双氯芬酸钠贴片的制备及体外释放、透皮吸收测定分析

目的探讨双氯芬酸钠贴片的制备方法,分析其体外释放与透皮吸收能力。方法制备以聚丙烯酸酯为骨架的双氯芬酸钠贴片,进行体外透皮与释放度试验、制备DCF标准曲线、进行DCF贴片释放度试验,用蛇皮进行体外经皮渗透试验,以改进Franz扩散池检验药物的经皮渗透性能。结果成功制作了以聚丙烯酸酯为骨架的双氯芬酸钠贴片,测定显示,双氯芬酸钠贴片的体外释放速率为21.98μg/(cm2 h1/2),体外透皮速率为17.97μg/(cm2 h1/2)。结论本次研究制定的双氯芬酸钠贴片的释放度曲线与24h累计渗透量与Higuchi方程相符合,是一种新型的缓释型外用制剂。     

咳喘穴位贴片的体外透皮实验研究

目的 研究咳喘穴位贴片的经皮吸收的可行性.方法 采用高效液相色谱法测定透皮接受液和释放液中指标成分麻黄碱、丁香酚的浓度.结果 体外透皮实验和体外释放结果表明麻黄碱、丁香酚分别以一定的速率6.467 9μg·cm-2·h-1/2、3.833 4 mg·cm-2·h-1/2恒速渗透,其体外释药速率分别为21.382μg·cm-2·h-1/2、21.433mg·cm-2·h-1/2,其释放符合Higuchi方程.结论 咳喘穴位贴片为皮肤限速型的骨架控释系统.     

咳喘穴位贴片体外透皮速率和体外释放规律研究

目的:研究咳喘穴位贴片体外透皮速率和体外释放规律。方法:采用高效液相色谱法测定透皮接受液和释放液中指标成分盐酸麻黄碱的浓度,计算其渗透速率和体外释药速率。结果:麻黄碱以6.4679μg.cm-2.h-1/2的速率恒速渗透,其体外释药速率为21.382μg.cm-2.h-1/2,其释放过程符合Higuchi方程。结论:咳喘穴位贴片可研制为皮肤限速型的骨架控释系统。     

盐酸西替利嗪巴布剂的研制及体外释放特性

目的:制备盐酸西替利嗪(CET)巴布剂并研究其体外释药性能和透皮吸收行为.方法:以水溶性高分子材料为基质制备CET巴布剂,采用HPLC法测定制剂中CET的含量.按2000年版中华人民共和国药典方法进行体外释放度的测定,利用Franz扩散池研究巴布剂的透皮吸收行为.结果:CET巴布剂含量稳定,体外释药符合Higuchi方程,释放速率为0.557 7mg·cm-2·h-1/2.透皮吸收符合零级动力学过程,渗透速率为14.58μg·cm-2·h-1.结论:CET巴布剂为皮肤控释型透皮给药系统,为临床治疗过敏性疾病提供了新的给药途径.     

丁香贴片的制备及其体外释放度测定

目的：制备丁香贴片并考察其体外释放度。方法：以聚丙烯酸酯、月桂氮革酮为材料制备丁香贴片，采用改良Franz扩散池考察贴片的体外释放性能。结果：3％月桂氮革酮为促透剂对丁香贴片的促渗透作用最好，其体外渗透速率为0．0187mg·cm-2·h-1。结论：该贴片制备工艺简单，所制备的贴片体外经皮渗透作用良好。     

来氟米特贴片的制备及体外释药特性

目的制备来氟米特贴片,研究其体外释药特性和离体透皮吸收行为。方法以聚异丁烯为压敏胶制备来氟米特贴片,采用HPLC法测定制剂中来氟米特的含量,按《中华人民共和国药典》(2000年版)方法进行体外释放度的测定,利用改良Franz扩散池研究贴片的透皮吸收行为。结果该药体外释药特性符合Higuchi方程,释放速率为64.57μg·cm-2·h-1/2。离体透皮吸收行为符合零级动力学过程,渗透速率为5.99μg·cm-2·h-1。结论来氟米特贴片是皮肤控释型透皮给药制剂,为临床治疗类风湿性关节炎提供了新的给药途径。     

酮洛芬醇质体体外经皮渗透研究

目的:考察酮洛芬醇质体的体外经皮渗透特性。方法:乙醇注入法制备酮洛芬醇质体,采用Franz扩散池,以离体小鼠皮为皮肤屏障,对酮洛芬醇质体的体外经皮渗透量、稳态透皮速率进行研究,并测定24 h时皮肤中的滞留量。结果:酮洛芬醇质体体外24 h累积渗透量Q为(720.88±2.04)μg.cm-2,稳态透皮速率J为(28.15±0.20)μg.cm-2.h-1,24 h皮肤中的滞留量(50.86±1.44)μg.cm-2,与同剂量酮洛芬脂质体及其30%醇溶液相比,均有明显提高(P<0.05)。结论:醇质体可显著增加酮洛芬的体外经皮渗透,值得进一步研发。     

细辛挥发油对颅痛定的裸鼠体外促透的作用

目的 考察细辛挥发油对颅痛定的体外促透皮作用,筛选中药透皮促进剂.方法 采用改良的Franz扩散池进行体外透皮实验,以裸鼠皮肤为渗透屏障、5%氮酮为对照,观察5%细辛挥发油对颅痛定的促透皮作用.采用HPLC法测定颅痛定的含量,计算24 h平均累积渗透量与12 h平均透皮速率常数.结果 15 mg·ml-1颅痛定加入5%细辛挥发油或5%氮酮后,24 h平均累积渗透量分别为5.723×103、4.384×103μg·cm-12 h平均透皮速率常数分别为284.29、223.18 μg·cm-2· h-1;增渗倍数分别为37.09、29.12.与阴性对照组相比,透皮速率常数在数值上差异有非常显著性意义.结论 5%细辛挥发油对颅痛定有较强的促透皮作用,其效果优于5%氮酮.     

双藤巴布剂中青藤碱、雷公藤甲素的体外释放与体外透皮机制研究

目的:研究双藤巴布剂中青藤碱、雷公藤甲素的体外释放与体外透皮机制;比较以化学单体入药(青藤碱雷公藤甲素巴布剂,STP)与浸膏入药(双藤巴布剂,STEP)释放速率与透皮速率的差异。方法:通过释放度测定法测定体外释放度;通过Franze扩散池法测定药物的体外透皮性,皮肤为裸鼠背部皮肤。结果:STP与STEP中青藤碱、雷公藤甲素的体外释放以Higuchi方程拟合度较优(STP:r青=0.9955,r甲=0.9958;STEP:r青=0.9920,r甲=0.9963)。经皮渗透较好地拟合了零级动力学方程,青藤碱在STP、STEP中的r分别为0.9951与0.9926,透皮速率分别为21.729μg.cm-2.h-1与20.063μg.cm-2.h-1;雷公藤甲素在STP、STEP中的r分别为0.9942与0.9902,透皮速率分别为0.4783μg.cm-2.h-1与0.4168μg.cm-2.h-1。结论:青藤碱、雷公藤甲素在STP、STEP中的释放速率大于其经皮渗透速率,属于皮肤限速型经皮给药制剂。     

传递体作为双氯芬酸钠经皮渗透载体的体外研究

目的传递体作为双氯芬酸钠经皮渗透载体的体外研究.方法采用改良Franz扩散池体外经皮渗透实验技术,对双氯芬酸钠传递体、普通脂质体及其凝胶剂的经皮渗透作用进行了比较.结果24 h后双氯芬酸钠传递体、普通脂质体及其凝胶剂的累积透皮量分别为598.16μg·cm-2,209.15μg·cm-2,391.33μg·cm-2.皮肤内滞留量Q滞分别为191.54μg·cm-2,419.28μg·cm-2,8.77μg·cm-2.结论以传递体作为双氯芬酸钠的载体可以促进其经皮渗透,且皮内的滞留药物还表现出一定的贮库效应.而普通脂质体不能很好地促进药物透过皮肤,但利于药物在皮内的大量滞留.     

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.     

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.