Melanotropin ligands for skin care

Patent metadata

Field	Value
Publication number	US-9539301-B2
Application number	US-201615050671-A
Country	US
Kind code	B2
Filing date	Feb 23, 2016
Priority date	May 17, 2011
Publication date	Jan 10, 2017
Grant date	Jan 10, 2017

Abstract

A melanocortin 1 receptor (MC1R) peptide ligand-elastic vesicle complex. The MC1R peptide ligand is modified by coupling the MC1R ligand to a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, elastic vesicles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The MC1R peptide ligand-elastic vesicle complex is prepared as a topical formulation.

First claim

What is claimed:

1. A topical composition for transdermal delivery of a gamma melanocyte stimulation hormone (MSH) analogue, said topical composition comprising:
a. the gamma MSH analogue selected from the group consisting of:

(SEQ ID NO: 4)

H-Lys(hex-5-ynoyl)-Tyr-Val-Nle-Gly-His-DNal(2′)-

Arg-DTrp-Asp-Arg-Phe-Gly-NH 2 ;

(SEQ ID NO: 5)

H-Lys(hex-5-ynoyl)-Tyr-Val-Nle-Gly-His-DNal(2′)-

Arg-DPhe-Asp-Arg-Phe-Gly-NH 2 ;

(SEQ ID NO: 18)

H-Tyr-Val-Leu-Gly-His-DPhe-Arg-DNal(2′)-Asp-Arg-

Phe-Gly-NH 2 ;

and

(SEQ ID NO: 19)

H-Tyr-Val-Ile-Gly-His-DPhe-Arg-DNal(2′)-Asp-Arg-

Phe-Gly-NH 2 ;

b. at least one non-toxic solvent;
c. a solute modifier comprising at least one compound selected from the group consisting of 3,3′-thiodipropionic acid or an ester or salt thereof, an oxindole alkaloid, a polyphenolic flavonoid, a sugar adduct of a gluconuride, an isoflavone, phosphatidyl serine, phosphatidyl choline, Vitamin D 3 and Vitamin K 1 ;
d. at least one substance that induces in situ generation of cAMP or cGMP; and
e. a skin stabilizer comprising at least one compound selected from the group consisting of an aliphatic carboxylic acid having from about 8 to 32 carbon atoms, an ester of said aliphatic carboxylic acid with an aliphatic alcohol having about 2 to 20 carbon atoms, wherein said ester has a total of about 9 to 36 carbon atoms, and Vitamin D 3 .

2. The composition of claim 1 , wherein the gamma-MSH analogue is present at about 0.001 to 20% by weight of the composition.

3. The composition of claim 1 , wherein the gamma-MSH analogue is present at about 0.05 to 10% by weight of the composition.

4. The composition of claim 1 , wherein the gamma-MSH analogue is effective for inducing melanogenesis in epidermal tissue without inducing homologous desensitization of melanocortin-1 receptors.

5. The composition of claim 1 , wherein the substance that induces in situ generation of cAMP or cGMP comprises forskolin.

6. The composition of claim 1 , wherein the non-toxic solvent is selected from the group consisting of lower aliphatic mono- and poly-hydroxy compounds.

7. The composition of claim 1 further comprising methylsulfonylmethane.

8. The composition of claim 1 further comprising at least one absorption modifier selected from the group consisting of isopropyl myristate and benzophenone.

9. The composition of claim 1 further comprising at least one fragrance selected from the group consisting of limonene and lemon oil.

10. The composition of claim 1 , wherein the composition is in a form selected from the group consisting of a lotion, a cream, and a gel.

11. A topical composition effective for inducing melanogenesis in epidermal tissue without inducing homologous desensitization of melanocortin-1 receptors, said topical composition comprising a gamma melanocyte stimulation hormone (MSH) analogue, wherein said gamma-MSH analogue is selected from the group consisting of:

(SEQ ID NO: 4)

H-Lys(hex-5-ynoyl)-Tyr-Val-Nle-Gly-His-DNal(2′)-

Arg-DTrp-Asp-Arg-Phe-Gly-NH 2 ;

(SEQ ID NO: 5)

H-Lys(hex-5-ynoyl)-Tyr-Val-Nle-Gly-His-DNal(2′)-

Arg-DPhe-Asp-Arg-Phe-Gly-NH 2 ;

(SEQ ID NO: 18)

H-Tyr-Val-Leu-Gly-His-DPhe-Arg-DNal(2′)-Asp-Arg-

Phe-Gly-NH 2 ;

and

(SEQ ID NO: 19)

H-Tyr-Val-Ile-Gly-His-DPhe-Arg-DNal(2′)-Asp-Arg-

Phe-Gly-NH 2 .

12. The composition of claim 11 , wherein the gamma-MSH analogue is present at about 0.001 to 20% by weight of the composition.

13. The composition of claim 11 , wherein the gamma-MSH analogue is present at about 0.05 to 10% by weight of the composition.

14. The composition of claim 11 , wherein the composition is in a form selected from the group consisting of a lotion, a cream, and a gel.

15. A topical composition for transdermal delivery of a gamma melanocyte stimulation hormone (MSH) analogue, said topical composition comprising:
a. the gamma MSH analogue selected from the group consisting of:

(SEQ ID NO: 4)

H-Lys(hex-5-ynoyl)-Tyr-Val-Nle-Gly-His-DNal(2′)-

Arg-DTrp-Asp-Arg-Phe-Gly-NH 2 ;

(SEQ ID NO: 5)

H-Lys(hex-5-ynoyl)-Tyr-Val-Nle-Gly-His-DNal(2′)-

Arg-DPhe-Asp-Arg-Phe-Gly-NH 2 ;

(SEQ ID NO: 18)

H-Tyr-Val-Leu-Gly-His-DPhe-Arg-DNal(2′)-Asp-Arg-

Phe-Gly-NH 2 ;

and

(SEQ ID NO: 19)

H-Tyr-Val--Ile-Gly-His-DPhe-Arg-DNal(2′)-Asp-Arg-

Phe-Gly-NH 2 ;

Assignees

• Univ Arizona

Inventors

• Cai Minying
• Hruby Victor J
• Shelby Sean

Classifications

• C07K14/68

  Melanocyte-stimulating hormone [MSH] · CPC title

• C07K14/685

  Alpha-melanotropin · CPC title

• C07K7/08

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title

• A61K38/10 Primary

  Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• A61L15/00

  Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads (for liquid bandages A61L26/00; radioactive dressings {A61N5/1029}) · CPC title