【作者】 叶祖光； 王智民； 王跃生； 王金华； 梁国刚； 杜贵友； 梁爱华；

【Author】 Ye Zuguang~1 Wang Zhimin~2 Wang Yuesheng~2 WangJinhua~2 Liang Guogang~2 Du Guiyou~2 Liang’ Aihua~2 Xue Baoyun~2 (Beijng Zhongyuan Tongrentang Chinese Medicine R&D CO.,Ltd.Institute of Chinese Matetia Medica,China Academy of Traditional Chinese Medicine)

【机构】 北京中研同仁堂医药研发有限公司； 中国中医研究院中药所；

【摘要】 目的:研究安宫牛黄丸中朱砂、雄黄在复方中的药效学存在的必要性和安全性,明确汞和砷在成药中和体内的化学存在形态,以及它们的药代动力学特点。方法:利用化学手段首次合成了若干个化学结构明确的汞和砷的络合物,并以此为对照品,对汞和砷在安宫牛黄丸成药中、大鼠血液以及组织器官中的化学存在状态均进行分析检测。并采用与安宫牛黄丸药效学相关的多项指标,对安宫牛黄丸及其简化方（安宫牛黄丸去掉朱砂和雄黄）进行了药效和毒理学的比较研究,采用药代动力学的方法研究汞和砷在大鼠体内的吸收、分布、血药浓度和排泄。结果:建立了简便、快速的合成汞、砷络合物的方法,并揭示了安宫牛黄丸中汞、砷在体内外的化学存在状态;药代动力学研究证明了朱砂和雄黄中的HgS 和As₂S₂为不被机体所吸收的无活性成分,而其生物活性成分可能为酸可溶性或水可溶性汞和砷部分:经镇静、抗惊厥、解热、缺氧模型以及毒性试验等多项药理学指标证明,安宫牛黄丸原方的药理学作用和简化方无明显统计学差异。结论安宫牛黄丸中朱砂和雄黄的主成分HgS 和As₂S₂是不能被机体所吸收的无活性成分,而其生物活性成分（具有一定的药效学作用）为酸可溶性的汞和砷部分,药理学试验说明安宫牛黄丸和简化方未见明显区别。更多还原

【Abstract】 Objective:To explore pharmacological and Toxicological contribution of cinnabarand realgar to their preparation Angong Niuhuang pill,their existing chemical status inthe pill,and pharmacokinetic profile.Methods:several of cinnabar and realgar complexwere synthesized as reference compounds to determine chemical status of cinnabar and realgarin the pill and in the blood and the organs following their administration into rats.Pharmacodynamic and toxicological comparison was carried out between Angong Niuhuang pilland its simplified preparation without cinnabar and realgar.And absorption,distribution, blood concentrations and excretion,pharmacokinetic,methods were used to investigate toof the arsenic and the mercury complexes.Results:cinnabar and realgar complexes weresynthesized and their structures were identified by spectral evidence.Using these complexesand analytic techniques,the chemical status of arsenic and mercury contained in the pilltaken orally by the rats were essentially clarified.The pharmacokinetic data revealed thatHgS and As₂S₂,which,respectively,account for more than 90% of cinnabar and realgarcomposition,cannot be absorbed in digestive tract,indicating that biological active partof cinnabar and realgar relies on their acid-soluble or water-soluble composition.Littlestatistical difference （P>0.05） was found between the pill and its simplified preparationwithout cinnabar and realgar in multiple pharmacological experiments such as sedative,anticonvultion,antipyretic hypoxia tolerant tests,as well as toxicological studies,although there was tendency that the pill was more potent than the simplified one inpharmacodynamic activity.Conclusion:The mercuric sulfide and the arsenic sulfide,mainpart of cinnabar and realgar,respectively are their inactive constituents,and not absorbedin gastrointestinal tract,while their water or acid-soluble composition is biologicallyactive part.The pharmacological evidence demonstrates no difference between the pill andthe simplified preparation.更多还原