A kind of preparation method of thiamine hydrochloride crystal product

Abstract

The invention discloses a method for preparing a thiamine hydrochloride crystal product. Thiamine mononitrate is dispersed into a solvent, and thiamine mononitrate turbid liquid with the concentration of 0.05 g / ml to 0.2 g / ml is obtained, and heated to 50 DEG C to 70 DEG. Chlorosulfonic acid is dropwise added to concentrated hydrochloric acid to generate hydrogen chloride gas, and the gas is introduced into to concentrated sulfuric acid to be dried, and is introduced into the thiamine mononitrate turbid liquid under stirring action. After introduction of the hydrogen chloride gas is completed, heat preservation is carried out for 15 min to 30 min, then the temperature is reduced to 10 DEG C, the cooling rate ranges from 0.1 DEG C / min to 0.5 DEG C / min, filtering, washing and drying are carried out, and then thiamine hydrochloride crystals are prepared. The crystals are rhabdolith, the angle of repose ranges from 31 DEG C to 36.4 DEG C, and the bulk density ranges from 0.50 g / ml to 0.608 g / ml. The thiamine hydrochloride crystal product is good in liquidity. According to the method, the process that thiamine hydrochloride methyl alcohol solvent compounds are formed firstly, then drying is carried out to remove methyl alcohol is avoided, and therefore environmental pollution is reduced, and cost and solvent residues are reduced. The method can be suitable for large-scale production.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical crystallization, and in particular relates to a preparation method of thiamine hydrochloride crystals. Background technique [0002] Thiamine Hydrochloride, Vitamin B 1 Hydrochloride, also known as thiamine hydrochloride, English name thiaminehydrochloride, molecular formula C 12 h 17 ClN 4 OS HCl, molecular weight 337.27, CAS No. 67-03-8, chemical name 3-[(4-amino-2-methyl-5-pyrimidinyl)-methyl]-5-(2-hydroxyethyl chloride) base)-4-methylthiazole, its molecular structure is shown below. [0003] [0004] Thiamine hydrochloride is a vitamin B 1 A form of , commonly used as a nutritional supplement. Vitamin B 1 It is a compound composed of a pyrimidine ring and a thiazole ring. Because the molecule contains sulfur and amine, it is also named thiamine. Vitamin B 1 It naturally exists in rice bran, bran, lean meat, peanuts and other foods. The pure product is usually prepared by che...

AI Technical Summary

Problems solved by technology

The crystals prepared by this process are thiamine hydrochloride methanol solvent compound. The methanol in the crystal lattice is removed through the drying process, but this process will cause environmental pollution and waste of methanol, and there is also the risk of solvent residue

In addition, the product prepared by this process is a flaky crystal, which has the problems of poor fluidity, low bulk density, and easy agglomeration of the product

[0006] In Chinese patent CN103387573 A, a preparation process of thiamine hydrochloride is disclosed. The difference between it and the traditional process is that the patent adopts the method of heating concentrated hydrochloric acid to generate hydrogen chloride gas, which can avoid the use of dangerous chemical chlorosulfonic acid. However, the process The same prepared methanol solvent compound of thiamine hydrochloride is removed through the drying process, while the product is still a flaky crystal, which has the problem of poor fluidity and easy agglomeration

[0007] Chinese patent CN1459449 A discloses a new method for preparing thiamine hydrochloride from thiol thiamine, which is to use thiol thiamine, an intermediate of vitamin B1, as a raw material, oxidize hydrogen peroxide to generate thiamine hydrochloride, and add barium chloride to react with it , directly complete the conversion from thiamine sulfate to thiamine hydrochloride, and then use methanol hydrochloride to convert thiamine nitrate to thiamine hydrochloride, but barium ions are introduced during the conversion process, which is difficult to remove in subsequent processes, and the purity is unqualified. Moreover, the whole process uses a large amount of inorganic compounds for neutralization or salt-forming reactions, which cannot be recycled and applied mechanically, resulting in increased process costs and cumbersome operation steps

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