Paclitaxel purifying method of paclitaxel crude product produced by Chinese yew cell culture

Abstract

The invention discloses a paclitaxel purifying method of a paclitaxel crude product produced by Chinese yew cell culture and belongs to the field of compound purification. With the combination of a crystallization method and a normal phase column-chromatography method, paclitaxel is purified. Firstly, a paclitaxel crude product produced by Chinese yew cell culture is dissolved in an organic solvent with high polarity, and a reverse organic solvent is dropwisely added so as to obtain paclitaxel with purity being more than 85.0%. And then, paclitaxel is further separated and purified by column chromatography. A stationary phase is silica gel of 200 meshes-300 meshes, and a mobile phase is a binary gradient mixed solvent of dichloromethane and ethyl acetate or hexane and acetone. Combining the two methods, the defect that paclitaxel and cephalomannine cannot be separated effectively by a previous separation method is solved, and unknown impurities which are hard to separate can be removed. Thus, a paclitaxel bulk drug which accords with United States Pharmacopeia (USP) standards can be obtained. The method has advantages of good repeatability and reasonable technology, is simple to operate, and is green and safe.

Description

technical field [0001] The present invention relates to a purification method of paclitaxel, in particular to a method for preparing a paclitaxel raw material drug conforming to the USP standard by removing difficult-to-separate cephalomannine and unknown impurities from crude paclitaxel produced by yew cell culture. Compound purification field. Background technique [0002] Paclitaxel is a new type of anticancer drug isolated from Taxus genus with a taxane diterpene skeleton. It is also the only drug known to promote microtubule polymerization and stabilize the polymerized microtubules. It has a strong inhibitory effect on most solid tumors, but basically has no effect on normal cells, especially for advanced ovarian cancer, breast cancer, non-small cell lung cancer and Kaposi's sarcoma, with definite curative effect and less side effects. With the further development of research, the anticancer effect of paclitaxel drugs has been more widely used, and has now become a fir...

AI Technical Summary

Problems solved by technology

The important thing is that the cumbersome operation steps reduce the yield of paclitaxel and increase the production cost. Although relatively pure paclitaxel can be obtained, the structure of cephalomannine has been changed, so it can only be discarded as waste, which is a waste of resources and pollution surroundings

Although reversed-phase column chromatography does not need to change the chemical structure of the separation object, in practical application, this method needs to use a special and expensive reversed-phase column silica gel, which greatly increases the production cost of paclitaxel separation and limits its wide application.

The crystallization method makes the yield of paclitaxel low and the loss is large, which undoubtedly increases the production cost of separating paclitaxel, and this method cannot completely and effectively separate and remove taxane compounds-cephalomannine and paclitaxel which are very similar in structure. A certain amount of unknown substances that are difficult to remove

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