WO2007143063A2 - Drug delivery spiral coil construct - Google Patents

Drug delivery spiral coil construct Download PDF

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Publication number
WO2007143063A2
WO2007143063A2 PCT/US2007/012889 US2007012889W WO2007143063A2 WO 2007143063 A2 WO2007143063 A2 WO 2007143063A2 US 2007012889 W US2007012889 W US 2007012889W WO 2007143063 A2 WO2007143063 A2 WO 2007143063A2
Authority
WO
WIPO (PCT)
Prior art keywords
medical device
construct
implantable medical
helical
spiral coils
Prior art date
Application number
PCT/US2007/012889
Other languages
French (fr)
Other versions
WO2007143063A3 (en
Inventor
Klaus Kleine
David C. Gale
Fozan El-Nounou
Syed Faiyaz Ahmed Hossainy
Florian N. Ludwig
Original Assignee
Abbott Cardiovascular Systems Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Abbott Cardiovascular Systems Inc. filed Critical Abbott Cardiovascular Systems Inc.
Publication of WO2007143063A2 publication Critical patent/WO2007143063A2/en
Publication of WO2007143063A3 publication Critical patent/WO2007143063A3/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M31/00Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A61M31/002Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/88Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure the wire-like elements formed as helical or spiral coils
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/88Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure the wire-like elements formed as helical or spiral coils
    • A61F2/885Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure the wire-like elements formed as helical or spiral coils comprising a coil including a plurality of spiral or helical sections with alternate directions around a central axis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2250/00Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0014Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
    • A61F2250/0039Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis differing in diameter
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2250/00Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/0067Means for introducing or releasing pharmaceutical products into the body

Definitions

  • This invention is directed to a local drug delivery implant. More specifically, the invention is related to a spiral or coil drug delivery construct.
  • Stents are metallic or polymeric implantable structures that have been modified for local delivery of a drug.
  • a polymer dissolved in a solvent including a drug can be applied to the stent.
  • the solvent is removed, leaving behind a polymer coated stent capable of delivering a drug.
  • a disadvantage of using a stent includes the trauma caused to the lumen, such as a blood vessel, during implantation of the stent. Radial pressure applied by the stent can lead to inflammation and tissue damage, which can cause the onset of restenosis or amplify the degree of vascular smooth muscle cell proliferation and migration. Hyper-proliferation and migration of vascular smooth muscle cells caused by the application of radial pressure by a stent can mitigate the effects of local therapeutic substance application.
  • radial pressure applied by a stent can cause more sever damage than just inducement of restenosis.
  • vulnerable plaque develops within the arterial walls.
  • Vulnerable plaque can exist without the symptomatic characteristic of a substantially narrow arterial lumen.
  • the intrinsic histological features that may characterize a vulnerable plaque include increased lipid content, increased macrophage, foam cell and T lymphocyte content, and reduced collagen and smooth muscle cell content. This fibroatheroma type of vulnerable plaque is often referred to as "soft" collagen, whose reduced concentration combined with macrophage derived enzyme degradations cause the fibrous cap of these lesions to rupture under unpredictable circumstances.
  • ACS acute coronary syndrome
  • This type of atherosclerosis is coined “vulnerable” because of unpredictable tendency of the plaque to rupture. It is thought that hemodynamic and cardiac forces, which yield to circumferential stress, shear stress, and flexation stress, may cause disruption of fibroatheroma type of vulnerable plaque. These forces may arise as the result of simple movements, such as getting out of bed in the morning, in vivo forces related to blood flow and the beating of the heart, as well as radial force applied by a stent. Accordingly, it is desirable to treat conditions such as vulnerable plaque with adequate source of drug delivery without the drawbacks associated with a stent.
  • Vascular paving can be performed by loading a monomer, pre-polymer or polymer in a balloon catheter, and then applying the composition directly to the inside of a tissue lumen within a zone occluded by the catheter balloon.
  • the application can be through pores of the balloon, for example.
  • the process is followed by curing or polymerizing the applied composition.
  • the tissue surface may be an internal or external surface, and can include the interior of a tissue lumen or hollow space whether naturally occurring or occurring as a result of surgery, percutaneous techniques, trauma or disease.
  • the polymeric material can be reconfigured to form a coating or "paving" layer in intimate and conforming contact with the surface.
  • the resulting paving layer optionally can have a sealing function.
  • the coating preferably has a thickness on the tissue surface on the order of 0.001-1.0 mm; however, coatings having a thickness outside that range may be used as well.
  • Drawbacks associated with vascular paving include the downstream flow and waste of the paving material prior to the curing of the composition and difficult and cumbersome procedural steps for the surgeon including the necessity to occlude the vessel in which the procedure is performed and the curing or polymerization of the polymer to achieve conformal coating about the location where its benefit is most desired. In sum, vascular paving has been considered a difficult procedure which can certainly out weight its benefits.
  • Particle drug delivery includes release of particles having a drug at the treatment site. If the particles are delivered so as to be embedded within the treatment site, they can cause sever trauma to the vessel, which would present the same issues as a stent as described above. If the particles are simply delivered without being embedded within the lumen, the therapeutic effect of the particles can depend on their size. Too small of particles can simply wash away with blood flow, resulting in negligible therapeutic treatment at the desired site. Moreover, other areas of the body not in need of treatment will be exposed to the drug, which in effect would be equivalent to systemic delivery of the drug. If the particles are too large, they form an embolus, causing cell damage or death.
  • vascular conditions such as vulnerable plaque, a disease that is often seen in diabetics
  • a device which does not provide the above described drawbacks. It is also desirable to have a device which provides a sustained delivery of therapeutic agents to long or extended portions of coronary vessels or to a multitude of focal manifestations of a disease site.
  • the use of the implantable device of the present invention is certainly not limited to coronary vessels as it can have a multitude of applications in a variety of biological lumens and cavities.
  • an implantable medical device for the treatment of various disorders including vascular disorders.
  • the implant comprises a helical construct including a set of spiral coils for local in vivo application of a therapeutic substance in a biological lumen.
  • the construct is intended to conform against the lumen or cavity wall but to apply minimum force or pressure against the wall.
  • minimum force is defined as less force as applied by any commonly used balloon expandable or self-expandable stent or a stent-graft.
  • the construct is not intended to maintain patency of the vessel, but only to provide a means for delivery of a drug.
  • the helical construct is configured to apply less than 0.75 Bar of pressure to the biological lumen.
  • the construct can have a coil pitch from about 0.5 mm to about 10 mm.
  • the coil pitch can be constant or variable along the length of the device.
  • a proximal or distal segment of the helical construct can have a coil pitch that is different than a middle segment of the construct.
  • the helical construct has a coil contact angle of 0 to 80 degrees against the biological lumen. In some embodiments, it can be between 10 to 70 degrees.
  • the helical construct includes a first set and a second set of spiral coils such that the first set of spiral coils has a counter helical configuration or direction to the second set of spiral coils (i.e., opposing "helicity").
  • the first set of spiral coils can be connected to the second set of spiral coils by a V-shaped or U-shaped connector. They can also be connected by a polymeric connector.
  • the connector can be biodegradable.
  • the helical construct can be made from a polymeric material, a metallic material or a combination of polymers and/or metals.
  • the helical construct can be biodegradable.
  • the therapeutic substance can be mixed, embedded, or blended in the body of the construct or can be coated on the construct.
  • a method of treating a disorder such as a vascular disorder, comprises inserting or implanting the helical construct at a target location within a patient such as a mammalian or human subject.
  • the disorder can be vulnerable plaque or restenosis.
  • the device can be used in any body cavity, lumen or blood vessel, including the urethra, peripheral blood vessels, lower or upper gastric intestinal structures and the like.
  • Figure 1 illustrates a spiral or helical drug delivery construct according to one embodiment of the invention
  • Figure 2 is a schematic side elevation view of the construct of Figure 1 depicting coil pitch and coil contact angle;
  • Figure 3 illustrates a spiral or helical drug delivery construct according to another embodiment of the invention.
  • FIGS 4 and 5 illustrate various delivery techniques in accordance with embodiments of the invention.
  • Figure 1 illustrates a helical drug delivery construct 10 having a coil body 12 in a spiral configuration.
  • the construct 10 can include a drug or therapeutic substance, terms which can be used interchangeably, in the body of the construct itself or on a coating (not illustrated) deposited on a surface of the construct 10.
  • the construct 10 is intended to conform against a lumen or cavity wall but to apply minimum force or pressure against the wall. In some embodiments, minimum force is defined as less force as applied by a balloon expandable or self-expandable stent or a stent-graft used in the U.S. or European market. In some embodiments, the construct 10 is not intended to maintain patency of the vessel, but only to provide a means for drug delivery.
  • the force or pressure applied to the lumen wall during and post deployment is less than 0.75 Bar (10.88 psi or about 11 psi) as measured by the application of pressure by the total surface area of contact.
  • the pressure applied by spiral or helical construct 10 is less than 0.5 Bar (7.25 psi).
  • the applied pressure can be less than: 0.25 Bar.(3.62 psi), 0.2 Bar (2.9 psi), 0.1 Bar (1.45 psi), 0.05 Bar (0.725 psi), 0.01
  • spiral or helical construct 10 does not inflict trauma on the lumen wall which may cause inflammation and hyper-proliferation and migration of vascular smooth muscle cells.
  • spiral or helical construct 10 provides for a drug delivery means while minimizing the risk of causing plaque rupture.
  • an inwardly radial pressure of over 0.75 Bar can cause inward compression or collapse of the construct 10.
  • the radial pressure of greater than 0.5 Bar can cause radial collapse of the construct 10.
  • the radial pressure of great than 0.25, 0.2, 0.1, 0.05, 0.01, 0.001, or 0.0001 Bar can cause the collapse or inward compression of the construct 10.
  • construct 10 is soft, pliable, easily collapsible and compressible.
  • the overall length of the construct 10 can be from 10 mm to 300 mm. In some embodiments, it must be at least 40 mm. In some embodiments the length should not exceed 200 mm or alternatively 100 mm.
  • the inner diameter of the spiral or helical construct 10 can range from 1 mm to 50 mm — as measured in its natural state.
  • the cross-section of the coil 12 can be circular, oval, or in a "ribbon" form.
  • the coil pitch P, as illustrated in Figure 2, or the distance between individual coils 12 or helical turns of the coil 12 can be consistent throughout the body or variable, such as along a segment of the body.
  • the coil pitch P is measured at the construct's natural or "undisturbed” state, with no application of pressure or force so as to vary the length of the construct 10.
  • coil pitch P can be from 0.15 mm to 10 mm. In some embodiment, it can be from 1 mm to 5 mm.
  • pitch variation can be P 2 > Pi and/or P 2 > P 3 . It should be noted that proximal and distal segments include at least two coils, the remaining coils defining the middle segment.
  • Individual coils 12 can have a coil contact angle ⁇ with a lumen wall in a range from 0 degrees (coils being perpendicular to the lumen wall) to 80 degrees (coils being almost parallel to the lumen wall).
  • the contact angle can be 10 degrees to 70 degrees; 20 degrees to 60 degrees; and 30 degrees to 50 degrees.
  • axis x is normal to the issue wall and axis y is along the coil, as best illustrated by Figure 2.
  • helical construct 10 can include at least two coil segments 12a and 12b having opposing helical configuration. The two coil segments 12a and 12b can be joined by any means including a V- or U-shaped connector 14, a polymeric coupler or the like.
  • the coils and connector 14 can be made from a single, uniform piece or the connector can be a separate segment, joint to the coils by an adhesive or the like.
  • the connector can be biodegradable.
  • the coil segments 12a and 12b can have the same general shape including pitch and contact angle. In some embodiments, the pitch and contact angle of one segment 12a and be different that the other segment 12b. Moreover, each segment 12a and 12b can have its own individual pitch and contact angle pattern, such as a variable pitch pattern along a designated segment thereof.
  • Coil segments 12a and 12b can be made from the same material or different materials and can include the same drug or different drugs. In some embodiments, each can include a different amount of the same drug.
  • compressed coil segments 12a and 12b can "uncoil” in opposite directions in the lumen or cavity of the patient.
  • the "right- handed” and “left-handed” corkscrew configuration is advantageous in that each spiral coil segment 12a and 12b acts to counter-balance the rotation of the coil of the other. Less rotational motion can lead to reduction in trauma or injury to the vessel wall during deployment and a more controlled delivery of the implantable medical device.
  • the construct of the present invention can include three coil segments such that the middle coil segment has a different helical configuration or opposing rotation than the end coil segments. The lengths of the end coils segments can be less than the middle coil segment and provide for counter balance of the rotational expansion of the middle segment upon deployment.
  • the helical construct 10 can be made from a biodegradable polymer, biostable polymer, a metallic material or a combination of such material.
  • Biostable refers to polymers that are not biodegradable.
  • biodegradable, bioabsorbable, and bioerodable are used interchangeably and refer to materials that are capable of being completely degraded and/or eroded when exposed to bodily fluids such as blood and can be gradually resorbed, absorbed and/or eliminated by the body.
  • the processes of breaking down and absorption of the polymer can be caused by, for example, hydrolysis and metabolic processes.
  • the construct 10 can also be made from biodegradable metals (e.g., magnesium, iron, tungsten, or ferrous oxide), alone or in combination with other metals and polymers.
  • the construct 10 can be a combination of biodegradable metal(s) with biodegradable polymer(s).
  • the metal can form the core with a polymer shell enclosing the core.
  • the metal and the polymer can be blended or layered as well.
  • the metal can be distributed in particle form in the polymer.
  • the construct 10 can be made from a soft, flexible filament including monofilaments or braided string filaments.
  • the construct 10 can be a continuous wire or a wire having connections.
  • the construct 10 can be an extruded polymer tube.
  • the construct 10 can be fabricated as a polymer matrix loaded, embedded or blended with a drug or therapeutic agent.
  • the construct 10 may have drug- loaded micro- or nano-particles embedded within the body of the construct 10 or coated on the construct 10.
  • the particles may include metallic material such as alkaline earth metals (magnesium) or transition metals (gold) having a coating of the drug with or without a polymeric material.
  • the particles may be fullerenes including a drug, with or without metallic or polymeric components.
  • the particles can be ceramic or bioglass.
  • the particles can be micelles (e.g., polymer micelles), liposomes, polyliposo ⁇ es, polymerosomes, or membrane vesicles with a membrane that includes a polymerosomes, as is well understood by one of ordinary skill in the art.
  • the micro- or nano-particles are spherical or quasi-spherical formed of a polymer encapsulating the drug. When the device is in contact with body fluids, the polymer can swell and/or hydrolyze, thus releasing the drug.
  • the construct 10 may include a coating on its surface of a pure drug, such a heparin, or a drug with a polymeric carrier.
  • polymers that may be used to fabricate the construct 10 include, but are not limited to, poly(hydroxyvalerate), poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polyorthoester, polyanhydride, poly(glycolic acid), poly(glycolide), poly(L-lactic acid), poly(L-lactide), poly(D,L-lactic acid), poly(L-lactide-co-glycolide); poly(D,L-lactide), poly(caprolactone), poly(trimethylene carbonate), polyethylene amide, polyethylene acrylate, poly(glycolic acid-co-trimethylene carbonate), co-poly(ether-esters) (e.g.
  • PEO/PLA polyphosphazenes
  • biomolecules such as fibrin, fibrinogen, cellulose, starch, collagen and hyaluronic acid
  • polyurethanes silicones
  • polyesters polyolefins, polyisobutylene and ethylene-alphaolefin copolymers
  • acrylic polymers and copolymers other than polyacrylates vinyl halide polymers and copolymers (such as polyvinyl chloride), polyvinyl ethers (such as polyvinyl methyl ether), polyvinylidene halides (such as polyvinylidene chloride), polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics (such as polystyrene), polyvinyl esters (such as polyvinyl acetate), acrylonitrile-styrene copolymers, ABS resins, polyamides (such as Nylon 66 and polycaprolactam), polycarbonates, polyoxymethylenes, polyimides,
  • the drug or therapeutic agent includes agents that have anti-proliferative or antiinflammatory properties or can have other properties such as antineoplastic, antiplatelet, anti-coagulant, anti-fibrin, antithrombogenic, antimitotic, antibiotic, antiallergic, antifibrotic, and antioxidant.
  • the agents can be cystostatic agents, agents that promote the healing of the endothelium such as NO releasing or generating agents, agents that attract endothelial progenitor cells, agents that promote the attachment, migration or proliferation of endothelial cells (e.g., natriuretic peptides such as CNP, ANP or BNP peptide or an RGD or cRGD peptide), while impeding smooth muscle cell proliferation.
  • suitable therapeutic and prophylactic agents include synthetic inorganic and organic compounds, proteins and peptides, polysaccharides and other sugars, lipids, and DNA and RNA nucleic acid sequences having therapeutic, prophylactic or diagnostic activities.
  • bioactive agent include antibodies, receptor ligands, enzymes, adhesion peptides, blood clotting factors, inhibitors or clot dissolving agents such as streptokinase and tissue plasminogen activator, antigens for immunization, hormones and growth factors, oligonucleotides such as antisense oligonucleotides, small interfering RNA (siRNA), small hairpin RNA (shRNA), aptamers, ribozymes and retroviral vectors for use in gene therapy.
  • siRNA small interfering RNA
  • shRNA small hairpin RNA
  • aptamers ribozymes and retroviral vectors for use in gene therapy.
  • anti-proliferative agents examples include rapamycin and its functional or structural derivatives, 40-0-(2-hydroxy)ethyl-rapamycin (everolimus), and its functional or structural derivatives, paclitaxel and its functional and structural derivatives.
  • examples of rapamycin derivatives include 40-epi-(Nl-tetrazolyl)-rapamycin (ABT-578), 40-O-(3-hydroxy)propyl-rapamycin, 40-0-[2-(2-hydroxy)ethoxy]ethyl- rapamycin, and 40-0-tetrazole-rapamycin.
  • paclitaxel derivatives examples include docetaxel.
  • antineoplastics and/or antimitotics examples include methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride (e.g. Adriamycin ® from Pharmacia & Upjohn, Peapack NJ.), and mitomycin (e.g. Mutamycin ® from Bristol-Myers Squibb Co., Stamford, Conn.).
  • antiplatelets examples include sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein Ilb/IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, thrombin inhibitors such as Angiomax (Biogen, Inc., Cambridge, Mass.), calcium channel blockers (such as nifedipine), colchicine, fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand name Mevacor ® from Merck & Co., Inc
  • anti-inflammatory agents including steroidal and non-steroidal anti-inflammatory agents include tacrolimus, dexamethasone, clobetasol, mometasone, or combinations thereof.
  • cytostatic substances include angiopeptin, angiotensin converting enzyme inhibitors such as captopril (e.g. Capoten ® and Capozide ® from Bristol-Myers Squibb Co., Stamford, Conn.), cilazapril or lisinopril (e.g. Prinivil ® and Prinzide ® from Merck & Co., Inc., Whitehouse Station, NJ).
  • An example of an antiallergic agent is permirolast potassium.
  • Other therapeutic substances or agents which may be appropriate include alpha-interferon, pimecrolimus, imatinib mesylate, midostauri ⁇ , bioactive RGD, SIKVAV peptides, elevating agents such as cANP or cGMP peptides, and genetically engineered endothelial cells.
  • the foregoing substances can also be used in the form of prodrugs or co-drugs thereof.
  • the foregoing substances also include metabolites thereof and/or prodrugs of the metabolites.
  • the foregoing substances are listed by way of example and are not meant to be limiting. Other active agents which are currently available or that may be developed in the future are equally applicable.
  • Construct 10 can further include or be made from a biobeneficial material.
  • the biobeneficial material can be a polymeric material or non-polymeric material.
  • the biobeneficial material is preferably non-toxic, non-antigenic and non-immunogenic.
  • a biobeneficial material is one which enhances the biocompatibility of the device by being non-fouling, hemocompatible, actively non-thrombogenic, or anti-inflammatory, all without depending on the release of a pharmaceutically active agent.
  • Representative biobeneficial materials include, but are not limited to, polyethers such as poly(ethylene glycol), copoly(ether-esters) (e.g.
  • PEO/PLA polyalkylene oxides such as poly(ethylene oxide), poly(propylene oxide), poly(ether ester), polyalkylene oxalates, polyphosphazenes, phosphoryl choline, choline, poly(aspirin), polymers and co-polymers of hydroxyl bearing monomers such as hydroxyethyl methacrylate (HEMA), hydroxypropyl methacrylate (HPMA), hydroxypropylmethacrylamide, poly (ethylene glycol) acrylate (PEGA), PEG methacrylate, 2-methacryloyloxyethylphosphorylcholine (MPC) and n-vinyl pyrrolidone
  • HEMA hydroxyethyl methacrylate
  • HPMA hydroxypropyl methacrylate
  • MPC 2-methacryloyloxyethylphosphorylcholine
  • VP carboxylic acid bearing monomers such as methacrylic acid (MA), acrylic acid (AA), alkoxymethacrylate, alkoxyacrylate, and 3-trimethylsilylpropyl methacrylate (TMSPMA), poly(styrene-isop ⁇ ene-styrene)-PEG (SIS-PEG), polystyrene-PEG, polyisobutylene-PEG, polycaprolactone-PEG (PCL-PEG), PLA-PEG, poly(methyl methacrylate)-PEG (PMMA- PEG), polydimethylsiloxane-co-PEG (PDMS-PEG), poly(vinylidene fluoride)-PEG (PVDF-PEG), PLURONICTM surfactants (polypropylene oxide-co-polyethylene glycol), poly(tetramethylene glycol), hydroxy functional poly(vinyl pyrrolidone), biomolecules such as fibrin, fibrinogen, cellulose, starch
  • the construct 10 may be made from or to include shape memory polymers or metals. Most polymers exhibit some shape memory when deformed and stored at a temperature below T g . The best shape memory polymers have light cross- linking or crystalline domains that serve to fix the locations of the polymeric chains. After a polymer is deformed and kept at a temperature below T g , the polymer chains are in a non-equilibrium extended conformation. Upon heating above T g , the polymer chains have sufficient mobility to return to their desired lower-energy "coiled" conformation. The cross-links or crystalline domains serve to prevent the migration of portions of the polymer chains, and thus the gross structure is forced to return to its original shape.
  • Representative examples of a shape memory polymers include, but are not limited to, copolymers of poly(caprolactone) and poly(L-lactide-co-trimethylene carbonate).
  • a representative example of a shape memory metal includes Nitinol.
  • the construct 10 may also include a binder or a plasticizer for changing the properties of the device.
  • Plasticizers can be added, for example, to reduce crystallinity, lower the glass-transition temperature (T 8 ), or reduce the intermolecular forces between polymers.
  • the mechanical properties that are modified include, but are not limited to, Young's modulus, impact resistance (toughness), tensile strength, and tear strength. Impact resistance, or "toughness,” is a measure of energy absorbed during fracture of a polymer sample of standard dimensions and geometry when subjected to very rapid impact loading.
  • plasticizing agents include, but are not limited to, low molecular weight polymers (such as single-block polymers, multi-block copolymers, and other copolymers such as graft copolymers), oligomers (such as ethyl-terminated oligomers of lactic acid), small organic molecules, hydrogen bond forming organic compounds with and without hydroxyl groups, polyols (such as low molecular weight polyols having aliphatic hydroxyls), alkanols (such as butanols, pentanols and hexanols), sugar alcohols and anhydrides of sugar alcohols, polyethers (such as poly(alkylene glycols)), esters (such as citrates, phthalates, sebacates and adipates), polyesters, aliphatic acids, proteins (such as animal proteins and vegetable proteins), oils (such as, for example, the vegetable oils and animal oils), silicones, acetylated monoglycerides, amides, acet
  • Figure 4 depicts spiral construct 10 supported on a catheter assembly 16.
  • a retractable sheath 18 is being drawn back allowing the spiral construct 10 to self-expand for implantation (i.e., the construct is a self-expandable construct).
  • spiral construct 10 can be balloon expandable such that application of radial pressure causes the radial expansion of the coils 12.
  • Figure 5 is similar to Figurer 4 but depicts two spiral constructs 10 being delivered in tandem. Thus, many diseased areas can be treated with one procedure rather than many separate procedures. Navigation of such catheter systems, including use of guidewires, is well known in the art.
  • the spiral construct 10 may be crimped in a manner that segments of the coil 12 may overlap, particularly for the "ribbon" shaped coils so as to reduce the length of the delivered construct 10.
  • reduction of the length of the construct 10 for delivery may counterbalance flexibility that is required to navigate the device through tortuous paths.
  • the construct 10 of the present invention may be delivered with a viscous solution containing a biologically benign matrix and therapeutics for regional therapy of the target vessel.
  • a viscous solution containing a biologically benign matrix and therapeutics for regional therapy of the target vessel.
  • examples include, but are not limited to, hyaluronic acid or carboxymethyl cellulose, or PVP, suspended with PEA nano-particles containing everolimus.
  • This type of solution may act as a lubricant for smooth delivery of the device and may also start .biological therapy at the start of deployment.
  • the viscous solution may be placed on the devices, generally within the sheath or on the outside of the sheath.
  • the solution can also be applied or injected by the catheter. Application of compositions with catheters is well known in the art.
  • the viscous solution may contain an ampiphilic, surface active molecule to plasticize the device for both mechanical properties and therapeutic release modulation.
  • examples include PLURONIC and 2- methacryloyloxyethyl phosphorylcholine-co-lauryl methacrylate (MPC-co-LMA).
  • MPC-co-LMA 2- methacryloyloxyethyl phosphorylcholine-co-lauryl methacrylate
  • the viscous solution of this embodiment may be applied to devices made from shape memory polymers discussed previously.
  • the addition of the viscous solution to the delivery system may allow for increased conformation of the device to the vessel wall and an increase in biological therapy associated with the treatment needed at the site of deployment.
  • the viscous solution should have a viscosity of not less than 5 centipoise at room temperature, hi some embodiments, the viscosity is not less than 10 centipoise at room temperature.
  • the construct 10 of the present invention can be preferably used for the treatment of vascular conditions such as restenosis and vulnerable plaque.
  • the construct 12 is used for regional therapy which requires sustained delivery of drug or therapeutic agents to long portions of coronary vessels, or alternatively to a multitude of focal manifestations of a diseased condition.
  • Constructs or scaffoldings having other geometrical shapes can also be included within the scope of the present invention.
  • the construct can be made from a series of joined V or U shaped struts or elements that are rolled into a cylindrical configuration around the axis orthogonal to the plane of the Vs or Us. Tightly wound in this configuration, the construct can be delivered to the target site where it is deployed through unwinding.
  • THE scaffolding or construct can be made including hollow bodies such that a hydrogel and/or drug can be included in the hollow body. While particular embodiments of the present invention have been shown and described, it will be obvious to those skilled in the art that changes and modifications can be made without departing from this invention in its broader aspects.
  • absorptive material such as dyes can be doped into the construct 10 for allowing heat or UV modification of the mechanical properties of the construct 10. Accordingly, the claims are to encompass all such changes and modifications.

Abstract

An implantable medical device is disclosed having a helical construct including a set of spiral coils for local in vivo application of a therapeutic substance in a biological lumen. The helical construct is configured to apply less than 0.75 Bar of pressure to the biological lumen wall. The helical construct can have at least two sets of spiral coils having opposing helical directions. The device can be used for the treatment of vascular disorders such as restenosis and vulnerable plaque.

Description

DRUG DELIVERY SPIRAL COIL CONSTRUCT
FIELD
This invention is directed to a local drug delivery implant. More specifically, the invention is related to a spiral or coil drug delivery construct.
BACKGROUND
Various devices and methods have been proposed for local application of a therapeutic agent or drug such as stents, vascular paving, and particle delivery. Stents are metallic or polymeric implantable structures that have been modified for local delivery of a drug. A polymer dissolved in a solvent including a drug can be applied to the stent. The solvent is removed, leaving behind a polymer coated stent capable of delivering a drug. A disadvantage of using a stent includes the trauma caused to the lumen, such as a blood vessel, during implantation of the stent. Radial pressure applied by the stent can lead to inflammation and tissue damage, which can cause the onset of restenosis or amplify the degree of vascular smooth muscle cell proliferation and migration. Hyper-proliferation and migration of vascular smooth muscle cells caused by the application of radial pressure by a stent can mitigate the effects of local therapeutic substance application.
For some applications such as vulnerable plaque, radial pressure applied by a stent can cause more sever damage than just inducement of restenosis. Unlike occlusive plaques that impede blood flow, vulnerable plaque develops within the arterial walls. Vulnerable plaque can exist without the symptomatic characteristic of a substantially narrow arterial lumen. The intrinsic histological features that may characterize a vulnerable plaque include increased lipid content, increased macrophage, foam cell and T lymphocyte content, and reduced collagen and smooth muscle cell content. This fibroatheroma type of vulnerable plaque is often referred to as "soft" collagen, whose reduced concentration combined with macrophage derived enzyme degradations cause the fibrous cap of these lesions to rupture under unpredictable circumstances. When ruptured, the lipid core contents, thought to include tissue factor, contact the arterial bloodstream, causing a blood clot to form that can completely block the artery resulting in acute coronary syndrome (ACS). This type of atherosclerosis is coined "vulnerable" because of unpredictable tendency of the plaque to rupture. It is thought that hemodynamic and cardiac forces, which yield to circumferential stress, shear stress, and flexation stress, may cause disruption of fibroatheroma type of vulnerable plaque. These forces may arise as the result of simple movements, such as getting out of bed in the morning, in vivo forces related to blood flow and the beating of the heart, as well as radial force applied by a stent. Accordingly, it is desirable to treat conditions such as vulnerable plaque with adequate source of drug delivery without the drawbacks associated with a stent.
Vascular paving can be performed by loading a monomer, pre-polymer or polymer in a balloon catheter, and then applying the composition directly to the inside of a tissue lumen within a zone occluded by the catheter balloon. The application can be through pores of the balloon, for example. The process is followed by curing or polymerizing the applied composition. The tissue surface may be an internal or external surface, and can include the interior of a tissue lumen or hollow space whether naturally occurring or occurring as a result of surgery, percutaneous techniques, trauma or disease. The polymeric material can be reconfigured to form a coating or "paving" layer in intimate and conforming contact with the surface. The resulting paving layer optionally can have a sealing function. The coating preferably has a thickness on the tissue surface on the order of 0.001-1.0 mm; however, coatings having a thickness outside that range may be used as well. By appropriate selection of the material employed and of the configuration of the paving material, the process can be tailored to satisfy a wide variety of biological or clinical situations. Drawbacks associated with vascular paving include the downstream flow and waste of the paving material prior to the curing of the composition and difficult and cumbersome procedural steps for the surgeon including the necessity to occlude the vessel in which the procedure is performed and the curing or polymerization of the polymer to achieve conformal coating about the location where its benefit is most desired. In sum, vascular paving has been considered a difficult procedure which can certainly out weight its benefits.
Particle drug delivery includes release of particles having a drug at the treatment site. If the particles are delivered so as to be embedded within the treatment site, they can cause sever trauma to the vessel, which would present the same issues as a stent as described above. If the particles are simply delivered without being embedded within the lumen, the therapeutic effect of the particles can depend on their size. Too small of particles can simply wash away with blood flow, resulting in negligible therapeutic treatment at the desired site. Moreover, other areas of the body not in need of treatment will be exposed to the drug, which in effect would be equivalent to systemic delivery of the drug. If the particles are too large, they form an embolus, causing cell damage or death.
It is desirable to address and treat vascular conditions, such as vulnerable plaque, a disease that is often seen in diabetics, with a use of a device that does not provide the above described drawbacks. It is also desirable to have a device which provides a sustained delivery of therapeutic agents to long or extended portions of coronary vessels or to a multitude of focal manifestations of a disease site. The use of the implantable device of the present invention, as can be appreciated by one having ordinary skill in the art, is certainly not limited to coronary vessels as it can have a multitude of applications in a variety of biological lumens and cavities.
SUMMARY In accordance with one aspect of the present invention, an implantable medical device is provided for the treatment of various disorders including vascular disorders. The implant comprises a helical construct including a set of spiral coils for local in vivo application of a therapeutic substance in a biological lumen. The construct is intended to conform against the lumen or cavity wall but to apply minimum force or pressure against the wall. In some embodiments, minimum force is defined as less force as applied by any commonly used balloon expandable or self-expandable stent or a stent-graft. In some embodiments, the construct is not intended to maintain patency of the vessel, but only to provide a means for delivery of a drug. In some embodiment, the helical construct is configured to apply less than 0.75 Bar of pressure to the biological lumen. In some embodiments, the construct can have a coil pitch from about 0.5 mm to about 10 mm. The coil pitch can be constant or variable along the length of the device. In some embodiments, a proximal or distal segment of the helical construct can have a coil pitch that is different than a middle segment of the construct. In some embodiments, the helical construct has a coil contact angle of 0 to 80 degrees against the biological lumen. In some embodiments, it can be between 10 to 70 degrees.
In some embodiments, the helical construct includes a first set and a second set of spiral coils such that the first set of spiral coils has a counter helical configuration or direction to the second set of spiral coils (i.e., opposing "helicity"). The first set of spiral coils can be connected to the second set of spiral coils by a V-shaped or U-shaped connector. They can also be connected by a polymeric connector. The connector can be biodegradable.
The helical construct can be made from a polymeric material, a metallic material or a combination of polymers and/or metals. The helical construct can be biodegradable. The therapeutic substance can be mixed, embedded, or blended in the body of the construct or can be coated on the construct.
In accordance with another aspect, a method of treating a disorder, such as a vascular disorder, is provided. The method comprises inserting or implanting the helical construct at a target location within a patient such as a mammalian or human subject. The disorder can be vulnerable plaque or restenosis. The device can be used in any body cavity, lumen or blood vessel, including the urethra, peripheral blood vessels, lower or upper gastric intestinal structures and the like.
BRIEF DESCRIPTION Figure 1 illustrates a spiral or helical drug delivery construct according to one embodiment of the invention;
Figure 2 is a schematic side elevation view of the construct of Figure 1 depicting coil pitch and coil contact angle;
Figure 3 illustrates a spiral or helical drug delivery construct according to another embodiment of the invention; and
Figures 4 and 5 illustrate various delivery techniques in accordance with embodiments of the invention. DETAILED DESCRIPTION
Figure 1 illustrates a helical drug delivery construct 10 having a coil body 12 in a spiral configuration. The construct 10 can include a drug or therapeutic substance, terms which can be used interchangeably, in the body of the construct itself or on a coating (not illustrated) deposited on a surface of the construct 10. The construct 10 is intended to conform against a lumen or cavity wall but to apply minimum force or pressure against the wall. In some embodiments, minimum force is defined as less force as applied by a balloon expandable or self-expandable stent or a stent-graft used in the U.S. or European market. In some embodiments, the construct 10 is not intended to maintain patency of the vessel, but only to provide a means for drug delivery. In one embodiment, the force or pressure applied to the lumen wall during and post deployment is less than 0.75 Bar (10.88 psi or about 11 psi) as measured by the application of pressure by the total surface area of contact. In one preferred embodiment, the pressure applied by spiral or helical construct 10 is less than 0.5 Bar (7.25 psi). In some embodiments, the applied pressure can be less than: 0.25 Bar.(3.62 psi), 0.2 Bar (2.9 psi), 0.1 Bar (1.45 psi), 0.05 Bar (0.725 psi), 0.01
Bar (0.145 psi), 0.001 Bar (0.014 psi), or 0.0001 Bar (0.00145 psi). In some embodiments, it has to be at least slightly above 0 Bar so that the spiral or helical coil structure is at least maintained in the exact vicinity or general vicinity of implantation such that there is little to no post-movement of the construct 10 subsequent to the retraction of the catheter which delivers the construct 10. Accordingly, spiral or helical construct 10 does not inflict trauma on the lumen wall which may cause inflammation and hyper-proliferation and migration of vascular smooth muscle cells. Moreover, for vulnerable plaque application, spiral or helical construct 10 provides for a drug delivery means while minimizing the risk of causing plaque rupture. In some embodiments application of an inwardly radial pressure of over 0.75 Bar can cause inward compression or collapse of the construct 10. In some embodiments, the radial pressure of greater than 0.5 Bar can cause radial collapse of the construct 10. Yet in some embodiments the radial pressure of great than 0.25, 0.2, 0.1, 0.05, 0.01, 0.001, or 0.0001 Bar can cause the collapse or inward compression of the construct 10. As indicative of these forces, construct 10 is soft, pliable, easily collapsible and compressible. The overall length of the construct 10 can be from 10 mm to 300 mm. In some embodiments, it must be at least 40 mm. In some embodiments the length should not exceed 200 mm or alternatively 100 mm. This extended length provides an elongated source of drug delivery with a flexible and conformal platform that allows for navigation through tortuous vascular structure which otherwise would be unachievable with the use of common stents. The inner diameter of the spiral or helical construct 10 can range from 1 mm to 50 mm — as measured in its natural state. The cross-section of the coil 12 can be circular, oval, or in a "ribbon" form. The coil pitch P, as illustrated in Figure 2, or the distance between individual coils 12 or helical turns of the coil 12 can be consistent throughout the body or variable, such as along a segment of the body. The coil pitch P is measured at the construct's natural or "undisturbed" state, with no application of pressure or force so as to vary the length of the construct 10. Variability in the coil pitch can allow for areas where a greater amount or concentration of drug is released. In some embodiments, coil pitch P can be from 0.15 mm to 10 mm. In some embodiment, it can be from 1 mm to 5 mm. In some embodiments helical construct 10 can have pitches Pi, P2 and P3 at the proximal, middle and distal segments thereof such that: Pi = P3; Pi > P2; Pi > P3; P3 > Pi; and/or P3 > P2. In some embodiments, pitch variation can be P2 > Pi and/or P2 > P3. It should be noted that proximal and distal segments include at least two coils, the remaining coils defining the middle segment.
Individual coils 12 can have a coil contact angle Φ with a lumen wall in a range from 0 degrees (coils being perpendicular to the lumen wall) to 80 degrees (coils being almost parallel to the lumen wall). In some embodiments, the contact angle can be 10 degrees to 70 degrees; 20 degrees to 60 degrees; and 30 degrees to 50 degrees. It should be noted that axis x is normal to the issue wall and axis y is along the coil, as best illustrated by Figure 2. In one embodiment, as illustrated by Figure 3, helical construct 10 can include at least two coil segments 12a and 12b having opposing helical configuration. The two coil segments 12a and 12b can be joined by any means including a V- or U-shaped connector 14, a polymeric coupler or the like. The coils and connector 14 can be made from a single, uniform piece or the connector can be a separate segment, joint to the coils by an adhesive or the like. The connector can be biodegradable. The coil segments 12a and 12b can have the same general shape including pitch and contact angle. In some embodiments, the pitch and contact angle of one segment 12a and be different that the other segment 12b. Moreover, each segment 12a and 12b can have its own individual pitch and contact angle pattern, such as a variable pitch pattern along a designated segment thereof. Coil segments 12a and 12b can be made from the same material or different materials and can include the same drug or different drugs. In some embodiments, each can include a different amount of the same drug. Upon deployment, compressed coil segments 12a and 12b can "uncoil" in opposite directions in the lumen or cavity of the patient. The "right- handed" and "left-handed" corkscrew configuration is advantageous in that each spiral coil segment 12a and 12b acts to counter-balance the rotation of the coil of the other. Less rotational motion can lead to reduction in trauma or injury to the vessel wall during deployment and a more controlled delivery of the implantable medical device. It should also be appreciated that the construct of the present invention can include three coil segments such that the middle coil segment has a different helical configuration or opposing rotation than the end coil segments. The lengths of the end coils segments can be less than the middle coil segment and provide for counter balance of the rotational expansion of the middle segment upon deployment.
The helical construct 10 can be made from a biodegradable polymer, biostable polymer, a metallic material or a combination of such material. Biostable refers to polymers that are not biodegradable. The terms biodegradable, bioabsorbable, and bioerodable are used interchangeably and refer to materials that are capable of being completely degraded and/or eroded when exposed to bodily fluids such as blood and can be gradually resorbed, absorbed and/or eliminated by the body. The processes of breaking down and absorption of the polymer can be caused by, for example, hydrolysis and metabolic processes. The construct 10 can also be made from biodegradable metals (e.g., magnesium, iron, tungsten, or ferrous oxide), alone or in combination with other metals and polymers. In one embodiment, the construct 10 can be a combination of biodegradable metal(s) with biodegradable polymer(s). The metal can form the core with a polymer shell enclosing the core. The metal and the polymer can be blended or layered as well. The metal can be distributed in particle form in the polymer.
The construct 10 can be made from a soft, flexible filament including monofilaments or braided string filaments. The construct 10 can be a continuous wire or a wire having connections. The construct 10 can be an extruded polymer tube. In some embodiment, the construct 10 can be fabricated as a polymer matrix loaded, embedded or blended with a drug or therapeutic agent. The construct 10 may have drug- loaded micro- or nano-particles embedded within the body of the construct 10 or coated on the construct 10. The particles may include metallic material such as alkaline earth metals (magnesium) or transition metals (gold) having a coating of the drug with or without a polymeric material. In some embodiments the particles may be fullerenes including a drug, with or without metallic or polymeric components. In some embodiments, the particles can be ceramic or bioglass. The particles can be micelles (e.g., polymer micelles), liposomes, polyliposoπαes, polymerosomes, or membrane vesicles with a membrane that includes a polymerosomes, as is well understood by one of ordinary skill in the art. In one embodiment, the micro- or nano-particles are spherical or quasi-spherical formed of a polymer encapsulating the drug. When the device is in contact with body fluids, the polymer can swell and/or hydrolyze, thus releasing the drug.
The construct 10 may include a coating on its surface of a pure drug, such a heparin, or a drug with a polymeric carrier.
Representative examples of polymers that may be used to fabricate the construct 10 include, but are not limited to, poly(hydroxyvalerate), poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polyorthoester, polyanhydride, poly(glycolic acid), poly(glycolide), poly(L-lactic acid), poly(L-lactide), poly(D,L-lactic acid), poly(L-lactide-co-glycolide); poly(D,L-lactide), poly(caprolactone), poly(trimethylene carbonate), polyethylene amide, polyethylene acrylate, poly(glycolic acid-co-trimethylene carbonate), co-poly(ether-esters) (e.g. PEO/PLA), polyphosphazenes, biomolecules (such as fibrin, fibrinogen, cellulose, starch, collagen and hyaluronic acid), polyurethanes, silicones, polyesters, polyolefins, polyisobutylene and ethylene-alphaolefin copolymers, acrylic polymers and copolymers other than polyacrylates, vinyl halide polymers and copolymers (such as polyvinyl chloride), polyvinyl ethers (such as polyvinyl methyl ether), polyvinylidene halides (such as polyvinylidene chloride), polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics (such as polystyrene), polyvinyl esters (such as polyvinyl acetate), acrylonitrile-styrene copolymers, ABS resins, polyamides (such as Nylon 66 and polycaprolactam), polycarbonates, polyoxymethylenes, polyimides, polyethers, polyurethanes, rayon, rayon-triacetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, and carboxymethyl cellulose.
The drug or therapeutic agent includes agents that have anti-proliferative or antiinflammatory properties or can have other properties such as antineoplastic, antiplatelet, anti-coagulant, anti-fibrin, antithrombogenic, antimitotic, antibiotic, antiallergic, antifibrotic, and antioxidant. The agents can be cystostatic agents, agents that promote the healing of the endothelium such as NO releasing or generating agents, agents that attract endothelial progenitor cells, agents that promote the attachment, migration or proliferation of endothelial cells (e.g., natriuretic peptides such as CNP, ANP or BNP peptide or an RGD or cRGD peptide), while impeding smooth muscle cell proliferation. Examples of suitable therapeutic and prophylactic agents include synthetic inorganic and organic compounds, proteins and peptides, polysaccharides and other sugars, lipids, and DNA and RNA nucleic acid sequences having therapeutic, prophylactic or diagnostic activities. Some other examples of the bioactive agent include antibodies, receptor ligands, enzymes, adhesion peptides, blood clotting factors, inhibitors or clot dissolving agents such as streptokinase and tissue plasminogen activator, antigens for immunization, hormones and growth factors, oligonucleotides such as antisense oligonucleotides, small interfering RNA (siRNA), small hairpin RNA (shRNA), aptamers, ribozymes and retroviral vectors for use in gene therapy. Examples of anti-proliferative agents include rapamycin and its functional or structural derivatives, 40-0-(2-hydroxy)ethyl-rapamycin (everolimus), and its functional or structural derivatives, paclitaxel and its functional and structural derivatives. Examples of rapamycin derivatives include 40-epi-(Nl-tetrazolyl)-rapamycin (ABT-578), 40-O-(3-hydroxy)propyl-rapamycin, 40-0-[2-(2-hydroxy)ethoxy]ethyl- rapamycin, and 40-0-tetrazole-rapamycin. Examples of paclitaxel derivatives include docetaxel. Examples of antineoplastics and/or antimitotics include methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride (e.g. Adriamycin® from Pharmacia & Upjohn, Peapack NJ.), and mitomycin (e.g. Mutamycin® from Bristol-Myers Squibb Co., Stamford, Conn.). Examples of such antiplatelets, anticoagulants, antifibrin, and antithrombins include sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein Ilb/IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, thrombin inhibitors such as Angiomax (Biogen, Inc., Cambridge, Mass.), calcium channel blockers (such as nifedipine), colchicine, fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand name Mevacor® from Merck & Co., Inc., Whitehouse Station, NJ), monoclonal antibodies (such as those specific for Platelet-Derived Growth Factor (PDGF) receptors), nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitors, suramin, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), nitric oxide or nitric oxide donors, super oxide dismutases, super oxide dismutase mimetic, 4-amino- 2,2,6,6-tetramethylpiperidine-l-oxyl (4-amino-TEMPO), estradiol, anticancer agents, dietary supplements such as various vitamins, and a combination thereof. Examples of anti-inflammatory agents including steroidal and non-steroidal anti-inflammatory agents include tacrolimus, dexamethasone, clobetasol, mometasone, or combinations thereof. Examples of cytostatic substances include angiopeptin, angiotensin converting enzyme inhibitors such as captopril (e.g. Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.), cilazapril or lisinopril (e.g. Prinivil® and Prinzide® from Merck & Co., Inc., Whitehouse Station, NJ). An example of an antiallergic agent is permirolast potassium. Other therapeutic substances or agents which may be appropriate include alpha-interferon, pimecrolimus, imatinib mesylate, midostauriπ, bioactive RGD, SIKVAV peptides, elevating agents such as cANP or cGMP peptides, and genetically engineered endothelial cells. The foregoing substances can also be used in the form of prodrugs or co-drugs thereof. The foregoing substances also include metabolites thereof and/or prodrugs of the metabolites. The foregoing substances are listed by way of example and are not meant to be limiting. Other active agents which are currently available or that may be developed in the future are equally applicable.
Construct 10 can further include or be made from a biobeneficial material. The biobeneficial material can be a polymeric material or non-polymeric material. The biobeneficial material is preferably non-toxic, non-antigenic and non-immunogenic. A biobeneficial material is one which enhances the biocompatibility of the device by being non-fouling, hemocompatible, actively non-thrombogenic, or anti-inflammatory, all without depending on the release of a pharmaceutically active agent. Representative biobeneficial materials include, but are not limited to, polyethers such as poly(ethylene glycol), copoly(ether-esters) (e.g. PEO/PLA), polyalkylene oxides such as poly(ethylene oxide), poly(propylene oxide), poly(ether ester), polyalkylene oxalates, polyphosphazenes, phosphoryl choline, choline, poly(aspirin), polymers and co-polymers of hydroxyl bearing monomers such as hydroxyethyl methacrylate (HEMA), hydroxypropyl methacrylate (HPMA), hydroxypropylmethacrylamide, poly (ethylene glycol) acrylate (PEGA), PEG methacrylate, 2-methacryloyloxyethylphosphorylcholine (MPC) and n-vinyl pyrrolidone
(VP), carboxylic acid bearing monomers such as methacrylic acid (MA), acrylic acid (AA), alkoxymethacrylate, alkoxyacrylate, and 3-trimethylsilylpropyl methacrylate (TMSPMA), poly(styrene-isopτene-styrene)-PEG (SIS-PEG), polystyrene-PEG, polyisobutylene-PEG, polycaprolactone-PEG (PCL-PEG), PLA-PEG, poly(methyl methacrylate)-PEG (PMMA- PEG), polydimethylsiloxane-co-PEG (PDMS-PEG), poly(vinylidene fluoride)-PEG (PVDF-PEG), PLURONIC™ surfactants (polypropylene oxide-co-polyethylene glycol), poly(tetramethylene glycol), hydroxy functional poly(vinyl pyrrolidone), biomolecules such as fibrin, fibrinogen, cellulose, starch, collagen, dextran, dextrin, hyaluronic acid, fragments and derivatives of hyaluronic acid, heparin, fragments and derivatives of heparin, glycosamino glycan (GAG), GAG derivatives, polysaccharide, elastin, chitosan, alginate, silicones, PolyActive™, and combinations thereof.
In some embodiments, the construct 10 may be made from or to include shape memory polymers or metals. Most polymers exhibit some shape memory when deformed and stored at a temperature below Tg. The best shape memory polymers have light cross- linking or crystalline domains that serve to fix the locations of the polymeric chains. After a polymer is deformed and kept at a temperature below Tg, the polymer chains are in a non-equilibrium extended conformation. Upon heating above Tg, the polymer chains have sufficient mobility to return to their desired lower-energy "coiled" conformation. The cross-links or crystalline domains serve to prevent the migration of portions of the polymer chains, and thus the gross structure is forced to return to its original shape. Representative examples of a shape memory polymers include, but are not limited to, copolymers of poly(caprolactone) and poly(L-lactide-co-trimethylene carbonate). A representative example of a shape memory metal includes Nitinol.
The construct 10 may also include a binder or a plasticizer for changing the properties of the device. Plasticizers can be added, for example, to reduce crystallinity, lower the glass-transition temperature (T8), or reduce the intermolecular forces between polymers. The mechanical properties that are modified include, but are not limited to, Young's modulus, impact resistance (toughness), tensile strength, and tear strength. Impact resistance, or "toughness," is a measure of energy absorbed during fracture of a polymer sample of standard dimensions and geometry when subjected to very rapid impact loading.
Examples of plasticizing agents include, but are not limited to, low molecular weight polymers (such as single-block polymers, multi-block copolymers, and other copolymers such as graft copolymers), oligomers (such as ethyl-terminated oligomers of lactic acid), small organic molecules, hydrogen bond forming organic compounds with and without hydroxyl groups, polyols (such as low molecular weight polyols having aliphatic hydroxyls), alkanols (such as butanols, pentanols and hexanols), sugar alcohols and anhydrides of sugar alcohols, polyethers (such as poly(alkylene glycols)), esters (such as citrates, phthalates, sebacates and adipates), polyesters, aliphatic acids, proteins (such as animal proteins and vegetable proteins), oils (such as, for example, the vegetable oils and animal oils), silicones, acetylated monoglycerides, amides, acetamides, sulfoxides, sulfones, pyrrolidones oxa acids, diglycolic acids, and any analogs, derivatives, copolymers and combinations of the foregoing. Figure 4 depicts spiral construct 10 supported on a catheter assembly 16. A retractable sheath 18 is being drawn back allowing the spiral construct 10 to self-expand for implantation (i.e., the construct is a self-expandable construct). In some embodiment, spiral construct 10 can be balloon expandable such that application of radial pressure causes the radial expansion of the coils 12. Figure 5 is similar to Figurer 4 but depicts two spiral constructs 10 being delivered in tandem. Thus, many diseased areas can be treated with one procedure rather than many separate procedures. Navigation of such catheter systems, including use of guidewires, is well known in the art. The spiral construct 10 may be crimped in a manner that segments of the coil 12 may overlap, particularly for the "ribbon" shaped coils so as to reduce the length of the delivered construct 10. However, reduction of the length of the construct 10 for delivery may counterbalance flexibility that is required to navigate the device through tortuous paths.
The construct 10 of the present invention may be delivered with a viscous solution containing a biologically benign matrix and therapeutics for regional therapy of the target vessel. Examples include, but are not limited to, hyaluronic acid or carboxymethyl cellulose, or PVP, suspended with PEA nano-particles containing everolimus. This type of solution may act as a lubricant for smooth delivery of the device and may also start .biological therapy at the start of deployment. The viscous solution may be placed on the devices, generally within the sheath or on the outside of the sheath. The solution can also be applied or injected by the catheter. Application of compositions with catheters is well known in the art.
In some embodiments, the viscous solution, as mentioned above, may contain an ampiphilic, surface active molecule to plasticize the device for both mechanical properties and therapeutic release modulation. Examples include PLURONIC and 2- methacryloyloxyethyl phosphorylcholine-co-lauryl methacrylate (MPC-co-LMA). The plasticizer can suppress the Tg to make the polymer or polymeric matrix pliable and flexible. The viscous solution of this embodiment may be applied to devices made from shape memory polymers discussed previously. The addition of the viscous solution to the delivery system may allow for increased conformation of the device to the vessel wall and an increase in biological therapy associated with the treatment needed at the site of deployment. In some embodiment, the viscous solution should have a viscosity of not less than 5 centipoise at room temperature, hi some embodiments, the viscosity is not less than 10 centipoise at room temperature.
The construct 10 of the present invention can be preferably used for the treatment of vascular conditions such as restenosis and vulnerable plaque. In some embodiment, the construct 12 is used for regional therapy which requires sustained delivery of drug or therapeutic agents to long portions of coronary vessels, or alternatively to a multitude of focal manifestations of a diseased condition.
Constructs or scaffoldings having other geometrical shapes can also be included within the scope of the present invention. For example, the construct can be made from a series of joined V or U shaped struts or elements that are rolled into a cylindrical configuration around the axis orthogonal to the plane of the Vs or Us. Tightly wound in this configuration, the construct can be delivered to the target site where it is deployed through unwinding. Additionally, THE scaffolding or construct can be made including hollow bodies such that a hydrogel and/or drug can be included in the hollow body. While particular embodiments of the present invention have been shown and described, it will be obvious to those skilled in the art that changes and modifications can be made without departing from this invention in its broader aspects. For example, absorptive material such as dyes can be doped into the construct 10 for allowing heat or UV modification of the mechanical properties of the construct 10. Accordingly, the claims are to encompass all such changes and modifications.

Claims

CLAIMSWhat is claimed is:
1. An implantable medical device, comprising: a helical construct including a set of spiral coils for local in vivo application of a therapeutic substance in a biological lumen, wherein the helical construct is configured to apply less than 0.75 Bar of pressure to a wall of the biological lumen.
2. The implantable medical device of claim 1 wherein the pressure is less than 0.5 Bar.
3. The implantable medical device of claim 1 wherein the pressure is less than 0.25 Bar.
4. The implantable medical device of claim 1 wherein the pressure is less than 0.2 Bar.
5. The implantable medical device of claim 1 wherein the pressure is less than 0.1 Bar.
6. The implantable medical device of claim 1 wherein a coil pitch of the helical construct is from about 0.15 mm to about 10 mm.
7. The implantable medical device of claim 1 wherein the helical construct has a variable coil pitch.
8. The implantable medical device of claim 1 wherein the helical construct comprises a proximal segment, a distal segment, and a middle segment there between, and wherein a coil pitch of the proximal segment is different than a coil pitch of the middle segment and/or a coil pitch of the distal segment is different than a coil pitch of the middle segment.
9. The implantable medical device of claim 1 wherein the helical construct has a coil contact angle of 0 to 80 degrees against the wall of the biological lumen.
10. The implantable medical device of claim 1 wherein the helical construct has a coil contact angle of 10 to 70 degrees against the wall the biological lumen.
11. The implantable medical device of claim 1 wherein the helical construct includes a first set and a second set of spiral coils such that the first set of spiral coils has a counter helical configuration than the second set of spiral coils.
12. The implantable medical device of claim 11 wherein the first set of spiral coils is connected to the second set of spiral coils by a V-shaped or U-shaped connector.
13. The implantable medical device of claim 11 wherein the first set of spiral coils is connected to the second set of spiral coils witli a polymeric connector.
14. The implantable medical device of claim 1 wherein the first set of spiral coils is connected to the second set of spiral coils with a biodegradable connector.
15. The implantable medical device of claim 1 wherein the helical construct is made from a polymeric material.
16. The implantable medical device of claim 1 wherein the helical construct is made from a biodegradable polymeric material.
17. The implantable medical device of claim 1 wherein the helical construct is made from a biodegradable polymeric material and a bioerodable metallic material.
18. The implantable medical device of claim 1 wherein a therapeutic substance is embedded within or coated on the helical construct.
19. The implantable medical device of claim 1 wherein the length of the helical construct is at least 40 mm.
20. The implantable medical device of claim 1 wherein the helical construct is self- expandable.
21. A method of treating a vascular disorder comprising implanting the device of claim 1 in a human patient.
22. The method of claim 21 wherein the disorder is vulnerable plaque.
23. The method of claim 21 wherein the disorder is restenosis.
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9173973B2 (en) 2006-07-20 2015-11-03 G. Lawrence Thatcher Bioabsorbable polymeric composition for a medical device
US9211205B2 (en) 2006-10-20 2015-12-15 Orbusneich Medical, Inc. Bioabsorbable medical device with coating
US10596330B2 (en) 2015-08-26 2020-03-24 Medtronic Xomed, Inc. Resorbable, drug-eluting submucosal turbinate implant device and method

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1793744B1 (en) 2004-09-22 2008-12-17 Dendron GmbH Medical implant
CA2626717C (en) * 2005-12-30 2014-10-21 C.R. Bard Inc. Stent with bio-resorbable connector and methods
KR20100015521A (en) 2007-03-13 2010-02-12 마이크로 테라퓨틱스 인코포레이티드 An implant, a mandrel, and a method of forming an implant
CN102164565B (en) * 2008-08-19 2014-07-23 帝秀简公司 Self-expanding medical device
WO2013039829A1 (en) * 2011-09-13 2013-03-21 Stryker Corporation Vaso-occlusive device
US9011480B2 (en) 2012-01-20 2015-04-21 Covidien Lp Aneurysm treatment coils
US9687245B2 (en) 2012-03-23 2017-06-27 Covidien Lp Occlusive devices and methods of use
US9211374B2 (en) * 2012-05-25 2015-12-15 Robert F. Wallace Therapeutic implantable device
US9277983B2 (en) 2013-03-13 2016-03-08 Abbott Cardiovascular Systems Inc. Drug delivery device for peripheral artery disease
US10092735B2 (en) 2013-10-09 2018-10-09 Matthew Q. Shaw Therapeutic delivery device
US9713475B2 (en) 2014-04-18 2017-07-25 Covidien Lp Embolic medical devices
WO2016176509A1 (en) 2015-04-28 2016-11-03 University Of Washington Ferromagnetic shaped memory alloy nano-actuator and method of use
WO2017015571A1 (en) 2015-07-23 2017-01-26 Novaflux, Inc. Implants and constructs including hollow fibers
US10232154B2 (en) 2015-07-28 2019-03-19 Boston Scientific Scimed, Inc. Implantable medical devices and related methods of use
WO2023220251A2 (en) * 2022-05-12 2023-11-16 Celanese Eva Performance Polymers Llc Implantable medical device for the delivery of an antipsychotic

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3892238A (en) * 1971-09-16 1975-07-01 Abbott Lab Drug supporting anchor
EP0388234A1 (en) * 1989-03-17 1990-09-19 Carter Holt Harvey Plastic Products Group Limited A drug administering device for insertion in a body cavity of an animal
WO2000018331A2 (en) * 1998-09-29 2000-04-06 C. R. Bard, Inc. Drug delivery systems
WO2002049544A1 (en) * 2000-12-19 2002-06-27 Vascular Architects, Inc. Biologically active agent delivery apparatus and method
US20030028245A1 (en) * 2000-06-30 2003-02-06 Vascular Architects, Inc. Function-enhanced thrombolytic AV fistula and method
WO2005079387A2 (en) * 2004-02-13 2005-09-01 Conor Medsystems, Inc. Implantable drug delivery device including wire filaments
US20050228473A1 (en) * 2004-04-05 2005-10-13 David Brown Device and method for delivering a treatment to an artery

Family Cites Families (339)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US669592A (en) * 1898-05-13 1901-03-12 Purl C Plasterer Fountain-penholder.
FR732895A (en) 1932-10-18 1932-09-25 Consortium Elektrochem Ind Articles spun in polyvinyl alcohol
US2386454A (en) 1940-11-22 1945-10-09 Bell Telephone Labor Inc High molecular weight linear polyester-amides
US3849514A (en) 1967-11-17 1974-11-19 Eastman Kodak Co Block polyester-polyamide copolymers
US3773737A (en) 1971-06-09 1973-11-20 Sutures Inc Hydrolyzable polymers of amino acid and hydroxy acids
US4329383A (en) 1979-07-24 1982-05-11 Nippon Zeon Co., Ltd. Non-thrombogenic material comprising substrate which has been reacted with heparin
US4226243A (en) 1979-07-27 1980-10-07 Ethicon, Inc. Surgical devices of polyesteramides derived from bis-oxamidodiols and dicarboxylic acids
SU790725A1 (en) 1979-07-27 1983-01-23 Ордена Ленина Институт Элементоорганических Соединений Ан Ссср Process for preparing alkylaromatic polyimides
SU872531A1 (en) 1979-08-07 1981-10-15 Институт Физиологии Им.И.С.Бериташвили Ан Гсср Method of producing polyurethans
SU811750A1 (en) 1979-08-07 1983-09-23 Институт Физиологии Им.С.И.Бериташвили Bis-bicarbonates of aliphatic diols as monomers for preparing polyurethanes and process for producing the same
SU876663A1 (en) 1979-11-11 1981-10-30 Институт Физиологии Им. Академика И.С.Бериташвили Ан Гсср Method of producing polyarylates
US4529792A (en) 1979-12-17 1985-07-16 Minnesota Mining And Manufacturing Company Process for preparing synthetic absorbable poly(esteramides)
US4343931A (en) 1979-12-17 1982-08-10 Minnesota Mining And Manufacturing Company Synthetic absorbable surgical devices of poly(esteramides)
SU1016314A1 (en) 1979-12-17 1983-05-07 Институт Физиологии Им.И.С.Бериташвили Process for producing polyester urethanes
SU905228A1 (en) 1980-03-06 1982-02-15 Институт Физиологии Им. Акад.И.С. Бериташвили Ан Гсср Method for preparing thiourea
SU1293518A1 (en) 1985-04-11 1987-02-28 Тбилисский зональный научно-исследовательский и проектный институт типового и экспериментального проектирования жилых и общественных зданий Installation for testing specimen of cross-shaped structure
US4656242A (en) 1985-06-07 1987-04-07 Henkel Corporation Poly(ester-amide) compositions
US4733665C2 (en) 1985-11-07 2002-01-29 Expandable Grafts Partnership Expandable intraluminal graft and method and apparatus for implanting an expandable intraluminal graft
US4611051A (en) 1985-12-31 1986-09-09 Union Camp Corporation Novel poly(ester-amide) hot-melt adhesives
US4649922A (en) * 1986-01-23 1987-03-17 Wiktor Donimik M Catheter arrangement having a variable diameter tip and spring prosthesis
US4882168A (en) 1986-09-05 1989-11-21 American Cyanamid Company Polyesters containing alkylene oxide blocks as drug delivery systems
JPH0696023B2 (en) 1986-11-10 1994-11-30 宇部日東化成株式会社 Artificial blood vessel and method for producing the same
US5721131A (en) 1987-03-06 1998-02-24 United States Of America As Represented By The Secretary Of The Navy Surface modification of polymers with self-assembled monolayers that promote adhesion, outgrowth and differentiation of biological cells
US4800882A (en) 1987-03-13 1989-01-31 Cook Incorporated Endovascular stent and delivery system
US6387379B1 (en) 1987-04-10 2002-05-14 University Of Florida Biofunctional surface modified ocular implants, surgical instruments, medical devices, prostheses, contact lenses and the like
US4894231A (en) 1987-07-28 1990-01-16 Biomeasure, Inc. Therapeutic agent delivery system
US4886062A (en) 1987-10-19 1989-12-12 Medtronic, Inc. Intravascular radially expandable stent and method of implant
US5019096A (en) 1988-02-11 1991-05-28 Trustees Of Columbia University In The City Of New York Infection-resistant compositions, medical devices and surfaces and methods for preparing and using same
JP2561309B2 (en) 1988-03-28 1996-12-04 テルモ株式会社 Medical material and manufacturing method thereof
US4931287A (en) 1988-06-14 1990-06-05 University Of Utah Heterogeneous interpenetrating polymer networks for the controlled release of drugs
US5328471A (en) 1990-02-26 1994-07-12 Endoluminal Therapeutics, Inc. Method and apparatus for treatment of focal disease in hollow tubular organs and other tissue lumens
US4977901A (en) 1988-11-23 1990-12-18 Minnesota Mining And Manufacturing Company Article having non-crosslinked crystallized polymer coatings
IL90193A (en) 1989-05-04 1993-02-21 Biomedical Polymers Int Polurethane-based polymeric materials and biomedical articles and pharmaceutical compositions utilizing the same
US5272012A (en) 1989-06-23 1993-12-21 C. R. Bard, Inc. Medical apparatus having protective, lubricious coating
US5971954A (en) 1990-01-10 1999-10-26 Rochester Medical Corporation Method of making catheter
US5496557A (en) 1990-01-30 1996-03-05 Akzo N.V. Article for the controlled delivery of an active substance, comprising a hollow space fully enclosed by a wall and filled in full or in part with one or more active substances
WO1991012846A1 (en) 1990-02-26 1991-09-05 Slepian Marvin J Method and apparatus for treatment of tubular organs
US5306501A (en) 1990-05-01 1994-04-26 Mediventures, Inc. Drug delivery by injection with thermoreversible gels containing polyoxyalkylene copolymers
US5292516A (en) 1990-05-01 1994-03-08 Mediventures, Inc. Body cavity drug delivery with thermoreversible gels containing polyoxyalkylene copolymers
US5298260A (en) 1990-05-01 1994-03-29 Mediventures, Inc. Topical drug delivery with polyoxyalkylene polymer thermoreversible gels adjustable for pH and osmolality
US5300295A (en) 1990-05-01 1994-04-05 Mediventures, Inc. Ophthalmic drug delivery with thermoreversible polyoxyalkylene gels adjustable for pH
WO1991017724A1 (en) 1990-05-17 1991-11-28 Harbor Medical Devices, Inc. Medical device polymer
US6060451A (en) 1990-06-15 2000-05-09 The National Research Council Of Canada Thrombin inhibitors based on the amino acid sequence of hirudin
CA2038605C (en) 1990-06-15 2000-06-27 Leonard Pinchuk Crack-resistant polycarbonate urethane polymer prostheses and the like
WO1991019529A1 (en) 1990-06-15 1991-12-26 Cortrak Medical, Inc. Drug delivery apparatus and method
US5112457A (en) 1990-07-23 1992-05-12 Case Western Reserve University Process for producing hydroxylated plasma-polymerized films and the use of the films for enhancing the compatiblity of biomedical implants
US5455040A (en) 1990-07-26 1995-10-03 Case Western Reserve University Anticoagulant plasma polymer-modified substrate
US6248129B1 (en) 1990-09-14 2001-06-19 Quanam Medical Corporation Expandable polymeric stent with memory and delivery apparatus and method
US5163952A (en) 1990-09-14 1992-11-17 Michael Froix Expandable polymeric stent with memory and delivery apparatus and method
US5258020A (en) 1990-09-14 1993-11-02 Michael Froix Method of using expandable polymeric stent with memory
US5462990A (en) 1990-10-15 1995-10-31 Board Of Regents, The University Of Texas System Multifunctional organic polymers
GB9027793D0 (en) 1990-12-21 1991-02-13 Ucb Sa Polyester-amides containing terminal carboxyl groups
US5330768A (en) 1991-07-05 1994-07-19 Massachusetts Institute Of Technology Controlled drug delivery using polymer/pluronic blends
US5500013A (en) 1991-10-04 1996-03-19 Scimed Life Systems, Inc. Biodegradable drug delivery vascular stent
US5573934A (en) 1992-04-20 1996-11-12 Board Of Regents, The University Of Texas System Gels for encapsulation of biological materials
US5599352A (en) 1992-03-19 1997-02-04 Medtronic, Inc. Method of making a drug eluting stent
GB9206736D0 (en) 1992-03-27 1992-05-13 Sandoz Ltd Improvements of organic compounds and their use in pharmaceutical compositions
US5219980A (en) 1992-04-16 1993-06-15 Sri International Polymers biodegradable or bioerodiable into amino acids
DE69325845T2 (en) 1992-04-28 2000-01-05 Terumo Corp Thermoplastic polymer composition and medical devices made therefrom
DE4224401A1 (en) 1992-07-21 1994-01-27 Pharmatech Gmbh New biodegradable homo- and co-polymer(s) for pharmaceutical use - produced by polycondensation of prod. from heterolytic cleavage of aliphatic polyester with functionalised (cyclo)aliphatic cpd.
US5399665A (en) 1992-11-05 1995-03-21 Massachusetts Institute Of Technology Biodegradable polymers for cell transplantation
FR2699168B1 (en) 1992-12-11 1995-01-13 Rhone Poulenc Chimie Method of treating a material comprising a polymer by hydrolysis.
EP0604022A1 (en) 1992-12-22 1994-06-29 Advanced Cardiovascular Systems, Inc. Multilayered biodegradable stent and method for its manufacture
US20020055710A1 (en) 1998-04-30 2002-05-09 Ronald J. Tuch Medical device for delivering a therapeutic agent and method of preparation
US5464650A (en) 1993-04-26 1995-11-07 Medtronic, Inc. Intravascular stent and method
US5824048A (en) 1993-04-26 1998-10-20 Medtronic, Inc. Method for delivering a therapeutic substance to a body lumen
JPH0767895A (en) 1993-06-25 1995-03-14 Sumitomo Electric Ind Ltd Antimicrobial artificial blood vessel and suture yarn for antimicrobial operation
US5994341A (en) 1993-07-19 1999-11-30 Angiogenesis Technologies, Inc. Anti-angiogenic Compositions and methods for the treatment of arthritis
EG20321A (en) 1993-07-21 1998-10-31 Otsuka Pharma Co Ltd Medical material and process for producing the same
DE4327024A1 (en) 1993-08-12 1995-02-16 Bayer Ag Thermoplastically processable and biodegradable aliphatic polyesteramides
US5380299A (en) 1993-08-30 1995-01-10 Med Institute, Inc. Thrombolytic treated intravascular medical device
WO1995010989A1 (en) 1993-10-19 1995-04-27 Scimed Life Systems, Inc. Intravascular stent pump
US5723004A (en) 1993-10-21 1998-03-03 Corvita Corporation Expandable supportive endoluminal grafts
FR2714815B1 (en) * 1994-01-10 1996-03-08 Microfil Ind Sa Elastic prosthesis to widen a duct, in particular a blood vessel.
WO1995019796A1 (en) 1994-01-21 1995-07-27 Brown University Research Foundation Biocompatible implants
US6051576A (en) 1994-01-28 2000-04-18 University Of Kentucky Research Foundation Means to achieve sustained release of synergistic drugs by conjugation
CA2190121A1 (en) 1994-03-15 1995-09-21 Edith Mathiowitz Polymeric gene delivery system
US5567410A (en) 1994-06-24 1996-10-22 The General Hospital Corporation Composotions and methods for radiographic imaging
US5857998A (en) 1994-06-30 1999-01-12 Boston Scientific Corporation Stent and therapeutic delivery system
US5670558A (en) 1994-07-07 1997-09-23 Terumo Kabushiki Kaisha Medical instruments that exhibit surface lubricity when wetted
US5788979A (en) 1994-07-22 1998-08-04 Inflow Dynamics Inc. Biodegradable coating with inhibitory properties for application to biocompatible materials
US5516881A (en) 1994-08-10 1996-05-14 Cornell Research Foundation, Inc. Aminoxyl-containing radical spin labeling in polymers and copolymers
US5578073A (en) 1994-09-16 1996-11-26 Ramot Of Tel Aviv University Thromboresistant surface treatment for biomaterials
US5649977A (en) 1994-09-22 1997-07-22 Advanced Cardiovascular Systems, Inc. Metal reinforced polymer stent
US5485496A (en) 1994-09-22 1996-01-16 Cornell Research Foundation, Inc. Gamma irradiation sterilizing of biomaterial medical devices or products, with improved degradation and mechanical properties
FR2724938A1 (en) 1994-09-28 1996-03-29 Lvmh Rech POLYMERS FUNCTIONALIZED BY AMINO ACIDS OR AMINO ACID DERIVATIVES, THEIR USE AS SURFACTANTS, IN PARTICULAR, IN COSMETIC COMPOSITIONS AND IN PARTICULAR NAIL POLISH.
EP0785774B1 (en) 1994-10-12 2001-01-31 Focal, Inc. Targeted delivery via biodegradable polymers
US5554114A (en) * 1994-10-20 1996-09-10 Micro Therapeutics, Inc. Infusion device with preformed shape
US5637113A (en) 1994-12-13 1997-06-10 Advanced Cardiovascular Systems, Inc. Polymer film for wrapping a stent structure
US5569198A (en) 1995-01-23 1996-10-29 Cortrak Medical Inc. Microporous catheter
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
US5919570A (en) 1995-02-01 1999-07-06 Schneider Inc. Slippery, tenaciously adhering hydrogel coatings containing a polyurethane-urea polymer hydrogel commingled with a poly(N-vinylpyrrolidone) polymer hydrogel, coated polymer and metal 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
US5702754A (en) 1995-02-22 1997-12-30 Meadox Medicals, Inc. Method of providing a substrate with a hydrophilic coating and substrates, particularly medical devices, provided with such coatings
US5869127A (en) 1995-02-22 1999-02-09 Boston Scientific Corporation Method of providing a substrate with a bio-active/biocompatible coating
US5854376A (en) 1995-03-09 1998-12-29 Sekisui Kaseihin Kogyo Kabushiki Kaisha Aliphatic ester-amide copolymer resins
US5605696A (en) 1995-03-30 1997-02-25 Advanced Cardiovascular Systems, Inc. Drug loaded polymeric material and method of manufacture
US6120536A (en) 1995-04-19 2000-09-19 Schneider (Usa) Inc. Medical devices with long term non-thrombogenic coatings
US6099562A (en) 1996-06-13 2000-08-08 Schneider (Usa) Inc. Drug coating with topcoat
US20020091433A1 (en) 1995-04-19 2002-07-11 Ni Ding Drug release coated stent
US5837313A (en) 1995-04-19 1998-11-17 Schneider (Usa) Inc Drug release stent coating process
RU2169742C2 (en) 1995-04-19 2001-06-27 Катаока Казунори Heterotelochelate block copolymer and method of preparation thereof
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
US6010530A (en) 1995-06-07 2000-01-04 Boston Scientific Technology, Inc. Self-expanding endoluminal prosthesis
US7550005B2 (en) 1995-06-07 2009-06-23 Cook Incorporated Coated implantable medical device
US7611533B2 (en) 1995-06-07 2009-11-03 Cook Incorporated Coated implantable medical device
US6129761A (en) 1995-06-07 2000-10-10 Reprogenesis, Inc. Injectable hydrogel compositions
US5609629A (en) 1995-06-07 1997-03-11 Med Institute, Inc. Coated implantable medical device
CA2223889A1 (en) 1995-06-07 1996-12-19 The American National Red Cross Supplemented and unsupplemented tissue sealants, methods of their production and use
WO1998017331A1 (en) 1995-06-07 1998-04-30 Cook Incorporated Silver implantable medical device
CA2178541C (en) 1995-06-07 2009-11-24 Neal E. Fearnot Implantable medical device
US5820917A (en) 1995-06-07 1998-10-13 Medtronic, Inc. Blood-contacting medical device and method
US5667767A (en) 1995-07-27 1997-09-16 Micro Therapeutics, Inc. Compositions for use in embolizing blood vessels
US5877224A (en) 1995-07-28 1999-03-02 Rutgers, The State University Of New Jersey Polymeric drug formulations
US5723219A (en) 1995-12-19 1998-03-03 Talison Research Plasma deposited film networks
US5658995A (en) 1995-11-27 1997-08-19 Rutgers, The State University Copolymers of tyrosine-based polycarbonate and poly(alkylene oxide)
DE19545678A1 (en) 1995-12-07 1997-06-12 Goldschmidt Ag Th Copolymers of polyamino acid esters
DK2111876T3 (en) 1995-12-18 2011-12-12 Angiodevice Internat Gmbh Crosslinked polymer preparations and methods for their use
US6033582A (en) 1996-01-22 2000-03-07 Etex Corporation Surface modification of medical implants
US6054553A (en) 1996-01-29 2000-04-25 Bayer Ag Process for the preparation of polymers having recurring agents
US5932299A (en) 1996-04-23 1999-08-03 Katoot; Mohammad W. Method for modifying the surface of an object
US5955509A (en) 1996-05-01 1999-09-21 Board Of Regents, The University Of Texas System pH dependent polymer micelles
US5610241A (en) 1996-05-07 1997-03-11 Cornell Research Foundation, Inc. Reactive graft polymer with biodegradable polymer backbone and method for preparing reactive biodegradable polymers
JP2000511161A (en) 1996-05-24 2000-08-29 アンジオテック ファーマシュウティカルズ,インコーポレイテッド Compositions and methods for treating or preventing diseases of the body passages
US5876433A (en) 1996-05-29 1999-03-02 Ethicon, Inc. Stent and method of varying amounts of heparin coated thereon to control treatment
US5874165A (en) 1996-06-03 1999-02-23 Gore Enterprise Holdings, Inc. Materials and method for the immobilization of bioactive species onto polymeric subtrates
NL1003459C2 (en) 1996-06-28 1998-01-07 Univ Twente Copoly (ester amides) and copoly (ester urethanes).
US5711958A (en) 1996-07-11 1998-01-27 Life Medical Sciences, Inc. Methods for reducing or eliminating post-surgical adhesion formation
US5830178A (en) 1996-10-11 1998-11-03 Micro Therapeutics, Inc. Methods for embolizing vascular sites with an emboilizing composition comprising dimethylsulfoxide
US6060518A (en) 1996-08-16 2000-05-09 Supratek Pharma Inc. Polymer compositions for chemotherapy and methods of treatment using the same
DE19633901A1 (en) * 1996-08-22 1998-02-26 Thomas Prof Dr Med Ischinger Vascular support in the form of a tube section-like support structure
AU4090997A (en) 1996-08-30 1998-03-19 Helix Medical Corporation Medical devices having microbial resistant material properties
US5783657A (en) 1996-10-18 1998-07-21 Union Camp Corporation Ester-terminated polyamides of polymerized fatty acids useful in formulating transparent gels in low polarity liquids
US6530951B1 (en) 1996-10-24 2003-03-11 Cook Incorporated Silver implantable medical device
US6120491A (en) 1997-11-07 2000-09-19 The State University Rutgers Biodegradable, anionic polymers derived from the amino acid L-tyrosine
US5980972A (en) 1996-12-20 1999-11-09 Schneider (Usa) Inc Method of applying drug-release coatings
US5997517A (en) 1997-01-27 1999-12-07 Sts Biopolymers, Inc. Bonding layers for medical device surface coatings
DE69828387T2 (en) 1997-01-28 2005-12-08 United States Surgical Corp., Norwalk POLYESTERAMIDE, ITS PRESENTATION AND SURGICAL FABRICATED SURGICAL ARTICLES
DE69826639T2 (en) 1997-01-28 2005-10-06 United States Surgical Corp., Norwalk SURGICAL ARTICLES MADE FROM POLYESTERAMIDES WITH GROUPS DERIVED FROM AMINO ACIDS AND ALTERNATIVELY WITH GROUPS DERIVED FROM ALPHA HYDROXYLIC ACIDS
WO1998032779A1 (en) 1997-01-28 1998-07-30 United States Surgical Corporation Polyesteramide, its preparation and surgical devices fabricated therefrom
WO1998036784A1 (en) 1997-02-20 1998-08-27 Cook Incorporated Coated implantable medical device
US8172897B2 (en) * 1997-04-15 2012-05-08 Advanced Cardiovascular Systems, Inc. Polymer and metal composite implantable medical devices
US6240616B1 (en) 1997-04-15 2001-06-05 Advanced Cardiovascular Systems, Inc. Method of manufacturing a medicated porous metal prosthesis
US5879697A (en) 1997-04-30 1999-03-09 Schneider Usa Inc Drug-releasing coatings for medical devices
US6159978A (en) 1997-05-28 2000-12-12 Aventis Pharmaceuticals Product, Inc. Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases
US6245760B1 (en) 1997-05-28 2001-06-12 Aventis Pharmaceuticals Products, Inc Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases
US6180632B1 (en) 1997-05-28 2001-01-30 Aventis Pharmaceuticals Products Inc. Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases
US6056993A (en) 1997-05-30 2000-05-02 Schneider (Usa) Inc. Porous protheses and methods for making the same wherein the protheses are formed by spraying water soluble and water insoluble fibers onto a rotating mandrel
US6110483A (en) 1997-06-23 2000-08-29 Sts Biopolymers, Inc. Adherent, flexible hydrogel and medicated coatings
EA200000087A1 (en) 1997-07-01 2000-08-28 Атеродженикс, Инк. EFFICIENCY EFFICIENCY IMPROVEMENT OF HYPERPROLIFERATIVE STATE THERAPY WITH THE HELP OF ANTIOXIDANT
US6211249B1 (en) 1997-07-11 2001-04-03 Life Medical Sciences, Inc. Polyester polyether block copolymers
US5980928A (en) 1997-07-29 1999-11-09 Terry; Paul B. Implant for preventing conjunctivitis in cattle
AU8901798A (en) 1997-08-08 1999-03-01 Procter & Gamble Company, The Laundry detergent compositions with amino acid based polymers to provide appearance and integrity benefits to fabrics laundered therewith
US6121027A (en) 1997-08-15 2000-09-19 Surmodics, Inc. Polybifunctional reagent having a polymeric backbone and photoreactive moieties and bioactive groups
US6316522B1 (en) 1997-08-18 2001-11-13 Scimed Life Systems, Inc. Bioresorbable hydrogel compositions for implantable prostheses
US6890546B2 (en) 1998-09-24 2005-05-10 Abbott Laboratories Medical devices containing rapamycin analogs
US6120788A (en) 1997-10-16 2000-09-19 Bioamide, Inc. Bioabsorbable triglycolic acid poly(ester-amide)s
US6015541A (en) 1997-11-03 2000-01-18 Micro Therapeutics, Inc. Radioactive embolizing compositions
US6221425B1 (en) 1998-01-30 2001-04-24 Advanced Cardiovascular Systems, Inc. Lubricious hydrophilic coating for an intracorporeal medical device
US6110188A (en) 1998-03-09 2000-08-29 Corvascular, Inc. Anastomosis method
US6063111A (en) * 1998-03-31 2000-05-16 Cordis Corporation Stent aneurysm treatment system and method
US6258371B1 (en) 1998-04-03 2001-07-10 Medtronic Inc Method for making biocompatible medical article
US20030040790A1 (en) 1998-04-15 2003-02-27 Furst Joseph G. Stent coating
US20010029351A1 (en) 1998-04-16 2001-10-11 Robert Falotico Drug combinations and delivery devices for the prevention and treatment of vascular disease
US7658727B1 (en) 1998-04-20 2010-02-09 Medtronic, Inc Implantable medical device with enhanced biocompatibility and biostability
US20020188037A1 (en) 1999-04-15 2002-12-12 Chudzik Stephen J. Method and system for providing bioactive agent release coating
EP1555036B1 (en) 1998-04-27 2010-05-05 Surmodics Inc. Bioactive agent release coating
US6113629A (en) 1998-05-01 2000-09-05 Micrus Corporation Hydrogel for the therapeutic treatment of aneurysms
KR100314496B1 (en) 1998-05-28 2001-11-22 윤동진 Non-thrombogenic heparin derivatives, process for preparation and use thereof
WO1999063981A2 (en) 1998-06-11 1999-12-16 Cerus Corporation Use of alkylating compounds for inhibiting proliferation of arterial smooth muscle cells
US6153252A (en) 1998-06-30 2000-11-28 Ethicon, Inc. Process for coating stents
DE19829701C1 (en) * 1998-07-03 2000-03-16 Heraeus Gmbh W C Radially expandable support device IV
AU4645299A (en) 1998-07-08 2000-02-01 Advanced Biocompatible Coatings Inc. Biocompatible metallic stents with hydroxy methacrylate coating
WO2000010622A1 (en) 1998-08-20 2000-03-02 Cook Incorporated Coated implantable medical device
US6248127B1 (en) 1998-08-21 2001-06-19 Medtronic Ave, Inc. Thromboresistant coated medical device
US6335029B1 (en) 1998-08-28 2002-01-01 Scimed Life Systems, Inc. Polymeric coatings for controlled delivery of active agents
CA2338788A1 (en) 1998-09-02 2000-03-09 Scimed Life Systems, Inc. Drug delivery device for stent
WO2000018446A1 (en) 1998-09-25 2000-04-06 Cathnet-Science S.A. Multi-layered sleeve for intravascular expandable device
US6011125A (en) 1998-09-25 2000-01-04 General Electric Company Amide modified polyesters
US6458092B1 (en) * 1998-09-30 2002-10-01 C. R. Bard, Inc. Vascular inducing implants
US6051548A (en) * 1998-11-05 2000-04-18 International Flavors & Fragrances Inc. Trimethylcyclohexenylcyclopropyl ketones perfume composition
US6530950B1 (en) 1999-01-12 2003-03-11 Quanam Medical Corporation Intraluminal stent having coaxial polymer member
US6419692B1 (en) 1999-02-03 2002-07-16 Scimed Life Systems, Inc. Surface protection method for stents and balloon catheters for drug delivery
US6143354A (en) 1999-02-08 2000-11-07 Medtronic Inc. One-step method for attachment of biomolecules to substrate surfaces
US6248122B1 (en) * 1999-02-26 2001-06-19 Vascular Architects, Inc. Catheter with controlled release endoluminal prosthesis
WO2000064506A1 (en) 1999-04-23 2000-11-02 Agion Technologies, L.L.C. Stent having antimicrobial agent
US6258121B1 (en) 1999-07-02 2001-07-10 Scimed Life Systems, Inc. Stent coating
US6283947B1 (en) 1999-07-13 2001-09-04 Advanced Cardiovascular Systems, Inc. Local drug delivery injection catheter
US6494862B1 (en) 1999-07-13 2002-12-17 Advanced Cardiovascular Systems, Inc. Substance delivery apparatus and a method of delivering a therapeutic substance to an anatomical passageway
US6177523B1 (en) 1999-07-14 2001-01-23 Cardiotech International, Inc. Functionalized polyurethanes
FI19991852A (en) 1999-09-01 2001-03-01 Yli Urpo Antti New multilayer material with a biologically active agent, and its preparation
US6759054B2 (en) 1999-09-03 2004-07-06 Advanced Cardiovascular Systems, Inc. Ethylene vinyl alcohol composition and coating
US6503556B2 (en) 2000-12-28 2003-01-07 Advanced Cardiovascular Systems, Inc. Methods of forming a coating for a prosthesis
US6790228B2 (en) 1999-12-23 2004-09-14 Advanced Cardiovascular Systems, Inc. Coating for implantable devices and a method of forming the same
US20040029952A1 (en) 1999-09-03 2004-02-12 Yung-Ming Chen Ethylene vinyl alcohol composition and coating
US20070032853A1 (en) 2002-03-27 2007-02-08 Hossainy Syed F 40-O-(2-hydroxy)ethyl-rapamycin coated stent
US6749626B1 (en) 2000-03-31 2004-06-15 Advanced Cardiovascular Systems, Inc. Actinomycin D for the treatment of vascular disease
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
US6503954B1 (en) 2000-03-31 2003-01-07 Advanced Cardiovascular Systems, Inc. Biocompatible carrier containing actinomycin D and a method of forming the same
US6203551B1 (en) 1999-10-04 2001-03-20 Advanced Cardiovascular Systems, Inc. Chamber for applying therapeutic substances to an implant device
US6331313B1 (en) 1999-10-22 2001-12-18 Oculex Pharmaceticals, Inc. Controlled-release biocompatible ocular drug delivery implant devices and methods
US6251136B1 (en) 1999-12-08 2001-06-26 Advanced Cardiovascular Systems, Inc. Method of layering a three-coated stent using pharmacological and polymeric agents
US6338739B1 (en) * 1999-12-22 2002-01-15 Ethicon, Inc. Biodegradable stent
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
US6283949B1 (en) 1999-12-27 2001-09-04 Advanced Cardiovascular Systems, Inc. Refillable implantable drug delivery pump
AU2599501A (en) 1999-12-29 2001-07-09 Advanced Cardiovascular Systems Inc. Device and active component for inhibiting formation of thrombus-inflammatory cell matrix
AU2623201A (en) 1999-12-30 2001-07-16 Kam W Leong Controlled delivery of therapeutic agents by insertable medical devices
EP1421855A3 (en) 2000-01-11 2004-07-14 Intralytix Inc. Method and device for sanitation using bacteriophages
US6527801B1 (en) 2000-04-13 2003-03-04 Advanced Cardiovascular Systems, Inc. Biodegradable drug delivery material for stent
US6270779B1 (en) 2000-05-10 2001-08-07 United States Of America Nitric oxide-releasing metallic medical devices
US20020007214A1 (en) 2000-05-19 2002-01-17 Robert Falotico Drug/drug delivery systems for the prevention and treatment of vascular disease
US6776796B2 (en) 2000-05-12 2004-08-17 Cordis Corportation Antiinflammatory drug and delivery device
US20020007213A1 (en) 2000-05-19 2002-01-17 Robert Falotico Drug/drug delivery systems for the prevention and treatment of vascular disease
US20020007215A1 (en) 2000-05-19 2002-01-17 Robert Falotico Drug/drug delivery systems for the prevention and treatment of vascular disease
US20020005206A1 (en) 2000-05-19 2002-01-17 Robert Falotico Antiproliferative drug and delivery device
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
US6673385B1 (en) 2000-05-31 2004-01-06 Advanced Cardiovascular Systems, Inc. Methods for polymeric coatings stents
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
AU2001279288A1 (en) 2000-07-06 2002-01-21 Biosurface Engineering Technologies, Inc. Drug diffusion coatings, applications and methods
US6555157B1 (en) 2000-07-25 2003-04-29 Advanced Cardiovascular Systems, Inc. Method for coating an implantable device and system for performing the method
WO2002009768A2 (en) 2000-07-27 2002-02-07 Rutgers, The State University Therapeutic polyesters and polyamides
US6808533B1 (en) * 2000-07-28 2004-10-26 Atrium Medical Corporation Covered stent and method of covering a stent
US6451373B1 (en) 2000-08-04 2002-09-17 Advanced Cardiovascular Systems, Inc. Method of forming a therapeutic coating onto a surface of an implantable prosthesis
US6503538B1 (en) 2000-08-30 2003-01-07 Cornell Research Foundation, Inc. Elastomeric functional biodegradable copolyester amides and copolyester urethanes
US6585926B1 (en) 2000-08-31 2003-07-01 Advanced Cardiovascular Systems, Inc. Method of manufacturing a porous balloon
WO2002026162A2 (en) 2000-09-26 2002-04-04 Advanced Cardiovascular Systems, Inc. A method of loading a substance onto an implantable device
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
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
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
US7261735B2 (en) 2001-05-07 2007-08-28 Cordis Corporation Local drug delivery devices and methods for maintaining the drug coatings thereon
US20020111590A1 (en) 2000-09-29 2002-08-15 Davila Luis A. Medical devices, drug coatings and methods for maintaining the drug coatings thereon
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
US6783793B1 (en) 2000-10-26 2004-08-31 Advanced Cardiovascular Systems, Inc. Selective coating of medical devices
US6558733B1 (en) 2000-10-26 2003-05-06 Advanced Cardiovascular Systems, Inc. Method for etching a micropatterned microdepot prosthesis
US6758859B1 (en) 2000-10-30 2004-07-06 Kenny L. Dang Increased drug-loading and reduced stress drug delivery device
US6824559B2 (en) 2000-12-22 2004-11-30 Advanced Cardiovascular Systems, Inc. Ethylene-carboxyl copolymers as drug delivery matrices
ATE369817T1 (en) 2000-12-22 2007-09-15 Avantec Vascular Corp DEVICE FOR DELIVERING THERAPEUTIC ACTIVE INGREDIENTS
US20030033007A1 (en) * 2000-12-22 2003-02-13 Avantec Vascular Corporation Methods and devices for delivery of therapeutic capable agents with variable release profile
US20020082679A1 (en) 2000-12-22 2002-06-27 Avantec Vascular Corporation Delivery or therapeutic capable agents
US7077859B2 (en) 2000-12-22 2006-07-18 Avantec Vascular Corporation Apparatus and methods for variably controlled substance delivery from implanted prostheses
US6544543B1 (en) 2000-12-27 2003-04-08 Advanced Cardiovascular Systems, Inc. Periodic constriction of vessels to treat ischemic tissue
US6540776B2 (en) 2000-12-28 2003-04-01 Advanced Cardiovascular Systems, Inc. Sheath for a prosthesis and methods of forming the same
US6663662B2 (en) 2000-12-28 2003-12-16 Advanced Cardiovascular Systems, Inc. Diffusion barrier layer for implantable devices
US20020087123A1 (en) 2001-01-02 2002-07-04 Hossainy Syed F.A. Adhesion of heparin-containing coatings to blood-contacting surfaces of medical devices
US6544223B1 (en) 2001-01-05 2003-04-08 Advanced Cardiovascular Systems, Inc. Balloon catheter for delivering therapeutic agents
US6544582B1 (en) 2001-01-05 2003-04-08 Advanced Cardiovascular Systems, Inc. Method and apparatus for coating an implantable device
US6645195B1 (en) 2001-01-05 2003-11-11 Advanced Cardiovascular Systems, Inc. Intraventricularly guided agent delivery system and method of use
GB0100761D0 (en) * 2001-01-11 2001-02-21 Biocompatibles Ltd Drug delivery from stents
US6740040B1 (en) 2001-01-30 2004-05-25 Advanced Cardiovascular Systems, Inc. Ultrasound energy driven intraventricular catheter to treat ischemia
US20030032767A1 (en) 2001-02-05 2003-02-13 Yasuhiro Tada High-strength polyester-amide fiber and process for producing the same
WO2002064014A2 (en) 2001-02-09 2002-08-22 Endoluminal Therapeutics, Inc. Endomural therapy
WO2002072014A2 (en) 2001-03-08 2002-09-19 Volcano Therapeutics, Inc. Medical devices, compositions and methods for treating vulnerable plaque
US6613077B2 (en) 2001-03-27 2003-09-02 Scimed Life Systems, Inc. Stent with controlled expansion
US6780424B2 (en) 2001-03-30 2004-08-24 Charles David Claude Controlled morphologies in polymer drug for release of drugs from polymer films
US6645135B1 (en) 2001-03-30 2003-11-11 Advanced Cardiovascular Systems, Inc. Intravascular catheter device and method for simultaneous local delivery of radiation and a therapeutic substance
US6623448B2 (en) 2001-03-30 2003-09-23 Advanced Cardiovascular Systems, Inc. Steerable drug delivery device
US6625486B2 (en) 2001-04-11 2003-09-23 Advanced Cardiovascular Systems, Inc. Method and apparatus for intracellular delivery of an agent
US6764505B1 (en) 2001-04-12 2004-07-20 Advanced Cardiovascular Systems, Inc. Variable surface area stent
US6712845B2 (en) 2001-04-24 2004-03-30 Advanced Cardiovascular Systems, Inc. Coating for a stent and a method of forming the same
EP1383504A1 (en) 2001-04-26 2004-01-28 Control Delivery Systems, Inc. Sustained release drug delivery system containing codrugs
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
US6656506B1 (en) 2001-05-09 2003-12-02 Advanced Cardiovascular Systems, Inc. Microparticle coated medical device
US7651695B2 (en) 2001-05-18 2010-01-26 Advanced Cardiovascular Systems, Inc. Medicated stents for the treatment of vascular disease
US6605154B1 (en) 2001-05-31 2003-08-12 Advanced Cardiovascular Systems, Inc. Stent mounting device
US7862495B2 (en) 2001-05-31 2011-01-04 Advanced Cardiovascular Systems, Inc. Radiation or drug delivery source with activity gradient to minimize edge effects
US6743462B1 (en) 2001-05-31 2004-06-01 Advanced Cardiovascular Systems, Inc. Apparatus and method for coating implantable devices
US6666880B1 (en) 2001-06-19 2003-12-23 Advised Cardiovascular Systems, Inc. Method and system for securing a coated stent to a balloon catheter
US7247313B2 (en) 2001-06-27 2007-07-24 Advanced Cardiovascular Systems, Inc. Polyacrylates coatings for implantable medical devices
US6695920B1 (en) 2001-06-27 2004-02-24 Advanced Cardiovascular Systems, Inc. Mandrel for supporting a stent and a method of using the mandrel to coat a stent
US6572644B1 (en) 2001-06-27 2003-06-03 Advanced Cardiovascular Systems, Inc. Stent mounting device and a method of using the same to coat a stent
US6673154B1 (en) 2001-06-28 2004-01-06 Advanced Cardiovascular Systems, Inc. Stent mounting device to coat a stent
US6565659B1 (en) 2001-06-28 2003-05-20 Advanced Cardiovascular Systems, Inc. Stent mounting assembly and a method of using the same to coat a stent
US6527863B1 (en) 2001-06-29 2003-03-04 Advanced Cardiovascular Systems, Inc. Support device for a stent and a method of using the same to coat a stent
US6585755B2 (en) 2001-06-29 2003-07-01 Advanced Cardiovascular Polymeric stent suitable for imaging by MRI and fluoroscopy
US6656216B1 (en) 2001-06-29 2003-12-02 Advanced Cardiovascular Systems, Inc. Composite stent with regioselective material
US6706013B1 (en) 2001-06-29 2004-03-16 Advanced Cardiovascular Systems, Inc. Variable length drug delivery catheter
EP1273314A1 (en) 2001-07-06 2003-01-08 Terumo Kabushiki Kaisha Stent
US6641611B2 (en) 2001-11-26 2003-11-04 Swaminathan Jayaraman Therapeutic coating for an intravascular implant
US8303651B1 (en) 2001-09-07 2012-11-06 Advanced Cardiovascular Systems, Inc. Polymeric coating for reducing the rate of release of a therapeutic substance from a stent
US20030083739A1 (en) 2001-09-24 2003-05-01 Robert Cafferata Rational drug therapy device and methods
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
US20030059520A1 (en) 2001-09-27 2003-03-27 Yung-Ming Chen Apparatus for regulating temperature of a composition and a method of coating implantable devices
US20030073961A1 (en) 2001-09-28 2003-04-17 Happ Dorrie M. Medical device containing light-protected therapeutic agent and a method for fabricating thereof
US20030065377A1 (en) 2001-09-28 2003-04-03 Davila Luis A. Coated medical devices
US6939376B2 (en) * 2001-11-05 2005-09-06 Sun Biomedical, Ltd. Drug-delivery endovascular stent and method for treating restenosis
DE60235775D1 (en) 2001-11-08 2010-05-06 Ziscoat N V Intraluminal device with a therapeutic agent-containing coating
US7585516B2 (en) 2001-11-12 2009-09-08 Advanced Cardiovascular Systems, Inc. Coatings for drug delivery devices
US6663880B1 (en) 2001-11-30 2003-12-16 Advanced Cardiovascular Systems, Inc. Permeabilizing reagents to increase drug delivery and a method of local delivery
US6939374B2 (en) * 2001-12-21 2005-09-06 Scimed Life Systems, Inc. Stents, stenting systems, and related methods for agent delivery
US6709514B1 (en) 2001-12-28 2004-03-23 Advanced Cardiovascular Systems, Inc. Rotary coating apparatus for coating implantable medical devices
US7105198B2 (en) * 2002-01-14 2006-09-12 Medtronic Vascular, Inc. Method for coating stent
US7445629B2 (en) 2002-01-31 2008-11-04 Boston Scientific Scimed, Inc. Medical device for delivering biologically active material
US6887270B2 (en) 2002-02-08 2005-05-03 Boston Scientific Scimed, Inc. Implantable or insertable medical device resistant to microbial growth and biofilm formation
AU2003225882A1 (en) 2002-03-20 2003-10-08 Advanced Cardiovascular Systems, Inc. Biodegradable hydrophobic polymer for stents
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
US6865810B2 (en) 2002-06-27 2005-03-15 Scimed Life Systems, Inc. Methods of making medical devices
US7491233B1 (en) 2002-07-19 2009-02-17 Advanced Cardiovascular Systems Inc. Purified polymers for coatings of implantable medical devices
US7608058B2 (en) * 2002-07-23 2009-10-27 Micrus Corporation Stretch resistant therapeutic device
US20040034405A1 (en) * 2002-07-26 2004-02-19 Dickson Andrew M. Axially expanding polymer stent
US7255710B2 (en) * 2002-08-06 2007-08-14 Icon Medical Corp. Helical stent with micro-latches
US20040054104A1 (en) 2002-09-05 2004-03-18 Pacetti Stephen D. Coatings for drug delivery devices comprising modified poly(ethylene-co-vinyl alcohol)
US20040063805A1 (en) 2002-09-19 2004-04-01 Pacetti Stephen D. Coatings for implantable medical devices and methods for fabrication thereof
US7087263B2 (en) 2002-10-09 2006-08-08 Advanced Cardiovascular Systems, Inc. Rare limiting barriers for implantable medical devices
US6733536B1 (en) * 2002-10-22 2004-05-11 Scimed Life Systems Male urethral stent device
JP3880504B2 (en) * 2002-10-28 2007-02-14 インターナショナル・ビジネス・マシーンズ・コーポレーション Structured / hierarchical content processing apparatus, structured / hierarchical content processing method, and program
US8088404B2 (en) 2003-03-20 2012-01-03 Medtronic Vasular, Inc. Biocompatible controlled release coatings for medical devices and related methods
EP1470828A1 (en) * 2003-04-25 2004-10-27 Medtronic Vascular, Inc. Plasticized stent coatings
US20040236410A1 (en) * 2003-05-22 2004-11-25 Atrium Medical Corp. Polymeric body formation
US7318944B2 (en) 2003-08-07 2008-01-15 Medtronic Vascular, Inc. Extrusion process for coating stents
US20050038497A1 (en) 2003-08-11 2005-02-17 Scimed Life Systems, Inc. Deformation medical device without material deformation
US20050037052A1 (en) 2003-08-13 2005-02-17 Medtronic Vascular, Inc. Stent coating with gradient porosity
US20050043786A1 (en) 2003-08-18 2005-02-24 Medtronic Ave, Inc. Methods and apparatus for treatment of aneurysmal tissue
US20050049693A1 (en) 2003-08-25 2005-03-03 Medtronic Vascular Inc. Medical devices and compositions for delivering biophosphonates to anatomical sites at risk for vascular disease
JP4300938B2 (en) * 2003-08-27 2009-07-22 株式会社日立製作所 Media recognition site search method and system
US20050055078A1 (en) 2003-09-04 2005-03-10 Medtronic Vascular, Inc. Stent with outer slough coating
US20050054774A1 (en) 2003-09-09 2005-03-10 Scimed Life Systems, Inc. Lubricious coating
US7544381B2 (en) 2003-09-09 2009-06-09 Boston Scientific Scimed, Inc. Lubricious coatings for medical device
US20050060020A1 (en) 2003-09-17 2005-03-17 Scimed Life Systems, Inc. Covered stent with biologically active material
US7371228B2 (en) 2003-09-19 2008-05-13 Medtronic Vascular, Inc. Delivery of therapeutics to treat aneurysms
US7789891B2 (en) 2003-09-23 2010-09-07 Boston Scientific Scimed, Inc. External activation of vaso-occlusive implants
US20050065501A1 (en) 2003-09-23 2005-03-24 Scimed Life Systems, Inc. Energy activated vaso-occlusive devices
US7060319B2 (en) 2003-09-24 2006-06-13 Boston Scientific Scimed, Inc. method for using an ultrasonic nozzle to coat a medical appliance
US8801692B2 (en) 2003-09-24 2014-08-12 Medtronic Vascular, Inc. Gradient coated stent and method of fabrication
US7055237B2 (en) 2003-09-29 2006-06-06 Medtronic Vascular, Inc. Method of forming a drug eluting stent
US20050074406A1 (en) 2003-10-03 2005-04-07 Scimed Life Systems, Inc. Ultrasound coating for enhancing visualization of medical device in ultrasound images
US6984411B2 (en) 2003-10-14 2006-01-10 Boston Scientific Scimed, Inc. Method for roll coating multiple stents
US20050171596A1 (en) * 2004-02-03 2005-08-04 Furst Joseph G. Stents with amphiphilic copolymer coatings
CA2502018A1 (en) * 2004-04-16 2005-10-16 Conor Medsystems, Inc. Bioresorbable stent delivery system
US7229471B2 (en) * 2004-09-10 2007-06-12 Advanced Cardiovascular Systems, Inc. Compositions containing fast-leaching plasticizers for improved performance of medical devices
US7914570B2 (en) * 2004-10-07 2011-03-29 Boston Scientific Scimed, Inc. Non-shortening helical stent
US8323333B2 (en) * 2005-03-03 2012-12-04 Icon Medical Corp. Fragile structure protective coating

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3892238A (en) * 1971-09-16 1975-07-01 Abbott Lab Drug supporting anchor
EP0388234A1 (en) * 1989-03-17 1990-09-19 Carter Holt Harvey Plastic Products Group Limited A drug administering device for insertion in a body cavity of an animal
WO2000018331A2 (en) * 1998-09-29 2000-04-06 C. R. Bard, Inc. Drug delivery systems
US20030028245A1 (en) * 2000-06-30 2003-02-06 Vascular Architects, Inc. Function-enhanced thrombolytic AV fistula and method
WO2002049544A1 (en) * 2000-12-19 2002-06-27 Vascular Architects, Inc. Biologically active agent delivery apparatus and method
WO2005079387A2 (en) * 2004-02-13 2005-09-01 Conor Medsystems, Inc. Implantable drug delivery device including wire filaments
US20050228473A1 (en) * 2004-04-05 2005-10-13 David Brown Device and method for delivering a treatment to an artery

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9173973B2 (en) 2006-07-20 2015-11-03 G. Lawrence Thatcher Bioabsorbable polymeric composition for a medical device
US9211205B2 (en) 2006-10-20 2015-12-15 Orbusneich Medical, Inc. Bioabsorbable medical device with coating
US10596330B2 (en) 2015-08-26 2020-03-24 Medtronic Xomed, Inc. Resorbable, drug-eluting submucosal turbinate implant device and method
US11654250B2 (en) 2015-08-26 2023-05-23 Medtronic Xomed, Inc. Resorbable, drug-eluting submucosal turbinate implant device and method

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