Methods of administering epothilone analogs for the...

A - Human Necessities – 61 – K

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A61K 31/425 (2006.01) A61K 9/00 (2006.01) A61K 31/427 (2006.01) A61K 47/02 (2006.01) A61K 47/10 (2006.01) A61K 47/12 (2006.01) A61K 47/44 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2434526

A process for formulating certain epothilone analogs for parenteral administration is disclosed wherein the analog is dissolved in a mixture of at least 50 % by volume tertiary-butanol in water, the mixture is lyophilized, the resulting lyophilized product is packaged in one vial with a sufficient amount of solvent comprising anhydrous ethanol and a suitable nonionic surfactant in a second vial. All steps are carried out with protection from light. In use, the contents of the second or diluent vial are added to the lyophilized product and mixed to constitute the epothilone analog and the resulting solution is diluted with a suitable diluent to produce a solution for intravenous injection containing the epothilone analog in a concentration of from about 0.1 mg/mL to about 0.9 mg/mL. A preferred surfactant is polyethoxylated castor oil and a preferred diluent is Lactated Ringer's Injection.

L'invention concerne un procédé pour la formulation de certains analogues de l'épothilone aux fins d'administration parentérale. L'analogue est dissous dans un mélange d'au moins 50 %, en volume, de butanol tertiaire et d'eau. Ce mélange est lyophilisé, et le produit lyophilisé résultant est conditionné dans un premier flacon. On conditionne dans un second flacon une quantité suffisante de solvant qui renferme de l'éthanol anhydre et un tensioactif non anionique approprié. Une protection contre la lumière est assurée pour la conduite de toutes les opérations. A l'utilisation, le contenu du second flacon (renfermant le diluant) est ajouté au produit lyophilisé, et le mélange du contenu des deux flacons donne un analogue de l'épothilone. On dilue la solution résultante avec un diluant approprié, pour donner une solution d'injection intraveineuse renfermant l'analogue considéré, selon une concentration comprise entre environ 0,1 mg/mL et environ 0,9 mg/mL. De préférence, le tensioactif est de l'huile de ricin polyéthoxylée et le diluant est un soluté injectable de Ringer au lactate.

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