紫外分光光度法测定洛索洛芬钠片中洛索洛芬钠的含量

目的：建立紫外分光光度法测定洛索洛芬钠片中洛索洛芬钠含量的方法。方法：采用紫外分光光度法,以水为空白对照,检测波长为223 nm,测定洛索洛芬钠的吸光度。结果：洛索洛芬钠浓度在6.384～21.280μg/ml范围内线性关系良好（r=0.999 9,n=6）,平均回收率99.58%,RSD为0.81%。结论：该法操作快速简便,结果准确,适于洛索洛芬钠片中洛索洛芬钠含量的快速测定及质量控制。     

洛索洛芬钠贴片的研制及质量控制

制备洛索洛芬钠贴片并建立HPLC法测定洛索洛芬钠含量的方法。方法：以羧甲基纤维素钠（CMCNa）和聚乙烯醇（PVP）为材料制备洛索洛芬钠贴片,采用高效液相色谱法测定洛索洛芬钠的含量。结果：洛索洛芬钠的线性范围为4～24μg·ml^-1,r=0．9997。平均回收率为99．99％,RSD为0．99％（n=6）。结论：本制备方法处方组成合理,工艺简单,制剂稳定,建立的HPLC法专属性强、准确可靠,可用于测定贴片中洛索洛芬钠的含量。     

HPLC法测定洛索洛芬钠缓释微丸中洛索洛芬钠的含量

哈药集团三精制药股份有限公司摘要目的:本文通过对洛索洛芬钠微丸的含量测定研究,建立一种高效的含量测定方法,为制备洛索洛芬钠微丸型制剂的安全有效和稳定行提供科学依据。进而为剂型选择,处方设计,工艺及质量控制提供理论基础。方法:采用高效液相色谱法对洛索洛芬钠的含量进行测定。结果:通过方法学考察发现,洛索洛芬钠缓释微丸中洛索洛芬钠的含量稳定性良好,方法适宜。     

RP-HPLC法测定洛索洛芬钠片的含量及有关物质

目的:改进测定洛索洛芬钠片中主成分含量及有关物质的方法。方法:采用反相高效液相色谱法。色谱柱为迪马Inspire C_(18),流动相为乙腈-0.01 mol/L磷酸二氢钾溶液(含0.2%三乙胺,磷酸调节p H至3.0±0.1)(62∶38,V/V),流速为1.0 mL/min,柱温为40℃,检测波长为221 nm,进样量为20μL。结果:洛索洛芬钠峰与相邻杂质峰达到良好分离(分离度>1.5);洛索洛芬钠检测质量浓度线性范围为30.0~90.0μg/mL(r=0.999 8);洛索洛芬钠检测限为0.3μg/mL;精密度、稳定性、重复性试验的RSD<1.0%;回收率为99.00%~99.87%,RSD=0.33%(n=9)。结论:该方法准确、简便、快速,适用于洛索洛芬钠片的质量控制。     

洛索洛芬钠缓释微丸的制备与体外释放度研究

摘 要 目的：制备洛索洛芬钠缓释微丸,并考察其体外释药行为。方法: 采用挤出滚圆法制备洛索洛芬钠载药丸芯,再用Eudragit RL 30D和Eudragit RS 30D 进行包衣,制成洛索洛芬钠缓释微丸,并考察缓释微丸的体外释药行为。结果: 以Eudragit RL 30D和Eudragit RS 30D的比例为20∶80作为洛索洛芬钠载药丸芯的缓释包衣材料,包衣增重为20%,增塑剂用量为10%,滑石粉用量为45%时,制备的洛索洛芬钠缓释微丸在12 h内能够平稳释药且释药完全。结论:制备的洛索洛芬钠缓释微丸释药行为较好,有望应用于工业生产。     

离心造粒包衣法制备洛索洛芬钠缓释微丸及体外释放度考察

目的:制备洛索洛芬钠缓释微丸。方法:采用离心造粒包衣法制备洛索洛芬钠微丸。首先制备微晶纤维素空白母核和洛索洛芬钠含药素丸,并在此基础上进行丙烯酸树脂水分散体(Eudragit NE30D、Eudragit L30D-55)包衣,并对包衣微丸的释药特征进行探讨。结果:微晶纤维素(MCC)空白母核32～40目的收率约78.6%,含药素丸18～24目收率约88.2%,使用Eudragit NE30D和Eudragit L30D-55比例是20:1的包衣液,包衣增重10%。包衣干燥后,即得洛索洛芬钠缓释微丸,洛索洛芬钠缓释胶囊体外释药行为较好地符合Higuchi方程。结论:在优化的工艺条件下可制得表面光滑、圆整度高的洛索洛芬钠缓释微丸。     

洛索洛芬钠缓释微球的制备及体外释药特性考察

目的延缓洛索洛芬钠在局部的作用时间,了解洛索洛芬钠缓释微球的体外释药特性。方法采用乳化-化学交联法制备明胶微球,采用正交试验优化明胶微球的处方和制备工艺;采用流化床包衣技术制备缓释微球;采用透析法考察体外释药特性。结果制备明胶微球最优处方和工艺为:洛索洛芬钠5.0 g,质量分数为20%的明胶溶液100 mL作为水相,含质量分数0.5%Span 80的液体石蜡混合液400 mL作为油相,55℃搅拌下将水相缓缓加入至油相中,500 r.min-1乳化20 min,冰水浴20 min,加入戊二醛使体积分数为50%,交联90 min,4000 r.min-1离心分离10 min,用丙酮、乙醚交替洗涤3次,40℃真空干燥12 h;制备的明胶微球平均粒径为18.25μm,载药量为19.37%,包封率为87.72%,包衣后质量增加25%;洛索洛芬钠缓释微球体外释药过程符合Higuchi方程。结论制备的洛索洛芬钠缓释微球具有明显的缓释作用。     

紫外分光光度法测定洛索洛芬钠片的含量

目的：建立洛索洛芬钠含量的紫外分光光度测定法。方法：采用紫外分光光度法,以水为空白对照,223nm为测定波长,测定洛索洛芬钠的含量。结果：洛索洛芬钠浓度在4.016～20.080μg/ml范围内线性关系良好（r=0.9994,n=5）,平均加样回收率99.13%。结论：该法操作简便、精密度好、结果可靠,适用洛索洛芬钠片含量的快速测定。     

洛索洛芬钠片溶出度测定及体内外相关性评价

参照中国药典2005年版溶出度试验第二法，建立了UV法测定洛索洛芬钠片体外溶出度的试验方法，并用HPLC法测定洛索洛芬钠片的人体药物动力学，进行了体内外相关性的评价。结果表明洛索洛芬钠片体内外相关性良好，提示体外溶出度试验方法合理。     

洛索洛芬钠片剂的人体相对生物利用度研究

目的 :考察健康受试者口服洛索洛芬钠片的药代动力学 ,判断其与进口洛索洛芬钠 2种制剂是否生物等效。方法 :2 0例健康受试者按体重指数进行分层随机交叉服用洛索洛芬钠被试制剂或参比制剂 6 0mg ,采用高效液相色谱法测定血浆中洛索洛芬钠的浓度。结果 :口服 6 0mg洛索洛芬钠被试制剂和参比制剂的主要药代动力学参数分别为 :t1/ 2ke为 (96 .2± 2 3.1)和 (98.2± 17.1)min ;AUC0～t为 (5 6 3.1± 6 7.5 )和 (5 6 5 .4± 90 .8) μg·min·mL-1,Cmax为 (6 .36± 1.32 )和 (6 .0 9± 1.4 0 ) μg·mL-1,Tmax为 (2 3.5± 14 .2 )和 (2 3.0± 10 .2 )min。被试制剂的相对生物利用度为 (10 1.5± 17.4 ) %。结论 :2种制剂具有生物等效性。     

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.