富马酸喹硫平缓释片在不同释放介质中的体外释放研究

目的:考察自制富马酸喹硫平缓释片的体外释放情况及其释放机制。方法:以国外上市制剂为参比,采用篮法进行2种制剂分别在3种释放介质(水、0.1mol/L盐酸溶液、pH6.8磷酸盐缓冲液)中体外释放行为的相似性比较;采用紫外分光光度法测定释放度,以相似因子(f2)进行相似度评价;并对自制制剂进行释放行为模型的拟合。结果:在3种释放介质中,2种制剂比较,f2值均大于50;自制制剂在水和pH6.8磷酸盐缓冲液中体外释放拟合模型更接近Higuchi方程和Peppas方程,在0.1mol/L盐酸溶液中更接近一级方程和Peppas方程。结论:自制制剂与参比制剂在不同释放介质中的体外释放行为一致,释放机制以扩散为主。     

复方辛伐他汀烟酸缓释片中烟酸在不同释放介质中的释放度研究

目的研究辛伐他汀烟酸缓释片在不同释放介质中烟酸的释放度,分析其在体外的释放行为。方法用UV法测定自制与进口辛伐他汀烟酸缓释片在四种不同介质中的烟酸释放情况,并对其释放模型和f2相似因子进行比较。结果自制和进口缓释片的烟酸体外释放度符合Ritger-Peppas方程,在四种介质中方程拟合的n值均在0.45～0.89之间,说明该药物释放是药物扩散和骨架溶蚀共同作用的。与参比制剂相比,自制缓释片在水、0.1 mol/L盐酸、pH4.5醋酸盐缓冲液及pH 6.8磷酸盐缓冲液释放介质中,f2值分别为67.59、80.24、67.27和65.57,均大于50。结论自制制剂与进口制剂的缓释部分体外释放行为相似。     

美乐托宁缓释片在不同介质中的释放试验

目的:制备美乐托宁缓释片,以国外上市制剂美乐托宁缓释片为参比制剂,考察自研制剂和参比制剂在不同pH释放介质中体外释放行为的相似性及体外释药机制。方法:采用释放度测定法转篮法的装置进行体外释放实验,用HPLC法测定释放度,采用f2相似因子对2种制剂释放曲线的相似度进行评价,并进行释放行为模型的拟合。结果:在不同pH的释放介质中,自制制剂释放度曲线与参比制剂比较,f2相似因子均大于50;美乐托宁缓释片在4种释放介质中体外释药拟合模型更接近一级方程、Higuchi方程和Peppas方程。结论:参比制剂与自制制剂在不同pH释放介质中的体外释放一致,释放机制为扩散释药。     

多条溶出曲线评价氨氯地平阿托伐他汀钙分散片的质量

目的比较自制氨氯地平阿托伐他汀钙分散片与参比制剂在不同溶出介质中溶出曲线的相似性。方法分别以水、pH 1.0盐酸溶液、pH 4.5醋酸盐缓冲液和pH 6.8磷酸盐缓冲液为溶出介质,测定自制制剂与参比制剂的体外溶出曲线,采用f2相似因子法考察其相似性。结果在不同pH值的溶出介质中,自制制剂中的氨氯地平和阿托伐他汀钙的溶出曲线与参比制剂比较,f2相似因子均大于50。结论在不同pH值的溶出介质中,自制制剂和参比制剂的体外溶出行为相似。     

不同介质中头孢地尼干混悬剂溶出曲线相似性比较的研究

目的：评价自制头孢地尼干混悬剂与市售原研品头孢地尼胶囊体外溶出行为的相似性,同时为难溶性药物制剂质量判断提供参考.方法：分别考查自制试验制剂头孢地尼干混悬和参比制剂头孢地尼胶囊在纯水、pH 1.2人工胃液、pH 4.0与pH 6.8磷酸盐缓冲液4种溶出介质中的体外溶出行为,以紫外-可见分光光度法进行测定,并采用f2相似因子法评价受试制剂和市售参比制剂溶出曲线的相似性.结果：在4种介质中,自制样品与参比制剂相似因子f2均大于50.结论：在这4种介质中,自制试验制剂与参比制剂溶出行为相似,说明受试制剂的处方工艺合理.     

某国产卡马西平缓释片与参比制剂的释放度比较

比较了国内某一厂家3批卡马西平缓释片(受试制剂)与Tegretol(参比制剂)在不同pH介质中的体外释放度。采用桨板法,转速75 r/min,分别考察了受试制剂和参比制剂在不同释放介质(水、pH 4.5乙酸盐缓冲液和pH 6.8磷酸盐缓冲液)900 ml中的释放行为。结果显示,在上述3种介质中,受试制剂的批间差异显著,同批产品在不同介质中的释放行为也有显著差异。受试制剂的内在品质不如参比制剂。     

国内外硝苯地平缓释片体外释放行为一致性考察

目的：考察原研与国产仿制制剂硝苯地平缓释片体外释放行为的一致性。方法：参照日本橙皮书的释放度试验条件,分别考察国产制剂与原研制剂在pH 1.2溶出介质、pH 4.0醋酸盐溶出介质、pH 6.8磷酸盐溶出介质及水溶液中的体外释放行为,采用f2因子计算国产制剂与原研制剂释放曲线的相似性。结果：13家国产的硝苯地平缓释片在4种溶出介质中的释放行为存在一定差异,与参比制剂均不相似。结论：该药国产仿制制剂与原研制剂体外释放行为不一致。     

自制氨氯缬沙噻嗪片与Exforge HCT的体外溶出行为比较

测定了自制氨氯缬沙噻嗪片与原研制剂(Exforge HCT)在4种溶出介质(pH 6.8磷酸盐缓冲液、pH 4.5磷酸盐缓冲液、0.1 mol/L盐酸和水)中的溶出曲线,并进行相似性评价.结果表明,自制样品与原研制剂在4种溶出介质中溶出曲线相似因子f2大于50,差异因子f1小于15,表明两种制剂体外溶出行为相似.     

f2因子法评价头孢克洛干混悬剂溶出曲线的相似性

目的:评价自制粉末状头孢克洛干混悬剂与市售颗粒状头孢克洛干混悬剂体外溶出行为的相似性。方法:参考2010年版《中华人民共和国药典》规定的头孢克洛干混悬剂溶出方法,分别考察自制受试制剂和市售头孢克洛干混悬剂在纯水、pH 1.2人工胃液、pH 5.5与pH 6.8磷酸盐缓冲液4种溶出介质中的体外溶出行为,以高效液相色谱法进行测定,并采用f2相似因子法评价受试制剂和市售参比制剂溶出曲线的相似度。结果:在4种溶出介质纯水、pH 1.2人工胃液、pH 5.5与pH 6.8磷酸盐缓冲液下,受试制剂与参比制剂的f2因子分别为66.81,58.25,60.19和68.19。结论:两种组方及制法不同的头孢克洛干混悬剂的溶出曲线相似,初步提示受试制剂的处方及工艺合理。     

盐酸多奈哌齐口崩片的溶出曲线相似性研究

目的考察盐酸多奈哌齐口崩片自研制剂与参比制剂(规格均为5 mg)在4种不同pH介质中溶出行为的相似性。方法以日本卫材公司的盐酸多奈哌齐口崩片为参比制剂,测定自研制剂在4种不同介质中(pH=1.0盐酸溶液、pH=3.0醋酸盐缓冲液、pH=6.8磷酸盐缓冲液和水)的溶出曲线,采用高效液相色谱法检测并用相似因子(f2)法对溶出曲线的相似性进行评价。结果在pH=1.0、3.0、6.8不同介质中,自研制剂与参比制剂15 min时的溶出度均>85%;在水中两者的f2>50。结论自研制剂与参比制剂在4种不同溶出介质中的体外溶出行为相似。     

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.     

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.     

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.