应用药物溶出/吸收仿生系统研究三七总皂苷与冰片的配伍规律

Studies on the compatibility principles of panax notoginseng saponins with borneol using a novel simulating system

[目的]以三七总皂苷(PNS)中3种主要活性成分人参皂苷Rg1(Rg1)、人参皂苷Rb(1Rb1)和三七皂苷R1(R1)为质控成分,应用药物溶出/吸收仿生系统(DDASS)研究PNS与冰片配伍前后的肠透过规律,并探讨其吸收机制,以期将该系统用于创新中药开发和处方筛选,为传统中药研究提供新的方法。[方法]建立同时测定PNS中Rg1、Rb1和R1的高效液相色谱(HPLC)方法;应用DDASS法,考察PNS与冰片配伍前后3种成分的肠累积透过量(Qt)及表观渗透系数(Papp)的变化;SPSS软件进行统计学分析。[结果]PNS单用时Rg1、Rb1和R1的Papp值分别为(0.49±0.09)cm/秒、(0.07±0.03)cm/秒、(0.58±0.04)cm/秒;PNS与冰片配伍后Rg1、Rb1和R1的Papp分别为(1.17±0.08)cm/秒、(0.16±0.02)cm/秒、(1.57±0.50)cm/秒,分别是单用PNS的2.4、2.2和2.7倍;而与外排转运蛋白P-糖蛋白(P-gp)抑制剂环孢素A(CsA)合用时,这3种成分的Papp值分别为(0.62±0.09)cm/秒、(0.12±0.04)cm/秒、(0.90±0.26)cm/秒,与PNS单用组均无统计学意义(P>0.05)。[结论]PNS中Rg1、Rb1和R13种成分均为低渗透性成分;冰片可显著提高PNS的Qt和Papp,促进其口服吸收;CsA对PNS的Qt和Papp没有显著影响,推测Rg1、Rb1和R1不是P-gp的底物,冰片提高其Qt和Papp可能主要受细胞旁路机制影响。

[Objective] The three main components of panax notoginseng saponins（ginsenoside Rg1,Rb1 and notoginsenoside R1） as quality control components,using a drug dissolution/absorption simulating system to study the change of the membrane permeability of panax notoginseng saponins after compatibility with borneol and study its possible mechanism.The system will be used to study traditional Chinese medicine,to provide a new method for the development of traditional Chinese medicine.[Methods] HPLC method was established to determine the three main constituents of PNS（ginsenoside Rg1、Rb1 and notoginsenoside R1） simultaneously.DDASS was used to study the changes of cumulative permeation amount and the apparent permeability coefficients（Papp） of PNS after compatibility with borneol.Variance analysis was used to analyze the differences between the mean values of Papp by SPSS.[Results] Papp values of ginsenoside Rg1,Rb1 and notoginsenoside R1 respectively were（0.49 ± 0.09） cm/s,（0.07 ± 0.03） cm/s,（0.58 ± 0.04） cm/s,and it was significantly increased after compatibility with borneol 2.4、2.2 and 2.7 times,respectively（P0.05） compared with PNS group.[Conclusion] Borneol can increase the membrane permeability of the PNS（ginsenoside Rg1,Rb1 and notoginsenoside R1）,and it can promote PNS oral absorption and enhance its bioavailability.CsA does not improve the PNS membrane permeability.Rg1,Rb1 and R1 maybe not the substrate of P-glycoprotein.The mechanism of enhancing permeation by borneol maybe influence by the paracellular route transport.