摘要
目的:以便秘大鼠为实验动物模型,观察其每日灌服不同次数大黄提取物后的药物反应,以药效成分大黄酸药动学为佐证,初步建立日服用大黄次数合理性的研究模式。方法:采用复方地芬诺酯造大鼠便秘模型后分别每日灌服大黄提取物3.6g·kg^(-1)1次、1.8g·k^(-1)2次和1.2g·kg^(-1)3次。给药后24h内观察首便时间、统计总排便次数以及总排便质量。给药后不同时间点眼眶后静脉取血,高效液相色谱法测定大黄酸血药浓度。结果:便秘大鼠每日灌服不同次数的大黄提取物后,每日给药两次的排便总次数分别是每日给药1次和3次的2.57倍和2.97倍,排便总质量分别是每日给药1次和3次的1.58倍和2.35倍。血药浓度-时间数据采用3P97药代动力学软件进行分析。每日给药两次时,大黄酸血药浓度在24h内能够维持在较高水平并保持较长时间,泻下作用明显。效应动力学试验和成分药动学试验都表明,大黄治疗便秘时每日服用两次为佳。结论:以"效"为核心、成分药动学为佐证的模式可以用于中药日服用次数的研究。
This study aimed to establish constipation rat model for the observation of drug reactions to Rhubarb extraction with different daily administration frequency. Rhein was evaluated as an effective component in the pharma cokinetics. The reasonable daily administration frequency of Rhubarb for constipation rats was primarily established. Compound diphenoxylate was used in the establishment of constipation rat model. The model rats were administrated with 3.6g·kg^-1 Rhubarb extract once a day, 1.8g·kg^-1 twice a day and 1.2g·kg^-1 three times a day, respectively. The first defection time, average defecation times and average dejecta weight were observed within 24h after drugadministration. Blood samples were collected from the retro-orbital plexus of rats after different administration intervals. The HPLC method was applied in the determination of rheinic acid concentration in the blood plasma. The pharmacokinetic parameters were calculated with 3p97 software. Total defecation times of the rats administered twice a day was 2.57 times and 2.97 times higher than that of once a day administration and three times a day adminis tration, respectively. And the total dejecta weight was 1.58 times and 2.35 times higher than that of the other two administration methods, respectively. The concentration of rheinic acid in the blood maintained at a relatively high level and lasted for long time with obvious purgative effect. Both pharmacodynamics and pharmacokinetics components showed that the best daily administration frequency of Rhubarb for the treatment of constipation is twice a day. It is concluded that this combination mode can be used in the study of daily administration frequency of Chinese Materia Medica.
出处
《世界科学技术-中医药现代化》
2011年第3期518-522,共5页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家自然科学基金资助项目(81073069):中药日服次数合理性的评价模式和方法的研究
负责人:袁海龙
国家"重大新药创制"科技重大专项课题(2009ZX09502-022):符合中药特点的质量评价方法和体系研究
负责人:肖小河
关键词
中药
大黄
日服次数
效应动力学
成分药动学
Chinese Materia Medica, Rhubarb, daily administration times, pharmacodynamics, pharmacokineticscomponents
