帕利哌酮缓释微丸的处方优化

该研究采用挤出滚圆法制备了帕利哌酮丸芯，再用甲基丙烯酸共聚物(Eudragit)包衣制备缓释微丸，并采用正交设计分别优化了载药丸芯和缓释微丸的处方包衣工艺参数。结果表明，采用Eudragit RS30D与Eudragit RL30D作为包衣材料，且Eudragit RS30D占包衣材料总量65%时得到的优化缓释微丸在不同pH介质中的体外释放行为符合一级动力学方程。     

硝酸异山梨酯缓释微丸处方及工艺优化

目的制备硝酸异山梨酯缓释微丸,优化处方及制备过程。方法采用粉末层积法和流化床喷雾法制备膜控缓释微丸,用单因素考察实验优化处方及工艺,采用HPLC法测定缓释微丸的累积释放度。结果确定以Eudragit RS30D和Eudragit RL30D混合分散体为包衣材料,Eudragit RS30D与Eudragit RL30D的比例是4∶1,包衣增重为5%,热处理温度、时间为40℃、24小时,抗静电剂、增塑剂分别占包衣聚合物量的0.5%、20%。在体外释放度实验中,微丸累积释放硝酸异山梨酯百分率,0.5小时为10.71%,2小时为45.80%,8小时90.79%,24小时为99.14%。结论体外释放度实验中,Eudragit RS30D与Eudragit RL30D的比例对微丸累积释放度的影响较大,随着包衣量增加,释放度略有降低。本制剂为膜控制剂。     

非诺贝特缓释微丸的制备及释放度研究

目的：制备非诺贝特缓释微丸。方法：采用BZJ-360M离心包衣造粒机制备微晶纤维素空白丸核和非诺贝特含药素丸，并在此基础上进行丙烯酸树脂水分散体（Eudragit NE 30D）包衣。用释放度测定法考察影响药物释放的各种因素，对包衣微丸体外释药机制进行研究。结果：包衣材料为Eudragit NE 30D，增重3％时包衣微丸呈现良好的缓释效果，体外释药过程基本符合Higuchi方程：Q=0．436＋30．316t^1/2／（r=0．9997）。结论：成功的制备了非诺贝特缓释微丸。     

克拉霉素缓释包衣微丸的制备及体外释放度研究

目的制备克拉霉素缓释包衣微丸,并对其体外释放度进行考察。方法采用挤出滚圆技术制备克拉霉素含药微丸。以优化的丙烯酸树脂类Eudragit NE30D和Eudragit L30D-55混和水分散体为包衣材料,采用流化床包衣技术,制备缓释包衣微丸。考察自制缓释微丸的体外释药速率,并与市售的克拉霉素缓释胶囊进行比较。结果通过释药行为的评价,得到优化的包衣处方为5∶1的Eudragit NE30D和Eudragit L30D-55混和包衣材料,其体外释放行为在不同的pH溶出介质中与市售制剂产品没有明显差异,体外释药过程符合一级释放模型。结论采用挤出滚圆和流化床技术,以及优化的Eudragit NE30D和Eudragit L30D-55混和水分散体包衣材料,成功制备了克拉霉素缓释包衣微丸。     

对乙酰氨基酚缓释微丸的制备及释放度研究

目的制备对乙酰氨基酚缓释微丸,考察包衣处方等因素对微丸释放度的影响。方法采用离心-造粒法制备微晶纤维素空白丸核和对乙酰氨基酚微丸,并在此基础上采用甲基丙烯酸树脂(Eudragit RS30D/RL30D)包衣,制备对乙酰氨基酚缓释微丸。采用HPLC法测定对乙酰氨基酚缓释微丸释放度,单因素筛选包衣处方的优化参数。结果以Eudragit RS30D/RL30D比例为15:1(w/w),包衣增重为10%,柠檬酸三乙酯占包衣材料量的25%,滑石粉占包衣材料量的40%为包衣液,制备的对乙酰氨基酚释微丸释药曲线具有较好的缓释特性。结论制备的对乙酰氨基酚缓释微丸具有缓释特性且操作简便、工艺稳定。     

酒石酸美托洛尔缓释微丸的制备及处方因素考察

目的：选用Eudragit RS 30 D与Eudragil RL30D两种包衣材料，制备日服2次的酒石酸美托洛尔缓释徽丸，并对其处方因素进行考察。方法：采用Glatt流化床底喷溶液上药法制备载药微丸，考察缓释聚合物Eudragit RS 30D与Eudragit RL 30D的不同质量配比（2：3，7：3和9：1）、聚合物包衣增重（10％，20％和30％）以及增塑利嗣量（10％，20％和40％）和放置时间对药物释放的影响。结果：当Eudragit RS 30D与Eudragit RL 30D的质量比为9：1，聚合物包衣增重为20％，增塑剂用量为20％时，药物的释放行为符合中国药典对缓释制剂释放度的相关规定。结论：通过调整Eudragit RS 30D与Eudragit RL 30D之间的比例，或提高聚合物包衣增重等手段，能使酒石酸美托洛尔载药徽丸具备较理想的缓释效果。     

苦黄缓释微丸的制备及其质量考察

目的:考察苦黄缓释微丸的制备及其质量指标。方法:利用流化床包衣设备,采用薄膜包衣法制备苦黄缓释微丸,以总蒽醌为指标性成分,测定缓释微丸的释放度,并考察了包衣处方工艺因素对药物释放的影响。结果:流化床薄膜包衣法成功制备了苦黄缓释微丸,其Eudragit RS 30D与Eudragit RL 30D的用量比例为1∶0时,包衣增重为14%;累积释放百分率2h26%,6h70%,12h90%。结论:水性薄膜包衣技术制备苦黄缓释微丸,具有良好的体外缓释行为。     

盐酸青藤碱缓释微丸的研制

目的：制备盐酸青藤碱缓释微丸，并对其体外释药行为进行研究。方法：采用离心造粒技术制备盐酸青藤碱素丸，在流化床内采用丙烯酸树脂水分散体对其包衣，制备盐酸青藤碱缓释微丸。对包衣材料种类、配比及用量进行选择，对包衣微丸体外释药机理进行研究。结果：包衣材料Eudragit NE30D增重5％时，包衣微丸在水中呈现良好的缓释效果，体外释药过程基本符合Higuchi方程：Y=0．0938＋0．0846t（r=0．9965）。结论：采用离心造粒技术和丙烯酸树脂流化床包衣，成功地制备了盐酸青藤碱缓释微丸，其体外释药缓慢、平稳。     

盐酸青藤碱缓释微丸的研制

目的制备盐酸青藤碱缓释微丸,并对其体外释药情况进行研究。方法采用离心造粒技术制备微晶纤维素空白丸核和盐酸青藤碱含药丸芯,以聚丙烯酸树脂Eudragit NE 30D为包衣液制成膜控缓释微丸,考察包衣增重、抗粘剂用量等因素对缓释微丸释放度的影响。结果通过单因素考察确定了包衣液处方,所制备的微丸具有明显的缓释特征,体外释药过程符合一级动力学模型。结论用聚丙烯酸树脂Eudragit NE30D作为包衣材料所得缓释微丸符合24 h缓释要求。     

洛索洛芬钠缓释微丸的制备与体外释放度研究

摘 要 目的：制备洛索洛芬钠缓释微丸,并考察其体外释药行为。方法: 采用挤出滚圆法制备洛索洛芬钠载药丸芯,再用Eudragit RL 30D和Eudragit RS 30D 进行包衣,制成洛索洛芬钠缓释微丸,并考察缓释微丸的体外释药行为。结果: 以Eudragit RL 30D和Eudragit RS 30D的比例为20∶80作为洛索洛芬钠载药丸芯的缓释包衣材料,包衣增重为20%,增塑剂用量为10%,滑石粉用量为45%时,制备的洛索洛芬钠缓释微丸在12 h内能够平稳释药且释药完全。结论:制备的洛索洛芬钠缓释微丸释药行为较好,有望应用于工业生产。     

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.