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Cefoperazone sodium compound and sulbactam sodium compound prepared with strong-field coupling crystallization technology as well as prepared composition

A technology of cefoperazone sodium and sulbactam sodium, which is applied in the field of medicine and can solve problems affecting the quality of preparations, poor stability, and poor purity

Inactive Publication Date: 2017-02-22
陕西顿斯制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The raw materials of cefoperazone sodium and sulbactam sodium on the market all have poor purity and poor stability, which affects the quality of their preparations

Method used

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  • Cefoperazone sodium compound and sulbactam sodium compound prepared with strong-field coupling crystallization technology as well as prepared composition
  • Cefoperazone sodium compound and sulbactam sodium compound prepared with strong-field coupling crystallization technology as well as prepared composition
  • Cefoperazone sodium compound and sulbactam sodium compound prepared with strong-field coupling crystallization technology as well as prepared composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Embodiment 1: the preparation of cefoperazone sodium compound

[0043] (1) Dissolve 500g cefoperazone acid in a mixed solvent of 500ml water and 500ml ethanol, and control the temperature at 30°C to dissolve the raw materials;

[0044] (2) Dissolve 65.12g of sodium bicarbonate in 500ml of water, control the reaction temperature at 30°C, slowly add the aqueous solution of sodium bicarbonate into the raw material solution, and stir the reaction until the pH value is 6.0;

[0045] (3) filter, filtrate is poured in the crystallizer, reduce temperature to 15 ℃, slowly add 2L acetone, lay ultrasonic field in crystallizer interior, carry out the ultrasonic field strengthening of cefoperazone sodium crystallization process, the frequency of ultrasonic field is 100kHz, power is 15W / L solution, filtered, washed the filter cake with acetone, and dried under reduced pressure to obtain 453 g of cefoperazone sodium.

[0046] The X-ray powder diffraction pattern of the product has ch...

Embodiment 2

[0047] Embodiment 2: the preparation of cefoperazone sodium compound

[0048] (1) Dissolve 500g of cefoperazone acid in a mixed solvent of 500ml of water and 750ml of chloroform, and control the temperature at 40°C to dissolve the raw materials;

[0049] (2) Dissolve 104g of sodium lactate in 600ml of water, control the reaction temperature at 40°C, slowly add the aqueous solution of sodium lactate into the raw material solution, and stir the reaction until the pH value is 6.7;

[0050] (3) filter, filtrate is poured in crystallizer, reduce temperature to 20 ℃, slowly add 2L ethyl acetate, lay ultrasonic field in crystallizer interior, carry out the ultrasonic field strengthening of cefoperazone sodium crystallization process, the frequency of ultrasonic field is 20kHz, The power was 5W / L solution, filtered, the filter cake was washed with ethyl acetate, and dried under reduced pressure to obtain 442 g of cefoperazone sodium.

[0051] The X-ray powder diffraction pattern of t...

Embodiment 3

[0052] Embodiment 3: the preparation of sulbactam sodium compound

[0053] (1) Dissolve 650g of 6,6-dibromopenicillane sulfone in a mixed solvent of 500ml of water and 750ml of methanol, and dissolve the raw materials at a temperature of 25°C;

[0054] (2) Dissolve 285g of sodium isooctanoate in water, control the reaction temperature at 25°C, slowly add the aqueous solution of sodium isooctanoate into the raw material liquid, and stir the reaction until the pH value is 4.5;

[0055] (3) Control the temperature at 20°C for carbon adsorption, filter, pour the filtrate into a crystallizer, lower the temperature to 5°C, slowly add acetone, lay out an ultrasonic field inside the crystallizer, and carry out ultrasonication of the crystallization process of sulbactam sodium Field strengthening, the frequency of the ultrasonic field is 20kHz, the power is 5W / L, the solution is filtered, the filter cake is washed with acetone, and dried under reduced pressure to obtain 542g of sulbact...

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Abstract

The invention discloses a cefoperazone sodium compound and a sulbactam sodium compound. The cefoperazone sodium compound and the sulbactam sodium compound are both prepared with a strong-field coupling crystallization technology, specifically, ultrasonic out-field strengthened crystals are added in the compound crystallization process, and the high-purity compounds are prepared. 'Research & Development of the Industrialization Project of High-end Medicine Product Refining Crystallization Technologies' wins the 2015 national scientific and technological progress second prize, and the high-field coupling crystallization technology belongs to one of high-end medicine product refining crystallization technologies. The two compounds have the characteristics of high purity and good stability. Besides, the invention further discloses cefoperazone sodium and sulbactam sodium medicinal composition. The cefoperazone sodium and sulbactam sodium medicinal composition is prepared from components in parts by weight as follows: 0.25-2 parts of cefoperazone sodium (on the basis of C25H27N9O8S2) and 0.25-2 parts of sulbactam sodium (on the basis of C8H11NO5S).

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a cefoperazone sodium compound, a sulbactam sodium compound and a combined preparation prepared by a strong field coupling crystallization technique. Background technique [0002] The R&D and industrialization project of refined crystallization technology for high-end pharmaceutical products of one of the inventors, Tianjin University and Xi'an Lijun Pharmaceutical Co., Ltd., won the second prize of the 2015 National Science and Technology Progress Award. [0003] The strong field coupling crystallization technology is one of the refined crystallization technologies for high-end pharmaceutical products. It aims to break through the blockade of related pharmaceutical product crystal forms and crystallization technology patents at home and abroad, and realize a leap in the level of high-end pharmaceutical product research and development and crystallization technology, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/36C07D501/12C07D499/86C07D499/18A61K31/43A61K31/546A61P31/04A61K9/14
CPCC07D501/36A61K9/0019A61K9/141A61K31/43A61K31/546C07B2200/13C07D499/18C07D499/86C07D501/12
Inventor 王坤
Owner 陕西顿斯制药有限公司
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