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Refining method of enalapril maleate

A technology of enalapril maleate and a refining method, which is applied in the field of refining enalapril maleate, can solve the problems such as impurity cannot be removed, and achieve low production cost, high product purity, and improved yield and purity Effect

Inactive Publication Date: 2019-05-10
CISEN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, the traditional refining method of "alkali dissolution and acid precipitation" cannot remove the impurity stably and completely

Method used

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  • Refining method of enalapril maleate
  • Refining method of enalapril maleate
  • Refining method of enalapril maleate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Add 20.0 g of enalapril maleate crude product into 320 ml of purified water, heat to 60 ° C, stir for 2 hours, cool to 5 ° C, stand for crystallization for 2 hours, filter, and wash the filter cake with purified water at 5 ° C for two Once, vacuum drying at 50° C. for 4 hours gave 18.0 g of enalapril maleate with a yield of 90.0%. Detected by HPLC, the peak eluting time of 13.7 minutes was enalapril, and the peak area was 99.52%.

Embodiment 2

[0024] Add 20.0 g of enalapril maleate crude product into 100 ml of acetonitrile-water (9:1), heat to 80 ° C, stir until the solid is completely dissolved, continue stirring for 30 minutes, cool to 10 ° C, and stand for crystallization 4 hours, filtered, and the filter cake was washed twice with acetonitrile-water (9:1) at 10°C, and dried in vacuum at 30°C for 4 hours to obtain 18.2 g of enalapril maleate with a yield of 91.0%. Detected by HPLC, the peak eluting time of 15.6 minutes was enalapril, and the peak area was 99.75%.

Embodiment 3

[0026] Add 20.0g of enalapril maleate crude product into 100ml of dichloromethane-methanol-water (5:3:2) containing 0.5g of Qingjiangtane A, heat to 80°C, stir until the solid is completely dissolved, then continue Stir for 30 minutes, cool to 3°C, stand for crystallization for 4 hours, filter, wash the filter cake twice with 3°C dichloromethane-methanol-water (5:3:2), and vacuum dry at 40°C for 4 hours, 19.4 g of enalapril maleate was obtained with a yield of 97.1%. Detected by HPLC, the peak eluting time of 13.7 minutes was enalapril, and the peak area was 99.68%.

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Abstract

The invention belongs to the technical field of preparation of drugs, and relates to a refining method of enalapril maleate. The refining method comprises the following steps of adding an enalapril maleate crude product into a water-organic solvent mixed solvent system, heating the system to 30-80 DEG C, conducting stirring dissolution, after stirring is conducted for 30 min, cooling to 0-20 DEG Cfor crystallization, conducting filtering, utilizing a mixed solvent which is cooled to 0-10 DEG C for washing a filter cake twice, and conducting vacuum drying at 20-60 DEG C to obtain enalapril maleate with the purity of 99.5% or above. Compared with the prior art, the refining method of enalapril maleate has the advantages that enalapril maleate is refined through the method of combining the difference of solubility properties of enalapril maleate in various solvents with the temperature control, the quality of the obtained product is stable, the yield and purity are further increased, theyield is 84% or above, the quality is higher than the pharmacopoeia criterion, and as is detected by HPLC, the purity is larger than 99.5%, and the total impurity content is lower than 0.04.

Description

technical field [0001] The invention belongs to the technical field of medicine preparation, and in particular relates to a method for refining enalapril maleate. Background technique [0002] Enalapril Maleate, also known as Yiyali, CAS registration number: 76095-16-4, chemical name: N-[(s)-ethoxycarbonyl-3-phenylpropyl]-L -Alanyl-L-proline maleate, the chemical structural formula is as follows: [0003] [0004] Enalapril maleate is one of the main components of the oral antihypertensive drug Eustatin, which was developed by Merck & Co Inc and approved for the treatment of various stages of essential hypertension, renal Vascular hypertension, heart failure of all levels, prevention of symptomatic heart failure and prevention of coronary ischemic events in patients with left ventricular dysfunction. [0005] Enalapril maleate can lower blood pressure in hypertensive patients and improve symptoms and signs of chronic heart failure. Enalapril maleate is an angiotensin-c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K5/062C07K1/36C07K1/34C07K1/30
Inventor 孙守飞刘佩佩
Owner CISEN PHARMA