奥沙普秦及其片剂的HPLC测定

建立了测定奥沙普秦及其片剂含量的高效液相色谱法。采用Ｓｈｉｍ－ｐａｃｋ ＣＬＣ－ＯＤＳ为色谱柱，甲醇－水（７８：２２）为流动相，流速１．０ｍｌ／ｍｉｎ，检测波长为２５４ｎｍ，以二苯胺为内标。结果表明奥沙普秦在１３￣７６μｇ／ｍｌ浓度范围内奥沙普秦与内标物峰面积之比与其浓度呈良好线性关系，ｒ＝０．９９９９。精密度试验ＲＳＤ０．１９％，方法回收率为１００．１％。     

奥沙普秦凝胶剂的制备与质量控制

目的:制备奥沙普秦凝胶剂并建立质量标准。方法:以奥沙普秦为主药,卡波姆为辅料制备凝胶剂,采用高效液相色谱法测定奥沙普秦的含量。结果:奥沙普秦在1-6μg·ml-1浓度范围内线性关系良好(r=0．999 8)。结论:奥沙普秦凝胶剂制备工艺可行,含量测定方法简便、准确。     

双点电位滴定法测定奥沙普秦及其片剂的含量

目的：潮定奥沙普秦及其片剂的含量。方法：双点电位滴定法。结果：回收率为99．87％，RSD为0．22％。结论：操作简便、快速、准确取得了满意的结果。     

奥沙普秦肠溶片在健康人体内的药动学

目的建立一种测定人体血浆中奥沙普秦含量的方法,并应用于奥沙普秦肠溶片的药动学研究。方法采用Agilent HPLC系统;色谱柱:Diamoniltm C18柱(150 mm×4．0 mm,5μm)。流动相为乙酸缓冲液(20 mmol·L-1,pH 4．0):甲醇=23:77,流速1．0 mL·min-1,λ=280 nm。结果奥沙普秦线性关系为Y=16．32×ρ-9．03(n=7,r=0．999 7);线性范围0．04～80 mg·L-1;最低检测限为0．012 mg·L-1;日内、日间RSD分别<5．05％、9．75％。结论本方法简便、准确、灵敏,可以作为奥沙普秦肠溶片血药浓度监测的有效方法。     

奥沙普秦壳聚糖-海藻酸钠缓释微球的制备

目的：目的：选择奥沙普秦作为模型药制备壳聚糖-海藻酸钠缓释微球。方法：采用滴制法制备奥沙普秦壳聚糖-海藻酸钠缓释微球，通过正交试验设计优化了处方和工艺，考察其理化特征及体外释药行为。结果：优化处方制得的微球包封率及载药量分别为98．36％和16．26％，平均粒径为（346．6&#177;164．1）μm；1h药物释放达到36％，随后药物的释药行为是一个缓释过程。结论：制得了载药量较大，包封率较高的奥沙普秦壳聚糖-海藻酸钠缓释微球。     

奥沙普秦肠溶片治疗类风湿关节炎的III期临床试验

目的：评价奥沙普秦肠溶片治疗类风湿关节炎的疗效和安全性。方法：多中心开放性临床试验８１２例类风湿关节炎病人（男性３１３例,女性４９９例,年龄４６ａ±ｓ１７ａ）,每日口服奥沙普秦肠溶片２片（４００ｍｇ）,４ｗｋ为一个疗程,连用２～４个疗程。结果：总有效率为７７．１％,不良反应发生率为９．０％,主要出现在胃肠道,程度轻微。结论：奥沙普秦肠溶片治疗类风湿关节炎,不良反应少且轻微,为长效的抗炎、镇痛药。     

指示剂显色比色法测定奥沙普秦含量的研究

目的 :测定奥沙普秦含量。方法 :在 6 0 %中性乙醇 (p H=7.0 )条件下 ,奥沙普秦与甲基红作用显色而进行的指示剂显色比色法。结果 :线形范围为 1～ 2 0 μg/ ml,回收率为 (10 0 .2 4± 0 .72 ) % ,RSD=0 .7(n=5 )。结论 :该法快速准确、操作方便 ,用于样品及原料药中的奥沙普秦的含量测定 ,结果令人满意。     

HPLC法测定奥沙普秦肠溶片的含量

目的 建立高效液相色谱法测定奥沙普秦肠溶片的含量.方法 采用高效液相色谱法,色谱条件:SHIMADZU shim-pack C18色谱柱;流动相:乙腈水(磷酸调节pH至2.5,50∶50):检测波长:286nm;流速:1.0 mL·min1.结果 奥沙普秦在4.224～105.6 μg·mL-1的浓度范围内与峰面积呈良好的线性关系(r=0.999 9),最低检出限为0.02 μg·mL-1,回收率为99.9％,RSD为0.3％.结论 本方法专属性好、准确、灵敏,适用于奥沙普秦肠溶片的含量测定.     

HPLC法测定人血浆中奥沙普秦浓度

目的:建立固相萃取高效液相色法测定人血浆中奥沙普秦浓度的方法,并应用于人体血浆药物浓度测定。方法:固相萃取净化和富集血浆样品。色谱柱为Kromasil C18柱,流动相为0.02 mol/L磷酸二氢钾缓冲液(pH 5.0)-甲醇(85∶15),流速为1.0 ml/min,紫外检测波长285 nm。血浆中内源性物质对样品测定无干扰。结果:本方法奥沙普秦线性范围为0.1～100μg/ml(r=0.999 2),最低定量浓度为0.1μg/ml,回收率为99.39%,日内、日间RSD均小于2%。结论:本法简便、准确,适用于奥沙普秦临床药物浓度测定。     

高效液相色谱法测定人血浆中奥沙普秦的浓度及其生物等效性评价

目的建立人血浆中奥沙普秦浓度的HPLC测定方法,并评价奥沙普秦的药动学特征及2种奥沙普秦的生物等效性。方法 22名男性健康受试者分别单剂量交叉口服受试和参比制剂各0.4 g,采用HPLC法测定人血浆中奥沙普秦的药物浓度,利用Winnonlin 7.0计算药代动力学参数,并计算生物利用度。结果人血浆中奥沙普秦在0.5015～80.24μg·mL~(-1)与峰面积线性关系良好,最低定量限可达0.5μg·mL~(-1);奥沙普秦平均提取回收率大于87.0%;高、中、低3种浓度的批内和批间精密度的RSD值均小于15.0%;受试制剂与参比制剂的主要药代动力学参数如下:t1/2分别为(55.76±10.14)和(50.85±12.34)h,tmax分别为(7.773±9.35)和(6.091±2.599)h,Cmax分别为(59.24±12.07)和(56.05±11.85)μg·mL~(-1);AUC0～264 h分别为(3099±1393)和(3228±1078)h·μg·m L~(-1);受试制剂的相对生物利用度F0～264 h、F0～∞分别为(95.49±17.46)%、(96.12±18.10)%。结论该方法专属性强、简便、准确,适合于奥沙普秦血药浓度的测定。两种奥沙普秦肠溶胶囊生物等效。     

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.

---

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.     

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.     

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.