注射用盐酸帕洛诺司琼的制备、质量控制及稳定性考察

目的:制备注射用盐酸帕洛诺司琼,建立其质量控制方法并考察其稳定性.方法:制备注射用盐酸帕洛诺司琼;采用高效液相色谱法测定其含量及有关物质,并对制剂进行稳定性试验.结果:本品处方以10%甘露醇作为填充剂,用磷酸二氢钠调节溶液pH值为4.5～6.0;盐酸帕洛诺司琼在 12.00 μg·mL-1～150.01 μg·mL-1浓度范围内线性关系良好(r＝0.999 9),恒温加速试验6个月及长期留样18个月时主药含量及有关物质未见明显变化.结论:该制剂处方工艺可行,质量可控,稳定性良好;所建立的含量测定方法重复性好,专属性强,结果准确可靠.     

复方盐酸利多卡因栓稳定性研究

目的:研究复方盐酸利多卡因栓的稳定性.方法:高效液相色谱法测定盐酸利多卡因的含量及其有关物质,分别用强光照射法、高湿试验、加速试验法对复方盐酸利多卡因栓进行稳定性试验.结果:本品对强光不太稳定,在日光及高湿的环境中非常稳定,在3个月的加速试验期内稳定.结论:本品在遮光、阴凉条件下性质稳定.     

注射用头孢噻肟钠他唑巴坦钠(6:1)的稳定性研究

目的 考察注射用头孢噻肟钠他唑巴坦钠制剂(6∶1)的稳定性,为确定产品有效期提供依据.方法 本品经影响因素试验、加速试验和长期留样的稳定性试验,考察其性状、pH 值、溶液的澄清度与颜色、有关物质、头孢噻肟聚合物、水分及含量等变化.结果 稳定性试验结果表明,本品稳定性好,可推荐其有效期暂定为二年.     

pH对酒石酸溴莫尼定滴眼液稳定性的影响

目的:考察pH对酒石酸溴莫尼定滴眼液稳定性的影响,确定本品最佳的pH范围及贮存条件.方法:采用HPLC法测定酒石酸溴莫尼定滴眼液的含量及有关物质,考察本品在强光、高温条件下的稳定性.结果:酒石酸溴莫尼定滴眼液对强光、高温较敏感,且随着pH值的升高,稳定性下降.结论:本品最适宜的pH范围为偏酸性,最适宜的贮存条件为低温、避光.     

溶菌酶眼用凝胶剂的制备及体外性质考察

目的通过制备溶菌酶眼用凝胶制剂提高溶菌酶的稳定性,延长溶菌酶与眼部的作用时间。方法按照部颁标准测定了溶菌酶活性,通过对基质的筛选,确定了最优处方及工艺,考察了溶菌酶眼用凝胶剂的基本性质如:黏度、表面张力、渗透压、体外释放、稳定性,以及眼用凝胶剂的体外抑菌性。结果以质量分数1%HPMC K4M为凝胶基质,制备的溶菌酶眼用凝胶剂的黏度为95.83 m Pa·s,表面张力为39.696 m N·m-1,渗透压为277 m Osm·kg-1,p H为6.56,效价为10 300 U·m L-1,溶菌酶凝胶剂体外释放5 h时,累计释放率接近100%。溶菌酶眼用凝胶剂对革兰氏阳性菌抑菌效果较好,而对革兰氏阴性菌抑菌效果较差。加速试验和长期稳定性试验表明该制剂性质稳定。结论制备的溶菌酶眼用凝胶制剂相关性质均符合眼用制剂标准。     

消咳喘糖浆稳定性考察试验

目的:考察消咳喘糖浆药物稳定性.方法:制剂进行加速试验和长期试验研究,按药物稳定性试验指导原则,以糖浆剂稳定性重点考察项目,性状、鉴别、相对密度、含量等为评价指标,考察其在贮存期间的稳定性.结果:本品经过加速试验6个月和长期试验6个月考察,其各项指标均在质量标准规定的范围内.结论:消咳喘糖浆药物性质比较稳定.     

透明质酸钠在阿托品眼凝胶制剂中的应用

目的:利用透明质酸钠的特殊的保湿、保水作用,研究对阿托品眼凝胶稳定性的影响.方法:利用离心试验,耐热、耐寒试验,采用对比的方法,观察对阿托品眼凝胶稳定性影响,通过回收试验,pH检查等有关常规检验、对其制剂质量的影响.结果:加入透明质酸钠的阿托品眼凝胶产品无变稀、分层现象,并对其质量及刺激性无明显影响.结论:透明质酸钠对维持阿托品眼凝胶制剂的稳定性起到了显著作用.     

安神益心液的稳定性考察

目的:考察安神益心液的稳定性。方法:用HPLC法测定有效成分含量,并考察性状、鉴别、相对密度、pH、微生物限度等其他指标。结果:影响因素试验结果表明本品可受高温及强光影响;加速试验和长期试验结果表明各项考察指标无明显变化。结论:本品在贮存及运输过程中应避免高温及强光照射;本品的工艺及包装等设计合理,符合制剂稳定的要求。     

复方盐酸左氧氟沙星滴眼液的稳定性试验研究

目的:考察复方盐酸左氧氟沙星滴眼液的稳定性。方法:采用高效液相色谱法同时测定3种主药(盐酸左氧氟沙星、盐酸萘甲唑啉及地塞米松磷酸钠)的含量,并进行包括强光照射试验、高温试验的影响因素试验及加速试验、长期试验的稳定性试验。结果:影响因素试验结果表明本品在该条件下性状发生了变化,颜色有所加深,3种主药的含量均呈下降趋势,但仍在合格范围内;加速试验和长期试验结果表明各项考察指标均无明显变化。结论:本品符合制剂稳定性的要求,但在贮存及运输过程中应避免高温及强光照射。     

注射用头孢哌酮钠他唑巴坦钠细菌内毒素检查法的研究

目的:建立注射用头孢哌酮钠他唑巴坦钢细菌内毒素检查法.方法:凝胶法鲎试验.结果:本品细菌内毒素限位为0.15Eu·ml~(-1),在3.333至0.400mg·ml~(-1)的浓度范围内,不干扰细菌内毒素试验.结论:细菌内毒素凝胶法较家兔热原法具有灵敏度高、快速、简便、重现性好等优点,本品可用细菌内毒素检查凝胶法代替家兔热原法.     

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.