【作者】 孟舒献；

【导师】 冯亚青；

【作者基本信息】 天津大学 ， 应用化学， 2005， 博士

【摘要】 慢性肾功能衰竭是一种以临床中毒症状为特征的严重疾病,病因主要是体内积蓄了大量的毒素—尿素、肌酐和尿酸。研制高效、广谱、副作用小的口服吸附剂用于延缓发病进程具有重要意义。本文以纤维素为载体,开发了一系列纤维素衍生物:氧化纤维素(DAC)、包醛氧纤维素(CDAC)、环氧化纤维素(EC)、交联纤维素(CLC)、硝基纤维素(NC)和纤维素接枝环糊精(CDGC),用于清除体内三种毒素。采用正交实验等方法,以α-纤维素为原料,高碘酸钠为氧化剂,合成氧化纤维素。在反应温度45℃, pH=2,纤维素与高碘酸钠质量比为1/2,反应时间为4h时得到醛基含量84%的氧化纤维素。氧化纤维素经过明胶和壳聚糖包覆处理得到包醛氧纤维素。通过吸附动力学曲线、一级吸附速率方程和二级吸附速率方程详细研究了各种条件下氧化纤维素和包醛氧纤维素对尿素的吸附能力,结果表明吸附过程可分为两个阶段:8 h以前符合一级吸附速率方程,8 h以后符合二级吸附速率方程,最大吸附容量可达59.22 mg/g。用环氧氯丙烷和乙二醇二缩水甘油醚作为交联剂制备环氧化纤维素和交联纤维素。通过条件筛选,确定了环氧基含量达到最大的反应条件:纤维素/环氧氯丙烷/30%NaOH(g/mL/mL)=1/6/8,反应温度40℃,反应时间2.5h。研究了环氧化纤维素和交联纤维素对肌酐的吸附作用,结果表明环氧化基含量2.53mmol/g的环氧化纤维素对肌酐的吸附容量为1.1mg/g,交联纤维素的吸附容量为5.12mg/g。以环氧化纤维素为载体,接枝上3,5-二硝基苯甲酰氯、β-环糊精和甲基β-环糊精,合成了硝基纤维素、纤维素接枝β-环糊精和纤维素接枝甲基β-环糊精三种聚合物,分别利用硝基苯环与肌酐形成络合物,环糊精对尿酸的包合作用,分别达到吸附肌酐和尿酸的目的。模拟人体环境,将合成的系列纤维素衍生物放入成纤维细胞中,通过MTT实验,观察到纤维素衍生物对细胞具有一定程度的刺激性。建立慢性肾功能衰竭模型,将包醛氧纤维素通过灌胃方式给药,发现包醛氧化纤维可显著降低大鼠的肌酐和尿酸浓度,起到较好的治疗效果。更多还原

【Abstract】 Chronic renal failture(CRF) is a serious disease with clinical poisonous symptom,The pathogeny is that many toxins such as urea, creatinine and uric acid are saved inhuman body. The development of novel oral adsorbents with high adsorption capacity,broad spectrum and less side effect is significant for delaying disease progress. In thispaper a series of cellulose derivatives were developed with cellulose as carrier toremove three toxins. These derivatives are 2,3-dialdehyde cellulose(DAC), coated2,3-dialdehyde cellulose(CDAC), epoxycellulose(EC), cross-linked cellulose(CLC),nitrocellulose(NC) and cyclodextrin grafted cellulose (CDGC).The orthogonal experiments study on oxidizing α-cellulose to DAC with sodiumperiodate (NaIO4) was carried out. The principal factors influencing the aldehydegroup content of DAC were found out and the better oxidation conditions were as thefollowing: The pH was 2. The reaction temperature was 45℃. The weight ratio ofcellulose to NaIO4 was 1:2. The reaction time was 4h. The high aldehyde groupcontent was obtained under above condition. The CDAC was prepared by coatingwith gelatin and chitosan. The kinetic curves of adsorption, the first-order and thesecond-order kinetic models were used to describe the adsorption ability of DAC andCDAC for urea under various conditions. The adsorption for urea has two steps. Oneis first-order kinetic model before 8h, Another is second-order kinetic model after 8h.The most high adsorption capability is 59.22 mg/g.The synthesis of epoxycellulose and cross-linked cellulose from epoxychloropropane (ECH) and ethanodiol diglycidyl ether ( EGDE ) in the presence ofalkali medium were described. The principal factors affecting the epoxy group contentwere found out and the best conditions were as the following: the weight ratio ofcellulose, epoxy chloropropane and 30%NaOH(g/mL/mL) was1:6:8, The reactiontemperature was 40℃. The reaction time was 2.5h. The adsorption capacity forcreatinine was observed with epoxycellulose and cross-linked cellulose. Theadsorption capabilities are 1.1mg/g and 5.12mg/g, respectively.NC, β-cyclodextrin(β-CD) grafted cellulose, and methyl-β-cyclodextrin graftedcellulose were synthesized from EC carrier by grafting with 3,5-dinitrobenzoicchloride(DNBC-Cl), β-CD and methyl-β-CD. Nitrobenzene ring and creatinineformed complex. The CDs had inclusion for uric acid. Thus creatinine and uric acidwere adsorpted.The cellulose derivatives were put into fibroblast for the cytotoxicity experimentto imitate the human body environment. The MTT method assay showed that abovederivatives had hormesis.The rats were treated with CDAC by input-stomach after the chronic renal failurerat model was established. The creatinine and uric acid were obviously reduced in thetreatment rats model with CDAC. The CDAC had good curing effect.更多还原