將相圖分析與製程設計結合：薑黃中薑黃素的萃取與純化案例

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陳郁軒(Yu-Hsuan Chen) 查詢紙本館藏

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化學工程與材料工程學系

論文名稱

將相圖分析與製程設計結合：薑黃中薑黃素的萃取與純化案例
(Integrating Phase Diagram Analysis with Process Design: The Case of Curcumin Extraction and Purification from Turmeric)

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至系統瀏覽論文 (2025-8-31以後開放)

摘要(中)

溶液結晶被廣泛認為是純化薑黃素的首選方法。然而，從該方法衍生的純化程序通常是在沒有正確了解薑黃素及其雜質的材料特性的情況下開發的。因此，本研究的目的是：（1）透過建構相圖來闡明薑黃素及其雜質的固態特性，以及（2）開發一種基於此的純化方法。
基於固態表徵，令人驚訝地發現薑黃素及其雜質去甲氧基薑黃素（DMC）和雙去甲氧基薑黃素（BDMC）形成固溶體，其被定義為具有相似晶格的兩種結晶固體的均勻混合物。由於薑黃素與DMC和BDMC的分子結構相似，這些雜質能夠滲透薑黃素的晶格空隙並破壞其晶格。這項發現解釋了為什麼先前的薑黃素純化研究儘管添加了反溶劑或使用了種子，但仍需要多個冷卻結晶步驟。
從薑黃中萃取薑黃素通常會產生含有純度為 25% 的薑黃素的固體。由於DMC和BDMC雜質的存在，固體與薑黃素形成固溶體，使得傳統的冷卻結晶方法無效。從建構的相圖來看，固-液平衡的方法被發現是合適的方法。但由於薑黃素的純度越高，固-固-液三元相圖中的聯絡線變得越垂直，顯示隨著固-液平衡階段的進行，純化效率降低。因此，僅用固-液平衡的方法不足以有效純化薑黃素。比較好的策略是用固液平衡從25% 的油樹脂中獲得純度高達80%的CUR，再利用冷卻結晶的方式將純度提升，直到提升至>98%。基於5個標準(1)達到>80%純度所需的階層、(2)固體產物的產率、(3)溶劑消耗量、(4) 溶劑的毒性、及(5)沸點，挑選出AZE(Water/EtOH/ACN)為最佳實驗溶劑，並按照策略進行。驚訝的發現僅需一次equilibrium-based就可以將純度從25到81.3%，產率為8.5%以及三次冷卻結晶將純度提升至94.4、97.2、98.2%，產率為39.4、53.3、60%。僅需4個階段即可從油樹脂中獲得98%的CUR 純度，而不是僅基於8個階段平衡。

摘要(英)

Solution crystallization is widely regarded as the method of choice for the purification of curcumin. However, the purification procedures derived from this method were usually developed without a proper understanding of the material properties of curcumin and its impurities. Therefore, this research aims to: (1) elucidate the solid-state properties of curcumin and its impurities by the construction of phase diagram, and (2) develop a purification method based on it.
Based on the solid-state characterization, it was surprisingly revealed that curcumin and its impurities, desmethoxycurcumin (DMC) and bisdesmethoxycurcumin (BDMC), formed a solid solution, which is defined as a homogeneous mixture of two crystalline solids with similar lattices. Due to the similar molecular structures of curcumin with DMC and BDMC, those impurities are capable of infiltrating the lattice voids of curcumin and disrupt its lattice. This discovery answers why previous studies of curcumin purification always necessitates multiple cooling crystallization steps despite of the addition of antisolvent or the use of seed.
Extraction of curcumin from turmeric typically produced solids containing curcumin at 25% purity. Due to the presence of DMC and BDMC impurities, the solids formed a solid solution with curcumin, rendering the conventional method of cooling crystallization to be ineffective. By judging from the constructed phase diagram, solid-liquid equilibrium approach was found to be the suitable method. The higher the purity of curcumin, the more vertical the tie-line becomes in the solid-solid-liquid ternary phase diagram, indicating the reduced purification efficiency as the solid-liquid equilibrium stage progressed. Therefore, solid-liquid equilibrium method alone is insufficient to purify curcumin effectively. A better strategy is to obtain high-purity CUR from 25% oleoresin using solid-liquid equilibrium to achieve a purity of up to 80%, followed by cooling crystallization to further increase the purity to over 98%. Based on the five criteria of : (1) number of stages required to achieve the purity of > 80%, (2) yield of the solid product, (3) solvent consumption, (4) toxicity, and (5) boiling point, AZE(Water/EtOH/ACN) was selected as the optimal experimental solvent. Following the strategy, it was surprisingly discovered that only one equilibrium-based stage was required to increase the purity from 25% to 81.3%, with a yield of 8.5%. Three subsequent cooling crystallization stages raised the purity to 94.4%, 97.2%, and 98.2%, with yields of 39.4%, 53.3%, and 60%, respectively. Thus, only four stages are needed to obtain 98% purity CUR from oleoresin, as opposed to the previously assumed eight equilibrium stages.

關鍵字(中)

★ 薑黃素
★ 萃取
★ 固溶體
★ 共沸溶劑
★ 溶劑

關鍵字(英)

★ curcumin
★ extraction
★ solid solution
★ azeotrope
★ solvent

論文目次

摘要 i
Abstract iii
Acknowledgment v
Chapter 1 Introduction 1
1.1 Brief Introduction of Turmeric 1
1.1.1 Turmeric 1
1.1.2 Composition of Turmeric 1
1.2 Turmeric Extraction 3
1.3 Phase Diagram 6
1.4 Solid Solutions 9
1.5 Conceptual Framework 11
Chapter 2 Experiment Materials and Methods 12
2.1 Materials 12
2.1.1 Chemicals 12
2.1.2 Solvents 12
2.2 Experimental Methods 13
2.2.1 Preparation of Curcumin Standard 13
2.2.2 Preparation of the Positive Azeotropes 13
2.2.3 Investigation of the Presence of Solid Solution 14
2.2.4 Construction of Ternary Phase Diagram 15
2.2.5 Extraction and Purification of Curcumin from Turmeric 19
2.2.6 High Performance Liquid Chromatography (HPLC) 22
Chapter 3 Results and Discussion 24
3.1 Solid-State Properties of Curcuminoids 24
3.2 Solvent Selection Based on the Phase Diagram 29
3.2.1 Simplified Ternary Phase Diagrams of Different CUR Purity Levels 29
3.2.2 Solvent Selection 32
3.3 Extraction and Purification of Curcumin from Turmeric 40
3.3.1 Kinetic Study of Turmeric Extraction and Oleoresin Purification 40
3.3.2 Turmeric Extraction and Oleoresin Purification for Azeotrope 45
3.3.3 Turmeric Extraction and Oleoresin Purification for Pure Solvent 49
Chapter 4 Conclusion and Future Work 53
4.1 Conclusion 53
4.2 Future Work 55
References 56

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指導教授

李度(Tu Lee)

審核日期

2024-7-30

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