Implantable medical device with enhanced biocompatibility and biostability

• US 7,658,727 B1
• Filed: 04/29/1999
• Issued: 02/09/2010
• Est. Priority Date: 04/20/1998
• Status: Expired due to Fees

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Fernandes, Brian C. A., Torrianni, Mark W., Casas-Bejar, Jesus W., Sparer, Randall V., Donovan, Maura G.
• Primary Examiner(s): Lam; Ann Y
• Application Number:
  US09/301,842
• Time in Patent Office: 3,939 Days
• Field of Search: 604263-265, 604/266, 424424-426
• US Class Current: 604/265
• CPC Class Codes: A61F 2/2403 with pivoting rigid closure members check valves with hinged closure members in general F16K15/03
• CPC Class Codes: A61F 2/2445 Annuloplasty rings in direct contact with the valve annulus
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/102 Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/40 Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: C08L 75/04 Polyurethanes

Abstract

An implantable medical device comprising a drug-loaded polymer overlaid with a fabric that promotes tissue ingrowth is useful in a wide variety of tissue engineering applications. The invention includes, for example, prosthetic heart valves, annuloplasty rings, and grafts, having enhanced biocompatibility and biostability. Methods of making and using the implantable medical devices of the invention are also included.

Claims

1. A heart valve prosthesis comprising a sewing ring comprising an annular support initially formed from a biostable polymer mixed with a steroidal agent, said annular support overlayed by a polyester fabric overlayer, wherein said annular support provides at least one therapeutic effect to the fabric overlayer.

2. The heart valve prosthesis of claim 1, wherein the biostable polymer is selected from the group consisting of polyurethanes, silicones and combinations thereof.

3. The heart valve prosthesis of claim 1, wherein the steroidal agent comprises an anti-inflammatory agent selected from the group consisting of dexamethasone, a derivative thereof, or a salt thereof.

4. The heart valve prosthesis of claim 1, which is a bioprosthetic heart valve.

5. The heart valve prosthesis of claim 1, which is a mechanical heart valve.

6. A heart valve prosthesis comprising a sewing ring comprising a body portion initially formed from a polymer mixed with a steroidal agent, said body portion overlayed by a polyester fabric overlayer, and wherein said body portion provides at least one therapeutic effect to the fabric overlayer.

7. The heart valve prosthesis of claim 6, wherein the heart valve prosthesis additionally comprises metal or metal alloy components.

8. The heart valve prosthesis of claim 6, wherein the steroidal agent comprises and anti-inflammatory agent selected from the group consisting of dexamethasone, a derivative thereof, or a salt thereof.

9. A bioprosthetic heart valve comprising a polymer insert containing struts attached to tissue leaflets to form a valve housing, wherein a fabric sheath encloses the polymer insert to form a sewing ring, said sewing ring attached circumferentially to the base of the valve housing, the improvement comprising the polymer insert is initially formed with a releasable steroidal agent wherein the releasable steroidal agent provides at least one therapeutic effect to the fabric overlayer.

10. The bioprosthetic heart valve of claim 9, wherein the polymer insert comprises silicone.

11. The bioprosthetic heart valve of claim 10, wherein the polymer insert comprises radiopaque flexible silicone rubber and the steroidal agent.

12. The bioprosthetic heart valve of claim 9, wherein the steroidal agent comprises an anti-inflammatory agent.

13. The bioprosthetic heart valve of claim 12, wherein the anti-inflammatory agent is dexamethasone, a derivative thereof, or a salt thereof.

14. The bioprosthetic heart valve of claim 9, wherein the polymer insert further comprises an antimicrobial agent.

15. The bioprosthetic heart valve of claim 9, wherein the flow occluder comprises pericardium or aortic root tissue from an animal.

16. The bioprosthetic heart valve of claim 15, wherein the flow occluder comprises pericardium or aortic root tissue from a pig.

17. An annuloplasty ring comprising a body portion overlaid by a polyester fabric overlayer, the body portion initially formed from a biostable polymer mixed with a releasable steroidal agent wherein the releasable steroidal agent provides at least one effect to the fabric overlayer.

18. The annuloplasty ring of claim 17, wherein the biostable polymer is selected from the group consisting of polyurethanes, silicones and combinations thereof.

19. The annuloplasty ring of claim 17, wherein the steroidal agent comprises an anti-inflammatory agent selected from the group consisting of dexamethasone, a derivative thereof, or a salt thereof.

20. The annuloplasty ring of claim 17, wherein the annuloplasty ring further comprises an antimicrobial agent.

21. A method for replacing a heart valve in a patient comprising implanting a prosthetic heart valve into the patient, wherein the prosthetic heart valve comprises a sewing ring comprising a body portion initially formed from a polymer mixed with a steroidal agent, said body portion additionally overlayed by a fabric overlayer.

22. The method of claim 21, wherein the constituent material of the body portion comprises a biostable polymer.

23. The method of claim 22, wherein the biostable polymer comprises a polymer selected from the group consisting of polyurethanes, silicones and combinations thereof.

24. The method of claim 22, wherein the metal or metal alloy comprises titanium.

25. The method of claim 21, wherein the constituent material of the body portion additionally comprises a metal or a metal alloy.

26. The method of claim 21, wherein the therapeutic agent comprises an anti-inflammatory agent.

27. The method of claim 26, wherein the anti-inflammatory agent is dexamethasone, a derivative thereof, or a salt thereof.

28. A method for ameliorating the inflammatory response associated with heart valve replacement in a patient comprising implanting a prosthetic heart valve into the patient, wherein the prosthetic heart valve comprises a sewing ring comprising a body portion comprising a polymer initially formed with a releasable anti-inflammatory agent, said body portion overlayed by a fabric overlayer wherein the releasable anti-inflammatory agent provides at least one therapeutic effect to at least one additional component of the heart valve.

29. The method of claim 28, wherein the fabric overlayer comprises polyester.

30. The method of claim 28, wherein the anti-inflammatory agent is dexamethasone, a derivative thereof, or a salt thereof.

31. The method of claim 28, wherein implantation of the prosthetic heart valve is accompanied by reduced pannus formation at the implant site.

32. A method for ameliorating the inflammatory response associated with heart valve repair in a patient comprising implanting an annuloplasty ring into the patient, wherein the annuloplasty ring comprises a body portion comprising a biostable polymer initially formed with a releasable anti-inflammatory agent, said body portion overlaid by a fabric overlayer wherein the releasable anti-inflammatory agent provides at least one therapeutic effect to the fabric overlayer.

33. The method of claim 32, wherein the fabric overlayer comprises polyester.

34. The method of claim 32, wherein the anti-inflammatory agent is dexamethasone, a derivative thereof, or a salt thereof.

35. The method of claim 32, wherein implantation of the annuloplasty ring is accompanied by reduced pannus formation at the implant site.

36. A method of making a medical sewing ring comprising:

initially forming the annular insert by mixing a releasable steroidal agent with a biocompatible polymer; and

enclosing the annular insert in a fabric sheath;

wherein the releasable steroidal agent provides at least one therapeutic effect to the fabric sheath.

37. The method of claim 36, wherein the constituent material comprises a polymer.

38. The method of claim 37, wherein the constituent material comprises a biostable polymer.

39. The method of claim 38, wherein the biostable polymer is selected from the group consisting of polyurethanes, silicones and combinations thereof.

40. The method of claim 36, wherein the constituent material comprises a metal or a metal alloy.

41. The method of claim 40, wherein the metal or metal alloy is selected from the group consisting of titanium, tantalum, titanium alloys, cobalt chrome alloys, nickel chrome alloys, stainless steels, and combinations thereof.

42. The method of claim 36, wherein the fabric sheath comprises polyester.

43. The method of claim 36, wherein the steroidal agent comprises an anti-inflammatory agent.

44. The method of claim 43, wherein the anti-inflammatory agent is dexamethasone, a derivative thereof, or a salt thereof.

45. The method of claim 36, wherein the annular insert further comprises an antimicrobial agent.