Modified hyaluronic acid polymers

• US 20040110722A1
• Filed: 11/05/2003
• Published: 06/10/2004
• Est. Priority Date: 05/27/1999
• Status: Abandoned Application

• Current Assignee: Pharmacia Corporation (Pfizer Inc.)
• Original Assignee: Pharmacia Corporation (Pfizer Inc.)
• Inventors: Udipi, Kishore, Ornberg, Richard L., Riley, Dennis P., Brethauer, Kerry, Forster, Denis, Henke, Susan, Thurmond, Kenneth B., Joardar, Saikat
• Application Number:
  US10/702,764
• Publication Number:
  US 20040110722A1
• Time in Patent Office: Days
• US Class Current: 514/54
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: C07F 13/005 Compounds without a metal-carbon linkage
• CPC Class Codes: C07F 15/025 without a metal-carbon linkage
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

The present invention relates to hyaluronic acid polymers modified with non-proteinaceous catalysts for the dismutation of superoxide, and processes for making such materials. The invention further provides pharmaceutical compositions comprising the modified biopolymer and therapeutic methods comprising administering the modified biopolymer to a subject in need thereof.

Claims

1. A modified hylauronic acid polymer comprising hyaluronic acid bound to at least one non-proteinaceous catalyst capapble of dismutating superoxide in the biological system or precursor ligand thereof, wherein the modified hyaluronic acid polymer exhibits a lower molecular weight by size exclusion chromatography than unmodified hyaluronic acid.

2. The modified hyaluronic acid polymer of claim 1 wherein the modified hyaluronic acid does not demonstrate substantial loss of viscosity or molecular weight with free radical challenge when compared with unmodified hyaluronic acid.

3. The modified hyaluronic acid polymer of claim 1 wherein the non-proteinaceous catalyst capable of dismutating superoxide in the biological system is selected from the group consisting of manganese and iron chelates of pentaazacyclopentadecane compounds, which are represented by the following formula:

4. The modified hyaluronic acid polymer of claim 1, wherein the hyaluronic acid polymer is an ester of hyaluronic acid.

5. The modified hyaluronic acid polymer of claim 4, wherein the ester of hyaluronic acid polymer is chosen from the group consisting of total esters and partial esters.

6. The modified hyaluronic acid polymer of claim 4, wherein the ester of hyaluronic acid polymer is a benzyl ester.

7. A thread comprising the modified hyaluronic acid polymer of claim 4.

8. A polymeric matrix structure comprising the modified hyaluronic acid polymer of claim 4.

9. A nerual growth guide channel comprising the modified hyaluronic acid polymer of claim 4.

10. A method for in vivo regrowth of nerve tissue in a subject in need thereof comprising placement of the neural growth guide channel of claim 9 in the subject under conditions sufficient to stimulate regrowth of nerve tissue.

11. The modified hyalronic acid polymer of claim 1, wherein the non-proteinaceous catalyst capable of dismutating superoxide comprises a reactive moiety to provide a means for covalent conjugation to the unmodified biopolymer.

12. The modified hyaluronic acid polymer of claim 11, wherein the reactive moiety is chosen from the group consisting of amino, carboxyl, isocyanate, mercapto, hydroxy, silyl chloride, acid halide, halide, glycidyl, and substituted or unsubstituted alkenyl, alkynyl, and aryl.

13. The modified hyaluronic acid polymer of claim 3, wherein the non-proteinaceous catalyst capable of dismutating superoxide is chosen from the group consisting of:

14. A pharmaceutical composition comprising the modified hyaluronic acid polymer of claim 1 and a pharmaceutically acceptable carrier or diluent.

15. A method for treating joint pain in a subject in need thereof comprising administering to the subject the pharmaceutical composition of claim 14.

16. A method for treating osteoarthritis in a subject in need thereof comprising administering to the subject the pharmaceutical composition of claim 14.

17. A method for treating inflammation in a subject in need thereof comprising administering to the subject the pharmaceutical composition of claim 14.

18. The method of claim 15, wherein the pharmaceutical composition is administered to the subject by injection.

19. The method of claim 16, wherein the pharmaceutical composition is administered to the subject by injection.

20. The method of claim 17, wherein the pharmaceutical composition is administered to the subject by injection.