维生素A醋酸酯/环糊精包合及性质研究

doi:10.11949/0438-1157.20240291

摘要/Abstract

摘要：

通过冷冻干燥法制备了维生素A醋酸酯（VAA）和β环糊精（β-CD）及其衍生物羟丙基β环糊精（HP-β- CD）、磺丁基醚β环糊精（SBE-β-CD）的包合物，采用傅里叶红外光谱（FT-IR）、核磁共振氢谱（¹H NMR）和扫描电子显微镜（SEM）对包合物进行了表征，并对包合物的相溶解度、热稳定性、溶解度和分子结合模式进行了分析。相溶解度实验结果表明三种环糊精均与VAA形成包合比为1∶1的包合物，其中HP-β-CD的稳定常数最高，对VAA的包合效果要优于另外两种环糊精。热稳定性和溶解度变化测试实验结果表明，与游离VAA相比，三种包合物的热稳定性和水溶性均有大幅提高，其中VAA/HP-β-CD的效果最好，热损失率由52.6%下降至5.2%；水溶解度由1.9×10^-4增至100 g/100 g。分子对接结果表明，HP-β-CD扩大了β-CD空腔长度，使VAA被完全包裹，并和VAA形成了分子间氢键，与VAA形成的包合物具有最小结合能。上述研究结果表明HP-β-CD是VAA的优良包合载体，能有效提高VAA的应用性能。

关键词: 维生素A醋酸酯, 环糊精, 稳定性, 溶解性, 分子模拟

Abstract:

The inclusion complexes of VAA with β-cyclodextrin (β-CD) and its derivatives hydroxypropyl β- cyclodextrin (HP-β-CD) and sulfobutyl ether β-cyclodextrin (SBE-β-CD) were prepared by freeze-drying method, and the inclusion complexes were characterized by Fourier infrared spectroscopy (FT-IR), nuclear magnetic resonance hydrogen spectroscopy (¹H NMR), and scanning electron microscope (SEM), and phase solubility, thermal stability, solubility and molecular binding mode were analyzed. The results of the phase solubility experiments showed that all the three cyclodextrins formed an inclusion ratio of 1∶1 with VAA, among which HP-β-CD had the highest stability constant and was more effective than the other two cyclodextrins in the inclusion of VAA. The experimental results of thermal stability and solubility change tests showed that the thermal stability and water solubility of the three inclusion compounds were substantially improved compared with free VAA, with VAA/HP-β-CD being the best, with the heat loss rate decreasing from 52.6% to 5.2%; and the water solubility increasing from 1.9×10^-4 to 100 g/100 g. The results of the molecular docking showed that HP-β-CD enlarged the β-CD cavity length so that VAA was completely encapsulated and formed intermolecular hydrogen bonding with VAA, and the inclusion complex formed with VAA had minimal binding energy. The above results indicate that HP-β-CD is an excellent encapsulation carrier for VAA and can effectively improve the application performance of VAA.

Key words: vitamin A acetate, cyclodextrin, stability, solubility, molecular simulation

中图分类号:

O 648.25

王新月, 徐小虎, 张海洋, 尹春华. 维生素A醋酸酯/环糊精包合及性质研究[J]. 化工学报, 2024, 75(S1): 321-328.

Xinyue WANG, Xiaohu XU, Haiyang ZHANG, Chunhua YIN. Study on encapsulation and properties vitamin A acetate/cyclodextrin[J]. CIESC Journal, 2024, 75(S1): 321-328.

图/表 9

图1 维生素A醋酸酯、环糊精与其物理混合物和包合物的红外光谱a—VAA; b—β-CD; c—VAA/β-CD物理混合物; d—VAA/β-CD包合物; e—HP-β-CD; f—VAA/HP-β-CD物理混合物; g—VAA/HP-β- CD包合物; h—SBE-β-CD; i—VAA/SBE-β-CD物理混合物; j—VAA/SBE-β-CD包合物

Fig.1 FT-IR spectra of VAA, cyclodextrins, physical mixtures, inclusion complexes

图2 维生素A醋酸酯、环糊精及其包合物的核磁共振谱图a—β-CD; b—VAA/β-CD; c—HP-β-CD; d—VAA/HP-β-CD; e—SBE-β-CD; f—VAA/SBE-β-CD

Fig.2 1HNMR spectra of VAA, cyclodextrins and inclusion complexes

表1 β-CD、HP-β-CD、SBE-β-CD与VAA包合物的核磁共振氢谱化学位移值

Table 1 1H NMR chemical shift changes of β-CD， HP-β-CD， SBE-β-CD with VAA inclusion complexes

样品化学位移	H-1	H-3	H-6	H-5	H-2	H-4
δ(free β-CD)	5.009	3.910	3.821	3.806	3.602	3.527
δ(VAA/β-CD)	4.997	3.885	3.818	3.785	3.593	3.524
Δδ (VAA/β-CD)	-0.012	-0.025	-0.003	-0.021	-0.009	-0.003
δ(free HP-β-CD)	4.989	3.853	3.784	3.761	3.638	3.520
δ(VAA/ HP-β-CD)	4.981	3.828	3.782	3.734	3.636	3.511
Δδ(VAA/ HP-β-CD)	-0.008	-0.025	-0.002	-0.027	-0.002	-0.009
δ(free SBE-β-CD)	4.978	3.880	3.792	3.768	3.579	3.497
δ(VAA/SBE-β-CD)	4.966	3.844	3.783	3.735	3.565	3.498
Δδ (VAA/SBE-β-CD)	-0.012	-0.036	-0.009	-0.033	-0.014	0.001

图3 VAA、CDs、物理混合物及其包合物的SEM图

Fig.3 SEM images of VAA, CDs, physical mixtures and inclusion complexes

图4 VAA与β-CD(a)、HP-β-CD(b)、SBE-β-CD(c)的相溶解度图

Fig.4 Phase solubility diagram of β-CD (a), HP-β-CD (b), SBE-β-CD (c)

表2 在不同温度下VAA/β-CD、VAA/HP-β-CD、VAA/SBE-β-CD的相溶解度系数（K）及热力学参量（ΔG、ΔH和ΔS）

Table 2 Phase solubility coefficients （K） and the estimated thermodynamic quantities for formation of VAA/β-CD， VAA/HP-β-CD， VAA/SBE-β-CD at various temperatures.

样品	T/K	S₀/mol	Slope×10^-3	K×10³/(1/mol)	ΔG/(kJ/mol)	ΔH/(kJ/mol)	ΔS/(kJ/mol)
	283	(1.264±0.018)×10^-6	3.333±0.026	2.646±0.017	-18.543±0.016	-82.520±0.384	-0.226±0.001
β-CD	285	(0.958±0.027)×10^-6	2.08±0.004	2.176±0.057	-18.210±0.063	-82.520±0.384	-0.226±0.002
	288	(1.409±0.015)×10^-6	2.037±0.008	1.448±0.009	-17.427±0.015	-82.520±0.384	-0.226±0.001
	283	(1.175±0.014)×10^-7	5.049±0.026	43.185±0.29	-25.113±0.016	-252.085±0.593	-0.802±0.002
HP-β-CD	285	(2.191±0.053)×10^-7	5.281±0.025	24.242±0.47	-23.922±0.046	-252.085±0.593	-0.801±0.002
	288	(7.731±0.128)×10^-7	5.279±0.065	6.864±0.029	-21.153±0.010	-252.085±0.593	-0.802±0.002
	283	(1.368±0.001) ×10^-6	5.896±0.007	4.337±0.007	-19.705±0.004	-100.383±0.270	-0.285±0.001
SBE-β-CD	285	(2.133±0.003)×10^-6	5.427±0.017	2.646±0.017	-18.594±0.004	-100.383±0.270	-0.287±0.001
	288	(2.651±0.011)×10^-6	5.304±0.002	2.646±0.017	-18.214±0.009	-100.383±0.270	-0.285±0.001

图5 在40℃条件下7 d内VAA的含量损失

Fig.5 The content loss of VAA within 7 d at 40℃

表3 游离VAA和VAA/β-CD、VAA/HP-β-CD、VAA/SBE-β-CD的水溶性

Table 3 Water solubility of free VAA and VAA/β-CD， VAA/HP-β-CD， VAA/SBE-β-CD

样品	溶解度/(g/100 g)
Free VAA	1.9×10^-4
VAA/β-CD	0.85±0.05
VAA/HP-β-CD	100±0.04
VAA/SBE-β-CD	1.48±0.05

图6 β-CD(a)、HP-β-CD (b)、SBE-β-CD (c)与VAA的最优结合模式

Fig.6 The optimal binding modes by docking for the complexes of VAA with β-CD (a), HP-β-CD (b), SBE-β-CD (c)

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