更昔洛韦眼用即型凝胶剂的制备及质量评价

目的 研究更昔洛韦眼用即型凝胶剂的制备及其质量评价.方法 以泊洛沙姆407(Lutrol(*) F127)为凝胶基质,采用HP-β-CD增溶手段,使用紫外扫描和高效液相色谱法.结果 紫外扫描显示,更昔洛韦原料药在254nm处有最大吸收;HPLC测定显示,在4.408～17.632mg·L-1内药物质量浓度(p)与峰面积(A)线性关系良好(p=0.0159A+ 0.2320,r2=0.9998);所制备的更昔洛韦即型凝胶剂在高热、低温及离心条件下稳定性良好.结论 更昔洛韦即型凝胶剂制备工艺简单,性质稳定,质量控制方法可行.     

复方更昔洛韦/曲安奈德眼用凝胶的制备及其质量控制

目的:制备复方更昔洛韦/曲安奈德眼用凝胶,并对其进行质量控制。方法:以卡波姆为基质,制备复方更昔洛韦/曲安奈德眼用凝胶。采用高效液相色谱法测定其中更昔洛韦和曲安奈德的含量,并对其外观形状、黏度、渗透压、pH进行检测。结果:制得的眼用凝胶无色澄清透明,外观均一稳定,黏度为92 mpa·s,渗透压为921.66 mosmol/kg,pH为6.91;更昔洛韦和曲安奈德的检测质量浓度线性范围分别为30.3⁹0.9、10.590.9、10.5⁷3.5μg/ml(r=0.999 8),平均回收率分别为99.20%73.5μg/ml(r=0.999 8),平均回收率分别为99.20%⁹9.88%、100.29%99.88%、100.29%¹00.64%,RSD分别为0.81%100.64%,RSD分别为0.81%⁰.90%、0.24%0.90%、0.24%¹.03%(n=3)。结论:该制剂制备方法简单,质量可控。     

盐酸伐昔洛韦泡腾片的制备与质量控制

目的研究盐酸伐昔洛韦泡腾片的制备方法，并对其进行质量控制。方法处方量的盐酸伐昔洛韦、碳酸氢钠和枸橼酸等用混合制粒方法制备泡腾片，采用高效液相色谱（HPLC）法测定盐酸伐昔洛韦含量。结果盐酸伐昔洛韦泡腾片可在5 min内崩解，伐昔洛韦在10.1～50.5 μg·mL-1浓度范围内线性关系良好，r＝0.999 8。结论盐酸伐昔洛韦泡腾片的制备工艺简单，稳定性好，含量测定方法准确可靠，精密度高。     

盐酸伐昔洛韦栓的制备及质量控制

目的:制备盐酸伐昔洛韦栓并建立其质量控制方法。方法:以明胶等为基质制备栓剂;采用高效液相色谱法测定盐酸伐昔洛韦的含量,并考察其稳定性。结果:所制栓剂软硬度合适;盐酸伐昔洛韦检测浓度线性范围为10.1～50.5μg·mL-1(r=0.9998),平均回收率为98.73%(RSD=0.76%,n=3)。结论:该处方制备工艺简单,制剂质量稳定、可控。     

回顾性分析本院用更昔洛韦与阿昔洛韦治疗单纯疱疹病毒性角膜炎的疗效

目的 回顾性分析本院用更昔洛韦与阿昔洛韦治疗单纯疱疹病毒性角膜炎的疗效.方法 收集近年在本院门诊就诊的100例(106眼)单纯疱疹病毒性角膜炎患者,其中48例用更昔洛韦眼用凝胶;37例用阿昔洛韦眼液.比较两者疗效.结果 更昔洛韦组与阿昔洛韦组总有效率分别为91.7%,75.7%,显示更昔洛韦眼用凝胶的有效率好于阿昔洛韦眼液(P＜0.05).结论 更昔洛韦眼用凝胶治疗单纯疱疹病毒性角膜炎的效果较好.     

更昔洛韦凝胶剂的制备及质量控制

目的制备更昔洛韦凝胶剂.方法以卡波普水凝胶为基质制备更昔洛韦凝胶剂,采用紫外分光光度法进行含量测定,并进行稳定性和皮肤刺激性试验.结果更昔洛韦在252nm处有最大吸收,在4～16μg/ml浓度与吸收度线性关系良好.结论更昔洛韦凝胶剂性质稳定,皮肤刺激性小,制备简单,易于质量控制,适用于医院配制.     

正交试验优选盐酸伐昔洛韦缓释片处方

目的:以羟丙甲基纤维素为主要材料,制备盐酸伐昔洛韦水溶性骨架片.方法:通过正交设计优化伐昔洛韦缓释片处方,按中国药典2000年版所载溶出方法的第一法测其释放度.结果:所制备的盐酸伐昔洛韦缓释片优选处方2 h体外累积释放量为24.67%,控制在规定的15%～40%之间,5 h体外累积释放量为69.61%,10 h体外累积释放量在90%以上.结论:经正交设计优化的盐酸伐昔洛韦缓释片处方可行.     

双黄连滴眼液联合更昔洛韦眼用凝胶治疗单疱病毒性角膜炎的临床研究

目的：观察双黄连滴眼液与更昔洛韦眼用凝胶治疗单疱病毒性角膜炎的效果。方法：回顾性分析我院2013年10～12月收治的单疱病毒性角膜炎30例患者的临床资料,随机分为对照组和实验组。实验组给予双黄连滴眼液联合更昔洛韦眼用凝胶治疗,对照组给予更昔洛韦眼用凝胶治疗,比较两组患者的治疗效果。结果：双黄连滴眼液联合更昔洛韦眼用凝胶临床疗效评价15例,总有效率为93.3%,更昔洛韦眼用凝胶临床疗效评价15例,总有效率为86.7%,两组治疗后角膜情况、视力、患者主观感受均比治疗前有明显改善,但实验组改善优于对照组。结论：双黄连滴眼液与更昔洛韦眼用凝胶两组药物联合治疗单疱病毒性角膜炎比单纯采取更昔洛韦眼用凝胶滴眼治疗,效果更好,值得推广。     

盐酸伐昔洛韦有关物质的合成

为了控制抗病毒药盐酸伐昔洛韦产品质量,分别合成了欧洲药典7.0版收载的两个有关物质:以氢化钠为碱,在乙二醇二丁醚中用N-Cbz伐昔洛韦分别与碘甲烷和碘乙烷反应生成N-甲基-N-Cbz伐昔洛韦和N-乙基-N-Cbz伐昔洛韦,随后在钯炭催化下氢解脱保护制得N-甲基伐昔洛韦(2)和N-乙基伐昔洛韦(3).该方法是立体位阻较大的N-Cbz氨基酸衍生物的N-烷基化反应的改进方法.     

更昔洛韦凝胶剂的制备及质量控制

目的　制备更昔洛韦凝胶剂。方法　以卡波普水凝胶为基质制备更昔洛韦凝胶剂 ,采用紫外分光光度法进行含量测定 ,并进行稳定性和皮肤刺激性试验。结果　更昔洛韦在 2 5 2nm处有最大吸收 ,在 4～ 16 μg ml浓度与吸收度线性关系良好。结论　更昔洛韦凝胶剂性质稳定 ,皮肤刺激性小 ,制备简单 ,易于质量控制 ,适用于医院配制。     

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.     

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.