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栀子中熊果酸的制备和结构修饰研究
Studies on the Preparation and Structure Modification of Ursolic Acid from Gardenial
【作者】 廖晓峰;
【导师】 陈正行;
【作者基本信息】 江南大学 , 粮食油脂及植物蛋白工程, 2006, 博士
【摘要】 栀子是一种药食两用植物,在我国大面积种植,资源极为丰富,熊果酸是其主要药用成分。本文运用提取、纯化、脱色、化学富集和重结晶组合技术以及大孔吸附树脂吸附技术进行了从栀子中制备熊果酸的工艺研究,旨在得到熊果酸回收率和纯度较高的易于工业化的工艺流程,为栀子的深加工利用奠定基础。熊果酸膜透过性差,生物利用度低,应用受到限制。因此,通过熊果酸结构修饰,寻找生物利用度高、疗效更好的熊果酸衍生物类药物,有重要的临床价值及理论意义论文首先建立了熊果酸的检测方法,采用分光光度法快速测定栀子中熊果酸的含量,采用反相高压液相色谱方法准确测定栀子中熊果酸的含量。论文对采用溶剂回流法,从栀子中制备熊果酸的工艺进行了研究,通过正交实验得出最佳的浸提工艺条件为:栀子粉末粒度应控制在20目左右,以10 : 1的液固比在85.4℃回流提取2次,每次2.5小时,浸提溶剂乙醇浓度为90%。熊果酸浸出率是92.6%。研究了除杂剂和脱色剂对熊果酸含量及回收率的影响及栀子乙醇提取液中纯化熊果酸的工艺,利用不同pH条件下存在于提取液中各类物质的溶解性差异,有效地分离了熊果酸,避免了沉淀过程中乳化现象,提高了熊果酸的回收率,使熊果酸纯化过程简便和低成本。论文进行了用大孔吸附树脂吸附法制备熊果酸的研究,对影响吸附的因素进行了研究。通过溶剂梯度洗脱去除杂质,确定了最佳的洗脱体系,此洗脱体系能有效洗脱分离杂质,纯化富集熊果酸,该工艺较传统的溶剂回流法,产品纯度高,方法简便,适宜工业化生产,熊果酸产品纯度达到90.2%。对产品进行了结构鉴定,通过IR、EI-MS、NMR等现代化检测手段对产品进行了结构鉴定,证实产品为熊果酸。论文对熊果酸进行结构修饰,用化学法合成了熊果酸羟基和羧基的系列酯衍生物,对催化剂和反应条件进行了研究,对洗脱剂进行筛选,用硅胶色谱柱对产物进行纯化,用IR、EI-MS、NMR对合成产物进行了结构表征。通过动物毒性实验,证实合成的产品均无毒性。通过建立动物模型,研究栀子浸提物、熊果酸及其酯衍生物在小鼠化学性肝损伤的保护作用,初步研究了熊果酸药物的构效关系。
【Abstract】 Gardenia is a plant having medicine and food function and Ursolic is the main pharmacological component of it. the study in this assay is to use the technologies of abstraction, purification, decoloration, chemical accumulation and recrystal to separate Ursolic from gardenia. The aim is to get technics prosess which can get high callback ratio and high purification Ursolic. It is to establish the foundation of industrialization. The results indicate that the prosess is designed well and reaches the high level in the purification and callback ratio of the products. We modify the structure of Ursolic and synthesize ramification of the ursolic with the chemical method. Establishing the animal model to study the function of Ursolic and ramification of the Ursolic on Protective effects on the mice’s damaged liver cells .It is the spectrophotometer to mensurate quickly the amount of Ursolic in gardenia. We use HPLC to mensurate Ursolic accurately in gardenia.The ethanol which is low toxin and friendly to suroundings is used to soak and abstract Ursolic in gardenia. The best processing conditions are: the powder can pass 20目, the ratio of liquid and solid is 10:1,the temperature is 85.4℃,the times of abstraction is 2, the time is 2.5h and concentration of alcohol is 90%.Ursolic lixiviate rate is 92.6%.The influence of devide impurity and decolor reagent in the abstraction is studied.The prosessing technics is studied about the purification and accumulation of Ursolic. The best conditions are investigated for the first times.the product by purification is 80%, callback ratio is 90%.Macrofeticulaf Resin is used to absorb and abstract Ursolic in gardenia.the condition of absorb and wash has been researched, the optimization condition of absorb and wash is confirmed. the purification of Ursolic is 90. To identify the structure of the product, we use the modern detecting methods such as IR,EI-MS,NMRand so on. It is proved that the product is Ursolic.
【Key words】 Gardenia jasminodes Ellis; Ursolic acid; Isolation Purification Modification of Structure; the mice’s damaged liver cells;