藏药铁棒锤炮制“减毒存效”的质量评价初步研究

【作者】 蒲友明；

【导师】 张艺；

【作者基本信息】 成都中医药大学 ， 药物化学， 2008， 硕士

【摘要】 铁棒锤为常用藏药,收载于《卫生部药品标准·藏药》（第一册）,具有驱寒止痛,祛风定惊的功效。铁棒锤在民问和临床上应用广泛,疗效确切。但原植物品种繁多复杂,乌头属多种植物在各地均采挖入药,造成市场上药材品种十分混乱。铁棒锤为剧毒药材,炮制后方能入药。现代研究表明,铁棒锤所含的乌头碱类成分,既是抗炎有效成分,又为毒性成分。因此,如何在降低毒性的同时,保证临床疗效是铁棒锤炮制研究中的重点。本文以此为切入点,对铁棒锤的品种、资源分布、民族民间应用经验进行调查整理,进而初步探讨铁棒锤地方习用品康定乌头炮制前后生物碱成分变化及其与药效、毒性的相关性。目的:1.调查铁棒锤原植物和民族民间应用情况;2.分析铁棒锤地方习用品康定乌头炮制前后急性毒性、抗炎作用与生物碱成分变化相关性。方法:1.采用文献研究、关键人物访谈和证据标本采集等民族植物学研究方法;2.采用常规方法测定LD₅₀,以二甲苯致小鼠耳肿胀炎症模型评价抗炎作用;3.采用酸碱滴定法、TLC、HPLC、UV等现代化学分析方法。结果:1.收集和整理了铁棒锤民族民间炮制经验5种,发现了在甘孜藏族自治州南派藏医药体系中,康定乌头（Aconitum tatsienense Finet et Gagnep.）在临床上作为铁棒锤药材的地方习用品。2.康定乌头炮制前后相应的LD₅₀或最大给药量为:炮制品B、生品、炮制品C、炮制品E的LD₅₀分别为0.1636 g/kg、0.1763 g/kg、0.3290 g/kg、2.3955g/kg;炮制品D的最大给药量为11.4280g/kg,故毒性顺序为:炮制品B＞生品＞炮制品C＞炮制品E＞炮制品D。3.康定乌头炮制前后对抗二甲苯致小鼠耳廓肿胀的作用:炮制品B、生品、炮制品C、炮制品E均有明显对抗二甲苯致小鼠耳廓肿胀的作用,作用强度趋势为炮制品B＞生品＞炮制品C＞炮制品E,炮制品D没有明显的抑制作用。4.康定乌头炮制前后滇乌碱和印乌碱含量大小为炮制品B＞炮制品C＞炮制品D;炮制品B、C、D中酯型生物碱含量分别为0.468%、0.180%、0.285%,总生物碱含量分别为1.49%、1.02%、1.45%;同时炮制品C产生新峰a,炮制品D有a、b、c三个新峰产生,其生物碱成分变化与康定乌头炮制直接相关。5.康定乌头炮制前后滇乌碱和印乌碱为主的双酯型生物碱的含量多少与毒性大小和抗炎作用强弱基本成正相关,是影响康定乌头“减毒存效”的关键。结论:本研究为铁棒锤的原植物品种澄清,以及康定乌头质量控制、临床合理应用提供了科学依据,也可以为其它有毒民族药研究提供思路与方法。创新点:本文运用炮制前后毒性、抗炎作用变化可能与生物碱成分变化相关思路,进行了铁棒锤地方习用品康定乌头炮制“减毒存效”的质量评价初步研究,一定程度上填补了康定乌头质量控制和炮制研究的空白。更多还原

【Abstract】 Radix Aconiti,as a commonly used Tibetan medicine,is recorded in Tibet Departmental Standard,with the function of removing cold and wind,stopping pain, and quieting uneasiness.It is extensive and effective in the civil and clinical application,however,for the varieties of primary plants are complex,many plants of Aconitum are used in different areas which induce confusion in the medical materials market.As a virulent medicine,it should not be used without processing.Recent research indicates that aconitum alkaloids of Radix Aconiti are not only anti-inflammatory but toxic components,therefore,how to reduce toxicity and ensure clinical efficacy is the focus of the research.This article mainly investigated varieties, distribution of resources and experience of ethical application of Radix Aconiti,and primarily explored the relevance of the change of chemical composition, pharmacodynamic effects and toxicity before and after processing of Aconitum tatsienense Finet et Gagnep which was applied as Radix Aconiti in local places.Objective:1.The investigation of original plants and ethical application of Radix Aconiti;2.The correlation analysis between the effects of toxicity,anti-inflammatory and the change of alkaloids of Aconitum tatsienense.Methods:1.By the methods of ethnopharmacology,including the research of literature,the interview of key characters,the collection of evidence and specimens and so on;2.By routine method and the swelling of auricle in rats caused by xylol;3.By the modern analysis methods,such as TLC,HPLC,UV,Acid-Base titration.Results:1.Collect and sort five kinds of folk processing experiences.Aconitum tatsienense Finet et Gagnep is used as one source of Radix Aconiti in the Southern Tibetan medicine system in Ganzi.2.Aconitum tatsienense was studied on the acute toxicity before and after processing with toxicological index LD₅₀,and the results showed that the sequencing of corresponding LD₅₀ or maximum dose was 0.1636 g/kg,0.1763 g/kg,0.3290 g/ kg,2.3955 g/kg,11.4280g/kg in processed product B,raw product,processed products C,processed products E and processed product E;and so was the toxicity from high to low.3.Processed product B/C/E and raw product,except processed product D,could significantly lighten the swelling of auricle in rats caused by xylol and the effect intensity from strong to weak was processed product B＞raw product＞processed product C＞processed product E.4.The alternations of the chemical constituents before and after processing showed that the content of yunaconitine and indaconitine is processed product B＞processed product C＞processed product D from high to low;the content of Ester alkaloids in processed products B/C/D are 0.468%,0.180%,0.285%respectively;and total alkaloid in the processed products B/C/D are 1.49%,1.02%,1.45%;and processed products C,D had respectively produced one and three new components,which were directly relevance to processing.5.How much is the content of diester alkaloids,such as yunaconitine and indaconitine,is directly proportional to the effects of toxicity and anti-inflammatory.It was the key influencing factor of "attenuated toxic and kept effect".Conclusions:This article provides science for the investigation of varieties,quality control, reasonable application at a clinica,and provides train of thought and method for the research of other toxic ethnic medicine.Innovation:This article used the train of thought that acute toxicity and anti-inflammatory maybe have to do with chemical composition changes before and after processing, carry out quality research of "attenuated toxic and kept effect" preliminary in Aconitum tatsienense Finer et Gagnep which was applied as Radix Aconiti in local places.更多还原