萜类中药有效成分BCS分类的研究进展
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摘要
萜类中药有效成分大多存在于高等植物中,具有抗肿瘤、抗氧化、抗敏、抗炎等药理作用。在新药的研发和剂型的选择中,溶解性和渗透性至关重要,但目前并不清楚萜类中药有效成分的溶解性及渗透性。溶解性和渗透性是生物药剂学分类系统(Biopharmaceutics classification system,BCS)的重要组成部分,因此需要研究萜类中药有效成分的溶解性和渗透性,并对其进行BCS分类。本综述主要是通过对近几年国内外所发表的关于萜类中药有效成分的溶解度和渗透性的文献进行研究以及对评价BCS分类的方法进行总结。目前评价BCS分类方法有体内和体外两种,体内一般是指大鼠的肠灌流;体外目前应用较多的是PAMPA模型、Caco-2细胞模型、MDCK细胞模型。本综述对萜类中药有效成分的BCS分类方法进行展望,和为后期萜类中药有效成分的生物药剂学评价体系的构建及模型药物的剂型研究提供理论依据。
Most of the active ingredients of Chinese herbal medicines are found in higher plants, and have various pharmacological effects such as anti-tumor, anti-oxidation, anti-allergic and anti-inflammatory and other pharmacological effects.Solubility and permeability are crucial in the development of new drugs and in the selection of dosage forms, but the solubility and permeability of the active ingredients of steroids are not known at present.Solubility and permeability are important components of the Biopharmaceutics classification system(BCS). Therefore, it is necessary to study the solubility and permeability of the active ingredients of terpenoids and classify them by BCS. This review is mainly based on the literature published in recent years on the solubility and permeability of active ingredients of steroids and the methods for evaluating BCS classification. At present, there are two methods for evaluating BCS classification in vivo and in vitro. In vivo experiments generally refer to intestinal perfusion in rats. In vitro, there are a lot of methods,such as PAMPA models, Caco-2 cell models and MDCK cell models have been used,but in order to reduce the use of animals,people always use cell type models. This review prospects the BCS classification method for the active constituents of Chinese herbal medicines, and provides a theoretical basis for the construction of biopharmaceutical evaluation system for the active ingredients of Chinese traditional Chinese medicines and the formulation of model drugs.
Most of the active ingredients of Chinese herbal medicines are found in higher plants, and have various pharmacological effects such as anti-tumor, anti-oxidation, anti-allergic and anti-inflammatory and other pharmacological effects.Solubility and permeability are crucial in the development of new drugs and in the selection of dosage forms, but the solubility and permeability of the active ingredients of steroids are not known at present.Solubility and permeability are important components of the Biopharmaceutics classification system(BCS). Therefore, it is necessary to study the solubility and permeability of the active ingredients of terpenoids and classify them by BCS. This review is mainly based on the literature published in recent years on the solubility and permeability of active ingredients of steroids and the methods for evaluating BCS classification. At present, there are two methods for evaluating BCS classification in vivo and in vitro. In vivo experiments generally refer to intestinal perfusion in rats. In vitro, there are a lot of methods,such as PAMPA models, Caco-2 cell models and MDCK cell models have been used,but in order to reduce the use of animals,people always use cell type models. This review prospects the BCS classification method for the active constituents of Chinese herbal medicines, and provides a theoretical basis for the construction of biopharmaceutical evaluation system for the active ingredients of Chinese traditional Chinese medicines and the formulation of model drugs.
引文
[1]谢燕,马越鸣,王长虹,等.改善中药制剂口服生物利用度的研究概况与思考[J].国际药学研究杂志,2011,38(3):195.
[2]赵静,梁爱华.Caco2细胞模型及其在中药吸收转运研究中的应用[J]中国实验方剂学杂志,2009,15(5):79.
[3]Amidon G L,Lennernas H,Shah V P,et al.A theroretical basis for biopharmaceutical drug classification system:the correlation of dissolution and in vivo bioavailability[J].Pharm Res,1995,12(3):413-420.
[4]梁会,曹佩雪,邱净英,等.艾纳香化学成分的研究[J].时珍国医国药,2011,22(2):308.
[5]黄永林,朱廷春,文永新,等.艾纳香化学成分的分离与鉴定[J].广西植物,2010,30(4):560.
[6]Ashour M,Wink M,Gershenzon J.Biochemistry of terpenoids:Monoterpenes,sesquiterpenes and diterpenes[M]//Wink M.Biochemistry of Plant Secondary Metabolism.2rd ed.Wiley-Blackwell,2010:258-303.
[7]梁宗锁,方誉民,杨东风.植物萜类化合物生物合成与调控及其代谢工程研究进展[J].浙江理工大学学报(自然科学版),2017,37:255-264.
[8]辛凤姣,王凤忠,李淑英,等.萜类化合物的合成生物学研究进展[J]生物技术通报,2017,33:64-75.
[9]付佳,王洋,阎秀峰.萜类化合物的生理生态功能及经济价值[J].东北林业大学学报,2003,31:59-62.
[10]Wright C W.Traditional antimalarials and the development of nove antimalarial drugs[J].J Ethnopharmacol,2005,100:67-71.
[11]Jennewein S,Croteau R.Taxol:biosynthesis,molecular genetics,and biotechnological applications[J].Appl Microbiol Biotech,2001,57:13-19.
[12]Zhang L B,Duan J A,Lv J L.Phytochemistry and bioactivities of sesquiterpenoids from the Artemisia species[J].J Chin Pharm Sci,2017,26(5):317.
[13]田光辉,刘存芳,赖普辉.显脉香茶菜籽的挥发性成分及其抗菌活性的研究[J].食品科学,2008,29(2):97-100.
[14]Li D,Wu L J,Tashiro S,et al.Oridonin induces human epidermoid carcinoma A431 cell apoptosis through tyrosine kinase and mito-chondrial pathway[J].JAsian Nat Prod Res,2008,10(1/2):77-87.
[15]庾石山.三萜化学[M].北京:化学工业出版社,2008.
[16]Ukiya M,Akihisa T,Yasukawa K,et al.Anti-inflammatory and antitumor-promoting effects of cucurbitane glycosides from the roots of Bryoniadioica[J].Journal of Natural Products,2002,65:179-183.
[17]斯陆通,黄建耿,等.生物药剂学分类系统及其应用(上)[J].中国药师,2008,11(2):160-162.
[18]FDA.Waiver of In Vivo Bioavailability and Bioequivalence Studies for ImmediateRelease Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System[S].
[19]Tolle-Sander,Polli J E.Method considerations for Caco-2 permeability assessment in the biopharmaceutics classification system[J].Pharmacopoeia Forum,2002,28(1):164-168.
[20]Leon Shargel,Susanna Wu-Pong Andrew B.C.Yu.Applied Bio-pharmaceutics&Pharmacokinetics[M].李安良,吴艳芬.译.北京:化学工业出版社,2006:272.Leon Shargel,Susanna Wu-Pong Andrew B.C.Yu.Applied Biopharmaceutics﹠Pharmacokinetics[M].Li A L,Wu Y F.main interpreter Bei Jing:Chemical Industry Pres,2006:272.
[21]Amidon G L,Lennerns H,Shah V P,et al.A theoretical basis for a biopharmaceutic drug classification:the correlation of in vitro drug product dissolution and in vivo bioavailability[J].Pharm Res,1995,12(3):413.
[22]Dahan A,Miller J M,Amidon G L.Prediction of solubility and permeability class membership:provisional BCS classification of the world's top oral drug[J].AAPS J,2009,11(4):740.
[23]Wu C Y,Benet L Z.Predicting drug disposition via application of BCS:transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system[J].Pharm Res,2005,22(1):11.
[24]Urban Fagerholm.The role of permeability in drug ADME/PK,interactions and toxicity-presentation of a permeability-based classification system(PCS)for prediction of ADME/PK in humans[J].Pharm Res,2008,3(25):625.
[25]Butler J M,Dressman J B.The developability classification system application of biopharmaceutics concepts to formulation development[J].JPharm Sci,2010,99(12):4940.
[26]Volpe D A.Variability in Caco-2 and MDCK cell-based intestinal permeability assays[J].J Pharm Sci,2008,97(2):712-725.
[27]Guidance for industry:Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceuticals classification system[S].2000.
[28]Lipinski C A,Lombardo F,Dominy B W,et al.Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings[J].Adv Drug Deliv Rev,2001,46(1/3):3-26.
[29]Schurgers N,Bijdendijk J,Tukker J J,et al.Comparison of four experimenta techniques for studying drug absorption kinetics in the anesthetized rat in situ[J].J Pharm Sci,1986,75(2):117-119.
[30]潘璐琳.脑得生片有效成分葛根素及阿魏酸的胃肠吸收代谢及其药代动力学研究[D].镇江:江苏大学,2009.
[31]许英爱,范国荣,高申,等.山楂叶总黄酮的在体肠吸收研究[J].中成药,2007,29(12):1745-8.
[32]刘璐,崔景斌,方洪壮.替硝唑大鼠小肠吸收的研究[J].中国医院药学杂志,2003,23(1):4-6.
[33]张向荣,潘卫三.丹参酚酸A在大鼠小肠的吸收动力学研究[J].沈阳药科大学学报,2002,19(1):14-7.
[34]Fagerholm U,Johansson M,Lennernas H.Comparison between permeability coefficients in rat and human jejunum[J].Pharm Res,1996,13(9):336-42.
[35]Kansy M,Senner F,Gubernator K.Physicochemical high throughput screening:parallel artificial membrane permeation assay in the description of passive absorption processes[J].J Med Chem,1998,41:1007-1010.
[36]李楠,叶英杰,杨明,等.平行人造膜通透性测定方法(PAMPA)在吸收研究中的应用[J].中药与临床,2011,2(01):28-30.
[37]贺秀云,宋捷民.Caco-2细胞模型在中药药物研究中的应用[J].浙江中医杂志,2012(10):773-775.
[38]曾宝,王春玲,吴安国,等.Caco-2细胞模型的建立及其在中药吸收研究中的应用探讨[J].中药新药与临床药理,2010(06):570-573.
[39]沈凯,王景田.药物肠吸收实验研究方法进展[J].中国新药杂志,2003(12):988-991.
[40]Mohamed HF.Molecular analysis and anticancer properties of two identified isolates,Fusarium solaniand Emericella nidulansisolated from Wady ElNatron soil in Egypt against Caco-2(ATCC)cell line[J].Asian Pacific Journa of Tropical Biomedicine,2012,2(11):863-869
[41]Gupta V,Doshi N,Mitragotri S.Permeation of Insulin,Calcitonin and Exenatide across Caco-2 Monolayers:Measurement Using a Rapid,3-Day System[J].Plo S one,2013,8(2):e57136
[42]MADIN S H,DARBY N B J.Established kidney cell lines of normal adult bovine and ovine origin[J].Proc Soc Exp Biol Med,1958,98(3):574-576.
[43]Li J,Wang Y,Hidalgo IJ.Kinetic analysis of human and canine Pglycoprotein mediated drug transport in MDR1-MDCK cell model:Approaches to reduce false negative substrate classification[J].Journal of pharmaceutical sciences2013,98(13):423-435
[44]Nkansah P,Antipas A,Lu Y,et al.Development and Evaluation of Novel Solid Nanodispersion System for Oral Delivery of Poorly Water-Soluble Drugs[J].Journal of Controlled Release,2013,1(8):385-399
[45]Wang M,Sun B,Feng J,et al.Investigation of Transport Mechanism of Exendin-4 across Madin Darby Canine Kidney Cell Monolayers[J].Biologica and Pharmaceutical Bulletin,2012,35(5):745-752
[46]杨秀伟,郭洁,徐嵬.芍药苷类化合物在人源肠Caco-2细胞单层模型中的吸收转运研究[J].中草药,2013,44(15):2097-2104.
[47]李东芬,尹蓉莉,吕懿平,等.芍药苷油水分配系数的测定及pH对其的影响[J].中药与临床,2011,2(04):21-23.
[48]韩丽妹.银杏内酯在Caco-2细胞中的摄取、转运研究[A].中华中医药学会中药制剂分会.2009全国中药创新与研究论坛学术论文集[C].中华中医药学会中药制剂分会,2009:7.
[49]刘丹,贾晓斌,萧伟.质量分数权重系数法表征银杏内酯组分溶解性及表观油水分配系数的探讨[J].中国中药杂志,2013,38(12):1865-1870.
[2]赵静,梁爱华.Caco2细胞模型及其在中药吸收转运研究中的应用[J]中国实验方剂学杂志,2009,15(5):79.
[3]Amidon G L,Lennernas H,Shah V P,et al.A theroretical basis for biopharmaceutical drug classification system:the correlation of dissolution and in vivo bioavailability[J].Pharm Res,1995,12(3):413-420.
[4]梁会,曹佩雪,邱净英,等.艾纳香化学成分的研究[J].时珍国医国药,2011,22(2):308.
[5]黄永林,朱廷春,文永新,等.艾纳香化学成分的分离与鉴定[J].广西植物,2010,30(4):560.
[6]Ashour M,Wink M,Gershenzon J.Biochemistry of terpenoids:Monoterpenes,sesquiterpenes and diterpenes[M]//Wink M.Biochemistry of Plant Secondary Metabolism.2rd ed.Wiley-Blackwell,2010:258-303.
[7]梁宗锁,方誉民,杨东风.植物萜类化合物生物合成与调控及其代谢工程研究进展[J].浙江理工大学学报(自然科学版),2017,37:255-264.
[8]辛凤姣,王凤忠,李淑英,等.萜类化合物的合成生物学研究进展[J]生物技术通报,2017,33:64-75.
[9]付佳,王洋,阎秀峰.萜类化合物的生理生态功能及经济价值[J].东北林业大学学报,2003,31:59-62.
[10]Wright C W.Traditional antimalarials and the development of nove antimalarial drugs[J].J Ethnopharmacol,2005,100:67-71.
[11]Jennewein S,Croteau R.Taxol:biosynthesis,molecular genetics,and biotechnological applications[J].Appl Microbiol Biotech,2001,57:13-19.
[12]Zhang L B,Duan J A,Lv J L.Phytochemistry and bioactivities of sesquiterpenoids from the Artemisia species[J].J Chin Pharm Sci,2017,26(5):317.
[13]田光辉,刘存芳,赖普辉.显脉香茶菜籽的挥发性成分及其抗菌活性的研究[J].食品科学,2008,29(2):97-100.
[14]Li D,Wu L J,Tashiro S,et al.Oridonin induces human epidermoid carcinoma A431 cell apoptosis through tyrosine kinase and mito-chondrial pathway[J].JAsian Nat Prod Res,2008,10(1/2):77-87.
[15]庾石山.三萜化学[M].北京:化学工业出版社,2008.
[16]Ukiya M,Akihisa T,Yasukawa K,et al.Anti-inflammatory and antitumor-promoting effects of cucurbitane glycosides from the roots of Bryoniadioica[J].Journal of Natural Products,2002,65:179-183.
[17]斯陆通,黄建耿,等.生物药剂学分类系统及其应用(上)[J].中国药师,2008,11(2):160-162.
[18]FDA.Waiver of In Vivo Bioavailability and Bioequivalence Studies for ImmediateRelease Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System[S].
[19]Tolle-Sander,Polli J E.Method considerations for Caco-2 permeability assessment in the biopharmaceutics classification system[J].Pharmacopoeia Forum,2002,28(1):164-168.
[20]Leon Shargel,Susanna Wu-Pong Andrew B.C.Yu.Applied Bio-pharmaceutics&Pharmacokinetics[M].李安良,吴艳芬.译.北京:化学工业出版社,2006:272.Leon Shargel,Susanna Wu-Pong Andrew B.C.Yu.Applied Biopharmaceutics﹠Pharmacokinetics[M].Li A L,Wu Y F.main interpreter Bei Jing:Chemical Industry Pres,2006:272.
[21]Amidon G L,Lennerns H,Shah V P,et al.A theoretical basis for a biopharmaceutic drug classification:the correlation of in vitro drug product dissolution and in vivo bioavailability[J].Pharm Res,1995,12(3):413.
[22]Dahan A,Miller J M,Amidon G L.Prediction of solubility and permeability class membership:provisional BCS classification of the world's top oral drug[J].AAPS J,2009,11(4):740.
[23]Wu C Y,Benet L Z.Predicting drug disposition via application of BCS:transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system[J].Pharm Res,2005,22(1):11.
[24]Urban Fagerholm.The role of permeability in drug ADME/PK,interactions and toxicity-presentation of a permeability-based classification system(PCS)for prediction of ADME/PK in humans[J].Pharm Res,2008,3(25):625.
[25]Butler J M,Dressman J B.The developability classification system application of biopharmaceutics concepts to formulation development[J].JPharm Sci,2010,99(12):4940.
[26]Volpe D A.Variability in Caco-2 and MDCK cell-based intestinal permeability assays[J].J Pharm Sci,2008,97(2):712-725.
[27]Guidance for industry:Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceuticals classification system[S].2000.
[28]Lipinski C A,Lombardo F,Dominy B W,et al.Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings[J].Adv Drug Deliv Rev,2001,46(1/3):3-26.
[29]Schurgers N,Bijdendijk J,Tukker J J,et al.Comparison of four experimenta techniques for studying drug absorption kinetics in the anesthetized rat in situ[J].J Pharm Sci,1986,75(2):117-119.
[30]潘璐琳.脑得生片有效成分葛根素及阿魏酸的胃肠吸收代谢及其药代动力学研究[D].镇江:江苏大学,2009.
[31]许英爱,范国荣,高申,等.山楂叶总黄酮的在体肠吸收研究[J].中成药,2007,29(12):1745-8.
[32]刘璐,崔景斌,方洪壮.替硝唑大鼠小肠吸收的研究[J].中国医院药学杂志,2003,23(1):4-6.
[33]张向荣,潘卫三.丹参酚酸A在大鼠小肠的吸收动力学研究[J].沈阳药科大学学报,2002,19(1):14-7.
[34]Fagerholm U,Johansson M,Lennernas H.Comparison between permeability coefficients in rat and human jejunum[J].Pharm Res,1996,13(9):336-42.
[35]Kansy M,Senner F,Gubernator K.Physicochemical high throughput screening:parallel artificial membrane permeation assay in the description of passive absorption processes[J].J Med Chem,1998,41:1007-1010.
[36]李楠,叶英杰,杨明,等.平行人造膜通透性测定方法(PAMPA)在吸收研究中的应用[J].中药与临床,2011,2(01):28-30.
[37]贺秀云,宋捷民.Caco-2细胞模型在中药药物研究中的应用[J].浙江中医杂志,2012(10):773-775.
[38]曾宝,王春玲,吴安国,等.Caco-2细胞模型的建立及其在中药吸收研究中的应用探讨[J].中药新药与临床药理,2010(06):570-573.
[39]沈凯,王景田.药物肠吸收实验研究方法进展[J].中国新药杂志,2003(12):988-991.
[40]Mohamed HF.Molecular analysis and anticancer properties of two identified isolates,Fusarium solaniand Emericella nidulansisolated from Wady ElNatron soil in Egypt against Caco-2(ATCC)cell line[J].Asian Pacific Journa of Tropical Biomedicine,2012,2(11):863-869
[41]Gupta V,Doshi N,Mitragotri S.Permeation of Insulin,Calcitonin and Exenatide across Caco-2 Monolayers:Measurement Using a Rapid,3-Day System[J].Plo S one,2013,8(2):e57136
[42]MADIN S H,DARBY N B J.Established kidney cell lines of normal adult bovine and ovine origin[J].Proc Soc Exp Biol Med,1958,98(3):574-576.
[43]Li J,Wang Y,Hidalgo IJ.Kinetic analysis of human and canine Pglycoprotein mediated drug transport in MDR1-MDCK cell model:Approaches to reduce false negative substrate classification[J].Journal of pharmaceutical sciences2013,98(13):423-435
[44]Nkansah P,Antipas A,Lu Y,et al.Development and Evaluation of Novel Solid Nanodispersion System for Oral Delivery of Poorly Water-Soluble Drugs[J].Journal of Controlled Release,2013,1(8):385-399
[45]Wang M,Sun B,Feng J,et al.Investigation of Transport Mechanism of Exendin-4 across Madin Darby Canine Kidney Cell Monolayers[J].Biologica and Pharmaceutical Bulletin,2012,35(5):745-752
[46]杨秀伟,郭洁,徐嵬.芍药苷类化合物在人源肠Caco-2细胞单层模型中的吸收转运研究[J].中草药,2013,44(15):2097-2104.
[47]李东芬,尹蓉莉,吕懿平,等.芍药苷油水分配系数的测定及pH对其的影响[J].中药与临床,2011,2(04):21-23.
[48]韩丽妹.银杏内酯在Caco-2细胞中的摄取、转运研究[A].中华中医药学会中药制剂分会.2009全国中药创新与研究论坛学术论文集[C].中华中医药学会中药制剂分会,2009:7.
[49]刘丹,贾晓斌,萧伟.质量分数权重系数法表征银杏内酯组分溶解性及表观油水分配系数的探讨[J].中国中药杂志,2013,38(12):1865-1870.