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 PDFInfo
- 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
- Authority
- US
- United States
- Prior art keywords
- coating layer
- stent
- polymer
- ethylene
- styrene
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/606—Coatings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/08—Coatings 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
- 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.
- 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.
- 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.
- 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.
- where
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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).
- 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.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/526,126 US20070016284A1 (en) | 2001-09-07 | 2006-09-22 | Polymeric coating for reducing the rate of release of a therapeutic substance from a stent |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/948,513 US8303651B1 (en) | 2001-09-07 | 2001-09-07 | Polymeric coating for reducing the rate of release of a therapeutic substance from a stent |
US11/526,126 US20070016284A1 (en) | 2001-09-07 | 2006-09-22 | Polymeric coating for reducing the rate of release of a therapeutic substance from a stent |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/948,513 Division US8303651B1 (en) | 2001-09-07 | 2001-09-07 | Polymeric coating for reducing the rate of release of a therapeutic substance from a stent |
Publications (1)
Publication Number | Publication Date |
---|---|
US20070016284A1 true US20070016284A1 (en) | 2007-01-18 |
Family
ID=25487935
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/948,513 Expired - Fee Related US8303651B1 (en) | 2001-09-07 | 2001-09-07 | Polymeric coating for reducing the rate of release of a therapeutic substance from a stent |
US11/526,126 Abandoned US20070016284A1 (en) | 2001-09-07 | 2006-09-22 | Polymeric coating for reducing the rate of release of a therapeutic substance from a stent |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/948,513 Expired - Fee Related US8303651B1 (en) | 2001-09-07 | 2001-09-07 | Polymeric coating for reducing the rate of release of a therapeutic substance from a stent |
Country Status (2)
Country | Link |
---|---|
US (2) | US8303651B1 (en) |
WO (1) | WO2003022323A1 (en) |
Cited By (14)
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)
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 |
US7807211B2 (en) * | 1999-09-03 | 2010-10-05 | Advanced Cardiovascular Systems, Inc. | Thermal treatment of an implantable medical device |
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 |
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 |
US20040047911A1 (en) * | 2002-08-13 | 2004-03-11 | Medtronic, Inc. | Active agent delivery system including a poly(ethylene-co-(meth)Acrylate), medical device, and method |
US7169178B1 (en) * | 2002-11-12 | 2007-01-30 | Advanced Cardiovascular Systems, Inc. | Stent with drug coating |
US7776926B1 (en) | 2002-12-11 | 2010-08-17 | Advanced Cardiovascular Systems, Inc. | Biocompatible coating for implantable medical devices |
US7758880B2 (en) | 2002-12-11 | 2010-07-20 | Advanced Cardiovascular Systems, Inc. | Biocompatible polyacrylate compositions for medical applications |
US20040230298A1 (en) * | 2003-04-25 | 2004-11-18 | Medtronic Vascular, Inc. | Drug-polymer coated stent with polysulfone and styrenic block copolymer |
US8246974B2 (en) | 2003-05-02 | 2012-08-21 | Surmodics, Inc. | Medical devices and methods for producing the same |
AU2004237774B2 (en) | 2003-05-02 | 2009-09-10 | Surmodics, Inc. | Implantable controlled release bioactive agent delivery device |
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)
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 |
US6051648A (en) * | 1995-12-18 | 2000-04-18 | Cohesion Technologies, Inc. | Crosslinked polymer compositions and methods for their use |
US6051576A (en) * | 1994-01-28 | 2000-04-18 | University Of Kentucky Research Foundation | Means to achieve sustained release of synergistic drugs by conjugation |
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 |
US6503538B1 (en) * | 2000-08-30 | 2003-01-07 | Cornell Research Foundation, Inc. | Elastomeric functional biodegradable copolyester amides and copolyester urethanes |
US6503954B1 (en) * | 2000-03-31 | 2003-01-07 | Advanced Cardiovascular Systems, Inc. | Biocompatible carrier containing actinomycin D and a method of forming the same |
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 |
US20030028244A1 (en) * | 1995-06-07 | 2003-02-06 | Cook Incorporated | Coated implantable medical device |
US20030028243A1 (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 |
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 |
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 |
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 |
US6673385B1 (en) * | 2000-05-31 | 2004-01-06 | Advanced Cardiovascular Systems, Inc. | Methods for polymeric coatings stents |
US6673154B1 (en) * | 2001-06-28 | 2004-01-06 | Advanced Cardiovascular Systems, Inc. | Stent mounting device to coat a stent |
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 |
US20040054104A1 (en) * | 2002-09-05 | 2004-03-18 | Pacetti Stephen D. | Coatings for drug delivery devices comprising modified poly(ethylene-co-vinyl alcohol) |
US20040052858A1 (en) * | 2001-05-09 | 2004-03-18 | Wu Steven Z. | Microparticle coated medical device |
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)
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 |
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 |
SU872531A1 (en) | 1979-08-07 | 1981-10-15 | Институт Физиологии Им.И.С.Бериташвили Ан Гсср | Method of producing polyurethans |
SU876663A1 (en) | 1979-11-11 | 1981-10-30 | Институт Физиологии Им. Академика И.С.Бериташвили Ан Гсср | Method of producing polyarylates |
US4343931A (en) | 1979-12-17 | 1982-08-10 | Minnesota Mining And Manufacturing Company | Synthetic absorbable surgical devices of poly(esteramides) |
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 |
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 |
AU651084B2 (en) | 1990-01-30 | 1994-07-14 | 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 |
AU7998091A (en) | 1990-05-17 | 1991-12-10 | Harbor Medical Devices, Inc. | Medical device polymer |
CA2038605C (en) | 1990-06-15 | 2000-06-27 | Leonard Pinchuk | Crack-resistant polycarbonate urethane polymer prostheses and the like |
AU8074591A (en) | 1990-06-15 | 1992-01-07 | Cortrak Medical, Inc. | Drug delivery apparatus and method |
US6060451A (en) | 1990-06-15 | 2000-05-09 | The National Research Council Of Canada | Thrombin inhibitors based on the amino acid sequence of hirudin |
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 |
US5417981A (en) | 1992-04-28 | 1995-05-23 | Terumo Kabushiki Kaisha | Thermoplastic polymer composition and medical devices made of the same |
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 |
US20020055710A1 (en) | 1998-04-30 | 2002-05-09 | Ronald J. Tuch | Medical device for delivering a therapeutic agent and method of preparation |
US5824048A (en) | 1993-04-26 | 1998-10-20 | Medtronic, Inc. | Method for delivering a therapeutic substance to a body lumen |
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 |
AU710504B2 (en) | 1994-03-15 | 1999-09-23 | Brown University Research Foundation | 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 |
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 |
AU5346896A (en) | 1995-04-19 | 1996-11-07 | Kazunori Kataoka | Heterotelechelic block copolymers and process for producing the same |
US6099562A (en) | 1996-06-13 | 2000-08-08 | Schneider (Usa) Inc. | Drug coating with topcoat |
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 |
CA2279270C (en) | 1997-01-28 | 2007-05-15 | United States Surgical Corporation | Polyesteramides with amino acid-derived groups alternating with alpha-hydroxyacid-derived groups and surgical articles made therefrom |
WO1998032779A1 (en) | 1997-01-28 | 1998-07-30 | United States Surgical Corporation | Polyesteramide, its preparation and surgical devices fabricated therefrom |
ES2235312T3 (en) | 1997-01-28 | 2005-07-01 | United States Surgical Corporation | POLYESTERAMIDE, ITS PREPARATION AND SURGICAL DEVICES MANUFACTURED FROM THE SAME. |
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 |
US6790228B2 (en) | 1999-12-23 | 2004-09-14 | Advanced Cardiovascular Systems, Inc. | Coating for implantable devices and a method of forming the same |
US6759054B2 (en) | 1999-09-03 | 2004-07-06 | Advanced Cardiovascular Systems, Inc. | Ethylene vinyl alcohol composition and coating |
US6287628B1 (en) | 1999-09-03 | 2001-09-11 | Advanced Cardiovascular Systems, Inc. | Porous prosthesis and a method of depositing substances into the pores |
US6749626B1 (en) | 2000-03-31 | 2004-06-15 | Advanced Cardiovascular Systems, Inc. | Actinomycin D for the treatment of vascular disease |
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 |
US20010007083A1 (en) | 1999-12-29 | 2001-07-05 | Roorda Wouter E. | 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 |
CA2771263A1 (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 |
US6254632B1 (en) | 2000-09-28 | 2001-07-03 | Advanced Cardiovascular Systems, Inc. | Implantable medical device having protruding surface structures for drug delivery and cover attachment |
US6716444B1 (en) | 2000-09-28 | 2004-04-06 | Advanced Cardiovascular Systems, Inc. | Barriers for polymer-coated implantable medical devices and methods for making the same |
US6746773B2 (en) | 2000-09-29 | 2004-06-08 | Ethicon, Inc. | Coatings for medical devices |
US7261735B2 (en) | 2001-05-07 | 2007-08-28 | Cordis Corporation | Local drug delivery devices and methods for maintaining the drug coatings thereon |
US20020051730A1 (en) | 2000-09-29 | 2002-05-02 | Stanko Bodnar | Coated medical devices and sterilization thereof |
US20020111590A1 (en) | 2000-09-29 | 2002-08-15 | Davila Luis A. | Medical devices, drug coatings and methods for maintaining the drug coatings thereon |
US20070276473A1 (en) | 2000-09-29 | 2007-11-29 | Llanos Gerard H | Medical Devices, Drug Coatings and Methods for Maintaining the Drug Coatings Thereon |
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 |
US6544223B1 (en) | 2001-01-05 | 2003-04-08 | Advanced Cardiovascular Systems, Inc. | Balloon catheter for delivering therapeutic agents |
US6645195B1 (en) | 2001-01-05 | 2003-11-11 | Advanced Cardiovascular Systems, Inc. | Intraventricularly guided agent delivery system and method of use |
US6740040B1 (en) | 2001-01-30 | 2004-05-25 | Advanced Cardiovascular Systems, Inc. | Ultrasound energy driven intraventricular catheter to treat ischemia |
JP2004533277A (en) | 2001-02-09 | 2004-11-04 | エンドルミナル セラピューティクス, インコーポレイテッド | Intramural therapy |
US6623448B2 (en) | 2001-03-30 | 2003-09-23 | Advanced Cardiovascular Systems, Inc. | Steerable drug delivery device |
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 |
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 |
US6605154B1 (en) | 2001-05-31 | 2003-08-12 | Advanced Cardiovascular Systems, Inc. | Stent mounting device |
US6743462B1 (en) | 2001-05-31 | 2004-06-01 | Advanced Cardiovascular Systems, Inc. | Apparatus and method for coating implantable devices |
US7862495B2 (en) | 2001-05-31 | 2011-01-04 | Advanced Cardiovascular Systems, Inc. | Radiation or drug delivery source with activity gradient to minimize edge effects |
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 |
US6585755B2 (en) | 2001-06-29 | 2003-07-01 | Advanced Cardiovascular | Polymeric stent suitable for imaging by MRI and fluoroscopy |
US6656216B1 (en) | 2001-06-29 | 2003-12-02 | Advanced Cardiovascular Systems, Inc. | Composite stent with regioselective material |
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 |
EP1429689A4 (en) | 2001-09-24 | 2006-03-08 | Medtronic Ave Inc | 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 |
-
2001
- 2001-09-07 US US09/948,513 patent/US8303651B1/en not_active Expired - Fee Related
-
2002
- 2002-08-28 WO PCT/US2002/027521 patent/WO2003022323A1/en not_active Application Discontinuation
-
2006
- 2006-09-22 US US11/526,126 patent/US20070016284A1/en not_active Abandoned
Patent Citations (101)
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 |
US6010530A (en) * | 1995-06-07 | 2000-01-04 | Boston Scientific Technology, Inc. | Self-expanding endoluminal prosthesis |
US20030028243A1 (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 |
US20030036794A1 (en) * | 1995-06-07 | 2003-02-20 | Cook Incorporated | Coated implantable medical device |
US5609629A (en) * | 1995-06-07 | 1997-03-11 | Med Institute, Inc. | Coated implantable medical device |
US20030028244A1 (en) * | 1995-06-07 | 2003-02-06 | Cook Incorporated | Coated implantable medical device |
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 |
US6214901B1 (en) * | 1998-04-27 | 2001-04-10 | Surmodics, Inc. | Bioactive agent release coating |
US6344035B1 (en) * | 1998-04-27 | 2002-02-05 | Surmodics, Inc. | Bioactive agent release coating |
US20030031780A1 (en) * | 1998-04-27 | 2003-02-13 | Chudzik Stephen J. | Bioactive agent release coating |
US20020032434A1 (en) * | 1998-04-27 | 2002-03-14 | 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 |
US6689099B2 (en) * | 1999-07-13 | 2004-02-10 | Advanced Cardiovascular Systems, Inc. | Local drug delivery injection catheter |
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 |
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 |
US6713119B2 (en) * | 1999-09-03 | 2004-03-30 | Advanced Cardiovascular Systems, Inc. | Biocompatible coating for a prosthesis and a method of forming the same |
US20040029952A1 (en) * | 1999-09-03 | 2004-02-12 | Yung-Ming Chen | Ethylene vinyl alcohol composition and coating |
US6203551B1 (en) * | 1999-10-04 | 2001-03-20 | Advanced Cardiovascular Systems, Inc. | Chamber for applying therapeutic substances to an implant device |
US6346110B2 (en) * | 1999-10-04 | 2002-02-12 | Advanced Cardiovascular Systems, Inc. | Chamber for applying therapeutic substances to an implantable 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 |
US20040018296A1 (en) * | 2000-05-31 | 2004-01-29 | Daniel Castro | Method for depositing a coating onto a surface of a prosthesis |
US6673385B1 (en) * | 2000-05-31 | 2004-01-06 | Advanced Cardiovascular Systems, Inc. | Methods for polymeric coatings stents |
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 |
US6503556B2 (en) * | 2000-12-28 | 2003-01-07 | Advanced Cardiovascular Systems, Inc. | Methods of forming a coating for a prosthesis |
US20040047980A1 (en) * | 2000-12-28 | 2004-03-11 | Pacetti Stephen D. | Method of forming a diffusion barrier layer for implantable devices |
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 |
US6706013B1 (en) * | 2001-06-29 | 2004-03-16 | Advanced Cardiovascular Systems, Inc. | Variable length drug delivery catheter |
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 |
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)
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 |
Also Published As
Publication number | Publication date |
---|---|
US8303651B1 (en) | 2012-11-06 |
WO2003022323A1 (en) | 2003-03-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8303651B1 (en) | Polymeric coating for reducing the rate of release of a therapeutic substance from a stent | |
US6753071B1 (en) | Rate-reducing membrane for release of an agent | |
US8173199B2 (en) | 40-O-(2-hydroxy)ethyl-rapamycin coated stent | |
US7887871B2 (en) | Method and system for irradiation of a drug eluting implantable medical device | |
US7247313B2 (en) | Polyacrylates coatings for implantable medical devices | |
US6713119B2 (en) | Biocompatible coating for a prosthesis and a method of forming the same | |
US7682647B2 (en) | Thermal treatment of a drug eluting implantable medical device | |
US8377462B2 (en) | PEA-TEMPO/PEA-BZ coatings for controlled delivery of drug from implantable medical devices | |
US8551446B2 (en) | Poly(vinyl acetal) coatings for implantable medical devices | |
WO2005051453A1 (en) | Biologically beneficial coatings for implantable devices containing fluorinated polymers and methods for fabricating the same | |
JP2008513117A (en) | Drug-containing coating for implantable medical devices containing polyacrylate | |
US7645504B1 (en) | Coatings for implantable medical devices comprising hydrophobic and hydrophilic polymers | |
US10064982B2 (en) | PDLLA stent coating |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |