Process for reducing mineralization of tissue used in transplantation

• US 7,078,163 B2
• Filed: 12/02/2002
• Issued: 07/18/2006
• Est. Priority Date: 03/30/2001
• 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:
  US10/307,600
• Publication Number:
  US 20030118981A1
• Time in Patent Office: 1,324 Days
• Field of Search: 435/1.1, 424/423
• US Class Current: 435/1.1
• 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 for making an implantable vascular bioprosthesis, the method comprising

excising tissue from an animal, the excised tissue selected from the group consisting of porcine aortic root 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 one oxidizing agent prior to significant degradation of the excised tissue;

rinsing the oxidizing agent-contacted tissue to remove at least a portion of the oxidizing agent wherein the rinsing step comprises;

contacting the excised tissue with a non-ionic detergent composition and contacting the excised tissue with a second, ionic detergent composition.

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

3. The method of claim 1 wherein the oxidizing agent is selected from the group of sodium hypochlorite, sodium bromate, sodium hydroxide, sodium iodate, performic acid, sodium periodate, periodic acid, potassium dichromate, potassium permanganate, chloramine T, peracetic acid, and combinations thereof.

4. The method of claim 3 wherein the oxidizing agent is selected from the group of sodium hypochlorite, performic acid, periodic acid, peracetic acid, and combinations thereof.

5. The method of claim 4 wherein the sodium hypochlorite is in a concentration of about 2 mM to about 20 mM.

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

7. The method of claim 6 wherein the chelating agent is selected from the group of ethylenediaminetetraacetic acid, ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA), citric acid, salts thereof, and combinations thereof.

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

9. The method of claim 8 wherein the buffering agent has a pKa of about 7.0 to about 7.5.

10. The method of claim 8 wherein the buffering agent is an organic buffer.

11. The method of claim 10 wherein the buffering agent is selected from the group of HEPES, TES, BBS, MOPS, PIPES, MES, and combinations thereof.

12. 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.

13. The method of claim 1 wherein contacting the tissue with the detergent compositions is carried out at a temperature of at least about 30°

C.

14. The method of claim 11 wherein contacting the tissue with the detergent compositions further comprises sonicating the tissue while immersed in the composition.

15. 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 rinsing step comprises;

contacting the excised tissue with a non-ionic detergent composition and contacting the excised tissue with a second, ionic detergent composition.

16. The method of claim 15 wherein the oxidizing agent is selected from the group of sodium hypochlorite, sodium bromate, sodium hydroxide, sodium iodate, performic acid, sodium periodate, periodic acid, potassium dichromate, potassium permanganate, chloramine T, peracetic acid, and combinations thereof.

17. The method of claim 16 wherein the oxidizing agent is selected from the group of sodium hypochlorite, performic acid, periodic acid, peracetic acid, and combinations thereof.

18. The method of claim 17 wherein the sodium hypochlorite is in a concentration of about 2 mM to about 20 mM.

19. The method of claim 15 wherein the composition comprising an oxidizing agent further comprises at least one chelating agent.

20. The method of claim 19 wherein the chelating agent is selected from the group of ethylenediaminetetraacetic acid, ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA), citric acid, salts thereof, and combinations thereof.

21. The method of claim 15 wherein the composition comprising at least one oxidizing agent further comprises at least one buffering agent.

22. The method of claim 21 wherein the buffering agent has a pKa of about 7.0 to about 7.5.

23. The method of claim 21 wherein the buffering agent is an organic buffer.

24. The method of claim 23 wherein the buffering agent is selected from the group of HEPES, TES, BES, MOPS, PIPES, MES, and combinations thereof.

25. The method of claim 15 wherein contacting the tissue with a composition comprising at least one oxidizing agent is carried out for at least about 24 hours.

26. The method of claim 15 wherein contacting the tissue with the detergent compositions is carried out at a temperature of at least about 30°

C.

27. The method of claim 15 wherein contacting the tissue with the detergent compositions comprises sonicating the tissue while immersed in the compositions.

28. The method of claim 15 further comprising contacting the rinsed tissue with a composition comprising at least one reducing agent.

29. The method of claim 28 further comprising treating the reducing agent contacted-tissue with a fixative composition.