载胰岛素海藻酸盐微球的生理条件解聚  

A study on disaggregating method of insulin-loaded alginate microspheres

作　　者：黄可可[1] 薛伟明[1] 刘袖洞[2] 马小军[2] 

机构地区：[1]西北大学化工学院,陕西西安710069 [2]中国科学院大连化学物理研究所生物技术部,辽宁大连116023

出　　处：《西北大学学报（自然科学版）》2006年第6期924-928,共5页Journal of Northwest University（Natural Science Edition）

基　　金：国家自然科学基金资助项目(50373046);中国科学院知识创新工程领域前沿基金资助项目(K2002A2)

摘　　要：目的建立载胰岛素海藻酸盐微球的解聚方法。方法以柠檬酸-柠檬酸钠缓冲液为微球解聚介质,通过正交设计对微球解聚的影响因素进行显著性分析和统计分析。结果缓冲液pH值及柠檬酸根离子强度M是影响微球解聚速率的显著因素。当pH>5.6时,微球解聚速率显著增大而胰岛素相对活性显著下降;M能显著影响微球解聚速率但对胰岛素相对活性无显著影响。采用pH为5.6,M为0.153 mol/L缓冲液对微球解聚并测定被包封胰岛素活性,信度α=0.05,α=0.1时药物相对活性分布区间为(89.13,91.63)和(89.35,91.41)。结论在有效保持蛋白质药物活性的前提下,建立了使海藻酸盐微球完全、快速解聚的方法,为定量研究脉冲电场工艺条件对微球中蛋白质药物活性的影响提供了方法支持。Aim Establishment of a method to chemically disaggregate insulin-loaded alginate microspheres in order to make a quantitative assessment of insulin activity on which factors during microsphere preparation influence. Methods With the disaggregating solution composed of citric acid/sodium citrate buffer, the significance analysis of factors influencing the disaggregating rate of alginate microspheres and relative activity of insulin was carried out through orthogonal experiments. The influence of significant factors on disaggregating rate and relative activity of insulin were studied respectively. Finally, the statistic analysis of relative activity of insulin loaded in microspheres after disaggegation was conducted. Results The pH value of buffer and the citrate ionic strength M influenced significantly on the disaggregating rate of microspheres. When pH 〉 5.6, the disaggregating rate significantly increased whereas the activity decreased obviously. With the increase of M, the disaggregating rate was increase obviously whereas the relative activity of insulin hardly changed. After disaggregated by the buffer composed of pH = 5.6 and M = 0. 153 mol/L, the statistic analysis showed that when confidence level was a =0. 05, and a =0. 1 ,confidence interval of relative activity of insulin loaded in microspheres could be （89. 13,91.63 ） and （89. 35,91.41 ） correspondingly, suggesting that there is good repeatability and reliability for this chemical aggregating method. Conclusion With effectively keeping drug activity, a method to disaggregating insulin-loaded alginate microspheres rapidly and sufficiently was established which provided facility to quantitatively estimate the factors influencing on protein activity during preparation of protein-loaded microspheres.

关 键 词：胰岛素 海藻酸盐 微球 解聚 活性 

分 类 号：TQ46[化学工程—制药化工] R944.9[医药卫生—药剂学]