柴胡纳米乳的制备工艺、质量评价及退热药效学研究

Preparation Process, Quality Evaluation and Antipyretic Pharmacodynamics of Bupleurum Nanoemulsion

关键词:  柴胡纳米乳  制备工艺  伪三元相图  质量评价  药效学研究

Key words:  Bupleurum nanoemulsion  preparation process  pseudo-ternary phase diagram  quality evaluation  pharmacodynamic study

摘要:

目的 筛选柴胡纳米乳的处方和制备方法，并对其进行质量评价和退热药效作用的研究。方法 对乳化剂和助乳化剂进行初步筛选，再通过伪三元相图筛选处方，并对制备的柴胡纳米乳的外观性状、粒径分布、结构类型、稳定性及含量进行质量评价。进一步将Wistar大鼠随机分成空白对照组，模型对照组，阳性对照组(阿司匹林组)，柴胡纳米乳高、中、低剂量组(18.00，9.00，3.00 g·kg^-1)；除空白对照组外，其余各组大鼠制备发热大鼠病理模型。按照预定的实验要求分别给予相应的药物，于0.5，1，1.5，2，3 h记录各组大鼠的体温变化情况，观察柴胡纳米乳的退热作用。结果 柴胡纳米乳的最佳处方为吐温-80 6 g与正丁醇3 g，柴胡提取物溶于纯水为水相20 mL，柴胡油为油相2 g。室温下制剂为黄褐色澄清透明液体，水包油型纳米乳，平均粒径为(77.21±3.66)nm，多分散系数为0.28±0.04，Zeta电位为(–18.81±1.42)mV，所含柴胡皂苷为3.071 mg·mL^-1，具备良好的稳定性。动物实验中，与模型对照组比较，阿司匹林组、柴胡纳米乳高剂量组首次给药后的各时间段肛温明显降低(P<0.01)，柴胡纳米乳中剂量组首次给药2，3 h后肛温明显降低(P<0.01)。结论 所制备的柴胡纳米乳外观透明，稳定性好，并且对发热大鼠模型具有较好的解热作用。

Abstract:

OBJECTIVE To screen the prescription and preparation method of Bupleurum nanoemulsion, and evaluate its quality, study the antipyretic effect. METHODS The emulsifier and co-emulsifier of the nanoemulsion were preliminarily screened, and then the prescription was screened by pseudo-ternary phase diagram. The quality evaluation of the appearance, particle size distribution, structure type, stability and content of the prepared Bupleurum nanoemulsion was performed. Wistar rats were further randomly divided into blank control group, model control group, positive control group(aspirin group), Bupleurum nanoemulsion high-dose, medium-dose and low-dose groups(18.00, 9.00, 3.00 g·kg^-1). Except for the blank control group, the pathological model of fever rats was prepared in the other groups. According to the scheduled experimental requirements, rats in each group were given the corresponding drugs. And the temperature changes of rats in each group were recorded at 0.5, 1, 1.5, 2, 3 h to observe the antipyretic effect of Bupleurum nanoemulsion. RESULTS The best prescription of Bupleurum nanoemulsion: Tween-80 6 g and n-butanol 3 g, Bupleurum extract dissolved in pure water as water phase 20 mL, Bupleurum oil as oil phase 2 g. At room temperature, the Bupleurum nanoemulsion was a yellow-brown clear and transparent liquid, O/W nanoemulsion, with an average particle size of (77.21±3.66)nm, polydispersity index of 0.28±0.04, Zeta potential of (–18.81±1.42)mV, and saikosaponin content of 3.071 mg·mL^-1, with good stability. In animal experiments, compared with the model control group, the rectal temperature of aspirin group and Bupleurum nanoemulsion high-dose group was significantly lower after the first administration(P<0.01), the rectal temperature of Bupleurum nanoemulsion middle-dose group was significantly lower after the first administration 2, 3 h(P<0.01). CONCLUSION The Bupleurum nanoemulsion is transparent and stable, and it has good antipyretic effect on fever rat model.