- 學位論文
超臨界流體與模擬移動床之整合與應用以及模擬移動床的多成份分離
The Integration of Simulated Moving Bed and Supercritical Fluid and Its Application and the Ternary Separation by Simulated Moving Bed
摘要
分離純化是重要的基礎工業技術之一，在石化、特化、生技、製藥等產業，從原料預處理到產品都需要進行分離純化，而相對於薄膜、蒸餾等純化技術，層析技術具有固體吸附劑高選擇性，及操作溫度低的優點，一直都是生技製藥產業的關鍵技術。模擬移動床層析(Simulated Moving Bed chromatography，SMB)技術因為其連續式操作方式，可有效提升設備產能以及吸附劑效能，並大大地降低操作成本以及溶劑耗量，是目前最廣泛使用的連續式層析技術。 本論文分成兩大部份，第一部分為結合超臨界流體與模擬移動床技術，將傳統層析的液體移動相以超臨界流體取代，簡稱SF-SMB，以避免後續產品濃縮或溶劑回收所導致的高能耗問題。本研究首先針對芝麻素與芝麻醚素的分離進行探討，並依據三角形理論進行操作測試，結果獲得芝麻素純度99.4%，回收率98.1%；接著以分離牛樟芝三萜類成份進行測試，比較正相(bare silica gel)與反相(C18)固定相在超臨界流體輔溶劑濃度等梯度(iso-SF-SMB)及梯度模式(grad-SF-SMB)下的分離效果，結果顯示正相填料搭配grad-SF-SMB系統的分離效果最好，同時比較了傳統液相SMB的分離效果。 論文的第二部份則是以串級SMB 對多成份分離進行探討，針對兩種不同滯留行為的進料，(A) KA＜KB＜＜KC 以及(B) KA＜＜KB＜KC，進行分離方法的開發，其中K是吸附常數，A、B、和C 的下標表示不同的成份，其中成份A是弱滯留性成份，成份B是中間滯留性成份，成份C是強滯留成份。針對兩種進料，本論文分別使用來自醱酵母液和天然粗萃物中具有不易脫附的超強滯留性成份進行試作，並成功由其中分離出中間滯留性成份，同時克服超強滯留性物質對系統的干擾問題。對於從天然物或醱酵產物所得到的粗萃物，本研究建立了一種可以不需要詳盡成份資訊也能進行層析分離的方法，可有效推廣串級SMB在多成份分離的產業應用。
關鍵字
none並列摘要
Separation and purification is the basic technology for industry. It works for the pretreatment of raw materials and the purification of final products for petrochemicals, specialities, biotechnologies, pharmaceuticals. Compared to distillation and membrane separation, chromatography is more widely apply in biotechnology and pharmaceutical industries because of low-temperature operation and high selectivity of adsorbent. SMB(Simulated Moving Bed), one of the continuous chromatographic technique, can greatly increase the productivity of solid adsorbent and reduce the solvent consumption. SMB gains its importance in the last two decade in pharmaceutical industry. This study is divided into two major parts. The first part aims to combine the use of supercritical fluid and the simulated moving bed, and the second part aims to use a 6 zones SMB with an additional CIP section for the ternary separation with very strong retention components in the feedstock. SF-SMB is a continuous chromatography with supercritical fluid as the desorbent, which can avoid the problem of high energy consumption for the down stream concentration and solvent recovery. By using the SF-SMB, which was designed and manufactured in our laboratory, sesamin and sesamolin can be separated, and the Triterpenoids can also be separated from the crude extract of Taiwanofugus camphorata. The results show that the purity of sesamin is 99.4% and the recovery is 98.1%. In the study of separating Triterpenoids from other impurities, the results reveal that the design of grad-SF-SMB with silica has the highest effectiveness on removing the impurities. It is also found that an iso-SF-SMB with silica also can successfully remove the impurities, and an iso-SF-SMB with RP-18 can also be used for removing the impurities with little lost of the triterpenoids. However, a traditional SMB with RP-18 is not suitable for removing the impurities. Both studies demonstrate that SF-SMB would be a useful technology for developing botanical drugs and provides greener alternative for industries. The second part of this thesis aims to use a SMB cascade for the multi-component separation. This study presents two three-step procedures for the SMB cascade to separate the intermediate retention component from a feedstock with very strong retention component. The feedstock is classified into two categories: (A) KA＜KB＜＜KC; and (B) KA＜＜KB＜KC. Based on the procedures, this study can successfully separate the intermediate retention component from two crude extracts. The experimental results for both crude extracts shows that the separation of the intermediate retention component with near 90% purity and recovery can be achieved without knowing the adsorption isotherms foe each impurity. This study provides a quick and simple method to operate a SMB cascade for the ternary separation.