Method for preparing ranitidine carboxylic acid bismuth

Abstract

The invention discloses a method for preparing a ranitidine carboxylic acid bismuth composite. The method comprises the following steps of: adding ranitidine, carboxylic acid bismuth, acid or alkali into water, controlling the pH of the reaction system at 6-12, reacting at low temperature (0-50 DEG C), stirring till the solution is basically clarified, filtering, dropping absolute ethyl alcohol into the filtrate, stirring, and separating the product from the filtrate by using an azeotropic dehydration technology or a spray drying technology or a freeze drying technology; or dissolving the crude product in water, sufficiently stirring, dropping the absolute ethyl alcohol, and obtaining the product by carrying azeotropic dehydration and refining. With pharmaceutically acceptable auxiliary materials in rational amounts, the product can be produced into troches and capsules.

Description

technical field [0001] The invention relates to a preparation method of bismuth ranitidine carboxylate, which belongs to the technical field of medicine. Background technique [0002] Ranitidine bismuth citrate is a salt formed by combining ranitidine and bismuth citrate under certain conditions. The compounding process is as follows: [0003] [0004] The chemical name is N-[2-[5-[(dimethylamino)methyl]-2-furylmethylthio]ethyl]-N-methyl-2-nitro-1,1-ethylenedi Bismuth amine-2-hydroxy-1,2,3-propanetricarboxylate. It has unique physical and chemical properties and anti-ulcer mechanisms such as inhibiting gastric acid secretion, protecting gastric mucosa, inhibiting pepsin activity, and inhibiting the growth of Helicobacter pylori (HP). The reaction process of ranitidine bismuth tartrate is the same. [0005] Chinese Patent Publication No.: CN 1039419A Publication Date: February 7, 1990. The name of the invention is: Preparation method of furan derivatives. Process for ...

AI Technical Summary

Problems solved by technology

Its weak point is: 1, the thermal instability of ranitidine and bismuth ranitidine carboxylate, easily oxidizes at high temperature, and the resulting product purity is low; 2, citric acid is insoluble in water and makes reflection in two phase 3. Solvent crystallization method is used for the final purification, because bismuth ranitidine carboxylate is easy to hydrogen bond with the solvent, resulting in high residual solvent, which is about the national standard about 10 times

4. Adding too much ammonia water makes it difficult to steam out ammonia gas. It takes about 100 times of water and more than 10 times of vacuum distillation, resulting in low production efficiency and high impurity content due to long-term heating

Its shortcomings are: there are two-phase reactions, low yield (about 50%), long reaction time, low production efficiency and solvent residue problems

[0007] Chinese patent publication number: CN 1236779A publication date: December 1, 1999, the name of the invention is: the preparation method of ranitidine carboxylate bismuth salt, This application discloses a preparation method of ranitidine carboxylate bismuth salt, and its disadvantage is that a large amount of ethanol is required when the patented liquid crystallizes, resulting in difficulty in post-processing and low production efficiency

Its disadvantage is that the catalyst used affects the purity of the product

The disadvantage is that bismuth citrate reacts preferentially with ammonia

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