A Study On The New Technology For Preparation Of Phenoxymethylpenicillin Potassium

Phenoxymethylpenicillin potassium is an important API,which is widely used to manufacture no-sterile dosage, semi-synthetical penicillins and cefpHalosporins. Phenoxymethylpenicillin potassium now covers 25% of the total penicillins amount in the international market. Benzylpenicillin industry developed very quickly in recent years in China, the quantity covers 2/3 of the global output. However, phenoxymethylpenicillin potassium industry develops very slowly because of the technology problems, including the low fenmentation level, the low quality and the high cost. Most of the penilllin factory in China can only produce benzylpenicillin.The producing process of penicillin consistes many steps. The present work investigates the whole producing process of phenoxymethylpenicillin potassium, including the spore incubate, fenmentation, filtration, extraction and crystallization process. Some factors that influence the fenmentation level, the purifiction yield, product quality are studied. Some methods to improve the product quality are put forward.The common producing process of phenoxymethylpenicillin potassium is as follwing. The fermentation liquid is first filtrated by plate filter, extracted by butyl acetate, then crysterlized by adding potassium acetate and finally the product is dried. The product quality thus obtained is bad. For example, the purity is usually lower than 96% and the impurity of high polymer is higher than 0.6%. Furthermore, the solvent amount used is very large. All these problems lead to the high manufacture cost and the serious environment pollution.Some efforts were made to improve the productivity and the quality of phenoxymethylpenicillin potassium in this work. In the fementation process, the potential effect factors including the culture mediun, the solved oxygen, pH or fermentation liquidand so on were systematically studied. In the filrtation process, the plate filter commonly used was substituted by the membrane filter. The experimental results show that the membrane filter can improve the quality of filted liqid. In the extraction process, the emulsification-breaking reagent is retrenched. In the purification process, the crude phenoxymethylpenicillin potassium was first solved with water. Phenoxymethylpenicillin acid was obtained by adding sulpHate acid into the above solution. Then potassium...