Nonpolymeric epoxy compounds for cross linking biological tissue and bioprosthetic grafts prepared thereby

• US 5,880,242 A
• Filed: 08/19/1997
• Issued: 03/09/1999
• Est. Priority Date: 03/04/1996
• Status: Expired due to Term

• Current Assignee: Edwards Lifesciences Corporation
• Original Assignee: Baxter International Inc.
• Inventors: Myers, Keith E., Hu, Can B., Nguyen-Thien-Nhon, Diana, Kafesjian, Ralph
• Primary Examiner(s): KRASS, FREDERICK F
• Application Number:
  US08/914,558
• Time in Patent Office: 567 Days
• Field of Search: 623/1, 623/2, 623/66, 623/13, 623/15, 527/200, 527/205
• US Class Current: 527/200
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 2430/40 Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
• CPC Class Codes: A61L 27/24 Collagen
• 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 27/362 Skin, e.g. dermal papillae
• CPC Class Codes: A61L 27/3625 Vascular tissue, e.g. heart valves
• CPC Class Codes: A61L 27/3641 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• 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: C08H 1/06 derived from horn, hoofs, hair, skin or leather

Abstract

A solution containing a nonpolymeric epoxy compound for cross linking biological tissues and bioprosthetic materials prepared thereby. The nonpolymeric epoxy compound has the general structural formula:

R.sub.1 --CH.sub.2 --O--X--O--CH.sub.2 --R.sub.2

wherein, X is a straight chain aliphatic hydrocarbon having at least four (4) and no more than five (5) carbon atoms bonded directly to one another, said straight chain aliphatic hydrocarbon being devoid of side branches and having terminal carbon atoms at either end thereof, the terminal carbon atoms at the ends of said straight chain aliphatic hydrocarbon being bonded to the oxygen atoms shown in the foregoing general formula, wherein at least one of the terminal groups R₁, or R₂ is an epoxy group and the other of said terminal groups R₁ or R₂ is either a) an epoxy group, or b) an aldehyde group. One preferred crosslinking agent of the above general formula is 1,4, butanediol diglycidyl ether. The solution of the present invention contains no other chemical compounds which would react with either collagen or with the crosslinking agent of the present invention.

Claims

1. A biological tissue graft comprising a collagen-containing tissue which has been cross linked by immersion in a solution comprising a fixative compound having the general formula:

space="preserve" listing-type="equation">R.sub.1 --CH.sub.2 --O--X--O--CH.sub.2 --R.sub.2

wherein, the molecular backbone X is an aliphatic hydrocarbon having a straight carbon chain consisting of at least four and no more than five carbon atoms bonded directly to one another, said straight carbon chain being devoid of side branches and having terminal carbon atoms at either end thereof, the terminal carbon atoms at the ends of said straight carbon chain being bonded to the oxygen atoms shown in general formula, wherein at least one of the terminal groups R₁, R₂ is an epoxy group and the other of the such terminal groups R₁, R₂ is either a) an epoxy group, or b) an aldehyde group,

said solution being substantially devoid of additional chemical compounds that react with collagen or with said fixative compound during cross linking.

2. The biological tissue graft of claim 1 wherein said collagen containing tissue comprises a mammalian heart value.

3. The biological tissue graft of claim 1 wherein said collagen containing tissue comprises a mammalian cardiovascular valve.

4. The biological tissue graft of claim 1 wherein said collagen containing tissue comprises a segment of blood vessel.

5. The biological tissue graft of claim 1 wherein said collagen containing tissue comprises a tendon.

6. The biological tissue graft of claim 1 wherein said collagen containing tissue comprises skin.

7. The biological tissue graft of claim 1 wherein X is a straight chain aliphatic hydrocarbon of four carbon atoms bonded directly to one another.

8. The biological tissue graft of claim 1 wherein X is a straight chain aliphatic hydrocarbon selected from the group consisting of n-butyl and n-pentyl.

9. The biological tissue graft of claim 1 wherein both R₁ and R₂ are epoxy groups.

10. The biological tissue graft of claim 1 wherein one of R₁ and R₂ is an epoxy group and the other is an aldehyde group.

11. The biological tissue graft of claim 1 wherein said compound is soluble in aqueous solution at concentrations of at least 4% (v/v).

12. The biological tissue graft of claim 1 wherein said compound is soluble in aqueous solution at concentrations of at least 10% (v/v).

13. The biological tissue graft of claim 1 wherein said compound is 1,4-butanediol diglycidyl ether.