PLC法测定刺五加制剂中异皮定的含量

目的 :建立测定刺五加制剂中异皮定的高效液相色谱法。方法 :采用YMC -ODS (4 6mm× 15 0mm)色谱柱 ,以乙腈 -水 -甲酸 (15∶85∶1)为流动相 ,检测波长 34 5nm ,外标法定量。结果 :异皮定在 0 0 5～0 4μg·mL-1内呈线性关系 ,片剂及浸膏的方法回收率分别为 97 14%和 99 32 % (n =5 ) ,RSD分别为 1 8%和1 1%。结论 :此法简便 ,准确 ,重现性好。     

高效液相色谱法测定氯麻滴鼻液中氯霉素和盐酸麻黄碱的含量

目的 :建立测定氯麻滴鼻液中氯霉素和盐酸麻黄碱含量的高效液相色谱法。方法 :采用反相 μ Bondpak色谱柱 ,甲醇- 0 .0 2mol·L-1磷酸二氢钾 (5 5∶45 ,磷酸调 pH值3.5 )为流动相 ,检测波长 2 5 4nm。结果 :氯霉素和盐酸麻黄碱的线性范围分别为 2 0～ 12 0 μg·ml-1(r =0 .9998) ,80～ 480 μg·ml-1(r =0 .9998) ;加样回收率分别为 10 1.4% ,RSD =0 .5 %及 10 0 .8% ,RSD =0 .9% (n =5 ) ,日内RSD分别为 0 .9%和 0 .4% (n =5 ) ,日间RSD分别为 1.0 %和 0 .8% (n =4)。结论 :HPLC法可用于本制剂的含量测定和质量控制 ,方法简便、灵敏、结果准确     

祛白酊中补骨脂素和异补骨脂素透皮效果的实验研究

目的 :考察祛白酊中君药补骨脂有效成分补骨脂素和异补骨脂素的透皮效果。方法 :采用简单小室法 ,以离体大鼠皮肤为透皮屏障 ,用双波长薄层扫描法测定体外接收液中补骨脂素和异补骨脂素的含量 ,进而计算累积透皮量和透皮率 ,并与未加月桂氮酮和二甲基亚砜的祛白酊透皮效果进行了实验性比较。结果 :补骨脂素的 8h累积透皮量与透皮率分别为 (92 6 5±2 91) μg·ml-1和 (84 6 6± 2 6 6 ) % ,异补骨脂素的 8h累积透皮量与透皮率分别为 (86 37± 2 6 7) μg·ml 1和 (82 2 9± 2 5 4 ) % ,与未加月桂氮酮和二甲基亚砜制剂的透皮效果比较 ,有显著性差异 (P <0 0 1)。结论 :祛白酊的透皮效果良好     

高效液相色谱法检测人血浆中氟西汀及其代谢产物的浓度

目的 :建立一种快速测定人血浆中氟西汀及其代谢产物去甲氟西汀的反相高效液相色谱法。方法 :用正己烷 -乙腈(98∶2 )提取血浆样品中氟西汀、去甲氟西汀及氯丙帕明 (内标 ) ,在EclipseXDB -C8柱上 ,以 0 0 5mol·L-1磷酸二氢钾 -乙腈 -甲醇 (5 5∶40∶5 )为流动相进行分离 ,流速 1 2mL·min-1,于 2 2 6nm检测。结果 :线性范围为 10～ 5 0 0ng·mL-1,氟西汀和去甲氟西汀相对回收率分别为 99 1%～ 10 4 2 %和 98 2 %～ 10 0 3 % ,日内RSD分别为 4 1%～ 4 8%和 4 5 %～5 8% ,日间RSD分别为 3 5 %～ 5 9%和 4 9%～ 6 8%。结论 :本法简便、精密度高、重现性好 ,结果准确可靠。     

兔血浆中霉酚酸酯的活性代谢物霉酚酸的HPLC测定及其药代动力学研究

目的建立霉酚酸兔血药浓度测定方法 ,并进行了灌胃后药代动力学研究。方法采用HPLC 二极管阵列检测器测定血药浓度。血样采用乙醚萃取 ;色谱柱 :HypersilODS2 (2 0 0mm×4 6mm ,5 μm) ;流动相 :0 0 5mol·L-1KH2 PO4 CH3 CN(5 5∶45 ,pH 2 5 ) ;检测波长 :2 1 5nm ;流速 :1 0mL·min-1。结果霉酚酸血药浓度线性范围为 0 1 6～ 1 9 98μmol·L-1(r =0 9996,n =8) ,血浆最低检测浓度为 0 0 3 μmol·L-1,高、中、低 3种浓度平均回收率分别为 :(1 0 3 2 5± 6 3 2 ) %、(99 63± 2 75 ) %、(1 0 2 47± 3 1 8) % ,兔灌胃后主要的药代动力学参数分别为 :达峰浓度cmax为(8 2 7± 6 1 2 ) μmol·L-1,达峰时间tmax为 (0 49± 0 1 7)h ,消除半衰期t1/ 2 为 (3 1 2± 0 94)h ,药时曲线下面积AUC0 -t为 (1 3 0 8± 9 0 8) μmol·h·L-1,AUC0 -∞ 为 (1 3 80± 8 93 )mg·h·L-1。结论为霉酚酸的血药浓度监测及药动学研究提供了实验方法。     

反相高效液相色谱法测定雷贝拉唑的血药浓度

目的　建立测定雷贝拉唑血药浓度的高效液相色谱(HPLC)方法。方法　色谱条件 :luna C8色谱柱 ,流动相为 2 0mmol·L-1 磷酸盐缓冲液 (pH7 0 ) /乙腈 (70 / 30 ,V/V) ,流速1 2ml·min-1 ,测定波长 2 88nm ,以雷贝拉唑峰面积定量。结果　雷贝拉唑的标准曲线为 ^Y =1 2 4 95 0X - 80 6 0 5 (r =0 999) ,线性范围为 0 0 1～ 0 75mg·L-1 ,具有良好的线性关系 ;其 0 0 5、0 1、0 5mg·L-1 3个浓度的血清样本回收率分别为 75 2 3%± 3 0 2 %、84 2 3%± 3 33%、91 0 5 %± 7 5 1 % ;日内变异分别为 5 0 9%、9 2 0 %、6 75 % ;日间变异分别为8 2 5 %、3 5 1 %、4 1 9%。结论　该方法简便、快速且无干扰 ,满足测定要求 ,可用于雷贝拉唑的药代动力学研究     

葛根素氯化钠注射液细菌内毒素检查法的质量标准

目的 :建立葛根素氯化钠注射液细菌内毒素检查法。方法 :对葛根素氯化钠注射液的 1～ 2 (0 .8mg·ml-1)、1～ 4 (0 .4mg·ml1-)、 1～ 8(0 .2mg·ml-1)、 1～ 16(0 .1mg·ml-1)进行干扰试验。结果 :其回收率分别为 :1～ 2(0 .8mg·ml-1) 5 2 %、1～ 4 (0 .4mg·ml-1) 76 %、1～ 8(0 .2mg·ml-1) 89%、1～ 16 (0 .1mg·ml-1) 10 9%。结论 :葛根素氯化钠注射液经 1- 2 (0 .8mg·ml-1)稀释后对细菌内毒素检查法无干扰作用     

氢溴酸右美沙芬片健康人体生物等效性

目的 :研究氢溴酸右美沙芬片在健康人体的药动学及相对生物利用度。方法 :8名健康受试者单剂量随机交叉口服氢溴酸右美沙芬片参比制剂和被试制剂 6 0mg ,采用HPLC法测定用药后不同时间的血药浓度。结果 :2种制剂的体内过程均符合一房室开放模型 ,参比制剂和被试制剂的tmax分别为 (2 72± 0 2 1)h和 (2 74± 0 19)h ,cmax分别为 (5 5 1± 0 4 4) μg·L-1和(5 5 8± 0 2 7) μg·L-1,AUC分别为 (4 5 3± 2 9) μg·h·L-1和 (4 5 7± 3 0 ) μg·h·L-1,被试制剂的相对生物利用度为 (10 1±5 9) %。结论 :2种制剂具有生物等效性。     

HPLC法同时测定非索伪麻缓释双层片中盐酸非索非那定与盐酸伪麻黄碱的含量

目的测定非索伪麻缓释双层片中 2组分含量。方法采用氰基键合硅胶 (HypersilCN ,4 6mm× 2 0 0mm ,5 μm)为填充剂 ;流动相为乙腈 5mmol·L-1NH4H2 PO4(pH3 5 ,5 3∶4 7,V∶V )的高效液相色谱法 ;检测波长为 2 10nm ;柱温为 30℃ ;流速为 1 0mL·min-1。结果盐酸非索非那定与盐酸伪麻黄碱分别在质量浓度 2 0 2 8～ 10 1 4mg·L-1与 39 6 6～ 198 3mg·L-1内线性关系良好 ,相关系数r分别为 0 9999和 1。方法精密度RSD分别为 0 6 0 %和 0 35 % (n =6 ) ,平均回收率分别为 99 9%和 99 8% ,方法RSD分别为 0 5 1%和 0 38% (n =9)。结论该方法为评价非索伪麻双层片的质量提供了可靠的方法     

高效液相色谱法同时测定氯氟滴眼剂中氯霉素和地塞米松磷酸钠的含量

目的 :建立高效液相色谱法同时测定氯氟滴眼剂中氯霉素和地塞米松磷酸钠的含量。方法 :流动相为甲醇 0 .34%磷酸二氢钾 (5 5∶5 0 ) ,流速 1mL·min-1,SpherisorbC18色谱柱 ,检测波长 2 4 0nm。结果 :氯霉素和地塞米松磷酸钠分别在 12 5～10 0 0mg·L-1(r =0 .9992 )、2 5～ 2 0 0mg·L-1(r =0 .9998)内线性关系良好。加样回收率分别为 (10 1.5± 1.93) %、(10 1.0±1.5 9) % (n =3)。日内RSD分别为 0 .6 3% ,0 .5 8% (n =5 ) ,日间RSD分别为 0 .99% ,0 .86 % (n =3)。结论 :该法简单、迅速 ,结果准确可靠。     

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.     

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.     

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.