Compositions and methods for systemic inhibition of cartilage degradation

Abstract

Methods and compositions for inhibiting articular cartilage degradation. The compositions preferably include multiple chondroprotective agents, including at least one agent that promotes cartilage anabolic activity and at least one agent that inhibits cartilage catabolism. The compositions may also include one or more pain and inflammation inhibitory agents. The compositions may be administered systemically, such as to treat patients at risk of cartilage degradation at multiple joints, and suitably may be formulated in a carrier or delivery vehicle that is targeted to the joints. Alternatively the compositions may be injected or infused directly into the joint.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] The present application is a continuation of copending U.S. patent application Ser. No. 10 / 356,649, filed Jan. 21, 2003, which claims the benefit of U.S. Provisional Application No. 60 / 353,552 filed Feb. 1, 2002 and is a continuation-in-part of U.S. application Ser. No. 10 / 031,546 filed Jan. 18, 2002, which is a U.S. National phase of International Application No. PCT / US00 / 19864 filed Jul. 21, 2000 designating the United States, which claims priority from U.S. Provisional Application No. 60 / 144,904 filed Jul. 21, 1999, and also is a continuation-in-part of U.S. application Ser. No. 09 / 839,633 filed Apr. 20, 2001, which is a continuation-in-part of International Application No. PCT / US99 / 26330 filed Nov. 5, 1999 designating the United States, which claims priority from U.S. Provisional Application No. 60 / 107,256 filed Nov. 5, 1998, and of International Application No. PCT / US99 / 24625 filed Oct. 20, 1999 designating the United States, which...

AI Technical Summary

Benefits of technology

The present invention provides methods and compositions for reducing or preventing damage to articular cartilage in joints by administering a combination of metabolically active chondroprotective agents that act on different molecular targets. The agents can include antagonists of receptors for interleukin-1 family of proteins, antagonists of tumor necrosis factor receptors, agonists of insulin-like growth factors, agonists of transforming growth factor-β superfamily, inhibitors of matrix metalloproteinases, inhibitors of cyclooxygenase-2, inhibitors of p38 MAP kinase, inhibitors of nitric oxide synthase, inhibitors of protein kinase C, inhibitors of protein tyrosine kinase, inhibitors of protein kinase B, inhibitors of protein kinase A, inhibitors of protein SH2 domains, and other growth factors. The combination of agents can provide both anti-inflammatory and anabolic effects, promoting cartilage matrix synthesis and inhibiting degradation.

Problems solved by technology

Although various therapeutic approaches may provide relief of symptoms, no therapeutic regimen has been proven to retard progression of articular cartilage degradation.

The progressive deterioration and loss of articular cartilage leads to an irreversible impairment of joint motion.

Cartilage destructive processes may also be associated with or initiated by surgical procedures of the joint.

Conventional physiologic irrigation fluids do not provide analgesic, anti-inflammatory or anti-cartilage degradation effects.

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