Use of peptides for promoting wound healing
View Patent ↗The current invention relates to the use of a peptide comprising an amino acid sequence in the preparation of a medicament for the regeneration of tissue, preferably for the treatment of a wound. Further the invention relates to compositions comprising such peptides, and use of said peptides in both medical and nonmedical (cosmetic) applications.
1. A method of preparation of a medicament for the treatment of a wound, comprising the step of including an effective amount of a cyclic peptide in the medicament, the cyclic peptide comprising at least six contiguous residues of the amino acid sequence of SEQ. ID NO: 2 or a variant peptide thereof in which one amino acid residue is substituted, deleted or inserted within said at least six contiguous residues, wherein the cyclic peptide has a relative wound closure activity that is equal to the relative wound closure activity of 1 μM concentration of the linear peptide of SEQ ID NO: 4 but at a concentration of cyclic peptide that is at least 5 times lower.
2. The method of claim 1 , wherein the peptide comprises the amino acid sequence selected from the group consisting of SEQ ID NO: 4 and SEQ ID NO: 5.
3. The method of claim 1 , wherein the peptide comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 7-20, 23-25, and 28-29.
4. The method of claim 1 , wherein the peptide is at least 10 amino acid residues in length.
5. The method of claim 1 , wherein the peptide is at least 20 amino acid residues in length.
6. The method of claim 1 , wherein the peptide is in the range of 12 to 39 amino acid residues in length.
7. The method of claim 1 , wherein the peptide is not more than about 100 residues in length.
8. The method of claim 1 , wherein the peptide is a L-peptide.
9. The method of claim 1 , wherein the cyclic peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 4, 5, 7-20, 23-25, and 28-29 or a variant thereof in which one amino acid residue in any of SEQ ID NOs: 4, 5, 7-20, 23-25, and 28-29 is substituted, deleted or inserted and the one residue substitution, deletion or insertion is not within a subsequence of SEQ ID NO: 2.
10. A method of preparation of a medicament for the treatment of a wound, comprising the step of including an effective amount of a cyclic peptide in the medicament, the cyclic peptide comprising at least six contiguous residues of the amino acid sequence of SEQ ID NO: 5 or a variant peptide thereof in which one amino acid residue is substituted, deleted or inserted within said at least six contiguous residues, wherein the cyclic peptide has a relative wound closure activity that is equal to the relative wound closure activity of 1 μM concentration of the linear peptide of SEQ ID NO: 4 but at a concentration of cyclic peptide that is at least 5 times lower.
11. The method of claim 1 , wherein the peptide is a dimer or multimer of a monomer of (i) said at least six contiguous residues of SEQ ID NO: 2 or (ii) a variant of (i) in which one amino acid residue is substituted, deleted or inserted within said at least six contiguous residues.
12. The method of claim 1 , wherein the peptide is a dimer or multimer of a monomer consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 4, 5, 7-20, 23-25, and 28-29.
13. The method of claim 1 , wherein the peptide is conjugated.
14. The method of claim 1 , wherein the conformational freedom of the peptide has been constrained by chemical treatment.
15. The method of claim 14 , wherein conformational freedom of the peptide has been constrained by cross-linking or disulfide bonds.
16. The method of claim 1 , wherein the medicament further comprises a growth factor, wherein the growth factor is selected from the group consisting of platelet derived growth factor (PDGF), insulin like-growth factor (IGF), transforming growth factor (TGF), hepatocyte growth factor (HGF), epidermal growth factor (EGF), and fibroblast growth factor (FGF).
17. The method of claim 1 , wherein the treatment treats a wound selected from the group consisting of: a wound in the eye, a wound in the conjunctiva, an internal wound, an oral wound, a skin wound, an external wound, an ulcer, and a decubitus wound.
18. The method of claim 1 , wherein the treatment promotes wound closure.
19. A method of preparation of a medicament for the treatment of a wound, comprising the step of including an effective amount of a peptide in the medicament, the peptide comprising at least six contiguous residues of the amino acid sequence of SEQ ID NO: 2 or a variant peptide thereof in which one amino acid residue is substituted, deleted or inserted within said at least six contiguous residues, wherein the peptide is a dimer or multimer of a monomer of (i) said at least six contiguous residues of SEQ ID NO: 2 or (ii) a variant of (i) in which one amino acid residue is substituted, deleted or inserted within said at least six contiguous residues.
20. The method of claim 19 , wherein the peptide is a dimer or multimer of a monomer consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 4, 5, 7-20, 23-25, and 28-29.
21. The method of claim 19 , wherein the peptide is a cyclic peptide.
22. The method of claim 21 , wherein the cyclic peptide has a relative wound closure activity that is equal to the relative wound closure activity of 1 μM concentration of the linear peptide of SEQ ID NO: 4 but at a concentration of cyclic peptide that is at least 5 times lower.
23. The method of claim 19 , wherein the peptide is at least 10 amino acid residues in length.
24. The method of claim 19 , wherein the peptide is not more than about 100 residues in length.
25. The method of claim 19 , wherein the conformational freedom of the peptide has been constrained by chemical treatment.
26. The method of claim 25 , wherein conformational freedom of the peptide has been constrained by cross-linking or disulfide bonds.
27. The method of claim 19 , wherein the medicament further comprises a growth factor, wherein the growth factor is selected from the group consisting of platelet derived growth factor (PDGF), insulin like-growth factor (IGF), transforming growth factor (TGF), hepatocyte growth factor (HGF), epidermal growth factor (EGF), and fibroblast growth factor (FGF).
28. The method of claim 19 , wherein the treatment treats a wound selected from the group consisting of: a wound in the eye, a wound in the conjunctiva, an internal wound, an oral wound, a skin wound, an external wound, an ulcer, and a decubitus wound.
29. The method of claim 19 , wherein the treatment promotes wound closure.
30. The method of claim 10 , wherein the peptide is at least 10 amino acid residues in length.
31. The method of claim 10 , wherein the peptide is not more than about 100 residues in length.
32. The method of claim 10 , wherein the cyclic peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-29 or a variant thereof in which one amino acid residue in any of SEQ ID NOs: 1, and 3-29 is substituted, deleted or inserted and the one residue substitution, deletion or insertion is not within a subsequence of SEQ ID NO: 2.
33. The method of claim 10 , wherein the peptide is a dimer or multimer of a monomer of (i) said at least six contiguous residues of SEQ ID NO: 5 or (ii) a variant of (i) in which one amino acid residue is substituted, deleted or inserted within said at least six contiguous residues.
34. The method of claim 10 , wherein the conformational freedom of the peptide has been constrained by chemical treatment.
35. The method of claim 34 , wherein conformational freedom of the peptide has been constrained by cross-linking or disulfide bonds.
36. The method of claim 10 , wherein the medicament further comprises a growth factor, wherein the growth factor is selected from the group consisting of platelet derived growth factor (PDGF), insulin like-growth factor (IGF), transforming growth factor (TGF), hepatocyte growth factor (HGF), epidermal growth factor (EGF), and fibroblast growth factor (FGF).
37. The method of claim 10 , wherein the treatment treats a wound selected from the group consisting of: a wound in the eye, a wound in the conjunctiva, an internal wound, an oral wound, a skin wound, an external wound, an ulcer, and a decubitus wound.
38. The method of claim 10 , wherein the treatment promotes wound closure.