| 摘要 |
1. Process for the preparation of quick-dissolving solid compositions for pharmaceutical use and aqueous solutions thereof, comprising: a) dissolving in ethanol a taxoid, paclitaxel or docetaxel, or a salt or hydrate or solvate thereof and thereafter performing either of the following steps: i) adding solid acetyl-γ-cyclodextrin or hydroxypropyl-β-cyclodextrin and optionally other water-soluble auxiliary materials usual in pharmaceuticals for parenteral purposes, dissolving the mixture in an aqueous solvent and lyophilising to obtain a solid; or ii) adding lyophilised solid acetyl-γ-cyclodextrin or hydroxypropyl-β-cyclodextrin and optionally other water-soluble auxiliary materials usual in pharmaceuticals for parenteral purposes, evaporating the solvent and drying to obtain a solid; or iii) admixing the solution with solid large surface area preferably lyophilised acetyl-γ-cyclodextrin or hydroxypropyl-β-cyclodextrin, and optionally other water-soluble auxiliary materials usual in pharmaceuticals for parenteral purposes and thereafter dissolving with an aqueous solvent optionally in the presence of an isotonizing additive to obtain a solution, containing: A. as an active ingredient the said taxoid and B. the said cyclodextrin derivative and C. optionally other water-soluble auxiliary materials usual in pharmaceuticals for parenteral purposes, whereby the weight ratio of taxoid:cyclodextrin ranges between 1:25 and 1:400; - with proviso that hydroxypropyl-β-cyclodextrin is used in combination only with docetaxel in weight ratio of taxoid:cyclodextrin ranging between 1:25 and 1:100 -; and optionally: b) when steps i) or ii) were used dissolving the solid in an aqueous solvent, to obtain a solution ready for direct medical treatment. 2. The process according to Claim 1 characterized by using as the aqueous solvent or diluent any of the following: water of injectable quality, an aqueous solution of isotonizing additive such as sodium chloride, glucose or dextrose containing these ingredients in an effective amount to isotonize the aqueous solution. 3. The process according to any of Claims 1 and 2 characterized by using as the cyclodextrin component any of the following: acetyl-γ-cyclodextrin having a degree of acetylation between about 2 to about 12 acetyl groups per cyclodextrin ring, acetyl-γ-cyclodextrin having a degree of acetylation of about 8 acetyl groups per cyclodextrin ring. 4. The process according to any of Claims 1-3 characterized by using paclitaxel in its hydrated polymorphic form or in its solvate form such as the ethanol solvate. 5. The process according to any of Claims 1 and 2 characterized by using as the cyclodextrin component any of the following: hydroxypropyl-β-cyclodextrin, preferably hydroxypropyl-β-cyclodextrin having degree of substitution between about 2 to about 10 hydroxypropyl groups per cyclodextrin ring, hydroxypropyl-β-cyclodextrin having a degree of substitution between about 4 to about 6 hydroxypropyl groups per cyclodextrin ring. 6. Water-soluble solid pharmaceutical compositions and their solutions in aqueous solvents, said compositions containing: a) as an active ingredient a finely dispersed large surface area amorphous preferably lyophilized taxoid preferably paclitaxel or docetaxel, their salts or their polymorphic hydrates or solvates such as solvates formed with ethanol and b) finely dispersed large surface area, solid, amorphous preferably lyophilized acetyl-γ-cyclodextrin or hydroxypropyl-β-cyclodextrin whereby the weight ratio of said taxoid : said cyclodextrin ranges between 1:25 and 1:400, - with proviso that hydroxypropyl-β-cyclodextrin is used in combination only with docetaxel in weight ratio of taxoid:cyclodextrin ranging between 1:25 and 1:100; c) and optionally other water-soluble auxiliary materials usual in pharmaceuticals for parenteral purposes. 7. A composition according to Claim 6 wherein weight ratio of paclitaxel: acetyl-γ-cyclodextrin is from 1:100 to 1:250. 8. Quick-dissolving solid compositions for pharmaceutical use and aqueous solutions thereof, comprising any of the products prepared according to Claims 1 to 5. 9. A method for prevention of self-aggregation and premature precipitation of a taxoid of the group paclitaxel and docetaxel and their salts, solvates and hydrates in aqueous solutions and to prolongate the oversaturated dissolved state of the drug by using the taxoids in the form of pharmaceutical compositions according to any of Claims 6 to 8. 10. Method of treatment of unwanted cell proliferation by with effective amounts of pharmaceutical compositions according to any of Claims 6 to 8 characterized by administering to a patient in need of such treatment a dosage form containing the pharmaceutical composition according to any of Claims 6 to 9 containing an effective amount of paclitaxel and docetaxel and their salts and solvates and hydrates. 11. A method according to Claim 10 characterized by administering to a patient in need of such treatment a dosage form containing paclitaxel, its salts, solvates and hydrates and acetyl-γ-cyclodextrin in 1:100 to 1:250 weight ratio. 12. A method according to Claim 10 characterized by administering to a patient in need of such treatment a dosage form containing docetaxel, its salts, solvates and hydrates and hydroxypropyl-β-cyclodextrin in 1:25 to 1:100 weight ratio. |
