Coated implantable medical device

• US 7,611,533 B2
• Filed: 08/19/2002
• Issued: 11/03/2009
• Est. Priority Date: 06/07/1995
• Status: Expired due to Fees

• Current Assignee: Cook Medical Technologies, LLC (Cook Group Incorporated)
• Original Assignee: Cook Incorporated (Cook Group Incorporated)
• Inventors: Ragheb, Anthony O., Bates, Brian L., Fearnot, Neal E., Kozma, Thomas G., Voorhees, William D. III, Osborne, Thomas A.
• Primary Examiner(s): PREBILIC, PAUL B
• Application Number:
  US10/223,415
• Publication Number:
  US 20030036794A1
• Time in Patent Office: 2,633 Days
• Field of Search: 623 142- 146, 604/264, 604/265, 604/891.1, 604/892.1
• US Class Current: 623/1.42
• CPC Class Codes: A61F 2/24 Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• CPC Class Codes: A61K 51/1282 Devices used in vivo and carrying the radioactive therapeutic or diagnostic agent, therapeutic or in vivo diagnostic kits, stents
• CPC Class Codes: A61L 2300/256 Antibodies, e.g. immunoglobulins, vaccines
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 27/306 Other specific inorganic materials not covered by A61L27/303 - A61L27/32
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/106 Inorganic materials other than carbon
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/088 Other specific inorganic materials not covered by A61L31/084 or A61L31/086
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61L 33/022 Metal or alloys
• CPC Class Codes: A61N 5/1002 Intraluminal radiation therapy
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C08L 65/04 : Polyxylenes

Abstract

A coated implantable medical device 10 includes a structure 12 adapted for introduction into the vascular system, esophagus, trachea, colon, biliary tract, or urinary tract, and at least one layer 18 of an immunosuppressive agent posited over at least one surface of the structure 12. Optionally, the device 10 can include at least one porous, preferably polymeric layer 20 posited over the layer 18 of immunosuppressive agent, and can alternatively or additionally include at least one coating layer 16 posited on one surface of the structure 12, the at least one layer 18 of immunosuppessive agent being posited in turn on at least a portion of the coating layer 16. The porous layer 20 and the coating layer 16 each provide for the controlled release of the bioactive material from the device 10. The structure 12 is preferably configured as a coronary stent. The polymer of the porous layer 20 is preferably applied by vapor or plasma deposition. It is particularly preferred that the polymer is a polyamide, parylene or a parylene derivative which is deposited without solvents, heat or catalysts, but rather by condensation of a monomer vapor.

Claims

1. An implantable medical device, comprising:

an expandable stent sized and shaped for introduction into a vascular system of a patient, the expandable stent having at least one surface;

a coating layer in direct contact with the at least one surface and comprising a first polymer posited between the at least one surface of the expandable stent and at the least one layer comprising a bioactive agent;

the porous layer comprising a second polymer posited over the at least one layer comprising a bioactive agent and controlling the release of the bioactive agent, the first polymer and the second polymer being the same or different;

wherein the expandable stent is capable of eluting the bioactive agent from the bioactive layer through the porous layer when the expandable stent is placed in the vascular system of the patient;

wherein said stent is a metal stent, and said at least one surface is a metal surface;

wherein said coating layer is in contact with said metal surface; and

wherein said first polymer is a parylene or a parylene derivative polymer.

4. The medical device of claim 1, wherein the metal surface comprises stainless steel.

5. The medical device of claim 1, wherein the expandable stent surface forms at least a portion of at least one hole, well, groove or slot in which the bioactive agent is contained.

6. The medical device of claim 1, wherein the porous layer comprises a biocompatible polymer selected from the group consisting of:

parylene, poly(n-butyl-acrylate), poly(n-butyl methacrylate), poly 2-ethyihexyl acrylate, poly lauryl-acrylate, poly 2-hydroxy-propyl acrylate, polyvinyl chloride, polyvinyl methyl ether, polyvinylidene fluoride, polyvinylidene chloride, polyacrylonitrile, polystyrene, polyvinyl acetate, ethylenemethyl methacrylate copolymers, acrylonitrile-styrene copolymers, ethylene glycol diacrylate, ethylene glycol dimethacrylate, trimethylopropane triacrylate, trimethylopropane trimethacrylate, pentaerythritol tetraacrylate, pentaerythritol tetramethacrylate, 1,6-hexanediol dimethacrylate, diethyleneglycol dimethacrylate, N-methylol methacrylamide butyl ether, N-vinyl pyrrolidone, vinyl oleate, polyvinyl chloride, polyvinylidene fluoride, acrylonitrile butadiene styrene resins, polyamides, rayon, rayon-triacetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, carboxymethyl cellulose, poly(L-lactic acid), polycaprolactone, poly(lactide-co-caprolactone), poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), poly(glycolic acid), poly(D,L-lactic acid), poly(glycolic acid-co-trimethylene carbonate), poly(trimethylene carbonate), poly(ethylene oxide), poly(D-lactic acid), fibrin, fibrinogen, cellulose, starch, collagen, phosphatidylcholine, hyaluronic acid, and polymers, copolymers and mixtures thereof.

2. An implantable medical device, comprising:

an expandable stent sized and shaped for introduction into a vascular system of a patient, the expandable stent having at least one surface;

a coating layer in direct contact with the at least one surface and comprising a first polymer posited between the at least one surface of the expandable stent and at least one layer comprising a bioactive agent;

the at least one layer comprising a bioactive agent posited over the coating layer and under a porous layer consisting essentially of one or more biocompatible polymers selected from the group consisting of;

a parylene polymer, a poly(alkylmethacrylate) polymer, and an ethylene-vinyl acetate copolymer;

the porous layer posited over the bioactive agent and controlling the release of the bioactive agent;

wherein the expandable stent is capable of eluting the bioactive agent from the at least one layer comprising a bioactive agent through the porous layer when the expandable stent is placed in the vascular system of the patient; and

wherein the porous layer comprises a material selected from the group consisting of;

parylene and poly(n-butyl methacrylate).

7. The medical device of claim 2, wherein the expandable stent surface comprises at least one of a material selected from the group consisting of:

stainless steel, tantalum, titanium, nitinol, gold, platinum, inconel, iridium, silver, tungsten, any biocompatible metal, any alloy of the aforementioned metals, carbon, carbon fiber, cellulose acetate, cellulose nitrate, silicone, polyethylene teraphthalate, polyurethane, polyamide, polyester, polyorthoester, polyanhydride, polyether sulfone, polycarbonate, polypropylene, high molecular weight polyethylene, polytetrafluoroethylene, any biocompatible polymeric material, polylactic acid, polyglycolic acid, a polyanhydride, polycaprolactone, polyhydroxybutyrate valerate, any biodegradable polymer, a protein, an extracellular matrix component, collagen, and fibrin.

8. The medical device of claim 2, wherein the expandable stent surface forms a portion of at least one well that is a groove or slot in which the bioactive agent is contained.

9. The medical device of claim 2, where the coating layer comprises a material selected from the group consisting of:

parylene, poly(n-butyl-acrylate), poly(n-butyl methacrylate), poly 2-ethylhexyl acrylate, poly lauryl-acrylate, poly 2-hydroxy-propyl acrylate, polyvinyl chloride, polyvinyl methyl ether, polyvinylidene fluoride, polyvinylidene chloride, polyacrylonitrile, polystyrene, polyvinyl acetate, ethylenemethyl methacrylate copolymers, acrylonitrile-styrene copolymers, ethylene glycol diacrylate, ethylene glycol dimethacrylate, trimethylopropane triacrylate, trimethylopropane trimethacrylate, pentaerythritol tetraacrylate, pentaerythritol tetramethacrylate, 1,6-hexanediol dimethacrylate, diethyleneglycol dimethacrylate, N-methylol methacrylamide butyl ether, N-vinyl pyrrolidone, vinyl oleate, polyvinyl chloride, polyvinylidene fluoride, acrylonitrile butadiene styrene resins, polyamides, rayon, rayon-triacetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, carboxymethyl cellulose, poly(L-lactic acid), polycaprolactone, poly(lactide-co-caprolactone), poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), poly(glycolic acid), poly(D,L-lactic acid), poly(glycolic acid-co-trimethylene carbonate), poly(trimethylene carbonate), poly(ethylene oxide), poly(D-lactic acid), fibrin, fibrinogen, cellulose, starch, collagen, phosphatidylcholine, hyaluronic acid, and polymers, copolymers and mixtures thereof.

10. The medical device of claim 2, wherein the bioactive agent consists essentially of an immunosuppressive agent.

11. The implantable medical device of claim 2, wherein:

said stent is a metal stent, and said at least one surface is a metal surface;

said coating layer is in contact with said metal surface; and

said coating layer consists of a parylene or a parylene derivative polymer.

12. The implantable medical device of claim 2, wherein:

said coating layer consists of a parylene or a parylene derivative polymer.

3. An implantable medical device, comprising:

an expandable stent sized and shaped for introduction into a vascular system of a patient, the expandable stent having at least one surface;

a coating layer in direct contact with the at least one surface and comprising a first polymer posited between the at least one surface of the expandable stent and at least one layer comprising a bioactive agent;

the at least one layer comprising a bioactive agent posited over the coating layer and under a porous layer consisting essentially of one or more biocompatible polymers selected from the group consisting of;

a parylene polymer, a poly(alkylmethacrylate) polymer, and an ethylene-vinyl acetate copolymer;

the porous layer posited over the bioactive agent and controlling the release of the bioactive agent;

wherein the expandable stent is capable of eluting the bioactive agent from the at least one layer comprising a bioactive agent through the porous layer when the expandable stent is placed in the vascular system of the patient; and

wherein the bioactive agent consists essentially of an immunosuppressive agent and the porous layer consists essentially of a biocompatible polymer selected from the group consisting of;

a parylene polymer, a poly(alkylmethacrylate) polymer and an ethylene-vinyl acetate copolymer.