海藻酸钙凝胶微球中模型药物的pH值依赖性释放

目的:考察海藻酸钙凝胶微球中模型药物的pH值依赖性释放.方法:以硝苯地平为模型药,采用滴制法制备了含药微球;考察了含药微球在不同pH值介质中的释放特性.结果:含药微球在水及pH 1.0的介质中几乎不溶胀,12 h累积释放百分率为23.1%和23.4%;在pH6.8的介质中微球溶胀至完全溶蚀,且呈现缓慢释放的趋势,12 h药物的累积释放百分率为92.5%;换介质的释放中,0～2 h微球几乎不溶胀,2 h累积释放8.4%,介质pH改变后微球很快崩解,3 h累积释放82.4%.结论:海藻酸钙凝胶微球中硝苯地平的释放具有pH值依赖性,在pH 6.8的介质中缓释.     

海藻酸钙凝胶微丸作为口服缓释给药载体的研究

将海藻酸钠溶液滴入胶凝剂氯化钙溶液中制备了海藻酸钙凝胶微丸。以胶凝过程中凝胶微丸重量变化 (失水量 )研究了胶凝速率及不同浓度海藻酸钠溶液 ( 1 %～ 4 % )与氯化钙溶液 ( 0 0 5～0 2 0mol/L)对胶凝速率的影响 ,结果是 6h前胶凝速率快 ,随后减慢 ,约 70h胶凝完全 ,氯化钙溶液的浓度≥ 0 1mol/L对胶凝速率无明显影响。干燥的凝胶微丸在不同水性介质中溶胀试验结果表明 :在温度约 37℃时 ,微丸在蒸馏水和 0 1mol/L盐酸 ( pH1 0 )中几乎不溶胀 ,而在磷酸盐缓冲溶液( pH6 8)中1h溶胀 ,溶胀后的微丸直径是干燥前湿微丸直径的 1 80 %。海藻酸钙凝胶微丸这种溶胀的 pH敏感性 ,使它能成为口服药物缓释制剂的载体。以硝苯地平为模型药物制备的海藻酸钙凝胶微丸 ,其体外释放试验结果 ,2h累积释放量为 2 0 %～ 30 % ,6h为 6 0 %～ 80 % ,1 2h时大于85 %。药物从微丸中的释放是以扩散和骨架溶蚀相结合的方式。由此可见 ,硝苯地平的海藻酸钙凝胶微丸具有缓释作用     

双氯芬酸钠海藻酸钙凝胶微球的制备及其性质分析

目的制备双氯芬酸钠海藻酸钙凝胶微球，并对凝胶微球的性质进行分析。方法采用滴制法制备双氯芬酸钠海藻酸钙凝胶微球，紫外分光光度法测定药物的含量，对凝胶微球的粒度、圆整度、休止角和堆密度进行测定，并用扫描电镜观察凝胶微球的形态。结果制备的双氯芬酸钠海藻酸钙凝胶微球包封率较高，粉体学性质良好，球形均匀圆整。结论该方法适用于双氯芬酸钠海藻酸钙凝胶微球的制备。     

龟板水提物缓释微球的制备及其特性

目的：制备高包封率的龟板水提物缓释微球。方法：分别采用海藻酸钙凝胶珠、海藻酸钙-壳聚糖微胶囊和海藻酸钙-羧甲基纤维素钠微胶囊体系制备龟板水提物缓释微球,并考察其外观形态、包封率和体外释药等特性。结果：制得的龟板-海藻酸钙凝胶珠、龟板-海藻酸钙—壳聚糖微球和龟板-海藻酸钙-羧甲基纤维素钠微球外观圆整,表面光滑,且粒径均匀;包封率分别是46．7％、49．9％和82．3％;海藻酸钙凝胶珠有明显的突释现象,海藻酸钠—壳聚糖微球的突释现象和缓释效果有所改善,而海藻酸钙-羧甲基纤维素钠微球无突释现象,其缓释可达14小时以上。结论：龟板-海藻酸钙-羧甲基纤维素钠微球包封率高,同时具有优良的缓释性能。     

卡维地洛pH敏感性N-琥珀酰壳聚糖-海藻酸钙水凝胶的制备工艺优选

目的:优选卡维地洛pH敏感性N-琥珀酰壳聚糖-海藻酸钙水凝胶的最佳制备工艺,并考察其pH敏感性。方法:以包封率和载药量为考察指标,采用L9(34)正交试验优选其制备工艺。评价水凝胶在不同pH值溶液中的pH敏感性。结果:优选的最佳工艺为2%(w/v)N-琥珀酰壳聚糖,2%(w/v)海藻酸钠,2%(w/v)氯化钙,药物与海藻酸钠的质量比为1∶4(g/g)。水凝胶在pH1.5的溶液中几乎不溶胀,在pH6.8的溶液中溶胀度最大。结论:优选的制备工艺合理可行,制备的水凝胶具有明显的pH敏感性及缓释效果。     

酮洛芬果胶钙凝胶小球和海藻酸钙凝胶小球的制备及性能比较

目的酮洛芬果胶钙凝胶小球和酮洛芬海藻酸钙凝胶小球的制备及性能比较。方法利用果胶、海藻酸钠及二者不同比例,以酮洛芬为模型药物采用滴制法制备凝胶小球,考察2种多糖物质对药物包封率和释放行为的影响。利用大鼠肠囊外翻实验对凝胶小球的生物黏附性能进行比较,通过对释放机理的探讨和凝胶小球溶胀性的测定进一步证明2种凝胶小球释药行为的不同。结果酮洛芬果胶钙凝胶小球和酮洛芬海藻酸钙凝胶小球均具有良好的生物黏附性能,果胶钙凝胶小球主要通过溶胀作用缓慢释药,而海藻酸钙凝胶小球的释药与凝胶小球慢慢吸水后骨架溶蚀有关。结论酮洛芬果胶钙凝胶小球和酮洛芬海藻酸钙凝胶小球通过与生物黏膜的紧密结合缓慢释药,而二者的释放行为有所不同。     

多柔比星海藻酸钙微球的制备及其载药、释药性质的研究

目的：考察多柔比星海藻酸钙微球的制备工艺及载药、释药性质。方法：考察不同处方微球的粒径、机械强度、降解等性质，筛选出最佳处方；以多柔比星为模型药物研究其对药物的承载能力及体外释药特性。结果：制备的微球圆整且分散性好，粒径均匀。多柔比星海藻酸钙微球的载药量达30％以上，包封率在90％以上；在体外37℃生理氯化钠溶液中释放显示具有缓释作用。结论：该微球对多柔比星具有较高的承载能力，并有较好的缓释作用，可满足临床治疗动脉栓塞需要。     

避蚊胺-海藻酸钙微球的制备及其体外透皮吸收研究

目的 制备海藻酸钙空白微球,减少避蚊胺(DEET)的透皮吸收,延长其作用时间.方法采用溶剂挥发法制备海藻酸钙微球,采用光学显微镜和激光粒度仪考察微球特性;吸附DEET后制成霜荆,通过Franz扩散池,用气相色谱法考察含药微球的透皮吸收.结果所得微球外观圆整,平均粒径42.5μm,吸附量为1.2177 g·g-1.透皮试验结果表明,海藻酸钙空白微球能延长DEET的释放,减少皮肤渗透.结论 海藻酸钙微球具有显著的缓释效果,并减少DEET对人体及皮肤的不良反应.     

α-细辛脑海藻酸钙微球的制备及体外释放药物考察

目的研究α-细辛脑海藻酸钙微球的制备工艺,测定微球中α-细辛脑的体外释放度。方法采用乳化-内部凝胶化法制备海藻酸钙微球,正交试验设计优化制备工艺,分光光度法测定α-细辛脑的含量。结果最优工艺微球球形圆整,载药量为1.17%,包封率为2.40%,微球的平均粒径为17.97μm,大部分微球粒径分布在7~30μm（93.67%）,体外释放符合双相动力学方程Q/100=0.8276-0.0506exp（-1909t）-0.777exp（-0.4405t）。结论以海藻酸钠为载体、乳化-内部凝胶化法制备了海藻酸钙微球,获得微球制备工艺。     

一种新的缓释载体──海藻酸钙凝胶小球的研究概况

海藻酸及海藻酸盐是来源于褐藻的亲水性胶态多聚糖，是由β－（1，4）－D-甘露糖醛酸（M）和α－（1，4）－L-古罗糖醛酸（G）形成的线性高分子化合物，具有与多价阳离子形成凝胶的特性，如海藻酸钠与钙离子形成海藻酸钙凝胶，电镜扫描为三维网状结构，被称为“鸡蛋箱”结构，非常形象。因此海藻酸及海藻酸盐广泛应用于药学、食品、生物技术领域，作为药物的载体或用于细胞及酶的固定［1，2］。海藻酸钙凝胶小球具有以下特点：（1）溶胀特性，可作为缓控释给药的载体。（2）其溶胀特性受pH值的影响，故可防止酸敏感性药物在胃中被降解。（…     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

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.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.