Carbohydrate crosslinker

Patent metadata

Field	Value
Publication number	US-11530301-B2
Application number	US-201616066810-A
Country	US
Kind code	B2
Filing date	Dec 28, 2016
Priority date	Dec 29, 2015
Publication date	Dec 20, 2022
Grant date	Dec 20, 2022

Abstract

The invention relates to a hydrogel product comprising glycosaminoglycan molecules as the swellable polymer, wherein the glycosaminoglycan molecules are covalently crosslinked via crosslinks comprising a spacer group selected from the group consisting of di-, tri-, tetra-, and oligosaccharides.

First claim

The invention claimed is:

1. A process of preparing a hydrogel product comprising crosslinked hyaluronic acid (HA) molecules, the process comprising:
(a) activating carboxyl groups on the HA molecules with a coupling agent to form activated HA molecules;
(b) crosslinking the activated HA molecules via their activated carboxyl groups using diaminotrehalose to obtain crosslinked HA molecules; and
(c) hydrolyzing ester bonds in the crosslinked HA molecules via alkaline hydrolysis to obtain a hydrogel product having less than 50% non-crosslinked HA molecules by weight of the hydrogel product, and
wherein the crosslinked HA molecules are free from synthetic non-carbohydrate structures and synthetic non-carbohydrate linkers.

2. The process according to claim 1 , wherein the crosslinking provides amide bonds between HA molecules and crosslinkers.

3. The process according to claim 1 , wherein the coupling agent is a triazine-based coupling reagent.

4. The process according to claim 1 , wherein hydrolyzing the ester bonds comprises swelling the crosslinked HA molecules in an alkaline solution for at least 1 hour.

5. The process according to claim 4 , further comprising:
(d) neutralizing the crosslinked HA molecules to a neutral pH;
(e) precipitating the neutralized crosslinked HA molecules;
(f) drying the precipitated crosslinked HA molecules; and
(g) swelling the dried crosslinked HA molecules in a phosphate buffer.

6. The process according to claim 1 , wherein (a) and (b) occur simultaneously.

7. The process according to claim 4 , wherein the alkaline solution comprises a hydroxide.

8. The process according to claim 1 , wherein less than 20% by weight of the hydrogel product obtained in (c) comprises HA molecules that are not crosslinked.

9. The process according to claim 1 , wherein the crosslinked HA molecules are in the form of gel particles.

10. The process according to claim 9 , wherein the gel particles are 0.01 mm to 1 mm in size.

11. The process according to claim 1 , wherein the HA molecules, prior to crosslinking, have a molecular weight of about 1,000 kDa.

Assignees

• Galderma Sa
• Galderma Holding SA

Inventors

• Mojarradi Hotan
• Olsson Johan
• Harris Craig Steven
• Boiteau Jean-Guy
• Gerfaud Thibaut
• Tomas Loïc

Classifications

• A61K9/0019

  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 title

• C08J2305/08

  Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof · CPC title

• C08B37/0069 Primary

  Chondroitin-4-sulfate, i.e. chondroitin sulfate A; Dermatan sulfate, i.e. chondroitin sulfate B or beta-heparin; Chondroitin-6-sulfate, i.e. chondroitin sulfate C; Derivatives thereof · CPC title

• C07C269/06

  by reactions not involving the formation of carbamate groups · CPC title

• C08J3/075 Primary

  Macromolecular gels · CPC title