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.     

避蚊胺缓释霜剂的研制及其体外的经皮渗透

目的 制备避蚊胺缓释霜剂,并研究其体外经皮渗透情况.方法 用正交筛选法优化避蚊胺缓释霜剂的处方,采用HPLC法测定避蚊胺的含量.利用Franz扩散池,进行体外经皮渗透试验.结果 HPLC测定避蚊胺含量的回收率为101.6%,RSD=1.05%.避蚊胺缓释霜剂的体外渗透系数为0.0157 mg·cm-2·h-1,8 h累积渗透量为0.13 mg·cm-2.结论 避蚊胺缓释霜剂中避蚊胺的体外经皮渗透明显减慢,累积渗透量大大减少.     

丹皮酚聚乳酸微球的制备及药剂学性质

目的：制备丹皮酚聚乳酸微球，并考察其药剂学性质。方法：采用乳化溶剂挥发法制备丹皮酚聚乳酸微球，用光学显微镜考察微球的粒径，用扫描电镜观察微球的形状和表面形态，用差示扫描量热法研究药物在载体中的分散状态及相互作用。结果：所制得的丹皮酚聚乳酸微球外形圆整，平均粒径为（23．25±0．15）μm（n=300），载药量为（11．4±0．5）％（n=3），药物包封率为（63．8±1．6）％（n=3），24h体外累计释药量44．63％。结论：丹皮酚聚乳酸微球制备工艺稳定，具有良好的缓控释能力。     

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。     

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.     

甲硝唑缓释微球结肠溶胶囊的制备及体外释放

目的：研制甲硝唑缓释微球并装于结肠溶胶囊，评价其体外释放特性。方法：用乳化交联法制备甲硝唑羧甲基壳聚糖微球，测定平均粒径、载药量、包封存率等指标；将微球和原料药分别装于结肠溶胶囊，测定微球、原料药及结肠溶胶囊剂型在人工胃液、人工小肠液、人工结肠液中的释放性能。结果：重复制备6批微球，微球平均粒径为（197．1±3．9）μm，载药量为（48．2±1．5）％，包封率为（37．5±1．9）％；体外释放甲硝唑原料药0．75h释放完全，甲硝唑微球7h释放完全；甲硝唑原料药结肠溶胶囊和甲硝唑微球结肠溶胶囊，在人工胃液、人工小肠液5h均无释放，移至人工结肠液后，前者于6．25h释放完全，后者于13h释放完全。结论：甲硝唑羧甲基壳聚糖微球的制备工艺稳定，甲硝唑羧甲基壳聚糖微球结肠囊胶囊具有结肠定位及缓释性能。     

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。     

美罗培南-海藻酸钙微球的制备与性能研究

目的 针对野战条件下战创伤感染缺乏长效抑菌杀菌药物现状,研制一种高效、安全、易用的新型外用抗感染复合材料.方法 应用天然高分子海藻酸钠、无水氯化钙为基质材料,强效抗生素美罗培南为包被药物,采用静电液滴法及冷冻干燥等制备工艺,制备美罗培南-海藻酸钙微球,并对其包封率、载药量、膨胀性及体外释药性进行检测,采用模拟药敏纸片法对其抑菌效果进行评估.结果 所制备的载药微球包封率为62.27%,载药量为19.40%,膨胀率可达80%;微球的释药模式符合缓释特征,可长效抑菌.结论 静电液滴法制备美罗培南-海藻酸钙微球具有可行性,微球性质稳定,释药模式理想、抑菌效果好.     

多功能载鲣鱼肽海藻酸钙微球的制备与表征

目的 通过制剂手段掩盖鲣鱼肽原料的不良嗅味,降低其吸湿性,提高在胃中的稳定性。方法 通过微胶囊造粒仪制备载鲣鱼肽海藻酸钙微球,分别对微球的外观、鲣鱼肽含量进行表征。在25 ℃、65%RH的环境下,检测所得微球吸湿增重。分别测定在模拟胃肠液中鲣鱼肽从微球中的释放。通过顶空进样GC-MS对在热水中孵育的载鲣鱼肽微球进行检测,使用面积归一化法对有异味的挥发性组分进行定量。结果 载鲣鱼肽海藻酸钙微球微球外观圆整且大小均一,鲣鱼肽含量为18.9%。在25 ℃、65%RH的环境下,制备所得微球吸湿增重显著低于鲣鱼肽原料粉末。在模拟胃肠液中,鲣鱼肽从微球中的释放达到了肠溶制剂的标准,预示微球口服后在生理条件严苛且吸收较差的胃部对鲣鱼肽起到保护作用。通过顶空进样GC-MS法发现所制备的海藻酸钙微球可在冲泡过程中掩盖80%的异味。结论 所制备的海藻酸钙微球同时解决了鲣鱼肽原料吸湿性强、在胃中易失活和感官刺激大的缺点,为活性肽保健食品制剂的开发提供了新的思路。     

阿霉素载药栓塞微球的制备和性能表征

目的：研究离子交换型阿霉素载药透明质酸栓塞微球（DHAMs）的制备方法及性能表征。方法：采用油包水（W/O）乳化交联法,以改性透明质酸（HA）为载药基质,通过离子交换原理制备载阿霉素的透明质酸栓塞微球。采用光学显微镜、扫描电子显微镜观察表面形态,考察粒径和溶胀率;采用恒温摇床模拟体内环境初步测定透明质酸微球降解率;采用紫外分光光度法测定DHAMs载药量、包封率和体外释放率;采用傅里叶变换红外光谱（FT-IR）和粉末X射线衍射法（PXRD）对DHAMs进行表征。结果：透明质酸微球形态圆整、表面光滑,平均粒径为（111.83 ± 12.21）μm,溶胀率为201.81%;微球56 d体外降解率为34.31%;微球载药量和包封率分别为（22.09% ± 0.05%）和（99.41% ± 0.21%）,且72 h累计释放量可达50%;FT-IR和PXRD分析显示,阿霉素在微球中以无定形形式存在。结论：阿霉素透明质酸微球有较好的载药性能,理化性能良好,具有动脉化疗栓塞的应用前景。     

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.