姜黄素纳米晶混悬液制备、表征及体内外药剂学性质评价

目的:为提高姜黄素的口服生物利用度，采用“Top-down”法中的高压均质法制备姜黄素纳米晶混悬液(Cur-NCS),并对其进行物性表征、体外释放、体内生物利用度及内外抗炎活性研究。方法:以粒径、Zeta电位等为评价指标，优化处方和工艺参数；采用透射电镜对样品形态进行表征，HPLC法测定姜黄素纳米混悬液体外释放，LC-MS/MS法检测大鼠体内姜黄素的血药浓度；RAW264.7炎症细胞模型考察其抗炎活性，支气管哮喘气道炎症小鼠模型考察姜黄素纳米混悬液对小鼠气道炎症的治疗作用。结果:制备工艺：姜黄素16 000 r·min^-1转速下高速剪切2 min, 800 bar循环40次。处方：姜黄素用量为0.2%,维生素E聚乙二醇琥珀酸酯(TPGS)用量为0.20%,大豆卵磷脂用量为0.16%;原料药与Cur-NCS累积释药量分别为11.67%和27.44%;大鼠灌胃后，Cur-NCS生物利用度提高了1.86倍；在体外炎症细胞模型和体内支气管哮喘小鼠模型中，Cur-NCS显著抑制炎症因子NO,IL-6,TNF-α的表达及MDA,IgE和ICAM-1水平，提高IL-10的表达与...     

姜黄素白蛋白纳米粒的制备与评价

目的:优化姜黄素白蛋白纳米粒的处方工艺并对其特性进行表征。方法:以牛血清白蛋白为载体、通过反溶剂沉淀法制备载姜黄素纳米粒,以粒径为评价指标优选制剂处方及工艺,并考察所得纳米粒的放置稳定性、饱和溶解度及体外溶出度。结果:当有机相和水相体积之比为1∶20、药物与白蛋白用量之比为1∶1.5、保护剂为0.5%(V/V)甘露醇时,所得纳米粒冻干粉平均粒径约为320 nm。其在水、p H 6.8、p H 7.4 PBS中的溶解度显著高于原料药及物理共混物,体外溶出更快,且冻干粉的放置稳定性优于纳米混悬液。结论:白蛋白纳米粒处方能够改善姜黄素的水溶性及溶出度,放置稳定性较佳。     

姜黄素固体分散体的制备和溶出度考察

目的通过姜黄素固体分散体的制备,提高姜黄素的体外溶出度。方法采用溶剂法和熔融法制备固体分散体,考察不同载体的姜黄素固体分散体的性状及体外溶出度实验,筛选并优化处方和工艺。固体分散体的形成通过X-射线衍射及DSC分析证实。结果姜黄素与聚乙烯吡咯烷酮(polyvinyl pyrrolidone,PVP)-K29/32用溶剂法制备的固体分散体的体外溶出最好,最优处方中姜黄素与PVP-K29/32的质量比为1∶6,最优处方中姜黄素在溶出介质人工胃液中30 min累积溶出质量高达98%。结论制备成姜黄素固体分散体可以显著提高姜黄素的体外溶出度。     

尼索地平纳米混悬液的制备及其体外溶出度

目的制备、优化尼索地平纳米混悬液,检测研磨介质残留,评价尼索地平纳米混悬液的体外溶出度。方法采用介质研磨法制备尼索地平纳米混悬液,以粒径为指标筛选、优化处方,利用电感耦合等离子体质谱仪测定研磨介质的残留,采用浆法评价尼索地平纳米混悬液的体外溶出。结果最优处方为尼索地平与PVP-K30质量比4∶1,其平均粒径为(445.5±2.8)nm,zeta电位为(0.294±1.00)m V,20 min时纳米混悬液累积溶出(87.0±4.5)%,在4℃和20℃条件下,该纳米混悬液30 d内物理稳定性良好。结论采用介质研磨法制备的纳米混悬液可以提高尼索地平的体外溶出度。     

美洛昔康纳米混悬液的制备及质量评价

为改善美洛昔康(1)的水溶性,该研究采用超声辅助沉淀法制备其纳米混悬液,并采用单因素试验优化了处方和工艺参数。所得优化处方工艺为：以0.2%的泊洛沙姆188和0.2%的羟丙甲纤维素作为联合稳定剂,水、油两相体积比为30∶1,超声功率比为50%,超声35 min。制备的1纳米混悬液粒径为263.8 nm,多分散性指数(PDI)为0.189,ζ电位为–20.54 mV。将所得纳米混悬液冻干粉末复溶后,药物颗粒的粒径和PDI相比冻干前增大、ζ电位减小。透射电镜(TEM)、X射线衍射法(XRD)表征结果显示,纳米混悬液中1以原晶体的形式存在。分子动力学模拟结果显示,药物、泊洛沙姆188和羟丙甲纤维素之间形成了分子间氢键。体外溶出试验结果显示,1纳米混悬液在pH 6.0和pH 6.8的磷酸盐缓冲液中的溶出速度和程度明显高于原料药及其与联合稳定剂的物理混合物。     

紫杉醇纳米晶混悬液的制备及表征

目的 对紫杉醇纳米晶混悬液的处方和制备工艺进行优化,对所优化的混悬液进行物理表征,并考察其体外释放特征。方法 采用单因素试验法筛选高压均质机制备紫杉醇纳米晶混悬液的处方工艺;使用透射电镜等考察纳米晶外观形态、粒径分布;采用高效液相色谱法考察其平衡溶解度、体外释放特征。结果 制备的纳米晶的平均粒径为(239.5±1.98)nm,PDI为0.111±0.011,Zeta电位为-(24.6±1.13)mV;电镜下紫杉醇纳米晶呈短棒状,均匀分布;纳米晶体在水和pH 7.4的PBS溶液中的平衡溶解度分别是原料药的1 800倍和250倍;在0.5%SDS-PBS(pH 7.4)溶液中紫杉醇纳米晶体5 min释放91.6%,物理混合物2 h释放67.7%。结论 制备的紫杉醇纳米晶混悬液粒径分布均匀,处方简单,制备工艺简便可行,且显著提高了紫杉醇的溶解度和释放速率。     

介质研磨法制备他达拉非纳米混悬液研究

目的:采用介质研磨法制备他达拉非纳米混悬液,以提高他达拉非的溶出度和生物利用度。方法:以粒径、多分散指数(PDI)、Zeta电位和物理稳定性为评价指标,优化处方和工艺参数;采用扫描电镜(SEM)、X-射线粉末衍射法(XRPD)、差示扫描量热法(DSC)对样品进行表征,HPLC法测定他达拉非纳米混悬液体外溶出度,UPLC-MS/MS法检测大鼠中他达拉非的血药浓度。结果:他达拉非纳米混悬液最优处方为他达拉非质量分数2%、HPC 1%和SDS 0.1%;最优工艺为粒径0.1 mm氧化锆珠,转速3 000 r·min^-1,研磨时间30 min。制备的他达拉非纳米混悬液PDI为0.173±0.013,Zeta电位为(－22.6±0.4) mV,纳米颗粒为棒状结晶,粒径为(218.2±1.3) nm,分布均匀,晶型稳定;体外溶出度10 min内达到99%,大鼠体内生物利用度为原料药的4.01倍,在室温条件下放置6个月稳定性良好。结论:介质研磨法制备他达拉非纳米混悬液方法简单,产品稳定性好,能显著提高他达拉非溶出度和生物利用度。     

口服槲皮素纳米结构脂质载体的制备及体外评价

目的 筛选口服槲皮素纳米结构脂质载体的处方和制备工艺,并对其进行体外评价.方法 采用溶解度考察和正交优化设计法结合,优选出较优的处方,并通过伪三元相图验证,评价其粒子形态、多分散性、包封率.通过测定不同稀释倍数、不同缓冲液对粒径的影响及药物的体外溶出行为,对槲皮素纳米结构脂质载体进行体外评价.结果 最佳处方组成为硬脂酸-Labrafac lipophile WL1349-Cremophor EL-Transcutol P(3:5:5:2),所得纳米结构脂质载体为圆整的类球形粒子,平均粒径为69 nm,包封率为89.0%,PDI=0.251.同槲皮素混悬液比较,槲皮素纳米结构脂质载体的体外溶出明显提高.结论 口服纳米结构脂质载体释药系统制备工艺简便,粒子性状符合要求,可提高难溶性药物的体外溶出.     

姜黄素固体分散体处方工艺优化及体外溶出度评价

目的优化姜黄素固体分散体(CUR SD)的处方工艺。方法根据溶解度参数及溶出结果,优选CUR SD最佳载体及药物与载体的比例。采用差示扫描量热(DSC)法、X-射线粉末衍射分析(XRPD)法和傅立叶红外光谱分析(FTIR)法对制备的CUR SD进行表征,并考察体外溶出度。结果根据溶解度参数及体外溶出结果,优选聚维酮K30(PVP K30)为CUR SD的最佳载体,优选的药物与载体质量比为1∶3和1∶1.5。DSC法和XRPD法分析结果表明,CUR与胡椒碱(PIP)在载体中以无定型存在;FTIR法证实药物与载体间存在分子间氢键的相互作用;体外溶出试验证实,CUR SD的累积溶出率及溶出速率均显著升高。结论通过优化处方工艺,制备的CUR SD能有效改善CUR和PIP的体外溶出度。     

湿法研磨结合液相层积技术制备呋喃妥因缓释微丸

目的制备呋喃妥因缓释微丸,研究药物的晶型稳定性并评价微丸的缓释作用。方法通过湿法研磨技术制备呋喃妥因纳米混悬液;以差示扫描量热法(differential scanning calorimeter,DSC)及粉末X射线衍射法(powder X-ray diffraction,PXRD)研究药物晶型变化;采用液相层积技术制备呋喃妥因缓释微丸;通过体外释放度筛选处方;采用UPLC-MS/MS法测定Beagle犬血浆样品。结果药物经湿法研磨后,粒径由约40μm降至455 nm,晶型稳定。体外释放试验结果表明,在模拟体内胃肠道消化液环境的溶出介质中该制剂在释放前期符合零级释放,后期则符合一级释放。体内试验结果表明,呋喃妥因缓释微丸相对于市售肠溶包衣片的生物利度为143.8%;前者的消除半衰期(t1/2)及平均滞留时间(mean residence time,MRT)均较后者有所延长。结论湿法研磨技术可显著降低药物粒径,提高溶出速率,药物体外释放符合要求,该微丸具有一定缓释效果。     

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.