酮咯酸氨丁三醇微囊的研究

目的制备酮咯酸氨丁三醇的海藻酸钠-壳聚糖微囊，对其体外释药特性进行考察。方法采用滴液法制备微囊，以均匀设计优化制备工艺，溶出度测定法考察微囊体外释药特性。结果80％微囊粒径在200-250μm，微囊表面光滑圆整无粘连，包封率达90．56％，载药量达43．65％；微囊在人工胃液和蒸馏水中的释药规律符合Higuchi方程。结论酮咯酸氨丁三醇的海藻酸钠-壳聚糖微囊在人工胃液和蒸馏水中具有缓释作用。     

正交实验设计优化岩白菜素微囊的制备工艺

目的优化岩白菜素微囊的制备工艺,并对制备的岩白菜素微囊进行质量评价。方法以明胶为囊材,单凝聚法制备岩白菜素微囊,通过正交实验设计优化其制备工艺,并对包封率、载药量、平均粒径、体外溶出率进行研究。结果明胶制备岩白菜素微囊的最佳工艺条件为:明胶质量分数为6%,囊心囊材质量比为1∶2,搅拌速度为750r·min^-1。此最佳工艺制备的岩白菜素微囊包封率为75.90%,载药量为23.09%,体外溶出度测定30min为28.6%,12h累计释放达到90%以上。结论以最佳工艺条件制备岩白菜素微囊工艺稳定,包封率高,同时体外释放实验表明,该微囊具有较好的缓释作用。     

左旋多巴微囊制备工艺的研究

目的以乙基纤维素为囊材,优选左旋多巴微囊的制备工艺。方法以微囊的包封率及载药量为评价指标,采用正交实验优选左旋多巴微囊液中干燥法制备工艺条件,并对制备的微囊进行质量检查。结果优选出的制备工艺为:囊材与药量比例为0.6∶1.4,油水相比例为105∶30,PVP量为0.2g,验证实验表明,优化工艺所制左旋多巴微囊的平均载药量为54.94%,平均包封率为89.2%。质量检查结果表明,微囊外观圆整且无粘连现象,大部分微囊的粒径分布在300～600μm范围内。优选出的左旋多巴微囊在体外具有明显的缓释效果。结论采用液中干燥法制备左旋多巴微囊,工艺稳定可靠,操作简便,工艺条件合理、可行。     

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。     

他克莫司纳米微球的制备及其体外释药性能

目的采用甲氧基聚乙二醇-聚乳酸聚合物（PEG—PLA）制备他克莫司微球（PPT），研究其体外释药特性。方法考察PPT的载药量、包封率、粒径大小、粒径分布和药物体外释放实验。结果PPT的制备工艺稳定、重复性好，微球外形圆整，表面光滑，分布均匀，平均粒径为（545．1±0．9）nm，平均载药量为（18．90±3．22）％，平均包封率为（25．0±1．6）％，35d的药物累积释放率为67．21％。结论他克莫司微球缓释时间长达35d，能够满足临床治疗的要求。     

硫酸特布他林干粉吸入剂制备工艺的优化研究

目的:优化硫酸特布他林干粉吸入剂的制备工艺。方法:采用喷雾干燥技术制备硫酸特布他林干粉吸入剂,采用双层液体碰撞器测定其体外肺沉积率,扫描电镜观察干粉的表观形貌,热重分析仪测定干粉的水分含量,激光粒度测定仪测定粒径大小,以产品收率、水分含量、粉末的空气动力学粒径及体外肺沉积率为考察指标,通过正交设计结合多指标综合评价法优化最佳制备工艺。结果:通过正交试验-多指标综合评价,最佳制备工艺为:喷雾压力190 kPa,干燥风速0.7 m3.min-1,供液速度7.0 mL.min-1,入口温度120℃。结论:按最佳制备工艺制得的干粉收率为50.54%,水分含量为0.467%,空气动力学粒径为1.80μm,体外肺沉积率为55.19%。正交试验结合多指标综合评价法用于硫酸特布他林干粉吸入剂制备工艺的优化有效可用。     

羟基喜树碱半固体脂质纳米粒的制备和体外释药特性

目的：制备羟基喜树碱的半固体脂质纳米粒（HCPT-SSLN），初步考察其体外释药规律。方法：采用乳化蒸发-低温固化法制备HCPT-SSLN；用激光粒度仪测定其粒径和ξ电位；考察其混悬液和冻千粉的物理稳定性；用透析法考察其体外释药性质。结果：HCPT-SSLN纳米粒平均粒径为130．5nm，裁药量为2．51％，包封率为79．19％，ξ电位为-33．1mV;室温（25℃）和4℃下放置6个月，纳米粒冻干粉和混悬液外观、粒径及包封率无明显变化；体外释药规律符合Weibull方程lnln[1／（1-Q）]=0．26331nt＋0．0509（R^2=0．9485）。结论：制备的HCPT-SSLN包封率高，稳定性好，大小均匀，体外释药具有缓释特点。     

对乙酰氨基酚复合微囊缓释栓的制备及体外释放度研究

目的:采用复凝聚法制备对乙酰氨基酚(AAP)微囊并考察其体外释药行为。制备AAP复合微囊栓剂,具有良好释放效果。方法:考察复凝聚法制备AAP微囊过程的处方和工艺因素,并进行正交试验设计,筛选出最佳条件制备AAP微囊并考察其体外释药行为。同时采用复合缓释技术(速释部分+微囊缓释)制备复合微囊缓释栓剂,考察其释药行为。结果:建立了复凝聚法制备AAP微囊方法,优化后的制备条件为:明胶阿拉伯胶囊材用量各为7 g(溶液浓度7%),药物用量为8 g,搅拌速度为300 r·min^-1,制备温度55℃。此条件制备的微囊形态圆整,粒径均匀,重复性好,包封率为(79.71±0.10)%,载药量为23.11±0.69%。微囊有缓释效果,拟合缓释方程符合一级方程。制备的复合微囊栓与普通栓剂相比,具有更好的释放效果,其中缓释过程药物释放符合Higuchi方程。结论:基于普通栓剂与复合微囊技术制备的新型AAP栓具有更佳的释药特性。     

盐酸黄连素肠溶微囊的制备及评价

目的：以聚丙烯酸树脂Ⅱ号为囊材，制备盐酸黄连素肠溶微囊，并测定其体外溶出度。方法：采用溶剂挥发法制备盐酸黄连素肠溶微囊，通过正交实验进行优化，以微囊的包封率及栽药量为指标。结果：应用优化工艺制备的盐酸黄连素肠溶微囊，栽药量为11．18％，包封率为85．00％，盐酸黄连素肠溶微囊在pH为6．8、7．4的溶出介质中60min内溶出度超过70％。结论：采用溶剂挥发法制备盐酸黄连素肠溶微囊，工艺稳定可靠，操作简便，栽药量高，具有肠溶特性，显示出良好的应用前景。     

壳聚糖-三七总皂苷缓释微囊的制备及体外溶出研究

目的探讨制备壳聚糖（CTS）-三七总皂苷（PNS）缓释微囊的工艺条件，确定微囊的缓释作用。方法以壳聚糖为载体，采用乳化学学交联技术，制备壳聚糖-三七总皂苷微囊，并考察微囊的基本特性及其体外溶出性能。结果微囊的最优工艺条件为3％壳聚糖溶液，壳聚糖／三七总皂苷为2：1，在60％下交联2h.结论体外释放度试验表明，药物释放速度较缓慢，缓释效果明显。     

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.