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

关键词:  人参皂苷R_g1  人参皂苷Rb₁  三七皂苷R₁  药物溶出/吸收仿生系统(DDASS)  表观渗透系数(P_app)

Key words:  ginsenoside R_g1  ginsenoside Rb₁  notoginsenoside R₁  Drug dissolution/absorption simulating system (DDASS)  permeability coefficients (P_app)

摘要:

[目的] 以三七总皂苷(PNS)中3种主要活性成分人参皂苷R_g1 (R_g1)、人参皂苷Rb₁(Rb₁)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R_g1、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(P_app)的变化;SPSS软件进行统计学分析。[结果] PNS单用时R_g1、Rb₁和R₁的P_app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R_g1、Rb₁和R₁的P_app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P_app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R_g1、Rb₁和R₁ 3种成分均为低渗透性成分;冰片可显著提高PNS的Qt和P_app,促进其口服吸收;CsA对PNS的Qt和P_app没有显著影响,推测R_g1、Rb₁和R₁不是P-gp的底物,冰片提高其Qt和P_app可能主要受细胞旁路机制影响。

Abstract:

[Objective] The three main components of panax notoginseng saponins (ginsenoside R_g1, 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 R_g1、Rb₁ and notoginsenoside R₁) simultaneously. DDASS was used to study the changes of cumulative permeation amount and the apparent permeability coefficients (P_app) of PNS after compatibility with borneol. Variance analysis was used to analyze the differences between the mean values of P_app by SPSS. [Results] P_app values of ginsenoside R_g1, 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 (P<0.05). The P_app values of R_g1, Rb₁ and R₁ after compatibility with CsA were (0.66 ± 0.07) cm/s, (0.14 ± 0.05) cm/s, (0.92 ± 0.27) cm/s. There were no significant difference (P>0.05) compared with PNS group. [Conclusion] Borneol can increase the membrane permeability of the PNS (ginsenoside R_g1, Rb₁ and notoginsenoside R₁), and it can promote PNS oral absorption and enhance its bioavailability. CsA does not improve the PNS membrane permeability. R_g1, Rb₁ and R₁ maybe not the substrate of P-glycoprotein. The mechanism of enhancing permeation by borneol maybe influence by the paracellular route transport.