AGENT DELIVERY
TECHNICAL FIELD
[0001] This invention relates to therapeutic-agent containing medical devices, and more particularly, to medical devices having porous coatings which control therapeutic agent release.
BACKGROUND OF THE INVENTION
[0002] The in-situ delivery of therapeutic agents within the body of a patient is common in the practice of modern medicine. In-situ delivery of therapeutic agents is often implemented using medical devices that may be temporarily or permanently placed at a target site within the body. These medical devices can be maintained, as required, at their target sites for short or prolonged periods of time, in order to deliver therapeutic agents to the target site.
[0003] Nanoporous materials have the potential to revolutionize drug delivery. For example,
[0004] iMEDD, Inc. has created silicon membranes with parallel channels ranging from 4 to 50 nm. Diffusion rates of various solutes through such membranes have been measured and conform to zero-order kinetics in some instances (i.e., release is constant with time). This is in contrast with typical situations in which drug diffusion rates decay with time, because the concentration gradient, and thus the driving force for diffusion, is also decaying with time. One explanation for zero order behavior is that, by making the diameter of the nanopores only slightly larger than that of the drug, the nanopores act as bottlenecks, forcing the drugs to proceed in a substantially single-file fashion through the membrane, iMedd claims that the membranes can be engineered to control rates of diffusion by adjusting channel width in relation to the size of solutes. When the proper balance is struck, zero-order diffusion kinetics is possible. [0005] iMedd has produced a drug delivery device which consists of a drug-filled enclosure which is fitted with a nanoporous membrane as the only connection between the internal reservoir of the device and the external medium. These devices, however, do not have any function beyond drug delivery.
[0006] H. Wieneke, et al., "Synergistic effects of a novel nanoporous stent coating and tacrolimus on intima proliferation in rabbits," Catheterization and Cardiovascular Interventions, Volume 60, Issue 3, pp. 399-407, describe stainless steel coronary stents that are provided with a ceramic nanoporous aluminum oxide (AI2O3) coating, which is used as a carrier for tacrolimus. Similarly, U.S. Patent Appln. Pub. No.2005/0070989, describes implantable medical devices such as stents, which have nanoporous layers that are loaded with therapeutic agents. However, because the nanoporous layers in these devices also serve as the drug reservoirs, the amount of drug that may be loaded is limited.
SUMMARY OF THE INVENTION
[0007] The above and other drawbacks of the prior art are addressed by the present invention in which implantable or insertable medical devices are provided which contain the following (a) one or more depressions that contain at least one therapeutic agent, and
(b) one or more nanoporous regions, disposed over the therapeutic-agent-containing depressions, which regulate transport of species between the therapeutic-agent-containing depressions and the exterior of the device. These implantable or insertable devices are configured to perform a role beyond regulating transport, for example, providing mechanical, thermal, magnetic and/or electrical functions within the body, among other functions.
[0008] An advantage of the present invention is that medical devices may be provided, in which the transport of species into the medical device, out of the medical device, or both are tightly controlled, potentially displaying zero order kinetics.
[0009] Another advantage of the present invention is that medical devices may be provided, which hold quantities of therapeutic agents far exceeding the void volume within the nanoporous coatings, while at the same time providing functionality that extends beyond regulating species transport.
[0010] These and other embodiments and advantages of the present invention will become immediately apparent to those of ordinary skill in the art upon review of the
Detailed Description and Claims to follow.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] Fig. 1 is a schematic cross-sectional view of two drug-filled depressions, which are capped with nanoporous region, in accordance with an embodiment of the invention.
[0012] Figs. 2A-2G and 3A-3E are schematic top views illustrating various depression configurations and arrays of the same, in accordance with various embodiments of the invention.
[0013] Figs. 4A-4E and 5A-5C are schematic cross-sectional views illustrating various depression configurations, in accordance with various embodiments of the invention.
[0014] Fig. 6 is a schematic illustration of an idealized pore.
[0015] Fig.7A is a schematic top view of a strut portion of a vascular stent, in accordance with an embodiment of the invention.
[0016] Fig. 7B is a schematic cross-sectional view of the strut portion of Fig. 7A, taken along line A-A.
[0017] Fig. 8 is a schematic diagram illustrating examples of ways by which a depression within a medical device surface may be loaded with a therapeutic agent and provided with a nanoporous coating.
[0018] Figs. 9A-B and 10A-B are schematic diagrams illustrating two ways by which an empty depression within a medical device surface may be capped with a nanoporous layer, without filling the depression.
[0019] Fig. 11 is a schematic diagram illustrating examples of ways by which a depression within a medical device surface may be loaded with a therapeutic agent and provided with a nanoporous coating.
DETAILED DESCRIPTION
[0020] According to an aspect of the invention, medical devices are provided which contain (a) one or more depressions that contain at least one therapeutic agent, and (b) one or more nanoporous regions, disposed over the therapeutic-agent-containing depressions, which regulate transport of species between the therapeutic-agent-containing depressions and the exterior of the device.
[0021] For example, a therapeutic agent may be transported from the therapeutic-agent- containing depressions such that it is released in vivo, an in vivo species may be transported into the therapeutic-agent-containing depressions where it reacts with the
therapeutic agent to form another species (e.g., a less detrimental or more beneficial species) which is then transported from the depressions, and so forth. [0022] The implantable or insertable medical devices of the invention are also configured to provide a therapeutic function beyond species transport, for instance, providing mechanical, thermal, magnetic and/or electrical functions within the body, among other possible functions. Consequently, medical devices in accordance with the present invention vary widely and include numerous implantable or insertable medical devices, for example, catheters (e.g., renal or vascular catheters such as balloon catheters and various central venous catheters), guide wires, balloons, filters (e.g., vena cava filters), stents (including coronary vascular stents, peripheral vascular stents, cerebral, urethral, ureteral, biliary, tracheal, gastrointestinal and esophageal stents), stent grafts, vascular grafts, vascular access ports, embolization devices including cerebral aneurysm filler coils (including Guglilmi detachable coils and metal coils), myocardial plugs, patches, pacemakers and pacemaker leads, left ventricular assist hearts and pumps, total artificial hearts, heart valves, vascular valves, anastomosis clips and rings, and other prostheses, including tissue engineering scaffolds for cartilage, bone, skin and other in vivo tissue regeneration, among others.
[0023] The medical devices of the present invention may be implanted or inserted within a variety of tissues or organs of a subject, including tumors; organs and organ systems including but not limited to the heart, coronary and peripheral vascular system (referred to overall as "the vasculature"), lungs, trachea, esophagus, brain, liver, kidney, urogenital system (including, vagina, uterus, ovaries, prostate, bladder, urethra and ureters), eye, intestines, stomach, and pancreas; skeletal muscle; smooth muscle; breast; cartilage; and bone. Preferred subjects (also referred to as "patients") are vertebrate subjects, more preferably mammalian subjects and more preferably human subjects. [0024] By way of example, Fig. 1 is a schematic cross-section illustrating two therapeutic-agent-containing depressions 12Ot within a portion 110 of a medical device 100 such as those described above. The therapeutic-agent-containing depressions are capped by a transport-regulating nanoporous region 140.
[0025] Multiple (e.g., 2 to 5 to 10 to 25 to 50 to 100 or more) or single therapeutic agent filled depressions 12Ot and/or multiple or single nanoporous coatings 140 may be provided, if desired. Therapeutic-agent-containing depression(s) 120t with associated
porous region(s) 140 may be provided over the entire device or only over one or more distinct portions of the device. For example, for tubular devices such as stents (which can comprise, for example, a laser or mechanically cut tube, among other designs), therapeutic-agent-filled depression(s) 12Ot with associated porous region(s) 140 may be provided on the luminal device surfaces, on the abluminal device surfaces, and/or on the lateral device surfaces between the luminal and abluminal surfaces. It is therefore possible, for example, to provide different therapeutic agents at different locations on the medical device. For example, it is possible to provide one or more first depressions filled with a first therapeutic agent (e.g., an antithrombotic agent) at the inner, luminal surface of the device, and one or more second depressions filled with a second therapeutic agent that differs from the first therapeutic agent (e.g., an antiproliferative agent) at the outer, abluminal surface. One may also provide more than one therapeutic agent in separate depressions on the luminal surface or the abluminal surface.
[0026] The depressions which contain the therapeutic agents may come in various shapes and sizes and can extend partially or completely through the substrate. Examples include depressions whose lateral dimensions are circular (see, e.g., the circular hole of Fig. 2A, in which the depressed area 12Od within the medical device portion 110 is designated with a darker shade of grey), oval (see Fig. 2B), polygonal, for instance triangular (see Fig. 2C), rectangular (see Fig. 2D), pentagonal (see Fig. 2E), as well as holes of various other regular and irregular shapes and sizes. Multiple holes 12Od can be provided in a near infinite variety of arrays. See, e.g., Figs.2F and 2G (one hole numbered in each). Further examples include trenches, such as simple linear trenches (see Fig. 3A, one trench numbered), trenches formed from linear segments whose direction undergoes an angular change (see Fig. 3B, one trench numbered), wavy trenches (see Fig. 3C, one trench numbered), trenches intersecting at right angles (see Fig. 3D) as well as other angles (see Fig. 3E), as well as other regular and irregular trench configurations. [0027] In general, the medical devices of the invention contain drug-containing depressions whose smallest lateral dimension (e.g., the diameter for a cylindrical depression, the width for an elongated depression such a trench, etc.) is less than 1 mm (1000 μm), for example, ranging from 1000 μm to 500 μm to 250 μm to 100 μm to 50 μm to 10 μm to 5 μm to 2.5 μm to 1 μm or less.
[0028] In some embodiments, the depressions 12Od extend only partially into the medical
device portion 110, for example, being in the form of blind holes, trenches, etc. Such depressions may have a variety of cross-sections, such as polygonal cross-sections, including triangular (see, e.g., Fig. 4A), quadrilateral (see, e.g., Figs. 4B and 4C) and pentalateral (see, e.g., Fig.4D) cross-sections, and semicircular cross-sections (see, e.g., Fig. 4E), as well as other regular and irregular cross-sections. In certain embodiments, the depressions are high aspect ratio depressions, meaning that the depth of the depression is greater than or equal to the smallest lateral dimension of the depression, for example, ranging from 1 to 1.5 to 2 to 2.5 to 5 to 10 to 25 or more times the smallest lateral dimension (e.g., the depth for a cylindrical depression is greater than or equal to its diameter, the depth for an elongated depression such as a trench is greater than or equal to its width, etc.). Fig.4B illustrates two high aspect depressions 12Od in cross-section. In some embodiments the depressions 12Od may extend through the medical device portion 110, for example, being in the form of through-holes, slots, etc. See, e.g., the cross- sections of Figs. 5A-5D.
[0029] Examples of techniques for forming depressions (e.g., blind holes, through holes, slots, trenches, etc.) for use in the invention include molding techniques, direct-write techniques, and mask-based techniques, in which masking is used to protect material that is not to be removed .
[0030] In molding techniques, a mold may be provided with various protrusions, which after casting the medical article of interest, create depressions for use in the invention. [0031] Direct write techniques include those in which depressions are created through contact with solid tools (e.g., microdrilling, micromachining, etc., using high precision equipment such as high precision milling machines and lathes) and those that form depressions without the need for sotid tools (e.g., those based on directed energetic beams such as laser, electron, and ion beams). In the latter cases, techniques based on diffractive optical elements (DOEs), holographic diffraction, and/or polarization trepanning, among other beam manipulation methods, may be employed to generate direct-write patterns as desired. Using these and other techniques multiple voids can be ablated in a material layer at once.
[0032] Mask-based techniques include those in which the masking material contacts the layer to be machined (e.g., where masks that are formed using known lithographic "techniques, including optical, ultraviolet, deep ultraviolet, electron beam, and x-ray
lithography) and techniques in which the masking material does not contact the layer to be machined, but which is provided between a directed source of excavating energy and the material to be machined (e.g., opaque masks having apertures formed therein, as well as semi-transparent masks such as gray-scale masks which provide variable beam intensity and thus variable machining rates). One process, known as columnated plasma lithography, is capable of producing X-rays for lithography having wavelengths on the order of 10 nm. Material is removed in regions not protected by the above masks using any of a range of processes including physical processes (e.g., thermal sublimation and/or vaporization of the material that is removed), chemical processes (e.g., chemical breakdown and/or reaction of the material that is removed), or a combination of both. Specific examples of removal processes include wet and dry (plasma) etching techniques, and ablation techniques based on directed energetic beams such as electron, ion and laser beams.
[0033] In those embodiments of the invention where laser light is used for material removal, shorter wavelength light is often preferred. There are several reasons for this. For example, shorter wavelength iight such as UV and deep-UV light can be imaged to a smaller spot size than light of longer wavelengths (e.g., because the minimum feature size is limited by diffraction, which increases with wavelength). Such shorter wavelength light is also typically relatively photolytic, displaying less thermal influence on surrounding material. Moreover, many materials have high absorption coefficients in the ultraviolet region. This means that the penetration depth is small, with each pulse removing only a thin layer of material, thereby allowing precise control of the drilling depth. Various lasers are available for laser ablation, including excimer lasers, solid state lasers such as those based on Nd: YAG and Nd: vanadate, among other crystals, metal vapor lasers, such as copper vapor lasers, and femtosecond lasers. Further information on lasers and laser ablation may be found in Lippert T, and Dickinson JT, "Chemical and spectroscopic aspects of polymer ablation: Special features and novel directions," Chem. Rev., 103(2): 453-485 Feb. 2003; Meijer J, et al., "Laser Machining by short and ultrashort pulses, state of the art and new opportunities in the age of photons," Annals of (he CIRP, 51(2), 531-550, 2002, and U.S. Patent No. 6,517,888 to Weber, each of which is hereby incorporated by reference.
[0034] It is noted that there is a great amount of available know-how in the
semiconductor industry for etching holes (e.g., vias), trenches and other depressions in various materials. For this reason, in some embodiments of the invention, depressions for use in the present invention are formed in materials for which processing is routine in the semiconducting industry including semiconducting materials such as silicon, insulating materials such as silicon oxide, silicon nitride, and various metal oxides, and conductive materials, including a variety of metals and metal alloys. In certain embodiments, a layer of such a material is provided over another material that, for example, provides the device with desired mechanical characteristics. As one specific example, a silicon layer may be grown on a stainless steel or nitinol substrate and further processed to form depressions using known techniques.
[0035] Using the above and other techniques, depressions of almost any desired shape and depth may be formed in a wide variety of materials including (a) organic materials (e.g., materials containing 50 wt% or more organic species) such as polymeric materials and biologies (b) inorganic materials (e.g., materials containing 50 wt% or more inorganic species), such as metallic materials (e.g., metals and metal alloys) and non- metallic materials (e.g., including carbon, semiconductors, glasses and ceramics, which may contain various metal- and non-metal-oxides, various metal- and non-metal-nitrides, various metal- and non-metal-carbides, various metal- and non-metal-borides, various metal- and non-metal-phosphates, and various metal- and non-metal-sul fides, among others).
[0036] Specific examples of non-metallic inorganic materials may be selected, for example, from materials containing one or more of the following: metal oxides, including aluminum oxides and transition metal oxides (e.g., oxides of titanium, zirconium, hafnium, tantalum, molybdenum, tungsten, rhenium, iron, niobium, and iridium); silicon; silicon-based ceramics, such as those containing silicon nitrides, silicon carbides and silicon oxides (sometimes referred to as glass ceramics); calcium phosphate ceramics (e.g., hydroxyapatite); carbon; and carbon-based, ceramic-like materials such as carbon nitrides.
[0037] Specific examples of metallic inorganic materials may be selected, for example, from metals (e.g., metals such as gold, iron, niobium, platinum, palladium, iridium, osmium, rhodium, titanium, tantalum, tungsten, ruthenium, and magnesium), metal alloys comprising iron and chromium (e.g., stainless steels, including platinum-enriched
radiopaque stainless steel), alloys comprising nickel and titanium (e.g., Nitinol), alloys comprising cobalt and chromium, including alloys that comprise cobalt, chromium and iron (e.g., elgiloy alloys), alloys comprising nickel, cobalt and chromium (e.g., MP 35N) and alloys comprising cobalt, chromium, tungsten and nickel (e.g., L605), alloys comprising nickel and chromium (e.g., inconel alloys), and alloys of magnesium and iron (e.g., their alloys with combinations of Ce, Ca, Zn, Zr and Li). [0038] Specific examples of organic materials include polymers (biostable or biodegradable) and other high molecular weight organic materials, and may be selected, for example, from suitable materials containing one or more of the following: polycarboxylic acid polymers and copolymers including polyacrylic acids; acetal polymers and copolymers; acrylate and methacrylate polymers and copolymers (e.g., n- butyl methacrylate); cellulosic polymers and copolymers, including cellulose acetates, cellulose nitrates, cellulose propionates, cellulose acetate butyrates, cellophanes, rayons, rayon triacetates, and cellulose ethers such as carboxymethyl celluloses and hydroxyalkyl celluloses; polyoxymethylene polymers and copolymers; polyimide polymers and copolymers such as polyether block imides, polyamidimides, polyesterimides, and polyetherimides; polysulfone polymers and copolymers including polyarylsulfones and polyethersulfones; polyamide polymers and copolymers including nylon 6,6, nylon 12, polyether-block co-polyamide polymers (e.g., Pebax® resins), polycaprolactams and polyacrylamides; resins including alkyd resins, phenolic resins, urea resins, melamine resins, epoxy resins, allyl resins and epoxide resins; polycarbonates; polyacrylonitriles; polyvinylpyrrolidones (cross-linked and otherwise); polymers and copolymers of vinyl monomers including polyvinyl alcohols, polyvinyl halides such as polyvinyl chlorides, ethylene-vinylacetate copolymers (EVA), polyvinylidene chlorides, polyvinyl ethers such as polyvinyl methyl ethers, vinyl aromatic polymers and copolymers such as polystyrenes, styrene-maleic anhydride copolymers, vinyl aromatic-hydrocarbon copolymers including styrene-butadiene copolymers, styrene-ethylene-butylene copolymers (e.g., a polystyrene-polyethylene/butylene-polystyrene (SEBS) copolymer, available as Kraton® G series polymers), styrene-isoprene copolymers (e.g., polystyrene- polyisoprene-polystyrene), acrylonitrile-styrene copolymers, acrylonitrile-butadiene- styrene copolymers, styrene-butadiene copolymers and styrene-isobutylene copolymers (e.g., polyisobutylene-polystyrene block copolymers such as SIBS), polyvinyl ketones,
polyvinylcarbazoles, and polyvinyl esters such as polyvinyl acetates; polybenzimidazoles; ionomers; potyalkyl oxide polymers and copolymers including polyethylene oxides (PEO); polyesters including polyethylene terephthalates,, polybutylene terephthalates and aliphatic polyesters such as polymers and copolymers of lactide (which includes lactic acid as well as d-,1- and meso lactide), epsilon-caprolactone, glycolide (including glycolic acid), hydroxybutyrate, hydroxyvalerate, para-dioxanone, trimethylene carbonate (and its alky 1 derivatives), 1 ,4-dioxepan-2-one, l,5-dioxepan-2-one, and 6,6>dimethyl-l,4-dioxan- 2-one (a copolymer of polylactic acid and polycaprolactone is one specific example); polyether polymers and copolymers including polyarylethers such as polyphenylene ethers, polyether ketones, polyether ether ketones; polyphenylene sulfides; polyisocyanates; polyolefin polymers and copolymers, including polyalkylenes such as polypropylenes, polyethylenes (low and high density, low and high molecular weight), polybutylenes (such as polybut-1-ene and polyisobutylene), polyolefin elastomers (e.g., santoprene), ethylene propylene diene monomer (EPDM) rubbers, poly-4-methyl-pen-l- enes, ethylene-alpha-olefm copolymers, ethylene-methyl methacrylate copolymers and ethylene-vinyl acetate copolymers; fluorinated polymers and copolymers, including polytetrafluoroethylenes (PTFE), poly(tetrafluoroethylene-co-hexafluoropropene) (FEP), modified ethylene-tetrafluoroethylene copolymers (ETFE), and polyvinylidene fluorides (PVDF); silicone polymers and copolymers; polyurethanes; p-xylylene polymers; polyiminocarbonates; copoly(ether-esters) such as polyethylene oxide-polylactic acid copolymers; polyphosphazϊnes; polyalkylene oxalates; polyoxaamides and polyoxaesters (including those containing amines and/or amido groups); polyorthoesters; biopolymers, such as polypeptides, proteins, polysaccharides and fatty acids (and esters thereof), including fibrin* fibrinogen, collagen, elastin, chitosan, gelatin, starch, glycosaminoglycans such as hyaluronic acid; as well as blends and further copolymers of the above.
[0039] As previously indicated, the medical devices of the present invention contain depressions, which further contain (i.e., they are at least partially filled with) one or more therapeutic agents (i.e., they may be used singly or in combination). The therapeutic agents may be present in pure form or admixed with another material, for example, a diluent, filter, matrix material, etc. Suitable materials for these purposes may be selected, for example, from suitable members of the polymers listed above, among many other
possible materials. Where therapeutic agents are used in combination, one therapeutic agent may provide a matrix for another therapeutic agent.
[0040] By varying the size (i.e., volume) and number of the depressions, as well as the concentration of the therapeutic agents within the depressions, a range of therapeutic agent loading levels can be achieved. The amount of loading may be determined by those of ordinary skill in the art and will ultimately depend, for example, upon the disease or condition being treated, the age, sex and health of the subject, the nature of the therapeutic agent, and so forth.
[00411 "Biologically active agents," "drugs," "therapeutic agents," "pharmaceutically active agents," "pharmaceutically active materials," and other related terms may be used interchangeably herein and include genetic therapeutic agents, non-genetic therapeutic agents and cells. A wide variety of therapeutic agents can be employed in conjunction with the present invention. Numerous therapeutic agents are described here. [0042] Suitable non-genetic therapeutic agents for use in connection with the present invention may be selected, for example, from one or more of the following', (a) antithrombotic agents such as heparin, heparin derivatives, urokinase, and PPack (dextrophenylalanine proline arginine chloromethylketone); (b) anti-inflammatory agents such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine and mesalamine; (c) antineoplastic/antiprσliferative/anti-miotic agents such as paclitaxel, 5-fluorouracil, cisplatin, "vinblastine, vincristine, epothilones, endostatin, angiostatin, angiopeptin, monoclonal antibodies capable of blocking smooth muscle cell proliferation, and thymidine kinase inhibitors; (d) anesthetic agents such as lidocaine, bupivacaine and ropivacaine; (e) anti-coagulants such as D-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containing compound, heparin, hirudin, antithrombin compounds, platelet receptor antagonists, anti-thrombin antibodies, anti-platelet receptor antibodies, aspirin, prostaglandin inhibitors, platelet inhibitors and tick antiplatelet peptides; (f) vascular cell growth promoters such as growth factors, transcriptional activators, and translational promotors; (g) vascular cell growth inhibitors such as growth factor inhibitors, growth factor receptor antagonists, transcriptional repressors, translational repressors, replication inhibitors, inhibitory antibodies, antibodies directed against growth factors, bifunctional molecules consisting of a growth factor and a cytotoxin, bifunctional molecules consisting of an antibody and a cytotoxin; (h) protein kinase and tyrosine kinase
inhibitors (e.g., tyrphostins, genistein, quinoxalines); (i) prostacyclin analogs; (j) cholesterol-lowering agents; (k) angiopoietins; (I) antimicrobial agents such as triclosan, cephalosporins, antimicrobial peptides such as magainins, aminoglycosides and nitrofurantoin; (m) cytotoxic agents, cytostatic agents and cell proliferation affectors; (n) vasodilating agents; (o)agents that interfere with endogenous vasoactive mechanisms, (p) inhibitors of leukocyte recruitment, such as monoclonal antibodies; (q) cytokines; (r) hormones; (s) inhibitors of HSP 90 protein (i.e., Heat Shock Protein, which is a molecular chaperone or housekeeping protein and is needed for the stability and function of other client proteins/signal transduction proteins responsible for growth and survival of cells) including geldanamycin, (t) beta-blockers, (u) bARKct inhibitors, (v) phospholamban inhibitors, (w) Serca 2 gene/protein, (x) immune response modifiers including amϊnoquizolines, for instance, imidazoquinolines such as resiquimod and imiquimod, (y) human apolioproteins (e.g., AI, All, AIlI, AIV, AV, etc.).
[0043] Preferred non-genetic therapeutic agents include paclitaxel (including particulate forms thereof, for instance, protein-bound paclitaxel particles such as albumin-bound paclitaxel nanoparticles, e.g., ABRAXANE), sirolimus, everolimus, tacrolimus, Epo D, dexamethasone, estradiol, halofuginone, cilostazole, geldanamycin, ABT-578 (Abbott Laboratories), trapidtl, liprostiπ, Actinomcin D, Resten-NG, Ap- 17, abciximab, clopidogrel, Ridogrel, beta-blockers, bARKct inhibitors, phospholamban inhibitors, Serca 2 gene/protein, imiquimod, human apolioproteins (e.g., AI-AV), growth factors (e.g., VEGF -2) , as well a derivatives of the forgoing, among others. [0044] Exemplary genetic therapeutic agents for use in connection with the present invention include anti-sense DNA and RNA as well as DNA coding for: (a) anti-sense RNA, (b) tRNA or rRNA to replace defective or deficient endogenous molecules, (c) angiogenic factors including growth factors such as acidic and basic fibroblast growth factors, vascular endothelial growth factor, epidermal growth factor, transforming growth factor α and β, platelet-derived endothelial growth factor, platelet-derived growth factor, tumor necrosis factor α, hepatocyte growth factor and insulin-like growth factor, (d) cell cycle inhibitors including CD inhibitors, and (e) thymidine kinase ("TK") and other agents useful for interfering with cell proliferation. Also of interest is DNA encoding for the family of bone morphogenϊc proteins ("BMP's"), including BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7 (OP-I), BMP-8, BMP-9, BMP-IO, BMP-11, BMP-12,
BMP-13, BMP-14, BMP-15, and BMP-16. Currently preferred BMP's are any of BMP- 2, BMP-3, BMP-4, BMP-5, BMP-6 and BMP-7. These dimeric proteins can be provided as homodimers, heterodimers, or combinations thereof, alone or together with other molecules. Alternatively, or in addition, molecules capable of inducing an upstream or downstream effect of a BMP can be provided. Such molecules include any of the "hedgehog" proteins, or the DNA's encoding them.
[0045] Vectors for delivery of genetic therapeutic agents include viral vectors such as adenoviruses, gutted adenoviruses, adeno-associated virus, retroviruses, alpha virus (Semliki Forest, Sindbis, etc.), Antiviruses, herpes simplex virus, replication competent viruses (e.g., ONYX-015) and hybrid vectors; and non-viral vectors such as artificial chromosomes and mini-chromosomes, plasmid DNA vectors (e.g., pCOR), cationic polymers (e.g., polyethyleneimine, polyethyleneimine (PEI)), graft copolymers (e.g., polyether-PEI and polyethylene oxide-PEI), neutral polymers PVP, SP 1017 (SUPRATEK), lipids such as cationic lipids, liposomes, lipoplexes, nanoparticles, or microparticles, with and without targeting sequences such as the protein transduction domain (PTD).
(00461 Cells for use in connection with the present invention include cells of human origin (autologous or allogeneic), including whole bone marrow, bone marrow derived mono-nuclear cells, progenitor cells (e.g., endothelial progenitor cells), stem cells (e.g., mesenchymal, hematopoietic, neuronal), pluripotent stem cells, fibroblasts, myoblasts, satellite cells, pericytes, cardiomyocytes, skeletal myocytes or macrophage, or from an animal, bacterial or fungal source (xenogeneic), which can be genetically engineered, if desired, to deliver proteins of interest.
[0047] Numerous therapeutic agents, not necessarily exclusive of those listed above, have been identified as candidates for vascular treatment regimens, for example, as agents targeting restenosis. Such agents are useful for the practice of the present invention and suitable examples may be selected from one or more of the following: (a) Ca-channel blockers including benzothiazapines such as diltiazem and clentiazem, dihydropyridines such as nifedipine, amlodipine and nicardapine, and phenylalkylamines such as verapamil, (b) serotonin pathway modulators including: 5-HT antagonists such as ketanserin and naftidrofuryl, as well as 5-HT uptake inhibitors such as fluoxetine, (c) cyclic nucleotide pathway agents including phosphodiesterase inhibitors such as
cilostazole and dipyridamole, adenylate/Guanylate cyclase stimulants such as forskolin, as well as adenosine analogs, (d) catecholamine modulators including α-antagonists such as prazosin and bunazosine, β-antagonists such as propranolol and α/β-antagonists such as labetalol and carvedilol, (e) endothelin receptor antagonists, (f) nitric oxide donors/releasing molecules including organic nitrates/nitrites such as nitroglycerin, isosorbide dinitrate and amyl nitrite, inorganic nitroso compounds such as sodium nitroprusside, sydnonimines such as molsidomine and Hnsidomine, nonoates such as diazenium diolates and NO adducts of alkanediamines, S-nitroso compounds including low molecular weight compounds (e.g., S-nitroso derivatives of captopril, glutathione and N-acetyl penicillamine) and high molecular weight compounds (e.g., S-nitroso derivatives of proteins, peptides, oligosaccharides, polysaccharides, synthetic polymers/oligomers and natural polymers/oligomers), as well as C-nitroso-compounds, O-nitroso-compounds, N-nitroso-compounds and L-arginine, (g) Angiotensin Converting Enzyme (ACE) inhibitors such as cilazapril, fosinopril and enalapril, (h) ATII-receptor antagonists such as saralasin and losartin, (i) platelet adhesion inhibitors such as albumin and polyethylene oxide, Q) platelet aggregation inhibitors including cilostazole, aspirin and thienopyridine (ticlopidine, clopidogrel) and GP Ilb/IIIa inhibitors such as abciximab, epitifibatide and tirofiban, (k) coagulation pathway modulators including heparinoids such as heparin, low molecular weight heparin, dextran sulfate and β-cyclodextrin tetradecasulfate, thrombin inhibitors such as hirudin, hirulog, PPACK(D-phe-L-propyl-L-arg~chloromethylketone) and argatroban, FXa inhibitors such as antistatin and TAP (tick anticoagulant peptide), Vitamin K inhibitors such as warfarin, as well as activated protein C, (1) cyclooxygenase pathway inhibitors such as aspirin, ibuprofen, flurbiprofen, indomethacin and sulfinpyrazone, (m) natural and synthetic corticosteroids such as dexamethasone, prednisolone, methprednisolone and hydrocortisone, (n) lipoxygenase pathway inhibitors such as nordihydroguairetic acid and caffeic acid, (o) leukotriene receptor antagonists, (p) antagonists of E- and P-selectins, (q) inhibitors of VCAM-I and ICAM-I interactions, (r) prostaglandins and analogs thereof including prostaglandins such as PGEl and PG12 and prostacyclin analogs such as ciprostene, epoprostenol, carbacyclin, iloprost and beraprost, (s) macrophage activation preventers including bisphosphonates, (t) HMG-CoA reductase inhibitors such as lovastatin, pravastatin, fluvastatin, simvastatin and cerivastatin, (u) fish oils and omega-3-fatty acids, (v) free-radical scavengers/antioxidants such as probucol,
vitamins C and E5 βbselen, trans-retinoic acid and SOD mimics, (w) agents affecting various growth factors including FGF pathway agents such as bFGF antibodies and chimeric fusion proteins, PDGF receptor antagonists such as trapidil, IGF pathway agents including somatostatin analogs such as angiopeptin and ocreotide, TGF-β pathway agents such as polyanionic agents (heparin, fucoidin), decorin, and TGF-β antibodies, EGF pathway agents such as EGF antibodies, receptor antagonists and chimeric fusion proteins, TNF-α pathway agents such as thalidomide and analogs thereof, Thromboxane A2 (TXA2) pathway modulators such as sulotroban, vapiprost, dazoxiben and ridogrel, as well as protein tyrosine kinase inhibitors such as tyrphostin, genistein and quinoxaline derivatives, (x) MMP pathway inhibitors such as marimastat, ilomastat and metastat, (y) cell motility inhibitors such as cytochalasin B5 (z) antiproliferative/antineoplastic agents including antimetabolites such as purine analogs (e.g., 6-mercaptopurine or cladribine, which is a chlorinated purine nucleoside analog), pyrimidine analogs (e.g., cytarabine and 5-fluorouracil) and methotrexate , nitrogen mustards, alkyl sulfonates, ethylenimines, antibiotics (e.g., daunorubicin, doxorubicin), nitrosoureas, cisplatin, agents affecting microtubule dynamics (e.g., vinblastine, vincristine, colchicine, Epo D, paclitaxel and epothilone), caspase activators, proteasome inhibitors, angiogenesis inhibitors (e.g., endostatin, angiostatin and squalamine), rapamycin, cerivastatin, flavopiridol and suramin, (aa) matrix deposition/organization pathway inhibitors such as halofuginone or other quinazolinone derivatives and tranilast, (bb) endothelialization facilitators such as VEGF and RGD peptide, and (cc) blood rheology modulators such as pentoxifylline. (0048] Numerous additional therapeutic agents useful for the practice of the present invention are also disclosed in U.S. Patent No. 5,733,925 assigned toNeoRx Corporation, the entire disclosure of which is incorporated by reference. [0049] In the medical devices of the present invention, transport of species into the therapeutic-agent-containing depressions, from these depressions, or both, is regulated by the nanoporous regions that are disposed over the depressions. The pores of these transport-controlling regions are generally substantially smaller than the smallest lateral dimensions (e.g., smaller than the width of a hole or trench, etc.) of the therapeutic-agent- containing depressions over which they are positioned. The pores of the release- controlling regions may be parallel to one another, they may be interconnected or both. They may be regular (e.g., cylindrical, etc.) or irregular in geometry.
[0050] Nanoporous regions for use in the present invention are not limited to any particular material and can be selected from a range of materials, including suitable members of the organic and inorganic materials listed above. [0051] As used herein, a "nanoporous" region is one that contains nanopores. A "nanopore" is a void having at least one dimension (e.g., pore width) that does not exceed 100 nm in length. Typically nanopores have at least two orthogonal (i.e., perpendicular) dimensions that do not exceed 100 nm and a third orthogonal dimension, which can be greater than 100 nm. By way of example, an idealized cylindrical nanopore is illustrated in Fig. 6. Being a nanopore, the cylindrical pore of Fig. 6 has at least one dimension (in this instance, the orthogonal dimensions "x" and "y," each of which correspond to the width of the nanopore) that does not exceed 100 nm in length. The third orthogonal dimension "z" of the cylindrical pore of Fig. 4 can be greater than 100 nm in length. Nanoporous coatings may further comprise pores that are not nanopores. [0052] Depending on the pore size, it is known that nanoporous regions having parallel or near parallel pore structures can release species such as therapeutic agents in accordance with zero order kinetics. In other less-structured release-controlling regions, the species may travel through the region via interconnected networks of pores. In some instances, the lateral dimensions (e.g., the radii) of the interconnected pores approach the lateral dimensions (e.g., the hydrated radius) of the species that is being transported. Consequently, the species may move within, and ultimately be released from, pores of these diameters (as opposed to being trapped by pores having smaller radii). Under such circumstances, the interactions between the species and the walls of the nanopores will have a significant effect upon the transport that is observed. Indeed, as the diameter of the pore approaches the diameter of the species that is being transported, the surface interactions begin to dominate transport. See, e.g., Tejal A. Desai, Derek Hansford and Mauro Ferrari, "Characterization of micromachined silicon membranes for irnmunoisσlation and bioseparation applications" J. Membrane Science, 159 (1999) 221- 231 , which describes insulin release through silicone nanomembranes. As with parallel pore structures, the interconnected pore structures are capable of transporting species in a highly controlled manner, and they have the potential to approach zero order transport kinetics where pore diameters approach the size of the species that is being transported. The transport rate may also be affected by the depth and tortuousity of the pores within
the interconnected porous network. Furthermore, nanoporous regions in which pores form an interconnected network may allow species to diffuse laterally, for example, allowing a therapeutic agent to be released laterally beyond the boundaries of an underlying therapeuticagent-containing depression. Pores that are positioned too far laterally from the therapeutic-agent-containing depression to participate in species transport may, nonetheless, promote cell adhesion. See, e.g., E.E.L. Swan, K.C. Popat, CA. Grimes, T.A. Desai, "Fabrication and evaluation of nanoporous alumina membranes for osteoblast culture," Journal of Biomedical Materials Research Part A, Volume 72A, Issue 3, Pages 288-295, Published Online: 14 Jan 2005, which describes osteoblast response to surface topography in anodized nanoporous alumina membranes. [0053] Various examples of techniques which may be employed for forming nanoporous regions are summarized below.
[0054] In some embodiments, a precursor region is formed, which is subsequently converted into a nanoporous region. For example, a mask with nano-scale apertures may be formed on a precursor region using known lithographic techniques, including optical, ultraviolet, deep ultraviolet, electron beam, and x-ray lithography, and subjected to further processing. For instance, a process for forming nanoporous silicon is described in L. Leoni, D. Attiah and T.A. Desai, "Nanoporous Platforms for Cellular Sensing and Delivery," Sensors 2002, 2, 111-120.
[0055] In some embodiments, a precursor region is formed which comprises first and second materials. Subsequently, the precursor region is subjected to conditions where the first material is either reduced in volume or eliminated from the precursor region. By providing nanodomains of the first material within the precursor region, a nanoporous region may be formed- Materials for forming such removable or size-reducible nanodomains include (a) materials that are converted into gaseous species upon heating, for example, materials that sublime, materials that melt and then evaporate, and materials that form gaseous reaction products such as combustible materials, (b) metal oxides which may be reduced to their corresponding metal, resulting in a loss in volume, (c) materials which are dissolved or otherwise removed in a solution, and so forth. [0056] Some of these techniques rely on the ability of certain materials to phase separate into nanodomains. For example, nanoporous regions may be produced from a metal alloy that contains two or more metals of differing nobility and at least one of the less noble
metals is oxidized and remove from the alloy, thereby forming a nanoporoυs region. In these embodiments, the at least one less noble metal corresponds to the nanodomains described above. Various methods are available for oxidizing and removing the less noble metal(s) from the metal mixture, including (i) contact with an appropriate acid (e.g., nitric acid), (ii) application of a voltage of sufficient magnitude and bias during immersion in a suitable electrolyte, and (iii) heating in the presence of oxygen, followed by dissolution of the resultant oxide. Examples include alloys of essentially any substantially non-oxidizing noble metal (e.g., gold, platinum, etc.) having nanodomains of essentially any metal that can be removed (e.g. Zn, Fe, Cu, Ag, etc.). Specific examples of suitable alloys include alloys comprising gold and silver (in which the silver is oxidized and removed), alloys comprising gold and copper (in which the copper is oxidized and removed), and so forth. Further details concerning de-alloying can be found, for example, in J. Erlebacher et al.s "Evolution of nanoporosity in de-alloying," Nature, Vo.410, 22 March 2001, 450-453; AJ. Forty, "Corrosion micromorphology of noble metal alloys and depletion gilding," Nature, Vol. 282, 6 December 1979, 597-598; RX. Newman et al., "Alloy Corrosion," MRS Bulletin, July 1999, 24-28; and U.S. Patent Appln. Pub. No. 2004/0148015 assigned to Setagon.
[0057] High-density arrays of nanopores with high aspect ratios may also be formed based on the self-assembly of incompatible nanodomains using block copolymers. Cylindrical nanopores may be formed, for example, using diblock copolymers composed of polymethylmethacrylate (PMMA) and polystyrene (PS). The molecular weight and volume fraction of styrene may be selected such that the copolymer self-assembles into arrays of PMMA cylinders hexagonally packed in a PS matrix. The PMMA cylinders may be oriented parallel to each other by applying an electric field, while the copolymer film is heated above the glass transition temperature. Deep ultraviolet exposure may be used to degrade the PMMA domains and simultaneously crosslink the PS matrix. The PMMA domains may be selectively removed by rinsing the film with acetic acid, yielding a PS film with ordered nanopores. For further information, see, e.g., H. X. He and NJ. Tao, "Electrochemical fabrication of metal nanowires" in Encyclopedia of Nanoscience and Nanotechnology, Eds., N.S. Nalwa, American Scientific Publishers, 2003, and the references cited therein.
[0058] In some embodiments, nanoporous regions are formed using physical vapor
deposition (PVD) techniques. For example, films grown by PVD techniques at lower temperatures (e.g., where the ratio of the temperature of the substrate, Ts, relative to the melting point of the deposited of the film, T1n, is less than 0.3) have been observed to produce films that tend to be more porous than films produced at higher temperatures. [0059] PVD techniques can also be used to deposit two or more materials, followed by removal of one or more of the materials to produce a nanoporous region. For example, two or more metals may be simultaneously deposited via PVD (e.g., by sputtering separate targets of a single metal or by sputtering a single target containing multiple metals), followed by annealing if necessary to cause phase separation, which is followed by de-alloying, for example, using techniques such as those described above. [0060] Some embodiments of the invention employ chemical vapor deposition (CVD) techniques, including low-pressure chemical vapor deposition (LPCVD) processes and plasma-enhanced chemical vapor deposition (PECVD) processes, in the formation of nanoporous regions. For example, it is known to deposit nanoporous silicon dielectric films (e.g., silicon oxide films such as silicon dioxide) by PECVD using organosol icate precursor compounds such as tetraethylorthosilicate (TEOS), typically in the presence of an oxidant such as N2O, O2, O3, H2O2, etc.. See e.g., United States Patent Application No.2002/0142579 to Vincent et al.
[0061] As another example, it is known to deposit nanoporous silicon oxycarbide films (specifically SiOCH, also known as hydrogenated silicon oxycarbide) by PECVD oxidation of (CH3)3SiH in the presence of an oxidant (i.e., N2O). See, e.g., D. Shamiryan et al., "Comparative study of SiOCH low-k films with varied porosity interacting with etching and cleaning plasma," J. Vac. Sd. Technol. B, 20(5), Sept/Oct 2002, pp. 1923- 1928.
[0062] As another example, in a process known as particle-precipitation-aided chemical vapor deposition (PP-CVD), an aerosol of particles is first formed by a gas phase reaction at elevated temperature. The particles are then deposited on a substrate, for example, due to the forces of electrophoresis, therm ophoresis, or forced flow. In certain embodiments, a heterogeneous reaction occurs simultaneously with deposition to interconnect the particles and form a nanoporous layer, or the deposited particles are sintered to form a nanoporous layer, or both. As a specific example, a CO2 laser may be used to heat metallorganic precursor compounds in the gas phase, resulting in decomposition of the
precursor with concomitant formation of an aerosol of ceramic nanodomains. The particles are then deposited on a substrate as a result of a thermal gradient that naturally exists between the heated reaction zone created by the laser and the cooler substrate. In this example, heterogeneous reactions at the substrate surface can be controlled independently of the gas phase reactions. Further information can be found in Handbook ofNcmophase and Nanostructured Materials. Vol. 1. Synthesis, Zhong Lin Wang, Yi Liu, and Ze Zhang, Editors; Kluwer Academic/Plenum Publishers, Chapter 5, "Chemical Vapor Deposition".
[0063] As another exampte, in hot-filament CVD (HFCVD), also known as pyrolytic or hot-wire CVD, a precursor gas is thermally decomposed by a resistively heated filament. The resulting pyrolysis products then adsorb onto a substrate maintained at a lower temperature (typically around room temperature) and react to form a film. One advantage associated with pyrolytic CVD is that the underlying substrate can be maintained at or near room temperature. As a result, films can be deposited over underlying regions that comprise a wide range of therapeutic agents, including many therapeutic agents that cannot survive other higher-temperature processes due to their thermal sensitivities. For example, in some embodiments, a fluorocarbon polymer film is prepared by exposing a fluorocarbon monomer (e.g., hexafluoropropylene oxide, among others) to a source of heat having a temperature sufficient to pyrolyze the monomer and produce a reactive species that promotes polymerization. By maintaining the substrate region in the vicinity of the reactive species and maintaining the substrate region at a substantially lower temperature than that of the heat source, deposition and polymerization of the reactive species on the structure surface are induced. In other embodiments, fluorocarbon- organosilicon copolymer films are prepared by exposing a fluorocarbon monomer (e.g., hexafluoropropylene oxide, among others) and an organosol icon monomer (e.g., hexamethylcyclotrisiloxane or octamethylcyclotetrasiloxane, among others) to the heat source. Due to the nucleation and growth mechanisms in the HFCVD processes, nanoporous films can be made using HFCVD. For further information, see, e.g., United States Patent Application No. 2003/013S645 to Gleason et al., U.S. Patent No. 6,156,435 to Gleason et al., and K.K.S. Lau et al., "Hot-wire chemical vapor deposition (HWCVD) of fluorocarbon and organosilicon thin films," Thin Solid Films, 395 (2001) pp. 288-291, each of which is incorporated by reference in its entirety.
[0064] In some cases, multiple deposition techniques are combined to form nanostructured regions on medical devices. One specific example is the deposition of polymers (e.g., by plasma enhanced polymerization) concurrently with PVD-type deposition of metals to produce mixed metal-polymer films. See "Plasma Polymer-Metal Composite Films,: H. Biedermann and L. Nartinu, p. 269 in Plasma Deposition, Treatment and Etching o/Polymers, Riccardo d'Agostino, Ed., Academic Press (1990). Nanoporous regions may be formed by selectively removing the polymer or the metal phase from the mixed film.
[0065] In still other embodiments of the present invention, nanoporous regions are formed by processes that comprise a technique commonly referred to as "kinetic metallization." In the kinetic metallization technique, metal particles (e.g., metal nanoparticles) are impacted with a substrate at high speed (e.g., at supersonic or near supersonic velocities) and at a temperature that is well below the melting point(s) of the metal particles (e.g., at a low temperature, such as ambient temperature). In certain embodiments, the metal particles are mixed with a relatively inert gas such as helium and/or nitrogen in a powder fluidizing unit, and the resulting fluidized powder is sprayed at high velocity onto the substrate. When the particles strike the substrate, fresh active metal is exposed, leading to adhesive and cohesive metallurgical bonding of the metal particles with the substrate and with one another. Because the particles are deposited at well below their respective melting points, the particles remain solid. Hence, like many of the above deposition techniques, they can form mixtures of metals that may be immiscible as liquids. Moreover, heat distortion of the substrate and interdiffusion of multi-layer coatings can be minimized or avoided. Additional information on this process can be found, for example, in U.S. Patent Nos. 5,795,626 and 6,074,135, U. S. Patent Application Nos. 2002/0168466 Al and 2003/0006250 Al, and International Publication Number WO 02/085532 Al, all to Howard Gabel and Ralph Tapphorn. [0066] The metal particles in this technique may be, for example, particles of metal alloy, a mixture of pure metal particles, a mixture alloy particles, and so forth. Examples of particles for use in these methods include particles of the various metals described herein, including particles of gold, platinum, aluminum, cobalt, titanium, niobium, zinc, iron, copper, silver, tungsten, nickel, chromium, as well as alloys based on these and other metals. These and other particles can be used coat metal substrates (e.g., aluminum,
titanium, stainless steel and nitinol substrates), as well as semiconductor, ceramic and polymer substrates, for example, those formed from the various substrate materials described herein. Once a nanostmctured surface containing a mixture of metal nanoparticles is formed, one metal may be preferentially removed using techniques such as those discussed above (e.g., de-alloying), thereby producing a nanoporous region. [0067] In some embodiments, nanoporous regions are formed using electrochemical methods. For example, materials with nanodomains may be formed by first incorporating suspended nanoparticles into a matrix that is formed by electrodeposition and/or electroless deposition. (For example, nanoparticles that are dispersed by adsorbing cations on their surfaces, are known to travel to the cathode where electrodeposition takes place, such that the nanoparticles are incorporated into the deposited layer.). Once formed, such nanodomains are subsequently reduced in size as discuss above (e.g., by sublimation, evaporation, combustion, dissolution, etc.).
[0068] Another example of an electrochemical technique is the anodization of aluminum to form nanoporous alumina. The individual nanopores that are formed in the alumina upon anodization may be ordered into a hexagonally packed structure, with the diameter of each pore and the separation between two adjacent pores being controlled by changing the anodization conditions. Pore ordering has been shown to be improved using high- purity aluminum films, which are preannealed and electropolished Pore ordering also depends on anodization conditions, such as anodization voltage and the electrolyte. Pore ordering may be promoted through the use of a pre-texturing process in which an array of shallow concave features is initially formed on aluminum by indentation. Pore ordering may also be promoted by employing a two-step anodization method. The first step involves anodization of high purity aluminum to form a porous alumina layer. This layer is then dissolved, yielding a patterned aluminum substrate with an ordered array of concave features formed during the First anodization step. The ordered concave features then serve as the initial sites to form a highly ordered nanopore array in a second anodization step. Aluminum anodization normally results in a porous alumina structure which is separated from the aluminum substrate by a layer of AI2O3. The AI2O3 layer and aluminum substrate may then be removed to form a free-standing porous alumina membrane. For further information, see, e.g., H.X. He and NJ. Tao, "Electrochemical fabrication of metal nanowires" in Encyclopedia of Nanoscience and Nanotechnology,
Eds., N.S. Nalwa, American Scientific Publishers, 2003, and the references cited therein. See also E.E.L. Swan, K.C. Popat, CA. Grimes, T.A. Desai, "Fabrication and evaluation of nanoporous alumina membranes for osteoblast culture," Journal of Biomedical Materials Research Part A, Volume 72A, Issue 3, Pages 288 - 295, Published Online: 14 Jan 2005, which describes osteoblast response to surface topography in anodized nanoporous alumina membranes. Alumina membranes with pore sizes ranging from 30 to 80 nm are reported.
[0069] In some embodiments of the invention, nanoporous regions are formed using sol- gel techniques. The starting materials that are used in the preparation of sol-gel regions are frequently inorganic metal salts, metallic complexes (e.g., metal acetylacetonate complexes), or organometallic compounds (e.g., metal alkoxides). Typically, the starting material is subjected to hydrolysis and polymerization (sometimes referred to as a condensation) reactions to form a colloidal suspension, or "sol". Further processing of the sol enables ceramic materials to be made in a variety of different forms. For instance, thin films can be produced on a substrate, for example, by spray coating, coating with an applicator (e.g., by roller or brush), spin-coating, or dip-coating of the sol onto the substrate, whereby a wet gel is formed. Where dip coating is employed, the rate of withdrawal from the sol can be varied to influence the properties of the film. The wet gel is then dried. The porosity of the gel can be regulated in a number of ways, including, for example, varying the solvent/water content, varying the aging time, varying the drying method and rate, and so forth. In certain embodiments, sol-gel processing is carried out at low temperatures (e.g., temperatures of 15-35 0C). In other embodiments, the sol-gel is subjected to high temperatures, for example, temperatures of 1000C, 2000C, 3000C, 4000C, 5000C, or more. Such high temperatures commonly reduce the porosity of the sol-gel, while at the same time increasing its mechanical strength. Where the biologically active agent is present at high temperatures, care should be taken to avoid thermal damage to the same. Further information concerning sol-gel materials can be found, for example, in Viitala R. et ah, "Surface properties of in vitro bioactive and non-bioactive sol-gel derived materials," Biomaterials.2002 Aug; 23 (15):3073-86; Radin, S. et al., "In vitro bioactivity and degradation behavior of silica xerogels intended as controlled release materials," Biomaterials. 2002 Aug; 23 (15):3113-22; Nicoll S.B., et ah, "In vitro release kinetics of biologically active transforming growth factor-beta 1 from a novel porous
glass carrier," Biomaterials. 1997 Jun; 18 (12):853-9; Santos, E.M. et al., "Sol-gel derived carrier for the controlled release of proteins," Biomaterials. 1999 Sep; 20 (18): 1695-700; Radin, S. et al., "Silica sol-gel for the controlled release of antibiotics. I. Synthesis, characterization, and in vitro release," J Biomed Mater Res. 2001 Nov; 57 (2):313-20; Aughenbaυgh, W. et al., "Silica sol-gel for the controlled release of antibiotics. II. The effect of synthesis parameters on the in vitro release kinetics of vancomycin," J Biomed Mater Res. 2001 Dec 5; 57 (3):321-6; Santos, E.M. et al., "Si-Ca-P xerogels and bone morphogenetic protein act synergistically on rat stromal marrow cell differentiation in vitro," J Biomed Mater Res. 1998 JuI; 41 (l):87-94.
[0070] High porosity, uniform-pore-size mesoporous silicon oxide and aluminum oxide films may also be prepared by sol-gel methods using block copolymers as the structure- directing agents. For example, J.-A. Paik et al. "Micromachining of mesoporous oxide films for microelectromechanical system structures," J. Mater. Res., Vol. 17, No. 8, Aug 2002, 2121 has reported the formation of films that are over 50% porous with uniform pores of 8-nm average diameter.
[0071] Further information on nanoporous regions and methods for making them can be found, for example, in U.S. Patent Serial No. 11/007,867 entitled "Medical Devices Having Nanostructured Regions For Controlled Tissue Biocompatibility And Drug Delivery" and U.S. Patent Serial No. 11/007,877 entitled "Medical Devices Having Vapor Deposited Nanoporous Coatings For Controlled Therapeutic Agent Delivery," each filed 9 December 2004 and each of which is hereby incorporated by reference in its entirety.
[0072] Using methods such as the above and other techniques, nanoporous region may be formed on, or formed and then attached to, a wide range of substrates. The depressions within the substrates may or may not contain a therapeutic agent at the time the nanoporous region is introduced to the substrate.
[0073] With reference now to Fig. 7A a portion of a medical device is shown, specifically, a strut 110 of a stent 100, which may be formed from an organic or inorganic material (e.g., a metallic material such as stainless steel or nitinol, or a polymeric material such as a biodegradable polyester, among many other possibilities). Depressions, specifically an interconnecting network of trenches 12Ow, 12Ox, 12Oy, 12Oz, in the embodiment shown, are formed within the strut 110, which subsequently act as
therapeutic agent reservoirs as discussed above. A cross section of the strut 110 and trench 12Ow is illustrated in Fig. 7B, which is take along line A-A of Fig. 7A . [00741 While the specific structure shown contains intersecting linear trenches having rectangular cross-sections, myriad other possibilities exist, as previously indicated, including the use of trenches that are non-linear, the use of non-intersecting trenches, the use of multiple holes instead of or in addition to trenches, the use of trenches and/or holes that have non-rectangular cross-sections, the use of trenches and/or holes that have high aspect ratio or extend through the strut, and so forth.
[00751 Fig 8 schematically illustrates a few processes whereby a depression 12Od within a medical device portion 110 may be loaded with a therapeutic agent 12Ot and whereby a porous transport-controlling layer 140 may be established between the therapeutic agent 12Ot and outside environment O.
[0076] For example, in step Al of Fig. 8, the depression 12Od is first loaded with one or multiple therapeutic agents using any of a number of processes, including, for example, dipping, spraying, extrusion, coating with an applicator (e.g., by roller or brush), spin- coating, web coating, techniques involving coating via mechanical suspension including air suspension, ink jet techniques, and combinations of these processes, among other techniques. As noted above, the therapeutic agent(s) may be supplied in pure form or in combination with a supplemental material, such as a polymer matrix. The therapeutic agent(s) and any supplemental material may be supplied, for example, in particle form, in the form of a melt, in the form of a solution, etc.
[0077] A porous transport-controlling layer 140 is then provided over the therapeutic agent 12Ot as illustrated in step A2. As noted above, the porous transport-controlling layer 140 may be formed over the therapeutic agent 12Ot, or it may be first formed and then adhered over the therapeutic agent 12Ot.
[0078] In another variation, a porous transport-controlling layer 140 is first provided over the depression 120d, forming a cavity 120c as illustrated in step Cl. The porous transport-controlling layer 140 may first be formed and then adhered over the depression 12Od or it may be formed over the depression 120d. Processes for conducting the latter procedure will now described in conjunction with Figs. 9A, 9B, 1OA and 1OB. In Fig. 9A, a PVD material source, such as a magnetron sputtering source, is positioned over a depression 12Od within medical device portion 110. Due to the size and relative
proximity of the source as well as the line of sight nature of the PVD deposition process, deposition initially proceeds as depicted in Fig. 9A, until the PVD deposited material 140 creates cavity 120c as illustrated in Fig. 9B. In Fig. 1OA, the PVD material source is positioned to the left of the depression 12Od within medical device portion 110. Again, based to the size and location of the source, as well as the line of sight nature of the PVD deposition process, deposition initially proceeds as depicted in Fig. 1OA until the PVD deposited material 140 creates cavity 120c as illustrated in Fig. 1OB. To the extent that the PVD deposited material 140 is not nanoporous as desposited, it may be rendered nanoporous using techniques such as those discussed above. As a specific example, an aluminum or titanium layer may be deposited, followed by processing which renders the metal nanoporous, for example, using anodic processing as described above. As noted above, with anodic processing, pore size may be controlled. For example the pore size may be tailored to approach the diameter of the hydrated therapeutic agent so as to achieve zero-order or near-zero-order release. Of course, other techniques may be used in addition to those illustrated in Figs. 9 A, 9B, 1OA and 1OB to create cavity 120c, including further line of sight techniques such as kinetic metallization, among others. [00791 PVD processes may also be employed in order to increase resistance to species transport to and from the depression 12Od, for example, by proceeding as illustrated in Fig. 9 A or 1OA, thereby forming a layer of PVD deposited material 140 with an aperture that is narrowed to nanopore dimensions, but stopping short of completely closing aperture in the PVD deposited material 140 as illustrated in Fig. 9B or 1OB. [0080] A similar effect may also be achieved by off-angle sputtering as in Fig. I OA, but with a heavy, non-layer-forming species such as Argon. Where a malleable material such as a metal is employed for the medical device portion 110, the sputtered species may act to "hammer" the aperture in the device portion 110 to the dimensions of a nanopore. [0081] Returning to Fig. 8, once process step Cl is completed, the resulting cavity 120c is then loaded with a therapeutic agent 120t by conveying the therapeutic agent through the porous region 140, as illustrated in step C2. For example, a fluid containing dissolved or dispersed therapeutic agent (and suitable supplemental material(s), if desired) may be contacted with the porous region 140, for instance, by dipping, spraying, extrusion, coating with an applicator (e.g., by roller or brush), spin-coating, web coating, techniques involving coating via mechanical suspension including air suspension, ink jet techniques,
and combinations of these processes, among other techniques. Water, organic solvents, subcritical fluids, critical point fluids, supercritical fluids, and so forth can be used as carriers for the therapeutic agent. In one preferred technique, the solvent is a supercritical solvent. Further information on supercritical solvent loading may be found in Serial No. 11/007,866, filed 9 December 2004 and entitled "Use of Supercritical Fluids to Incorporate Biologically Active Agents into Nanoporous Medical Articles." [0082] In a further variation shown in Fig. 8, depression 12Od is first filled with a material 120m that can subsequently uptake significant amounts of drug (e.g., a sponge- like material), as illustrated in step Bl. Subsequently, as illustrated in step B2, the material 120m is loaded with a therapeutic agent 12Ot and a porous region 140 is provided over the medical device portion 110 (or vice versa).
[0083] In yet another variation, in step Bl of Fig. 8, the depression 120d is filled with a removable material 120m. Then a porous transport-controlling layer 140 is formed over the removable-material-filled depression 120m which removable material 120m is subsequently removed through the porous region 140 producing a cavity 120c as illustrated in step B3. Removable material 120m may be removed by various processes, including melting, sublimation, combustion, dissolution, supercritical extraction, or other process. The cavity 120c is then loaded with a therapeutic agent 12Ot by conveying the therapeutic agent through the porous region 140, as illustrated in step C2 (discussed above).
[0084] The use of depressions 120 that extend entirely through the device affords the opportunity to first form the nanoporous region 140 over the depression, and then load the depression with therapeutic agent 12Ot, without having to pass the therapeutic agent through the nanoporous region 140. For example, with reference to Fig. 11, in which a depression 120d is shown that extends completely through the medical device portion 110, a porous transport-controlling layer 140 may be established over one surface of the device portion 110. This can be done directly as shown in step Al (e.g., using techniques such as those described in conjunction with step Cl of Fig. 8 above). This can also be done indirectly, for example by first filling the depression 120 with a removable material 120m such as those described above, followed by the formation of a porous transport- controlling layer 140 over the device portion 110 and removable material 120m as shown
in Fig. 11, step Bl. The removable material 120m is then removed as illustrated in step
B2-
[00851 The depression 12Od (now capped on one end by porous transport-controlling layer 140) is then filled with a therapeutic agent 12Ot as shown in step A2 (e.g., using techniques such as those described above in conjunction with Fig. 8, step Al). Finally, an additional layer 150, which may or may not be a nanoporous layer, is provided over the therapeutic-agent-loaded depression 12Ot and the medical device portion 110 as illustrated in Fig. 11, step A3. Non nanoporous materials for this purpose may be selected from suitable members of the numerous organic and inorganic materials described above.
[0086] Finally, in addition to trenches that are all found at a single depth within the substrate, one may also provide trenches that form crisscrossing grids at different depths within the substrate (including submerged trenches, or "veins"), thereby creating interconnected paths for loading and release of drug.
[0087] Although various embodiments are specifically illustrated and described herein, it will be appreciated that modifications and variations of the present invention are covered by the above teachings and are within the purview of the appended claims without departing from the spirit and intended scope of the invention.
Claims
1. An implantable or insettable medical device comprising: (a) a region comprising a depression (b) a therapeutic-agent-containing region within said depression, said therapeutic-agent-containing region comprising a first therapeutic agent, and (c) a nanoporous region disposed over the depression and regulating transport of molecular species between the depression and an exterior of the device, wherein said medical device provides a therapeutic function beyond its function as a therapeutic agent depot.
2. The implantable or insertable medical device of claim 1, wherein said region comprises a plurality of depressions.
3. The implantable or insertable medical device of claim 1, wherein said depression is a through-hole or a slot.
4. The implantable or insertable medical device of claim I, wherein said depression is a blind hole or a trench.
5. The implantable or insertable medical device of claim 1, wherein the smallest lateral dimension of said depression is less than 1000 μm.
6. The implantable or insertable medical device of claim 1, wherein the smallest lateral dimension of said depression is less than 100 μm.
7. The implantable or insertable medical device of claim 1, wherein the depression has an aspect ratio of greater than or equal to 1.
8. The implantable or insertable medical device of claim 1, wherein said region comprising said depression is a metallic region.
9. The implantable or insertable medical device of claim 1, wherein said region comprising said depression is a polymeric region.
10. The implantable or insertable medical device of claim 1, wherein said, region comprising said depression is a silicon region.
1 1. The implantable or insertable medical device of claim 1, wherein said region comprising said depression is a ceramic region.
12. The implantable or insertable medical device of claim I9 wherein said nanoporous region is a nanoporous polymeric region.
13. The implantable or insertable medical device of claim 1, wherein said nanoporous region is a nanoporous metallic region.
14. The implantable or insertable medical device of claim 1, wherein said nanoporous region is a nanoporous ceramic region.
15. The implantable or insertable medical device of claim 14, wherein said nanoporous ceramic region selected from a nanoporous alumina region, a nanoporous titania region, and a nanoporous silica region.
16. The implantable or insertable medical device of claim 1, wherein said nanoporous region comprises a parallel pore structure.
17. The implantable or insertable medical device of claim 1, wherein said nanoporous region comprises an interconnected pore structure.
18. The implantable or insertable medical device of claim 1, wherein said therapeutic function is selected from a mechanical function, an electrical function, a thermal function and a magnetic function.
19. The implantable or insertable medical device of claim 1, wherein said device is selected from catheters, guide wires, balloons, filters, stents, grafts, stent grafts, vascular access ports, embolization devices, myocardial plugs, patches, pacemakers, pacemaker leads, left ventricular assist devices, total artificial hearts, heart valves, vascular valves, anastomosis clips and rings, and tissue engineering scaffolds.
20. The implantable or insertable medical device of claim I, wherein said medical device is adapted for implantation or insertion into the coronary vasculature, peripheral vascular system, esophagus, trachea, colon, biliary tract, urogenital system, or brain.
21. The implantable or insertable medical device of claim 1, wherein said medical device is a stent and wherein said region comprising said depression is a stent strut.
22. The implantable or insertable medical device of claim 1, further comprising a material in addition to said first therapeutic agent within said therapeutic-agent-containing region.
23. The implantable or insertable medical device of claim 1, further comprising a second therapeutic agent within said therapeutic-agent-containing region.
24. The implantable or insertable medical device of claim 1, wherein said therapeutic agent is released from said device.
25. The implantable or insertable medical device of claim 24, wherein the release is zero- order release.
26. The implantable or insertable medical device of claim I5 wherein said therapeutic agent is selected from one or more of the group consisting of anti-thrombotic agents, antiproliferative agents, anti-inflammatory agents, anti-migratory agents, agents affecting extracellular matrix production and organization, antineoplastic agents, anti-mitotic agents, anesthetic agents, anti-coagulants, vascular cell growth promoters, vascular cell growth inhibitors, cholesterol-lowering agents, vasodilating agents, TGF-β elevating agents, and agents that interfere with endogenous vasoactive mechanisms.
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2009501430A JP5424865B2 (en) | 2006-03-24 | 2007-02-26 | Medical device with nanoporous coating for controlled therapeutic agent delivery |
EP07751464A EP2010241A2 (en) | 2006-03-24 | 2007-02-26 | Medical devices having nanoporous coatings for controlled therapeutic agent delivery |
CA002661456A CA2661456A1 (en) | 2006-03-24 | 2007-02-26 | Medical devices having nanoporous coatings for controlled therapeutic agent delivery |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/388,604 US20070224235A1 (en) | 2006-03-24 | 2006-03-24 | Medical devices having nanoporous coatings for controlled therapeutic agent delivery |
US11/388,604 | 2006-03-24 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2007111801A2 true WO2007111801A2 (en) | 2007-10-04 |
WO2007111801A3 WO2007111801A3 (en) | 2008-06-19 |
Family
ID=38512124
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2007/004704 WO2007111801A2 (en) | 2006-03-24 | 2007-02-26 | Medical devices having nanoporous coatings for controlled therapeutic agent delivery |
Country Status (5)
Country | Link |
---|---|
US (2) | US20070224235A1 (en) |
EP (1) | EP2010241A2 (en) |
JP (1) | JP5424865B2 (en) |
CA (1) | CA2661456A1 (en) |
WO (1) | WO2007111801A2 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009038870A1 (en) * | 2007-09-19 | 2009-03-26 | Boston Scientific Scimed, Inc. | Stent design allowing extended release of drug and/or enhanced adhesion of polymer to od surface |
JP2011509809A (en) * | 2008-01-24 | 2011-03-31 | ボストン サイエンティフィック サイムド,インコーポレイテッド | Stent for delivering therapeutic agent from side surface of stent strut |
Families Citing this family (92)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7713297B2 (en) | 1998-04-11 | 2010-05-11 | Boston Scientific Scimed, Inc. | Drug-releasing stent with ceramic-containing layer |
US8458879B2 (en) * | 2001-07-03 | 2013-06-11 | Advanced Bio Prosthetic Surfaces, Ltd., A Wholly Owned Subsidiary Of Palmaz Scientific, Inc. | Method of fabricating an implantable medical device |
CN103251449B (en) | 2005-10-13 | 2016-03-02 | 斯恩蒂斯有限公司 | Drug-impregnated encasement |
US20070224235A1 (en) | 2006-03-24 | 2007-09-27 | Barron Tenney | Medical devices having nanoporous coatings for controlled therapeutic agent delivery |
US8187620B2 (en) | 2006-03-27 | 2012-05-29 | Boston Scientific Scimed, Inc. | Medical devices comprising a porous metal oxide or metal material and a polymer coating for delivering therapeutic agents |
US8815275B2 (en) | 2006-06-28 | 2014-08-26 | Boston Scientific Scimed, Inc. | Coatings for medical devices comprising a therapeutic agent and a metallic material |
CA2655793A1 (en) | 2006-06-29 | 2008-01-03 | Boston Scientific Limited | Medical devices with selective coating |
DE102006038241A1 (en) * | 2006-08-07 | 2008-02-14 | Biotronik Vi Patent Ag | Stent with a genisteinhaltigen coating or Kavitätenfüllung |
JP2010503469A (en) | 2006-09-14 | 2010-02-04 | ボストン サイエンティフィック リミテッド | Medical device having drug-eluting film |
US7666179B2 (en) * | 2006-10-10 | 2010-02-23 | Boston Scientific Scimed, Inc. | Medical devices having porous regions for controlled therapeutic agent exposure or delivery |
US7981150B2 (en) * | 2006-11-09 | 2011-07-19 | Boston Scientific Scimed, Inc. | Endoprosthesis with coatings |
US8221496B2 (en) | 2007-02-01 | 2012-07-17 | Cordis Corporation | Antithrombotic and anti-restenotic drug eluting stent |
US8070797B2 (en) | 2007-03-01 | 2011-12-06 | Boston Scientific Scimed, Inc. | Medical device with a porous surface for delivery of a therapeutic agent |
US8431149B2 (en) * | 2007-03-01 | 2013-04-30 | Boston Scientific Scimed, Inc. | Coated medical devices for abluminal drug delivery |
US8067054B2 (en) | 2007-04-05 | 2011-11-29 | Boston Scientific Scimed, Inc. | Stents with ceramic drug reservoir layer and methods of making and using the same |
US8703168B2 (en) * | 2007-04-25 | 2014-04-22 | Boston Scientific Scimed, Inc. | Medical devices for releasing therapeutic agent and methods of making the same |
US7976915B2 (en) | 2007-05-23 | 2011-07-12 | Boston Scientific Scimed, Inc. | Endoprosthesis with select ceramic morphology |
US7942926B2 (en) | 2007-07-11 | 2011-05-17 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US8002823B2 (en) | 2007-07-11 | 2011-08-23 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
WO2009012353A2 (en) | 2007-07-19 | 2009-01-22 | Boston Scientific Limited | Endoprosthesis having a non-fouling surface |
US7931683B2 (en) | 2007-07-27 | 2011-04-26 | Boston Scientific Scimed, Inc. | Articles having ceramic coated surfaces |
US8815273B2 (en) | 2007-07-27 | 2014-08-26 | Boston Scientific Scimed, Inc. | Drug eluting medical devices having porous layers |
WO2009018340A2 (en) | 2007-07-31 | 2009-02-05 | Boston Scientific Scimed, Inc. | Medical device coating by laser cladding |
JP2010535541A (en) | 2007-08-03 | 2010-11-25 | ボストン サイエンティフィック リミテッド | Coating for medical devices with large surface area |
JP2009050773A (en) * | 2007-08-24 | 2009-03-12 | Fujifilm Corp | Cross-flow filtration method and cross-flow filtration device |
JP2010536534A (en) * | 2007-08-24 | 2010-12-02 | ブラウン ユニヴァーシティ | Method for generating nanostructures on the surface of a medical implant |
US8216632B2 (en) | 2007-11-02 | 2012-07-10 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US8029554B2 (en) | 2007-11-02 | 2011-10-04 | Boston Scientific Scimed, Inc. | Stent with embedded material |
US7938855B2 (en) | 2007-11-02 | 2011-05-10 | Boston Scientific Scimed, Inc. | Deformable underlayer for stent |
US7833266B2 (en) | 2007-11-28 | 2010-11-16 | Boston Scientific Scimed, Inc. | Bifurcated stent with drug wells for specific ostial, carina, and side branch treatment |
EP2229192A2 (en) * | 2007-12-12 | 2010-09-22 | Boston Scientific Scimed, Inc. | Medical devices having porous component for controlled diffusion |
EP2271380B1 (en) | 2008-04-22 | 2013-03-20 | Boston Scientific Scimed, Inc. | Medical devices having a coating of inorganic material |
WO2009132176A2 (en) | 2008-04-24 | 2009-10-29 | Boston Scientific Scimed, Inc. | Medical devices having inorganic particle layers |
US20090274740A1 (en) * | 2008-05-01 | 2009-11-05 | Boston Scientific Scimed, Inc. | Drug-loaded medical devices and methods for manufacturing drug-loaded medical devices |
EP2303350A2 (en) | 2008-06-18 | 2011-04-06 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
CA2728668A1 (en) * | 2008-06-25 | 2009-12-30 | Boston Scientific Scimed, Inc. | Medical devices containing therapeutic agents |
US7951193B2 (en) | 2008-07-23 | 2011-05-31 | Boston Scientific Scimed, Inc. | Drug-eluting stent |
US8337878B2 (en) * | 2008-08-27 | 2012-12-25 | Boston Scientific Scimed, Inc. | Medical devices having coatings for therapeutic agent delivery |
US8231980B2 (en) | 2008-12-03 | 2012-07-31 | Boston Scientific Scimed, Inc. | Medical implants including iridium oxide |
DE102008054403A1 (en) * | 2008-12-09 | 2010-06-10 | Robert Bosch Gmbh | Implant for implanting in human or animal body, has surface structure on its surface area, where surface structure has nanostructure for attaching implant to body part |
KR101087088B1 (en) * | 2008-12-29 | 2011-11-25 | 한국과학기술연구원 | Method for preparing drug-eluting stent having nano-structured pattern and drug-eluting stent prepared therefrom |
US8734829B2 (en) * | 2009-02-13 | 2014-05-27 | Boston Scientific Scimed, Inc. | Medical devices having polymeric nanoporous coatings for controlled therapeutic agent delivery and a nonpolymeric macroporous protective layer |
US8071156B2 (en) | 2009-03-04 | 2011-12-06 | Boston Scientific Scimed, Inc. | Endoprostheses |
US20100233288A1 (en) * | 2009-03-11 | 2010-09-16 | Teleflex Medical Incorporated | Medical devices containing nitroprusside and antimicrobial agents |
US11219706B2 (en) | 2009-03-11 | 2022-01-11 | Arrow International Llc | Enhanced formulations for coating medical devices |
US8287937B2 (en) | 2009-04-24 | 2012-10-16 | Boston Scientific Scimed, Inc. | Endoprosthese |
US8562670B2 (en) * | 2010-04-01 | 2013-10-22 | Abbott Cardiovascular Systems Inc. | Implantable prosthesis with depot retention feature |
MX2012012567A (en) | 2010-04-28 | 2012-11-21 | Kimberly Clark Co | Method for increasing permeability of an epithelial barrier. |
EP2563450B1 (en) | 2010-04-28 | 2017-07-26 | Kimberly-Clark Worldwide, Inc. | Device for delivery of rheumatoid arthritis medication |
JP5871907B2 (en) | 2010-04-28 | 2016-03-01 | キンバリー クラーク ワールドワイド インコーポレイテッド | Nanopatterned medical device with enhanced cell-cell interaction |
RU2585138C2 (en) | 2010-04-28 | 2016-05-27 | Кимберли-Кларк Ворлдвайд, Инк. | Medical devices for delivery of sirna |
US20130131629A1 (en) * | 2010-05-19 | 2013-05-23 | The Board of Regents of the Unversity of Texas System | Nanochanneled device and related methods |
US8616040B2 (en) * | 2010-09-17 | 2013-12-31 | Medtronic Vascular, Inc. | Method of forming a drug-eluting medical device |
US9132194B2 (en) | 2011-07-12 | 2015-09-15 | Warsaw Orthopedic, Inc. | Medical devices and methods comprising an adhesive sheet containing a drug depot |
US9205241B2 (en) | 2011-07-12 | 2015-12-08 | Warsaw Orthopedic, Inc. | Medical devices and methods comprising an adhesive material |
CN102499798A (en) * | 2011-09-29 | 2012-06-20 | 微创医疗器械(上海)有限公司 | Interventional medical device and preparation method thereof |
CN102397119A (en) * | 2011-09-29 | 2012-04-04 | 微创医疗器械(上海)有限公司 | Interventional medical appliance and manufacturing method thereof |
JP6535464B2 (en) * | 2011-10-27 | 2019-06-26 | ソレント・セラピューティクス・インコーポレイテッド | Implantable device for delivery of bioactive agents |
US20170246439A9 (en) | 2011-10-27 | 2017-08-31 | Kimberly-Clark Worldwide, Inc. | Increased Bioavailability of Transdermally Delivered Agents |
BR112014009713A2 (en) | 2011-10-27 | 2017-04-18 | Kimberly Clark Co | transdermal administration of high viscosity bioactive agents |
TWI590843B (en) | 2011-12-28 | 2017-07-11 | 信迪思有限公司 | Films and methods of manufacture |
US9526640B2 (en) | 2013-08-18 | 2016-12-27 | Boston Scientific Scimed, Inc. | Anti-migration micropatterned stent coating |
US8735504B2 (en) | 2012-05-02 | 2014-05-27 | Warsaw Orthopedic, Inc. | Methods for preparing polymers having low residual monomer content |
DE102012021222B4 (en) * | 2012-10-27 | 2015-02-05 | Forschungszentrum Jülich GmbH | Process for producing a nanoporous layer on a substrate |
JP6247009B2 (en) * | 2013-03-15 | 2017-12-13 | Hoya株式会社 | Open device |
EP3010560B1 (en) | 2013-06-21 | 2020-01-01 | DePuy Synthes Products, Inc. | Films and methods of manufacture |
WO2015023966A1 (en) * | 2013-08-16 | 2015-02-19 | Simpore Inc. | Nanoporous silicon nitride membranes |
FR3011191B1 (en) * | 2013-09-27 | 2019-07-26 | Centre National De La Recherche Scientifique (C.N.R.S) | CATIONIC SUPPORT FORMING HYBRID ANIONIC MEMBRANE |
CN103565558B (en) * | 2013-10-21 | 2015-07-01 | 西安交通大学 | High-strength double-network hydrogel/bioceramic composite stent and preparation method thereof |
US10828400B2 (en) | 2014-06-10 | 2020-11-10 | The Research Foundation For The State University Of New York | Low temperature, nanostructured ceramic coatings |
US9925797B2 (en) | 2014-08-07 | 2018-03-27 | Orbotech Ltd. | Lift printing system |
US10193004B2 (en) | 2014-10-19 | 2019-01-29 | Orbotech Ltd. | LIFT printing of conductive traces onto a semiconductor substrate |
WO2016062764A1 (en) * | 2014-10-23 | 2016-04-28 | Biotronik Se & Co. Kg | Method for treating a medical implant |
DE102015101425B4 (en) * | 2014-10-31 | 2018-02-01 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Process for producing a component based on a structurable substrate with a three-dimensional membrane structure having pores in the nm range |
US10727122B2 (en) | 2014-12-08 | 2020-07-28 | International Business Machines Corporation | Self-aligned via interconnect structures |
CN106999284A (en) * | 2014-12-25 | 2017-08-01 | 奥林巴斯株式会社 | Bone engagement implant and its manufacture method |
EP3247816A4 (en) | 2015-01-19 | 2018-01-24 | Orbotech Ltd. | Printing of three-dimensional metal structures with a sacrificial support |
US10661261B2 (en) | 2015-03-13 | 2020-05-26 | The Research Foundation For The State University Of New York | Metal oxide nanofibrous materials for photodegradation of environmental toxins |
KR101653275B1 (en) * | 2015-06-29 | 2016-09-02 | 경희대학교 산학협력단 | Method for patterning nitinol substrate |
US10471538B2 (en) | 2015-07-09 | 2019-11-12 | Orbotech Ltd. | Control of lift ejection angle |
WO2017085712A1 (en) | 2015-11-22 | 2017-05-26 | Orbotech Ltd | Control of surface properties of printed three-dimensional structures |
ITUA20162094A1 (en) * | 2016-03-29 | 2017-09-29 | Cid S P A | IMPROVEMENT IN STENTS FOR RELEASING ACTIVE PRINCIPLES |
US9609874B1 (en) * | 2016-07-21 | 2017-04-04 | Kuwait Institute For Scientific Research | Metallic glassy alloy powders for antibacterial coating |
US10874768B2 (en) * | 2017-01-20 | 2020-12-29 | Covidien Lp | Drug eluting medical device |
EP3606566A4 (en) * | 2017-04-07 | 2020-12-09 | The Board Of Trustees Of The University Of Illinois | Nanostructured titanium-based compositions and methods to fabricate the same |
TW201901887A (en) | 2017-05-24 | 2019-01-01 | 以色列商奧寶科技股份有限公司 | Electrical interconnection circuit components on the substrate without prior patterning |
EP3466485B1 (en) * | 2017-10-05 | 2022-11-30 | Heraeus Deutschland GmbH & Co. KG | Internal cermet routing for complex feedthroughs |
KR102128809B1 (en) | 2018-04-13 | 2020-07-01 | 전남대학교산학협력단 | Non-polymer Tacrolimus eluting stent and method of manufacturing the Same |
US11478245B2 (en) | 2019-05-08 | 2022-10-25 | Covidien Lp | Surgical stapling device |
US11596403B2 (en) | 2019-05-08 | 2023-03-07 | Covidien Lp | Surgical stapling device |
WO2023031065A2 (en) * | 2021-08-30 | 2023-03-09 | Medicaltree Patents Ltd. | Drug delivery system |
WO2023031062A2 (en) * | 2021-08-30 | 2023-03-09 | Medicaltree Patents Ltd | Drug delivery system |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0875218A2 (en) * | 1997-04-15 | 1998-11-04 | Advanced Cardiovascular Systems, Inc. | Porous medicated stent |
WO2002047581A1 (en) * | 2000-12-15 | 2002-06-20 | Badari Narayan Nagarada Gadde | Stent with drug-delivery system |
EP1319416A1 (en) * | 2001-12-12 | 2003-06-18 | Hehrlein, Christoph, Dr. | Porous metallic stent with a ceramic coating |
US6709379B1 (en) * | 1998-11-02 | 2004-03-23 | Alcove Surfaces Gmbh | Implant with cavities containing therapeutic agents |
WO2006063157A2 (en) * | 2004-12-09 | 2006-06-15 | Boston Scientific Scimed, Inc. | Medical devices having vapor deposited nanoporous coatings for controlled therapeutic agent delivery |
Family Cites Families (939)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US783776A (en) * | 1904-03-07 | 1905-02-28 | Charles H Cornell | Milk-can. |
AT232704B (en) | 1959-03-31 | 1964-04-10 | Plastic Textile Access Ltd | Device for extrusion |
NL135500C (en) | 1964-03-04 | |||
SU393044A1 (en) | 1968-09-03 | 1973-08-10 | METHOD OF REINFORCEMENT OF METAL PRODUCTS BY GRAIN SOLID | |
US3751283A (en) | 1971-03-08 | 1973-08-07 | Remington Arms Co Inc | Armored metal tools and production thereof |
US3758396A (en) | 1971-08-31 | 1973-09-11 | Research Corp | Ition preparation of immobilized enzymemembrane complexes by electrocodepos |
US3948254A (en) | 1971-11-08 | 1976-04-06 | Alza Corporation | Novel drug delivery device |
US3910819A (en) | 1974-02-19 | 1975-10-07 | California Inst Of Techn | Treatment of surfaces to stimulate biological cell adhesion and growth |
US3970445A (en) | 1974-05-02 | 1976-07-20 | Caterpillar Tractor Co. | Wear-resistant alloy, and method of making same |
GB1527592A (en) | 1974-08-05 | 1978-10-04 | Ici Ltd | Wound dressing |
US3993072A (en) | 1974-08-28 | 1976-11-23 | Alza Corporation | Microporous drug delivery device |
US3952334A (en) | 1974-11-29 | 1976-04-27 | General Atomic Company | Biocompatible carbon prosthetic devices |
US4101984A (en) | 1975-05-09 | 1978-07-25 | Macgregor David C | Cardiovascular prosthetic devices and implants with porous systems |
DE2620907C3 (en) | 1976-05-12 | 1984-09-20 | Battelle-Institut E.V., 6000 Frankfurt | Anchoring for highly stressed endoprostheses |
US4143661A (en) | 1977-12-12 | 1979-03-13 | Andros Incorporated | Power supply for body implant and method for operation |
SE416175B (en) | 1979-03-07 | 1980-12-08 | Per Ingvar Branemark | FOR IMPLANTATION IN BODY TISSUE Separate Bone Tissue, Dedicated Material |
US4237559A (en) | 1979-05-11 | 1980-12-09 | General Electric Company | Bone implant embodying a composite high and low density fired ceramic construction |
US4334327A (en) | 1979-12-21 | 1982-06-15 | University Of Utah | Ureteral prosthesis |
US4321311A (en) | 1980-01-07 | 1982-03-23 | United Technologies Corporation | Columnar grain ceramic thermal barrier coatings |
US4309996A (en) * | 1980-04-28 | 1982-01-12 | Alza Corporation | System with microporous releasing diffusor |
US4308868A (en) * | 1980-05-27 | 1982-01-05 | The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration | Implantable electrical device |
CH649578A5 (en) | 1981-03-27 | 1985-05-31 | Ulvac Corp | HIGH-SPEED CATHODE SPRAYING DEVICE. |
US4475972A (en) | 1981-10-01 | 1984-10-09 | Ontario Research Foundation | Implantable material |
US5968640A (en) | 1985-04-23 | 1999-10-19 | The Boeing Company | Conductive, thermally stable oligomers |
US4407695A (en) | 1981-12-31 | 1983-10-04 | Exxon Research And Engineering Co. | Natural lithographic fabrication of microstructures over large areas |
SE445884B (en) | 1982-04-30 | 1986-07-28 | Medinvent Sa | DEVICE FOR IMPLANTATION OF A RODFORM PROTECTION |
US4587121A (en) | 1983-06-14 | 1986-05-06 | Miles Laboratories, Inc. | High titer Pseudomonas immune serum globulin |
US4565744A (en) * | 1983-11-30 | 1986-01-21 | Rockwell International Corporation | Wettable coating for reinforcement particles of metal matrix composite |
US4657544A (en) | 1984-04-18 | 1987-04-14 | Cordis Corporation | Cardiovascular graft and method of forming same |
US4585652A (en) | 1984-11-19 | 1986-04-29 | Regents Of The University Of Minnesota | Electrochemical controlled release drug delivery system |
DE3516411A1 (en) | 1985-05-07 | 1986-11-13 | Plasmainvent AG, Zug | COATING OF AN IMPLANT BODY |
US4635515A (en) * | 1985-05-29 | 1987-01-13 | Altman James E | Guide fence having rollers to reduce friction |
US4665896A (en) | 1985-07-22 | 1987-05-19 | Novacor Medical Corporation | Power supply for body implant and method of use |
US4705502A (en) | 1985-11-06 | 1987-11-10 | The Kendall Company | Suprapubic catheter with dual balloons |
US4733665C2 (en) | 1985-11-07 | 2002-01-29 | Expandable Grafts Partnership | Expandable intraluminal graft and method and apparatus for implanting an expandable intraluminal graft |
US4738740A (en) | 1985-11-21 | 1988-04-19 | Corvita Corporation | Method of forming implantable vascular grafts |
US4743252A (en) | 1986-01-13 | 1988-05-10 | Corvita Corporation | Composite grafts |
DE3608158A1 (en) * | 1986-03-12 | 1987-09-17 | Braun Melsungen Ag | VESSELED PROSTHESIS IMPREGNATED WITH CROSSLINED GELATINE AND METHOD FOR THE PRODUCTION THEREOF |
GB2189738B (en) | 1986-03-24 | 1989-11-15 | Ethicon Inc | Apparatus for producing fibrous structures electrostatically |
SE453258B (en) | 1986-04-21 | 1988-01-25 | Medinvent Sa | ELASTIC, SELF-EXPANDING PROTEST AND PROCEDURE FOR ITS MANUFACTURING |
US4800882A (en) * | 1987-03-13 | 1989-01-31 | Cook Incorporated | Endovascular stent and delivery system |
US5527337A (en) | 1987-06-25 | 1996-06-18 | Duke University | Bioabsorbable stent and method of making the same |
US4886062A (en) | 1987-10-19 | 1989-12-12 | Medtronic, Inc. | Intravascular radially expandable stent and method of implant |
DE3821544C2 (en) | 1988-06-25 | 1994-04-28 | H Prof Dr Med Just | Dilatation catheter |
US5091205A (en) * | 1989-01-17 | 1992-02-25 | Union Carbide Chemicals & Plastics Technology Corporation | Hydrophilic lubricious coatings |
US5163958A (en) | 1989-02-02 | 1992-11-17 | Cordis Corporation | Carbon coated tubular endoprosthesis |
JPH02279575A (en) | 1989-04-18 | 1990-11-15 | Nkk Corp | Production of sintered ceramic body having dense ceramic film |
US4994071A (en) * | 1989-05-22 | 1991-02-19 | Cordis Corporation | Bifurcating stent apparatus and method |
US5073365A (en) | 1989-06-01 | 1991-12-17 | Advanced Polymer Systems | Clinical and personal care articles enhanced by lubricants and adjuvants |
US5061914A (en) | 1989-06-27 | 1991-10-29 | Tini Alloy Company | Shape-memory alloy micro-actuator |
EP0405556B1 (en) | 1989-06-30 | 1996-05-22 | TDK Corporation | Living hard tissue replacement, its preparation, and preparation of integral body |
US5647858A (en) | 1989-07-25 | 1997-07-15 | Smith & Nephew, Inc. | Zirconium oxide and zirconium nitride coated catheters |
DE69002295T2 (en) | 1989-09-25 | 1993-11-04 | Schneider Usa Inc | MULTILAYER EXTRUSION AS A METHOD FOR PRODUCING BALLOONS FOR VESSEL PLASTICS. |
US5304121A (en) | 1990-12-28 | 1994-04-19 | Boston Scientific Corporation | Drug delivery system making use of a hydrogel polymer coating |
US5439446A (en) | 1994-06-30 | 1995-08-08 | Boston Scientific Corporation | Stent and therapeutic delivery system |
US5674192A (en) | 1990-12-28 | 1997-10-07 | Boston Scientific Corporation | Drug delivery |
US5843089A (en) | 1990-12-28 | 1998-12-01 | Boston Scientific Corporation | Stent lining |
US5477864A (en) | 1989-12-21 | 1995-12-26 | Smith & Nephew Richards, Inc. | Cardiovascular guidewire of enhanced biocompatibility |
US5171607A (en) | 1990-01-29 | 1992-12-15 | Bausch & Lomb Incorporated | Method of depositing diamond-like carbon film onto a substrate having a low melting temperature |
US5378146A (en) * | 1990-02-07 | 1995-01-03 | Ormco Corporation | Polyurethane biomedical devices & method of making same |
US5545208A (en) | 1990-02-28 | 1996-08-13 | Medtronic, Inc. | Intralumenal drug eluting prosthesis |
US5236413B1 (en) | 1990-05-07 | 1996-06-18 | Andrew J Feiring | Method and apparatus for inducing the permeation of medication into internal tissue |
AU7998091A (en) | 1990-05-17 | 1991-12-10 | Harbor Medical Devices, Inc. | Medical device polymer |
DE69016433T2 (en) | 1990-05-19 | 1995-07-20 | Papyrin Anatolij Nikiforovic | COATING METHOD AND DEVICE. |
US5587507A (en) | 1995-03-31 | 1996-12-24 | Rutgers, The State University | Synthesis of tyrosine derived diphenol monomers |
US5120322A (en) | 1990-06-13 | 1992-06-09 | Lathrotec, Inc. | Method and apparatus for treatment of fibrotic lesions |
US5102403A (en) | 1990-06-18 | 1992-04-07 | Eckhard Alt | Therapeutic medical instrument for insertion into body |
US4976692A (en) | 1990-09-13 | 1990-12-11 | Travenol Laboratories (Israel) Ltd. | Catheter particularly useful for inducing labor and/or for the application of a pharmaceutical substance to the cervix of the uterus |
US5258020A (en) | 1990-09-14 | 1993-11-02 | Michael Froix | Method of using expandable polymeric stent with memory |
US5160790A (en) | 1990-11-01 | 1992-11-03 | C. R. Bard, Inc. | Lubricious hydrogel coatings |
US6524274B1 (en) | 1990-12-28 | 2003-02-25 | Scimed Life Systems, Inc. | Triggered release hydrogel drug delivery system |
US5205921A (en) | 1991-02-04 | 1993-04-27 | Queen's University At Kingston | Method for depositing bioactive coatings on conductive substrates |
DE4104359A1 (en) * | 1991-02-13 | 1992-08-20 | Implex Gmbh | CHARGING SYSTEM FOR IMPLANTABLE HOERHILFEN AND TINNITUS MASKERS |
US5195969A (en) | 1991-04-26 | 1993-03-23 | Boston Scientific Corporation | Co-extruded medical balloons and catheter using such balloons |
US5326354A (en) | 1991-05-09 | 1994-07-05 | Howmedica Inc. | Method for forming attachment surfaces on implants |
US5147370A (en) | 1991-06-12 | 1992-09-15 | Mcnamara Thomas O | Nitinol stent for hollow body conduits |
US5258098A (en) | 1991-06-17 | 1993-11-02 | Cycam, Inc. | Method of production of a surface adapted to promote adhesion |
US5242706A (en) | 1991-07-31 | 1993-09-07 | The United States Of America As Represented By The Secretary Of The Navy | Laser-deposited biocompatible films and methods and apparatuses for producing same |
US5811447A (en) * | 1993-01-28 | 1998-09-22 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US6515009B1 (en) * | 1991-09-27 | 2003-02-04 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US5219611A (en) | 1991-09-30 | 1993-06-15 | Cornell Research Foundation, Inc. | Preparing densified low porosity titania sol gel forms |
US5464450A (en) | 1991-10-04 | 1995-11-07 | Scimed Lifesystems Inc. | Biodegradable drug delivery vascular stent |
US5500013A (en) | 1991-10-04 | 1996-03-19 | Scimed Life Systems, Inc. | Biodegradable drug delivery vascular stent |
WO1993006792A1 (en) | 1991-10-04 | 1993-04-15 | Scimed Life Systems, Inc. | Biodegradable drug delivery vascular stent |
US5366504A (en) | 1992-05-20 | 1994-11-22 | Boston Scientific Corporation | Tubular medical prosthesis |
WO1993007924A1 (en) | 1991-10-18 | 1993-04-29 | Spire Corporation | Bactericidal coatings for implants |
US6001289A (en) * | 1991-12-04 | 1999-12-14 | Materials Innovation, Inc. | Acid assisted cold welding and intermetallic formation |
US5314453A (en) | 1991-12-06 | 1994-05-24 | Spinal Cord Society | Position sensitive power transfer antenna |
US5193540A (en) | 1991-12-18 | 1993-03-16 | Alfred E. Mann Foundation For Scientific Research | Structure and method of manufacture of an implantable microstimulator |
US5348553A (en) | 1991-12-18 | 1994-09-20 | Whitney Douglass G | Method for promoting blood vessel healing |
US5591224A (en) * | 1992-03-19 | 1997-01-07 | Medtronic, Inc. | Bioelastomeric stent |
US5282823A (en) | 1992-03-19 | 1994-02-01 | Medtronic, Inc. | Intravascular radially expandable stent |
US6071567A (en) | 1992-03-25 | 2000-06-06 | Reeves Brothers, Inc. | Formation of compressible ply containing high melting point thermoplastic microspheres and printing blankets comprising same |
JPH07505316A (en) | 1992-03-31 | 1995-06-15 | ボストン サイエンティフィック コーポレーション | medical wire |
US5807407A (en) | 1992-05-04 | 1998-09-15 | Biomet, Inc. | Medical implant device and method for making same |
IL106013A (en) | 1992-07-13 | 1994-12-29 | Litton Systems Inc | Flip-up mount for night vision system |
CA2074318A1 (en) * | 1992-07-22 | 1994-01-23 | Morteza Shirkhanzadeh | Prosthetic implant with self-generated current for early fixation in skeletal bone |
US5614549A (en) | 1992-08-21 | 1997-03-25 | Enzon, Inc. | High molecular weight polymer-based prodrugs |
US5578075B1 (en) | 1992-11-04 | 2000-02-08 | Daynke Res Inc | Minimally invasive bioactivated endoprosthesis for vessel repair |
US5449382A (en) | 1992-11-04 | 1995-09-12 | Dayton; Michael P. | Minimally invasive bioactivated endoprosthesis for vessel repair |
US5322520A (en) | 1992-11-12 | 1994-06-21 | Implemed, Inc. | Iontophoretic structure for medical devices |
ES2166370T3 (en) | 1993-01-19 | 2002-04-16 | Schneider Usa Inc | IMPLANTABLE FILAMENT IN COMPOSITE MATERIAL. |
US5607463A (en) | 1993-03-30 | 1997-03-04 | Medtronic, Inc. | Intravascular medical device |
US5380298A (en) * | 1993-04-07 | 1995-01-10 | The United States Of America As Represented By The Secretary Of The Navy | Medical device with infection preventing feature |
US5464650A (en) | 1993-04-26 | 1995-11-07 | Medtronic, Inc. | Intravascular stent and method |
US20020055710A1 (en) | 1998-04-30 | 2002-05-09 | Ronald J. Tuch | Medical device for delivering a therapeutic agent and method of preparation |
US5824048A (en) | 1993-04-26 | 1998-10-20 | Medtronic, Inc. | Method for delivering a therapeutic substance to a body lumen |
US5368881A (en) | 1993-06-10 | 1994-11-29 | Depuy, Inc. | Prosthesis with highly convoluted surface |
US20030203976A1 (en) * | 1993-07-19 | 2003-10-30 | William L. Hunter | Anti-angiogenic compositions and methods of use |
US5994341A (en) | 1993-07-19 | 1999-11-30 | Angiogenesis Technologies, Inc. | Anti-angiogenic Compositions and methods for the treatment of arthritis |
US5776748A (en) | 1993-10-04 | 1998-07-07 | President And Fellows Of Harvard College | Method of formation of microstamped patterns on plates for adhesion of cells and other biological materials, devices and uses therefor |
US6776094B1 (en) | 1993-10-04 | 2004-08-17 | President & Fellows Of Harvard College | Kit For Microcontact Printing |
US5397307A (en) | 1993-12-07 | 1995-03-14 | Schneider (Usa) Inc. | Drug delivery PTCA catheter and method for drug delivery |
US5788687A (en) | 1994-02-01 | 1998-08-04 | Caphco, Inc | Compositions and devices for controlled release of active ingredients |
US5449373A (en) | 1994-03-17 | 1995-09-12 | Medinol Ltd. | Articulated stent |
JPH07257079A (en) | 1994-03-25 | 1995-10-09 | Dainippon Printing Co Ltd | Optical card |
ATE310839T1 (en) | 1994-04-29 | 2005-12-15 | Scimed Life Systems Inc | STENT WITH COLLAGEN |
US5788979A (en) | 1994-07-22 | 1998-08-04 | Inflow Dynamics Inc. | Biodegradable coating with inhibitory properties for application to biocompatible materials |
US6514289B1 (en) | 2000-01-30 | 2003-02-04 | Diamicron, Inc. | Diamond articulation surface for use in a prosthetic joint |
US5504385A (en) | 1994-08-31 | 1996-04-02 | At&T Corp. | Spaced-gate emission device and method for making same |
DE4431862C2 (en) | 1994-09-07 | 1997-12-11 | Dot Duennschicht Und Oberflaec | Process for coating metal and ceramic surfaces with hydroxyapatite |
US5891108A (en) | 1994-09-12 | 1999-04-06 | Cordis Corporation | Drug delivery stent |
US5649977A (en) | 1994-09-22 | 1997-07-22 | Advanced Cardiovascular Systems, Inc. | Metal reinforced polymer stent |
EP0705911B1 (en) * | 1994-10-04 | 2001-12-05 | General Electric Company | Thermal barrier coating |
BE1008955A3 (en) | 1994-11-14 | 1996-10-01 | Univ Catholique Louvain | Process for obtaining and products obtained biomaterials. |
CA2163824C (en) | 1994-11-28 | 2000-06-20 | Richard J. Saunders | Method and apparatus for direct laser cutting of metal stents |
US5755722A (en) | 1994-12-22 | 1998-05-26 | Boston Scientific Corporation | Stent placement device with medication dispenser and method |
US6017577A (en) * | 1995-02-01 | 2000-01-25 | Schneider (Usa) Inc. | Slippery, tenaciously adhering hydrophilic polyurethane hydrogel coatings, coated polymer substrate materials, and coated medical devices |
US6231600B1 (en) | 1995-02-22 | 2001-05-15 | Scimed Life Systems, Inc. | Stents with hybrid coating for medical devices |
DE19506188C2 (en) | 1995-02-22 | 2003-03-06 | Miladin Lazarov | Implant and its use |
US7204848B1 (en) | 1995-03-01 | 2007-04-17 | Boston Scientific Scimed, Inc. | Longitudinally flexible expandable stent |
US6306144B1 (en) | 1996-11-01 | 2001-10-23 | Scimed Life Systems, Inc. | Selective coating of a balloon catheter with lubricious material for stent deployment |
US5605696A (en) | 1995-03-30 | 1997-02-25 | Advanced Cardiovascular Systems, Inc. | Drug loaded polymeric material and method of manufacture |
US5837313A (en) | 1995-04-19 | 1998-11-17 | Schneider (Usa) Inc | Drug release stent coating process |
DE29624503U1 (en) | 1995-04-19 | 2004-09-16 | Boston Scientific Scimed, Inc. | Drug-releasing coated stent |
US6099562A (en) | 1996-06-13 | 2000-08-08 | Schneider (Usa) Inc. | Drug coating with topcoat |
US6120536A (en) | 1995-04-19 | 2000-09-19 | Schneider (Usa) Inc. | Medical devices with long term non-thrombogenic coatings |
US5795626A (en) * | 1995-04-28 | 1998-08-18 | Innovative Technology Inc. | Coating or ablation applicator with a debris recovery attachment |
WO1996037165A1 (en) | 1995-05-26 | 1996-11-28 | Bsi Corporation | Method and implantable article for promoting endothelialization |
US5674242A (en) | 1995-06-06 | 1997-10-07 | Quanam Medical Corporation | Endoprosthetic device with therapeutic compound |
US6774278B1 (en) | 1995-06-07 | 2004-08-10 | Cook Incorporated | Coated implantable medical device |
US5609629A (en) | 1995-06-07 | 1997-03-11 | Med Institute, Inc. | Coated implantable medical device |
US7550005B2 (en) * | 1995-06-07 | 2009-06-23 | Cook Incorporated | Coated implantable medical device |
AU716005B2 (en) * | 1995-06-07 | 2000-02-17 | Cook Medical Technologies Llc | Implantable medical device |
US5733924A (en) | 1995-06-16 | 1998-03-31 | Kyowa Hakko Kogyo Co., Ltd. | DC 107 derivatives and treatment methods |
US6209621B1 (en) | 1995-07-07 | 2001-04-03 | Depuy Orthopaedics, Inc. | Implantable prostheses with metallic porous bead preforms applied during casting and method of forming the same |
NZ315995A (en) | 1995-09-01 | 1999-09-29 | Millenium Biologix Inc | Artificial sintered composition comprising stabilised calcium phosphate phases capable of supporting bone cell activity |
US6846493B2 (en) * | 1995-09-01 | 2005-01-25 | Millenium Biologix Inc. | Synthetic biomaterial compound of calcium phosphate phases particularly adapted for supporting bone cell activity |
US5758562A (en) | 1995-10-11 | 1998-06-02 | Schneider (Usa) Inc. | Process for manufacturing braided composite prosthesis |
US5603556A (en) * | 1995-11-20 | 1997-02-18 | Technical Services And Marketing, Inc. | Rail car load sensor |
DE19544750A1 (en) | 1995-11-30 | 1997-06-05 | Christoph Rehberg | Implantable device with internal electrode to promote tissue growth |
ATE219165T1 (en) | 1995-12-14 | 2002-06-15 | Imperial College | FILM OR LAYER DEPOSITION AND POWDER PRODUCTION |
US5852088A (en) | 1995-12-27 | 1998-12-22 | Exxon Research And Engineering Company | Nanoporous ceramics with catalytic functionality |
US5874134A (en) * | 1996-01-29 | 1999-02-23 | Regents Of The University Of Minnesota | Production of nanostructured materials by hypersonic plasma particle deposition |
US5672242A (en) | 1996-01-31 | 1997-09-30 | Integrated Device Technology, Inc. | High selectivity nitride to oxide etch process |
US5772864A (en) | 1996-02-23 | 1998-06-30 | Meadox Medicals, Inc. | Method for manufacturing implantable medical devices |
US6441025B2 (en) | 1996-03-12 | 2002-08-27 | Pg-Txl Company, L.P. | Water soluble paclitaxel derivatives |
US6355198B1 (en) | 1996-03-15 | 2002-03-12 | President And Fellows Of Harvard College | Method of forming articles including waveguides via capillary micromolding and microtransfer molding |
CA2199890C (en) | 1996-03-26 | 2002-02-05 | Leonard Pinchuk | Stents and stent-grafts having enhanced hoop strength and methods of making the same |
EP0927006B1 (en) | 1996-04-26 | 2006-01-18 | Boston Scientific Scimed, Inc. | Intravascular stent |
US6241760B1 (en) | 1996-04-26 | 2001-06-05 | G. David Jang | Intravascular stent |
US5922021A (en) | 1996-04-26 | 1999-07-13 | Jang; G. David | Intravascular stent |
US6783543B2 (en) | 2000-06-05 | 2004-08-31 | Scimed Life Systems, Inc. | Intravascular stent with increasing coating retaining capacity |
US20040106985A1 (en) | 1996-04-26 | 2004-06-03 | Jang G. David | Intravascular stent |
US5888591A (en) | 1996-05-06 | 1999-03-30 | Massachusetts Institute Of Technology | Chemical vapor deposition of fluorocarbon polymer thin films |
US5951881A (en) | 1996-07-22 | 1999-09-14 | President And Fellows Of Harvard College | Fabrication of small-scale cylindrical articles |
US5830480A (en) | 1996-05-09 | 1998-11-03 | The Trustees Of The University Of Pennsylvania | Stabilization of sol-gel derived silica-based glass |
EP0806211B1 (en) | 1996-05-10 | 2002-10-23 | IsoTis N.V. | Implant material and process for producing it |
US6764690B2 (en) * | 1996-05-29 | 2004-07-20 | Delsitech Oy | Dissolvable oxides for biological applications |
US5693928A (en) | 1996-06-27 | 1997-12-02 | International Business Machines Corporation | Method for producing a diffusion barrier and polymeric article having a diffusion barrier |
US5769884A (en) | 1996-06-27 | 1998-06-23 | Cordis Corporation | Controlled porosity endovascular implant |
US5797898A (en) | 1996-07-02 | 1998-08-25 | Massachusetts Institute Of Technology | Microchip drug delivery devices |
US5741331A (en) | 1996-07-29 | 1998-04-21 | Corvita Corporation | Biostable elastomeric polymers having quaternary carbons |
US6174329B1 (en) | 1996-08-22 | 2001-01-16 | Advanced Cardiovascular Systems, Inc. | Protective coating for a stent with intermediate radiopaque coating |
US6756060B1 (en) | 1996-09-19 | 2004-06-29 | Usbiomaterials Corp. | Anti-inflammatory and antimicrobial uses for bioactive glass compositions |
EP1275352A3 (en) | 1996-09-20 | 2003-06-11 | Converge Medical, Inc. | Radially expanding prostheses and systems for their deployment |
US6074135A (en) * | 1996-09-25 | 2000-06-13 | Innovative Technologies, Inc. | Coating or ablation applicator with debris recovery attachment |
US5761775A (en) | 1996-10-17 | 1998-06-09 | Legome; Mark J. | Mushroom and loop material closure system for high shear strength and low peel strength applications |
US5824045A (en) | 1996-10-21 | 1998-10-20 | Inflow Dynamics Inc. | Vascular and endoluminal stents |
US6099561A (en) | 1996-10-21 | 2000-08-08 | Inflow Dynamics, Inc. | Vascular and endoluminal stents with improved coatings |
US6387121B1 (en) | 1996-10-21 | 2002-05-14 | Inflow Dynamics Inc. | Vascular and endoluminal stents with improved coatings |
US6530951B1 (en) | 1996-10-24 | 2003-03-11 | Cook Incorporated | Silver implantable medical device |
US6331289B1 (en) * | 1996-10-28 | 2001-12-18 | Nycomed Imaging As | Targeted diagnostic/therapeutic agents having more than one different vectors |
US6106473A (en) | 1996-11-06 | 2000-08-22 | Sts Biopolymers, Inc. | Echogenic coatings |
ZA9710342B (en) | 1996-11-25 | 1998-06-10 | Alza Corp | Directional drug delivery stent and method of use. |
US6495579B1 (en) | 1996-12-02 | 2002-12-17 | Angiotech Pharmaceuticals, Inc. | Method for treating multiple sclerosis |
US5871437A (en) | 1996-12-10 | 1999-02-16 | Inflow Dynamics, Inc. | Radioactive stent for treating blood vessels to prevent restenosis |
US6780491B1 (en) | 1996-12-12 | 2004-08-24 | Micron Technology, Inc. | Microstructures including hydrophilic particles |
IT1289815B1 (en) | 1996-12-30 | 1998-10-16 | Sorin Biomedica Cardio Spa | ANGIOPLASTIC STENT AND RELATED PRODUCTION PROCESS |
US6013591A (en) * | 1997-01-16 | 2000-01-11 | Massachusetts Institute Of Technology | Nanocrystalline apatites and composites, prostheses incorporating them, and method for their production |
US5858556A (en) * | 1997-01-21 | 1999-01-12 | Uti Corporation | Multilayer composite tubular structure and method of making |
US5980551A (en) | 1997-02-07 | 1999-11-09 | Endovasc Ltd., Inc. | Composition and method for making a biodegradable drug delivery stent |
EP1007139A4 (en) | 1997-02-12 | 2000-06-14 | Prolifix Medical Inc | Apparatus for removal of material from stents |
ES2130062B1 (en) | 1997-02-19 | 2000-04-01 | Pons Creus Joan Maria | ELECTRODE SUPPORT FOR CARDIOLOGY. |
KR100526913B1 (en) | 1997-02-20 | 2005-11-09 | 쿡 인코포레이티드 | Coated implantable medical device |
WO1998038947A1 (en) | 1997-03-05 | 1998-09-11 | Scimed Life Systems, Inc. | Conformal laminate stent device |
US20020133222A1 (en) | 1997-03-05 | 2002-09-19 | Das Gladwin S. | Expandable stent having a plurality of interconnected expansion modules |
AU6584498A (en) | 1997-03-25 | 1998-10-20 | G. David Jang | Intravascular stent |
US5954724A (en) | 1997-03-27 | 1999-09-21 | Davidson; James A. | Titanium molybdenum hafnium alloys for medical implants and devices |
ES2388248T3 (en) | 1997-03-31 | 2012-10-11 | Boston Scientific Scimed Limited | Dosage form comprising taxol in crystalline form |
AU6946198A (en) | 1997-04-01 | 1998-10-22 | Cap Biotechnology, Inc. | Calcium phosphate microcarriers and microspheres |
US5977204A (en) | 1997-04-11 | 1999-11-02 | Osteobiologics, Inc. | Biodegradable implant material comprising bioactive ceramic |
US6240616B1 (en) | 1997-04-15 | 2001-06-05 | Advanced Cardiovascular Systems, Inc. | Method of manufacturing a medicated porous metal prosthesis |
US6273913B1 (en) | 1997-04-18 | 2001-08-14 | Cordis Corporation | Modified stent useful for delivery of drugs along stent strut |
IT1292295B1 (en) | 1997-04-29 | 1999-01-29 | Sorin Biomedica Cardio Spa | ANGIOPLASTIC STENT |
US5879697A (en) | 1997-04-30 | 1999-03-09 | Schneider Usa Inc | Drug-releasing coatings for medical devices |
US5891192A (en) | 1997-05-22 | 1999-04-06 | The Regents Of The University Of California | Ion-implanted protein-coated intralumenal implants |
US6025036A (en) | 1997-05-28 | 2000-02-15 | The United States Of America As Represented By The Secretary Of The Navy | Method of producing a film coating by matrix assisted pulsed laser deposition |
GB2325934A (en) | 1997-06-03 | 1998-12-09 | Polybiomed Ltd | Treating metal surfaces to enhance bio-compatibility and/or physical characteristics |
US6203536B1 (en) | 1997-06-17 | 2001-03-20 | Medtronic, Inc. | Medical device for delivering a therapeutic substance and method therefor |
US5749809A (en) | 1997-06-20 | 1998-05-12 | Lin; Ting Fung | Stepping and swinging exerciser |
US20020169493A1 (en) | 1997-07-10 | 2002-11-14 | Widenhouse Christopher W. | Anti-thrombogenic coatings for biomedical devices |
US5817046A (en) | 1997-07-14 | 1998-10-06 | Delcath Systems, Inc. | Apparatus and method for isolated pelvic perfusion |
FR2766092B1 (en) | 1997-07-16 | 1999-10-08 | Centre Nat Rech Scient | IMPLANTABLE DEVICE COATED WITH A POLYMER CAPABLE OF RELEASING BIOLOGICALLY ACTIVE SUBSTANCES |
DE19731021A1 (en) * | 1997-07-18 | 1999-01-21 | Meyer Joerg | In vivo degradable metallic implant |
JP3411559B2 (en) | 1997-07-28 | 2003-06-03 | マサチューセッツ・インスティチュート・オブ・テクノロジー | Pyrolytic chemical vapor deposition of silicone films. |
US6174330B1 (en) * | 1997-08-01 | 2001-01-16 | Schneider (Usa) Inc | Bioabsorbable marker having radiopaque constituents |
US5980564A (en) | 1997-08-01 | 1999-11-09 | Schneider (Usa) Inc. | Bioabsorbable implantable endoprosthesis with reservoir |
US5899935A (en) | 1997-08-04 | 1999-05-04 | Schneider (Usa) Inc. | Balloon expandable braided stent with restraint |
US6884429B2 (en) | 1997-09-05 | 2005-04-26 | Isotechnika International Inc. | Medical devices incorporating deuterated rapamycin for controlled delivery thereof |
US6342507B1 (en) * | 1997-09-05 | 2002-01-29 | Isotechnika, Inc. | Deuterated rapamycin compounds, method and uses thereof |
US5972027A (en) | 1997-09-30 | 1999-10-26 | Scimed Life Systems, Inc | Porous stent drug delivery system |
US6273908B1 (en) | 1997-10-24 | 2001-08-14 | Robert Ndondo-Lay | Stents |
AU1282499A (en) | 1997-10-28 | 1999-05-17 | Hills, Inc. | Synthetic fibres for medical use and method of making the same |
US6309414B1 (en) | 1997-11-04 | 2001-10-30 | Sorin Biomedica Cardio S.P.A. | Angioplasty stents |
AU749980B2 (en) | 1997-11-07 | 2002-07-04 | Advanced Bio Prosthetic Surfaces, Ltd. | Metallic Intravascular Stent and Method of Manufacturing a Metallic Intravascular Stent |
ATE307110T1 (en) | 1997-11-07 | 2005-11-15 | Univ Rutgers | RADIATION TRANSPARENT POLYMERIC BIOMATERIAL |
NO311781B1 (en) * | 1997-11-13 | 2002-01-28 | Medinol Ltd | Metal multilayer stents |
US6212434B1 (en) | 1998-07-22 | 2001-04-03 | Cardiac Pacemakers, Inc. | Single pass lead system |
US6077413A (en) | 1998-02-06 | 2000-06-20 | The Cleveland Clinic Foundation | Method of making a radioactive stent |
US6120660A (en) | 1998-02-11 | 2000-09-19 | Silicon Genesis Corporation | Removable liner design for plasma immersion ion implantation |
US6623521B2 (en) | 1998-02-17 | 2003-09-23 | Md3, Inc. | Expandable stent with sliding and locking radial elements |
US6139585A (en) | 1998-03-11 | 2000-10-31 | Depuy Orthopaedics, Inc. | Bioactive ceramic coating and method |
US6736849B2 (en) | 1998-03-11 | 2004-05-18 | Depuy Products, Inc. | Surface-mineralized spinal implants |
US6187037B1 (en) | 1998-03-11 | 2001-02-13 | Stanley Satz | Metal stent containing radioactivatable isotope and method of making same |
US7547445B2 (en) | 1998-03-19 | 2009-06-16 | Surmodics, Inc. | Crosslinkable macromers |
US7208010B2 (en) | 2000-10-16 | 2007-04-24 | Conor Medsystems, Inc. | Expandable medical device for delivery of beneficial agent |
US7208011B2 (en) | 2001-08-20 | 2007-04-24 | Conor Medsystems, Inc. | Implantable medical device with drug filled holes |
EP1222941B2 (en) | 1998-03-30 | 2009-04-22 | Conor Medsystems, Inc. | Flexible medical device |
US20040254635A1 (en) | 1998-03-30 | 2004-12-16 | Shanley John F. | Expandable medical device for delivery of beneficial agent |
US6241762B1 (en) | 1998-03-30 | 2001-06-05 | Conor Medsystems, Inc. | Expandable medical device with ductile hinges |
DE19916086B4 (en) | 1998-04-11 | 2004-11-11 | Inflow Dynamics Inc. | Implantable prosthesis, especially vascular prosthesis (stent) |
US5980566A (en) | 1998-04-11 | 1999-11-09 | Alt; Eckhard | Vascular and endoluminal stents with iridium oxide coating |
US7713297B2 (en) | 1998-04-11 | 2010-05-11 | Boston Scientific Scimed, Inc. | Drug-releasing stent with ceramic-containing layer |
US6364856B1 (en) | 1998-04-14 | 2002-04-02 | Boston Scientific Corporation | Medical device with sponge coating for controlled drug release |
US20030040790A1 (en) | 1998-04-15 | 2003-02-27 | Furst Joseph G. | Stent coating |
US6436133B1 (en) | 1998-04-15 | 2002-08-20 | Joseph G. Furst | Expandable graft |
US6206916B1 (en) | 1998-04-15 | 2001-03-27 | Joseph G. Furst | Coated intraluminal graft |
US20020099438A1 (en) | 1998-04-15 | 2002-07-25 | Furst Joseph G. | Irradiated stent coating |
US6270831B2 (en) | 1998-04-30 | 2001-08-07 | Medquest Products, Inc. | Method and apparatus for providing a conductive, amorphous non-stick coating |
JP4583597B2 (en) | 1998-05-05 | 2010-11-17 | ボストン サイエンティフィック リミテッド | Smooth end stent |
US6206283B1 (en) | 1998-12-23 | 2001-03-27 | At&T Corp. | Method and apparatus for transferring money via a telephone call |
US6280411B1 (en) | 1998-05-18 | 2001-08-28 | Scimed Life Systems, Inc. | Localized delivery of drug agents |
US6503231B1 (en) * | 1998-06-10 | 2003-01-07 | Georgia Tech Research Corporation | Microneedle device for transport of molecules across tissue |
DE59913189D1 (en) | 1998-06-25 | 2006-05-04 | Biotronik Ag | Implantable, bioabsorbable vessel wall support, in particular coronary stent |
US6153252A (en) | 1998-06-30 | 2000-11-28 | Ethicon, Inc. | Process for coating stents |
US6122564A (en) | 1998-06-30 | 2000-09-19 | Koch; Justin | Apparatus and methods for monitoring and controlling multi-layer laser cladding |
US6022812A (en) | 1998-07-07 | 2000-02-08 | Alliedsignal Inc. | Vapor deposition routes to nanoporous silica |
US6652581B1 (en) | 1998-07-07 | 2003-11-25 | Boston Scientific Scimed, Inc. | Medical device with porous surface for controlled drug release and method of making the same |
US8070796B2 (en) | 1998-07-27 | 2011-12-06 | Icon Interventional Systems, Inc. | Thrombosis inhibiting graft |
US20010032011A1 (en) | 1999-07-20 | 2001-10-18 | Stanford Ulf Harry | Expandable stent with array of relief cuts |
US20040088041A1 (en) | 1999-07-20 | 2004-05-06 | Stanford Ulf Harry | Expandable stent with array of relief cuts |
US20020038146A1 (en) | 1998-07-29 | 2002-03-28 | Ulf Harry | Expandable stent with relief cuts for carrying medicines and other materials |
JP4898991B2 (en) | 1998-08-20 | 2012-03-21 | クック メディカル テクノロジーズ エルエルシー | Sheathed medical device |
US6248127B1 (en) | 1998-08-21 | 2001-06-19 | Medtronic Ave, Inc. | Thromboresistant coated medical device |
US7235096B1 (en) | 1998-08-25 | 2007-06-26 | Tricardia, Llc | Implantable device for promoting repair of a body lumen |
US6335029B1 (en) * | 1998-08-28 | 2002-01-01 | Scimed Life Systems, Inc. | Polymeric coatings for controlled delivery of active agents |
BR9914498A (en) | 1998-09-23 | 2001-06-26 | Phycogen Inc | Safe and effective biopellicle inhibiting compounds and health-related uses thereof |
US6206915B1 (en) | 1998-09-29 | 2001-03-27 | Medtronic Ave, Inc. | Drug storing and metering stent |
US6245104B1 (en) | 1999-02-28 | 2001-06-12 | Inflow Dynamics Inc. | Method of fabricating a biocompatible stent |
US6217607B1 (en) | 1998-10-20 | 2001-04-17 | Inflow Dynamics Inc. | Premounted stent delivery system for small vessels |
US6293967B1 (en) | 1998-10-29 | 2001-09-25 | Conor Medsystems, Inc. | Expandable medical device with ductile hinges |
US6348960B1 (en) | 1998-11-06 | 2002-02-19 | Kimotot Co., Ltd. | Front scattering film |
US6214042B1 (en) | 1998-11-10 | 2001-04-10 | Precision Vascular Systems, Inc. | Micro-machined stent for vessels, body ducts and the like |
US6361780B1 (en) | 1998-11-12 | 2002-03-26 | Cardiac Pacemakers, Inc. | Microporous drug delivery system |
US20010014821A1 (en) | 1998-11-16 | 2001-08-16 | Mohamad Ike Juman | Balloon catheter and stent delivery system having enhanced stent retention |
US20020077520A1 (en) | 1998-11-18 | 2002-06-20 | Jerome Segal | Device and method for dilating and irradiating a vascular segment or body passageway |
US6984404B1 (en) * | 1998-11-18 | 2006-01-10 | University Of Florida Research Foundation, Inc. | Methods for preparing coated drug particles and pharmaceutical formulations thereof |
US6063101A (en) | 1998-11-20 | 2000-05-16 | Precision Vascular Systems, Inc. | Stent apparatus and method |
DE59904296D1 (en) * | 1998-11-26 | 2003-03-20 | Siemens Ag | COMPLEX CONNECTION OF A SUB IV GROUP ELEMENT |
US20060178727A1 (en) | 1998-12-03 | 2006-08-10 | Jacob Richter | Hybrid amorphous metal alloy stent |
US20070219642A1 (en) | 1998-12-03 | 2007-09-20 | Jacob Richter | Hybrid stent having a fiber or wire backbone |
EP1316323A1 (en) | 1998-12-31 | 2003-06-04 | Angiotech Pharmaceuticals, Inc. | Stent grafts with bioactive coatings |
US6955661B1 (en) | 1999-01-25 | 2005-10-18 | Atrium Medical Corporation | Expandable fluoropolymer device for delivery of therapeutic agents and method of making |
US6383519B1 (en) | 1999-01-26 | 2002-05-07 | Vita Special Purpose Corporation | Inorganic shaped bodies and methods for their production and use |
WO2000044822A2 (en) | 1999-01-27 | 2000-08-03 | The United States Of America, As Represented By The Secretary Of The Navy | Fabrication of conductive/non-conductive nanocomposites by laser evaporation |
US6419692B1 (en) | 1999-02-03 | 2002-07-16 | Scimed Life Systems, Inc. | Surface protection method for stents and balloon catheters for drug delivery |
DE19948783C2 (en) | 1999-02-18 | 2001-06-13 | Alcove Surfaces Gmbh | Implant |
US6558422B1 (en) | 1999-03-26 | 2003-05-06 | University Of Washington | Structures having coated indentations |
US6312457B1 (en) | 1999-04-01 | 2001-11-06 | Boston Scientific Corporation | Intraluminal lining |
US6325825B1 (en) | 1999-04-08 | 2001-12-04 | Cordis Corporation | Stent with variable wall thickness |
US6607598B2 (en) | 1999-04-19 | 2003-08-19 | Scimed Life Systems, Inc. | Device for protecting medical devices during a coating process |
US6368658B1 (en) | 1999-04-19 | 2002-04-09 | Scimed Life Systems, Inc. | Coating medical devices using air suspension |
US7371400B2 (en) | 2001-01-02 | 2008-05-13 | The General Hospital Corporation | Multilayer device for tissue engineering |
US6461731B1 (en) | 1999-05-03 | 2002-10-08 | Guardian Industries Corp. | Solar management coating system including protective DLC |
US6726712B1 (en) | 1999-05-14 | 2004-04-27 | Boston Scientific Scimed | Prosthesis deployment device with translucent distal end |
US6610035B2 (en) | 1999-05-21 | 2003-08-26 | Scimed Life Systems, Inc. | Hydrophilic lubricity coating for medical devices comprising a hybrid top coat |
US7171263B2 (en) | 1999-06-04 | 2007-01-30 | Impulse Dynamics Nv | Drug delivery device |
US6406745B1 (en) | 1999-06-07 | 2002-06-18 | Nanosphere, Inc. | Methods for coating particles and particles produced thereby |
US6139913A (en) | 1999-06-29 | 2000-10-31 | National Center For Manufacturing Sciences | Kinetic spray coating method and apparatus |
US6504292B1 (en) * | 1999-07-15 | 2003-01-07 | Agere Systems Inc. | Field emitting device comprising metallized nanostructures and method for making the same |
IT1307263B1 (en) | 1999-08-05 | 2001-10-30 | Sorin Biomedica Cardio Spa | ANGIOPLASTIC STENT WITH RESTENOSIS ANTAGONIST ACTION, RELATED KIT AND COMPONENTS. |
US6458162B1 (en) | 1999-08-13 | 2002-10-01 | Vita Special Purpose Corporation | Composite shaped bodies and methods for their production and use |
US6869701B1 (en) | 1999-08-16 | 2005-03-22 | Carolyn Aita | Self-repairing ceramic coatings |
US20070032853A1 (en) | 2002-03-27 | 2007-02-08 | Hossainy Syed F | 40-O-(2-hydroxy)ethyl-rapamycin coated stent |
US6713119B2 (en) | 1999-09-03 | 2004-03-30 | Advanced Cardiovascular Systems, Inc. | Biocompatible coating for a prosthesis and a method of forming the same |
EP1214108B1 (en) | 1999-09-03 | 2007-01-10 | Advanced Cardiovascular Systems, Inc. | A porous prosthesis and a method of depositing substances into the pores |
US6379381B1 (en) | 1999-09-03 | 2002-04-30 | Advanced Cardiovascular Systems, Inc. | Porous prosthesis and a method of depositing substances into the pores |
US6287628B1 (en) | 1999-09-03 | 2001-09-11 | Advanced Cardiovascular Systems, Inc. | Porous prosthesis and a method of depositing substances into the pores |
US6790228B2 (en) | 1999-12-23 | 2004-09-14 | Advanced Cardiovascular Systems, Inc. | Coating for implantable devices and a method of forming the same |
JP2001098308A (en) | 1999-09-24 | 2001-04-10 | Asahi Optical Co Ltd | Porous calcium phosphate series compound/metal composite sintered body and producing method |
US6845212B2 (en) | 1999-10-08 | 2005-01-18 | 3M Innovative Properties Company | Optical element having programmed optical structures |
DE19950386A1 (en) | 1999-10-19 | 2001-05-10 | Miladin Lazarov | Biocompatible item |
DE19951477A1 (en) | 1999-10-26 | 2001-05-03 | Biotronik Mess & Therapieg | Stent |
US6733513B2 (en) | 1999-11-04 | 2004-05-11 | Advanced Bioprosthetic Surfaces, Ltd. | Balloon catheter having metal balloon and method of making same |
US6761736B1 (en) | 1999-11-10 | 2004-07-13 | St. Jude Medical, Inc. | Medical article with a diamond-like carbon coated polymer |
AU2004202073B2 (en) | 1999-11-17 | 2007-01-04 | Boston Scientific Limited | Microfabricated devices for the delivery of molecules into a carrier fluid |
US6337076B1 (en) * | 1999-11-17 | 2002-01-08 | Sg Licensing Corporation | Method and composition for the treatment of scars |
US6491666B1 (en) | 1999-11-17 | 2002-12-10 | Microchips, Inc. | Microfabricated devices for the delivery of molecules into a carrier fluid |
US7195641B2 (en) | 1999-11-19 | 2007-03-27 | Advanced Bio Prosthetic Surfaces, Ltd. | Valvular prostheses having metal or pseudometallic construction and methods of manufacture |
US6936066B2 (en) | 1999-11-19 | 2005-08-30 | Advanced Bio Prosthetic Surfaces, Ltd. | Complaint implantable medical devices and methods of making same |
US6458153B1 (en) | 1999-12-31 | 2002-10-01 | Abps Venture One, Ltd. | Endoluminal cardiac and venous valve prostheses and methods of manufacture and delivery thereof |
US7235092B2 (en) | 1999-11-19 | 2007-06-26 | Advanced Bio Prosthetic Surfaces, Ltd. | Guidewires and thin film catheter-sheaths and method of making same |
US6379383B1 (en) | 1999-11-19 | 2002-04-30 | Advanced Bio Prosthetic Surfaces, Ltd. | Endoluminal device exhibiting improved endothelialization and method of manufacture thereof |
US6416820B1 (en) | 1999-11-19 | 2002-07-09 | Epion Corporation | Method for forming carbonaceous hard film |
US6849085B2 (en) | 1999-11-19 | 2005-02-01 | Advanced Bio Prosthetic Surfaces, Ltd. | Self-supporting laminated films, structural materials and medical devices manufactured therefrom and method of making same |
US7335426B2 (en) | 1999-11-19 | 2008-02-26 | Advanced Bio Prosthetic Surfaces, Ltd. | High strength vacuum deposited nitinol alloy films and method of making same |
US6537310B1 (en) | 1999-11-19 | 2003-03-25 | Advanced Bio Prosthetic Surfaces, Ltd. | Endoluminal implantable devices and method of making same |
US20060013850A1 (en) * | 1999-12-03 | 2006-01-19 | Domb Abraham J | Electropolymerizable monomers and polymeric coatings on implantable devices prepared therefrom |
US6251136B1 (en) | 1999-12-08 | 2001-06-26 | Advanced Cardiovascular Systems, Inc. | Method of layering a three-coated stent using pharmacological and polymeric agents |
AU778651B2 (en) | 1999-12-16 | 2004-12-16 | Isotis N.V. | Porous ceramic body |
US6613432B2 (en) * | 1999-12-22 | 2003-09-02 | Biosurface Engineering Technologies, Inc. | Plasma-deposited coatings, devices and methods |
US6908624B2 (en) | 1999-12-23 | 2005-06-21 | Advanced Cardiovascular Systems, Inc. | Coating for implantable devices and a method of forming the same |
US6471721B1 (en) | 1999-12-30 | 2002-10-29 | Advanced Cardiovascular Systems, Inc. | Vascular stent having increased radiopacity and method for making same |
US6967023B1 (en) | 2000-01-10 | 2005-11-22 | Foamix, Ltd. | Pharmaceutical and cosmetic carrier or composition for topical application |
JP2003520830A (en) * | 2000-01-25 | 2003-07-08 | エドワーズ ライフサイエンシーズ コーポレイション | Delivery system for treatment of restenosis and anastomotic intimal hyperplasia |
CA2393330A1 (en) * | 2000-01-25 | 2001-08-02 | Boston Scientific Limited | Manufacturing medical devices by vapor deposition |
US6488715B1 (en) | 2000-01-30 | 2002-12-03 | Diamicron, Inc. | Diamond-surfaced cup for use in a prosthetic joint |
US6367412B1 (en) | 2000-02-17 | 2002-04-09 | Applied Materials, Inc. | Porous ceramic liner for a plasma source |
AU780539B2 (en) | 2000-02-25 | 2005-03-24 | Cordis Corporation | Use of cladribine on a stent to prevent restenosis |
US6440503B1 (en) | 2000-02-25 | 2002-08-27 | Scimed Life Systems, Inc. | Laser deposition of elements onto medical devices |
EP1132058A1 (en) | 2000-03-06 | 2001-09-12 | Advanced Laser Applications Holding S.A. | Intravascular prothesis |
US20160287708A9 (en) | 2000-03-15 | 2016-10-06 | Orbusneich Medical, Inc. | Progenitor Endothelial Cell Capturing with a Drug Eluting Implantable Medical Device |
DE10110503A1 (en) | 2000-03-16 | 2001-09-20 | Volkswagen Ag | Small-area painting error elimination process involves removal of paint in region, diameter of which is not more than 10 times diameter of paint fault position |
US6695865B2 (en) | 2000-03-20 | 2004-02-24 | Advanced Bio Prosthetic Surfaces, Ltd. | Embolic protection device |
US6315708B1 (en) | 2000-03-31 | 2001-11-13 | Cordis Corporation | Stent with self-expanding end sections |
US6527801B1 (en) | 2000-04-13 | 2003-03-04 | Advanced Cardiovascular Systems, Inc. | Biodegradable drug delivery material for stent |
US7066234B2 (en) | 2001-04-25 | 2006-06-27 | Alcove Surfaces Gmbh | Stamping tool, casting mold and methods for structuring a surface of a work piece |
US6327504B1 (en) | 2000-05-10 | 2001-12-04 | Thoratec Corporation | Transcutaneous energy transfer with circuitry arranged to avoid overheating |
US6776796B2 (en) | 2000-05-12 | 2004-08-17 | Cordis Corportation | Antiinflammatory drug and delivery device |
US8845713B2 (en) | 2000-05-12 | 2014-09-30 | Advanced Bio Prosthetic Surfaces, Ltd., A Wholly Owned Subsidiary Of Palmaz Scientific, Inc. | Self-supporting laminated films, structural materials and medical devices manufactured therefrom and methods of making same |
US6395325B1 (en) | 2000-05-16 | 2002-05-28 | Scimed Life Systems, Inc. | Porous membranes |
US8252044B1 (en) | 2000-11-17 | 2012-08-28 | Advanced Bio Prosthestic Surfaces, Ltd. | Device for in vivo delivery of bioactive agents and method of manufacture thereof |
ES2277926T3 (en) | 2000-05-19 | 2007-08-01 | Advanced Bio Prosthetic Surfaces, Ltd. | PROCEDURES AND DEVICES FOR MANUFACTURING AN INTRAVASCULAR STENT. |
KR100360364B1 (en) | 2000-05-22 | 2002-11-13 | 주식회사 정성메디칼 | A metal stent for installation in the coronary artery |
US20040211362A1 (en) | 2000-05-31 | 2004-10-28 | Daniel Castro | System for coating a stent |
US6395326B1 (en) | 2000-05-31 | 2002-05-28 | Advanced Cardiovascular Systems, Inc. | Apparatus and method for depositing a coating onto a surface of a prosthesis |
US6986818B2 (en) | 2000-06-02 | 2006-01-17 | The Regents Of The University Of California | Method for producing nanostructured metal-oxides |
AU6539101A (en) | 2000-06-05 | 2001-12-17 | G David Jang | Intravascular stent with increasing coating retaining capacity |
JP4656697B2 (en) | 2000-06-16 | 2011-03-23 | キヤノンアネルバ株式会社 | High frequency sputtering equipment |
US6627974B2 (en) | 2000-06-19 | 2003-09-30 | Nichia Corporation | Nitride semiconductor substrate and method for manufacturing the same, and nitride semiconductor device using nitride semiconductor substrate |
US6585765B1 (en) | 2000-06-29 | 2003-07-01 | Advanced Cardiovascular Systems, Inc. | Implantable device having substances impregnated therein and a method of impregnating the same |
US20020077693A1 (en) | 2000-12-19 | 2002-06-20 | Barclay Bruce J. | Covered, coiled drug delivery stent and method |
US20030077200A1 (en) | 2000-07-07 | 2003-04-24 | Craig Charles H. | Enhanced radiopaque alloy stent |
US20030018380A1 (en) * | 2000-07-07 | 2003-01-23 | Craig Charles H. | Platinum enhanced alloy and intravascular or implantable medical devices manufactured therefrom |
US20020144757A1 (en) | 2000-07-07 | 2002-10-10 | Craig Charles Horace | Stainless steel alloy with improved radiopaque characteristics |
AU2001273276A1 (en) * | 2000-07-10 | 2002-01-21 | Epion Corporation | Improving effectiveness of medical stents by gcib |
US6709451B1 (en) | 2000-07-14 | 2004-03-23 | Norman Noble, Inc. | Channeled vascular stent apparatus and method |
NZ505774A (en) | 2000-07-17 | 2002-12-20 | Ind Res Ltd | Oxalate stabilised titania solutions and coating compositions and catalysts formed therefrom |
US6924004B2 (en) | 2000-07-19 | 2005-08-02 | Regents Of The University Of Minnesota | Apparatus and method for synthesizing films and coatings by focused particle beam deposition |
US20050113798A1 (en) | 2000-07-21 | 2005-05-26 | Slater Charles R. | Methods and apparatus for treating the interior of a blood vessel |
DE10040897B4 (en) * | 2000-08-18 | 2006-04-13 | TransMIT Gesellschaft für Technologietransfer mbH | Nanoscale porous fibers of polymeric materials |
US6399528B1 (en) | 2000-09-01 | 2002-06-04 | Fraunhofer-Gesellschaft Zur Forderung Der Angewandten Forschung E.V. | Porous aluminum oxide structures and processes for their production |
US6390967B1 (en) | 2000-09-14 | 2002-05-21 | Xoft Microtube, Inc. | Radiation for inhibiting hyperplasia after intravascular intervention |
US6478815B1 (en) | 2000-09-18 | 2002-11-12 | Inflow Dynamics Inc. | Vascular and endoluminal stents |
US7101391B2 (en) | 2000-09-18 | 2006-09-05 | Inflow Dynamics Inc. | Primarily niobium stent |
US7402173B2 (en) | 2000-09-18 | 2008-07-22 | Boston Scientific Scimed, Inc. | Metal stent with surface layer of noble metal oxide and method of fabrication |
US20020062154A1 (en) | 2000-09-22 | 2002-05-23 | Ayers Reed A. | Non-uniform porosity tissue implant |
US6953560B1 (en) | 2000-09-28 | 2005-10-11 | Advanced Cardiovascular Systems, Inc. | Barriers for polymer-coated implantable medical devices and methods for making the same |
US6254632B1 (en) | 2000-09-28 | 2001-07-03 | Advanced Cardiovascular Systems, Inc. | Implantable medical device having protruding surface structures for drug delivery and cover attachment |
US6805898B1 (en) | 2000-09-28 | 2004-10-19 | Advanced Cardiovascular Systems, Inc. | Surface features of an implantable medical device |
US6716444B1 (en) | 2000-09-28 | 2004-04-06 | Advanced Cardiovascular Systems, Inc. | Barriers for polymer-coated implantable medical devices and methods for making the same |
US7261735B2 (en) | 2001-05-07 | 2007-08-28 | Cordis Corporation | Local drug delivery devices and methods for maintaining the drug coatings thereon |
US6746773B2 (en) | 2000-09-29 | 2004-06-08 | Ethicon, Inc. | Coatings for medical devices |
US20020051730A1 (en) | 2000-09-29 | 2002-05-02 | Stanko Bodnar | Coated medical devices and sterilization thereof |
KR200227881Y1 (en) | 2000-09-29 | 2001-06-15 | 주식회사이오니아테크놀로지 | Image storag system of dental diagnosis |
US20020111590A1 (en) | 2000-09-29 | 2002-08-15 | Davila Luis A. | Medical devices, drug coatings and methods for maintaining the drug coatings thereon |
AU2001296702A1 (en) | 2000-10-16 | 2002-04-29 | 3M Innovative Properties Company | Method of making ceramic aggregate particles |
AU9463401A (en) | 2000-10-16 | 2002-04-29 | Conor Medsystems Inc | Expandable medical device for delivery of beneficial agent |
US6506437B1 (en) * | 2000-10-17 | 2003-01-14 | Advanced Cardiovascular Systems, Inc. | Methods of coating an implantable device having depots formed in a surface thereof |
US6663664B1 (en) | 2000-10-26 | 2003-12-16 | Advanced Cardiovascular Systems, Inc. | Self-expanding stent with time variable radial force |
US6558733B1 (en) | 2000-10-26 | 2003-05-06 | Advanced Cardiovascular Systems, Inc. | Method for etching a micropatterned microdepot prosthesis |
US6365222B1 (en) | 2000-10-27 | 2002-04-02 | Siemens Westinghouse Power Corporation | Abradable coating applied with cold spray technique |
US6758859B1 (en) | 2000-10-30 | 2004-07-06 | Kenny L. Dang | Increased drug-loading and reduced stress drug delivery device |
US7803149B2 (en) | 2002-07-12 | 2010-09-28 | Cook Incorporated | Coated medical device |
JP4583756B2 (en) | 2000-10-31 | 2010-11-17 | クック インコーポレイテッド | Medical instruments |
DE10055686A1 (en) | 2000-11-03 | 2002-05-08 | Biotronik Mess & Therapieg | Device for influencing cell proliferation mechanisms in vessels of the human or animal body |
US8372139B2 (en) | 2001-02-14 | 2013-02-12 | Advanced Bio Prosthetic Surfaces, Ltd. | In vivo sensor and method of making same |
US8062098B2 (en) * | 2000-11-17 | 2011-11-22 | Duescher Wayne O | High speed flat lapping platen |
US6517888B1 (en) | 2000-11-28 | 2003-02-11 | Scimed Life Systems, Inc. | Method for manufacturing a medical device having a coated portion by laser ablation |
US6638246B1 (en) | 2000-11-28 | 2003-10-28 | Scimed Life Systems, Inc. | Medical device for delivery of a biologically active material to a lumen |
NL1016779C2 (en) | 2000-12-02 | 2002-06-04 | Cornelis Johannes Maria V Rijn | Mold, method for manufacturing precision products with the aid of a mold, as well as precision products, in particular microsieves and membrane filters, manufactured with such a mold. |
DE10061057A1 (en) | 2000-12-08 | 2002-06-13 | Pharmed Holding Gmbh | Chip systems for the controlled emission of chemically sensitive substances |
US6545097B2 (en) | 2000-12-12 | 2003-04-08 | Scimed Life Systems, Inc. | Drug delivery compositions and medical devices containing block copolymer |
DE10064596A1 (en) | 2000-12-18 | 2002-06-20 | Biotronik Mess & Therapieg | Application of a marker element to an implant, especially a stent, comprises introducing a solidifiable material into a recess and solidifying the material in the recess |
US7244272B2 (en) | 2000-12-19 | 2007-07-17 | Nicast Ltd. | Vascular prosthesis and method for production thereof |
US20040030377A1 (en) | 2001-10-19 | 2004-02-12 | Alexander Dubson | Medicated polymer-coated stent assembly |
JP2004523275A (en) | 2000-12-22 | 2004-08-05 | アバンテク バスキュラー コーポレーション | Delivery of therapeutic drugs |
US7077859B2 (en) * | 2000-12-22 | 2006-07-18 | Avantec Vascular Corporation | Apparatus and methods for variably controlled substance delivery from implanted prostheses |
US7083642B2 (en) | 2000-12-22 | 2006-08-01 | Avantec Vascular Corporation | Delivery of therapeutic capable agents |
US20030033007A1 (en) | 2000-12-22 | 2003-02-13 | Avantec Vascular Corporation | Methods and devices for delivery of therapeutic capable agents with variable release profile |
US6471980B2 (en) | 2000-12-22 | 2002-10-29 | Avantec Vascular Corporation | Intravascular delivery of mycophenolic acid |
US6398806B1 (en) | 2000-12-26 | 2002-06-04 | Scimed Life Systems, Inc. | Monolayer modification to gold coated stents to reduce adsorption of protein |
US6913617B1 (en) | 2000-12-27 | 2005-07-05 | Advanced Cardiovascular Systems, Inc. | Method for creating a textured surface on an implantable medical device |
US6663662B2 (en) | 2000-12-28 | 2003-12-16 | Advanced Cardiovascular Systems, Inc. | Diffusion barrier layer for implantable devices |
US6635082B1 (en) | 2000-12-29 | 2003-10-21 | Advanced Cardiovascular Systems Inc. | Radiopaque stent |
US6641607B1 (en) | 2000-12-29 | 2003-11-04 | Advanced Cardiovascular Systems, Inc. | Double tube stent |
US20020087123A1 (en) | 2001-01-02 | 2002-07-04 | Hossainy Syed F.A. | Adhesion of heparin-containing coatings to blood-contacting surfaces of medical devices |
US6544582B1 (en) | 2001-01-05 | 2003-04-08 | Advanced Cardiovascular Systems, Inc. | Method and apparatus for coating an implantable device |
JP4657577B2 (en) | 2001-01-09 | 2011-03-23 | マイクロチップス・インコーポレーテッド | Flexible microchip device for ocular and other applications |
US6583048B2 (en) * | 2001-01-17 | 2003-06-24 | Air Products And Chemicals, Inc. | Organosilicon precursors for interlayer dielectric films with low dielectric constants |
US6752829B2 (en) | 2001-01-30 | 2004-06-22 | Scimed Life Systems, Inc. | Stent with channel(s) for containing and delivering a biologically active material and method for manufacturing the same |
JP2002308683A (en) | 2001-01-31 | 2002-10-23 | Toshiba Ceramics Co Ltd | Ceramic member with roughened surface and method for manufacturing the same |
US6964680B2 (en) | 2001-02-05 | 2005-11-15 | Conor Medsystems, Inc. | Expandable medical device with tapered hinge |
US6767360B1 (en) | 2001-02-08 | 2004-07-27 | Inflow Dynamics Inc. | Vascular stent with composite structure for magnetic reasonance imaging capabilities |
DE10106186A1 (en) | 2001-02-10 | 2002-08-14 | Oxeno Olefinchemie Gmbh | Process for the condensation of aldehydes with ketones by means of a multi-phase reaction |
DE10127011A1 (en) | 2001-06-05 | 2002-12-12 | Jomed Gmbh | Implant used for treating vascular narrowing or occlusion, especially for controlling restenosis contains FK506 in chemically bound or physically fixed form |
CA2435306C (en) | 2001-02-16 | 2010-12-21 | Stephan Wnendt | Implants with fk506 |
DE10107339A1 (en) | 2001-02-16 | 2002-09-05 | Jomed Gmbh | Implant used for treating vascular narrowing or occlusion, especially for controlling restenosis contains FK506 in chemically bound or physically fixed form |
US6679911B2 (en) | 2001-03-01 | 2004-01-20 | Cordis Corporation | Flexible stent |
US6998060B2 (en) | 2001-03-01 | 2006-02-14 | Cordis Corporation | Flexible stent and method of manufacture |
EP1368075B1 (en) | 2001-03-02 | 2006-04-12 | Université Laval | Plasma surface graft process for reducing thrombogenicity |
WO2002069848A2 (en) | 2001-03-06 | 2002-09-12 | Board Of Regents, The University Of Texas System | Apparatus for stent deployment with delivery of bioactive agents |
US20020133225A1 (en) | 2001-03-13 | 2002-09-19 | Gordon Lucas S. | Methods and apparatuses for delivering a medical agent to a medical implant |
WO2002074431A1 (en) | 2001-03-21 | 2002-09-26 | Max-Planck-Gesellschaft Zur Förderung Der Wissenschaften | Hollow spheres from layered precursor deposition on sacrificial colloidal core particles |
US20020138136A1 (en) | 2001-03-23 | 2002-09-26 | Scimed Life Systems, Inc. | Medical device having radio-opacification and barrier layers |
US6709622B2 (en) | 2001-03-23 | 2004-03-23 | Romain Billiet | Porous nanostructures and method of fabrication thereof |
US6780424B2 (en) | 2001-03-30 | 2004-08-24 | Charles David Claude | Controlled morphologies in polymer drug for release of drugs from polymer films |
US6673105B1 (en) * | 2001-04-02 | 2004-01-06 | Advanced Cardiovascular Systems, Inc. | Metal prosthesis coated with expandable ePTFE |
US6764505B1 (en) | 2001-04-12 | 2004-07-20 | Advanced Cardiovascular Systems, Inc. | Variable surface area stent |
ES2173817B1 (en) | 2001-04-16 | 2003-10-16 | Fundacion Inasmet | METHOD FOR THE MANUFACTURE OF ENDO-OSEOS IMPLANTS OR MEDICAL PROTESIS THROUGH THE IONIC IMPLEMENTATION TECHNIQUE. |
WO2002085253A1 (en) | 2001-04-20 | 2002-10-31 | The Board Of Trustees Of The Leland Stanford Junior University | Drug delivery platform and methods for the inhibition of neointima formation |
US7048939B2 (en) | 2001-04-20 | 2006-05-23 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for the inhibition of neointima formation |
US7056339B2 (en) * | 2001-04-20 | 2006-06-06 | The Board Of Trustees Of The Leland Stanford Junior University | Drug delivery platform |
US6915964B2 (en) | 2001-04-24 | 2005-07-12 | Innovative Technology, Inc. | System and process for solid-state deposition and consolidation of high velocity powder particles using thermal plastic deformation |
US6712845B2 (en) | 2001-04-24 | 2004-03-30 | Advanced Cardiovascular Systems, Inc. | Coating for a stent and a method of forming the same |
US7232460B2 (en) | 2001-04-25 | 2007-06-19 | Xillus, Inc. | Nanodevices, microdevices and sensors on in-vivo structures and method for the same |
US6660034B1 (en) | 2001-04-30 | 2003-12-09 | Advanced Cardiovascular Systems, Inc. | Stent for increasing blood flow to ischemic tissues and a method of using the same |
US6613083B2 (en) | 2001-05-02 | 2003-09-02 | Eckhard Alt | Stent device and method |
EP1254673B1 (en) | 2001-05-02 | 2005-11-09 | InFlow Dynamics, Inc. | Immuno-tolerant stent with surface microstructure |
US8182527B2 (en) * | 2001-05-07 | 2012-05-22 | Cordis Corporation | Heparin barrier coating for controlled drug release |
WO2002089702A2 (en) * | 2001-05-09 | 2002-11-14 | Epion Corporation | Method and system for improving the effectiveness of artificial joints by the application of gas cluster ion beam technology |
US6656506B1 (en) | 2001-05-09 | 2003-12-02 | Advanced Cardiovascular Systems, Inc. | Microparticle coated medical device |
DE60237813D1 (en) | 2001-05-11 | 2010-11-11 | Epion Corp | METHOD FOR IMPROVING THE EFFECTIVENESS OF MEDICAL DEVICES BY MOUNTING MEDICAMENTS ON THE SURFACE |
US7247338B2 (en) | 2001-05-16 | 2007-07-24 | Regents Of The University Of Minnesota | Coating medical devices |
US6973718B2 (en) | 2001-05-30 | 2005-12-13 | Microchips, Inc. | Methods for conformal coating and sealing microchip reservoir devices |
US7862495B2 (en) | 2001-05-31 | 2011-01-04 | Advanced Cardiovascular Systems, Inc. | Radiation or drug delivery source with activity gradient to minimize edge effects |
US6712844B2 (en) | 2001-06-06 | 2004-03-30 | Advanced Cardiovascular Systems, Inc. | MRI compatible stent |
WO2002100454A1 (en) | 2001-06-11 | 2002-12-19 | Boston Scientific Limited | COMPOSITE ePTFE/TEXTILE PROSTHESIS |
US7201940B1 (en) | 2001-06-12 | 2007-04-10 | Advanced Cardiovascular Systems, Inc. | Method and apparatus for thermal spray processing of medical devices |
US6527938B2 (en) | 2001-06-21 | 2003-03-04 | Syntheon, Llc | Method for microporous surface modification of implantable metallic medical articles |
US6585755B2 (en) * | 2001-06-29 | 2003-07-01 | Advanced Cardiovascular | Polymeric stent suitable for imaging by MRI and fluoroscopy |
US6676987B2 (en) * | 2001-07-02 | 2004-01-13 | Scimed Life Systems, Inc. | Coating a medical appliance with a bubble jet printing head |
US20030050687A1 (en) | 2001-07-03 | 2003-03-13 | Schwade Nathan D. | Biocompatible stents and method of deployment |
EP1273314A1 (en) | 2001-07-06 | 2003-01-08 | Terumo Kabushiki Kaisha | Stent |
US6715640B2 (en) * | 2001-07-09 | 2004-04-06 | Innovative Technology, Inc. | Powder fluidizing devices and portable powder-deposition apparatus for coating and spray forming |
ATE330564T1 (en) | 2001-07-20 | 2006-07-15 | Sorin Biomedica Cardio Srl | STENT |
WO2003009778A2 (en) | 2001-07-26 | 2003-02-06 | Avantec Vascular Corporation | Methods and devices for delivery of therapeutic capable agents with variable release profile |
JP4151884B2 (en) | 2001-08-08 | 2008-09-17 | 独立行政法人理化学研究所 | Method for producing a material in which a composite metal oxide nanomaterial is formed on a solid surface |
US6979346B1 (en) | 2001-08-08 | 2005-12-27 | Advanced Cardiovascular Systems, Inc. | System and method for improved stent retention |
US6585997B2 (en) | 2001-08-16 | 2003-07-01 | Access Pharmaceuticals, Inc. | Mucoadhesive erodible drug delivery device for controlled administration of pharmaceuticals and other active compounds |
US7056338B2 (en) | 2003-03-28 | 2006-06-06 | Conor Medsystems, Inc. | Therapeutic agent delivery device with controlled therapeutic agent release rates |
AU2002323457A1 (en) | 2001-08-27 | 2003-05-19 | James C. Thomas Jr. | Implant for partial disc and cancellous bone replacement |
US20060224234A1 (en) | 2001-08-29 | 2006-10-05 | Swaminathan Jayaraman | Drug eluting structurally variable stent |
GB0121980D0 (en) | 2001-09-11 | 2001-10-31 | Cathnet Science Holding As | Expandable stent |
US20030047505A1 (en) | 2001-09-13 | 2003-03-13 | Grimes Craig A. | Tubular filter with branched nanoporous membrane integrated with a support and method of producing same |
MXPA04002476A (en) | 2001-09-14 | 2004-05-31 | Anthony A Boiarski | Microfabricated nanopore device for sustained release of therapeutic agent. |
US20030158598A1 (en) | 2001-09-17 | 2003-08-21 | Control Delivery Systems, Inc. | System for sustained-release delivery of anti-inflammatory agents from a coated medical device |
US6669980B2 (en) | 2001-09-18 | 2003-12-30 | Scimed Life Systems, Inc. | Method for spray-coating medical devices |
US20030060873A1 (en) | 2001-09-19 | 2003-03-27 | Nanomedical Technologies, Inc. | Metallic structures incorporating bioactive materials and methods for creating the same |
US7776379B2 (en) | 2001-09-19 | 2010-08-17 | Medlogics Device Corporation | Metallic structures incorporating bioactive materials and methods for creating the same |
EP1429819B1 (en) | 2001-09-24 | 2010-11-24 | Boston Scientific Limited | Optimized dosing for paclitaxel coated stents |
US6827737B2 (en) | 2001-09-25 | 2004-12-07 | Scimed Life Systems, Inc. | EPTFE covering for endovascular prostheses and method of manufacture |
US7195640B2 (en) | 2001-09-25 | 2007-03-27 | Cordis Corporation | Coated medical devices for the treatment of vulnerable plaque |
US6753071B1 (en) | 2001-09-27 | 2004-06-22 | Advanced Cardiovascular Systems, Inc. | Rate-reducing membrane for release of an agent |
AU2002341959A1 (en) | 2001-10-04 | 2003-04-14 | Case Western Reserve University | Drug delivery devices and methods |
DE10150995A1 (en) | 2001-10-08 | 2003-04-10 | Biotronik Mess & Therapieg | Implant e.g. a stent, comprises a decomposable substance which allows contact between the cell proliferation inhibitor and the stent surroundings only after a specified time |
US6709397B2 (en) | 2001-10-16 | 2004-03-23 | Envisioneering, L.L.C. | Scanning probe |
WO2003055414A1 (en) | 2001-10-18 | 2003-07-10 | Advanced Stent Technologies, Inc. | Stent for vessel support, coverage and side branch accessibility |
US8562664B2 (en) | 2001-10-25 | 2013-10-22 | Advanced Cardiovascular Systems, Inc. | Manufacture of fine-grained material for use in medical devices |
DE10152055A1 (en) | 2001-10-25 | 2003-05-08 | Nttf Gmbh | Mechanically and thermodynamically stable amorphous carbon layers for temperature-sensitive surfaces |
EP1308179A1 (en) | 2001-10-30 | 2003-05-07 | Boehringer Ingelheim Pharma GmbH & Co.KG | Improved endoprosthetic device |
EP1448807A4 (en) * | 2001-10-30 | 2005-07-13 | Massachusetts Inst Technology | Fluorocarbon-organosilicon copolymers and coatings prepared by hot-filament chemical vapor deposition |
US20030083614A1 (en) | 2001-10-30 | 2003-05-01 | Boehringer Ingelheim Pharma Kg | Controlled release endoprosthetic device |
US20030088307A1 (en) | 2001-11-05 | 2003-05-08 | Shulze John E. | Potent coatings for stents |
US6939376B2 (en) | 2001-11-05 | 2005-09-06 | Sun Biomedical, Ltd. | Drug-delivery endovascular stent and method for treating restenosis |
US6764709B2 (en) | 2001-11-08 | 2004-07-20 | Scimed Life Systems, Inc. | Method for making and measuring a coating on the surface of a medical device using an ultraviolet laser |
US6807440B2 (en) | 2001-11-09 | 2004-10-19 | Scimed Life Systems, Inc. | Ceramic reinforcement members for MRI devices |
EP1310242A1 (en) | 2001-11-13 | 2003-05-14 | SORIN BIOMEDICA CARDIO S.p.A. | Carrier and kit for endoluminal delivery of active principles |
CN1301757C (en) | 2001-11-27 | 2007-02-28 | 多喜兰株式会社 | Implant material and process for producing the same |
US20030104028A1 (en) | 2001-11-29 | 2003-06-05 | Hossainy Syed F.A. | Rate limiting barriers for implantable devices and methods for fabrication thereof |
US6465052B1 (en) | 2001-11-30 | 2002-10-15 | Nanotek Instruments, Inc. | Method for production of nano-porous coatings |
US7014654B2 (en) | 2001-11-30 | 2006-03-21 | Scimed Life Systems, Inc. | Stent designed for the delivery of therapeutic substance or other agents |
US6752826B2 (en) | 2001-12-14 | 2004-06-22 | Thoratec Corporation | Layered stent-graft and methods of making the same |
US6866805B2 (en) | 2001-12-27 | 2005-03-15 | Advanced Cardiovascular Systems, Inc. | Hybrid intravascular stent |
US7575759B2 (en) | 2002-01-02 | 2009-08-18 | The Regents Of The University Of Michigan | Tissue engineering scaffolds |
DE10200387B4 (en) | 2002-01-08 | 2009-11-26 | Translumina Gmbh | stent |
US6506972B1 (en) * | 2002-01-22 | 2003-01-14 | Nanoset, Llc | Magnetically shielded conductor |
US6949590B2 (en) | 2002-01-10 | 2005-09-27 | University Of Washington | Hydrogels formed by non-covalent linkages |
TW200730152A (en) * | 2002-01-10 | 2007-08-16 | Novartis Ag | Drug delivery systems for the prevention and treatment of vascular diseases |
US6864418B2 (en) | 2002-12-18 | 2005-03-08 | Nanoset, Llc | Nanomagnetically shielded substrate |
US6906256B1 (en) | 2002-01-22 | 2005-06-14 | Nanoset, Llc | Nanomagnetic shielding assembly |
EP1476882A4 (en) | 2002-01-22 | 2007-01-17 | Nanoset Llc | Nanomagnetically shielded substrate |
WO2003062824A1 (en) | 2002-01-23 | 2003-07-31 | Boditech Inc. | Lateral flow quantitative assay method and strip and laser-induced fluoerescence detection device therefor |
US7060089B2 (en) | 2002-01-23 | 2006-06-13 | Boston Scientific Scimed, Inc. | Multi-layer stent |
US20030153901A1 (en) | 2002-02-08 | 2003-08-14 | Atrium Medical Corporation | Drug delivery panel |
US8685427B2 (en) | 2002-07-31 | 2014-04-01 | Boston Scientific Scimed, Inc. | Controlled drug delivery |
US20040029706A1 (en) | 2002-02-14 | 2004-02-12 | Barrera Enrique V. | Fabrication of reinforced composite material comprising carbon nanotubes, fullerenes, and vapor-grown carbon fibers for thermal barrier materials, structural ceramics, and multifunctional nanocomposite ceramics |
US20030153971A1 (en) | 2002-02-14 | 2003-08-14 | Chandru Chandrasekaran | Metal reinforced biodegradable intraluminal stents |
KR20040097126A (en) * | 2002-02-15 | 2004-11-17 | 씨브이 쎄러퓨틱스, 인코포레이티드 | Polymer coating for medical devices |
WO2003072287A1 (en) | 2002-02-27 | 2003-09-04 | University Of Virginia Patent Foundation | Methods for making implantable medical devices having microstructures |
US20030170605A1 (en) | 2002-03-11 | 2003-09-11 | Egan Visual Inc. | Vapor deposited writing surfaces |
US6743463B2 (en) | 2002-03-28 | 2004-06-01 | Scimed Life Systems, Inc. | Method for spray-coating a medical device having a tubular wall such as a stent |
EP1348402A1 (en) | 2002-03-29 | 2003-10-01 | Advanced Laser Applications Holding S.A. | Intraluminal endoprosthesis, radially expandable, perforated for drug delivery |
US7462366B2 (en) | 2002-03-29 | 2008-12-09 | Boston Scientific Scimed, Inc. | Drug delivery particle |
US7691461B1 (en) | 2002-04-01 | 2010-04-06 | Advanced Cardiovascular Systems, Inc. | Hybrid stent and method of making |
US20030211135A1 (en) | 2002-04-11 | 2003-11-13 | Greenhalgh Skott E. | Stent having electrospun covering and method |
JP3714471B2 (en) | 2002-04-24 | 2005-11-09 | 学校法人慶應義塾 | Medical covering material |
US20030204168A1 (en) | 2002-04-30 | 2003-10-30 | Gjalt Bosma | Coated vascular devices |
US7008979B2 (en) | 2002-04-30 | 2006-03-07 | Hydromer, Inc. | Coating composition for multiple hydrophilic applications |
AU2003228858A1 (en) | 2002-05-02 | 2003-11-17 | Scimed Life Systems, Inc. | Energetically-controlled delivery of biologically active material from an implanted medical device |
US7122048B2 (en) | 2002-05-03 | 2006-10-17 | Scimed Life Systems, Inc. | Hypotube endoluminal device |
GB0210786D0 (en) | 2002-05-10 | 2002-06-19 | Plasma Coatings Ltd | Orthopaedic and dental implants |
DE60303705T2 (en) | 2002-05-14 | 2006-10-19 | Terumo K.K. | Coated stent for the release of active substances |
CN1655738A (en) | 2002-05-20 | 2005-08-17 | 奥勃斯医学技术股份有限公司 | Drug eluting implantable medical device |
US20040000540A1 (en) * | 2002-05-23 | 2004-01-01 | Soboyejo Winston O. | Laser texturing of surfaces for biomedical implants |
US7048767B2 (en) | 2002-06-11 | 2006-05-23 | Spire Corporation | Nano-crystalline, homo-metallic, protective coatings |
US8211455B2 (en) * | 2002-06-19 | 2012-07-03 | Boston Scientific Scimed, Inc. | Implantable or insertable medical devices for controlled delivery of a therapeutic agent |
US20040002755A1 (en) * | 2002-06-28 | 2004-01-01 | Fischell David R. | Method and apparatus for treating vulnerable coronary plaques using drug-eluting stents |
US7314484B2 (en) | 2002-07-02 | 2008-01-01 | The Foundry, Inc. | Methods and devices for treating aneurysms |
AU2003250913A1 (en) | 2002-07-08 | 2004-01-23 | Abbott Laboratories Vascular Enterprises Limited | Drug eluting stent and methods of manufacture |
US7159163B2 (en) | 2002-07-08 | 2007-01-02 | Qualcomm Incorporated | Feedback for data transmissions |
US8337893B2 (en) | 2002-07-10 | 2012-12-25 | Florida Research Foundation, Inc, University Of | Sol-gel derived bioactive glass polymer composite |
US20050096731A1 (en) | 2002-07-11 | 2005-05-05 | Kareen Looi | Cell seeded expandable body |
WO2004006807A2 (en) | 2002-07-11 | 2004-01-22 | University Of Virginia Patent Foundation | Methods and apparatuses for repairing aneurysms |
AU2003256499A1 (en) | 2002-07-11 | 2004-02-02 | Setagon, Inc. | Expandable body having deployable microstructures and related methods |
ATE291396T1 (en) * | 2002-07-24 | 2005-04-15 | Zimmer Gmbh | METHOD FOR PRODUCING AN IMPLANT AND METHOD FOR DECONTAMINATING A SURFACE TREATED WITH RADIATION PARTICLES |
JP2005533604A (en) | 2002-07-25 | 2005-11-10 | アバンテック バスキュラー コーポレーション | Apparatus for delivering therapeutic agents and methods related thereto |
US6974805B2 (en) | 2002-08-01 | 2005-12-13 | Min Hu | Configuration of glycosaminoglycans |
US7745532B2 (en) | 2002-08-02 | 2010-06-29 | Cambridge Polymer Group, Inc. | Systems and methods for controlling and forming polymer gels |
US7255710B2 (en) | 2002-08-06 | 2007-08-14 | Icon Medical Corp. | Helical stent with micro-latches |
US6962822B2 (en) | 2002-08-07 | 2005-11-08 | International Business Machines Corporation | Discrete nano-textured structures in biomolecular arrays, and method of use |
US7029495B2 (en) | 2002-08-28 | 2006-04-18 | Scimed Life Systems, Inc. | Medical devices and methods of making the same |
US6951053B2 (en) | 2002-09-04 | 2005-10-04 | Reva Medical, Inc. | Method of manufacturing a prosthesis |
ATE392864T1 (en) | 2002-09-20 | 2008-05-15 | Abbott Lab Vascular Entpr Ltd | STENT PROVIDED WITH A ROUGH SURFACE AND METHOD OF PRODUCTION THEREOF |
US7758636B2 (en) | 2002-09-20 | 2010-07-20 | Innovational Holdings Llc | Expandable medical device with openings for delivery of multiple beneficial agents |
US7001422B2 (en) | 2002-09-23 | 2006-02-21 | Cordis Neurovascular, Inc | Expandable stent and delivery system |
US20040059409A1 (en) | 2002-09-24 | 2004-03-25 | Stenzel Eric B. | Method of applying coatings to a medical device |
US6915796B2 (en) | 2002-09-24 | 2005-07-12 | Chien-Min Sung | Superabrasive wire saw and associated methods of manufacture |
US7060051B2 (en) | 2002-09-24 | 2006-06-13 | Scimed Life Systems, Inc. | Multi-balloon catheter with hydrogel coating |
US6830598B1 (en) | 2002-09-24 | 2004-12-14 | Chien-Min Sung | Molten braze coated superabrasive particles and associated methods |
US7261752B2 (en) | 2002-09-24 | 2007-08-28 | Chien-Min Sung | Molten braze-coated superabrasive particles and associated methods |
EP1551569B1 (en) | 2002-09-26 | 2017-05-10 | Advanced Bio Prosthetic Surfaces, Ltd. | Implantable materials having engineered surfaces and method of making same |
JP2006500996A (en) | 2002-09-26 | 2006-01-12 | エンドバスキュラー デバイセス インコーポレイテッド | Apparatus and method for delivering mitomycin via an eluting biocompatible implantable medical device |
US6971813B2 (en) | 2002-09-27 | 2005-12-06 | Labcoat, Ltd. | Contact coating of prostheses |
US7794494B2 (en) | 2002-10-11 | 2010-09-14 | Boston Scientific Scimed, Inc. | Implantable medical devices |
DE60336158D1 (en) * | 2002-10-11 | 2011-04-07 | Univ Connecticut | ON SEMICRISTALLINE THERMOPLASTIC POLYURETHANES BASED FOR NANOSTRUCTURED HARD SEGMENTS BASED FORM MEMORY PILARMERS |
US7976936B2 (en) | 2002-10-11 | 2011-07-12 | University Of Connecticut | Endoprostheses |
US20060149365A1 (en) | 2002-10-22 | 2006-07-06 | Medtronic Vascular, Inc. | Stent with eccentric coating |
US20040088038A1 (en) | 2002-10-30 | 2004-05-06 | Houdin Dehnad | Porous metal for drug-loaded stents |
SE0203224D0 (en) | 2002-10-31 | 2002-10-31 | Cerbio Tech Ab | Method of making structured ceramic coatings and coated devices prepared with the method |
US20040086674A1 (en) | 2002-11-01 | 2004-05-06 | Holman Thomas J. | Laser sintering process and devices made therefrom |
DE60331854D1 (en) | 2002-11-07 | 2010-05-06 | Abbott Lab | METHOD FOR ATTACHING A MEDICAMENT TO A PROSTHESIS BY MEANS OF A LIQUID AMOUNT |
US8221495B2 (en) | 2002-11-07 | 2012-07-17 | Abbott Laboratories | Integration of therapeutic agent into a bioerodible medical device |
US20040142014A1 (en) | 2002-11-08 | 2004-07-22 | Conor Medsystems, Inc. | Method and apparatus for reducing tissue damage after ischemic injury |
JP2006505364A (en) | 2002-11-08 | 2006-02-16 | コナー メドシステムズ, インコーポレイテッド | Expandable medical device and method for treating chronic total infarction using a local supply of angiogenic factors |
KR20130032407A (en) | 2002-11-08 | 2013-04-01 | 코너 메드시스템즈, 엘엘씨 | Method and apparatus for reducing tissue damage after ischemic injury |
US7169178B1 (en) | 2002-11-12 | 2007-01-30 | Advanced Cardiovascular Systems, Inc. | Stent with drug coating |
US20050070989A1 (en) * | 2002-11-13 | 2005-03-31 | Whye-Kei Lye | Medical devices having porous layers and methods for making the same |
KR100826574B1 (en) | 2002-11-13 | 2008-04-30 | 유니버시티 오브 버지니아 페이턴트 파운데이션 | Medical devices having porous layers and methods for making same |
US9770349B2 (en) | 2002-11-13 | 2017-09-26 | University Of Virginia Patent Foundation | Nanoporous stents with enhanced cellular adhesion and reduced neointimal formation |
US20060121080A1 (en) | 2002-11-13 | 2006-06-08 | Lye Whye K | Medical devices having nanoporous layers and methods for making the same |
US8449601B2 (en) | 2002-11-19 | 2013-05-28 | Boston Scientific Scimed, Inc. | Medical devices |
US6923829B2 (en) | 2002-11-25 | 2005-08-02 | Advanced Bio Prosthetic Surfaces, Ltd. | Implantable expandable medical devices having regions of differential mechanical properties and methods of making same |
JP4119230B2 (en) | 2002-11-26 | 2008-07-16 | 株式会社 日立ディスプレイズ | Display device |
US7491234B2 (en) | 2002-12-03 | 2009-02-17 | Boston Scientific Scimed, Inc. | Medical devices for delivery of therapeutic agents |
JP2004188314A (en) | 2002-12-11 | 2004-07-08 | Kawasaki Heavy Ind Ltd | Composite substrate having hydrophilic surface |
US7371256B2 (en) | 2002-12-16 | 2008-05-13 | Poly-Med, Inc | Composite vascular constructs with selectively controlled properties |
US7666216B2 (en) | 2002-12-24 | 2010-02-23 | Novostent Corporation | Delivery catheter for ribbon-type prosthesis and methods of use |
US7846198B2 (en) | 2002-12-24 | 2010-12-07 | Novostent Corporation | Vascular prosthesis and methods of use |
US20050165469A1 (en) | 2002-12-24 | 2005-07-28 | Michael Hogendijk | Vascular prosthesis including torsional stabilizer and methods of use |
US6725901B1 (en) | 2002-12-27 | 2004-04-27 | Advanced Cardiovascular Systems, Inc. | Methods of manufacture of fully consolidated or porous medical devices |
WO2004060405A2 (en) | 2002-12-30 | 2004-07-22 | Angiotech International Ag | Tissue reactive compounds and compositions and uses thereof |
US7105018B1 (en) | 2002-12-30 | 2006-09-12 | Advanced Cardiovascular Systems, Inc. | Drug-eluting stent cover and method of use |
US6803070B2 (en) | 2002-12-30 | 2004-10-12 | Scimed Life Systems, Inc. | Apparatus and method for embedding nanoparticles in polymeric medical devices |
US6896697B1 (en) | 2002-12-30 | 2005-05-24 | Advanced Cardiovascular Systems, Inc. | Intravascular stent |
US20040236415A1 (en) | 2003-01-02 | 2004-11-25 | Richard Thomas | Medical devices having drug releasing polymer reservoirs |
US7169177B2 (en) * | 2003-01-15 | 2007-01-30 | Boston Scientific Scimed, Inc. | Bifurcated stent |
US20040143317A1 (en) | 2003-01-17 | 2004-07-22 | Stinson Jonathan S. | Medical devices |
KR100495875B1 (en) | 2003-01-18 | 2005-06-16 | 사회복지법인 삼성생명공익재단 | Stent for percutaneous coronary intervention coated with drugs for the prevention of vascular restenosis |
GB2397233A (en) | 2003-01-20 | 2004-07-21 | Julie Gold | Biomedical device with bioerodable coating |
US6852122B2 (en) | 2003-01-23 | 2005-02-08 | Cordis Corporation | Coated endovascular AAA device |
US6918929B2 (en) | 2003-01-24 | 2005-07-19 | Medtronic Vascular, Inc. | Drug-polymer coated stent with pegylated styrenic block copolymers |
EP1610752B1 (en) | 2003-01-31 | 2013-01-02 | Boston Scientific Limited | Localized drug delivery using drug-loaded nanocapsules and implantable device coated with the same |
US7311727B2 (en) | 2003-02-05 | 2007-12-25 | Board Of Trustees Of The University Of Arkansas | Encased stent |
US20080038146A1 (en) | 2003-02-10 | 2008-02-14 | Jurgen Wachter | Metal alloy for medical devices and implants |
FR2851181B1 (en) | 2003-02-17 | 2006-05-26 | Commissariat Energie Atomique | METHOD FOR COATING A SURFACE |
US20050079199A1 (en) | 2003-02-18 | 2005-04-14 | Medtronic, Inc. | Porous coatings for drug release from medical devices |
AU2004213021B2 (en) | 2003-02-18 | 2010-12-09 | Medtronic, Inc. | Occlusion resistant hydrocephalic shunt |
US20040167572A1 (en) | 2003-02-20 | 2004-08-26 | Roth Noah M. | Coated medical devices |
ES2354605T3 (en) | 2003-02-21 | 2011-03-16 | Sorin Biomedica Cardio S.R.L. | STENTS PRODUCTION PROCEDURE AND THE CORRESPONDING STENT. |
US7001421B2 (en) | 2003-02-28 | 2006-02-21 | Medtronic Vascular, Inc. | Stent with phenoxy primer coating |
US6699282B1 (en) | 2003-03-06 | 2004-03-02 | Gelsus Research And Consulting, Inc. | Method and apparatus for delivery of medication |
US6932930B2 (en) | 2003-03-10 | 2005-08-23 | Synecor, Llc | Intraluminal prostheses having polymeric material with selectively modified crystallinity and methods of making same |
US8281737B2 (en) * | 2003-03-10 | 2012-10-09 | Boston Scientific Scimed, Inc. | Coated medical device and method for manufacturing the same |
US20040202692A1 (en) * | 2003-03-28 | 2004-10-14 | Conor Medsystems, Inc. | Implantable medical device and method for in situ selective modulation of agent delivery |
US20050070996A1 (en) | 2003-04-08 | 2005-03-31 | Dinh Thomas Q. | Drug-eluting stent for controlled drug delivery |
US7163555B2 (en) | 2003-04-08 | 2007-01-16 | Medtronic Vascular, Inc. | Drug-eluting stent for controlled drug delivery |
US20060142853A1 (en) | 2003-04-08 | 2006-06-29 | Xingwu Wang | Coated substrate assembly |
US20050107870A1 (en) | 2003-04-08 | 2005-05-19 | Xingwu Wang | Medical device with multiple coating layers |
US20050216075A1 (en) | 2003-04-08 | 2005-09-29 | Xingwu Wang | Materials and devices of enhanced electromagnetic transparency |
WO2004092315A1 (en) | 2003-04-14 | 2004-10-28 | Kao Corporation | Cleaning agent composition |
US20050221072A1 (en) | 2003-04-17 | 2005-10-06 | Nanosys, Inc. | Medical device applications of nanostructured surfaces |
US20050038498A1 (en) | 2003-04-17 | 2005-02-17 | Nanosys, Inc. | Medical device applications of nanostructured surfaces |
US20040236399A1 (en) | 2003-04-22 | 2004-11-25 | Medtronic Vascular, Inc. | Stent with improved surface adhesion |
US20040215313A1 (en) | 2003-04-22 | 2004-10-28 | Peiwen Cheng | Stent with sandwich type coating |
US20040230176A1 (en) | 2003-04-23 | 2004-11-18 | Medtronic Vascular, Inc. | System for treating a vascular condition that inhibits restenosis at stent ends |
US7482034B2 (en) * | 2003-04-24 | 2009-01-27 | Boston Scientific Scimed, Inc. | Expandable mask stent coating method |
JP4734236B2 (en) | 2003-04-25 | 2011-07-27 | ボストン サイエンティフィック サイムド,インコーポレイテッド | Device for the storage and controlled release of solid drugs and method of manufacturing the same |
US7288084B2 (en) | 2003-04-28 | 2007-10-30 | Boston Scientific Scimed, Inc. | Drug-loaded medical device |
US8246974B2 (en) | 2003-05-02 | 2012-08-21 | Surmodics, Inc. | Medical devices and methods for producing the same |
ATE476960T1 (en) | 2003-05-02 | 2010-08-15 | Surmodics Inc | SYSTEM FOR THE CONTROLLED RELEASE OF A BIOACTIVE INGREDIENT IN THE BACK OF THE EYE |
US7279174B2 (en) | 2003-05-08 | 2007-10-09 | Advanced Cardiovascular Systems, Inc. | Stent coatings comprising hydrophilic additives |
US6846323B2 (en) * | 2003-05-15 | 2005-01-25 | Advanced Cardiovascular Systems, Inc. | Intravascular stent |
US20040230290A1 (en) | 2003-05-15 | 2004-11-18 | Jan Weber | Medical devices and methods of making the same |
AU2004238517A1 (en) | 2003-05-16 | 2004-11-25 | Cinvention Ag | Method for coating substrates with a carbon-based material |
US7524527B2 (en) | 2003-05-19 | 2009-04-28 | Boston Scientific Scimed, Inc. | Electrostatic coating of a device |
US20040236416A1 (en) | 2003-05-20 | 2004-11-25 | Robert Falotico | Increased biocompatibility of implantable medical devices |
US20050211680A1 (en) | 2003-05-23 | 2005-09-29 | Mingwei Li | Systems and methods for laser texturing of surfaces of a substrate |
US7041127B2 (en) | 2003-05-28 | 2006-05-09 | Ledergerber Walter J | Textured and drug eluting coronary artery stent |
US20030216803A1 (en) | 2003-05-28 | 2003-11-20 | Ledergerber Walter J. | Textured and drug eluting stent-grafts |
DK1626749T3 (en) | 2003-05-28 | 2009-02-09 | Cinv Ag | Implants with functionalized carbon surfaces |
US7297644B2 (en) | 2003-05-28 | 2007-11-20 | Air Products Polymers, L.P. | Nonwoven binders with high wet/dry tensile strength ratio |
US7270679B2 (en) | 2003-05-30 | 2007-09-18 | Warsaw Orthopedic, Inc. | Implants based on engineered metal matrix composite materials having enhanced imaging and wear resistance |
US6904658B2 (en) | 2003-06-02 | 2005-06-14 | Electroformed Stents, Inc. | Process for forming a porous drug delivery layer |
US6979348B2 (en) | 2003-06-04 | 2005-12-27 | Medtronic Vascular, Inc. | Reflowed drug-polymer coated stent and method thereof |
JP4971580B2 (en) | 2003-06-05 | 2012-07-11 | テルモ株式会社 | Stent and method for manufacturing stent |
US7169179B2 (en) | 2003-06-05 | 2007-01-30 | Conor Medsystems, Inc. | Drug delivery device and method for bi-directional drug delivery |
EP1650868A1 (en) | 2003-07-02 | 2006-04-26 | Sony Corporation | Mems type oscillator, process for fabricating the same, filter, and communication unit |
WO2005006325A1 (en) | 2003-07-10 | 2005-01-20 | Koninklijke Philips Electronics N.V. | Embedding watermarks for protecting multiple copies of a signal |
US20050021127A1 (en) | 2003-07-21 | 2005-01-27 | Kawula Paul John | Porous glass fused onto stent for drug retention |
US20050021128A1 (en) * | 2003-07-24 | 2005-01-27 | Medtronic Vascular, Inc. | Compliant, porous, rolled stent |
US7682603B2 (en) * | 2003-07-25 | 2010-03-23 | The Trustees Of The University Of Pennsylvania | Polymersomes incorporating highly emissive probes |
US7056591B1 (en) | 2003-07-30 | 2006-06-06 | Advanced Cardiovascular Systems, Inc. | Hydrophobic biologically absorbable coatings for drug delivery devices and methods for fabricating the same |
US20050027350A1 (en) | 2003-07-30 | 2005-02-03 | Biotronik Mess-Und Therapiegeraete Gmbh & Co Ingenieurbuero Berlin | Endovascular implant for the injection of an active substance into the media of a blood vessel |
US20050033417A1 (en) | 2003-07-31 | 2005-02-10 | John Borges | Coating for controlled release of a therapeutic agent |
US20070038289A1 (en) | 2003-08-05 | 2007-02-15 | Kaneka Corporation | Stent to be placed in vivo |
US20050037047A1 (en) | 2003-08-11 | 2005-02-17 | Young-Ho Song | Medical devices comprising spray dried microparticles |
US20050055085A1 (en) | 2003-09-04 | 2005-03-10 | Rivron Nicolas C. | Implantable medical devices having recesses |
US20050055080A1 (en) | 2003-09-05 | 2005-03-10 | Naim Istephanous | Modulated stents and methods of making the stents |
CA2539751C (en) | 2003-09-05 | 2016-04-26 | Norian Corporation | Bone cement compositions having fiber-reinforcement and/or increased flowability |
US7488343B2 (en) | 2003-09-16 | 2009-02-10 | Boston Scientific Scimed, Inc. | Medical devices |
US20050060020A1 (en) | 2003-09-17 | 2005-03-17 | Scimed Life Systems, Inc. | Covered stent with biologically active material |
CN101094622A (en) | 2003-09-18 | 2007-12-26 | 先进生物假体表面有限公司 | Medical devices having mems functionality and methods of making same |
US7785653B2 (en) | 2003-09-22 | 2010-08-31 | Innovational Holdings Llc | Method and apparatus for loading a beneficial agent into an expandable medical device |
US20050070990A1 (en) | 2003-09-26 | 2005-03-31 | Stinson Jonathan S. | Medical devices and methods of making same |
US7247166B2 (en) | 2003-09-29 | 2007-07-24 | Advanced Cardiovascular Systems, Inc. | Intravascular stent with extendible end rings |
US7055237B2 (en) | 2003-09-29 | 2006-06-06 | Medtronic Vascular, Inc. | Method of forming a drug eluting stent |
US7198675B2 (en) | 2003-09-30 | 2007-04-03 | Advanced Cardiovascular Systems | Stent mandrel fixture and method for selectively coating surfaces of a stent |
US7618647B2 (en) | 2003-10-03 | 2009-11-17 | Boston Scientific Scimed, Inc. | Using bucky paper as a therapeutic aid in medical applications |
US7284677B2 (en) | 2003-10-08 | 2007-10-23 | Elizabeth Ann Guevara | Bottle holding appliance and method for its use |
US20050118229A1 (en) * | 2003-10-21 | 2005-06-02 | Imedd, Inc. | Implantable drug delivery device for sustained release of therapeutic agent |
US20050087520A1 (en) | 2003-10-28 | 2005-04-28 | Lixiao Wang | Method and apparatus for selective ablation of coatings from medical devices |
FR2861740B1 (en) | 2003-10-29 | 2005-12-16 | Inst Rech Developpement Ird | ATTENUATED VIRULENCE PROTOZOATIC STRAINS AND THEIR USE |
US20050113936A1 (en) | 2003-10-30 | 2005-05-26 | Brustad John R. | Surface treatments and modifications using nanostructure materials |
US7208172B2 (en) | 2003-11-03 | 2007-04-24 | Medlogics Device Corporation | Metallic composite coating for delivery of therapeutic agents from the surface of implantable devices |
GB0325647D0 (en) | 2003-11-03 | 2003-12-10 | Finsbury Dev Ltd | Prosthetic implant |
US7435256B2 (en) | 2003-11-06 | 2008-10-14 | Boston Scientific Scimed, Inc. | Method and apparatus for controlled delivery of active substance |
WO2005044361A1 (en) | 2003-11-07 | 2005-05-19 | Merlin Md Pte Ltd | Implantable medical devices with enhanced visibility, mechanical properties and biocompatibility |
US20050100577A1 (en) | 2003-11-10 | 2005-05-12 | Parker Theodore L. | Expandable medical device with beneficial agent matrix formed by a multi solvent system |
CA2536168A1 (en) | 2003-11-10 | 2005-05-26 | Angiotech International Ag | Intravascular devices and fibrosis-inducing agents |
EP1687032B1 (en) | 2003-11-14 | 2010-02-24 | Genvec, Inc. | Pharmaceutical composition for treating unresectable, locally advanced pancreatic cancer (lapc). |
US8435285B2 (en) | 2003-11-25 | 2013-05-07 | Boston Scientific Scimed, Inc. | Composite stent with inner and outer stent elements and method of using the same |
EP1688155A4 (en) | 2003-11-28 | 2008-02-20 | Zeon Medical Inc | Cell growth-inhibiting film, medical instrument and stent for digestive organs |
US20050119723A1 (en) | 2003-11-28 | 2005-06-02 | Medlogics Device Corporation | Medical device with porous surface containing bioerodable bioactive composites and related methods |
JP4610885B2 (en) | 2003-11-28 | 2011-01-12 | ゼオンメディカル株式会社 | Cell growth suppression film and medical device |
JP4512351B2 (en) | 2003-11-28 | 2010-07-28 | ゼオンメディカル株式会社 | Gastrointestinal stent |
US20060085062A1 (en) | 2003-11-28 | 2006-04-20 | Medlogics Device Corporation | Implantable stent with endothelialization factor |
US20050131522A1 (en) | 2003-12-10 | 2005-06-16 | Stinson Jonathan S. | Medical devices and methods of making the same |
DE10358502B3 (en) | 2003-12-13 | 2005-04-07 | Daimlerchrysler Ag | Production of a hollow profile used as a branched part for pipes comprises stamping a secondary molding element to connect to a further component in a pre-curved region before winding |
US8017178B2 (en) | 2003-12-16 | 2011-09-13 | Cardiac Pacemakers, Inc. | Coatings for implantable electrodes |
WO2005063318A1 (en) | 2003-12-17 | 2005-07-14 | Pfizer Products Inc. | Stent with therapeutically active drug coated thereon |
US20050137684A1 (en) | 2003-12-17 | 2005-06-23 | Pfizer Inc | Stent with therapeutically active drug coated thereon |
US20050137677A1 (en) | 2003-12-17 | 2005-06-23 | Rush Scott L. | Endovascular graft with differentiable porosity along its length |
US8652502B2 (en) | 2003-12-19 | 2014-02-18 | Cordis Corporation | Local vascular delivery of trichostatin A alone or in combination with sirolimus to prevent restenosis following vascular injury |
US8043311B2 (en) | 2003-12-22 | 2011-10-25 | Boston Scientific Scimed, Inc. | Medical device systems |
US7563324B1 (en) | 2003-12-29 | 2009-07-21 | Advanced Cardiovascular Systems Inc. | System and method for coating an implantable medical device |
US7153411B2 (en) | 2003-12-30 | 2006-12-26 | Boston Scientific Scimed, Inc. | Method for cleaning and polishing metallic alloys and articles cleaned or polished thereby |
WO2005070338A1 (en) | 2004-01-20 | 2005-08-04 | Cook Incorporated | Multiple stitches for attaching stent to graft |
US20050159805A1 (en) | 2004-01-20 | 2005-07-21 | Jan Weber | Functional coatings and designs for medical implants |
US7854756B2 (en) | 2004-01-22 | 2010-12-21 | Boston Scientific Scimed, Inc. | Medical devices |
US7211108B2 (en) | 2004-01-23 | 2007-05-01 | Icon Medical Corp. | Vascular grafts with amphiphilic block copolymer coatings |
US7393589B2 (en) | 2004-01-30 | 2008-07-01 | Ionbond, Inc. | Dual layer diffusion bonded chemical vapor coating for medical implants |
ITTO20040056A1 (en) | 2004-02-05 | 2004-05-05 | Sorin Biomedica Cardio Spa | STENT FOR THE ENDOLIMINAL DELIVERY OF PRINCIPLES OR ACTIVE AGENTS |
US7442681B2 (en) | 2004-02-10 | 2008-10-28 | University Of Virginia Patent Foundation | Method of inhibiting vascular permeability |
US20050180919A1 (en) | 2004-02-12 | 2005-08-18 | Eugene Tedeschi | Stent with radiopaque and encapsulant coatings |
US8049137B2 (en) | 2004-02-13 | 2011-11-01 | Boston Scientific Scimed, Inc. | Laser shock peening of medical devices |
US7981441B2 (en) | 2004-02-18 | 2011-07-19 | The Board Of Trustees Of The Leland Stanford Junior University | Drug delivery systems using mesoporous oxide films |
US8097269B2 (en) | 2004-02-18 | 2012-01-17 | Celonova Biosciences, Inc. | Bioactive material delivery systems comprising sol-gel compositions |
US20050187608A1 (en) | 2004-02-24 | 2005-08-25 | O'hara Michael D. | Radioprotective compound coating for medical devices |
US8137397B2 (en) | 2004-02-26 | 2012-03-20 | Boston Scientific Scimed, Inc. | Medical devices |
US20050197687A1 (en) | 2004-03-02 | 2005-09-08 | Masoud Molaei | Medical devices including metallic films and methods for making same |
US8591568B2 (en) | 2004-03-02 | 2013-11-26 | Boston Scientific Scimed, Inc. | Medical devices including metallic films and methods for making same |
US20050196518A1 (en) | 2004-03-03 | 2005-09-08 | Stenzel Eric B. | Method and system for making a coated medical device |
FR2867059B1 (en) | 2004-03-03 | 2006-05-26 | Braun Medical | ENDOPROTHESIS WITH MARKERS FOR CONDUCTING A LIVING BODY |
US20050203606A1 (en) | 2004-03-09 | 2005-09-15 | Vancamp Daniel H. | Stent system for preventing restenosis |
JP5150895B2 (en) * | 2004-03-12 | 2013-02-27 | 国立大学法人長岡技術科学大学 | Membrane electrode assembly, method for producing membrane electrode assembly, and polymer electrolyte fuel cell |
US6979473B2 (en) | 2004-03-15 | 2005-12-27 | Boston Scientific Scimed, Inc. | Method for fine bore orifice spray coating of medical devices and pre-filming atomization |
US7744644B2 (en) | 2004-03-19 | 2010-06-29 | Boston Scientific Scimed, Inc. | Medical articles having regions with polyelectrolyte multilayer coatings for regulating drug release |
CN1938224B (en) | 2004-03-30 | 2011-03-30 | 东洋先进机床有限公司 | Method for treating surface of base, surface-treated base, material and instrument for medical use |
JP2007195883A (en) | 2006-01-30 | 2007-08-09 | Toyo Advanced Technologies Co Ltd | Stent and its production method |
US20050220853A1 (en) | 2004-04-02 | 2005-10-06 | Kinh-Luan Dao | Controlled delivery of therapeutic agents from medical articles |
CN1964748A (en) | 2004-04-06 | 2007-05-16 | 苏莫迪克斯公司 | Coating compositions for bioactive agents |
US7635515B1 (en) | 2004-04-08 | 2009-12-22 | Powdermet, Inc | Heterogeneous composite bodies with isolated lenticular shaped cermet regions |
US20050228477A1 (en) | 2004-04-09 | 2005-10-13 | Xtent, Inc. | Topographic coatings and coating methods for medical devices |
US20050228491A1 (en) | 2004-04-12 | 2005-10-13 | Snyder Alan J | Anti-adhesive surface treatments |
US20050230039A1 (en) | 2004-04-19 | 2005-10-20 | Michael Austin | Stent with protective pads or bulges |
US20050251245A1 (en) | 2004-05-05 | 2005-11-10 | Karl Sieradzki | Methods and apparatus with porous materials |
US7955371B2 (en) | 2004-05-12 | 2011-06-07 | Medtronic Vascular, Inc. | System and method for stent deployment and infusion of a therapeutic agent into tissue adjacent to the stent ends |
US20060100696A1 (en) | 2004-11-10 | 2006-05-11 | Atanasoska Ljiljana L | Medical devices and methods of making the same |
US7758892B1 (en) | 2004-05-20 | 2010-07-20 | Boston Scientific Scimed, Inc. | Medical devices having multiple layers |
US20050266039A1 (en) | 2004-05-27 | 2005-12-01 | Jan Weber | Coated medical device and method for making the same |
US20050266040A1 (en) | 2004-05-28 | 2005-12-01 | Brent Gerberding | Medical devices composed of porous metallic materials for delivering biologically active materials |
US7695775B2 (en) | 2004-06-04 | 2010-04-13 | Applied Microstructures, Inc. | Controlled vapor deposition of biocompatible coatings over surface-treated substrates |
KR20050117361A (en) | 2004-06-10 | 2005-12-14 | 류용선 | Titanium oxide coating stent and manufaturing method thereof |
US7332101B2 (en) | 2004-06-25 | 2008-02-19 | Massachusetts Institute Of Technology | Permanently linked, rigid, magnetic chains |
US7078108B2 (en) | 2004-07-14 | 2006-07-18 | The Regents Of The University Of California | Preparation of high-strength nanometer scale twinned coating and foil |
US20060015361A1 (en) * | 2004-07-16 | 2006-01-19 | Jurgen Sattler | Method and system for customer contact reporting |
US7144840B2 (en) | 2004-07-22 | 2006-12-05 | Hong Kong University Of Science And Technology | TiO2 material and the coating methods thereof |
US7269700B2 (en) * | 2004-07-26 | 2007-09-11 | Integrated Device Technology, Inc. | Status bus accessing only available quadrants during loop mode operation in a multi-queue first-in first-out memory system |
CA2474367A1 (en) | 2004-07-26 | 2006-01-26 | Jingzeng Zhang | Electrolytic jet plasma process and apparatus for cleaning, case hardening, coating and anodizing |
US20060025848A1 (en) | 2004-07-29 | 2006-02-02 | Jan Weber | Medical device having a coating layer with structural elements therein and method of making the same |
US7601382B2 (en) | 2004-08-05 | 2009-10-13 | Boston Scientific Scimed, Inc. | Method of making a coated medical device |
US20060034884A1 (en) | 2004-08-10 | 2006-02-16 | Stenzel Eric B | Coated medical device having an increased coating surface area |
KR20070063511A (en) | 2004-08-13 | 2007-06-19 | 세타곤 인코포레이티드 | Medical devices having nanoporous layers and methods for making the same |
US20060275554A1 (en) | 2004-08-23 | 2006-12-07 | Zhibo Zhao | High performance kinetic spray nozzle |
US7507433B2 (en) | 2004-09-03 | 2009-03-24 | Boston Scientific Scimed, Inc. | Method of coating a medical device using an electrowetting process |
DE102004043231A1 (en) | 2004-09-07 | 2006-03-09 | Biotronik Vi Patent Ag | Endoprosthesis made of magnesium alloy |
DE102004043232A1 (en) | 2004-09-07 | 2006-03-09 | Biotronik Vi Patent Ag | Endoprosthesis made of magnesium alloy |
US7229471B2 (en) | 2004-09-10 | 2007-06-12 | Advanced Cardiovascular Systems, Inc. | Compositions containing fast-leaching plasticizers for improved performance of medical devices |
DE102004044738A1 (en) | 2004-09-15 | 2006-03-16 | Technische Universität München | Process for producing a structuring of metal surfaces and components produced by this process |
US7901451B2 (en) | 2004-09-24 | 2011-03-08 | Biosensors International Group, Ltd. | Drug-delivery endovascular stent and method for treating restenosis |
US20060075044A1 (en) | 2004-09-30 | 2006-04-06 | Fox Kevin D | System and method for electronic contact list-based search and display |
US20060075092A1 (en) | 2004-10-06 | 2006-04-06 | Kabushiki Kaisha Toshiba | System and method for determining the status of users and devices from access log information |
US20060079863A1 (en) | 2004-10-08 | 2006-04-13 | Scimed Life Systems, Inc. | Medical devices coated with diamond-like carbon |
US7344560B2 (en) | 2004-10-08 | 2008-03-18 | Boston Scientific Scimed, Inc. | Medical devices and methods of making the same |
US20060085065A1 (en) | 2004-10-15 | 2006-04-20 | Krause Arthur A | Stent with auxiliary treatment structure |
US20060085058A1 (en) | 2004-10-20 | 2006-04-20 | Rosenthal Arthur L | System and method for delivering a biologically active material to a body lumen |
US7862835B2 (en) | 2004-10-27 | 2011-01-04 | Boston Scientific Scimed, Inc. | Method of manufacturing a medical device having a porous coating thereon |
US20060088566A1 (en) | 2004-10-27 | 2006-04-27 | Scimed Life Systems, Inc.,A Corporation | Method of controlling drug release from a coated medical device through the use of nucleating agents |
US20060093646A1 (en) | 2004-10-28 | 2006-05-04 | Cima Michael J | Orthopedic and dental implant devices providing controlled drug delivery |
US20060093643A1 (en) | 2004-11-04 | 2006-05-04 | Stenzel Eric B | Medical device for delivering therapeutic agents over different time periods |
US7628807B2 (en) | 2004-11-04 | 2009-12-08 | Boston Scientific Scimed, Inc. | Stent for delivering a therapeutic agent having increased body tissue contact surface |
US20060122694A1 (en) | 2004-12-03 | 2006-06-08 | Stinson Jonathan S | Medical devices and methods of making the same |
GB0426841D0 (en) | 2004-12-07 | 2005-01-12 | Univ Brunel | Medical implant |
US20060129215A1 (en) | 2004-12-09 | 2006-06-15 | Helmus Michael N | Medical devices having nanostructured regions for controlled tissue biocompatibility and drug delivery |
US20060127442A1 (en) * | 2004-12-09 | 2006-06-15 | Helmus Michael N | Use of supercritical fluids to incorporate biologically active agents into nanoporous medical articles |
JP2006171800A (en) * | 2004-12-10 | 2006-06-29 | Fujitsu Ltd | Data-totaling device, its method, and program |
US20060125144A1 (en) | 2004-12-14 | 2006-06-15 | Jan Weber | Stent and stent manufacturing methods |
US20060129225A1 (en) | 2004-12-15 | 2006-06-15 | Kopia Gregory A | Device for the delivery of a cardioprotective agent to ischemic reperfused myocardium |
US7632307B2 (en) | 2004-12-16 | 2009-12-15 | Advanced Cardiovascular Systems, Inc. | Abluminal, multilayer coating constructs for drug-delivery stents |
DE102004062394B4 (en) * | 2004-12-23 | 2008-05-29 | Siemens Ag | Intravenous pacemaker electrode and process for its preparation |
PT1674117T (en) | 2004-12-24 | 2018-11-26 | Hexacath | Mechanical piece with improved deformability |
US20060140867A1 (en) | 2004-12-28 | 2006-06-29 | Helfer Jeffrey L | Coated stent assembly and coating materials |
US7727273B2 (en) | 2005-01-13 | 2010-06-01 | Boston Scientific Scimed, Inc. | Medical devices and methods of making the same |
WO2006074550A1 (en) | 2005-01-14 | 2006-07-20 | National Research Council Of Canada | Implantable biomimetic prosthetic bone |
US8057543B2 (en) | 2005-01-28 | 2011-11-15 | Greatbatch Ltd. | Stent coating for eluting medication |
US8535702B2 (en) | 2005-02-01 | 2013-09-17 | Boston Scientific Scimed, Inc. | Medical devices having porous polymeric regions for controlled drug delivery and regulated biocompatibility |
KR20070100836A (en) | 2005-02-03 | 2007-10-11 | 신벤션 아게 | Drug delivery materials made by sol/gel technology |
US20070003589A1 (en) * | 2005-02-17 | 2007-01-04 | Irina Astafieva | Coatings for implantable medical devices containing attractants for endothelial cells |
DE102005010100A1 (en) | 2005-03-02 | 2006-09-14 | Hehrlein, Friedrich Wilhelm, Prof. Dr. Dr. | Medical instrument with an asymmetrical microcrater in outer surface and a medicament holding fatty acid layer useful in administration of slow release drugs, e.g. in angioplasty, where medicament fatty acid layer can be mxied with acetone |
WO2006110197A2 (en) | 2005-03-03 | 2006-10-19 | Icon Medical Corp. | Polymer biodegradable medical device |
US20060200229A1 (en) | 2005-03-03 | 2006-09-07 | Robert Burgermeister | Geometry and material for use in high strength, high flexibility, controlled recoil drug eluting stents |
US20060199876A1 (en) | 2005-03-04 | 2006-09-07 | The University Of British Columbia | Bioceramic composite coatings and process for making same |
US7837726B2 (en) | 2005-03-14 | 2010-11-23 | Abbott Laboratories | Visible endoprosthesis |
US20060229715A1 (en) | 2005-03-29 | 2006-10-12 | Sdgi Holdings, Inc. | Implants incorporating nanotubes and methods for producing the same |
US9125968B2 (en) | 2005-03-30 | 2015-09-08 | Boston Scientific Scimed, Inc. | Polymeric/ceramic composite materials for use in medical devices |
JP2008538089A (en) | 2005-03-31 | 2008-10-09 | コナー・ミッドシステムズ・インコーポレイテッド | Method for loading a beneficial substance into a medical device |
US7641983B2 (en) | 2005-04-04 | 2010-01-05 | Boston Scientific Scimed, Inc. | Medical devices including composites |
CA2604419C (en) | 2005-04-05 | 2015-03-24 | Elixir Medical Corporation | Degradable implantable medical devices |
US20060233941A1 (en) | 2005-04-15 | 2006-10-19 | Boston Scientific Scimed, Inc. | Method of coating a medical device utilizing an ion-based thin film deposition technique, a system for coating a medical device, and a medical device produced by the method |
US8734851B2 (en) | 2005-04-29 | 2014-05-27 | Wisconsin Alumni Research Foundation | Localized delivery of nucleic acid by polyelectrolyte assemblies |
WO2006125086A2 (en) | 2005-05-19 | 2006-11-23 | Isoflux, Inc. | Multi-layer coating system and method |
US20060276910A1 (en) | 2005-06-01 | 2006-12-07 | Jan Weber | Endoprostheses |
WO2006133223A2 (en) | 2005-06-06 | 2006-12-14 | Innovational Holdings, Llc | Implantable medical device with openings for delivery of beneficial agents with combination release kinetics |
US8273117B2 (en) | 2005-06-22 | 2012-09-25 | Integran Technologies Inc. | Low texture, quasi-isotropic metallic stent |
US7368065B2 (en) | 2005-06-23 | 2008-05-06 | Depuy Products, Inc. | Implants with textured surface and methods for producing the same |
US20070038176A1 (en) | 2005-07-05 | 2007-02-15 | Jan Weber | Medical devices with machined layers for controlled communications with underlying regions |
US20090118838A1 (en) | 2005-08-05 | 2009-05-07 | Christian Debry | Materials Useful for Support and/or Replacement of Tissue and the Use Thereof for Making Prostheses |
US7914809B2 (en) | 2005-08-26 | 2011-03-29 | Boston Scientific Scimed, Inc. | Lubricious composites for medical devices |
US20070048452A1 (en) | 2005-09-01 | 2007-03-01 | James Feng | Apparatus and method for field-injection electrostatic spray coating of medical devices |
EP1764116A1 (en) | 2005-09-16 | 2007-03-21 | Debiotech S.A. | Porous coating process using colloidal particles |
US20070073385A1 (en) | 2005-09-20 | 2007-03-29 | Cook Incorporated | Eluting, implantable medical device |
US20070065418A1 (en) | 2005-09-20 | 2007-03-22 | Franco Vallana | Method and device for cellular therapy |
US20070073390A1 (en) | 2005-09-23 | 2007-03-29 | Medlogics Device Corporation | Methods and devices for enhanced adhesion between metallic substrates and bioactive material-containing coatings |
US8008395B2 (en) | 2005-09-27 | 2011-08-30 | Boston Scientific Scimed, Inc. | Organic-inorganic hybrid particle material and polymer compositions containing same |
WO2007044229A2 (en) | 2005-09-28 | 2007-04-19 | Calcitec, Inc. | Surface treatments for calcium phosphate-based implants |
GB0522569D0 (en) | 2005-11-04 | 2005-12-14 | Univ Bath | Biocompatible drug delivery device |
DE102005053247A1 (en) | 2005-11-08 | 2007-05-16 | Martin Fricke | Implant, in particular stent, and method for producing such an implant |
US20070106347A1 (en) | 2005-11-09 | 2007-05-10 | Wun-Chen Lin | Portable medical and cosmetic photon emission adjustment device and method using the same |
US7935379B2 (en) | 2005-11-14 | 2011-05-03 | Boston Scientific Scimed, Inc. | Coated and imprinted medical devices and methods of making the same |
US20070112421A1 (en) | 2005-11-14 | 2007-05-17 | O'brien Barry | Medical device with a grooved surface |
US8147860B2 (en) | 2005-12-06 | 2012-04-03 | Etex Corporation | Porous calcium phosphate bone material |
US20070135908A1 (en) | 2005-12-08 | 2007-06-14 | Zhao Jonathon Z | Absorbable stent comprising coating for controlling degradation and maintaining pH neutrality |
US20070134288A1 (en) | 2005-12-13 | 2007-06-14 | Edward Parsonage | Anti-adhesion agents for drug coatings |
US7638156B1 (en) | 2005-12-19 | 2009-12-29 | Advanced Cardiovascular Systems, Inc. | Apparatus and method for selectively coating a medical article |
US20070148251A1 (en) | 2005-12-22 | 2007-06-28 | Hossainy Syed F A | Nanoparticle releasing medical devices |
US8834912B2 (en) | 2005-12-30 | 2014-09-16 | Boston Scientific Scimed, Inc. | Medical devices having multiple charged layers |
US8840660B2 (en) | 2006-01-05 | 2014-09-23 | Boston Scientific Scimed, Inc. | Bioerodible endoprostheses and methods of making the same |
US20070173923A1 (en) | 2006-01-20 | 2007-07-26 | Savage Douglas R | Drug reservoir stent |
US20070190104A1 (en) | 2006-02-13 | 2007-08-16 | Kamath Kalpana R | Coating comprising an adhesive polymeric material for a medical device and method of preparing the same |
US9526814B2 (en) | 2006-02-16 | 2016-12-27 | Boston Scientific Scimed, Inc. | Medical balloons and methods of making the same |
US20070191931A1 (en) | 2006-02-16 | 2007-08-16 | Jan Weber | Bioerodible endoprostheses and methods of making the same |
ATE551966T1 (en) | 2006-02-28 | 2012-04-15 | Straumann Holding Ag | TWO-PIECE IMPLANT WITH HYDROXYLATED CONTACT SURFACE FOR SOFT TISSUE |
DE102006010040B3 (en) | 2006-03-04 | 2007-10-11 | Eisenbau Krämer mbH | straightener |
US8585753B2 (en) | 2006-03-04 | 2013-11-19 | John James Scanlon | Fibrillated biodegradable prosthesis |
US8597341B2 (en) | 2006-03-06 | 2013-12-03 | David Elmaleh | Intravascular device with netting system |
US20070212547A1 (en) | 2006-03-08 | 2007-09-13 | Boston Scientific Scimed, Inc. | Method of powder coating medical devices |
EP1834606B1 (en) | 2006-03-16 | 2013-04-24 | CID S.p.A. | Stents |
US20070224244A1 (en) | 2006-03-22 | 2007-09-27 | Jan Weber | Corrosion resistant coatings for biodegradable metallic implants |
US20070224235A1 (en) | 2006-03-24 | 2007-09-27 | Barron Tenney | Medical devices having nanoporous coatings for controlled therapeutic agent delivery |
US8187620B2 (en) | 2006-03-27 | 2012-05-29 | Boston Scientific Scimed, Inc. | Medical devices comprising a porous metal oxide or metal material and a polymer coating for delivering therapeutic agents |
US8048150B2 (en) | 2006-04-12 | 2011-11-01 | Boston Scientific Scimed, Inc. | Endoprosthesis having a fiber meshwork disposed thereon |
US7879086B2 (en) | 2006-04-20 | 2011-02-01 | Boston Scientific Scimed, Inc. | Medical device having a coating comprising an adhesion promoter |
US9155646B2 (en) | 2006-04-27 | 2015-10-13 | Brs Holdings, Llc | Composite stent with bioremovable ceramic flakes |
US20070254091A1 (en) | 2006-04-28 | 2007-11-01 | Boston Scientific Scimed, Inc. | System and method for electrostatic-assisted spray coating of a medical device |
US20070264303A1 (en) | 2006-05-12 | 2007-11-15 | Liliana Atanasoska | Coating for medical devices comprising an inorganic or ceramic oxide and a therapeutic agent |
EP1891988A1 (en) | 2006-08-07 | 2008-02-27 | Debiotech S.A. | Anisotropic nanoporous coatings for medical implants |
JP5290962B2 (en) | 2006-05-17 | 2013-09-18 | デビオテック ソシエテ アノニム | Anisotropic nanoporous coating |
US8092818B2 (en) | 2006-05-17 | 2012-01-10 | Boston Scientific Scimed, Inc. | Medical devices having bioactive surfaces |
WO2007143433A1 (en) | 2006-05-31 | 2007-12-13 | Setagon, Inc. | Nanoporous stents with enhanced cellular adhesion and reduced neointimal formation |
US8778376B2 (en) | 2006-06-09 | 2014-07-15 | Advanced Cardiovascular Systems, Inc. | Copolymer comprising elastin pentapeptide block and hydrophilic block, and medical device and method of treating |
GB0612028D0 (en) | 2006-06-16 | 2006-07-26 | Imp Innovations Ltd | Bioactive glass |
US20100280599A1 (en) | 2006-06-21 | 2010-11-04 | Pui Hung Manus Tsui | Calcium phosphate coated implantable medical devices, and electrochemical deposition processes for making same |
US8815275B2 (en) * | 2006-06-28 | 2014-08-26 | Boston Scientific Scimed, Inc. | Coatings for medical devices comprising a therapeutic agent and a metallic material |
CA2655793A1 (en) * | 2006-06-29 | 2008-01-03 | Boston Scientific Limited | Medical devices with selective coating |
US20080008654A1 (en) * | 2006-07-07 | 2008-01-10 | Boston Scientific Scimed, Inc. | Medical devices having a temporary radiopaque coating |
WO2008016713A2 (en) | 2006-08-02 | 2008-02-07 | Inframat Corporation | Lumen-supporting devices and methods of making and using |
US20080069854A1 (en) | 2006-08-02 | 2008-03-20 | Inframat Corporation | Medical devices and methods of making and using |
US20080058921A1 (en) | 2006-08-09 | 2008-03-06 | Lindquist Jeffrey S | Improved adhesion of a polymeric coating of a drug eluting stent |
US20080057102A1 (en) | 2006-08-21 | 2008-03-06 | Wouter Roorda | Methods of manufacturing medical devices for controlled drug release |
US20080050413A1 (en) | 2006-08-23 | 2008-02-28 | Ronald Adrianus Maria Horvers | Medical stent provided with a combination of melatonin and paclitaxel |
US20080051881A1 (en) | 2006-08-24 | 2008-02-28 | Feng James Q | Medical devices comprising porous layers for the release of therapeutic agents |
US20080050415A1 (en) | 2006-08-25 | 2008-02-28 | Boston Scientic Scimed, Inc. | Polymeric/ceramic composite materials for use in medical devices |
DE102006041023B4 (en) | 2006-09-01 | 2014-06-12 | Biocer Entwicklungs Gmbh | Structured coatings for implants and process for their preparation |
JP2010503469A (en) | 2006-09-14 | 2010-02-04 | ボストン サイエンティフィック リミテッド | Medical device having drug-eluting film |
WO2008034030A2 (en) | 2006-09-15 | 2008-03-20 | Boston Scientific Limited | Magnetized bioerodible endoprosthesis |
EP2066363A2 (en) | 2006-09-15 | 2009-06-10 | Boston Scientific Limited | Endoprosthesis containing magnetic induction particles |
EP2068780A2 (en) | 2006-09-15 | 2009-06-17 | Boston Scientific Limited | Medical devices |
DE602007011114D1 (en) | 2006-09-15 | 2011-01-20 | Boston Scient Scimed Inc | BIODEGRADABLE ENDOPROTHESIS WITH BIOSTABILES INORGANIC LAYERS |
WO2008034047A2 (en) | 2006-09-15 | 2008-03-20 | Boston Scientific Limited | Endoprosthesis with adjustable surface features |
US20080071349A1 (en) | 2006-09-18 | 2008-03-20 | Boston Scientific Scimed, Inc. | Medical Devices |
WO2008036554A2 (en) | 2006-09-18 | 2008-03-27 | Boston Scientific Limited | Endoprostheses |
WO2008036548A2 (en) | 2006-09-18 | 2008-03-27 | Boston Scientific Limited | Endoprostheses |
WO2008045184A1 (en) | 2006-10-05 | 2008-04-17 | Boston Scientific Limited | Polymer-free coatings for medical devices formed by plasma electrolytic deposition |
US8394488B2 (en) | 2006-10-06 | 2013-03-12 | Cordis Corporation | Bioabsorbable device having composite structure for accelerating degradation |
US20080097577A1 (en) | 2006-10-20 | 2008-04-24 | Boston Scientific Scimed, Inc. | Medical device hydrogen surface treatment by electrochemical reduction |
CA2668408A1 (en) | 2006-11-03 | 2008-05-15 | Boston Scientific Limited | Ion bombardment of medical devices |
US7981150B2 (en) | 2006-11-09 | 2011-07-19 | Boston Scientific Scimed, Inc. | Endoprosthesis with coatings |
CA2668769A1 (en) | 2006-11-09 | 2008-05-22 | Boston Scientific Limited | Endoprosthesis with coatings |
US20080294236A1 (en) | 2007-05-23 | 2008-11-27 | Boston Scientific Scimed, Inc. | Endoprosthesis with Select Ceramic and Polymer Coatings |
US8414525B2 (en) | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Drug releasing coatings for medical devices |
CN101199873B (en) | 2006-12-14 | 2013-06-19 | 乐普(北京)医疗器械股份有限公司 | Medicament elution instrument nanometer class colon washer machineole drug releasing structure and preparing method thereof |
US7939095B2 (en) | 2006-12-21 | 2011-05-10 | Cordis Corporation | Crosslinked silane coating for medical devices |
EP2114480B1 (en) | 2006-12-28 | 2016-01-06 | Boston Scientific Limited | Medical devices and methods of making the same |
US20080171929A1 (en) | 2007-01-11 | 2008-07-17 | Katims Jefferson J | Method for standardizing spacing between electrodes, and medical tape electrodes |
EP2125064B1 (en) | 2007-01-26 | 2017-04-26 | Boston Scientific Limited | Implantable medical endoprostheses |
US7575593B2 (en) | 2007-01-30 | 2009-08-18 | Medtronic Vascular, Inc. | Implantable device with reservoirs for increased drug loading |
US8187255B2 (en) | 2007-02-02 | 2012-05-29 | Boston Scientific Scimed, Inc. | Medical devices having nanoporous coatings for controlled therapeutic agent delivery |
US8070797B2 (en) | 2007-03-01 | 2011-12-06 | Boston Scientific Scimed, Inc. | Medical device with a porous surface for delivery of a therapeutic agent |
US8431149B2 (en) | 2007-03-01 | 2013-04-30 | Boston Scientific Scimed, Inc. | Coated medical devices for abluminal drug delivery |
CA2680886A1 (en) * | 2007-03-15 | 2008-09-18 | Boston Scientific Limited | Methods to improve the stability of cellular adhesive proteins and peptides |
US20080243240A1 (en) | 2007-03-26 | 2008-10-02 | Medtronic Vascular, Inc. | Biodegradable Metal Barrier Layer for a Drug-Eluting Stent |
US8067054B2 (en) | 2007-04-05 | 2011-11-29 | Boston Scientific Scimed, Inc. | Stents with ceramic drug reservoir layer and methods of making and using the same |
US20080249600A1 (en) | 2007-04-06 | 2008-10-09 | Boston Scientific Scimed, Inc. | Stents with drug reservoir layer and methods of making and using the same |
US20080255657A1 (en) | 2007-04-09 | 2008-10-16 | Boston Scientific Scimed, Inc. | Stent with unconnected stent segments |
US8703168B2 (en) | 2007-04-25 | 2014-04-22 | Boston Scientific Scimed, Inc. | Medical devices for releasing therapeutic agent and methods of making the same |
US20080275543A1 (en) | 2007-05-02 | 2008-11-06 | Boston Scientific Scimed, Inc. | Stent |
US7976915B2 (en) | 2007-05-23 | 2011-07-12 | Boston Scientific Scimed, Inc. | Endoprosthesis with select ceramic morphology |
US7888719B2 (en) | 2007-05-23 | 2011-02-15 | Taiwan Semiconductor Manufacturing Co., Ltd. | Semiconductor memory structures |
US20080306584A1 (en) | 2007-06-05 | 2008-12-11 | Pamela Kramer-Brown | Implantable medical devices for local and regional treatment |
US7901452B2 (en) | 2007-06-27 | 2011-03-08 | Abbott Cardiovascular Systems Inc. | Method to fabricate a stent having selected morphology to reduce restenosis |
US7909864B2 (en) * | 2007-07-06 | 2011-03-22 | Boston Scientific Scimed, Inc. | Implantable medical devices having adjustable pore volume and methods for making the same |
US8002823B2 (en) * | 2007-07-11 | 2011-08-23 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US7942926B2 (en) * | 2007-07-11 | 2011-05-17 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US20090018644A1 (en) * | 2007-07-13 | 2009-01-15 | Jan Weber | Boron-Enhanced Shape Memory Endoprostheses |
WO2009012353A2 (en) | 2007-07-19 | 2009-01-22 | Boston Scientific Limited | Endoprosthesis having a non-fouling surface |
US20090028785A1 (en) * | 2007-07-23 | 2009-01-29 | Boston Scientific Scimed, Inc. | Medical devices with coatings for delivery of a therapeutic agent |
US20090157172A1 (en) | 2007-07-24 | 2009-06-18 | Boston Scientific Scrimed, Inc. | Stents with polymer-free coatings for delivering a therapeutic agent |
US7931683B2 (en) | 2007-07-27 | 2011-04-26 | Boston Scientific Scimed, Inc. | Articles having ceramic coated surfaces |
US20090030504A1 (en) * | 2007-07-27 | 2009-01-29 | Boston Scientific Scimed, Inc. | Medical devices comprising porous inorganic fibers for the release of therapeutic agents |
JP2010535541A (en) | 2007-08-03 | 2010-11-25 | ボストン サイエンティフィック リミテッド | Coating for medical devices with large surface area |
US8052745B2 (en) | 2007-09-13 | 2011-11-08 | Boston Scientific Scimed, Inc. | Endoprosthesis |
US9248219B2 (en) | 2007-09-14 | 2016-02-02 | Boston Scientific Scimed, Inc. | Medical devices having bioerodable layers for the release of therapeutic agents |
US20100233226A1 (en) | 2007-10-15 | 2010-09-16 | Université Catholique de Louvain | Drug-eluting nanowire array |
US20090118813A1 (en) | 2007-11-02 | 2009-05-07 | Torsten Scheuermann | Nano-patterned implant surfaces |
US20090118812A1 (en) | 2007-11-02 | 2009-05-07 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US8029554B2 (en) | 2007-11-02 | 2011-10-04 | Boston Scientific Scimed, Inc. | Stent with embedded material |
US20090118818A1 (en) | 2007-11-02 | 2009-05-07 | Boston Scientific Scimed, Inc. | Endoprosthesis with coating |
US20090118809A1 (en) | 2007-11-02 | 2009-05-07 | Torsten Scheuermann | Endoprosthesis with porous reservoir and non-polymer diffusion layer |
US20090118821A1 (en) | 2007-11-02 | 2009-05-07 | Boston Scientific Scimed, Inc. | Endoprosthesis with porous reservoir and non-polymer diffusion layer |
US8216632B2 (en) | 2007-11-02 | 2012-07-10 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US20090118815A1 (en) | 2007-11-02 | 2009-05-07 | Boston Scientific Scimed, Inc. | Stent |
US20090118823A1 (en) | 2007-11-02 | 2009-05-07 | Boston Scientific Scimed, Inc. | Endoprosthesis with porous reservoir |
EP2214738B1 (en) | 2007-11-02 | 2012-05-02 | Boston Scientific Limited | Degradable endoprosthesis |
US7938855B2 (en) | 2007-11-02 | 2011-05-10 | Boston Scientific Scimed, Inc. | Deformable underlayer for stent |
EP2229192A2 (en) | 2007-12-12 | 2010-09-22 | Boston Scientific Scimed, Inc. | Medical devices having porous component for controlled diffusion |
WO2009079389A2 (en) * | 2007-12-14 | 2009-06-25 | Boston Scientific Limited | Drug-eluting endoprosthesis |
US7722661B2 (en) | 2007-12-19 | 2010-05-25 | Boston Scientific Scimed, Inc. | Stent |
US8303650B2 (en) | 2008-01-10 | 2012-11-06 | Telesis Research, Llc | Biodegradable self-expanding drug-eluting prosthesis |
EP2257971A4 (en) | 2008-01-18 | 2012-11-28 | Nanosurface Technologies Llc | Nanofilm protective and release matrices |
US20090186068A1 (en) | 2008-01-18 | 2009-07-23 | Chameleon Scientific Corporation | Atomic plasma deposited coatings for drug release |
ES2371380T3 (en) | 2008-01-24 | 2011-12-30 | Boston Scientific Scimed, Inc. | STENT TO SUPPLY A THERAPEUTIC AGENT FROM A SIDE SURFACE OF A STENT STEM. |
WO2009102787A2 (en) | 2008-02-12 | 2009-08-20 | Boston Scientific Scimed, Inc. | Medical implants with polysaccharide drug eluting coatings |
US20100042206A1 (en) | 2008-03-04 | 2010-02-18 | Icon Medical Corp. | Bioabsorbable coatings for medical devices |
WO2009126766A2 (en) | 2008-04-10 | 2009-10-15 | Boston Scientific Scimed, Inc. | Medical devices with an interlocking coating and methods of making the same |
EP2271380B1 (en) | 2008-04-22 | 2013-03-20 | Boston Scientific Scimed, Inc. | Medical devices having a coating of inorganic material |
US7998192B2 (en) | 2008-05-09 | 2011-08-16 | Boston Scientific Scimed, Inc. | Endoprostheses |
US20090287301A1 (en) | 2008-05-16 | 2009-11-19 | Boston Scientific, Scimed Inc. | Coating for medical implants |
US8236046B2 (en) | 2008-06-10 | 2012-08-07 | Boston Scientific Scimed, Inc. | Bioerodible endoprosthesis |
EP2303350A2 (en) | 2008-06-18 | 2011-04-06 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US8242037B2 (en) | 2008-07-24 | 2012-08-14 | The Regents Of The University Of Michigan | Method of pressureless sintering production of densified ceramic composites |
US7985252B2 (en) | 2008-07-30 | 2011-07-26 | Boston Scientific Scimed, Inc. | Bioerodible endoprosthesis |
WO2010014690A2 (en) | 2008-07-31 | 2010-02-04 | Boston Scientific Scimed, Inc. | Medical devices for therapeutic agent delivery |
CN102196826A (en) | 2008-08-27 | 2011-09-21 | 波士顿科学医学有限公司 | Medical devices having inorganic coatings for therapeutic agent delivery |
JP2010063768A (en) | 2008-09-12 | 2010-03-25 | Fujifilm Corp | Stent having porous film and method of manufacturing the same |
US20100070022A1 (en) | 2008-09-12 | 2010-03-18 | Boston Scientific Scimed, Inc. | Layer by layer manufacturing of a stent |
US20100070013A1 (en) | 2008-09-18 | 2010-03-18 | Medtronic Vascular, Inc. | Medical Device With Microsphere Drug Delivery System |
US9283304B2 (en) | 2008-11-25 | 2016-03-15 | CARDINAL HEALTH SWITZERLAND 515 GmbH | Absorbable stent having a coating for controlling degradation of the stent and maintaining pH neutrality |
-
2006
- 2006-03-24 US US11/388,604 patent/US20070224235A1/en not_active Abandoned
-
2007
- 2007-02-26 CA CA002661456A patent/CA2661456A1/en not_active Abandoned
- 2007-02-26 EP EP07751464A patent/EP2010241A2/en not_active Withdrawn
- 2007-02-26 JP JP2009501430A patent/JP5424865B2/en not_active Expired - Fee Related
- 2007-02-26 WO PCT/US2007/004704 patent/WO2007111801A2/en active Application Filing
-
2010
- 2010-05-25 US US12/787,209 patent/US8574615B2/en not_active Expired - Fee Related
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0875218A2 (en) * | 1997-04-15 | 1998-11-04 | Advanced Cardiovascular Systems, Inc. | Porous medicated stent |
US6709379B1 (en) * | 1998-11-02 | 2004-03-23 | Alcove Surfaces Gmbh | Implant with cavities containing therapeutic agents |
WO2002047581A1 (en) * | 2000-12-15 | 2002-06-20 | Badari Narayan Nagarada Gadde | Stent with drug-delivery system |
EP1319416A1 (en) * | 2001-12-12 | 2003-06-18 | Hehrlein, Christoph, Dr. | Porous metallic stent with a ceramic coating |
WO2006063157A2 (en) * | 2004-12-09 | 2006-06-15 | Boston Scientific Scimed, Inc. | Medical devices having vapor deposited nanoporous coatings for controlled therapeutic agent delivery |
Non-Patent Citations (2)
Title |
---|
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; August 2002 (2002-08), WIENEKE H ET AL: "Synergistic effects of a novel nanoporous stent coating and tacrolimus on intima proliferation in rabbits." XP002474123 Database accession no. PREV200300229450 cited in the application & EUROPEAN HEART JOURNAL, vol. 23, no. Abstract Supplement, August 2002 (2002-08), page 692, CONGRESS OF THE EUROPEAN SOCIETY OF CARDIOLOGY; BERLIN, GERMANY; AUGUST 31-SEPTEMBER 04, 2002 ISSN: 0195-668X * |
DATABASE EMBASE [Online] ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL; 6 May 2003 (2003-05-06), SOUSA J E ET AL: "New frontiers in cardiology: Drug-eluting stents: Part I" XP002474124 Database accession no. EMB-2003187048 & CIRCULATION 20030506 US, vol. 107, no. 17, 6 May 2003 (2003-05-06), pages 2274-2279, ISSN: 0009-7322 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009038870A1 (en) * | 2007-09-19 | 2009-03-26 | Boston Scientific Scimed, Inc. | Stent design allowing extended release of drug and/or enhanced adhesion of polymer to od surface |
JP2011509809A (en) * | 2008-01-24 | 2011-03-31 | ボストン サイエンティフィック サイムド,インコーポレイテッド | Stent for delivering therapeutic agent from side surface of stent strut |
Also Published As
Publication number | Publication date |
---|---|
JP5424865B2 (en) | 2014-02-26 |
US20100233238A1 (en) | 2010-09-16 |
US8574615B2 (en) | 2013-11-05 |
JP2009530022A (en) | 2009-08-27 |
US20070224235A1 (en) | 2007-09-27 |
WO2007111801A3 (en) | 2008-06-19 |
CA2661456A1 (en) | 2007-10-04 |
EP2010241A2 (en) | 2009-01-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8574615B2 (en) | Medical devices having nanoporous coatings for controlled therapeutic agent delivery | |
US8734829B2 (en) | Medical devices having polymeric nanoporous coatings for controlled therapeutic agent delivery and a nonpolymeric macroporous protective layer | |
EP2131882B1 (en) | Medical devices having nanoporous coatings for controlled therapeutic agent delivery | |
US8388678B2 (en) | Medical devices having porous component for controlled diffusion | |
US8586072B2 (en) | Medical devices having coatings for controlled therapeutic agent delivery | |
EP2190493B1 (en) | Medical devices having a metal particulate composition for controlled diffusion | |
EP1838361B1 (en) | Medical devices having vapor deposited nanoporous coatings for controlled therapeutic agent delivery | |
US8974809B2 (en) | Medical devices having a filter insert for controlled diffusion | |
US20110014264A1 (en) | Medical Devices Having Nanostructured Regions For Controlled Tissue Biocompatibility And Drug Delivery | |
EP2175903B1 (en) | Drug eluting medical devices having porous layers |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 2009501430 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2661456 Country of ref document: CA |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2007751464 Country of ref document: EP |