Process for reducing mineralization of tissue used in transplantation

• US 6,509,145 B1
• Filed: 03/30/2001
• Issued: 01/21/2003
• Est. Priority Date: 09/30/1998
• Status: Expired due to Term

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Torrianni, Mark W.
• Primary Examiner(s): TATE, CHRISTOPHER ROBIN
• Application Number:
  US09/806,380
• Time in Patent Office: 662 Days
• Field of Search: 435/1.1, 424/423
• US Class Current: 435/1.1
• CPC Class Codes: A61F 2/2412 with soft flexible valve members, e.g. tissue valves shaped like natural valves check valves with flexible valve members in general F16K15/14
• CPC Class Codes: A61L 2400/02 Treatment of implants to prevent calcification or mineralisation in vivo
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/3625 Vascular tissue, e.g. heart valves
• CPC Class Codes: A61L 27/3645 Connective tissue
• CPC Class Codes: A61L 27/3687 characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents

Abstract

A method of making a tissue-derived implantable medical device that includes contacting the tissue with a composition comprising at least one oxidizing agent prior to implantation of the medical device.

Claims

1. A method of making a tissue-derived, implantable vascular bioprosthesis, the method comprising:

excising tissue from an animal, the excised tissue selected form the group consisting of porcine aortic toot tissue, bovine aortic root tissue, porcine pericardium, bovine pericardium, bovine veins, porcine veins, bovine arteries, and porcine arteries; and

removing cell debris from the excised tissue by a method which comprises;

contacting the excised tissue with a composition comprising at least on oxidizing agent prior to significant degradation of the excised tissue; and

rinsing the oxidizing agent-contacted tissue to remove at least a portion of the oxidizing agent, wherein the oxidizing agent is selected from the group of sodium hypochlorite, performic acid, periodic acid, peracetic acid, and combinations thereof.

2. The method of claim 1 wherein the sodium hypochlorite is in a concentration of about 2 mM to about 20 mM.

3. The method of claim 1 wherein the composition comprising an oxidizing agent further comprises at least one chelating agent.

4. The method of claim 3 wherein the chelating agent is selected from the group of ethylenediaminetetraacetic acid, ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA), citric acid, salts thereof, and combinations thereof.

5. The method of claim 1 wherein the composition comprising at least one oxidizing agent further comprises at least one buffering agent.

6. The method of claim 5 wherein the buffering agent has a pKa of about 7.0 to about 7.5.

7. The method of claim 5 wherein the buffering agent is an organic buffer.

8. The method of claim 7 wherein the buffering agent is selected from the group of HEPES, TES, BES, MOPS, PIPES, MES, and combinations thereof.

9. The method of claim 1 wherein contacting the tissue with a composition comprising at least one oxidizing agent is carried out for at least about 24 hours.

10. The method of claim 1 wherein the rinsing step includes contacting the tissue with a detergent composition.

11. The method of claim 10 wherein the detergent composition comprises at least one reducing agent.

12. The method of claim 10 wherein the detergent composition comprises an ionic detergent or a nonionic detergent.

13. The method of claim 10 wherein contacting the tissue with the detergent composition is carried out at a temperature of at least about 30°

C.

14. The method of claim 10 wherein contacting the tissue with the detergent composition comprises sonicating the tissue while immersed in the composition.

15. The method of claim 10 wherein contacting the tissue with a detergent composition comprises contacting it with a first and a second detergent composition.

16. The method of claim 15 wherein the first detergent composition comprises an ionic detergent and the second detergent composition comprises a nonionic detergent.

17. The method of claim 16 wherein the first and/or the second detergent compositions comprise at least one reducing agent.

18. The method of claim 1 further comprising treating the rinsed tissue with a fixative composition.

19. The method of claim 18 wherein treating the tissue with a fixative composition comprises using a glutaraldehyde- or a carbodiimide-based process.

20. The method of claim 19 wherein the fixative composition further comprises at least one buffering agent.

21. A method for making a tissue-derived implantable medical device from freshly excised tissue of an animal, the method comprising:

excising fresh tissue from an animal, the tissue selected from the group consisting porcine aortic root tissue, bovine aortic root tissue, porcine pericardium, bovine pericardium, bovine veins, porcine veins, bovine arteries, and porcine arteries;

contacting the freshly excised tissue with a composition comprising at least one oxidizing agent prior to significant degradation of the excised tissue, wherein the oxidizing agent is selected from the group of sodium hypochlorite, performic acid, periodic acid, peracetic acid, and combinations thereof;

rinsing the oxidizing agent-contacted tissue to remove at least a portion of the oxidizing agent; and

contacting the rinsed tissue with a composition comprising at least one reducing agent.

22. The method of claim 21 wherein the sodium hypochlorite is in a concentration of about 2 mM to about 20 mM.

23. The method of claim 21 wherein the composition comprising an oxidizing agent further comprises at least one chelating agent.

24. The method of claim 23 wherein the chelating agent is selected from the group of ethylenediaminetetraacetic acid, ethylenebis(oxyethyleneitrilo)tetraacetic acid (EGTA), citric acid, salts thereof, and combinations thereof.

25. The method of claim 21 wherein the composition comprising at least one oxidizing agent further comprises at least one buffering agent.

26. The method of claim 25 wherein the buffering agent has a pKa of about 7.0 to about 7.5.

27. The method of claim 25 wherein the buffering agent is an organic buffer.

28. The method of claim 27 wherein the buffering agent is selected from the group of HEPES, TES, BES, MOPS, PIPES, MES, and combinations thereof.

29. The method of claim 21 wherein contacting the tissue with a composition comprising at least one oxidizing agent is carried out for at least about 24 hours.

30. The method of claim 21 also comprising contacting the reducing agent-contacted tissue with a detergent composition.

31. The method of claim 30 wherein the detergent composition comprises an ionic detergent or a nonionic detergent.

32. The method of claim 30 wherein contacting the tissue with the detergent composition is carried out at a temperature of at least about 30°

C.

33. The method of claim 30 wherein contacting the tissue with the detergent composition comprises sonicating the tissue while immersed in the composition.

34. The method of claim 30 wherein contacting the tissue with a detergent composition comprises contacting it with a first and a second detergent composition.

35. The method of claim 34 wherein the first detergent composition comprises an ionic detergent and the second detergent composition comprises a nonionic detergent.

36. The method of claim 21 further comprising treating the reducing agent contacted-tissue with a fixative composition.

37. The method of claim 36 wherein treating the tissue with a fixative composition comprises using a glutaraldehyde- or a carbodiimide-based process.

38. The method of claim 37 wherein the fixative composition further comprises at least one buffering agent.

39. A method of making a tissue-derived heart valve bioprosthesis, the method comprising:

excising heart valve tissue from an animal, the excised tissue including valvular leaflets and supporting structure; and

removing cell debris from the excised tissue by a method which comprises;

contacting the excised tissue with a composition comprising at least one oxidizing agent prior to significant degradation of the excised tissue; and

rinsing the oxidizing agent-contacted tissue to remove at least a portion of the oxidizing agent, wherein the oxidizing agent is selected from the group of sodium hypochlorite, performic acid, periodic acid, peracetic acid, and combinations thereof.

40. The method of claim 39 wherein the sodium hypochlorite is in a concentration of about 2 mM to about 20 mM.

41. The method of claim 39 wherein the composition comprising an oxidizing agent further comprises at least one chelating agent.

42. The method of claim 41 wherein the chelating agent is selected from the group of ethylenediaminetetraacetic acid, ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA), citric acid, salts thereof, and combinations thereof.

43. The method of claim 39 wherein the composition comprising at least one oxidizing agent further comprises at least one buffering agent.

44. The method of claim 43 wherein the buffering agent has a pKa of about 7.0 to about 7.5.

45. The method of claim 43 wherein the buffering agent is an organic buffer.

46. The method of claim 45 wherein the buffering agent is selected from the group of HEPES, TES, BES, MOPS, PIPES, MES, and combinations thereof.

47. The method of claim 39 wherein contacting the tissue with a composition comprising at least one oxidizing agent is carried out for at least about 24 hours.

48. The method of claim 39 also comprising contacting the oxidizing agent-contacted tissue with a detergent composition.

49. The method of claim 48 wherein the detergent composition comprises an ionic detergent or a nonionic detergent.

50. The method of claim 48 wherein contacting the tissue with the detergent composition is carried out at a temperature of at least about 30°

C.

51. The method of claim 48 wherein contacting the tissue with the detergent composition comprises sonicating the tissue while immersed in the composition.

52. The method of claim 48 wherein contacting the tissue with a detergent composition comprises contacting it with a first and a second detergent composition.

53. The method of claim 52 wherein the first detergent composition comprises an ionic detergent and the second detergent composition comprises a nonionic detergent.

54. The method of claim 39 further comprising contacting the rinsed tissue with a composition comprising at least one reducing agent.

55. The method of claim 54 further comprising treating the reducing agent contacted-tissue with a fixative composition.

56. The method of claim 55 wherein treating the tissue with a fixative composition comprises using a glutaraldehyde- or a carbodiimide-based process.

57. The method of claim 56 wherein the fixative composition further comprises at least one buffering agent.