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

A taxus cell and paclitaxel technology, applied in the direction of organic chemistry and the like, can solve the problems of increasing the production cost of separating paclitaxel, being expensive, polluting the environment, etc., and achieving the effects of good application prospects, reduced production costs, and simple operation.

Active Publication Date: 2014-05-28
HENAN ACADEMY OF SCI CHEM RES INST CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

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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

Method used

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

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Experimental program
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Effect test

Embodiment 1

[0022] In a 150 mL single-necked flask, add paclitaxel crude product produced by Taxus chinensis cell culture (manufactured by a pharmaceutical company in Guangdong, in which paclitaxel content is 63.0%, cephalomannine and unknown substances are 1.74% and 3.56% respectively) 1.20 g, then add 18.9 mL of a more polar organic solvent-analytical grade propanol, so that the mass of paclitaxel g / propanol volume mL=0.04 g / mL, stir well until the sample is completely dissolved, and then slowly drop into the system Reverse organic solvent-2.10 mL of analytically pure pentane, make pentane:propanol=10:90 (volume ratio), stir well for 10 min; then add 2.63 mL of pentane dropwise, make pentane:propanol=20 : 80 (volume ratio), fully stirred for 10 min; 10.0% increasing rate gradually increased the volume content of pentane, slowly added dropwise until the solution in the single-necked flask appeared flocculent, fully stirred for more than 1.5 h; then remained at 10.0 % Gradually increase t...

Embodiment 2

[0026] In a 100 mL single-necked flask, add paclitaxel crude product produced by yew cell culture (provided by a pharmaceutical company in Guangdong, in which paclitaxel content is 65.0%, cephalomannine and unknown substance content are 1.80% and 3.51%, respectively) 1.20 g, and then add 11.1 mL of a relatively polar organic solvent-analytical pure ethyl acetate, so that the paclitaxel mass g / ethyl acetate volume mL=0.07 g / mL, stir well until the sample is completely dissolved, and then slowly add to the system Slowly add 2.78 mL of reverse organic solvent-analytical grade n-hexane to make n-hexane:ethyl acetate=20:80 (volume ratio), and stir thoroughly for 10 min; then add 1.98 mL of n-hexane dropwise to make n-hexane: Ethyl acetate=30:70 (volume ratio), fully stir for 10 min; gradually increase the volume content of n-hexane at a rate of 10.0%, slowly add dropwise until flocs appear in the solution in the one-necked flask, fully stir for more than 1.5 h ; Then gradually incr...

Embodiment 3

[0030] In a 100 mL single-necked flask, add paclitaxel crude product produced by yew cell culture (provided by a pharmaceutical company in Guangdong, in which paclitaxel content is 68.0%, cephalomannine and unknown substance content are 1.86% and 3.95%, respectively) 1.20 g, then add 8.16 mL of a more polar organic solvent-analytical pure dichloromethane, make paclitaxel mass g / dichloromethane volume mL=0.10 g / mL, stir well until the sample is completely dissolved, and then slowly add to the system Slowly add 3.50 mL of reverse organic solvent-analytical pure isooctane to make isooctane:dichloromethane=30:70 (volume ratio), and stir thoroughly for 10 min; then add 1.94 mL of isooctane dropwise to make Isooctane:dichloromethane=40:60 (volume ratio), fully stir for 10 min; gradually increase the volume content of isooctane at a rate of 10.0%, and slowly add it dropwise until flocs appear in the solution in the one-necked flask. Stir fully for more than 1.5 h; then gradually incr...

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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...

Claims

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Application Information

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IPC IPC(8): C07D305/14
CPCC07D305/14
Inventor 赵俊宏李文锋樊燕鸽薛宝玉段显英
Owner HENAN ACADEMY OF SCI CHEM RES INST CO LTD
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