Method for preparing ceftizoxime sodium

A technology of ceftizoxime sodium and ceftizoxime acid, which is applied in the field of medicine, can solve the problems of increasing operating procedures, production costs, and long reaction steps, and achieve the effects of health and environmental protection, crystallization state improvement, and quality improvement.

Active Publication Date: 2011-04-13
哈药集团股份有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This route has long reaction steps, which increa

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0025] Example 1.

[0026] I. Preparation of ceftizoxime acid:

[0027] Dichloromethane 1000L, purified water 5L, add 7-ANCA (7-amino-3-H-cephem-4-carboxylic acid) 100Kg, stir to dissolve, cool to -5 / 5℃, add 68Kg of organic base triethylamine to dissolve 195 kg of AE active ester (2-(2-amino-4-thiazolyl)-2-methoxyimine-acetyl-benzothiazole thioester) was added, and the reaction temperature was maintained at -5 / 5°C and the reaction was stirred for 5 hours. Add 530L of purified water and stir to extract. Add 500L of dichloromethane to the water phase and wash twice. Add 0.01mol / l hydrochloric acid to the water phase material and adjust the pH to 5.5-6.0. Add 303 activated carbon 5.0Kg to the water phase. And aluminum oxide (model XFA-75150, particle size 150 mesh ≥90%) 20.0Kg, stir and decolorize for 20 minutes, and then filter separately, add 350L of dispersant medicinal ethanol, and add 3mol / l hydrochloric acid aqueous solution to a large amount of crystals After precipitation, t...

Example Embodiment

[0030] Example 2.

[0031] The influence of hydrochloric acid on the content of the product

[0032] When preparing ceftizoxime acid in the prior art, hydrochloric acid is usually used to adjust the pH value to 2.0-2.5. In the process of preparing ceftizoxime acid in the present invention, the water phase material solution is added with 0.01 mol / l before adding activated carbon for decolorization. Hydrochloric acid, adjust the PH value of 5.5-6.0, the intermediate product ceftizoxime acid content (HPLC method) control average increase by more than 2%, the laboratory determines the control effect data as follows (parallel 6 batches):

[0033] .

Example Embodiment

[0034] Example 3.

[0035] In the preparation process of ceftizoxime sodium, the original process solvent crystallization operation, the crystallization solvent is continuously added at a certain speed, the product yield is high, but the crystal grains are small, the crystal shape is uneven, the product stability is relatively poor, and the batch effect is certain During the period, the clarification exceeded the standard. At the same time, there was feedback in the process of aseptic raw powder packaging, and certain batches were not easy to be packaged.

[0036] The preparation method of the present invention is as follows: slowly adding the crystallization solvent until the crystallization liquid appears slightly muddy, stop adding the solvent, slowly stir the crystal for 0.5 hour, then continue to add the remaining solvent, and then stir for 1 hour after the addition. Although the yield of the optimized process product is reduced by 1.0-1.5%, the quality is significantly impr...

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PUM

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Abstract

The invention relates to synthetic ceftizoxime acid and a method for preparing ceftizoxime sodium from the synthetic ceftizoxime acid. The preparation process comprises the following steps: slowly adding a crystallization solvent in a crystallization liquid until the crystallization liquid becomes slightly turbid, stopping adding the solvent, slowly stirring and growing crystals for 0.5 hour, continuously adding the residual solvent, and stirring and growing the crystals for 1 hour after the residual solvent is completely added. The product prepared by the optimized process in the invention has remarkably improved quality although the yield is lowered by 1.0-1.5%; and the product crystallization state is obviously improved and the product quality problem of clarity stability in the period of validity is solved.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a method for synthesizing ceftizoxime acid and preparing ceftizoxime sodium therefrom. Background technique [0002] Ceftizoxime sodium has a complex antibacterial effect and is stable against broad-spectrum β-lactamases produced by a variety of Gram-positive and Gram-negative bacteria. The process parameters used in the current process are not optimal process parameters, crystallization temperature, solvent Factors such as dropping speed and stirring speed have an impact on the crystal form of the finished product. [0003] Ceftizoxime Sodium was first developed by Japan Fujisawa Pharmaceutical Co., Ltd., and was first listed in Japan in 1982. The trade name is epocelin (Yibao Shiling). This product belongs to the third generation cephalosporin antibiotic. It has broad-spectrum, It has the characteristics of high efficiency, enzyme resistance, low toxicity and abil...

Claims

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Application Information

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IPC IPC(8): C07D501/20C07D501/06C07D501/04C07D501/12
Inventor 马杰陈玉山韩东胜崔嵘徐淑明李国峰余威
Owner 哈药集团股份有限公司
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