手性液液萃取拆分氧氟沙星对映体的研究

发布时间：2018-12-21 10:32

【摘要】：氧氟沙星是第三代氟喹诺酮类抗菌剂,在临床运用中极为广泛。氧氟沙星是手性药物,其左旋体L-氧氟沙星与其消旋体相比具有毒副作用小、给药量小和抗药活性高等优点。研究表明,L-氧氟沙星的抗菌活性是右旋体D-氧氟沙星的8-128倍,是其消旋体的2倍。利用手性拆分技术获得光学纯度的L-氧氟沙星是近些年国内外的研究热点之一。目前有许多学者利用手性萃取剂对其进行液液萃取手性拆分。这种方法易于实现大规模生产,具有低能耗、设备简单、操作条件温和的特点。本文采用手性液液萃取法对氧氟沙星消旋体的拆分过程进行研究。研究内容包括:1.针对氧氟沙星水溶性不大,萃取容量小的问题,本文选择乙酸作为助溶剂,以获得较高浓度的氧氟沙星水溶液(10000ppm),再利用L-酒石酸二乙酯(L-TADE)为萃取剂拆分较高浓度的氧氟沙星水溶液,并研究了乙酸浓度、萃取温度、萃取剂浓度、氧氟沙星浓度等对萃取效果的影响,优化得到了合适的萃取条件。当c(L-TADE)= 0.5 mol/L,c(HAc)=0.1 mol/L,c(ofloxacin)= 12000 ppm,t=25℃时,选择性系数达到 1.39。相比于已有的研究成果,研究结果实现了氧氟沙星拆分浓度与对映体选择性系数的同步提升。为了从微观层次上理解实验结果,采用分子动力学模拟分别对手性拆分剂和氧氟沙星对映体的相互作用能进行分子动力学模拟研究分析。2.为了进一步提高氧氟沙星的手性液液萃取拆分过程的选择性,对混合萃取剂的拆分效果进行探讨。采用L-酒石酸二乙酯和L-(-)-二苯甲酰酒石酸(L-DBTA)作为混合萃取剂,并优化分析了萃取工艺条件和对其萃取过程的影响。研究结果表明:当t=25℃,c(L-TADE)=0.5mol/L,c(HAc)=0.1mol/L,c(L-DBTA)=0.1mol/L,c(ofloxacin)=8000 ppm 时,选择性系数为1.58。采用该混合萃取剂的拆分效果要优于单一萃取剂的拆分效果。3.利用Aspen Plus流程模拟软件对萃取剂酒石酸二乙酯与稀释剂正辛醇的精馏分离过程进行模拟。对精馏过程参数进行优化分析,确定了最佳塔板数、进料位置和回流比。针对常压塔操作温度过高和高压蒸汽成本高的缺点,设计了减压精馏工艺,并对不同操作压力的减压塔进行了分析。
[Abstract]:Ofloxacin is the third generation fluoroquinolone antibacterial agent, which is widely used in clinic. Ofloxacin is a chiral drug. Compared with its racemes, levofloxacin has many advantages, such as less side effects, less dosage and higher drug resistance. The results showed that the antibacterial activity of L- ofloxacin was 8-128 times of that of dextral Dofloxacin and 2 times of that of racemes. The optical purity of L-ofloxacin obtained by chiral resolution is one of the hot research topics at home and abroad in recent years. At present, many scholars use chiral extractants for chiral resolution by liquid-liquid extraction. This method is easy to realize mass production, has the characteristics of low energy consumption, simple equipment and mild operating conditions. The resolution of ofloxacin racemes was studied by chiral liquid-liquid extraction. The research contents include: 1. Because ofloxacin is not water-soluble and its extraction capacity is small, acetic acid is chosen as cosolvent to obtain high concentration ofloxacin aqueous solution (10000ppm). Diethyl L-tartrate (L-TADE) was used as extractant for the separation of high concentration ofloxacin aqueous solution. The effects of acetic acid concentration, extraction temperature, extractant concentration and ofloxacin concentration on the extraction efficiency were studied. The optimum extraction conditions were obtained. When c (L-TADE) = 0. 5 mol/L,c (HAc) = 0. 1 mol/L,c (ofloxacin) = 12000 ppm,t=25 鈩，

本文编号：2388787