Cross-linked gels of hyaluronic acid and products containing such gels

• US 4,605,691 A
• Filed: 07/18/1985
• Issued: 08/12/1986
• Est. Priority Date: 12/06/1984
• Status: Expired due to Term

• Current Assignee: Genzyme Biosurgery Corporation (Sanofi )
• Original Assignee: Biomatrix, Inc. (Sanofi )
• Inventors: Balazs, Endre A., Leshchiner, Adolf
• Primary Examiner(s): GRIFFIN, RONALD
• Application Number:
  US06/755,976
• Time in Patent Office: 390 Days
• Field of Search: 536/4.1, 524/27
• US Class Current: 524/27
• 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 8/042 Gels
• CPC Class Codes: A61K 8/73 Polysaccharides
• CPC Class Codes: A61K 8/731 Cellulose; Quaternized cellulose derivatives
• CPC Class Codes: A61K 8/735 Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• 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: C08L 2666/02 Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

Disclosed are cross-linked gels of hyaluronic acid, alone or mixed with other hydrophilic polymers and containing various substances or covalently bonded low molecular weight substances and processes for preparing them. These products are useful in numerous applications including cosmetic formulations and as drug delivery systems.

Claims

1. A method of preparing a cross-linked gel of hyaluronic acid comprising subjecting sodium hyaluronate in a dilute aqueous alkaline solution at a pH of not less than about 9 to a cross-linking reaction with divinyl sulfone at about 20°

C.

2. A method according to claim 1 wherein sodium hyaluronate has a molecular weight of about 50,000 to about 8×

10⁶.

3. A method according to claim 1 wherein the concentration of sodium hyaluronate in the reaction mixture is 1-8% by weight.

4. A method according to claim 1 wherein the ratio of the sodium hyaluronate to divinyl sulfone is from 15:

1 to 1;

5 by weight.

5. A method according to claim 1 and further comprising adding an alkali metal chloride, sulfate, phosphate or acetate to the reaction mixture in an amount sufficient to provide up to about 20% by weight concentration in the mixture.

6. A cross-linked gel of hyaluronic acid produced by the method according to claim 1.