Methods for using macrocyclic lactone compounds as multidrug...

A - Human Necessities – 61 – K

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A61K 31/365 (2006.01) A61K 45/06 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2289086

This invention describes methods for increasing the toxicity of a cytostatic hydrophobic chemotherapeutic agent against resistant tumor cells which comprise administering to a mammal an effective amount of a multidrug resistant reversing agent, wherein the multidrug resistant reversing agent is a macrocyclic lactone compound. Examples of macrocyclic lactone compounds useful in the present invention include, but are not limited to, the LL-F28249.alpha.-.lambda. series, the 23- oxo or 23-imino derivatives thereof, the avermectings, the 22,23-dihydro derivatives thereof and the milbemycins. Compositions comprising the macrocyclic lactone compounds and the chemotherapeutic agents are also described herein.

Cette invention concerne des procédés permettant d'accroître la toxicité d'un agent de chimiothérapie hydrophobe et cytostatique contre les cellules cancéreuses résistantes. Ce procédé consiste à administrer à un mammifère une quantité efficace d'un agent d'inversion de la résistance aux médicaments polyvalents, agent qui consiste en un composé de lactone macrocyclique. Parmi les exemples de composés de lactone macrocycliques utiles et faisant l'objet de cette invention, on peut citer la série LL-F28249 alpha - lambda , les dérivés 22-oxo ou 23-imino de celle-ci, les avermectines, les dérivés 22,23-dihydro de celles-ci ainsi que les milbémycines. Cette invention concerne également des compositions comprenant ces composés de lactone macrocycliques, ainsi que des agents de chimiothérapie.

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