Polysaccharide crosslinking, hydrogel preparation, resulting polysaccharide(s) and hydrogel(s), uses thereof

• US 20030148995A1
• Filed: 01/13/2003
• Published: 08/07/2003
• Est. Priority Date: 07/19/2000
• Status: Active Grant

• Current Assignee: Allergan Industrie SAS (Abbvie Incorporated)
• Original Assignee: Laboratories D'Esthetique Appliquee
• Inventors: Piron, Estelle, Tholin, Raymonde
• Granted Patent: US 6,921,819 B2
• Time in Patent Office: Days
• US Class Current: 514/54
• CPC Class Codes: A61K 2800/91 Injection
• CPC Class Codes: A61K 8/042 Gels
• CPC Class Codes: A61K 8/735 Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: C08B 37/00 Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof cellulose D21; microbiological processes C12P
• 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 3/075 Macromolecular gels
• CPC Class Codes: C08J 3/24 Crosslinking, e.g. vulcanising, of macromolecules mechanical aspects B29C35/00; crosslinking agents C08K
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

The invention relates to a process for the crosslinking of polysaccharides. The process of the invention is a process for the crosslinking of at least one polymer selected from polysaccharides and their derivatives, under the action of at least one polyfunctional crosslinking agent, characterized in that said polyfunctional crosslinking agent is reacted with said polymer, in the solid state, during hydration. The invention is applied to the manufacture of hydrogels and gels that can be used, in particular, in plastic or cosmetic surgery.

Claims

1. A process for the crosslinking of at least one polymer selected from polysaccharides and their derivatives, under the action of at least one polyfunctional crosslinking agent, characterized in that said polyfunctional crosslinking agent is reacted with said polymer, in the solid state, during hydration.

2. The crosslinking process according to claim 1, characterized in that said polyfunctional crosslinking agent reacts with said solid polymer in basic solution.

3. The crosslinking process according to claim 1 or 2, characterized in that said polyfunctional crosslinking agent is an epoxide advantageously selected from 1,4-butanediol diglycidyl ether, 1,2-bis(2,3-epoxypropoxy)ethylene and 1-(2,3-epoxypropyl)-2,3-epoxycyclohexane.

4. The crosslinking process according to claim 3, characterized in that said polyfunctional crosslinking agent consists of 1,4-butanediol diglycidyl ether.

5. The crosslinking process according to any one of claims 1 to 4, characterized in that said polymer is selected from hyaluronic acid, its salts and their mixtures, and in that said polymer advantageously consists of sodium hyaluronate.

6. The crosslinking process according to claim 5, characterized in that said polymer is crosslinked, via its hydroxyl groups, by means of said crosslinking agent to a degree of crosslinking defined by a ratio

7. A process for the preparation of an injectable hydrogel of at least one crosslinked polymer selected from polysaccharides and their derivatives, characterized in that it comprises the crosslinking of said polymer according to any one of claims 1 to 6, followed by the swelling of said crosslinked polymer by hydration.

8. The preparative process according to claim 7, characterized in that it comprises:

the crosslinking of said polymer according to any one of claims 1 to 6;

the swelling of said crosslinked polymer;

the purification of said swollen crosslinked polymer; and

the sterilization, if necessary, of said purified swollen crosslinked polymer.

9. A crosslinked polymer obtainable by carrying out a crosslinking process according to any one of claims 1 to 6.

10. An injectable hydrogel obtainable by carrying out a preparative process according to claim 7 or 8.

11. A filling gel useful in plastic or cosmetic surgery, characterized in that it is based on a charged or uncharged hydrogel according to claim 10.

12. The filling gel according to claim 11, characterized in that it consists of a monophase hydrogel according to claim 10.