艾塞那肽长效缓释微球的研制  

Preparation of Exenatide Long-acting Sustained-release Microspheres

作　　者：王猛 张宇桐 郜珍叶 吴飞[1] 金拓[1] WANG Meng;ZHANG Yutong;GAO Zhenye;WU Fei;JIN Tuo(School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240)

机构地区：[1]上海交通大学药学院,上海200240

出　　处：《中国医药工业杂志》2021年第11期1480-1486,共7页Chinese Journal of Pharmaceuticals

摘　　要：艾塞那肽作为胰高血糖素样肽-1受体激动药,用于改善2型糖尿病患者的血糖控制。为提高患者的用药依从性、减轻药物的不良反应,本试验研发了一种粒径均一、释放曲线理想的艾塞那肽长效缓释微球。在前期研发的膜乳化沉降技术的基础上,采用本实验室发明的膜乳化沉降装置制备艾塞那肽聚乳酸-羟基乙酸共聚物微球,并进行微球体外表征。通过改变处方中辅料的种类和添加量考察对微球释放曲线的影响。结果显示,通过膜乳化沉降法制备的微球粒径大小均一,平均粒径为50~100µm,微球呈球形,表面光滑平整,包封率在90%以上。通过在微球处方中分别添加酸碱调节辅料、中性促进释放辅料,可实现30 d的连续平稳缓释,且突释率低,不超过30%,30 d累积释放率接近100%,有效地调节释放动力学过程。Exenatide is used as a glucagon-like peptide-1 receptor agonist to improve glycemic control in patients with type 2 diabetes. To improve patients’ compliance and reduce the adverse effects of the drug, the longacting sustained-release microspheres of exenatide with uniform particle size and ideal release profiles were developed. In this paper, a membrane emulsification and sedimentation microsphere preparation device was designed. It was based on the previously developed membrane emulsification and sedimentation technology in our laboratory. The prepared microspheres with poly(lactide-co-glycolide)(PLGA) as a carrier were characterized in vitro, and the release profiles of microspheres were investigated through changing the composition and addition amount of excipients. The results showed that the microspheres prepared by the membrane emulsification and sedimentation method were uniform in size, with the average particle size from 50 μm to 100 μm. The microspheres were spherical with smooth and flat surface, and the encapsulation rate was above 90%. The release rate of exenatide from the microspheres could be adjusted by adding some pH adjusting excipients and some neutral promotion release excipients. Accroding to the formulation modulation, it could achieve the sustained release over one month. The burst release rate was lower than 30%. The cumulative release amount of exenatide was close to 100% within 30 days. In conclusion, formulation modulation could effectively regulate the release kinetic process.

关 键 词：艾塞那肽 长效缓释 膜乳化沉降 微球 

分 类 号：R944.9[医药卫生—药剂学]