Method for purifying taxane compound

Abstract

The invention provides a method for purifying a taxane compound. The method comprises the processes of solvent drying, double recrystallization, once pulping and drying, can effectively remove impurities, water, ignition residues, mechanical and inorganic impurities and a residual solvent generated in the processes of preparing and storing the taxane compound; and the method has mild condition, simple and convenient operation and higher yield and is easy to control. The content of any single impurity of a refined product is lower than 0.1 percent by the detection of a high performance liquid chromatograph, and the total impurity content is lower than 0.5 percent; and the obtained refined product is the anhydrous crystallization taxane compound with high stability and content.

Description

technical field [0001] The present invention relates to a method for purifying taxane compounds, in particular to a method for treating the raw materials of taxane compounds by means of recrystallization, so as to prepare anhydrous crystalline taxanes with good stability and high purity compound method. Background technique [0002] Taxanes are a class of compounds extracted or semi-synthesized from the bark and needles of Taxus celebica, which have high-efficiency and broad-spectrum anti-tumor activity. Taxanes are new anti-tumor drugs that have been researched and developed in recent years. They can bind to tubulin subunits to inhibit microtubule dynamics, and can also induce tumor cell apoptosis by activating multiple signal transduction pathways. Different from other plant alkaloids, taxanes inhibit the cell in G phase and M phase by promoting the assembly of microtubule dimers into microtubules, and stabilizing microtubules by preventing the process of depolymerization...

AI Technical Summary

Problems solved by technology

[0008] Column chromatography is divided into two types: normal pressure and high pressure: normal pressure column chromatography has a slow separation speed and low efficiency, and cannot adapt to industrial continuous production; high pressure column chromatography is often used in the production of taxane products, but It is necessary to customize a special high-pressure chromatography column (or preparative chromatography column) system and silica gel filler, and the investment in equipment and consumables is large; at the same time, the batch size can only reach 200-300 grams, and the operation cycle is long

In addition, normal-pressure and high-pressure column chromatography can only be used for preliminary purification, and cannot be qualified once; in the process of column chromatography, due to the generation of exchange heat, the product will be degraded in a small amount; and column chromatography requires a large amount of solvent

[0009] Chinese patent CN101177421 discloses a method for preparing high-purity taxane compounds using macroporous adsorption resin, using an aqueous solution of an organic solvent as an eluent, and adopting a separation method of atmospheric pressure column chromatography; although this method reduces the amount of organic solvent However, the chromatographic separation speed is slow, the operation cycle is long, and the amount of resin is large, and the cost is high

However, due to the large number of alcoholic hydroxyl groups in taxane compounds, for anhydrous crystals, solvents such as ethanol and n-hexane can easily form hydrogen bonds with the compound molecules, resulting in solvation, and the solvent residue often stays at a relatively high level and is difficult to reduce.

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