中药注射剂中药材的微生物污染  

Identification and Removal of Microbial Contaminants from Herbal Drugsfor Traditional Chinese Medicine Injection

作　　者：段金连 李月 张路梅 董鲜祥 杨榕 殷华 郭良 段为钢 DUAN Jinlian;LI Yue;ZHANG Lumei;DONG Xianxiang;YANG Rong;YIN Hua;GUO Liang;DUAN Weigang(Key Laboratory of Molecular Biology for Sinomedicine,Yunnan University of Chinese Medicine,Kunming 650500,China;Institute of Pharmaceutical Research,Shiyao Yinhu Pharmaceutical Co.,Ltd.,Yuncheng 044000,China)

机构地区：[1]云南中医药大学中医药学分子生物学实验室,云南昆明650500 [2]石药银湖制药有限公司,山西运城044000

出　　处：《云南中医学院学报》2019年第4期1-8,共8页Journal of Yunnan University of Traditional Chinese Medicine

基　　金：国家自然科学基金(81560645);云南省科技厅—云南中医学院应用基础研究联合专项(2017FF117-032)。

摘　　要：目的本研究主要探究药材的沾染性微生物及其去除的可行性,以提高中药注射剂的安全性。方法选取药用部位为地下部分的丹参和药用部位为地上部分的红花。模拟注射剂的生产步骤检测主要步骤药材沾染的微生物杂质。通过洗涤和冷冻干燥收集药材沾染的微生物,通过16S rRNA(细菌)和18S rRNA(真菌)高通量测序鉴定微生物的种类和丰度。通过鲎试剂检测各步骤样品中的脂多糖(LPS)的量。结果 2种中药材均沾染有高丰度的细菌和真菌,其中真菌沾染更为严重;相比之下,红花的微生物沾染比丹参严重。且沾染的LPS很大程度上可被洗除。结论中药材的微生物及大分子沾染不容忽视,但可被洗涤进行大部分去除。Objective The main aim of the present study was to limit contaminant microbes and their macromolecules in raw herbal drugs,then decrease TCMIs’safety problems.Methods A raw herbal drug from underground part(Danshen,root and rhizome of Salvia miltiorrhiza Bge.)and that from aboveground part(Honghua,flower of Carthamus tinctorius L.)were introduced.The contaminant microbes were assayed at steps of the mimic process of TCMI manufacturing.Microbes adhered to raw herbal drugs Honghua or Danshen were collected,and their DNA encoded 16S rRNA(for bacteria)and 18S rRNA(for fungi)were identified by high-throughput sequencing.The feasibility of removable lipopolysaccharide(LPS)adhered to the raw drugs was investigated with TAL(Tachypleus Amebocyte Lysate)kits by detecting flushing fluid and the mimic injections.Results The results showed that both raw drugs were contaminated with microbes,and the abundance of fungi was heavier than that of bacteria.As a raw herbal drug from aerial part,Honghua contained more bacteria and fungi than Danshen.The contaminant LPS was able to be largely removed by washing.Conclusion All the results suggested that the contaminant microbes,especially fungi,and their macromolecular impurities should be taken into account for TCMI manufacturing,and they were able to be removed largely by washing.

关 键 词：微生物沾染 细菌 真菌 脂多糖 中药注射剂 

分 类 号：R285.5[医药卫生—中药学]