HPLC法同时测定吡诺克辛钠滴眼液中不同抑菌剂的含量

目的：建立同时测定吡诺克辛钠滴眼液中不同抑菌剂（硫柳汞钠、羟苯甲酯、羟苯乙酯、羟苯丙酯）含量的HPLC法。方法：采用C18色谱柱（4.6 mm×150 mm,5 μm）,流动相为0.005 mol·L^-1的醋酸铵溶液（每1000 mL中含三乙胺10 mL,用冰醋酸调节pH值至5.0±0.5）-乙腈（70：30）,流速为1.0 mL·min^-1,检测波长为256 nm,柱温为30℃。结果：硫柳汞钠、羟苯甲酯、羟苯乙酯和羟苯丙酯在各自的检测质量浓度范围内线性关系良好,r为0.9993~1.0000,检测限分别为2.3、0.4、0.7、1.1 ng;4种抑菌剂的平均回收率为100.4%~102.7%（RSD≤1.4,n=9）。结论：本文建立的方法结果准确可靠,可作为吡诺克辛钠滴眼液中不同抑菌剂的质量控制方法。     

3种内服液体制剂中羟苯甲酯和羟苯乙酯的含量测定

目的 :建立内服液体制剂中羟苯甲酯和羟苯乙酯的反相高效液相色谱测定方法。方法 :色谱柱 :Nova -ParkC18 柱(3 9mm×150mm ,5μm) ;流动相 :乙腈 -水 (25∶75) ;流速 :1ml/min ;检测波长 :254nm ;灵敏度 :0 01AUFS。结果 :羟苯甲酯浓度在0 4412～13 2360μg/ml范围内线性关系良好 (r=0 9999) ;羟苯乙酯浓度在0 6672～20 0160μg/ml范围内线性关系良好(r=0 9998)。结论 :该方法简便、快速、准确 ,可用于医院制剂中防腐剂的检测。     

LC-MS测定醋酸甲羟孕酮中对甲苯磺酸甲酯及对甲苯磺酸乙酯的含量

目的 建立醋酸甲羟孕酮中的基因毒性杂质对甲苯磺酸甲酯及对甲苯磺酸乙酯的LC-MS检测方法。方法 采用XDB-C₁₈（50 mm×4.6 mm,1.8 μm）色谱柱;10 mmol·L^-1醋酸铵（氨水pH 7.0）-乙腈为流动相;质谱：正离子模式,检测离子m/z 187.1,201.1。结果 对甲苯磺酸甲酯和对甲苯磺酸乙酯在0.05~5.08 μg·mL^-1内线性关系良好。对甲苯磺酸甲酯定量限为0.1 ng,检测限均为0.05 ng;对甲苯磺酸乙酯定量限为0.03 ng,检测限为0.02 ng;对甲基苯磺酸甲酯平均回收率101.6%,RSD为3.46%;对甲基苯磺酸乙酯平均回收率98.7%,RSD为2.22%。结论 本方法适用于样品醋酸甲羟孕酮中对甲基苯磺酸甲酯和对甲基苯磺酸乙酯的检测。     

高效液相色谱法同时测定人体润滑剂中苯氧乙醇和羟苯甲酯含量

目的建立同时测定人体润滑剂中苯氧乙醇和羟苯甲酯含量的高效液相色谱法。方法采用反相高效液相色谱法,色谱柱为Acclaim 120 C18柱(150mm×4.6mm,5μm),以乙腈-水-冰醋酸(310∶690∶2)为流动相A,乙腈为流动相B,梯度洗脱,检测波长为265 nm。结果苯氧乙醇质量浓度在3.02～60.39μg/mL范围内,羟苯甲酯质量浓度在1.33～26.64μg/mL范围内与峰面积均呈良好线性关系,线性方程分别为Y=0.086 X+0.004 34(r=0.999 99,n=5)和Y=0.598 8 X+0.017 39(r=0.999 99,n=5),平均回收率分别为95.66%(RSD=0.92%)和96.37%(RSD=0.53%),人体润滑剂中苯氧乙醇和羟苯甲酯的含量分别为2.85 mg/g和2.00 mg/g。结论该方法简便、可靠,可用于人体润滑剂中苯氧乙醇和羟苯甲酯的含量测定。     

HPLC法同时测定滴眼剂中羟苯酯类和季铵盐类抑菌剂含量的方法研究

建立同时测定滴眼剂中羟苯酯类和季铵盐类抑菌剂含量的通用型方法。方法:采用Agilent C18色谱柱(4.6 mm×250 mm,5 μm),以1%三乙胺溶液（用磷酸调pH至5.0）为流动相A,以甲醇为流动相B,梯度洗脱,柱温为40 ℃;检测波长为214 nm,流速为1 mL·min^-1,进样体积20 μL。结果: 羟苯甲酯、羟苯乙酯、羟苯丙酯、羟苯丁酯、苯扎氯铵及苯扎溴铵分别在0.11~559.0、0.10~513.0、0.10~258.8、0.11~270.5、1.07~537.0及1.03~512.8 μg·mL^-1范围内线性关系良好（r＞0.999）,羟苯乙酯、苯扎溴铵、苯扎氯铵的平均加样回收率分别为104.7%（RSD=1.3%）、102.6%（RSD=1.1%）、100.9%（RSD=1.1%）。对12家企业36个品种的100批次滴眼液中抑菌剂含量进行测定,得到了较为准确的结果。结论:本法可为滴眼剂中抑菌剂含量测定质量控制和安全评价提供参考。     

甲钴胺的引湿性探讨

目的：了解甲钴胺的引湿特性,探讨化学对照品使用和贮存中应注意的问题。方法：采用动态水分吸附分析技术（DVS）研究甲钴胺在不同湿度条件下吸收水分的趋势和程度,以容量滴定法测定其水分的均匀性。结果：甲钴胺具有引湿性,且在一定湿度条件下吸水后仍具有较强的引湿性。结论：本研究为确定甲钴胺适宜的分装条件、包装用瓶和使用方式等提供了数据支持和参考依据。     

羟苯磺酸钙分散片联合百令胶囊治疗糖尿病肾病Ⅳ期临床观察

摘 要 目的： 观察百令胶囊联合羟苯磺酸钙分散片治疗糖尿病肾病Ⅳ期,对患者血糖、血脂,肾功能等指标的影响。方法: 216例糖尿病肾病Ⅳ期患者随机分为两组各108例。对照组在常规治疗基础上加服羟苯磺酸钙分散片0.5 g,po,tid,观察组在对照组基础上再加服百令胶囊2.5 g,po,tid。疗程均为3个月。观察两组患者治疗前后血糖、血脂、糖化血红蛋白,以及血肌酐（Cr）、尿素氮（BUN）、内皮素（ET-1)、β2微球蛋白（β2-MG）、胱抑素（CYC）、24h尿蛋白定量（UAER）等指标变化情况,观察治疗期间药品不良反应发生情况。结果:治疗后,两组BUN、Cr、ET-1、UAER、β2-MG、CYC等指标均较治疗前显著下降（P<0.05）,且观察组上述指标均明显低于对照组（P<0.05）。 两组患者治疗前后血糖、血脂、糖化血红蛋白等指标无明显变化(P>0.05)。两组药品不良反应发生率比较,差异无统计学意义（P>0.05)。结论: 百令胶囊联合羟苯磺酸钙分散片治疗糖尿病肾病Ⅳ期,能明显改善患者肾功能指标,优于单用羟苯磺酸钙分散片,对血糖、血脂无明显影响,且安全性好。     

强心扩血管药羟苯氨酮对离体心肌与血管的作用

为阐明强心扩血管药羟苯氨酮对心肌与血管的直接影响,采用离体心脏,离体心肌与血管制备,以心肌张力、心率、冠脉流量及血管平滑肌张力为观察指标。结果显示:给离体大鼠心脏灌流羟苯氨酮0.1～1μmol·L^-1可使心肌收缩力和冠脉流量明显增加,心率轻度减慢。羟苯氨酮剂量依赖性地增加豚鼠乳头肌和左房肌张力,并减慢右房频率。羟苯氨酮(1～50μmol·L^-1)非竞争性地对抗KCl,5-HT和CaCl₂致狗冠状动脉,基底动脉和肠系膜动脉的收缩,显示它有松弛血管平滑肌的作用。与磷酸二酯酶抑制剂类药物米力农作比较,两者的正性肌力作用与扩血管作用相似。然而,羟苯氨酮减慢心搏频率,米力农则增加心率。提示羟苯氨酮有直接正性肌力、负性频率与扩血管作用。     

羟苯氨酮对豚鼠心肌细胞膜Na+和Ca2+ 离子通道的影响羟苯氨酮对豚鼠心肌细胞膜Na+和Ca2+ 离子通道的影响

目的探讨羟苯氨酮(oxyphenamone)的正性肌力作用机制。方法用膜片钳全细胞记录技术测定心肌细胞膜Na⁺ 电流与L型Ca²⁺电流。结果羟苯氨酮剂量依赖性地明显抑制豚鼠心肌细胞膜Na⁺ 电流，促进Na⁺ 通道失活，并延长其恢复时间；它对Ca²⁺电流的影响呈双向性，2～10 μmol·L^-1 使电流增加，促进钙通道的激活过程；20与50 μmol·L^-1时则使Ca²⁺电流明显抑制。结论羟苯氨酮的正性肌力作用不是通过激活钠通道，也不完全依赖于激活L型钙通道，它对钠通道的抑制和在高浓度时对L型钙通道的抑制提示该药可能具有抗心律失常作用。     

纤维素三苯甲酯手性填料稳定性初步研究

对手性填料纤维素三苯甲酯的水解稳定性进行了初步考察,结果表明,其在常温及低温使用时具有很长的使用寿命。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.