Preparation method of polaprezinc and polaprezinc preparation

Abstract

The invention provides a preparation method of polaprezinc and a polaprezinc preparation. The preparation method of polaprezinc comprises the steps that benzylamine, 3-halopyruvic aldehyde, a first acid reagent and a first organic solvent are mixed for a reaction, then ammonium halide and polyformaldehyde are added, and 1-phenylmethyl-4-(halomethyl)-1H-imidazole is obtained through a reaction; thematerial is added in a reaction mixture of 2-aminoacetonitrile, an alkaline reagent and a second organic solvent, and the materials are reacted to obtain 3-amino-nitrogen-(2-(1-phenylmethyl-1H-4-imidazole)-1-cyanoethyl) propanamide; the material is mixed with a reducing agent, a second acidic reagent and a third organic solvent, and the materials are reacted to obtain 3-amino-nitrogen-(1-carboxyl-2-(1hydrogen-4-imidazole) ethyl) propionamide; and the obtained product and zinc salt are dissolved in a fourth organic solvent, and a reaction is carried out to obtain the polaprezinc. According tothe technical scheme, almost no pollution is caused to the environment, no potential safety hazard exists in the preparation process, the steps are short, the conditions are simple, purification is easy, the yield is high, the preparation cost of the polaprezinc is low, and the polaprezinc is suitable for industrial production.

Description

technical field [0001] The invention relates to the technical field of pharmacy, in particular to a preparation method of polyprezinc and a polyprezinc preparation. Background technique [0002] The chemical name of polaprezinc is L-carnosine zinc, which is a new anti-ulcer drug jointly developed by Japan Hamari Chemical Co., Ltd. and Zeria Pharmaceutical Company. Among them, L-carnosine is a dipeptide composed of β-alanine and L-histidine, which belongs to an antioxidant, and zinc can promote wound healing, so polyprezinc can accelerate the healing of chronic gastric ulcer, And can stimulate the proliferation of epithelial cells. 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 mucosal cells; at the same time, polyprezinc can also promote wound healing and enhance defense factors role, to achieve the role of prevention and treatment of pepti...

AI Technical Summary

Problems solved by technology

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

[0007] 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, obtains L-carnosine. The reaction steps of this method are long, and the production cost is too high, so it is not suitable for industrialized production

[0008] 4. Sifferd et al. synthesized N-benzyloxycarbonyl-β-alanine from β-alanine, then reacted with sodium nitrite to generate N-benzyloxycarbonyl azide, and then reacted with L-histidine methyl ester , and then obtain L-carnosine through hydrolysis and hydrogenolysis. The intermediate of this method involves explosive azide, and there are potential safety hazards in the preparation process, which is not suitable for industrial production

[0009] 5. In the KR2017023417 patent, L-carnosine is used as a raw material, and an alkali metal salt of self-made alcohol is added to the alcohol suspension of L-carnosine and zinc acetate to prepare polypre zinc, and then purified water is added to refine polypre zinc. In order to remove the by-product acetate, the alkali metal salt of alcohol used in this method is an organic strong base, which is too strong to easily generate impurities and side reactions, making subsequent refining of the product difficult

[0010] 6. In Japanese Patent No. 07-116160 and Japanese Patent No. 2007-204397, after the salt-forming reaction of L-carnosine, it is coordinated in an alcohol solvent to obtain crystalline polyprezinc. However, the resulting Polyprezinc contains a large amount of alkali metal salts, which need to be washed with a large amount of water to remove such salts. After washing with water, polyprezinc has a high viscosity and contains a large amount of water, which requires a long time for filtration and drying, and After drying, polyprezinc is a hard block or a hard ball, and it takes a long time to crush to reach the target particle size

[0011] Based on the above existing methods for preparing polyprezinc, the disadvantages include: complex reaction steps, low yield, poor quality, waste water or intermediate products that pollute the environment, difficult and time-consuming refining, and intermediate products that are harmful to the preparation process. Security risks, etc.

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