共聚维酮-Soluplus喷雾干燥微球包合肉桂油研究  

Including preparation of cinnamon oil by vinyl pyrrolidone/vinyl acetate copolymer VA64-Soluplus spray-dried microspheres

作　　者：张焕焕 王云[2,3] 张振海[2,3] 何丹丹[2,3] 鞠建明[2,3] ZHANG Huan-huan;WANG Yun;ZHANG Zhen-hai;HE Dan-dan;JU Jian-ming(School of Pharmacy,Anhui University of Chinese Medicine,Hefei 230031,China;Affiliated Hospital of Integrated Traditional Chinese and Western Medicine,Nanjing University of Chinese Medicine,Nanjing 210028,China;Jiangsu Academy of Traditional Chinese Medicine,Nanjing 210028,China)

机构地区：[1]安徽中医药大学药学院,安徽合肥230031 [2]江苏省中医药研究院,江苏南京210028 [3]南京中医药大学附属中西医结合医院,江苏南京210028

出　　处：《中草药》2020年第22期5723-5729,共7页Chinese Traditional and Herbal Drugs

基　　金：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)。

摘　　要：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AUC0~∞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 ofβ-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 andβ-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 andβ-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 andβ-cyclodextrin inclusion complex;Pharmacokinetics showed that the AUC0—∞of cinnamon essential oil,microsphere inclusion complex andβ-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 v

关 键 词：肉桂油 共聚维酮 Soluplus 微球 Β-环糊精 表征 生物利用度 镇痛药效 

分 类 号：R283.6[医药卫生—中药学]