Methods and compositions for remediation of disc herniation by modifying structure

• US 20070258941A1
• Filed: 05/01/2007
• Published: 11/08/2007
• Est. Priority Date: 05/02/2006
• Status: Abandoned Application

• Current Assignee: Brian E. Pfister
• Original Assignee: Brian E. Pfister
• Inventors: Pfister, Brian E.
• Application Number:
  US11/799,393
• Publication Number:
  US 20070258941A1
• Time in Patent Office: Days
• US Class Current: 424/78.270
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 31/718 Starch or degraded starch, e.g. amylose, amylopectin
• CPC Class Codes: A61K 31/722 Chitin, chitosan
• CPC Class Codes: A61K 31/785 Polymers containing nitrogen
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue

Abstract

A therapeutic method and compositions are provided that involve injection of a cation solution into extracellular matrix of a tissue. In the preferred embodiment, a percutaneous (performed through the skin) injection of a polylysine solution into the nucleus of a herniated disc is provided, to reduce intradiscal pressure.

Claims

1. A pharmaceutical composition for remediating a cartilage disease comprising an effective dose of a cationic compound in an effective dose, and a pharmaceutically acceptable salt or buffer.

2. The composition according to claim 1, wherein the compound is a polymer of a cationic monomer.

3. The composition according to claim 1, wherein the compound is a polymer of an amino acid.

4. The composition according to claim 3, wherein the amino acid is at least one selected from a group consisting of D-lysine, L-lysine, D-arginine, L-arginine, D-histidine, and L-histidine.

5. The composition according to claim 1, wherein the compound is at least one selected from the group consisting of a dextran, an arabinogalactan, a pullulan, a cellulose, an inulin, a chitosan, an ornithine polymer, a spermine polymer, a spermidine polymer, and polyethylenimine.

6. The composition according to claim 5, wherein the dextran is a branched poly-α

-D-glucoside.

7. The composition according to claim 5, wherein the arabinogalactan comprises D-galactose and L-arabinose.

8. The composition according to claim 5, wherein the arabinogalactan is produced by a plant, a fungus, or a bacterium.

9. The composition according to claim 5, wherein the pullulan comprises maltotriose.

10. The composition according to claim 9, wherein the pullulan is produced by Aureobasidium pullulans.

11. The composition according to claim 5, wherein the inulin comprises fructosyl oligosaccharides.

12. The composition according to claim 5, wherein the chitosan is produced by at least one selected from the group consisting of:

a fungus, an arthropod, or a marine invertebrate.

13. The composition according to claim 1, wherein the cationic compound is a protein.

14. The composition according to claim 13, wherein the protein is lysozyme.

15. The composition according to claim 3, wherein the polymer is at least about 2 kDa in average size.

16. The composition according to claim 15, wherein the polymer is at least about 300 kDa in size.

17. The composition according to claim 3, wherein the polymer is a polylysine, and the polylysine is about 100 kDa to about 300 kDa in size.

18. The composition according to claim 3, wherein the polymer is of sufficient size to bind to a plurality of proteoglycan molecules.

19. The composition according to claim 1, comprising a plurality of polycationic compounds selected for varying molecular weights, wherein a half-life of the compound in a cartilage is a function of the molecular weight.

20. The composition according to claim 1, further comprising a growth factor or an enzyme inhibitor such as a matrix metalloproteinase inhibitor.

21. The composition according to claim 20, wherein the growth factor is at least one selected from the group of a bone morphogenesis protein such as BMP-2 and BMP-7, an insulin like growth factor (IGF), a transforming growth factor (TGF), a growth differentiation factor (GDF) such as GDF-5, and a platelet-derived growth factor (PDGF).

22. The composition according to claim 20, wherein the growth factor or enzyme inhibitor is covalently bound to the compound.

23. A method for remediating a cartilage disease in a subject, the method comprising:

contacting the cartilage with a composition comprising a cationic compound; and

observing remediation of the cartilage disease in the subject.

24. The method according to claim 23, wherein the cartilage is an intervertebral disc.

25. The method according to claim 24, wherein the disc is herniated.

26. The method according to claim 23, wherein contacting the cartilage is injecting a solution of the composition.

27. The method according to claim 26, wherein injecting is percutaneous.

28. The method according to claim 23, wherein remediation is observing a reduction in at least one of disc height, back pain, sciatica, pinched nerve, extrusion, herniation, foot drop, and loss of ankle reflex.

29. The method according to claim 23, wherein the remediation is disc regeneration.

30. The method according to claim 23, wherein the compound is polylysine.

31. The method according to claim 30, wherein the polylysine comprises L-lysine.

32. The method according to claim 30, wherein the polylysine is a D- and L-heteropolymer.

33. The method according to claim 24, wherein the compound is at least one selected from the group consisting of a dextran, an arabinogalactan, a pullulan, a cellulose, an inulin, a chitosan, an alginate, an ornithine polymer, a spermine polymer, a spermidine polymer, and polyethylenimine.

34. A kit for treating a herniated disc, comprising a cationic compound, a container, and instructions for use in treating a herniated disc.

35. The kit according to claim 34, wherein the compound is present in a unit dose for administering by hypodermic intravertebral injection.