Method of using pyruvate and/or its derivatives for the...

A - Human Necessities – 61 – K

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A61K 31/19 (2006.01) A61K 31/195 (2006.01) A61K 31/22 (2006.01)

Patent

CA 2440480

This invention is directed to a method of using a therapeutic composition comprising a compound of an alpha-ketoalkanoic acid (pyruvate) and/or its derivatives for the treatment of cytokine-mediated inflammatory conditions. The compound is an alpha-ketoalkanoic acid, a physiologically acceptable salt of an alpha-ketoalkanoic acid, an ester of an alpha-ketoalkanoic acid, or an amide of an alpha-ketoalkanoic acid. A component for inducing and stabilizing the enol resonance form of the ester at physiological pH values is also disclosed. The cytokine-mediated inflammatory conditions are mediated by, for example, an "early" (Tumor Necrosis Factor (TNF), interleukin-1.beta.) or "late" (high mobility group B-1 (HMGB-1)) mediator of inflammation. Exemplary cytokine-mediated inflammatory conditions include, but are not limited to, local and systemic inflammation, inflammatory bowel disease (Crohn's disease and ulcerative colitis), rheumatoid arthritis, asthma (including status asthmaticus), sepsis or septic shock, also including inflammatory skin conditions, for example, psoriasis and eczema.

Cette invention porte sur un procédé d'utilisation d'une composition thérapeutique comprenant un composé d'un acide alpha-cétoalcanoïque (pyruvate) et/ou ses dérivés dans le traitement d'états inflammatoires induits par des cytokines. Le composé est un acide alpha-cétoalcanoïque, un sel de celui-ci acceptable d'un point de vue physiologique, un ester ou un amide de celui-ci. L'invention porte également sur un composant destiné à induire et à stabiliser la forme de résonance enol de l'ester à des valeurs physiologiques du pH. Les états inflammatoires induits par des cytokines sont induits, par exemple, par un inducteur d'inflammation <= précoce >= (Facteur de nécrose tumorale (TNF), l'interleukine-1.beta.) ou<= tardif >= (groupe de haute mobilité B-1 (HMGB-1)). Certains états inflammatoires induits par les cytokines sont, mais pas exclusivement, l'inflammation locale et systémique, l'affection intestinale inflammatoire (maladie de Crohn et colite ulcéreuse), l'arthrite rhumatoïde, l'asthme (y compris l'état de mal asthmatique), la septicémie ou le choc septique, et des états inflammatoires tels que le psoriasis et l'eczéma.

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