Method for separating lisinopril ester

A separation method and a technology of primate, which are applied in the field of process-strengthening extraction technology to separate medicines or intermediates, can solve the problems of many extraction times, high extraction energy consumption, complicated operations, etc., and achieve high extraction rate, low solvent consumption, The effect of three wastes and less energy consumption

Inactive Publication Date: 2011-03-16
ZHEJIANG UNIV OF TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The still-type extraction and separation method used in traditional industrial production, due to the high water solubility of lisinopril ester, leads to many extraction times, low efficiency, complicated operation, and high energy consumption for extraction

Method used

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  • Method for separating lisinopril ester
  • Method for separating lisinopril ester
  • Method for separating lisinopril ester

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] With the feed liquid containing lisinopril ester (15%, mass content, liquid chromatography detection), take ethyl acetate as extraction agent, operating temperature is 25 ℃, extraction equipment is D20 centrifugal extractor, and rotating speed is 3000 rpm Min, the volumetric flow rate V of the operating flow ratio of the extractant 1 / Volume flow rate of feed liquid V 2 =0.5 / 1.0, the total flow rate of extractant and feed liquid is 40mL / min, extraction stage 5 (5 sets of D20 centrifugal extractors connected in series), carry out centrifugal extraction, extract phase is through concentrating and reclaiming organic solvent, obtains lisinopril ester , the extraction rate was 91.0%, and the lisinopril purity was 95.2% (detected by liquid chromatography).

Embodiment 2

[0031] With the feed liquid that contains lisinopril ester (15%, mass content), take cyclohexane as extraction agent, operating temperature is 40 ℃, and extraction equipment is D20 centrifugal extractor, and rotating speed is 5000 revs / min, operating flow ratio The volumetric flow rate V of the extractant 1 / Volume flow rate of feed liquid V 2 =1.0 / 1.0, the total flow rate of extractant and feed liquid is 40mL / min, extraction stage 3 (3 sets of D20 centrifugal extractors connected in series), carry out centrifugal extraction, extract phase is through concentrating and reclaiming organic solvent, obtains lisinopril ester , the extraction rate is 93.3%, and the purity of lisinopril is 94.3%.

Embodiment 3

[0033] With the feed liquid that contains lisinopril ester (15%, mass content), take cyclohexane as extraction agent, operating temperature is 25 ℃, and extraction equipment is D20 centrifugal extractor, and rotating speed is 5000 rev / mins, and operating flow ratio The volumetric flow rate V of the extractant 1 / Volume flow rate of feed liquid V 2 =2.0 / 1.0, the total flow rate of extractant and feed liquid is 40mL / min, extraction stage 2 (2 sets of D20 centrifugal extractors connected in series), carry out centrifugal extraction, the organic solvent is reclaimed through concentration of extraction phase, obtains lisinopril ester , the extraction rate is 89.6%, and the purity of lisinopril is 93.9%.

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Abstract

The invention discloses a method for separating lisinopril ester. The method comprises the following steps of: performing annular gap type centrifugal extraction on lisinopril ester-containing material liquid by using a two to eight-stage serial countercurrent centrifugal extraction system consisting of annular gap types centrifugal extractors and by taking an organic solvent as an extracting agent; and concentrating the obtained extract phase and recovering the organic solvent to obtain the lisinopril ester. Compared with the conventional production process, the method has the advantages of a small amount of solvent, stable quality, high extraction rate, short period, low three-waste energy consumption (waste water, waste gas and industrial residues), safe and reliable production, and high implementation value and social economic benefit.

Description

(1) Technical field [0001] The invention relates to a method for separating medicines or intermediates by process-intensified extraction technology, more specifically to a method for separating lisinopril ester. (2) Background technology [0002] Lisinopril (Lisinopril) was developed by Merck (Merck) in the United States and was launched in 1987. Lisinopril is a lysine derivative of enalaprilat, a third-generation long-acting angiotensin-converting enzyme inhibitor drug, the structure of which can treat hypertension and other cardiovascular and cerebrovascular diseases is enalapril The lysine derivative of the active metabolite Enalaprilate, which is more hydrophilic than other ACE inhibitors, has long-acting antihypertensive effects and is well tolerated. [0003] [0004] Lisinopril ester (I) [0005] The key intermediate of lisinopril, lisinopril ester (I), contains two peptide bonds, a carboxyl group, and a carboxylate group; due to the carboxyl group, the substance...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K5/065C07K1/14
Inventor 李坚军夏建胜苏为科谢媛媛
Owner ZHEJIANG UNIV OF TECH
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