【作者】 吴丹；

【导师】 崔京浩；

【作者基本信息】 苏州大学 ， 药剂学， 2011， 硕士

【摘要】 目的:通过缬草提取物的药效学研究、缬草油-β-环糊精包合物及其包衣片的制备与评价,为缬草制剂的进一步研究开发提供依据。方法:（1）通过考察缬草提取物及挥发油对小鼠自主活动、“失望”和“不动”行为、阈下催眠剂量戊巴比妥钠作用与小鼠睡眠时间的影响,初步确定给药剂量。（2）饱和水溶液‐超声细胞粉碎法制备缬草油-β-环糊精包合物。单因素法研究影响包合的因素,选择以β-环糊精与缬草油的比例、乙醇与缬草油的体积比、超声次数和超声频率作为影响因素,包合物得率和缬草油包封率作为指标,均匀设计法[U13*（134）]优化处方与制备工艺。通过紫外分光光度法（UV）、差示扫描量热法（DSC）和X射线粉末衍射法（X-RD）验证包合物的形成。（3）采用湿法制粒压片工艺,通过单因素试验对辅料进行筛选,优化处方组成,并考察了缬草油包合物制备对缬草片芯稳定性的影响。（4）在比较多种包衣液的基础上,优选OPADRYⅡ对缬草片芯进行包衣。选用正交设计L9（3⁴）,考察包衣增重、喷液流量、喷雾压力和包衣锅温度对包衣效率、包衣片外观、耐湿度和溶出度的影响,优选包衣工艺。（5）实施缬草提取物包衣片在高温、高湿和光照条件下的影响因素试验。结果:（1）药效学实验数据表明,缬草提取物能显著降低小鼠自主活动次数;显著延长“失望”小鼠尾悬挂和漂浮不动时间;增加戊巴比妥钠阈下催眠剂量小鼠的入睡数;延长戊巴比妥钠睡眠时间,表明缬草制剂与戊巴比妥钠有协同作用。（2）均匀设计得到缬草油-β-环糊精包合物的优化制备工艺:饱和水溶液‐超声细胞粉碎法,β-CD与缬草油的比例为3:1,乙醇与缬草油体积比为1:1。包合物收得率为（84.78±3.23）%,包封率为（86.23±2.48）%,UV、DSC、X-RD结果验证缬草油-β-环糊精包合物的形成。（3）优选的片芯制备辅料:稀释剂为微晶纤维素和淀粉、崩解剂为交联聚维酮、润滑剂为硬脂酸镁和滑石粉、润湿剂为70%乙醇。稳定性试验数据表明,包合物的制备有效提高了缬草油的稳定性,并在一定程度上掩盖了缬草油的不愉快气味。（4）应用正交设计,得到包衣片的最佳制备工艺:包衣增重25%、喷液流量1.5².0 g·min^-1、喷雾压力0.1 MPa、包衣锅温度45℃。（5）影响因素试验数据表明,缬草包衣片在高温、高湿和光照条件下比较稳定。结论:缬草提取物具有良好的镇静安神作用,缬草油-β-环糊精包合物提高了缬草油的稳定性,缬草提取物片剂经OPADRYⅡ包衣后不仅提高了耐湿性且掩盖了缬草油的气味。更多还原

【Abstract】 Objectives: To provide evidences for the further research and development of the preparation containing Valerian extract through the pharmacodynamic studies, manufacturing and evaluation of Valerian oil-β-cyclodextrin inclusion complex and its coated tablets.Method: (1) Effect of the mixture of Valerian extract and oil on the spontaneous and passive movement, disappointment with tail hanging-up and swimming test and the sleeping time induced by pentobarbital sodium in subthreshold hypnotic dose after oral administration to mice were investigated, and the preliminary dose of clinical application was determined. (2) Valerian oil-β-cyclodextrin inclusion complex was prepared by saturated water solution-ultrasonication method. Single factor method was used to observe the effect of different factors such as ratio of Valerian oil andβ-cyclodextrin, Valerian oil concentration, ultrasonication times and frequency on the productivity of inclusion complex and Valerian oil content, and subsequently optimized using Uniform Design U13*(13~4) table. The formations of inclusion complex were confirmed by UV spectrophotometry, differential scanning calorimetry (DSC) and X-ray powder diffraction (X-RD) method. (3) Valerian extract tablets were prepared by wet granulation method. Single-factor test was used to screening the excipients. The influences of Valerian oil inclusion complex on the stability of Valerian tablets were observed, too. (4) After comparing different kinds of coating solution, OPADRYⅡwas selected as coating material in present studies. The effect of coating weight, delivery speed of coating solution, pressure of spraying and coating temperature on coating efficiency, appearance and humidity resistance of coated tablets and dissolution were investigated and optimized using Orthogonal Design L9(3~4). (5) The accelerate stability tests of coated tablets containing Valerian extract were carried out under high temperature, high humidity and strong light condition.Result: (1) The pharmacodynamic test showed that the mixture of Valerian oil and Valerian extract could reduce spontaneous movement significantly and prolong tail hanging-up and swimming time of mice. The sleeping times of mice produced by pentobarbital sodium was increased, improved the quantity of sleeping animals caused by pentobarbital sodium in subthreshold hypnotic dose, too. (2) The optimal preparation process of Valerian oil-β-cyclodextrin inclusion complex was obtained by the Uniform Design: the ratio of Valerian oil toβ-cyclodextrin was 3:1, the ratio of Valerian oil to ethanol was 1:1, ultrasonic times and frequency were 220 and 780 MHZ, respectively. Inclusion complex yield was (84.78±3.23)% and entrapment efficiency of the Valerian oil was (86.23±2.48)%. The results of UV, DSC, and X-RD were indicated the formation of inclusion complex. (3) The optimized formulation of the core tablet was as following: the mixture of MCC and starch, PVPP, magnesium stearate and talc were used as filler, disintegrant and lubricant, while using 70% ethanol as moistening agent. The stability test showed that the preparation of inclusion complex could improve the stability of Valerian oil efficiently and cover its unpleasant smell to some extent. (4) According to the Orthogonal Design, the optimal preparation process of Valerian extract coated tablets as follows: coating weight 25%, spray liquid flow rate 1.5-2.0 g·min-1, spray pressure 0.1 MPa, coating temperature 45℃. (5) The accelerated stability test showed that the stability of Valerian extract coated tablets was improved significantly.Conclusion: Valerian extract and oil showed significant tranquilizing effect. The preparation of inclusion complex could improve the stability of Valerian oil efficiently. The humidity resistance of Valerian extract tablets was improved and unpleasant smell of Valerian oil was covered after coating with OPADRYⅡ.更多还原