褪黑素固体脂质纳米粒的制备及理化性质

考察不同的处方对褪黑素固体脂质纳米粒粒径和包封率等理化性质的影响，并进行其体外释放实验。结果表明，以单硬脂酸甘油酯为脂质材料，乳化超声法制备固体脂质纳米粒，平均粒径为（62．4±1．5）nm，ζ电位为（-7．0±0．2）mV，平均包封率为（64．6±3．8）％；药物的体外释放符合Weibull模型。     

蓝萼甲素固体脂质纳米粒的制备及理化性质研究

目的:制备蓝萼甲素固体脂质纳米粒,并对其理化性质进行研究。方法:用乳化-溶剂挥发法制得蓝萼甲素固体脂质纳米粒,并对其粒径、形态、表面电位、包封率、体外释药性质等进行研究。结果:所得蓝萼甲素固体脂质纳米粒的粒径分布均匀,平均粒径为(190±10·3)nm,Zeta电位为—31·2mV,平均包封率为(50·45±0·804)%;药物体外释放符合Higuchi线性方程,具有显著缓释作用。结论:固体脂质纳米粒可作为蓝萼甲素新型缓释给药系统。     

N-琥珀酰壳聚糖纳米粒的制备及体外评价

目的制备N-琥珀酰壳聚糖纳米粒并对其进行体外评价。方法采用乳化溶剂挥发法制备N-琥珀酰壳聚糖纳米粒;以包封率、载药量及粒径为指标,采用正交设计法对处方进行优化;考察其理化特征及体外释药行为。结果纳米粒包封率及载药量分别为62.36%和18.98%,平均粒径及zeta电位分别为(206.6±64.7)nm和(-27.2±0.2)mV;1 h药物释放达到45%,随后药物的释药行为是一个缓释过程。结论作者采用乳化溶剂挥发法成功制得N-琥珀酰壳聚糖纳米粒。该方法制得纳米粒包封率较高,制备工艺简单。     

吡喹酮固体脂质纳米粒的制备及其理化性质研究

目的:制备吡喹酮固体脂质纳米粒(PZQ-SLN),并考察其理化性质。方法:以山嵛酸甘油酯和乙酸丁酯为脂质材料,超声分散法制备PZQ-SLN,透射电镜观察纳米粒形态,测定其粒径、Zeta电位和药物包封率,并进行体外释放试验及考察样品的稳定性。结果:所得脂质纳米粒为类圆球状,粒径分布较均匀。样品粒径为(100±21)nm,包封率为(79.3±0.69)%,平均Zeta电位值为—66.3mV。药物体外释放符合Weibull方程。4℃放置3mo后粒径、包封率和Zeta电位均无明显变化。结论:制备的PZQ-SLN理化性质较为理想,能使药物缓慢释放。4℃条件下贮存比较稳定。     

醋酸地塞米松PEG-PLGA纳米粒的制备及表征

目的 研究醋酸地塞米松PEG-PLGA纳米粒的制备工艺及影响因素,并优化冻干粉针工艺.方法 采用乳化/溶剂蒸发法制备醋酸地塞米松PEG-PLGA纳米粒,并考察其粒径分布、包封率、载药量等;采用单因素试验筛选出合适的冻干保护剂.结果 醋酸地塞米松PEG-PLGA纳米粒的粒径为91.43±1.00 nm,Zeta电位为-22.73 ±0.57 mv,包封率为88.78％ ±2.10％,载药量为4.95％-±0.23％;10％蔗糖作为冻干保护剂的效果最好,冻于复溶后粒径约117.27 nm.结论 所用制备工艺简单易行,可用于制备醋酸地塞米松PEG-PLGA纳米粒.     

薄膜-超声法制备芦丁固体脂质纳米粒的研究

目的优化薄膜-超声法制备芦丁固体脂质纳米粒的处方。方法以包封率为指标,采用正交设计优化法考察硬脂酸和大豆卵磷脂的用量、吐温-80和聚乙二醇-400的体积分数对包封率的影响,优选最佳处方。用透射电镜观察外观形态,用电位/纳米粒度分析仪分析纳米粒的粒径及Zeta电位,用透析法评价体外释药特征。结果以最佳处方制备的芦丁固体脂质纳米粒呈类球形,平均粒径为195.8±11nm,Zeta电位为-20.65±0.6mV,平均包封率为86.31%,72h体外累积释放87.32%。结论按最佳处方工艺制备的芦丁固体脂质纳米粒具有较高的包封率和较好的缓释效果。     

依托泊苷固体脂质纳米粒的研制

目的:制备依托泊苷固体脂质纳米粒(ET-SLN)并考察其药剂学性质。方法:采用乳化-超声分散法制备ET-SLN,以单硬脂酸甘油酯(A)、大豆磷脂(B)、泊洛沙姆188(C)、依托泊苷(D)的处方用量为考察因素,包封率为指标设计正交试验,筛选最优处方。考察纳米粒的粒径、表面电位、包封率、体外释放情况等。结果:A、B、C、D分别为0.020、0.010、0.015、0.015mg;所制纳米粒平均粒径(83±0.5)nm,表面电位(-23±0.3)mV,包封率81.2%,可持续48h缓释。结论:所制ET-SLN符合药剂学性质要求。     

以叶酸修饰的乳酸-羟基乙酸共聚物为载体的紫杉醇靶向纳米粒的构建与评价

目的 以叶酸修饰的生物可降解材料乳酸-羟基乙酸共聚物(PLGA-PEG-FOL)为载体,构建紫杉醇靶向纳米粒并进行评价。方法 采用乳化-分散法,以溶液稳定性、粒径和包封率为评价指标,通过考察乳化剂的用量、有机相种类、水相与有机相比例、聚合物分子量、药载比、剪切速度等因素对纳米粒制备的影响,确定最优处方和制备工艺,并对纳米粒的形态、粒径、Zeta电位、包封率及载药量进行评价。结果 合成了载体PLGA-PEG-FOL;制备的紫杉醇靶向纳米粒为均匀球形粒子,粒径为(88.2±6.7)nm,Zeta电位为(56.5±4.2)mV,包封率为(92.9±3.2)%,载药量为(4.8±1.3)%。结论 纳米粒制备方法简便易行,重现性好。制备的纳米粒大小均匀,粒度分布较窄,包封率和载药量较高。     

以PLGA-PEG-FOL为载体的紫杉醇靶向纳米粒的构建与评价

目的 以叶酸修饰的生物可降解材料乳酸-羟基乙酸共聚物(PLGA-PEG-FOL)为载体,构建紫杉醇靶向纳米粒并进行评价。方法 采用乳化-分散法,以溶液稳定性、粒径和包封率为评价指标,通过考察乳化剂的用量、有机相种类、水相与有机相比例、聚合物分子量、药载比、剪切速度等因素对纳米粒制备的影响,确定最优处方和制备工艺,并对纳米粒的形态、粒径、Zeta电位、包封率及载药量进行评价。结果 合成了载体PLGA-PEG-FOL;制备的紫杉醇靶向纳米粒为均匀球形粒子,粒径为(88.2±6.7)nm,Zeta电位为(56.5±4.2)mV,包封率为(92.9±3.2)%,载药量为(4.8±1.3)%。结论 纳米粒制备方法简便易行,重现性好。制备的纳米粒大小均匀,粒度分布较窄,包封率和载药量较高。     

紫杉醇MPEG-PCL纳米粒的制备、表征及其体外释药行为研究

目的 以聚乙二醇单甲醚-聚己内酯(MPEG-PCL)为载体制备紫杉醇MPEG-PCL纳米粒并对其体外释放行为进行考察。方法 采用开环聚合法合成MPEG-PCL共聚物,采用核磁共振波谱仪(¹H-NMR)、傅里叶红外光谱仪(FTIR)对其进行表征;通过共沉淀法制备了紫杉醇MPEG-PCL纳米粒,并测定了粒径分布、Zeta电位、结构特征、包封率以及载药量;同时以磷酸盐缓冲溶液(pH=7.4)为释放介质考察其体外释放行为。结果 成功合成了相对分子质量为4 875的MPEG-PCL共聚物。透射电镜结果显示紫杉醇MPEG-PCL纳米粒具有规则的球形结构,纳米粒的平均粒径为(102.3±3.5)nm,PDI=0.102,药物包封率和载药量分别为(95.6±3.2)%和(8.5±0.4)%。体外释放结果显示紫杉醇可以缓慢的从MPEG-PCL纳米粒中释放出来。结论 MPEG-PCL共聚物是紫杉醇的良好载体,所制备的纳米粒具有包封率和载药量高、药物释放缓慢的特点。     

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.     

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.     

血管内皮生长因子的异常与子(癎)前期发病的关系

目的:研究血浆可溶性细胞间黏附分子-1(sICAM-1)浓度和胎盘组织血管内皮生长因子(VEGF)、胎盘生长因子(PLGF)及其血管内皮生长因子受体1(VEGFR1,Flt-1)、可溶性血管内皮生长因子受体1(sVEGFR1,sFlt-1)mRNA的表达与子前期的关系.方法:采用酶联免疫吸附测定法(ELISA)检测45例子前期患者和45例健康产妇血清sICAM-1的浓度,逆转录-聚合酶链反应(RT-PCR)方法检测胎盘组织中VEGF、PLGF、Flt-1、sFlt-1 mRNA的表达.结果:(1)子前期组sICAM-1水平为(218.45±29.93) μg/L,显著高于对照组的(168.84±19.39) μg/L(P < 0.01).(2)子前期患者胎盘组织VEGF、PLGF、Flt-1、sFlt-1 mRNA的相对表达量显著高于对照组(均P < 0.01).(3)血清sICAM-1浓度与胎盘组织中sFlt-1mRNA的相对表达量呈正相关(r = 0.90,P < 0.01).结论:子前期患者血清sICAM-1浓度升高,其胎盘组织VEGF、PLGF、Flt-1、sFlt-1 mRNA的相对表达量也升高.胎盘组织sFlt-1mRNA的高表达与子前期内皮损伤等有密切关系.     

Antiparasitic protozoan vaccines

Parasitic infections caused by pathogenic protozoa affect over 1 billion people worldwide and impose a substantial health and economic burden, particularly on inter-tropical less-developed countries where they are more prevalent. Despite encouraging progress in vaccine development, chemotherapy remains the single most effective, efficient and inexpensive means to control most parasitic infections [1]. However, day to day parasites are becoming increasingly resistant to drugs currently in use, such as Plasmodium towards chloroquine, lending to the start of a promising future for vaccines. Patent applications regarding vaccines for the prevention, control and diagnosis of parasitic protozoan infections are reviewed for the period December 1996 - October 2000. However, vaccines for some of the protozoan infections do not appear in the literature in the period reviewed; only, vaccines against malaria, leishmaniasis, trypanosomiasis, cryptosporidiosis, pneumocystosis, eimeriosis, toxoplasmosis and neosporosis, as well as Babesia microti infections have been found.     

Binding affinity in drug design: experimental and computational techniques

ABSTRACT

Introduction: In pharmaceutical design where future drugs are developed by targeting a specific chosen protein, the evaluation of ligand affinity is crucial. For this very purpose are a multitude of diverse methods which are continuously being improved, which, in turn, makes it difficult to choose which techniques to use in practice.

Areas covered: In this review, the authors discuss both experimental and computational approaches for affinity evaluation. Basic principles, general limitations and advantages, as well as main areas of application in drug discovery, are overviewed for some of the most popular ligand binding assays. The authors further provide a guide to affinity predictions, collectively covering several techniques that are used in the first stages of rational drug design.

Expert opinion: All affinity estimation methods have limitations and advantages that partially overlap and complement one another. Some of the suggested best practices include cross-verification of data using at least two different techniques and careful data interpretation.