Method for resolving metoprolol enantiomers by using simulated moving bed chromatography

A technology for simulating moving bed and chromatographic separation, applied in the field of separation of chiral drugs, can solve problems such as no public reports, and achieve the effects of simple process, stable product quality, and continuous automation of production

Inactive Publication Date: 2014-05-14
江苏汉邦科技股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In recent years, simulated moving bed chromatography technology has achieved rapid development in the separation of drugs,

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

Separation example one

1. Sample preparation: Dissolve the sample with mobile phase to make a concentration of 5g / L, and filter it through a 0.45um organic filter membrane for later use;

2. Selection of simulated moving bed parameters: Determine the parameters as follows: injection flow rate 0.2mL / min, elution flow rate 2.0mL / min, extract flow rate 1.2mL / min, raffinate flow rate 1.0mL / min, switching time 12min, The temperature is controlled at 20-30°C;

3. Product collection: After the simulated moving bed system runs stably, the products are collected from the two outlets respectively, concentrated under reduced pressure, and recrystallized to obtain the final product;

4. Finished product inspection: After the obtained product is dissolved in mobile phase, the purity of the two export products R-metoprolol and S-metoprolol are detected by analytical conditions to be 98.3% and 99.2% respectively;

Each kilogram of stationary phase can produce 0.52kg of R-metoprolol and S-m...

Example Embodiment

Separation example two

1. Sample preparation: Dissolve the sample with mobile phase to make a concentration of 10g / L, and filter it through a 0.45um organic filter membrane for later use;

2. Selection of simulated moving bed parameters: Determine the parameters as follows: injection flow rate 0.6mL / min, elution flow rate 4.0mL / min, extract flow rate 2.4mL / min, raffinate flow rate 2.2mL / min, switching time 10min, The temperature is controlled at 20-30°C;

3. Product collection: After the simulated moving bed system runs stably, the products are collected from the two outlets respectively, concentrated under reduced pressure, and recrystallized to obtain the final product;

4. Finished product inspection: After the obtained product is dissolved in mobile phase, the purity of the two export products R-metoprolol and S-metoprolol are detected by analytical conditions to be 97.6% and 98.5% respectively;

Each kilogram of stationary phase can produce 1.25kg of R-metoprolol and S-...

Example Embodiment

Separation example three

1. Sample preparation: Dissolve the sample in mobile phase to make a concentration of 20g / L, and filter it through a 0.45um organic filter membrane for later use;

2. Selection of simulated moving bed parameters: Determine the parameters as follows: injection flow rate 1.2mL / min, elution flow rate 6.6mL / min, extract flow rate 4.0mL / min, raffinate flow rate 3.8mL / min, switching time 11min, The temperature is controlled at 20-30°C;

3. Product collection: After the simulated moving bed system runs stably, the products are collected from the two outlets respectively, concentrated under reduced pressure, and recrystallized to obtain the final product;

4. Finished product inspection: after dissolving the obtained product with the mobile phase, the purity of the two export products R-metoprolol and S-metoprolol were detected by analytical conditions to be 97.2% and 98.1% respectively;

Each kilogram of stationary phase can produce 2.12kg of R-metoprolol a...

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PUM

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Abstract

The invention discloses a method for resolving metoprolol enantiomers by using simulated moving bed chromatography. The method is characterized in that the simulated moving bed chromatography is adopted, an amylose-tris(3,5-dimethylphenylcarbamate) is used as a filler and n-hexane and an alcohol organic modifier are used as a mobile phase, to resolve the metoprolol enantiomers under a positive phase condition, thus obtaining high-pure R-metoprolol and S-metoprolol. The simulated moving bed chromatography is continuous production, has high automatic degree and high production efficiency.

Description

technical field [0001] The invention relates to a separation technology of chiral drugs, in particular to a simulated moving bed chromatographic separation method of metoprolol. Background technique Metoprolol is a selective β1 receptor blocker, which is widely used clinically in the treatment of cardiovascular diseases. Metoprolol is an optically active compound with a pair of enantiomers, and it is currently administered in the form of a racemate clinically. Studies have shown that the receptor affinity of the S-enantiomer is 25 times that of its R-enantiomer. In isolated hearts, its S-enantiomer blocked isoproterenol-activated adenylate cyclase activity 33-fold more than its enantiomer. There is also stereoselectivity in the metabolic process, and the first-pass effect of its S-enantiomer is lower. Due to the significant differences in pharmacodynamics and pharmacokinetics of the two enantiomers, enantiomer separation is of great significance for further research on ...

Claims

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Application Information

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IPC IPC(8): C07C217/32C07C213/10
Inventor 张大兵张宁罗军侠刘玉明王亚辉
Owner 江苏汉邦科技股份有限公司
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