经典恒温法和多元线性模型预测阿魏酸钠注射液的有效期

目的　研究阿魏酸钠注射液的热降解动力学过程,并预测制得的阿魏酸钠注射液的有效期。方法　采用HPLC法测定含量,采用经典恒温法和多元线性模型两种方法计算药物的有效期,同时比较两种方法的特点。结果　阿魏酸钠注射液的降解动力学过程符合一级动力学过程,用经典恒温法和多元线性模型预测阿魏酸钠注射液的有效期分别为1 . 72、1 . 90年。结论　两种方法预测得到的有效期基本一致,多元线性模型可作为一种简便方法用于注射液的有效期的预测。     

经典恒温加速法和多元线性模型预测头孢米诺钠水溶液的稳定性

目的研究头孢米诺钠水溶液的稳定性,并预测其有效期。方法采用高效液相色谱法测定含量,用经典恒温加速法和多元线性模型研究温度对头孢米诺钠水溶液稳定性的影响。结果头孢米诺钠水溶液的降解符合一级动力学过程,测得有2种主要降解物,用经典恒温加速法和多元线性模型预测头孢米诺钠水溶液的有效期分别为3.70、4.17d。结论头孢米诺钠水溶液的热稳定性差,2种方法预测得到的有效期基本一致。     

经典恒温法和多元线性模型预测氯霉素亚砜涂剂的有效期

目的:研究氯霉素亚砜涂剂(氯霉素-二甲基亚砜)的热降解动力学过程,并预测其有效期。方法:采用高效液相色谱法测定氯霉素亚砜涂剂在75、80、85、95℃恒温水浴中放置0、8、16、20、24 h的氯霉素含量;采用经典恒温法和多元线性模型两种方法预测制剂的有效期,同时比较两种方法的特点。结果:经典恒温法取20个数据经5次拟合可得回归方程为lg K=-4 825.3×(1/T)+11.349(r=0.999 0),K25℃为1.470 88×10-5h-1,t0.9为7 165.76 h,活化能为92.46 k J/mol。多元线性模型取8个数据经1次拟合可得回归方程为lnt=1.016 1ln(lnc0-lnc)+11 026.550 1×1/T-25.866 3(r=0.994 2),t0.9为6 794.18 h,活化能为91.73 k J/mol。氯霉素亚砜涂剂降解符合一级动力学方程。用经典恒温法和多元线性模型预测氯霉素亚砜涂剂的有效期分别为9.8、9.3个月。结论:氯霉素亚砜涂剂的有效期约为9.5个月;采用多元线性模型法预测有效期更简便。     

聚维酮碘泡腾栓的稳定性

目的：考察不同条件下聚维酮碘泡腾栓的稳定性。方法：采用加速试验，经典恒温法和多元线性模型预测其有效期。结果：经典恒温法和多元线性模型预测室温贮存期分别为432d和419d。两种方法结果差异无显著性。结论：聚维酮碘泡腾栓贮存期可定为1年，且密闭，阴凉，干燥处保存。     

注射用阿洛西林钠在5%木糖醇注射液中的稳定性考察

目的研究注射用阿洛西林钠在5%木糖醇注射液中的稳定性。方法用高效液相色谱法测定阿洛西林钠的含量,用经典恒温加速法和多元线性模型研究温度对阿洛西林钠在5%木糖醇注射液中稳定性的影响。结果各温度下阿洛西林钠百分含量的对数（lgC）与时间（t）具有线性关系,符合一级动力学反应。用经典恒温加速法和多元线性模型预测阿洛西林钠在5%木糖醇注射液的有效期分别为5.09d,5.59d。结论2种方法预测得到的有效期基本一致。在25℃,注射用阿洛西林钠在5%木糖醇注射液应在5d内稳定。     

复方天宁滴丸制备工艺效应面优化模型的研究

目的 应用星点设计-效应面法优化复方天宁滴丸制备工艺。方法 以PEG6000和棕榈山梨坦(司盘40)为联合基质,以药物的质量分数及PEG6000质量分数为自变量,以丸重差异、溶散时限以及一定时间的阿魏酸溶出度为因变量,对试验数据进行多元线性模型和二项式模型拟合,得出最佳数学模型,绘制效应图和等高线图,再根据效应图优选最佳条件。结果 二项式模型相关系数优于多元线性模型,复相关系数为0.970,复方天宁滴丸最佳处方为药物质量分数23%,PEG6000质量分数47%,模型的理论预测值与实测值偏差较小,模型具有良好的预测性。结论 星点设计-效应面法建立的模型预测性良好,可用于对复方天宁滴丸制备工艺的优化。     

离子电位法测定枸橼酸钾溶液含量及有效期预测

目的建立测定枸橼酸钾溶液含量方法,并考察稳定性,确定有效期。方法运用离子电位法测定枸橼酸钾溶液含量,并与离子交换树脂法比较,同时用经典恒温加速法和留样观察法考察稳定性,确定有效期。结果离子电位法平均回收率99.68%,RSD为0.70%,含量变化符合一级动力学过程,预测有效期为19.9月。结论离子电位法操作简便,测定结果准确,重复性好,可用于枸橼酸钾溶液含量测定。经典恒温加速法可快速预测有效期。     

穿琥宁注射液降解动力学研究

目的：研究穿琥宁注射液在不同pH值、不同温度、不同光照条件下降解反应的动力学参数。方法：用高效液相色谱法测定含量，井运用经典恒温法、多元线性模型探讨其稳定性，用阿累尼乌斯公式预测其有效期和活化能。结果：穿琥宁注射液的降解反应为假一级动力学。结论：穿琥宁注射液在pH值6．0时最稳定，有效期为24个月。为进一步探讨其阵解机制提供必要的实验结果和数据。     

经典恒温法和初匀速法考察注射用替卡西林钠/克拉维酸钾溶液的稳定性

目的研究注射用替卡西林钠/克拉维酸钾(TCS/CLP)的稳定性和有效期。方法用HPLC测定TCS/CLP的含量和有关物质,采用经典恒温法和初匀速法计算有效期。结果TCS/CLP在水溶液中的降解符合一级动力学方程。经典恒温法测得25℃时降解5%的时间分别为25.73、13.94 h。初匀速法测得值分别为24.89、14.00 h。结论两种方法测得数据基本一致,初匀速法可用于预测有效期。TCS/CLP在水溶液中不稳定,应随配随用。     

氧氟沙星注射液的稳定性考察

采用温度指数法和经典恒温法预测氧氟沙星注射液的稳定性，结果表明：氧氟沙星注射液的有效期约为2．5年，两种方法测定结果一致。     

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.