Amorphous cabazitaxel and preparation method thereof

A technology of cabazitaxel and amorphous substances, which is applied in the direction of pharmaceutical formulations, medical preparations containing active ingredients, organic active ingredients, etc., can solve the problems of inconvenient industrial production, unstable physical and chemical state of products, and easy changes. Reach the effect of difficult crystal form conversion, suitable for industrial application, and low solvent residue

Inactive Publication Date: 2012-09-12
JIANGSU HENGRUI MEDICINE CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] Based on the above crystal forms and their synthesis methods, we can see that the synthesis methods of these crystal forms require some specific experimental conditions, which are not convenient for industrial production, and the physical and chemical states of the products are not very stable. Under different storage conditions It is easy to change. Considering the broad prospect of cabazitaxel in medicine, it is of great research significance to develop a new type of cabazitaxel that is easy to operate, has low solvent residue and good stability.

Method used

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  • Amorphous cabazitaxel and preparation method thereof
  • Amorphous cabazitaxel and preparation method thereof
  • Amorphous cabazitaxel and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0040] Weigh 500 mg of Cabazitaxel in Form A (prepared with reference to patent WO2005028462) and dissolve it in 2 ml of methanol. The above methanol solution of cabazitaxel was added dropwise to 18ml of water within 5 minutes at room temperature, and a large amount of white solids were precipitated immediately. After stirring at room temperature for 30 minutes, it was suction-filtered, washed with 5 ml of methanol / water=1 / 9 mixed solvent, and vacuum-dried to obtain 472 mg of a white solid with a yield of 94%. The X-ray diffraction spectrum of the sample is shown in figure 1 , see the DSC spectrum figure 2 , the compound was judged to be amorphous.

Embodiment 2

[0042] Weigh 500 mg of Cabazitaxel in Form B (synthesized with reference to patent CN101918385, the same below) and dissolve it in 2 ml of ethanol. The above ethanol solution of cabazitaxel was added dropwise to 18ml of water within 5 minutes at room temperature, and a large amount of white solids were precipitated immediately. After stirring at room temperature for 30 minutes, it was suction-filtered, washed with 5 ml of ethanol / water=1 / 9 mixed solvent, and dried in vacuo to obtain 481 mg of a white solid with a yield of 96%. The X-ray diffraction and DSC spectra of the sample are studied and compared, and it is determined that the product is amorphous.

Embodiment 3

[0044] Weigh 500 mg of Cabazitaxel in Form B and dissolve it in 2 ml of acetonitrile. The acetonitrile solution of the above-mentioned cabazitaxel was added dropwise to 18 ml of water within 5 minutes at room temperature, and a large amount of white solids were precipitated immediately. After stirring at room temperature for 30 minutes, it was filtered with suction, washed with 5 ml of acetonitrile / water=1 / 9 mixed solvent, and dried in vacuo to obtain 428 mg of a white solid with a yield of 86%. The X-ray diffraction and DSC spectra of the sample are studied and compared, and it is determined that the product is amorphous.

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Abstract

The invention relates to an amorphous cabazitaxel and a preparation method thereof and further relates to a medical application of a cabazitaxel amorphous substance. The amorphous cabazitaxel prepared according to the preparation method provided by the invention is low in solvent residual, is excellent in appearance form and stability and is preferably applied to clinic treatment.

Description

technical field [0001] The present invention relates to amorphous cabazitaxel and its preparation method. Background technique [0002] Cabazitaxel belongs to taxane antineoplastic drugs, mainly used in the treatment of hormone refractory metastatic prostate cancer. Prepared by semisynthesis with precursors extracted from yew. The US FDA approved this product on June 17, 2010. It is used in combination with prednisone to treat patients with hormone-refractory metastatic prostate cancer (hormone-refractory metastatic prostate cancer, MHRPC) who have previously received docetaxel-containing regimens. . Its chemical name is 4-acetoxy-2α-benzoyloxy-5β,20-epoxy-1-hydroxy-7β,10β-dimethoxy-9-oxotaxane-11-ene- 13α-yl (2R, 3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate, molecular formula C45H57NO14, structural formula as follows (I). [0003] [0004] Due to the good curative effect of cabazitaxel, people have done a lot of research on it. Based on the general und...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D305/14A61K31/337A61P35/00
Inventor 孙飘扬武乖利邱振均陈永江
Owner JIANGSU HENGRUI MEDICINE CO LTD
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