Li Yue, Duan Jinlian, Xia Heng, Shu Bin, Duan Weigang
Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Traditional Chinese Medicine, 1076, Yuhua Rd., Kunming 650500, China.
Jiangsu Center for Safety Evaluation of Drugs, Nanjing Tech University, 30, South Puzhu Rd., Nanjing 211899, China.
Toxicol Res (Camb). 2020 May 21;9(3):323-330. doi: 10.1093/toxres/tfaa024. eCollection 2020 Jun.
Macromolecular substances in traditional Chinese medicine injections (TCMIs) are expected to be a main dangerous factor causing anaphylactic or anaphylactoid reaction. The main aim of the study was to verify the macromolecular substances' anaphylactic or anaphylactoid reaction in guinea pigs and establish a size-exclusive chromatographic method to detect them. The macromolecular substances from six TCMIs (Danshen injection, Dengzhanxixin injection, Honghua injection, Qingkailing injection, Shuanghuanglian injection and Shuxuening injection) were prepared by removing substances with molecular weight less than 10 kDa with an ultra-filter. The anaphylactic and anaphylactoid reactions caused by original TCMIs, injections rich in or free of macromolecules were assayed in guinea pigs. The relationship between the amount of the macromolecular substances and peak area of chromatogram was established by size-exclusive chromatography. Injections free of macromolecules were not likely to cause anaphylactic and anaphylactoid reactions, but injections rich in macromolecular substances were more likely to do so. If the macromolecular substances with molecular weight bigger than 10 kDa were removed, the signal of macromolecular substances in TCMIs was quantitatively reduced. All the results suggested that macromolecular substances in TCMIs are a dangerous factor causing safety problems, and the macromolecular substances can be quantitatively detected with size-exclusive chromatography.
中药注射剂中的大分子物质被认为是引发过敏或类过敏反应的主要危险因素。本研究的主要目的是在豚鼠中验证大分子物质的过敏或类过敏反应，并建立一种尺寸排阻色谱法来检测它们。通过超滤去除分子量小于10 kDa的物质，制备了六种中药注射剂（丹参注射液、灯盏细辛注射液、红花注射液、清开灵注射液、双黄连注射液和舒血宁注射液）中的大分子物质。在豚鼠中测定了原始中药注射剂、富含或不含大分子的注射剂引起的过敏和类过敏反应。通过尺寸排阻色谱法建立了大分子物质的量与色谱峰面积之间的关系。不含大分子的注射剂不太可能引起过敏和类过敏反应，但富含大分子物质的注射剂更有可能引起此类反应。如果去除分子量大于10 kDa的大分子物质，中药注射剂中大分子物质的信号会定量降低。所有结果表明，中药注射剂中的大分子物质是导致安全问题的危险因素，并且可以用尺寸排阻色谱法定量检测大分子物质。
