米托蒽醌-胰岛素偶联物的制备及其性质初步研究  

Primary Studies on Synthesis and Properties of Mitoxantrone-Insulin Conjugates

作　　者：刘文胜[1] 张志荣[1] 黄园[1] 李炎[1] 

机构地区：[1]四川大学华西药学院药剂学教研室,成都610041

出　　处：《四川大学学报（医学版）》2004年第2期264-266,共3页Journal of Sichuan University(Medical Sciences)

基　　金：国家杰出青年基金 (批准号 3 992 5 0 3 9)资助

摘　　要：目的　探讨以胰岛素为抗癌药物导向载体的米托蒽醌 -胰岛素偶联物的合成与体外稳定性。方法　通过间隔基连接米托蒽醌和胰岛素 ;用核磁共振氢谱 (1 H NMR)、红外图谱 (IR)、质谱 (MS)、紫外图谱 (U V)等鉴定反应中间产物及偶联产物 ;考察偶联物在 37℃下不同 p H值缓冲液中及小鼠血浆中的降解情况。结果　偶联物药物结合率为 11.6 8% ,其在 37℃下 p H 2～ 8的磷酸盐缓冲溶液和小鼠血浆中稳定。结论　得到了稳定的米托蒽醌-胰岛素偶联物 。Objective Mitoxantrone-insulin conjugate was prepared through covalent bond, where mitoxantrone was an anticancer model drug and insulin acted as a vector. Its stability in vitro was discussed. Methods Spacer was used to join insulin and mitoxantrone. The intermediate and the final conjugate were characterized by infra-red spectroscopy (IR), 1H NMR, mass spectrometray (MS) and ultra-violet spectrophotometry (UV). Stability trials of the conjugate were carried out in different pH buffer solutions and mouse plasma at 37 ℃. Results Drug loading of the conjugate was 11.68%. The conjugate was stable in phosphate buffer solution of pH 2-8 and mouse plasma at 37 ℃. Conclusion Stable mitoxantrone-insulin conjugate was obtained to ensure further tumor targeted study in vivo.

关 键 词：胰岛素 导向载体 米托蒽醌 米托蒽醌-胰岛素偶联物 稳定性 

分 类 号：TQ460[化学工程—制药化工]