国产尼莫地平片的溶出度比较

目的:比较国内不同药厂尼莫地平片剂的溶出情况。方法:参照日本在"药品品质再评价"拟定流程中对溶出度试验条件的规定,分别考察不同批次尼莫地平片在水、pH1.2人工胃液、pH4.0醋酸盐缓冲液、pH6.8磷酸盐缓冲液4种溶出介质中的体外溶出行为,溶出方法采用桨法,转速为50r·min~(-1),同时和中国药典2005年版规定的尼莫地平片溶出方法进行比较。结果:按照中国药典方法进行溶出时,14个药厂的尼莫地平在6h内溶出均超过80%;在其他介质中溶出时,只有1家药厂的产品能够在6h溶出超过70%,其他药厂产品均不太满意。结论:同一批尼莫地平片在不同溶出介质中溶出差异很大;不同药厂尼莫地平片剂的质量有显著性差异,国产药品的质量亟待提高。     

尼莫地平片抽验结果质量分析

目的通过对全国34个生产厂家的850批次尼莫地平片抽验结果的分析,考察国内市场上尼莫地平片的质量情况。方法采用中国药典2005版对本品进行全检,并参照日本在"药品品质再评价"拟定流程中对溶出度试验条件的规定,分别考察6个主要厂家尼莫地平片在水、pH 1.2人工胃液、pH 4.0醋酸盐缓冲液、pH 6.8磷酸盐缓冲液4种溶出介质中的体外溶出行为。结果经按中国药典2005版对全国850批样品检验,仅4批样品不合格,不合格率为0.47%,不合格项目为溶出度。同一批尼莫地平片在不同溶出介质中溶出差异很大;不同药厂尼莫地平片在同一溶出介质中溶出行为亦存在显著差异。结论尼莫地平片的生产工艺成熟,性质较稳定,总体质量情况较好,主要质量问题体现在体外溶出行为上。     

尼莫地平片的体外溶出度考察

本文采用紫外分光光度法(λmax239±1nm)对国产三厂四批尼莫地平片进行体外溶出度测定。求得Td参数具有极显著差异(P<0.01)。各厂产品在30min内溶出均大于60%,并建议尼莫地平片溶出标准[以转篮法:转速100r/min,无水乙醇:水(3:7)作溶出介质,介质容积1000ml]为30min内溶出量不低于60%。     

尼莫地平干乳的溶出度测定

目的测定尼莫地平脂肪乳干乳的体外溶出度，并比较其与尼莫地平进口片、尼莫地平脂肪乳、尼莫地平国产片及国产胶囊的体外溶出度差异。方法以紫外分光光度法作为定量方法，以人工胃液为溶出介质，采用转篮法测定溶出度。以相似因子法评价尼莫地平脂肪乳干乳的溶出度。结果尼莫地平脂肪乳干乳、尼莫地平脂肪乳和进口片的溶出度明显高于尼莫地平国产片和国产胶囊的溶出度，尼莫地平干乳的溶出度与尼莫地平脂肪乳和尼莫地平进口片的溶出度均相似，且与尼莫地平脂肪乳的相似程度更高。尼莫地平干乳的溶出度与国产片和国产胶囊的溶出度均不相似。结论尼莫地平干乳明显优于国产片和国产胶囊，而与进口片质量相似。     

尼莫地平缓释胶囊的释放度与其普通片的溶出度比较

目的 在相同介质中将尼莫地平缓释胶囊的释放度与普通片的溶出度作比较。方法 利用ZRS-8C型药物智能释放仪,采用转篮法,溶出介质为0.55%的十二烷基硫酸钠水溶液,溶出杯内温度为(37±0.5)℃,转速为50±1r/min,分别在不同的时间点取样,在波长为360nm处测定吸收度,计算出释放度和溶出度。结果 尼莫地平缓释胶囊在60min的累积释放率为44.17%,而普通片的累积溶出率达到了90.91%。结论 尼莫地平缓释胶囊与普通片相比,血药浓度明显平稳,从而使药效延长,达到了提高人体生物利用度的目的。     

尼莫地平缓释胶囊的释放度与其普通片的溶出度比较

目的　在相同介质中将尼莫地平缓释胶囊的释放度与普通片的溶出度作比较。方法　利用ZRS 8C型药物智能释放仪 ,采用转篮法 ,溶出介质为 0 5 5 %的十二烷基硫酸钠水溶液 ,溶出杯内温度为 ( 37± 0 5 )℃ ,转速为 5 0± 1r/min ,分别在不同的时间点取样 ,在波长为 36 0nm处测定吸收度 ,计算出释放度和溶出度。结果　尼莫地平缓释胶囊在 6 0min的累积释放率为 4 4 17% ,而普通片的累积溶出率达到了 90 91%。结论　尼莫地平缓释胶囊与普通片相比 ,血药浓度明显平稳 ,从而使药效延长 ,达到了提高人体生物利用度的目的     

尼莫地平体外溶出度考察

本文采用紫外分光光度法对国内３个厂家及进口尼莫地平片进行体外溶出度测定，溶出介质为３０％乙醇溶液。实验数据经计算机处理而得出溶出参数（τ、ｔ０、ｍ、Ｔ５０、Ｔｄ、Ｔ９０），将溶出参数进行方差分析，可看出四个厂家的尼莫地平片溶出度都具著性差异（Ｐ＜０．０１），其结果显示国产三个厂家生产的尼莫地平片的溶出度不低于进口尼莫地平片。     

光纤传感系统在线监测不同厂家尼莫地平片溶出度

目的:使用光纤药物溶出度实时测定仪FODT-601,实时监测国内6个不同厂家尼莫地平片的溶出度曲线,以评价其工艺质量.方法:设定测定波长238 nm、基准校正波长550 nm、温度37℃、转速75 r·min-1、数据采集间隔时间30 s、监测时间30 min,以900 mL 醋酸盐缓冲液(pH4.5;含0.3%十二烷基硫酸钠)为溶出介质,桨法,用光程为2 mm的光纤探头监测尼莫地平片的溶出曲线.结果:6个不同厂家尼莫地平片的溶出度均符合<中国药典>规定,但各溶出曲线存在差异.结论:光纤药物溶出度实时测定仪准确、连续、定量地反映了药物的溶出过程,获得的数据信息更加完整、真实,可比较出不同厂家之间同种药品的溶出过程差异.     

尼莫地平片溶出度测定方法改进及不同样品比较

目的通过改进药典标准中尼莫地平片溶出度方法及测定方法,以达到区分不同厂家尼莫地平片质量差异的目的。方法建立高效液相色谱法（HPLC）测定尼莫地平片的体外溶出度,以尼莫地平溶解度、稳定性和区分能力为评价指标,筛选溶出介质。结果与结论采用HPLC法,以Kromasil KR100-5C18（4.6mm×150mm,5μm）为色谱柱,以乙腈-四氢呋喃-水（1∶1∶3）为流动相,流速1.0mL·min^-1,柱温40℃,检测波长235nm,以pH4.5醋酸盐缓冲溶液（含0.1%十二烷基硫酸钠）为溶出介质,可良好区分不同厂家尼莫地平片溶出曲线的差异。     

尼莫地平口服固体制剂溶出度的研究

目的 测定尼莫地平口服固体制剂在不同溶出介质中的溶出度,并对测定方法进行评价.方法 采用0.25％十二烷基硫酸钠(SDS)、水、pH=1.2人工胃液、pH=4.5醋酸盐缓冲液、pH=6.8磷酸盐缓冲液作为溶出介质,测定尼莫地平的溶出度并绘制曲线.结果 尼莫地平片在含0.25％ SDS溶出介质中的溶出度与生物利用度不相关,而在其他溶出介质具有一定的相关性.结论 SDS掩盖了该制剂内在品质的表达,不能反映该制剂在体内的溶出情况;中国药典收载的溶出度方法可能难以满足本品的测定需要.     

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.