Polymeric micelle complexes of low molecular weight...

A - Human Necessities – 61 – K

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Details

A61K 47/48 (2006.01) A61K 9/51 (2006.01) A61K 33/24 (2006.01) A61K 45/06 (2006.01) A61K 47/18 (2006.01) A61K 47/32 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2489259

The present invention relates to polymeric antitumor agents in which polymeric complex micelle structures are formed by intermolecular binding or mutual interaction between styrene maleic acid copolymer (SMA) and a low molecular antitumor agent which is an anthracyclin drug such as pirarubicin, doxorubicin, epirbicin, daunorbicin, aclarubicin, or alkaloid antitumor agent such as cis-platinum or taxol. These polymeric micelle antitumor agents may improve selective accumulation of drugs to cancer tissue for improved antitumor effect, while concentrating less at normal organs or tissues, so that a lesser adverse effect may be accomplished. These polymeric antitumor agents may be prepared by dissolving SMA and a low molecular antitumor agent in aqueous solution, then in the presence of aqueous soluble carbodiimide, amino acids, or polyamine, adjusting pH to form micelle complexes, and separating and recovering the polymeric micelle component.

L'invention concerne un agent antitumeur de type polym­re contenant une structure ~ complexe de polym­re et de micelle form~e en r~sultat ~ une liaison ou une interaction intermol~culaire entre un agent antitumeur ~ faible teneur mol~culaire et un agent antitumeur anthracycline (par exemple, pirarubicine, doxorubicine, ~pirubicine, daunorubicine ou aclarubicine), cisplatine ou un agent antitumeur alcalo~de (par exemple taxol), et un copolym­re styr­ne/acide mal~ique (SMA). Cet agent antitumeur de type polym­re exerce d'excellents effets notamment en am~liorant l'accumulation s~lective de m~dicament sur une r~gion tumorale de mani­re ~ augmenter l'efficacit~ antitumeur tout en ~vitant l'accumulation sur des organes et des tissus normaux de mani­re ~ en r~duire les effets secondaires. Cet agent antitumeur de type polym­re peut Útre obtenu par un proc~d~ consistant ~ dissoudre le SMA ainsi qu'un agent antitumeur dans un solvant ~ base aqueuse, ~ effectuer un ajustement du pH en la pr~sence de carbodiimide soluble, d'un acide amin~ ou d'une polyamine de mani­re ~ former une structure ~ complexe de micelle et ~ s~parer puis ~ r~cup~rer la composante polym­re.

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