羟基喜树碱微球的制备及其小鼠体内分布研究

目的:制备肺靶向性羟基喜树碱(HCPT)微球,评价其体外释药特性及其在小鼠体内的肺靶向性。方法:以聚乳酸为主要辅料,采用溶剂挥发法制备微球,考察其粒径、包封率、载药量,比较微球及原料药的体外释药性;取12只小鼠分别尾静脉注射HCPT微球及原料药,30min后分别测定血浆及各组织的药物浓度并计算相对分布率。结果:所制微球粒径在7～30μm者达81.6%,平均粒径为(14.2±3.1)μm,包封率为72.36%,载药量为(40.6±3.6)%,微球及原料药体外释药参数T50分别为85、18min。微球给药组在肺中的药物浓度最高(32.2±2.48)μg.mL-1,相对分布率58.1%;原料药给药组在血浆中的药物浓度最高(13.52±2.58)μg.mL-1,相对分布率25.24%。结论:所制HCPT微球具有明显的缓释性及肺靶向性。     

紫杉醇肺靶向微球的制备及体内外评价

目的用生物可降解材料聚乳酸-聚羟基乙酸共聚物(PLGA)制备肺靶向紫杉醇缓释微球。方法在单因素考察的基础上进行正交试验设计,筛选出肺靶向紫杉醇PLGA微球的最佳制备工艺条件;利用桨板法研究了微球的体外释药规律;用小鼠为实验对象,研究了紫杉醇聚乳酸微球的体内组织药物分布。结果制得的微球形态圆整,粒径在5~15μm范围内的占总体积的87.18%,微球平均粒径为9.65μm;包封率为83.8%;载药量为19.7%;体外释药符合Higuchi方程Q=-2.193 7 22.009t0.5,r=0.990 4;体内实验表明紫杉醇微球混悬剂较普通注射剂更趋于聚集在肺组织。结论微球制备工艺稳定,具有明显的缓释作用和肺靶向性。     

卡铂肺靶向明胶微球的实验研究

目的：研制卡铂肺靶向微球。方法：用乳化法制备卡铂微球，正交试验设计考察影响制备工艺的因素。体外长烃药试验研究其缓释性，以微球在家兔的体内分布初步考察其靶向性。结果：所制备微球88.6%的粒径在5-25μm。药物包封率为79.2%。8小时体外药物累积释放百分率达95%并有良好的靶向性。结论：用乳化法制备的卡铂肺靶向微球有良好的应用研究前景。     

肺靶向多西紫杉醇壳聚糖微球的制备与工艺优化

目的：研制肺靶向多西紫杉醇壳聚糖微球,并对处方工艺进行筛选。方法：以壳聚糖为载体,采用乳化-化学交联法制备多西紫杉醇壳聚糖微球。在单因素考察的基础上,利用正交试验设计优化微球制备工艺,采用HPLC法测定微球的载药量与包封产率。结果：制得的微球显微观察形态圆整、表面光滑,无粘连;平均粒径为（8．63±0．27）μm,粒径7—12μm的微球平均占总数的83．5％,载药量为（25．01±1．80）％,包封产率为（85．54±2．21）％。结论：筛选的最佳处方工艺制备的微球粒径大小适宜,可满足肺靶向微球的要求;该制剂有可能成为临床肺部肿瘤治疗的一种靶向制剂。     

肺靶向利福平聚乳酸微球的研究

在单因素考察的基础上进行正交试验设计,筛选出肺靶向利福平聚乳酸微球的最佳制备工艺条件;利用桨板法研究了微球的体外释药规律;考察了微球在不同温度下的稳定性;用新西兰兔为实验对象,研究了利福平聚乳酸微球的体内药动学及组织药物分布。结果制得的微球形态圆整,粒径在5～15μm范围内的占总体积的86.54%,微球平均粒径为9.00±4.08μm;包封率为31.9%;载药量为16.0%;体外释药方程为Q=20.77+10.12T_1/2(γ=0.9892);微球在冰箱4℃和室温(20～25℃)条件下性质稳定;体内实验表明微球具有长效和肺靶向双重作用。     

盐酸川芎嗪肺靶向微球理化性质的研究

考察了盐酸川芎嗪肺靶向微球的微粉学性质、热解稳定性、载药量和体外释药模式。结果表明，微球为类白色圆球状粉末，平均算术粒径为１２．６５μｍ，５～２４．９μｍ，粒径范围的微球数占总数的８７．５％，平均堆密度为０．５９ｇ／ｍｌ，休止角为６８．６３°，临界相对湿度为５６％，热解活化能为８１．６ｋＪ／ｍｏｌ，反应级数为１。用ＵＶ法测得微球载药量为１７．０％，微球体外释药符合一级动力学规律。微球粒径符合肺靶向要求     

骨载异烟肼缓释微球的制备及其在动物模型中的释放研究

目的：观察探讨骨载异烟肼聚乳酸微球的设计和制备方法及其在动物模型中的释放效果。方法：选择24只雄性新西兰大白兔作为实验动物模型,采用复乳法制备缓释微球,对微球进行形态学观察、粒径分布观察、体内释药和体外释药观察。结果：平均微球粒径（10.59±0.3）μm,平均包封率（44.9±0.9）%,平均载药率（13.0±0.6）%。在24h、72h、1w、3w微球组滑膜药物浓度明显高于口服组和原药组,P＜0.05。与口服组和原药组对比,微球组0～24h药物波动差值明显更低,P＜0.05。结论：本研究制备的骨载异烟肼缓释微球具有良好的缓释性,能够在抗结核治疗中置入骨结核病灶对术后病灶发挥持久的疗效。     

苦参碱壳聚糖微球的制备及体外释药

目的:以壳聚糖为囊材制备苦参碱结肠靶向给药微球及评价其体外释药情况。方法:用乳化化学交联法制备微球,以微球的粒径分布百分数、载药量及包封率为优化指标对影响微球制备的主要因素用正交试验设计优化制备条件;并对最佳制备工艺制得的微球进行3种不同递质(人工胃液、人工肠液及大鼠结肠液)中的体外释放度评价。结果:制得的苦参碱壳聚糖微球在电镜下,球形表面圆整,粒径分布适宜,微球平均粒径为(68.3±2.7)μm,平均载药量为(16.0±0.5)%,平均包封率为(66.3±4.2)%。苦参碱壳聚糖微球在人工胃液中2h不释药;在人工肠液中4h内释放不到1%,96h释药不到10%;在含大鼠结肠内容物的磷酸盐缓冲液(pH6.8)中4h释放10%左右,36h释药近50%,此后释药趋于缓慢,96h释药近80%。结论:苦参碱壳聚糖微球几乎不在上消化道释药,而是在结肠靶向释药。     

紫杉醇壳聚糖肺靶向微球的制备

目的研制具有肺靶向性的紫杉醇壳聚糖微球,并对处方工艺进行优化。方法以壳聚糖为载体,采用乳化一化学交联法制备紫杉醇壳聚糖微球。单因素试验考察了油／水体积比、紫杉醇浓度、乳化时间、乳化剂量等因素,采用正交设计优化微球制备工艺,以HPLC法测定微球载药量、包封率。结果制得的微球显微观察形态圆整、表面光滑,无黏连;平均粒径为（8．23±0．25）μm,粒径在7～12μm平均占微球总数的84．2％,载药量为16．20％±1．15％,包封率为81．29％±1．62％。结论筛选的最佳处方工艺制备的微球粒径大小适宜,可满足肺靶向微球的要求并免除过敏试剂的加入。     

盐酸川芎嗪肺靶向微球的研究

用乳化法制备盐酸川芎嗪明肢微球,优化了工艺。对微球的外观、粒径与其分布、含量、体外释药、稳定性及体内分布等进行研究。结果表明平均粒径为12.65μm,粒径范围5.0～24.9μm占总数的87.5%,球内含药量平均为16.49%±0.49%(n=3),冰箱或室温放置稳定,体外释药符合一级动力学规律,释药t_1/2比原药延长约5倍。小鼠静注微球后20 min,在肺内的相对分布百分率明显高于其它组织与血液,与溶液对照组相比,提高近6倍。     

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.