Anticalcification treatments for fixed biomaterials

• US 6,479,079 B1
• Filed: 12/13/1999
• Issued: 11/12/2002
• Est. Priority Date: 12/13/1999
• Status: Expired due to Term

• Current Assignee: Sulzer Carbomedics Inc. (Zimmer Biomet Holdings, Inc.)
• Original Assignee: Sulzer Carbomedics Inc. (Zimmer Biomet Holdings, Inc.)
• Inventors: Pathak, Chandrashenkhar P., Moore, Mark A., Phillips, Richard E.
• Primary Examiner(s): Witz, Jean C.
• Application Number:
  US09/459,429
• Time in Patent Office: 1,065 Days
• Field of Search: 435/40.5, 435/520, 435/569
• US Class Current: 424/520
• 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 27/3687 characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials

Abstract

A method for treating biomaterial is provided in which a biological tissue, typically after being cross-linked, is contacted with an anticalcification treatment solution under condition effective to render the biomaterial resistant to in vivo calcification upon implantation in a host animal. The anticalcification treatment solutions comprise higher alcohol solutions, a polyol solutions and/or a polar aprotic organic solvent solutions.

Claims

1. A method for treating a biomaterial comprising contacting a biomaterial with an anticalcification treatment solution, said anticalcification treatment solution comprising a compound selected from the group consisting of higher alcohols and polyols, wherein the higher alcohol or polyol comprises less than 50% by volume of said anticalcification treatment solution.

2. The method of claim 1, wherein the biomaterial is an animal tissue.

3. The method of claim 1, wherein the biomaterial is a cross-linked animal tissue.

4. The method of claim 1, wherein the biomaterial is an aldehyde cross-linked animal tissue.

5. The method of claim 1, wherein the higher alcohol or polyol is a linear or branched C4-C36 alcohol or polyol.

6. The method of claim 1, wherein the higher alcohol or polyol is a linear or branched C6-C18 alcohol or polyol.

7. The method of claim 1, wherein the higher alcohol or polyol is linear or branched C7-C9 alcohol or polyol.

8. The method of claim 1, wherein the higher alcohol is heptanol, octanol, or nonanol.

9. The method of claim 1, wherein the polyol is 1,2-octanediol, 1,8-octanediol, 1,10-decanol, 1,10-dodecanol, 1,2-dihydroxydecane or 1,2-dihydroxydodecane.

10. The method of claim 1, wherein the higher alcohol or polyol comprises less than about 25% by volume of said anticalcification treatment solution.

11. The method of claim 1, wherein the higher alcohol or polyol comprises less than about 10% by volume of said anticalcification treatment solution.

12. The method of claim 1, wherein the anticalcification treatment solution further comprises at least one organic solvent.

13. The method of claim 12, wherein the organic solvent is selected from a C₁-C₃ alcohol, acetone, ethyl acetate, ethyl lactate, 1,4-butaenediol or polyethylene glycol.

14. The method of claim 12, wherein the anticalcification treatment solution further comprises water or an aqueous solvent.

15. The method of claim 1, wherein the anticalcification treatment solution further comprises water or an aqueous solvent.

19. The method of claim 4, wherein contacting the aldehyde cross-linked biomaterial with said anticalcification treatment solution reduces the pathological calcification of the biomaterial following implantation into a mammalian host when compared to an aldehyde-cross-linked biomaterial that is not contacted with said anticalcification treatment solution.

45. The method of claim 12, wherein the polyol is 1,2-octanediol, the organic solvent is ethanol and the anticalcification treatment further comprises an aqueous buffer selected from the group consisting of phosphate-buffered saline, N-N-2-hydroxyethylpiperzine-N′

-2-ethanesulfonic acid, morpholine propanesulphonic acid and buffers that include borate, bicarbonate, carbonate or cacodylate.

46. The method of claim 45, wherein the anticalcification treatment comprises 40% by volume ethanol;

5% by volume 1.2-octanediol and 55% by volume N-N-2-hydroxyethylpiperzine-N′

-2-ethanesulfonic buffer.

16. A method for treating a biomaterial comprising contacting a biomaterial with an anticalcification treatment solution, said anticalcification treatment solution comprising a polar aprotic organic solvent, wherein the contacting is performed for a period of time sufficient to render the biomaterial more resistant to in vivo pathologic calcification than a biomaterial not treated with the anticalcification treatment solution.

17. The method of claim 16, wherein the polar aprotic organic solvent has a dielectric constant greater than about 20.

18. The method of claim 17, wherein the polar aprotic organic solvent has a dielectric constant greater than about 30.

20. A method for treating a biomaterial, comprising contacting an aldehyde cross-linked biomaterial with an anticalcification treatment solution, said anticalcification treatment solution comprising at least one organic solvent and from about 0.1% to about 25% by volume of a C6-C18 alcohol or polyol.

21. The method of claim 20, wherein the C₆-C₁₈ alcohol is a C₇-C₉ alcohol.

22. The method of claim 20, wherein the C₆-C₁₈ alcohol is heptanol, octanol or nonanol.

23. The method of claim 20, wherein the C₆-C₁₈ polyol is 1,2-octanediol, 1,8-octanediol, 1,10-decanol, 1,10-dodecanol, 1,2-dihydroxydecane or 1,2-dihydroxydodecane.

24. The method of claim 20, wherein the organic solvent is selected from C₁-C₃ alcohol, acetone, ethyl acetate, ethyl lactate, 1,4-butaenediol or polyethylene glycol.

25. The method of claim 20, wherein the organic solvent is ethanol.

26. The method of claim 20, wherein the anticalcification treatment solution further comprises water or an aqueous solvent.

27. The method of claim 26, wherein the organic solvent is present at about 35% to about 49% by volume of said anticalcification treatment solution, the remainder being comprised of said water or aqueous solvent.

28. The method of claim 26, wherein said water or aqueous solvent is present at greater than about 50% by volume of said anticalcification treatment solution.

29. The method of claim 20, wherein contacting the aldehyde cross-linked biomaterial with said anticalcification treatment solution reduces the pathological calcification of the biomaterial following implantation into a mammalian host when compared to an aldehyde-cross-linked biomaterial that is not contacted with said anticalcification treatment solution.

30. A method for treating a biomaterial, comprising contacting an aldehyde cross-linked animal tissue with an anticalcification treatment solution comprised of about 0.1% to about 25% by volume of a C₇-C₉ alcohol or polyol, about 25% to about 99% by volume of a C₁-C₃ alcohol, the remaining volume, if any, being comprised of water or an aqueous solvent;

under conditions effective to reduce pathologic calcification of the tissue following implantation into a mammalian host.

31. The method of claim 30, wherein the C₁-C₃ alcohol is present at about 35% to about 45% by volume of the anticalcification treatment solution.

32. The method of claim 30, wherein the C₇-C₉ alcohol or polyol is present at about 1% to about 10% by volume of the anticalcification treatment solution.

33. The method of claim 30, wherein the C₇-C₉ alcohol is octanol.

34. The method of claim 30, wherein the C₇-C₉ polyol is 1,2-octanediol or 1,8-octanediol.

35. A method for treating a biomaterial, comprising contacting an aldehyde-cross-linked animal tissue with an anticalcification treatment solution comprising a polar aprotic organic solvent selected from the group consisting of N-methyl pyrolidinone, N,N-dimethylacetamide, N,N-dimethylformamide and N,N-dimethylpropionamide, under conditions effective to reduce pathologic calcification of the tissue following implantation into a mammalian host.

36. A method for treating a biomaterial, comprising contacting a cross-linked biomaterial with an anticalcification treatment solution at a temperature between about 30°

and 60°

C. under conditions effective to reduce pathologic calcification of the biomaterial following implantation into a mammalian host, said anticalcification treatment solution comprising between about 10% and about 50% by volume of a C1-C3 alcohol, the remaining volume being comprised of water or an aqueous buffer.

37. The method of claim 36, wherein the biomaterial is an animal tissue.

38. The method of claim 36, wherein the biomaterial is a cross-linked animal tissue.

39. The method of claim 36, wherein the biomaterial is an aldehyde cross-linked animal tissue.

40. The method of claim 36, wherein the C₁-C₃ alcohol is methanol, ethanol, propanol, or isopropanol.

41. The method of claim 36, wherein the aqueous buffer comprises HEPES.

42. The method of claim 36, wherein the C₁-C₃ alcohol comprises about 25 to about 50% by volume of the anticalcification treatment solution.

43. The method of claim 36, wherein the aldehyde cross-linked biomaterial is contacted with an anticalcification treatment solution at a temperature between about 30°

C. and 60°

C.

44. The method of claim 36, wherein the aldehyde cross-linked biomaterial is contacted with an anticalcification treatment solution for at least 12 hours.