【作者】 成朋；

【导师】 刁兆玉；

【作者基本信息】 山东师范大学 ， 物理化学， 2011， 硕士

【摘要】 表面活性剂分子可以形成多种缔合结构,溶致液晶和微乳液是近年来应用较为广泛两种表面活性剂分子聚集体。溶致液晶具有相态丰富、结构可调控等特殊的优点,因而在食品、药品、材料合成、家具产品等领域受到越来越多的关注;微乳液是由表面活性剂、油、助表面活性剂和水形成的各向同性,外观透明或半透明的热力学稳定体系。微乳液具有粒径小、透皮能力强、良好的增溶性和靶向性,因而被广泛应用于制药工程、纳米材料的制备、农药喷洒、燃料、化妆品及三次采油等领域。本论文从扩展溶致液晶和微乳液在药物载体方面应用角度出发,首先,选取了几种低毒性的非离子表面活性剂和大分子嵌段共聚物,并研究了这几类表面活性剂以及其复配体系的溶血性,在此基础上分别绘制了三个溶致液晶体系和三个微乳液体系的拟三元相图。其次,利用偏光显微镜和流变学方法等手段考察了C₁₂APG/油酸/0.9%生理盐水体系、C₁₂APG/油酸/水体系以及C₁₂APG/0.9%生理盐水/香叶醇体系三个溶致液晶体系溶致液晶的形成、动态流变性质、稳态流变性质以及体系的相态展开研究,得到创新性结果;利用电导率法和循环伏安法等手段考察了Tween80/异丙醇/丁酸乙酯/生理盐水体系和Tween80/EPE/异丙醇/丁酸乙酯/生理盐水体系以及Tween80/C₁₂APG/异丙醇/丁酸乙酯/生理盐水体系的相行为及其相结构转变。进一步研究了以上体系作为药物载体在药物控释方面的应用。以上工作在表面活性剂的实际应用和基础理论方面具有重要的参考价值和指导意义。论文包括如下五章内容:1.表面活性剂聚集体溶致液晶和微乳液的性质本章中系统的阐述了溶致液晶（立方状、六角状和层状）和微乳液（油包水型、双连续型和水包油型）的性质和应用以及表面活性剂的复配。烷基糖苷类和聚氧乙烯类表面活性剂已成为药物传输系统的重要成分,但是以药物载体为目标的烷基糖苷类溶致液晶和聚氧乙烯类微乳液的报道相对较少,因此在论文的三、四章我们展开了对烷基糖苷类溶致液晶和聚氧乙烯类微乳液的相态及性质的研究。2.表面活性剂溶血作用以及低溶血表面活性剂体系的探索本章首先介绍了各类表面活性剂的溶血作用,介绍了具体的溶血试验和溶血机理以及抗溶血和降溶血,然后通过具体的实验以新鲜的兔血为对象研究了烷基糖苷类和聚氧乙烯类表面活性剂及其复配体系的溶血作用。实验结果表明:1、相同浓度下吐温80和大分子嵌段共聚物都使烷基糖苷的溶血性数值降低,但从总的溶血趋势看,吐温使烷基糖苷的溶血作用趋于平和而大分子嵌段共聚物使烷基糖苷的溶血趋势更加明显;2、当吐温和大分子嵌段共聚物同时作用于烷基糖苷时,吐温对烷基糖苷的影响起主导作用;3、C₁₂APG、EPE（Al-4）以及吐温80在低浓度下溶血活性都相对较低,并且都属于非离子类型的表面活性剂,因此可以考虑将C₁₂APG、EPE（Al-4）以及吐温80或者其复配体系应用于制药工业。3.非离子表面活性剂烷基糖苷体系的液晶相行为及流变性质本章以香叶醇油酸为药物辅料,开展了对C₁₂APG/油酸/0.9%生理盐水体系、C₁₂APG/油酸/水体系以及C₁₂APG/0.9%生理盐水/香叶醇体系三个溶致液晶体系相态和流变性质的研究。首先在37℃绘制了C₁₂APG/油酸/0.9%生理盐水体系、C₁₂APG/油酸/水体系以及C₁₂APG /0.9%生理盐水/香叶醇体系三个溶致液晶体系拟三元相图,然后通过流变技术和偏光显微镜对三个体系展开了流变性质的研究。研究表明三个体系所形成的溶致液晶都为层状液晶。4.非离子表面活性剂Tween80体系的微乳相行为及其相结构本章以丁酸乙酯为油相以异丙醇为助表面活性剂,开展了对Tween80/异丙醇/丁酸乙酯/生理盐水体系和Tween80/EPE/异丙醇/丁酸乙酯/生理盐水体系以及Tween80/C₁₂APG/异丙醇/丁酸乙酯/生理盐水体系三个微乳液体系相行为及其相结构转变的研究。首先在37℃绘制了Tween80/异丙醇/丁酸乙酯/生理盐水体系和Tween80/EPE/异丙醇/丁酸乙酯/生理盐水体系以及Tween80/C₁₂APG/异丙醇/丁酸乙酯/生理盐水体系三个拟三元相图,然后通过电导率法和循环伏安法对其相结构转变进行了研究。研究表明:微乳结构在较低盐水浓度下形成油包水型微乳,在中等盐水浓度转变为双连续型结构,在高盐水浓度连续转变为水包油型结构。5.姜黄素在烷基糖苷液晶体系以及Tween80微乳体系中的释放行为溶致液晶和微乳液体系具有热力学稳定,生物可降解性,类似于生物膜,包封和缓释药物并且能够保护被包封的药物等优点,因此,它们作为药物载体的研究引起越来越多的人们的大关注。本章中我们分别用三种溶致液晶和三种微乳液作为药物载体,以姜黄素作为被载药物进行了药物载体方面的研究。研究表明:六种体系都对姜黄素产生了不同程度的缓释。更多还原

【Abstract】 Surfactant molecules can form a variety of associative structure, lyotropic liquid crystalline phase (LLC) and microemulsions are widely used in recent years. As the abundant of structures, LLC is studied widely and applied in several fields, such as synthesis, houseproduction, foods, pharmaceutics, and so on. Microemulsions are clear, thermodynamically stable, isotropic mixtures of oil, water and surfactant, frequently in combination with a cosurfactant. Microemulsions which have small particle size, penetration ability, good solubilization and targeting, are widely used in pharmaceutical engineering, nano-materials preparation, pesticide spraying, fuel, cosmetics and enhanced oil recovery and other fields. In order to expand the application of LLC and microemulsions as the drug delivery system, we select several non-ionic surfactants and block copolymer molecules which have low toxicity, and then studied the hemolytic of these types of surfactants and their compounded system. On this basis, the pseudo-ternary phase diagram of the three lyotropic liquid crystalline systerms and the three microemulsions systerms was drawn based on experimental data. In order to study the steady and dynamic rheological properties of lyotropic crystalline phases, the three lyotropic liquid crystalline phase systerms of C12APG/oleic acid/physiological saline, C12APG/oleic acid/water and C12APG/physiological saline/gernaniol have been observed, with the aid of polarizing optical microscopy and rheological techniques. The structural transformation of the Tween80/isopropanol/ethyl butyrate/physiological saline system, Tween80/EPE/isopropanol/ethyl butyrate/physiological saline system and the Tween80/C12APG/isopropanol/ethyl butyrate/physiological saline system were studied by cyclic voltammetric and conductivity measurements. Furthermore, application in drug carrier study of these systerms has been investigation. All these results will enrich the surfactant researches both theoretically and practically. In details, the thesis includes five chapters as following:1. Properties of lyotropic liquid crystalline and microemulsions.The properties and applications of lyotropic liquid crystals, lamellar, hexagonal and cubic phases are summarized. The structure and applications of microemulsion were also overviewed. Significance and various types of mixed surfactants systems were introduced Study on lyotropic liquid crystals and microemulsions of alkypolyglucosides and polyoxyethylene surfactants for drug delivery system purpose is rather limited. Therefore, the main properties of lyotropic liquid crystals and microemulsions systems have been studied in the third, fourth parts of the thesis.2. Hemolytic Action of Surfactants and the exploration of low-hemolytic systerms.In this chapter we first introduce the hemolytic action of various surfactants and the hemolysis test, the mechanism of hemolysis, the resistance to hemolysis and the descending to hemolysis. We studied the hemolytic action of alkypolyglucosides and polyoxyethylene surfactants using fresh rabbit blood. The results show: First, at the same concentration, both Tween80 and EPE can reduce the hemolytic action of APG, but from the general trend, Tween80 makes the hemolytic action to be calm, and EPE makes the hemolytic action to be clear. Second, when Tween80 and EPE were coexist, Tween80 plays a leading role. Tween80, EPE and APG are all nonionic surfactant, at low concentration, they all play low hemolysis activity, so we can consider to use them in pharmaceutical industry.3. Phase behavior and rheological properties of liquid crystalline phases formed in nonionic surfactant APG systems.In this chapter the Phase behavior and rheological properties of the three lyotropic liquid crystalline phase systerms of C12APG/oleic acid/physiological saline, C12APG/oleic acid/water and C12APG/physiological saline/gernaniol have been observed using oleic acid and gernaniol as accessories. The pseudo-ternary phase diagrams of C12APG/oleic acid/physiological saline, C12APG/oleic acid/water and C12APG/physiological saline/gernaniol systerms were drawn at 37oC, and then they were studied by the aid of polarizing optical microscopy and rheological techniques. The results show that the three lyotropic liquid crystallines were all lamellar.4. Phase behavior and the structural transformation of microemulsions in nonionic surfactant Tween80 systems.In this chapter the Phase behavior and the structural transformation of the three microemulsions of Tween80/isopropanol/ethyl butyrate/physiological saline system, Tween80/EPE/isopropanol/ethyl butyrate/physiological saline system and the Tween80/C12APG/isopropanol/ethyl butyrate/physiological saline system have been observed. The pseudo-ternary phase diagrams of Tween80/isopropanol/ethyl butyrate/physiological saline system, Tween80/EPE/isopropanol/ethyl butyrate/physiological saline system and the Tween80/C12APG/isopropanol/ethyl butyrate/physiological saline system were drawn at 37oC, then the structural transformation of them were studied by cyclic voltammetric and conductivity measurements. The results show that the structural transition from a water-in-oil microemulsion at low brine content to a bicontinuous structure at intermediate brine content and a structure of oil-in-water at high brine content happened completely continuously.5. The release kinetics of curcumin in APG lyotropic liquid crystals and Tween80 microemulsions.Both lyotropic liquid crystals and microemulsions have many characteristics: thermodynamic stability, similarity to bio-membrane, embedding and long-time releasing drugs, protecting the drugs in it and so on. so they have attracted increasing interests as drug carrier. The studies on lyotropic liquid crystals and microemulsions as drug delivery systems are involved in this chapter. The results show that both the lyotropic liquid crystals and microemulsions as carriers produced sustained release to curcumin.更多还原