【作者】 柴传柯；

【导师】 虞心红； 殷海峰；

【作者基本信息】 华东理工大学 ， 制药工程， 2012， 硕士

【摘要】 牛磺熊去氧胆酸(TUDCA)属于胆酸类药物,具有溶解胆固醇结石和保护肝细胞等多项生理功能。本文在文献阅译和工艺原理分析的基础上,尝试与评估了合成TUDCA的各条工艺路线。研究了以熊去氧胆酸(UDCA)为原料,首先在三乙胺作用下与氯甲酸苯酯形成羧酸-碳酸苯酯的混酐,再与牛磺酸钠发生氨解反应合成TUDCA的工艺。确定了较优合成工艺过程为：1当量UDCA溶解于4倍质量体积的四氢呋喃中,加入1.5当量的三乙胺,在0～5℃下滴加1.5当量的氯甲酸苯酯,10℃以下反应60～80min,过滤,滤液降温在5℃以下滴加入2当量的牛磺酸钠(1.27mo1/L)水溶液,在15℃反应100～160min,盐酸酸化之后浓缩,加乙醇溶解之后过滤,滤液浓缩即可得到收率为75%的TUDCA。在小试研究基础上,设计了工艺流程、操作方法、物料回收套用措施等。为生产工艺流程及操作的进一步设计优化提供了良好的理论依据和可参考的工艺参数。更多还原

【Abstract】 Tauroursodeoxycholic acid(TUDCA) is a kind of bile acid drugs. It has many physiological functions such as dissolved cholesterol stone and protective liver cell and so on.Based on the relevant literature and the analysis of the principle of reactions, several synthesis routes are collected and the synthesis route that is suitable for industrial production is selected. In this paper, the TUDCA was synthesized by aminolysis of sodium taurine with carboxy-carbonate mixed anhydride prepared by reacting UDCA with phenyl chloroformate at the present of triethylamine. substitution. The influences of anhydride reaction and aminolysis reaction were investigated in molar ratio, temperature, time and so on. on. Optimum reaction conditions were selectred as follows:1 equivalent UDCA dissolved in four times,in the size of the quality, tetrahydrofuran. Then joined 1.5 equivalent of triethylamine.1.5 equivalent of the chlorine acid benzene ester was droped in the solution should be keeped at 0-5℃. This solution was keeped in 10℃for 60-80min,then filter. The filtrate under 5℃droped join 2 equivalent of taurine sodium aqueous solution(1.27mol/L), then keeped in 15℃for 100-160min. The alkaline liquor was acidize by hydrochloric acid. The absolute ethyl alcohol dissolve the residue that get by moved water in reduced pressure distillation. After filter, the ethyl alcohol was moved out from filtrate in reduced pressure distillation. According to the conditions described,TUDCA yields 75%.Based on the results of experiments, the rational scheme for the renovating of the process was discussed. The technological process、operational approach material recycling etc. were designed. It provided the theoretical basis and process parameters for the industrial production of TUDCA.更多还原