【作者】 赵斌；

【导师】 董小萍；

【作者基本信息】 成都中医药大学 ， 中药学， 2008， 博士

【摘要】 螃蟹甲为唇形科糙苏属植物植物螃蟹甲Phlomis younghusbandii Muker jee的干燥块根,藏药名为“露木尔”,为常用藏药,已被中华人民共和国卫生部颁发的《药品标准》（藏药第一册）所收载。螃蟹甲味苦、性凉,有疏风清热,散寒润喉,镇咳祛痰,生肌敛疮之功效,用于治疗培根寒症,咽喉疫疬,风热感冒,咳嗽痰多,支气管炎,疮疡久溃不敛,肺病等症。为促进其进一步合理开发利用,本课题对螃蟹甲的化学成份、药理作用、质量控制进行了系统研究。通过小鼠氨水引咳法、小鼠呼吸道酚红排泌法、豚鼠组胺致喘法以及二甲苯致小鼠耳肿胀法、醋酸致小鼠腹腔毛细血管通透性实验等五个药理实验,对螃蟹甲镇咳、祛痰、平喘、抗炎有效部位进行了较为全面的筛选,研究结果表明,螃蟹甲的乙酸乙酯部位和正丁醇部位均有较好的镇咳、祛痰、平喘以及抗炎作用,是其主要有效部位。化学成分预试验结果表明,螃蟹甲中可能含有氨基酸、蛋白质、多糖、鞣质、酚类、有机酸、黄酮、香豆素、蒽醌、三萜、甾体、皂苷等成分。本课题对螃蟹甲进行醇提和部位分离后,通过柱色谱及制备薄层等手段分离纯化,从其有效部位乙酸乙酯部位中共分离得到12个化合物,通过ESI-MS,HR-MS,UV,IR,¹H-NMR,¹³C-NMR,DEPT,H-HCOSY,HMQC和HMBC等现代波谱分析技术,并结合理化性质鉴定出其中10个化合物的结构。它们分别是phlomisosideⅥ（1）、山栀苷甲酯（2）、木犀草素（3）、山奈素（4）、小檗碱（5）、熊果酸（6）、大黄素（7）、大黄酸（8）、β-胡萝卜苷（9）、β-谷甾醇（10）,除化合物2、7、8外,其余化合物均为首次从该植物中分离得到,其中化合物5为首次从该属植物中分离得到,化合物1为新化合物。对螃蟹甲药材质量控制方法进行了系统的研究。首次提供了螃蟹甲质量标准控制用的糙苏苷F（phlomisosideⅥ）对照品,并通过对其来源、提取工艺、结构鉴定、纯度检查、含量测定等方面的研究,制定了糙苏苷F对照品的质量标准。对药材性状、显微和薄层鉴别进行了研究;首次采用RP-HPLC法对药材中含量相对较高的环烯醚萜苷类成分山栀苷甲酯及分得的新化合物糙苏苷F进行了定量分析;在定性鉴别和定量分析的基础上,对螃蟹甲药材质量标准进行全面的修订和完善。建立了螃蟹甲药材指纹图谱的高效液相色谱测定方法,研究结果表明,其甲醇提取物中各化学成分在选定的色谱条件下,相对保留时间基本一致,各批药材色谱峰貌极其相似。在螃蟹甲有效成分尚不完全明确的情况下,本方法作为其质量控制手段具有一定的意义。综上,本课题对螃蟹甲所含的化学成分进行了系统研究,初步揭示了其镇咳、平喘、祛痰、抗炎药效作用的物质基础。在化学及药理研究的基础上,针对性地建立了药效成分的定性定量控制方法,对其质量控制标准进行了全面的修改与完善。这一研究对于规范螃蟹甲药材的质量具有十分重要的借鉴意义,为该药材的进一步研究、开发和应用提供了理论依据和科学参考,同时对于推动藏药现代化的发展也具有一定的意义。更多还原

【Abstract】 RADⅨPHLOMⅡis the dried root of perennial herbage Phlomis younghusbandii Mukerjee which belongs to the genus Phlomis of family Labiate. RADⅨPHLOMⅡis commonly used in Tibetan medicine named as "Lumue" in Tibet. According to traditional medical the theories of Tibetan,RADⅨPHLOMⅡtastes bitter,cool in nature and belongs to the lung,it has the functions of dispelling wind and clearing heat,relieving cough and reducing phlegm,promoting tissue regeneration and wound healing,it is used to treat common cold due to wind heat, cough with profuse sputum,pyogenic skin infection without healing for along time, etc.For further reasonable development and application,we have systematically studied on chemical constituents,pharmacological effects and quality control methods of RADⅨPHLOMⅡ.Five pharmacodynamic experiments firstly done on different extracted parts approved the acetic acid ethyl ester part and the n-butyl alcohol part of RADⅨPHLOMⅡhad prominent biological activities,such as relieving cough,reducing phlegm,appeasing asthma and anti-inflammatory.These results showed the two parts are the effective parts of RADⅨPHLOMⅡ.The chemical element study done by us indicated that RADⅨPHLOMⅡmay contains amino acid,protein,amylase,tannins,phenols,organic acid,flavonoids, coumarins,anthraquinones,triterpenes,steroids and saponins,etc.In due to find the material basis of RADⅨPHLOMⅡthat relate to pharmacodynamic action,we investigated chemical constituents of RADⅨPHLOMⅡby chemical and spectroscopic analysis.By phytochemical researches,12 compounds were isolated from the acetic acid ethyl ester of RADⅨPHLOMⅡand ten of them were identified as follows:phlomisosideⅥ(1),shanzhiside methyl ester(2),luteolin(3), kaempferol(4),berberine(5),ursolic acid(6),emodin(7),rhein(8),β-daucosterol(9),β-sitosterol(10).They were first obtained from this plant for the first time besides compound 2,7,8,among them compound 5 was isolated from the genus of Phlomis for the first time,and compound 1 was a new compound.Reference Substance solution used for the quality control of RADⅨPHLOMⅡwas firstly provided by us.After these reseaches,such as resorce,extractive technics, chemical structure confirmation,purity examination,content determination,etc.we drafted the quality standard for phlomisosideⅥ.In aspect of the quality standard for RADⅨPHLOMⅡ,the identification of characteristics,micro-construction and TLC was carried out;shanzhiside methyl ester and phlomisosideⅥwere determined by RP-HPLC for the first time;The quality standard protocol for RADⅨPHLOMⅡwere recensed and perfected on the basis of the reaseaches mentioned above.The research about fingerprint chromatogram of RADⅨPHLOMⅡshowed that under the chosen experimental conditions,chemical components of the methanol extract had similar retention times and chromatograms.This method is meaningful as a measure of quality control when the chemical components are not entirely known.In short,through the studies mentioned above on RADⅨPHLOMⅡ,it partially revealed the pharmacodynamic material basis and supplied a gap of identification of micro-construction and TLC,quantitation determination,fingerprint chromatogram. Our study provided the theoretical basis and scientific reference for the further study, development and application of RADⅨPHLOMⅡ,and had great referential significance of the modifying and consummating of the quality standard for RADⅨPHLOMⅡ.Meanwhile,these researches highly promotes modernization of Tibetan Medicine.更多还原