司帕沙星注射液的研制及稳定性考察

目的:考察司帕沙星注射液的稳定性,判定其有效期.方法:通过光照、高温、低温等影响因素试验,特定条件(40,50,60℃)下恒温15周加速试验及室温留样观察,测定其色泽、pH值、含量及有关物质变化,其中含量及有关物质均采用高效液相色谱法测定,其线性关系、重现性良好,回收率高.结果:通过恒温(恒湿)稳定性试验仪考核测定的数据在15周内可知处方的稳定性,与室温留样观察结果一致.结论:司帕沙星注射液处方合理、质量稳定,有效期可达2年以上.     

盐酸洛美沙星阴道泡腾栓的研制及质量控制

目的:考察盐酸洛美沙星阴道泡腾栓的稳定性,为制定其有效期提供依据.方法:通过光照、高湿、高温、低温影响因素试验,恒温、恒湿加速试验及室温留样观察,并测定洛美沙星含量及有关物质含量,观察该制剂的稳定性.结果:盐酸洛美沙星阴道泡腾栓怕光、怕湿,用铝塑包装后,加速试验和室温留样观察结果表明,其发泡量、洛美沙星含量、有关物质(分解产物)含量相当稳定.结论:盐酸洛美沙星阴道泡腾栓组方合理,以铝塑包装,质量稳定,有效期可达2年.     

美洛西林钠皮试液稳定性考察及有效期预测

目的 考察美洛西林钠皮试液的稳定性及有效贮存期。方法 采用经典恒温试验法及留样观察法考察外观及pH值变化，紫外分光光度法测定其中美洛西林钠含量。结果 皮试液室温（25℃）有效期为20d，夏季（37℃）有效期为6d，与留样观察结果基本一致。结论 美洛西林钠皮试液在室温下20d内稳定。     

紫虹溶液的稳定性考察

目的：预测医院消毒剂紫虹溶液的稳定性，为临床提供贮存期依据。方法：采用经典恒温加速法和初匀速法，预测其室温（20℃）有效期，同时进行留样观察。结果：其稳定性与温度有关，符合Arrhenius公式。结论：本制剂在室温（20℃）时贮存期为33－34h，与留样观察结果34h基本相符。     

胃镜滑润胶化学稳定性的考察

目的考察胃镜滑润胶的化学稳定性,预测其室温存放的有效期。方法采用经典恒温加速实验法,分别在65、70、75、80℃恒温条件下,在不同时间间隔测定主要成分盐酸丁卡因的含量。结果盐酸丁卡因稳定性与温度有关,符合Arrhenius公式。结论胃镜滑润胶有效期约为13个月。留样观察结果与加速实验预测的有效期基本一致。     

经典恒温法考察复方曲安奈德乳膏的稳定性

目的:考察复方曲安奈德乳膏的稳定性.方法:采用分光光度法于波长485 nm处测定醋酸曲安奈德的含量,通过经典恒温法对复方曲安奈德乳膏作稳定性试验,并留样观察.结果:经典恒温法测得复方曲安奈德乳膏的室温贮存期为1年,与留样观察结果相符.结论:复方曲安奈德乳膏可以通过经典恒温法预测有效期,该方法简便、快速.     

初探复方左氧氟沙星替硝唑注射液的稳定性

目的 研究左氧氟沙星替硝唑复方注射液的稳定性。方法 按Rogers法，采用变温加速稳定试验对注射液的有效期（t0．9）进行预测。结果 在25℃温度下，t0．9为替硝唑5．6h，左氧氟沙星4．6h。结论 Rogers法测得的25℃下有效期太短，可能是复方制剂对热比较敏感，其稳定性考察应进一步采用经典恒温法或室温留样观察法来测定。     

双氯芬酸钠滴眼液稳定性研究

采用高效液相色谱法测定双氯芬酸钠滴眼液的含量，方法简便，准确，能将药与杂质峰完全分离。应用化学动力学原理以恒温加试验预测双氯芬酸钠滴眼液稳定性及有效期，室温下有效期ｔ＾２５℃０．９约为２．５７年，与留样观察结果相符。     

硫酸阿托品滴眼剂稳定性的考察

目的：观察硫酸阿托品滴眼剂在不同环境下有效成分的改变，预测该制剂的有效期。方法：采用高效液相色谱法测定硫酸阿托品滴眼剂的含量，分别对该制剂进行不同酸度环境下考察、光加速试验、恒温加速试验、留样观察试验。结果：该制剂最适pH为3．5～5．5；对光敏感；室温下制剂的有效期为13个月。结论：该制剂酸性条件下稳定，贮存应避光保存。     

有机金属抗癌原料药二氯二茂钛的稳定性试验

目的考察二氯二茂钛原料药的稳定性，并预测其有效期。方法采用正相高效液相色谱法测定原料药含量和有关物质，以正己烷一二氯甲烷（50：50）为流动相考察加速和长期稳定性试验，经典恒温法预测其有效期。结果含量和有关物质测定方法的平均回收率为99．9％（n=9），RSD为0．45％。拟市售包装，40℃加速试验6个月，长期室温试验24个月，有关物质稍有增加，其他各考察指标无明显变化。经典恒温法预测本原料药在25℃贮存时有效期大于10年。结论拟市售包装条件下二氯二茂钛稳定性较好，有效期暂定2年。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.