Chitosan-derivative compounds and methods of controlling microbial populations

• US 9,732,164 B2
• Filed: 04/10/2015
• Issued: 08/15/2017
• Est. Priority Date: 06/02/2006
• Status: Active Grant

• Current Assignee: Synedgen, Inc.
• Original Assignee: Synedgen, Inc.
• Inventors: Baker, Shenda, Wiesmann, William P.
• Primary Examiner(s): BERRY, LAYLA D
• Application Number:
  US14/684,017
• Publication Number:
  US 20160060362A1
• Time in Patent Office: 858 Days
• Field of Search: None
• CPC Class Codes: A61K 31/722 Chitin, chitosan
• CPC Class Codes: A61K 8/736 Chitin; Chitosan; Derivatives thereof
• CPC Class Codes: A61L 2/232 layered or coated
• CPC Class Codes: A61L 2/235 cellular, porous or foamed
• CPC Class Codes: A61L 2202/23 Containers, e.g. vials, bottles, syringes, mail
• CPC Class Codes: A61L 2202/24 Medical instruments, e.g. endoscopes, catheters, sharps
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61Q 11/00 Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
• CPC Class Codes: A61Q 17/005 Antimicrobial preparations
• CPC Class Codes: C08B 37/003 Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• 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

The present invention is directed to chitosan-derivative compounds and structures, methods of making chitosan-derivative compounds and methods for controlling, inhibiting and enhancing microbial populations in a variety of environments. The present invention is also directed to the control, inhibition and enhancement of microbial populations in animals, particularly humans. The microbial populations include bacteria, viruses and other pathogens where control of microbial populations are a necessity. The chitosan-derivative compounds of the present invention include chitosan-arginine compounds, related chitosan-L/D unnatural amino acid compounds, chitosan-acid amine compounds, chitosan-L/D natural amino acid derivative compounds, co-derivatives of the chitosan-derivative compounds, salts of the chitosan derivative compounds, and chitosan-guanidine compounds.

Claims

1. A method of making a compound of Formula (I), the method comprising:

2. The method of claim 1, wherein the acid is:

hydrochloric acid, hydrofluoric acid, trifluoroacetic acid (TFA) or sulfuric acid.

3. The method of claim 1, wherein the method proceeds for between 2 and 24 hours.

4. The method of claim 1, wherein the compound of Formula (IV) is made by a method that comprises reacting a compound of Formula (V),

5. The method of claim 4, wherein the method further comprises addition of an activation reagent.

6. The method of claim 5, wherein the activation reagent is a N-hydroxysuccinimide.

7. The method of claim 4, wherein the coupling agent is a carbodiimide.

8. The method of claim 7, wherein the carbodiimide is N,N′

-dicyclohexylcarbodiimide (DCC), N,N′

-diisopropylcarbodiimide (DIC), or N-(3-Dimethylaminopropyl)-N′

-ethylcarbodiimide (EDC).

9. The method of claim 8, wherein the method takes place in the presence of a solvent.

10. The method of claim 9, wherein the solvent is an aqueous solution.

11. The method of claim 10, wherein the aqueous solution is acidic.

12. The method of claim 1, wherein the acid is an organic acid, acetic acid or hydrochloric acid.

13. The method of claim 11, wherein the pH of the aqueous solution is ≦

5.

14. The method of claim 9, wherein the solvent is an organic solvent.

15. The method of claim 14, wherein the organic solvent is methanol, dimethylsulfoxide or dimethylformamide.

18. The method of claim 1 or 16, wherein the compound of Formula (I) is purified by dialysis.

19. The method of claim 1, wherein the method comprises the use of ultra-filtration, dialysis filtration (UFDF), or transverse flow filtration (TFF) in-line systems.

16. A method of making a compound of Formula (I) in a single reaction vessel, the method comprising:

17. The method of claim 16, wherein the compound of Formula (V) and activation agent are added to the reaction with Formula (III) before the coupling agent.