双糖密度半乳糖基胰岛素的合成及肝靶向性初步研究  

Preparation of Galactosyl Insulin with Double Saccharide Density and a Study of Its Hepatic Targeting Property

作　　者：梁正路[1] 付騂 管昌田[1] 钟裕国[1] 李云春[1] 

机构地区：[1]华西医科大学附属第一医院,成都610041

出　　处：《华西医科大学学报》2000年第1期1-4,共4页Journal of West China University of Medical Sciences

基　　金：国家重点科技项目 (攻关 )计划资助 !(编号 96-90 1-0 1-3 4 )

摘　　要：为有效提高半乳糖基化合物的糖密度以增加其趋肝性 ,作者采用分枝化合物 3,5 -二羟基苯甲酸为偶联桥 ,将半乳糖与胰岛素偶联 ,得到糖密度较单链桥法高一倍的双糖密度半乳糖基胰岛素 ,而后用 1 31 分别标记双糖密度半乳糖基胰岛素、单链桥偶联半乳糖基胰岛素和普通胰岛素 ,通过家兔体内示踪实验对比研究它们的肝靶向性。结果显示 :双糖密度偶联物的趋肝性最大 ,单糖偶联物次之 ,普通胰岛素最差 ,其肝最大摄取率分别为5 9.5 %、43.8%和 2 1 .5 %。而 3种标记物的鸡全身显像皆未见肝脏特异性浓聚 ,从而证明以分枝化合物为偶联桥 ,可以有效地提高半乳糖基化合物的糖密度 ,大幅度提高其趋肝性。This study was intended to improve the technical procedure so as to increase the saccharide density of galactosyl recombinant insulin and elevate its liver targeting property. Using a branched compound 3,5 dihydroxy benzoic acid as the base of a conjugating bridge, the authors prepared a new double galactosyl recombinant insulin, whose saccharide density being two times as high as that of galactosyl recombinant insulin. The double gal insulin conjugate, gal insulin conjugate and original insulin were labeled with 131 Ⅰ, and then the three kinds of 131 I labeled compounds were tested in rabbit whole body imaging to measure their properties of liver targeting. The peak values of rabbit liver concentration for double gal insulin, gal insulin and original insulin were 59.5%, 43.8% and 21.5%, respectively. These results demonstrate that for elevating the liver targeting property of galactosyl recombinant compounds, a branched agent like 3,5 dihydroxyl benzoic acid can be adopted as an effective medium.

关 键 词：肝受体显像 肝靶向药物 无唾液酸 糖蛋白受体 

分 类 号：R914[医药卫生—药物化学]