CN1055289C

CN1055289C - Process for one-shot crystallization of sodium penicillin

Info

Publication number: CN1055289C
Application number: CN97119879A
Authority: CN
Inventors: 钟建西; 张金根; 李艳平; 张寿南; 于伯周; 田丹霞; 张敬申; 李庆伟; 刘广春
Original assignee: HUABEI PHARMACEUTICAL CO Ltd
Current assignee: HUABEI PHARMACEUTICAL CO Ltd
Priority date: 1997-12-31
Filing date: 1997-12-31
Publication date: 2000-08-09
Anticipated expiration: 2017-12-31
Also published as: CN1191221A

Abstract

The present invention relates to a one-step crystallization method for preparing sodium penicillin. The method mainly comprises the following steps: extracting purified penicillin filtrated solution by using a solvent to obtain penicillin butyl acetate extracted solution; adding aqueous solution of carbonate; extracting the mixed solution at least twice to phase-transform the penicillin into water; then, acidifying, purifying and concentrating the penicillin in butyl acetate to obtain the secondary extracted solution of the penicillin butyl acetate; adding activated carbon; carrying out refrigeration, decolorization and filtration; extracting and phase-transforming the solution with sodium carbonate; adding a solvent with a low boiling point; carrying out one-step azeotropical crystallization by reducing pressure; carrying out filtration, solvent washing and drying to obtain finished products. The one-step crystallization method overcomes the defects of large consumption of raw materials, high cost, complicated operation, low yield and the like in the prior art, and has the advantages that the procedure is simplified, the processing time is shortened, the yield is increased, the raw materials are saved, the production cost is reduced, etc.

Description

Process for one-shot crystallization of sodium penicillin

The present invention relates to a kind of process for one-shot crystallization of sodium penicillin.

At present obtain benzylpenicillin sodium with the penicillin fermentation stoste that biological fermentation obtained, the existing operational path that all adopts secondary crystal both at home and abroad, its concrete grammar has three kinds: a, sodium-acetate-aqueous ethanolic solution crystallization; B, resin method change the sodium crystallization of n-butanol azeotropic; The carbonate aqueous solution extracting crystallization of n-butanol azeotropic of c, sodium, above-mentioned three kinds of methods in various degree exist raw materials consumption height, cost height, to intermediate specification of quality height, complex operation, wayward, shortcoming such as its crystallization loss is also all big.

The object of the present invention is to provide a kind of process for one-shot crystallization of sodium penicillin, have operational path weak point, constant product quality, yield height, low cost and other advantages.

Integrated artistic step of the present invention is:

Process for one-shot crystallization of sodium penicillin, after it is characterized in that penicillin filtrate is purified, extract under acidic conditions with N-BUTYL ACETATE again and obtain penicillin N-BUTYL ACETATE extracting solution one time, the aqueous solution that adds carbonate again, the extracting solution that divides at least twice extracting to obtain having nothing in common with each other, transfer to through acidifying again and obtain secondary penicillin N-BUTYL ACETATE extracting solution in the N-BUTYL ACETATE, add the freezing decolouring of gac then, the filtering gac, the penicillin N-BUTYL ACETATE extracting solution that obtains decolouring, add carbonate aqueous solution and penicillin is transferred to water and obtain the benzylpenicillin sodium aqueous solution, and adding lower boiling solvent, carry out disposable underpressure distillation azeotropic crystalization, obtain the benzylpenicillin sodium crystal, after filtration, the solvent washing, drying makes finished product.

Concrete processing step of the present invention or processing condition also have:

Obtain with the purified penicillin filtrate of N-BUTYL ACETATE extraction that pH value is 1.8-3.5 in the penicillin N-BUTYL ACETATE extracting solution reaction, tiring is 5-10 ten thousand u/ml.

The amount that adds carbonate aqueous solution in a penicillin N-BUTYL ACETATE extracting solution is the carbonate aqueous solution 0.38-6.65 liter that per 1,000,000,000 penicillin units add concentration 2-35%, divides at least twice extracting.

With the different extract acidifying that obtains, pH value is 1.8-3.5 in the reaction of preparation secondary penicillin N-BUTYL ACETATE extracting solution.

Condition is that per 1,000,000,000 penicillin units add the 10-300g gac in the freezing decoloring reaction of adding gac, the penicillin N-BUTYL ACETATE extracting solution that obtains decolouring after freezing under-5 ℃ of-25 ℃ of conditions, decolouring, filtration.

The carbonate aqueous solution that adds sodium is transferred to water with penicillin, and to obtain the benzylpenicillin sodium aqueous ph value be 5.5-7.0.

The underpressure distillation primary crystallization gets benzylpenicillin sodium, 8-40 ten thousand u/ml that tire in the reaction, water content 10-25%, vacuum tightness (0.090)-(0.1) MPa.

Below in conjunction with embodiment the present invention is further described:

The production method of present embodiment is:

Behind penicillin filtrate purifying, react under the PH2 condition with N-BUTYL ACETATE and to obtain penicillin N-BUTYL ACETATE extracting solution one time, tire and be controlled at 80,000 u/ml, add 6.65 liters of 2% sodium carbonate solutions by per 1,000,000,000 penicillin units, divide three extractings, obtain different benzylpenicillin sodium solutions, be that extraction obtains secondary penicillin N-BUTYL ACETATE extracting solution under 2 the condition at pH value with N-BUTYL ACETATE again, add the 100g gac by per 1,000,000,000 penicillin units, freezing under-20 ℃ of conditions, the penicillin N-BUTYL ACETATE solution that filtration obtains decolouring, add aqueous sodium carbonate again and obtain the benzylpenicillin sodium aqueous solution (pH value is 7), add butanols as crystal solution, control 120,000 u/ml that tire, water content 10%, by underpressure distillation, vacuum tightness is-0.095MPa that after filtration, butanols washs, the prewashing vinyl acetic monomer, the dry benzylpenicillin sodium finished product that gets.

The obtained remarkable technological progress of the present invention is:

The present invention has reached the purpose that primary crystallization is produced Benzylpenicillin sodium salt, has reduced operation, when having shortened technology Between, improved yield, saved raw material, reduced cost.

Claims

1, process for one-shot crystallization of sodium penicillin, after it is characterized in that penicillin filtrate is purified, extract under acidic conditions with N-BUTYL ACETATE again and obtain penicillin N-BUTYL ACETATE extracting solution one time, the aqueous solution that adds carbonate again, the extracting solution that divides at least twice extracting to obtain having nothing in common with each other, transfer to through acidifying again and obtain secondary penicillin N-BUTYL ACETATE extracting solution in the N-BUTYL ACETATE, add the freezing decolouring of gac then, the filtering gac, the penicillin N-BUTYL ACETATE extracting solution that obtains decolouring, add carbonate aqueous solution and penicillin is transferred to water and obtain the benzylpenicillin sodium aqueous solution, and adding lower boiling solvent, carry out disposable underpressure distillation azeotropic crystalization, obtain the benzylpenicillin sodium crystal, after filtration, the solvent washing, drying makes finished product.

2, process for one-shot crystallization of sodium penicillin according to claim 1 is characterized in that obtaining with the purified penicillin filtrate of N-BUTYL ACETATE extraction that pH value is 1.8-3.5 in the penicillin N-BUTYL ACETATE extracting solution reaction, and tiring is 5-10 ten thousand u/ml.

3, process for one-shot crystallization of sodium penicillin according to claim 1, the amount that it is characterized in that adding carbonate aqueous solution in penicillin N-BUTYL ACETATE extracting solution is the carbonate aqueous solution 0.38-6.65 liter that per 1,000,000,000 penicillin units add concentration 2-35%, divides at least twice extracting.

4, process for one-shot crystallization of sodium penicillin according to claim 1 is characterized in that the different extract acidifying that will obtain, and pH value is 1.8-3.5 in the reaction of preparation secondary penicillin N-BUTYL ACETATE extracting solution.

5, process for one-shot crystallization of sodium penicillin according to claim 1, it is characterized in that adding that condition is that per 1,000,000,000 penicillin units add the 10-300g gac in the freezing decoloring reaction of gac, the penicillin N-BUTYL ACETATE extracting solution that obtains decolouring in freezing under-5 ℃ of-25 ℃ of conditions, decolouring, after filtering.

6, process for one-shot crystallization of sodium penicillin according to claim 1, the carbonate aqueous solution that it is characterized in that adding sodium is transferred to water with penicillin, and to obtain the benzylpenicillin sodium aqueous ph value be 5.5-7.0.

7, process for one-shot crystallization of sodium penicillin according to claim 1 is characterized in that the underpressure distillation primary crystallization gets benzylpenicillin sodium, 8-40 ten thousand u/ml that tire in the reaction, water content 10-25%, vacuum tightness (0.090)-(0.1) MPa.