CROSS-LINKED COLLAGEN AND USES THEREOF

• US 20100099624A1
• Filed: 12/29/2009
• Published: 04/22/2010
• Est. Priority Date: 05/23/2007
• Status: Active Grant

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: Dapper, Gregory S., Olson, Kenneth C., Schroeder, Jacqueline A.
• Granted Patent: US 8,338,375 B2
• 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 packaged product, comprising:

a syringe;

a needle; and

a composition in the syringe, the composition comprising a cross-linked collagen comprising a 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.

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

3. The product of claim 1 wherein the cross-linked collagen derives from telo-containing collagen, atelo-collagen or derivatized collagen, or a combination thereof.

4. The product 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.

5. The product of claim 1 wherein the cross-linking agent is selected from the group consisting of carbodiimides, polyaldehydes, polysulfones, activated PEGs, epoxides, imidazoles and diisocyanates.

6. The product of claim 1 wherein the cross-linking agent is glutaraldehyde.

7. The product of claim 1 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.

8. The product of claim 1 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.

9. The product of claim 1 wherein the cross-linked collagen is in a gel but not fibrous state.

10. The product of claim 9 wherein the cross-linked collagen locks water in the gel and does not disperse like a fibrous collagen suspension.

11. The product of claim 9 wherein the cross-linked collagen in the gel state maintains its shape in vivo better than cross-linked collagen in the fibrous state.

12. The product of claim 1 wherein the fibers of the cross-linked collagen are smaller than those of fibrous collagen cross-linked at a neutral pH.

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

14. The product of claim 1 wherein the concentration of the micro to non-fibrillar collagen is in the range of 38-52 mg/mL.

15. The product of claim 1 wherein the composition further comprises a local anesthetic agent admixed with the cross-linked collagen.

16. The product of claim 15, wherein the local anesthetic agent is lidocaine.

17. The product of claim 1 wherein the cross-linked collagen is prepared by a method comprising the steps of obtaining micro to non-fibrillar collagen, treating the micro to non-fibrillar collagen with a cross-linking agent, and isolating cross-linked collagen.

18. The product of claim 17 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.

19. The product of claim 17 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.

20. The product of claim 17 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.

21. A packaged product comprising:

a syringe; and

a composition useful as a dermal filler, the composition being loaded into the syringe, the composition comprising a cross-linked collagen prepared by a method comprising the steps of obtaining micro to non-fibrillar collagen, treating the micro to non-fibrillar collagen with a cross-linking agent, and isolating cross-linked collagen, the composition further comprising a local anesthetic agent admixed with the cross-linked collagen.

22. The product of claim 21 further comprising a needle that is connectable to the syringe.