离子液体中结晶分离熊果酸和齐墩果酸研究

doi:10.11949/0438-1157.20200003

摘要/Abstract

摘要：

为拓展结晶溶剂的范围和提高结晶分离熊果酸和齐墩果酸的性能，引入离子液体作为结晶溶剂。测定了熊果酸和齐墩果酸在六种离子液体+乙醇溶液中的溶解度数据，根据该数据，选取1-辛基-3-甲基咪唑六氟磷酸+乙醇混合溶液作为溶剂对熊果酸和齐墩果酸进行了结晶分离，并采用单因素实验对结晶工艺进行了初步优化。结果表明：在1-辛基-3-甲基咪唑六氟磷酸质量分数5%，熊果酸和齐墩果酸质量比1.5∶1，结晶温度30℃，结晶时间14 h的条件下，结晶产物中齐墩果酸的质量分数可以达到85%左右。

关键词: 熊果酸, 齐墩果酸, 离子液体, 溶解度, 结晶分离

Abstract:

To expand the scope of crystallization solvent and improve the performance of crystallization separation of ursolic acid and oleanolic acid, ionic liquids were introduced as the crystallization solvent. The solubility data of ursolic acid and oleanolic acid in six ionic liquids + ethanol mixed solutions were measured. Then the 1-octyl-3-methylimidazole hexafluorophosphate + ethanol mixed solution was selected as the solvent for crystallization separation of ursolic acid and oleanolic acid, and the crystallization process was optimized by single factor experiments. The best process conditions are as follows: mass fraction of 1-octyl-3-methylimidazole hexafluorophosphat 5%, mass ratio of ursolic acid to oleanolic acid 1.5∶1, crystallization temperature 30℃, crystallization time 14 h. In this case, the mass fraction of oleanolic acid in the crystals can reach about 85%.

Key words: ursolic acid, oleanolic acid, ionic liquid, solubility, crystallization separation

中图分类号:

TQ 028.8

高意, 曹亚慧, 范杰平. 离子液体中结晶分离熊果酸和齐墩果酸研究[J]. 化工学报, 2020, 71(8): 3633-3643.

Yi GAO, Yahui CAO, Jieping FAN. Study on crystallization separation of ursolic acid and oleanolic acid in ionic liquid[J]. CIESC Journal, 2020, 71(8): 3633-3643.

图/表 17

参考文献 35

1	张明发, 沈雅琴. 熊果酸和齐墩果酸抗脑瘤作用的研究进展[J]. 药物评价研究, 2016, 39(1): 132-135.
	Zhang M F, Shen Y Q. Research progress of ursolic acid and oleanolic acid against brain tumors[J]. Drug Evaluation Research, 2016, 39(1): 132-135.
2	Ginerlarza E M, Máñez S, Recio M C, et al. Oleanonic acid, a 3-oxotriterpene from Pistacia, inhibits leukotriene synthesis and has anti-inflammatory activity[J]. European Journal of Pharmacology, 2001, 428(1): 137-143.
3	Shyu M H, Kao T C, Yen G C. Ursolic acid and oleanolic acid induce apoptosis in HuH7 human hepatocellular carcinoma cells through a mitochondrial-dependent pathway and downregulation of XIAP[J]. Journal of Agricultural & Food Chemistry, 2010, 58(10): 6110.
4	Wang X, Li Y L, Wu H, et al. Antidiabetic effect of oleanolic acid: a promising use of a traditional pharmacological agent[J]. Phytotherapy Research Ptr., 2011, 25(7): 1031.
5	Cheng K G, Su C H, Yang L D, et al. Synthesis of oleanolic acid dimers linked at C-28 and evaluation of anti-tumor activity[J]. European Journal of Medicinal Chemistry, 2015, 89: 480-489.
6	Culhaoğlu B, Hatipoğlu S D, Dönmez A, et al. Antioxidant and anticholinesterase activities of lupane triterpenoids and other constituents of salvia trichoclada[J]. Medicinal Chemistry Research, 2015, 24(11): 1-7.
7	Hsu H Y, Yang J J, Lin C C. Effects of ursolic acid and oleanolic acid on inhibiting tumor growth and enhancing the recovery of hematopoietic system postirradiation in mice[J]. Cancer Letters, 1997, 111(1/2): 7-13.
8	Anicetoa J P S, Azenhab I S, Domingues F M J, et al. Design and optimization of a simulated moving bed unit for the separation of betulinic, oleanolic and ursolic acids mixtures: experimental and modeling studies[J]. Separation and Purification Technology, 2018, 192: 401-411.
9	René C, Bianka S. A convenient separation of ursolic and oleanolic acid[J]. Tetrahedron Letters, 2011, 52: 6616-6618.
10	Konuki K, Hirasawa I. Kinetic crystallization separation process of the inositol isomers by controlling metastable zones[J]. Journal of Crystal Growth, 2013, 373(1): 123-127.
11	聂强. 类质同晶甾体化合物的分离过程研究[D]. 天津: 天津大学, 2007.
	Nie Q. Study on the preparation process of isomorphic steroids[D]. Tianjin: Tianjin University, 2007.
12	张成. 油酸与亚油酸物系溶剂结晶分离过程的研究[D]. 天津: 天津大学, 2004.
	Zhang C. Study on the crystallization separation process of oleic acid and linoleic acid solvents[D]. Tianjin: Tianjin University, 2004.
13	邹汉波, 董新法, 林维明. 离子液体及其在绿色有机合成中的应用[J]. 化学世界, 2004, 45(2): 107-110.
	Zou H B, Dong X F, Lin W M. Ionic liquids and their applications in green organic synthesis[J]. Chemical World, 2004, 45(2): 107-110.
14	李汝雄, 王建基. 离子液体的合成与应用[J]. 化学试剂, 2001, 23(4): 211-215.
	Li R X, Wang J J. Synthesis and application of ionic liquids[J]. Chemical Reagents, 2001, 23(4): 211-215.
15	Zhao H. Current studies on some physical properties of ionic liquids (p)[J]. Cheminform, 2010, 6(41): 545-557.
16	赵东滨, 寇元. 室温离子液体:合成、性质及应用[J]. 大学化学, 2002, 17(1): 42-46.
	Zhao D B, Kou Y. Room temperature ionic liquids: synthesis, properties and applications[J]. University Chemistry, 2002, 17(1): 42-46.
17	石家华, 孙逊, 杨春, 等. 离子液体研究进展[J]. 化学通报, 2002, 65(4): 243-250.
	Shi J H, Sun X, Yang C, et al. Research progress of ionic liquids[J]. Chemical Bulletin, 2002, 65(4): 243-250.
18	黄碧纯, 黄仲涛. 离子液体的研究开发及其在催化反应中的应用[J]. 工业催化, 2003, 11(2): 1-6.
	Huang B C, Huang Z T. Research and development of ionic liquids and their applications in catalytic reactions[J]. Industrial Catalysis, 2003, 11(2): 1-6.
19	Muldoon M J, Nockemann P, Lagunas M C. Crystal engineering with ionic liquids[J]. CrystEngComm, 2012, 14(15): 4873.
20	Fan J P, Kong T, Zhang X H, et al. Solubilities of ursolic acid and oleanolic acid in (ethanol+water) mixed solvents from T=(292.2 to 328.2K)[J]. Journal of Chemical Thermodynamics, 2012, 47: 372-375.
21	Fan J P, Cao Y H, Zhang X H, et al. Determination and modeling of the solubilities of ursolic acid and oleanolic acid in ethanol+ sodium hydroxide+ water mixed solvents from T= 283.2 to 323.2 K[J]. Journal of Chemical & Engineering Data, 2017, 62(11): 3991-3997.
22	Fan J P, Kong T, Zhang L, et al. Solubilities of ursolic acid and oleanolic acid in four solvents from (283.2 to 329.7) K[J]. Journal of Chemical & Engineering Data, 2011, 56(5): 2723-2725.
23	Schneider P, Hosseiny S S, Szczotka M, et al. Rapid solubility determination of the triterpenes ursolic acid and oleanolic acid by UV-spectroscopy in different solvents[J]. Phytochemistry Letters, 2009, 2(2): 85-87.
24	Ge L, Guo L, Yang K, et al. Solubility of diosgenin in several imidazolium-based ionic liquids[J]. Journal of Chemical and Engineering Data, 2015, 60: 11-15.
25	Lee B S, Lin S T. Prediction and screening of solubility of pharmaceuticals in single- and mixed-ionic liquids using COSMO-SAC model[J]. AIChE Journal, 2017, 63(7): 3096-3104.
26	骆健美, 金志华. 纳他霉素在不同溶剂中溶解度的测定与关联[J]. 高校化学工程学报, 2008, 21(5): 733-738.
	Luo J M, Jin Z H. Measurement and correlation of the solubility of natamycin in different solvents [J]. Journal of Chemical Engineering of Chinese Universities, 2008, 21(5): 733-738.
27	Zhang Q, Hu Y, Yang Y, et al. Thermodynamic models for determination of the solubility of the (1∶1) complex of (urea + l-malic acid) in (methanol + acetonitrile) binary solvent mixtures[J]. Journal of Chemical Thermodynamics, 2015, 80(6): 7-12.
28	Fan J P, Yang X M, Xu X K, et al. Solubility of rutaecarpine and evodiamine in (ethanol+water) mixed solvents at temperatures from (288.2 to 328.2)K[J]. Journal of Chemical Thermodynamics, 2015, 83: 85-89.
29	Jiang S, Qin Y, Wu S, et al. Solubility correlation and thermodynamic analysis of sorafenib free base and sorafenib tosylate in monosolvents and binary solvent mixtures[J]. Journal of Chemical & Engineering Data, 2016, 62(1): 259-267.
30	Aniya V, De D, Mohammed A M, et al. Measurement and modeling of solubility of para-tert-butylbenzoic acid in pure and mixed organic solvents at different temperatures[J]. Journal of Chemical & Engineering Data, 2017, 62(4): 1411-1421.
31	Shakeel F, Haq N, Salem-Bekhit M M, et al. Solubility and dissolution thermodynamics of sinapic acid in (DMSO + water) binary solvent mixtures at different temperatures[J]. Journal of Molecular Liquids, 2017, 225: 833-839.
32	Shan Y, Fu M, Yan W. Solubilities of 4,5,7-triacetoxyflavanone in fourteen organic solvents at different temperatures[J]. Journal of Chemical & Engineering Data, 2016, 62(1): 568-574.
33	徐衡, 董奕, 马沛生. 顺丁烯二酸酐在邻苯二甲酸酯中溶解度的研究[J]. 石油化工, 2000, 29(7): 502-504.
	Xu H, Dong Y, Ma P S. Study on the solubility of maleic anhydride in phthalates[J]. Petrochemical Industry, 2000, 29(7): 502-504.
34	邹莹, 刘永琼, 祝宏, 等. 替硝唑在水溶液中溶解度的实验测定及关联[J]. 武汉工程大学学报, 2008, 30(1): 7-9.
	Zou Y, Liu Y Q, Zhu H, et al. Experimental determination and correlation of the solubility of tinidazole in aqueous solution[J]. Journal of Wuhan University of Technology, 2008, 30(1): 7-9.
35	Lan N, Ahn M K, Koo Y M. Methods for recovery of ionic liquids—a review[J]. Process Biochemistry, 2014, 49(5): 872-881.

T/K	A	B	C	D	E	F
293.2	2.58701	4.62446	3.91696	4.08962	4.21600	4.95054
298.2	3.29014	5.50223	4.81039	5.10499	5.29339	5.10910
303.2	6.43360	7.16866	5.35800	6.73191	7.45408	7.41121
308.2	7.26193	7.37772	5.73489	7.14156	7.94014	8.12856
313.2	7.76808	7.72152	6.34713	7.28522	8.14792	9.20341
318.2	9.23542	8.46756	9.97358	9.03714	8.20060	10.14640
323.2	11.99561	10.87394	11.60734	10.82879	9.76161	11.87940
328.2	13.93287	10.97432	12.10037	11.91585	11.95445	12.84131
333.2	14.36265	11.72096	13.70408	12.14856	14.51312	19.50879

T/K	A	B	C	D	E	F
293.2	2.58701	4.62446	3.91696	4.08962	4.21600	4.95054
298.2	3.29014	5.50223	4.81039	5.10499	5.29339	5.10910
303.2	6.43360	7.16866	5.35800	6.73191	7.45408	7.41121
308.2	7.26193	7.37772	5.73489	7.14156	7.94014	8.12856
313.2	7.76808	7.72152	6.34713	7.28522	8.14792	9.20341
318.2	9.23542	8.46756	9.97358	9.03714	8.20060	10.14640
323.2	11.99561	10.87394	11.60734	10.82879	9.76161	11.87940
328.2	13.93287	10.97432	12.10037	11.91585	11.95445	12.84131
333.2	14.36265	11.72096	13.70408	12.14856	14.51312	19.50879

T/K	A	B	C	D	E	F
293.2	3.66277	3.90568	3.18137	3.82803	4.55719	4.82319
298.2	4.11362	4.95578	4.31056	4.99628	5.06101	5.14561
303.2	5.06655	5.27193	4.72241	5.20969	5.64367	5.38338
308.2	5.48627	5.85894	5.47927	5.51890	6.01389	5.94459
313.2	7.41711	7.05214	6.22817	5.99910	7.70761	7.04455
318.2	8.12955	7.52216	6.90739	8.61030	8.26677	7.94869
323.2	8.32516	8.86441	7.81490	9.39422	9.87569	9.81278
328.2	9.94503	10.66226	10.42502	11.90057	10.83787	10.30029
333.2	12.56636	14.51072	13.08634	15.93602	15.17506	14.08778

T/K	A	B	C	D	E	F
293.2	3.66277	3.90568	3.18137	3.82803	4.55719	4.82319
298.2	4.11362	4.95578	4.31056	4.99628	5.06101	5.14561
303.2	5.06655	5.27193	4.72241	5.20969	5.64367	5.38338
308.2	5.48627	5.85894	5.47927	5.51890	6.01389	5.94459
313.2	7.41711	7.05214	6.22817	5.99910	7.70761	7.04455
318.2	8.12955	7.52216	6.90739	8.61030	8.26677	7.94869
323.2	8.32516	8.86441	7.81490	9.39422	9.87569	9.81278
328.2	9.94503	10.66226	10.42502	11.90057	10.83787	10.30029
333.2	12.56636	14.51072	13.08634	15.93602	15.17506	14.08778

溶剂体系	a	b	c	R²	RAD	RMSD×10⁴
A	692.52	-35383.00	-100.48	0.9653	0.0903	0.6476
B	190.14	-10580.53	-26.84	0.9470	0.0447	0.4667
C	152.68	-9827.87	-20.75	0.9429	0.0813	0.7159
D	272.51	-14774.22	-38.85	0.9638	0.0445	0.4517
E	-283.51	11096.12	43.53	0.9226	0.0861	0.7177
F	-613.83	25985.89	92.75	0.9359	0.0842	0.9308