盐酸恩丹西酮缓释胶囊的制备及质量控制

目的:制备盐酸恩丹西酮缓释胶囊并建立其质量控制方法。方法:制备盐酸恩丹西酮缓释胶囊;测定盐酸恩丹西酮释放度,进行释放机制及影响因素研究;用高效液相色谱法测定主药盐酸恩丹西酮的含量。结果:制得盐酸恩丹西酮胶囊体外释放曲线符合一级动力学方程和Higuchi方程;盐酸恩丹西酮检测浓度在9.93～79.44μg/ml范围内与峰面积积分值线性关系良好,平均回收率为100.15%(RSD=0.44%)。结论:该制剂具有明显的缓释作用,制备工艺简单,值得推广。     

盐酸恩丹西酮鼻用凝胶剂的制备与质量控制

目的设计盐酸恩丹西酮鼻用凝胶剂处方,并建立其质量控制方法.方法以卡波姆-940和甘油作为凝胶基质和主要辅料,用三乙醇胺调节pH值,制备盐酸恩丹西酮鼻用凝胶剂,采用紫外分光光度法对凝胶剂中盐酸恩丹西酮的含量进行测定.结果所得凝胶剂质量稳定,含量准确,盐酸恩丹西酮平均回收率为100.15%.结论该制剂制备工艺简便、稳定性好,质量控制方法简便、快速、准确.     

盐酸恩丹西酮缓释胶囊质量标准研究

目的:制定盐酸恩丹西酮缓释胶囊的质量标准。方法:采用 HPLC 法测定盐酸恩丹西酮的含量和溶出度。结果:盐酸恩丹西酮缓释胶囊含量在90.0%～110.0%范围内;体外释放曲线符合一级动力学方程和 Higuchi 方程;有关物质检查未见。结论:本法简便、准确,专属性强,可用于盐酸恩丹西酮缓释胶囊的质量标准研究。     

盐酸恩丹西酮口服液的制备及质量控制

目的研究盐酸恩丹西酮口服液的制备及质量控制方法,考察其稳定性并预测室温贮存有效期。方法确定了盐酸恩丹西酮口服液的处方,应用紫外分光光度法测定口服液中盐酸恩丹西酮的含量,用初均速法预测有效期。结果盐酸恩丹西酮口服液质量浓度在4.236～21.18μg/mL范围内与吸光度线性关系良好,低、中、高3种质量浓度样品的回收率分别为100.74%,103.56%,102.86%,日内和日间精密度均较好;在室温(20℃)下,盐酸恩丹西酮口服液有效期为1.5年。结论该制剂制备工艺简单,质量易于控制,稳定性较好。     

盐酸恩丹西酮注射液与注射用卡铂配伍的稳定性考察

目的 :考察盐酸恩丹西酮注射液与注射用卡铂的配伍稳定性。方法 :采用紫外分光光度法测定盐酸恩丹西酮注射液与注射用卡铂配伍后在室温下8h内的含量变化 ,并观察外观及测定其 pH值的变化。结果 :配伍液外观、pH值及含量均无明显变化。结论 :盐酸恩丹西酮注射液与注射用卡铂在配伍后8h内稳定。     

RP-HPLC法测定盐酸恩丹西酮氯化钠注射液的含量

目的：建立反相高效液相色谱法测定盐酸恩丹西酮氯化钠注射液含量的方法。方法：采用ODS反相柱，流动相为甲醇-0.02M磷酸二氢钾（58：42，pH=6.0),检测波长为308nhm。结果；盐酸昂丹司琼在辅料中的回收率为100.14%。日内与日间精密度分别为0.41%和0.54%。结论：本法准确，快捷，适用于测定盐酸恩丹西酮氯化钠注射液的含量。     

RP-HPLC测定盐酸恩丹西酮注射液中盐酸恩丹西酮的含量

盐酸恩丹西酮(ondansetron hydrochloride)是一种高效并有高度选择性的5-羟色胺受体拮抗剂。临床上用于癌症药物化疗和放射性治疗引起的恶心呕吐。有文献用紫外分光光度法和高效毛细管区带电泳技术测定含量。未见用RP-HPLC法测定的报道，本文建立了用RP-HPLC法测定盐酸恩丹西酮注射液制剂中的盐酸恩丹西酮含量，经方法考察，本法简便、快速、准确、结果可靠，可用于本品质量控制和临床应用检测。     

盐酸恩丹西酮葡萄糖注射液稳定性研究

目的 :研究盐酸恩丹西酮葡萄糖注射液的稳定性。方法 :以高效液相色谱法测定盐酸恩丹西酮及其有关物质的含量 ,分别用强光照射法、加速试验法和室温留样观察法对盐酸恩丹西酮葡萄糖注射液进行稳定性试验。结果 :除强光照射条件下本品含量略有下降外 ,加速试验和室温留样观察各项指标均符合质量标准的规定。结论 :本品在避光、密闭的贮存条件下性质稳定 ,室温下贮存期可定为2年。     

恩丹西酮对化疗性呕吐的疗效观察

目的 :观察国产止吐剂恩丹西酮对化疗性呕吐治疗的作用。方法 :对 40例大剂量化疗的患者 ,分为治疗组和对照组进行比较。结果 :恩丹西酮的止吐效果明显 ,在化疗患者组呕吐发生率为 2 5 %,明显低于对照组的 10 0 %;呕吐程度也明显较对照组轻 ,并经统计学处理 ,均有显著的差异 (P<0 .0 1)。结论 :对大剂量药物化疗的患者 ,恩丹西酮是有效的止吐药物。     

托烷司琼用于预防神经外科术后恶心呕吐的研究

目的：观察5-HL受体拮抗剂盐酸托烷司琼与盐酸恩丹西酮预防神经外科开颅术患者术后恶心呕吐（PONV）的有效性和安全性。方法：选择神经外科行幕上开颅手术患者150例，随机分为3组：盐酸托烷司琼组、盐酸恩丹西酮组和空白对照组，每组50例。各组于手术至缝合硬膜时分别静脉滴注盐酸托烷司琼5mg，盐酸恩丹西酮4mg及注射用水。术后中、重度呕吐患者追加使用抗呕吐药物盐酸恩丹西酮。术后观察并记录以下指标：（1）恶心发生率。（2）呕吐发生率。（3）疼痛视觉模拟评分（VAS）。（4）镇静评分（OAA／S）。（5）平均动脉压（MAP）、心率（HR）。（6）追加使用抗呕吐药物的药名及剂量。（7）不良反应的发生情况。结果：术后2h内托烷司琼组、恩丹西酮组恶心及呕吐的发生率低于对照组（P〈0．01或P〈0．05）；但两治疗组间差别无统计学意义（P〉0．05）。恩丹西酮组术后24h内恶心的发生率较托烷司琼组呈增加趋势，但差异无统计学意义（X^2=3．326，P〉0．05）。结论：托烷司琼、恩丹西酮均可降低恶心呕吐的发生率。托烷司琼作用时限较恩丹西酮长，可能具有更好的预防效果。     

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.     

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.     

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.