盐酸雷尼替丁胶囊溶出度试验方法探讨

目的:测定盐酸雷尼替丁胶囊的溶出度以控制产品质量.方法:照 2000年版<中国药典(二部)>溶出度测定法中第一法(转篮法),以水为溶剂,转速为 100 r/min,45 min时采样;用紫外分光光度法测定盐酸雷尼替丁胶囊的溶出度.结果:盐酸雷尼替丁线性范围为 6～ 20 μ g/mL(r=0.999 9),回收率为 99.7% (RSD=0.9% ,n=5).结论:所用方法准确、可靠、简便、易行,可作为制剂的溶出度测定方法.     

地巴唑片溶出度测定方法的研究

目的:建立地巴唑片溶出度测定方法.方法:以0.1mol/L盐酸溶液为溶出介质,采用紫外分光光度法测定.结果:该方法线性关系良好(r=0.9997),平均回收率为99.82%(RSD=0.51%).结论:本方法适用于地巴唑片的溶出度测定.     

盐酸氯吡格雷片溶出度方法研究

目的:建立盐酸氯吡格雷片溶出度测定方法。方法:根据《中国药典》2010年版溶出度测定方法中的第二法(桨法),以0.1mol·L-1盐酸溶液为溶出介质,转速为50r·min-1,于30min时取样,采用紫外分光光度法在波长270nm处测定吸光度并计算溶出度。结果:盐酸氯吡格雷检测浓度线性范围为50～320μg·mL-1(r=0.9998);平均回收率为99.46%,RSD=0.57%;3批样品溶出度30min时均在85%以上。结论:建立的溶出度测定方法准确、简便,可用于测定盐酸氯吡格雷片的溶出度。     

复方地芬诺酯片体外溶出度试验方法的建立

目的:建立复方地芬诺酯片的体外溶出度测定方法。方法:采用桨法,以盐酸溶液(9→1 000)为溶出介质,转速为75 r/min,溶出取样时间为60 min;采用高效液相色谱法测定制剂中主成分盐酸地芬诺酯的含量。色谱柱为Welchrom C18,流动相为三乙胺磷酸溶液-乙腈(45∶55,pH 3.1),流速为1.0 ml/min,检测波长为230 nm,柱温为30℃。取同批样品6片进行溶出度均一试验。结果:盐酸地芬诺酯检测质量浓度线性范围为0.634⁶.34μg/ml(r=0.999 8),平均回收率为99.30%(RSD=0.89%,n=3);样品溶出度均一性良好(RSD=1.45%,n=6)。11批样品溶出60 min时溶出量为72%6.34μg/ml(r=0.999 8),平均回收率为99.30%(RSD=0.89%,n=3);样品溶出度均一性良好(RSD=1.45%,n=6)。11批样品溶出60 min时溶出量为72%⁹4%。结论:建立的方法快速、简便,可以用于复方地芬诺酯片的质量控制。     

盐酸贝尼地平片溶出度的测定

目的:建立盐酸贝尼地平片溶出度的测定方法。方法:根据《中国药典》2005年版溶出度测定方法第三法(小杯法),以0.1mo·lL~(-1)盐酸为介质,转速为50r·min~(-1),于30min时取样,采用紫外分光光度法在359nm波长处测定吸光度,并计算累积溶出度。结果:盐酸贝尼地平检测浓度线性范围为5～30μg·mL~(-1)(r=0.9999);平均回收率为99.76%,RSD=0.47%;3批样品30min时累积溶出度均在80%以上。结论:所建立的溶出度方法简单、可靠,可用于盐酸贝尼地平片溶出度的测定。     

人工牛黄甲硝唑胶囊中甲硝唑溶出度测定方法考察

目的建立人工牛黄甲硝唑胶囊中甲硝唑的最佳溶出度测定方法。方法采用《中国药典》2010年版二部溶出度测定法第一法(转篮法),以0.1 mol/L盐酸溶液900mL为溶出介质,转速为75r/min,取样时间为20min,采用紫外分光光度法测定溶出量。结果甲硝唑在4.228~21.14μg/mL范围内线性关系良好(r=0.9999);平均回收率为99.8%,RSD为0.5%(n=9)。结论本方法符合溶出度方法的建立原则,可控制人工牛黄甲硝唑胶囊的内在质量。     

盐酸吡格列酮片的溶出度研究

目的　建立盐酸吡格列酮片的溶出度试验方法。方法　以 0 .1mol/L盐酸为溶出介质 ,采用桨法进行溶出度测定 ,转速为 5 0r/min ,温度为 37± 0 .5℃ ,进行累积溶出百分率测定。用紫外分光光度法在 2 6 9nm的波长处测定。结果　该方法线性关系良好 ,回归方程为A =0 .0 2 2C +0 .0 2 9,r=0 .9999(n =8) ,平均回收率为 10 0 .1% ,RSD为 0 .4 4 % (n =9) ,盐酸吡格列酮片各时间的累积溶出量和拟合后提取的参数均无显著性差异。结论　测定方法简便 ,结果准确可靠     

巴洛沙星片溶出度测定方法学研究

目的:建立巴洛沙星片溶出度的测定方法。方法:采用《中国药典》(2005年版)溶出度测定法第二法[1],以盐酸溶液(9→1000)为溶出介质,转速为50 r/m in,进行溶出度测定试验,用紫外分光光度法[1]在294 nm波长处测定吸光度,计算溶出量和累积溶出度。结果:在2~10μg/m l范围内,浓度与吸收度呈良好的线性关系(r=0.999 9),平均回收率为99.8%,RSD为0.64%(n=9),溶出均匀性良好。结论:该方法准确可靠,重现性良好,可用于巴洛沙星片的质量控制。     

盐酸地芬尼多片溶出度测定法的实验研究

目的建立盐酸地芬尼多片的溶出度测定法.方法按照中国药典2000年版二部溶出度测定方法第二法,以水900 mL为溶出介质,转速为50 r·min-1,溶出液采用HPLC法测定盐酸地芬尼多的浓度.HPLC法中选用DiamonsilTM C18柱(200 mm×4.6 mm,5 μm),以甲醇-0.5%三乙胺溶液(用磷酸调节pH至4.0)(60:40,v/v)为流动相,检测波长为220 nm.结果该方法线性范围为6.88～68.80 μg·mL-1,回收率为99.61%,RSD为0.6%(n=9).结论本法简便、准确,为中国药典2005年版建立盐酸地芬尼多片溶出度测定方法提供了依据.     

盐酸洛美利嗪胶囊溶出度研究

目的建立盐酸洛美利嗪胶囊的溶出度测定方法。方法采用桨法,以0.1 mol/L的盐酸溶液为溶出介质,转速为50 r/min,采用反相高效液相色谱法测定。结果盐酸洛美利嗪质量浓度在1.0～12.0μg/mL范围内与峰面积呈良好线性关系(r=0.999 3),平均回收率为99.6%,RSD=1.2%;盐酸洛美利嗪在45 min时平均溶出量均大于75%,且均一性较好。结论该方法快速、简便,结果准确、可靠,重复性好。     

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.

     

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.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.