非离子表面活性剂囊泡对头孢菌素药物的缓释作用

用超声法制备了Span系列非离子表面活性剂囊泡,研究了它们对几种水溶性头孢菌素药物的包封作用及影响包封率的因素,通过透射电镜对囊泡的形态和大小进行了鉴定.实验表明,制得的囊泡多为球形单室囊泡,且包封后的药物在模拟肠液和模拟胃液中均有缓释作用.     

类脂囊泡包封药物顺铂的研究

用司盘(Span)系列非离子表面活性剂和胆固醇(CHOL)为主要膜材,通过薄膜-超声波法制备了顺铂囊泡,研究了影响包封率的主要因素,考察了顺铂囊泡在体外的释放性能.实验表明:在50℃超声50 m in的条件下,由Span20与CHOL(摩尔比为5∶3)制备的囊泡对0.60 g.L-1注射用顺铂包封率可达65%以上,且包封后的药物在模拟肠流体和模拟胃流体中均有缓释作用.     

离子键交联聚合物囊泡的制备及对药物的负载与释放

通过双亲性接枝共聚物海藻酸钠接枝聚N-异丙基丙烯酰胺(SA-g-PNIPAM)与Ca2+之间的静电作用,在水溶液中制备了温度敏感性离子键交联聚合物囊泡,并以5-氟尿嘧啶(5-FU)为模型药物,研究了聚合物囊泡对5-FU的负载与释放性能。该囊泡疏水性的膜由海藻酸钠与Ca2+之间的静电作用复合形成。透射电镜研究表明,囊泡具有空心结构,直径在100~150nm左右。聚合物囊泡的最低临界溶解温度(LCST)为34.5℃左右。聚合物囊泡对5-FU具有较高的载药量和包封率,其药物释放速率随溶液p H值的增加而降低,随离子强度的增大而增大,表现出良好的环境响应性。     

类脂囊泡作为头孢噻肟钠药物载体的研究

用司盘(Span)系列非离子表面活性剂和胆固醇(CHOL)通过真空旋转一超声波法制备了头孢噻肟钠囊泡,研究了包封条件对包封率的影响及包封后的药物在体外的模拟释放,考察了头孢噻肟钠囊泡的形态和构造。实验表明:Span20与CHOL摩尔比为2∶1,50°C超声30m in,对1.00g/L的注射用头孢噻肟钠的包封率可达55%以上,而且在模拟肠流体和模拟胃流体中均有缓释作用。     

非离子表面活性剂囊泡包封药物头孢唑啉钠的研究

实验通过超声波法制备了吐温类非离子表面活性剂囊泡，研究了它们对药物质奖励不孢唑啉钠（CEZ）的包封作用以及被包封的CEZ在模拟胃液及模拟肠液中的释放情况。实验表明，吐温40与胆固醇体积比为1：1时形成的非离子表面活性剂囊泡对1mg/mL的CEZ的包封率是20％，而且在模拟胃液和模拟肠液中，对包封的药物都有一定的缓释作用，因此有可能作为临床上的药物缓释剂。     

N,N-双十二烷基壳聚糖/胆固醇混合单分子膜及自组装囊泡性质

研究了添加胆固醇对N,N-双十二烷基壳聚糖(N,N-dilauryl chitosan, DLCS)单分子膜以及自组装囊泡性质的影响. 结果表明, 引入少量胆固醇会导致DLCS膜的凝聚性下降; 当胆固醇含量增加到一定程度后, 混合膜的凝聚性增强. 添加胆固醇可显著改变DLCS载药囊泡的药物释放行为, 少量胆固醇可以提高载药囊泡的释放速率和平衡药物释放百分率; 而较高含量胆固醇则可抑制囊泡的释放速率和降低平衡药物释放百分率. 此外, 囊泡平衡药物释放率与其单分子膜压缩模量呈现一定线性关系, 这说明胆固醇的引入导致囊泡分子膜凝聚性的改变, 从而改变囊泡的通透性. 通过调节胆固醇的加入量, 可以制得药物释放行为在一定范围内可控的自组装囊泡.     

赖氨酸在甘草次酸弹性囊泡形成过程中的作用机制

制备和评价含赖氨酸的甘草次酸弹性囊泡, 并考察赖氨酸在囊泡形成过程中的作用机制. 在水合介质中加入赖氨酸, 利用薄膜-高压均质法制备甘草次酸弹性囊泡. 并合成了甘草次酸赖氨酸盐及其弹性囊泡作为对比制剂. 通过对粒径、zeta电位、包封率、相转变温度、变形性和体外经皮渗透性的测试, 考察赖氨酸在甘草次酸弹性囊泡中的存在形式及作用. 结果显示加入赖氨酸后, 甘草次酸弹性囊泡的粒径略有降低, 膜相转变温度降低, 包封率和囊泡变形性显著提高, 载药量提高近30倍(1.5 mg·mL-1), 并显著高于其赖氨酸盐所形成囊泡的载药量和弹性. 此外, 赖氨酸的加入使弹性囊泡的变形能力增加, 8 h累积透过量和皮肤驻留量分别提高4.3倍和9.2倍. 表明赖氨酸与甘草次酸形成离子缔合物, 促进甘草次酸参与膜的形成, 使膜的流动性增加, 赖氨酸与弹性囊泡对提高囊泡载药量起协同作用.     

高包封率异烟肼类脂质体的制备与性质研究

以异烟肼为模型药物, 合成了异烟肼取代卵磷脂疏水链的两亲性异烟肼磷脂衍生物. 用薄膜超声分散法将其制备成脂质体, 从而将异烟肼脂质体的药脂比从0.1～0.3提高至2.0, 包封率由2%提高到接近100%. 通过调节超声处理时间和磷脂浓度可制得粒径大小可控的脂质体. 体外释药研究表明, 该脂质体具有明显的控制释放性能. 这种以药物分子取代卵磷脂疏水链的两亲性磷脂衍生物制备脂质体的方法, 为难包封于脂质体的药物实现高包封率提供了新途径.     

失水山梨醇脂肪酸酯-聚乙二醇嫁接的聚乙烯醇化磁性药物载体的制备及应用

通过丁二酸酐将失水山梨醇脂肪酸酯(Span80)和聚乙二醇(PEG400)联接在一起,合成了一种新的非离子表面活性剂.然后将其嫁接在聚乙烯醇(PVA)化的Fe3O4磁性粒子上,合成了一种新型靶向药物载体.这种载体兼备了Span80/PEG400类脂囊泡和磁性材料的特点,具有良好的稳定性和靶向作用.将这种新型载体用于两性霉素的包封,包封率可达96.6%,且方法简便.实验过程中采用了FTIR, NMR, XRD和TEM等多种手段进行表征.     

温度敏感性壳聚糖基聚电解质载药纳米粒子的制备及表征

以天然高分子壳聚糖(CS)、羧甲基纤维素(CMC)和温度敏感性单体N-异丙基丙烯酰胺(NIPAM)为原料,通过自组装制备了温度敏感性聚电解质复合纳米粒子CS-g-PNIPAM/CMC-g-PNIPAM,并以5-氟尿嘧啶(5-FU)为模型药物研究了纳米粒子对药物的负载与可控释放性能。当CMC-g-PNIPAM与CS-g-PNIPAM的质量比为3:7时,形成的纳米粒子结构最稳定,动态光散射(DLS)测得其平均粒径为116nm,粒径分布较窄。载药纳米粒子对5-FU具有较高的载药量和包封率。在磷酸盐缓冲溶液中的释药行为表明,其累积药物释放量随pH和温度的增加而增大,表现出良好的pH与温度可控性能。     

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%.     

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

Different approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.     

A general and convenient synthesis of 4-(tosylmethyl)semicarbazones and their use in amidoalkylation of hydrogen,heteroatom, and carbon nucleophiles

A general synthesis of previously unknown semicarbazone-based α-amidoalkylating reagents, 4-(tosylmethyl)semicarbazones, has been developed. The synthesis involved three-component condensation of semicarbazones of aliphatic or aromatic aldehydes with the same or other aldehydes and p-toluenesulfinic acid. The scope and limitations of this reaction were investigated. The compounds obtained were demonstrated to be an efficient α-(4-semicarbazono)alkylating agents. They were reacted with H- (sodium borohydride), O- (sodium methylate), S- (sodium phenylthiolate), N- (pyrrolidine, sodium succinimide), P- (trialkyl phosphites), and C-nucleophiles (sodium diethyl malonate) to give the corresponding products of the tosyl group substitution, 4-substituted semicarbazones, including analogues of nitrofurazone. Among the prepared compounds tested in vitro for antibacterial and antifungal activity, three nitrofuryl-containing semicarbazones exhibited high biological activities with minimum inhibitory concentration (MIC) values of 8–32 μg/mL.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

Synthesis of novel chiral bidentate hydroxyalkyl-N-heterocyclic carbene ligands and their application in palladium-catalyzed Mizoroki–Heck couplings and asymmetric addition of diethylzinc to benzaldehyde

A small library of new chiral bidentate hydroxyalkyl-imidazolium salts 1 is conveniently synthesized on multi-gram scale from inexpensive and commercially available chiral pool amino acids. The corresponding carbenes, generated by deprotonation of imidazolium salts 1, in combination with palladium(II) chloride were tested in the Mizoroki–Heck coupling reaction. The most significant results in terms of yields and reactivities were achieved with low catalyst loading. The catalytic activities of these imidazolium salts were also investigated in the asymmetric addition of diethylzinc to benzaldehyde. The use of MgO nanoparticles as an additive in conjunction with these ligands played a crucial role in increasing the efficiency of these reactions.     

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.     

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.     

Microwave-assisted copper-catalyzed stereoselective ring expansion of three-membered heterocycles with α-diazo-β-dicarbonyl compounds

Microwave-assisted copper-catalyzed ring expansions of three-membered heterocycles with α-diazo-β-dicarbonyl compounds were investigated. Thiiranes generated 3-acyl-5,6-dihydro-1,4-oxathiines in the presence of copper sulfate and trans-3-acyl-5,6-dihydro-1,4-oxathiines as stereospecific products for 1,2-disubstituted cis-thiiranes through an intramolecular S_N2 process. Oxiranes gave rise to 2-acyl-5,6-dihydro-1,4-dioxines under the catalysis of copper hexafluoroacetylacetonate and cis-3-acyl-5,6-dihydro-1,4-dioxines as stereospecific products for 1,2-disubstituted cis-oxiranes via an intimate ion-pair mechanism. The current method provides a direct and simple strategy in efficient preparation of 3-acyl-5,6-dihydro-1,4-oxathiines and 2-acyl-5,6-dihydro-1,4-dioxines, important agents in medicinal and agricultural chemistry, from readily available thiiranes and oxiranes, respectively.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.