Pharmaceutical compositions for treating/preventing motor organ diseases

• US 8,395,037 B2
• Filed: 03/23/2006
• Issued: 03/12/2013
• Est. Priority Date: 03/23/2005
• Status: Active Grant

• Current Assignee: Mitsubishi Corporation, Stmarianna University School of Medicine
• Original Assignee: Mitsubishi Corporation, Stmarianna University School of Medicine
• Inventors: Yudoh, Kazuo
• Primary Examiner(s): ARNOLD, ERNST V
• Application Number:
  US11/909,264
• Publication Number:
  US 20090104280A1
• Time in Patent Office: 2,546 Days
• Field of Search: None
• US Class Current: 977/915
• CPC Class Codes: A61K 33/44 Elemental carbon, e.g. charcoal, carbon black
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Fullerene inhibited the decrease in cell proliferation ability of chondrocytes which is observed when cultured chondrocytes are treated with a cartilage degenerating factor (IL-1β or H₂O₂). Fullerene inhibited production of cartilage matrix-degrading enzymes (matrix metalloprotease (MMP)-1, 3 and 13) which is induced in cultured chondrocytes by cartilage degenerating factors. Fullerene restored the decrease in cartilage matrix (proteoglycan) synthesizing ability which is observed in treating cultured chondrocytes with cartilage degenerating factors. In an analysis using an osteoarthritis rabbit model, the progress of cartilage degeneration was reduced by administering fullerene. Moreover, the dynamic friction coefficient was decreased by adding fullerene to synovial fluid.

Claims

1. A method for treating cartilage degeneration, comprising intraarticularly administering in a subject in need thereof a pharmaceutically effective amount of at least one active ingredient selected from the group consisting of an un-substituted fullerene, a clathrate fullerene, a heterofullerene, a norfullerene, a homofullerene, a secofullerene, a fullerene polymer, a chemically modified fullerene selected from the group consisting of a hydrogenated fullerene, a fullerene substituted with a hydroxyl group, an amino group, or a carboxyl group, and a fullerene conjugated with polyethylene glycol or hyaluronic acid, and a salt thereof, wherein the dosage is 0.1 micro Molar to 100 micro Molar per affected part, and wherein the active ingredient induces cartilage matrix production.

2. The method of claim 1, wherein the active ingredient is C60 fullerene.

3. The method of claim 1, wherein the active ingredient is hydroxylated C60 fullerene.

4. The method of claim 1, wherein the cartilage degeneration is caused by oxidative stress.

5. The method of claim 1, wherein the cartilage degeneration is osteoarthritis.

6. The method of claim 1, wherein the active ingredient inhibits production of a cartilage matrix-degrading enzyme.

7. The method of claim 6, wherein the cartilage matrix-degrading enzyme is a matrix metalloprotease induced by a cartilage degenerating factor in a chondrocyte.

8. The method of claim 6, wherein the cartilage matrix-degrading enzyme is MMP-1, 3, and/or 13.

9. The method of claim 1, wherein the active ingredient induces cartilage matrix production which has been decreased by a cartilage degenerating factor in a chondrocyte.

10. The method of claim 1, wherein the cartilage matrix is proteoglycan and/or type II collagen.