Crystallization method for cefotaxime sodium

A kind of technology of cefotaxime sodium and cefotaxime acid, which is applied in the crystallization field of cefotaxime sodium

Inactive Publication Date: 2013-09-25
NORTH CHINA PHARMA HEBEI HUAMIN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method is easy to operate and has a short production cycle, but the prepared product has a high residual organic solvent, it is difficult to reuse the solvent, and the clarity of the product solution is poor.
WO2011042776A1 discloses a crystallization method using glyme and methoxyethanol as the solvent system. The quality of the crystals prepared by this method is good, but the fluidity of the product is poor, and the solvent selected by this method is expensive , the loss of solvent in the production process leads to its high cost
In order to overcome the problems existing in the crystallization method of the anhydrous system, CN101486719A discloses a crystallization method using acetone aqueous solution as the solvent system. The method is simple and overcomes the difficulty in controlling the crystallization process. poor

Method used

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  • Crystallization method for cefotaxime sodium
  • Crystallization method for cefotaxime sodium
  • Crystallization method for cefotaxime sodium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Take 20g of cefotaxime acid and 4.43g of sodium bicarbonate, add them into 150ml of water-containing solvent system (the water-containing solvent system is composed of 15ml of water and 135ml of methanol), control the temperature at -10°C, and stir to dissolve. Add 0.2 g of activated carbon, decolorize for 30 minutes, and filter; wash the filtered carbon layer with methanol, and combine the filtrate and washing liquid. Control the temperature at -10°C, add 100ml of acetone (crystal precipitation agent) dropwise within 60 minutes, add 0.3g of seed crystals, and grow the crystal for 60 minutes; within 100 minutes, add dropwise 600ml of acetone (crystal precipitation agent) to crystallize; The obtained crystals are washed; dried at 40° C. and a vacuum of 0.093 MPa until the moisture content and residual solubility are qualified.

[0024] Its yield: 95.0%; content: 96.7%; single largest impurity: 0.3%; total impurity: 1.2%; solution color: 2+; clarity 0.25-.

Embodiment 2

[0026] Take 20g of cefotaxime acid and 4.32g of sodium acetate, add it to 100ml of water-containing solvent system (the water-containing solvent system is composed of 20ml of water and 80ml of ethanol), control the temperature at 0°C, and stir to dissolve. Add 0.2 g of activated carbon, decolorize for 30 minutes, and filter; wash the filtered carbon layer with ethanol, and combine the filtrate and washing liquid. Control the temperature at 0°C, add 80ml of butyl acetate dropwise within 100min, add 0.25g of seed crystal, and grow the crystal for 50min; within 250min, add 600ml of acetone and butyl acetate (v / v=1 / 1) dropwise, filter, and use Wash the crystals obtained by filtration; dry at 35° C. and a vacuum of 0.095 MPa until the water content and residual solubility are qualified.

[0027] Its yield: 95.6%, content: 96.2%, single largest impurity: 0.3%, sum of impurities: 1.3%, solution color: 2+, clarity 0.25-.

Embodiment 3

[0029] Take 20g of cefotaxime acid and 8.76g of sodium isooctanoate, add it to 120ml of water-containing solvent system (the water-containing solvent system is composed of 10ml of water and 110ml of isopropanol), control the temperature at 5°C, and stir to dissolve. Add 0.2 g of activated carbon, decolorize for 30 minutes, and filter; wash the filtered carbon layer with a mixture of water and isopropanol, and combine the filtrate and washing liquid. Control the temperature at 5°C, within 200 minutes, add 90ml of isopropanol dropwise, add 0.4g of seed crystals, and grow the crystals for 40 minutes; within 300 minutes, add 200ml of butyl acetate dropwise, filter, and wash the filtered crystals with butyl acetate; Dry at 38°C and vacuum degree of 0.095MPa until the water content and residual solubility are qualified.

[0030] Its yield: 95.1%, content: 96.7%, single largest impurity: 0.3%, sum of impurities: 1.1%, solution color: 2+, clarity 0.25-.

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Abstract

The invention discloses a crystallization method for cefotaxime sodium. According to the method, the cefotaxime sodium is prepared by an organic solvent precipitation method in a water-containing system. The method comprises the following preparation steps: adding cefotaxime acid and a sodium salt into a solvent to perform a salt forming reaction at a certain temperature; decoloring, filtering and washing the salt; merging filtrate; adding the solvent dropwise; growing crystals after adding seed crystals; adding a crystallization solvent dropwise for crystallizing; filtering, washing and drying the crystals in vacuum. The cefotaxime sodium obtained by the method has uniform crystal forms, low specific volume and high fluidity, and is easy to package; the cefotaxime sodium is high in clarity, high in purity, light in solution color, low in impurity content, and high in stability, and is easy to store; the process disclosed by the invention is easy to operate and high in product yield. By utilizing the method, the cefotaxime sodium crystals are prepared in the water-containing system, so that the traditional concept that the quality of the product prepared in the water-containing system is poor is broken.

Description

technical field [0001] The invention relates to a compound crystallization method, in particular to a crystallization method of cefotaxime sodium in an aqueous system. Background technique [0002] Cefotaxime sodium is a third-generation cephalosporin semi-synthetic broad-spectrum antibiotic. Its product is white, off-white or light yellow-white crystal, odorless or slightly special odor. Soluble in water, slightly soluble in methanol, ethanol, acetone, insoluble in chloroform, n-hexane, dichloromethane, diethyl ether and ethyl acetate. Molecular formula: C 16 h 16 N 5 o 7 S 2 Na, molecular weight: 477.44, molecular structure formula is as follows: [0003] [0004] The stability of cefotaxime sodium is poor, and its amide side chain, lactam ring and acetyl group may be degraded, and it is easily hydrolyzed in the presence of water molecules. It hydrolyzes. [0005] The crystallization method of cefotaxime sodium usually adopts the crystallization method of anhydr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/34C07D501/04C07D501/12
Inventor 魏青杰高志刚蔡秋琴刘华赵洪娥陈建军杨晓慧
Owner NORTH CHINA PHARMA HEBEI HUAMIN PHARMA
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