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Preparation method for esomeprazole magnesium trihydrate crystalline form

A technology of esomeprazole magnesium trihydrate and esomeprazole magnesium, applied in the field of preparation of esomeprazole magnesium trihydrate crystal form, can solve the problem of not providing XRPD spectrum and data, etc. Achieve high crystallinity and good stability

Active Publication Date: 2015-12-02
YANGTZE RIVER PHARM GRP CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] CN103788069 discloses the trihydrate crystal form and preparation method of esomeprazole magnesium, but it does not provide spectra and data such as XRPD and DSC

Method used

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  • Preparation method for esomeprazole magnesium trihydrate crystalline form
  • Preparation method for esomeprazole magnesium trihydrate crystalline form
  • Preparation method for esomeprazole magnesium trihydrate crystalline form

Examples

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Embodiment 1

[0047] Embodiment 1 Preparation of esomeprazole magnesium trihydrate crystal form

[0048] Put 100g of crude esomeprazole magnesium in 500ml of methanol and stir at 10°C until dissolved. Use 2g of activated carbon as a filter aid, filter, and concentrate the filtrate to 1 / 2 of the original volume at 40°C under reduced pressure. Add 500 ml of acetone, and stir at 10° C. for 2 hours. After filtering, the filter cake was stirred and washed with 200 ml of methanol / acetone (v / v=1 / 3) mixed solvent for 10 minutes. Filter, dissolve the filter cake in 150ml of methanol, stir to dissolve, add 600ml of water, stir and crystallize at 30°C for 3 hours. Filter and dry the filter cake under vacuum at 40°C to obtain 85g of off-white solid, with a molar yield of 85%, a moisture content of 7.1%, a chromatographic purity of 99.92%, and an optical purity of 99.89%. figure 1 .

Embodiment 2

[0049] Embodiment 2 Preparation of esomeprazole magnesium trihydrate crystal form

[0050] Put 100g of crude esomeprazole magnesium in 1000ml of methanol and stir at 25°C until dissolved. Use 5g of activated carbon as a filter aid, filter, and concentrate the filtrate to 1 / 3 of the original volume at 45°C under reduced pressure. Add 1000 ml of acetone, and stir at 20° C. for 4 hours. After filtering, the filter cake was stirred and washed twice with 350 ml of methanol / acetone (v / v=1 / 4) mixed solvent, 20 minutes each time. Filtrate, dissolve the filter cake in 200ml of methanol, stir and dissolve, add 1200ml of water, stir and crystallize at 35°C for 4 hours. Filtrate, and dry the filter cake under vacuum at 45°C to obtain 90g of off-white solid, with a molar yield of 90%, a moisture content of 7.4%, a chromatographic purity of 99.95%, and an optical purity of 99.90%. figure 1 unanimous.

Embodiment 3

[0051] Embodiment 3 Preparation of esomeprazole magnesium trihydrate crystal form

[0052] 100g of crude esomeprazole magnesium was dissolved in 1500ml of methanol at 30°C until dissolved. Use 10 g of activated carbon as a filter aid, filter, and concentrate the filtrate under reduced pressure at 50°C to 1 / 5 of the original volume. Add 1500 ml of acetone, and stir at 30° C. for 6 hours. After filtering, the filter cake was stirred and washed with 600 ml of methanol / acetone (v / v=1 / 5) mixed solvent for 30 minutes. Filtrate, dissolve the filter cake in 300ml of methanol, stir and dissolve, add 3000ml of water, stir and crystallize at 45°C for 5 hours. Filtrate, and dry the filter cake under vacuum at 50°C to obtain 92g of off-white solid, with a molar yield of 92%, a moisture content of 7.0%, a chromatographic purity of 99.96%, and an optical purity of 99.91%. figure 1 unanimous.

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Abstract

The present invention discloses a preparation method for an esomeprazole magnesium trihydrate crystalline form. The preparation method comprises: (a)dissolving esomeprazole magnesium crude into C1-C3 alkanol; (b) taking activated carbon as a filter aid to filter, and then concentrating filtrate under reduced pressure; (c) adding acetone; (d) filtering a mixture which is subjected to temperature-preserving and stirring to obtain a filter cake 1, and stirring and washing the filter cake 1 with a mixed solvent of C1-C3 alkanol and acetone; (e) filtering the mixture to obtain a filter cake 2, dissolving the filter cake 2 with C1-C3 alkanol, adding water into the dissolved filter cake, and separating out a crystal while stirring; and (f) filtering the mixture to obtain a filter cake 3, carrying out vacuum drying on the filter cake 3 at the temperature of 40-50 DEG C to obtain the esomeprazole magnesium trihydrate . The method provided by the present invention is good in repeatability, simple in operation and high in product yield, purity and crystallinity and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a preparation method of esomeprazole magnesium trihydrate crystal form. Background technique [0002] Esomeprazole Magnesium (Esomeprazole Magnesium), the chemical name is bis-(S)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methanol Base] sulfinyl] -1H-benzimidazole magnesium. Esomeprazole is a class of proton pump inhibitors (protonpumpinhibitors, PPIs) developed by AstraZeneca. In recent years, the drug has been at the forefront of the world's best-selling drugs and has broad market prospects. The listed esomeprazole magnesium is a trihydrate, and its chemical structure is as follows: [0003] [0004] WO9427988A1 discloses sodium, magnesium, lithium, potassium, calcium and quaternary ammonium salts of esomeprazole and a preparation method thereof. This patent does not conduct a detailed study on the crystal form. [0005] WO9854171A2 discloses esomepra...

Claims

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Application Information

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IPC IPC(8): C07D401/12
CPCC07B2200/13C07D401/12
Inventor 袁峰泉韦洪霞陈杨杨蔡明君孙春艳陈令武杨菡郑少波赵鹏
Owner YANGTZE RIVER PHARM GRP CO LTD
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