Esomeprazole sodium polymorph and application of esomeprazole sodium polymorph in drugs for injection

Abstract

The present invention relates to an esomeprazole sodium polymorph and an application of the esomeprazole sodium polymorph in drugs for injection. According to the present invention, esomeprazole sodium compositions for injection have characteristics of good stability and high purity, a preparation process of the esomeprazole sodium compositions is easily industrialized, and the esomeprazole sodium compositions can be used for treatments of diseases related to gastric acid parasecretion, wherein the esomeprazole sodium compositions are prepared from the esomeprazole sodium polymorph having good stability and excellent solubility in the present invention.

Description

[0001] technical field [0002] The invention belongs to the field of medicinal chemistry, and relates to preparation of an esomeprazole sodium composition for injection by obtaining an esomeprazole sodium polymorph with good stability and excellent solubility. [0003] Background technique [0004] Common name for 5-methoxy-2-((S)-((4-methoxy-3,5-dimethyl-2-pyridyl)methyl)sulfinyl-1H-benzimidazole sodium Esomeprazole sodium (Esomeprazole sodium), the left-handed isomer of omeprazole sodium, is the world's first single-isomer proton pump inhibitor (PPI) developed by AstraZeneca, Sweden. Sexually inhibit the proton pump of gastric parietal cells to reduce gastric acid secretion. Esomeprazole sodium for injection was approved by the US FDA on March 31, 2005, and is used as a prescription drug for the treatment of short-term gastroesophageal reflux disease (GERD). Its chemical structure is as follows: [0005] [0006] Because esomeprazole sodium can have many different cr...

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Problems solved by technology

However, the defect of this method is that toluene is not very suitable as a solvent for the last step; WO 01 / 014367 describes the process of preparing sodium salt of esomeprazole in tetrahydrofuran, but the selection of tetrahydrofuran has similar defects to the above-mentioned toluene; WO 03 / 089408, WO 04 / 052882 and WO 07 / 013743 disclose the preparation of esomeprazole sodium from methyl isobutyl ketone, the recrystallization of the sodium salt is obtained through acetonitrile with a purity of 99.8%, but the dextro isomer impurity Larger, the high-purity single isomer required for medicine cannot be obtained; WO 06 / 001755 describes the preparation of another new polymorph, but the preparation method is to use pure water as a solvent to cultivate single crystals. Not suitable for industrialization; US2007 / 0259921 has described the method for preparing the higher esomeprazole sodium of purity by sodium methylate and esomeprazole reaction in different solvent systems, but the esomeprazole sodium that this method generates If the crystal form is changed when the solvent system is refined, the crystal form is easy to change, the repeatability of industrial production is poor, and the consistency of the crystal form of industrial production samples cannot be guaranteed; WO 10 / 003974 introduces a new preparation method of esomeprazole sodium with high chemical purity , but the crude new crystal form of esomeprazole sodium prepared by it contains 5-15% methanol, which is the methanolate of esomeprazole sodium. The drying method used for the raw material drug that exceeds the standard (10.0%) (this drying method: the product is blown into the product at 40°C with water-saturated nitrogen for at least 6 hours, and further vacuum-dried at 35°C for 10-16h, which can contain 10.0% Methanol residues reduced to 0.5% methanol residues) is peculiar, the residual solvent in the finished product is difficult to control, and this drying method is difficult to realize in industrial production

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