US20070016284A1 - Polymeric coating for reducing the rate of release of a therapeutic substance from a stent - Google Patents

Polymeric coating for reducing the rate of release of a therapeutic substance from a stent Download PDF

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Publication number
US20070016284A1
US20070016284A1 US11/526,126 US52612606A US2007016284A1 US 20070016284 A1 US20070016284 A1 US 20070016284A1 US 52612606 A US52612606 A US 52612606A US 2007016284 A1 US2007016284 A1 US 2007016284A1
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Prior art keywords
coating layer
stent
polymer
ethylene
styrene
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US11/526,126
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Stephen Pacetti
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Abbott Cardiovascular Systems Inc
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Advanced Cardiovascular Systems Inc
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Priority to US11/526,126 priority Critical patent/US20070016284A1/en
Publication of US20070016284A1 publication Critical patent/US20070016284A1/en
Abandoned legal-status Critical Current

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08Materials for coatings
    • A61L31/10Macromolecular materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602Type of release, e.g. controlled, sustained, slow
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606Coatings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00Materials or methods for coatings medical devices
    • A61L2420/08Coatings comprising two or more layers

Definitions

  • a medical device such as a stent, for delivering a therapeutic substance is disclosed.
  • the stent includes a polymeric coating for reducing the rate of release of the therapeutic substance.
  • Blood vessel occlusions are commonly treated by mechanically enhancing blood flow in the affected vessels, such as by employing a stent.
  • Stents act as scaffoldings, functioning to physically hold open and, if desired, to expand the wall of the passageway.
  • stents are capable of being compressed, so that they can be inserted through small lumens via catheters, and then expanded to a larger diameter once they are at the desired location. Examples in the patent literature disclosing stents include U.S. Pat. No. 4,733,665 issued to Palmaz, U.S. Pat. No. 4,800,882 issued to Gianturco, and U.S. Pat. No. 4,886,062 issued to Wiktor.
  • Stents are used not only for mechanical intervention but also as vehicles for providing biological therapy. Biological therapy can be achieved by medicating the stents. Medicated stents provide for the local administration of a therapeutic substance at the diseased site. Local delivery of a therapeutic substance is a preferred method of treatment because the substance is concentrated at a specific site and thus smaller total levels of medication can be administered in comparison to systemic dosages that often produce adverse or even toxic side effects for the patient.
  • One method of medicating a stent involves the use of a polymeric carrier coated onto the surface of the stent.
  • a composition including a solvent, a polymer dissolved in the solvent, and a therapeutic substance dispersed in the blend is applied to the stent by immersing the stent in the composition or by spraying the composition onto the stent.
  • the solvent is allowed to evaporate, leaving on the stent strut surfaces a coating of the polymer and the therapeutic substance impregnated in the polymer.
  • the therapeutic substance may be required to be released at an efficacious concentration for an extended duration of time.
  • Increasing the quantity of the therapeutic substance in the polymeric coating can lead to poor coating mechanical properties, inadequate coating adhesion, and overly rapid rate of release.
  • Increasing the quantity of the polymeric compound by producing a thicker coating can perturb the geometrical and mechanical functionality of the stent as well as limit the procedures for which the stent can be used.
  • the present invention discloses a stent for delivery of a therapeutic agent.
  • the stent includes a polymer coating for reducing the rate of release of the therapeutic agent.
  • the polymer has a crystalline lattice structure, wherein the polymer is capable of significantly maintaining the crystalline lattice structure while the therapeutic agent is released from the stent such that the aqueous environment to which the stent is exposed subsequent to the implantation of the stent does not significantly convert the crystalline lattice structure of the polymer to an amorphous structure.
  • the coating can contain the therapeutic agent.
  • the melting point of the polymer is greater than or equal to about 135° C. at ambient pressure.
  • the polymer is a hydrophobic polymer having a solubility parameter not greater than about 10.7 (cal/cm 3 ) 1/2 .
  • the method includes applying a first composition including a polymeric material to at least a portion of the stent to form a polymer coating supported by the stent.
  • the polymer has a crystalline structure, wherein the aqueous environment to which the coating is exposed subsequent to the implantation of the stent does not significantly convert the crystalline structure of the polymer to an amorphous structure for the duration of time which the agent is released from the stent.
  • the present invention additionally discloses a composition for coating a stent.
  • the composition includes a fluid and a polymer dissolved in the fluid.
  • the polymer includes a crystalline structure during the duration of delivery of an active agent from the stent, and the aqueous environment to which the stent is exposed subsequent to the implantation procedure does not significantly change the crystalline stricture to an amorphous structure.
  • the stent for delivering a therapeutic agent to an implanted site.
  • the stent includes a radially expandable body structure and a polymeric coating supported by the body structure for extending the residence time of the therapeutic agent at the implanted site.
  • the polymeric coating is made from a hydrophobic polymer having a degree of crystallinity that remains at or above about 10% at least until a significant amount of the therapeutic substance has been released from the stent.
  • One mechanism through which the release rate of an active agent from a medical device can be controlled is the crystallinity of the polymer with which the medical device is coated.
  • a polymer in which the molecules are arranged in a highly ordered and regular pattern formed by folding and stacking of the polymer chains is said to be crystalline.
  • amorphous polymers have molecules that are arranged randomly with no regularity of orientation with respect to one another.
  • the factors that affect polymer crystallinity are the stereoregularity of the polymer, the tacticity of the polymer, the presence of branching, the degree of polymerization, and the strength of the intermolecular forces between the polymer chains.
  • the structural arrangement and regularity of a polymer is an important factor in the determination of polymer crystallinity.
  • a regular arrangement along the polymer chains provides the polymer structure with a high degree of symmetry, allowing the chains to pack into crystals. Irregularity along the polymer chains, however, prevents the chains from packing closely to one another, thereby decreasing crystallinity.
  • Polymers with regular, linear, and rigid structures tend to form ordered crystals.
  • polymers with large side groups, mixed tacticity or an atactic structure, a mix of side or functional groups, or composed of more than one monomer tend not to pack well into crystalline structures.
  • the degree of polymerization also contributes to the determination of the crystallinity of a polymer. Relatively short chains organize themselves into crystalline structures more readily than longer molecules, as longer molecules tend to become tangled and thus have difficulty arranging themselves in an ordered manner, resulting in a more amorphous structure.
  • the polymer for forming the rate-reducing coating should be selected to have sufficient crystallinity such that the active agent may not readily diffuse therethrough.
  • the degree of crystallinity of the polymer can be measured by the amount of the polymer that is in the form of crystallites or a detectable pattern of crystals as may be observed using conventional techniques such as x-ray diffraction, measurement of specific volume, infrared spectroscopy, and thermal analysis.
  • the polymer can have a crystallinity of not less than about 10%, alternatively not less than about 25%. In accordance with another embodiment the degree of crystallinity should not be less than about 50%.
  • the polymer When exposed to an aqueous environment such as blood, can have a crystalline of not less than about 10%, alternatively not less than 25%.
  • the polymer can have a crystallinity of at least 50% or at least 25% in an aqueous environment, such as in contact with blood.
  • the crystalline polymers for use in the rate-reducing coating of the present invention should be capable of maintaining their crystallinity in the aqueous in vivo environment in which the coated medical device will be employed.
  • the crystallinity of some polymers decreases when exposed to water. This is due to absorption of water by the polymer, which is also known as polymer swelling. The absorbed water can reduce or eliminate the polymer crystallinity. In extreme cases, such absorption can lead to complete dissolution of the polymer.
  • Polymers that contain ionic, polar, or hydrogen bonding groups have the potential to absorb water. In general, if the interaction of the polymer with water is stronger than that of the polymer with itself or of water with itself, the polymer will swell with water.
  • the polymers for use in the rate-reducing coating of the present invention should be selected to maintain their crystallinity, and thus their rate-reducing capabilities, in an aqueous environment.
  • the value of the solubility parameter ⁇ is inversely proportional to the degree of hydrophobicity of a polymer.
  • Polymers that are very hydrophobic may have a low solubility parameter value. This general proposition is particularly applicable for polymers having a glass transition temperature below physiological temperature.
  • a polymer that is sufficiently hydrophobic for use in the rate-limiting membrane of the present invention can have a solubility parameter of not more than about 10.7 (cal/cm 3 ) 1/2 .
  • Such crystalline, hydrophobic polymers include polytetrafluoroethylene, ethylene-tetrafluoroethylene copolymer, fluoroethylene-alkyl vinyl ether copolymer, polyhexafluoropropene, low density linear polyethylenes having high molecular weights, ethylene-olefin copolymers, styrene-ethylene-styrene block copolymers, styrene-butylene-styrene block copolymers, styrene-ethylene/butylene-styrene block copolymers, styrene-butadiene-styrene block copolymers, styrenic block copolymers including KRATONTM polymers (available from KRATONTM Polymers, Houston, Tex.), ethylene-anhydride copolymers, ethylene-acrylic acid copolymers, poly(vinylidene fluoride), ethylene methacrylic acid copo
  • Polymers of relatively high crystallinity can also maintain their crystallinity in an aqueous environment.
  • Highly crystalline polymers are typically rigid, have high melting temperatures, and are minimally affected by solvent penetration. Since the degree and strength of crystallinity of a polymer can be roughly approximated by the melting temperature of the polymer, sufficiently high crystallinity for use with the present invention is possessed by polymers having a melting temperature greater than or equal to about 135° C. at ambient pressure. Representative examples of polymers having a melting temperature of at least 135° C.
  • nylon 6 poly(vinylidene fluoride), poly(vinylidene fluoride-co-hexafluoropropene), polytetrafluoroethylene, polyetheretherketone (PEEK), polyimide, polysulfone, ethylene-co-methacrylic acid, ethylene-co-acrylic acid, and styrenic block copolymers including KRATONTM polymers (available from KRATONTM Polymers, Houston, Tex.).
  • compositions for such a coating can be prepared by conventional methods wherein a predetermined amount of a suitable polymeric compound is added to a predetermined amount of a compatible solvent.
  • solvent is defined as a liquid substance or composition that is mutually compatible with a polymer and is capable of significantly dissolving the polymer at the concentration desired in the composition.
  • solvents include, but are not limited to, dimethylsulfoxide (DMSO), chloroform, acetone, xylene, methanol, ethanol, 1-propanol, tetrahydrofuran, 1-butanone, dimethylformamide, dimethylacetamide, cyclohexanone, ethyl acetate, methylethylketone, propylene glycol monomethylether, isopropanol, isopropanol admixed with water, N-methyl pyrrolidinone, toluene, hexafluoroisopropanol, methylene chloride, hexamethylphosphorous triamide, N-methylmorpholine, trifluoroethanol, formic acid, and phenol.
  • DMSO dimethylsulfoxide
  • chloroform acetone
  • xylene methanol
  • ethanol 1-propanol
  • tetrahydrofuran 1-butanone
  • dimethylformamide dimethylacet
  • the polymeric compound can be added to the solvent at ambient pressure and under anhydrous atmosphere.
  • the polymeric compound is soluble before crystallization in a solvent system at, for example, temperatures of less than or equal to about 80° C. If necessary, gentle heating and stirring and/or mixing can be employed to effect dissolution of the polymer into the solvent, for example 12 hours in a water bath at about 60° C.
  • composition can be by any conventional method, such as by spraying the composition onto the device or by immersing the device in the composition.
  • Operations such as wiping, centrifugation, blowing, or other web-clearing acts can also be performed to achieve a more uniform coating.
  • wiping refers to physical removal of excess composition from the surface of the stent
  • centrifugation refers to rapid rotation of the stent about an axis of rotation
  • blowing refers to application of air at a selected pressure to the deposited composition. Any excess composition can also be vacuumed off of the surface of the device.
  • the solvent is removed from the composition to form the rate-reducing coating by allowing the solvent to evaporate.
  • the evaporation can be induced by heating the device at a predetermined temperature for a predetermined period of time.
  • the device can be heated at a temperature of about 60° C. for about 1 hour to about 12 hours.
  • the heating can be conducted in an anhydrous atmosphere and at ambient pressure and should not exceed the temperature that would adversely affect the active agent.
  • the heating can, alternatively, be conducted under a vacuum condition. It is understood that essentially all of the solvent will be removed from the composition, but traces or residues may remain blended with the polymer.
  • a medical device for use in conjunction with the above-described rate-reducing coating is broadly defined to include any inter- or intraluminal device used for the release of an active agent and/or for upholding the luminal patency in a human or veterinary patient.
  • implantable devices include self-expandable stents, balloon-expandable stents, stent-grafts, grafts (e.g., aortic grafts), artificial heart valves, cerebrospinal fluid shunts, pacemaker electrodes, anastomosis devices such as axius coronary shunts and endocardial leads (e.g., FINELINE and ENDOTAK, available from Guidant Corporation).
  • the underlying structure of the device can be of virtually any design.
  • the device can be made of a metallic material or an alloy such as, but not limited to, cobalt chromium alloy (ELGILOY), stainless steel (316L), “MP35N,” “MP20N,” ELASTINITE (Nitinol), tantalum, nickel-titanium alloy, platinum-iridium alloy, gold, magnesium, or combinations thereof
  • MP35N and MP20N are trade names for alloys of cobalt, nickel, chromium and molybdenum available from standard Press Steel Co., Jenkintown, Pa.
  • “MP35N” consists of 35% cobalt, 35% nickel, 20% chromium, and 10% molybdenum.
  • MP20N consists of 50% cobalt, 20% nickel, 20% chromium, and 10% molybdenum.
  • Devices made from bioabsorbable or biostable polymers could also be used with the embodiments of the present invention.
  • the above-described rate-reducing coating can function as a barrier layer through which an underlying therapeutic substance or active agent must diffuse to be released from a device into a treatment site.
  • the active agent can be carried by the device, such as in porous cavities in the surface of the device, or can be impregnated in a reservoir polymer layer formed beneath the rate-reducing coating.
  • Such a rate-reducing barrier coating can be of any suitable thickness.
  • the thickness of the coating can be from about 0.01 microns to about 20 microns, more narrowly from about 0.1 microns to about 10 microns.
  • the rate-reducing barrier coating can have a thickness of about 3 microns.
  • the rate-reducing coating can additionally function as a reservoir for carrying the therapeutic substance or active agent.
  • sufficient amounts of an active agent can be dispersed in the blended composition of the suitably crystalline polymer and the solvent.
  • the polymer can comprise from about 0.1% to about 35%, more narrowly from about 2% to about 20% by weight of the total weight of the composition
  • the solvent can comprise from about 59.9% to about 99.8%, more narrowly from about 79% to about 89% by weight of the total weight of the composition
  • the active agent can comprise from about 0.1% to about 40%, more narrowly from about 1% to about 9% by weight of the total weight of the composition.
  • the active agent should be in true solution or saturated in the blended composition. If the active agent is not completely soluble in the composition, operations including mixing, stirring, and/or agitation can be employed to effect homogeneity of the residues.
  • the active agent may be added so that the dispersion is in fine particles.
  • the active agent can be for inhibiting the activity of vascular smooth muscle cells. More specifically, the active agent can be aimed at inhibiting abnormal or inappropriate migration and/or proliferation of smooth muscle cells for the inhibition of restenosis.
  • the active agent can also include any substance capable of exerting a therapeutic or prophylactic effect in the practice of the present invention.
  • the agent can be for enhancing wound healing in a vascular site or improving the structural and elastic properties of the vascular site.
  • agents include antiproliferative substances such as actinomycin D, or derivatives and analogs thereof (manufactured by Sigma-Aldrich 1001 West Saint Paul Avenue, Milwaukee, Wis. 53233; or COSMEGEN available from Merck).
  • actinomycin D examples include dactinomycin, actinomycin IV, actinomycin I 1 , actinomycin X 1 , and actinomycin C 1 .
  • the active agent can also fall under the genus of antineoplastic, antiinflammatory, anti platelet, anticoagulant, antifibrin, antithrombin, antimitotic, antibiotic, antiallergic and antioxidant substances.
  • antineoplastics and/or antimitotics include paclitaxel (e.g. TAXOLTM by Bristol-Myers Squibb Co., Stamford, Conn.), docetaxel (e.g.
  • Taxotere® from Aventis S.A., Frankfurt, Germany methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride (e.g. Adriamycin® from Pharmacia & Upjohn, Peapack N.J.), and mitomycin (e.g. Mutamycin® from Bristol-Myers Squibb Co., Stamford, Conn.).
  • antiplatelets examples include sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, and thrombin inhibitors such as AngiomaxTM (Biogen, Inc., Cambridge, Mass.).
  • AngiomaxTM Biogen, Inc., Cambridge, Mass.
  • cytostatic or antiproliferative agents examples include angiopeptin, angiotensin converting enzyme inhibitors such as captopril (e.g. Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.), cilazapril or lisinopril (e.g.
  • calcium channel blockers such as nifedipine), colchicine, fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand name Mevacor from Merck & Co., Inc., Whitehouse Station, N.J.), monoclonal antibodies (such as those specific for Platelet-Derived Growth Factor (PDGF) receptors), nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitors, suramin, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), and nitric oxide.
  • PDGF Platelet-Derived Growth Factor
  • an antiallergic agent is permirolast potassium.
  • Other therapeutic substances or agents which may be appropriate include alpha-interferon, genetically engineered epithelial cells, rapamycin and dexamethasone. Exposure of the active agent to the composition should not adversely alter the active agent's composition or characteristic. Accordingly, the particular active agent is selected for compatibility with the solvent or blended polymer-solvent.
  • an optional primer layer can be formed on the outer surface of the medical device. Formation of a primer layer, free from any active agents, can be by any conventional method, such as by spraying a primer composition containing a polymer and a compatible solvent onto the medical device or immersing the medical device in the primer composition followed by evaporation of the solvent.
  • the polymer selected can be any polymer suitable for coating a medical device.
  • the deposited primer composition should be exposed to a heat treatment at a temperature range greater than about the glass transition temperature (T g and less than about the melting temperature (T m ) of the selected polymer.
  • T g glass transition temperature
  • T m melting temperature
  • the medical device should be exposed to the heat treatment for any suitable duration of time that will allow for the formation of the primer layer on the outer surface of the device and for the evaporation of the solvent employed. It is understood that essentially all of the solvent will be removed from the primer composition but traces or residues can remain blended with the polymer.
  • the crystalline coating can be topcoated with one or more additional coating layers.
  • additional coating layers can be for increasing the biocompatibility of the device.
  • the additional coating layer can be formed from ethylene vinyl alcohol (EVAL), polyethylene glycol, polyethylene oxide, hyaluronic acid, heparin, or heparin derivatives having hydrophobic counterions, thereby providing biocompatibility to the outermost, tissue-contacting surface of the medical device.
  • EVAL ethylene vinyl alcohol
  • polyethylene glycol polyethylene glycol
  • polyethylene oxide polyethylene oxide
  • hyaluronic acid heparin
  • heparin derivatives having hydrophobic counterions thereby providing biocompatibility to the outermost, tissue-contacting surface of the medical device.
  • an additional coating layer can serve as yet another rate-reducing layer.
  • the additional rate-reducing layer does not contain active agents, the methods by which such a layer is deposited is not limited to the methods by which the polymer layers having active agents are applied. Therefore, in addition to application by conventional methods, such as by spraying a polymeric composition onto the device or by immersing the device in a polymeric composition, the additional rate-reducing layers can be deposited by physical vapor deposition (PVD) techniques, which are known to one of ordinary skill in the art.
  • PVD physical vapor deposition
  • barrier materials that can be deposited via PVD techniques include plasma-deposited polymers, parylene C, parylene N, parylene D, perfluoro parylene, tetrafluoro (AF4) parylene, metallic layers, metallic oxides, metal carbides, and metal nitrides.
  • plasma-deposited polymers parylene C, parylene N, parylene D, perfluoro parylene, tetrafluoro (AF4) parylene, metallic layers, metallic oxides, metal carbides, and metal nitrides.
  • an active agent can be applied to an implantable medical device or prosthesis, e.g., a stent, retained on the stent during delivery and expansion of the stent, and released at a desired control rate and for a predetermined duration of time at the site of implantation.
  • a stent having the above-described coating is useful for a variety of medical procedures, including, by way of example, treatment of obstructions caused by tumors in bile ducts, esophagus, trachea/bronchi and other biological passageways.
  • a stent having the above-described coating is particularly useful for treating occluded regions of blood vessels caused by abnormal or inappropriate migration and proliferation of smooth muscle cells, thrombosis, and restenosis.
  • Stents may be placed in a wide array of blood vessels, both arteries and veins. Representative examples of sites include the iliac, renal, and coronary arteries.
  • an angiogram is first performed to determine the appropriate positioning for stent therapy.
  • An angiogram is typically accomplished by injecting a radiopaque contrasting agent through a catheter inserted into an artery or vein as an x-ray is taken.
  • a guidewire is then advanced through the lesion or proposed site of treatment.
  • Over the guidewire is passed a delivery catheter that allows a stent in its collapsed configuration to be inserted into the passageway.
  • the delivery catheter is inserted either percutaneously or by surgery into the femoral artery, brachial artery, femoral vein, or brachial vein, and advanced into the appropriate blood vessel by steering the catheter through the vascular system under fluoroscopic guidance.
  • a stent having the above-described coating may then be expanded at the desired area of treatment.
  • a post-insertion angiogram may also be utilized to confirm appropriate positioning.
  • a 2% (w/w) solution of EVAL in dimethylacetamide (DMAC) is applied to a 13 mm TetraTM stent (available from Guidant Corporation) using an EFD 780S spray device (available from EFD Inc., East Buffalo, R.I.) until 50 micrograms of solids have been deposited onto the stent.
  • the stent is baked at 140° C. for 60 minutes to form a primer layer on the stent.
  • a solution of 1:9 (w/w) actinomycin D:EVAL and 2% (w/w) EVAL in DMAC is sprayed onto the primered stent until 100 micrograms of solids have been deposited.
  • the stent is baked at 50° C.
  • a 2% (w/w) solution of EVAL in DMAC is applied to a 13 mm TetraTM stent using an EFD 780S spray device until 50 micrograms of solids have been deposited onto the stent.
  • the stent is baked at 140° C. for 60 minutes to form a primer layer on the stent.
  • a solution of 1:3 (w/w) dexamethasone:poly(ethylene-co-vinyl-acetate) and 2% (w/w) polyethylene-co-vinyl-acetate) in cyclohexanone is sprayed onto the primered stent until 300 micrograms of solids have been deposited.
  • the stent is baked at 60° C.
  • KRATON G1650 available from KRATONTM Polymers, Houston, Tex.
  • a 2% (w/w) KRATON G1650 (available from KRATONTM Polymers, Houston, Tex.) solution in xylene is sprayed until 300 micrograms of solids have been deposited onto the stent.
  • the stent is baked at 60° C. for 2 hours to form a crystalline rate-reducing membrane of KRATON G1650.
  • a 2% (w/w) solution of EVAL in DMAC is applied to a 13 mm TetraTM stent using an EFD 780S spray device until 50 micrograms of solids have been deposited onto the stent.
  • the stent is baked at 140° C. for 60 minutes to form a primer layer on the stent.
  • a solution of 1:2 (w/w) estradiol:EVAL and 2% (w/w) EVAL in DMAC is sprayed onto the primered stent until 350 micrograms of solids have been deposited.
  • the stent is baked at 60° C. for 2 hours to form an estradiol-containing reservoir coating.
  • a 2% (w/w) poly(vinylidene fluoride-co-hexafluoropropene) solution in 1:1 (w/w) acetone:DMAC is sprayed until 300 micrograms of solids have been deposited onto the stent.
  • the stent is baked at 60° C. for 2 hours to form a crystalline rate-reducing membrane of poly(vinylidene fluoride-co-hexafluoropropene).
  • a 2% (w/w) solution of poly(n-butyl methacrylate) in 4:1 (w/w) acetone:cyclohexanone is applied to a 13 mm Tetra stent using an EFD 780S spray device until 50 micrograms of solids have been deposited onto the stent.
  • the stent is baked at 70° C. for 60 minutes to form a primer layer on the stent.
  • a solution of 1:2 (w/w) etoposide:EVAL and 2% (w/w) EVAL in DMAC is sprayed onto the primered stent until 300 micrograms of solids have been deposited.
  • the stent is baked at 60° C. for 2 hours to form an etoposide-containing reservoir coating.
  • the stent is baked at 60° C. for 2 hours to form a crystalline rate-reducing membrane of silicone-urethane Elast-EonTM 55D.

Abstract

A stent for delivery of a therapeutic agent is disclosed. The stent includes a polymer coating for reducing the rate of release of the therapeutic agent. The polymer has a crystalline structure wherein the polymer is capable of significantly maintaining the crystalline lattice structure while the therapeutic agent is released from the stent such that the aqueous environment to which the stent is exposed subsequent to the implantation of the stent does not significantly convert the crystalline lattice structure of the polymer to an amorphous structure.

Description

    CROSS-REFERENCE TO RELATED APPLICATION
  • This is a divisional application of U.S. application Ser. No. 09/948,513, filed on Sep. 7, 2001, the teachings of which are incorporated herein in their entirety by reference.
  • BACKGROUND OF THE INVENTION
  • 1. Field of the Invention
  • A medical device, such as a stent, for delivering a therapeutic substance is disclosed. The stent includes a polymeric coating for reducing the rate of release of the therapeutic substance.
  • 2. Description of the Background
  • Blood vessel occlusions are commonly treated by mechanically enhancing blood flow in the affected vessels, such as by employing a stent. Stents act as scaffoldings, functioning to physically hold open and, if desired, to expand the wall of the passageway. Typically stents are capable of being compressed, so that they can be inserted through small lumens via catheters, and then expanded to a larger diameter once they are at the desired location. Examples in the patent literature disclosing stents include U.S. Pat. No. 4,733,665 issued to Palmaz, U.S. Pat. No. 4,800,882 issued to Gianturco, and U.S. Pat. No. 4,886,062 issued to Wiktor.
  • Stents are used not only for mechanical intervention but also as vehicles for providing biological therapy. Biological therapy can be achieved by medicating the stents. Medicated stents provide for the local administration of a therapeutic substance at the diseased site. Local delivery of a therapeutic substance is a preferred method of treatment because the substance is concentrated at a specific site and thus smaller total levels of medication can be administered in comparison to systemic dosages that often produce adverse or even toxic side effects for the patient.
  • One method of medicating a stent involves the use of a polymeric carrier coated onto the surface of the stent. A composition including a solvent, a polymer dissolved in the solvent, and a therapeutic substance dispersed in the blend is applied to the stent by immersing the stent in the composition or by spraying the composition onto the stent. The solvent is allowed to evaporate, leaving on the stent strut surfaces a coating of the polymer and the therapeutic substance impregnated in the polymer.
  • Depending on the physiological mechanism targeted, the therapeutic substance may be required to be released at an efficacious concentration for an extended duration of time. Increasing the quantity of the therapeutic substance in the polymeric coating can lead to poor coating mechanical properties, inadequate coating adhesion, and overly rapid rate of release. Increasing the quantity of the polymeric compound by producing a thicker coating can perturb the geometrical and mechanical functionality of the stent as well as limit the procedures for which the stent can be used.
  • It is desirable to increase the residence time of a substance at the site of implantation, at a therapeutically useful concentration, without the addition of a greater percentage of the therapeutic substance to the polymeric coating and without the application of a significantly thicker coating.
  • SUMMARY OF THE INVENTION
  • The present invention discloses a stent for delivery of a therapeutic agent. The stent includes a polymer coating for reducing the rate of release of the therapeutic agent. The polymer has a crystalline lattice structure, wherein the polymer is capable of significantly maintaining the crystalline lattice structure while the therapeutic agent is released from the stent such that the aqueous environment to which the stent is exposed subsequent to the implantation of the stent does not significantly convert the crystalline lattice structure of the polymer to an amorphous structure.
  • The coating can contain the therapeutic agent. In one embodiment, the melting point of the polymer is greater than or equal to about 135° C. at ambient pressure. In another embodiment, the polymer is a hydrophobic polymer having a solubility parameter not greater than about 10.7 (cal/cm3)1/2.
  • Also disclosed is a method of forming a coating for a stent. The method includes applying a first composition including a polymeric material to at least a portion of the stent to form a polymer coating supported by the stent. The polymer has a crystalline structure, wherein the aqueous environment to which the coating is exposed subsequent to the implantation of the stent does not significantly convert the crystalline structure of the polymer to an amorphous structure for the duration of time which the agent is released from the stent.
  • The present invention additionally discloses a composition for coating a stent. The composition includes a fluid and a polymer dissolved in the fluid. The polymer includes a crystalline structure during the duration of delivery of an active agent from the stent, and the aqueous environment to which the stent is exposed subsequent to the implantation procedure does not significantly change the crystalline stricture to an amorphous structure.
  • Also disclosed is a stent for delivering a therapeutic agent to an implanted site. The stent includes a radially expandable body structure and a polymeric coating supported by the body structure for extending the residence time of the therapeutic agent at the implanted site. The polymeric coating is made from a hydrophobic polymer having a degree of crystallinity that remains at or above about 10% at least until a significant amount of the therapeutic substance has been released from the stent.
  • DETAILED DESCRIPTION Embodiments of the Rate-Reducing Coating
  • One mechanism through which the release rate of an active agent from a medical device can be controlled is the crystallinity of the polymer with which the medical device is coated. A polymer in which the molecules are arranged in a highly ordered and regular pattern formed by folding and stacking of the polymer chains is said to be crystalline. By contrast, amorphous polymers have molecules that are arranged randomly with no regularity of orientation with respect to one another. Among the factors that affect polymer crystallinity are the stereoregularity of the polymer, the tacticity of the polymer, the presence of branching, the degree of polymerization, and the strength of the intermolecular forces between the polymer chains.
  • The structural arrangement and regularity of a polymer is an important factor in the determination of polymer crystallinity. A regular arrangement along the polymer chains provides the polymer structure with a high degree of symmetry, allowing the chains to pack into crystals. Irregularity along the polymer chains, however, prevents the chains from packing closely to one another, thereby decreasing crystallinity. Polymers with regular, linear, and rigid structures tend to form ordered crystals. By contrast, polymers with large side groups, mixed tacticity or an atactic structure, a mix of side or functional groups, or composed of more than one monomer tend not to pack well into crystalline structures.
  • The degree of polymerization also contributes to the determination of the crystallinity of a polymer. Relatively short chains organize themselves into crystalline structures more readily than longer molecules, as longer molecules tend to become tangled and thus have difficulty arranging themselves in an ordered manner, resulting in a more amorphous structure.
  • Also influencing polymer crystallinity is the presence of intermolecular forces. The presence of polar and hydrogen bonding groups favors crystallinity because such groups promote dipole-dipole and hydrogen bonding intermolecular forces. Such strong interchain forces hold the polymer chains in a tightly packed configuration, thereby promoting crystallinity. By contrast, polymers with little or no intermolecular forces will tend to have random, non-crystalline structures as a result of thermal motion.
  • Typically, as the crystallinity of a polymer increases, so too does the polymer's ability to reduce the rate at which an active agent is released from a medical device coated with the polymer. This is because it is more difficult for an active agent to diffuse through a tightly packed, crystalline polymer than a more loosely packed, amorphous polymer. The purpose of the coating of the present invention is to decrease the rate of release of an active agent therefrom. Accordingly, the polymer for forming the rate-reducing coating should be selected to have sufficient crystallinity such that the active agent may not readily diffuse therethrough.
  • The degree of crystallinity of the polymer can be measured by the amount of the polymer that is in the form of crystallites or a detectable pattern of crystals as may be observed using conventional techniques such as x-ray diffraction, measurement of specific volume, infrared spectroscopy, and thermal analysis. For use with the embodiments of the present invention, the polymer can have a crystallinity of not less than about 10%, alternatively not less than about 25%. In accordance with another embodiment the degree of crystallinity should not be less than about 50%. When exposed to an aqueous environment such as blood, the polymer can have a crystalline of not less than about 10%, alternatively not less than 25%. In one example, the polymer can have a crystallinity of at least 50% or at least 25% in an aqueous environment, such as in contact with blood.
  • In addition, the crystalline polymers for use in the rate-reducing coating of the present invention should be capable of maintaining their crystallinity in the aqueous in vivo environment in which the coated medical device will be employed. The crystallinity of some polymers decreases when exposed to water. This is due to absorption of water by the polymer, which is also known as polymer swelling. The absorbed water can reduce or eliminate the polymer crystallinity. In extreme cases, such absorption can lead to complete dissolution of the polymer. Polymers that contain ionic, polar, or hydrogen bonding groups have the potential to absorb water. In general, if the interaction of the polymer with water is stronger than that of the polymer with itself or of water with itself, the polymer will swell with water. When a polymer swells, its chains move apart to form pores in the polymeric network, thereby increasing the diffusion rate of an active agent through the polymeric network. Accordingly, the polymers for use in the rate-reducing coating of the present invention should be selected to maintain their crystallinity, and thus their rate-reducing capabilities, in an aqueous environment.
  • Many crystalline polymers that are hydrophobic can maintain their crystallinity in an aqueous environment because hydrophobic materials are “water-avoiding.” One method of defining the hydrophobicity of a polymer is by the solubility parameter of the polymer, also known as the polymer's cohesive energy density. The solubility parameter is represented by Equation 1:
    δ=(ΔE/V)1/2  (Equation 1)
      • where
        • δ=solubility parameter ((cal/cm3)1/2)
        • ΔE=energy of vaporization (cal)
        • V=molar volume (cm3)
          (“Polymer Handbook”, 2nd Ed., Brandrup J. and E H Immergut, ed., Wiley-Interscience, John Wiley & Sons, N.Y. (1975)). Because polymers are typically non-volatile and thus cannot be vaporized without decomposition, the solubility parameter is measured indirectly. Briefly, solvents in which a polymer dissolves without a change in heat or volume are identified. The solubility parameter of the polymer is then defined to be the same as the solubility parameters of the identified solvents.
  • As a general rule, the value of the solubility parameter δ is inversely proportional to the degree of hydrophobicity of a polymer. Polymers that are very hydrophobic may have a low solubility parameter value. This general proposition is particularly applicable for polymers having a glass transition temperature below physiological temperature. A polymer that is sufficiently hydrophobic for use in the rate-limiting membrane of the present invention can have a solubility parameter of not more than about 10.7 (cal/cm3)1/2. Representative examples of such crystalline, hydrophobic polymers include polytetrafluoroethylene, ethylene-tetrafluoroethylene copolymer, fluoroethylene-alkyl vinyl ether copolymer, polyhexafluoropropene, low density linear polyethylenes having high molecular weights, ethylene-olefin copolymers, styrene-ethylene-styrene block copolymers, styrene-butylene-styrene block copolymers, styrene-ethylene/butylene-styrene block copolymers, styrene-butadiene-styrene block copolymers, styrenic block copolymers including KRATON™ polymers (available from KRATON™ Polymers, Houston, Tex.), ethylene-anhydride copolymers, ethylene-acrylic acid copolymers, poly(vinylidene fluoride), ethylene methacrylic acid copolymers, polylurethanes with a polydimethylsiloxane soft segment, poly(vinylidene fluoride-co-hexafluoropropene), and polycarbonate urethanes (e.g., BIONATE 55D and BIONATE 75D).
  • Polymers of relatively high crystallinity can also maintain their crystallinity in an aqueous environment. Highly crystalline polymers are typically rigid, have high melting temperatures, and are minimally affected by solvent penetration. Since the degree and strength of crystallinity of a polymer can be roughly approximated by the melting temperature of the polymer, sufficiently high crystallinity for use with the present invention is possessed by polymers having a melting temperature greater than or equal to about 135° C. at ambient pressure. Representative examples of polymers having a melting temperature of at least 135° C. at ambient pressure include, but are not limited to, nylon 6, poly(vinylidene fluoride), poly(vinylidene fluoride-co-hexafluoropropene), polytetrafluoroethylene, polyetheretherketone (PEEK), polyimide, polysulfone, ethylene-co-methacrylic acid, ethylene-co-acrylic acid, and styrenic block copolymers including KRATON™ polymers (available from KRATON™ Polymers, Houston, Tex.).
  • The above-described suitably crystalline polymers can be used to form a rate-reducing coating onto a medical device. The embodiments of the composition for such a coating can be prepared by conventional methods wherein a predetermined amount of a suitable polymeric compound is added to a predetermined amount of a compatible solvent. “Solvent” is defined as a liquid substance or composition that is mutually compatible with a polymer and is capable of significantly dissolving the polymer at the concentration desired in the composition. Examples of solvents include, but are not limited to, dimethylsulfoxide (DMSO), chloroform, acetone, xylene, methanol, ethanol, 1-propanol, tetrahydrofuran, 1-butanone, dimethylformamide, dimethylacetamide, cyclohexanone, ethyl acetate, methylethylketone, propylene glycol monomethylether, isopropanol, isopropanol admixed with water, N-methyl pyrrolidinone, toluene, hexafluoroisopropanol, methylene chloride, hexamethylphosphorous triamide, N-methylmorpholine, trifluoroethanol, formic acid, and phenol. The polymeric compound can be added to the solvent at ambient pressure and under anhydrous atmosphere. The polymeric compound is soluble before crystallization in a solvent system at, for example, temperatures of less than or equal to about 80° C. If necessary, gentle heating and stirring and/or mixing can be employed to effect dissolution of the polymer into the solvent, for example 12 hours in a water bath at about 60° C.
  • Application of the composition can be by any conventional method, such as by spraying the composition onto the device or by immersing the device in the composition. Operations such as wiping, centrifugation, blowing, or other web-clearing acts can also be performed to achieve a more uniform coating. Briefly, wiping refers to physical removal of excess composition from the surface of the stent; centrifugation refers to rapid rotation of the stent about an axis of rotation; and blowing refers to application of air at a selected pressure to the deposited composition. Any excess composition can also be vacuumed off of the surface of the device. The solvent is removed from the composition to form the rate-reducing coating by allowing the solvent to evaporate. The evaporation can be induced by heating the device at a predetermined temperature for a predetermined period of time. For example, the device can be heated at a temperature of about 60° C. for about 1 hour to about 12 hours. The heating can be conducted in an anhydrous atmosphere and at ambient pressure and should not exceed the temperature that would adversely affect the active agent. The heating can, alternatively, be conducted under a vacuum condition. It is understood that essentially all of the solvent will be removed from the composition, but traces or residues may remain blended with the polymer.
  • Examples of the Device
  • A medical device for use in conjunction with the above-described rate-reducing coating is broadly defined to include any inter- or intraluminal device used for the release of an active agent and/or for upholding the luminal patency in a human or veterinary patient. Examples of such implantable devices include self-expandable stents, balloon-expandable stents, stent-grafts, grafts (e.g., aortic grafts), artificial heart valves, cerebrospinal fluid shunts, pacemaker electrodes, anastomosis devices such as axius coronary shunts and endocardial leads (e.g., FINELINE and ENDOTAK, available from Guidant Corporation). The underlying structure of the device can be of virtually any design. The device can be made of a metallic material or an alloy such as, but not limited to, cobalt chromium alloy (ELGILOY), stainless steel (316L), “MP35N,” “MP20N,” ELASTINITE (Nitinol), tantalum, nickel-titanium alloy, platinum-iridium alloy, gold, magnesium, or combinations thereof “MP35N” and “MP20N” are trade names for alloys of cobalt, nickel, chromium and molybdenum available from standard Press Steel Co., Jenkintown, Pa. “MP35N” consists of 35% cobalt, 35% nickel, 20% chromium, and 10% molybdenum. “MP20N” consists of 50% cobalt, 20% nickel, 20% chromium, and 10% molybdenum. Devices made from bioabsorbable or biostable polymers could also be used with the embodiments of the present invention.
  • Use of the Rate-Reducing Coating
  • In one embodiment, the above-described rate-reducing coating, free from therapeutic substances or active agents, can function as a barrier layer through which an underlying therapeutic substance or active agent must diffuse to be released from a device into a treatment site. The active agent can be carried by the device, such as in porous cavities in the surface of the device, or can be impregnated in a reservoir polymer layer formed beneath the rate-reducing coating. Such a rate-reducing barrier coating can be of any suitable thickness. The thickness of the coating can be from about 0.01 microns to about 20 microns, more narrowly from about 0.1 microns to about 10 microns. By way of example, the rate-reducing barrier coating can have a thickness of about 3 microns.
  • In another embodiment, the rate-reducing coating can additionally function as a reservoir for carrying the therapeutic substance or active agent. In such an embodiment, sufficient amounts of an active agent can be dispersed in the blended composition of the suitably crystalline polymer and the solvent. The polymer can comprise from about 0.1% to about 35%, more narrowly from about 2% to about 20% by weight of the total weight of the composition, the solvent can comprise from about 59.9% to about 99.8%, more narrowly from about 79% to about 89% by weight of the total weight of the composition, and the active agent can comprise from about 0.1% to about 40%, more narrowly from about 1% to about 9% by weight of the total weight of the composition.
  • The active agent should be in true solution or saturated in the blended composition. If the active agent is not completely soluble in the composition, operations including mixing, stirring, and/or agitation can be employed to effect homogeneity of the residues. The active agent may be added so that the dispersion is in fine particles.
  • The active agent can be for inhibiting the activity of vascular smooth muscle cells. More specifically, the active agent can be aimed at inhibiting abnormal or inappropriate migration and/or proliferation of smooth muscle cells for the inhibition of restenosis. The active agent can also include any substance capable of exerting a therapeutic or prophylactic effect in the practice of the present invention. For example, the agent can be for enhancing wound healing in a vascular site or improving the structural and elastic properties of the vascular site. Examples of agents include antiproliferative substances such as actinomycin D, or derivatives and analogs thereof (manufactured by Sigma-Aldrich 1001 West Saint Paul Avenue, Milwaukee, Wis. 53233; or COSMEGEN available from Merck). Synonyms of actinomycin D include dactinomycin, actinomycin IV, actinomycin I1, actinomycin X1, and actinomycin C1. The active agent can also fall under the genus of antineoplastic, antiinflammatory, anti platelet, anticoagulant, antifibrin, antithrombin, antimitotic, antibiotic, antiallergic and antioxidant substances. Examples of such antineoplastics and/or antimitotics include paclitaxel (e.g. TAXOL™ by Bristol-Myers Squibb Co., Stamford, Conn.), docetaxel (e.g. Taxotere®, from Aventis S.A., Frankfurt, Germany) methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride (e.g. Adriamycin® from Pharmacia & Upjohn, Peapack N.J.), and mitomycin (e.g. Mutamycin® from Bristol-Myers Squibb Co., Stamford, Conn.). Examples of such antiplatelets, anticoagulants, antifibrin, and antithrombins include sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, and thrombin inhibitors such as Angiomax™ (Biogen, Inc., Cambridge, Mass.). Examples of such cytostatic or antiproliferative agents include angiopeptin, angiotensin converting enzyme inhibitors such as captopril (e.g. Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.), cilazapril or lisinopril (e.g. Prinivil® and Prinzide from Merck & Co., Inc., Whitehouse Station, N.J.); calcium channel blockers (such as nifedipine), colchicine, fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand name Mevacor from Merck & Co., Inc., Whitehouse Station, N.J.), monoclonal antibodies (such as those specific for Platelet-Derived Growth Factor (PDGF) receptors), nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitors, suramin, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), and nitric oxide. An example of an antiallergic agent is permirolast potassium. Other therapeutic substances or agents which may be appropriate include alpha-interferon, genetically engineered epithelial cells, rapamycin and dexamethasone. Exposure of the active agent to the composition should not adversely alter the active agent's composition or characteristic. Accordingly, the particular active agent is selected for compatibility with the solvent or blended polymer-solvent.
  • In one embodiment, an optional primer layer can be formed on the outer surface of the medical device. Formation of a primer layer, free from any active agents, can be by any conventional method, such as by spraying a primer composition containing a polymer and a compatible solvent onto the medical device or immersing the medical device in the primer composition followed by evaporation of the solvent. The polymer selected can be any polymer suitable for coating a medical device. With the use of thermoplastic polymers such as, but not limited to, ethylene vinyl alcohol copolymer, polycaprolactone, poly(lactide-co-glycolide), and poly(hydroxybutyrate), the deposited primer composition should be exposed to a heat treatment at a temperature range greater than about the glass transition temperature (Tg and less than about the melting temperature (Tm) of the selected polymer. Unexpected results have been discovered with treatment of the composition under this temperature range, specifically strong adhesion or bonding of the coating to the metallic surface of a stent. The medical device should be exposed to the heat treatment for any suitable duration of time that will allow for the formation of the primer layer on the outer surface of the device and for the evaporation of the solvent employed. It is understood that essentially all of the solvent will be removed from the primer composition but traces or residues can remain blended with the polymer.
  • In other embodiments, the crystalline coating can be topcoated with one or more additional coating layers. Such additional coating layers can be for increasing the biocompatibility of the device. For example, in one embodiment, the additional coating layer can be formed from ethylene vinyl alcohol (EVAL), polyethylene glycol, polyethylene oxide, hyaluronic acid, heparin, or heparin derivatives having hydrophobic counterions, thereby providing biocompatibility to the outermost, tissue-contacting surface of the medical device.
  • In another embodiment, an additional coating layer can serve as yet another rate-reducing layer. Because the additional rate-reducing layer does not contain active agents, the methods by which such a layer is deposited is not limited to the methods by which the polymer layers having active agents are applied. Therefore, in addition to application by conventional methods, such as by spraying a polymeric composition onto the device or by immersing the device in a polymeric composition, the additional rate-reducing layers can be deposited by physical vapor deposition (PVD) techniques, which are known to one of ordinary skill in the art. Representative examples of barrier materials that can be deposited via PVD techniques include plasma-deposited polymers, parylene C, parylene N, parylene D, perfluoro parylene, tetrafluoro (AF4) parylene, metallic layers, metallic oxides, metal carbides, and metal nitrides.
  • Methods of Use
  • In accordance with embodiments of the above-described method, an active agent can be applied to an implantable medical device or prosthesis, e.g., a stent, retained on the stent during delivery and expansion of the stent, and released at a desired control rate and for a predetermined duration of time at the site of implantation. A stent having the above-described coating is useful for a variety of medical procedures, including, by way of example, treatment of obstructions caused by tumors in bile ducts, esophagus, trachea/bronchi and other biological passageways. A stent having the above-described coating is particularly useful for treating occluded regions of blood vessels caused by abnormal or inappropriate migration and proliferation of smooth muscle cells, thrombosis, and restenosis. Stents may be placed in a wide array of blood vessels, both arteries and veins. Representative examples of sites include the iliac, renal, and coronary arteries.
  • Briefly, an angiogram is first performed to determine the appropriate positioning for stent therapy. An angiogram is typically accomplished by injecting a radiopaque contrasting agent through a catheter inserted into an artery or vein as an x-ray is taken. A guidewire is then advanced through the lesion or proposed site of treatment. Over the guidewire is passed a delivery catheter that allows a stent in its collapsed configuration to be inserted into the passageway. The delivery catheter is inserted either percutaneously or by surgery into the femoral artery, brachial artery, femoral vein, or brachial vein, and advanced into the appropriate blood vessel by steering the catheter through the vascular system under fluoroscopic guidance. A stent having the above-described coating may then be expanded at the desired area of treatment. A post-insertion angiogram may also be utilized to confirm appropriate positioning.
  • EXAMPLES
  • The embodiments of the invention will be illustrated by the following set forth prophetic examples, which are being given by way of illustration only and not by way of limitation. All parameters are not to be construed to unduly limit the scope of the embodiments of the invention.
  • Example 1
  • A 2% (w/w) solution of EVAL in dimethylacetamide (DMAC) is applied to a 13 mm Tetra™ stent (available from Guidant Corporation) using an EFD 780S spray device (available from EFD Inc., East Providence, R.I.) until 50 micrograms of solids have been deposited onto the stent. The stent is baked at 140° C. for 60 minutes to form a primer layer on the stent. A solution of 1:9 (w/w) actinomycin D:EVAL and 2% (w/w) EVAL in DMAC is sprayed onto the primered stent until 100 micrograms of solids have been deposited. The stent is baked at 50° C. for 2 hours to form an actinomycin D-containing reservoir coating. A 2% (w/w) polyvinylidene fluoride solution in DMAC is sprayed until 300 micrograms of solids have been deposited onto the stent. The stent is baked at 50° C. for 2 hours to form a crystalline rate-reducing membrane of polyvinylidene fluoride.
  • Example 2
  • A 2% (w/w) solution of EVAL in DMAC is applied to a 13 mm Tetra™ stent using an EFD 780S spray device until 50 micrograms of solids have been deposited onto the stent. The stent is baked at 140° C. for 60 minutes to form a primer layer on the stent. A solution of 1:3 (w/w) dexamethasone:poly(ethylene-co-vinyl-acetate) and 2% (w/w) polyethylene-co-vinyl-acetate) in cyclohexanone is sprayed onto the primered stent until 300 micrograms of solids have been deposited. The stent is baked at 60° C. for 2 hours to form a dexamethasone-containing reservoir coating. A 2% (w/w) KRATON G1650 (available from KRATON™ Polymers, Houston, Tex.) solution in xylene is sprayed until 300 micrograms of solids have been deposited onto the stent. The stent is baked at 60° C. for 2 hours to form a crystalline rate-reducing membrane of KRATON G1650.
  • Example 3
  • A 2% (w/w) solution of EVAL in DMAC is applied to a 13 mm Tetra™ stent using an EFD 780S spray device until 50 micrograms of solids have been deposited onto the stent. The stent is baked at 140° C. for 60 minutes to form a primer layer on the stent. A solution of 1:2 (w/w) estradiol:EVAL and 2% (w/w) EVAL in DMAC is sprayed onto the primered stent until 350 micrograms of solids have been deposited. The stent is baked at 60° C. for 2 hours to form an estradiol-containing reservoir coating. A 2% (w/w) poly(vinylidene fluoride-co-hexafluoropropene) solution in 1:1 (w/w) acetone:DMAC is sprayed until 300 micrograms of solids have been deposited onto the stent. The stent is baked at 60° C. for 2 hours to form a crystalline rate-reducing membrane of poly(vinylidene fluoride-co-hexafluoropropene).
  • Example 4
  • A 2% (w/w) solution of poly(n-butyl methacrylate) in 4:1 (w/w) acetone:cyclohexanone is applied to a 13 mm Tetra stent using an EFD 780S spray device until 50 micrograms of solids have been deposited onto the stent. The stent is baked at 70° C. for 60 minutes to form a primer layer on the stent. A solution of 1:2 (w/w) etoposide:EVAL and 2% (w/w) EVAL in DMAC is sprayed onto the primered stent until 300 micrograms of solids have been deposited. The stent is baked at 60° C. for 2 hours to form an etoposide-containing reservoir coating. A 1.5% (w/w) silicone-urethane Elast-Eon™ 55D (available from Elastomedic Pty Ltd., Australia) solution in 1:1 (w/w) THF:DMAC is sprayed until 300 micrograms of solids have been deposited onto the stent. The stent is baked at 60° C. for 2 hours to form a crystalline rate-reducing membrane of silicone-urethane Elast-Eon™ 55D.
  • While particular embodiments of the present invention have been shown and described, it will be obvious to those skilled in the art that changes and modifications can be made without departing from this invention in its broader aspects and, therefore, the appended claims are to encompass within their scope all such changes and modifications as fall within the true spirit and scope of this invention.

Claims (9)

1. A stent for delivery of a therapeutic agent, comprising:
a substrate; and
a polymer coating on the substrate having a first coating layer, a second coating layer, and a third coating layer,
wherein the third coating layer is over the second coating layer and the second coating layer is over the first coating layer,
wherein the first coating layer is a reservoir layer containing a therapeutic agent above the substrate, the second coating layer is free from therapeutic agents, and the third coating layer increases the biocompatibility of the device, and
wherein the third coating layer includes a polymer selected from a group consisting of ethylene vinyl alcohol, polyethylene glycol, and hyaluronic acid,
the polymer in the second coating layer being capable of substantially reducing the rate of release of the therapeutic agent, wherein the polymer in the second coating layer has a crystalline structure and is capable of significantly maintaining the crystalline structure while the therapeutic agent is released from the stent such that the aqueous environment to which the stent is exposed subsequent to the implantation of the stent does not significantly convert the crystalline structure of the polymer of the second layer to an amorphous structure.
2. The stent of claim 1, wherein the polymer in the first coating layer is capable of substantially reducing the rate of release of the therapeutic agent, wherein the polymer in the first coating layer has a crystalline structure and is capable of significantly maintaining the crystalline structure while the therapeutic agent is released from the stent such that the aqueous environment to which the stent is exposed subsequent to the implantation of the stent does not significantly convert the crystalline structure of the polymer of the second layer to an amorphous structure.
3. The stent of claim 1, wherein the polymer in the second coating layer and optionally the first coating layer is selected from a group consisting of fluoroethylene-alkyl vinyl ether copolymer, polyhexafluoropropene, low density linear polyethylenes having high molecular weights, ethylene-olefin copolymers, styrene-ethylene-styrene block copolymers, styrene-butylene-styrene block copolymers, styrene-ethylene/butylene-styrene block copolymers, styrene-butadiene-styrene block copolymers, ethylene-anhydride copolymers, ethylene-acrylic acid copolymers, styrenic block copolymers, ethylene methacrylic acid copolymers, polyurethanes with a polydimethylsiloxane soft segment, poly(vinylidene fluoride-co-hexafluoropropene), polycarbonate urethanes, and nylon 6.
4. A method of forming a coating for a stent that substantially reduces the rate of release of a therapeutic agent from the stent, comprising:
applying a first composition including a first polymeric material to at least a portion of the stent to form a first polymer coating layer supported by the stent,
applying a second composition including a second polymeric material over at least a portion of the first coating layer to form a second polymer coating layer over the first coating layer,
applying a third composition including a third polymeric material over at least a portion of the second coating layer to form a third polymer coating layer over the second coating layer, the third polymer coating layer increasing the biocompatibility of the device,
the second polymeric material having a crystalline structure, wherein the aqueous environment to which the second coating layer is exposed subsequent to the implantation of the stent does not significantly convert the crystalline structure of the second polymeric material to an amorphous structure for the duration of time which the agent is released from the coating layers,
the third polymeric material in the third polymer coating layer is selected from a group consisting of ethylene vinyl alcohol, polyethylene glycol, and hyaluronic acid.
5. The method of claim 4, wherein the first polymeric material has a crystalline structure, and wherein the aqueous environment to which the first coating layer is exposed subsequent to the implantation of the stent does not significantly convert the crystalline structure of the first polymeric material to an amorphous structure for the duration of time which the agent is released from the coating layers.
6. The method of claim 4, wherein the polymeric material in the first coating layer and the second coating layer is selected from a group consisting of fluoroethylene-alkyl vinyl ether copolymer, polyhexafluoropropene, low density linear polyethylenes having high molecular weights, ethylene-olefin copolymers, styrene-ethylene-styrene block copolymers, styrene-butylene-styrene block copolymers, styrene-ethylene/butylene-styrene block copolymers, styrene-butadiene-styrene block copolymers, ethylene-anhydride copolymers, ethylene-acrylic acid copolymers, styrenic block copolymers, ethylene methacrylic acid copolymers, polyurethanes with a polydimethylsiloxane soft segment, poly(vinylidene fluoride-co-hexafluoropropene), polycarbonate urethanes, and nylon 6.
7. A stent for delivering a therapeutic agent to an implanted site, comprising:
a radially expandable body structure; and
a polymeric coating supported by the body structure that substantially increases the residence time of the therapeutic agent at the implanted site,
wherein the polymeric coating includes a first coating layer, a second coating layer, and a third coating layer,
wherein the third coating layer is over the second coating layer, the second coating layer is over a first coating layer, the first coating layer is a reservoir layer containing a therapeutic agent above the substrate, the second coating layer is free from therapeutic agents, and the third coating layer increases the biocompatibility of the device,
wherein the second coating layer is made from a hydrophobic polymer having a degree of crystallinity that remains at or above about 10% at least until a significant amount of the therapeutic substance has been released from the stent, and
wherein the third coating layer includes a polymer selected from a group consisting of ethylene vinyl alcohol, polyethylene glycol, and hyaluronic acid.
8. The stent of claim 7, wherein the first coating layer is made from a hydrophobic polymer having a degree of crystallinity that remains at or above about 10% at least until a significant amount of the therapeutic substance has been released from the stent.
9. The stent of claim 7, wherein the polymer in the second coating layer and the first coating layer is selected from a group consisting of fluoroethylene-alkyl vinyl ether copolymer, polyhexafluoropropene, low density linear polyethylenes having high molecular weights, ethylene-olefin copolymers, styrene-ethylene-styrene block copolymers, styrene-butylene-styrene block copolymers, styrene-ethylene/butylene-styrene block copolymers, styrene-butadiene-styrene block copolymers, ethylene-anhydride copolymers, ethylene-acrylic acid copolymers, styrenic block copolymers, ethylene methacrylic acid copolymers, polyurethanes with a polydimethylsiloxane soft segment, poly(vinylidene fluoride-co-hexafluoropropene), polycarbonate urethanes, and nylon 6.
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Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080269105A1 (en) * 2006-12-05 2008-10-30 David Taft Delivery of drugs
US20090041845A1 (en) * 2007-08-08 2009-02-12 Lothar Walter Kleiner Implantable medical devices having thin absorbable coatings
US20090093875A1 (en) * 2007-05-01 2009-04-09 Abbott Laboratories Drug eluting stents with prolonged local elution profiles with high local concentrations and low systemic concentrations
US20090209558A1 (en) * 2007-12-04 2009-08-20 Landec Corporation Polymer formulations for delivery of bioactive materials
US20090246155A1 (en) * 2006-12-05 2009-10-01 Landec Corporation Compositions and methods for personal care
US20090252777A1 (en) * 2006-12-05 2009-10-08 Landec Corporation Method for formulating a controlled-release pharmaceutical formulation
US20090263346A1 (en) * 2006-12-05 2009-10-22 David Taft Systems and methods for delivery of drugs
US20090264912A1 (en) * 2000-10-03 2009-10-22 Nawrocki Jesse G Medical devices having durable and lubricious polymeric coating
US20100004124A1 (en) * 2006-12-05 2010-01-07 David Taft Systems and methods for delivery of materials for agriculture and aquaculture
US8183337B1 (en) 2009-04-29 2012-05-22 Abbott Cardiovascular Systems Inc. Method of purifying ethylene vinyl alcohol copolymers for use with implantable medical devices
US20150033118A1 (en) * 2009-03-23 2015-01-29 Adobe Systems Incorporated Transferring component hierarchies between applications
US20150365548A1 (en) * 2014-06-16 2015-12-17 Fujifilm Corporation Display processor, display processing method and ordering apparatus
US20180059882A1 (en) * 2016-08-29 2018-03-01 Canon Kabushiki Kaisha Information processing apparatus that performs image layout, method of controlling the same, and storage medium
US10137225B2 (en) * 2014-05-27 2018-11-27 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Crystalline coating and release of bioactive agents

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6790228B2 (en) 1999-12-23 2004-09-14 Advanced Cardiovascular Systems, Inc. Coating for implantable devices and a method of forming the same
US20070032853A1 (en) 2002-03-27 2007-02-08 Hossainy Syed F 40-O-(2-hydroxy)ethyl-rapamycin coated stent
US7682647B2 (en) * 1999-09-03 2010-03-23 Advanced Cardiovascular Systems, Inc. Thermal treatment of a drug eluting implantable medical device
US7807211B2 (en) * 1999-09-03 2010-10-05 Advanced Cardiovascular Systems, Inc. Thermal treatment of an implantable medical device
US8741378B1 (en) 2001-06-27 2014-06-03 Advanced Cardiovascular Systems, Inc. Methods of coating an implantable device
US7285304B1 (en) * 2003-06-25 2007-10-23 Advanced Cardiovascular Systems, Inc. Fluid treatment of a polymeric coating on an implantable medical device
US8506617B1 (en) 2002-06-21 2013-08-13 Advanced Cardiovascular Systems, Inc. Micronized peptide coated stent
ATE459380T1 (en) * 2002-08-13 2010-03-15 Medtronic Inc DOSAGE SYSTEMS OF ACTIVE INGREDIENTS WITH POLY(ETHYLENE-CO(METH)ACRYLATES, MEDICAL DEVICE AND METHOD
US7169178B1 (en) * 2002-11-12 2007-01-30 Advanced Cardiovascular Systems, Inc. Stent with drug coating
US7758880B2 (en) 2002-12-11 2010-07-20 Advanced Cardiovascular Systems, Inc. Biocompatible polyacrylate compositions for medical applications
US7776926B1 (en) 2002-12-11 2010-08-17 Advanced Cardiovascular Systems, Inc. Biocompatible coating for implantable medical devices
US20040230298A1 (en) * 2003-04-25 2004-11-18 Medtronic Vascular, Inc. Drug-polymer coated stent with polysulfone and styrenic block copolymer
EP1633320A2 (en) 2003-05-02 2006-03-15 SurModics, Inc. Implantable controlled release bioactive agent delivery device
US8246974B2 (en) 2003-05-02 2012-08-21 Surmodics, Inc. Medical devices and methods for producing the same
US7279174B2 (en) 2003-05-08 2007-10-09 Advanced Cardiovascular Systems, Inc. Stent coatings comprising hydrophilic additives
US20050118344A1 (en) 2003-12-01 2005-06-02 Pacetti Stephen D. Temperature controlled crimping
US7431959B1 (en) * 2003-07-31 2008-10-07 Advanced Cardiovascular Systems Inc. Method and system for irradiation of a drug eluting implantable medical device
US9114198B2 (en) * 2003-11-19 2015-08-25 Advanced Cardiovascular Systems, Inc. Biologically beneficial coatings for implantable devices containing fluorinated polymers and methods for fabricating the same
US8293890B2 (en) 2004-04-30 2012-10-23 Advanced Cardiovascular Systems, Inc. Hyaluronic acid based copolymers
US9561309B2 (en) 2004-05-27 2017-02-07 Advanced Cardiovascular Systems, Inc. Antifouling heparin coatings
US7563780B1 (en) 2004-06-18 2009-07-21 Advanced Cardiovascular Systems, Inc. Heparin prodrugs and drug delivery stents formed therefrom
US7494665B1 (en) 2004-07-30 2009-02-24 Advanced Cardiovascular Systems, Inc. Polymers containing siloxane monomers
US8357391B2 (en) * 2004-07-30 2013-01-22 Advanced Cardiovascular Systems, Inc. Coatings for implantable devices comprising poly (hydroxy-alkanoates) and diacid linkages
US8603634B2 (en) 2004-10-27 2013-12-10 Abbott Cardiovascular Systems Inc. End-capped poly(ester amide) copolymers
US7604818B2 (en) 2004-12-22 2009-10-20 Advanced Cardiovascular Systems, Inc. Polymers of fluorinated monomers and hydrocarbon monomers
US9561351B2 (en) 2006-05-31 2017-02-07 Advanced Cardiovascular Systems, Inc. Drug delivery spiral coil construct
US9028859B2 (en) 2006-07-07 2015-05-12 Advanced Cardiovascular Systems, Inc. Phase-separated block copolymer coatings for implantable medical devices
US8007857B1 (en) 2006-09-08 2011-08-30 Abbott Cardiovascular Systems Inc. Methods for controlling the release rate and improving the mechanical properties of a stent coating
US9056155B1 (en) 2007-05-29 2015-06-16 Abbott Cardiovascular Systems Inc. Coatings having an elastic primer layer
US8685433B2 (en) 2010-03-31 2014-04-01 Abbott Cardiovascular Systems Inc. Absorbable coating for implantable device
ITPO20110005A1 (en) * 2011-03-21 2012-09-22 Stefano Ciapetti NEW INTEGRATED SYSTEM FOR RESTORATION / CONSERVATION OF STONE MONUMENT ARCHITECTURAL ELEMENTS BASED ON POLYMERIC MATERIALS MIXED AND / OR LOADED, CALLED "FLUORMET SYSTEM".
CN106823017B (en) * 2016-12-12 2020-01-21 湖北大学 Preparation method of hybrid biological functional coating based on ammonia halide compound and zinc oxide nanoparticles

Citations (93)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2072303A (en) * 1932-10-18 1937-03-02 Chemische Forschungs Gmbh Artificial threads, bands, tubes, and the like for surgical and other purposes
US4656272A (en) * 1985-05-24 1987-04-07 Basf Aktiengesellschaft Preparation of s-triazine derivatives
US4733665A (en) * 1985-11-07 1988-03-29 Expandable Grafts Partnership Expandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft
US4800882A (en) * 1987-03-13 1989-01-31 Cook Incorporated Endovascular stent and delivery system
US4916193A (en) * 1987-12-17 1990-04-10 Allied-Signal Inc. Medical devices fabricated totally or in part from copolymers of recurring units derived from cyclic carbonates and lactides
US5100992A (en) * 1989-05-04 1992-03-31 Biomedical Polymers International, Ltd. Polyurethane-based polymeric materials and biomedical articles and pharmaceutical compositions utilizing the same
US5292516A (en) * 1990-05-01 1994-03-08 Mediventures, Inc. Body cavity drug delivery with thermoreversible gels containing polyoxyalkylene copolymers
US5298260A (en) * 1990-05-01 1994-03-29 Mediventures, Inc. Topical drug delivery with polyoxyalkylene polymer thermoreversible gels adjustable for pH and osmolality
US5300295A (en) * 1990-05-01 1994-04-05 Mediventures, Inc. Ophthalmic drug delivery with thermoreversible polyoxyalkylene gels adjustable for pH
US5306786A (en) * 1990-12-21 1994-04-26 U C B S.A. Carboxyl group-terminated polyesteramides
US5306501A (en) * 1990-05-01 1994-04-26 Mediventures, Inc. Drug delivery by injection with thermoreversible gels containing polyoxyalkylene copolymers
US5380299A (en) * 1993-08-30 1995-01-10 Med Institute, Inc. Thrombolytic treated intravascular medical device
US5485496A (en) * 1994-09-22 1996-01-16 Cornell Research Foundation, Inc. Gamma irradiation sterilizing of biomaterial medical devices or products, with improved degradation and mechanical properties
US5502158A (en) * 1988-08-08 1996-03-26 Ecopol, Llc Degradable polymer composition
US5605696A (en) * 1995-03-30 1997-02-25 Advanced Cardiovascular Systems, Inc. Drug loaded polymeric material and method of manufacture
US5607467A (en) * 1990-09-14 1997-03-04 Froix; Michael Expandable polymeric stent with memory and delivery apparatus and method
US5609629A (en) * 1995-06-07 1997-03-11 Med Institute, Inc. Coated implantable medical device
US5610241A (en) * 1996-05-07 1997-03-11 Cornell Research Foundation, Inc. Reactive graft polymer with biodegradable polymer backbone and method for preparing reactive biodegradable polymers
US5616338A (en) * 1988-02-11 1997-04-01 Trustees Of Columbia University In The City Of New York Infection-resistant compositions, medical devices and surfaces and methods for preparing and using same
US5624411A (en) * 1993-04-26 1997-04-29 Medtronic, Inc. Intravascular stent and method
US5711958A (en) * 1996-07-11 1998-01-27 Life Medical Sciences, Inc. Methods for reducing or eliminating post-surgical adhesion formation
US5716981A (en) * 1993-07-19 1998-02-10 Angiogenesis Technologies, Inc. Anti-angiogenic compositions and methods of use
US5718159A (en) * 1996-04-30 1998-02-17 Schneider (Usa) Inc. Process for manufacturing three-dimensional braided covered stent
US5721131A (en) * 1987-03-06 1998-02-24 United States Of America As Represented By The Secretary Of The Navy Surface modification of polymers with self-assembled monolayers that promote adhesion, outgrowth and differentiation of biological cells
US5723219A (en) * 1995-12-19 1998-03-03 Talison Research Plasma deposited film networks
US5735897A (en) * 1993-10-19 1998-04-07 Scimed Life Systems, Inc. Intravascular stent pump
US5858746A (en) * 1992-04-20 1999-01-12 Board Of Regents, The University Of Texas System Gels for encapsulation of biological materials
US5865814A (en) * 1995-06-07 1999-02-02 Medtronic, Inc. Blood contacting medical device and method
US5869127A (en) * 1995-02-22 1999-02-09 Boston Scientific Corporation Method of providing a substrate with a bio-active/biocompatible coating
US5871436A (en) * 1996-07-19 1999-02-16 Advanced Cardiovascular Systems, Inc. Radiation therapy method and device
US5873904A (en) * 1995-06-07 1999-02-23 Cook Incorporated Silver implantable medical device
US5876433A (en) * 1996-05-29 1999-03-02 Ethicon, Inc. Stent and method of varying amounts of heparin coated thereon to control treatment
US5877224A (en) * 1995-07-28 1999-03-02 Rutgers, The State University Of New Jersey Polymeric drug formulations
US5879713A (en) * 1994-10-12 1999-03-09 Focal, Inc. Targeted delivery via biodegradable polymers
US6011125A (en) * 1998-09-25 2000-01-04 General Electric Company Amide modified polyesters
US6010530A (en) * 1995-06-07 2000-01-04 Boston Scientific Technology, Inc. Self-expanding endoluminal prosthesis
US6015541A (en) * 1997-11-03 2000-01-18 Micro Therapeutics, Inc. Radioactive embolizing compositions
US6034204A (en) * 1997-08-08 2000-03-07 Basf Aktiengesellschaft Condensation products of basic amino acids with copolymerizable compounds and a process for their production
US6033582A (en) * 1996-01-22 2000-03-07 Etex Corporation Surface modification of medical implants
US6042875A (en) * 1997-04-30 2000-03-28 Schneider (Usa) Inc. Drug-releasing coatings for medical devices
US6051576A (en) * 1994-01-28 2000-04-18 University Of Kentucky Research Foundation Means to achieve sustained release of synergistic drugs by conjugation
US6051648A (en) * 1995-12-18 2000-04-18 Cohesion Technologies, Inc. Crosslinked polymer compositions and methods for their use
US6054553A (en) * 1996-01-29 2000-04-25 Bayer Ag Process for the preparation of polymers having recurring agents
US6172167B1 (en) * 1996-06-28 2001-01-09 Universiteit Twente Copoly(ester-amides) and copoly(ester-urethanes)
US6177523B1 (en) * 1999-07-14 2001-01-23 Cardiotech International, Inc. Functionalized polyurethanes
US6180632B1 (en) * 1997-05-28 2001-01-30 Aventis Pharmaceuticals Products Inc. Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases
US6203551B1 (en) * 1999-10-04 2001-03-20 Advanced Cardiovascular Systems, Inc. Chamber for applying therapeutic substances to an implant device
US6211249B1 (en) * 1997-07-11 2001-04-03 Life Medical Sciences, Inc. Polyester polyether block copolymers
US6214901B1 (en) * 1998-04-27 2001-04-10 Surmodics, Inc. Bioactive agent release coating
US6335029B1 (en) * 1998-08-28 2002-01-01 Scimed Life Systems, Inc. Polymeric coatings for controlled delivery of active agents
US20020005206A1 (en) * 2000-05-19 2002-01-17 Robert Falotico Antiproliferative drug and delivery device
US20020007213A1 (en) * 2000-05-19 2002-01-17 Robert Falotico Drug/drug delivery systems for the prevention and treatment of vascular disease
US20020007215A1 (en) * 2000-05-19 2002-01-17 Robert Falotico Drug/drug delivery systems for the prevention and treatment of vascular disease
US20020007214A1 (en) * 2000-05-19 2002-01-17 Robert Falotico Drug/drug delivery systems for the prevention and treatment of vascular disease
US20020009604A1 (en) * 1999-12-22 2002-01-24 Zamora Paul O. Plasma-deposited coatings, devices and methods
US20020016625A1 (en) * 2000-05-12 2002-02-07 Robert Falotico Drug/drug delivery systems for the prevention and treatment of vascular disease
US20020032414A1 (en) * 1998-08-20 2002-03-14 Ragheb Anthony O. Coated implantable medical device
US6358556B1 (en) * 1995-04-19 2002-03-19 Boston Scientific Corporation Drug release stent coating
US6379381B1 (en) * 1999-09-03 2002-04-30 Advanced Cardiovascular Systems, Inc. Porous prosthesis and a method of depositing substances into the pores
US20030004141A1 (en) * 2001-03-08 2003-01-02 Brown David L. Medical devices, compositions and methods for treating vulnerable plaque
US6503556B2 (en) * 2000-12-28 2003-01-07 Advanced Cardiovascular Systems, Inc. Methods of forming a coating for a prosthesis
US6503954B1 (en) * 2000-03-31 2003-01-07 Advanced Cardiovascular Systems, Inc. Biocompatible carrier containing actinomycin D and a method of forming the same
US6503538B1 (en) * 2000-08-30 2003-01-07 Cornell Research Foundation, Inc. Elastomeric functional biodegradable copolyester amides and copolyester urethanes
US6506437B1 (en) * 2000-10-17 2003-01-14 Advanced Cardiovascular Systems, Inc. Methods of coating an implantable device having depots formed in a surface thereof
US20030028243A1 (en) * 1995-06-07 2003-02-06 Cook Incorporated Coated implantable medical device
US20030028244A1 (en) * 1995-06-07 2003-02-06 Cook Incorporated Coated implantable medical device
US20030032767A1 (en) * 2001-02-05 2003-02-13 Yasuhiro Tada High-strength polyester-amide fiber and process for producing the same
US20030036794A1 (en) * 1995-06-07 2003-02-20 Cook Incorporated Coated implantable medical device
US6524347B1 (en) * 1997-05-28 2003-02-25 Avantis Pharmaceuticals Inc. Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases
US20030040790A1 (en) * 1998-04-15 2003-02-27 Furst Joseph G. Stent coating
US20030039689A1 (en) * 2001-04-26 2003-02-27 Jianbing Chen Polymer-based, sustained release drug delivery system
US20030040712A1 (en) * 1999-07-13 2003-02-27 Pinaki Ray Substance delivery apparatus and a method of delivering a therapeutic substance to an anatomical passageway
US6527801B1 (en) * 2000-04-13 2003-03-04 Advanced Cardiovascular Systems, Inc. Biodegradable drug delivery material for stent
US6527863B1 (en) * 2001-06-29 2003-03-04 Advanced Cardiovascular Systems, Inc. Support device for a stent and a method of using the same to coat a stent
US6530951B1 (en) * 1996-10-24 2003-03-11 Cook Incorporated Silver implantable medical device
US6530950B1 (en) * 1999-01-12 2003-03-11 Quanam Medical Corporation Intraluminal stent having coaxial polymer member
US20030059520A1 (en) * 2001-09-27 2003-03-27 Yung-Ming Chen Apparatus for regulating temperature of a composition and a method of coating implantable devices
US20030060877A1 (en) * 2001-09-25 2003-03-27 Robert Falotico Coated medical devices for the treatment of vascular disease
US20030065377A1 (en) * 2001-09-28 2003-04-03 Davila Luis A. Coated medical devices
US6673154B1 (en) * 2001-06-28 2004-01-06 Advanced Cardiovascular Systems, Inc. Stent mounting device to coat a stent
US6673385B1 (en) * 2000-05-31 2004-01-06 Advanced Cardiovascular Systems, Inc. Methods for polymeric coatings stents
US20040018296A1 (en) * 2000-05-31 2004-01-29 Daniel Castro Method for depositing a coating onto a surface of a prosthesis
US6689099B2 (en) * 1999-07-13 2004-02-10 Advanced Cardiovascular Systems, Inc. Local drug delivery injection catheter
US20040029952A1 (en) * 1999-09-03 2004-02-12 Yung-Ming Chen Ethylene vinyl alcohol composition and coating
US6695920B1 (en) * 2001-06-27 2004-02-24 Advanced Cardiovascular Systems, Inc. Mandrel for supporting a stent and a method of using the mandrel to coat a stent
US20040047980A1 (en) * 2000-12-28 2004-03-11 Pacetti Stephen D. Method of forming a diffusion barrier layer for implantable devices
US20040047978A1 (en) * 2000-08-04 2004-03-11 Hossainy Syed F.A. Composition for coating an implantable prosthesis
US6706013B1 (en) * 2001-06-29 2004-03-16 Advanced Cardiovascular Systems, Inc. Variable length drug delivery catheter
US20040052859A1 (en) * 2001-05-09 2004-03-18 Wu Steven Z. Microparticle coated medical device
US20040054104A1 (en) * 2002-09-05 2004-03-18 Pacetti Stephen D. Coatings for drug delivery devices comprising modified poly(ethylene-co-vinyl alcohol)
US6709514B1 (en) * 2001-12-28 2004-03-23 Advanced Cardiovascular Systems, Inc. Rotary coating apparatus for coating implantable medical devices
US6713119B2 (en) * 1999-09-03 2004-03-30 Advanced Cardiovascular Systems, Inc. Biocompatible coating for a prosthesis and a method of forming the same
US6712845B2 (en) * 2001-04-24 2004-03-30 Advanced Cardiovascular Systems, Inc. Coating for a stent and a method of forming the same

Family Cites Families (179)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2386454A (en) 1940-11-22 1945-10-09 Bell Telephone Labor Inc High molecular weight linear polyester-amides
US3178399A (en) 1961-08-10 1965-04-13 Minnesota Mining & Mfg Fluorine-containing polymers and preparation thereof
US3849514A (en) 1967-11-17 1974-11-19 Eastman Kodak Co Block polyester-polyamide copolymers
US3773737A (en) 1971-06-09 1973-11-20 Sutures Inc Hydrolyzable polymers of amino acid and hydroxy acids
US4459380A (en) * 1979-02-12 1984-07-10 General Electric Company Heat resisting ethylene-propylene rubber and insulated conductor product thereof
US4329383A (en) 1979-07-24 1982-05-11 Nippon Zeon Co., Ltd. Non-thrombogenic material comprising substrate which has been reacted with heparin
US4226243A (en) 1979-07-27 1980-10-07 Ethicon, Inc. Surgical devices of polyesteramides derived from bis-oxamidodiols and dicarboxylic acids
SU790725A1 (en) 1979-07-27 1983-01-23 Ордена Ленина Институт Элементоорганических Соединений Ан Ссср Process for preparing alkylaromatic polyimides
SU872531A1 (en) 1979-08-07 1981-10-15 Институт Физиологии Им.И.С.Бериташвили Ан Гсср Method of producing polyurethans
SU811750A1 (en) 1979-08-07 1983-09-23 Институт Физиологии Им.С.И.Бериташвили Bis-bicarbonates of aliphatic diols as monomers for preparing polyurethanes and process for producing the same
SU876663A1 (en) 1979-11-11 1981-10-30 Институт Физиологии Им. Академика И.С.Бериташвили Ан Гсср Method of producing polyarylates
US4529792A (en) 1979-12-17 1985-07-16 Minnesota Mining And Manufacturing Company Process for preparing synthetic absorbable poly(esteramides)
SU1016314A1 (en) 1979-12-17 1983-05-07 Институт Физиологии Им.И.С.Бериташвили Process for producing polyester urethanes
US4343931A (en) 1979-12-17 1982-08-10 Minnesota Mining And Manufacturing Company Synthetic absorbable surgical devices of poly(esteramides)
SU905228A1 (en) 1980-03-06 1982-02-15 Институт Физиологии Им. Акад.И.С. Бериташвили Ан Гсср Method for preparing thiourea
SU1293518A1 (en) 1985-04-11 1987-02-28 Тбилисский зональный научно-исследовательский и проектный институт типового и экспериментального проектирования жилых и общественных зданий Installation for testing specimen of cross-shaped structure
US4656242A (en) 1985-06-07 1987-04-07 Henkel Corporation Poly(ester-amide) compositions
US4611051A (en) 1985-12-31 1986-09-09 Union Camp Corporation Novel poly(ester-amide) hot-melt adhesives
US4882168A (en) 1986-09-05 1989-11-21 American Cyanamid Company Polyesters containing alkylene oxide blocks as drug delivery systems
JPH0696023B2 (en) 1986-11-10 1994-11-30 宇部日東化成株式会社 Artificial blood vessel and method for producing the same
US6387379B1 (en) 1987-04-10 2002-05-14 University Of Florida Biofunctional surface modified ocular implants, surgical instruments, medical devices, prostheses, contact lenses and the like
US4816339A (en) 1987-04-28 1989-03-28 Baxter International Inc. Multi-layered poly(tetrafluoroethylene)/elastomer materials useful for in vivo implantation
US4894231A (en) 1987-07-28 1990-01-16 Biomeasure, Inc. Therapeutic agent delivery system
US4886062A (en) 1987-10-19 1989-12-12 Medtronic, Inc. Intravascular radially expandable stent and method of implant
JP2561309B2 (en) 1988-03-28 1996-12-04 テルモ株式会社 Medical material and manufacturing method thereof
US4931287A (en) 1988-06-14 1990-06-05 University Of Utah Heterogeneous interpenetrating polymer networks for the controlled release of drugs
US5328471A (en) 1990-02-26 1994-07-12 Endoluminal Therapeutics, Inc. Method and apparatus for treatment of focal disease in hollow tubular organs and other tissue lumens
US4977901A (en) 1988-11-23 1990-12-18 Minnesota Mining And Manufacturing Company Article having non-crosslinked crystallized polymer coatings
US5272012A (en) 1989-06-23 1993-12-21 C. R. Bard, Inc. Medical apparatus having protective, lubricious coating
US5971954A (en) 1990-01-10 1999-10-26 Rochester Medical Corporation Method of making catheter
US5496557A (en) 1990-01-30 1996-03-05 Akzo N.V. Article for the controlled delivery of an active substance, comprising a hollow space fully enclosed by a wall and filled in full or in part with one or more active substances
WO1991017724A1 (en) 1990-05-17 1991-11-28 Harbor Medical Devices, Inc. Medical device polymer
US6060451A (en) 1990-06-15 2000-05-09 The National Research Council Of Canada Thrombin inhibitors based on the amino acid sequence of hirudin
WO1991019529A1 (en) 1990-06-15 1991-12-26 Cortrak Medical, Inc. Drug delivery apparatus and method
CA2038605C (en) 1990-06-15 2000-06-27 Leonard Pinchuk Crack-resistant polycarbonate urethane polymer prostheses and the like
US5112457A (en) 1990-07-23 1992-05-12 Case Western Reserve University Process for producing hydroxylated plasma-polymerized films and the use of the films for enhancing the compatiblity of biomedical implants
US5455040A (en) 1990-07-26 1995-10-03 Case Western Reserve University Anticoagulant plasma polymer-modified substrate
US5163952A (en) 1990-09-14 1992-11-17 Michael Froix Expandable polymeric stent with memory and delivery apparatus and method
US6248129B1 (en) 1990-09-14 2001-06-19 Quanam Medical Corporation Expandable polymeric stent with memory and delivery apparatus and method
US5462990A (en) 1990-10-15 1995-10-31 Board Of Regents, The University Of Texas System Multifunctional organic polymers
US5330768A (en) 1991-07-05 1994-07-19 Massachusetts Institute Of Technology Controlled drug delivery using polymer/pluronic blends
US5516781A (en) 1992-01-09 1996-05-14 American Home Products Corporation Method of treating restenosis with rapamycin
US5599352A (en) 1992-03-19 1997-02-04 Medtronic, Inc. Method of making a drug eluting stent
GB9206736D0 (en) 1992-03-27 1992-05-13 Sandoz Ltd Improvements of organic compounds and their use in pharmaceutical compositions
US5219980A (en) 1992-04-16 1993-06-15 Sri International Polymers biodegradable or bioerodiable into amino acids
DE69325845T2 (en) 1992-04-28 2000-01-05 Terumo Corp Thermoplastic polymer composition and medical devices made therefrom
DE4224401A1 (en) 1992-07-21 1994-01-27 Pharmatech Gmbh New biodegradable homo- and co-polymer(s) for pharmaceutical use - produced by polycondensation of prod. from heterolytic cleavage of aliphatic polyester with functionalised (cyclo)aliphatic cpd.
FR2699168B1 (en) 1992-12-11 1995-01-13 Rhone Poulenc Chimie Method of treating a material comprising a polymer by hydrolysis.
EP0604022A1 (en) 1992-12-22 1994-06-29 Advanced Cardiovascular Systems, Inc. Multilayered biodegradable stent and method for its manufacture
US5824048A (en) 1993-04-26 1998-10-20 Medtronic, Inc. Method for delivering a therapeutic substance to a body lumen
US20020055710A1 (en) 1998-04-30 2002-05-09 Ronald J. Tuch Medical device for delivering a therapeutic agent and method of preparation
IT1276342B1 (en) 1993-06-04 1997-10-30 Ist Naz Stud Cura Dei Tumori METAL STENT COVERED WITH BIOCOMPATIBLE POLYMERIC MATERIAL
JPH0767895A (en) 1993-06-25 1995-03-14 Sumitomo Electric Ind Ltd Antimicrobial artificial blood vessel and suture yarn for antimicrobial operation
EG20321A (en) * 1993-07-21 1998-10-31 Otsuka Pharma Co Ltd Medical material and process for producing the same
DE4327024A1 (en) 1993-08-12 1995-02-16 Bayer Ag Thermoplastically processable and biodegradable aliphatic polyesteramides
US5723004A (en) 1993-10-21 1998-03-03 Corvita Corporation Expandable supportive endoluminal grafts
WO1995019796A1 (en) 1994-01-21 1995-07-27 Brown University Research Foundation Biocompatible implants
CA2190121A1 (en) 1994-03-15 1995-09-21 Edith Mathiowitz Polymeric gene delivery system
DE69528216T2 (en) 1994-06-17 2003-04-17 Terumo Corp Process for the production of a permanent stent
US5567410A (en) 1994-06-24 1996-10-22 The General Hospital Corporation Composotions and methods for radiographic imaging
US5670558A (en) 1994-07-07 1997-09-23 Terumo Kabushiki Kaisha Medical instruments that exhibit surface lubricity when wetted
US5788979A (en) 1994-07-22 1998-08-04 Inflow Dynamics Inc. Biodegradable coating with inhibitory properties for application to biocompatible materials
US5516881A (en) 1994-08-10 1996-05-14 Cornell Research Foundation, Inc. Aminoxyl-containing radical spin labeling in polymers and copolymers
US5578073A (en) 1994-09-16 1996-11-26 Ramot Of Tel Aviv University Thromboresistant surface treatment for biomaterials
US5649977A (en) 1994-09-22 1997-07-22 Advanced Cardiovascular Systems, Inc. Metal reinforced polymer stent
FR2724938A1 (en) 1994-09-28 1996-03-29 Lvmh Rech POLYMERS FUNCTIONALIZED BY AMINO ACIDS OR AMINO ACID DERIVATIVES, THEIR USE AS SURFACTANTS, IN PARTICULAR, IN COSMETIC COMPOSITIONS AND IN PARTICULAR NAIL POLISH.
US5563145A (en) 1994-12-07 1996-10-08 American Home Products Corporation Rapamycin 42-oximes and hydroxylamines
US5637113A (en) 1994-12-13 1997-06-10 Advanced Cardiovascular Systems, Inc. Polymer film for wrapping a stent structure
US5569198A (en) 1995-01-23 1996-10-29 Cortrak Medical Inc. Microporous catheter
US6017577A (en) 1995-02-01 2000-01-25 Schneider (Usa) Inc. Slippery, tenaciously adhering hydrophilic polyurethane hydrogel coatings, coated polymer substrate materials, and coated medical devices
US5919570A (en) 1995-02-01 1999-07-06 Schneider Inc. Slippery, tenaciously adhering hydrogel coatings containing a polyurethane-urea polymer hydrogel commingled with a poly(N-vinylpyrrolidone) polymer hydrogel, coated polymer and metal substrate materials, and coated medical devices
US6231600B1 (en) 1995-02-22 2001-05-15 Scimed Life Systems, Inc. Stents with hybrid coating for medical devices
US5702754A (en) 1995-02-22 1997-12-30 Meadox Medicals, Inc. Method of providing a substrate with a hydrophilic coating and substrates, particularly medical devices, provided with such coatings
US5854376A (en) 1995-03-09 1998-12-29 Sekisui Kaseihin Kogyo Kabushiki Kaisha Aliphatic ester-amide copolymer resins
US6099562A (en) 1996-06-13 2000-08-08 Schneider (Usa) Inc. Drug coating with topcoat
RU2169742C2 (en) 1995-04-19 2001-06-27 Катаока Казунори Heterotelochelate block copolymer and method of preparation thereof
US6120536A (en) 1995-04-19 2000-09-19 Schneider (Usa) Inc. Medical devices with long term non-thrombogenic coatings
US20020091433A1 (en) 1995-04-19 2002-07-11 Ni Ding Drug release coated stent
US5674242A (en) 1995-06-06 1997-10-07 Quanam Medical Corporation Endoprosthetic device with therapeutic compound
US6129761A (en) 1995-06-07 2000-10-10 Reprogenesis, Inc. Injectable hydrogel compositions
US5667767A (en) 1995-07-27 1997-09-16 Micro Therapeutics, Inc. Compositions for use in embolizing blood vessels
US5658995A (en) 1995-11-27 1997-08-19 Rutgers, The State University Copolymers of tyrosine-based polycarbonate and poly(alkylene oxide)
DE19545678A1 (en) 1995-12-07 1997-06-12 Goldschmidt Ag Th Copolymers of polyamino acid esters
US5932299A (en) 1996-04-23 1999-08-03 Katoot; Mohammad W. Method for modifying the surface of an object
US5955509A (en) 1996-05-01 1999-09-21 Board Of Regents, The University Of Texas System pH dependent polymer micelles
US5874165A (en) 1996-06-03 1999-02-23 Gore Enterprise Holdings, Inc. Materials and method for the immobilization of bioactive species onto polymeric subtrates
US5830178A (en) 1996-10-11 1998-11-03 Micro Therapeutics, Inc. Methods for embolizing vascular sites with an emboilizing composition comprising dimethylsulfoxide
US6060518A (en) 1996-08-16 2000-05-09 Supratek Pharma Inc. Polymer compositions for chemotherapy and methods of treatment using the same
US5783657A (en) 1996-10-18 1998-07-21 Union Camp Corporation Ester-terminated polyamides of polymerized fatty acids useful in formulating transparent gels in low polarity liquids
US6120491A (en) 1997-11-07 2000-09-19 The State University Rutgers Biodegradable, anionic polymers derived from the amino acid L-tyrosine
US5980972A (en) * 1996-12-20 1999-11-09 Schneider (Usa) Inc Method of applying drug-release coatings
US5997517A (en) 1997-01-27 1999-12-07 Sts Biopolymers, Inc. Bonding layers for medical device surface coatings
DE69826639T2 (en) 1997-01-28 2005-10-06 United States Surgical Corp., Norwalk SURGICAL ARTICLES MADE FROM POLYESTERAMIDES WITH GROUPS DERIVED FROM AMINO ACIDS AND ALTERNATIVELY WITH GROUPS DERIVED FROM ALPHA HYDROXYLIC ACIDS
DE69828387T2 (en) 1997-01-28 2005-12-08 United States Surgical Corp., Norwalk POLYESTERAMIDE, ITS PRESENTATION AND SURGICAL FABRICATED SURGICAL ARTICLES
WO1998032779A1 (en) 1997-01-28 1998-07-30 United States Surgical Corporation Polyesteramide, its preparation and surgical devices fabricated therefrom
US6240616B1 (en) 1997-04-15 2001-06-05 Advanced Cardiovascular Systems, Inc. Method of manufacturing a medicated porous metal prosthesis
US6273913B1 (en) 1997-04-18 2001-08-14 Cordis Corporation Modified stent useful for delivery of drugs along stent strut
US6245760B1 (en) 1997-05-28 2001-06-12 Aventis Pharmaceuticals Products, Inc Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases
US6056993A (en) 1997-05-30 2000-05-02 Schneider (Usa) Inc. Porous protheses and methods for making the same wherein the protheses are formed by spraying water soluble and water insoluble fibers onto a rotating mandrel
US6723121B1 (en) 1997-06-18 2004-04-20 Scimed Life Systems, Inc. Polycarbonate-polyurethane dispersions for thrombo-resistant coatings
US6110483A (en) 1997-06-23 2000-08-29 Sts Biopolymers, Inc. Adherent, flexible hydrogel and medicated coatings
JPH1142284A (en) 1997-07-25 1999-02-16 Ube Ind Ltd Artificial blood vessel with stent
US5980928A (en) 1997-07-29 1999-11-09 Terry; Paul B. Implant for preventing conjunctivitis in cattle
US6306166B1 (en) 1997-08-13 2001-10-23 Scimed Life Systems, Inc. Loading and release of water-insoluble drugs
US6121027A (en) 1997-08-15 2000-09-19 Surmodics, Inc. Polybifunctional reagent having a polymeric backbone and photoreactive moieties and bioactive groups
US6120788A (en) 1997-10-16 2000-09-19 Bioamide, Inc. Bioabsorbable triglycolic acid poly(ester-amide)s
US6110188A (en) 1998-03-09 2000-08-29 Corvascular, Inc. Anastomosis method
US6258371B1 (en) 1998-04-03 2001-07-10 Medtronic Inc Method for making biocompatible medical article
US20010029351A1 (en) 1998-04-16 2001-10-11 Robert Falotico Drug combinations and delivery devices for the prevention and treatment of vascular disease
US7658727B1 (en) 1998-04-20 2010-02-09 Medtronic, Inc Implantable medical device with enhanced biocompatibility and biostability
US20020188037A1 (en) 1999-04-15 2002-12-12 Chudzik Stephen J. Method and system for providing bioactive agent release coating
US6113629A (en) 1998-05-01 2000-09-05 Micrus Corporation Hydrogel for the therapeutic treatment of aneurysms
KR100314496B1 (en) 1998-05-28 2001-11-22 윤동진 Non-thrombogenic heparin derivatives, process for preparation and use thereof
US6153252A (en) 1998-06-30 2000-11-28 Ethicon, Inc. Process for coating stents
US6248127B1 (en) 1998-08-21 2001-06-19 Medtronic Ave, Inc. Thromboresistant coated medical device
FR2785812B1 (en) 1998-11-16 2002-11-29 Commissariat Energie Atomique BIOACTIVE PROSTHESES, IN PARTICULAR WITH IMMUNOSUPPRESSIVE PROPERTIES, ANTISTENOSIS AND ANTITHROMBOSIS, AND THEIR MANUFACTURE
US6419692B1 (en) 1999-02-03 2002-07-16 Scimed Life Systems, Inc. Surface protection method for stents and balloon catheters for drug delivery
US6143354A (en) 1999-02-08 2000-11-07 Medtronic Inc. One-step method for attachment of biomolecules to substrate surfaces
US6258121B1 (en) 1999-07-02 2001-07-10 Scimed Life Systems, Inc. Stent coating
US6749626B1 (en) 2000-03-31 2004-06-15 Advanced Cardiovascular Systems, Inc. Actinomycin D for the treatment of vascular disease
US6759054B2 (en) 1999-09-03 2004-07-06 Advanced Cardiovascular Systems, Inc. Ethylene vinyl alcohol composition and coating
US6790228B2 (en) 1999-12-23 2004-09-14 Advanced Cardiovascular Systems, Inc. Coating for implantable devices and a method of forming the same
US6287628B1 (en) 1999-09-03 2001-09-11 Advanced Cardiovascular Systems, Inc. Porous prosthesis and a method of depositing substances into the pores
US6331313B1 (en) 1999-10-22 2001-12-18 Oculex Pharmaceticals, Inc. Controlled-release biocompatible ocular drug delivery implant devices and methods
US6251136B1 (en) 1999-12-08 2001-06-26 Advanced Cardiovascular Systems, Inc. Method of layering a three-coated stent using pharmacological and polymeric agents
US6908624B2 (en) 1999-12-23 2005-06-21 Advanced Cardiovascular Systems, Inc. Coating for implantable devices and a method of forming the same
US6283949B1 (en) 1999-12-27 2001-09-04 Advanced Cardiovascular Systems, Inc. Refillable implantable drug delivery pump
AU2599501A (en) 1999-12-29 2001-07-09 Advanced Cardiovascular Systems Inc. Device and active component for inhibiting formation of thrombus-inflammatory cell matrix
JP4473390B2 (en) 2000-01-07 2010-06-02 川澄化学工業株式会社 Stent and stent graft
US6585765B1 (en) 2000-06-29 2003-07-01 Advanced Cardiovascular Systems, Inc. Implantable device having substances impregnated therein and a method of impregnating the same
US20020077693A1 (en) 2000-12-19 2002-06-20 Barclay Bruce J. Covered, coiled drug delivery stent and method
US6555157B1 (en) 2000-07-25 2003-04-29 Advanced Cardiovascular Systems, Inc. Method for coating an implantable device and system for performing the method
WO2002009768A2 (en) 2000-07-27 2002-02-07 Rutgers, The State University Therapeutic polyesters and polyamides
US6585926B1 (en) 2000-08-31 2003-07-01 Advanced Cardiovascular Systems, Inc. Method of manufacturing a porous balloon
US6716444B1 (en) 2000-09-28 2004-04-06 Advanced Cardiovascular Systems, Inc. Barriers for polymer-coated implantable medical devices and methods for making the same
US6254632B1 (en) 2000-09-28 2001-07-03 Advanced Cardiovascular Systems, Inc. Implantable medical device having protruding surface structures for drug delivery and cover attachment
US6746773B2 (en) 2000-09-29 2004-06-08 Ethicon, Inc. Coatings for medical devices
US20070276473A1 (en) 2000-09-29 2007-11-29 Llanos Gerard H Medical Devices, Drug Coatings and Methods for Maintaining the Drug Coatings Thereon
US7261735B2 (en) 2001-05-07 2007-08-28 Cordis Corporation Local drug delivery devices and methods for maintaining the drug coatings thereon
US20020111590A1 (en) 2000-09-29 2002-08-15 Davila Luis A. Medical devices, drug coatings and methods for maintaining the drug coatings thereon
US20020051730A1 (en) 2000-09-29 2002-05-02 Stanko Bodnar Coated medical devices and sterilization thereof
US6558733B1 (en) 2000-10-26 2003-05-06 Advanced Cardiovascular Systems, Inc. Method for etching a micropatterned microdepot prosthesis
US6758859B1 (en) 2000-10-30 2004-07-06 Kenny L. Dang Increased drug-loading and reduced stress drug delivery device
US6824559B2 (en) 2000-12-22 2004-11-30 Advanced Cardiovascular Systems, Inc. Ethylene-carboxyl copolymers as drug delivery matrices
US7077859B2 (en) 2000-12-22 2006-07-18 Avantec Vascular Corporation Apparatus and methods for variably controlled substance delivery from implanted prostheses
US20020082679A1 (en) 2000-12-22 2002-06-27 Avantec Vascular Corporation Delivery or therapeutic capable agents
US6544543B1 (en) 2000-12-27 2003-04-08 Advanced Cardiovascular Systems, Inc. Periodic constriction of vessels to treat ischemic tissue
US6540776B2 (en) 2000-12-28 2003-04-01 Advanced Cardiovascular Systems, Inc. Sheath for a prosthesis and methods of forming the same
US20020087123A1 (en) 2001-01-02 2002-07-04 Hossainy Syed F.A. Adhesion of heparin-containing coatings to blood-contacting surfaces of medical devices
US6544582B1 (en) 2001-01-05 2003-04-08 Advanced Cardiovascular Systems, Inc. Method and apparatus for coating an implantable device
US6645195B1 (en) 2001-01-05 2003-11-11 Advanced Cardiovascular Systems, Inc. Intraventricularly guided agent delivery system and method of use
US6544223B1 (en) 2001-01-05 2003-04-08 Advanced Cardiovascular Systems, Inc. Balloon catheter for delivering therapeutic agents
US6740040B1 (en) 2001-01-30 2004-05-25 Advanced Cardiovascular Systems, Inc. Ultrasound energy driven intraventricular catheter to treat ischemia
WO2002064014A2 (en) 2001-02-09 2002-08-22 Endoluminal Therapeutics, Inc. Endomural therapy
US6645135B1 (en) 2001-03-30 2003-11-11 Advanced Cardiovascular Systems, Inc. Intravascular catheter device and method for simultaneous local delivery of radiation and a therapeutic substance
US6780424B2 (en) 2001-03-30 2004-08-24 Charles David Claude Controlled morphologies in polymer drug for release of drugs from polymer films
US6623448B2 (en) 2001-03-30 2003-09-23 Advanced Cardiovascular Systems, Inc. Steerable drug delivery device
US6625486B2 (en) 2001-04-11 2003-09-23 Advanced Cardiovascular Systems, Inc. Method and apparatus for intracellular delivery of an agent
US6764505B1 (en) 2001-04-12 2004-07-20 Advanced Cardiovascular Systems, Inc. Variable surface area stent
US6660034B1 (en) 2001-04-30 2003-12-09 Advanced Cardiovascular Systems, Inc. Stent for increasing blood flow to ischemic tissues and a method of using the same
US7651695B2 (en) 2001-05-18 2010-01-26 Advanced Cardiovascular Systems, Inc. Medicated stents for the treatment of vascular disease
US7862495B2 (en) 2001-05-31 2011-01-04 Advanced Cardiovascular Systems, Inc. Radiation or drug delivery source with activity gradient to minimize edge effects
US6743462B1 (en) 2001-05-31 2004-06-01 Advanced Cardiovascular Systems, Inc. Apparatus and method for coating implantable devices
US6605154B1 (en) 2001-05-31 2003-08-12 Advanced Cardiovascular Systems, Inc. Stent mounting device
US6666880B1 (en) 2001-06-19 2003-12-23 Advised Cardiovascular Systems, Inc. Method and system for securing a coated stent to a balloon catheter
US6572644B1 (en) 2001-06-27 2003-06-03 Advanced Cardiovascular Systems, Inc. Stent mounting device and a method of using the same to coat a stent
US6565659B1 (en) 2001-06-28 2003-05-20 Advanced Cardiovascular Systems, Inc. Stent mounting assembly and a method of using the same to coat a stent
US6656216B1 (en) 2001-06-29 2003-12-02 Advanced Cardiovascular Systems, Inc. Composite stent with regioselective material
US6585755B2 (en) 2001-06-29 2003-07-01 Advanced Cardiovascular Polymeric stent suitable for imaging by MRI and fluoroscopy
EP1273314A1 (en) 2001-07-06 2003-01-08 Terumo Kabushiki Kaisha Stent
US6641611B2 (en) 2001-11-26 2003-11-04 Swaminathan Jayaraman Therapeutic coating for an intravascular implant
US20030083739A1 (en) 2001-09-24 2003-05-01 Robert Cafferata Rational drug therapy device and methods
US6753071B1 (en) 2001-09-27 2004-06-22 Advanced Cardiovascular Systems, Inc. Rate-reducing membrane for release of an agent
US7108701B2 (en) 2001-09-28 2006-09-19 Ethicon, Inc. Drug releasing anastomosis devices and methods for treating anastomotic sites
US20030073961A1 (en) 2001-09-28 2003-04-17 Happ Dorrie M. Medical device containing light-protected therapeutic agent and a method for fabricating thereof
US7585516B2 (en) 2001-11-12 2009-09-08 Advanced Cardiovascular Systems, Inc. Coatings for drug delivery devices
US6663880B1 (en) 2001-11-30 2003-12-16 Advanced Cardiovascular Systems, Inc. Permeabilizing reagents to increase drug delivery and a method of local delivery
US20040063805A1 (en) 2002-09-19 2004-04-01 Pacetti Stephen D. Coatings for implantable medical devices and methods for fabrication thereof
US7087263B2 (en) 2002-10-09 2006-08-08 Advanced Cardiovascular Systems, Inc. Rare limiting barriers for implantable medical devices

Patent Citations (101)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2072303A (en) * 1932-10-18 1937-03-02 Chemische Forschungs Gmbh Artificial threads, bands, tubes, and the like for surgical and other purposes
US4656272A (en) * 1985-05-24 1987-04-07 Basf Aktiengesellschaft Preparation of s-triazine derivatives
US4733665A (en) * 1985-11-07 1988-03-29 Expandable Grafts Partnership Expandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft
US4733665C2 (en) * 1985-11-07 2002-01-29 Expandable Grafts Partnership Expandable intraluminal graft and method and apparatus for implanting an expandable intraluminal graft
US4733665B1 (en) * 1985-11-07 1994-01-11 Expandable Grafts Partnership Expandable intraluminal graft,and method and apparatus for implanting an expandable intraluminal graft
US5721131A (en) * 1987-03-06 1998-02-24 United States Of America As Represented By The Secretary Of The Navy Surface modification of polymers with self-assembled monolayers that promote adhesion, outgrowth and differentiation of biological cells
US4800882A (en) * 1987-03-13 1989-01-31 Cook Incorporated Endovascular stent and delivery system
US4916193A (en) * 1987-12-17 1990-04-10 Allied-Signal Inc. Medical devices fabricated totally or in part from copolymers of recurring units derived from cyclic carbonates and lactides
US5616338A (en) * 1988-02-11 1997-04-01 Trustees Of Columbia University In The City Of New York Infection-resistant compositions, medical devices and surfaces and methods for preparing and using same
US5502158A (en) * 1988-08-08 1996-03-26 Ecopol, Llc Degradable polymer composition
US5100992A (en) * 1989-05-04 1992-03-31 Biomedical Polymers International, Ltd. Polyurethane-based polymeric materials and biomedical articles and pharmaceutical compositions utilizing the same
US5298260A (en) * 1990-05-01 1994-03-29 Mediventures, Inc. Topical drug delivery with polyoxyalkylene polymer thermoreversible gels adjustable for pH and osmolality
US5300295A (en) * 1990-05-01 1994-04-05 Mediventures, Inc. Ophthalmic drug delivery with thermoreversible polyoxyalkylene gels adjustable for pH
US5306501A (en) * 1990-05-01 1994-04-26 Mediventures, Inc. Drug delivery by injection with thermoreversible gels containing polyoxyalkylene copolymers
US5292516A (en) * 1990-05-01 1994-03-08 Mediventures, Inc. Body cavity drug delivery with thermoreversible gels containing polyoxyalkylene copolymers
US5607467A (en) * 1990-09-14 1997-03-04 Froix; Michael Expandable polymeric stent with memory and delivery apparatus and method
US5306786A (en) * 1990-12-21 1994-04-26 U C B S.A. Carboxyl group-terminated polyesteramides
US5858746A (en) * 1992-04-20 1999-01-12 Board Of Regents, The University Of Texas System Gels for encapsulation of biological materials
US5624411A (en) * 1993-04-26 1997-04-29 Medtronic, Inc. Intravascular stent and method
US5716981A (en) * 1993-07-19 1998-02-10 Angiogenesis Technologies, Inc. Anti-angiogenic compositions and methods of use
US5380299A (en) * 1993-08-30 1995-01-10 Med Institute, Inc. Thrombolytic treated intravascular medical device
US5735897A (en) * 1993-10-19 1998-04-07 Scimed Life Systems, Inc. Intravascular stent pump
US6051576A (en) * 1994-01-28 2000-04-18 University Of Kentucky Research Foundation Means to achieve sustained release of synergistic drugs by conjugation
US5485496A (en) * 1994-09-22 1996-01-16 Cornell Research Foundation, Inc. Gamma irradiation sterilizing of biomaterial medical devices or products, with improved degradation and mechanical properties
US5879713A (en) * 1994-10-12 1999-03-09 Focal, Inc. Targeted delivery via biodegradable polymers
US5869127A (en) * 1995-02-22 1999-02-09 Boston Scientific Corporation Method of providing a substrate with a bio-active/biocompatible coating
US5605696A (en) * 1995-03-30 1997-02-25 Advanced Cardiovascular Systems, Inc. Drug loaded polymeric material and method of manufacture
US6358556B1 (en) * 1995-04-19 2002-03-19 Boston Scientific Corporation Drug release stent coating
US5865814A (en) * 1995-06-07 1999-02-02 Medtronic, Inc. Blood contacting medical device and method
US20030036794A1 (en) * 1995-06-07 2003-02-20 Cook Incorporated Coated implantable medical device
US20030028244A1 (en) * 1995-06-07 2003-02-06 Cook Incorporated Coated implantable medical device
US5873904A (en) * 1995-06-07 1999-02-23 Cook Incorporated Silver implantable medical device
US5609629A (en) * 1995-06-07 1997-03-11 Med Institute, Inc. Coated implantable medical device
US20030028243A1 (en) * 1995-06-07 2003-02-06 Cook Incorporated Coated implantable medical device
US6010530A (en) * 1995-06-07 2000-01-04 Boston Scientific Technology, Inc. Self-expanding endoluminal prosthesis
US5877224A (en) * 1995-07-28 1999-03-02 Rutgers, The State University Of New Jersey Polymeric drug formulations
US6051648A (en) * 1995-12-18 2000-04-18 Cohesion Technologies, Inc. Crosslinked polymer compositions and methods for their use
US5723219A (en) * 1995-12-19 1998-03-03 Talison Research Plasma deposited film networks
US6033582A (en) * 1996-01-22 2000-03-07 Etex Corporation Surface modification of medical implants
US6054553A (en) * 1996-01-29 2000-04-25 Bayer Ag Process for the preparation of polymers having recurring agents
US5718159A (en) * 1996-04-30 1998-02-17 Schneider (Usa) Inc. Process for manufacturing three-dimensional braided covered stent
US5610241A (en) * 1996-05-07 1997-03-11 Cornell Research Foundation, Inc. Reactive graft polymer with biodegradable polymer backbone and method for preparing reactive biodegradable polymers
US5876433A (en) * 1996-05-29 1999-03-02 Ethicon, Inc. Stent and method of varying amounts of heparin coated thereon to control treatment
US6172167B1 (en) * 1996-06-28 2001-01-09 Universiteit Twente Copoly(ester-amides) and copoly(ester-urethanes)
US5711958A (en) * 1996-07-11 1998-01-27 Life Medical Sciences, Inc. Methods for reducing or eliminating post-surgical adhesion formation
US5871436A (en) * 1996-07-19 1999-02-16 Advanced Cardiovascular Systems, Inc. Radiation therapy method and device
US6530951B1 (en) * 1996-10-24 2003-03-11 Cook Incorporated Silver implantable medical device
US6042875A (en) * 1997-04-30 2000-03-28 Schneider (Usa) Inc. Drug-releasing coatings for medical devices
US6180632B1 (en) * 1997-05-28 2001-01-30 Aventis Pharmaceuticals Products Inc. Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases
US6524347B1 (en) * 1997-05-28 2003-02-25 Avantis Pharmaceuticals Inc. Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases
US6528526B1 (en) * 1997-05-28 2003-03-04 Aventis Pharmaceuticals Inc. Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases
US6211249B1 (en) * 1997-07-11 2001-04-03 Life Medical Sciences, Inc. Polyester polyether block copolymers
US6034204A (en) * 1997-08-08 2000-03-07 Basf Aktiengesellschaft Condensation products of basic amino acids with copolymerizable compounds and a process for their production
US6015541A (en) * 1997-11-03 2000-01-18 Micro Therapeutics, Inc. Radioactive embolizing compositions
US20030040790A1 (en) * 1998-04-15 2003-02-27 Furst Joseph G. Stent coating
US6344035B1 (en) * 1998-04-27 2002-02-05 Surmodics, Inc. Bioactive agent release coating
US6214901B1 (en) * 1998-04-27 2001-04-10 Surmodics, Inc. Bioactive agent release coating
US20020032434A1 (en) * 1998-04-27 2002-03-14 Chudzik Stephen J. Bioactive agent release coating
US20030031780A1 (en) * 1998-04-27 2003-02-13 Chudzik Stephen J. Bioactive agent release coating
US20020032414A1 (en) * 1998-08-20 2002-03-14 Ragheb Anthony O. Coated implantable medical device
US6335029B1 (en) * 1998-08-28 2002-01-01 Scimed Life Systems, Inc. Polymeric coatings for controlled delivery of active agents
US6011125A (en) * 1998-09-25 2000-01-04 General Electric Company Amide modified polyesters
US6530950B1 (en) * 1999-01-12 2003-03-11 Quanam Medical Corporation Intraluminal stent having coaxial polymer member
US20030040712A1 (en) * 1999-07-13 2003-02-27 Pinaki Ray Substance delivery apparatus and a method of delivering a therapeutic substance to an anatomical passageway
US6689099B2 (en) * 1999-07-13 2004-02-10 Advanced Cardiovascular Systems, Inc. Local drug delivery injection catheter
US6177523B1 (en) * 1999-07-14 2001-01-23 Cardiotech International, Inc. Functionalized polyurethanes
US6379381B1 (en) * 1999-09-03 2002-04-30 Advanced Cardiovascular Systems, Inc. Porous prosthesis and a method of depositing substances into the pores
US20040029952A1 (en) * 1999-09-03 2004-02-12 Yung-Ming Chen Ethylene vinyl alcohol composition and coating
US6713119B2 (en) * 1999-09-03 2004-03-30 Advanced Cardiovascular Systems, Inc. Biocompatible coating for a prosthesis and a method of forming the same
US6346110B2 (en) * 1999-10-04 2002-02-12 Advanced Cardiovascular Systems, Inc. Chamber for applying therapeutic substances to an implantable device
US6203551B1 (en) * 1999-10-04 2001-03-20 Advanced Cardiovascular Systems, Inc. Chamber for applying therapeutic substances to an implant device
US20020009604A1 (en) * 1999-12-22 2002-01-24 Zamora Paul O. Plasma-deposited coatings, devices and methods
US6503954B1 (en) * 2000-03-31 2003-01-07 Advanced Cardiovascular Systems, Inc. Biocompatible carrier containing actinomycin D and a method of forming the same
US6527801B1 (en) * 2000-04-13 2003-03-04 Advanced Cardiovascular Systems, Inc. Biodegradable drug delivery material for stent
US20020016625A1 (en) * 2000-05-12 2002-02-07 Robert Falotico Drug/drug delivery systems for the prevention and treatment of vascular disease
US20020005206A1 (en) * 2000-05-19 2002-01-17 Robert Falotico Antiproliferative drug and delivery device
US20020007213A1 (en) * 2000-05-19 2002-01-17 Robert Falotico Drug/drug delivery systems for the prevention and treatment of vascular disease
US20020007214A1 (en) * 2000-05-19 2002-01-17 Robert Falotico Drug/drug delivery systems for the prevention and treatment of vascular disease
US20020007215A1 (en) * 2000-05-19 2002-01-17 Robert Falotico Drug/drug delivery systems for the prevention and treatment of vascular disease
US6673385B1 (en) * 2000-05-31 2004-01-06 Advanced Cardiovascular Systems, Inc. Methods for polymeric coatings stents
US20040018296A1 (en) * 2000-05-31 2004-01-29 Daniel Castro Method for depositing a coating onto a surface of a prosthesis
US20040047978A1 (en) * 2000-08-04 2004-03-11 Hossainy Syed F.A. Composition for coating an implantable prosthesis
US6503538B1 (en) * 2000-08-30 2003-01-07 Cornell Research Foundation, Inc. Elastomeric functional biodegradable copolyester amides and copolyester urethanes
US6506437B1 (en) * 2000-10-17 2003-01-14 Advanced Cardiovascular Systems, Inc. Methods of coating an implantable device having depots formed in a surface thereof
US20040047980A1 (en) * 2000-12-28 2004-03-11 Pacetti Stephen D. Method of forming a diffusion barrier layer for implantable devices
US6503556B2 (en) * 2000-12-28 2003-01-07 Advanced Cardiovascular Systems, Inc. Methods of forming a coating for a prosthesis
US20030032767A1 (en) * 2001-02-05 2003-02-13 Yasuhiro Tada High-strength polyester-amide fiber and process for producing the same
US20030004141A1 (en) * 2001-03-08 2003-01-02 Brown David L. Medical devices, compositions and methods for treating vulnerable plaque
US6712845B2 (en) * 2001-04-24 2004-03-30 Advanced Cardiovascular Systems, Inc. Coating for a stent and a method of forming the same
US20030039689A1 (en) * 2001-04-26 2003-02-27 Jianbing Chen Polymer-based, sustained release drug delivery system
US20040052859A1 (en) * 2001-05-09 2004-03-18 Wu Steven Z. Microparticle coated medical device
US20040052858A1 (en) * 2001-05-09 2004-03-18 Wu Steven Z. Microparticle coated medical device
US6695920B1 (en) * 2001-06-27 2004-02-24 Advanced Cardiovascular Systems, Inc. Mandrel for supporting a stent and a method of using the mandrel to coat a stent
US6673154B1 (en) * 2001-06-28 2004-01-06 Advanced Cardiovascular Systems, Inc. Stent mounting device to coat a stent
US6527863B1 (en) * 2001-06-29 2003-03-04 Advanced Cardiovascular Systems, Inc. Support device for a stent and a method of using the same to coat a stent
US6706013B1 (en) * 2001-06-29 2004-03-16 Advanced Cardiovascular Systems, Inc. Variable length drug delivery catheter
US20030060877A1 (en) * 2001-09-25 2003-03-27 Robert Falotico Coated medical devices for the treatment of vascular disease
US20030059520A1 (en) * 2001-09-27 2003-03-27 Yung-Ming Chen Apparatus for regulating temperature of a composition and a method of coating implantable devices
US20030065377A1 (en) * 2001-09-28 2003-04-03 Davila Luis A. Coated medical devices
US6709514B1 (en) * 2001-12-28 2004-03-23 Advanced Cardiovascular Systems, Inc. Rotary coating apparatus for coating implantable medical devices
US20040054104A1 (en) * 2002-09-05 2004-03-18 Pacetti Stephen D. Coatings for drug delivery devices comprising modified poly(ethylene-co-vinyl alcohol)

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090264912A1 (en) * 2000-10-03 2009-10-22 Nawrocki Jesse G Medical devices having durable and lubricious polymeric coating
US8956602B2 (en) 2006-12-05 2015-02-17 Landec, Inc. Delivery of drugs
US20100004124A1 (en) * 2006-12-05 2010-01-07 David Taft Systems and methods for delivery of materials for agriculture and aquaculture
US20110009571A1 (en) * 2006-12-05 2011-01-13 David Taft Systems and methods for delivery of materials
US20090246155A1 (en) * 2006-12-05 2009-10-01 Landec Corporation Compositions and methods for personal care
US20090252777A1 (en) * 2006-12-05 2009-10-08 Landec Corporation Method for formulating a controlled-release pharmaceutical formulation
US20090263346A1 (en) * 2006-12-05 2009-10-22 David Taft Systems and methods for delivery of drugs
US8524259B2 (en) 2006-12-05 2013-09-03 Landec Corporation Systems and methods for delivery of materials
US20080269105A1 (en) * 2006-12-05 2008-10-30 David Taft Delivery of drugs
US8399007B2 (en) 2006-12-05 2013-03-19 Landec Corporation Method for formulating a controlled-release pharmaceutical formulation
US9358096B2 (en) 2007-05-01 2016-06-07 Abbott Laboratories Methods of treatment with drug eluting stents with prolonged local elution profiles with high local concentrations and low systemic concentrations
US20090093875A1 (en) * 2007-05-01 2009-04-09 Abbott Laboratories Drug eluting stents with prolonged local elution profiles with high local concentrations and low systemic concentrations
US20090041845A1 (en) * 2007-08-08 2009-02-12 Lothar Walter Kleiner Implantable medical devices having thin absorbable coatings
US8114883B2 (en) 2007-12-04 2012-02-14 Landec Corporation Polymer formulations for delivery of bioactive materials
US20090209558A1 (en) * 2007-12-04 2009-08-20 Landec Corporation Polymer formulations for delivery of bioactive materials
US20150033118A1 (en) * 2009-03-23 2015-01-29 Adobe Systems Incorporated Transferring component hierarchies between applications
US8183337B1 (en) 2009-04-29 2012-05-22 Abbott Cardiovascular Systems Inc. Method of purifying ethylene vinyl alcohol copolymers for use with implantable medical devices
US10137225B2 (en) * 2014-05-27 2018-11-27 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Crystalline coating and release of bioactive agents
US20150365548A1 (en) * 2014-06-16 2015-12-17 Fujifilm Corporation Display processor, display processing method and ordering apparatus
US20180059882A1 (en) * 2016-08-29 2018-03-01 Canon Kabushiki Kaisha Information processing apparatus that performs image layout, method of controlling the same, and storage medium

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