Preparation method of ornithine aspartate

Abstract

The invention provides a preparation method of ornithine aspartate, which comprises the following steps: firstly dissolving ornithine salt in water, adjusting the pH to 8-11 with alkali liquor, obtaining free ornithine by an electrodialysis method, adjusting the pH of the solution to 7-9 with aspartic acid, performing concentration, and adding an alcoholic solution for crystallization. The method of the invention can realize desalting effect, needs no spherical or powdery ion exchange resin materials or column chromatography filling materials, is simple in production process, high in production efficiency, low in cost, more stable in materials during production process, high in product yield, high in purity, less in production waste liquid, and beneficial to environmental protection.

Description

technical field [0001] The invention relates to a method for preparing ornithine-aspartate, which belongs to the technical field of pharmaceutical chemical synthesis, and more specifically, relates to a method for preparing ornithine-aspartate with low cost, environmental protection and high purity. Background technique [0002] The production of blood ammonia comes from the absorption of intestinal ammonia. When the liver is dysfunctional, on the one hand, it can reduce the digestive function, lead to the active function of intestinal bacteria, increase the amino acids produced in the intestine, and increase the absorption of intestinal ammonia. Increased blood ammonia; on the other hand, when the liver is diseased, insufficient ATP supply to the ornithine cycle and severe damage to the enzyme system of the ornithine cycle all lead to a decrease in the synthesis of urea from blood ammonia and insufficient removal of ammonia, resulting in an increase in blood ammonia . [0...

AI Technical Summary

Problems solved by technology

This method produces highly toxic barium sulfate waste, which affects the environment, cannot guarantee the safety of medication, and still needs resin to remove heavy metal ions, so the operation process is complicated and industrial production is difficult.

[0016] Chinese patent CN 102102118 B uses ion exchange resin to react with potassium carbonate, hydrogen bromide, etc., adds arginase to prepare immobilized enzyme, converts arginine to ornithine, and then forms a salt with aspartic acid. It also involves a large amount of resin and a variety of organic solvents, and the operation is cumbersome and time-consuming, which is not conducive to environmental protection and industrial production

[0017] Chinese patent CN101880240A adopts the method of dissolving ornithine acetate in water, adding ammonia water to adjust the pH, adding a large amount of acetone to precipitate ammonium acetate, adding aspartic acid after filtration, heating and refluxing to form a salt with aspartic acid ornithine, Then add a solvent to carry out operations such as crystallization and beating to obtain ornithine aspartate. In the process of this method, a large amount of organic solvents such as acetone are used, and there is a heating and reflux operation. It is necessary to pay great attention to the production of explosion-proof operations, which is not conducive to labor protection. and environmental protection, time-consuming operation

[0018] Chinese patent CN 102093236 B discloses a method for refining ornithine aspartate, which uses the crude product of ornithine aspartate (content 96.5%), uses an alumina chromatography column, and a large amount of organic solvents such as acetone and acetonitrile As the eluent, it is separated by column chromatography to obtain high-purity ornithine aspartate. During the operation of this method, a large amount of organic solvents such as acetone and acetonitrile are used, and the organic solvent eluent needs to be heated and concentrated. The production safety is low, the production operation is cumbersome, the amount of sample separated by the chromatographic column is limited, the production efficiency is low, the operation time is long, and the industrial production is difficult.

[0019] Chinese patent CN 102863346A heats and hydrolyzes arginine under the action of ammonia water and an organic amine catalyst to obtain crude ornithine, concentrates and purifies the crude ornithine, and reacts with aspartic acid to generate ornithine aspartate , heated at 105-110°C for 2 hours during the operation, there is a large degree of change in ornithine, and more impurities are formed, which are difficult to remove, seriously affecting product quality and drug safety

[0020] The present inventor has obtained a kind of production process simpler, lower cost through a large amount of systematic creative research work, and the production process does not need the preparation process of powdery or spherical ion exchange resin material, precipitating agent or catalyst, and the obtained product yields The yield is high, the purity is high, and the problems of the prior art are solved creatively, and compared with the prior art, there are substantial differences and remarkable progress. The production of ornithine-aspartic acid by the method of the present invention produces unexpected results, So far, there have been no relevant reports and applications at home and abroad

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