一种新型速效人胰岛素类似物的制备及药效学研究  

Preparation and Pharmacodynamics Study of a Novel Rapid-Acting Analog of Human Insulin

作　　者：尤科军[1] 鲁勇[2] 林明[2] 孔婧[2] 曹荣月[2] 刘景晶[2] 范豪 宗莉[1] 

机构地区：[1]中国药科大学药物制剂研究所,江苏南京210009 [2]中国药科大学微基因药物实验室,江苏南京210009 [3]上海一就生物医药有限公司,上海200030

出　　处：《药物生物技术》2009年第4期334-337,共4页Pharmaceutical Biotechnology

基　　金：国家自然科学基金(No.30772570);江苏省自然科学基金资助项目(BK2007170)

摘　　要：制备一种新型速效胰岛素类似物PInsulin(PIns),利用Autoflex ToF/ToF质谱法对其进行鉴定,采取福林-酚试剂法测定其浓度;以人胰岛素、赖脯胰岛素作为对照品肌肉注射测定其对雄性SD大鼠的降血糖作用,并通过分子筛层析法考察其自聚合性质。质谱法测得PIns的Mr为6286.50,浓度为0.227mg/ml;动物实验表明注射PIns后,大鼠血糖降至最低基础血糖浓度百分数和恢复至基础血糖浓度所需时间均显著小于人胰岛素(P<0.01);注射PIns后基础血糖浓度百分数的最低值与人胰岛素相当;分子筛层析法结果显示PIns的滞留时间大于人胰岛素,表明PIns自身聚合能力低于人胰岛素,是一种具有良好发展前景的新型速效胰岛素类似物。A novel rapid acting analog of human insulin named PInsulin（PIns） was prepared, and its molecular weight was characterized by Autoflex ToF/ToF（Bruker Daitonics） mass spectrum, and the concentration of Pins was determined by Folin-phenol reagent method. Its pharmacodynamics was compared with human insulin and insulin Lispro by experiment carried out on male Sprague-Dawley rats. The self-association of Pins was also determined. The results showed that the Mr of Pins was 6286.50, and the concentration of Pins was 0. 227 mg/ml. The experiment carried out on rats after intramuscular adminis tration of Pins showed that time needed for the lowest percentage of blood glucose concentration（BGC） to emerge was significantly less than that with human insulin（P〈0. 01）. Same observation was made for the time for BGC to reach again its level as before injection（P〈 0.01） ; and the minor percentage of BGC was almost same as human insulin. The self-association of Pins was further studied by size-exclusion chromatography with a longer retention time than that of human insulin,and so the monomeric property of Pins is stronger than that of human insulin. Pins is a promising novel rapid-acting analog of human insulin.

关 键 词：单体胰岛素 胰岛素类似物 自聚合性质 降血糖 

分 类 号：R9[医药卫生—药学]