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Antineoplastic drug hydrate and preparation method thereof

An anti-tumor drug, hydrate technology, applied in the field of medicine, can solve problems such as inability to break through, and achieve the effects of improved solubility, high yield and good stability

Pending Publication Date: 2017-08-18
刘德鹏
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The poor solubility of olaparib raw materials has always been a technical difficulty in this field, and has been unable to break through

Method used

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  • Antineoplastic drug hydrate and preparation method thereof
  • Antineoplastic drug hydrate and preparation method thereof
  • Antineoplastic drug hydrate and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Embodiment 1: Preparation of olaparib 2.5 hydrate

[0060] (1) Take 100g of the crude product of olapanizan, add 1000ml of a mixed solution of dichloromethane / ethanol / water (10:10:1 by volume), heat and stir (30 rpm) to dissolve, decolorize with activated carbon, and filter with suction ;

[0061] (2) Lower the filtrate of step (1) to room temperature, slowly add (1.0 mL / min) 1000 ml of dichloromethane dropwise, and cool down (1°C every 10 minutes) to -5°C for crystallization;

[0062] (3) Insulate and stir until crystallization is complete, grow crystals for 1 hour, filter with suction, wash with water, and dry at 40°C to obtain 99.89g of white crystalline powder with a yield of 99.89% and a purity of 99.97%.

[0063] The X-ray powder diffraction spectrogram that the prepared white crystalline powder uses Cu-Kα ray measurement to obtain is shown in figure 1 .

Embodiment 2

[0064] Embodiment 2: Preparation of olaparib 2.5 hydrate

[0065] (1) Take 100 g of the crude product of olaparib, add 800 ml of a mixed solution of dichloromethane / ethanol / water (10:10:2 by volume), heat and stir (40 rpm) to dissolve, decolorize activated carbon, and filter with suction;

[0066] (2) Reduce the filtrate of step (1) to room temperature, slowly add (1.5mL / min) 400ml of dichloromethane dropwise, and cool down (3°C every 10 minutes) to -10°C for crystallization;

[0067] (3) Insulate and stir until crystallization is complete, grow crystals for 2 hours, filter with suction, wash with water, and dry at 45°C to obtain 99.88g of white crystalline powder with a yield of 99.88% and a purity of 99.98%.

[0068] The X-ray powder diffraction spectrum obtained by measuring the prepared white crystalline powder using Cu-Kα rays is similar to that of Example 1.

Embodiment 3

[0069] Embodiment 3: Preparation of olaparib 2.5 hydrate

[0070] (1) Take 100 g of the crude product of olaparib, add 900 ml of a mixed solution of dichloromethane / ethanol / water (10:10:1.5 by volume), heat and stir (30 rpm) to dissolve, decolorize activated carbon, and filter with suction;

[0071] (2) Lower the filtrate of step (1) to room temperature, slowly add (1.5mL / min) 720ml of dichloromethane dropwise, and cool down (the cooling range is 2°C every 10 minutes) to -7°C for crystallization;

[0072] (3) Insulate and stir until crystallization is complete, grow crystals for 2 hours, filter with suction, wash with water, and dry at 45°C to obtain 99.94g of white crystalline powder with a yield of 99.94% and a purity of 99.99%.

[0073] The X-ray powder diffraction spectrum obtained by measuring the prepared white crystalline powder using Cu-Kα rays is similar to that of Example 1.

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Abstract

The invention belongs to the technical field of medicines, discloses an antineoplastic drug hydrate and a preparation method thereof, and particularly discloses an Olaparib hydrate and a preparation method thereof. An X-ray powder diffraction pattern, represented by the diffraction angle of 2theta+ / -0.2 degrees, of the Olaparib hydrate shows characteristic diffraction peaks at 2.228 degrees, 4.309 degrees, 7.125 degrees, 14.613 degrees, 19.134 degrees, 24.672 degrees, 25.448 degrees, 26.317 degrees, 32.115 degrees, 34.451 degrees and 36.228 degrees, the X-ray powder diffraction pattern obtained by using Cu-Kalpha rays for measurement is shown in figure 1, and the Olaparib hydrate is completely different from the prior art. It is surprisingly found through experiments that the solubility of the Olaparib hydrate is remarkably improved. The preparation method of the antineoplastic drug hydrate is also disclosed and simple and easy to operate, the yield and the purity are high, the reaction condition is mild, and the antineoplastic drug hydrate is suitable for large-scale production. The dissolution and stability of capsules made from the Olaparib hydrate are significantly improved, and the Olaparib hydrate is very suitable for clinical application.

Description

technical field [0001] The invention belongs to the technical field of medicine, and discloses a hydrate of an antitumor drug and a preparation method thereof. Background technique [0002] Olaparib, the chemical name is 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one, the English name is Olaparib, and the structural formula is as follows Formula 1 shows: [0003] [0004] Olaparib, a small molecule developed by KuDOS Pharmaceuticals, a wholly owned subsidiary of AstraZeneca, is a potent PARP inhibitor that promotes tumor Apoptosis, which can enhance the efficacy of radiotherapy and chemotherapy with alkylating agents and platinum drugs, and is mainly used for the treatment of breast cancer gene 1 or 2 (BRCA-1 or BRCA-2) gene mutation cancer (mainly present in the breast cancer, ovarian and prostate cancer). Olaparib can selectively act on tumor cells, and normal cells are not destroyed due to the retention of the double-strand re...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D237/32A61K31/502A61P35/00
CPCC07D237/32C07B2200/13
Inventor 王鹏王绪飞黄小为
Owner 刘德鹏
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