【作者】 李伶；

【导师】 郭锦棠；

【作者基本信息】 天津大学 ， 材料学， 2005， 硕士

【摘要】 针对目前pH敏感性水凝胶制备和应用方面存在的对外界刺激响应慢和力学性能差等问题,本论文进行了pH敏感性水凝胶的研究开发,以制备高敏感性、力学性能优良的pH敏感性水凝胶为目的,通过自由基引发的溶液聚合和反相悬浮聚合分别制备了两种不同的水凝胶,并对它们的pH敏感性进行了较为深入的研究,同时对其用于药物控制释放进行了初步探索。以磺胺嘧啶(SD)为原料制备了磺胺单体(SDM),将其和N-乙烯基吡咯烷酮(NVP)进行自由基引发的溶液聚合,合成了具有pH敏感性的共聚物水凝胶P(SDM/NVP)。讨论了反应温度、反应时间、原料配比、交联程度等因素对水凝胶pH敏感性的影响;对产物采用IR和H-NMR表征以确定单体的特征结构;进行药物吸附与释放测试。结果表明:反应温度为85℃,反应时间进行10h,水凝胶的溶胀性最好,而随着磺胺单体在水凝胶中比例由20%增大至30%,水凝胶的pH敏感性得到加强,交联剂的加入要适中,占单体总质量的1%为最好。将最佳条件下制备的水凝胶用于药物水杨酸和氯霉素的释放实验时,释放结果显示:于人体体温环境(37℃)时,在肠液(pH7.4)条件下释放效果明显好于胃液(pH1.4)条件。选用衣康酸(IA)为功能单体,将其和丙烯酰胺(AM)进行自由基引发的反相悬浮聚合,制备出具有pH敏感性的水凝胶微球P(IA/AM)。讨论了加料方式、分散剂的种类与用量、分散介质的种类与用量、单体浓度与配比、交联剂的用量等因素对水凝胶微球成球性能和外观的影响;探讨了原料配比、交联程度等因素对水凝胶微球pH敏感性的影响;对产物采用IR和SEM表征以确定共聚物微球的特征结构和表观形态;进行药物吸附与释放测试。结果表明:以逐步滴加的方式,span60为分散剂,水油体积比控制在15:50,分散剂用量占单体总质量的2.5%,单体IA/AM(摩尔比)为1:5.5,在环己烷中对衣康酸和丙烯酰胺进行聚合能制备出溶胀性最好的凝胶微球;在微球溶胀度与表观形态两者兼顾时交联剂对单体存在最佳质量配比9.4～12.5%;随着衣康酸单体在水凝胶中比例的增大,水凝胶的pH敏感性得到加强。将最佳条件下制备的水凝胶微球用于药物水杨酸和氯霉素的释放实验时,实验结果显示:在人体体温环境(37℃)时,药物在肠液(pH7.4)条件下释放量明显大于在胃液(pH1.4)条件下的释放量。更多还原

【Abstract】 The main topic discussed in this thesis was preparation and characterization ofpH-sensitive hydrogel to resolve the problems in this kind of hydrogels’ preparationand application, such as slow responsibility and fragile mechanical strength. Tosynthesis fast-acting pH-sensitive hydrogels with high mechanical property, twodifferent kinds of pH-sensitive hydrogels were prepared by way of solutionpolymerization and inverse suspension polymerization induced by free radical. On theother hand, their pH-sensitivity was discussed in a deeper degree and their appliancein drug controlled delivery system (DCDS) was also investigated preliminarily in thisthesis.Firstly, sulfadiazine monomer (SDM) prepared from sulfadiazine (SD), wascopolymerized with N-vinylpyrrolidone (NVP) by free radical induced solutionpolymerization to form pH-sensitive copolymer hydrogel P(SDM/NVP). In this thesis,a large number of different factors which influence hydrogels’ pH sensitivity werediscussed such as reaction temperature, reaction time, ratio of different monomers andcrosslinked degree;and products were characterized by IR and H-NMR to affirmmonomer’s special structure;also drug absorbance and delivery experiments werecarried out to investigate the feasibility of prepared hydrogels used in DCDS: drug(salicylic acid and Chloramphenical) release experiments in vitro, P(SDM/NVP)prepared in optimal conditions as drug carrier, were processed at pH 1.4 (close tostomach’s pH) and pH7.4 (close to intestine’s pH) respectively at 37℃ (close tohuman’s body temperature). The results of the experiments above showed thatP(SDM/NVP) hydrogel prepared for 10h at 85℃ had the most desirable swellingproperties, and that hydrogels appeared more prominent pH-sensitivity withincreasing of SDM concentration from 20% to 30%, and that amount of crosslinkersshould be 1% to achieve appreciable mechanical property, and that drugs releasedmuch rapidly in pH7.4 buffered solution than in pH1.4 one.Secondly, functionalized monomer-itaconic acid (IA) was chose to copolymerizewith acrylamide (AM) by free radical induced inverse suspension polymerization toform pH-sensitive hydrogel P(IA/AM) microparticles. In this thesis, a lot of differentfactors which influence microparticles’ appearance and glomeration were studied suchas modes of adding materials, types and amount of dispersants, kinds and amount ofdispersion media, concentration and ratio of monomers and amounts of crosslinkers;and factors which affect microgels’ pH sensitivity were also discussed in this thesissuch as ratio of different monomers and crosslinked degree;and polymers werecharacterized by IR and SEM to affirm hygrogel’s special structure and particles’appearance;also drug absorbance and delivery experiments were carried out toinvestigate the feasibility of prepared microgels used in DCDS: drug (salicylic acidand Chloramphenical) release experiments in vitro, P(IA/AM) prepared in optimalconditions as drug carrier, were processed at pH 1.4 (close to stomach’s pH) andpH7.4 (close to intestine’s pH) respectively at 37 ℃ (close to human’s bodytemperature). The results of the experiments above showed that P(IA/AM)microparticles prepared on the condition of adding materials step by step, 2.5%span60 (/wmonomers) as dispersant, w/o (V/V)as 15:50, IA/AM (mol/mol) as 1:5.5,cyclohexane as dispersion media had the most desirable swelling properties, and thatmicrogels appeared more prominent pH-sensitivity with increasing of IAconcentration, and that amount of crosslinkers to monomers should be in a range9.4~12.5 % (w/w) to achieve excellent swelling properties and appreciableappearance, and that drugs released more in pH7.4 buffered solution than in pH1.4one.更多还原