制霉菌素口腔贴膜的处方优选

目的 优选制备制霉菌素口腔双层贴膜的最优处方. 方法 选择聚乙烯醇(PVA)和羧甲基纤维素钠(CMC-Na)、壳聚糖作为载药膜的成膜材料,采用L9(34)正交实验进一步筛选处方,以膜的外观、粘附力、口腔粘附时间为考察指标,选择载药膜的最优处方,同时考察不同浓度乙基纤维素空白膜的外观、柔韧性、脱膜性和铺展性,选择空白膜的最优配方. 结果2.5%乙基纤维素乙醇液作为空白隔离层成膜液,聚乙烯醇 羧甲基纤维素钠-壳聚糖(2：1：1)制成的含药膜为最优处方,粘附力适中,外观性状良好. 结论 乙基纤维素-制霉菌素-聚乙烯醇- 羧甲基纤维素钠-壳聚糖口腔双层贴膜可作为口腔念珠菌感染的新型颊膜给药制剂.     

丁卡因口腔粘附片的研制

目的:研制丁卡因口腔粘附片。考察不同辅料的体外膨胀行为及释药性能。方法:采用聚维酮(PVP)、羟丙甲纤维素(HPMC)、羟丙纤维素(L-HPC)及卡波姆934(CP_(934))为生物粘附材料,以不同配比制备丁卡因口腔粘附片,桨板法测定其释放度。结果:采用CP/HPC、CP/HPMC配比作为粘附材料取得良好效果。     

丁卡因口腔粘附片的研制

目的：研制丁卡因口腔粘附片。考察不同辅料的体外膨胀行为及释药性能。方法：采用聚维酮（PVP），羟丙甲纤维素（HPMC），羟丙纤维素（L-HPC）及卡波姆934（CP934）为生物粘附材料，以不同配比制备丁卡因口腔粘附片，桨板法测定其释放度。结果：采用CP/HPC，CP/HPMC配比作为粘附材料取得良好效果。     

大蒜油口腔黏附片的研究

目的 研制大蒜油口腔黏附片,并考察其生物黏附性及释药性能.方法 采用羟丙基甲基纤维素(HPMC)和卡波姆(Carbopol 934P)为黏附材料,制备不同处方配比的大蒜油口腔黏附片,测定其体外溶胀百分率、黏附力和黏附时间,并采用浆法测定释放度.结果 以HPMC: Carbopol 934P为3:1的处方制得的口腔黏附片较好.结论 成功制备了大蒜油口腔黏附片.     

盐酸地尔硫(卄卓)胃漂浮延迟缓释片的研制

采用干法包衣压片法制备盐酸地尔硫(卄卓)胃漂浮延迟缓释片.考察了溶出介质pH、助漂剂种类、碳酸氢钠及羟丙甲纤维素用量对制剂漂浮性能及释药行为的影响.对释药曲线的拟合结果显示,该制剂4～12h以零级动力学释药,释药机制为药物扩散和骨架溶蚀共同作用.     

肠溶性瑞巴派特壳聚糖胶囊的制备及大鼠口服给药吸收评价

目的评价肠溶性瑞巴派特壳聚糖胶囊的释药作用,考察其结肠定位效果。方法将瑞巴派特1 mg装入壳聚糖胶囊中,并用羟丙基甲基纤维素邻苯二甲酸酯(HPMCP)包裹胶囊,观察胶囊的体外释药性能。在乙醚麻醉下通过聚乙烯管大鼠口服给予瑞巴派特壳聚糖胶囊4 mg,对照组口服同剂量的明胶胶囊和羧甲基纤维素溶液。于给定的时间间隔取血,取出结肠组织,分离提取药物,用HPLC法测定大鼠血液及结肠中药物浓度。结果在6 h体外溶出试验中,即人工胃液2 h和人工肠液4 h中,瑞巴派特从壳聚糖胶囊中的释药量的质量分数小于10%。大鼠口服瑞巴派特壳聚糖胶囊时,在结肠黏膜中的药物含量-时间曲线下面积(AUCLI0-9,16.01 mg.h.L-1)分别是明胶胶囊和羧甲基纤维素溶液的2.5倍和4.4倍。口服瑞巴派特壳聚糖胶囊,大鼠血浆药物含量-时间曲线下面积(AUCPL0-9)为1.02 mg.h.L-1,同剂量的明胶胶囊和羧甲基纤维素溶液分别是2.16 mg.h.L-1和1.89 mg.h.L-1,表明在壳聚糖的作用下,与明胶胶囊或羧甲基纤维素溶液比较,瑞巴派特从胃肠道吸收进入血液循环的量较少。结论在HPMCP的保护下,壳聚糖是瑞巴派特在结肠释药的一种有效的载体。     

采用新型药用辅料制备口腔缓释贴膜的研究

目的:采用新型药用辅料制备口腔缓释贴膜.方法:采用正交设计,以卡波姆(CP)、羟丙甲基纤维素(HPMC)为两因素,在各自的3水平上进行筛选,考察各处方膜剂的粘附性和缓释性能.结果:以8% CP和6% HPMC作为第3层辅料制备的3层膜剂具有较理想的粘附性和缓释性.结论:新型药用辅料CP和HPMC作为成膜材料可以制备出较理想的口腔缓释贴膜.     

丁卡因口腔粘附片的研究

目的：研制丁卡因口腔粘附片，并考察不同辅料的体外膨胀情况及释药性能。方法：采用聚乙烯吡咯烷酮（PVP）、羟丙甲基纤维素（HPMC）、低取代羟丙基纤维素（L－HPC）及卡波普（CP 934）为生物粘附材料，以不同配比制备丁卡因口腔粘附片，照中国药典2000年版附录浆板法用HPLC测定其释放度。结果：用CP与HPC（或HPMC）以1：2的比率制备的丁卡因口腔粘附片在1－2分钟内起效，口腔内的粘附时间大于3小时，夜间使用可达10小时以上。结论：CP与HPC（或HPMC）作为粘附材料制备丁卡因口腔粘附片能获得良好效果。     

多索茶碱脉冲控释微丸的研制

目的 研究多索茶碱脉冲控释微丸的制备工艺,并考察其释药性能。方法 以微晶纤维素为骨架材料采用挤出滚圆法制备载药丸芯,通过流化床包衣法分别覆上交联羧甲基纤维素钠作为溶胀层、乙基纤维素和羟丙甲纤维素作为控释层制备多索茶碱脉冲微丸,通过单因素考察筛选丸芯、溶胀层、控释层的处方组成对体外释药性能的影响。结果 以微晶纤维素、羧甲基淀粉钠和乳糖为添加剂可制得性能良好的高载药微丸。随着溶胀层厚度的增加,药物释放时滞变短,速率显著增加;随着控释层包衣厚度的增加,时滞延长,释药减慢;控释层中羟丙甲纤维素用量或分子量增加,时滞缩短;控释层中增塑剂用量增加,时滞延长。结论 所得包衣微丸具有良好的脉冲释药性能,有广阔的应用前景。     

盐酸地尔硫[艹卓]胃漂浮延迟缓释片的研制

采用干法包衣压片法制备盐酸地尔硫[艹卓]胃漂浮延迟缓释片。考察了溶出介质pH、助漂剂种类、碳酸氢钠及羟丙甲纤维素用量对制剂漂浮性能及释药行为的影响。对释药曲线的拟合结果显示，该制剂4～12h以零级动力学释药，释药机制为药物扩散和骨架溶蚀共同作用。     

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.     

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.     

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.     

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.