Collagen wound healing matrices and process for their production

• US 4,950,483 A
• Filed: 12/16/1988
• Issued: 08/21/1990
• Est. Priority Date: 06/30/1988
• Status: Expired due to Term

• Current Assignee: Angiotech Pharmaceuticals Incorporated
• Original Assignee: Collagen Corp. (Abbvie Incorporated)
• Inventors: Ogawa, Yasushi, Ksander, George
• Primary Examiner(s): Page, Thurman
• Application Number:
  US07/286,303
• Time in Patent Office: 613 Days
• Field of Search: 424/422-426, 424/444, 424/484, 424/488, 623/16, 514/801
• US Class Current: 424/422
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61K 38/39 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: A61L 2300/25 Peptides having up to 20 amino acids in a defined sequence
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/426 Immunomodulating agents, i.e. cytokines, interleukins, interferons
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: Y10S 128/08 Collagen
• CPC Class Codes: Y10S 623/924 Material characteristic

Abstract

Collagen implants that are useful as wound healing matrices are characterized by being formed of collagen fibrils that are not chemically cross-linked, and having a bulk density of 0.01 to 0.3 g/cm³ and a pore population in which at least about 80% of the pores have an average pore size of 35 to 250 microns. The implants are capable of promoting connective tissue deposition, angiogenesis, reepithelialization, and fibroplasia. The wound healing matrix also serves an an effective sustained delivery system for synergistic combinations of FGF and TGF-B.

Claims

1. A collagen sponge composition, comprising:

a matrix having a density of about 0.01 to about 0.3 g/cm³, a thickness of about 1-20 mm, and having pores at least 80% of which are at least 35 um in diameter, wherein said matrix comprises

fibrillar atelopeptide collagen, wherein said fibrils are about 50-200 nm in diameter, and are not chemically cross-linked; and

a synergistic wound-healing effective amount of TGF-B and FGF.

2. The sponge composition of claim 1 which further comprises heparin in a concentration of between about 5 ug/mL and about 500 ug/mL.

3. The sponge composition of claim 1 wherein said synergistic wound-healing effective amount of TGF-B and FGF is about 0.07 to about 200 ug per cm² of composition.

4. The sponge composition of claim 3 wherein said TGF-B is native bovine TGF-B2.

5. The sponge composition of claim 3 wherein said FGF is recombinant human aFGF.

6. A method for promoting wound healing in a mammal having a wound, which method comprises:

applying to said wound a collagen sponge composition having a density of about 0.01 to about 0.3 g/cm³, a thickness of about 1-20 mm, and having pores at least 80% of which are at least 35 um in diameter, wherein said matrix comprises

fibrillar atelopeptide collagen, wherein said fibrils are about 50-200 nm in diameter, and are not chemically cross-linked; and

a synergistic wound-healing effective amount of TGF-B and FGF.

7. The method of claim 6 wherein said sponge composition further comprises heparin in a concentration of between about 5 ug/mL and about 500 ug/mL.

8. The method of claim 6 wherein said synergistic wound-healing effective amount of TGF-B and FGF is about 0.07 to about 200 ug per cm² of composition.

9. The method of claim 8 wherein said TGF-B is native bovine TGF-B2.

10. The method of claim 8 wherein said FGF is recombinant human aFGF.