溶媒法或喷雾干燥法制备头孢菌素C钠盐

目的　比较溶媒结晶法和喷雾干燥法两种制备头孢菌素 C钠盐的方法。方法　头孢菌素 C发酵液经提取纯化制成钠盐浓缩液于无水乙醇中结晶或喷雾干燥法制备头孢菌素 C钠盐。结果　溶媒结晶法制备的头孢菌素 C钠盐含量和透光率均值分别为 84 .0 3%和 98.90 % ,喷雾干燥法分别为 75 .4 9%和85 .90 % ,两方法相比 P<0 .0 5。溶媒结晶法合格率为 10 0 % ,而喷雾干燥法合格率仅为 2 0 %。结论　溶媒结晶法制备头孢菌素 C钠盐的质量优于喷雾干燥法。     

头孢菌素C钠盐最佳制备工艺探讨

为了探讨制备头孢菌素 C 钠盐的最佳工艺,采用溶媒结晶法和喷雾干燥法分别制备头孢菌素 C 钠盐。结果是,溶媒结晶法制备的头孢菌素 C 钠盐含量和透光率均值分别为84.03%和95.90%,分别与喷雾干燥法比较,P<0.05。溶媒结晶法合格率为100%,而喷雾干燥法合格率仅为20%。结论溶媒结晶法制备头孢菌素 C 钠盐的方法优于喷雾干燥法。     

头孢菌素C钠盐的制备

由头孢菌素C钠盐或钾盐经两步酶法直接裂解制备7-ACA，收率高，成本低，且污染少。但此法所用原料头C钠盐或钾盐极易溶于水，从水溶液中析晶很困难，且结晶剂不易寻找。本文即对头C钠盐的制备作初步的研究和介绍。采用醋酸-醋酸钠缓冲液将头孢菌素C从D-2004交换树脂上洗脱下来，得头孢菌素C钠盐溶液，再用纳滤浓缩至效价2万r／ml以上，以丙酮析晶，即得头孢菌素C钠盐。     

头孢菌素C酰化酶的分离

头孢菌素C酸化酶(CCA)可催化头孢菌素C侧链酰胺键的水解,生成β-内酰胺母核7-氨基头孢烷酸(7-ACA)和侧链α-氨基己二酸.利用CCA生产7-ACA只需一步反应过程.这种酶的工业应用将能取代目前使用的多步化学或酶促水解方法.     

超滤膜分离技术在头孢菌素C提纯中的应用

头孢菌素 C( 1 )是半合成头孢菌素类抗生素的起始原料 ,目前采用发酵法生产 ,发酵液中常存在菌丝体、蛋白质和悬浮微粒等杂质。现工艺是将发酵液预处理后用板框加压过滤或真空鼓式过滤的两步分离法除去这些杂质 ,操作工艺繁琐 ,滤液质量不高 ,收率较低。近十余年来 ,超滤膜技术作为一种新型的分离方法 ,在抗生素的提纯中得到了广泛的研究和应用 [1～ 4 ] ,但目前国内尚未见将此技术应用于 1发酵液提取分离的报道。本文采用 Ultra- flo超滤技术代替传统工艺一步截留发酵液中残留的菌丝体、蛋白质 (包括可溶性蛋白 )和悬浮微粒等杂质 ,简化了…     

优化培养基提高头孢菌素C产量

本文阐述了通过改变头孢菌素C发酵培养基中糖的组分,在不改变总糖含量的标准下,增加培养基中的葡萄糖含量,减少豆油含量的方法。加速菌体生长速度,达到缩短生产周期和提高产量的目的。经摇瓶试验得到优化培养基配方,然后在生产中验证。最终得到了预期结果,生产周期缩短了24小时,实现了单位时间内产量的提高。     

头孢菌素C生产工艺改进的研究Ⅰ.头孢菌素C新菌种C82—123发酵工艺研究

对Cephalosporium acremonium C82-123发酵过程中的温度,通气,pH调节,碳、氮源等组份的用量,氨水等的补料以及蛋氨酸的诱导作用进行了研究。采用改进后的发酵工艺,使该菌种在7 L 玻璃发酵罐中的发酵效价提高三倍以上。     

头孢菌素C发酵曲线的测定

摇瓶发酵过程中，不同时间测定各项参数的值，绘制出发酵曲线     

舒巴坦钠溶媒蒸馏法结晶工艺探讨

随着舒巴坦钠在联合用药中的广泛应用,舒巴坦钠原料药在全球的需求量不断上升,原有的舒巴坦钠常温微粒结晶法无法满足大批量生产的需求,而溶媒蒸馏结晶法可以大幅度提高单批产量,降低了成本,同时更易于控制晶型,得到比容适中的产品,易与哌拉西林钠等其他成分混合,进而提高产品质量。     

Studies on the cephalosporin C biosynthesis by fermentation

UsingCephalosporium acremonium ATCC 14553, we studied on the important factors in fermentation. Those factors were: carbon and nitrogen sources, methionine effect, adsorbent effect, fermentation variables in a batch fermentation, effect of reuse of its cellular biomass as a reusable nutrient, and 2,4-dinitrophenol effect on cephalosporin C production.     

The polarography of cephalosporin C derivatives

WE report some preliminary measurements on the polarographic reduction of cephalosporin C, cephalothin [7-(2-thienylacetamido)-cephalosporanic acid] and cephaloridine [7-(2-thienylacetamido)-3-(1-pyridylmethyl)-3-cephem-4-carboxylic acid betaine]. Green, Page & Staniforth (1965) have shown that cephalosporin C derivatives give well-defined infrared and nuclear magnetic resonance spectra that can be used for their qualitative identification. Martin & Shaw (1965) have reviewed the application of methods such as ultraviolet spectrophotometry, paper chromatography and paper electrophoresis for cephaloridine, while Chapman, Page & others (1968) have described infrared and X-ray powder measurements for this compound. The application of mass spectroscopy to the structural elucidation of cephalosporin derivatives has been reported by Richter & Biemann (1965).     

Strain improvement studies for cephalosporin C production by Cephalosporium acremonium

Treatment of spore suspension of Cephalosporium acremonium ATCC 48272 with UV rays and N-methyl-N-nitro-N-nitrosoguanidine (NTG) induced mutants capable of producing higher yields of cephalosporin C. Antibiotic yield was improved from 630 micrograms/ml to 1995 micrograms/ml of the broth resulting in a high yielding mutant.     

Monitoring of antisolvent crystallization of sodium scutellarein by combined FBRM-PVM-NIR

Antisolvent crystallization can be used as an alternative to cooling or evaporation for the separation and purification of solid product in the pharmaceutical industry. To improve the process understanding of antisolvent crystallization, the use of in-line tools is vital. In this study, the process analytical technology (PAT) tools including focused beam reflectance measurement (FBRM), particle video microscope (PVM), and near-infrared spectroscopy (NIRS) were utilized to monitor antisolvent crystallization of sodium scutellarein. FBRM was used to monitor chord count and chord length distribution of sodium scutellarein particles in the crystallizer, and PVM, as an in-line video camera, provided pictures imaging particle shape and dimension. In addition, a quantitative model of PLS was established by in-line NIRS to detect the concentration of sodium scutellarein in the solvent and good calibration statistics were obtained (r(2) = 0.976) with the residual predictive deviation value of 11.3. The discussion over sensitivities, strengths, and weaknesses of the PAT tools may be helpful in selection of suitable PAT techniques. These in-line techniques eliminate the need for sample preparation and offer a time-saving approach to understand and monitor antisolvent crystallization process.     

Production and optimization studies of cephalosporin C by solid state fermentation

Production of cephalosporin C employing a strain, Cephalosporium sp. NCIM 1039 under solid state fermentation was optimized. Different substrates like wheat bran, wheat grains, rice grains, barley and rice bran were studied to optimize the best substrate. Wheat bran showed the highest antibiotic yield. The physical and chemical parameters were optimized. The maximum productivity of cephalosporin C (750 U/g) was achieved by employing wheat bran and with optimized nutritional and process parameters such as potato starch as additive 1% w/w, urea as additive 1% w/w, incubation period of 7 days, incubation temperature at 30 degrees C, inoculum level 10% w/v, moisture content of solid substrate 80% and pH 7.0.     

舒巴坦钠结晶工艺的优化研究

目的 优化舒巴坦钠结晶工艺,降低产品比容。方法 以舒巴坦钠的比容为指标,采用单因素试验考察舒巴坦酸滴加方式、舒巴坦酸预加量、搅拌速度和晶种重量对产品比容的影响;选取舒巴坦酸预加量、搅拌速度和晶种重量为考察因素,通过正交试验优选最佳舒巴坦钠结晶工艺条件。通过30批大生产试验验证优化工艺,并选取前3批产品进行稳定性考察。结果 舒巴坦钠结晶的优化工艺为舒巴坦酸预加量50L、搅拌速度40r/min、晶种重量18kg。30批验证试验比容均值为2.38mL/g,较优化前降低32%,产品质量均符合中国药典质量标准。稳定性考察的各考察项目均符合中国药典(ChP2015)标准规定,质量稳定。结论 优化工艺稳定可行,可以有效降低产品比容,产生可观的经济效益。     

High performance liquid chromatography of natural products. I. Separation of cephalosporin C derivatives and cephalosporin antibiotics;isolation of cephalosporin C from fermentation broth.

Microbonded propylamine silica with a solvent system containing acetic acid, methanol, acetonitrile and water (2:4:7.5:86.5) is suitable for an efficient separation of mixtures containing several closely related cephem derivatives. The same system with preparative columns was used for the isolation of cephalosporin C directly from the filtered broth of C. acremonium fermentation.