Single phase gels for the prevention of adhesions

• US 6,521,223 B1
• Filed: 02/14/2000
• Issued: 02/18/2003
• Est. Priority Date: 02/14/2000
• Status: Expired due to Term

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Genzyme Corporation (Sanofi )
• Inventors: Miller, Robert J., Calias, Pericles
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): FUBARA, BLESSING M
• Application Number:
  US09/503,544
• Time in Patent Office: 1,100 Days
• Field of Search: 424/78.08, 424/400, 424/422, 424/423, 524/29, 514/781
• US Class Current: 424/78.08
• 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: A61L 31/042 Polysaccharides
• CPC Class Codes: C08B 11/20 Post-etherification treatments of chemical or physical type, e.g. mixed etherification in two steps, including purification
• CPC Class Codes: C08B 15/005 Crosslinking of cellulose derivatives
• CPC Class Codes: C08B 31/006 Crosslinking of derivatives of starch
• CPC Class Codes: C08B 37/0072 Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates

Abstract

Single phase gels for preventing the formation of surgical adhesions are disclosed. The gels are prepared by reacting an aqueous solution of a polyanionic polysaccharide, such as hyaluronic acid or carboxymethyl cellulose, with divinyl sulfone, to form a gel, the solution is neutralized, and a solid is precipitated from the solution. The solid can be redissolved in water to form a gel having properties which can be modified to suit a particular application.

Claims

1. A method for preparing a water insoluble biocompatible composition comprising

reacting a polyanionic polysaccharide with divinyl sulfone in an aqueous solution to form a gel, neutralizing the pH of the solution, and precipitating a solid from the neutral solution.

2. The method of claim 1, wherein the polyanionic polysaccharide is selected from the group consisting of hyaluronic acid, sodium hyaluronate, potassium hyaluronate, magnesium hyaluronate, calcium hyaluronate, carboxymethylcellulose, carboxymethyl amylose and a mixture of hyaluronic acid and carboxymethylcellulose.

3. The method of claim 1 or 2, wherein the solid precipitated from the solution is then rehydrated to form a gel.

4. The method of claim 3, wherein the rehydrated gel is then subjected to heat treatment.

5. The method of claim 4, wherein the rehydrated gel is heated to a temperature in the range from about 100°

C. to about 150°

C.

6. The method of claim 2, wherein the polyanionic polysaccharide is hyaluronic acid.

7. The method of claim 6, wherein the molar ratio of divinyl sulfone:

hyaluronic acid is from about 0.1;

1 to about 1;

1.

8. The method of claim 7, wherein the molar ratio of divinyl sulfone:

hyaluronic acid is from about 0.2;

1 to about 0.6;

1.

9. A single phase gel product formed by the method of claim 2, 6, 7 or 8.

10. The gel product of claim 9, which is sterilized.

11. The gel product of claim 9, which further comprises a drug.

12. The gel product of claim 10, which further comprises a drug.

13. A method for the inhibition of adhesions in a subject comprising applying the gel product of claim 9 to a region between two tissue surfaces to be separated during the healing process following surgery.

14. The method of claim 13, wherein the subject is a human patient.

15. The method of claim 14, wherein the surgery is selected from the group consisting of abdominal surgery, pelvic surgery, gynecological surgery, orthopedic surgery, and cardiac surgery.