右旋糖酐40制备过程中细菌内毒素含量的影响因素  

Factors Affecting Content of Bacterial Endotoxin in Preparation Process of Dextran 40

作　　者：问清江[1] 慕娟[1] 孙晓宇[1] 郑巧霞 丁浩[1] WEN Qing-jiang;MU Juan;SUN Xiao-yu;ZHENG Qiao-xia;DING Hao(Shanxi Inst.of Microbiol.,Xi′an 710043)

机构地区：[1]陕西省微生物研究所,陕西西安710043

出　　处：《微生物学杂志》2023年第6期81-88,共8页Journal of Microbiology

基　　金：陕西省科学院科学研究专项(2020K-06);西安市科技创新人才服务企业项目(2020KJRC0149)。

摘　　要：右旋糖酐40生产中分离纯化采用乙醇沉淀和超滤方法,将细菌内毒素作为分离纯化的一项指标,对影响因素进行探究,将细菌内毒素含量引入右旋糖酐40原料药产品标准,并且达到国际标准。随着乙醇浓度的增加,相应沉淀产品的细菌内毒素含量逐渐降低;在乙醇分步沉淀中,随着乙醇浓度逐级提高,分离产品的细菌内毒素含量也在降低。分离纯化用水和环境因素均会影响右旋糖酐40分离纯化的细菌内毒素指标。乙醇沉淀分离纯化的右旋糖酐40产品,细菌内毒素含量均<6.00 EU/g,最低含量<3.00 EU/g,优于国际标准(≤10 EU/g),重均分子量和分子量均符合《中国药典》质量标准。100 kDa+20 kDa二膜组合超滤分离纯化的右旋糖酐40的细菌内毒素含量可以达到10 EU/g以下。100 kDa+20 kDa+50 kDa三膜组合超滤分离纯化,右旋糖酐40的细菌内毒素含量达到3 EU/g以下,重均分子量及分子量分布达到《中国药典》标准。改进右旋糖酐40生产工艺,提高产品品质,细菌内毒素含量引入右旋糖酐40原料药质量指标,使其达到和超过国际最高质量标准。Ethanol precipitation and ultrafiltration were used for separation and purification during the production of dextrran 40.Endotoxin was taken as an indicator of separation and purification,and influencing factors were explored.The content of endotoxin was introduced into the product standard of dextrran 40 API and reached the international standard.With the increase of ethanol concentration,the endotoxin content of corresponding precipitated products gradually decreased.In the step precipitation of ethanol,with the gradual increase of ethanol concentration,the endotoxin content of the products was also decreasing.The results showed that dextrran 40 product separation and purification by ethanol precipitation had a endotoxin content<6.00 EU/g and a minimum content<3.00 EU/g,which was superior to the international standard.The weight average molecular weight and molecular weight distribution met the quality standard of the Chinese Pharmacopoeia.The endotoxin content of dextrran 40 product separated and purified by 100 kDa+20 kDa two-membrane combination ultrafiltration could reach below 10 EU/g.The bacterial endotoxin content of dextrran 40 separated and purified by 100 kDa+20 kDa+50 kDa triplemembrane combination ultrafiltration reached below 3 EU/g,and the weight average molecular weight and molecular weight distribution reached the standard of Chinese Pharmacopoeia.To conclude,the production process of dextran 40 was improved and the product quality was improved.The content of bacterial endotoxin was introduced into the quality index of dextran 40 API to make it reach and exceed the international highest quality standard.

关 键 词：右旋糖酐40 细菌内毒素 乙醇沉淀 超滤 分离纯化 

分 类 号：Q936[生物学—微生物学]