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双黄连注射液致类过敏物质筛选研究
引用本文:易艳,张宇实,李春英,赵海誉,肖红斌,李桂琴,卢禹婷,韩佳寅,赵雍,王宏洁,司南,梁爱华,边宝林.双黄连注射液致类过敏物质筛选研究[J].中国中药杂志,2015,40(14):2727-2731.
作者姓名:易艳  张宇实  李春英  赵海誉  肖红斌  李桂琴  卢禹婷  韩佳寅  赵雍  王宏洁  司南  梁爱华  边宝林
作者单位:中国中医科学院 中药研究所, 中药鉴定与安全性检测评估北京市重点实验室, 北京 100700,中国中医科学院 中药研究所, 中药鉴定与安全性检测评估北京市重点实验室, 北京 100700,中国中医科学院 中药研究所, 中药鉴定与安全性检测评估北京市重点实验室, 北京 100700,中国中医科学院 中药研究所, 中药鉴定与安全性检测评估北京市重点实验室, 北京 100700,中国中医科学院 中药研究所, 中药鉴定与安全性检测评估北京市重点实验室, 北京 100700,中国中医科学院 中药研究所, 中药鉴定与安全性检测评估北京市重点实验室, 北京 100700,中国中医科学院 中药研究所, 中药鉴定与安全性检测评估北京市重点实验室, 北京 100700;首都医科大学 中医药学院, 北京 100069,中国中医科学院 中药研究所, 中药鉴定与安全性检测评估北京市重点实验室, 北京 100700,中国中医科学院 中药研究所, 中药鉴定与安全性检测评估北京市重点实验室, 北京 100700,中国中医科学院 中药研究所, 中药鉴定与安全性检测评估北京市重点实验室, 北京 100700,中国中医科学院 中药研究所, 中药鉴定与安全性检测评估北京市重点实验室, 北京 100700,中国中医科学院 中药研究所, 中药鉴定与安全性检测评估北京市重点实验室, 北京 100700,中国中医科学院 中药研究所, 中药鉴定与安全性检测评估北京市重点实验室, 北京 100700
基金项目:国家自然科学基金项目(81202993,81374057);中国中医科学院自主选题项目(ZZ0808009);中国中医科学院中药所自主选题项目(ZZ2014023);中国中医科学院基本科研业务费自主选题(L201475)
摘    要:采用小鼠类过敏反应检测模型,以双黄连注射液(SHLI)为例,对双黄连注射液的中间体提取物、中间体的逐级萃取组分或成分进行类过敏反应筛选,确定双黄连注射液的主要致类过敏物质。结果显示双黄连注射液的3个中间体(黄芩提取物、金银花提取物、连翘提取物)中,连翘提取物致类过敏反应的作用较强;连翘提取物的致类过敏反应主要与其中极性较大的组分有关;进一步研究发现,此部分极性物质成分中所包含的连翘酯苷A和牛蒡苷可导致明显的类过敏反应。采用液质联用化学成分靶向切除技术剔除双黄连注射液中的连翘酯苷A后,与未剔除连翘酯苷A的双黄连注射液相比,前者诱发类过敏反应大大降低,安全性明显提高。该研究采用化学分离与体内类过敏检测模型相结合的方法,建立了一套筛选双黄连注射液致类过敏物质的技术,并找出了SHLI的主要致类过敏成分,不仅为SHLI的工艺改进和优化提供了科学基础,也为中药注射剂尤其是复方制剂类过敏物质筛选研究提供了思路和方法。

关 键 词:双黄连注射液  类过敏反应  物质基础  血管  连翘酯苷A  牛蒡苷  通透性
收稿时间:2015/3/19 0:00:00

Study of screening pseudoallergenic substances of Shuanghuanglian injection
YI Yan,ZHANG Yu-shi,LI Chun-ying,ZHAO Hai-yu,XIAO Hong-bin,LI Gui-qin,LU Yu-ting,HAN Jia-yin,ZHAO Yong,WANG Hong-jie,SI Nan,LIANG Ai-hua and BIAN Bao-lin.Study of screening pseudoallergenic substances of Shuanghuanglian injection[J].China Journal of Chinese Materia Medica,2015,40(14):2727-2731.
Authors:YI Yan  ZHANG Yu-shi  LI Chun-ying  ZHAO Hai-yu  XIAO Hong-bin  LI Gui-qin  LU Yu-ting  HAN Jia-yin  ZHAO Yong  WANG Hong-jie  SI Nan  LIANG Ai-hua and BIAN Bao-lin
Institution:Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Key Laboratory of Beijing for Identification and Safety of Chinese Medicine, Beijing 100700, China,Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Key Laboratory of Beijing for Identification and Safety of Chinese Medicine, Beijing 100700, China,Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Key Laboratory of Beijing for Identification and Safety of Chinese Medicine, Beijing 100700, China,Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Key Laboratory of Beijing for Identification and Safety of Chinese Medicine, Beijing 100700, China,Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Key Laboratory of Beijing for Identification and Safety of Chinese Medicine, Beijing 100700, China,Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Key Laboratory of Beijing for Identification and Safety of Chinese Medicine, Beijing 100700, China,Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Key Laboratory of Beijing for Identification and Safety of Chinese Medicine, Beijing 100700, China;Capital Medical University, Beijing 100069, China,Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Key Laboratory of Beijing for Identification and Safety of Chinese Medicine, Beijing 100700, China,Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Key Laboratory of Beijing for Identification and Safety of Chinese Medicine, Beijing 100700, China,Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Key Laboratory of Beijing for Identification and Safety of Chinese Medicine, Beijing 100700, China,Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Key Laboratory of Beijing for Identification and Safety of Chinese Medicine, Beijing 100700, China,Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Key Laboratory of Beijing for Identification and Safety of Chinese Medicine, Beijing 100700, China and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Key Laboratory of Beijing for Identification and Safety of Chinese Medicine, Beijing 100700, China
Abstract:In this study, chemistry, biology and pharmacology were combinated to screen pseudoallergenic substances of Shuanghuanglian injection (SHLI) so that to establish a scientific and systematic approach to screen pseudoallergenic substances of traditional Chinese medicine injections. The mouse pseudoallergic reaction models were used to screen the pseudoallergic reaction of SHLI's intermediate extract and the intermediate extract's component or ingredient.Among the three intermediates of Shuanghuanglian injection (extract of Scutellaria baicalensis, extract of Lonicera japonica, extract of Forsythia suspensa), pseudoallergic action of Forsythia suspensa was the strongest, Forsythia suspesnsa's pseudoallergic reaction mainly associated with the composition with largerchemical polarity. Further it was found that forsythiaside A and arctiin which existed in the the composition with largerchemical polaritycausedobvious pseudoallergic reactions. SHLI with removal forsythoside A with the technology of HPLC-MS displayed reduced pseudoallergic reaction and a significant improved safety. This study provided a scientific basis for SHLI process improvements and also offered idea and research foundation for screening pseudoallergenic substances injections in other TCM injections.
Keywords:Shuanghuanglian injection  pseudoallergenic reactions  pseudoallergenic substances  vascular permeablity  forsythiaside A  arctiin
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