三种泵用胰岛素体外对抗等电点沉淀的研究  

In vitro study on resistance towards isoelectric precipitation of insulin products used for continuous subcutaneous insulin infusion

作　　者：汤智慧[1,2] 金杨红[3] 母义明[1] 崔晓飞[4] 李久旭[2] 梁潇[2] 李芳[2] 

机构地区：[1]解放军总医院内分泌科,北京100071 [2]解放军总医院药品保障中心,北京100853 [3]河南濮阳市油田总医院药剂科,河南濮阳457001 [4]总后勤部卫生部药品仪器检验所,北京100071

出　　处：《实用药物与临床》2015年第11期1362-1364,共3页Practical Pharmacy and Clinical Remedies

摘　　要：目的比较三种市售泵用胰岛素对抗等电点沉淀的效果。方法通过加入稀释盐酸的方法模拟p H值下降过程中,用高效液相色谱(HPLC)测定三种胰岛素(重和林R、诺和灵R、优泌林R)等电点沉淀情况。并采用高斯拟合的方法绘制出沉淀曲线,并得出三种胰岛素发生沉淀时的p H值。结果重和林R、诺和灵R和优泌林R在出现10%和90%沉淀时的p H值分别为6.52和5.82,6.85和6.00,6.68和5.94。结论重和林R开始出现沉淀的p H值最低,对抗等电点的作用最强,其次是优泌林R,诺和灵R最差。胰岛素等电点会引起胰岛素构象改变发生沉淀,阻塞胰岛素泵,进而引起血糖控制不佳。但本研究仅在体外比较了胰岛素对抗等电点沉淀的不同,与临床中胰岛素泵堵塞之间作用的机制仍需进一步研究。Objective To compare the resistance towards isoelectric precipitation of three insulin products used for continuous subcutaneous insulin infusion. Methods The degree of isoelectric insulin precipitation of recombinant human insulin injection（ Sci Lin R）,Biosynthetic human insulin injection（ Novolin R）,and recombinant human insulin injection（ Humulin R） was examined by HPLC in the simulation of reducing p H with addition of diluted HCl. The modified Gaussian model was used to superimpose the percentage of precipitated insulin versus p H. Results The p H value at the time point of 10% and 90% precipitation occurred was 6. 52 and 5. 82 for Sci Lin R,6. 85 and 6. 00 for Novolin R,6. 68 and 5. 94 for Humulin R. Conclusion Resistance towards isoelectric precipitation is highest for Sci Lin R,while the p H value when the precipitation occurred is lowest. The resistance towards isoelectric precipitation of Novolin R is lowest. Isoelectric precipitation can alter the pharmacokinetic properties of the insulin and lead to the occlusion of the infusion catheter,result in poor control of blood sugar. The article compared the differences in resistance towards isoelectric precipitation of different insulin products,and the mechanism in the resistance and the formulation of catheter occlusion requirefurther studies.

关 键 词：胰岛素泵 等电点沉淀 高效液相色谱法 

分 类 号：R927.2[医药卫生—药学] O657.72[理学—分析化学]