Crosslinking hyaluronan and chitosanic polymers

• US 20050271729A1
• Filed: 05/19/2005
• Published: 12/08/2005
• Est. Priority Date: 05/20/2004
• Status: Active Grant

• Current Assignee: Menlo Worldwide LLC (XPO, Inc.)
• Original Assignee: Menlo Worldwide LLC (XPO, Inc.)
• Inventors: Wang, Wei
• Granted Patent: US 7,651,702 B2
• Time in Patent Office: Days
• US Class Current: 424/488
• CPC Class Codes: A61K 2800/57 Compounds covalently linked to a(n inert) carrier molecule, e.g. conjugates, pro-fragrances
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 8/735 Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
• CPC Class Codes: A61K 8/736 Chitin; Chitosan; Derivatives thereof
• 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: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• 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: C08B 37/0072 Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
• CPC Class Codes: C08J 2305/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08J 3/246 Intercrosslinking of at least two polymers
• CPC Class Codes: C08L 2666/26 Natural polymers, natural resins or derivatives thereof according to C08L1/00 - C08L5/00, C08L89/00, C08L93/00, C08L97/00 or C08L99/00
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

Materials and methods related to crosslinking hyaluronan and chitosan are described herein. Also described are products of the described methods.

Claims

1. A method of covalently linking hyaluronan and chitosan, the method comprising mixing a solution of hyaluronan and chitosan at a pH of at least 7.2 in the presence of a water soluble carbodiimide.

2. A method as claimed in claim 1, comprising the steps of:

(a) providing a solution of hyaluronan with a pH of 4.0 to 4.3;

(b) adding a solution of chitosan such that the resultant mixed solution has a pH of at least 7.2; and

(c) adding a water soluble carbodiimide.

3. A method as claimed in claim 1, further comprising the step of:

(d) washing the product of (c) with water or PBS.

4. A method as claimed in claim 1, wherein the pH of the mixed solution is 7.2 to 7.8.

5. A method as claimed in claim 1, further comprising the steps of:

(d) stirring the solution formed in (c) for 3 hours at room temperature; and

(e) washing the resultant hydrogel in PBS.

6. A method as claimed in claim 1, further comprising the steps of:

(d) stirring the solution formed in (c) for 3 hours at room temperature;

(e) washing the resultant hydrogel in PBS or water; and

(f) freeze-drying the hydrogel.

7. A method as claimed in claim 1, further comprising the steps of:

(d) stirring the solution formed in (c) for 30 minutes at room temperature;

(e) casting the solution into a desired form and allowing it to dry; and

(f) washing the resultant film with water or PBS.

8. A method as claimed in claim 1, wherein the water soluble carbodiimide is 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide methiodide or 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), or a derivative thereof.

9. A method as claimed in claim 1, wherein the pH of the mixed solution is 7.2 to 7.5.

10. A product comprising hyaluronan cross linked to chitosan formed by the method of claim 1.

11. The product as claimed in claim 10, wherein the product is for pharmaceutical or cosmetic use.

12. The product as claimed in claim 10, wherein the product is for use in medicine or surgery.

13. The product as claimed in claim 10, wherein the product is for delivery of anti-inflammatory agents, antibiotics, analgesics, anaesthetics, wound healing promoters, cytostatic agents, immunostimulants, immunosuppressants, or antivirals.

14. The product as claimed in claim 13, wherein the product is for the delivery of an anaesthetic.

15. The product as claimed in claim 14, wherein the anaesthetic is lidocaine.