Purifying method for rabeprazole sodium

Abstract

The invention discloses a purifying method for rabeprazole sodium. The method comprises the following steps: dissolving a crude product of rabeprazole sodium in aqueous alkali; adding methylbenzene; under the nitrogen protection, regulating pH value to 7.0-8.0; adding an adsorbent and then filtering; separating the organic phase and then adding sodium hydroxide aqueous solution and filtering; collecting solid, thereby acquiring a purified product of rabeprazole sodium. Compared with the present purifying method, the method provided by the invention has advantages; the crude product of rabeprazole sodium is unstable in the process of crystallizing in the solution or dewatering and is easy to degrade or decompose, so that the impurities are increased and the purity is reduced; an experiment proves that the pH value regulation before salt forming and the active carbon decoloration method for refining can greatly reduce the degradation and decomposition of the products; the product can meet the qualified requirement, without re-crystallizing after the salt forming; the re-crystallizing after the salt forming is not required, so that the dosage of the organic solvent can be effectively reduced, the yield can be increased and the residual solvent content also can be reduced.

Description

technical field [0001] The invention relates to a purification method of dextro-rabeprazole sodium, which belongs to the technical field of medicine. Background technique [0002] Dex-rabeprazole sodium, chemical name: 5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl Acyl]-1H-benzimidazole sodium, molecular formula: C18H20N3O3SNa, molecular weight: 381.1, structural formula is as follows: [0003] [0004] Proton pump inhibitors (PPIs) are the drugs of choice for the treatment of acid-related diseases such as peptic ulcers and gastroesophageal reflux disease. At present, there are five PPIs commonly used in clinical practice: omeprazole, lansoprazole, rabeprazole, pantoprazole and esomeprazole. Dex-rabeprazole sodium is a single isomer of rabeprazole sodium, the (R)-isomer. Due to its metabolic advantage, d-rabeprazole sodium has higher bioavailability and more consistent pharmacokinetics, resulting in increased drug arrival at the proton pump and be...

AI Technical Summary

Problems solved by technology

[0005] At present, the purification of dextro-rabeprazole sodium mainly has the following methods: direct dehydration under reduced pressure into a slurry, and then add ethers (including petroleum ether, diethyl ether, isopropyl ether, etc.) to separate out crystals to be purified. This method is not easy To remove impurities, the crude product of dex-rabeprazole sodium has high quality requirements, and the dehydration is not complete, and the crystals are fine and difficult to filter

[0006] Repeated extraction between the organic phase and the aqueous solution by using the difference in solubility at different pH values, then distilling off the organic solvent under reduced pressure, and recrystallizing in acetone for purification, this method can remove sulfone impurities very well, but The operation is cumbersome, and the solvent is highly toxic, and it is not easy to completely remove

[0007] After adding acetonitrile several times and concentrating under reduced pressure to take out water, add ethers (including petroleum ether, diethyl ether, isopropyl ether, etc.), acetone, methyl isobutyl ketone or ethyl acetate to precipitate dex-rabeprazole sodium , this method has a long reaction time and is easy to oxidize. At the same time, organic solvents such as acetone, methyl isobutyl ketone or ethyl acetate are more toxic and difficult to remove completely.

[0008] Therefore, in order to overcome the deficiencies in the purification and refining process of dex-rabeprazole sodium in the above-mentioned technology, and the disadvantages that the produced dex-rabeprazole sodium has a relatively poor degree, which easily leads to a sharp decline in the stability of the preparation, a simple and easy method is obtained by exploring The purification method of dextro-rabeprazole sodium

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