Coated implantable medical device

• US 7,611,532 B2
• Filed: 08/14/2002
• Issued: 11/03/2009
• Est. Priority Date: 06/07/1995
• Status: Expired due to Fees

• Current Assignee: Cook Medical Incorporated (Cook Group Incorporated)
• Original Assignee: Cook Incorporated (Cook Group Incorporated)
• Inventors: Bates, Brian L., Fearnot, Neal E., Kozma, Thomas G., Ragheb, Anthony O., Voorhees, William D. III
• Primary Examiner(s): PREBILIC, PAUL B
• Application Number:
  US10/218,308
• Publication Number:
  US 20030028244A1
• Time in Patent Office: 2,638 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 2/0077 Special surfaces of prostheses, e.g. for improving ingrowth A61F2/30767 takes precedence
• CPC Class Codes: A61F 2/02 Prostheses implantable into the body closure means for urethra or rectum or for artificial body openings therefor A61F2/0004
• CPC Class Codes: A61F 2/06 Blood vessels
• 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 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• CPC Class Codes: A61F 2210/0076 multilayered, e.g. laminated structures
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• 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

Disclosed in one embodiment is a medical device including an expandable metal vascular stent including at least one surface. A coating layer including parylene or a parylene derivative is positioned on the at least one surface. At least one layer comprising a bioactive agent is positioned on the coating layer, wherein the bioactive agent is selected from the group consisting of an immunosuppressive agent, anti-inflammatory agent and an anti-proliferative agent. A porous layer is positioned on the at least one layer including a bioactive agent, wherein upon implantation into a patient, the porous layer controls release of the bioactive agent from the at least one layer including the bioactive agent.

Claims

1. A medical device comprising:

a stent adapted for introduction into a patient, the stent having at least one surface;

at least one layer comprising an immunosuppressive agent posited over the at least one surface of the stent;

at least one porous layer posited over the at least one layer comprising the immunosuppressive agent; and

at least one coating layer posited over the at least one surface of the stent;

wherein the at least one layer comprising the immunosuppressive agent is posited over at least a portion of the at least one coating layer;

wherein the at least one porous layer comprises a polymer; and

wherein the stent further comprises at least one well formed in the at least one surface of the stent, the at least one well being a groove or slot in which the immunosuppressive agent of the at least one layer comprising the immunosuppressive agent is contained.

7. The medical device of claim 1, wherein the porous layer further comprises a biostable material.

8. The medical device of claim 1, wherein the porous layer further comprises a material 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, poly(hexamethylene adipamide), rayon, rayon-triacetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, carboxymethyl cellulose, and polymers, copolymers and mixtures thereof.

9. The medical device of claim 1, wherein the porous layer further comprises a material selected from the group consisting of phosphatidylcholine, and poly(butylmethacrylate).

10. The medical device of claim 1, wherein the porous layer further comprises a bioabsorbable material.

11. The medical device of claim 1, wherein the porous layer further comprises a material selected from the group consisting of poly(L-lactic acid), polycaprolactone, 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, hyaluronic acid, copolymers thereof and mixtures thereof.

12. The medical device of claim 1, wherein the porous layer further comprises a material selected from the group consisting of poly(L-lactic acid), poly(lactide-co-caprolactone) copolymer and poly(lactide-co-glycolide) copolymer.

19. The medical device of claim 1, wherein the stent comprises at least one hole or well defined in the surface of the stent, and wherein the layer comprising an immunosuppressive agent is received in the at least one hole or well.

20. The medical device of claim 19, wherein the stent comprises at least one hole defined in the surface of the stent, and wherein the layer comprising an immunosuppressive agent is received in the hole.

30. The medical device of claim 19, wherein the porous layer comprises a polymer, and wherein said polymer is a biostable polymer.

31. The medical device of claim 20, wherein the porous layer comprises a polymer, and wherein said polymer is a biostable polymer.

2. An implantable medical device, comprising:

a stent adapted for introduction into a patient, the stent having at least one surface;

at least one coating layer comprising a bioabsorbable polymer posited in contact with the at least one surface of the stent;

at least one layer comprising an immunosuppressive agent posited over the at least one coating layer;

at least one porous layer posited over the at least one layer comprising the immunosuppressive agent, wherein the least one porous layer comprises open pores upon deposition.

4. The device of claim 2, wherein the stent is configured as a vascular stent.

5. The device of claim 2, wherein the stent is composed of a base material comprising a material selected from the group consisting of stainless steel, tantalum, titanium, nitinol, gold, platinum, inconel, iridium, silver, tungsten, a bio compatible metal, any alloy of biocompatible 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, a biocompatible polymeric material, polylactic acid, polyglycolic acid, a polyanhydride, polycaprolactone, polyhydroxybutyrate valerate, a biodegradable polymer, a protein, an extracellular matrix component, collagen, fibrin, a biologic agent, and any combination of these materials.

6. The medical device of claim 2, wherein the at least one porous layer further comprises phosphatidylcholine.

13. The medical device of claim 2, wherein the coating layer comprises a poly(lactide-co-glycolide) polymer.

14. The medical device of claim 2, wherein the coating layer comprises poly(L-lactic acid, poly(D-lactic acid) or poly(D,L-lactic acid).

15. The medical device of claim 2, wherein the coating layer comprises poly(L-lactic acid).

16. The medical device of claim 2, wherein the stent has at least one well or hole defined in said surface.

17. The medical device of claim 2, wherein the coating layer comprises a material selected from the group consisting of poly(L-lactic acid), polycaprolactone, 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, hyaluronic acid, copolymers thereof and mixtures thereof.

18. The medical device of claim 2, wherein the coating layer comprises a poly(lactide-co-caprolactone) copolymer.

3. A medical device, comprising:

an expandable metal vascular stent comprising at least one metal surface;

a coating layer comprising parylene or a parylene derivative that is positioned directly against the at least one metal surface;

at least one layer comprising a bioactive agent selected from the group consisting of an immunosuppressive agent, anti-inflammatory agent and an anti-proliferative agent;

wherein the at least one layer comprising the bioactive agent is positioned on the coating layer;

a porous layer positioned on the at least one layer comprising the bioactive agent; and

wherein upon implantation into a patient, the porous layer controls release of the bioactive agent from the at least one layer comprising the bioactive agent.

21. The medical device of claim 3, wherein the porous layer comprises a polymer.

22. The medical device of claim 3, wherein the porous layer comprises phosphatidylcholine.

23. The medical device of claim 3, wherein the porous layer comprises at least one of an n-butyl-acrylate polymer, an n-butyl-methacrylate polymer, a 2-ethylhexyl-acrylate polymer, a lauryl-acrylate polymer, or a 2-hydroxypropyl-acrylate polymer.

24. The medical device of claim 23, wherein the porous layer comprises an n-butyl-methacrylate polymer.

25. The medical device of claim 3, wherein the coating layer comprises a parylene derivative prepared from dichloro-di-p-xylylene.

26. The medical device of claim 25, wherein the bioactive agent is an immunosuppressive agent.

27. The medical device of claim 25, wherein the bioactive agent is an anti-proliferative agent.

28. The medical device of claim 25, wherein the bioactive agent is an anti-inflammatory agent.

29. The medical device of claim 21, wherein said polymer is a biostable polymer.