使用高溶解性的共沸溶劑通過冷卻再結晶純化薑黃素

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研究生：	曾佳得 Jia De Tseng
論文名稱：	使用高溶解性的共沸溶劑通過冷卻再結晶純化薑黃素 Purification of Curcumin by Cooling Crystallization in Azeotropes of High Solvent Power
指導教授：	李度 Tu Lee
口試委員:
學位類別：	碩士 Master
系所名稱：	工學院 - 化學工程與材料工程學系 Department of Chemical & Materials Engineering
論文出版年：	2021
畢業學年度：	109
語文別：	英文
論文頁數：	105
中文關鍵詞：	薑黃素
相關次數：	點閱：10 下載：0
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工業製程會避免形成共沸組成的共溶劑，因其難以回收的特性，需要額外回收溶劑的製成而導致成本增加。本論文提出了共沸溶劑在回收的潛在優點，即在蒸發的製程後仍可保持共溶劑的組成。本篇主要之研究目的，是使用兩種共沸溶劑乙酸乙酯/乙醇(70/30重量百分濃度)與乙酸乙酯/異丙醇(75/25重量百分濃度)，通過冷卻再結晶的方式提高薑黃素的純度，並使用丙酮、乙醇、異丙醇與乙酸乙酯作為對照組，以探討溶劑對薑黃素的再結晶純化的影響。共沸溶劑的優勢在於，可透過蒸發方式分離再結晶完過濾後的母液，並保持原本的共沸溶劑的組成，無須擔心溶劑組成會因為蒸發而改變。
有關本篇的研究，由於薑黃素與類薑黃素具有相似的分子結構，導致薑黃素在溶劑中需要較長的時間結晶，為了要縮短製程時間以達到控制，將攪拌與加入晶種兩種參數加入實驗設計中。實驗一，粗薑黃素分別在六種溶劑中冷卻再結晶。實驗二，加入了攪拌。實驗三，加入了攪拌與晶種。透過液相層析儀分析冷卻再結晶的薑黃素晶體，和記錄溶劑的使用量與產物的重量，可以計算出薑黃素的純度、產物的產量與溶劑的容量。結論，六種溶劑都具有純化薑黃素的效果，都可以薑黃素的純度從71.8 wt%提升91-95 % wt%，再純度差異不大的前提下，透過產物的產量與溶劑的容量這兩個數值可以得出，乙酸乙酯/乙醇(70/30 wt%)的共沸組成在六種溶劑系統中，是最適合做為薑黃素的再結晶製程的溶劑，因為其良好的溶解度(28.8 mg/ml在25度C)可以減少溶劑的使用，也可以通過攪拌(300 rpm)和加入晶種這兩種參數有效地將薑黃素結晶的時間從三天縮短到一天，和將粗薑黃素經過一次再結晶將純度從71.8 wt% 提升至94.4 wt%。乙酸乙酯/乙醇的共沸溶劑也可通過蒸餾方法回收乙酸乙酯/乙醇的共沸溶劑，透過氣相層析儀分析溶劑組成為乙酸乙酯與乙醇70/30 wt%、溫度計測量溶劑沸點為71.8度C與密度計測量溶劑密度為0.860 mg/ml 確認共沸溶劑組成不會因蒸發而改變。

Industrial processes avoid the formation of azeotropic solvent solutions, because azeotropes cannot be recovered to pure solvents by distillation. If it is inevitable, additional processes may be required to recover the solvent and increase the operational costs. The potential advantage of azeotropic solvents in the crystallization process, that is, the azeotrope can be recovered after crystallization process by evaporation without worrying about changes in the co-solvent composition was proposed. In this thesis, six solvent systems, including acetone (ACE), ethyl acetate (EA), ethanol (EtOH), 2-propanol (IPA), the azeotropic mixture of EA/EtOH =70/30 wt% (AZE-EA/EtOH), and the azeotropic mixture of EA/IPA=75/25 wt% (AZE-EA/IPA), were investigated to separate and purify curcumin (CUR) from its structurally related impurities of desmethoxycurcumin (DMC) and bisdesmethoxycurcumin (BDMC) by cooling crystallization. The purified CUR crystals were harvested by filtration and drying at 40°C and the purity was determined by high performance liquid chromatography (HPLC). Utilizing the uniqueness of azeotropes, including AZE-EA/EtOH and AZE-EA/IPA can be recovered by evaporating the filtrate, then the ones of individual solvent components at a lower boiling point of azeotrope. The recovered azeotrope was analyzed by gas chromatography, and the boiling point and density at 25°C were measured at 1 atm to ensure the composition of the co-solvent. In my research, AZE-EA/EtOH is the most suitable solvent for CUR purification because of its high solubility power (28.8 mg/ml at 25°C) and solvent capacity (15.7 mg/ml), which has the advantage for solvent saving, and having almost the same purity about 94 wt% as EA and EtOH used in the food industry. Overall, the raw CUR of 71.8 wt% was purified to 94.4 wt% in AZE-EA/EtOH by one-step cooling crystallization, crystallization time was 1 day, and inoculation at 50°C and 300 rpm.

摘要    i
Abstract    iii
Chapter 1    Introduction    1
1    Brief Introduction of Curcumin:    1
1.1    Turmeric    1
1.2    Chemical Composition of Turmeric    1
1.3    Efficacy of Curcumin    2
2    Curcumin Extraction from Turmeric    4
2.1    Manufacturing Process of Curcumin Health Food BCM-95®    4
2.2    Curcumin Extraction with Solvents    5
2.3    Curcumin Extraction with Supercritical Fluid    8
3    Purification of Curcumin    9
3.1    Chromatography    9
3.2    Crystallization    10
4    Conceptual Framework    14
Chapter 2    15
1    Materials    15
1.1    Chemicals    15
1.2    Solvents    15
2    Experimental Methods    17
2.1    Solubility Test of Raw Curcumin    17
2.2    The Effect of Solvent, Stirring and Crystallization Time on Curcumin Purification    18
2.2.1    Experimental setups    18
2.2.2    Experiment 1: Crystallization Time of 3-6 Days without any Stirring and Seeding    19
2.2.3    Experiment 2: Crystallization Time of 1-3 Days with Stirring at 300 rpm and No Seeding    19
2.2.4    Experiment 3: Crystallization Time of 1 Day with Stirring at 300 rpm and Seeding    20
2.2.5    Curcumin Seed Preparation    20
2.2.6    Experiment 4: Large Scale Cooling Crystallization    21
2.3    Recycling of Azeotropic Mixtures by Simple Distillation    22
2.4    Boiling Point and Density Test    24
2.5    Phase Diagram    25
3    Analytical Measurements    26
3.1    Fourier Transform Infrared (FTIR) Spectroscopy    26
3.2    Powder X-Ray Diffraction (PXRD)    26
3.3    Optical Microscopy (OM)    26
3.4    High Performance Liquid Chromatography (HPLC)    27
3.5    Gas Chromatography (GC)    28
3.6    Differential Scanning Calorimetry (DSC)    28
Chapter 3    29
1    Raw CUR Powder Use Test    29
2    Solubility Test    34
3    Effects of Solvent, Stirring, Seeding and Crystallization Time on Curcumin Purification    39
4    Large Scale of Curcumin Purification in AZE- EA/EtOH System    61
5    Recycling AZE-EA/EtOH by simple distillation    67
6    Phase Diagram of CUR-EA-EtOH    71
Chapter 4    Conclusion and Future Work    76
1    Conclusion    76
2    Future Work    77

                                

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