Ivabradine hydrochloride impurity and preparation method and application thereof

Abstract

The invention discloses an ivabradine hydrochloride impurity and a preparation method and application thereof. The impurity has thermal sensitivity, it is found in preparation stability tests that the impurity content is gradually increased along with inspection time increasing, specially when the storage temperature is higher than 25 DEG C, the impurity content is obviously increased, the quality of ivabradine hydrochloride is restricted, and potential toxic and side effects exist. The ivabradine hydrochloride impurity can be used for quality control over the ivabradine hydrochloride raw material and a preparation thereof, and the safety and effectiveness of using a product in clinic are guaranteed. The method for preparing the ivabradine hydrochloride impurity is easy to operate, the reaction condition is mild, and the high-purity ivabradine hydrochloride impurity can be obtained.

Description

technical field [0001] The invention relates to the technical field of medicines, in particular to an ivabradine hydrochloride impurity and a preparation method and application thereof. Background technique [0002] Ivabradine hydrochloride (Ivabradinehydrochloride) was developed by the French company Servier and was first launched in Ireland in 2006. It has obvious curative effect on patients with chronic stable angina pectoris who are forbidden or intolerant of β-receptor blockers and have normal sinus rhythm. , can be used clinically to treat various myocardial ischemia, such as angina pectoris, myocardial infarction and related rhythm disorders, and is a new generation of cardiovascular drugs with very broad therapeutic prospects. Its chemical name is 3-{3-[{[(7S)-3,4-dimethoxybicyclo[4.2.0]oct-1,3,5-trien-7-yl]-methyl}( Methyl)amino]propyl}-1,3,4,5-tetrahydro-7,8-dimethoxy-2H-3-benzazepin-2-one hydrochloride, the structural formula is as follows: [0003] [0004] ...

AI Technical Summary

Problems solved by technology

The inventor found during the research and experiment of process route selection that no matter the preparation method based on the existing literature and patent reports or the self-developed preparation process, there will always be an impurity with unknown structure and large content in the final preparation. Its production cannot be avoided by optimizing the selection of the preparation process

Moreover, the impurity is also heat-sensitive. In the subsequent preparation stability experiment, it was found that the content of the impurity gradually increased as the investigation time increased, especially when the storage temperature was higher than 25°C, the content of the impurity increased significantly. The most abundant impurity, which has a potential risk to the safety of the formulated product

Images