模拟移动床色谱拆分酮洛芬对映体的模拟研究

利用平衡扩散模型对酮洛芬对映体在4区模拟移动床上的拆分进行模拟研究,考察了主要操作参数对分离效能的影响,具体包括:(a)切换时间对纯度、回收率的影响;(b)各区色谱柱配置对分离的影响;(c)Ⅱ区和Ⅲ区流量对纯度和回收率的影响。验证了模拟移动床操作参数的敏感性,对酮洛芬的中试生产具有一定的指导意义。     

溶剂梯度模拟移动床分离奥美拉唑对映体的研究

模拟移动床一般在平衡模式下操作,即在模拟移动床（SMB）各区中采用相同的温度、压力和流动相组成等操作条件。但最新研究表明,在SMB各区适当使用梯度操作,如温度梯度、压力梯度、溶剂梯度等,优化各区操作条件,可以显著改善分离性能。本文测定了奥美拉唑对映体在乙醇／正己烷中的吸附平衡,根据SG—SMB平衡理论,确定了分离奥美拉唑对映体的完全分离区域,并以此为指导初步选择了分离条件,使R—OME和S—OME纯度分别达到95．11％和96．34％。     

间歇色谱与模拟移动床色谱分离奥美拉唑对映体的比较

用纤维素三苯基氨基甲酸酯涂敷型手性固定相和含0.1%二乙胺的乙醇溶液,研究了模拟移动床色谱和间歇色谱对奥美拉唑对映体的拆分.其中,间歇色谱分离过程采用基于线性推动力模型的动力学模型研究,优化出生产能力最大的操作条件.以生产能力、溶剂消耗和回收率三个指标比较了这两种色谱操作模式.结果表明:模拟移动床色谱分离效果优于间歇色谱,生产能力为间歇色谱的5倍以上,回收率则高出1.28倍以上,溶剂消耗则可节省约22%,     

奥美拉唑对映体的模拟移动床色谱分离过程模拟

模拟移动床色谱已成为一种重要的手性药物制备技术,其技术关键在于最佳运行点的确定。由于其过程复杂,用数学模型来确定最佳运行点,求解难度大,计算时间长。今以考虑传质阻力与轴向弥散的模拟移动床模型为基础,采用线上求解法,将模型方程沿空间方向离散,得到一组常微分方程,然后运用MATLAB提供的常微分求解器求解这一偏微分方程组,模拟了奥美拉唑对映体的模拟移动床色谱分离过程。研究结果表明,线上求解法结合MATLAB常微分求解器可快速、准确地求解模拟移动床模型,用于模拟移动床色谱分离过程的实时控制与优化。     

高效液相色谱直链淀粉手性固定相拆分奥美拉唑对映体

建立了奥美拉唑对映体的高效液相色谱拆分方法。使用Chiralpak AD-H手性色谱柱,考察了流动相中极性调节剂的种类和体积分数、流动相中二乙胺体积分数、柱温以及流速对拆分奥美拉唑对映体的影响。确定了最佳拆分条件:流动相为V(正己烷)∶V(异丙醇)∶V(二乙胺)=75∶25∶0.05;流速为0.8 mL/min;检测波长302nm;柱温30℃,计算了奥美拉唑与固定相相互作用的焓变差值Δ(ΔH0)和熵变差值Δ(ΔS0),分别为-2.845 kJ/mol和-6.233 J/(mol.K),所建立的方法简便快速,重复性好,可用于奥美拉唑的质量研究和控制。该研究以(R)-联二萘酚作为包结拆分剂,拆分后的奥美拉唑对映体过量值(ee)可达96.7%以上。通过峰面积的显著差异,考察了在以乙醇或异丙醇为极性调节剂流动相中两对映体的出峰顺序。结果发现,在这两种流动相中出峰顺序是相反的。     

马拉硫磷对映体色谱拆分方法的建立

建立了马拉硫磷对映体的高效液相色谱正相体系拆分方法。分别应用了正己烷和石油醚两种流动相,在正己烷流动相体系中采用了乙醇、丙醇、异丙醇、丁醇和异丁醇有机改性剂,石油醚体系则以异丙醇为改性剂,考察,改性剂及其含量对拆分的影响。同时还考察了温度对分离的影响。实验结果显示,室温下正己烷流动相中含5％异丁醇可达最佳分离效果,分离因子为1．22。流动相中醇的含量减少使保留时间延长,分离效果增加。低温有利于对映体的分离。     

手性化合物对映体拆分方法概述

回顾了对映体的研究历史，综述了手性化合物对映体的拆分方法，展望了该领域未来的发展前景。     

间歇模拟移动床色谱分离过程的建模与优化

间歇模拟移动床(I-SMB)的过程是多列色谱过程,它是对传统模拟移动床(SMB)技术的改进。在I-SMB过程中,将两个端口切换的时间间隔分为两个子时间间隔,产品只在第一个子时间间隔中被收集。介绍了间歇模拟移动床的基本原理,并采用色谱平衡理论的基础上实现两组分的分离。然后通过SMB与I-SMB的比较结果证明无论在线性吸附等温线还是在非线性吸附等温线条件下,I-SMB都能够比SMB实现更高的分离性能。     

拜耳拟建模拟移动床

拜耳公司宣布,它将建设一座cGMF,中试车间,运用模拟移动床技术(SMB)来合成手性药物中间体及活性成份,其中SMB技术是一种用于分离手性对映体的层析方法。该车间将建在德国的勒沃库森市,定于2001年年中投产,年生产能力为5t。据拜耳公司说,SMB技术分离出来的对映体其纯度可达99％,     

三唑酮对映体的手性拆分研究

合成了纤维素—三(3，5-二甲基苯基氨基甲酸酯)(CDMPC)，涂敷于氨基丙烷化硅胶上制备成涂敷量15％的手性固定相。以正己烷-异丙醇为流动相，在高效液相色谱上实现了对三唑酮光学异构体的直接拆分，研究了流动相中异丙醇的比例对分离效果的影响，优化了色谱拆分条件。     

Continuous size fractionation of magnetic nanoparticles by using simulated moving bed chromatography

The size fractionation of magnetic nanoparticles is a technical problem, which until today can only be solved with great effort. Nevertheless, there is an important demand for nanoparticles with sharp size distributions, for example for medical technology or sensor technology. Using magnetic chromatography, we show a promising method for fractionation of magnetic nanoparticles with respect to their size and/or magnetic properties. This was achieved by passing magnetic nanoparticles through a packed bed of fine steel spheres with which they interact magnetically because single domain ferro-/ferrimagnetic nanoparticles show a spontaneous magnetization. Since the strength of this interaction is related to particle size, the principle is suitable for size fractionation. This concept was transferred into a continuous process in this work using a so-called simulated moving bed chromatography. Applying a suspension of magnetic nanoparticles within a size range from 20 to 120 nm, the process showed a separation sharpness of up to 0.52 with recovery rates of 100%. The continuous feed stream of magnetic nanoparticles could be fractionated with a space-time-yield of up to 5 mg/(L∙min). Due to the easy scalability of continuous chromatography, the process is a promising approach for the efficient fractionation of industrially relevant amounts of magnetic nanoparticles.     

基于一类组织P系统的模拟移动床的多目标优化

The binaphthol enantiomers separation process using simulation moving bed technology is simulated with the true moving bed approach （TMB）. In order to systematically optimize the process with multiple productive objectives, this article develops a variant of tissue P system （TPS）. Inspired by general tissue P systems, the special TPS has a tissue-like structure with several membranes. The key rules of each membrane are the communication rule and mutation rule. These characteristics contribute to the diversity of the population, the conquest of the multimodal of objective function, and the convergence of algorithm. The results of comparison with a popular algorithm——the non-dominated sorting genetic algorithm 2（NSGA-2） illustrate that the new algorithm has satisfactory performance. Using the algorithm, this study maximizes synchronously several conflicting objectives, purities of different products, and productivity.     

模拟移动床色谱分离吴茱萸碱和吴茱萸次碱

以C18为固定相、甲醇/水=70/30（体积比）为流动相,利用三区带模拟移动床分离了两种生物碱,吴茱萸碱和吴茱萸次碱。通过前沿分析法测定了两种生物碱的吸附等温线,在实验浓度范围内符合线性吸附等温线,吴茱萸碱和吴茱萸次碱的亨利系数分别为3.11和5.25。利用经验公式估算了轴向扩散系数和有效传质系数。分别利用三角形理论和基于模型的优化方法对三区带模拟移动床的操作条件进行设计,在优化的条件下,最大进料流量为0.55 ml?min^-1,两种产品纯度均大于99%。通过异步切换策略,在不增加设备投资及保证产品纯度大于99%的前提下,将进料流量提高至0.62 ml?min^-1。     

Prediction‐correction method for optimization of simulated moving bed chromatography

A systematic algorithm for simulated moving bed (SMB) chromatography process development that utilizes dynamic optimization, transient experimental data, and parameter estimation to arrive at optimal operating conditions is described. These operating conditions ensure both high purity constraints and optimal productivity are satisfied. This algorithm proceeds until the SMB process is optimized without manual tuning. In a case study, it has been shown with a linear isotherm system that the optimal operating conditions can be reached in only two changes of operating conditions following the proposed algorithm. Another case study with a linear isotherm system has shown that the algorithm is robust to optimize the SMB even if there is significant model mismatch at first. © 2012 American Institute of Chemical Engineers AIChE J, 59: 736–746, 2013     

Carrousel型模拟移动床在红霉素提取中的应用

为将模拟移动床技术推广到红霉素提取中,采取了以下步骤:首先通过固定床的吸附穿透和洗脱实验,确定树脂的基本吸附和洗脱参数;其次结合移动床设备指标,确定移动床循环工艺和运行参数;最终利用30柱Carrousel型模拟移动床,使用Amberlite XAD-16大孔吸附树脂,从实际的工业红霉素发酵液中提取红霉素。在树脂体积仅为2 700 mL,循环时间405 min,进料流速125 mL/min,进料液效价大约2 700 U/mL时,可连续提取得到效价高于45 000 U/mL的红霉素产品,同时产品收率在98%以上。该系统操作方便,运行成本低,环保压力轻,经计算其工业规模设备可替代红霉素提取工艺中的传统固定床系统。     

模拟移动床色谱技术的应用研究进展

模拟移动床色谱技术是一种高效的现代化分离技术。该技术具有分离能力强、设备体积小、投资成本低、环境污染少、便于实现自动控制等优点,特别有利于分离热敏性物质及难分离的物系,近年来,越来越受到工业界和研究者的关注,研究不断深人,应用领域也不断扩大。对模拟移动床色谱技术在石化、食品、制药三大领域的应用研究进展进行了详细的介绍,以期为相关研究提供参考。     

Separation of multicomponent aromatic/aliphatic mixtures by simulated moving bed adsorption: Modeling and experiments

Simulated moving bed (SMB) adsorption has potential for efficient separation of many valuable chemical mixtures, but considerably less attention has been devoted to multicomponent feeds relative to binary mixtures. We take a rigorous experimental and modeling approach to study multicomponent separation of aromatics and aliphatics with a mesoporous silica adsorbent, which is relevant in many petrochemical applications such as separation of reformate and distillate streams. Our approach involves refining multicomponent adsorption, mass transfer, and SMB process parameters based upon detailed experimental inputs, with progressive addition of components. We develop a robust model that quantitatively predicts the influence of key operating parameters such as stream flow rates, desorbent/feed ratio, and switch time on the separation results and concentration profiles. The model is validated as a function of feed complexity by SMB experiments and column concentration profile measurements in a 16-column mini-plant. Furthermore, conditions for clear separation of each mixture are developed.     

Model reduction for linear simulated moving bed chromatography systems using Krylov‐subspace methods

Simulated moving bed (SMB) chromatography is a well‐established technology for separating chemical compounds. To describe an SMB process, a finite‐dimensional multistage model arising from the discretization of partial differential equations is typically employed. However, its relatively high dimension poses severe computational challenges to various model‐based analysis. To overcome this challenge, two Krylov‐type model order reduction (MOR) methods are proposed to accelerate the computation of the cyclic steady states (CSSs) of SMB processes with linear isotherms. A “straightforward method” that carefully deals with the switching behavior in MOR is first proposed. Its improvement, a “subspace‐exploiting method,” thoroughly exploits each reduced model to achieve further acceleration. Simulation studies show that both methods achieve high accuracy and significant speedups. The subspace‐exploiting method turns out to be computationally much more efficient. Two challenging analyses of SMB processes, namely uncertainty quantification and CSS optimization, further demonstrate the accuracy, efficiency, and applicability of the proposed methods. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3773–3783, 2014