Method of preventing adhesion between body tissues, means for preventing such adhesion, and process for producing said means

• US 4,886,787 A
• Filed: 01/23/1986
• Issued: 12/12/1989
• Est. Priority Date: 07/23/1984
• Status: Expired due to Term

• Current Assignee: Pharmacia AB (Pharmacia Corp.)
• Original Assignee: Pharmacia AB (Pharmacia Corp.)
• Inventors: de Belder, Anthony N., Malson, Thomas
• Primary Examiner(s): Griffin, Ronald W.
• Assistant Examiner(s): Peselev, Elli
• Application Number:
  US06/847,171
• Time in Patent Office: 1,419 Days
• Field of Search: 536/55.1, 536/55.2, 536/112, 536/56, 536/58, 536/106, 514/57, 514/54, 514/59, 514/60, 514/62
• US Class Current: 514/57
• CPC Class Codes: A61L 31/042 Polysaccharides
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• 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 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

The invention is concerned with a method of preventing adhesions or accretions of body tissues inter se by means of employing a degradable gel of a crosslinked carboxyl-containing polysaccharide. The invention also covers a gel product to be used for this purpose, and a process for preparing said product by means of crosslinking with a di- or polyfunctional expoxide at a pH of from 2 to 5.

Claims

1. A gel of sodium hyaluronate or hylaluronic acid cross-linked with a di- or polyfunctional expoxide at a pH within the range of from 2 to 5.

2. A process for preparing a gel consisting of a cross-linked carboxyl-containing polysaccharide selected from the group consisting of carboxymethyl dextran, carboxymethyl starch, carboxymethyl cellulose and glucosminoglycans formed by reacting the polysaccharide at a pH of from 2 to 5 with a bi- or polyfunctional epoxide in the presence of an acid.

3. A process according to claim 2 wherein said pH is in the range of 2.5 to 4.5.

4. The process according to claim 2 in which said acid is selected from the group consisting of inorganic acids, organic acids and hydrogen salts thereof.

5. A process according to claim 2 in which said acid is selected from the group consisting of hydrochloric, sulfuric, nitric or phosphoric acid, or a hydrogen salt thereof.

6. A process according to claim 2 in which said acid is selected from among (a) lower aliphatic mono- or polycarboxylic acids or (b) aromatic mono- or polycarboxylic acids and sulfonic acids, or (c) hydrogen salts of acids belonging to group (a) or (b).

7. A process according to claim 2 in which said acid is selected from the group consisting of formic, acetic, propionic, lactic, trichloroacetic, succinic, benzoic, salicylic and p-toluene sulfonic.

8. A process according to claim 2 wherein said polysaccharide is hyaluronic acid.

9. A process according to claim 2 wherein said polysaccharide is sodium hyaluronate.

10. A process according to claim 4 wherein said polysaccharide is sodium hyaluronate.

11. A process according to claim 5 wherein said polysaccharide is sodium hyaluronate.

12. A method of preventing adhesions or accretions of body tissues in which one or more pieces of a gel of a crosslinked carboxylgroup-containing polysaccharide selected from the group consisting of carboxymethyl dextran, carboxymethyl starch, carboxymethyl cellulose and glucosaminoglycans, during the course of a surgical operation, is introduced into the interstices between the tissues to be maintained in a separated condition;

the gel being formed by reacting said polysaccharide with a bi- or polyfunctional epoxide.

13. A method according to claim 12 wherein the gel is form®

d by reacting the polysaccharide with a bi- or polyfunctional epoxide at a pH within the range of from 2 to 5.

14. A method according to claim 13 wherein said pH is from 2.5 to 4.5.

15. A method according to claim 12 wherein said polysaccharide is sodium hyaluronate.

16. A method according to claim 13 wherein said polysaccaride is sodium hyaluronate.