冠心宁注射液安全性再评价研究(Ⅱ)

目的为冠心宁注射液安全性再评价工作提供数据参考。方法采用不同药物浓度,按《中国药典》2010年版一部附录方法进行渗透压摩尔浓度测定和溶血与凝聚检查,同时采用分光光度法对样品及其稀释液进行溶血率的测定;采用显微镜法对样品及其稀释液进行血细胞凝聚检查。结果各厂家产品的渗透压摩尔浓度均为高渗,原液渗透压摩尔浓度(mOsmol/kg)A厂为400～799,F厂为400～999,B、C、D、E厂为600～1000,并可达到1000以上。用5%葡萄糖注射液对样品稀释后再进行测定,结果各厂的产品按使用说明书使用时,基本上都能达到等渗;溶血与凝聚检查结果 71批样品均符合规定;用分光光度法测定溶血率,结果各厂家样品原液均有一定的溶血(2批样品因凝聚,测定值偏低),除B厂家4批样品外,各厂家样品最小不溶血浓度均大于1∶8,B厂家3批样品的最小不溶血浓度为1∶16(相当于常规体外试管法药物浓度),1批样品的最小不溶血浓度为1∶32;红细胞凝聚检查,各厂家样品原液检查结果有58批样品未见凝聚,占总样品数的81.7%,A厂有3批样品凝聚严重,用5%葡萄糖注射液对样品稀释后,最小不凝聚浓度大于1∶8,D厂家血细胞变形、破损较严重,镜下可见大量细胞碎片。结论不同厂家生产的冠心宁注射液渗透压摩尔浓度、溶血率及红细胞凝聚存在一定的差异,建议用适当的渗透压摩尔浓度及溶血与凝聚检查方法来控制其质量,以保障临床用药的安全。     

溶血率测定法在莪术油葡萄糖注射液安全性再评价中的应用

目的 研究溶血率测定法在莪术油葡萄糖注射液安全性再评价中的应用,为提高莪术油葡萄糖注射液质量标准提供参考。方法 用《中国药典》2010年版二部附录“溶血与凝聚检查法”和紫外分光光度测定溶血率法,对3家厂家生产的22批莪术油葡萄糖注射液进行溶血与凝聚检查和分光光度法测定溶血率,比较实验结果,并对检查样品进行安全性评价。结果 溶血与凝聚检查试验和紫外分光光度法测定溶血率的试验结果有一定的相关性,部分批号莪术油葡萄糖注射液具溶血性,临床使用存在一定的风险。结论 莪术油葡萄糖注射液应检查溶血与凝聚,紫外分光光度测定溶血率方法可用于莪术油葡萄糖注射液的质量控制。     

参麦注射液渗透压和溶血率现状的调查

目的：为做好参麦注射液安全性再评价工作提供数据参考。方法：渗透压测定采用冰点测定法,对样品原液及其稀释液进行渗透压测定,并计算与氯化钠注射液渗透压的比值;溶血率测定采用分光光度法,对样品原液及其稀释液进行溶血率测定。结果：渗透压测定,样品原液均为低渗溶液,渗透压值在96～180mOsmol/kg,1→4～1→8稀释后与氯化钠注射液渗透压比可达0.9;溶血率测定,样品稀释倍数在小于1→16时,样品均存在不同程度的溶血（溶血率〉5%）,1→32倍稀释时,溶血率均小于等于5%。结论：不同厂家生产的参麦注射液的渗透压和溶血率均存在一定的差异,建议增加渗透压和溶血率测定来控制其质量。     

重组人干扰素α1b注射剂评价性抽验结果与质量分析

目的 评价重组人干扰素α1b注射剂的质量现状及存在问题。方法 抽取2个企业生产的31批注射用重组人干扰素α1b和11批重组人干扰素α1b注射液,按照《中国药典》2010年版三部标准进行检验,统计分析生物学活性、渗透压摩尔浓度、水分、pH值等检验结果,对国产重组人干扰素α1b注射剂的质量现状进行评价。结果 42批样品检验全部合格,各生产企业生产工艺比较稳定。结论 该品种总体质量状况良好,现行质量标准能够保证产品的安全有效,渗透压摩尔浓度项目的标准规定应进一步完善。     

冠心宁注射液安全性再评价研究(I)

目的为做好冠心宁注射液安全性再评价工作提供数据参考。方法采用不同给药剂量,按《中国药典》2010年版一部附录方法进行异常毒性检查、过敏反应检查及降压物质检查,根据样品注射后动物反应情况,进行分级评价。结果异常毒性检查:不同厂家的样品原液异常毒性检查结果差异明显,A、D及F3个厂家的产品异常毒性较小,均未出现动物死亡,其中A与F两个厂家均只有一批样品得3分;B厂的产品异常毒性变化较大,13批样品中,除一批样品未见明显毒性反应外,有8批样品出现动物死亡,占总数的53.3%;C和E厂的产品表现出较大的异常毒性,得分在2～5分,D厂产品最稳定,13批样品得分集中分布在2～3分,没有出现动物死亡情况;选用样品1︰2的稀释液,71批样品中,仅有1批出现动物死亡;不同来源、不同品种动物反应结果基本一致。降压物质检查:冠心宁注射液有一定的降压作用,注射0.2mL/kg样品原液,降压幅度大于组胺对照(0.1μg/kg)组,选用样品1︰3的稀释液,71批样品中,仅B厂有4批样品不合格,经换猫再试,有1批样品仍不合格,3批合格。过敏反应检查:取不同厂家样品24批进行过敏反应检查,结果均未出现明显的过敏反应。结论不同厂家、同一厂家不同生产批号的冠心宁注射液异常毒性、降压物质检查结果存在差异,可增加异常毒性、降压物质检查来控制其质量。     

国产重组人干扰素α2b注射剂渗透压摩尔浓度测定结果分析

摘 要 目的： 考察国产重组人干扰素α2b注射剂的渗透压摩尔浓度,为该品种渗透压摩尔浓度质量标准的完善提供依据。方法: 抽取9家企业的66批产品,根据《中国药典》2010年版三部测定其渗透压摩尔浓度,并对测定结果进行统计分析。结果: 渗透压摩尔浓度的合格率为98.5%,90%以上的批次渗透压摩尔浓度在企业规定的渗透压摩尔浓度中间值的85% ～ 115%之间。结论:对国产重组人干扰素α2b注射剂渗透压摩尔浓度的质控状况有了比较全面的了解,为渗透压摩尔浓度质量标准的完善提供了数据支持。     

天麻素注射液质量评价

目的 监测和评价天麻素注射液的质量现状。方法 采用法定检验与探索性研究相结合的模式,按法定标准检验200批样品,统计分析pH值、有关物质和含量测定等检验结果,围绕安全性有效性开展了有关物质、渗透压摩尔浓度、依地酸二钠（EDTA-2Na）筛查及注射剂局部安全性4个方面的研究。结果 按法定标准检验结果均符合规定,合格率100%。通过探索性研究建立了杂质谱,渗透压摩尔浓度研究发现部分企业说明书中对“辅料”描述不完全,EDTA-2Na筛查与注射剂局部安全性研究结果均呈阴性反应或符合规定。结论 天麻素注射液总体质量状况好。     

胞磷胆碱钠注射剂渗透压考察

摘 要 目的：对不同企业的胞磷胆碱钠注射剂进行渗透压分析,为提高该品种的国家标准提供试验依据。方法: 采用冰点降低法对国内45家生产企业的479 批胞磷胆碱钠注射剂的渗透压值进行测定。结果: 胞磷胆碱钠注射液渗透压值在359～692 mOsmol·kg^-1之间,注射用胞磷胆碱钠渗透压值在401～1 408 mOsmol·kg^-1之间,胞磷胆碱钠氯化钠注射液渗透压值在278～299 mOsmol·kg^-1之间。结论:国内不同厂家生产的胞磷胆碱钠注射液和注射用胞磷胆碱钠的渗透压值有较大差异,有必要在其质量标准中增设渗透压检查项,用以评价生产工艺的优劣。     

阿立哌唑注射液肌肉刺激、溶血及过敏试验研究

目的 评价阿立哌唑注射液的肌肉刺激性,观察其否具有溶血、凝聚及过敏反应。方法 采用兔股四头肌sc给药,观察阿立哌唑注射液对注射局部肌肉的刺激性;采用2%兔血红细胞混悬液检查阿立哌唑注射液有无溶血和红细胞凝聚反应;采用豚鼠全身主动过敏试验（ASA）评价阿立哌唑注射液有无过敏反应。结果 阿立哌唑注射液对兔红细胞无溶血及凝聚作用;新西兰兔单次及连续7 d sc给予阿立哌唑注射液,均发现其对股四头肌有刺激作用,以肌纤维的变性坏死为主,肌纤维崩解消失,病灶内可见散在的炎细胞浸润,停药14 d后刺激反应消失;每只3.75、7.50 mg剂量下给予阿立哌唑注射液,豚鼠未见过敏反应。结论 阿立哌唑注射液未见溶血和过敏反应,较高浓度下可能会引起肌肉刺激性反应。     

复方麝香注射液体外溶血反应研究

目的根据国家药典委员会对于中药注射剂质量标准提高工作的要求,研究复方麝香注射液体外溶血反应情况为其临床安全应用提供依据。方法将5家不同厂家生产的13批复方麝香注射液分别从原液检测起,按1：2倍逐步稀释至临床最大使用量相对应的稀释倍数（1：12．5倍）,分别通过两种方法：常规肉眼观察法、分光光度法检测其对新鲜兔血的溶血性。结果两种方法测得结果一致,各厂家的复方麝香注射液从1：6倍浓度稀释液（未超过临床最大使用量）起均无溶血与凝聚现象。结论复方麝香注射液在临床使用剂量时无体外溶血反应;建议紫外分光光度法作为溶血反应的仲裁方法。     

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.