WO2004037326A2 - Mixing and delivery medical syringe system for therapeutic compositions - Google Patents

Mixing and delivery medical syringe system for therapeutic compositions Download PDF

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Publication number
WO2004037326A2
WO2004037326A2 PCT/US2003/033674 US0333674W WO2004037326A2 WO 2004037326 A2 WO2004037326 A2 WO 2004037326A2 US 0333674 W US0333674 W US 0333674W WO 2004037326 A2 WO2004037326 A2 WO 2004037326A2
Authority
WO
WIPO (PCT)
Prior art keywords
syringe
conduit
compartment
particles
composition
Prior art date
Application number
PCT/US2003/033674
Other languages
French (fr)
Other versions
WO2004037326A3 (en
Inventor
Thomas V. Ii Casey
Bud Damiano
Original Assignee
Boston Scientific Limited
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 Boston Scientific Limited filed Critical Boston Scientific Limited
Priority to EP03777846A priority Critical patent/EP1553999A2/en
Priority to AU2003286639A priority patent/AU2003286639A1/en
Priority to CA002503052A priority patent/CA2503052A1/en
Publication of WO2004037326A2 publication Critical patent/WO2004037326A2/en
Publication of WO2004037326A3 publication Critical patent/WO2004037326A3/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
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178Syringes
    • A61M5/28Syringe ampoules or carpules, i.e. ampoules or carpules provided with a needle
    • A61M5/284Syringe ampoules or carpules, i.e. ampoules or carpules provided with a needle comprising means for injection of two or more media, e.g. by mixing
    • 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
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178Syringes
    • A61M5/19Syringes having more than one chamber, e.g. including a manifold coupling two parallelly aligned syringes through separate channels to a common discharge assembly
    • 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
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178Syringes
    • A61M5/28Syringe ampoules or carpules, i.e. ampoules or carpules provided with a needle
    • A61M5/285Syringe ampoules or carpules, i.e. ampoules or carpules provided with a needle with sealing means to be broken or opened
    • A61M5/286Syringe ampoules or carpules, i.e. ampoules or carpules provided with a needle with sealing means to be broken or opened upon internal pressure increase, e.g. pierced or burst

Definitions

  • This invention relates to mixing and delivery of therapeutic compositions.
  • Therapeutic vascular occlusions are induced by the introduction of various substances (embolic material, such as embolic particles) into a patient's circulatory system for the purpose of occluding vessels, either to arrest or to prevent hemorrhaging or to defunctionalize a structure or an organ.
  • embolic material such as embolic particles
  • hydrating material such as saline
  • contrast agent used for tracking the path of the embolic particles inside the body
  • the invention features a mixing and delivery medical syringe system.
  • the medical syringe system includes a barrel including first and second detachable sections, and first and second compartments communicable through a conduit.
  • the invention feature a mixing and delivery medical syringe system.
  • the medical syringe system includes a barrel having first and second compartments arranged in parallel along the barrel, the compartments communicable through a pressure-activated conduit.
  • the invention features a kit for medicant mixing and delivery, including a syringe system, which includes a barrel assembled from multiple sections, including a first section having a first chamber, and a second section having a second chamber.
  • the syringe system includes a conduit between the first and second chambers through which flow can be controlled.
  • the kit further includes a first container containing a first composition, and a second container containing a second composition.
  • the invention features a method for delivering injectable polymer particles by providing a syringe.
  • the syringe includes a first compartment and a second compartment.
  • a first component including injectable particles is loaded into at least one compartment, and the syringe is actuated to deliver the particles.
  • Embodiments can include one or more of the following.
  • the conduit can include a pressure-activated separator.
  • the separator can include a failure membrane.
  • the failure membrane can include a weakened region. The weakened region preferentially effects rupture about a central region of the membrane. The weakened region preferentially affects rupture such that an attachment portion is not ruptured.
  • the pressure-activated conduit can include a valve.
  • the first and the second compartments can be arranged serially along the syringe barrel.
  • the barrel can include a vent valve.
  • the barrel can include a fluid outlet and the outlet can include a valve.
  • the first section can include the first chamber and the second section can include the second chamber.
  • the conduit can be in one of the first or second sections.
  • the first composition can include injectable polymer particles.
  • the particles can be embolic particles.
  • the second composition can be a contrast agent.
  • the second composition can include an anticancer agent.
  • the syringe can include a conduit between the compartments.
  • a first component including injectable particles is loaded into at least one compartment and a second component is loaded into the second compartment.
  • the first component and the second component are mixed in the syringe by flowing at least one of the components through the conduit.
  • the second component can include a contrast agent.
  • the second component can include a drug.
  • the method can include loading a second composition in the second compartment.
  • the second composition can include polymer particles.
  • the first component and second component can be delivered sequentially.
  • the first component and the second component can include polymer particles of different sizes or alternatively, of different shapes.
  • the first component can include particles that are substantially spherical.
  • Embodiments may include one or more advantages. For example, pre-mixing the components may be undesirable because the shelf life of the mixed composition may be reduced for e.g., due to chemical interactions between a contrast agent and embolic particles.
  • pre-mixing the components may be undesirable because the shelf life of the mixed composition may be reduced for e.g., due to chemical interactions between a contrast agent and embolic particles.
  • FIG. 1 A is a cross-sectional schematic of a syringe apparatus for mixing and delivery of a composition into the body.
  • FIG. IB is an enlarged cross-sectional view showing a failure membrane of the syringe of FIG. 1A.
  • FIG. 1C is a top view of the failure membrane of the syringe of FIG. 1 A.
  • FIG ID illustrates mixing of the components using the syringe of FIG. 1 A.
  • FIG. IE illustrates delivery of a mixture through a catheter using the syringe of FIG. 1A.
  • FIG. 2 is a schematic of a kit for mixing and delivery of a composition.
  • FIG. 3 A is a cross-sectional schematic of a syringe apparatus for mixing and delivery of a composition into the body.
  • FIG. 3B is a top view of a failure membrane of the syringe of FIG. 3 A.
  • FIGS. 3C and 3D illustrate mixing of the components of a composition using the syringe system of FIG. 3 A.
  • FIG. 3E illustrates delivery of a mixture through a catheter using the syringe of FIG 3A.
  • FIG. 4A is a cross-sectional schematic of a syringe apparatus for mixing and delivery of a composition into the body.
  • FIG. 4B illustrates mixing of the components of a composition using the syringe of FIG. 4 A
  • FIG. 4C illustrates delivery of a composition through a catheter using the syringe of FIG. 4 A.
  • FIG. 4D is a top view of a plunger lock of the syringe of FIG. 4 A.
  • FIG. 5 A is a cross-sectional schematic of a syringe apparatus for mixing and delivery of particles of different sizes.
  • FIG. 5B is a cross-sectional schematic of a syringe apparatus for mixing and delivery of particles of different shapes. Like reference symbols in the various drawings indicate like elements.
  • a syringe apparatus 1 includes a body with an upper compartment 2, a lower compartment 3, a plunger 4 with a plunger base 11 , a membrane 5, and a connector 9, which could be a luer connector, fitted with a stopcock 10.
  • the lower compartment 3 contains a contrast agent 6 and the upper compartment 2 contains a combination of particles such as embolic particles 7 and a hydrating fluid such as saline 8.
  • the upper compartment 2 and lower compartment 3 are fitted together at junction 19.
  • the membrane 5 can be made of a polymer material or of cellulose based materials, such as cellulose acetate, that provides a liquid-tight seal between the upper and lower compartments so that the contrast agent may be isolated from interaction with the embolic material and saline mixture until the time of injection into the body.
  • the membrane 5 has a failure region 13 and a hinge region 14.
  • the failure and hinge regions can be regions of reduced thickness.
  • the thickness of the failure region 13 is less than the thickness of the hinge region 14 such that the membrane will fail preferentially at the failure region 13 and bend preferentially at the hinge region 14, in response to pressure increase in the upper compartment 2.
  • FIG. 1C a top view of the membrane 5 is illustrated showing the failure region 13 extending substantially around most of the circumference of the membrane, and the hinge region 14 extending along a short segment of the circumference.
  • the reduced thickness regions of the membrane can be formed by heating, scoring or laser ablation.
  • the embolic particles and saline in the upper compartment 2 travel to the lower compartment 3 and mix with the contrast agent to form the mixed embolic composition
  • the particles fall into the contrast solution in a turbulent manner which enhances mixing and the creation of a uniform suspension of the particles in the mixture.
  • the stopcock 10 is opened to allow the mixed embolic composition 15 to pass via the connector 9, through a catheter 16 for injection into the body (not shown).
  • the plunger can be further lowered to apply pressure for injecting the mixture into the body.
  • the stopcock 10 can be eliminated where the flow resistance of the syringe outlet and any attached delivery apparatus, such as a catheter, is sufficient to retard flow of solution in response to the pressure in the syringe after rupturing the membrane.
  • the plunger base 11 may be made of a flexible rubbery material, such as an elastomeric polymeric material, that can deflect or bend when it engages the membrane so that the plunger can be lowered beyond the membrane into the lower compartment for injection of the mixture into the body.
  • a flexible rubbery material such as an elastomeric polymeric material
  • the kit includes a syringe barrel made of two detachable sections, 20 and 22, defining the upper compartment 2 and the lower compartment 3, a plunger 4 with a base 11, a vial 24 of embolic material 7 in saline 8, and a vial 26 of contrast agent 6.
  • the upper section 20 of the syringe apparatus has a female-type connector 21 at its bottom end to fit with a male-type connector 23 at the top of the lower section 22.
  • the connection between the upper and lower sections can be, for example, a pressfit, threaded or luer type connection.
  • the lower section 22 has a connector 9 fitted with a stopcock 10.
  • Failure membrane 5 can be placed between the upper and lower sections or can be preattached to one of the sections; in FIG 2 the membrane is attached to the upper section.
  • the syringe apparatus is assembled as follows: Stopcock 10 is closed and contrast solution 6 from vial 26 is placed in the lower compartment 3 and the upper section is assembled with the lower section. Embolic material 7 along with saline solution 8 is placed in the upper compartment from vial 24. The plunger 4 is then placed in the upper compartment to complete the syringe assembly.
  • the syringe can be provided commercially as a kit with the compartments preloaded with the appropriate components.
  • FIGS. 3A-3E another embodiment of the syringe apparatus is illustrated.
  • the failure membrane 30 is weakened across the center 31, as illustrated in FIG 3B, for rupture on application of pressure.
  • the rest of the syringe apparatus is as in the first embodiment illustrated in FIG. 1.
  • the stopcock 10 is closed, and when pressure is applied to the upper compartment by depressing the plunger 4, the base 11 of the plunger conveys the applied pressure onto the failure membrane 30 causing its rupture at the weakened regions 31 (to form leaflets).
  • the contents of the upper compartment 2 travel to the lower compartment 3 and mix with it to form the mixed embolic composition 15.
  • the plunger 4 is withdrawn, which causes the embolic composition 15 to backfill the upper compartment. This causes further mixing of the components of the embolic mixture and also prepares the apparatus for delivery of the embolic composition 15.
  • stopcock 10 is opened and the plunger 4 is depressed to allow the embolic composition 15 to pass through the connector 9 to the catheter 16 for injection into the body (not shown).
  • the upper or lower compartments, or both upper and lower compartments can include a vent valve on the sidewall, (upper vent valve 33 shown in phantom in FIG. 3 A) to enable pressure control within the syringe apparatus.
  • a syringe barrel 40 is provided that has parallel compartments, including a left compartment 41 with a plunger 42, and a right compartment 43, with a plunger 44, both plungers 42 and 44 are fitted with a plunger lock 50.
  • the plunger locks 50 prevent accidental deployment of the plungers.
  • An expanded view of the plunger lock is illustrated in FIG. 4D.
  • the plunger lock 50 includes a frame 54 consisting of a stationary vertical strip 56 placed towards one end of the frame and a movable vertical strip 57 placed towards the other end of the frame, with a threaded hole 58 at the center of the strip 57, through which a screw 59 is passed.
  • the space between the two strips 56 and 57 houses the stem of the plunger.
  • the strip 57 is moved until the stem of the plunger is tightly held between strips 56 and 57.
  • Counterclockwise movement of the screw 59 further secures the plunger tightly between the two strips 56 and 57.
  • the screw 59 is turned clockwise and the strip 57 is moved away from the plunger which loosens the grip of the two strips 57 and 58 on the stem of the plunger and unlocks the plunger for deployment.
  • the plunger locks can be made of a metallic or polymeric material.
  • the plunger lock 50 is unlocked, the strip 57 is moved towards the frame, and the lock is slid onto the stem of the plunger from the top and is placed in any desired position on the stem of the plunger.
  • the compartments are divided by a central divider 45 with a pressure-activated two-way valve 46 at the end of the central divider 45, connecting the two compartments.
  • the pressure-activated valve can include a polymer membrane 47 that can flex into either compartment based on the pressure differential between the compartments.
  • a connector 48, at the bottom of the syringe assembly communicates with both compartments of the syringe and is fitted with a stopcock 49.
  • the left compartment 41 contains the contrast solution 6, and the right compartment 43 contains a mixture of embolic particles 7 and saline solution 8.
  • the stopcock 49 is closed, the two plunger locks 50 on the left and right plungers 42 and 44 are unlocked, and the right plunger 44 is lowered causing the membrane 47 to flex into the left compartment and the valve 46 to open. Embolic particles and saline travel to the left compartment (arrow) and mix with the contrast solution to form the embolic mixture 15. Further thorough mixing may be achieved by repeated alternate operation of the two plungers, 42 and 44.
  • the stopcock 49 is opened, the two plungers 42 and 44 are simultaneously depressed such that the embolic mixture 15 passes via the connector 48 through the catheter 16 for injection into the body (not shown). (Alternatively, the plungers can be depressed sequentially.)
  • the valve membrane can be a failure membrane.
  • FIG. 5 A and FIG. 5B another embodiment of the syringe apparatus is illustrated.
  • the central divider 45 extends up to the connector 48 at the bottom of the syringe assembly.
  • the left and right compartments 41 and 43 contain two different sizes of embolic particles, a smaller size 60, and a larger size 62, mixed with saline and/or contrast agent.
  • the left and right compartments 41 and 43 contain two different shapes, a spherical shape 64, and an irregular shape 66, of embolic particles mixed with saline and or contrast agent.
  • the rest of the syringe apparatus is as in the embodiment described in FIG. 4.
  • the arrangement allows delivery of two different sizes of embolic particles sequentially or simultaneously by sequential or simultaneous operation of the plungers. For example, smaller particles can be delivered first to travel to smaller diameter vessels, followed by larger particles to occlude vessels of larger diameter, upstream of the small diameter vessels.
  • two different shapes of embolic particles can be delivered sequentially (or simultaneously). For example, spherical particles may be delivered first to aggregate and occlude distal regions and the irregular particles may be delivered second for more proximal aggregation.
  • embolic particles in saline are disposed in the compartments from the top of the syringe, after removing the plungers. Contrast agent is drawn into each compartment from a supply in communication with the connector 48 by releasing the appropriate plunger lock and withdrawing the appropriate plunger.
  • the syringe can be provided commercially as a kit with the compartments preloaded with the appropriate components.
  • the embolic composition with the desired embolic particle size and shape is injected into the body by release of the appropriate plunger lock, opening the stopcock 49, and depressing the appropriate plunger.
  • Suitable embolic particles are polymer particles.
  • Preferred particles are spherical particles formed of poly vinyl alcohol, as discussed in "Embolization”, USSN 10/215,594, filed August 9, 2002, the entire contents of which is incorporated herein by reference.
  • a suitable contrast agent is Omnipaque 300 (Nycomed, Buckinghamshire, UK).
  • Omnipaque is an aqueous solution of iohexol, N.N.-Bis (2,3-dihydroxypropyl)-T-[N-(2,3-dihydroxypropyl)-acetamide]-2,4,6-trilodo- isophthalamide; Omnipaque 300 contains 647 mg of iohexol equivalent to 300 mg of organic iodine per ml).
  • the syringe system can be used to premix and deliver other agents.
  • the systems can be used for mixing of drug agents, such as anti- cancer agents, with polymer particles as described in USSN 10/232,265, filed August 30, 2002.
  • the system can be used to premix compositions without particles.
  • a valve such as in Fig. 4 A can be used instead of the failure membrane in Fig. 1 A.
  • a membrane can be used that is not pressure-activated.
  • the membrane can be deflected by a control lever operable from outside of the syringe barrel.
  • a sharpened member can be located on the plunger head that pierces the membrane. Still further embodiments are in the following claims.

Abstract

In one aspect the invention features a mixing and delivery medical syringe system including a barrel with first and second detachable sections, and first and second compartments communicable through a conduit. In another aspect the invention feature a mixing and delivery medical syringe system including a barrel having first and second compartments arranged in aprallel along the barrel, the compartments communicable through a pressure activated conduit. In still another aspect, the ivention features a kit for medicant mixing and delivery, including a syringe system, which includes a barrel assembled from multiple sections, including a first section having a first chamber, and a second section having a second chamber. The syringe system includes a conduit between the first and second chambers through which flow can be controlled. The kit further includes a first container containing a first composition, and a second container containing a second composition.

Description

MIXING AND DELIVERY OF THERAPEUTIC COMPOSITIONS
TECHNICAL FIELD
This invention relates to mixing and delivery of therapeutic compositions.
BACKGROUND
Therapeutic vascular occlusions (embolizations) are induced by the introduction of various substances (embolic material, such as embolic particles) into a patient's circulatory system for the purpose of occluding vessels, either to arrest or to prevent hemorrhaging or to defunctionalize a structure or an organ. Typically, the components of an embolic composition - embolic particles in hydrating material (such as saline) and contrast agent (used for tracking the path of the embolic particles inside the body) are stored separately and mixed together at the time of injection into the body by the physician.
SUMMARY
In one aspect the invention features a mixing and delivery medical syringe system. The medical syringe system includes a barrel including first and second detachable sections, and first and second compartments communicable through a conduit.
In another aspect the invention feature a mixing and delivery medical syringe system. The medical syringe system includes a barrel having first and second compartments arranged in parallel along the barrel, the compartments communicable through a pressure-activated conduit.
In another aspect, the invention features a kit for medicant mixing and delivery, including a syringe system, which includes a barrel assembled from multiple sections, including a first section having a first chamber, and a second section having a second chamber. The syringe system includes a conduit between the first and second chambers through which flow can be controlled. The kit further includes a first container containing a first composition, and a second container containing a second composition.
In another aspect, the invention features a method for delivering injectable polymer particles by providing a syringe. The syringe includes a first compartment and a second compartment. A first component including injectable particles is loaded into at least one compartment, and the syringe is actuated to deliver the particles.
Embodiments can include one or more of the following. The conduit can include a pressure-activated separator. The separator can include a failure membrane. The failure membrane can include a weakened region. The weakened region preferentially effects rupture about a central region of the membrane. The weakened region preferentially affects rupture such that an attachment portion is not ruptured. The pressure-activated conduit can include a valve.
The first and the second compartments can be arranged serially along the syringe barrel. The barrel can include a vent valve. The barrel can include a fluid outlet and the outlet can include a valve. The first section can include the first chamber and the second section can include the second chamber. The conduit can be in one of the first or second sections.
The first composition can include injectable polymer particles. The particles can be embolic particles. The second composition can be a contrast agent. Alternatively, the second composition can include an anticancer agent.
The syringe can include a conduit between the compartments. A first component including injectable particles is loaded into at least one compartment and a second component is loaded into the second compartment. The first component and the second component are mixed in the syringe by flowing at least one of the components through the conduit. The second component can include a contrast agent. The second component can include a drug.
The method can include loading a second composition in the second compartment. The second composition can include polymer particles. The first component and second component can be delivered sequentially.
The first component and the second component can include polymer particles of different sizes or alternatively, of different shapes. The first component can include particles that are substantially spherical.
Embodiments may include one or more advantages. For example, pre-mixing the components may be undesirable because the shelf life of the mixed composition may be reduced for e.g., due to chemical interactions between a contrast agent and embolic particles. The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, aspects, and advantages of the invention will be apparent from the description and drawings, and from the claims.
DESCRIPTION OF DRAWINGS
FIG. 1 A is a cross-sectional schematic of a syringe apparatus for mixing and delivery of a composition into the body.
FIG. IB is an enlarged cross-sectional view showing a failure membrane of the syringe of FIG. 1A.
FIG. 1C is a top view of the failure membrane of the syringe of FIG. 1 A.
FIG ID illustrates mixing of the components using the syringe of FIG. 1 A.
FIG. IE illustrates delivery of a mixture through a catheter using the syringe of FIG. 1A.
FIG. 2 is a schematic of a kit for mixing and delivery of a composition.
FIG. 3 A is a cross-sectional schematic of a syringe apparatus for mixing and delivery of a composition into the body.
FIG. 3B is a top view of a failure membrane of the syringe of FIG. 3 A.
FIGS. 3C and 3D illustrate mixing of the components of a composition using the syringe system of FIG. 3 A.
FIG. 3E illustrates delivery of a mixture through a catheter using the syringe of FIG 3A.
FIG. 4A is a cross-sectional schematic of a syringe apparatus for mixing and delivery of a composition into the body.
FIG. 4B illustrates mixing of the components of a composition using the syringe of FIG. 4 A
FIG. 4C illustrates delivery of a composition through a catheter using the syringe of FIG. 4 A.
FIG. 4D is a top view of a plunger lock of the syringe of FIG. 4 A.
FIG. 5 A is a cross-sectional schematic of a syringe apparatus for mixing and delivery of particles of different sizes.
FIG. 5B is a cross-sectional schematic of a syringe apparatus for mixing and delivery of particles of different shapes. Like reference symbols in the various drawings indicate like elements.
DETAILED DESCRIPTION
Referring to FIG. 1 A, a syringe apparatus 1 includes a body with an upper compartment 2, a lower compartment 3, a plunger 4 with a plunger base 11 , a membrane 5, and a connector 9, which could be a luer connector, fitted with a stopcock 10. The lower compartment 3 contains a contrast agent 6 and the upper compartment 2 contains a combination of particles such as embolic particles 7 and a hydrating fluid such as saline 8. The upper compartment 2 and lower compartment 3 are fitted together at junction 19. The membrane 5 can be made of a polymer material or of cellulose based materials, such as cellulose acetate, that provides a liquid-tight seal between the upper and lower compartments so that the contrast agent may be isolated from interaction with the embolic material and saline mixture until the time of injection into the body.
Referring to FIGS. IB and 1C, expanded views of the membrane 5 are illustrated. The membrane 5 has a failure region 13 and a hinge region 14. In one embodiment, the failure and hinge regions can be regions of reduced thickness. The thickness of the failure region 13 is less than the thickness of the hinge region 14 such that the membrane will fail preferentially at the failure region 13 and bend preferentially at the hinge region 14, in response to pressure increase in the upper compartment 2. Referring to FIG. 1C, a top view of the membrane 5 is illustrated showing the failure region 13 extending substantially around most of the circumference of the membrane, and the hinge region 14 extending along a short segment of the circumference. The reduced thickness regions of the membrane can be formed by heating, scoring or laser ablation.
Referring to FIG. ID, with the stopcock 10 closed, pressure is applied in the upper compartment by depressing the plunger. The applied pressure on the failure membrane 5 causes it to rupture at the failure region 13 and to bend at the hinge region
14. The embolic particles and saline in the upper compartment 2 travel to the lower compartment 3 and mix with the contrast agent to form the mixed embolic composition
15. Because the embolic particles are initially located in the upper compartment and the contrast in the lower compartment, the particles fall into the contrast solution in a turbulent manner which enhances mixing and the creation of a uniform suspension of the particles in the mixture.
Referring to FIG. IE, the stopcock 10 is opened to allow the mixed embolic composition 15 to pass via the connector 9, through a catheter 16 for injection into the body (not shown). The plunger can be further lowered to apply pressure for injecting the mixture into the body. In other embodiments, the stopcock 10 can be eliminated where the flow resistance of the syringe outlet and any attached delivery apparatus, such as a catheter, is sufficient to retard flow of solution in response to the pressure in the syringe after rupturing the membrane. The plunger base 11, particularly its circumference, may be made of a flexible rubbery material, such as an elastomeric polymeric material, that can deflect or bend when it engages the membrane so that the plunger can be lowered beyond the membrane into the lower compartment for injection of the mixture into the body.
Referring to FIG. 2, a syringe kit is illustrated. The kit includes a syringe barrel made of two detachable sections, 20 and 22, defining the upper compartment 2 and the lower compartment 3, a plunger 4 with a base 11, a vial 24 of embolic material 7 in saline 8, and a vial 26 of contrast agent 6. The upper section 20 of the syringe apparatus has a female-type connector 21 at its bottom end to fit with a male-type connector 23 at the top of the lower section 22. The connection between the upper and lower sections can be, for example, a pressfit, threaded or luer type connection. The lower section 22 has a connector 9 fitted with a stopcock 10. Failure membrane 5 can be placed between the upper and lower sections or can be preattached to one of the sections; in FIG 2 the membrane is attached to the upper section. For use, the syringe apparatus is assembled as follows: Stopcock 10 is closed and contrast solution 6 from vial 26 is placed in the lower compartment 3 and the upper section is assembled with the lower section. Embolic material 7 along with saline solution 8 is placed in the upper compartment from vial 24. The plunger 4 is then placed in the upper compartment to complete the syringe assembly. The syringe can be provided commercially as a kit with the compartments preloaded with the appropriate components.
Referring to FIGS. 3A-3E, another embodiment of the syringe apparatus is illustrated. Here the failure membrane 30 is weakened across the center 31, as illustrated in FIG 3B, for rupture on application of pressure. The rest of the syringe apparatus is as in the first embodiment illustrated in FIG. 1. Referring to FIG. 3C, the stopcock 10 is closed, and when pressure is applied to the upper compartment by depressing the plunger 4, the base 11 of the plunger conveys the applied pressure onto the failure membrane 30 causing its rupture at the weakened regions 31 (to form leaflets). The contents of the upper compartment 2 travel to the lower compartment 3 and mix with it to form the mixed embolic composition 15. Because the embolic particles are initially located in the upper compartment and the contrast in the lower compartment, the particles fall into the contrast solution in a turbulent manner which enhances mixing and the creation of a uniform suspension of the particles in the mixture. Referring to FIG. 3D, the plunger 4 is withdrawn, which causes the embolic composition 15 to backfill the upper compartment. This causes further mixing of the components of the embolic mixture and also prepares the apparatus for delivery of the embolic composition 15. Referring to FIG. 3E, stopcock 10 is opened and the plunger 4 is depressed to allow the embolic composition 15 to pass through the connector 9 to the catheter 16 for injection into the body (not shown). In other embodiments, the upper or lower compartments, or both upper and lower compartments can include a vent valve on the sidewall, (upper vent valve 33 shown in phantom in FIG. 3 A) to enable pressure control within the syringe apparatus.
Referring to FIG. 4A, in another embodiment, a syringe barrel 40 is provided that has parallel compartments, including a left compartment 41 with a plunger 42, and a right compartment 43, with a plunger 44, both plungers 42 and 44 are fitted with a plunger lock 50. The plunger locks 50 prevent accidental deployment of the plungers. An expanded view of the plunger lock is illustrated in FIG. 4D. The plunger lock 50 includes a frame 54 consisting of a stationary vertical strip 56 placed towards one end of the frame and a movable vertical strip 57 placed towards the other end of the frame, with a threaded hole 58 at the center of the strip 57, through which a screw 59 is passed. The space between the two strips 56 and 57 houses the stem of the plunger. In use, to lock the plunger and prevent its deployment, the strip 57 is moved until the stem of the plunger is tightly held between strips 56 and 57. Counterclockwise movement of the screw 59 further secures the plunger tightly between the two strips 56 and 57. To unlock the plunger for deployment, the screw 59 is turned clockwise and the strip 57 is moved away from the plunger which loosens the grip of the two strips 57 and 58 on the stem of the plunger and unlocks the plunger for deployment. The plunger locks can be made of a metallic or polymeric material. To place the plunger lock 50 on the stem of the plunger, the plunger lock 50 is unlocked, the strip 57 is moved towards the frame, and the lock is slid onto the stem of the plunger from the top and is placed in any desired position on the stem of the plunger.
The compartments are divided by a central divider 45 with a pressure-activated two-way valve 46 at the end of the central divider 45, connecting the two compartments. The pressure-activated valve can include a polymer membrane 47 that can flex into either compartment based on the pressure differential between the compartments. A connector 48, at the bottom of the syringe assembly communicates with both compartments of the syringe and is fitted with a stopcock 49. The left compartment 41 contains the contrast solution 6, and the right compartment 43 contains a mixture of embolic particles 7 and saline solution 8.
Referring to FIG. 4B, the stopcock 49 is closed, the two plunger locks 50 on the left and right plungers 42 and 44 are unlocked, and the right plunger 44 is lowered causing the membrane 47 to flex into the left compartment and the valve 46 to open. Embolic particles and saline travel to the left compartment (arrow) and mix with the contrast solution to form the embolic mixture 15. Further thorough mixing may be achieved by repeated alternate operation of the two plungers, 42 and 44. Referring to Fig 4C, the stopcock 49 is opened, the two plungers 42 and 44 are simultaneously depressed such that the embolic mixture 15 passes via the connector 48 through the catheter 16 for injection into the body (not shown). (Alternatively, the plungers can be depressed sequentially.) In other embodiments, the valve membrane can be a failure membrane.
Referring to FIG. 5 A and FIG. 5B, another embodiment of the syringe apparatus is illustrated. In this embodiment, there is no two-way valve connecting the two compartments. The central divider 45 extends up to the connector 48 at the bottom of the syringe assembly. Referring to FIG. 5 A, the left and right compartments 41 and 43 contain two different sizes of embolic particles, a smaller size 60, and a larger size 62, mixed with saline and/or contrast agent. Referring to FIG. 5B, the left and right compartments 41 and 43 contain two different shapes, a spherical shape 64, and an irregular shape 66, of embolic particles mixed with saline and or contrast agent. The rest of the syringe apparatus is as in the embodiment described in FIG. 4. The arrangement allows delivery of two different sizes of embolic particles sequentially or simultaneously by sequential or simultaneous operation of the plungers. For example, smaller particles can be delivered first to travel to smaller diameter vessels, followed by larger particles to occlude vessels of larger diameter, upstream of the small diameter vessels. Alternatively, two different shapes of embolic particles can be delivered sequentially (or simultaneously). For example, spherical particles may be delivered first to aggregate and occlude distal regions and the irregular particles may be delivered second for more proximal aggregation.
In use, embolic particles in saline are disposed in the compartments from the top of the syringe, after removing the plungers. Contrast agent is drawn into each compartment from a supply in communication with the connector 48 by releasing the appropriate plunger lock and withdrawing the appropriate plunger. The syringe can be provided commercially as a kit with the compartments preloaded with the appropriate components. For injection into the body, the embolic composition with the desired embolic particle size and shape is injected into the body by release of the appropriate plunger lock, opening the stopcock 49, and depressing the appropriate plunger.
The mixing and delivery system discussed above can be used to deliver a number of compositions. Suitable embolic particles are polymer particles. Preferred particles are spherical particles formed of poly vinyl alcohol, as discussed in "Embolization", USSN 10/215,594, filed August 9, 2002, the entire contents of which is incorporated herein by reference. A suitable contrast agent is Omnipaque 300 (Nycomed, Buckinghamshire, UK). (Omnipaque is an aqueous solution of iohexol, N.N.-Bis (2,3-dihydroxypropyl)-T-[N-(2,3-dihydroxypropyl)-acetamide]-2,4,6-trilodo- isophthalamide; Omnipaque 300 contains 647 mg of iohexol equivalent to 300 mg of organic iodine per ml). The syringe system can be used to premix and deliver other agents. For example, the systems can be used for mixing of drug agents, such as anti- cancer agents, with polymer particles as described in USSN 10/232,265, filed August 30, 2002. The system can be used to premix compositions without particles. A valve, such as in Fig. 4 A can be used instead of the failure membrane in Fig. 1 A. A membrane can be used that is not pressure-activated. For example, the membrane can be deflected by a control lever operable from outside of the syringe barrel. In another example, a sharpened member can be located on the plunger head that pierces the membrane. Still further embodiments are in the following claims.

Claims

WHAT IS CLAIMED IS:
1. A mixing and delivery medical syringe system, comprising: a barrel including first and second detachable sections, and first and second compartments communicable through a conduit.
2. The system of claim 1, wherein the conduit includes a pressure-activated separator.
3. The system of claim 2, wherein the separator includes a failure membrane.
4. The system of claim 3, wherein the failure membrane includes a weakened region.
5. The system of claim 4, wherein the weakened region preferentially effects rupture about a center region of the membrane.
6. The system of claim 4 wherein the weakened region preferentially affects rupture such that an attachment portion is not ruptured.
7. The system of claim 1, wherein the pressure-activated conduit includes a valve.
8. The system of claim 1, wherein the first compartment and the second compartment are arranged serially along the barrel.
9. The system of claim 1, wherein the barrel includes a vent valve.
10. The system of claim 1, wherein the barrel includes a fluid outlet and the outlet includes a valve.
11. The system of claim 1 , wherein the first section includes the first chamber and the second section includes the second chamber.
12. The system of claim 11, wherein the conduit is in one of the first or second sections.
13. A mixing and delivery medical syringe system including a barrel having first and second compartments arranged in parallel along the barrel, the compartments communicable through a pressure-activated conduit.
14. The system of claim 13 wherein the conduit includes a valve.
15. A kit for medicant mixing and delivery, comprising: a syringe system including a barrel assembled from multiple sections, including a first section having a first chamber, and a second section having a second chamber, the syringe system including a conduit between the first and second chambers through which flow can be controlled, and a first container of a first composition, and a second container of a second composition.
16. The kit of claim 15 wherein the first composition includes injectable polymer particles.
17. The kit of claim 16 wherein the particles are embolic particles.
18. The kit of claims 15 or 16 wherein the second composition is a contrast agent.
19. The kit of claims 15 or 16 wherein the second composition is an anticancer agent.
20. A method for delivering injectable polymer particles, the method comprising: providing a syringe including a first compartment and a second compartment, loading a first component including injectable particles into at least one compartment, and actuating the syringe to deliver said particles.
21. The method of claim 20, the method comprising: providing a syringe including a conduit between said compartments, and loading a second component into said second compartment, and mixing said first component and said second component in the syringe by flowing at least one of said components through said conduit.
22. The method of claim 21 , wherein said second component includes contrast agent.
23. The method of claim 21, wherein said second component includes a drug.
24. The method of claim 20, the method comprising loading a second composition in said second compartment, said second composition including polymer particles and delivering said first component and second component sequentially.
25. The method of claim 24, wherein the first and second components include polymer particles of different sizes.
26. The method of claim 24, wherein the first and second components include polymer particles of different shapes.
27. The method of claim 26, wherein the first component includes particles that are substantially spherical.
PCT/US2003/033674 2002-10-23 2003-10-22 Mixing and delivery medical syringe system for therapeutic compositions WO2004037326A2 (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2010101255B4 (en) * 2010-11-15 2011-09-22 Lumsden, Andrew A prefilled syringe for administering buffered lignocaine
EP2806921A4 (en) * 2012-01-23 2015-11-25 Merit Medical Systems Inc Mixing syringe
WO2017089280A1 (en) * 2015-11-27 2017-06-01 Sanofi-Aventis Deutschland Gmbh Injection apparatus
US9751056B2 (en) 2012-01-23 2017-09-05 Merit Medical Systems, Inc. Mixing syringe

Families Citing this family (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE01918975T1 (en) 2000-03-24 2006-04-13 Biosphere Medical, Inc., Rockland Microspheres for active embolization
US20030212022A1 (en) * 2001-03-23 2003-11-13 Jean-Marie Vogel Compositions and methods for gene therapy
US7462366B2 (en) 2002-03-29 2008-12-09 Boston Scientific Scimed, Inc. Drug delivery particle
US7053134B2 (en) * 2002-04-04 2006-05-30 Scimed Life Systems, Inc. Forming a chemically cross-linked particle of a desired shape and diameter
US7842377B2 (en) * 2003-08-08 2010-11-30 Boston Scientific Scimed, Inc. Porous polymeric particle comprising polyvinyl alcohol and having interior to surface porosity-gradient
US8012454B2 (en) * 2002-08-30 2011-09-06 Boston Scientific Scimed, Inc. Embolization
US7976823B2 (en) 2003-08-29 2011-07-12 Boston Scientific Scimed, Inc. Ferromagnetic particles and methods
US7901770B2 (en) 2003-11-04 2011-03-08 Boston Scientific Scimed, Inc. Embolic compositions
US7736671B2 (en) 2004-03-02 2010-06-15 Boston Scientific Scimed, Inc. Embolization
US8173176B2 (en) 2004-03-30 2012-05-08 Boston Scientific Scimed, Inc. Embolization
US7998106B2 (en) 2004-05-03 2011-08-16 Thorne Jr Gale H Safety dispensing system for hazardous substances
US7311861B2 (en) * 2004-06-01 2007-12-25 Boston Scientific Scimed, Inc. Embolization
GB2409162B (en) * 2004-10-06 2005-12-14 Bhk Holding Ltd Materials,methods,and apparatus for treating a body cavity
US7581899B2 (en) * 2004-11-30 2009-09-01 James Alexander Corporation Dispenser and process
US8425550B2 (en) 2004-12-01 2013-04-23 Boston Scientific Scimed, Inc. Embolic coils
US7727555B2 (en) 2005-03-02 2010-06-01 Boston Scientific Scimed, Inc. Particles
US7858183B2 (en) 2005-03-02 2010-12-28 Boston Scientific Scimed, Inc. Particles
US7963287B2 (en) 2005-04-28 2011-06-21 Boston Scientific Scimed, Inc. Tissue-treatment methods
CN104815331A (en) 2005-05-09 2015-08-05 生物领域医疗公司 Compositions and methods using microspheres and non-ionic contrast agents
US9463426B2 (en) 2005-06-24 2016-10-11 Boston Scientific Scimed, Inc. Methods and systems for coating particles
US8007509B2 (en) 2005-10-12 2011-08-30 Boston Scientific Scimed, Inc. Coil assemblies, components and methods
US8152839B2 (en) 2005-12-19 2012-04-10 Boston Scientific Scimed, Inc. Embolic coils
US8101197B2 (en) 2005-12-19 2012-01-24 Stryker Corporation Forming coils
US7947368B2 (en) 2005-12-21 2011-05-24 Boston Scientific Scimed, Inc. Block copolymer particles
WO2007090127A2 (en) 2006-01-30 2007-08-09 Surgica Corporation Compressible intravascular embolization particles and related methods and delivery systems
WO2007090130A2 (en) * 2006-01-30 2007-08-09 Surgica Corporation Porous intravascular embolization particles and related methods
DE102006015238A1 (en) * 2006-03-30 2007-10-04 S&C Polymer Silicon- und Composite-Spezialitäten GmbH Disposable packaging for storage, mixing and extraction of multi-component materials for e.g. medicinal and dental applications, includes membrane ruptured by pointed object to permit mixing
US7976234B2 (en) 2006-04-28 2011-07-12 James Alexander Corporation Multi-chambered dispenser and process
US8414927B2 (en) 2006-11-03 2013-04-09 Boston Scientific Scimed, Inc. Cross-linked polymer particles
US8382704B2 (en) 2006-12-29 2013-02-26 Medrad, Inc. Systems and methods of delivering a dilated slurry to a patient
US8910830B2 (en) 2007-12-18 2014-12-16 James Alexander Corporation Container assembly
US8100294B2 (en) 2007-12-18 2012-01-24 James Alexander Corporation Container assembly
US8403178B2 (en) 2007-12-18 2013-03-26 James Alexander Corporation Container assembly
ATE548285T1 (en) 2008-01-29 2012-03-15 James Alexander Corp DONOR
US8834014B2 (en) * 2008-03-24 2014-09-16 Sashco, Inc. System for providing custom colored sealing compound
US8800816B2 (en) * 2009-03-24 2014-08-12 Sashco, Inc. System and method of providing individual quantities of custom colored sealing compound
US9107668B2 (en) * 2008-03-25 2015-08-18 Cook Medical Technologies Llc Embolic particle mixing syringe
CN102143996A (en) * 2008-10-30 2011-08-03 大卫·刘 Micro-spherical porous biocompatible scaffolds and methods and apparatus for fabricating same
US20100256646A1 (en) * 2009-04-01 2010-10-07 Frank Pinal Orthobiologics delivery tool
US8657481B2 (en) 2010-01-15 2014-02-25 Spine Wave, Inc. Systems and methods for mixing fluids
WO2012064761A2 (en) * 2010-11-08 2012-05-18 Aktivpak, Inc. Beneficial agent dispenser
WO2012063825A1 (en) * 2010-11-10 2012-05-18 オリンパスメディカルシステムズ株式会社 Surgical device and ultrasonic treatment method
EP2508219B1 (en) * 2011-04-05 2018-06-06 Kpr U.S., Llc Buffering agent delivery system for anesthetic syringe
WO2015006444A1 (en) * 2013-07-10 2015-01-15 Merit Medical Systems, Inc. Pre-loaded syringes and methods related thereto
US11260177B1 (en) * 2014-03-18 2022-03-01 Yasser Sadek Dental anesthetic buffer system
US20180085555A1 (en) * 2016-09-26 2018-03-29 Boston Scientific Scimed, Inc. Injection catheter
US11324673B2 (en) 2016-11-18 2022-05-10 Miraki Innovation Think Tank Llc Cosmetic appearance of skin
US11266761B2 (en) * 2016-12-05 2022-03-08 Cast21, Inc. System for forming a rigid support
KR102589816B1 (en) 2017-04-05 2023-10-16 미라키 이노베이션 씽크 탱크 엘엘씨 Low-temperature slurry containment
MX2019011995A (en) 2017-04-05 2020-01-20 Miraki Innovation Think Tank Llc Point of delivery cold slurry generation.
US10500342B2 (en) 2017-08-21 2019-12-10 Miraki Innovation Think Tank Llc Cold slurry syringe
AU2020325205B2 (en) * 2019-08-06 2023-11-02 Microvention, Inc. Syringe

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1099362A (en) * 1954-04-23 1955-09-05 D Antibiotiques Et De Biolog L Capsule syringe for drugs that only need to be mixed at the time of use
GB743789A (en) * 1953-02-22 1956-01-25 Hubert Percival Schofield Improvements in or relating to cartridges and the like tubular containers for use in dispensing liquids
FR1478062A (en) * 1965-04-30 1967-04-21 Ile D Etudes Et De Brevets Nov Injection syringe
US4254768A (en) * 1979-09-14 1981-03-10 Ty Perla J Hypodermic syringe
US4412836A (en) * 1979-04-27 1983-11-01 The West Company, Incorporated Syringe assembly
US4453934A (en) * 1981-11-11 1984-06-12 Contraves Ag Injection syringe for the successive injection of two liquids into the blood vessels of living bodies
EP0112574A1 (en) * 1982-12-27 1984-07-04 Meditec S.A. Two-compartment prefilled syringe
US5704918A (en) * 1992-12-01 1998-01-06 Higashikawa; Tetsuro Syringe

Family Cites Families (335)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2275154A (en) 1940-07-10 1942-03-03 United Drug Company Method for making capsules
US2609347A (en) 1948-05-27 1952-09-02 Wilson Christopher Lumley Method of making expanded polyvinyl alcohol-formaldehyde reaction product and product resulting therefrom
JPS4820019B1 (en) 1969-06-05 1973-06-18
US3737398A (en) 1969-11-13 1973-06-05 D Yamaguchi Method of making a polyvinyl acetal sponge buff
CS179075B1 (en) 1974-11-26 1977-10-31 Stoy Vladimir Mode of manufacture of spherical particles from polymer
US4076640A (en) 1975-02-24 1978-02-28 Xerox Corporation Preparation of spheroidized particles
US3957933A (en) 1975-03-05 1976-05-18 General Atomic Company Apparatus for producing microspherical particles and method for operating such apparatus
JPS51135958A (en) 1975-05-20 1976-11-25 Fuji Photo Film Co Ltd Method of making fine powder polymer having pores
US4025686A (en) 1975-06-26 1977-05-24 Owens-Corning Fiberglas Corporation Molded composite article and method for making the article
US4034759A (en) 1975-08-27 1977-07-12 Xomed, Inc. Moisture-expandable prosthesis
US4098728A (en) 1976-01-02 1978-07-04 Solomon Rosenblatt Medical surgical sponge and method of making same
US4055377A (en) 1976-08-03 1977-10-25 Minnesota Mining And Manufacturing Company Magnetically orientable retroreflectorization particles
GB1591924A (en) 1976-10-25 1981-07-01 Berger Jenson & Nicholson Ltd Polymer aggregates
US4159719A (en) 1977-05-09 1979-07-03 Xomed, Inc. Moisture-expandable ear wick
US4437858A (en) * 1978-01-16 1984-03-20 Ty Perla J Separator disc and hypodermic syringe incorporating the same and method
ES478736A1 (en) 1978-03-23 1979-06-01 Hoechst Ag Polyvinyl alcohol pellets containing a plasticizer, and method for their preparation.
DE2834539A1 (en) 1978-08-07 1980-02-21 Basf Ag MACROPOROUS POLYMERS AS CARRIER MATERIAL FOR THE COVALENT BINDING OF PROTEINS
US4793980A (en) 1978-09-21 1988-12-27 Torobin Leonard B Hollow porous microspheres as substrates and containers for catalyst
US4243794A (en) 1978-10-10 1981-01-06 Minnesota Mining And Manufacturing Company Mixture of rough and spheroidized resin particles
US4198318A (en) 1978-11-24 1980-04-15 Conoco, Inc. Production of high strength alumina spheres by hydrogelling corresponding slurries
US4268495A (en) 1979-01-08 1981-05-19 Ethicon, Inc. Injectable embolization and occlusion solution
US4246208A (en) 1979-03-22 1981-01-20 Xerox Corporation Dust-free plasma spheroidization
US4346712A (en) 1979-04-06 1982-08-31 Kuraray Company, Ltd. Releasable balloon catheter
US4246794A (en) * 1979-07-23 1981-01-27 Huntington Alloys, Inc. Apparatus and method for ultrasonic inspection of round stock such as tubing, pipe and rod
HU184722B (en) 1980-02-18 1984-10-29 Laszlo Lazar Therapeutically suitable silicone rubber mixture and therapeuticaid
US4271281A (en) 1980-05-29 1981-06-02 American Hoechst Corporation Process for preparing styrenic polymer particles
DE3031737A1 (en) 1980-08-22 1982-04-01 Bayer Ag, 5090 Leverkusen METHOD FOR PRODUCING PEARL POLYMERISATS OF UNIFORM PARTICLE SIZE
CA1166413A (en) 1980-10-30 1984-05-01 Edward E. Timm Process and apparatus for preparing uniform size polymer beads
US4681119A (en) 1980-11-17 1987-07-21 Schering Aktiengesellschaft Method of production and use of microbubble precursors
US4442843A (en) 1980-11-17 1984-04-17 Schering, Ag Microbubble precursors and methods for their production and use
US4657756A (en) 1980-11-17 1987-04-14 Schering Aktiengesellschaft Microbubble precursors and apparatus for their production and use
NZ199916A (en) 1981-03-11 1985-07-12 Unilever Plc Low density polymeric block material for use as carrier for included liquids
US4413070A (en) 1981-03-30 1983-11-01 California Institute Of Technology Polyacrolein microspheres
US4622362A (en) 1981-03-30 1986-11-11 California Institute Of Technology Polyacrolein microspheres
US4678814A (en) 1981-03-30 1987-07-07 California Institute Of Technology Polyacrolein microspheres
CA1177811A (en) 1981-04-13 1984-11-13 Theo G. Spek Process for the preparation of silica particles; silica particles with a narrow pore diameter distribution, catalysts made therefrom and use of these catalysts
US4428869A (en) 1981-08-20 1984-01-31 International Flavors & Fragrances Inc. Cologne consisting of microcapsule suspension
US4456693A (en) 1982-03-08 1984-06-26 W. R. Grace & Co. Hydrocracking catalyst
US4452773A (en) 1982-04-05 1984-06-05 Canadian Patents And Development Limited Magnetic iron-dextran microspheres
US4472552A (en) 1982-09-27 1984-09-18 W. R. Grace & Co. Continuous process for making solid, free-flowing water dispersible PVA-aldehyde reaction product
US4459145A (en) 1982-09-30 1984-07-10 The United States Of America As Represented By The United States Department Of Energy Fabrication of glass microspheres with conducting surfaces
JPS59131355A (en) 1983-01-17 1984-07-28 森下仁丹株式会社 Multiple soft capsule
DE3834705A1 (en) 1988-10-07 1990-04-12 Schering Ag ULTRASONIC CONTRASTING AGENTS FROM GAS BUBBLES AND MICROPARTICLES CONTAINING FATTY ACID
DE3313946A1 (en) 1983-04-15 1984-10-18 Schering AG, 1000 Berlin und 4709 Bergkamen MICROPARTICLES AND GAS BUBBLES CONTAINING ULTRASONIC CONTRASTING AGENTS
DE3313947A1 (en) 1983-04-15 1984-10-18 Schering AG, 1000 Berlin und 4709 Bergkamen MICROPARTICLES AND GAS BUBBLES CONTAINING ULTRASONIC CONTRASTING AGENTS
CA1225585A (en) 1983-06-30 1987-08-18 Maria T. Litvinova Composition for embolization of blood vessels
US4492720A (en) 1983-11-15 1985-01-08 Benjamin Mosier Method of preparing microspheres for intravascular delivery
US4573967A (en) 1983-12-06 1986-03-04 Eli Lilly And Company Vacuum vial infusion system
US4671954A (en) 1983-12-13 1987-06-09 University Of Florida Microspheres for incorporation of therapeutic substances and methods of preparation thereof
US4597505A (en) * 1984-04-09 1986-07-01 Continental Disc Corporation Rupture disc with selectively positioned initial buckling
US4551436A (en) 1984-04-11 1985-11-05 General Electric Company Fabrication of small dense silicon carbide spheres
DE3414924A1 (en) 1984-04-19 1985-10-31 Klaus Dr.med. Dr.med.habil. 8000 München Draenert COATED ANCHORAGE PART FOR IMPLANTS
US4674480A (en) 1984-05-25 1987-06-23 Lemelson Jerome H Drug compositions and methods of applying same
FR2566384B1 (en) 1984-06-21 1986-09-05 Saint Gobain Vitrage IMPROVEMENTS IN TECHNIQUES FOR THE PRODUCTION OF GLASS MICROSPHERES
DE3527482A1 (en) 1984-07-31 1986-02-06 Fuji Spinning Co., Ltd., Tokio/Tokyo METHOD FOR PRODUCING GRAINY POROUS CHITOSAN
GB8419708D0 (en) 1984-08-02 1984-09-05 Shell Int Research Preparation of silica spheres
US4623706A (en) 1984-08-23 1986-11-18 The Dow Chemical Company Process for preparing uniformly sized polymer particles by suspension polymerization of vibratorily excited monomers in a gaseous or liquid stream
JPS61101242A (en) 1984-10-22 1986-05-20 Showa Denko Kk Production of coated substance
US4789501A (en) 1984-11-19 1988-12-06 The Curators Of The University Of Missouri Glass microspheres
US4675113A (en) 1984-11-28 1987-06-23 University Patents, Inc. Affinity chromatography using dried calcium alginate-magnetite separation media in a magnetically stabilized fluidized bed
DE3568442D1 (en) 1984-12-06 1989-04-06 Kanegafuchi Chemical Ind A method of preparation of droplets
US5106903A (en) 1984-12-17 1992-04-21 Lehigh University Preparation of large particle size monodisperse latexes
US4897255A (en) 1985-01-14 1990-01-30 Neorx Corporation Metal radionuclide labeled proteins for diagnosis and therapy
JPH0678460B2 (en) 1985-05-01 1994-10-05 株式会社バイオマテリアル・ユニバース Porous transparent polyvinyl alcohol gel
JPS61293911A (en) 1985-06-24 1986-12-24 Teisan Seiyaku Kk Sustained release preparation
SE459005B (en) 1985-07-12 1989-05-29 Aake Rikard Lindahl SET TO MANUFACTURE SPHERICAL POLYMER PARTICLES
USH915H (en) 1985-07-22 1991-05-07 Gibbs Marylu B Controlled macroporous copolymer properties by removal of impurities in the diluent
US4742086A (en) 1985-11-02 1988-05-03 Lion Corporation Process for manufacturing porous polymer
DE3543348A1 (en) 1985-12-07 1987-06-11 Bayer Ag PEARL-SHAPED CROSS-NETWORKED MIXED POLYMERS WITH EPOXY AND BASIC AMINO GROUPS, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE
JPS62169723A (en) 1986-01-22 1987-07-25 Teisan Seiyaku Kk Sustained release preparation
GB8610024D0 (en) 1986-04-24 1986-05-29 Unilever Plc Porous structures
US4929400A (en) 1986-04-28 1990-05-29 California Institute Of Technology Production of monodisperse, polymeric microspheres
US5262176A (en) 1986-07-03 1993-11-16 Advanced Magnetics, Inc. Synthesis of polysaccharide covered superparamagnetic oxide colloids
JPS6317904A (en) 1986-07-09 1988-01-25 Mitsubishi Chem Ind Ltd Production of crosslinked porous polyvinyl alcohol particle
US4743507A (en) 1986-09-12 1988-05-10 Franses Elias I Nonspherical microparticles and method therefor
US5114421A (en) 1986-09-22 1992-05-19 Polak Robert B Medicament container/dispenser assembly
CA1287459C (en) 1986-10-01 1991-08-13 Mukesh Jain Process for the preparation of hollow microspheres
US4859711A (en) 1986-10-01 1989-08-22 Alcan International Limited Hollow microspheres
US5263992A (en) 1986-10-17 1993-11-23 Bio-Metric Systems, Inc. Biocompatible device with covalently bonded biocompatible agent
EP0265924B2 (en) 1986-10-29 1998-04-22 Kanegafuchi Kagaku Kogyo Kabushiki Kaisha Uniform polymer particles
US5292814A (en) 1987-04-29 1994-03-08 Ernst Bayer Process for the preparation of monodispersed polymer beads
US4795741A (en) 1987-05-06 1989-01-03 Biomatrix, Inc. Compositions for therapeutic percutaneous embolization and the use thereof
GB8713263D0 (en) 1987-06-05 1987-07-08 Unilever Plc Spheroidal silica
JPH0612993B2 (en) 1987-08-10 1994-02-23 株式会社クラレ Method for producing spherical microbe-immobilized moldings
US4819637A (en) 1987-09-01 1989-04-11 Interventional Therapeutics Corporation System for artificial vessel embolization and devices for use therewith
JPH0762054B2 (en) 1987-10-13 1995-07-05 倉敷紡績株式会社 Crosslinked polymer particles
US4850978A (en) 1987-10-29 1989-07-25 Baxter International Inc. Drug delivery cartridge with protective cover
US4804366A (en) 1987-10-29 1989-02-14 Baxter International Inc. Cartridge and adapter for introducing a beneficial agent into an intravenous delivery system
US4981625A (en) 1988-03-14 1991-01-01 California Institute Of Technology Monodisperse, polymeric microspheres produced by irradiation of slowly thawing frozen drops
US4935009A (en) * 1988-06-10 1990-06-19 Caldwell James B Emergency drug injection system
FR2634376B1 (en) 1988-07-21 1992-04-17 Farmalyoc NOVEL SOLID AND POROUS UNIT FORM COMPRISING MICROPARTICLES AND / OR NANOPARTICLES, AS WELL AS ITS PREPARATION
AU4191989A (en) 1988-08-24 1990-03-23 Marvin J. Slepian Biodegradable polymeric endoluminal sealing
DE3829938A1 (en) 1988-09-02 1990-03-29 Hermann Hofmann ORGANO-MINERAL DUENGER AND METHOD FOR THE PRODUCTION THEREOF
US5047438A (en) 1988-09-26 1991-09-10 Supelco, Inc. Porous rigid resins and process of preparation
US4933372A (en) 1988-09-26 1990-06-12 Supelco, Inc. Porous rigid resins and process of preparation
US5681576A (en) 1988-11-16 1997-10-28 Mdv Technologies, Inc. Method and composition for post surgical adhesion reduction
DE3841401A1 (en) 1988-12-08 1990-06-13 Martin Lemperle ALLOPLASTIC IMPLANT
US5258028A (en) 1988-12-12 1993-11-02 Ersek Robert A Textured micro implants
US4946899A (en) 1988-12-16 1990-08-07 The University Of Akron Thermoplastic elastomers of isobutylene and process of preparation
GB8900376D0 (en) 1989-01-09 1989-03-08 Nycomed As Iodinated esters
FR2641692A1 (en) 1989-01-17 1990-07-20 Nippon Zeon Co Plug for closing an opening for a medical application, and device for the closure plug making use thereof
US5091205A (en) 1989-01-17 1992-02-25 Union Carbide Chemicals & Plastics Technology Corporation Hydrophilic lubricious coatings
US5032117A (en) 1989-01-30 1991-07-16 Motta Louis J Tandem syringe
GB8905934D0 (en) 1989-03-15 1989-04-26 Dow Europ Sa A process for preparing adsorptive porous resin beads
US5888930A (en) * 1989-03-27 1999-03-30 Bend Research, Inc. Asymmetric microporous beads for controlled release
US5354290A (en) 1989-05-31 1994-10-11 Kimberly-Clark Corporation Porous structure of an absorbent polymer
CA2017570C (en) 1989-05-31 2000-12-19 James R. Gross Porous structure of an absorbent polymer
US5158573A (en) 1989-06-09 1992-10-27 American Medical Systems, Inc. Injectable polymeric bodies
US5007940A (en) 1989-06-09 1991-04-16 American Medical Systems, Inc. Injectable polymeric bodies
US5116387A (en) 1989-06-09 1992-05-26 American Medical Systems, Inc. Preparation of injectable polymeric bodies
US5190760A (en) 1989-07-08 1993-03-02 Coopers Animal Health Limited Solid pharmaceutical composition
US5698271A (en) 1989-08-22 1997-12-16 Immunivest Corporation Methods for the manufacture of magnetically responsive particles
US5253991A (en) 1989-11-20 1993-10-19 Sumitomo Cement Co., Ltd. Apparatus for producing spheroidal inorganic particulate material
US5409125A (en) 1989-12-11 1995-04-25 Aktiebolaget Astra Unit dose container
US5580575A (en) 1989-12-22 1996-12-03 Imarx Pharmaceutical Corp. Therapeutic drug delivery systems
US5585112A (en) 1989-12-22 1996-12-17 Imarx Pharmaceutical Corp. Method of preparing gas and gaseous precursor-filled microspheres
US5922304A (en) 1989-12-22 1999-07-13 Imarx Pharmaceutical Corp. Gaseous precursor filled microspheres as magnetic resonance imaging contrast agents
US5469854A (en) 1989-12-22 1995-11-28 Imarx Pharmaceutical Corp. Methods of preparing gas-filled liposomes
US5542935A (en) 1989-12-22 1996-08-06 Imarx Pharmaceutical Corp. Therapeutic delivery systems related applications
US6306427B1 (en) 1989-12-28 2001-10-23 Rhone-Poulenc Nutrition Animale Pellets containing active ingredients protected against degradation in the rumen of ruminants
US5435645A (en) 1989-12-29 1995-07-25 Tecres Spa Process and apparatus for the mixing and direct emplacement of a two-component bone cement
US5147937A (en) 1990-03-22 1992-09-15 Rohm And Haas Company Process for making controlled, uniform-sized particles in the 1 to 50 micrometer range
US5556610A (en) 1992-01-24 1996-09-17 Bracco Research S.A. Gas mixtures useful as ultrasound contrast media, contrast agents containing the media and method
JPH03297475A (en) 1990-04-16 1991-12-27 Ken Ishihara Controlling method for emission of medicine by means of resonance sound wave
US5514090A (en) 1990-04-24 1996-05-07 Science Incorporated Closed drug delivery system
US5137928A (en) 1990-04-26 1992-08-11 Hoechst Aktiengesellschaft Ultrasonic contrast agents, processes for their preparation and the use thereof as diagnostic and therapeutic agents
CA2016870C (en) 1990-05-15 1994-03-29 Arnie Drudik Dispenser for storing and mixing several components
AU636481B2 (en) 1990-05-18 1993-04-29 Bracco International B.V. Polymeric gas or air filled microballoons usable as suspensions in liquid carriers for ultrasonic echography
JP2514087Y2 (en) 1990-05-25 1996-10-16 幸三 牧田 Balloon with detachable double-sided check valve
US6291605B1 (en) 1990-06-06 2001-09-18 Clarence S. Freeman Polymerization process with spraying step
WO1991019483A1 (en) 1990-06-20 1991-12-26 Advanced Polymer Systems, Inc. Compositions and methods for the controlled release of soluble active substances
ATE130517T1 (en) 1990-08-08 1995-12-15 Takeda Chemical Industries Ltd INTRAVASCULAR EMBOLIZING AGENT CONTAINING A SUBSTANCE INHIBITING ANGIOGENESIS.
US5484584A (en) 1990-10-02 1996-01-16 Board Of Regents, The University Of Texas System Therapeutic and diagnostic use of modified polymeric microcapsules
US5149543A (en) 1990-10-05 1992-09-22 Massachusetts Institute Of Technology Ionically cross-linked polymeric microcapsules
US5120349A (en) 1990-12-07 1992-06-09 Landec Labs, Inc. Microcapsule having temperature-dependent permeability profile
US5171214A (en) 1990-12-26 1992-12-15 Abbott Laboratories Drug storage and delivery system
US5171217A (en) 1991-02-28 1992-12-15 Indiana University Foundation Method for delivery of smooth muscle cell inhibitors
US5147631A (en) 1991-04-30 1992-09-15 Du Pont Merck Pharmaceutical Company Porous inorganic ultrasound contrast agents
FR2676927B1 (en) 1991-05-29 1995-06-23 Ibf MICROSPHERES FOR USE IN THERAPEUTIC VASCULAR OCCLUSIONS AND INJECTABLE SOLUTIONS CONTAINING THEM.
EP0586524B2 (en) 1991-06-03 2000-11-02 Nycomed Imaging As Improvements in or relating to contrast agents
GB9116610D0 (en) 1991-08-01 1991-09-18 Danbiosyst Uk Preparation of microparticles
US5216096A (en) 1991-09-24 1993-06-01 Japan Synthetic Rubber Co., Ltd. Process for the preparation of cross-linked polymer particles
US5811447A (en) 1993-01-28 1998-09-22 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
KR100259989B1 (en) 1991-10-01 2000-08-01 모리다 가쓰라 Prolonged release microparticle preparation and production of the same
JP3356447B2 (en) 1991-10-16 2002-12-16 テルモ株式会社 Vascular lesion embolic material composed of dried polymer gel
US5258042A (en) 1991-12-16 1993-11-02 Henry Ford Health System Intravascular hydrogel implant
ATE168040T1 (en) 1991-12-20 1998-07-15 Allied Signal Inc LOW DENSITY, HIGH SPECIFIC SURFACE MATERIALS AND ARTICLES MOLDED THEREOF FOR USE IN METAL RECOVERY
US5260002A (en) 1991-12-23 1993-11-09 Vanderbilt University Method and apparatus for producing uniform polymeric spheres
BR9207043A (en) 1991-12-24 1995-12-05 Du Pont Double stabilized microparticles and coating composition
GB9200391D0 (en) 1992-01-09 1992-02-26 Nycomed As Improvements in or relating to contrast agents
GB9200388D0 (en) 1992-01-09 1992-02-26 Nycomed As Improvements in or relating to contrast agents
US6537574B1 (en) 1992-02-11 2003-03-25 Bioform, Inc. Soft tissue augmentation material
US5480644A (en) 1992-02-28 1996-01-02 Jsf Consultants Ltd. Use of injectable biomaterials for the repair and augmentation of the anal sphincters
IL104963A (en) 1992-03-06 1997-09-30 Nycomed Imaging As Contrast agents comprising methylene diester unit- containing biodegradable polymers
AU3941293A (en) 1992-04-06 1993-11-08 Uroplasty, Inc. Treatment of reflux disorder by microparticles injection
DE69306844T2 (en) 1992-04-10 1997-07-10 Mitsubishi Chem Corp Process for the preparation of spherical cross-linked acrylonitrile copolymers
US6235313B1 (en) 1992-04-24 2001-05-22 Brown University Research Foundation Bioadhesive microspheres and their use as drug delivery and imaging systems
AU4198793A (en) 1992-07-24 1994-01-27 Takeda Chemical Industries Ltd. Microparticle preparation and production thereof
US5807323A (en) * 1992-08-13 1998-09-15 Science Incorporated Mixing and delivery syringe assembly
US6592859B1 (en) 1992-08-20 2003-07-15 Ethicon, Inc. Controlled expansion sphincter augmentation media
US5512604A (en) 1992-08-28 1996-04-30 The Dow Chemical Company Porous copolymers having a cellular polymeric structure suitable for preparing ion-exchange resins and adsorbents
DE69319438T2 (en) 1992-09-16 1998-12-03 Nycomed Imaging As IMPROVEMENTS TO CONTRAST AGENTS
AU4926193A (en) 1992-09-21 1994-04-12 Vitaphore Corporation Embolization plugs for blood vessels
KR960001417B1 (en) 1992-09-26 1996-01-27 한국과학기술원 Method for preparing an improved porous polymer bead
DE4232755A1 (en) 1992-09-26 1994-03-31 Schering Ag Microparticle preparations made from biodegradable copolymers
GB9221329D0 (en) 1992-10-10 1992-11-25 Delta Biotechnology Ltd Preparation of further diagnostic agents
US5382260A (en) 1992-10-30 1995-01-17 Interventional Therapeutics Corp. Embolization device and apparatus including an introducer cartridge and method for delivering the same
US5369163A (en) 1992-11-13 1994-11-29 Rohm And Haas Company Process for preparing large dimension emulsion polymer particles, polymer product and uses thereof
US5690666A (en) 1992-11-18 1997-11-25 Target Therapeutics, Inc. Ultrasoft embolism coils and process for using them
US5349957A (en) 1992-12-02 1994-09-27 Sterling Winthrop Inc. Preparation and magnetic properties of very small magnetite-dextran particles
JP3256583B2 (en) 1992-12-10 2002-02-12 株式会社リコー Electrophotographic toner and method for producing the same
US5288763A (en) 1992-12-23 1994-02-22 The Johns Hopkins University School Of Medicine Porous, polymer beads and process of their preparation
US6482436B1 (en) 1993-01-29 2002-11-19 Ferx Incorporated Magnetically responsive composition
US5328936A (en) 1993-02-01 1994-07-12 Rohm And Haas Company Polymerization process for making porous polymeric particles
US6090925A (en) 1993-03-09 2000-07-18 Epic Therapeutics, Inc. Macromolecular microparticles and methods of production and use
US5320639A (en) 1993-03-12 1994-06-14 Meadox Medicals, Inc. Vascular plug delivery system
US5701899A (en) 1993-05-12 1997-12-30 The Board Of Regents Of The University Of Nebraska Perfluorobutane ultrasound contrast agent and methods for its manufacture and use
US5567415A (en) 1993-05-12 1996-10-22 The Board Of Regents Of The University Of Nebraska Ultrasound contrast agents and methods for their manufacture and use
US5695740A (en) 1993-05-12 1997-12-09 The Board Of Regents Of The University Of Nebraska Perfluorocarbon ultrasound contrast agent comprising microbubbles containing a filmogenic protein and a saccharide
US5344867A (en) 1993-06-14 1994-09-06 The Bfgoodrich Company Vinylidene chloride emulsion interpolymer composition
US5716346A (en) 1993-07-02 1998-02-10 Farris; Barry Method and apparatus for loading syringes without the need for hypodermic needles
US5994341A (en) 1993-07-19 1999-11-30 Angiogenesis Technologies, Inc. Anti-angiogenic Compositions and methods for the treatment of arthritis
ATE502664T1 (en) 1993-07-19 2011-04-15 Angiotech Pharm Inc METHOD OF PRODUCTION OF A STENT WITH ANTI-ANGIOGENIC COMPOSITION
US5397303A (en) 1993-08-06 1995-03-14 River Medical, Inc. Liquid delivery device having a vial attachment or adapter incorporated therein
US5398851A (en) 1993-08-06 1995-03-21 River Medical, Inc. Liquid delivery device
US5443495A (en) 1993-09-17 1995-08-22 Scimed Lifesystems Inc. Polymerization angioplasty balloon implant device
US5531716A (en) 1993-09-29 1996-07-02 Hercules Incorporated Medical devices subject to triggered disintegration
US5556391A (en) 1993-10-01 1996-09-17 Merocel Corporation Surgical sponge device
US5445614A (en) * 1993-10-20 1995-08-29 Habley Medical Technology Corporation Pharmaceutical storage and mixing syringe
EP1258262A3 (en) 1993-10-28 2002-12-18 Medrad, Inc. Total system for contrast delivery
CZ208995A3 (en) 1993-12-15 1996-01-17 Bracco Research Sa Injectable ultrasound medium, process of its preparation and use
CN1075959C (en) 1994-01-21 2001-12-12 瑟泰克斯医学有限公司 Particulate material
US5569468A (en) 1994-02-17 1996-10-29 Modi; Pankaj Vaccine delivery system for immunization, using biodegradable polymer microspheres
US5417982A (en) 1994-02-17 1995-05-23 Modi; Pankaj Controlled release of drugs or hormones in biodegradable polymer microspheres
ATE173160T1 (en) 1994-02-17 1998-11-15 Pankaj Modi DRUGS, VACCINES AND HORMONES IN POLYLACTIDE-COATED MICROPARTICLES
WO1995025480A1 (en) 1994-03-18 1995-09-28 Cook Incorporated Helical embolization coil
US5431174A (en) 1994-04-04 1995-07-11 Via Medical Corporation Method of fluid delivery and collection
EP0757553B1 (en) 1994-04-28 2000-08-02 Primed Halberstadt Medizintechnik Gmbh One-piece dispensing device for the contamination-free administration of medicaments (cytostatica)
US5534589A (en) 1994-05-04 1996-07-09 Minnesota Mining And Manufacturing Company Repulpable plastic films
ATE203755T1 (en) 1994-05-15 2001-08-15 Apbiotech Aktiebolag METHOD FOR PRODUCING PARTICLES AND PARTICLES THAT CAN BE PRODUCED USING THIS PROCESS
JP2535785B2 (en) 1994-06-03 1996-09-18 工業技術院長 Vascular embolic agent
US5583162A (en) 1994-06-06 1996-12-10 Biopore Corporation Polymeric microbeads and method of preparation
US5639710A (en) 1994-07-06 1997-06-17 Zeneca Limited Solid microspheres for agriculturally active compounds and process for their production
ES2096521B1 (en) 1994-08-10 1997-11-16 Univ La Laguna BIODEGRADABLE SYNTHETIC POLYMER MICROSPHERES IN THE MANUFACTURE AND ELABORATION OF REACTIVE EQUIPMENT FOR THE PREPARATION OF RADIOPHARMACEUTICAL MEDICINES.
KR100341192B1 (en) * 1994-08-17 2002-08-22 보스톤 사이언티픽 코포레이션 Implant, and method and device for inserting the implant
US6099864A (en) 1994-12-02 2000-08-08 The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration In situ activation of microcapsules
US5827531A (en) 1994-12-02 1998-10-27 The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration Microcapsules and methods for making
DK175166B1 (en) 1995-01-03 2004-06-21 Cook William Europ Method of manufacturing an assembly for placing an embolization coil in the vascular system and such assembly as well as an apparatus for advancing the assembly
DE69632392T2 (en) 1995-01-27 2004-09-16 Scimed Life Systems, Inc., Maple Grove Embolisation
US6179817B1 (en) 1995-02-22 2001-01-30 Boston Scientific Corporation Hybrid coating for medical devices
DE69521025T2 (en) 1995-03-07 2001-10-04 Menlo Care Inc Means to improve sphincter function with controlled expansion
US5876372A (en) 1995-03-22 1999-03-02 Abbott Laboratories Syringe system accomodating seperate prefilled barrels for two constituents
US5785682A (en) 1995-03-22 1998-07-28 Abbott Laboratories Pre-filled syringe drug delivery system
US5637087A (en) 1995-03-22 1997-06-10 Abbott Laboratories Prefilled, two-constituent syringe
US5569193A (en) 1995-03-22 1996-10-29 Abbott Laboratories Syringe system accommodating separately storable prefilled containers for two constituents
ATE212545T1 (en) 1995-03-28 2002-02-15 Fidia Advanced Biopolymers Srl NANOSPHERES WITH A BIOCOMPATIBLE POLYSACCHARIDE
US5779668A (en) 1995-03-29 1998-07-14 Abbott Laboratories Syringe barrel for lyophilization, reconstitution and administration
US5566729A (en) 1995-04-06 1996-10-22 Abbott Laboratories Drug reconstitution and administration system
US6428771B1 (en) 1995-05-15 2002-08-06 Pharmaceutical Discovery Corporation Method for drug delivery to the pulmonary system
US6312407B1 (en) 1995-06-05 2001-11-06 Medtronic Percusurge, Inc. Occlusion of a vessel
US6214331B1 (en) 1995-06-06 2001-04-10 C. R. Bard, Inc. Process for the preparation of aqueous dispersions of particles of water-soluble polymers and the particles obtained
US5657756A (en) 1995-06-07 1997-08-19 Ctf Systems Inc. Method and systems for obtaining higher order gradiometer measurements with lower order gradiometers
US5766147A (en) 1995-06-07 1998-06-16 Winfield Medical Vial adaptor for a liquid delivery device
US6143211A (en) 1995-07-21 2000-11-07 Brown University Foundation Process for preparing microparticles through phase inversion phenomena
US5877224A (en) 1995-07-28 1999-03-02 Rutgers, The State University Of New Jersey Polymeric drug formulations
US5840387A (en) 1995-07-28 1998-11-24 Aegis Biosciences L.L.C. Sulfonated multiblock copolymer and uses therefor
US6096344A (en) 1995-07-28 2000-08-01 Advanced Polymer Systems, Inc. Bioerodible porous compositions
US5558822A (en) 1995-08-16 1996-09-24 Gas Research Institute Method for production of spheroidized particles
US5888546A (en) 1995-08-28 1999-03-30 The Regents Of The University Of California Embolic material for endovascular occlusion of abnormal vasculature and method for using the same
US5833361A (en) 1995-09-07 1998-11-10 Funk; James E. Apparatus for the production of small spherical granules
CA2161863A1 (en) 1995-10-31 1997-05-01 Michael Vivian Sefton Angiogenic material and uses thereof
US5752974A (en) 1995-12-18 1998-05-19 Collagen Corporation Injectable or implantable biomaterials for filling or blocking lumens and voids of the body
DK0928182T3 (en) 1996-01-11 2002-08-26 Duoject Inc Delivery system for medicines packed in pharmaceutical bottles
US5702361A (en) 1996-01-31 1997-12-30 Micro Therapeutics, Inc. Method for embolizing blood vessels
US5895398A (en) 1996-02-02 1999-04-20 The Regents Of The University Of California Method of using a clot capture coil
US6051247A (en) 1996-05-30 2000-04-18 University Of Florida Research Foundation, Inc. Moldable bioactive compositions
US5855615A (en) 1996-06-07 1999-01-05 Menlo Care, Inc. Controller expansion sphincter augmentation media
US5792478A (en) 1996-07-08 1998-08-11 Advanced Uro Science Tissue injectable composition and method of use
US5830178A (en) 1996-10-11 1998-11-03 Micro Therapeutics, Inc. Methods for embolizing vascular sites with an emboilizing composition comprising dimethylsulfoxide
US5695480A (en) 1996-07-29 1997-12-09 Micro Therapeutics, Inc. Embolizing compositions
US5741331A (en) 1996-07-29 1998-04-21 Corvita Corporation Biostable elastomeric polymers having quaternary carbons
TW421658B (en) 1996-07-31 2001-02-11 Kanebo Ltd Porious spherical particles and the preparation process for preparing thereof
US5823198A (en) 1996-07-31 1998-10-20 Micro Therapeutics, Inc. Method and apparatus for intravasculer embolization
US5813411A (en) 1996-08-20 1998-09-29 Menlo Care, Inc. Method of deforming tissue with a swollen hydrogel
US5902832A (en) 1996-08-20 1999-05-11 Menlo Care, Inc. Method of synthesizing swollen hydrogel for sphincter augmentation
US5785642A (en) 1996-10-18 1998-07-28 Micro Therapeutics, Inc. Methods for treating urinary incontinence in mammals
US5756127A (en) 1996-10-29 1998-05-26 Wright Medical Technology, Inc. Implantable bioresorbable string of calcium sulfate beads
US6139963A (en) 1996-11-28 2000-10-31 Kuraray Co., Ltd. Polyvinyl alcohol hydrogel and process for producing the same
DE29724255U1 (en) 1996-12-18 2000-10-05 Alpha Bioverfahrenstechnik Gmb Microcapsules
US6090800A (en) 1997-05-06 2000-07-18 Imarx Pharmaceutical Corp. Lipid soluble steroid prodrugs
JP4570696B2 (en) 1997-04-10 2010-10-27 ジョンズ・ホプキンズ・ユニバーシティ Gas syringe device
JP4102459B2 (en) 1997-05-14 2008-06-18 森下仁丹株式会社 Seamless capsule for synthesizing biopolymer and method for producing the same
US6056844A (en) 1997-06-06 2000-05-02 Triton Systems, Inc. Temperature-controlled induction heating of polymeric materials
JP2002503991A (en) 1997-06-13 2002-02-05 マイクロ・テラピューティクス・インコーポレーテッド Syringe and luer hub having novel shape and method of forming embolus
US6048908A (en) 1997-06-27 2000-04-11 Biopore Corporation Hydrophilic polymeric material
US5959073A (en) 1997-07-07 1999-09-28 Southwest Research Institute Method for preparing polymeric beads
US6056721A (en) 1997-08-08 2000-05-02 Sunscope International, Inc. Balloon catheter and method
EP1009317A4 (en) 1997-08-28 2001-01-24 Boston Scient Corp System for implanting a cross-linked polysaccharide fiber and methods of forming and inserting the fiber
US6476069B2 (en) 1997-09-11 2002-11-05 Provasis Therapeutics Inc. Compositions for creating embolic agents and uses thereof
US6538026B1 (en) 1997-09-11 2003-03-25 Provasis Therapeutics, Inc. Compositions useful for remodeling body spaces
AU739610B2 (en) 1997-11-07 2001-10-18 Salviac Limited Implantable occluder devices for medical use
US5951160A (en) 1997-11-20 1999-09-14 Biomet, Inc. Method and apparatus for packaging, mixing and delivering bone cement
DE19752585B4 (en) 1997-11-27 2007-06-28 Inotech Ag Device and method for encapsulating microbial, plant and animal cells or of biological and chemical substances
US6019750A (en) 1997-12-04 2000-02-01 Baxter International Inc. Sliding reconstitution device with seal
DK1062278T3 (en) 1998-02-23 2006-09-25 Mnemoscience Gmbh Polymers with shape memory
RU2215542C2 (en) 1998-02-23 2003-11-10 Массачусетс Инститьют Оф Текнолоджи Biodecomposing polymers able recovery of form
US6003566A (en) 1998-02-26 1999-12-21 Becton Dickinson And Company Vial transferset and method
US6059766A (en) 1998-02-27 2000-05-09 Micro Therapeutics, Inc. Gynecologic embolotherapy methods
US6660301B1 (en) 1998-03-06 2003-12-09 Biosphere Medical, Inc. Injectable microspheres for dermal augmentation and tissue bulking
ATE262976T1 (en) 1998-03-07 2004-04-15 Inotech Ag METHOD AND DEVICE FOR ENCAPSULATING MICROBIAL, PLANT AND ANIMAL CELLS OR OF BIOLOGICAL AND CHEMICAL SUBSTANCES
US6047861A (en) 1998-04-15 2000-04-11 Vir Engineering, Inc. Two component fluid dispenser
US6224794B1 (en) 1998-05-06 2001-05-01 Angiotech Pharmaceuticals, Inc. Methods for microsphere production
US6224630B1 (en) 1998-05-29 2001-05-01 Advanced Bio Surfaces, Inc. Implantable tissue repair device
CA2334223C (en) 1998-06-04 2008-11-18 New York University Endovascular thin film devices and methods for treating and preventing stroke
US6267154B1 (en) 1998-06-05 2001-07-31 Abbott Laboratories System for storing mixing and administering a drug
EP1091783A4 (en) * 1998-06-29 2002-08-21 Orbon Corp Drug dispenser
US6165193A (en) 1998-07-06 2000-12-26 Microvention, Inc. Vascular embolization with an expansible implant
US6099064A (en) 1998-07-10 2000-08-08 Lund Industries, Inc. Windshield visor for motor vehicles
US6264861B1 (en) 1998-08-05 2001-07-24 Xeikon Nv Method for producing rounded polymeric particles
US6315709B1 (en) 1998-08-07 2001-11-13 Stereotaxis, Inc. Magnetic vascular defect treatment system
US6152943A (en) 1998-08-14 2000-11-28 Incept Llc Methods and apparatus for intraluminal deposition of hydrogels
US6296622B1 (en) 1998-12-21 2001-10-02 Micrus Corporation Endoluminal device delivery system using axially recovering shape memory material
CA2248592A1 (en) 1998-08-31 2000-02-29 Christopher D. Batich Microspheres for use in the treatment of cancer
FR2784580B1 (en) 1998-10-16 2004-06-25 Biosepra Inc POLYVINYL-ALCOHOL MICROSPHERES AND METHODS OF MAKING THE SAME
US6238335B1 (en) 1998-12-11 2001-05-29 Enteric Medical Technologies, Inc. Method for treating gastroesophageal reflux disease and apparatus for use therewith
JP2000189511A (en) 1998-12-25 2000-07-11 Kaneka Medeikkusu:Kk Embolization material
US6162377A (en) 1999-02-23 2000-12-19 Alberta Research Council Inc. Apparatus and method for the formation of uniform spherical particles
US6296604B1 (en) 1999-03-17 2001-10-02 Stereotaxis, Inc. Methods of and compositions for treating vascular defects
US6306425B1 (en) 1999-04-09 2001-10-23 Southern Research Institute Injectable naltrexone microsphere compositions and their use in reducing consumption of heroin and alcohol
US6368658B1 (en) 1999-04-19 2002-04-09 Scimed Life Systems, Inc. Coating medical devices using air suspension
WO2000071196A1 (en) 1999-05-21 2000-11-30 Micro Therapeutics, Inc. Interface needle and method for creating a blunt interface between delivered liquids
US6280457B1 (en) 1999-06-04 2001-08-28 Scimed Life Systems, Inc. Polymer covered vaso-occlusive devices and methods of producing such devices
ATE280579T1 (en) 1999-08-27 2004-11-15 Southern Res Inst INJECTABLE BUPRENORPHINE MICROSPHERES COMPOSITIONS AND USE THEREOF FOR REDUCING HEROIN AND ALCOHOL CONSUMPTION
FR2797769B1 (en) 1999-09-01 2003-07-25 Cis Bio Int RADIOPHARMACEUTICAL PRODUCTS AND THEIR PREPARATION PROCESS
JP2001079011A (en) 1999-09-14 2001-03-27 Akira Morimoto Embolization coil and its manufacture
US6277392B1 (en) 1999-09-16 2001-08-21 Carbon Medical Technologies, Inc. Tissue injectable composition
US6602261B2 (en) 1999-10-04 2003-08-05 Microvention, Inc. Filamentous embolic device with expansile elements
US6238403B1 (en) 1999-10-04 2001-05-29 Microvention, Inc. Filamentous embolic device with expansible elements
KR100335866B1 (en) 2000-01-06 2002-05-10 박호군 Microspheric Embolic Materials Having Duel Structure of Poly(Vinyl Acetate) Core/Poly(Vinyl Alcohol) Shell, and Method for Preparing The Same
US6306419B1 (en) 2000-02-23 2001-10-23 Aegis Biosciences, Llc Medical uses of styrene sulfonate polymers
WO2001066016A1 (en) 2000-03-06 2001-09-13 Scimed Life Systems, Inc. Embolic agents visible under ultrasound
US6652883B2 (en) 2000-03-13 2003-11-25 Biocure, Inc. Tissue bulking and coating compositions
AU4566001A (en) * 2000-03-13 2001-09-24 Biocure Inc Embolic compositions
US6423332B1 (en) 2000-05-26 2002-07-23 Ethicon, Inc. Method and composition for deforming soft tissues
DE10026620A1 (en) 2000-05-29 2002-03-07 Gerhard Quelle Biocompatible material for cell and tissue implantation, useful e.g. for drug release or cosmetic tissue augmentation, consisting of spherical particles having (semi-)permeable or porous outer shell and internal cavity
US6355275B1 (en) 2000-06-23 2002-03-12 Carbon Medical Technologies, Inc. Embolization using carbon coated microparticles
US6764463B1 (en) 2000-06-27 2004-07-20 Barry Farris Method and needleless apparatus for the storage of a first substance followed by subsequent mixing with a second substance and transfer without ambient air incursion
JP2002017848A (en) 2000-07-12 2002-01-22 Terumo Corp Intravitally injectable particulate and method for preparing the same
WO2002011696A2 (en) 2000-08-08 2002-02-14 Ev & M Active tissue augmentation materials and method
ATE449596T1 (en) 2000-08-15 2009-12-15 Univ Illinois METHOD FOR PRODUCING MICROPARTICLES
US6394965B1 (en) 2000-08-15 2002-05-28 Carbon Medical Technologies, Inc. Tissue marking using biocompatible microparticles
AU2001294772A1 (en) 2000-09-27 2002-04-08 Microtek Laboratories, Inc. Macrocapsules containing microencapsulated phase change materials
AUPR098400A0 (en) 2000-10-25 2000-11-16 Sirtex Medical Limited Production of radionuclide coated microspheres and seeds
AUPR098300A0 (en) 2000-10-25 2000-11-16 Sirtex Medical Limited Polymer based radionuclide containing microspheres
AUPR098200A0 (en) 2000-10-25 2000-11-16 Sirtex Medical Limited Production of low density radionuclide containing microspheres
US6545097B2 (en) 2000-12-12 2003-04-08 Scimed Life Systems, Inc. Drug delivery compositions and medical devices containing block copolymer
JP2005513081A (en) 2000-12-13 2005-05-12 パーデュー・リサーチ・ファウンデイション Microencapsulation of drugs by solvent exchange
US6632531B2 (en) 2001-02-15 2003-10-14 Rohm And Haas Company Porous particles, their aqueous dispersions, and method of preparation
US6887857B2 (en) 2001-04-27 2005-05-03 Scimed Life Systems, Inc. Microparticle protection of therapeutic agents
US6723067B2 (en) * 2001-07-26 2004-04-20 David H. Nielson Apparatus for delivering aerosolized fibrin endoscopically to a wound
US20030032935A1 (en) * 2001-08-10 2003-02-13 Scimed Life Systems, Inc. Packages facilitating convenient mixing and delivery of liquids
US6692515B2 (en) * 2001-11-07 2004-02-17 Frank H. Boehm, Jr. Surgical kit for repairing leaks in fluid carrying vessels and organs and method thereof
US7094369B2 (en) 2002-03-29 2006-08-22 Scimed Life Systems, Inc. Processes for manufacturing polymeric microspheres
CA2480630A1 (en) 2002-03-29 2003-10-09 Boston Scientific Limited Tissue treatment
US7462366B2 (en) 2002-03-29 2008-12-09 Boston Scientific Scimed, Inc. Drug delivery particle
US7218962B2 (en) 2002-03-29 2007-05-15 Boston Scientific Scimed, Inc. Magnetically enhanced injection catheter
US7131997B2 (en) * 2002-03-29 2006-11-07 Scimed Life Systems, Inc. Tissue treatment
US7053134B2 (en) 2002-04-04 2006-05-30 Scimed Life Systems, Inc. Forming a chemically cross-linked particle of a desired shape and diameter
US7838699B2 (en) 2002-05-08 2010-11-23 Biosphere Medical Embolization using degradable crosslinked hydrogels
US7449236B2 (en) 2002-08-09 2008-11-11 Boston Scientific Scimed, Inc. Porous polymeric particle comprising polyvinyl alcohol and having interior to surface porosity-gradient
US20040076582A1 (en) 2002-08-30 2004-04-22 Dimatteo Kristian Agent delivery particle
US8012454B2 (en) 2002-08-30 2011-09-06 Boston Scientific Scimed, Inc. Embolization
US7792568B2 (en) 2003-03-17 2010-09-07 Boston Scientific Scimed, Inc. MRI-visible medical devices
US7906148B2 (en) 2003-07-31 2011-03-15 Boston Scientific Scimed, Inc. Latex medical articles for release of antimicrobial agents
US20050037047A1 (en) 2003-08-11 2005-02-17 Young-Ho Song Medical devices comprising spray dried microparticles

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB743789A (en) * 1953-02-22 1956-01-25 Hubert Percival Schofield Improvements in or relating to cartridges and the like tubular containers for use in dispensing liquids
FR1099362A (en) * 1954-04-23 1955-09-05 D Antibiotiques Et De Biolog L Capsule syringe for drugs that only need to be mixed at the time of use
FR1478062A (en) * 1965-04-30 1967-04-21 Ile D Etudes Et De Brevets Nov Injection syringe
US4412836A (en) * 1979-04-27 1983-11-01 The West Company, Incorporated Syringe assembly
US4254768A (en) * 1979-09-14 1981-03-10 Ty Perla J Hypodermic syringe
US4453934A (en) * 1981-11-11 1984-06-12 Contraves Ag Injection syringe for the successive injection of two liquids into the blood vessels of living bodies
EP0112574A1 (en) * 1982-12-27 1984-07-04 Meditec S.A. Two-compartment prefilled syringe
US5704918A (en) * 1992-12-01 1998-01-06 Higashikawa; Tetsuro Syringe

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2010101255B4 (en) * 2010-11-15 2011-09-22 Lumsden, Andrew A prefilled syringe for administering buffered lignocaine
EP2806921A4 (en) * 2012-01-23 2015-11-25 Merit Medical Systems Inc Mixing syringe
US9751056B2 (en) 2012-01-23 2017-09-05 Merit Medical Systems, Inc. Mixing syringe
WO2017089280A1 (en) * 2015-11-27 2017-06-01 Sanofi-Aventis Deutschland Gmbh Injection apparatus
CN108495670A (en) * 2015-11-27 2018-09-04 赛诺菲-安万特德国有限公司 Injection device
JP2018535060A (en) * 2015-11-27 2018-11-29 サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング Injection device

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US20040092883A1 (en) 2004-05-13
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US7883490B2 (en) 2011-02-08
AU2003286639A1 (en) 2004-05-13
AU2003286639A8 (en) 2004-05-13
WO2004037326A3 (en) 2004-12-23

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