Compositions and methods of reducing tissue levels of drugs...

A - Human Necessities – 61 – K

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A61K 31/167 (2006.01) A61K 31/513 (2006.01) A61K 31/704 (2006.01) C07H 15/252 (2006.01)

Patent

CA 2658313

This invention is in the field of chemical restructuring of pharmaceutical agents known to cause tissue toxicity as a side effect, by producing their orotate derivatives. More particularly, it concerns orotate derivatives of the anthracyclines, doxorubicin and daunorubicin, that are found to reduce levels of the pharmaceutical agent in noncancerous tissues. There orotate derivatives are equally efficacious in inhibiting the SCCAKI-I kidney tumor in animals and the reduction in the heart tissue of doxorubicin compared with doxorubicin HC1 suggests a reduction in toxicity induced by free radical generation by the anthracyclines.

La présente invention concerne le domaine de la restructuration chimique d'agents pharmaceutiques connus pour leur effet secondaire de toxicité tissulaire, par la production de leurs dérivés d'orotate. Plus précisément, la présente invention concerne des dérivés d'orotate des anthracyclines, de la doxorubicine et de la daunorubicine, qui se sont avérés réduire les taux de l'agent pharmaceutique dans les tissus non cancéreux. Leurs dérivés d'orotate sont aussi efficaces pour inhiber la tumeur du rein SCCAKI-I chez les animaux, et la baisse dans le tissu cardiaque de la doxorubicine par rapport à la doxorubicine HC1 semble indiquer une baisse de la toxicité induite par la génération de radicaux libres par les anthracyclines.

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