高分子前药预水解玉米朊-5-氟尿嘧啶的制备与表征  

Synthesis and Characterization of 5-Fluorouracil Macromolecule Prodrug Carried by Prehydrolyzed Zein Protein Polymer

作　　者：张帆 鲁传华 李国俊 汪佳凤 

机构地区：[1]合肥市口腔医院药剂科,安徽合肥230001 [2]安徽中医药大学药学院,安徽合肥230012 [3]安徽省中医药科学院药物化学研究所,安徽合肥230012

出　　处：《安徽化工》2017年第6期56-59,62,共5页Anhui Chemical Industry

摘　　要：目的:制备预水解玉米朊-5-氟尿嘧啶高分子前药,并对其进行表征。方法:采用α-氯乙酰氯与5-氟尿嘧啶反应制备3-α-氯乙酰-5-氟尿嘧啶,预水解玉米朊用异丙醇溶解后,再分批加入3-α-氯乙酰-5-氟尿嘧啶反应,制备预水解玉米朊-5-氟尿嘧啶高分子前药;用紫外分光光度计测定载药量,研究pH值、反应温度和反应时间三种制备条件对载药量和产率的影响。结果:以5-FU玉米醇溶蛋白前药的产率和载药量为评价指标,pH=9,反应温度为35℃,反应时间为4h的反应条件对前药的产率和载药量最优;产物的结构采用红外、紫外、粒径、Zeta电位和DSC进行了表征,证明5-氟尿嘧啶成功接到预水解玉米朊的末端。结论:该方法合成的5-FU玉米醇溶蛋白前药产率和载药量较高,可以作为合成制备预水解玉米朊-5-氟尿嘧啶高分子前药的方法。Objective:Synthesis and characterization of 5-Fluorouracil macromolecule prodrug carried by prehydrolyzed zein protein polymer. Methods:3-α-chloracetyl-5-Fluorouracil were synthesized by the reaction of the α-chloroacetyl chloride and 5-fluorouracil. Pre-hydrolyzed zein was dissolved in isopropanol and then reacted with 3-α-chloroacetyl-5-Fluorouracil,preparation of prehydrolyzed zeatin-5-Fluorouracil polymer prodrug. The loaded capacity and yield were measured by ultraviolet-visible spectroscopy,and the influence of reaction conditions such as pH value,reaction temperature and time was also discussed. The prodrug was characterized by infrared,particle size,Zeta potential and DSC. Results:The yield and drug loading of 5-FU zein prodrug were evaluated as the evaluation index,pH=9,reaction temperature 35℃,reaction time 4 h. The structure was characterized by IR,UV,particle size,Zeta potential and DSC,5-FU was successfully grafted on the end of prehydrolyzed Zein protein. Conclusion:The method has the advantages of high yield and drug loading of5-FU zeolytic protein synthesized by this method,and can be used as a method for the preparation of pre-hydrolyzed zeatin-5-Fluorouracil polymer prodrug.

关 键 词：5-氟尿嘧啶 玉米朊 高分子前药 

分 类 号：O626.41[理学—有机化学]