Method for preparing ampicillin sodium

A technology for ampicillin sodium and ampicillin, applied in the field of compound preparation, can solve the problems of increasing manufacturing cost and environmental protection pressure, increasing the difficulty of solvent recovery, and low content of active ingredients, avoiding difficulty in solvent recovery and omitting granulation. Process, the effect of high content of active ingredients

Inactive Publication Date: 2009-07-22
NORTH CHINA PHARMA COMPANY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Though this method has improved ampicillin sodium finished product quality to a certain extent, it still has the weak point of the following aspects: 1) because this method has introduced in the system the boiling point that is close to methyl acetate (57 ℃ of boiling point) Anhydrous ethanol (boiling point 78°C), thus increasing the difficulty of solvent recovery, increasing manufacturing costs and environmental protection pressure; 2) In the crystallization system, due to the influence of ethanol, most of the crystals are amorphous powder, resulting in fine particles , many impurities, low active ingredient content; 3) the crystallization liquid produced by this method has a high viscosity, so it increases the difficulty of separation, washing, drying, granulation and other processes

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] a) Preparation of liquid sodium isooctanoate: first add 250L of purified water to the alkali preparation tank, weigh 75kg of sodium hydroxide and add, stir until dissolved. Calculate the amount of isooctanoic acid added according to the molar ratio of sodium hydroxide to 1:1.1, and draw the isooctanoic acid into the reaction tank. Stir the prepared sodium hydroxide solution and press it into the reaction tank with isooctanoic acid, control the pH between 6.5 and 7.5, and stir for 30 minutes.

[0026] Open the jacket steam valve, heating temperature 85 ~ 100 ℃, vacuum gauge pressure <-0.06MPa, steam out about 250L of water under reduced pressure, add 200L of n-butanol to the residual liquid and heat to carry out azeotropic water banding, and determine the end point of detection When the water content of the sodium isooctanoate solution is less than 1.25%, open cold brine to cool down to ≤35°C, add about 800L of dichloromethane, and dilute the sodium isooctanoate solution...

Embodiment 2

[0031] a) Preparation of liquid sodium isooctanoate: first add 250L of purified water to the alkali preparation tank, weigh 75kg of sodium hydroxide and add, stir until dissolved. Calculate the amount of isooctanoic acid according to the molar ratio of sodium hydroxide to 1:0.8, and pump the isooctanoic acid into the reaction tank. The prepared sodium hydroxide solution was stirred and pressed into the reaction tank with isooctanoic acid, and stirred for 60 minutes. Open the steam valve of the jacket, decompress and steam out about 200L of water, add 300L of isobutanol to the residual liquid and heat to carry out azeotropic water removal. When the water content of the sodium isooctanoate solution is determined to be <1.25% at the end of the test, add Isobutanol, diluted to a concentration of 50% sodium isooctanoate solution for later use.

[0032] b) Preparation of ampicillin amine salt: take 100kg of ampicillin, according to the molar ratio of ampicillin and diisopropylamine...

Embodiment 3

[0036] a) Preparation of liquid sodium isooctanoate: first add 250L of purified water to the alkali preparation tank, weigh 75kg of sodium hydroxide and add, stir until dissolved. Calculate the amount of isooctanoic acid according to the molar ratio of sodium hydroxide to 1:1.3, and pump the isooctanoic acid into the reaction tank. The prepared sodium hydroxide solution was stirred and pressed into the reaction tank with isooctanoic acid, and stirred for 60 minutes. Evaporate about 250L of water under reduced pressure. After cooling down to about 25°C, add dichloromethane and dilute to 15% sodium isooctanoate solution for later use.

[0037]b) Preparation of ampicillin amine salt: take 100kg of ampicillin, according to the molar ratio of ampicillin and diisopropylamine is 1: 3.0, take diisopropylamine; Ampicillin is dissolved in 1000L methylene chloride to make ampicillin Penicillin organic solution; add 40kg of anhydrous magnesium sulfate, dehydrate the ampicillin organic so...

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PUM

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Abstract

The invention discloses a preparation method of ampicillin sodium, which comprises the steps: (a) a 15%-50% sodium iso-octoate solution is prepared; (b) ampicillin amine slat is prepared: firstly, ampicillin is dissolved in an organic solvent to prepare an organic ampicillin solution which is then dehydrated till the moisture thereof is lower than 1% and then reacts with diisopropylamine; (c) the amine salt obtained from step (b) is pressed into a crystallizing tank and added with the sodium iso-octoate solution for two times, and after crystallization the growing of crystal is carried out; and (d) after the crystallization reaction is finished, separation, washing and menstruum recovering processes are carried out. The preparation method has simple processes and easy operation, is capable of further improving the quality of the finished ampicillin sodium products and being beneficial to the recovery of the menstruum in the technical system, and can effectively reduce the production costs simultaneously.

Description

technical field [0001] The present invention relates to the preparation method of compound, specifically a kind of preparation method of ampicillin sodium salt. Background technique [0002] Ampicillin is a semi-synthetic broad-spectrum penicillin. It is the first broad-spectrum semi-synthetic penicillin drug used clinically in the world. It is mainly used for penicillin-sensitive Gram-positive cocci, E. coli, Proteus, aerogenes and Infections such as influenza bacillus, used for the treatment of urinary system, respiratory system, biliary tract, intestinal infection and other infections. At present, there are three methods for industrialized production of ampicillin sodium: spray drying, freeze drying and solvent crystallization. Among them, the spray drying method and the freeze drying method need to use a strong alkali agent and need to be carried out at a relatively high temperature, so the β-lactam ring is easily damaged and degraded. The indicators are not satisfacto...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D499/70A61P31/04
Inventor 李秋元王欣杨京霞周静李颜茹贾永华刘珺刘丹刘娜吴立强李志浩崔雅莉田新玉韩杰
Owner NORTH CHINA PHARMA COMPANY
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