秦皮乙素纳米结晶的制备与抗炎活性评价  

Preparation,characterization and anti-inflammatory of esculetin nanocrystals

作　　者：程雯 朱洁 张永帅 王征[1] 梁艳妮[1] CHENG Wen;ZHU Jie;ZHANG Yong-shuai;WANG Zheng;LIANG Yan-ni(Co-Construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi&Education Ministry/State Key Laboratory of Research&Development of Characteristic Qin Medicine Resources(Cultivation)/Shaanxi Innovative Drug Research Center,Shaanxi University of Chinese Medicine,Xianyang Shaanxi 712083)

机构地区：[1]陕西中医药大学陕西中药资源产业化省部共建协同创新中心/秦药特色资源研究开发国家重点实验室(培育)/陕西省创新药物研究中心,陕西咸阳712083

出　　处：《中南药学》2022年第12期2746-2751,共6页Central South Pharmacy

基　　金：陕西省创新人才推进计划-青年科技新星项目(No.2019KJXX-025);陕西省教育厅重点项目(No.20JY012);陕西高校青年科技创新团队(No.陕教[2019]90号);陕西省科技厅项目(No.2022SF-222);陕西中医药大学研究生创新实践能力提升项目(No.ZG035)。

摘　　要：目的优化秦皮乙素纳米结晶的制备工艺并对所得纳米结晶进行初步评价。方法将适量秦皮乙素溶于乙醇(良溶剂)并超声助溶,均匀加入到搅拌条件下的水溶液(不良溶剂)中,使之过饱和而析出结晶。考察良溶剂与不良溶剂比例、稳定剂种类、稳定剂浓度、药物浓度、冻干保护剂种类对纳米结晶粒径的影响;比较秦皮乙素纳米结晶和秦皮乙素的体外溶出度;利用小鼠单核巨噬细胞RAW264.7分析秦皮乙素纳米结晶的抗炎活性。结果最优制备工艺为:以4 mg·mL-1聚乙烯吡咯烷酮作为单一稳定剂;良溶剂与不良溶剂比例为1∶20,药物质量浓度为7 mg·mL-1,超声120 min,得到的秦皮乙素纳米结晶粒径为(18.68±0.56)nm,多分散系数为(0.357±0.008)。冻干保护剂选择D-山梨醇制得的ES-NC冻干粉效果好,粒径为(30.74±3.00)nm。体外抗炎实验表明秦皮乙素纳米结晶可以抑制脂多糖诱导M1型巨噬细胞RAW264.7产生一氧化氮,下调促炎性细胞因子肿瘤坏死因子-α、白介素-8水平,上调抑炎性细胞因子白介素-4水平。结论秦皮乙素纳米结晶制备工艺简便,可显著提高秦皮乙素的溶解度和体外溶出度,并具有很好的体外抗炎活性,为其新剂型开发提供理论依据。Objective To optimize the preparation of esculetin nanocrystals(ES-NC)and evaluate it preliminarily.Methods An appropriate amount of esculetin(ES)was dissolved in ethanol by ultrasonic method.It is uniformly added to the water under stirring conditions to make it supersaturate and crystallize.Several factors were optimized,including ratio of good solvent and poor solvent,types of stabilizer,concentrations of stabilizer,drug concentrations and types of lyoprptectant.Their effect on the nanocrystals was also observed.The dissolution rates in vitro of ES-NC and ES were determined.RAW264.7 cells were used to analyze the anti-inflammatory activity of ES-NC.Results The optimal conditions for the preparation of ES-NC included 4 mg·mL-1 polyvinylpyrrolidone as a single stabilizer;the ratio of good solvent and poor solvent was 1∶20,the drug concentration was 7 mg·mL-1 and the ultrasonic time was 120 min.The obtained particle size of ES-NC was(18.68±0.56)nm,and the polydispersity index was(0.357±0.008).D-sorbitol as the lyophilized protective agent for the preparation of lyophilized powder had good resolubility,and the partical size was(30.74±3.00)nm.In vitro anti-inflammatory experiments showed that ES-NC reduced the production of nitric oxide,TNF-αand IL-8,and increased the levels of IL-4 in LPS-induced macrophage RAW264.7.Conclusion The preparation process of ES-NC is simple and convenient,which can significantly improve the solubility and dissolution in vitro of ES,with fairly good anti-inflammatory effect.This study provides a theoretical basis for the development of new dosage forms of ES.

关 键 词：秦皮乙素 纳米结晶 反溶剂沉淀法 体外溶出度 粒径 抗炎 

分 类 号：R284[医药卫生—中药学] R285[医药卫生—中医学]