Process for augmenting connective mammalian tissue with in situ polymerizable native collagen solution

• US 3,949,073 A
• Filed: 11/18/1974
• Issued: 04/06/1976
• Est. Priority Date: 11/18/1974
• Status: Expired due to Term

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Daniels, John R., Knapp, Terry R.
• Primary Examiner(s): Gotts, Lewis
• Assistant Examiner(s): Suyat, Reginald J.
• Application Number:
  US05/524,672
• Time in Patent Office: 505 Days
• Field of Search: 424/177, 424/89
• US Class Current: 514/17.2
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: C07K 14/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
• CPC Class Codes: Y10S 128/08 Collagen
• CPC Class Codes: Y10S 623/92 Method or apparatus for preparing or treating prosthetic

Abstract

A method for augmenting hard or soft connective tissue, such as skin, tendon, cartilage, bone or interstitium, in a living mammal comprising implanting a proteolytic enzyme-solubilized, purified, native, in situ polymerizable collagen solution into the mammal at the augmentation site. The solution polymerizes at the site into a stable, non-reactive fibrous mass of tissue which is rapidly colonized by host cells and vascularized.

Claims

1. Method of augmenting connective tissue in a living mammal comprising administering a solution of solubilized, purified, native, in situ polymerizable collagen to the mammal at the augmentation site which polymerizes at said site into a fibrous mass of tissue.

2. The method of claim 1 in which the solution is implanted into the mammal by injection.

3. The method of claim 1 in which the solution is administered by coating the augmentation site.

4. The method of claim 1 in which the collagen source is heterologous skin or tendon.

5. The method of claim 1 in which the mammal is a human.

6. The method of claim 1 in which the concentration of collagen in the solution is up to 20 mg/ml.

7. The method of claim 1 in which the concentration of collagen in the solution is about 12 to about 15 mg/ml.

8. The method of claim 1 in which the pH of the solution is about 6 to about 8.

9. The method of claim 1 in which the solution contains a polymerization promoter which causes the solution to be isotonic.

10. The method of claim 9 in which the promoter is a buffered, neutral salt solution.

11. The method of claim 10 in which the buffered, neutral salt solution is a solution of NaCl and NaHPO₄, pH 7.4.

12. The method of claim 1 in which the collagen has been solubilized by treatment with a proteolytic enzyme.

13. The method of claim 12 in which the treatment with a proteolytic enzyme is made in an acid medium, pH of 1 to 4.5 at a temperature in the range of 0°

C to 15°

C.

14. The method of claim 13 in which the temperature is 11°

C.

15. The method of claim 14 in which the proteolytic enzyme is pepsin.

16. The method of claim 1 in which the solubilized collagen has been purified by salt precipitation.

17. The method of claim 9 in which the temperature of the solution is kept below about 5°

C until it is administered.

18. The method of claim 1 in which particles of insoluble collagen microfibrils are added to the solution before it is administered.

19. The method of claim 1 in which the solution is administered to the skin as a sealer to cover a burn or an abrasion.

20. The method of claim 19 in which the solution contains a drug to prevent secondary infection.

21. The method of claim 1 in which the collagen has been solubilized by treatment with a proteolytic enzyme, the concentration of collagen in the solution is up to 20 mg/ml, the pH of the solution is about 6 to about 8 and the solution contains a polymerization promoter which causes the solution to be isotonic.