天麻素鼻腔原位凝胶在大鼠体内的药动学及脑靶向性研究

Pharmacokinetics and Brain-targeting Ability of Gastrodin Nasal in Situ Gel in Rats

目的:研究以TMC-P407-P188-卡波姆为基质的天麻素鼻腔温敏凝胶的药动学参数,初步研究其脑靶向性。方法:以大鼠为动物模型,实验组天麻素鼻腔原位凝胶给药,对照组静注天麻素注射液,给药后分别取两组大鼠体内血液与脑组织(大脑和小脑),采用HPLC法分别测定两组血液中的天麻素含量和脑组织中天麻苷元的浓度,绘制药时曲线,计算曲线下面积(AUC)和平均滞留时间(MRT)等药动学参数,比较两组生物利用度F(%)和脑靶向性参数(BTI)。结果:与静注天麻素注射液相较,经鼻给予天麻素温敏凝胶的大鼠脑组织中的天麻苷元含量显著增加(P<0.05),大脑和小脑的药时曲线下面积显著增加,BTI分别为2.38和1.93,药物平均滞留时间MRT增加了近2倍。生物利用度F(%)也较大的增加。结论:以TMC-P407-P188-卡波姆为基质的天麻素鼻腔温敏凝胶能很好的发挥药效作用,且具有一定的脑靶向性和药物缓释性。

Objective ： To study the pharmacokinetic parameters of gastrodin nasal in situ gel （ISG） with the base of TMC-P407- P188-carbomer, and evaluate its brain-targeting ability preliminarily. Methods： Rats were used as the model animals. The experiment group was treated with gastrodin nasal in situ gel, and the control group was treated with gastrodin solution with intravenous administra- tion. The plasma sample and brain tissue （ cerebrum and cerebellum） were taken out at the predetermined time points, and the concen- tration of gastrodin in plasma and gastrodigenin in brain tissues were determined by HPLC to draw the curve of concentration vs time. The pharmacokinetic parameters such as MRT and AUC were calculated by 3P97 software. The bioavailability F （ % ） and the brain- targeting index BTI were compared between the groups. Results： The concentration of gastrodigenin in the brain tissues of grastrodin in situ gel was higher than that of gastrodin solution with intravenous administration （P 〈 0.05）. AUC of cerebrum and cerebellum both increased significantly with BTI of 2.38 and 1.93, respectively. MRT increased by nearly twa-fold in the gel group when compared with that in the control group, and F（ % ） increased significantly in cerebrum and cerebellum as well. Conclusion： Gastrodin nasal in situ gel with the base of TMC-P407-P188-carbomer has promising effectiveness. Meanwhile, it can improve the brain-targeting ability of gastrodin with sustained release.