Preparation method of L-ornithine-L-asparate double salt compound

Abstract

The invention provides a preparation method of an L-ornithine-L-asparate double salt compound. The preparation method includes: 1) dissolving L-ornithine in a proper amount of water, adding L-asparatefor salt forming reaction, adding a proper amount of alkali to neutralize after salt forming reaction is complete so as to obtain a reaction system containing the L-ornithine-L-asparate double salt compound, and cooling, wherein the mole ratio between the L-ornithine and the L-asparate is 1:1; 2) filtering after cooling, adding obtained filtrate into a proper amount of preheated hydrophilic solution, stirring at a constant temperature, cooling, filtering, washing and drying to obtain the L-ornithine-L-asparate double salt compound. The preparation method has few processing steps, the obtainedL-ornithine-L-asparate double salt compound is high in purity and stability and can be sterilized by a terminal excessive killing method, potential medication safety hazards are reduced greatly, andproduction cost is reduced remarkably.

Description

technical field [0001] The invention belongs to the field of chemical medicines, in particular, relates to a double salt compound of ornithine aspartate, molecular formula is (I), chemical name: (S)-2,5-diaminovaleric acid-(S) -The preparation method of 2-aminosuccinate. Background technique [0002] Aspartic acid ornithine double salt compound (referred to as "aspartic acid ornithine") is a stable dipeptide compound prepared by chemical synthesis of L-ornithine and L-aspartic acid. It was listed in Germany in the 1970s by the German Merz pharmaceutical company, and it was included in the German Pharmacopoeia in 1991. The US FDA approved it for the treatment of hepatic encephalopathy, and was recommended by the FDA as the drug of choice for the treatment of hepatic encephalopathy. When ornithine aspartate enters the human body, it is decomposed into aspartic acid and ornithine, which can directly participate in the metabolism of liver cells and activate two key enzymes in ...

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Problems solved by technology

[0006] This method has the following technical defects: on the one hand, because the method uses ornithine hydrochloride as a raw material, anion and cation resins are used to remove chloride ions, resulting in a large amount of waste water, resulting in complicated post-treatment and increased production costs

[0013] (1), many process steps, cumbersome operation, difficult to control

[0014] (2), the structure of L-ornithine-base generated after the neutralization of L-ornithine acetate and ammonia water is unstable, and it is easy to generate various impurities in the reaction system. Subsequent L-ornithine-base and L - Impurities are also generated during the reaction of aspartic acid, which leads to low purity of aspartic acid ornithine in the reaction system and many impurities, which significantly increases the hidden danger of drug safety

However, the third method above introduces ammonia water into the reaction system, resulting in ammonium ions in the product, which is in contradiction with the therapeutic mechanism of ornithine-aspartate, and has a greater hidden danger in drug safety.

[0016] In addition, we found in the process of repeated experiments that the ornithine-aspartic acid products obtained according to the above-mentioned methods 1 to 3 are not stable, and are prone to discoloration and swelling during storage, which affects the storage quality of the product. It has brought a lot of difficulty and also increased the safety hazard of ornithine-aspartic acid.

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