辛伐他汀固体脂质纳米粒的制备及在大鼠体内的药动学研究

摘 要 目的： 制备辛伐他汀固体脂质纳米粒,并研究其经灌胃给药后在大鼠体内的药动学特征。方法: 采用热熔乳化超声 低温固化法制备辛伐他汀固体脂质纳米粒,考察辛伐他汀固体脂质纳米粒的粒径分布、Zeta电位、包封率、微观形态及体外药物释放特性。研究辛伐他汀固体脂质纳米粒经灌胃给药后在大鼠体内的药动学特征。结果: 辛伐他汀固体脂质纳米粒平均粒径为(242.5±62.1) nm,多聚分散系数为0.225±0.031,Zeta电位为(-32.1±4.2) mV,包封率为(95.7±2.6) %,在24 h内平稳缓慢释药。辛伐他汀固体脂质纳米粒在大鼠体内的Cmax和AUC0 t分别为辛伐他汀混悬液的2.89倍和1.83倍。结论:辛伐他汀固体脂质纳米粒在大鼠体内能快速吸收,显著提高了药物在大鼠体内的生物利用度。     

美洛昔康固体脂质纳米粒的制备及体外透皮研究

摘 要 目的： 制备美洛昔康固体脂质纳米粒,并考察其透皮吸收行为。方法: 采用热熔乳化超声 低温固化法制备美洛昔康固体脂质纳米粒,并考察其包封率、粒径分布、Zeta电位、微观形态及体外药物释放特性,采用Franz扩散池考察其透皮吸收行为。结果: 美洛昔康固体脂质纳米粒的包封率为（85.6±2.7）%,平均粒径为（213.5±52.6）nm,Zeta电位为（-32.2±3.9）mV,透射电镜显示美洛昔康固体脂质纳米粒粒径均一,成球状分布。其12 h药物累积透皮量显著高于美洛昔康溶液。结论: 美洛昔康固体脂质纳米粒可以显著提高药物累积透皮量,有望成为美洛昔康的新型局部给药制剂。     

重楼总皂苷固体脂质纳米粒的制备及药剂学性质研究

摘 要 目的：基于质量源于设计（QbD）理念设计和开发重楼总皂苷固体脂质纳米粒。方法: 根据重楼总皂苷固体脂质纳米粒剂型及给药特点确立了目标产品概况,并根据理论知识和实际经验,通过风险评估工具确定影响固体脂质纳米粒制剂学性质的关键性变量。首先应用Plackett Burman试验筛选出对重楼总皂苷固体脂质纳米粒制剂学性质影响显著的关键变量,然后对筛选出的变量应用Box-Behnken效应面法进一步优化。评价重楼总皂苷固体脂质纳米粒的粒径分布、多聚分散系数（PdI）、Zeta电位、微观形态等理化性质,考察固体脂质纳米粒体外释药情况。结果: 最佳处方和制备工艺为：单硬脂酸甘油酯浓度为5.5%,大豆磷脂浓度为8.0%,均质次数为6次,固定药物浓度为5.0%,表面活性剂种类为吐温80,均质压力为600 bar,均质温度为65 ℃。采用优化后处方工艺制得的重楼总皂苷固体脂质纳米粒平均粒径为（116.5±32.1）nm, PdI为0.198±0.018,Zeta电位为（-23.6.5±0.9）mV,透射电镜显示固体脂质纳米粒呈球状分布,体外释放结果表明具有缓释效果,24 h累积释药为63.5%。结论: 运用QbD理念设计和开发重楼总皂苷固体脂质纳米粒切实可行,能确保产品质量符合要求。     

伏立康唑白蛋白纳米粒大鼠体内药动学与组织分布

摘 要 目的：制备伏立康唑白蛋白纳米粒,并考察其在大鼠体内药动学与及组织分布。 方法: 采用超高压微射流技术制备伏立康唑白蛋白纳米粒,并评价了白蛋白纳米粒的粒径分布、Zeta电位、外观形态以及体外释药行为;考察了伏立康唑白蛋白纳米粒在大鼠体内的药动学与组织分布特征。 结果: 本研究制备的伏立康唑白蛋白纳米粒平均粒径为（121.9±41.6）nm,PdI为0.197,Zeta电位为（-42.1±0.9）mV,呈球形或类球形分布;伏立康唑白蛋白纳米粒在0.5%吐温80磷酸盐缓冲液（pH 7.4）中24 h累积释放67.5%;大鼠体内药动学研究表明,伏立康唑白蛋白纳米粒和伏立康唑注射剂的AUC0-24分别为（98.27±1.42）和（105.32±1.45）g?h?L^-1,MRT0-24分别为（4.48±0.38）和（4.86±0.51）h;伏立康唑白蛋白纳米粒能增加药物在大鼠肝、脾、脑中的靶向性。 结论:伏立康唑白蛋白纳米粒在大鼠体内具有良好的肝、脾、脑中靶向性,可以提高药物治疗疗效。     

壳聚糖修饰的托氟啶固体脂质纳米粒的制备

摘 要 目的： 研究托氟啶固体脂质纳米粒及壳聚糖修饰的托氟啶固体脂质纳米粒的制备方法。方法: 采用薄膜 超声分散法制备托氟啶固体纳米脂质粒（TFu-SLNs）及壳聚糖修饰的TFu-SLNs,并对纳米粒的形态、粒径和表面电位进行测定,通过单因素考察及正交设计优化制备方法,同时考察处方稳定性。结果: 薄膜 超声分散法制备的TFu-SLNs平均粒径为160.2 nm,Zeta电位为－33.12 mV,壳聚糖修饰TFu-SLNs平均粒径为400.3 nm,Zeta电位为+12.87 mV。经壳聚糖修饰后,随着壳聚糖浓度的增加,电位逐渐增大。优化后的处方重复性、稳定性良好。结论:通过采用正交设计法对TFu固体脂质纳米粒处方进行优化,得到TFu固体脂质纳米粒及壳聚糖修饰的TFu固体脂质纳米粒的优化处方。     

酮洛芬固体脂质纳米粒的制备与评价

摘 要 目的：制备酮洛芬固体脂质纳米粒的处方并对其进行质量评价。方法: 以包封率为评价指标,通过正交试验优化制剂处方并对其从形态、粒径、Zeta电位、药物存在状态进行表征,采用透析法进行体外释放并对释放过程进行拟合。结果: 酮洛芬固体脂质纳米粒的最优处方为酮洛芬50 mg、泊洛沙姆0.1 g、吐温 80 0.2 g、卵磷脂0.15 g、单硬脂酸甘油酯0.05 g,其包封率为61.95%,粒径151.7 nm,Zeta电位为-30.2 mv,形态圆整,差示扫描量热（DSC）分析表明药物以非结晶形式分散于纳米粒骨架中;体外释药曲线显示纳米粒体外释药先快后慢,12 h累积释放药物（85.11±7.62）%,包封于降解材料骨架内的药物通过骨架溶蚀缓慢释放,药物的体外释放符合Higuchi方程。结论: 酮洛芬固体脂质纳米粒制备方法简便、可行,质量评价较好,值得进一步研究。     

塞来昔布纳米结构脂质载体的制备及大鼠组织分布研究

摘 要 目的： 制备塞来昔布纳米结构脂质载体,并考察其在大鼠体内的组织分布特性。方法: 采用热熔乳化超声 低温固化法制备塞来昔布纳米结构脂质载体,并考察其粒径分布、Zeta电位和形态学性质。研究塞来昔布纳米结构脂质载体在大鼠体内各组织的分布特征。结果: 塞来昔布纳米结构脂质载体的平均粒径为（103.5±32.6）nm,Zeta电位为（-37.3±5.1）mV,透射电镜显示塞来昔布纳米结构脂质载体粒径均一,成球状分布。大鼠体内各组织分布结果表明,塞来昔布纳米结构脂质载体在大鼠肝、脾、脑、肌肉组织内的re值分别为塞来昔布注射液的3.43,2.99,2.38和2.93倍。结论:将塞来昔布制备成纳米结构脂质载体,能够改变其在大鼠组织的分布情况,有望提高药物疗效。     

阿魏酸川芎嗪长循环固体脂质纳米粒的制备及体外巨噬细胞摄取研究

摘 要 目的：研究阿魏酸川芎嗪长循环固体脂质纳米粒( PEG-FATM-SLN) 的制备方法,并考察其体外释放及细胞摄取性能。 方法: 采用乳化超声分散法,以包封率及粒径为考察指标,通过正交试验优化处方及工艺。以小鼠腹腔巨噬细胞( MPM) 为模型做体外细胞摄取试验。 结果:制备PEG-FATM-SLN最优处方为阿魏酸川芎嗪10 mg,单硬脂酸甘油酯0.3 g,乙酸丁酯1.5 ml,蛋黄卵磷脂0.4 g,泊洛沙姆1 880.6 g,硬脂酸钠0.02 g,水20 ml,二硬脂酰基磷脂酰乙醇胺 聚乙二醇2000（DSPE PEG2000） 0.02 g。制备的样品粒径为(107.1±1.1) nm,包封率为(53.3±3.0)%。体外释放试验和巨噬细胞摄取试验结果表明,该制剂具有明显的缓释性能和抗巨噬细胞吞噬作用。 结论:本研究制备了粒径小,包封率高的阿魏酸川芎嗪长循环固体脂质纳米粒,为其新剂型的研究提供了理论依据和试验基础。     

地塞米松棕榈酸酯脂肪乳注射液的制备

摘 要 目的：制备地塞米松棕榈酸酯脂肪乳注射液,并评价其理化性质。方法: 采用热熔乳化 高压均质法制备地塞米松棕榈酸酯脂肪乳注射液,并对脂肪乳的粒径分布、PdI、Zeta电位和微观形态进行评价;初步考察地塞米松棕榈酸酯脂肪乳注射液的稳定性。结果: 制备的地塞米松棕榈酸酯脂肪乳注射液的平均粒径为（215.1±38.2）nm,PdI 为0.218,Zeta电位为（-18.1±2.3）mV;经透射电镜观察显示,地塞米松棕榈酸酯脂肪乳呈球形,大小分布较为均匀;长期稳定性试验结果表明,地塞米松棕榈酸酯脂肪乳注射液在6个月内稳定性良好。结论:采用热熔乳化 高压均质法制备地塞米松棕榈酸酯脂肪乳注射液工艺简单易行,有望应用于工业化生产之中。     

去甲斑蝥素白蛋白纳米粒的制备及质量评价

摘 要 目的：制备去甲斑蝥素白蛋白纳米粒,并考察其理化性质。方法: 采用超高压微射流技术制备去甲斑蝥素白蛋白纳米粒,以白蛋白纳米粒的平均粒径和药物包封率作为评价指标,首先应用Plackett Burman试验设计法筛选出对白蛋白纳米粒性质影响显著的处方和工艺变量,再通过Box Behnken试验设计法对筛选的变量进一步优化。考察了去甲斑蝥素白蛋白纳米粒的外观形态、粒径分布和Zeta电位及体外释药行为。结果:通过优化制备的去甲斑蝥素白蛋白纳米粒呈类球形分布,平均粒径为（105.2±30.1）nm,PdI为0.127,Zeta电位为（-24.7±1.9）mV,在0.5%吐温80磷酸盐缓冲液（pH 7.4）中24 h的累积释放度为81.4%。结论:采用超高压微射流技术制备去甲斑蝥素白蛋白纳米粒,工艺简便可行,重复性好,有望工业化生产。     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Emerging drugs for epilepsy

Epilepsy affects ≤ 1% of the world's population. Antiepileptic drugs (AEDs) are the mainstay of treatment, although more than a third of patients are not rendered seizure free with existing medications. Uncontrolled epilepsy is associated with increased mortality and physical injuries, and a range of psychosocial morbidities, posing a substantial economic burden on individuals and society. Limitations of the present AEDs include suboptimal efficacy and their association with a host of adverse reactions. Continued efforts are being made in drug development to overcome these shortcomings employing a range of strategies, including modification of the structure of existing drugs, targeting novel molecular substrates and non-mechanism-based drug screening of compounds in traditional and newer animal models. This article reviews the need for new treatments and discusses some of the emerging compounds that have entered clinical development. The ultimate goal is to develop novel agents that can prevent the occurrence of seizures and the progression of epilepsy in at risk individuals.     

盐酸达泊西汀中甲磺酸甲酯、甲磺酸乙酯及甲磺酸异丙酯的顶空毛细管GC-ECD法测定

建立了衍生化顶空毛细管气相色谱-电子捕获检测器(ECD)法测定盐酸达泊西汀中的甲磺酸甲酯(MMS)、甲磺酸乙酯(EMS)和甲磺酸异丙酯(IMS).应用碘化钠衍生技术,使用PW-5毛细管柱,载气为氮气,ECD检测,程序升温.MMS、EMS和IMS分别在0.03～0.30、0.05～0.50和0.05～0.50 μg/ml浓度范围内线性关系良好,平均回收率分别为63.5％、100.3％和96.2％,最低检测限分别为0.30、0.50和0.50 ng/ml.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.