Docetaxel composition for injection and preparation method thereof

Abstract

The present invention provides a docetaxel composition for injection and a preparation method thereof. The composition comprises the following components in parts by weight: 1 part of docetaxel, 20-60parts of cyclodextrin, 5-80 parts of a cosolvent, 0-20 parts of a first stabilizer, 0.2-30 parts of a second stabilizer and 0.001-1.0 part of an additive. Besides, the composition is free of ethanoland polysorbate, and the ethanol is not used in the preparation process. Due to the fact that the composition does not contain the polysorbate and ethanol, the composition is reduced in allergic, irritating, addictive, drunk risks and other side effects.

Description

[0001] field of invention [0002] The invention relates to the technical field of pharmaceutical preparations, in particular to a docetaxel composition for injection and a preparation method thereof. [0003] technical background [0004] Docetaxel is white or off-white powder, almost insoluble in water, soluble in ethanol, and unstable under alkaline conditions. The chemical name is: [2aR-(2aα, 4β, 4aβ, 6β, 9α, (aR*, βS*), 11α, 12α, 12aα, 12bα)]-β-[[(1,1-Dimethylethoxy base)carbonyl]amino]-α-hydroxyphenylpropanoic acid[12b-acetoxy-12-benzoyloxy-2a,3,4,4a,5,6,9,10,11,12,12a,12b- Dodecahydro-4,6,11-trihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methylene-1H-cyclodecapenta-[3,4 ]benzo[1,2-b]oxetan-9-yl]ester. [0005] The chemical structural formula is: [0006] [0007] The molecular formula is: C 43 h 53 NO 14 [0008] Molecular weight: 807.89. [0009] Docetaxel is a new generation of taxane anti-tumor drugs, which can be prepared by semi-synthesis of precursors ext...

AI Technical Summary

Problems solved by technology

[0024] Although T-80 is not used in the above invention patents, ethanol is inevitably used to aid in dissolution, and it is removed under reduced pressure. In fact, there is a certain amount of residue, so that they can only exist as a solid composition after removing ethanol. , it is difficult to achieve a liquid form that is convenient for clinical use, and this step of dilution is required. At the same time, these patents that use ethanol to solubilize cyclodextrin to solubilize paclitaxel are all prepared by removing ethanol in solid form. The composition of these patents When it is further compounded into a liquid form, the stability time of paclitaxel substances in the solution will be greatly shortened, and generally it will be precipitated within 24 hours. Therefore, in the existing patents, ethanol is necessary for the stability of the liquid composition, such as ZHAO WilliamW. and other invention patents WO2016 / 149162 (Pharmaceutial compositions containing Taxane-cyclodextrincomplexes, method of making and methods of use) clearly stated that ethanol must be used in this combination, and the mass ratio of ethanol to taxane is 5:1~ 40:1, although the invention is prepared as a liquid composition, paclitaxel can be stored stably for a long time, but the composition contains a large amount of ethanol, which poses a risk of clinical use

[0025] Invention patents such as Lajo Szente US 6284746 (Inclusion Complexes Of Taxol OrTaxotere Of Taxus Extract Formed With Cyclodextrins, Its Preparation And Use), which directly use the aqueous solution or buffer solution of cyclodextrin and its derivatives or the preparation containing a small amount of ethanol containing paclitaxel or Compositions of docetaxel or yew extracts, the maximum solubility of the API in water does not exceed 1mg / mL, indicating that it is difficult to make docetaxel with a concentration that meets clinical use without using ethanol or using a very small amount of ethanol preparation

Images