Implantable biological tissue and process for preparation thereof

• US 4,647,283 A
• Filed: 11/13/1984
• Issued: 03/03/1987
• Est. Priority Date: 03/23/1982
• Status: Expired due to Term

• Current Assignee: Edwards Lifesciences Corporation
• Original Assignee: American Hospital Supply Corp. (Baxter International Inc.)
• Inventors: Carpentier, Alain, Carpentier, Sophie, Nashef, Aws S.
• Primary Examiner(s): Apley, Richard J.
• Assistant Examiner(s): Beaucage, Gregory
• Application Number:
  US06/670,786
• Time in Patent Office: 840 Days
• Field of Search: 3/1.4, 3/1.5, 3/1, 8/94.11, 623/1, 623/2, 623/11, 623/66
• US Class Current: 128/898
• 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 27/3687 characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
• CPC Class Codes: Y10S 623/918 Heart
• CPC Class Codes: Y10S 623/92 Method or apparatus for preparing or treating prosthetic
• CPC Class Codes: Y10S 623/922 Heart

Abstract

A process for the preparation of implantable biological tissue, and in particular bioprosthetic heart valves, which are prone to calcification after implantation. The process includes treatment of tissue with solutions prior to implantation which have been found effective in reducing calcification of the implanted tissue.

Claims

1. A process for treating biological tissue prior to implantation which comprises the steps of:

a. fixing said tissue under tissue fixing conditions;

b. contacting said fixed tissue with a solution effective in reducing calcification of said tissue after implantation;

said calcification reducing solution comprising an amount of a calcium-binding competing divalent cation effective in reducing calcification and having a level of phosphate decreased to an amount effective in reducing calcification of tissue after implantation; and

c. maintaining the tissue in contact with a solution having said reduced level of phosphate to a time just prior to implantation.

3. The process of claim 1 wherein the divalent cation is a magnesium ion or salt thereof.

4. The process of claim 3 wherein the magnesium salt is selected from the group consisting of MgCl₂, MgSO₄, and MgCO₃.

5. The process of claim 3 wherein the magnesium salt is magnesium chloride.

6. The process of claim 1 wherein the tissue is treated with an amount of divalent cation sufficient to saturate the tissue.

7. The process of claim 1 wherein the biological tissue is used in the preparation of a heart valve.

8. The process of claim 5 wherein the tissue is used in the preparation of a heart valve and the concentration of magnesium chloride is about 0.26 weight percent.

2. A method of increasing the durability of implantable biological tissue which comprises the steps of:

a. fixing said tissue under tissue fixing conditions;

b. contacting said fixed tissue with a solution effective in reducing calcification of said tissue after implantation;

said calcification reducing solution comprising an amount of a calcium-binding competing divalent cation effective in reducing calcification and having a level of phosphate decreased to an amount effective in reducing calcification of tissue after implantation; and

c. maintaining the tissue in contact with a solution having said reduced level of phosphate to a time just prior to implantation.

9. The method of claim 2 wherein the divalent cation is a magnesium ion or salt thereof.

10. The method of claim 9 wherein the magnesium salt is selected from the group consisting of MgCl₂, MgSO₄, and MgCO₃.

11. The method of claim 9 wherein the magnesium salt is magnesium chloride.

12. The method of claim 2 wherein the tissue is treated with an amount of divalent cation sufficient to saturate the tissue.

13. The method of claim 2 wherein the biological tissue is used in the preparation of a heart valve.

14. The method of claim 11 wherein the tissue is used in the preparation of a heart valve and the concentration of magnesium chloride is about 0.26 weight percent.