Method of cross-linking tissue with a bis-maleimide compound

• US 6,596,471 B2
• Filed: 12/21/2000
• Issued: 07/22/2003
• Est. Priority Date: 12/21/2000
• Status: Expired due to Fees

• Current Assignee: Carbomedics Inc. (Snia SpA)
• Original Assignee: Carbomedics Inc. (Snia SpA)
• Inventors: Pathak, Chandrashekhar P., Moore, Mark A., Phillips, Richard E. Jr.
• Primary Examiner(s): Saucier, Sandra E.
• Assistant Examiner(s): Afremova, Vera
• Application Number:
  US09/747,023
• Publication Number:
  US 20020119563A1
• Time in Patent Office: 943 Days
• Field of Search: 424/423, 435/29, 435/40.5, 435/40.52, 435/1.1
• US Class Current: 435/1.1
• CPC Class Codes: A61L 2430/40 Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
• 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

Herein is disclosed a method of cross-linking a tissue, comprising treating the tissue under effective cross-linking conditions with a diunsaturated organic compound comprising structure I:

wherein R, R′, and R″ are each independently an organic moiety having from 1 to 20 carbon atoms.

Also disclosed is a cross-linked biological tissue produced by treating the tissue according to the above method.

Claims

1. A method of cross-linking a biological tissue, comprising:

treating the biological tissue under effective cross-linking conditions with a bis-maleimide compound having the structure;

wherein R is —

(CH₂)₆—

, to yield a cross-linked biological tissue.

2. The method of claim 1, wherein the biological tissue is derived from an animal selected from the group consisting of humans, cattle, pigs, horses, sheep, rats, rabbits, ostriches, and kangaroos.

3. The method of claim 1, wherein the biological tissue is selected from the group consisting of tendon, ligament, heart valve, dura mater, pericardium, skin patch, pericardial patch, aortic patch, and tympanic membrane.

4. The method of claim 1, wherein the bis-maleimide compound is provided as a solute in a fluid comprising a solvent.

5. The method of claim 4, wherein the solvent is dimethyl sulfoxide.

6. The method of claim 4, wherein the solvent is water.

7. The method of claim 4, wherein the fluid has a pH between about pH 6 and about pH 10.

8. The method of claim 7, wherein the fluid has a pH between about pH 6.5 and about pH 8.

9. The method of claim 8, wherein the fluid has a pH between about pH 6.8 and about pH 7.5.

10. The method of claim 4, wherein the fluid has a temperature between about 0°

C. and about 60°

C.

11. The method of claim 10, wherein the fluid has a temperature between about 2°

C. and about 30°

C.

12. The method of claim 1, wherein the treating is performed for at least about 30 min.

13. The method of claim 12, wherein the treating is performed for at least about 6 hr.