蔗糖酯的HPLC-ELSD法分离与测定

用HPLC-ELSD法分离与测定蔗糖酯,考察了蔗糖酯的HPLC-ELSD分析条件。用Hypersil C8色谱柱(250 mm,4.6 mm,5μm),以〔V(甲醇)∶V(四氢呋喃)=90∶10〕-水二元溶剂系统为流动相,梯度洗脱,流动相流速1.0 mL/m in,柱温40℃,对商品蔗糖酯和合成蔗糖酯进行了定性和定量分析。研究结果表明,在该条件下,HPLC-ELSD有效地分离了蔗糖酯产品中的蔗糖、蔗糖单酯、蔗糖二酯、脂肪酸、硬脂酸甲酯和蔗糖多酯,不但可用于蔗糖酯合成中的终点控制,而且可以对精制后的产品进行分析,从而监控产品的质量,也可用于蔗糖酯的结构鉴定,是一种连续、快速、方便、高效的蔗糖酯的定性和定量分析方法。     

Efficient Encapsulation of a Water-Soluble Molecule into Lipid Vesicles Using W/O/W Multiple Emulsions via Solvent Evaporation

We developed a novel method for preparing lipid vesicles with high entrapment efficiency and controlled size using water‐in‐oil‐in‐water (W/O/W) multiple emulsions as vesicle templates. Preparation consists of three steps. First, a water‐in‐oil (W/O) emulsion containing to‐be‐entrapped hydrophilic molecules in the water phase and vesicle‐forming lipids in the oil phase was formulated by sonication. Second, this W/O emulsion was introduced into a microchannel emulsification device to prepare a W/O/W multiple emulsion. In this step, sodium caseinate was used as the external emulsifier. Finally, organic solvent in the oil phase was removed by simple evaporation under ambient conditions to afford lipid vesicles. The diameter of the prepared vesicles reflected the water droplet size of the primary W/O emulsions, indicating that vesicle size could be controlled by the primary W/O emulsification process. Furthermore, high entrapment yields for hydrophilic molecules (exceeding 80 % for calcein) were obtained. The resulting vesicles had a multilamellar vesicular structure, as confirmed by transmission electron microscopy.     

改性纳米碳酸钙用于硅酮胶挤出性研究

采用碳化法合成纳米碳酸钙,在反应过程中,调整反应起始温度合成不同晶型大小的纳米碳酸钙。通过透射电镜（TEM）、激光粒度仪对碳酸钙的物相、形貌、粒度进行分析,将改性纳米碳酸钙应用于硅酮胶基料制备及挤出性研究,分析改性纳米碳酸钙的颗粒大小、分散性、流变性能及表面改性剂对挤出性的影响。结果表明：粒径介于50~90 nm,屈服值介于66.4~148.9 Pa,黏度介于0.5~0.75 mPa·s,硬脂酸钠与LH-2、LH-3两种包覆剂进行复配改性的纳米碳酸钙用于硅酮胶基料具有较好的挤出性能。     

Phase behavior of some sucrose surfactants with water and n-decane

The phase behavior of some sucrose esters in water and n-decane is reported. The type of liquid crystal formed and the extent of a particular phase region are correlated with the hydrocarbon chain length of the fatty acid.     

Nanovesicles Based on Mixtures of a Biantennary Glycolipid with Ionic Co‐Surfactants

A biantennary surfactant based on a synthetic C₁₆‐maltoside was chosen to prepare vesicles for a potential vesicular drug delivery system. The synthesis comprised of three stages: Initial synthesis of β‐d ‐maltose octaacetate was followed by glycosidation of 2‐hexyl‐decanol and final glycolipid deacetylation. Both α‐ and β‐anomers were prepared and their anomeric purity was evaluated by ¹H NMR. Owing to the low water solubility of the glycolipid, addition of ionic co‐surfactants was believed to promote the surfactant distribution, thus leading to smaller and more uniform vesicles. The assembly behavior of the surfactant systems was studied by contact penetration under an optical polarizing microscope, while interfacial properties were determined by surface tension measurements. Vesicles were prepared by injection of an ethanolic solution into bulk water and investigated by dynamic light scattering and field emission scanning electron microscopy. Contact of the surfactant mixtures with water indicated a high tendency to exhibit the lamellar phase and confirmed the expected low molecular solubility. These findings suggest a potential of the surfactant to form stable vesicles. Injection of an ethanolic surfactant solution into bulk water gave sub‐micrometer sized vesicles with a narrow size distribution. Application of ionic co‐surfactants reduced the vesicle size. In particular ～20 % of anionic SDS proved highly effective, lowering the vesicle size by nearly one decade, thus accessing nano‐sized vesicles. Encapsulation of a water‐soluble drug was achieved in a 76 ± 10 % efficiency.     

Flow Behavior of Oleic Acid Liposomes in Sucrose Ester Glycolipid Oil-in-Water Emulsions

Liposomes have been used widely as carriers for active ingredients in cosmetics because of their ability to encapsulate both hydrophilic and hydrophobic compounds. In this work, fatty acid liposomes were prepared and introduced into olive oil-in-water emulsions stabilized by C₁₄–C₁₈ sucrose ester mixtures at pH 8.5. Light microscopy images of the emulsions showed evidence of the coexistence of oleic acid liposomes with the emulsions. As the alkyl chain length of the sucrose ester increased, the average droplet size decreased, while the zeta potential became more negative. Further decrease in droplet size was observed when borate buffer was added to the aqueous phase. The free fatty acids in the sucrose esters and olive oil are neutralized in borate buffer; consequently, fatty acid salts were produced and served as co-surfactants. The synergistic stabilization of emulsions by the mixture of sucrose esters and fatty acid salt resulted in higher stability, smaller droplet size, and lower polydispersity. The drastic increase in negative zeta potential was possibly due to the presence of free fatty acid salts in the emulsion systems. The flow curves at steady rate displayed five distinctive regions. The polydispersity of droplets enhanced the shear thickening effect at low shear rates and shear-banding effect at middle shear rates. Formation of fatty acid salts as co-surfactants caused the viscosities of the emulsions to increase by an order of magnitude. The presence of oleic acid liposome significantly reduced the viscosities of the emulsion by half an order of magnitude; this decreased viscosity helped enhance better spreadability.     

Sol–Gel Synthesis and Characterization of Alumina–Calcium Hexaaluminate Composites

Boehmite sol was prepared by hot water hydrolysis of aluminum iso-propoxide using nitric acid as the catalyst. Calcium nitrate to yield 0–20 vol% calcia was added to the boehmite sol. The boehmite with additives was calcined at 600°C for 3 h. The calcined powder was milled at 230 rpm for 6 h and particle size was measured using Laser particle size analyzer. The powder samples were calcined at 1600°C for 3 h and the formation of calcium hexaaluminate was discussed using phase diagram, transmission electron microscope, energy dispersive spectra, and X-ray diffraction spectra. The powder samples calcined at 600°C for 3 h were compacted into cylindrical pellets and sintered at temperatures ranging from 1400° to 1600°C for 6 h and the formation of hexaaluminate (platelike) grains were confirmed using Scanning electron microscope and optical microscopy.     

Preparation and Physicochemical Properties of Lauroyl-Glutamyl-Lysil-Lauroyl-Glutamate Vesicles

We investigate the compositions of vesicle formulation by assembling phase diagrams of the ternary components of lauroyl‐glutamyl‐lysil‐lauroyl‐glutamate (C₁₂‐GLG‐C₁₂) peptide‐based gemini‐type amphiphile/citric acid/water using visual and microscopic observations. To clarify interactions between C₁₂‐GLG‐C₁₂ and citric acid, turbidity and zeta potential of the mixtures were investigated. To improve the stability of metastable vesicles, appropriate additives were examined by measuring particle size and zeta potential, visual observation and transmission electron microscopy. The turbidity increased and the absolute value of zeta potential decreased with increasing citric acid concentration in C₁₂‐GLG‐C₁₂/citric acid solutions. Then, a metastable γ region having vesicles was formed. The stability of vesicles increased with increasing cholesterol concentrations. This result suggests that a coacervation has occurred due to the effective cross‐sectional area decreasing with increasing C₁₂‐GLG‐C₁₂ hydrophobicity, which was derived from inhibition of the carboxyl group dissociation. Furthermore, we hypothesized that the orientation of cholesterol between vesicle membranes is a contributing factor to improve the vesicle stability. From transmission electron microscopic observations, it was made clear that the vesicles consisting of cholesterol and C₁₂‐GLG‐C₁₂ at a molar ratio of 2:1 showed multilayered structures. The vesicles consisting of C₁₂‐GLG‐C₁₂, cholesterol and citric acid are expected to be used as transdermal drug delivery system carriers, as they can be easily prepared using biocompatible compounds without the use of organic solvents such as chloroform.     

Synthesis of Al2O3–CeO2 Mixed Oxide Nano-Powders

Ceria (CeO₂)-doped alumina (Al₂O₃) composite nano-particles were synthesized using sucrose as a chelating agent and template material. As-synthesized powders were characterized using X-ray diffraction technique for their phase analysis, BET surface area analyzer for specific average surface area, and transmission electron microscope for particle size and morphology. Both CeO₂ and Al₂O₃ delayed the amorphous to crystalline phase transformation for each other. These composite nano-powders had particle size in the range of 20–50 nm with an aspect ratio of 1.5 with platelet morphology and surface area between 100 and 300 m²/g. Synthesis parameters were optimized varying the sucrose to metal ion ratio, calcinations time and temperature. This method can be applied to synthesize various monolithic and mixed metal oxide based ceramic nano-particles.     

Development of ZrO2‐MgO nanocomposite powders by the modified sol‐gel method

The ZrO₂‐MgO nanocomposites were synthesized using a new sol‐gel method with sucrose and tartaric acid as a gel agent. The samples were characterized by thermal analysis (TG/DTA), X‐ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FESEM), energy‐dispersive X‐ray mapping (EDX mapping), and Ultraviolet‐visible spectroscopy (UV‐vis). The results showed that the cubic phase of ZrO₂‐MgO was formed in the presence of both gel agents. The average particle size of the samples synthesized with sucrose was lower (30 nm) than that of tartaric acid (50 nm). Finally, the formation mechanism and the optical properties of zirconia‐magnesia have been discussed.     

干扰素脂质体的质量控制研究

目的建立稳定的干扰素脂质体质控体系。方法采用电子显微镜、粒度分析仪、气相色谱仪以及酶标仪等仪器和检测手段,对干扰素脂质体的形态、粒径、包封率、有机物的残留量以及稳定性等进行分析。结果干扰素脂质体透射电镜下观察为圆形,直径50~350nm,粒径呈正态分布,平均粒径为200~210nm,跨距为0.80~1.10,包封率达到90%以上。有机物残留量低于《中国药典》二部(2005版)规定的标准。在2~8℃下保存6个月,渗漏率不高于20%,而总活性基本不变。结论该干扰素脂质体的质控体系的检测项目比较全面,检测结果稳定,可用于产品的质量控制。     

6-羧基荧光素琥珀酰亚胺酯的合成

在甲基磺酸溶剂中，间苯二酚和偏苯三甲酸酐反应，得到6-和5-羧基荧光素异构体的混合物，反应产物与特戊酰氯，二异丙胺反应，分离得到带有二特戊酰基保护的6-羧基荧光素二异丙胺盐，水解后酯化，得到6-羧基荧光素琥珀酰亚胺酯。     

High performance liquid chromatographic separation of sucrose fatty acid esters

The synthesis of sucrose fatty acid esters always results in complex mixtures. Two procedures for quantitative analysis of sucrose monoesters, respectively sucrose diesters, by means of high performance liquid chromatography on reversed-phase columns, are described. A mixture of methanol and water (85:15, v/v) was used for the separation of the monoesters, while methanol, ethyl acetate and water (65:25:10, v/v/v) was used for the separation of diesters. These methods gave information about the amount of monoesters and diesters in the product; the ratio between sucrose monopalmitate and sucrose monostearate, and the number of the most important structure isomers. A complete separation of all the possible diester products seemed to be impossible, due to the presence of more complex structure isomers. The described procedures can give important support during preparative work on sucrose fatty acid esters and also in the evaluation of these products for application purposes.     

A solvent-free synthesis of sucrose polyesters

A solvent-free reaction system is described for making sucrose polyesters (SPE) by interesterification of sucrose and long chain fatty acid methyl esters. The process avoids the usual toxic solvents by using a novel two-stage reaction sequence. In the first stage a 3:1 mole ratio of methyl esters to sucrose is reacted in the presence of potassium soaps to form a one phase melt containing mainly lower esters of sucrose. In the second stage more methyl esters are added and reacted to produce SPE in yields up to 90% based on sucrose. Sucrate ion generated in situ with alkali metal hydrides or Na-K alloy proved to be a superior catalyst for formation of sucrose esters during both stages.     

Efficient Solvent-Free Synthesis of Sucrose Esters via Sand-Milling Pretreatment on Solid–Liquid Mixtures

A general and efficient method, involving sand-milling pretreatment and base-catalyzed transesterification of sucrose and fatty acid methyl ester (FAME), was presented for the solvent-free synthesis of sucrose esters. A metastable homogeneous paste with a solid particle size of 13 μm (D₅₀) was obtained by milling at 1000 rpm for 1 h. This reaction mixture generated a total SE yield of 88.2% with a methyl stearate (MS) conversion of 91.4% using K₂CO₃ as a catalyst at 135 °C for 3 h at a stirring rate of 500 rpm, while those without milling (D₅₀, 153 μm) yielded a total sucrose fatty acid esters (SE) of 49.3% with a MS conversion of 83.1% under the same reaction conditions. The reaction kinetics revealed that the reaction mixture with milling pretreatment displays a shorter induction time and a faster reaction rate for the formation of SE. The promotion of the solvent-free synthesis of SE in the current study could be attributed to the reduction of solid particle sizes and the increased compatibility of solid–liquid phases. We believe that this strategy could be used as a general way for strengthening other heterogeneous reactions in the organic synthesis.     

Effect of Freeze-Thawing Study on Curcumin Liposome for Obtaining Better Freeze-Dried Product

Liposomes are widely used in the pharmaceutical, biopharmaceutical, cosmetic, and nutraceutical sectors as an efficacious drug-delivery system for improving the bioavailability and protection of the entrapped drug molecule. The present study evaluates freeze-thaw as a simple approach for screening the most appropriate lyoprotectant. The freeze-thaw study is based on the principle that an excipient, which protects liposomes during the first step of freezing, is likely to be an effective lyoprotectant. Curcumin liposomes with high entrapment efficiency were prepared using a lipid film hydration technique. The freeze-thawing study was carried out using various lyoprotectants such as sucrose, mannitol, lactose, dextrose, and maltose. Sucrose showed minimal particle size change with better cryoprotection after the freeze-thaw study. The internal and external addition of sucrose during formulation has shown significant effects on the retention of particle size and curcumin content during the freeze-thawing and drying studies, respectively. Scanning electron microscopy revealed round vesicles with a size ～131 nm, which correlated well with zeta sizer particle size measurements. Infrared spectra and X-ray diffraction suggested interaction between the sugar and the liposomes and amorphization of the final freeze-dried product. The good correlation between freeze thawing and freeze drying suggests the freeze-thaw study as a simple and quick approach for screening optimal cryoprotectant for freeze drying.     

The enzymatic hydrolysis and tissue oxidation of fatty acid esters of sucrose

Summary Various preparations of sucrose fatty acid esters were hydrolyzed by wheat germ or pancreatic lipase, pancreatin, pancreatic juice, α-amylase, invertase, or liver homogenates to yield sucrose and free fatty acids as products. The greatest activity was observed with the liver homogenate. None of the enzymes studied cleaved the glycosidic linkage as indicated by the lack of appearance of reducing groups and by paper chromatography of the products. The greatest hydrolysis by pancreatic lipase was observed with sucrose esters having a greater preponderance of unsaturated fatty acids, namely, sucrose trilinoleate, sucrose dilinoleate, sucrose tetralinoleate, and “Sequol 260” (69% unsaturated fatty acids). Sodium taurocholate was required for hydrolysis by pancreatic lipase but not by wheat germ lipase. Sucrose ester was inhibitory to the hydrolysis of triolein by all lipolytic preparations. Tetra-ethyl pyrophosphate and cupric ions were not inhibitory to the hydrolysis of sucrose ester. Sucrose fatty acid esters supported respiration by rat liver homogenates and to a much lesser extent by rat intestinal mucosa. The rate of oxidation was greater than that observed with sucrose and the corresponding fatty acid. The greatest activity was observed with esters of fatty acids having a greater preponderance of unsaturated fatty acids, namely, “Sequol 260,” sucrose di-, tri-, and tetralinoleate. This work was carried out under U.S.P.H.S. Grant No. A-1808 and Sugar Research Foundation Grant No. 109.     

Application of lipases to the regioselective synthesis of sucrose fatty acid monoesters

A regioselective synthesis of 6′-O-acyl sucrose monoesters has been developed through the lipase-catalyzed esterification of sucrose acetals with fatty acids in both organic solvents and under solvent-free conditions. The products were obtained in overall yields of 20–27% after hydrolysis of the isopropylidene groups with aqueous acids. The strict selectivity of the enzymes used also enabled the preparation of a monoester fraction that was highly enriched in 6-O-acyl sucrose. This was accomplished by lipase-catalyzed transesterification of sucrose monoesters, prepared by conventional chemical methods, in propan-2-ol. After removal of the transesterification products (sucrose and fatty acid isopropyl esters) and column chromatography on silica gel, the obtained monoester product contained 80% of the single regioisomer, 6-O-acyl sucrose.     

可生物降解聚乳酸纳米粒的制备及表征

采用乳化 -溶剂蒸发法 ( O/W)制备聚乳酸 ( PLA)纳米粒 ,用透射电子显微镜和激光粒度仪对纳米粒进行了表征 ,纳米粒具有规整的球形且正态分布 ,同时从有机相和水相的体积比、聚合物的浓度、表面活性剂的选择及表面活性剂的浓度等几个因素对纳米粒粒径大小的影响作了较详细地讨论。有机相与水相的体积比从 1∶ 3减小到 1∶ 30 ,纳米粒的粒径从 ( 30 6.2 + 1 1 ) nm减小到( 1 87.1 + 2 .4) nm;聚合物在有机相的浓度从 1 %(质量分数 )增加到 5 %(质量分数 ) ,纳米粒的粒径从 1 94nm增加到 32 1 nm;随着水相中表面活性剂浓度从 0 .5 (质量体积分数 )增大到 3.5 %(质量体积分数 ) ,纳米粒粒径从 2 0 2 nm减小 1 78nm且有一个低的多分散指数。而且还比较了搅拌蒸发法和减压抽提法对纳米粒表面形态的影响     

Recovery of short,medium, and long chain fatty acid methyl esters using wet halogenated hydrocarbons

Fatty acid methyl esters are prepared and analyzed by gas liquid chromatography using a simple procedure that does not involve evaporation steps or drying of the final extract. The esters of fatty acids down to caproate (C₆) are recovered quantitatively. The long chain fatty acid esters, including the polyunsaturated esters, are also recovered quantitatively and are at least as stable as esters isolated by conventional procedures. Preparation of the esters in methanolic reagents is followed by partition of the mixture between a small volume of ethylene chloride and a large volume of water. The lower halogenated hydrocarbon phase contains the methyl esters ready for analysis, and the aqueous phase contains the methanol, catalysts, and other water-soluble materials.