CYCLIC DIPEPTIDES AND WOUND HEALING

• US 20190314449A1
• Filed: 11/16/2017
• Published: 10/17/2019
• Est. Priority Date: 11/16/2016
• Status: Active Application

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: PRASAD, Anand
• Application Number:
  US16/461,084
• Publication Number:
  US 20190314449A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/722 Chitin, chitosan
• CPC Class Codes: A61K 33/30 Zinc; Compounds thereof
• CPC Class Codes: A61K 38/05 Dipeptides
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like

Abstract

A pharmaceutical composition comprising a cyclo-dipeptide and use thereof for treatment of a wound. The cyclo-dipep-tide can be Cyclo-His-Pro and the pharmaceutical composition can suitable for topical application to a wound. The compositions can be used to treat a wound, reduce tissue damage in a wound, prevent and/or reduce oxidative damage in a wound, and/or reduce the amount of heme in a wound.

Claims

1. A wound care composition comprising an active ingredient comprising Cyclo-His-Pro.

2. The wound care composition of claim 1, wherein the composition further comprises a pharmaceutically acceptable carrier.

3. The would care composition of claim 1, wherein the composition is formulated for topical application onto a wound.

4. The wound care composition of claim 1, wherein the Cyclo-His-Pro is the only active ingredient.

5. The wound care composition of claim 1, wherein the composition further comprises an additional active ingredient selected from one or a combination of agents capable of moisturizing, increasing cellular uptake of compounds, increasing neovascularization, providing anti-microbial activity, elevating nitrogen monoxide levels, increasing Vascular Endothelial Growth Factor activity and/or concentration, enhancing re-epithelialization, and/or decreasing inflammation.

6. The wound care composition of claim 5, wherein the agent capable of increasing cellular uptake of compounds is a hydrogel, increasing neovascularization is a hydrogel, providing anti-microbial activity is Cyclo-Leu-Pro, Cyclo-Phe-Pro, chitosan, and/or zinc oxide, elevating nitrogen monoxide levels is arginine, increasing Vascular Endothelial Growth Factor activity and/or concentration is arginine, enhancing re-epithelialization is zinc oxide, and/or decreasing inflammation is zinc oxide.

7. The wound care composition of claim 1, wherein the composition further comprises one or more additional cyclic dipeptide(s).

8. The wound care composition of claim 7, wherein the one or more additional cyclic dipeptide(s) comprise proline as at least one of the two amino acids.

9. A method of treating a wound, the method comprising administering the composition of claim 1 to a subject having a wound.

10. The method of claim 9, wherein the composition of claim 1 is administered topically to the wound.

11. A method of reducing tissue damage in a wound, the method comprising administering the composition of claim 1 to a subject having a wound.

12. The method of claim 11, wherein the composition of claim 1 is administered topically to the wound.

13. A method of preventing and/or reducing oxidative damage in a wound, the method comprising administering the composition of claim 1 to a subject having a wound.

14. The method of claim 13, wherein the composition of claim 1 is administered topically to the wound.

15. A method of reducing the amount of heme in a wound, the method comprising administering the composition of claim 1 to a subject having a wound.

16. The method of claim 15, wherein the composition of claim 1 is administered topically to the wound.

30. The method of claim 29, wherein the composition of claim 1 is administered topically to the wound.

17. A wound care composition comprising one or a combination of cyclic dipeptide(s) and a pharmaceutically acceptable carrier.

18. The wound care composition of claim 17, wherein the one or a combination of cyclic dipeptide(s) comprises proline as at least one of the two amino acids.

19. The wound care composition of claim 17, wherein the one or a combination of cyclic dipeptide(s) is one or a combination of:

Cyclo-Ala-Pro;

Cyclo-Arg-Pro;

Cyclo-Asn-Pro;

Cyclo-Asp-Pro;

Cyclo-Cys-Pro;

Cyclo-Glu-Pro;

Cyclo-Gly-Pro;

Cyclo-His-Pro;

Cyclo-Ile-Pro;

Cyclo-Leu-Pro;

Cyclo-Lys-Pro;

Cyclo-Met-Pro;

Cyclo-Phe-Pro;

Cyclo-Pro-Pro;

Cyclo-Ser-Pro;

Cyclo-Thr-Pro;

Cyclo-Trp-Pro;

Cyclo-Tyr-Pro;

Cyclo-Val-Pro; and

/or Cyclo-Gln-Pro.

20. The would care composition of claim 17, wherein the composition is formulated for topical application onto a wound.

21. The wound care composition of claim 17, wherein the composition further comprises an additional active ingredient selected from one or a combination of agents capable of moisturizing, increasing heme-scavenging, increasing cellular uptake of compounds, increasing neovascularization, providing anti-microbial activity, elevating nitrogen monoxide levels, increasing Vascular Endothelial Growth Factor activity and/or concentration, enhancing re-epithelialization, and/or decreasing inflammation.

22. The wound care composition of claim 21, wherein the agent capable of increasing heme-scavenging is Cyclo-His-Pro, increasing cellular uptake of compounds is a hydrogel, increasing neovascularization is a hydrogel, providing anti-microbial activity is Cyclo-Leu-Pro, Cyclo-Phe-Pro, chitosan, and/or zinc oxide, elevating nitrogen monoxide levels is arginine, increasing Vascular Endothelial Growth Factor activity and/or concentration is arginine, enhancing re-epithelialization is zinc oxide, and/or decreasing inflammation is zinc oxide.

23. A method of treating a wound, the method comprising administering the composition of claim 17 to a subject having a wound.

24. The method of claim 23, wherein the composition of claim 17 is administered topically to the wound.

25. A method of reducing tissue damage in a wound, the method comprising administering the composition of claim 17 to a subject having a wound.

26. The method of claim 25, wherein the composition of claim 17 is administered topically to the wound.

27. A method of preventing and/or reducing oxidative damage in a wound, the method comprising administering the composition of claim 17 to a subject having a wound.

28. The method of claim 27, wherein the composition of claim 17 is administered topically to the wound.

29. A method of reducing the amount of heme in a wound, the method comprising administering the composition of claim 17 to a subject having a wound.

31. A method of reducing scarring of a wound, the method comprising administering the composition of claim 17 to a subject having a wound.