多条实时溶出曲线对阿昔洛韦片的质量再评价

目的:以多条实时溶出曲线评价阿昔洛韦片的内在质量。方法:分别以pH1.0的盐酸溶液、pH4.0的醋酸盐缓冲液、pH6.8的磷酸盐缓冲液和水为溶出介质,设定检测波长254 nm、参比波长550 nm、转速50 r.min-1、光程0.5 mm和桨法,用光纤溶出度实时测定仪测定阿昔洛韦片的溶出曲线。结果:测定了9个厂家生产的阿昔洛韦片在4种溶出介质中的实时溶出曲线,结果显示3个厂家生产的阿昔洛韦片的4条溶出曲线不一致,反映出3个厂家的生产工艺尚不成熟。结论:不同pH溶出介质中的实时溶出曲线可全面反映药物在不同体内环境下的溶出行为,能更有效地评价制剂的内在质量。     

氨茶碱片的实时溶出度相似性分析研究

目的:考察不同厂家生产的氨茶碱片体外实时溶出曲线,比较各厂家之间及与日本橙皮书中氨茶碱片溶出曲线之间的差异,分析现行溶出度方法的质量可控性及各厂家处方设计合理性,为进一步加强"治疗窗"狭窄类药物的质量控制及处方设计提供思路及有效手段,也为合理制定氨茶碱片溶出度方法提供依据。方法:采用光纤药物溶出度实时测定仪,测定各厂家氨茶碱片在水、pH 1.2、pH 4.0和pH 6.8缓冲溶液这4种溶出介质中的实时溶出曲线。结果:31家企业的氨茶碱片在5 min时的溶出量均大于40%,均产生突释;部分厂家的氨茶碱片在4种溶出介质中实时溶出行为差异较大,内在质量存在较大差异,且部分生产企业生产的氨茶碱片批内均一性较差,工艺不稳定,产品质量不均一。结论:对于氨茶碱片这类"治疗窗"狭窄类药物,溶出度单点控制法不能满足要求,不能有效地监控产品质量。国内绝大部分氨茶碱片生产企业在处方工艺设计时未考虑本品属于"治疗窗"狭窄药物,处方设计不合理。对于"治疗窗"狭窄类药物质量及安全性应进行再评价,以保证此类药物的安全有效。     

光纤传感过程分析比较不同厂家缬沙坦胶囊的溶出度

目的:考察不同厂家缬沙坦胶囊体外溶出度曲线,比较不同厂家药品的内在质量,为药品质量控制和临床用药提供参考。方法:用光纤传感过程分析技术监测4个厂家缬沙坦胶囊在pH 6.8,pH 4.5,pH 1.2及水4种溶出介质的溶出过程。采用f2因子法对溶出曲线的相似性进行评价。结果:4个厂家缬沙坦胶囊在pH 6.8磷酸盐缓冲液中30 min时溶出度均大于80%符合药典规定,但溶出曲线差异很大;在其他3种介质中的溶出度偏低且存在较大差异;比较结果说明不同药厂缬沙坦胶囊的质量存在显著性差异。结论:采用FODT法过程分析检测固体制剂的溶出曲线比单点溶出度测定更能直观反映不同厂家制剂工艺、均匀度和药品质量的差异。对不同来源的相同制剂考察不同溶出介质的溶出曲线是非常有必要的。     

光纤传感系统在线监测不同厂家尼莫地平片溶出度

目的:使用光纤药物溶出度实时测定仪FODT-601,实时监测国内6个不同厂家尼莫地平片的溶出度曲线,以评价其工艺质量.方法:设定测定波长238 nm、基准校正波长550 nm、温度37℃、转速75 r·min-1、数据采集间隔时间30 s、监测时间30 min,以900 mL 醋酸盐缓冲液(pH4.5;含0.3%十二烷基硫酸钠)为溶出介质,桨法,用光程为2 mm的光纤探头监测尼莫地平片的溶出曲线.结果:6个不同厂家尼莫地平片的溶出度均符合<中国药典>规定,但各溶出曲线存在差异.结论:光纤药物溶出度实时测定仪准确、连续、定量地反映了药物的溶出过程,获得的数据信息更加完整、真实,可比较出不同厂家之间同种药品的溶出过程差异.     

光纤传感过程分析法评价不同厂家氨茶碱片的体外溶出度

目的:采用光纤传感过程分析法评价不同厂家氨茶碱片的体外溶出度,以考察不同厂家样品的质量差异。方法:采用对照品法,对5个厂家的片剂在4种溶出介质(水、pH1.2盐酸溶液、pH4.5醋酸盐缓冲液和pH6.8磷酸盐缓冲液)中的溶出行为进行测定,并以相似因子法进行比较。结果:氨茶碱片在不同溶剂中的溶出行为不一致,只有B厂样品在4种介质中均具有较好的溶出度;以B厂样品为参比制剂,其他4个厂样品与其比较的相似因子值均小于50%。结论:光纤传感过程分析法能够准确、方便地提供药物的溶出数据、反映药物的溶出行为,为全面考察药物的内在质量提供了良好的检测手段;不同厂家氨茶碱片质量有明显差异。     

辛伐他汀片的实时溶出度对比分析研究

目的:采用光纤药物溶出度实时测定仪考察不同药厂生产的辛伐他汀片的体外溶出度曲线,比较产品的内在质量差异,分析现行溶出度方法的质量可控性,为进一步加强药品质量控制提供思路与有效手段,为合理制订溶出度方法与检查标准提供依据。方法:分别按照国家标准 WS_1-(X-240)-2004Z 和 WS_1-(X-066)-2003Z 中规定的溶出度方法进行单点溶出度及实时溶出曲线测定。结果:在2种溶出度条件下,单点溶出度符合现行法定标准要求的进口及国产辛伐他汀片,从实时溶出曲线比较来看,其内存的质量仍存在较大差异。进口辛伐他汀片和部分国产辛伐他汀片的实时溶出曲线显示其片间差异小,部分国产企业产品间的实时溶出曲线存在较大差异,个别企业同一批号产品间实时溶出度的差异都较大,反映出产品内在质量的稳定性和均一性较差。结论:用单点溶出度控制药物学溶出行为,对很多产品而言不能全面准确地反映产品的溶出性能与内存质量,特别是不能反映出产品之间的质量差异。单点溶出度测定方法的质量可控性较差,建议加强对药品溶出度的实时监测,确保不同企业生产的同一药品质量的稳定性与均一性,确保用药质量及临床疗效的一致性。     

光纤药物溶出仪在线考察头孢克洛片和胶囊溶出度

目的 利用光纤药物溶出仪对溶出、取样和测定全程测试的实时、原位特点,测定头孢克洛片和胶囊的实时溶出度,评价药品制剂工艺和内在品质的差异.方法 实时在线过程分析同一厂家不同批号的头孢克洛片和胶囊在多种溶出介质中的溶出度,并与中国药典方法测定结果进行比较.结果 溶出度检测结果均符合中国药典规定.不同批次和剂型之间的溶出曲线基本一致,但在不同溶出介质之间略有差异.结论 与中国药典方法比较,光纤药物溶出仪法对样品溶出的实时过程分析更能真实反映不同批次药品之间的工艺和内在质量的可能差异.     

11厂家国产头孢氨苄片的溶出度比较

目的:比较国内11个厂家头孢氨苄片的溶出情况。方法:参照《中国药典》2005年版和日本在"药品品质再评价"拟定流程中对溶出度试验条件的规定,分别考察不同批次头孢氨苄片在水、pH1.2人工胃液、pH4.0醋酸盐缓冲液、pH6.8磷酸盐缓冲液4种溶出介质中的体外溶出度,溶出方法采用转篮法,转速为100r·min-1,测定方法为紫外分光光度法,检测波长为262nm;以其中溶出效果最优的E厂家样品为对照采用相似因子法进行各厂家样品间溶出行为的比较。结果:在上述4种溶出介质中,分别只有4个、3个、5个、8个厂家的样品在45min时累积溶出度在80%以上;多数厂家样品的相似因子结果都远小于50。结论:不同厂家样品的溶出行为不但有显著性差异,且溶出度不符合质量要求。     

不同厂家奈韦拉平片的溶出度对比研究

目的 考察国产奈韦拉平片与进口制剂的体外溶出度情况,并比较其体外溶出相似性.方法 分别考察各厂家奈韦拉平片在pH 2.0磷酸盐缓冲液中的溶出度,并比较了国产奈韦拉平片与进口制剂分别在pH 1.2盐酸水溶液、pH 2.0磷酸盐缓冲液、pH 4.5醋酸盐缓冲液、pH 6.8磷酸盐缓冲液4种介质中溶出行为相似性.结果 各厂家奈韦拉平片在pH 2.0磷酸盐缓冲液60min时溶出度均高于75%;有3个厂家的奈韦拉平片在4种溶出介质中的溶出曲线与进口制剂相似.结论不同厂家生产的奈韦拉平片溶出行为有显著差异,可能会影响药物在体内的生物利用度.     

过程分析考察不同厂家盐酸维拉帕米片的溶出度

目的：利用光纤溶出度过程分析方法,监测盐酸维拉帕米片的溶出度,反映不同厂家及同一厂家不同批号盐酸维拉帕米片间的质量差异.方法：采用《中国药典》盐酸维拉帕米片溶出度检测方法中的条件,利用光纤传感溶出度实时过程分析方法考察4个不同厂家及同一厂家5个不同批号盐酸维拉帕米片的溶出度.结果：过程溶出曲线反映每一药片溶出过程全部信息.4个不同厂家盐酸维拉帕米片的溶出度均符合《中国药典》2010年版规定,但溶出速度和曲线存在差异.结论：光纤溶出度过程分析原位实时反映了药物体外溶出特性,并真实地反映了同一药物的药片存在明显的差异.对考察体内外相关性、评价药品品质和评价生物等效性提供了有效途径.     

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.

---

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.