Pyruvate ester composition and method of use for...

A - Human Necessities – 61 – K

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A61K 31/235 (2006.01) A61K 31/22 (2006.01) A61K 33/00 (2006.01)

Patent

CA 2386461

A therapeutic composition comprising an alkyl, aralkyl, alkoxyalkyl, or carboxyalkyl ester of 2-ketoalkanoic acid and a component for inducing and stabilizing the enol resonance form of the ester at physiological pH values is disclosed. The composition of the invention further comprises a pharmaceutically acceptable carrier vehicle in which the enol resonance form of the ester is stabilized at physiological pH values. Formulations containing the compositions of the invention permit the successful use of 2-ketoalkanoic acid esters, e.g., pyruvic acid esters, to treat, e.g., ischemic events, shock, organ reanimation, resuscitation and other recognized pyruvate- effective treatments. The compositions of the inventions are also useful in a process for preserving organ parts, organs or limbs removed from a living mammal and in need of preservation, e.g., for later transplantation to an organ recipient. The figure shows the structures of the preferred 2- ketoalkanoic acid esters in the composition of the invention.

L'invention se rapporte à une composition thérapeutique comportant un alkyl-, aralkyl-, alkoxyalkyl- ou carboxyalkyl-ester d'acide 2-cétoalcanoique et un composant destiné à induire et stabiliser la forme à résonance énol de l'ester pour des valeurs de pH physiologiques. Cette composition comporte un excipient pharmaceutiquement acceptable dans lequel la forme à résonance énol de l'ester est stabilisée pour les valeurs de pH physiologiques. L'invention se rapporte à des formulations contenant ces compositions et permettant d'utiliser avec succès des esters d'acide 2-cétoalcanoique, par exemple des esters d'acide pyruvique, pour traiter, entre autres, les accidents ischémiques cérébraux, les commotions électriques, et permettre la réanimation et d'autres traitements à efficacité reconnue à base de pyruvate. Les compositions de cette invention s'avèrent également utiles s'agissant de conserver des parties d'organes, des organes ou des membres prélevés sur un mammifère vivant et devant être conservés aux fins, par exemple, d'une transplantation ultérieure sur un receveur d'organe. La figure représente les structures des esters d'acide 2-cétoalcanoique préférés de la composition de l'invention.

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