结肠定位给药系统载体的设计、合成及降解性能的研究  

Studies on design,synthesis and biodegradation of carrier for colon-site specific drug delivery system

作　　者：陈建海[1] 陈清元[1] 沈家瑞[2] 罗奇志[1] 

机构地区：[1]第一军医大学南方医院药学部,广东广州510515 [2]华南理工大学高分子材料系,广东广州510641

出　　处：《药学学报》2004年第3期223-226,共4页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金课题资助项目(3 9970 876)

摘　　要：目的　设计与合成结肠定位给药系统新型载体 ,探讨其模拟结肠环境下降解特性与载体结构关系。方法用甲基丙烯酸羟乙酯 (HEMA)、甲基丙烯酸甲酯 (MMA)和甲基丙烯酸 (MAA)为单体 ,对二乙烯基偶氮苯 (DVAB)为偶联剂 ,偶氮二异丁腈 (AIBN)为引发剂 ,合成了聚甲基丙烯酸羟乙酯 甲基丙烯酸甲酯 甲基丙烯酸 [P(HEMA MMA MAA) ]三元偶氮共聚物 ,用紫外、红外、核磁共振谱进行结构表征。测定该聚合物溶胀性能 ,建立体外厌氧菌条件下模拟结肠内容液环境模型。用GPC ,DSC与SEM比较聚合物降解前后 ,分子量、结构与形态变化。结果　载体材料溶胀指标Q随材料中HEMA和MAA含量增加而增加。该材料在模拟结肠内容液环境下 ,发生降解程度与材料中三组分相对比例直接相关。结论　合理调节材料中HEMA ,MMA和MAA三组分比例 。Aim To design and synthesize a novel vector for colon-site specific drug delivery system and investigate the relationship between the biodegradation properties and composition of materials in the simulated colon fluid. Methods The azocopolymer P(HEMA-MMA-MAA) was synthesized using 2-hydroxy-ethylmethacrylate (HEMA), methyl methacrylate (MMA) and methacrylic acid (MAA) as comonmer, azobisisobutyronitrilel (AIBN) as initiator, cross-linked with divinylazobezene (DVAB). The chemical structure of the synthesized series of azocopolymer is examined by UV, FTIR spectroscopy and nuclear magnetic resonance data. Their swelling behavior is evaluated by the swelling equilibrium parameter Q , the biodegradation tests of the materials were carried out at physiologically relevant buffer designed to mimic the colon environment. The biodegradation properties were assessed using the differential scanning calorimeters (DSC) and gel permeation chromatography (GPC) and the morphology on the surface of materials before and after degradation was observed by scanning electron microscopy (SEM). Results The swelling equilibrium parameter Q increased with increasing the contents of HEMA and MAA in the materials. The degradation behavior was relevant to the ratio of three components in the copolymers. Conclusion This materials may become a good carrier for the colon-site specific drug delivery system if the contents of commoners HEMA, MMA and MAA are adjusted reasonably.

关 键 词：结肠定位给药系统 载体设计 系统合成 降解性能 结肠疾病 

分 类 号：R574.62[医药卫生—消化系统]