Preparation method of Meropenem trihydrate crystals

A technology of meropenem and trihydrate, which is applied in the direction of organic chemistry, can solve the problem of reducing the solvent residue of meropenem trihydrate that is difficult to achieve and has not been seen, and achieve the effect of less raw material loss and simple and easy process

Active Publication Date: 2010-12-15
SHENZHEN HAIBIN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Meropenem trihydrate standards in the United States Pharmacopoeia have extremely strict requirements on solvent residues, among which acetone residues should not exceed 0.05%, which is generally difficult to achieve
[0007] There is no report on reducing the solvent residue of meropenem trihydrate in published literature and patents

Method used

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  • Preparation method of Meropenem trihydrate crystals

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Under nitrogen atmosphere, heat 200ml of distilled water to 65°C-70°C. Add 10.0 g of the crude meropenem product (test = 92%) into distilled water, stir at 65°C-70°C for 2 minutes, add 1.0 g of activated carbon, then rapidly cool to 10°C-15°C, remove the activated carbon by filtration, and cool the filtrate to At about 10°C, add a small amount of seed crystals, stir at a relatively fast speed for 4 hours, keep the temperature at 2-5°C, and filter to obtain 6.3 g of meropenem trihydrate. The related substances of the obtained crystals are measured by the Pharmacopoeia method, and the single impurity is less than 0.1%, the total impurity is less than 0.3%, and the residue of various organic solvents is less than 0.5‰. Add 400ml of acetone to the mother liquor, keep stirring at 2-5°C for 1 hour, then start to add 400ml of acetone dropwise, finish dropping after 30 minutes, keep stirring at this temperature for 2 hours, then filter, and recover 2.3g of meropenem.

Embodiment 2

[0025] Under nitrogen atmosphere, heat 200ml of distilled water to 65°C-70°C. Add 10.0 g of the crude meropenem product (test = 92%) into distilled water, stir at 65°C-70°C for 2 minutes, add 1.0 g of activated carbon, then rapidly cool to 10°C-15°C, remove the activated carbon by filtration, and cool the filtrate to 10°C, without adding seed crystals, stirred at a relatively fast speed for 4 hours, kept the temperature at 2-5°C, and filtered to obtain 5.4 g of meropenem trihydrate crystals. The related substances of the obtained crystals are measured by the Pharmacopoeia method, and the single impurity is less than 0.1%, the total impurity is less than 0.3%, and the residue of various organic solvents is less than 0.5‰. Add 400ml of acetone to the mother liquor, keep stirring at 2-5°C for 1 hour, then start to add 400ml of acetone dropwise, finish dropping after 30 minutes, keep stirring at this temperature for 2 hours, then filter, and recover 3.1g of meropenem.

Embodiment 3

[0027] Under nitrogen atmosphere, 300ml of distilled water was heated to 50°C-55°C. Add 10.0 g of the crude meropenem product (test = 92%) into distilled water, stir at 50°C-55°C for 2 minutes, add 1.0 g of activated carbon, then rapidly cool to 10°C-15°C, remove the activated carbon by filtration, and cool the filtrate to At 10°C, add a small amount of seed crystals, stir at a relatively fast speed for 4 hours, keep the temperature at 2-5°C, and filter to obtain 5.6 g of meropenem trihydrate crystals. The related substances of the obtained crystals are measured by the Pharmacopoeia method, and the single impurity is less than 0.1%, the total impurity is less than 0.3%, and the residue of various organic solvents is less than 0.5‰. Add 600ml of acetone to the mother liquor, keep stirring at 2-5°C for 1 hour, then start to add 600ml of acetone dropwise, finish dropping after 30 minutes, keep stirring at this temperature for 2 hours, then filter, and recover 2.4g of meropenem. ...

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Abstract

The invention discloses a refining method of Meropenem trihydrate crystals, comprising the following steps of: dissolving a crude Meropenem product in water the temperature of which is 30-70 DEG C to obtain a solution I; treating the solution I by activated carbon and filtering at 5-30 DEG C to obtain a solution II; crystallizing the solution II at 0-10 DEG C and filtering to obtain a solution III and the Meropenem trihydrate crystals; adding an organic solvent to the solution III further, and recovering Meropenem. The method is simple and easy to implement, and the obtained Meropenem trihydrate crystals have super high purity and super-low solvent residuals, meet the requirements of the method for preparing the Meropenem and is suitable for industrial production.

Description

technical field [0001] The invention relates to a method for preparing a compound, in particular to a method for refining meropenem trihydrate crystals. Background technique [0002] Carbapenem antibiotics are a new type of fully synthetic β-lactam antibiotics, which have strong antibacterial activity against Gram-positive and negative bacteria, aerobic bacteria, and anaerobic bacteria. Since the discovery of thiamycin in 1976, the research on carbapenem antibiotics has made great progress. In particular, 1β-methyl carbapenem antibiotics have good chemical stability and are stable to β-lactamase and renal dehydropeptide-I enzymes. They are currently one of the first-choice drugs for the treatment of severe and multidrug-resistant bacterial infections. It has been more and more widely used in clinical practice. [0003] Currently commercialized 1β-methyl carbapenem antibiotics include meropenem, biapenem, doripenem, and ertapenem. Meropenem is the first 1β-methyl carbapene...

Claims

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Application Information

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IPC IPC(8): C07D477/20C07D477/06
Inventor 任鹏朱喜宗汪小华
Owner SHENZHEN HAIBIN PHARMA
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