Cross-linked collagen and uses thereof

• US 20080293637A1
• Filed: 05/22/2008
• Published: 11/27/2008
• Est. Priority Date: 05/23/2007
• Status: Abandoned Application

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: Dapper, Gregory S., Olson, Kenneth C., Schroeder, Jacqueline Anne
• Application Number:
  US12/125,337
• Publication Number:
  US 20080293637A1
• Time in Patent Office: Days
• US Class Current: 514/17.2
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]

Abstract

The present invention discloses collagen cross-linked in a micro to non-fibrillar form and at a high concentration. The cross-linked collagen gel has improved volume stability or persistence than collagen cross-linked at a neutral pH. Also disclosed are methods for preparing the inventive cross-linked collagen and using such for augmenting soft tissues in mammals.

Claims

1. A method for preparing cross-linked collagen, comprising:

obtaining micro to non-fibrillar collagen;

treating the micro to non-fibrillar collagen with a cross-linking agent; and

isolating cross-linked collagen.

2. The method of claim 1, wherein the micro to non-fibrillar collagen is obtained by incubating fibrillar collagen in a suspension or solution of pH 2-5 or pH 9-12.

3. The method of claim 2, wherein the micro to non-fibrillar collagen is obtained by incubating the fibrillar collagen in a suspension or solution of pH 4.2-5.0.

4. The method of claim 1, wherein the concentration of the micro to non-fibrillar collagen is in the range of 3-150 mg/mL.

5. The method of claim 4, wherein the concentration of the micro to non-fibrillar collagen is in the range of 38-52 mg/mL.

6. The method of claim 1, wherein the treating step includes treating the micro to non-fibrillar collagen with the cross-linking agent at pH 2-5 or pH 9-12, followed by treating the micro to non-fibrillar collagen with the cross-linking agent at pH 6-8.

7. The method of claim 1, wherein the cross-linked collagen derives from type I, II, III, IV or V collagen, or a combination thereof.

8. The method of claim 7, wherein the cross-linked collagen derives from telo-containing collagen, atelo-collagen or derivatized collagen, or a combination thereof.

9. The method of claim 1, wherein the cross-linking agent is capable of forming covalent bonds between amino acid residues in the micro to non-fibrillar collagen.

10. The method of claim 9, wherein the cross-linking agent is selected from the group consisting of carbodiimides, polyaldehydes, polysulfones, activated PEGs, epoxides, imidazoles and diisocyanates.

11. The method of claim 10, wherein the cross-linking agent is glutaraldehyde.

12. The method of claim 1, further comprising admixing a local anesthetic agent with the cross-linked collagen.

13. The method of claim 12, wherein the local anesthetic agent is lidocaine.

14. A method for filling voids and defects and increasing tissue volume in a mammal, comprising administering to a mammal the cross-linked collagen prepared according to the method of claim 1.

15. The method of claim 14, wherein the cross-linked collagen is administered by intradermal or subcutaneous injection.

16. Cross-linked collagen prepared according to the method of claim 1.

17. The cross-linked collagen of claim 16, wherein the number of free hydroxy lysine and lysine residues per 1000 amino acid residues in the cross-linked collagen is in the range of 22-32.

18. The cross-linked collagen of claim 17, wherein the number of free hydroxy lysine and lysine residues per 1000 amino acid residues in the cross-linked collagen is in the range of 24-29.

19. The cross-linked collagen of claim 16, wherein the cross-linked collagen is in a gel but not fibrous state.

20. The cross-linked collagen of claim 19, wherein the cross-linked collagen locks water in the gel and does not disperse like a fibrous collagen suspension.

21. The cross-linked collagen of claim 19, wherein the cross-linked collagen in the gel state maintains its shape in vivo better than cross-linked collagen in a fibrous state.

22. The cross-linked collagen of claim 19, wherein the fibers of the cross-linked collagen are smaller than those of fibrous collagen cross-linked at a neutral pH.

23. A composition comprising the cross-linked collagen of claim 16 and a local anesthetic agent admixed with the cross-linked collagen.

24. The composition of claim 23, wherein the local anesthetic agent is lidocaine.

25. A packaged product, comprising a syringe and a needle, wherein the syringe is loaded with the cross-linked collagen of claim 16.

26. Cross-linked collagen, comprising:

micro to non-fibrillar collagen; and

a cross-linking agent,

wherein the micro to non-fibrillar collagen is cross-linked by the cross-linking agent.

27. The cross-linked collagen of claim 26, wherein the cross-linked collagen derives from type I, II, III, IV or V collagen, or a combination thereof.

28. The cross-linked collagen of claim 27, wherein the cross-linked collagen derives from telo-containing collagen, atelo-collagen or derivatized collagen, or a combination thereof.

29. The cross-linked collagen of claim 26, wherein the cross-linking agent is capable of forming covalent bonds between amino acid residues in the micro to non-fibrillar collagen.

30. The cross-linked collagen of claim 29, wherein the cross-linking agent is selected from the group consisting of carbodiimides, polyaldehydes, polysulfones, activated PEGs, epoxides, imidazoles and diisocyanates.

31. The cross-linked collagen of claim 30, wherein the cross-linking agent is glutaraldehyde.

32. The cross-linked collagen of claim 26, wherein the number of free hydroxy lysine and lysine residues per 1000 amino acid residues in the cross-linked collagen is in the range of 22-32.

33. The cross-linked collagen of claim 32, wherein the number of free hydroxy lysine and lysine residues per 1000 amino acid residues in the cross-linked collagen is in the range of 24-29.

34. The cross-linked collagen of claim 26, wherein the cross-linked collagen is in a gel but not fibrous state.

35. The cross-linked collagen of claim 34, wherein the cross-linked collagen locks water in the gel and does not disperse like a fibrous collagen suspension.

36. The cross-linked collagen of claim 34, wherein the cross-linked collagen in the gel state maintains its shape in vivo better than cross-linked collagen in the fibrous state.

37. The cross-linked collagen of claim 34, wherein the fibers of the cross-linked collagen are smaller than those of fibrous collagen cross-linked at a neutral pH.

38. A composition comprising the cross-linked collagen of claim 26 and a local anesthetic agent admixed with the cross-linked collagen.

39. The composition of claim 38, wherein the local anesthetic agent is lidocaine.

40. A packaged product, comprising a syringe and a needle, wherein the syringe is loaded with the cross-linked collagen of claim 26.

41. A method for filling voids and defects and increasing tissue volume in a mammal, comprising administering to a mammal the cross-linked collagen of claim 26.

42. The method of claim 41, wherein the cross-linked collagen is administered by intradermal or subcutaneous injection.