Biopolymers modified with superoxide dismutase mimics

• US 20040116332A1
• Filed: 11/05/2003
• Published: 06/17/2004
• Est. Priority Date: 05/27/1999
• Status: Active Grant

• Current Assignee: Pharmacia Corporation (Pfizer Inc.)
• Original Assignee: Pharmacia Corporation (Pfizer Inc.)
• Inventors: Joardar, Saikat, Udipi, Kishore, Ornberg, Richard L., Riley, Dennis P., Brethauer, Kerry, Forster, Denis, Henke, Susan, Thurmond, Kenneth B.
• Granted Patent: US 7,004,976 B2
• Time in Patent Office: Days
• US Class Current: 514/6
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 31/042 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: C08B 15/00 Preparation of other cellulose derivatives or modified cellulose , e.g. complexes
• CPC Class Codes: C08B 15/05 Derivatives containing elements other than carbon, hydrogen, oxygen, halogens or sulfur esters or phosphorous acids C08B5/00
• CPC Class Codes: C08B 37/00 Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof cellulose D21; microbiological processes C12P
• CPC Class Codes: C08B 37/003 Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
• 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: C08G 18/10 Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
• CPC Class Codes: C08G 18/3228 acyclic
• CPC Class Codes: C08G 18/4854 Polyethers containing oxyalkylene groups having four carbon atoms in the alkylene group
• CPC Class Codes: C08G 18/6685 with compounds of group C08G18/3225 or polyamines of C08G18/38
• CPC Class Codes: C08G 18/718 containing silicon
• CPC Class Codes: C08G 18/73 acyclic
• CPC Class Codes: C08H 1/06 derived from horn, hoofs, hair, skin or leather
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

This invention provides modified biopolymers comprising biopolymers attached to at least one non-proteinaceous catalyst capable of dismutating superoxide in the biological system or precursor ligand thereof. 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 biopolymer comprising a biopolymer chosen from the group consisting of chitin, chitosan, cellulose, methyl cellulose, hyaluronic acid, keratin, fibroin, collagen, elastin, and saccharide polymers attached to at least one non-proteinaceous catalyst capable of dismutating superoxide in the biological system or precursor ligand thereof.

2. The modified biopolymer 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:

3. The modified biopolymer of claim 2, wherein the biopolymer is hyaluronic acid.

4. The modified biopolymer of claim 2, wherein the biopolymer is an ester of hyaluronic acid.

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

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

7. A thread comprising the modified biopolymer of claim 4.

8. A polymeric matrix structure comprising the modified biopolymer of claim 4.

9. A nerual growth guide channel comprising the modified biopolymer 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 biopolymer of claim 2, 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 biopolymer 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 biopolymer of claim 2, wherein the non-proteinaceous catalyst capable of dismutating superoxide is chosen from the group consisting of:

15. A pharmaceutical composition comprising the modified biopolymer of claim 1 and a pharmaceutically acceptable carrier or diluent.

16. A pharmaceutical composition comprising the compound of claim 13 and a pharmaceutically acceptable carrier or diluent.

18. A method for treating joint pain in a subject in need thereof comprising administering to the subject the pharmaceutical composition of claims 15, 16, or 17.

19. A method for treating osteoarthritis in a subject in need thereof comprising administering to the subject the pharmaceutical composition of claims 15, 16, or 17.

20. A method for treating inflammation in a subject in need thereof comprising administering to the subject the pharmaceutical composition of claims 15, 16, or 17.

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

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

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

14. Modified hyaluronic acid prepared by reaction of hylauronic acid with a non-proteinaceous catalyst capable of dismutating superoxide having the structure:

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