Preparation method of cephalosporin C sodium salt and 7-amino-cephalosporanic acid

A technology of amino cephalosporanic acid and cephalosporin, which is applied in the field of preparation of cephalosporin C sodium salt and 7-amino cephalosporanic acid, can solve the problem of inability to perform ultrafiltration, waste acid water and resin regeneration waste liquid, easy blockage Membrane holes and other problems, to meet the needs of high-end customers, high product quality, and improve the effect of quality

Active Publication Date: 2019-11-08
SHANXI WEIQIDA PHARMA IND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In this process, the fermentation broth is directly subjected to first-stage ultrafiltration with a molecular weight cut-off of 10,000-30,000 without pretreatment, and the mycelium, protein, colloid, etc. in it can easily block the membrane pores and cannot be used for ultrafiltration; in addition, There is also the problem of waste acid water and resin regeneration waste liquid

Method used

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  • Preparation method of cephalosporin C sodium salt and 7-amino-cephalosporanic acid

Examples

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preparation example Construction

[0021] In the preparation method of cephalosporin C sodium salt provided by the present invention, in the preparation of said step (1) containing cephalosporin C filtrate, after cephalosporin C fermented liquid is acidified, adopt 50~100 nanometer ceramic Membrane filtration removes mycelium and protein in the fermentation broth, and then adopts an ultrafiltration membrane with a molecular weight cut-off of 20KD to 100KD to remove pigment and impurities in the filtrate to obtain a cephalosporin C-containing filtrate.

[0022] Wherein, the cephalosporin C fermentation liquid is the fermentation liquid prepared by the conventional biological fermentation method in the field after the biological fermentation of cephalosporin C, the general pH is 4.50-6.00, and the supernatant contains about 20g / L-30g / L cephalosporin Factor C, the fermentation broth also contains a large amount of mycelium, protein, polysaccharide, colloid and so on.

[0023] The acidification treatment of the cep...

Embodiment 1

[0037] Get 4.5L cephalosporin C fermented liquid, pH is 4.65, contains about 22g / L cephalosporin C (supernatant liquid), uses the sulfuric acid of 15% (v / v) to adjust pH to 2.50, then at 5 ℃~10 Under the condition of ℃, after filtering through 50nm ceramic membrane and 20KD ultrafiltration membrane, 5.2L filtrate (including ceramic membrane top wash water) was obtained, the concentration of cephalosporin C was 7.50g / L, and the light transmittance at 425nm wavelength was 72%.

[0038] Add 15.6L of ethyl acetate pre-cooled to 5-10°C to the filtrate, mix thoroughly, and collect 15.0L of the light phase after standing and layering, the concentration of cephalosporin C is 2.52g / L; then, at about 5°C, add 83mL of 20wt% sodium isooctanoate ethyl acetate solution to the collected light phase at a uniform speed within 15min, let it stand for 20min after the addition, separate layers, collect 175mL of the heavy phase, and the concentration of cephalosporin C is 211.8 g / L; at 5°C, 175ml...

Embodiment 2

[0041] Get 4.5L cephalosporin C fermented liquid, pH is 4.72, contains about 23g / L cephalosporin C (supernatant liquid), uses the sulfuric acid of 15% (v / v) to adjust pH to 2.56, then at 5 ℃~10 Under the condition of ℃, after filtering through 50nm ceramic membrane and 20KD ultrafiltration membrane, 5.4L filtrate (including ceramic membrane top wash water) was obtained, the concentration of cephalosporin C was 7.32g / L, and the light transmittance at 425nm wavelength was 76%.

[0042] Add 16.2L of ethyl acetate pre-cooled to 5-10°C to the filtrate, mix thoroughly, and collect 15.7L of the light phase after standing and layering, the concentration of cephalosporin C is 2.43g / L; then, at about 5°C, add 84mL of 20wt% ethyl acetate solution of sodium isooctanoate dropwise to the collected light phase at a uniform speed within 15min, let it stand for 20min after the addition, separate the layers, collect 195mL of the heavy phase, and the concentration of cephalosporin C is 193.0 g / ...

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Abstract

The invention relates to a preparation method of cephalosporin C sodium salt and 7-aminocephalosporanic acid. The method comprises the following steps: separating a cephalosporin C filtrate from a fermentation liquid by a membrane filtration manner; then extracting cephalosporin C from the filtrate by using an organic solvent to obtain a cephalosporin C extraction solution; mixing the cephalosporin C extraction solution and sodium 2-ethylhexanoate, carrying out a salt formation reaction, performing standing stratification, and collecting a heavy phase; adding an anti-solvent into the heavy phase for crystallization to obtain cephalosporin C sodium salt; and then dissolving cephalosporin C sodium salt by using purified water to obtain an aqueous solution of cephalosporin C sodium salt, adding an immobilized cephalosporin C acylase, and performing enzymatic hydrolysis, crystallization, filtration, washing and drying on cephalosporin C sodium salt to obtain 7-amino-cephalosporanic acid. Cephalosporin C sodium salt and 7-aminocephalosporanic acid prepared by the method are significantly superior to a conventional process, the product is used for preparation of cephalosporin downstreamproducts, the obtained products have higher quality, and medication is safer.

Description

technical field [0001] The invention belongs to the technical field of pharmacy and relates to a preparation method of cephalosporin C sodium salt and 7-aminocephalosporanic acid. Background technique [0002] 7-amino-cephalosporanic acid (7-Amino-Cephalosporanic acid), the structural formula is as follows: [0003] [0004] 7-Aminocephalosporanic acid, referred to as 7-ACA, is the most commonly used core in cephalosporins. It has two active groups, the 3-position acetoxy group and the 7-position amino group. Different side chains are connected on the group to form cephalosporin antibiotics with different properties. Therefore, 7-ACA is a very important intermediate of cephalosporin (β-lactam) antibiotics. The cephalosporin antibiotics can effectively inhibit the synthesis of bacterial cell walls, but human cells have no cell walls, so they have excellent selectivity, good safety, and strong bactericidal power. They are currently the best type of antibiotics used clinica...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/12C07D501/18C07D501/28C12P35/02
CPCC07D501/12C07D501/18C07D501/28C12P35/02
Inventor 苗瑞春李雄王雁幸华龙李建平冯涛刘君臣
Owner SHANXI WEIQIDA PHARMA IND
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