三七总皂苷多成分经鼓室给药的体内分布及药代动力学研究  

In vivo distribution and pharmacokinetics of multiple effective components contained in Panax notoginseng saponins after intratympanic administration

作　　者：陈钢[1] 牧磊[1] 张晓[1] 侯世祥[2] 南海军[3] 

机构地区：[1]广东药学院药剂学系,广东广州510006 [2]四川大学华西药学院,四川成都610041 [3]广东药学院中药学院,广东广州510006

出　　处：《中国中药杂志》2011年第13期1815-1820,共6页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(30801553);广东药学院师资队伍建设经费项目

摘　　要：目的:考察三七总皂苷(PNS)经鼓室给药后人参皂苷Rb1(Rb1)、人参皂苷Rg1(Rg1)和三七皂苷R1(R1)在豚鼠的体内行为,探索中药多种成分经内耳途径转运至脑的可行性。方法:PNS分别经鼓室和静脉给药,于不同时间点采集内耳外淋巴液、脑脊液(CSF)、脑组织和血浆,采用HPLC测定各组织中Rb1,Rg1和R1的浓度,计算上述成分在各组织的药代动力学参数;根据各成分的药时曲线下面积(AUC)所占比值自定义为权重系数,并进一步估算PNS整合后的药代动力学参数。结果:PNS经鼓室给药,其Rb1,Rg1和R1均能穿过圆窗膜进入内耳外淋巴并转运进入脑部,但3种成分在体内各组织的药代动力学参数差异较大。PNS整合药代动力学参数显示,PNS采用鼓室给药能增加进入脑部的药量,提高局部生物利用度,在CSF和脑组织的Cmax分别比静脉给药高1.1,0.4倍,AUC分别增加0.4,0.2倍;并且,PNS在血浆的分布减少,Cmax和AUC分别比静脉给药降低45.9%,33.1%。结论:经耳入脑有望成为中药脑内输送的一种新方法。Objective： To investigate in vivo distribution and pharmacokinetics of ginsenoside Rb1（Rb1）,ginsenoside Rg1（Rg1） and sanchinoside R1（R1） after intratympanic administration（IT） or intravenous administration（IV） of Panax notoginseng saponions（PNS） solution,and provide a novel route for delivering traditional Chinese medicine（TCM） to the brain.Method： The guinea pigs were employed as experimental animal.Perilymph（PL）,cerebrospinal fluid（CSF）,brain tissue and plasma were collected periodically after IT and IV of PNS solution.The concentrations of Rb1,Rg1 and R1 were measured by high performance liquid chromatography（HPLC）,and statistic program DAS was applied to the calculation of pharmacokinetic parameters.The self-defined weighting coefficients based on area under curve（AUC） of each component were created to obtain the holistic pharmacokinetic profiles of PNS.The integrated pharmacokinetic parameters were then calculated from non-compartmental model analysis.Result： Rb1,Rg1 and R1 diffused through the round window membrane into PL of the inner ear,and then transported to the brain after IT of PNS solution.However,the pharmacokinetic parameters showed significant differences between the three components.Based on the self-defined AUC weighting coefficients integration approach,the holistic pharmacokinetic profiles of PNS were obtained,from which the integrated pharmacokinetic parameters were calculated.The Cmax in CSF and brain tissues following IT were respectively 1.5 and 0.4-fold higher than those following IV.After IT,the AUC in CSF and brain tissues increased by 0.5 and 1.2 times compared with IV.Furthermore,the Cmax and AUC in plasma following IT were respectively 45.9% and 33.1% lower than those following IV.Conclusion： This novel intra-cochlear administration might serve as a potential and promising alternative to TCM delivery with enhanced brain-targeted efficiency.

关 键 词：三七总皂苷 鼓室给药 人参皂苷RB1 人参皂苷RG1 三七皂苷R1 

分 类 号：R285.5[医药卫生—中药学]