Amorphous ivabradine hydrochloride and preparation method thereof

An ivabradine hydrochloride, amorphous technology, applied in cardiovascular system diseases, active ingredients of heterocyclic compounds, drug combinations, etc., can solve problems such as easy water absorption, low production efficiency, instability, etc., and achieve simple operation and good performance , the effect of stable quality

Inactive Publication Date: 2015-08-12
YANGTZE RIVER PHARMA GRP BEIJING HAIYAN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Patents CN200810111115.2 and CN200910013935.2 report two different crystal forms of amorphous ivabradine hydrochloride, but the two amorphous ivabradine hydrochloride are easy to absorb water and unstable
However, the amorphous ivabradine hydrochloride disclosed in the patent CN200910013935.2 is prepared by a concentration method. This method needs to prepare qualified crystalline ivabradine hydrochloride in advance, then dissolve it in a solvent, concentrate to dryness, and the production efficiency is low.

Method used

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  • Amorphous ivabradine hydrochloride and preparation method thereof
  • Amorphous ivabradine hydrochloride and preparation method thereof
  • Amorphous ivabradine hydrochloride and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] Mix 90ml of purified water and 10ml of absolute ethanol, then add 10g of ivabradine hydrochloride in batches, while stirring, until the solution is complete. The resulting clear solution was heated at 50 °C for an additional 0.5 h, then gradually cooled to ambient temperature. Turn on the freeze dryer and set the freeze-drying curve: -50°C, 10 5 Pa(4h); -20°C, 10Pa(12h); 0°C, 10Pa(2h); 15°C, 10Pa(2h); 30°C, 10Pa(2h); 50°C, 10Pa(10h), the product was 9.7g , which was detected as an amorphous powder by XRD, and the test results were as follows figure 1 .

[0064] The amorphous ivabradine hydrochloride prepared in Example 1 was characterized by differential scanning calorimetry (DSC). see results figure 2 .

[0065] Depend on figure 2 The results show that the differential scanning calorimetry curve has an endothermic peak at about 195.99°C.

Embodiment 2

[0067] Mix 70ml of purified water and 30ml of absolute ethanol, then add 10g of ivabradine hydrochloride in batches, while stirring, until the solution is complete. The resulting clear solution was heated at 50 °C for an additional 0.5 h, then gradually cooled to ambient temperature. Turn on the freeze dryer, set the freeze-drying curve -40°C, 10 5 Pa(4h); -30℃, 10Pa(12h); 0℃, 10Pa(2h); 10℃, 10Pa(2h); 30℃, 10Pa(2h); 50℃, 10Pa(10h), the product was 9.6g , which was detected as an amorphous powder by XRD, and the test results were as follows figure 1 , DSC detection result is the same as embodiment 1.

Embodiment 3

[0069] Mix 90ml of purified water and 10ml of tert-butanol, then add 10g of ivabradine hydrochloride in batches, while stirring, until the solution is complete. The resulting clear solution was heated at 50 °C for an additional 0.5 h, then gradually cooled to ambient temperature. Turn on the freeze dryer and set the freeze-drying curve: -60°C, 10 5 Pa(4h); -30℃, 10Pa(12h); 0℃, 10Pa(2h); 20℃, 10Pa(2h); 40℃, 10Pa(2h); 80℃, 10Pa(10h), the product 9.6g was obtained , which was detected as an amorphous powder by XRD, and the test results were as follows figure 1 , DSC detection result is the same as embodiment 1.

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PUM

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Abstract

The invention relates to the field of medicinal chemistry, and discloses a new amorphous ivabradine hydrochloride, a preparation method thereof and a pharmaceutical composition containing the same. The amorphous ivabradine hydrochloride has good stability. The preparation method for amorphous ivabradine hydrochloride provided by the invention is easy to operate, and has high amorphous ivabradine hydrochloride yield, thus being suitable for laboratory development and industrial production, and having wide application. The amorphous ivabradine hydrochloride product prepared by the method provided by the invention has stable quality and can be directly used for preparation of heart rate decreasing drugs.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to amorphous ivabradine hydrochloride, a preparation method thereof and a pharmaceutical composition containing it. Background technique [0002] Ivabradine Hydrochloride (Ivabradine Hydrochloride), the chemical name is 3-[3-[[(8S)-3,4-dimethoxy-8-bicyclo[4.2.0]octane-1,3,5-tri En]methyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepin-4-one hydrochloride. Its chemical formula is [0003] [0004] Ivabradine and its addition salts with pharmaceutically acceptable acids, more particularly its hydrochloride, possess extremely valuable pharmacological and therapeutic properties, especially bradycardic properties, making these compounds It is useful in the treatment or prophylaxis of various clinical conditions of myocardial ischemia such as angina pectoris, myocardial infarction and associated arrhythmias, as well as various pathological conditions involving arrhyth...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D223/16A61K31/55A61P9/10A61P9/06A61P9/04
CPCC07D223/16
Inventor 王建耀何艳刘伟闫利颖王海盛于宝辉
Owner YANGTZE RIVER PHARMA GRP BEIJING HAIYAN PHARMA
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