非诺贝特体外溶出度考察及其微粉化制剂的研究

目的考察不同厂家非诺贝特固体制剂体外溶出度以及微粉化对非诺贝特溶出度的影响。方法分别以 40 % (φ)乙醇溶液、5 0 % (φ)乙醇溶液、5g/L十二烷基硫酸钠溶液、1 0g/L十二烷基硫酸钠溶液为溶出介质 ,对 4种市售非诺贝特固体制剂的体外溶出度进行考察。采用球磨机制备微粉化非诺贝特 ,对其溶出度进行测定。结果 1 0 g/L十二烷基硫酸钠溶液中微粉化制剂的溶出速率明显快于其余 3种非微粉化制剂 ,初步探讨了非诺贝特固体制剂体外溶出度标准。用相似因子法对自制微粉化胶囊和法国生产的微粉化胶囊的溶出实验数据进行统计分析 ,结果表明两者溶出行为相似 ,相似因子f2 =72 4(5 0≤f2 ≤ 1 0 0 )。结论不同厂家非诺贝特固体制剂的溶出度差异较大 ,微粉化工艺能显著提高非诺贝特的溶出度     

微粉化工艺对羊血提取物中氯高铁血红素溶出度的影响

目的研究微粉化工艺对羊血提取物中氯高铁血红素溶出度的影响。方法采用溶出度参数T50值对比了原药粉和3种原料药与乳糖的混合工艺(包括微粉化处理、高速粉碎机粉碎、简单混合)对氯高铁血红素溶出度的影响。结果原料药与乳糖混合后3种不同的处理方法对氯高铁血红素溶出度均有不同程度的改善,它们的T50值依次为2.36,3.79和10.29min,而原料药为28.03min。其中经过微粉化的样品溶出最快,比原料药加快了近12倍。结论将氯高铁血红素与乳糖一起微粉化是改善溶出度行之有效的方法。     

熔融乳化法制备非诺贝特纳米混悬剂

采用熔融乳化法制备非诺贝特纳米混悬剂,以粒径和ζ电位为指标,筛选优化处方.体外溶出试验显示,所制纳米混悬剂溶出速率显著高于原药和微粉化原药.大鼠体内药动学试验表明,纳米混悬剂组的AUC和Cmax显著高于原药组和微粉化原药组.     

微粉化和固体分散体技术对吡罗昔康在Beagle犬体内口服生物利用度的影响

为增加吡罗昔康(1)的溶出速度,采用气流粉碎法对1原药进行微粉化处理,或采用溶剂法以共聚维酮S630为载体制备固体分散体.将所得的微粉化药物和固体分散体分别制成片剂,并以市售1片为参比制剂,采用Beagle犬为模型进行药动学研究.结果表明,微粉化处理对1在Beagle犬体内的药动学行为无显著影响,但制备固体分散体能有效提高1的口服生物利用度.与参比制剂相比,采用微粉化1制备的片剂口服相对生物利用度为103.6％;当固体分散体片剂中1与共聚维酮S630质量比为1∶3和1∶5时,口服相对生物利用度为128.9％和138.9％.     

微粉化原料药的比卡鲁胺片的溶出度研究

目的：建立比卡鲁胺片溶出度试验的方法，并考察微粉化比卡鲁胺片溶出度的改善情况。方法：使用溶出度试验法Ⅱ法，采用紫外分光光度法测定溶出度。分别以pH6．8磷酸盐缓冲溶液和不同浓度的十二烷基硫酸钠溶液（0．1％，0．25％，0．5％，1％）为溶出介质，体积为1000mL，桨法，转速50r·min^-1，比较比卡鲁胺片的溶出行为。结果：经过气流微粉化加工成平均粒径为3．6μm的比卡鲁胺原料药压制成薄膜衣片自制片和进口片在上述溶剂中的溶出行为相似，而未经微粉化的自制片的溶出极差。结论：通过微粉化技术能够提高难溶性药物的溶出度，达到进口产品一样的效果。     

微粉化对中药疗效影响的研究进展

查阅近年来有关中药微粉化后对疗效影响的资料,结果显示,大部分中药经过超微粉碎后活性成分溶出度增加,提取率提高,药效增强,从而影响中药制剂疗效. 大多数为疗效增强效应,而且用药剂量减少,疗效可以大幅提高. 但是,中药微粉化后制备成制剂用于临床,可能使无效或有害成分也同时增加. 该文对近年来有关中药微粉化对临床疗效的影响进行论述.     

盐酸二甲双胍与微粉化格列苯脲复方片的制剂研究

将格列苯脲微粉化至50－100μm,并与微粉硅胶混匀、分散,与盐酸二甲双胍一起制成复方片,经体外溶出试验和体内动物药代试验证明;格列苯脲经微粉化并与微粉硅胶分散后可达到体外溶出出度和体内生物利用度与国外上市的微粉化格列苯脲与盐酸二甲双胍组成的复方片（Glucovance)等效。     

盐酸地尔硫卓控释微丸的研究

采用包衣法制备含有速释和缓释两部分的地尔硫控释微丸。体外溶出试验表明，微丸在最初１ｈ溶出主药２０％之后以缓慢平稳的速度持续释药，其释药曲线与对照制剂恬尔心缓释胶囊接近，零级释药速率常数为７．２５％／ｈ。其释药速度受介质ｐＨ的影响，但受转速的影响较小。控释微丸在４０℃、相对湿度７５％时贮存３个月，质量稳定。     

格列喹酮片的处方考查及溶出度测定

目的:研究难溶性药物格列喹酮的片剂工艺制备及提高溶出度测定结果的方法。方法:通过球磨机对原料进行不同程度的微粉化,通过三因素三水平正交设计法优化处方,并进行溶出度试验。结果:格列喹酮原料经过2、4和6h不同时间微粉化处理后进行观察,发现经4和6 h微粉化后其粒径能被控制在50μm以下,其中以4 h微粉化结果较好,不产生强吸附,易于进行制剂操作,且所制片剂较未微粉化原料所制片剂的溶出度有明显提高。结论:经4h微粉化处理格列喹酮后,粒径较小且可操作性强,明显提高了片剂的溶出度,工艺比较简单,适用于大生产。     

微粉化技术提高格列美脲片溶出度

目的:提高格列美脲片的体外溶出度。方法:用气流粉碎机制备微粉化物,HPLC法测定体外溶出曲线,与亚莫利片进行相似性比较。结果:微粉化物的D50粒径为1.026μm,3批片剂溶出度曲线相似因子为80。结论:微粉化可提高格列美脲片的体外溶出度,其溶出行为与参比制剂非常相似。     

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.     

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.     

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.