利用接枝微球CPVA-g-PMAA与酮洛芬分子间的氢键相互作用构建结肠定位释药体系

通过表面引发接枝聚合,在交联聚乙烯醇（CPVA）微球表面实施了甲基丙烯酸（MAA）的表面引发接枝聚合,制备了高接枝度的接枝微球CPVA-g-PMAA。利用接枝微球CPVA-g-PMAA与酮洛芬（KPF）主-客体之间的氢键相互作用构建结肠定位释药体系。分析了接枝微球CPVA-g-PMAA对KPF的吸附（载药）性能与吸附机理,深入研究了载药微球在不同pH介质中的释放行为。实验结果表明,在酸性介质中,受主-客体之间强氢键作用的驱动,接枝微球CPVA-g-PMAA对KPF分子表现出强吸附能力,吸附容量接近10mg/g,可实现有效载药。载药微球的释药行为具有强烈的pH依赖性,在pH=1的介质中,释药程度很低;而在pH=7.4的介质中,则发生突释,表现出良好的结肠定位释放行为。     

5-氟尿嘧啶/壳聚糖载药纳米微球的制备及性能

以三聚磷酸钠为交联剂,采用离子交联法制备了5-氟尿嘧啶/壳聚糖纳米微球,评价其性能、体外释药性能及对人肺癌细胞GLC-82的体外杀伤效应,并通过Zeta电位和红外光谱分析载药纳米微球形成机理.结果表明,所制备的5-Fu/CS纳米微球平均包封率为32.3%,平均载药量为25.6%,平均粒径为253nm,平均zeta电势为+8.38mV,成球性及分散性良好.CS载药纳米微球具有缓释性能,体外释药行为符合双向动力学规律.在体外作用72h,CS载药纳米微球对人肺癌细胞GLC-82的杀伤率达66.6%,杀伤效果明显优于5-Fu对照组.     

5-氟尿嘧啶分子表面印迹微球MIP-PSSS/CPVA的制备及其体外结肠定位释药特性研究

以对苯乙烯磺酸钠(SSS)为功能单体, 以N,N'-亚甲基双丙烯酰胺(MBA)为交联剂, 采用铈盐-羟基氧化还原引发体系, 在交联聚乙烯醇(CPVA)微球表面实施了5-氟尿嘧啶(5-FU)分子的表面印迹, 在微球CPVA表面形成印迹聚合物(MIP)层, 即制备了5-FU分子印迹微球MIP-PSSS/CPVA. 采用红外光谱(FTIR)和扫描电子显微镜(SEM)法, 对印迹微球进行了表征. 重点考察分析了印迹微球对5-氟尿嘧啶(5-FU)的结合(载药)性能与结合机理, 考察探索了载药微球在不同pH介质中的释放行为. 实验结果表明, 基于本体系特殊的羟基-铈盐表面引发体系, 可有效地实现5-FU分子的表面印迹, 在微球CPVA表面形成分布有大量5-FU分子印迹空穴的聚合物层. 在酸性介质中, 受强静电相互作用的驱动, 印迹微球MIP-PSSS/CPVA对5-FU分子表现出很强的结合能力, 结合容量达110 mg/g, 可实现有效载药. 载药微球的释药行为既具有强烈的pH依赖性, 又具有时滞性: 在模拟胃液中(pH＝1), 基本不释药; 在模拟小肠液中(pH＝6.8), 释药量很小; 在模拟结肠液中(pH＝7.4), 则发生突释, 表现出高效的结肠定位释放行为.     

壳聚糖-g-聚甲基丙烯酸凝胶粒的制备及其药物释放行为

以壳聚糖和甲基丙烯酸为原料,硝酸铈铵为引发剂,合成了不同接枝率的壳聚糖-g-聚甲基丙烯酸(CS-g-PMAA),用FTIR、1H NMR和元素分析表征了产物的结构,以柠檬酸三钠和戊二醛为交联剂制备了具有核壳结构的CS-g-PMAA载药体系。 用UV/Vis检测了CS-g-PMAA粒子对模型药物的释放行为。 结果表明,CS-g-PMAA接枝率为12.21%时药物释放速率最慢,其在pH=1.8介质中药物累积释放量(11 h)为44.18%,而壳聚糖粒子的累积释放量高达65.24%,即接枝改性壳聚糖粒子对药物的缓慢控制释放性能较好; CS-g-PMAA粒子的释药行为还依赖于介质的pH值和盐浓度,在低pH值和低盐浓度下,药物释放速率较快;酶环境下由于载体材料的降解使药物释放速率加快。 分析了不同条件下CS-g-PMAA载药粒子中药物的释放机理。     

淫羊藿苷壳聚糖/明胶微球的制备及其体外释放研究

本试验以壳聚糖、明胶为载药基质,以中药淫羊藿苷为模拟药物,通过乳化交联的方法制备淫羊藿苷/壳聚糖/明胶微球。考察微球的理化特性,建立持续流动释放系统,检测了微球的体外释放特性和影响因素。微球的理化特性受工艺条件如搅拌速度、乳化剂用量、交联剂用量等因素影响。微球的体外释放速率与微球的粒径、交联度负相关,与载药量正相关。试验结果表明,壳聚糖、明胶可作为缓释微球的载体基质,微球制备工艺简单稳定,微球的释放速率可控,淫羊藿苷/壳聚糖/明胶微球是一种良好的药物释放体系。     

5-氟尿嘧啶壳聚糖微球的制备及其释药性能

5-氟尿嘧啶壳聚糖微球的制备及其释药性能;药物缓释剂     

阿司匹林-蒙脱土-壳聚糖缓释微球的制备及其体外释放性能

利用溶液法预先制备壳聚糖(Cs)-蒙脱土(MMT)复合材料(Cs-MMT),以Cs-MMT、Cs为原料,采用反相悬浮聚合法制得一种新型药物缓释体系阿司匹林-蒙脱土-壳聚糖载药微球(Asp-MMT-Cs)。采用FT-IR、SEM表征了Cs-MMT和Asp-MMT-Cs载药微球的结构及形态;设计正交实验优化了Asp-MMT-Cs载药微球的制备工艺;通过体外释放实验探讨了载药微球在不同模拟释放液中的释药规律。结果表明:所得微球球形度好,粒径分布较均匀;最优工艺制得的载药微球平均粒径为81.20μm,载药量为9.61%,包封率为76.78%。该缓释体系具有pH敏感性,更倾向于在pH较高的磷酸盐缓冲溶液中释放。     

接枝微球CPVA-g-PSSS的制备及其对5-氟尿嘧啶载药及体外结肠定位释药特性研究

在具有生物相容性的交联聚乙烯醇(CPVA)微球表面,采用铈盐-羟基氧化还原引发体系,实施了对苯乙烯磺酸钠(SSS)的表面引发接枝聚合,制得了接枝有聚阴离子的接枝微球CPVA-g-PSSS,采用红外光谱(FTIR)、扫描电子显微镜(SEM)及zeta电位测定等法,对接枝微球的化学结构及物理化学特性进行了表征.在此基础上重点考察分析了接枝微球CPVA-g-PSSS对5-氟尿嘧啶(5-FU)的吸附(载药)性能与吸附机理,考察探索了载药微球在不同pH介质中的释放行为.实验结果表明,羟基-铈盐氧化还原引发体系可有效地引发SSS在CPVA微球的表面接枝聚合,在适宜的反应条件下,可制得PSSS接枝度为16.1 g/100g的接枝微球CPVA-g-PSSS.在酸性介质中,受强静电相互作用的驱动,接枝微球CPVA-g-PSSS对5-FU分子表现出很强的吸附能力,吸附容量达105 mg/g,可实现有效载药.载药微球的释药行为具有强烈的pH依赖性,在pH=1的介质中,基本不释药;而在pH=7.4的介质中,则发生突释,表现出良好的结肠定位释放行为.     

先辐射后冻融法制备聚乙烯醇/水溶性壳聚糖/甘油水凝胶的云南白药药物释放性能研究

采用先辐射后冻融的方法制备了一系列聚乙烯醇(PVA)/水溶性壳聚糖/甘油水凝胶,通过浸泡法在水凝胶中载入云南白药,并且研究了溶液pH值、离子强度、冻融次数和PVA浓度对水凝胶溶胀性能和云南白药释放性能的影响.研究发现水凝胶的溶胀度随溶液离子强度的增大而下降,且酸性溶液大于中性溶液.水溶性壳聚糖的加入有利于云南白药载入凝胶,同时使云南白药的释放具有pH和离子强度敏感性.云南白药的释放量在模拟体液中最大,在中性溶液中次之,在水和酸性溶液中最小,与溶胀度变化关系相反.而水凝胶的溶胀度和云南白药释放量均随冻融次数和PVA浓度的增大而下降.分析表明,云南白药在不同介质中的释放量主要取决于药物和溶液中离子的交换能力;在相同介质中,不同凝胶的药物释放量受溶胀度影响明显.凝胶溶胀速率远大于药物释放速率说明后者主要由扩散过程控制.药物释放的pH敏感性表明该水凝胶具备用作云南白药的口服载体的潜力.     

羧甲基壳聚糖离子络合微球的制备及其溶胀性能研究

以羧甲基壳聚糖为主要原料,采用静电脉冲液滴发生器制备了羧甲基壳聚糖离子络合微球。扫描电镜分析结果显示,干球粒径约为100μm。粒径分布均匀。表面呈多孔结构。微球的溶胀行为对溶液pH很敏感,增大pH会促进其溶胀,溶胀速度和最大溶胀度均有提高。pH同时影响载药微球的药物释放性能。微球的溶胀性能受到羧甲基壳聚糖溶液浓度、金属离子种类及其浓度等制备条件的影响。增大羧甲基壳聚糖溶液浓度或金属离子浓度均能提高最大溶胀度,C—Ca微球较C-Al微球更易溶胀。通过改变CaCl2溶液浓度,初步考察了制备条件对药物释放性能时影响。研究对微球进一步应用于药物释放等领域具有重要意义。     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

Highly regioselective Buchwald–Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries

The highly regioselective Buchwald–Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodology is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald–Hartwig amination at higher temperature to enable rapid exploration of the chemical space at C-4 and to provide a library of 2,4-bisaminopyridines.     

Sulfur-directed metal-free and regiospecific methyl C(sp3)–H imidation of thioanisoles

Regiospecific and direct imidation of the methyl C(sp³)–H bond of thioanisoles is realized under mild and metal-free conditions with N-fluorobis(benzenesulfonyl)imide as an oxidant and nitrogen source. Proposed mechanism suggests that thionium ion intermediates and a Pummerer-type reaction are involved. The imidation has advantages such as high step-economy, excellent functionality tolerance, and regiospecificity, giving structurally diverse imidation products.