Industrial method for refining esomeprazole sodium salt

A technology of esomeprazole sodium salt and refining method is applied in the refining field of industrialized esomeprazole sodium salt, and can solve the problems of large production gap, high cost, complicated operation and the like, and achieves qualified clarity and loss of Reduced, easy-to-filter effects

Active Publication Date: 2012-02-15
NANJING YOKO PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, its single enantiomer S-omeprazole is separated from the neutral racemate omeprazole by chiral column chromatography, and the purity requirement is very high, at least 99.0%, otherwise the amount of residual impurities cannot be guaranteed It is removed in the final step of processing esomeprazole sodium, so the preparation of starting materials using this method is cumbersome and difficult to prepare in large quantities, which is far behind industrialized production
[0014] The control of impurities in raw materials is crucial to

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Weigh 2.4Kg of crude esomeprazole sodium, suspend in 12L ethyl acetate at 50°C, keep stirring at this temperature, slowly add 2L of ethanol, filter while hot, cool to room temperature, stand for crystallization for 6h, filter, Wash with 4 L of ethyl acetate-ethanol 6:1 mixed solution, and vacuum-dry to obtain 1.86 Kg of refined product of esomeprazole sodium salt. Tested by HPLC, the content is >99.5%, and the single impurity is <0.1%.

[0032] HPLC test conditions:

[0033] Chromatographic column: C18 column

[0034] Mobile phase: acetonitrile-phosphate buffer (1.4g / L disodium hydrogen phosphate aqueous solution, adjust the pH to 7.6 with phosphoric acid) (27:73)

[0035] Detection wavelength: 280nm

[0036] Flow rate: 1ml / min

[0037] Determination method: An appropriate amount of esomeprazole sodium salt refined product is dissolved in mobile phase to make a solution containing 0.1mg per milliliter, and then 20 μl is precisely measured, injected into the liquid c...

Embodiment 2

[0039] Weigh 2.0Kg of the crude product of esomeprazole sodium, dissolve it in 8L tetrahydrofuran at 40°C, keep stirring at this temperature, slowly add 1L methanol, filter while it is hot, cool to room temperature, stand for crystallization for 6h, filter, and dissolve in tetrahydrofuran - Wash with 2L of methanol 8:1 mixed solution, and vacuum dry to obtain 1.58Kg of esomeprazole sodium refined product. Tested by HPLC, the content is >99.5%, and the single impurity is <0.1%.

[0040]Tested by HPLC, the content is >99.5%, and the single impurity is <0.1%.

[0041] Liquid phase condition is the same as embodiment 1.

Embodiment 3

[0043] Weigh 3.0Kg of the crude product of esomeprazole sodium, dissolve it in 22.5L of refluxing methyl tert-butyl ether, keep stirring at this temperature, slowly add 2.25L of methanol, filter while it is hot, cool to room temperature, and stand for crystallization After 6 hours, filter, wash with 1.5L of methyl tert-butyl ether-methanol 10:1 mixed solution, and vacuum-dry to obtain 2.43Kg of esomeprazole sodium refined product. Tested by HPLC, content>99.5%, single impurity<0.1%

[0044] Liquid phase condition is the same as embodiment 1.

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Abstract

The invention relates to an industrial method for refining esomeprazole sodium salt. The method is mainly characterized by comprising the following steps of: suspending the esomeprazole sodium salt in a hot poor solvent in an amount which is 1 to 10 times weight of the esomeprazole sodium salt, slowly adding a good solvent such as methanol and ethanol in an amount which is 0.5 to 1.5 times weightof the mixture, filtering while heat to obtain a clarified solution, cooling to room temperature, separating out a solid, filtering, washing and performing vacuum drying. The method is easy and convenient to implement, and inorganic impurities and organic impurities contained in the crude product of esomeprazole sodium salt, including a peroxide sulphone impurity and an R-esomeprazole impurity can be effectively removed. The esomeprazole sodium salt refined by the method has the content of over 99.5 percent, and has the single impurity content of less than 0.1 percent.

Description

technical field [0001] The invention belongs to the technical field of medicine and relates to a kind of industrialized esomeprazole sodium salt (formula ), esomeprazole sodium salt is a very effective ulcer treatment drug for the treatment of conditions such as gastric ulcer, duodenal ulcer and reflux esophagitis. [0002] [0003] Mode Background technique [0004] Omeprazole, chemical name 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfonamido]-1H-benzo Imidazole, a well-known proton pump inhibitor of gastric parietal cells, can specifically inhibit the secretion of microtubules formed by the apical membrane of parietal cells and the H + , K + -ATPase, thereby inhibiting the secretion of gastric acid. Omeprazole is a chiral compound of sulfoxide class, the sulfur atom is its stereocenter, and omeprazole is the exosome of its two monoenantiomers R-omeprazole and S-omeprazole. racemic mixture. The latter has the generic name esomeprazole. [0005] ...

Claims

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Application Information

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IPC IPC(8): C07D401/12
Inventor 晁阳闵涛史为龙陈敏徐晓霞陈雷
Owner NANJING YOKO PHARMA
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