Pharmaceutical composition containing docetaxel-cyclodextrin inclusion complex and its preparing process

Abstract

A docetaxel inclusion complex having improved water-solubility (up to 5 mg/ml) and stability (stability constant Ka=2056M −1 -13051M −1 ), comprises docetaxel and hydroxypropyl-beta-cyclodextrin and/or sulfobutyl-beta-cyclodextrin in a ratio of 1:10-150. The method includes steps as follows: docetaxel dissolved in ethanol is added into water solution of cyclodextrin via stirring, until docetaxel is completely dissolved; said solution is filtered in 0.2-04 μm microporous membrane then ethanol is removed through reduced pressure to obtain the inclusion complex in a liquid form; or ethanol, followed by water is removed through reduced pressure, then dried to obtain the inclusion complex in a solid form.

We claim: 
     
         1 . A pharmaceutical composition comprising cyclodextrin/doectaxel inclusion, which consists of docetaxel, cyclodextrin and a pharmaceutically acceptable excipient, wherein the mass ratio of the docetaxel to cyclodextrin is 1:10˜150, the said cyclodextrin is hydroxypropyl-sulfobutyl-β-cyclodextrin or sulfobutyl-β-cyclodextrin or their mixture; the stability constant of the cyclodextrin/docetaxel inclusion is Ka=2056M −1 −13051M −1 . 
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein, the preparation method of said cyclodextrin/docetaxel inclusion pharmaceutical composition is as follows: a solution of docetaxel in ethanol is added dropwise to an aqueous solution of hydroxypropyl-sulfobutyl-β-cyclodextrin or sulfobutyl-β-cyclodextrin or their mixture while stirring;
 the resulting mixture is filtered through microporous membrane of 0.2˜0.4 μm after being dissolved; the ethanol is removed from the filtrate under reduced pressure, then water is also removed under reduced pressure, the resulting product is dried giving a solid inclusion, or the ethanol is removed under reduced pressure giving a liquid inclusion. 
 
     
     
         3 . A preparation method of the pharmaceutical composition comprising cyclodextrin/docetaxel inclusion according to in  claim 1  is as follows: a solution of docetaxel in ethanol is added dropwise to an aqueous solution of hydroxypropyl-sulfobutyl-β-cyclodextrin or sulfobutyl-3-cyclodextrin or their mixture while stirring; the resulting mixture is filtered through microporous membrane of 0.2˜0.4 μm after being dissolved; the ethanol is removed from the filtrate under reduced pressure giving a liquid inclusion, or the ethanol is removed under reduced pressure, then the water is removed under reduced pressure, the resulting product is dried giving a solid inclusion. 
     
     
         4 . The preparation method o according to  claim 3 , wherein, the specific steps are as follows:
 the docetaxel and cyclodextrin in a mass ratio of 1:17 are used to prepare an aqueous solution of cyclodextrin; the solution prepared with hydroxypropyl-sulfobutyl-β-cyclodextrin or sulfobutyl-β-cyclodextrin, or their mixture and 2˜10 times of pure water (in weight) is added with a mixed solution prepared by docetaxel and appropriate amount of ethanol while heating and stirring at room temperature or at a temperature of 25˜65° C.; after the inclusion forms, filtered through microporous membrane of 0.2˜0.4 μm; then the ethanol is removed under reduced pressure, and then continues to reduce pressure until water is removed. The resulting product is dried under a vacuum condition to give a solid inclusion.