苦远胶囊的药理学研究

【作者】 付琳媛；

【导师】 张宏；

【作者基本信息】 辽宁中医药大学 ， 药理学， 2010， 硕士

【摘要】 目的:考察苦远胶囊的镇静、催眠作用,为开发出一种疗效好,毒性小,质量可控的治疗失眠的中药新药提供实验依据。方法:通过采用特异的药效学跟踪实验来确定苦远胶囊的最佳处方及最佳提取工艺;对苦远胶囊进行急性毒性实验,利用Bliss法得出苦远胶囊的LD50并计算出其95%可信限;通过苦远胶囊对小白鼠自主活动的影响,对小白鼠戊巴比妥钠阈下催眠剂量作用的影响,对小白鼠延长戊巴比妥钠催眠时间的影响以及对正常大鼠睡眠脑电图(EEG)的分析,将行为学观察法与神经电生理实验方法结合起来对苦远胶囊进行药效学研究。结果:1.处方2组能显著增加小白鼠翻正反射消失数(P<0.01),处方1组可显著缩短阈剂量戊巴比妥钠所致小白鼠睡眠的入睡潜伏期,并能延长小白鼠的睡眠时间(P<0.05),采用综合评分法对实验结果进行综合评定,以得分高者为最佳处方,最终确定苦远胶囊的最佳处方为处方2。2.工艺1组和工艺4组均能显著增加小白鼠翻正反射消失数(P<0.05),工艺2组可显著延长阈剂量戊巴比妥钠所致小白鼠睡眠的睡眠时间(P<0.01),工艺4组可显著缩短阈剂量戊巴比妥钠所致小白鼠睡眠的入睡潜伏期,并能延长小白鼠的睡眠时间(P<0.05)。综合以上的实验结果,确定工艺4为苦远胶囊的最佳提取工艺。3.苦远胶囊小白鼠口服灌胃给药LD50为42.61g/kg,其95%可信限为36.97～49.10g/kg。4.苦远胶囊中、高剂量组能够明显地减少小白鼠的自主活动次数(P<0.05);苦远胶囊低、中、高剂量组均能显著增加小白鼠翻正反射消失数(P<0.01);苦远胶囊中、高剂量组可显著延长阈剂量戊巴比妥钠所致小白鼠睡眠的睡眠时间(P<0.05);苦远胶囊高剂量组能显著延长正常大鼠睡眠时相中的SWS1期,并且能够显著增加脑电波中δ波的百分比(P<0.01),表明高剂量的苦远胶囊对正常大鼠的睡眠脑电波具有改善作用。结论:1.苦远胶囊的最佳处方为处方2。2.苦远胶囊的最佳提取工艺为工艺4。3.苦远胶囊小白鼠口服灌胃给药LD50为42.61g/kg,其95%可信限为36.97～49.10g/kg。4.药效学实验表明苦远胶囊具有较好的镇静、催眠作用。更多还原

【Abstract】 Purpose:The purpose is to investigate the sedation and hypnosis effect of Kuyuan capsule.The topic will provide an experimental evidence for new TCM drugs in treating insomnia which with definite material basis,good efficacy,low toxicity,and controllable quality.Method:This research subject through the special pharmacodynamics tracking test to determine the best prescription and the optimum extraction process. Detect median lethal dose(LD50) and the confidence limit of 95% of Kuyuan capsule by the bliss method. Through the effect of Kuyuan capsule on locomotor activity in mice,the effect on mice hypnosis of pentobarbital sodium of subthreshold dosage,the hypnotic time experiment on mice by pentobarbital sodium in threshold dosage and the analysis of electroencephalogram on rats,we carry out the pharmacodynamic study of Kuyuan capsule with the behavior experiments and electrophysiological techniques.Results:1.Prescription No.2 could enhance the number of asleep mice of pentobarbital sodium in subthreshold hypnotic dosage(P<0.01).Prescription No.1 could shorten substantially the rats’ sleep latent period and prolong obviously the rats’ sleep time which induced by pentobarbital sodium at threshold dosage(P<0.05). Prescription No.2 was certified as the optimal prescription by using comprehensive scoring method.2.Process No.1 and No.4 drug group could enhance the number of asleep mice of pentobarbital sodium in subthreshold hypnotic dosage(P<0.05), process No.2 drug group could prolong obviously the rats’ sleep time which induced by pentobarbital sodium at threshold dosage(P<0.01),process No.4 drug group could shorten substantially the rats’ sleep latent period and prolong obviously the rats’ sleep time which induced by pentobarbital sodium at threshold dosage (P<0.05). The results showed that process No.4 was the optimal process.3.The median lethal dose(LD50) of Kuyuan capsule was 42.61g/kg.The confidence limit of 95% was 36.97～49.10g/kg.4.The middle dosage and high dosage of Kuyuan capsule could significantly inhibit the locomotor activity in mice(P<0.05).Low dosage, middle dosage and high dosage of Kuyuan capsule could enhance the number of asleep mice of pentobarbital sodium in subthreshold hypnotic dosage(P<0.01). Middle dosage and high dosage of Kuyuan capsule could prolong obviously the rats’ sleep time which induced by pentobarbital sodium at threshold dosage(P<0.05).The experimental results indicated that contribution to sleep phase of the normal rats,SWS1 and the percentage of brain wave(δ)(P<0.01)of the normal rats were all significantly prolonged after administration of high dosage of Kuyuan capsule.Conclusion:1.Prescription No.2 was certified as the optimal prescription of Kuyuan capsule.2.Process No.4 was the optimal process of Kuyuan capsule.3.The median lethal dose(LD50) of Kuyuan capsule was 42.61g/kg.The confidence limit of 95% was 36.97～49.10g/kg.4.Pharmacodynamics proves that Kuyuan capsule really has hypnotic and sedative effects.更多还原