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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。
OBJECTIVE: To establish a method for the determination of 3,6’-diacyanoacylsucrose concentration in rat serum by RP-HPLC and to study the effect of 3,6’-di-erucylsucrose, The pharmacokinetics of 3,6’-alanylsucrose in rats with memory impairment model were evaluated. Methods: The model of memory impairment induced by scopolamine in rats was induced by intraperitoneal injection of 3,6’-alucate acyl sucrose reference substance, Polygala tenuifolia extract and water extract, abdominal aorta blood, centrifuged, the amount of serum plus 0.1 mmol potassium dihydrogen phosphate-acetonitrile precipitated protein, the supernatant was blown dry with nitrogen, dissolved in water, filtered, and analyzed by HPLC using C18 as the stationary phase and a mobile phase of acetonitrile -0.1% aqueous phosphoric acid gradient elution at 330 nm The blood concentration of 3,6’-uridoyl sucrose was measured and the data were processed by Kinetics 4.4 software. Results: The linear relationship between 3,6’-uridoyl sucrose serum and 0.052 ~ 2.08 mg.L-1 was good, and the lowest limit of quantitation in plasma was 52 μg.L-1. Rats with memory impairment model were given intragastric administration of 3,6’-acesulfonyl sucrose reference substance, Polygalaceae water extract and water extract of the happy - time curve were treated with non-compartmental model, the main pharmacokinetic parameters AUC0 ~ ∞, Cmax in the 3,6’-a-sinapyl sucrose reference substance, Polygalaceae extract and Kaixin powder were different between groups (P <0.05). Conclusion: The established RP-HPLC assay is specific, accurate and sensitive and is suitable for the pharmacokinetic study of 3,6’-uridoyl sucrose in rats. After oral administration of San San and Polygala extracts, the 3,6’-diaminoacyl sucrose showed bimodal absorption peak time of 15,150 min. The AUC value of 3,6’-diaminoacyl sucrose of orally administered Sanfang and Polygalaceae extracts was 1.60 times the single drug Polygalaceae, T1 / 2 is 1.57 times the single drug Polygalaceae Polygalaceae, indicating that through the compound compatibility, can improve bioavailability, speed up absorption, extend the effective time of plasma concentrations of various aspects of its pharmacokinetic properties , Which is more conducive to exert its medicinal effect.