叶黄素酯/α-环糊精包合研究

目的:研究叶黄素酯与α-环糊精的包合性能。方法:紫外法测定包合行为并计算表观包合常数;研磨法制备包合物;溶解度为指标确定包合比;DTA、DR-FTIR、UV-vis DRS验证包合物;与β-环糊精和混合环糊精的包合作用比较,测定其溶解度、稳定性。结果:叶黄素酯与α-环糊精表观包合常数Ka为127 L/mol;包合比1∶5时溶解度最佳;α-环糊精使叶黄素酯稳定性增强,溶解度提高为叶黄素酯原料的6倍以上。结论:α-环糊精应用于叶黄素酯性能优于β-环糊精和混合环糊精。     

番茄红素环糊精包合片剂的研制

目的:研制新型番茄红素制剂产品.方法:β-环糊精与羟丙基-β-环糊精混合包合番茄红素,紫外法测定表观包合常数;研磨法制备包合物并测定溶解度,以包合片稳定性、崩解时间及溶出度优化筛选片剂处方和制备方法.结果:不同比例混合的环糊精与番茄红素的表观包合常数为522～932L·mol-1,对番茄红素增溶47.6～116.7倍;包合片稳定性好,崩解溶出快,活性好.结论:混合环糊精改进番茄红素效果明显,其性能优于环糊精的简单加和,具有很高的经济性价比.     

响应面优化羟丙基-β-环糊精对血根碱的包合工艺

本文采用溶液搅拌法制备血根碱与羟丙基-β-环糊精包合物。以羟丙基-β-环糊精和血根碱包合比、包合温度、包合时间为考察因素,在单因素试验基础上,应用Box-Behnken中心组合方法进行3因素3水平的试验设计,以血根碱和羟丙基-β-环糊精包合率为响应值,采用响应面法对包合条件进行进一步优化。结果表明:最佳条件为:包合比10:1,包合温度60℃,包合时间190 min,血根碱和羟丙基-β-环糊精包合率为73.55%,与预测值(72.43%)接近(相对误差1.5%)。该方法稳定、重复性好,是一种高效制备血根碱羟丙基-β-环糊精包合物的方法。     

相溶解度法研究环糊精对纳他霉素的包合作用

目的:研究β-环糊精(β-CD)和羟丙基β-环糊精(HP-β-CD)对纳他霉素的增溶作用。方法:采用紫外分光光度测定纳他霉素含量,相溶解度法研究β-环糊精(β-CD)和羟丙基β-环糊精(HP-β-CD)对纳他霉素的包合作用、增溶作用及包合过程中热力学参数变化。结果:纳他霉素的溶解度随着β-环糊精浓度的增加而呈线性增加,相溶解度图呈AL型;纳他霉素的溶解度与羟丙基β-环糊精浓度在一定范围内呈线性,但随着羟丙基β-环糊精浓度的增加呈负向偏离型,相溶解度图呈AN型。纳他霉素与2种环糊精在包合过程中的吉布斯自由能变化(ΔG)、焓变(ΔH)均为负值,纳他霉素与β-CD在包合过程中的熵变(ΔS)为负值,而与HP-β-CD包合过程中的熵变(ΔS)为正值。结论:纳他霉素与2种环糊精增溶作用明显。     

莱菔素-羟丙基-β-环糊精包合物的制备工艺与表征

研究了莱菔素-羟丙基-β-环糊精包合物的制备工艺及表征,通过单因素试验和正交试验确定包合物的最佳包埋工艺为:芯壁比1∶6,包合温度70℃,包合时间3h。通过红外光谱仪对包合物的定性分析表明,莱菔素-羟丙基-β-环糊精包合物已经形成。     

叶黄素-β-环糊精包合物的制备及其光谱研究

以β-环糊精(β-CD)为主体,超声法制备叶黄素-β-环糊精(叶黄素-β-CD)包合物,通过X射线粉末衍射光谱、红外光谱及差示扫描量热分析对叶黄素-β-CD包合物进行表征。结果表明：叶黄素-β-CD包合物的适宜包合条件为叶黄素与β-CD的物质的量比1:4,超声功率400W,超声时间40min,包合率可达到75.8%以上;产物的光谱特征的变化证实叶黄素和β-CD形成了新的物相;而用相溶解度确定叶黄素和β-CD的相溶解度曲线属于AL型,叶黄素与β-CD形成1:1包合物,包结常数为346.97L/mol。经包合后,叶黄素的稳定性与水溶性得到明显提高。     

纳他霉素-羟丙基-β-环糊精包合物的制备及其抑菌性能研究

纳他霉素(Natamycin)是一种多烯大环内酯类抗生素,为了提高其在水中的溶解度和稳定性,增加其生物利用度,以羟丙基-β-环糊精为包合剂,采用冷冻干燥法制备纳他霉素-羟丙基-β-环糊精包合物。通过差热分析法和紫外光谱分析法验证,说明纳他霉素已经被羟丙基-β-环糊精完全包合。研究结果表明,包合物包合率100%,溶解度≥60g/L,60d后浓度为28.31mg/L。在105cfu/mL菌液浓度下,包合物和对照均对白色念珠菌、酵母菌、黑曲霉、绿色木霉、镰刀菌比较敏感,MIC值为2mg/kg,对米曲霉的抑菌效果最差,MIC值为12mg/kg。由此说明包合物的形成可以明显改善纳他霉素的水溶性和稳定性,且包合后不影响其对真菌的抑制效果。     

番茄红素水溶性包合物的研究

制备了番茄红素-2-羟丙基-β-环糊精包合物，测定了包合物的溶解度、稳定性，比较了包合物及番茄红素的紫外吸光光谱变化，差示扫描量热图谱．结果表明：番茄红素与2-HP-8-CD以摩尔比1：4混合，经研磨法包合处理后，2-羟丙基-β-环糊精与番茄红素形成一种新的物相，包合后番茄红素在水中的溶解度增大到0．5mg／mL，包合物在4℃下放置两个月番茄红素基本不损失，稳定性好。     

羟丙基-β-环糊精与4-羟基查尔酮的包合作用研究

本研究为了系统研究羟丙基-β-环糊精与查尔酮的包合作用,采用相溶解度法测定了β-环糊精(β-CD)和羟丙基-β-环糊精(HP-β-CD)包合4-羟基查尔酮过程中的热力学参数,并运用红外(IR)、X-射线衍射(XRD)、热重及差示扫描量热联用(TG/DSC)等分析手段对该包合物的理化性质进行了系统研究。相溶解度实验表明HP-β-CD对4-羟基查尔酮的包合效果优于β-CD,而热力学分析发现4-羟基查尔酮和HP-β-CD的包合是一个自由能降低过程,反应具有自发性,其结合过程受疏水作用力驱动。红外和X-射线衍射分析表明4-羟基查尔酮与HP-β-CD包合后,其物相发生了重大改变,4-羟基查尔酮以无定形的状态完全分散在HP-β-CD中。热重及差示扫描量热联用分析发现通过与羟丙基-β-环糊精的包合,4-羟基查尔酮的热稳定性得到了显著提高。     

响应面法优化八角茴香精油/羟丙基-β-环糊精包合物制备工艺

对八角茴香精油/羟丙基-β-环糊精包合物制备工艺进行了研究。以包合率(%)为响应值,主客比(mg∶mg)、包合时间(h)、包合温度(℃)为自变量,在单因素试验的基础上,通过响应面设计确定了最佳包合工艺为:主客比(mg∶mg)49.6,包合时间98.03h,包合温度33.1℃,此时包合率为72.29%。而且包合时间与包合温度的交互作用显著。UV光谱分析结果显示,体系中加入羟丙基-β-环糊精后,八角茴香精油的最大吸收波长由258nm移至257nm,且E带吸收和B带吸收均出现了蓝移,证明了包合物的形成。     

环糊精对青蒿素的包合工艺研究

通过单因素及正交试验确定青蒿素与3种环糊精形成包合物的最佳条件,在此条件下利用相溶解度法测定青蒿素与β-环糊精、羟丙基-β-环糊精、γ-环糊精的包合常数并计算包合反应前后的吉布斯自由能。结果表明：青蒿素与环糊精形成包合物的最佳条件为配比1:1(mol/mol)、包合温度40℃、包合时间5h、包合反应时溶液pH7,青蒿素与β-环糊精、羟丙基-β-环糊精、γ-环糊精的包合常数分别为80.06、58.68、116.96L/mol,反应前后的吉布斯自由能变化分别为－11.76、－10.93、－12.78kJ/mol。表明青蒿素与环糊精可以形成1:1型稳定的包合物,环糊精可以增大青蒿素的溶解度。     

An investigation into the supramolecular structure,solubility, stability and antioxidant activity of rutin/cyclodextrin inclusion complex

The formation of supramolecular inclusion complexes between rutin and four cyclodextrins, namely β-cyclodextrin (β-CD), (2-hydroxypropyl)-α-cyclodextrin (HP-α-CD), (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) and (2-hydroxypropyl)-γ-cyclodextrin (HP-γ-CD), and the effects of the complexation on the stability and antioxidant activity of rutin were investigated. Results from phase-solubility studies showed that rutin formed 1:1 stoichiometric inclusion complexes with HP-α-CD, β-CD, HP-β-CD and HP-γ-CD; the complexes formed with HP-γ-CD and HP-β-CD had the greatest stability constants, followed by β-CD and HP-α-CD. Thermodynamic studies demonstrate that the inclusion of rutin into HP-β-CD was an exothermic process which occurred spontaneously. Two-dimensional rotating-frame nuclear Overhauser effect spectroscopy (2D ROESY) ¹H NMR analyses show that the A ring of rutin was the part of the molecule that most likely inserted into the cavity of HP-β-CD, thus forming a supramolecular inclusion complex. Formation of such an inclusion complex conferred moderate degrees of protection to rutin from degradation by heat and UV radiation during storage, and significantly enhanced its antioxidant capacity as determined by three different procedures.     

青藤碱- 环糊精包合工艺的优化及包合常数测定

目的：考察青藤碱与环糊精形成包合物的最佳条件,测定青藤碱与不同环糊精的包合常数并进行体外释放研究。方法：通过单因素及正交试验确定青藤碱与不同环糊精形成包合物的最佳条件,并在此条件下利用相溶解度法测定青藤碱与β-环糊精、羟丙基-β-环糊精、γ-环糊精的包合常数,对包合物进行体外释放试验研究。结果：青藤碱与不同环糊精形成包合物的最佳条件为物质的量的1:1、包合温度50℃、包合反应3h、包合反应时溶液pH7,青藤碱与β-环糊精、羟丙基-β-环糊精、γ-环糊精的包合常数分别为501.1、150.0、600.3L/mol。结论：青藤碱与环糊精可以形成1:1型稳定的包合物,以环糊精为载体制备的不同青藤碱-环糊精包合物相对于青藤碱具有明显的缓释作用。     

Preparation and properties of phytosterols with hydroxypropyl β-cyclodextrin inclusion complexes

In order to enhance the solubility and bioavailability of phytosterols (PS), cyclodextrin–PS (CD–PS) inclusion complexes were prepared and the properties of PS-β-cyclodextrin (PS-β-CD) and the inclusion mechanism of its derivative hydroxypropyl β-cyclodextrin (PS-HP-β-CD) in solution were also evaluated. The effects of crucial parameters on cyclodextrin–sterol inclusion efficiency were optimized, including solvent type, β-CD/PS molar ratio, temperature, PS content and reaction time; 92–98?% inclusion efficiency was achieved under the conditions of HP-β-CD/PS ratio 3:1–4:1, PS concentration 15–20?mM, temperature 50–55?°C, reaction time 12?h. For β-CD host, butanol was a good solvent for PS inclusion reaction. The properties of CD–PS inclusion complexes were characterized by differential scanning calorimetric, scanning electron microscopy, UV–Vis scanning spectrophotometer (UV–Vis) and fourier transform infrared spectroscopy (FT-IR), which demonstrated that there are intermolecular hydrogen bonds between PS and HP-β-CD in inclusion complex, resulting in the formation of amorphous form. To clarify the mechanism of the increase in the solubility and bioactivity of HP-β-CD–PS inclusion complexes, the structure of CD as well as the interaction of the HP-β-CD–PS inclusion formation was elucidated. The conclusions indicated that PS-HP-β-CD showed higher water solubility with greater solubilizing and complexing capabilities than PS-β-CD and PS itself.     

Empirical,thermodynamic and quantum-chemical investigations of inclusion complexation between flavanones and (2-hydroxypropyl)-cyclodextrins

The inclusion complexation of (2-hydroxypropyl)-cyclodextrins with flavanones was investigated by phase solubility measurements, as well as thermodynamic and quantum chemical methods. Inclusion complexes were formed between (2-hydroxypropyl)-α-cyclodextrin (HP-α-CD), (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD), (2-hydroxypropyl)-γ-cyclodextrin (HP-γ-CD) and β-cyclodextrin (β-CD) and four flavanones (naringenin, naringin, hesperetin and dihydromyricetin) in aqueous solutions and their phase solubility was determined. For all the flavanones, the stability constants of their complexes formed with different CDs followed the rank order: HP-β-CD (MW 1540) > HP-β-CD (MW 1460) > HP-β-CD (MW 1380) > β-CD > HP-γ-CD > HP-α-CD. Experimental results and quantum chemical calculations showed that the ability of flavanones to form inclusion complex with (2-hydroxypropyl)-cyclodextrins was determined by both the steric effect and hydrophobicity of the flavanones. For flavanones that have similar molecular volumes, the hydrophobicity of the molecule was the main determining factor of its ability to form inclusion complexes with HP-β-CD, and the hydrophobicity parameter Log P is highly correlated with the stability constant of the complexes. Results of thermodynamic study demonstrated that hydrophobic interaction is the main driving force for the formation process of the flavanone–CD inclusion complexes. Quantum chemical analysis of the most active hydroxyl groups and HOMO (the highest occupied molecular orbital) showed that the B ring of the flavanones was most likely involved in hydrogen bonding with the side groups in the cavity of the CDs, through which the inclusion complex was stabilised.     

四种β-环糊精制备鞣花酸包合物的抗氧化性研究

利用鞣花酸（EA）与β-环糊精（β-CD）、羟丙基-β-环糊精（HP-β-CD）、二甲基-β-环糊精（DM-β-CD）、磺丁基-β-环糊精（SBE-β-CD）制备鞣花酸包合物,并使用高效液相色谱测定鞣花酸包合物的包合率,然后采用傅里叶红外光谱、X-射线衍射、扫描电镜对包合物进行表征,同时通过自由基清除能力评价鞣花酸包合物的抗氧化性。结果表明,EA/β-CD、EA/HP-β-CD、EA/DM-β-CD、EA/SBE-β-CD包合物的表观溶解度分别为0.037 3 mg/mL、0.123 2 mg/mL、0.093 8 mg/mL、0.095 6 mg/mL,包合率分别为82.58%、89.80%、87.42%、84.64%。鞣花酸与四种鞣花酸包合物清除DPPH自由基的半数清除率（EC50）值分别为6.47 μg/mL、6.31 μg/mL、3.45 μg/mL、3.63 μg/mL、3.92 μg/mL;清除ABTS自由基的EC50值分别为13.53 μg/mL、12.11 μg/mL、7.00 μg/mL、7.66 μg/mL、7.77 μg/mL;清除羟基自由基的EC50值分别为0.133 6 μg/mL、0.136 3 μg/mL、0.108 2 μg/mL、0.108 3 μg/mL、0.105 5 μg/mL;清除超氧阴离子自由基的EC50值分别为89.41 μg/mL、59.71 μg/mL、55.20 μg/mL、58.32 μg/mL、55.29 μg/mL。结果表明包合技术可以提高鞣花酸的溶解度与抗氧化能力。     

Characterisation of inclusion complex of trans-ferulic acid and hydroxypropyl-β-cyclodextrin

The inclusion complex of trans-ferulic acid (FA) with hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared by the freeze-drying method and its characterisation was investigated by different analytical techniques including UV–visible spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffractometry, and scanning electron microscopy. All these approaches indicated that FA was able to form an inclusion complex with HP-β-CD, and the FA/HP-β-CD inclusion compounds exhibited different spectroscopic features and properties from FA. The stoichiometry of the complex was 1:1. The calculated apparent stability constant of the FA/HP-β-CD complex was 166.3 M⁻¹, and the water solubility of FA was significantly improved by phase solubility studies. Moreover, the irradiation-induced decomposition of FA in aqueous solution was markedly reduced by complexation with HP-β-CD. The results showed that HP-β-CD was a proper excipient for increasing solubility and stability of FA.     

Physicochemical characterisation of the supramolecular structure of luteolin/cyclodextrin inclusion complex

The formation of supramolecular inclusion complexes between luteolin and five cyclodextrins namely β-cyclodextrin (β-CD), methyl-β-cyclodextrin (M-β-CD), hydroxyethyl-β-cyclodextrin (HE-β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) and glucosyl-β-cyclodextrin (G-β-CD) was investigated. Results from phase-solubility studies showed that luteolin formed 1:1 stoichiometric inclusion complexes with these cyclodextrins with the G-β-CD complex displaying the greatest stability constant. The supramolecular structure of the luteolin/G-β-CD complex was investigated by ultraviolet–visible spectroscopy (UV), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Results showed clearly the formation of a supramolecular complex in which the guest molecule, luteolin, was entrapped inside the cavity of the host, G-β-CD. The close association between luteolin and G-β-CD resulted in changes in some of the characteristic spectral, phase transitional and morphological properties of luteolin. Furthermore, molecular docking study showed that the complex was formed with the B ring of luteolin inserted into the cavity of G-β-CD.     

Influence of ligand structure and water interactions on the physical properties of β-cyclodextrins complexes

The water sorption and physical properties of freeze-dried β-cyclodextrin (BCD) and 2-hydroxypropyl-β-cyclodextrin (HBCD) were studied. The stability of the inclusion complexes of these cyclodextrins with different hydrophobic ingredients, such as myristic acid and α-terpineol, was investigated as a function of the storage time and water content of the systems. Besides increasing its solubility, BCD ring modification with hydroxypropyl groups conferred amorficity to the dehydrated matrices, and modified the sorption properties and their ability to form hydrates.     

Physicochemical properties and mechanism of solubilised neohesperidin system based on inclusion complex of hydroxypropyl-β-cyclodextrin

A solvent method was used to prepare the inclusion compound of neohesperidin (NH) and hydroxypropyl-β-cyclodextrin (HP-β-CD) to improve the water solubility and thermal stability of NH. The physical and chemical properties and supramolecular structure of the inclusion complex were investigated by UV–vis spectroscopy, FTIR, SEM, TG-DTG, PXRD, NMR and molecular docking techniques. The results showed that the C-ring of NH was embedded in the cavity of HP-β-CD to form an inclusion complex. The phase has changed significantly, NH is completely dispersed in HP-β-CD in an amorphous state, and the two are combined in the form of non-covalent bonds such as hydrogen bonds or van der Waals forces. Through inclusion of HP-β-CD, the solubility of NH in water at 37 °C increased from 161.81 μg ml⁻¹ to 1927.12 μg ml⁻¹, and its stability was also significantly improved.