灯盏花素注射液的含量测定及有关物质的检查

目的　建立灯盏花素注射液的含量测定和有关物质检查的方法。方法　采用HPLC法。结果　在0 . 32～1 . 6 0 μg范围内线性关系良好(r=0 .9993) ,平均回收率98. 9%,RSD =0 .5 5 %(n =9) ,日内及日间精密度分别为0 .5 9%、0 .80 %。有关物质检查的检测限为0 8ng(S/N =3) ,在0 .0 0 6 4～0 .0 32 0 μg范围内线性关系良好(r=0 .9993)。结论　所建立的方法简便、灵敏、准确,可用于灯盏花素注射液的质量控制及有关物质检查。     

高效液相色谱法测定灯盏花素缓释片的含量及释放度

目的建立测定灯盏花素缓释片含量的高效液相色谱法 ,测定体外释放度。方法采用ODS柱 ,0 .0 2mol/LK2 HPO4缓冲液 (用磷酸调pH 7.5 ) 甲醇 (6 0∶4 0 )为流动相 ;检测波长为 335nm ;流速为 1.0ml/min进行检测。转篮法测定释放度。结果灯盏花素浓度在 0 .996～ 99.6 μg/ml范围内与峰面积呈良好线性关系 ,高、中、低 3种浓度的平均回收率为 99.1%～ 99.5 % (n =5 ) ,日内、日间RSD分别为 0 .6 9% (n =6 )、0 .82 % (n =5 )。结论采用高效液相法测定灯盏花素缓释片的体外释放具有灵敏、准确、专属性高的优点。     

HPLC法测定灯盏花素注射液中野黄芩苷含量及有关物质

目的:建立用高效液相色谱法测定灯盏花素注射液中野黄芩苷含量及其有关物质。方法:采用Agilent TC C18(5μm,4.6 mm×250 mm)色谱柱,以甲醇-0.1 mol.L-1醋酸铵溶液(用磷酸调节pH 3.0)(32∶68)为流动相,流速1.0 mL.m in-1,检测波长335 nm。结果:主峰和相邻杂质峰能较好地分离;野黄芩苷浓度在26.02~312.24μg.mL-1范围内具有良好的线性关系(r=0.9994,n=5);最低检出量为2 ng;灯盏花素注射液中的主要有关物质为灯盏花甲素。结论:本法专属准确,可用于灯盏花素注射液的质量控制。     

灯盏花素注射液对脑梗死患者血液流变学的影响

目的　观察灯盏花素注射液对脑梗死患者血液流变学的影响。方法　将 16 3例脑梗死患者分为两组 ,即灯盏花素注射液组 (治疗组 ) 10 3例和复方丹参注射液组 (对照组 ) 6 0例 ,观察治疗前、后血液流变学的变化。结果　两组治疗后血液流变学均有明显改善 ,尤以灯盏花素注射液组为显著。另外 ,在治疗中发现灯盏花素注射液静脉滴注的 1个疗程最佳时间为 10天。结论　灯盏花素注射液在改变血液流变学指标方面优于复方丹参注射液     

高效液相-质谱联用法(HPLC-MS)测定灯盏乙素血药浓度及其临床药代动力学研究

目的:研究灯盏花素片在中国人体内的药代动力学。方法:2 0名健康志愿者单剂量口服12 0mg灯盏花素片,用高效液相 质谱联用法测定血浆中灯盏乙素总苷元。结果:本实验建立的血药浓度测定方法,血浆中杂质不干扰样品的测定,线性范围为0 .0 12 6～3.2 4mg·L-1;日内和日间精密度均小于12 .0 %。2 0名健康受试者单剂量口服灯盏花素片(12 0mg)后,主要药代动力学参数:Tmax =7.0±2 .3h、Cmax=0 .9±0 .5mg·L-1、AUC0 -tn =5 .6±1.6mg·h·L-1、AUC0 -∞=5 .8±1.6mg·h·L-1、MRT0 -tn=8.0±1.1h、MRT0 -∞=8.6±1.4h。结论:建立的LC MS法适用于灯盏乙素人体药代动力学研究。灯盏花素片口服药代动力学特点是达峰时间较长,约占受试者总人数4 5 %的药时曲线有双峰现象。     

HPLC法测定煤盏花素片含量

目的 　测定灯盏花素片的含量。 方法 　采用高效液相色谱法。色谱柱为 C1 8柱。 (10μm,4.6mm× 2 5 0 mm) ;流动相为甲醇 :水 (80∶ 2 0 ) ;流速 0 .9ml·min- 1 ,检测波长 3 3 5 nm;柱温 :室温。结果 　灯盏花素片在 2 0 μg～ 80 μg·ml- 1范围内 ,线性关系良好 ,平均回收率为 10 0 .2 % ,RSD为 1.5 3 %。 结论 　该法可用于灯盏花素片中灯盏花乙素的含量测定     

灯盏细辛注射液中灯盏花乙素在大鼠体内的药物动力学

目的 研究灯盏细辛注射液中灯盏花乙素在大鼠体内的过程.方法 采用甲醇沉淀法制备血液样品,用 HPLC法测定.结果 灯盏花乙素50.0～0.3 μg · ml-1范围内线性关系良好(r=0.9950);样品的回收率在97%～98%,日内和日间RSD均小于5%.灯盏花乙素在大鼠体内的过程符合二室模型,主要药动学参数为:β=8×10-4±3.1×10-4 min-1,α=0.3695±0.0654 min-1, T1/2α=1.875±0.856 min, T1/2β=626.12±225.64 min, AUC=2.894×103±892.1 μg · ml-1 · min,V(c)=21.558±2.124 ml · kg-1,Cl(s)=0.116±0.024 ml · kg-1 · min-1.结论 灯盏细辛注射液中灯盏花乙素在SD大鼠体内过程符合静脉注射二室模型.     

冰片对灯盏花素在大鼠体内药动学的影响

目的:观察冰片对灯盏花素在大鼠体内药动学的影响。方法:建立高效液相色谱(HPLC)方法测定大鼠血浆中灯盏乙素的浓度。大鼠尾静脉注射灯盏花素注射液(灯盏乙素24 mg.kg-1)及灯盏花素冰片注射液(灯盏乙素24 mg.kg-1 冰片0.96 mg.kg-1),用HPLC法测定大鼠给药后不同时间血浆灯盏乙素的浓度,BAPP数据处理软件计算药动学参数。结果:灯盏乙素在0.05~60μg.mL-1范围内线性良好(r=0.999 4)。灯盏花素与冰片配伍给药可使灯盏花素中灯盏乙素的药动学参数t1/2α,t1/2β和t1/2γ较单独给药时明显减小[t1/2α:(1.87±0.14)vs(3.46±0.45),P<0.01;t1/2β:(11.18±2.07)vs(14.74±2.89),P<0.05;t1/2γ:(53.31±8.21)vs(161.16±15.48),P<0.01],而K12较单独给药时明显增大[(0.120±0.042)vs(0.039±0.037),P<0.05]。结论:冰片可加快灯盏花素在大鼠体内的分布与消除。     

灯盏花素注射液对重症心力衰竭患者心功能及运动耐量的影响

目的 观察灯盏花素注射液对重症心力衰竭(心衰)患者心功能和运动耐量的影响.方法 将69例心衰患者,心功能(NYHA)分级为Ⅲ～Ⅳ级,随机分为两组:治疗组46例,在心衰常规治疗基础上给予灯盏花素注射液50 mg/d,共14 d.对照组23例予心衰常规治疗.观察心衰患者治疗前后超声心动图和6 min步行试验(6 MWT)的变化.结果 ①治疗组和对照组治疗后临床疗效显效率分别为63.0%和34.8%,差异有统计学意义(P＜0.05);②治疗后治疗组患者左心室射血分数显著升高(P＜0.05),左心室舒张末期内径显著降低(P＜0.05);③两组治疗后6 MWT距离均有所改善,但治疗组治疗后与治疗前比较差异有统计学意义(P＜0.05);④治疗组治疗前后6 MWT距离的升高水平与左心室射血分数增加呈正相关(r=0.72,P＜0.05),而与左心室舒张末期内径缩小呈正相关(r=-0.81,P＜0.05).结论 灯盏花素注射液能明显改善重症心衰患者心功能和运动耐量;6 MWT可作为评价灯盏花素注射液治疗慢性心衰患者疗效评估指标.     

不同厂家灯盏花素注射液指纹图谱研究

目的应用高效液色谱法比较不同厂家灯盏花素注射液的相似度。方法 Hanbon C18(5μm,250nm×4.6nm),柱温25℃,检测波长335nm,流速为1mL/min,流动相:甲醇(A)-0.4%磷酸缓冲液(B)梯度洗脱。结果不同厂家生产的灯盏花素注射液指纹图谱相似度存在较大差别。结论本方法操作简单,稳定可靠,为比较不同厂家的灯盏花素注射液质量提供依据。     

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.