Anti-scarring compositions comprising growth factor neutralizing antibodies

• US 5,662,904 A
• Filed: 09/27/1993
• Issued: 09/02/1997
• Est. Priority Date: 03/28/1991
• Status: Expired due to Term

• Current Assignee: Renovo Ltd. (Bentley Park Ltd.)
• Original Assignee: The Victoria University of Manchester
• Inventors: Foreman, David Michael, Ferguson, Mark William James, Shah, Mamta
• Primary Examiner(s): Scheiner, Toni R.
• Assistant Examiner(s): Johnson, Nancy A.
• Application Number:
  US08/122,508
• Time in Patent Office: 1,436 Days
• Field of Search: 530/387.1, 530/388.23, 530/388.22, 530/389.2, 530/412, 435/240.27, 435/70.21, 424/130.1, 424/143.1, 424/145.1, 424/158.1
• US Class Current: 424/130.1
• 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: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/71 for growth factors; for growth regulators
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators

Abstract

A composition for use in the treatment of wounds to inhibit scar tissue formation during healing, comprising an effective amount of an activity-inhibiting growth factor neutralizing agent or agents specific against all TGF-β, except for TGF-β₃, and PDGF, together with a pharmaceutically acceptable carrier. A method of preparing the composition and a method of administering the composition to a host suffering from tissue wounding is also disclosed.

Claims

1. A method of inhibiting scar tissue formation during the healing of wounds, comprising the steps of administering to a host suffering from tissue wounding a growth factor neutralizing antibody specific against a growth factor selected from the group consisting of TGF-β

₁, TGF-β

₂ and PDGF, wherein the antibody neutralizes the stimulation of macrophage infiltration, fibroblast migration, extracellular matrix synthesis or deposition by fibroblasts, in the wound area before the granulation phase in a dosage effective to reduce activity of the growth factor.

2. A method according to claim 1, wherein the growth factor neutralizing antibody is selected from the group consisting of anti-TGF-β

₁ antibody, anti-TGF-β

₂ antibody, and anti-PDGF-antibody.

5. A method according to claim 1, wherein the growth factor neutralizing antibody is encapsulated.

6. A method according to claim 5, wherein the capsule is degradable by an external stimulus to release the growth factor neutralizing antibody.

7. A method according to claim 6, wherein the external stimulus is selected from the group consisting of UV light, in vivo enzymes, ultrasound and heat.

8. A method according to claim 1, wherein the growth factor neutralizing antibody is bound to a binding molecule.

9. A method according to claim 8, further comprising the step of detaching the binding molecule from the growth factor neutralizing antibody.

10. A method according to claim 9 wherein the binding molecule is detached from the growth factor neutralizing antibody by an external stimulus selected from the group consisting of UV light, in vivo enzymes, ultrasound and heat.

11. A method according to claim 1, further comprising the step of administering the growth factor neutralizing antibody in a pharmaceutically acceptable carrier.

12. A method according to claim 11, wherein the pharmaceutically acceptable carrier is selected from the group consisting of a neutral sterile cream, gel, aerosol and powder for topical application.

13. A method according to claim 11, wherein the pharmaceutically acceptable carrier is selected from the group consisting of a sterile solution for injection, irrigation and inhalation.

14. A method according to claim 11, wherein the pharmaceutically acceptable carrier comprises a sterile dressing for topically covering a wound.

15. A method according to claim 11, wherein the pharmaceutically acceptable carrier is selected from the group consisting of a biopolymer and a polymer for implanting within the wound.

16. A method according to claim 1, further comprising the step of administering a fibroblast growth factor with the growth factor neutralizing antibody.

3. A method of inhibiting scar tissue formation during the healing of wounds, comprising the steps of administering to a host suffering from tissue wounding a growth factor neutralizing antibody specific against a growth factor selected from the group consisting of TGF-β

₁, TGF-β

₂ and PDGF, wherein the antibody neutralizes the stimulation of macrophage infiltration, fibroblast migration, extracellular matrix synthesis or deposition by fibroblasts, in the wound area during the granulation phase in a dosage effective to reduce activity of the growth factor.

4. A method according to claim 3, wherein the growth factor neutralizing antibody is selected from the group consisting of anti-TGF-β

₁ antibody, anti-TGF-β

₂ antibody, and anti-PDGF-antibody.

17. A method according to claim 3, wherein the growth factor neutralizing antibody is encapsulated.

18. A method according to claim 17, wherein the capsule is degradable by an external stimulus to release the growth factor neutralizing antibody.

19. A method according to claim 18, wherein the external stimulus is selected from the group consisting of UV light, in vivo enzymes, ultrasound and heat.

20. A method according to claim 3, wherein the growth factor neutralizing antibody is bound to a binding molecule.

21. A method according to claim 20, further comprising the step of detaching the binding molecule from the growth factor neutralizing antibody.

22. A method according to claim 21 wherein the binding molecule is detached from the growth factor neutralizing antibody by an external stimulus selected from the group consisting of UV light, in vivo enzymes, ultrasound and heat.

23. A method according to claim 3, further comprising the step of administering the growth factor neutralizing antibody in a pharmaceutically acceptable carrier.

24. A method according to claim 23, wherein the pharmaceutically acceptable carrier is selected from the group consisting of a neutral sterile cream, gel, aerosol and powder for topical application.

25. A method according to claim 23, wherein the pharmaceutically acceptable-carrier is selected from the group consisting of a sterile solution for injection, irrigation and inhalation.

26. A method according to claim 23, wherein the pharmaceutically acceptable carrier comprises a sterile dressing for topically covering a wound.

27. A method according to claim 23, wherein the pharmaceutically acceptable carrier is selected from the group consisting of a biopolymer and a polymer for implanting within the wound.

28. A method according to claim 3, further comprising the step of administering a fibroblast growth factor with the growth factor neutralizing antibody.