Cabazitaxel polymorphic form and preparation method thereof

A technology of cabazitaxel, which is applied in the field of medicine, can solve the problems that acetonide is not very stable, is not suitable for industrialized large-scale production, and the quality of raw materials has declined, so as to achieve good purity and content stability, little harm to the environment and personnel, and Good repeatability and reproducibility

Active Publication Date: 2013-04-24
JIANGSU AOSAIKANG PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, patents and patent applications related to the crystal form of cabazitaxel mainly include ZL200480026128.X, CN101918385A, CN102659722A, CN102675257A, etc. Among them, ZL200480026128.X discloses the acetonide crystal form of cabazitaxel and its preparation method, but according to the experimental results, acetonide It is not very stable, and it is easy to remove part of acetone under long-term storage or high temperature conditions, and the quality of the raw material drug will also decline; although CN101918385A discloses many crystal forms, its preparation method is very unique and is not suitable for large-scale industrial production; CN102659722A discloses an amorphous form of cabazitaxel; CN102675257A discloses a crystal of anhydrous form of cabazitaxel

Method used

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  • Cabazitaxel polymorphic form and preparation method thereof
  • Cabazitaxel polymorphic form and preparation method thereof
  • Cabazitaxel polymorphic form and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040]500 mg of cabazitaxel acetonide was weighed and dissolved in 5 ml of acetone with stirring, and 50 ml of purified water was added dropwise to the above solution at room temperature, resulting in a large amount of white solids. After stirring at room temperature for 30min, filter, the obtained white filter cake was washed with purified water for 3 times, and after vacuum drying, 458 mg of white solid powder was obtained with a yield of 98.0%; the XPRD spectrum of the product is shown in figure 1 , see DSC spectrum figure 2 , see TGA spectrum image 3 , according to the spectrum and data, the compound is in the form of anhydrous cabazitaxel.

Embodiment 2

[0042] 500 mg of cabazitaxel acetonide was weighed and dissolved in 10 ml of acetone with stirring, and 100 ml of purified water was added dropwise to the above solution at room temperature, resulting in a large amount of white solids. After stirring at room temperature for 45min, filter, the obtained white filter cake was washed 3 times with purified water, and 452 mg of white solid powder was obtained after vacuum drying, and the yield was 96.6%; Basically the same, the product is in the form of cabazitaxel anhydrous.

Embodiment 3

[0044] 500 mg of cabazitaxel acetonide was weighed and dissolved in 5 ml of ethanol with stirring, and 50 ml of purified water was added dropwise to the above solution at room temperature, resulting in a large amount of white solids. After stirring at room temperature for 30min, filter, the obtained white filter cake was washed 3 times with purified water, and after vacuum drying, 459 mg of white solid powder was obtained with a yield of 96.2%; the XPRD spectrum of this product is shown in Figure 4 , see DSC spectrum Figure 5 , see TGA spectrum Image 6 , and there is no organic solvent residue in the crystal form by gas phase detection. According to the spectrum and data, the product is in the form of cabazitaxel monohydrate.

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Abstract

The invention belongs to the technical field of medicines, relating to a cabazitaxel polymorphic form and a preparation method thereof, and particularly provides a novel crystalline form of anhydride, monohydrate and dehydrate of cabazitaxel and a preparation method thereof. The novel crystalline form provided by the invention is good in product stability, simple in preparation technology, good in quality reproducibility and easy to control for product purity, and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to a new polymorphic form of cabazitaxel and a preparation method thereof. Background technique [0002] Antineoplastic drug cabazitaxel, namely 7,10-dimethoxydocetaxel, chemical name is (2α,5β,7β,10β,13α)-4-acetoxy-13-({(2R,3S )-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropionyl}oxy)-1-hydroxy-7,10-dimethoxy-9-oxotaxane-5, 20-epoxy-11-ene-2-benzoate, its chemical structural formula is as follows: [0003] [0004] Cabazitaxel belongs to the taxane class of antitumor drugs, which is prepared semi-synthetically with a precursor extracted from Taxus chinensis, and is mainly used for the treatment of hormone-refractory metastatic prostate cancer. Cabazitaxel is a microtubule inhibitor that promotes the assembly of microtubule dimers into microtubules by binding to tubulin, while stabilizing microtubules by preventing demultimerization and inhibiting microtubule...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D305/14
Inventor 赵俊王孝雯刘文杰王易
Owner JIANGSU AOSAIKANG PHARMA CO LTD
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