Method for preparing cefamandole nafate powder injection preparation

A technology of sodium montoroleate powder and cephalosporin, applied in the field of medicine, can solve the problems of long reaction time and high content of impurities, and achieve the effects of short reaction time, low content of impurities and stable quality

Active Publication Date: 2018-04-17
NORTH CHINA PHARMA HEBEI HUAMIN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is exactly to provide a kind of preparation method of cefamandole sodium powder injection preparation, to solve the problem that existing method reaction time is long and cefamandole, impurity etc. content are high in the product

Method used

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  • Method for preparing cefamandole nafate powder injection preparation

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Experimental program
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Effect test

Embodiment 1

[0026] Add 75mL of dichloromethane, 25g of 7-ACT, and 28.8g of BSA into a 500mL four-neck flask, raise the temperature to 35°C, react for 30min, dissolve, and cool down after the reaction. Control the temperature at -5-0°C, add 15 mL of formylmandelic acid chloride dropwise, react for 5 minutes after the addition is complete, and detect that the 7-ACT residue is <2.0%, and the reaction is over. Add 50mL of purified water to another four-necked bottle, keep the temperature below 15°C, feed the reaction liquid into the four-necked bottle, and at the same time add 15wt% sodium hydroxide solution, control the pH=4.8±0.1, stir rapidly for 5min , stand still for phase separation, and recover the organic phase. Add 150 mL of ethyl acetate to the water phase, adjust the pH to 1.25 with 6 mol / L hydrochloric acid solution, stir rapidly for 10 min, let stand to separate the phases, and discard the water phase.

[0027] Add 2.5g of activated carbon and 2.5g of anhydrous magnesium sulfate...

Embodiment 2

[0030] Add 150mL of dichloromethane, 25g of 7-ACT, 20.6g of BSA, and 5.5g of trimethylchlorosilane into a 500mL four-neck flask, heat up to 42°C, react for 50min, dissolve and clear, and cool down after the reaction is complete. Control the temperature at -10~-5°C, add 15 mL of formylmandelic acid chloride dropwise, and react for 20 minutes after the addition is complete. The 7-ACT residual is detected to be <2.0%, and the reaction is over. Add 50mL of purified water to another four-necked flask, keep the temperature below 15°C, feed the reaction liquid into the four-necked flask, and at the same time add 10wt% sodium bicarbonate solution, control the pH=5.5±0.1, stir rapidly for 5min , stand still for phase separation, and recover the organic phase. Add 150 mL of ethyl acetate to the water phase, adjust the pH to 0.52 with 6 mol / L hydrochloric acid solution, stir rapidly for 10 min, let stand to separate the phases, and discard the water phase.

[0031] Add 2.5g of activated...

Embodiment 3

[0034] Add 125mL of dichloromethane, 25g of 7-ACT, and 30.5g of BSA into a 500mL four-neck flask, heat up to 30°C, react for 60min, dissolve and clear, and cool down after the reaction is complete. Control the temperature at -10~-5°C, add 15 mL of formylmandelic acid chloride dropwise, and react for 10 minutes after the addition is complete. The 7-ACT residual is detected to be <2.0%, and the reaction is over. Add 50mL of purified water into another four-necked flask, keep the temperature below 15°C, feed the reaction liquid into the four-necked flask, and at the same time add 10wt% sodium carbonate solution, control the pH=6.5±0.1, stir rapidly for 5min, Stand to separate the phases and recover the organic phase. Add 150 mL of ethyl acetate to the water phase, adjust the pH to 1.35 with 6 mol / L hydrochloric acid solution, stir rapidly for 10 min, let stand to separate the phases, and discard the water phase.

[0035] Add 2.5g of activated carbon and 2.5g of anhydrous magnesi...

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Abstract

The invention provides a method for preparing a cefamandole nafate powder injection preparation. The method comprises the following steps: (a) performing a silanization reaction on 7-ACT and a silanization agent in a dichloromethane solvent under temperature control, and reducing the temperature after the reaction is completed so as to obtain a reaction liquid 1, wherein the solid-liquid ratio of7-ACT to dichloromethane is 1g:(3-6)ml; (b) dropwise adding (R)-(-)-O-formylmandeloyl chloride into the reaction liquid 1, controlling the temperature, performing an acylation reaction so as to obtaina reaction liquid 2; (c) performing treatment of extraction, decoloring and dehydration on the reaction liquid 2; (d) performing temperature control crystallization; and (e) washing a solid with acetone, drying, performing sterile sub-packaging, thereby obtaining the cefamandole nafate powder injection preparation. Due to adoption of a high-concentration dichloromethane reaction system, the method is rapid in silanization and acylation process, short in reaction time, low in reaction residue, high in product yield and small in impurity. After the reactions, organic solvents such as dichloromethane can be easily recycled and repeatedly used, so that the method is relatively environment-friendly, low in cost and applicable to large-scale industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a preparation method of cefamandole sodium powder injection preparation. Background technique [0002] Cefamandole sodium belongs to the second generation cephalosporin antibiotics, the chemical name is 7-D-(2-formyloxyphenylacetamide)-3-[(1-methyl-1H-tetrazol-5 base) Mercaptomethyl]-3-cephem-4-carboxylic acid sodium salt is the prodrug of cefamandole, which is rapidly hydrolyzed into active ingredient cefamandole after intravenous or intramuscular injection, and has less side effects and higher safety. It is widely recognized by clinicians for its advantages of high efficacy and definite curative effect. It is suitable for lung infection, urinary tract infection, biliary tract infection, skin and soft tissue infection, bone and joint infection, sepsis and abdominal infection caused by sensitive bacteria. [0003] Cefamandole sodium was successfully created by U.S. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/36C07D501/06C07D501/12
Inventor 胡利敏石春利李庆伟贾全刘树斌任峰田洪年郭振军林建新张红蕾李惠芬贾丽辉李萌
Owner NORTH CHINA PHARMA HEBEI HUAMIN PHARMA
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