【作者】 陈爽；

【导师】 张洪斌；

【作者基本信息】 合肥工业大学 ， 制药工程， 2018， 硕士

【摘要】 右旋糖酐是一类生物多糖,它具有很高的药用价值,并且因其具有大量的羟基基团很适合用于化学改造,其中氧化是化学改造中常用的手段之一。右旋糖酐铁就是右旋糖酐氧化后与铁络合的重要衍生物之一,在临床上广泛用于缺铁性贫血的治疗。本研究在针对低分子量右旋糖酐进行氧化研究的基础上探索了右旋糖酐铁的络合工艺。论文首先选取不同的试剂氧化低分子量右旋糖酐并对氧化过程和氧化结果进行了深入细致研究,揭示低分子量右旋糖酐的氧化机制,随后又对右旋糖酐铁络合工艺进行了优化研究,研究结果为右旋糖酐铁的工艺改进,以获得溶解性好,含量铁高的右旋糖酐铁产品打下了基础。具体研究结果如下:(1)论文首先研究了不同氧化条件对低分子量右旋糖酐氧化过程的影响,实验结果表明氧化反应的最适温度为55°C。随着次氯酸钠和溴化钠用量的增加,羧基含量有所增加。随着氧化程度的加深,氧化产物的理化性质会发生显著的变化,并伴有降解发生。研究发现羧基含量的增加和晶体结构的变化以及分子量的改变使得水溶性得到了改善;并且氧化产物仍具有良好的热稳定性。氧化过程中葡萄糖环会被打开并将C1上的羟基氧化,并且随着氧化程度的增加,氧化部位不再单一。(2)其次,对不同氧化剂氧化右旋糖酐进行了对比研究。在碱性氧化过程中在氢氧化钠氧化过程中,右旋糖酐的降解是不可避免的,羧基含量相对较高时,分子降解剧烈,产物结构也复杂不再均一。而次氯酸钠-溴化钠氧化过程可以通过控制氧化的p H,使得氧化只发生在1号碳的羟基上,得到的右旋糖酐氧化物糖环完整,只氧化长链末端的半缩醛羟基。并且有着适中的分子量和羧基含量。(3)论文最后对右旋糖酐络合反应进行了优化,结果表明,对于Mw为5400 Da的右旋糖酐,最适的络合比为右旋糖酐用量:三氯化铁用量等于1:1.8。Mw为1000Da右旋糖酐的最优络合比为右旋糖酐用量:三氯化铁用量等于1:2.5。Mw为3000Da右旋糖酐的最优络合比为右旋糖酐用量:三氯化铁用量等于1:2.0。Mw为7000Da右旋糖酐的最优络合比为右旋糖酐用量:三氯化铁用量等于1:1.7。不同重均分子量的右旋糖酐络合得到的右旋糖酐铁的含量也是有所差异的,重均分子量越小络合得到的铁含量越高,溶解性也越好。综上所述,本论文通过对低分子量右旋糖酐的氧化研究以及氧化机制的阐明,为右旋糖酐氧化改性提供了理论依据,为右旋糖酐铁的制备和工业化应用打下了基础。更多还原

【Abstract】 Dextran is a kind of biological polysaccharides which has high medical values.Dextran has abundant hydroxyl functional groups that can be chemically modified.The oxidation is one of the methods that are commonly used in chemical modification.Iron dextran is one of the important dextran derivatization.Iron dextran is also used in treating severe anemia or iron deficiency.This work studied the process of oxidation in order to improve the process of iron dextran preparation.The oxidation process used different types of reagents.A detailed study has been made on the oxidation process and products.This work laid the foundation for improving the quality of iron dextran.The complextion process was improved in order to get the iron dextran with high water solubility and high iron contents.The research results are as follows:(1)Firstly,the oxidation process of low molecular weight dextran was studied by us.The results showed that 55°C is suitable for oxidation.The content of carboxyl groups increased in the oxidation due to the increase of reaction rate as a result of the increased amount of Na Cl O and Na Br.Interestingly,both the amount of Na Cl O and Na Br can affect the contents of carboxyl groups.However,the impact of Na Cl O was more pronounced.The physical and chemical properties of oxidized dextran were significantly changed.What’s more,the size of oxidation products decreased.The introduction of carboxyl groups as hydrophilic groups and the damage of crystal structure could improve the solubility of dextran.Moreover,the research result indicates the oxidized dextran with good thermal stability.Glucose rings of oxidized dextran partly opened and contained carboxyl groups in C-OH.However,with the increases of oxidation degree,the complex mixture of products produced.(2)Secondly,the comparative study has been carried by using different types of reagents.Degradation of oxidized dextran during Na OH modification is inevitable,particularly in conditions where higher carboxyl contents were obtained;moreover,dextran can undergo different degradation reactions.The oxidation reaction is highly influenced by the p H adjustment.Less concentration of Na OH could be applied to avoid the significant degradation brought about by Na Cl O/Na Br modification.With this,carboxyl-modified dextran with specific oxidation of the aldehyde end group,moderate molecular size,and carboxyl contents can be obtained.(3)Lastly,the complextion process was improved.For low molecular weight dextran(Mw 5400 Da),the uitable reaction ratio of the mass of dextran and Ferric chloride is 1:1.8.For low molecular weight dextran(Mw 1000 Da),the suitable reaction ratio of the mass of dextran and Ferric chloride is 1:2.5.For low molecular weight dextran(Mw 3000 Da),the suitable reaction ratio of the mass of dextran and Ferric chloride is 1:2.0.For low molecular weight dextran(Mw 7000 Da),the suitable reaction ratio of the mass of dextran and Ferric chloride is 1:1.7.The iron dextran has different iron contents because of dextran has different molecular weight.The smaller the molecular weight of dextran can complexed with more iron,so the iron dextran with higher iron contents and good solubility.All in all,this study researched on the oxidation of low molecular weight dextran and the mechanism of oxidation process,provides a theoretical basis for the oxidation of dextran.It lays a foundation for the preparation and industrial application of iron dextran.更多还原