螃蟹甲化学成分及质量控制研究
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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,~(13)C-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。
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.
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,~(13)C-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。
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.
引文
[1]国家药典委员会.中华人民共和国卫生部药品标准(藏药第一册).北京:化学工业出版社,1995:126,231
[2]中国科学院中国植物志编辑委员会.中国植物志(65卷曲第二分册).北京:科学出版社,1977:428-478
[3]国家中医药管理局中华本草委员会.中华本草(19卷).上海:上海科学技术出版社,2004:124-128
[4]青海省药品检验所,青海省藏医药研究所.中国藏药(第三卷).上海:上海科学技术出版社,1996:310-311
[5]国家药典委员会.中华人民共和国药典(2005年版一部).北京:化学工业出版社,2005:646
[6]十味龙胆花胶囊质量标准[WS_3-159(Z-021)-2004(Z)]
[7]刘明蓉,王晓慧,陈宜彬.露木尔口服液的制备及其临床试用效果.药学实践杂志,1996,14(1):32-34.
[8]王晓慧,刘明蓉,陈宜彬.露木尔口镇咳祛痰药理实验.西南国防医药,1993,3(6):332-333
[9]黄小平,张莉,杨大坚.露木尔镇咳祛痰有效部位研究.时珍国医国药,2005,16(1):6-7.
[10]黄小平,张莉,杨大坚.露木尔不同工艺产物药理活性比较研究.时珍国医国药,2004,15(8):475-476.
[11]陈奇主编.中药药理实验方法学.北京:人民卫生出版社,1993
[12]徐叔云,卡如廉,陈修,等.药理实验方法学(第2版).北京:人民卫生出版社,1991
[13]Katagiri M,Ohtani K.,Kasai R.,et al.Diterpenoid glycosyl esters from Phlomi younghusbandii and P.medicinalis roots.Phytochemistry,1994,35(2):439-442
[14]Kasai R.,Katagiri M.,Ohtani K.,et al.Iridoid glycosides from Phlomis younghusbandii roots.Phytochemistry,1994,36(4):967-970.
[15]边巴次仁,旺姆,魏锋,等.藏药螃蟹甲挥发油化学成分的GC-MS分析研究.中国药学杂志,2002,37(12):904-905.
[16]刘明蓉,王晓惠,陈宜彬.原子吸收分光光度法测定藏糙苏的十二种无机元素的含量.药学情报通讯,1994,12(3):65-66.
[17]肖崇厚主编.中药化学.上海:上海科学技术出版社,1997:595-597
[18]余振喜,王钢力,戴忠,等.萝卜秦艽化学成分的研究Ⅱ.中国药学杂志,2007,42(17):1295-1298
[19]杨永力、郭守军,孙坤,等.中药糙苏亲水性化学成分的研究.兰州大学学报(自然科学版),2004,40(2):67-71
[20]陈改敏,张建业,张向沛,等.马鞭草黄酮类化学成分的研究.中药材,2006,29(7):677-678
[21]张起辉,高慧媛,吴立军,等.吴茱萸的化学成分.沈阳药科大学学报,2005,22(1):12-14
[22]秦民坚,王衡奇.黄皮树树皮的化学成分研究.林产化学与工业,2003,23(4):42-46
[23]陈德昌主编.中药化学对照品工作手册.北京:中国医药科技出版社,2000:168,42
[24]张新凤,李翠环,裴基焕.大虎杖花蒽醌类化学成分的鉴定.浙江林学院学报.2005,22(2):185-187
[25]黄璐琦,王永炎主编.中药材质量标准研究.北京:人民卫生出版社,2006
[26]易进海,钟炽昌,罗泽渊,等.糙苏属和独一味属植物的化学成分及其分类学的意义.中草药,1992,23(7):382-387
[27]董娟娥,张靖.植物中环烯醚萜类化合物研究进展.西北林学院学报,2004,19(3):131-135
[28]U.Hersel,M.Steck,K.Seifert,et al.Anewroute to 2,7-and 7-functi-onalized labdanes.Eur.J.org.Chem,2000:1609-1615
[29]A.Delazar,M.Modarresi,M.Shoeb,et al.Eremostachiin:a new furano-labdane diterpene glycoside from Eremostachys glabra.Natural Product Research,2006,20(2):167-172
[30]国家食品药品监督管理局.中药注射剂指纹图谱的技术要求(暂行).中成药,2000,22(10):671
[31]谢培山主编.中药色谱指纹图谱.北京:人民卫生出版社,1991
[1]中国科学院中国植物志编辑委员会.中国植物志(65卷第二分册).北京:科学出版社,1977:428-478.
[2]国家中医药管理局中华本草委员会.中华本草(19卷).上海:上海科学技术出版社,2004:7124-128.
[3]Saracoglu I.,Inoue M.,Calis I.,et al.Studies on constituents with cytotoxic and tostatic activity of two Turkish medicinal plants Plomis armeniaca and scutellaria salviifolia.Biol Pharm Bull,1995,18(10):1396-1400.
[4]Saracoglu I.,Kojima K.,Harput U.S.,et al.A new phenylethanoid glycoside from Phlomis pungens Willd vat.pungens.Chem Pharm Bull,1998,46(4):726-727.
[5]Kamel M.S.,Mohained K.M.,Hassanean H.A,et al.Iridoid and megastigmane glycosides from Phlomis aurea.Phytochemistry,2000,55(4):353-357.
[6]Ersoz T.,Schuhly W.,Popov S.,et al.Iridoid and phenylethanoid glycosides from Phlomis longifolia vat.longifolia.Natural Product etters,2001,15(5):345-351.
[7]Takeda Y.,Matsumura H.,Masuda T.,et al.Phlorigidosides A-C,iridoid glucosides from Phlomis rigida.Phytochemistry,2000,53(8):931-935.
[8]Ihsan C.,Hasan K..Glycosides from Phlomis lunariifolia.Phytoche-mistry,2004,65:2619-2625.
[9]Zhang C.Z.,Li C.,Feng S.J.,et al.Iridoid glucosides from Phlomis rotata.Phytochemistry,1991,30(12):4156-4158
[10]张承忠,李冲,苏策,等.蒙古糙苏中的环烯醚菇昔.中国中药杂志,1996,21(1):36-37.
[11]Aboutabl E.A.,Meselhy M.R.,Afifi M.S.,et al.Iridoids from Phlomis aurea Decne growing in Egypt.Pharmazie,2002,57(9):646-647.
[12]Ersoz T.,Saracoglu I.,Harput,U.,et al.Iridoid and phenylpropanoid glycosides from Phlomis grandiflora var.fimbrilligera and Phlomis fruticosa.Turkish Journal of Chemistry,2002,26(2):171-178.
[13]Takeda Y.,Kinugawa M.,Masuda T.,et al.Phlomisethanoside,a phenylethanoid glycoside from Phlomis grandiflora vat.grandiflora.Phytochemistry,1999,51(2):323-325.
[14]Al-Khalil S.,Al-Douri N..Iridoids and flavonoids from Phlomis brachyodon.Alexandria Journal of Pharmaceutical Sciences,1997,11(1):33-37.
[15]Kasai R.,Katagiri M.,Ohtani K.,et al.Iridoid glycosides from Phlomis younghusbandii,root Phytochemistry,1994,36(4):967-970.
[16]Takeda Y.,Isai N.,Masuda,T.,et al.Phlomisflavosides A.and B,new flavonol bisglycosides from Phlomis spinidens.Chemical &Pharmaceutical Bulletin,2001,49(8):1039-1041.
[17]杨永力,郭守军,孙坤,等.中药糙苏亲水性化学成分的研究.兰州大学学报(自然科学版),2004,40(2):67-71.
[18]Ihsan C.,Kirmizibekmez H.,Ersoz T.,et al.Iridoid,phenylethanoid and flavonoid glycosides from Pfllomis sintenisii.Acta Pharmaceutica Turcica,2002,44(3):195-203.
[19]Saracoglu I.,Harput U.S.,Calls I.,et al.Phenolic constituents from PhIomis lycia.Turkish Journal of Chemistry,2002,26(1):133-142.
[20]Harput U.S.,Saracoglu L,Calis L.Iridoid and phenylethanoid glycosides from Phlomis bourgaei Boiss.Hacettepe Universitesi Eczacilik Fakultesi Dergisi,1999,19(1):1-11.
[21]Basaran A.A.,Saracoglu I.,Calls h.Iridoid glucosides isolated from Phlomis linearis.Hacettepe Univ.EczacilikFak Derg.,1991,11(2):81-88
[22]Calls I.,Basaran i.A.,Saracoglu I.,et al.Phlinosides D and E,phenylpropanoid glycosides,and iridoids from Phlomis linearis.Phytochemistry,1991,30(9):3073-3075
[23]Assaad A.M.,E1-Sebakhy N,Lahloub M.F.I.,et al.Iridoid glucosides of Phlomis floccosa D.Don.Alexandria J.Pharm.Sci 1992,6(2):183-185.
[24]Yalcin F.N.,Ersoz T.,Akbay P.,et al.Iridoid and phenylpropanoid glycosides from Phlomis samia,P.monocephala and P.carica.Turkish Journal of Chemistry,2003,27(3):295-305
[25]Ersoz T.,Harput U.S.,Calis I.,et al.Iridoid,phenylethanoid and monoterpene glycosides from Phlomis sieheana.Turkish Journal of Chemistry,2002,26(1):1-8.
[26]Alipieva K.I.,Jensen S.R.,Franzyk H,et al.Iridoid glucosides from Phlomis tuberosa L.and Phlomis herba-ventis L.Zeitschrift fuer Naturforschung,C Journal of Biosciences,2000,55(3/4):137-140.
[27]Ersoez T.,Alipieva K.I.,Yalcin F.N.,et al.Physocatycoside,a new phenylethanoid glycoside from Phlomis physocalyx Hub.-Mor.Zeitschrift fuer Naturforschung,C:Journal.Of Biosciences,2003,58(718):471-476.
[28]ErsozT.,SaracogluI.,KirmizibekmezH.,et al.Iridoid,phenylethanoid and phenol glycosides from Phlomis chimerae.Hacettepe Univer-sitesi Eczacilik Fakultesi Dergisi,2001,21(1):23-33.
[29]ErsozT.,IvanchevaS.,Akbay P.,et al.Iridoid and phenylethanoid glycosides from Phlomis tuberose L.Zeitschrif fuer Naturforschung C:Journal of Biosciences,2001,56(9/10):695-698.
[30]Ismailoglu U.B,Saracoglu I.,Harput U.S.,et al.Effects of phenylpropanoid and iridoid glycosides on free radical-induced impairment of endothelium- dependent relaxation in rat aortic rings.Journal of Ethnopharmacology,2002,79(2):193-197.
[31]Saracoglu I.,Harput U.S.,Kojima K.,et al.Iridoid and phen-lpropanoid glycosides from Phlomis pungens var.pungens.Hacettepe Universitesi Eczacilik Fakultesi Dergisi,1997,17(2):63-72.
[32]Fokina G.A.,Bukreeva,T.V.Lamiide from Phlomis cancellata.Khim.Prir.Soedin.,1990,(6):834-835.
[33]Maksudov M.S.,Maksimov E.S.,Umarova R.U.,et al.Phlomoside A,an iridoid glycoside from Phlomis thapsoides Khim.Prir.Soedin.,1995,(2):43-246.
[34]Maksudov M.S.,Maksimov E.S,Umarova R.U,et al.Phlomoside B,an iridoid glycoside from Phlomis regelii.Khim.Prir.Soedin,1996,(1):46-49.
[35]Maksudov M.S.,Maksimov E.S.,Saatov,Z.,et al.Phlomoside C,an iridoid glycoside from Phlomis regelii.Khimiya Prirodnykh Soedinenii,1996,(4):554-557
[36]Maksudov M.S.,Maksimov E.S.,Saatov Z.,et al.Phlomoside D,an iridoid glycoside from Phlomis regelii.Khimiya Prirodnykh Soedinenti,1996,(4):551-553.
[37]李冲,张承忠.蒙古糙苏的化学成分研究.中国中药杂志,2000,25(1):35-37
[38]Ersoz T.,Sticher O,Calls L.An iridoid glucoside from Phlomis longifolia var.longifolia.Hacettepe Universitesi Eczacilik Fakultesi Dergisi,2001,21(1):35-40.
[39]Guo S..J.,Gao L.M.,Cheng D.L.Iridoids from Phlomis umbrosa.Pharmazie,2001,56(2):178-180.
[40]Jung K.Y.,Do J.C.,Son K.H.A study on the iridoid constituents from the roots of Phlomis umbrosa.Saengyak Hakhoechi,1996,27(2):87-90
[41]Kyriakopoulou I.,Magiatis P.,Skaltsounis A.L,et al.Samioside,a New Phenylethanoid Glycoside with Free-Radical Scavenging and Antimicrobial Activities from Phlomis samia.Journal of Natural Products,2001,64(8):1095-1097.
[42]Calls L,Basaran A.A.,Saracoglu I.,et al.Phlinosides A,B and C,three phenylpropanoid glycosides from Phlomis linearis.Phytochemistry,1990,29(4):1253-1257.
[43]刘世旺,付宏征,林文翰糙苏的化学成分研究(Ⅰ).中草药,1999,30(3):161-163.
[44]赵静,杨秀伟,付宏征,等.糙苏化学成分的研究.中草药,1999,30(2):90-93.
[45]Calis I.,Kirmizibekmez H.,Tasdemir D,et al.Two new triterpene and a new nortriterpene glycosides from Phlomis viscoso.Helvetica Chimica Acta,2004,87(3):611-619
[46]Katagiri M,Ohtani K.,Kasai R.,et al.Diterpenoid glycosyl esters from Phlomi younghusbandii and P.medicinalis roots.Phytochemistry,1994,35(2):439-442.
[47]付宏征,刘世旺,林文翰·糙苏的化学成分·药学学报,1999,34(4):297-300.
[48]Ghassemi N,Sajjadi S.E.,Lame M.Al.Volatile constituents of Phlomis olivieri Benth.Daru,Journal of Faculty of Pharmacy,Tehran University of Medical Sciences,2001,9(1/2):48-50.
[49]Ersoz T,Saracoglu I.,Tasdemir D.,et al.Neolignan glucosides from Phiomis chimerae Boiss.Zeitschrift fuer Naturforschung,C:Journal of Biosciences,2002 57(3/4):221-225.
[50]Demirci B.,Dadandi M.Y.,Paper D.H.,et al.Chemical composition of the essential oil of Phlomis linearis Boiss.&Bal.,and biological effects on the CAM assay:A safety evaluation.Zeitschrift fuer Naturforschung,C.Journal of Biosciences,2003,58(11/12):826-829
[51]边巴次仁,旺姆,魏锋,等.藏药螃蟹甲挥发油化学成分的GC-MS分析研究.中国药学杂志,2002,37(12):904-905.
[52]Mirza M,Nik Z.B..Volatile constituents of Phlomis olivieri Benth.from Iran Flavour and Fragrance Journal,2003,18(2):131-132.
[53]Tsitsimi E.,Loukis A.,Verykokidou E..Composition of the essential oil of the flowers of PhJomis fruticosa L.from Greece.Journal of Essential Oil Research,2000,12(3):355-356
[54]Sokovic M.O.,Marin P.D.,Janackovic P,et al.Composition of the essential oils of Phlomis fruticosa L.(hamiaceae).Journal of Essential Oil Research,2002,14(3):167-168.
[55]Couladis M.,Tanimanidis A.,Tzakou O.,et al.Essential oil of Phlomis lanata growing in Greece:chemical composition and antimicrobial activity.Planta edica,2000,66(7):670-672.
[56]盛芬玲,汤军,张承忠,等.蒙古糙苏挥发油成份分析.兰州医学院学报,1997,23(3):11-12
[57]刘明蓉,王晓蕙,陈宜彬.原子吸收分光光度法测定藏糙苏的十二种无机元素的含量.药学情报通讯,1994,12(3):65-66.
[58]Kumar R.,Bhan S.,Kalla A.K,et al.28-Noroleana-16,21-diene triterpenes from Phlomis spectabilis.Phytochemistry,1992,31(8):2797-2799.
[59]Bucar F.,Ninov S.,Ionkova L,et al.Flavonoids from Phlomis nfssoli Phytochemistry,1998,48(3):573-575
[60]Saracoglu I.,Kojima K.,Harput U.S.,et al.A new phenylethanoid glycoside from Phlomis pungens Willd.var.pungens.Chem Pharm Bull,1998,46(4):726-727.
[61]余振喜,王钢力,戴忠,等.萝卜秦艽化学成分的研究Ⅱ.中国药学杂志,2007,42(17):1295-1298
[2]中国科学院中国植物志编辑委员会.中国植物志(65卷曲第二分册).北京:科学出版社,1977:428-478
[3]国家中医药管理局中华本草委员会.中华本草(19卷).上海:上海科学技术出版社,2004:124-128
[4]青海省药品检验所,青海省藏医药研究所.中国藏药(第三卷).上海:上海科学技术出版社,1996:310-311
[5]国家药典委员会.中华人民共和国药典(2005年版一部).北京:化学工业出版社,2005:646
[6]十味龙胆花胶囊质量标准[WS_3-159(Z-021)-2004(Z)]
[7]刘明蓉,王晓慧,陈宜彬.露木尔口服液的制备及其临床试用效果.药学实践杂志,1996,14(1):32-34.
[8]王晓慧,刘明蓉,陈宜彬.露木尔口镇咳祛痰药理实验.西南国防医药,1993,3(6):332-333
[9]黄小平,张莉,杨大坚.露木尔镇咳祛痰有效部位研究.时珍国医国药,2005,16(1):6-7.
[10]黄小平,张莉,杨大坚.露木尔不同工艺产物药理活性比较研究.时珍国医国药,2004,15(8):475-476.
[11]陈奇主编.中药药理实验方法学.北京:人民卫生出版社,1993
[12]徐叔云,卡如廉,陈修,等.药理实验方法学(第2版).北京:人民卫生出版社,1991
[13]Katagiri M,Ohtani K.,Kasai R.,et al.Diterpenoid glycosyl esters from Phlomi younghusbandii and P.medicinalis roots.Phytochemistry,1994,35(2):439-442
[14]Kasai R.,Katagiri M.,Ohtani K.,et al.Iridoid glycosides from Phlomis younghusbandii roots.Phytochemistry,1994,36(4):967-970.
[15]边巴次仁,旺姆,魏锋,等.藏药螃蟹甲挥发油化学成分的GC-MS分析研究.中国药学杂志,2002,37(12):904-905.
[16]刘明蓉,王晓惠,陈宜彬.原子吸收分光光度法测定藏糙苏的十二种无机元素的含量.药学情报通讯,1994,12(3):65-66.
[17]肖崇厚主编.中药化学.上海:上海科学技术出版社,1997:595-597
[18]余振喜,王钢力,戴忠,等.萝卜秦艽化学成分的研究Ⅱ.中国药学杂志,2007,42(17):1295-1298
[19]杨永力、郭守军,孙坤,等.中药糙苏亲水性化学成分的研究.兰州大学学报(自然科学版),2004,40(2):67-71
[20]陈改敏,张建业,张向沛,等.马鞭草黄酮类化学成分的研究.中药材,2006,29(7):677-678
[21]张起辉,高慧媛,吴立军,等.吴茱萸的化学成分.沈阳药科大学学报,2005,22(1):12-14
[22]秦民坚,王衡奇.黄皮树树皮的化学成分研究.林产化学与工业,2003,23(4):42-46
[23]陈德昌主编.中药化学对照品工作手册.北京:中国医药科技出版社,2000:168,42
[24]张新凤,李翠环,裴基焕.大虎杖花蒽醌类化学成分的鉴定.浙江林学院学报.2005,22(2):185-187
[25]黄璐琦,王永炎主编.中药材质量标准研究.北京:人民卫生出版社,2006
[26]易进海,钟炽昌,罗泽渊,等.糙苏属和独一味属植物的化学成分及其分类学的意义.中草药,1992,23(7):382-387
[27]董娟娥,张靖.植物中环烯醚萜类化合物研究进展.西北林学院学报,2004,19(3):131-135
[28]U.Hersel,M.Steck,K.Seifert,et al.Anewroute to 2,7-and 7-functi-onalized labdanes.Eur.J.org.Chem,2000:1609-1615
[29]A.Delazar,M.Modarresi,M.Shoeb,et al.Eremostachiin:a new furano-labdane diterpene glycoside from Eremostachys glabra.Natural Product Research,2006,20(2):167-172
[30]国家食品药品监督管理局.中药注射剂指纹图谱的技术要求(暂行).中成药,2000,22(10):671
[31]谢培山主编.中药色谱指纹图谱.北京:人民卫生出版社,1991
[1]中国科学院中国植物志编辑委员会.中国植物志(65卷第二分册).北京:科学出版社,1977:428-478.
[2]国家中医药管理局中华本草委员会.中华本草(19卷).上海:上海科学技术出版社,2004:7124-128.
[3]Saracoglu I.,Inoue M.,Calis I.,et al.Studies on constituents with cytotoxic and tostatic activity of two Turkish medicinal plants Plomis armeniaca and scutellaria salviifolia.Biol Pharm Bull,1995,18(10):1396-1400.
[4]Saracoglu I.,Kojima K.,Harput U.S.,et al.A new phenylethanoid glycoside from Phlomis pungens Willd vat.pungens.Chem Pharm Bull,1998,46(4):726-727.
[5]Kamel M.S.,Mohained K.M.,Hassanean H.A,et al.Iridoid and megastigmane glycosides from Phlomis aurea.Phytochemistry,2000,55(4):353-357.
[6]Ersoz T.,Schuhly W.,Popov S.,et al.Iridoid and phenylethanoid glycosides from Phlomis longifolia vat.longifolia.Natural Product etters,2001,15(5):345-351.
[7]Takeda Y.,Matsumura H.,Masuda T.,et al.Phlorigidosides A-C,iridoid glucosides from Phlomis rigida.Phytochemistry,2000,53(8):931-935.
[8]Ihsan C.,Hasan K..Glycosides from Phlomis lunariifolia.Phytoche-mistry,2004,65:2619-2625.
[9]Zhang C.Z.,Li C.,Feng S.J.,et al.Iridoid glucosides from Phlomis rotata.Phytochemistry,1991,30(12):4156-4158
[10]张承忠,李冲,苏策,等.蒙古糙苏中的环烯醚菇昔.中国中药杂志,1996,21(1):36-37.
[11]Aboutabl E.A.,Meselhy M.R.,Afifi M.S.,et al.Iridoids from Phlomis aurea Decne growing in Egypt.Pharmazie,2002,57(9):646-647.
[12]Ersoz T.,Saracoglu I.,Harput,U.,et al.Iridoid and phenylpropanoid glycosides from Phlomis grandiflora var.fimbrilligera and Phlomis fruticosa.Turkish Journal of Chemistry,2002,26(2):171-178.
[13]Takeda Y.,Kinugawa M.,Masuda T.,et al.Phlomisethanoside,a phenylethanoid glycoside from Phlomis grandiflora vat.grandiflora.Phytochemistry,1999,51(2):323-325.
[14]Al-Khalil S.,Al-Douri N..Iridoids and flavonoids from Phlomis brachyodon.Alexandria Journal of Pharmaceutical Sciences,1997,11(1):33-37.
[15]Kasai R.,Katagiri M.,Ohtani K.,et al.Iridoid glycosides from Phlomis younghusbandii,root Phytochemistry,1994,36(4):967-970.
[16]Takeda Y.,Isai N.,Masuda,T.,et al.Phlomisflavosides A.and B,new flavonol bisglycosides from Phlomis spinidens.Chemical &Pharmaceutical Bulletin,2001,49(8):1039-1041.
[17]杨永力,郭守军,孙坤,等.中药糙苏亲水性化学成分的研究.兰州大学学报(自然科学版),2004,40(2):67-71.
[18]Ihsan C.,Kirmizibekmez H.,Ersoz T.,et al.Iridoid,phenylethanoid and flavonoid glycosides from Pfllomis sintenisii.Acta Pharmaceutica Turcica,2002,44(3):195-203.
[19]Saracoglu I.,Harput U.S.,Calls I.,et al.Phenolic constituents from PhIomis lycia.Turkish Journal of Chemistry,2002,26(1):133-142.
[20]Harput U.S.,Saracoglu L,Calis L.Iridoid and phenylethanoid glycosides from Phlomis bourgaei Boiss.Hacettepe Universitesi Eczacilik Fakultesi Dergisi,1999,19(1):1-11.
[21]Basaran A.A.,Saracoglu I.,Calls h.Iridoid glucosides isolated from Phlomis linearis.Hacettepe Univ.EczacilikFak Derg.,1991,11(2):81-88
[22]Calls I.,Basaran i.A.,Saracoglu I.,et al.Phlinosides D and E,phenylpropanoid glycosides,and iridoids from Phlomis linearis.Phytochemistry,1991,30(9):3073-3075
[23]Assaad A.M.,E1-Sebakhy N,Lahloub M.F.I.,et al.Iridoid glucosides of Phlomis floccosa D.Don.Alexandria J.Pharm.Sci 1992,6(2):183-185.
[24]Yalcin F.N.,Ersoz T.,Akbay P.,et al.Iridoid and phenylpropanoid glycosides from Phlomis samia,P.monocephala and P.carica.Turkish Journal of Chemistry,2003,27(3):295-305
[25]Ersoz T.,Harput U.S.,Calis I.,et al.Iridoid,phenylethanoid and monoterpene glycosides from Phlomis sieheana.Turkish Journal of Chemistry,2002,26(1):1-8.
[26]Alipieva K.I.,Jensen S.R.,Franzyk H,et al.Iridoid glucosides from Phlomis tuberosa L.and Phlomis herba-ventis L.Zeitschrift fuer Naturforschung,C Journal of Biosciences,2000,55(3/4):137-140.
[27]Ersoez T.,Alipieva K.I.,Yalcin F.N.,et al.Physocatycoside,a new phenylethanoid glycoside from Phlomis physocalyx Hub.-Mor.Zeitschrift fuer Naturforschung,C:Journal.Of Biosciences,2003,58(718):471-476.
[28]ErsozT.,SaracogluI.,KirmizibekmezH.,et al.Iridoid,phenylethanoid and phenol glycosides from Phlomis chimerae.Hacettepe Univer-sitesi Eczacilik Fakultesi Dergisi,2001,21(1):23-33.
[29]ErsozT.,IvanchevaS.,Akbay P.,et al.Iridoid and phenylethanoid glycosides from Phlomis tuberose L.Zeitschrif fuer Naturforschung C:Journal of Biosciences,2001,56(9/10):695-698.
[30]Ismailoglu U.B,Saracoglu I.,Harput U.S.,et al.Effects of phenylpropanoid and iridoid glycosides on free radical-induced impairment of endothelium- dependent relaxation in rat aortic rings.Journal of Ethnopharmacology,2002,79(2):193-197.
[31]Saracoglu I.,Harput U.S.,Kojima K.,et al.Iridoid and phen-lpropanoid glycosides from Phlomis pungens var.pungens.Hacettepe Universitesi Eczacilik Fakultesi Dergisi,1997,17(2):63-72.
[32]Fokina G.A.,Bukreeva,T.V.Lamiide from Phlomis cancellata.Khim.Prir.Soedin.,1990,(6):834-835.
[33]Maksudov M.S.,Maksimov E.S.,Umarova R.U.,et al.Phlomoside A,an iridoid glycoside from Phlomis thapsoides Khim.Prir.Soedin.,1995,(2):43-246.
[34]Maksudov M.S.,Maksimov E.S,Umarova R.U,et al.Phlomoside B,an iridoid glycoside from Phlomis regelii.Khim.Prir.Soedin,1996,(1):46-49.
[35]Maksudov M.S.,Maksimov E.S.,Saatov,Z.,et al.Phlomoside C,an iridoid glycoside from Phlomis regelii.Khimiya Prirodnykh Soedinenii,1996,(4):554-557
[36]Maksudov M.S.,Maksimov E.S.,Saatov Z.,et al.Phlomoside D,an iridoid glycoside from Phlomis regelii.Khimiya Prirodnykh Soedinenti,1996,(4):551-553.
[37]李冲,张承忠.蒙古糙苏的化学成分研究.中国中药杂志,2000,25(1):35-37
[38]Ersoz T.,Sticher O,Calls L.An iridoid glucoside from Phlomis longifolia var.longifolia.Hacettepe Universitesi Eczacilik Fakultesi Dergisi,2001,21(1):35-40.
[39]Guo S..J.,Gao L.M.,Cheng D.L.Iridoids from Phlomis umbrosa.Pharmazie,2001,56(2):178-180.
[40]Jung K.Y.,Do J.C.,Son K.H.A study on the iridoid constituents from the roots of Phlomis umbrosa.Saengyak Hakhoechi,1996,27(2):87-90
[41]Kyriakopoulou I.,Magiatis P.,Skaltsounis A.L,et al.Samioside,a New Phenylethanoid Glycoside with Free-Radical Scavenging and Antimicrobial Activities from Phlomis samia.Journal of Natural Products,2001,64(8):1095-1097.
[42]Calls L,Basaran A.A.,Saracoglu I.,et al.Phlinosides A,B and C,three phenylpropanoid glycosides from Phlomis linearis.Phytochemistry,1990,29(4):1253-1257.
[43]刘世旺,付宏征,林文翰糙苏的化学成分研究(Ⅰ).中草药,1999,30(3):161-163.
[44]赵静,杨秀伟,付宏征,等.糙苏化学成分的研究.中草药,1999,30(2):90-93.
[45]Calis I.,Kirmizibekmez H.,Tasdemir D,et al.Two new triterpene and a new nortriterpene glycosides from Phlomis viscoso.Helvetica Chimica Acta,2004,87(3):611-619
[46]Katagiri M,Ohtani K.,Kasai R.,et al.Diterpenoid glycosyl esters from Phlomi younghusbandii and P.medicinalis roots.Phytochemistry,1994,35(2):439-442.
[47]付宏征,刘世旺,林文翰·糙苏的化学成分·药学学报,1999,34(4):297-300.
[48]Ghassemi N,Sajjadi S.E.,Lame M.Al.Volatile constituents of Phlomis olivieri Benth.Daru,Journal of Faculty of Pharmacy,Tehran University of Medical Sciences,2001,9(1/2):48-50.
[49]Ersoz T,Saracoglu I.,Tasdemir D.,et al.Neolignan glucosides from Phiomis chimerae Boiss.Zeitschrift fuer Naturforschung,C:Journal of Biosciences,2002 57(3/4):221-225.
[50]Demirci B.,Dadandi M.Y.,Paper D.H.,et al.Chemical composition of the essential oil of Phlomis linearis Boiss.&Bal.,and biological effects on the CAM assay:A safety evaluation.Zeitschrift fuer Naturforschung,C.Journal of Biosciences,2003,58(11/12):826-829
[51]边巴次仁,旺姆,魏锋,等.藏药螃蟹甲挥发油化学成分的GC-MS分析研究.中国药学杂志,2002,37(12):904-905.
[52]Mirza M,Nik Z.B..Volatile constituents of Phlomis olivieri Benth.from Iran Flavour and Fragrance Journal,2003,18(2):131-132.
[53]Tsitsimi E.,Loukis A.,Verykokidou E..Composition of the essential oil of the flowers of PhJomis fruticosa L.from Greece.Journal of Essential Oil Research,2000,12(3):355-356
[54]Sokovic M.O.,Marin P.D.,Janackovic P,et al.Composition of the essential oils of Phlomis fruticosa L.(hamiaceae).Journal of Essential Oil Research,2002,14(3):167-168.
[55]Couladis M.,Tanimanidis A.,Tzakou O.,et al.Essential oil of Phlomis lanata growing in Greece:chemical composition and antimicrobial activity.Planta edica,2000,66(7):670-672.
[56]盛芬玲,汤军,张承忠,等.蒙古糙苏挥发油成份分析.兰州医学院学报,1997,23(3):11-12
[57]刘明蓉,王晓蕙,陈宜彬.原子吸收分光光度法测定藏糙苏的十二种无机元素的含量.药学情报通讯,1994,12(3):65-66.
[58]Kumar R.,Bhan S.,Kalla A.K,et al.28-Noroleana-16,21-diene triterpenes from Phlomis spectabilis.Phytochemistry,1992,31(8):2797-2799.
[59]Bucar F.,Ninov S.,Ionkova L,et al.Flavonoids from Phlomis nfssoli Phytochemistry,1998,48(3):573-575
[60]Saracoglu I.,Kojima K.,Harput U.S.,et al.A new phenylethanoid glycoside from Phlomis pungens Willd.var.pungens.Chem Pharm Bull,1998,46(4):726-727.
[61]余振喜,王钢力,戴忠,等.萝卜秦艽化学成分的研究Ⅱ.中国药学杂志,2007,42(17):1295-1298