醋酸地塞米松片在中国健康受试者中的生物等效性研究

目的：评估中国健康成年受试者空腹及餐后口服醋酸地塞米松片受试制剂和参比制剂的生物等效性。方法：按照随机、开放、单剂量、两周期双交叉的生物等效性研究。空腹组纳入24名健康受试者，餐后组纳入32名健康受试者，每周期服用受试制剂(T)2片(0.75 mg/片)或参比制剂(R)3片(0.50 mg/片)，共两周期。使用液相色谱-质谱联用技术对人血浆中醋酸地塞米松的浓度进行测定，采用WinNonlin 8.0软件按非房室模型对药代动力学参数进行计算，并对受试制剂与参比制剂二者的生物等效性进行评价。结果：受试者空腹状态下口服醋酸地塞米松片受试制剂与参比制剂后药代动力学参数如下：Tmax分别为1.13(0.50,4.00)和1.00(0.50,5.00)h,AUC0-t分别为(72.25±21.55)和(69.23±17.76)ng·mL^-1·h,Cmax分别为(14.53±4.51)和(14.52±3.68)ng/mL,AUC0-∞分别为(74.63±23.01)和(71.32±19.12)ng·mL^-1·h；受试者餐后状态下口服醋酸地塞米松片受试制剂与...     

度他雄胺自微乳口腔膜剂的制备及其体内外评价

目的 制备度他雄胺自微乳口腔膜剂,并进行体内外评价.方法 用溶剂浇铸法制备度他雄胺自微乳口腔膜剂,考察其外观、崩解时间、体外溶出度、粒径等指标;比较自制的度他雄胺口腔膜剂(受试制剂)与度他雄胺软胶囊(参比制剂)在Beagle犬体内的药动学特征.结果 自制的度他雄胺自微乳口腔膜剂的外观光滑平整,崩解时间为26±2 s,体外溶出度在20 min时即可达87％±0.5％,平均粒径为147.9 nm,跨距0.83;受试制剂与参比制剂的AUCo-t分别为2.7838±0.7570、2.8866±0.8297μg·mL-1·h,AUC0-∞分别为2.8831±0.8646、2.8914 ±0.6299 μg·mL-1·h,t1/2分别为45.8±10.4、42.2±14.9 h,tmax分别为3.8±3.6、4.1±1.2h,Cmax分别为46.1±3.3、45.3±8.5 ng·mL-1.结论 度他雄胺自微乳口腔膜剂不仅保持了液体自微乳的特性,且能提高患者的顺应性.     

醋酸地塞米松凝胶剂的制备及含量测定

目的:制备0.1％醋酸地塞米松外用凝胶剂,并建立该制剂的含量测定方法。方法:以1％卡波普为凝胶基质,制备醋酸地塞米松外用凝胶剂。采用氯仿萃取、显色后比色法测定醋酸地塞米松含量。结果:本制剂易制备,含量测定方法可靠,平均回收率为100.4％(RSD=1.18％)。结论:该制剂适合临床使用,含量测定方法简单可行,适合凝胶剂中含羰基甾休类药物的提取分离及含量测定。     

复方奥硝唑口腔溃疡膜的研制与质量评价

目的对复方奥硝唑口腔溃疡膜的配制、含量测定和稳定性进行研究。方法用壳聚糖、甘油、明胶为主要辅料,流涎法制备复方奥硝唑口腔溃疡膜,用紫外分光光度法,分别对奥硝唑和醋酸地塞米松进行含量测定,并考察其稳定性。结果奥硝唑和醋酸地塞米松的平均回收率分别为99.4%和99.58%,RSD为1.07%和0.75%(n=3)。结论该制剂制备工艺简单,质量可控。     

复方奥硝唑口腔溃疡膜的研制与质量评价

目的对复方奥硝唑口腔溃疡膜的配制、含量测定和稳定性进行研究。方法用壳聚糖、甘油、明胶为主要辅料,流涎法制备复方奥硝唑口腔溃疡膜,用紫外分光光度法,分别对奥硝唑和醋酸地塞米松进行含量测定,并考察其稳定性。结果奥硝唑和醋酸地塞米松的平均回收率分别为99.4%和99.58%,RSD为1.07%和0.75%(n=3)。结论该制剂制备工艺简单,质量可控。     

盐酸坦洛新肠溶缓释微丸的制备及其体内外评价

目的:制备盐酸坦洛新肠溶缓释微丸,并与参比制剂进行体内外一致性评价。方法:分别以乙基纤维素和羟丙甲纤维素为缓释包衣材料,以聚丙烯酸树脂为肠溶性包衣材料,采用流化床底喷包衣技术对载药微丸包衣,制备肠溶缓释微丸;考察释放度主要影响因素;采用多条释放曲线对比考察受试制剂与参比制剂体外一致性;双周期交叉试验设计,考察Beagle犬口服单剂量受试制剂与参比制剂后血浆中的药物浓度,评价受试制剂与参比制剂的体内一致性;考察受试制剂的体内外相关性。结果:确定了影响盐酸坦洛新释放的主要处方工艺因素;多条释放曲线测定结果表明,所制备的微丸与参比制剂体外一致性较好;Beagle犬体内药动学研究结果表明,受试制剂与参比制剂生物等效且体内外相关性良好。结论:成功制备了盐酸坦洛新肠溶缓释微丸,且与参比制剂体内外一致性良好。     

醋酸地塞米松冰片霜的制备及质量控制

目的:制备醋酸地塞米松冰片霜并建立其质量控制方法。方法:以研磨法制备霜剂;采用薄层色谱法鉴别醋酸地塞米松与苯酚,紫外分光光度法测定其中主药的含量。结果:所制制剂鉴别、检查等均符合2005年版《中国药典》相关规定;醋酸地塞米松检测浓度的线性范围为12.06～28.14μg.mL-1(r=0.9997),平均回收率为98.52%(RSD=0.66%)。结论:本制剂组方合理,制备工艺简便可行,质量稳定可控。     

复方雌三醇阴道生物黏附膜的制备及质量控制

目的:制备复方雌三醇阴道生物黏附膜并建立其质量控制方法。方法:以雌三醇、盐酸环丙沙星和醋酸地塞米松为主药制备膜剂,采用高效液相色谱法测定其中主药的含量。结果:所制制剂为半透明淡黄色薄膜,鉴别、检查项均符合2005年版《中国药典》中的相关规定;雌三醇、盐酸环丙沙星、醋酸地塞米松检测浓度的线性范围分别为1.56~77.8、15.97~798.4、1.66~83.2μg·mL-1(r=0.9999),平均回收率分别为98.44%(RSD=0.87%)、99.67%(RSD=0.54%)、98.54%(RSD=0.42%)。结论:本制剂制备工艺简便可行,质量稳定可控。     

复曲膏的制备及质量控制

目的：制备复曲膏并建立其质量控制方法。方法：以醋酸曲安奈德和氧氟沙星为主药制备复曲膏，采用高效液相色语法测定复曲膏中醋酸曲安奈德和氧氟沙星的含量。结果：醋酸曲安奈德和氧氟沙星的平均回收率分别为100．3％和100．0％，RSD分别为0．38％和0．41％。结论：该制剂工艺简便易行，其质量控制方法简单、快速，准确。     

含替硝唑和醋酸地塞米松口腔溃疡双层膜的质量控制

目的对本院自制的含替硝唑和醋酸地塞米松口腔溃疡双层膜进行质量控制。方法建立HPLC法测定药物含量,并对膜剂的体内外黏附时间、溶出等指标进行测定和评价。结果替硝唑在2～180mg·L^-1、醋酸地塞米松在0．25-22．5mg·L^-1时线性关系良好,平均提取回收率分别为101．59％（n=5,RSD=0．89％）和99．18％（n=5,RSD=1．35％）。膜剂在溶菌酶生理盐水中的平均溶解时间为25min;体内外平均黏附时间分别为29．87和27．25min;在37℃人工唾液中药物呈一级释放,替硝唑和醋酸地塞米松最大溶出度为80％和70％;在口腔黏膜处药物呈一级释放,30min时释药率100％。结论本实验建立的膜剂药物HPLC测定方法及其他相应指标的测定方法简便合理,可很好控制该双层膜的质量。     

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.