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Olaparib dihydrate and preparation method thereof

A technology of dihydrate and purified water, which is applied in the field of medicine, can solve problems such as inability to break through, and achieve the effects of improved solubility, simple and easy-to-operate preparation method, and high purity

Inactive Publication Date: 2017-08-29
SHANDONG YUXIN PHARMA CO LTD
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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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  • Olaparib dihydrate and preparation method thereof
  • Olaparib dihydrate and preparation method thereof
  • Olaparib dihydrate and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Embodiment 1, the preparation of olaparib dihydrate

[0057] 1) Dissolve 100 g of the crude product of olaparib in (1500 ml) in a mixed solvent of dimethyl sulfoxide and water (dimethyl sulfoxide: water=2:1), stir and heat at a speed of 220 rpm to make the crude product completely Dissolve until the solution is clear and filter;

[0058] 2) Slowly lower the temperature of the solution obtained above at a rate of 3°C every 10 minutes. When it drops to 0°C, add 6000ml of pre-cooled purified water to the solution at a flow rate of 2.0mL / min until the crystals appear, and continue to cool down to -20 Crystallize at ℃, heat and stir until the crystallization is complete, and grow the crystal for 2 hours;

[0059] 3) The crystals were collected by suction filtration, washed with a small amount of purified water, and dried in vacuum at 50° C. for 4 hours to obtain 99.90 g of white crystalline powder with a yield of 99.90% and a purity of 99.98%.

[0060] The X-ray powder dif...

Embodiment 2

[0061] Embodiment 2, the preparation of olaparib dihydrate

[0062] 1) Dissolve 100 g of the crude product of olaparib in a mixed solvent of 2000 ml of dimethyl sulfoxide and water (dimethyl sulfoxide: water=3:1), stir and heat at a speed of 250 rpm to completely dissolve the crude product, To the solution clarification, filter;

[0063] 2) Slowly lower the temperature of the solution obtained above at a rate of 1°C every 10 minutes. When it drops to -5°C, add 6000ml of pre-cooled purified water to the solution at a flow rate of 2.2mL / min until the crystals appear, and continue to cool down to - Crystallize at 15°C, heat and stir until the crystallization is complete, and grow the crystal for 4 hours;

[0064] 3) The crystals were collected by suction filtration, washed with a small amount of purified water, and dried in vacuum at 45° C. for 5 hours to obtain 99.91 g of white crystalline powder with a yield of 99.91% and a purity of 99.99%.

[0065] The X-ray powder diffract...

Embodiment 3

[0066] Embodiment 3, the preparation of olaparib dihydrate

[0067] 1) Dissolve 100 g of the crude product of olaparib in a mixed solvent of 1800 ml of dimethyl sulfoxide and water (dimethyl sulfoxide: water=3:1), stir and heat at a speed of 240 rpm to completely dissolve the crude product, To the solution clarification, filter;

[0068] 2) Slowly lower the temperature of the solution obtained above at a rate of 2°C every 10 minutes. When it drops to -3°C, add 6300ml of pre-cooled purified water to the solution at a flow rate of 2.5mL / min until the crystals appear, and continue to cool down to - Crystallize at 15°C, heat and stir until the crystallization is complete, and grow the crystal for 3 hours;

[0069] 3) The crystals were collected by suction filtration, washed with a small amount of purified water, and dried in vacuum at 45° C. for 5 hours to obtain 99.94 g of white crystalline powder with a yield of 99.94% and a purity of 99.99%.

[0070] The X-ray powder diffract...

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Abstract

The invention belongs to the technical field of medicine, and discloses an olaparib dihydrate and a preparation method thereof. Characteristic diffraction peaks are displayed at 6.75 DEG, 7.04 DEG, 9.16 DEG, 10.53 DEG, 15.20 DEG, 17.46 DEG, 20.68 DEG, 22.21 DEG, 27.43 DEG, 28.62 DEG, 29.30 DEG, 35.23 DEG and 37.14 DEG of X-ray powder diffraction spectra of the crystalline compound expressed at diffraction angles of 2Theta+ / -0.2 DEG, and the X-ray powder diffraction spectra measured by the aid of Cu-K alpha rays are shown as a graph 1 and are totally different from X-ray powder diffraction spectra in the prior art. The experiment proves that the dissolvability of the olaparib dihydrate is obviously increased. The invention also discloses the preparation method of the olaparib dehydrate, the preparation method is simple and easy to carry out, the yield and purity are high, the reaction condition is mild, and the method is suitable for large scale production. A dissolution rate and the stability of the capsule prepared by the olaparib dihydrate are obviously increased, and the capsule is very suitable for clinical application.

Description

technical field [0001] The invention belongs to the technical field of medicine and discloses olaparib dihydrate 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 repair function...

Claims

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Application Information

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IPC IPC(8): C07D237/32A61K31/502A61P35/00
CPCC07D237/32C07B2200/13
Inventor 张作芳付艳肖高瑞照
Owner SHANDONG YUXIN PHARMA CO LTD
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