摘要
目的:在体外释放条件下,对PLGA微球制剂中艾塞那肽的酰化产物进行分离并进行活性研究。方法:通过制备液相分离PLGA微球制剂中艾塞那肽在体外释放条件下产生的酰化产物,分别采用SD大鼠和db/db糖尿病小鼠考察艾塞那肽酰化产物的体内药动学及药效学,细胞实验进行活性研究,并与艾塞那肽进行比较。结果:艾塞那肽酰化产物为连接一个羟基乙酸的产物,药动学结果显示,酰化产物与艾塞那肽有相似的Tmax和AUC,酰化产物的Cmax略小于艾塞那肽,但药效学考察显示酰化产物可以使db/db小鼠的血糖下降,且对RIN-m5f细胞具有相似的促进胰岛细胞增殖的作用。结论:PLGA微球制剂中艾塞那肽的酰化产物与艾塞那肽原型药物有相似的降血糖作用及促进胰岛细胞增殖的作用。
Objective:To separate the related substance of exenatide formed during incubation of drug-load- ed poly-( d, 1-lactide-co-glycolide) (PLGA) microspheres under in vitro release conditions and study its activity. Methods : The acylated exenatide of exenatide-loaded microspheres was finally separated and purified by preparation liquid chromatography. The pharmacokinetic characteristics and antidiabetic activity of the acylated exenatide were investigated in SD rats and db/db mice, respectively. RIN-m5f cells were used to study the activity, and the re- sults were compared with exenatide. Results:Structural characterizations of the acylated exenatide showed that one glycolic acid (GA) was connected to the primary amine group of exenatide. Pharmacokinetie study in rats revealed that exenatide and acylated exenatide had similar had a decreased C max. However,they had similar of islet cells. Conclusion:The acylated exenatide Tmax and AUC after s. c. administration, and acylated exenatide antidiabetic activity, and both of the m could promote proliferation has a similar hypoglyeemic effect and can promote proliferation ofislet cells.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2016年第7期745-750,759,共7页
Chinese Journal of New Drugs
基金
国家"重大新药创制"科技重大专项--天然药物与新制剂综合大平台(2013ZX09402201)
山东省自然科学基金(ZR2013HQ009)
关键词
艾塞那肽微球
酰化产物
分离
活性研究
exenatide microspheres
acylated exenatide
separation
activity study