杠柳毒苷、杠柳次苷及杠柳苷元生物药剂学分类研究
|
摘要
目的采用生物药剂学分类系统(Biopharmaceuticals Classification System,BCS)对杠柳毒苷、杠柳次苷及杠柳苷元进行生物药剂学分类研究。方法采用实验和计算机预测软件Pipeline Pilot 8.5、ChemDraw研究杠柳毒苷、杠柳次苷和杠柳苷元的溶解性和渗透性,根据实验值和预测值利用BCS分类方法对3者进行分类。结果根据实验结果杠柳毒苷、杠柳次苷和杠柳苷元均为BCSⅢ类药物,与不同软件预测的分类结果存在差异。基于Clg P的渗透性结果与实验结果一致;基于lg Cs的溶解性及基于Alg P、lg D的渗透性预测结果与实验结果相反。结论杠柳毒苷、杠柳次苷和杠柳苷元均为BCS Ⅲ类药物,3者溶解性依次降低,但仍都属于高溶解性成分。3者的渗透性是影响其吸收的关键因素。基于化学结构对甲型强心苷类药物活性成分进行的生物药剂学属性预测值与实验结果存在较大差异,对含此类成分的中药制剂的口服吸收进行BCS研究及体内外相关性评价时建议采用多种方法对数据进行校正,增加结果的可靠性。
Objective To investigate the biopharmaceutical classification of periplocin, periplocymarin and periplogenin by biopharmaceuticals classification system(BCS). Methods The solubility and permeability of periplocin, periplocymarin and periplogenin were studied by using experimental and computer prediction software Pipeline Pilot 8.5 and ChemDraw. These three substances were sorted based on experimental and predicted values by BCS classification method. Results According to the test results, periplocin, periplocymarin and periplogenin were classified as BCS Ⅲ, which are different from the classification results predicted by different software. The permeability results based on Clg P was consistent with the experimental results; The solubility based on lg Cs and the permeability based on Alg P and lg D were opposite to the experimental results. Conclusion The periplocin,periplocymarin and periplogenin are BCS Ⅲ drugs, the solubility is decreased in turn, but they are still highly soluble components. The permeability is the key factor affecting its absorption. The predicted value of biopharmaceutical properties of active ingredients of A-type cardiac glycosides based on the chemical structure are significant different with the test results, for the BCS study and the in vitro and in vivo correlation evaluation of oral absorption of traditional Chinese medicine preparations containing such ingredients, it is recommended to use a variety of methods to correct the data and increase the reliability of the results.
Objective To investigate the biopharmaceutical classification of periplocin, periplocymarin and periplogenin by biopharmaceuticals classification system(BCS). Methods The solubility and permeability of periplocin, periplocymarin and periplogenin were studied by using experimental and computer prediction software Pipeline Pilot 8.5 and ChemDraw. These three substances were sorted based on experimental and predicted values by BCS classification method. Results According to the test results, periplocin, periplocymarin and periplogenin were classified as BCS Ⅲ, which are different from the classification results predicted by different software. The permeability results based on Clg P was consistent with the experimental results; The solubility based on lg Cs and the permeability based on Alg P and lg D were opposite to the experimental results. Conclusion The periplocin,periplocymarin and periplogenin are BCS Ⅲ drugs, the solubility is decreased in turn, but they are still highly soluble components. The permeability is the key factor affecting its absorption. The predicted value of biopharmaceutical properties of active ingredients of A-type cardiac glycosides based on the chemical structure are significant different with the test results, for the BCS study and the in vitro and in vivo correlation evaluation of oral absorption of traditional Chinese medicine preparations containing such ingredients, it is recommended to use a variety of methods to correct the data and increase the reliability of the results.
引文
[1]中国药典[S].一部.2015.
[2]陈浩浩,王晓明,潘桂湘,等.杠柳毒苷、杠柳次苷、杠柳苷元与人血浆蛋白结合率测定[J].辽宁中医药大学学报,2017,19(7):32-35.
[3]孙达,张静,陈金堂,等.香加皮中强心苷类对大鼠离体心脏的强心作用比较[J].中华中医药学刊,2011,29(12):2633-2635.
[4]Zhang W J,Song Z B,Bao Y L,et al.Periplogenin induces necroptotic cell death through oxidative stress in HaCaT cells and ameliorates skin lesions in the TPA-and IMQ-induced psoriasis-like mouse models[J].Biochem Pharmacol,2016,105:66-79.
[5]王利萍,刘建利.香加皮的化学成分和药理作用研究进展[J].中草药,2009,40(3):493-496.
[6]阎雪梅.香加皮的化学成分药理作用及临床应用研究进展[J].天津药学,2011,23(5):48-52.
[7]Li L,Zhao L M,Dai S L,et al.Periplocin extracted from Cortex Periplocae induced apoptosis of gastric cancer cells via the ERK1/2-EGR1 pathway[J].Cell Physiol Biochem,2016,38(5):1939-1951.
[8]丁菲菲,张晓静,邓雁如.杠柳毒苷体外抑制肝癌细胞和乳腺癌细胞增殖的实验研究[J].药物评价研究,2014,37(1):30-33.
[9]卫银盘,赵丽迎,邓雁如.杠柳的化学成分及药理作用研究进展[J].天津中医药大学学报,2009,28(3):165-166.
[10]张辉云,贺清华,童珊珊,等.香加皮活性成分及其药理作用研究进展[J].药学进展,2013,37(9):449-453.
[11]高淑红,谢跃生,肖学凤,等.杠柳毒苷在大鼠体内的组织分布[J].现代药物与临床,2011,26(2):116-118.
[12]Amidon G L,Lennern?s 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):413-420.
[13]田俊生,李天祥,刘虹,等.HPLC法测定不同产地香加皮中杠柳毒苷的含量[J].中药材,2006,29(8):799-800.
[14]任晓亮,谢跃生,潘桂湘,等.香加皮强心成分杠柳毒苷肠菌代谢研究[J].天津中医药,2007,24(6):515-518.
[15]冯红,李倩,潘桂湘.香加皮提取物杠柳毒苷水解动力学研究[J].辽宁中医药大学学报,2012,14(9):41-44.
[16]Liang S,Deng F,Xing H,et al.P-glycoprotein-and organic anion-transporting polypeptide-mediated transport of periplocin may lead to drug-herb/drug-drug interactions[J].Drug Des Devel Ther,2014,8:475-483.
[17]Martey O N,He X,Xing H,et al.Periplocymarin is a potential natural compound for drug development:Highly permeable with absence of P-glycoprotein efflux and cytochrome P450 inhibitions[J].Biopharm Drug Dispos,2014,35(4):195-206.
[18]Liu H,Zhang D,Tang Z,et al.Tissue distribution study of periplocin and its two metabolites in rats by a validated LC-MS/MS method[J].Biomed Chromatogr,2018,32(10):e4302.
[19]王强,任晓亮,王焱,等.杠柳毒苷在大鼠体内排泄的初步研究[J].天津中医药大学学报,2008,27(1):29-32.
[20]Ghose A K,Viswanadhan V N,Wendoloski J J.Prediction of hydrophobic(lipophilic)properties of small organic molecules using fragmental methods:An analysis of ALOGP and CLOGP methods[J].Phys Chem A,1998,102(21):3762-3772.
[21]Guidance for industry:Waiver of in vivo bio-quivalence studies for immediate release solid oral dosage forms containing certain active moieties/active ingredients based on Biopharmaceutics Classification System[S].2000.
[22]王焱,任晓亮,潘桂湘,等.杠柳毒苷在模拟消化液中的稳定性研究[J].天津中医药大学学报,2007,26(2):74-76.
[23]胡程耀,黄培.固体溶解度测定方法的近期研究进展[J].药物分析杂志,2010,30(4):761-766.
[24]匡海学.中药化学[M].北京:中国中医药出版社,2014.
[25]邓逢春,李超,何新.杠柳毒苷及其降解产物杠柳次苷在MDCK细胞的跨膜透过特性研究[EB/OL].北京:中国科技论文在线,2012-01-10.http://www.paper.edu.cn/releasepaper/content/201201-312.
[26]Bloise E,Braca A,De Tommasi N,et al.Pro-apoptotic and cytostatic activity of naturally occurring cardenolides[J].Cancer Chemother Pharmacol,2009,64(4):793-802.
[27]贾雨萌,王相阳,褚扬,等.强心苷类药物药动学研究进展[J].中草药,2014,45(23):3472-3477.
[28]于慧斌,孙成春.阿奇霉素对地高辛小肠吸收及其P-糖蛋白表达的影响[J].中国医院药学杂志,2010,30(9):758-760.
[29]Hughes J,Crowe A.Inhibition of P-glycoprotein-mediated efflux of digoxin and its metabolites by macrolide antibiotics[J].J Pharmacol Sci,2010,113(4):315-324.
[30]Pauli-Magnus C,Mürdter T,Godel A,et al.P-glycoprotein-mediated transport of digitoxin,alphamethyldigoxin and beta-acetyldigoxin[J].Naunyn Schmiedebergs Arch Pharmacol,2001,363(3):337-343.
[31]Nokhodian A,Santos S R,Kirch W.Digitoxin and its metabolites in patients with liver cirrhosis[J].Eur J Drug Metab Pharmacokinet,1993,18(2):207-213.
[32]Lindenbaum J,Tse-Eng D,Butler V P,et al.Urinary excretion of reduced metabolites of digoxin[J].Am JMed,1981,1(1):67-74.
[2]陈浩浩,王晓明,潘桂湘,等.杠柳毒苷、杠柳次苷、杠柳苷元与人血浆蛋白结合率测定[J].辽宁中医药大学学报,2017,19(7):32-35.
[3]孙达,张静,陈金堂,等.香加皮中强心苷类对大鼠离体心脏的强心作用比较[J].中华中医药学刊,2011,29(12):2633-2635.
[4]Zhang W J,Song Z B,Bao Y L,et al.Periplogenin induces necroptotic cell death through oxidative stress in HaCaT cells and ameliorates skin lesions in the TPA-and IMQ-induced psoriasis-like mouse models[J].Biochem Pharmacol,2016,105:66-79.
[5]王利萍,刘建利.香加皮的化学成分和药理作用研究进展[J].中草药,2009,40(3):493-496.
[6]阎雪梅.香加皮的化学成分药理作用及临床应用研究进展[J].天津药学,2011,23(5):48-52.
[7]Li L,Zhao L M,Dai S L,et al.Periplocin extracted from Cortex Periplocae induced apoptosis of gastric cancer cells via the ERK1/2-EGR1 pathway[J].Cell Physiol Biochem,2016,38(5):1939-1951.
[8]丁菲菲,张晓静,邓雁如.杠柳毒苷体外抑制肝癌细胞和乳腺癌细胞增殖的实验研究[J].药物评价研究,2014,37(1):30-33.
[9]卫银盘,赵丽迎,邓雁如.杠柳的化学成分及药理作用研究进展[J].天津中医药大学学报,2009,28(3):165-166.
[10]张辉云,贺清华,童珊珊,等.香加皮活性成分及其药理作用研究进展[J].药学进展,2013,37(9):449-453.
[11]高淑红,谢跃生,肖学凤,等.杠柳毒苷在大鼠体内的组织分布[J].现代药物与临床,2011,26(2):116-118.
[12]Amidon G L,Lennern?s 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):413-420.
[13]田俊生,李天祥,刘虹,等.HPLC法测定不同产地香加皮中杠柳毒苷的含量[J].中药材,2006,29(8):799-800.
[14]任晓亮,谢跃生,潘桂湘,等.香加皮强心成分杠柳毒苷肠菌代谢研究[J].天津中医药,2007,24(6):515-518.
[15]冯红,李倩,潘桂湘.香加皮提取物杠柳毒苷水解动力学研究[J].辽宁中医药大学学报,2012,14(9):41-44.
[16]Liang S,Deng F,Xing H,et al.P-glycoprotein-and organic anion-transporting polypeptide-mediated transport of periplocin may lead to drug-herb/drug-drug interactions[J].Drug Des Devel Ther,2014,8:475-483.
[17]Martey O N,He X,Xing H,et al.Periplocymarin is a potential natural compound for drug development:Highly permeable with absence of P-glycoprotein efflux and cytochrome P450 inhibitions[J].Biopharm Drug Dispos,2014,35(4):195-206.
[18]Liu H,Zhang D,Tang Z,et al.Tissue distribution study of periplocin and its two metabolites in rats by a validated LC-MS/MS method[J].Biomed Chromatogr,2018,32(10):e4302.
[19]王强,任晓亮,王焱,等.杠柳毒苷在大鼠体内排泄的初步研究[J].天津中医药大学学报,2008,27(1):29-32.
[20]Ghose A K,Viswanadhan V N,Wendoloski J J.Prediction of hydrophobic(lipophilic)properties of small organic molecules using fragmental methods:An analysis of ALOGP and CLOGP methods[J].Phys Chem A,1998,102(21):3762-3772.
[21]Guidance for industry:Waiver of in vivo bio-quivalence studies for immediate release solid oral dosage forms containing certain active moieties/active ingredients based on Biopharmaceutics Classification System[S].2000.
[22]王焱,任晓亮,潘桂湘,等.杠柳毒苷在模拟消化液中的稳定性研究[J].天津中医药大学学报,2007,26(2):74-76.
[23]胡程耀,黄培.固体溶解度测定方法的近期研究进展[J].药物分析杂志,2010,30(4):761-766.
[24]匡海学.中药化学[M].北京:中国中医药出版社,2014.
[25]邓逢春,李超,何新.杠柳毒苷及其降解产物杠柳次苷在MDCK细胞的跨膜透过特性研究[EB/OL].北京:中国科技论文在线,2012-01-10.http://www.paper.edu.cn/releasepaper/content/201201-312.
[26]Bloise E,Braca A,De Tommasi N,et al.Pro-apoptotic and cytostatic activity of naturally occurring cardenolides[J].Cancer Chemother Pharmacol,2009,64(4):793-802.
[27]贾雨萌,王相阳,褚扬,等.强心苷类药物药动学研究进展[J].中草药,2014,45(23):3472-3477.
[28]于慧斌,孙成春.阿奇霉素对地高辛小肠吸收及其P-糖蛋白表达的影响[J].中国医院药学杂志,2010,30(9):758-760.
[29]Hughes J,Crowe A.Inhibition of P-glycoprotein-mediated efflux of digoxin and its metabolites by macrolide antibiotics[J].J Pharmacol Sci,2010,113(4):315-324.
[30]Pauli-Magnus C,Mürdter T,Godel A,et al.P-glycoprotein-mediated transport of digitoxin,alphamethyldigoxin and beta-acetyldigoxin[J].Naunyn Schmiedebergs Arch Pharmacol,2001,363(3):337-343.
[31]Nokhodian A,Santos S R,Kirch W.Digitoxin and its metabolites in patients with liver cirrhosis[J].Eur J Drug Metab Pharmacokinet,1993,18(2):207-213.
[32]Lindenbaum J,Tse-Eng D,Butler V P,et al.Urinary excretion of reduced metabolites of digoxin[J].Am JMed,1981,1(1):67-74.