Cefmetazole sodium for reducing anaphylaxis and preparation thereof

A technology for cefmetazole sodium and allergic reactions, applied in medical preparations containing active ingredients, organic active ingredients, organic chemistry, etc., can solve the problems of long production cycle, low product purity, high content of related substances, etc., and improve product quality. High quality, high purity, and good appearance formability

Active Publication Date: 2016-06-08
福安药业集团庆余堂制药有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Chinese patent application CN102127095A discloses a preparation method of cefmetazole sodium. After reacting cefmetazole acid and sodium isooctanoate, the finished product is obtained by crystallization, washing, and drying. This method uses a large amount of organic solvents, and the content of related substances is relatively high
Cefmetazole sodium is obtained by freeze-drying, which avoids a large amount of use of organic solvents, but this method needs to go through the steps of crystallization and drying of cefmetazole acid, the production cycle is relatively long, and bicarbonate is added to the cefmetazole acid solution Sodium, after lyophilization to obtain cefmetazole, the resulting product has a lower purity

Method used

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  • Cefmetazole sodium for reducing anaphylaxis and preparation thereof
  • Cefmetazole sodium for reducing anaphylaxis and preparation thereof
  • Cefmetazole sodium for reducing anaphylaxis and preparation thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] In a dry and clean three-neck flask, add 50g of 7-MAC, 600ml of chloroform and stir to dissolve, cool to -15°C, add 14g of pyridine, dropwise add 18g of cyanomethylmercaptoacetyl chloride, after the addition is complete, stir for 1 hour, add purified water: Sodium: 40ml of the mixed solution of concentrated hydrochloric acid (9:1:2) was used to terminate the reaction, and the layers were allowed to stand, and the organic phase was taken, dried, and concentrated to obtain 57.5g of cefmetazole diphenylmethyl ester, with a molar yield of 94.7%, HPLC purity 99.35%.

[0040]Cefmetazole diphenylmethyl ester purity test conditions (the same below): use octadecylsilane bonded silica gel as filler; use phosphate buffer (take 2.72g of potassium dihydrogen phosphate, add water to dissolve and dilute to 1000ml)- Acetonitrile (50:50) is the mobile phase; the detection wavelength is 214nm, and the resolution of the Mz-2 peak and the adjacent impurity peak should meet the requirements...

Embodiment 2

[0045] In a dry and clean three-neck flask, add 50g of 7-MAC, add 600ml of chloroform and stir to dissolve, cool to -15°C, add 10g of dimethylaminopyridine, dropwise add 18g of cyanomethylmercaptoacetyl chloride, after the addition is complete, stir for 1 hour, add the purified Water: Sodium chloride: 45ml of mixed solution of concentrated hydrochloric acid (9:1:2) to terminate the reaction, let stand to separate layers, take the organic phase, dry, and concentrate to obtain 58.1g of cefmetazole diphenylmethyl ester, and the molar yield is 95.7 %, HPLC purity 99.3%.

[0046] Take 800ml of dichloromethane and cool down to 5-10°C, add 45g of aluminum trichloride under stirring, add 115g of anisole dropwise, control the temperature at 15-20°C, and cool down to -20~-25°C after adding; keep stirring and add cephalosporin 50g of methazole diphenylmethyl ester, react for 0.5 hours, add 50ml of a mixture of acetone: water: concentrated hydrochloric acid (weight ratio 8:8.2:1) cooled t...

Embodiment 3

[0048] Embodiment 3, comparative study of product content and key impurities

[0049] Get respectively embodiment 1 of the present invention, embodiment 2 and Chinese invention patent CN104557978A embodiment 1 and 2 gained products, refer to the pharmacopoeia standard to measure the key impurity cefmetazolactone in the pharmacopoeia standard of the sample, 5-mercaptomethyl four Nitrozol was tested and the results are shown in the table below:

[0050]

[0051] The results show that, compared with the reference document, in the cefmetazole sodium product obtained in the present invention, the content of key impurities is significantly lower, and the total impurities are far lower than the standard.

[0052] Attachment: Measuring method: Take 20 μl of the control solution and inject it into the liquid chromatograph, adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 20% of the full scale, and accurately measure the bla...

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Abstract

The invention discloses a preparation method of cefmetazole sodium, comprising the following operation steps: (1) by taking 7-MAC as an initial material, reacting with cyano methylthio acetyl chloride, thus obtaining cefmetazole diphenylmethyl ester; (2) enabling the cefmetazole diphenylmethyl ester obtained in the step (1) to react in an alchlor-anisole system, thus obtaining an organic solution of cefmetazole acid; (3) preparing a sodium bicarbonate solution with the concentration being 5-20 weight percent, controlling the temperature to be -5 to 10 DEG C, adding the cefmetazole acid organic solution obtained in the step (2), stirring, controlling temperature, decoloring, filtering and freeze-drying, thus obtaining the cefmetazole sodium. According to the preparation method of the cefmetazole sodium, the obtained product has the advantages of high purity, low impurity content, good stability and the like, and is easy for industrial production, and anaphylaxis reducing and clinic application of a preparation are both obviously improved.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a preparation method of cefmetazole sodium. Background technique [0002] Cefmetazole sodium, developed by Japan Sankyo Pharmaceutical Co., Ltd., belongs to the second-generation cephalosporin antibiotics (the structural formula is shown below). It was first listed in Japan in 1980. It is a broad-spectrum, high-efficiency, and low-toxicity antibiotic. It has antibacterial effect on Gram-positive and negative bacteria and anaerobic bacteria, and has good antibacterial activity on Staphylococcus, hemolytic streptococcus, Escherichia coli, Klebsiella pneumoniae, indole-negative and positive Proteus, etc. . [0003] [0004] The structural formula of cefmetazole sodium [0005] Chinese patent application CN102127095A discloses a preparation method of cefmetazole sodium. After reacting cefmetazole acid and sodium isooctanoate, the finished product is obtain...

Claims

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Application Information

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IPC IPC(8): C07D501/57C07D501/04C07D501/12A61K31/546A61K9/19
CPCA61K9/0019A61K9/19A61K31/546C07D501/04C07D501/12C07D501/57
Inventor 蒋晨胡昌勤周晓东
Owner 福安药业集团庆余堂制药有限公司
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