转酯联合动态轴向色谱法制备高纯度二十碳五烯酸乙酯工艺优化

Preparation process optimization for high purity eicosapentaenoic acid ethyl ester by transesterification combined with dynamic axial chromatography

中文关键词:  二十碳五烯酸乙酯  高纯度  响应面法  优化  乙酯化

英文关键词:eicosapentaenoic acid ethyl ester  high purity  response surface methodology  optimization  ethylation

中文摘要:

      目的 优化转酯联合动态轴向色谱法制备高纯度二十碳五烯酸乙酯(eicosapentaenoic acid ethyl ester, EPA-EE)工艺。方法 首先对鱼油原料中杂质进行分析鉴定, 然后以EPA乙酯纯度为评价指标, 采用单因素实验结合响应面分析法, 探究NaOH浓度、油醇质量比、反应时间3个因素对EPA乙酯化的影响。原料在经最优乙酯化条件前处理后, 再通过单因素实验, 以EPA-EE回收率、纯度和洗脱时间为评价指标, 对动态轴向高压制备液相的工艺条件进行优化。结果 EPA乙酯化的最佳工艺条件为: NaOH浓度1.5%、油醇质量比1:2.8、反应时间4.2 h, 经转酯处理, 原料EPA-EE纯度由72%增加到82.69%; 制备液相(C18填料, 250 mm×50 mm, 10 μm)的最佳流动相为95%的甲醇、流速60 mL/min, 在此制备条件下, EPA-EE纯度可达98%, 回收率为80%。结论 通过一步乙酯化转酯反应, 在降低原料中杂质含量的同时可提高EPA-EE含量, 再通过动态轴向色谱法精制可获得纯度较高的EPA-EE, 本研究建立了转酯联合动态轴向色谱法制备高纯度EPA-EE的方法, 获得的工艺条件稳定可行, 可为高纯EPA-EE制备降低生产成本。

英文摘要:

      Objective To optimize the preparation process for high purity eicosapentaenoic acid ethyl ester (EPA-EE) preparation by transesterification combined with dynamic axial chromatography. Methods Firstly, the impurities in the raw material of fish oil were analyzed and identified. Then, taking the purity of EPA ethyl ester as the evaluation index, the single factor test combined with response surface analysis was used to explore the influence of 3 factors, namely, NaOH concentration, mass ratio of oil to alcohol, and reaction time, on the ethylation of EPA. After the raw materials were pretreated under optimal ethyl esterification conditions, the process conditions for the preparation of liquid phase under dynamic axial high pressure were optimized by single-factor experiments based on EPA-EE recovery, purity and elution time. Results The optimum technological conditions for the esterification of EPA were as follows: NaOH concentration 1.5%, oleanol mass ratio 1:2.8, reaction time 4.2 h. After transesterification, the purity of raw material EPA-EE increased from 72% to 82.69%; preparation of liquid phase (C18 filler, 250 mm×50 mm, 10 μm), the optimum mobile phase of EPA-EE was 95% methanol, the flow rate was 60 mL/min. Under this preparation condition, the purity of EPA-EE could reach 98%, and the recovery was 80%. Conclusion Through one-step esterification and transesterification reaction, the content of EPA-EE can be increased while the content of impurities in raw materials is reduced, and then purified by dynamic axial chromatography to obtain high-purity EPA-EE. In this study, a method of transesterification combined with dynamic axial chromatography to prepare high-purity EPA-EE is established. The process conditions are stable and feasible, which can reduce the production cost for the preparation of high purity EPA-EE.