应用复合磷脂脂质体人工皮肤膜表征香附四物汤活性部位生物药剂学性质
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摘要
目的评价应用复合磷脂脂质体人工皮肤膜(CPLASM)测定参数表征香附四物汤(XSD)活性部位透皮吸收生物药剂学性质的可行性。方法建立HPLC方法同时测定XSD活性部位中活性成分(阿魏酸、四氢非洲防己碱、延胡索乙素、洋川芎内酯I、洋川芎内酯H)的质量分数并测定其油水分配系数。制备CPLASM,用其测定XSD活性部位的体外透皮吸收参数,并与猪耳皮测得的透皮吸收参数进行比较。结果 XSD活性部位(pH 5.5)中阿魏酸、四氢非洲防己碱、延胡索乙素、洋川芎内酯I、洋川芎内酯H的油水分配系数分别为1.220±0.280、0.670±0.085、0.920±0.110、1.040±0.092、1.030±0.093(n=3)。应用CPLASM和猪耳皮测得的各成分透皮吸收参数显著相关,相关系数均高于0.9。与经典的油水分配系数相比,5种活性成分透过CPLASM 6 h的累积透过率可以有效表征其透过猪耳皮的渗透系数。结论应用CPLASM测定中药活性成分体外透皮吸收参数能够有效表征中药活性部位的生物药剂学性质。
Objective To evaluate the feasibility of the application of composite phospholipid liposome-based artificial skin membrane(CPLASM) for measuring biopharmaceutical properties of active fraction extracted from Xiangfu Siwu Decoction(XSD) via transdermal administration. Methods The HPLC method was established for the determination of active ingredients(ferulic acid, tetrahydrocolumbamine, tetrahydropalmatine, senkyunolide I, and senkyunolide H) in active fraction of XSD. The oil/water partition coefficient values of these active ingredients were measured. The CPLASM was prepared to determine the in vitro permeability parameters of active fraction of XSD. The obtained parameters were further compared with those obtained by porcine ear skin. ResultsThe oil-water partition coefficients of ferulic acid, tetrahydrocolumbamine, tetrahydropalmatine, senkyunolide I, and senkyunolide H in active fraction of XSD(pH 5.5) were measured to be 1.220 ± 0.280, 0.670 ± 0.085, 0.920 ± 0.110, 1.040 ± 0.092, 1.030 ± 0.093(n = 3), respectively. The permeability parameters of the active ingredients through porcine ear skin and CPLASM indicated a significant correlation(r > 0.9). Compared with the classical oil-water partition coefficients, the 6 h-cumulative permeation ratio of five active ingredients through CPLASM can be characterized as effectively predicting permeability parameters through porcine ear skin. Conclusion The biopharmaceutical properties of active fractions from Chinese material medica can be effectively characterized by the application of CPLASM for the determination of in vitro permeability parameters of active ingredients.
Objective To evaluate the feasibility of the application of composite phospholipid liposome-based artificial skin membrane(CPLASM) for measuring biopharmaceutical properties of active fraction extracted from Xiangfu Siwu Decoction(XSD) via transdermal administration. Methods The HPLC method was established for the determination of active ingredients(ferulic acid, tetrahydrocolumbamine, tetrahydropalmatine, senkyunolide I, and senkyunolide H) in active fraction of XSD. The oil/water partition coefficient values of these active ingredients were measured. The CPLASM was prepared to determine the in vitro permeability parameters of active fraction of XSD. The obtained parameters were further compared with those obtained by porcine ear skin. ResultsThe oil-water partition coefficients of ferulic acid, tetrahydrocolumbamine, tetrahydropalmatine, senkyunolide I, and senkyunolide H in active fraction of XSD(pH 5.5) were measured to be 1.220 ± 0.280, 0.670 ± 0.085, 0.920 ± 0.110, 1.040 ± 0.092, 1.030 ± 0.093(n = 3), respectively. The permeability parameters of the active ingredients through porcine ear skin and CPLASM indicated a significant correlation(r > 0.9). Compared with the classical oil-water partition coefficients, the 6 h-cumulative permeation ratio of five active ingredients through CPLASM can be characterized as effectively predicting permeability parameters through porcine ear skin. Conclusion The biopharmaceutical properties of active fractions from Chinese material medica can be effectively characterized by the application of CPLASM for the determination of in vitro permeability parameters of active ingredients.
引文
[1]张会,张黄琴,蒋秋冬,等.香附四物汤效应部位体外透皮吸收性质的研究[J].中草药,2015,46(20):3017-3022.
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[6]潘瑛,李振皓,钱大玮,等.不同促渗剂对香附四物汤外用贴剂中效应成分体内药动学的影响[J].中国中药杂志,2016,41(2):294-302.
[7]张会,陈军,蒋秋冬,等.脂质人工皮肤膜的研究进展[J].中国药学杂志,2016,51(10):780-785.
[8]Zhang H,Zhu X,Shen J,et al.Characterization of a liposome-based artificial skin membrane for in vitro permeation studies using Franz diffusion cell device[J].J Liposome Res,2016,27(4):302-311.
[9]汤清涵,张会,沈菁菁,等.复合磷脂组成对香附四物汤活性成分透过脂质体人工皮肤膜行为的影响[J].南京中医药大学学报,2017,33(4):371-375.
[10]姜雯,曾诚,于宁,等.星点设计-效应面法优化天山雪莲提取物复合磷脂脂质体制备工艺[J].中草药,2016,47(1):57-64.
[11]Engesland A,?kalko-basnet N,Flaten G E.In vitro models to estimate drug penetration through the compromised stratum conrneum barrier[J].Drug Dev IndPharm,2016,42(11):1742-1751.
[12]Flaten G E,Bunjes H,Luthman K,et al.Drug permeability across a phospholipid vesicle-based barrier2.Characterization of barrier structure,storage stability and stability towards p H changes[J].Eur J Pharm Sci,2006,28(4):336-343.
[13]陈军,张婷,蔡宝昌,等.马钱子总生物碱复合磷脂脂质体的药剂学性质研究[J].中国中药杂志,2010,35(1):32-36.
[14]Chen J,Cheng D,Li J,et al.Influence of lipid composition on the phase transition temperature of liposomes composed of both DPPC and HSPC[J].Drug Dev Ind Pharm,2013,39(2):197-204.
[15]Lan Y,Wang J,Li H,et al.Effect of menthone and related compounds on skin permeation of drugs with different lipophilicity and molecular organization of stratum corneum lipids[J].Pharm Dev Technol,2016,21(4):389-398.
[16]Ma M,Di H J,Zhang H,et al.Development of phospholipid vesicle-based permeation assay models capable of evaluating percutaneous penetration enhancing effect[J].Drug Dev Ind Pharm,2017,43(12):2055-2063.
[2]董其虎.香附四物汤治疗气滞血瘀型原发性痛经的临床疗效评价及作用机制初探[D].南京:南京中医药大学,2012.
[3]李炜.香附四物汤用于气滞血瘀证原发性痛经大鼠体内过程研究[D].南京:南京中医药大学,2013.
[4]刘培.四物汤类方用于妇科血瘀证原发性痛经的物质基础与配伍规律研究[D].南京:南京中医药大学,2011.
[5]李振皓,刘培,钱大玮,等.主成分分析用于香附四物汤效应部位体外经皮渗透的研究[J].药学学报,2013,48(6):933-939.
[6]潘瑛,李振皓,钱大玮,等.不同促渗剂对香附四物汤外用贴剂中效应成分体内药动学的影响[J].中国中药杂志,2016,41(2):294-302.
[7]张会,陈军,蒋秋冬,等.脂质人工皮肤膜的研究进展[J].中国药学杂志,2016,51(10):780-785.
[8]Zhang H,Zhu X,Shen J,et al.Characterization of a liposome-based artificial skin membrane for in vitro permeation studies using Franz diffusion cell device[J].J Liposome Res,2016,27(4):302-311.
[9]汤清涵,张会,沈菁菁,等.复合磷脂组成对香附四物汤活性成分透过脂质体人工皮肤膜行为的影响[J].南京中医药大学学报,2017,33(4):371-375.
[10]姜雯,曾诚,于宁,等.星点设计-效应面法优化天山雪莲提取物复合磷脂脂质体制备工艺[J].中草药,2016,47(1):57-64.
[11]Engesland A,?kalko-basnet N,Flaten G E.In vitro models to estimate drug penetration through the compromised stratum conrneum barrier[J].Drug Dev IndPharm,2016,42(11):1742-1751.
[12]Flaten G E,Bunjes H,Luthman K,et al.Drug permeability across a phospholipid vesicle-based barrier2.Characterization of barrier structure,storage stability and stability towards p H changes[J].Eur J Pharm Sci,2006,28(4):336-343.
[13]陈军,张婷,蔡宝昌,等.马钱子总生物碱复合磷脂脂质体的药剂学性质研究[J].中国中药杂志,2010,35(1):32-36.
[14]Chen J,Cheng D,Li J,et al.Influence of lipid composition on the phase transition temperature of liposomes composed of both DPPC and HSPC[J].Drug Dev Ind Pharm,2013,39(2):197-204.
[15]Lan Y,Wang J,Li H,et al.Effect of menthone and related compounds on skin permeation of drugs with different lipophilicity and molecular organization of stratum corneum lipids[J].Pharm Dev Technol,2016,21(4):389-398.
[16]Ma M,Di H J,Zhang H,et al.Development of phospholipid vesicle-based permeation assay models capable of evaluating percutaneous penetration enhancing effect[J].Drug Dev Ind Pharm,2017,43(12):2055-2063.