【作者】 刘雅婧；

【导师】 张连学； 张春红； 吴海东；

【作者基本信息】 吉林农业大学 ， 中药学， 2008， 硕士

【摘要】 细辛为马兜铃科植物北细辛、汉城细辛、或华细辛的根及根茎。始载于《神农本草经》,列为上品。具有祛风散寒、温肺化饮,通窍止痛的功效。细辛被国家医药管理局推荐为重点发展的63种紧缺中药材之一,同时又被列为国家两个重点中药材之一,是国际国内需求量较大的常用中药。据部颁成方制剂标准和《中国药典》等得不完全统计,处方中含有细辛的中成药有176个。细辛作为马兜铃科植物含有马兜铃酸,马兜铃酸有致癌及肾损害作用。“马兜铃酸肾病”曾在国际上引起了轩然大波,2000年5月31日,FDA发布了“FDA对卫生行业的有关含有马兜铃酸植物药物和食品的通告”,并附有相关药物的目录。其中,在可能混杂有马兜铃酸的植物药物(B类)中,包括细辛这位药。2000年6月9曰,FDA在“至今未收到类似不利事件报告”的情况下,命令停止进口、制造和销售已知含有和“怀疑含有马兜铃酸的原料和成品”。至此,含有马兜铃酸的中药材陆续遭到了不同程度的禁用,对我国中药产业产生了极不良影响。为解决细辛及众多含马兜铃酸药材的毒性问题,以去毒存效为目的,根据马兜铃酸的化学性质,采取碱制的炮制手段,将细辛中的马兜铃酸选择性的去除,而对其有效成分得以保留或少流失,在去除毒性成分的前提下,又保证不影响药材的药效。利用HPLC、GC手段对药典规定的三个品种、五个不同产地的细辛做了质量评价的研究,筛选出了有效成分含量高、马兜铃酸含量低的品种。对细辛的不同产地、不同入药部位的有效成分和马兜铃酸的含量做了差异比较分析。结果表明,华细辛的马兜铃酸含量最高,汉城细辛的有效成分含量最高。以华细辛为供试品,以马兜铃酸A含量为指标,从七种炮制方法中筛选出碱制为最佳炮制方法。并通过正交试验确定了碱制的最佳工艺。用HPLC、GC法对经碱制最佳工艺炮制后的细辛的毒性成分和有效成分含量做了考察。结果表明,经炮制后细辛中毒性成分马兜铃酸A含量下降了85%左右。马兜铃总酸含量下降了74%。细辛脂素含量无明显变化。细辛经炮制后马兜铃酸只痕量存在。说明碱制方法可以有效的去除细辛中的马兜铃酸而使有效成分可以大部份被保留。达到了去毒存效的炮制目的。为了从总体上探究生品与炮制品的化学成分的变化,对炮制前后细辛大中小极性浸出物的含量作了比较。实验结果表明,炮制品较生品四种浸出物百分比含量均有下降。水及乙醇浸出物含量下降最多,环己烷浸出物次之,乙酸乙酯浸出物最少。但浸出物含量的下降与有效成分含量的降低及药效的下降是否相关有待进一步考察。为了考察细辛炮制后的化学成分的具体变化,本文应用了当今国际上普遍承认的指纹图谱技术,对炮制前后的细辛的整体成分做了完整的比较和分析。经碱制后细辛的甲醇提取物部分变化明显。其中马兜铃酸A峰值减少。有两个峰消失。乙酸乙酯提取物部分有两组峰消失,共有峰峰面积均有减小。环己烷提取物部分无非共有峰,共有峰峰面积减小。更多还原

【Abstract】 Herba Asari is root and rhizoma from Aristolochia plant Asarum heterotropoides Fr.Schmidt var.mandshuricum（Maxim.）Kitag,Asarum sieboldii Miq.v&r.seoulense,and Asarun sieboldii Miq,were earliest listed in the "Shen NongBenCaoJing ",as Shangpin.With qufengsanha- n,wenfeihuaxin,tongqiaozhitong effect.As one of 63 kinds of Chinese herbal medicine in shortage,Asarum was recommended by the State Pharmaceutical Administration Bureau for focus developing.At the same time was also listed as two key medicines to our country,is now commonly used Traditional Chinese Medicine for great demand.According to Bubanchengfang preparation standards and the Chinese Pharmacopoeia’s incomplete summary,there were 176 prescriptions include Herba Asari.Herba Asari as Aristolochiac plant,contains aristolochic acid,that has renal toxicity and carcinogenesis. Aristolochic Acid Renal Toxicity has caused great turbulence all over the world.By May 31rd 2000,the FDA issued a ’FDA notice on health-related plants containing aristolochic acid in drugs and food’,which followed with a related-prescription catalog.Among the medicinal plants those may mixed with aristolochic acid mentioned（B）,Herba Asari was listed.By June 9th 2000,FDA pressed an order to prohibit importing,manufacturing,and selling any ’aristolochic acid suspected materials and products’,although they did not receive any reports of similar adverse events until then.By now,TCM within aristolochic acid were forbidden to different extent,caused great side-effect to domestic TCM industry.For removing the toxicity in Asarum and other aristolochic acid- containing medicines,in order to remove toxicity and maintain pharmacodynamic activity,according to the chemical nature of aristolochic acid,we adopted base-processing to remove aristolochic acid in Herba Asari selectively,and retain its active ingredients.By means of HPLC and GC,we studied queality standard of 3 spieces and 5 different habits, selected a high content of active ingredient,and low aristolochic acid spieces.Analysed effective components and aristolochic acid in Asarum from different habits,and different parts of the herb.The results showed that,the highest content of aristolochic acid was Asarun sieboldii Miq.the highest content of active ingredients was Asarum sieboldii Miq.var.seoulense.Asarun sieboldii Miq used as experiment material,and aristolochic acid as index,selected NaHCO₃ processing method from seven processes as the best,defined the optimal process by orthogonal experiment. GC and HPLC were used to measure toxicity components and active ingredients in Herba Asari after processing.The result indicated that after being processed aristolochic acid A in Herba Asari had been 85%off.Total aristolochic acid decreased 74%.Asarmin contents has no obvious change.It is verified that NaHCO₃ processing could reduce aristolochic acid A effectively and remain active ingredients mostly.Processing purpose is achieved.In order to study the change of chemical composition in crude and processed Asarun sieboldii Miq,we compared contents of extracts in crude and processed Asarun sieboldii Miq from different polar solvent.The result indicated that contents of all four extracts had decreased.The extracts from aqeous and ethanal decreased most,cycloh exane less,and acetic ether least.The relationship between decrease of extracts’ contents and pharmacodynamic action need to be investigated in future.To investigate the specific chemical change in crude and processed Herba Asari,the experiment uses the finger prints technology to compare and analsyse total components of Herba Asari.After being processed,methanol extracts had changed obviously.Aristolochic acid A’s chromatographic peak value decreased,and two chromatographic peaks vanished.Acetic ether extracts had two chromatographic peaks vanished.Chromatographic peak value owed by both had diminished.cyclohexane extracts chromatographic peak value decreased and composition of chromatographic peak had no change.更多还原