正交法考察盐酸洛美沙星葡萄糖注射液制备工艺

目的对盐酸洛美沙星葡萄糖注射液生产工艺过程的影响因素进行实验考察,寻求最佳生产工艺。方法通过正交设计考察pH、加炭量、温度和加热时间4个因素对盐酸洛美沙星含量的影响,选用L16（4^5）正交表进行实验。结果活性炭对盐酸洛美沙星有明显吸附作用,在pH值为4．8,加炭量为0．02％,温度为50℃及加热时间为10min的优化条件下,活性炭对盐酸洛美沙星的吸附量最小。结论生产过程中应对上述影响因素进行控制,提高产品质量。     

均匀设计法考察影响活性炭吸附替硝唑的因素

目的：对活性炭吸附替硝唑的因素进行实验考察。方法：通过均匀设计法对影响活性炭吸附替硝唑的影响因素如药物浓度、ｐＨ值、加炭量、温度和加热时间等进行考察。结果：实验证明,活性炭对替硝唑有明显的吸附作用,在替硝唑浓度为２．０％,ｐＨ值为４．０,加炭量为０．０２％,温度为６０℃及加热时间为１０ｍｉｎ的优化条件下时,活性炭对替硝唑的吸附量最小。结论：配制替硝唑葡萄糖注射液时要对上述影响因素进行控制,提高产品     

均匀设计法考察乳酸环丙沙星葡萄糖注射液制备工艺

目的:考察活性炭吸附环丙沙星的影响因素.方法:通过均匀设计法对药物浓度、pH值、加炭量、温度和加热时间等因素进行考察.结果:活性炭对环丙沙星有明显的吸附作用,在环丙沙星浓度为2.0%,pH值为5.0,加炭量为0.02%,温度为60℃及加热时间为10 min的优化条件下时,活性炭对环丙沙星的吸附量最小.环丙沙星在pH 3.0～5.0时稳定性好.结论:配制环丙沙星葡萄糖注射液时要对上述影响因素进行控制,提高产品质量.     

正交试验优选乳酸左氧氟沙星葡萄糖注射液的制备工艺

目的:优选乳酸左氧氟沙星葡萄糖注射液的制备工艺。方法:采用正交试验法,选用L16(45)正交表进行试验,考察pH值、加炭量、加热温度和加热时间4因素对乳酸左氧氟沙星含量的影响。结果:确定最佳制备工艺条件为pH=4.2～4.8、加炭量0.1%、加热温度50℃、加热时间10min。结论:按该工艺制备的成品质量符合要求。     

活性炭对盐酸洛美沙星的吸附考察

目的：考察不同量、不同温度、不同pH时活性炭对注射液中盐酸洛美沙星含量的影响。方法：注射液中分别加入不同量的活性炭在60℃恒温搅拌30min后过滤工，测定盐酸洛美沙星含量。结果：随活性炭用量增加，注射液中盐酸洛美沙星含量明显降低；随温度升高，活性炭吸附能力略有升高；活性炭吸附盐酸洛美水利生影响不大。结论：在实际工作中根据活性炭的加入量的情加大洛美沙星的投入量，在不增加投入的情况下，活性炭的用量宜控制在0.03%-0.1%左右。     

替硝唑注射液生产工艺的探讨与改进

目的探讨优化替硝唑生产工艺在实际工作中的应用。方法用正交试验优选法，考察了活性炭用量、初配液的pH值、初配液浓度、灭菌温度和灭菌时间几个因素对其成品质量的影响。结果采用活性炭用量为0．5％，初配液pH值为4．5，初配液浓度为50％，灭菌温度为110℃，灭菌时间为50min为最佳配制工艺条件，成品合格率和澄明度均提高。结论正交试验优选法是替硝唑注射液成品质量生产工艺中考察活性炭用量、初配液的pH值、初配液浓度、灭菌温度和灭菌时间等因素的最佳方法。     

活性炭的吸附作用对盐酸洛美沙星注射液含量的影响

目的：了解不同浓度的活性炭及不同的加热时间对盐酸洛美沙星的吸附作用。方法：考察不同的加热时间和不同的活性炭浓度,对盐酸洛美沙星注射液含量的影响。结果：随着活性炭用量的增加、加热时间的延长,其含量逐渐降低。结论：可采用直接投料配制。     

替硝唑葡萄糖注射液制备工艺研究

目的：探讨替硝唑葡萄糖注射液制备过程中相关因素对其质量的影响,以确定其最佳生产工艺。方法对pH值、药用炭加入量、配制时间、灭菌温度等因素进行考察,检查有关物质变化情况。结果根据实验考察数据,得出生产替硝唑葡萄糖注射液的最佳生产工艺条件为：控制配制pH值在4.0~4.5,药用炭使用量定为0.01%,放置时间不超过10 h。结论优化后的替硝唑葡萄糖注射液生产工艺可行,质量可控,适用于工业化大生产。     

影响活性炭吸附替硝唑的因素探讨

目的　考察影响活性炭吸附替硝唑的因素。方法　在不同炭量 ,不同温度 ,不同吸附时间下进行活性炭的吸附实验。结果　活性炭量 ,温度 ,吸附时间都分别对活性炭的吸咐产生影响。结论　将替硝唑药液加热 90℃ ,再加 0 .3g· L-1活性炭并保温吸液 2 0min。     

正交试验优选复方甘草酸单铵氯化钠注射液制备工艺

目的用正交试验方法优选复方甘草酸单铵氯化钠注射液的制备工艺。方法采用正交试验,选择活性炭用量、中间体pH、微孔滤芯孔径、活性炭吸附温度4个因素,每个因素安排4个水平,按L16（4^5）安排正交试验,用2个指标的加权评分值判定工艺优劣,试验结果进行方差分析。结果活性炭对甘草酸单铵有明显吸附作用,影响成品率的主要因素为活性炭及pH。在主药浓度、吸附时间固定时,加炭0．05％、中间体pH=6．5、吸附温度70℃、滤芯孔径0．22μm的优化条件下,活性炭对甘草酸单铵吸附较少、产品热原检查合格、澄明度、成品率最高。结论配制复方甘草酸单铵氯化钠注射液时要对各影响因素进行控制,避免原料损失,提高成品率及产品质量。     

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.