目的 考察共聚维酮-Soluplus（聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物）喷雾干燥微球包合肉桂油的适用性，并与传统β-环糊精包合技术进行比较研究。方法 采用HPLC法测定包合物的包封率；采用透射电子显微镜（TEM）、扫描电子显微镜（SEM）、差示扫描量热法（DSC）、X射线粉末衍射法（XRD）对包合物进行表征；采用体外释放试验和加速稳定性试验考察包合物的溶出度和稳定性；采用药动学和镇痛药效试验考察包合物的生物利用度和药效。结果 空白微球的包封率为（98.38±0.30）%，β-CD的包封率为（86.51±0.52）%；TEM下观察包合物呈现均匀的类球状结构，分散均匀；SEM下观察，包合物为表面有内凹的球形；DSC图中肉桂油的吸热峰和XRD图中衍射峰均消失，肉桂油以非聚集的形式分散包合于包合物中；体外溶出实验肉桂油、微球包合物和β-环糊精包合物累积释放率分别为为97.05%、93.36%、80.26%；60℃加速稳定性显示，微球包合物挥发油损失率明显低于肉桂油和β-环糊精包合物；药动学显示，肉桂油、微球包合物及β-环糊精包合物AUC_0～^∞基本一致；药效学显示，3组肉桂油镇痛率分别为53.0%、47.5%、21.1%。结论 肉桂油经共聚维酮-Soluplus喷雾干燥微球包合后增强了其稳定性，体外释药、生物利用度和镇痛药效与肉桂油基本保持一致，优于β-环糊精包合物，且聚维酮-Soluplus微球包合物具有较好的水溶性，为挥发油的包合提供了新方法。

Objective To investigate the applicability of the spray-dried microspheres of vinyl pyrrolidone/vinyl acetate copolymer VA64-Soluplus for inclusion of cinnamon oil (CO) and compare with traditional inclusion technology of β-cyclodextrin. Methods HPLC was used to determine the encapsulation rate of inclusion complex. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRD) were used to characterize the inclusion complex; The dissolution and stability of the inclusion complex was investigated by in vitro release test and accelerated stability test; The pharmacokinetic and analgesic efficacy tests were used to examine the bioavailability and efficacy of the inclusion complex. Results The encapsulation rate of microsphere inclusion complex and β-cyclodextrin inclusion complex was (98.38±0.30)% and (86.51±0.52)%, respectively. Observation of the inclusion complex under TEM showed a uniform spherical-like structure with uniform dispersion; Observation under SEM showed that the inclusion complex was spherical with a concave surface; The endothermic peak of volatile oil of cinnamon in DSC and the diffraction peak in XRD disappeared. The cinnamon volatile oil was dispersed in theinclusion complex in the form of non-aggregation; The cumulative release rates of cinnamon volatile oil, microsphere inclusion complex and β-cyclodextrin inclusion complex in in vitro dissolution experiments were 97.05%, 93.36% and 80.26%, respectively; Accelerated stability test at 60 ℃ showed that the loss rate of volatile oil of microsphere inclusion complex was significantly lower than that of cinnamon volatile oil and β-cyclodextrin inclusion complex; Pharmacokinetics showed that the AUC_0—∞ of cinnamon essential oil, microsphere inclusion complex and β-cyclodextrin inclusion complex were basically the same; Pharmacodynamics showed that the analgesic rates of cinnamon volatile oil in the three groups were 53.0%, 47.5% and 21.1%, respectively. Conclusion The stability of cinnamon volatile oil was enhanced by the combination of spray-dried microspheres of vinyl pyrrolidone/vinyl acetate copolymer VA64-Soluplus. The in vitro release, bioavailability and analgesic efficacy of microsphere were basically consistent with the volatile oil of cinnamon volatile oil, and it was superior to the inclusion compound of β-cyclodextrin. The vinyl pyrrolidone/vinyl acetate copolymer VA64-Soluplus microsphere inclusion compound had better water solubility. This study provides a new method for the inclusion of volatile oil.

R283.6

江苏省中医药管理局科技项目（FY201707）；江苏省药学会奥赛康临床药学科研项目（A201709）；江苏省研究生培养创新工程研究生科研与实践创新计划项目（SJCX20_0571）