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

• US 6,921,819 B2
• Filed: 07/16/2001
• Issued: 07/26/2005
• Est. Priority Date: 07/19/2000
• Status: Expired due to Term

• Current Assignee: Allergan Industrie SAS (Abbvie Incorporated)
• Original Assignee: Laboratories D'Esthetique Appliquee
• Inventors: Piron, Estelle, Tholin, Raymonde
• Primary Examiner(s): Wilson, James O.
• Assistant Examiner(s): WHITE, EVERETT NMN
• Application Number:
  US10/332,727
• Publication Number:
  US 20030148995A1
• Time in Patent Office: 1,471 Days
• Field of Search: 536/55.3, 536/55.1, 536/106, 536/124, 536/127
• US Class Current: 536/55.3
• 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 hyaluronic acid, its salts and their mixtures, 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 polymer in basic solution.

3. The cross linking process according to claim 1, 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 claim 1, characterized in that said polymer is crosslinked, via its hydroxyl groups, by means of a crosslinking agent to a degree of crosslinking defined by a ratio $R=\frac{\begin{array}{c}\mathrm{Total}\end{array}}{}$

 

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number⁢

 

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of⁢

 

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reactivegroups⁢

 

⁢

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crosslinking⁢

 

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agentTotal⁢

 

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number⁢

 

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of⁢

 

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disaccharide⁢

 

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units⁢

 

in⁢

 

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the⁢

 

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hyaluronic⁢

 

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acid⁢

 

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molecules

of between 0.10 and 0.50.

6. A process for the preparation of an injectable hydrogel of at least one crosslinked polymer selected from hyaluronic acid, its salts and their mixtures, characterized in that it comprises the crosslinking of said polymer according to claim 1, followed by the swelling of said crosslinked polymer by hydration.

7. A process for the preparation of an injectable hydrogel of at least one crosslinked polymer selected from hyaluronic acid, its salts and their mixtures, characterized in that it comprises:

a) the crosslinking of said polymer according to claim 1;

b) the swelling of said cross linked polymer;

c) the purification of said swollen crosslinked polymer; and

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

8. The process of claim 1 wherein the said polymer is sodium hyaluronate.