基于3,6'-二芥子酰基蔗糖在记忆障碍模型大鼠体内表征的 单体、远志及其经典方开心散药代动力学

目的:建立RP-HPLC测定大鼠血清中3,6′-二芥子酰基蔗糖浓度的方法,研究3,6′-二芥子酰基蔗糖、远志及开心散中3,6′-二芥子酰基蔗糖在记忆障碍模型大鼠体内的药动学特点,评价远志药材中其他成分和复方中其他配伍对3,6′-二芥子酰基蔗糖药动学的影响.方法:大鼠腹腔注射东莨菪碱致记忆障碍模型,分别灌胃给予3,6′-二芥子酰基蔗糖对照品、远志水提物和开心散水提物,腹主动脉采血,离心,取血清适量,加0.1 mmol磷酸二氢钾-乙腈沉淀蛋白,取上清液氮气吹干,水溶解,过滤,用HPLC分析,以C18为固定相,流动相为乙腈-0.1％磷酸水溶液梯度洗脱,在330 nm检测3,6′-二芥子酰基蔗糖血药浓度,Kinetics 4.4软件处理数据.结果:3,6′-二芥子酰基蔗糖血清在0.052 ～2.08 mg·L-1线性关系良好,血浆中最低定量限为52μg·L-1.记忆障碍模型大鼠灌胃给予3,6′-二芥子酰基蔗糖对照品、远志水提物和开心散水提物后的药-时曲线均使用非房室模型处理,主要药动学参数AUC0-∞,Cmax在3,6′-二芥子酰基蔗糖对照品、远志提取物和开心散各组间均有差异(P＜0.05).结论:建立的RP-HPLC测定法,专属、准确、灵敏,适用于3,6′-二芥子酰基蔗糖在大鼠体内的药动学研究.口服开心散全方和远志提取物后3,6′-二芥子酰基蔗糖呈现双峰吸收,达峰时间均为15,150 min,口服开心散全方的3,6′-二芥子酰基蔗糖AUC值是单味药远志的1.60倍,T1/2是单味药远志的1.57倍,表明通过复方配伍,可在提高生物利用度、加速吸收、延长有效血药浓度时间诸方面,调节其药动学特性,从而更有利于发挥其药效作用.

Comparative Pharmacokinetics of 3,6'-disinapoyl Sucrose after Oral Administration of Pure 3,6'-disinapoyl Sucrose, Radix Polygalae Extract and Kaixinsan in Acquired Dysmnesia Model Rats

Objective:To establish a method to determine the pharmacokinetics of 3,6′-disinapoyl sucrose and pharmacokinetic differences of 3,6′-disinapoyl sucrose following oral administration of pure 3,6′-disinapoyl sucrose,Radix Polygalae extract and Kaixinsan were investigated in acquired dysmnesia model rats with approximately the same dose of 3,6′-disinapoyl sucrose.Method: The rats were received injection of scopolamine to make the model of acquired dysmnesia,and orally treat with pure 3,6′-disinapoyl sucrose,Radix Polygalae extract and Kaixinsan respectively.Blood samples were collected via abdominal aorta.Serum samples were immediately separated by centrifugation at 4 000 r·min-1 for 10 min,and 0.1 mmol monopotassium phosphate and acetonitrile were added to deposit proteins.After centrifugation,the upper liquid evaporated to dryness by N2 at 50 ℃.The residue was added distilled water to dissolve and the concentation of 3,6′-disinapoyl sucrose was determined by HPLC.Result: A good linear relationship of 3,6′-disinapoyl sucrose was obtained from 0.052-2.08 mg·L-1,the lowest limits of determination were 52 μg·L-1.The pharmacokinetic parameters were estimated by non-compartmental methods using the Kinetica 4.4 program,and the pharmacokinetic parameters AUC0~∞,Cmax of 3,6′-disinapoyl sucrose showed significant differences between 3,6′-disinapoyl sucrose and other groups.Conclusion: The method applied for determination of 3,6′-disinapoyl sucrose content in blood was simple,feasible and accurate for the study of 3,6′-disinapoyl sucrose pharmacokinetics in rats.The results indicated the other components of Radix Polygalae and compatibility had remarkable influence on the pharmacokinectics of 3,6′-disinapoyl sucrose.