Crystallization purification method for paclitaxel

Abstract

The invention discloses a method for preparing a crude paclitaxel product prepared from a specific three-component system consisting of dichloromethane, acetone and alkane through crystallization purification and having a structure as shown in the following formula which is described in the specification. The method comprises the following steps: 1) dissolving the crude paclitaxel product in a mixed solution of dichloromethane and acetone; 2) adding alkane into the mixed solution drop by drop so as to allow paclitaxel to be precipitated; and 3) carrying out filtering and drying so as to obtain a high-purity paclitaxel product. The method provided by the invention has excellent purifying effect and can prepare paclitaxel with HPLC purity of 99% or above; the method has a wide application scope and exerts substantial purifying effect on almost all the impurities including specific impurities hard to purify, such as 7-epitaxol; the method is simple to operate, only needs simple reaction tanks and is suitable for large-scale production; and the method is high in purification yield, wherein crystallization yield is 92% or above.

Description

technical field

[0001] The present invention relates to the crystallization field of compounds; specifically, the present invention relates to a paclitaxel crystallization purification method. Background technique

[0002] Due to the change of living environment and lifestyle, as well as the aging of the population, the increase of living pressure and other objective factors, cancer has become one of the main factors of human death in the world. my country has a large population, the incidence of cancer continues to rise, and the number of patients is increasing day by day. Cancer has become the number one cause of death in my country. The global sales of antineoplastic drugs are rising, maintaining a steady and high-speed growth every year.

[0003] Taxane antineoplastic drugs are microtubule depolymerization inhibitors, and their mechanism of action is completely different from other chemically synthesized antineoplastic agents or plant anticancer drugs that have been mar...

Examples

Embodiment 1

[0060] Weigh 10g of paclitaxel (HPLC purity 93%, 7-epitaxol is 0.12%), add 44ml of dichloromethane, 88ml of acetone, heat to 40°C to dissolve, cool to 25°C, add dropwise 264ml of n-hexane to make it crystallize, After the dropwise addition was completed, the temperature was lowered to 5° C., filtered, and vacuum-dried at 50° C. to obtain 9.20 g of a white solid with an HPLC purity of 97.5% and 0.091% of 7-epitaxel. The molar yield is 92%.

Embodiment 2

[0062] Weigh 5g of paclitaxel (sample in Example 1), add 22ml of dichloromethane and 44ml of acetone, heat to 40°C to dissolve, cool to 25°C, add dropwise 110ml of n-heptane to crystallize, dropwise complete, cool to 5 °C, filtered, and vacuum-dried at 50 °C to obtain 4.66 g of a white solid with an HPLC purity of 99.5% and 0.088% of 7-epitaxel. The molar yield is 93.2%.

Embodiment 3

[0064] Weigh 10g of paclitaxel (HPLC purity 93%, 7-epitaxol is 0.12%), add 44ml of chloroform, 88ml of acetone, heat to 40°C to dissolve, cool to 25°C, add dropwise 264ml of n-hexane to crystallize, add dropwise After completion, the temperature was lowered to 5° C., filtered, and vacuum-dried at 50° C. to obtain 9.20 g of a white solid with an HPLC purity of 97.1% and 0.105% of 7-epitaxel. The molar yield is 92.2%.

technical field

[0001] The present invention relates to the crystallization field of compounds; specifically, the present invention relates to a paclitaxel crystallization purification method. Background technique

[0002] Due to the change of living environment and lifestyle, as well as the aging of the population, the increase of living pressure and other objective factors, cancer has become one of the main factors of human death in the world. my country has a large population, the incidence of cancer continues to rise, and the number of patients is increasing day by day. Cancer has become the number one cause of death in my country. The global sales of antineoplastic drugs are rising, maintaining a steady and high-speed growth every year.

[0003] Taxane antineoplastic drugs are microtubule depolymerization inhibitors, and their mechanism of action is completely different from other chemically synthesized antineoplastic agents or plant anticancer drugs that have been mar...

Examples

Embodiment 1

[0060] Weigh 10g of paclitaxel (HPLC purity 93%, 7-epitaxol is 0.12%), add 44ml of dichloromethane, 88ml of acetone, heat to 40°C to dissolve, cool to 25°C, add dropwise 264ml of n-hexane to make it crystallize, After the dropwise addition was completed, the temperature was lowered to 5° C., filtered, and vacuum-dried at 50° C. to obtain 9.20 g of a white solid with an HPLC purity of 97.5% and 0.091% of 7-epitaxel. The molar yield is 92%.

Embodiment 2

[0062] Weigh 5g of paclitaxel (sample in Example 1), add 22ml of dichloromethane and 44ml of acetone, heat to 40°C to dissolve, cool to 25°C, add dropwise 110ml of n-heptane to crystallize, dropwise complete, cool to 5 °C, filtered, and vacuum-dried at 50 °C to obtain 4.66 g of a white solid with an HPLC purity of 99.5% and 0.088% of 7-epitaxel. The molar yield is 93.2%.

Embodiment 3

[0064] Weigh 10g of paclitaxel (HPLC purity 93%, 7-epitaxol is 0.12%), add 44ml of chloroform, 88ml of acetone, heat to 40°C to dissolve, cool to 25°C, add dropwise 264ml of n-hexane to crystallize, add dropwise After completion, the temperature was lowered to 5° C., filtered, and vacuum-dried at 50° C. to obtain 9.20 g of a white solid with an HPLC purity of 97.1% and 0.105% of 7-epitaxel. The molar yield is 92.2%.

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