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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%和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 the in vivo behavior of ginsenoside Rb1 (Rb1), ginsenoside Rg1 (Rg1) and notoginsenoside R1 (R1) in guinea pigs after tympanic administration of Panax notoginseng saponins (PNS) To brain feasibility. Methods PNS were administered via the tympanic and intravenous administrations respectively. Peripheral lymphatic fluid, cerebrospinal fluid (CSF), brain tissue and plasma were collected at different time points. The concentrations of Rb1, Rg1 and R1 in each tissue were determined by HPLC. The pharmacokinetic parameters of each component were defined as the weight coefficients according to the ratio of the area under the curve of the time (AUC) of each component, and the pharmacokinetic parameters of PNS after integration were further estimated. Results After transnasal administration of PNS, Rb1, Rg1 and Rl all passed through the round window membrane into the outer ear lymph of the inner ear and translocated into the brain. However, the pharmacokinetic parameters of the three components differed greatly among the tissues in vivo. The PNS integration pharmacokinetic parameters showed that tympanic administration of PNS increased the dose into the brain and increased the local bioavailability. The Cmax in CSF and brain tissues were 1.1 and 0.4 times higher than that of intravenous administration, respectively, and the AUC was increased 0.4, 0.2 times; and PNS in the plasma distribution decreases, Cmax and AUC decreased by 45.9% and 33.1% respectively than intravenous administration. Conclusion The ear into the brain is expected to become a new method of intracerebral delivery of Chinese medicine.