Composition with high antimicrobial activity and low toxicity

• US 10,448,634 B2
• Filed: 04/22/2015
• Issued: 10/22/2019
• Est. Priority Date: 08/23/2010
• Status: Active Grant

• Current Assignee: Amicrobe, Inc., Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Bevilacqua, Michael P., Benitez, Diego, Deming, Timothy J., Hanson, Jarrod A., Koziol, Lucas
• Primary Examiner(s): Skowronek, Karlheinz R.
• Assistant Examiner(s): Kader, Khalid
• Application Number:
  US14/693,601
• Publication Number:
  US 20150366193A1
• Time in Patent Office: 1,644 Days
• CPC Class Codes: A01N 37/18 containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
• CPC Class Codes: A23L 3/3526 Organic compounds containing nitrogen
• CPC Class Codes: A61K 38/02 Peptides of undefined number of amino acids; Derivatives thereof
• CPC Class Codes: A61K 38/16 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 15/02 for disorders of the vagina
• 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 27/02 Ophthalmic agents
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/02 Local antiseptics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/001 by chemical synthesis
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Improved synthetic copolypeptide antimicrobials contain cationic amino acid residues and may be based on a blocky sequence. These antimicrobials show low mammalian toxicity and may undergo directed self-assembly. The inventive synthetic copolypeptides are useful in treatment of wounds and other infections.

Claims

1. A method for promoting hemostasis comprising applying a hemostatic composition comprising:

at least one species of synthetic copolypeptide of at least forty amino acid residues comprising;

at least one hydrophilic segment containing at least five contiguous cationic amino acid residues; and

at least one hydrophobic segment containing at least five contiguous hydrophobic amino acid residues;

wherein the hydrophilic segment contains a larger number of amino acid residues than the hydrophobic segment;

wherein said at least one species of synthetic copolypeptide forms multimeric structures in aqueous media;

wherein said at least one species of synthetic copolypeptide promotes platelet aggregation; and

wherein the composition promotes hemostasis.

2. The method of claim 1, wherein the composition promotes or causes an increase in platelet aggregation.

3. The method of claim 1, wherein the composition promotes or causes a decrease in fibrinolysis.

4. The method of claim 1, wherein the composition is directly applied to wounds.

5. The method of claim 1, wherein the composition inhibits or kills microbes.

6. The method of claim 1, wherein the synthetic copolypeptide inhibits or kills microbes.

7. The method of claim 1, wherein the cationic amino acid residues are independently selected from arginine, homoarginine, lysine, and ornithine.

8. The method of claim 1, wherein the hydrophobic amino acid residues are independently selected from alanine, isoleucine, leucine, phenylalanine, and valine.

9. The method of claim 1, wherein the cationic amino acid residues are independently selected from arginine, homoarginine, lysine, and ornithine;

and the hydrophobic amino acid residues are independently selected from alanine, isoleucine, leucine, phenylalanine, and valine.

10. The method of claim 1, wherein the molar fraction of hydrophobic amino acid residues in the synthetic copolypeptide is about 40%, about 35%, or about 25%.

11. The method of claim 1, wherein the composition inhibits or kills microbes and the synthetic copolypeptide inhibits or kills microbes.

12. The method of claim 1, wherein the concentration of the synthetic copolypeptide in the composition is about 100 μ

g/mL or about 1000 μ

g/mL.

13. The method of claim 1, wherein the synthetic copolypeptide forms fibrils in aqueous media.

14. The method of claim 1, wherein the synthetic copolypeptide forms micelles in aqueous media.

15. The method of claim 1, wherein the copolypeptide promotes hemostasis.

16. The method of claim 1, wherein the hydrophilic segment comprises at least ten contiguous cationic amino acid residues.