【摘要】：氧氟沙星是第三代氟喹諾酮類抗菌劑,在臨床運用中極為廣泛。氧氟沙星是手性藥物,其左旋體L-氧氟沙星與其消旋體相比具有毒副作用小、給藥量小和抗藥活性高等優(yōu)點。研究表明,L-氧氟沙星的抗菌活性是右旋體D-氧氟沙星的8-128倍,是其消旋體的2倍。利用手性拆分技術(shù)獲得光學(xué)純度的L-氧氟沙星是近些年國內(nèi)外的研究熱點之一。目前有許多學(xué)者利用手性萃取劑對其進行液液萃取手性拆分。這種方法易于實現(xiàn)大規(guī)模生產(chǎn),具有低能耗、設(shè)備簡單、操作條件溫和的特點。本文采用手性液液萃取法對氧氟沙星消旋體的拆分過程進行研究。研究內(nèi)容包括:1.針對氧氟沙星水溶性不大,萃取容量小的問題,本文選擇乙酸作為助溶劑,以獲得較高濃度的氧氟沙星水溶液(10000ppm),再利用L-酒石酸二乙酯(L-TADE)為萃取劑拆分較高濃度的氧氟沙星水溶液,并研究了乙酸濃度、萃取溫度、萃取劑濃度、氧氟沙星濃度等對萃取效果的影響,優(yōu)化得到了合適的萃取條件。當(dāng)c(L-TADE)= 0.5 mol/L,c(HAc)=0.1 mol/L,c(ofloxacin)= 12000 ppm,t=25℃時,選擇性系數(shù)達到 1.39。相比于已有的研究成果,研究結(jié)果實現(xiàn)了氧氟沙星拆分濃度與對映體選擇性系數(shù)的同步提升。為了從微觀層次上理解實驗結(jié)果,采用分子動力學(xué)模擬分別對手性拆分劑和氧氟沙星對映體的相互作用能進行分子動力學(xué)模擬研究分析。2.為了進一步提高氧氟沙星的手性液液萃取拆分過程的選擇性,對混合萃取劑的拆分效果進行探討。采用L-酒石酸二乙酯和L-(-)-二苯甲酰酒石酸(L-DBTA)作為混合萃取劑,并優(yōu)化分析了萃取工藝條件和對其萃取過程的影響。研究結(jié)果表明:當(dāng)t=25℃,c(L-TADE)=0.5mol/L,c(HAc)=0.1mol/L,c(L-DBTA)=0.1mol/L,c(ofloxacin)=8000 ppm 時,選擇性系數(shù)為1.58。采用該混合萃取劑的拆分效果要優(yōu)于單一萃取劑的拆分效果。3.利用Aspen Plus流程模擬軟件對萃取劑酒石酸二乙酯與稀釋劑正辛醇的精餾分離過程進行模擬。對精餾過程參數(shù)進行優(yōu)化分析,確定了最佳塔板數(shù)、進料位置和回流比。針對常壓塔操作溫度過高和高壓蒸汽成本高的缺點,設(shè)計了減壓精餾工藝,并對不同操作壓力的減壓塔進行了分析。
[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，

本文編號：2388787