Method for preparing polaprezinc

Abstract

The invention discloses a method for preparing polaprezinc, and belongs to the technical field of pharmacy. The method comprises the following steps: 1, preparing a solution to 2-cyano acetyl chlorideand dichloromethane, dropwise adding the solution to a trimethylsilyl-protected dichloromethane solution of L-histidine, and adding imidazole to obtain (s)-2-cyanoacetamido-3-(1H-imidazole-4-yl)propionic acid; carrying out a catalytic hydrogenation reaction to obtain crude L-carnosine; carryin gout alkaline macro-porous ion exchange resin adsorption, flushing the adsorbed L-carnosine with an aqueous solution of alkali metal acetate, and carrying out spray drying to obtain an alkali metal salt solid of the L-carnosine; and dissolving the alkali metal salt solid of the L-carnosine in methanol,adding a methanol solution of zinc acetate, and beating and refining the obtained solution by using a methanol-water solution to obtain refined polaprezinc. The method allows highly-pure L-carnosine sodium and polaprezinc to be obtained, and allows the time of the refining and drying process of the polaprezinc to be short, and the refined polaprezinc has the advantages of easiness in crushing, high yield and low cost, so the method is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of polyprezinc, which belongs to the technical field of pharmacy. Background technique [0002] Polyprezinc is a new type of anti-ulcer drug developed by Hamari Shinyaku Co., Ltd. in Japan. It is the first zinc-containing compound used in clinical practice. The drug was launched in Japan in 1994 under the trade name Promac in the form of granules. Polyprezinc is L-carnosine zinc complex, its structural formula is as follows: [0003] [0004] L-carnosine, a dipeptide consisting of beta-alanine and L-histidine, is an antioxidant; zinc promotes wound healing. Clinical experimental data show that polyprezinc has the effect of anti-oxidation and membrane stabilization, so as to maintain the homeostasis of gastric mucosa and protect gastric mucosa cells. At the same time, it can also promote wound healing, enhance the role of defense factors, and prevent and treat digestive The role of ulcers. [0005] The...

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Problems solved by technology

This method produces more impurities, poor product quality, and the production process produces toxic sulfides that seriously pollute the environment.

[0010] 3) Skoblik et al. and Zhang Guolin et al. used Boc-β-alanine or N-benzyloxycarbonyl-β-alanine as raw materials to react with succinyl hydroxylimide respectively to obtain the corresponding N-hydroxysuccinyl hydroxylimide Amino ester reacts with L-histidine to obtain dipeptide, and after deprotection group, L-carnosine is obtained. This method has long steps and high production cost, and is not suitable for industrial production

[0012] 4) Japanese patent P2005-306782 uses L-histidine and β-alanine as raw materials and reacts with p-toluenesulfonic acid respectively to generate the corresponding p-toluenesulfonate. These two salts react with heat to generate L- The p-toluenesulfonate of carnosine is exchanged with ion-exchange resin to obtain L-carnosine. This route is short, but produces a large amount of strong acid waste water, and the environmental protection cost pressure is great, and the yield and quality of the prepared product are all low. Suitable for large-scale industrial production

This method uses the alkali metal salt of alcohol as an organic strong base, which is too strong to easily generate impurities and side reactions, and the subsequent refining of the product is difficult.

[0020] In summary, the disadvantages of the above-mentioned method are: the intermediate L-carnosine has low purity and high impurity content, the refining and drying of polyprezinc takes a long time, produces a large amount of waste water, serious pollution, complex process, low yield, high cost, etc.

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