Water-insoluble derivatives of hyaluronic acid and their methods of preparation and use

• US 5,356,883 A
• Filed: 07/28/1992
• Issued: 10/18/1994
• Est. Priority Date: 08/01/1989
• Status: Expired due to Term

• Current Assignee: Anika Research Incorporated, The Research Foundation for The State University of New York (State University of New York)
• Original Assignee: Anika Research Incorporated, The Research Foundation for The State University of New York (State University of New York)
• Inventors: Prestwich, Glenn D., Kuo, Jing-Wen, Swann, David A.
• Primary Examiner(s): Robinson, Douglas W.
• Assistant Examiner(s): PRATS, FRANCISCO CHANDLER
• Application Number:
  US07/920,698
• Time in Patent Office: 812 Days
• Field of Search: 514/777, 514/54, 424/7.1, 424/488, 536/4.1, 252/315.3
• US Class Current: 514/54
• 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 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 47/6903 the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel
• 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: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61L 15/28 Polysaccharides or their derivatives A61L15/225 takes precedence
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 31/042 Polysaccharides
• 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

This invention describes a method for preparing water-insoluble biocompatible gels, films and sponges by reacting hyaluronic acid, or a salt thereof, with a carbodiimide in the absence of a nucleophile or a polyanionic polysaccharide. The water-insoluble gels, films and sponges of this invention may be used as surgical aids to prevent adhesions of body tissues and as drug delivery vehicles.

Claims

1. A method of separating healing tissues nd maintaining said separation during the healing process after surgery, said method comprising introducing into a surgical site, either during surgery or post-operatively, a water insoluble biocompatible gel comprising a modified hyaluronic acid in which at least about 5% of carboxyl functionalities have been derivatized, and wherein essentially all of the derivatized functionalities are O-acyl or N-acyl ureas, said gel causing said separation of the healing tissues to be established and maintained post-operatively for a period of at least about seven days.

2. A method of preventing post-operative adhesion between healing tissues during the healing process, said method comprising introducing into a surgical site, either during surgery or post-operatively, a water insoluble biocompatible gel comprising a modified hyaluronic acid in which at least about 5% of or more carboxyl functionalities have been derivatized, and wherein essentially all of the derivatized functionalities are O-acyl or N-acyl ureas, said gel preventing said adhesion of the healing tissues to be established and maintained post-operatively for a period of at least about 7 days.

3. A method of separating healing tissues and maintaining said separation during the healing process after surgery, said method comprising introducing into a surgical site, either during surgery or post-operatively, a biocompatible film comprising a modified hyaluronic acid in which at least about 5% of carboxyl functionalities have been derivatized, and wherein essentially all of the derivatized functionalities are O-acyl or N-acyl ureas, said film causing said separation of the healing tissues to be established and maintained post-operatively for a period of at least about seven days.

4. A method of preventing post-operative adhesion between healing tissues during the healing process, said method comprising introducing into a surgical site, either during surgery or post-operatively, a biocompatible film comprising modified hyaluronic acid in which at least about 5% of carboxyl functionalities have been derivatized, and wherein essentially all of the derivatized functionalities are O-acyl or N-acyl ureas, said film preventing said adhesion of the healing tissues to be established and maintained post-operatively for a period of at least about 7 days.

5. A method of separating healing tissues and maintaining said separation during the healing process after surgery, said method comprising introducing into a surgical site, either during surgery or post-operatively, a biocompatible sponge comprising a modified hyaluronic acid in which at least about 5% of carboxyl functionalities have been derivatized, and wherein essentially all of the derivatized functionalities are O-acyl or N-acyl ureas, said sponge causing said separation of the healing tissues to be established and maintained post-operatively for a period of at least about seven days.

6. A method of preventing post-operative adhesion between healing tissues during the healing process, said method comprising introducing into a surgical site, either during surgery or post-operatively, a biocompatible sponge comprising a modified hyaluronic acid in which at least about 5% of carboxyl functionalities have been derivatized, and wherein essentially all of the derivatized functionalities are O-acyl or N-acyl ureas, said sponge preventing said adhesion of the healing tissues to be established and maintained post-operatively for a period of at least about 7 days.