# US 6,248,716 B1 · Peptide, a method for its preparation and a pharmaceutical composition containing the peptide

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 6,248,716 B1
- Document ID: US6248716B1
- Status: Granted
- Kind: B1
- Application number: 09/320,667
- Filed: 1999-05-27
- Granted: 2001-06-19
- Earliest claimed: 1995-06-27
- Assignees: Immunotech Developments Inc.
- Inventors: Vladislav I. Deigin; Elena P. Yarova
- Web page: https://patentgrep.com/patent/US6248716B1

## CPC

- C07K 14/702: {with at least 1 amino acid in D-form}
- C07K 5/1016: {and aromatic or cycloaliphatic}
- 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)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

A peptide of the formula I X-Tyr-Y-Phe-Z-A I wherein X is hydrogen, arginine, D-arginine, ornithine, D-ornithine, lysine, D-lysine, homoarginine, D-homoarginine, citrulline, D-citrulline; Tyr is tyrosine; Y is D-alanine, D-valine, D-leucine, D-isoleucine, D-phenylalanine, D-asparagine, D-tryptophan, D-proline, D-serine, D-threonine, D-tyrosine, D-hydroxyproline, D-cysteine, D-cysteyl-cysteine, D-methionine, D-lysine, D-homoarginine, D-arginine, D-histidine, D-aspartic acid, D-glutamic acid, D-β-alanine, or D-ornithine; Phe is phenylalanine; Z is alanine, D-alanine, valine, D-valine, leucine, D-leucine, isoleucine, D-isoleucine, phenylalanine, D-phenylalanine, asparagine, D-asparagine, glycine, glutamine, D-glutamine, tryptophan, D-tryptophan, proline, D-proline, serine, D-serine, threonine, D-threonine, tyrosine, D-tyrosine, hydroxyproline, D-hydroxyproline, cysteine, D-cysteine, cysteyl-cysteine, cysteine-D-cysteine, D-cysteyl-cysteine, D-cysteine-D-cysteine, methionine, D-methionine, lysine, D-lysine, arginine, D-arginine, histidine, D-histidine, aspartic acid, D-aspartic acid, glutamic acid, D-glutamic acid, β-alanine, D-β-alanine, ornithine, or D-ornithine; and A is hydroxyl or substituted amide (C1-C3); compositions containing same and its use in modulating physiological processes such as weight gain, activities of the epithelium growth zone, hair growth, wound healing, and to stimulate reparative and anabolic processes, exert analgesic effects and to reduce stress.

## Claims

### Claim 1

A method for preventing or reducing conditions or complications resulting from stress in an animal in need thereof, comprising administering to said animal an effective amount of a peptide of the formula I,
X-Tyr-Y-Phe-Z-A I
wherein X is hydrogen, arginine, D-arginine, ornithine, D-ornithine, lysine, D-lysine, homoarginine, D-homoarginine, citrulline, D-citrulline; Tyr is tyrosine; Y is D-alanine, D-valine, D-leucine, D-isoleucine, D-phenylalanine, D-asparagine, D-tryptophan, D-proline, D-serine, D-threonine, D-tyrosine, D-hydroxyproline, D-cysteine, D-cysteyl-cysteine, D-methionine, D-lysine, D-homoarginine, D-arginine, D-histidine, D-aspartic acid, D-glutamic acid, D-β-alanine, or D-ornithine Phe is phenylalanine; Z is alanine, D-alanine, valine, D-valine, leucine, D-leucine, isoleucine, D-isoleucine, phenylalanine, D-phenylalanine, asparagine, D-asparagine, glycine, glutamine, D-glutamine, tryptophan, D-tryptophan, proline, D-proline, serine, D-serine, threonine, D-threonine, tyrosine, D-tyrosine, hydroxyproline, D-hydroxyproline, cysteine, D-cysteine, cysteyl-cysteine, cysteine-D-cysteine, D-cysteyl-cysteine, D-cysteine-D-cysteine, methionine, D-methionine, lysine, D-lysine, arginine, D-arginine, histidine, D-histidine, aspartic acid, D-aspartic acid, glutamic acid, D-glutamic acid, β-alanine, D-β-alanine, ornithine, or D-ornithine; and A is hydroxyl or an amide which may be substituted, wherein when X is H and Y is D-Arg Z-A is not Lys-NH2; and when X is H, and Y is Pro, Z-A is not Pro-OH or Pro-NH2.

### Claim 2 (depends on 1)

A method according to claim 1, wherein X is Arg, D-Arg, D-Orn, homoarginine, D-homoarginine, or citrulline; Y is D-Orn, D-Ala, or D-Arg; Z is D-Ala, Gly, Pro, D-Pro or β-Ala; and A is OH or NH2.

### Claim 3 (depends on 2)

method according to claim 2 wherein when X is Arg and Y is D-Ala, then Z is not Pro; and when X is D-Arg and Y is D-Ara then Z is not D-Ala.

### Claim 4 (depends on 3)

A method according to claim 3 wherein when X is Arg, Y is D-Ala, Z is D-Pro or β-Ala; and A is OH.

### Claim 5 (depends on 2)

A method according to claim 2 wherein when X is D-Arg and Y is D-Arg, then Z is not D-Ala.

### Claim 6 (depends on 1)

A method according to claim 1, wherein X is Arg, homoarginine, D-homoarginine, citrulline, or D-citrulline; Y is D-Ala, D-Orn, or D-Arg; Z is D-Ala; and A is OH or NH2.

### Claim 7 (depends on 1)

A method according to claim 1, wherein X is Arg; Y is D-Ala; Z is D-Pro, Pro, or β-Ala; and, A is OH.

### Claim 8 (depends on 1)

A method according to claim 1, wherein X is H-D-Arg-Tyr-D-Arg-Phe-D-Ala-NH2, H-D-Orn-Tyr-D-Ala-Phe-D-Ala-OH, H-Arg-Tyr-D-Ala-Phe-β-Ala-OH, H-Arg-Tyr-D-Ala-Phe-Gly-OH; H-Har-Tyr-D-Arg-Phe-D-Ala-NH2; H-D-Har-Tyr-D-Arg-Phe-D-Ala-NH2; H-Cyt-Tyr-D-Arg-Phe-D-Ala-NH2; H-D-Cyt-Tyr-D-Arg-Phe-D-Ala-NH2; H-Arg-Tyr-D-Ala-Phe-Pro-OH; H-Arg-Tyr-D-Ala-Phe-D-Pro-OH; H-Arg-Tyr-D-Ala-Phe-D-Ala-OH; H-Arg-Tyr-D-Orn-Phe-D-Ala-OH; H-Arg-Tyr-D-Arg-Phe-D-Ala-OH; H-Arg-Tyr-D-Arg-Phe-D-Ala-NH2; or H-Tyr-D-Orn-Phe-D-Glu-OH.

### Claim 9 (depends on 8)

A method according to claim 8 wherein the peptide is Arg-Tyr-D-Ala-Phe-Glyn-OH.

### Claim 10 (depends on 1)

A method according to claim 1 wherein the stress is physical stress.

### Claim 11 (depends on 10)

A method according to claim 10 wherein the physical stress is physical exercise.

### Claim 12 (depends on 1)

A method according to claim 1 wherein the stress is mental stress.

### Claim 13 (depends on 1)

A method according to claim 1 wherein the conditions or complications resulting from stress is an ulcer.