Peptide fragments for inducing synthesis of extracellular matrix proteins

• US 8,110,658 B2
• Filed: 06/12/2007
• Issued: 02/07/2012
• Est. Priority Date: 06/13/2006
• Status: Active Grant

• Current Assignee: Helix BioMedix, Inc.
• Original Assignee: Helix BioMedix, Inc.
• Inventors: Harris, Scott M., Falla, Timothy J., Zhang, Lijuan
• Primary Examiner(s): Lukton, David
• Application Number:
  US11/811,876
• Publication Number:
  US 20070299015A1
• Time in Patent Office: 1,701 Days
• Field of Search: 530/330, 514/18, 514/21.9, 514/17.2
• US Class Current: 530/330
• CPC Class Codes: A61K 2121/00 Preparations for use in therapy
• 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 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: A61K 38/07 Tetrapeptides
• CPC Class Codes: A61K 8/64 Proteins; Peptides; Derivatives or degradation products thereof
• 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: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels 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 17/16 Emollients or protectives, e.g. against radiation
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: A61Q 19/08 Anti-ageing preparations
• CPC Class Codes: C07K 14/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
• CPC Class Codes: C07K 5/1002 with the first amino acid being neutral
• CPC Class Codes: C07K 5/1008 the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
• CPC Class Codes: C07K 5/1024 with the first amino acid being heterocyclic

Abstract

Short biologically active tetrapeptides are disclosed that are comprised of the sequences GxxG and PxxP where G (glycine) and P (proline) are maintained and x is a variable amino acid. The peptides can be used singly or in combination to stimulate production of extracellular matrix proteins in skin. A rapid, low-cost method of producing heterogenous formulations of tetrapeptides is disclosed.

Claims

1. A tetrapeptide capable of inducing production of an extracellular matrix protein, wherein the tetrapeptide comprises SEQ ID NO:

3, SEQ ID NO;

4, SEQ ID NO;

5, SEQ ID NO;

8, SEQ ID NO;

25, SEQ ID NO;

27, SEQ ID NO;

30, SEQ ID NO;

40, or SEQ ID NO;

41.

2. The tetrapeptide of claim 1, wherein the tetrapeptide comprises SEQ ID NO:

5.

3. The tetrapeptide of claim 2, wherein the tetrapeptide is SEQ ID NO:

5.

4. The tetrapeptide of claim 1, wherein the tetrapeptide comprises SEQ ID NO:

3.

5. The tetrapeptide of claim 4, wherein the tetrapeptide is SEQ ID NO:

3.

6. The tetrapeptide of claim 1, wherein the tetrapeptide is amidated at the carboxy-terminus.

7. The tetrapeptide of claim 1, wherein the extracellular matrix protein is collagen.

8. A composition comprising at least one tetrapeptide of claim 1 and a pharmaceutically acceptable carrier.

9. The composition of claim 8, wherein the tetrapeptide is present in a concentration ranging from about 0.01 μ

g/mL to about 100 μ

g/mL.

10. The composition of claim 8, wherein the tetrapeptide is present in a concentration ranging from about 0.1 μ

g/mL to about 1 μ

g/mL.

11. The composition of claim 8, wherein the composition is in the form of an aerosol, emulsion, liquid, lotion, cream, paste, ointment, or foam.

12. A method for stimulating the production of collagen in a human, the method comprising administering to said human a therapeutically effective amount of the composition of claim 8.

13. The method of claim 12, wherein the therapeutically effective amount of the composition comprises about 0.1 μ

g/mL to about 50 μ

g/mL of tetrapeptide.

14. The method of claim 12, wherein the administering step comprises topically applying the composition to damaged skin.

16. The tetrapeptide of claim 1, wherein the tetrapeptide comprises SEQ ID NO:

8.

17. The tetrapeptide of claim 16, wherein the tetrapeptide is SEQ ID NO:

8.

18. The tetrapeptide of claim 1, wherein the tetrapeptide comprises SEQ ID NO:

25, SEQ ID NO;

27, SEQ ID NO;

30, SEQ ID NO;

40, or SEQ ID NO;

41.

19. The composition of claim 8, where said composition comprises the tetrapeptide of SEQ ID NO:

5.

20. The method of claim 14, wherein said damaged skin is a result of aging, disease, injury, trauma, or surgery.

21. The method of claim 14, wherein the composition comprises a tetrapeptide in combination with a pharmaceutically acceptable carrier, and wherein said tetrapeptide comprises SEQ ID NO:

5.

22. The method of claim 21, wherein the composition further comprises the tetrapeptides comprising SEQ ID NO:

6, SEQ ID NO;

7 and SEQ ID NO;

8.

23. The method of claim 14, wherein the composition comprises a tetrapeptide in combination with a pharmaceutically acceptable carrier, and wherein said tetrapeptide comprises SEQ ID NO:

8.

24. The composition of claim 19, wherein said composition further comprises the tetrapeptides comprising SEQ ID NO:

6, SEQ ID NO;

7 and SEQ ID NO;

8.

15. A tetrapeptide capable of inducing production of an extracellular matrix protein comprising the amino acid sequence PGPR (SEQ ID NO:

4).