高效液相测定聚甲酚磺醛栓剂中四种相关物质的含量

目的建立用HPLC法测定聚甲酚磺醛栓剂中四种相关物质的含量。方法色谱柱为DiamonsilC18柱（150mm×4．6mm,5um）,检测波长为265nm,流动相为1％的乙酸铵溶液：甲醇（90：10）条件下测定m-甲酚-4,6-二磺酸铵、m-甲酚-4-磺酸铵,m-甲酚-6-磺酸铵;在捡测波长为280nm,以1％的乙酸铵溶液：甲醇（70：30）为流动相下聚甲酚磺醛二聚体铵,流速均为1．0mL／min,进样量5uL,柱温30℃。结果间甲酚-4,6-二磺酸铵、间甲酚-4-磺酸铵、间甲酚-6-磺酸铵与聚甲酚磺醛二聚体铵分别在0．0402-0．9636μg、0．0567-1．3608μg、0．0526-1．2624μg、0．0572-1．143μg范围内线性关系良好。间甲酚-4,6-二磺酸铵的线性方程为：Y=89806X＋615,r=0．9999;间甲酚-4-磺酸铵的线性方程为：Y=112889X＋1798,r=0．9997;间甲酚-6-磺酸铵的线性方程为：Y=136254X-2164,r=0．9997;聚甲酚磺醛二聚体铵线性方程为Y=259112X-3650,r=0．9994。各组分精密度,稳定性,重复性和回收率RSD均〈3％。结论该法准确性和重复性好,可用于聚甲酚磺醛栓剂的质量控制。     

高效液相色谱法测定聚甲酚磺醛溶液中间甲酚-6-磺酸二聚体含量

目的:用高效液相色谱法测定聚甲酚磺醛溶液中间甲酚-6-磺酸二聚体的含量.方法:采用ODS色谱柱(Shim-pack CLC-ODS,150 mm×6 mm,5μm),流动相为甲醇-1%醋酸铵水溶液(40∶60),检测波长为280 nm,流速为1.0 mL·min-1.采用外标法测定间甲酚-6-磺酸二聚体的含量.结果:间甲酚-6-磺酸铵二聚体在8.24～98.88 mg·L-1浓度范围内线性关系良好,r=0.999 5.结论:本方法快速、可靠、简单、灵敏,适用于该制剂的质量分析检验.     

聚甲酚磺醛原料药及其有关物质的制备

目的 解决聚甲酚磺醛原料的国产化问题.方法 通过间甲酚的磺化、分离和聚合，合成了聚甲酚磺醛原料及其4个有关物质.结果 经HPLC法测定，聚甲酚磺醛和4个有关物质均符合要求，4个有关物质经元素分析、IR、1H NMR和MS确证.结论 国产聚甲酚磺醛原料符合制剂要求。     

聚甲酚磺醛原料药及其有关物质的制备

目的解决聚甲酚磺醛原料的国产化问题。方法通过间甲酚的磺化、分离和聚合,合成了聚甲酚磺醛原料及其4个有关物质。结果经HPLC法测定,聚甲酚磺醛和4个有关物质均符合要求,4个有关物质经元素分析I、R1、H NMR和MS确证。结论国产聚甲酚磺醛原料符合制剂要求。     

HPLC法测定聚甲酚磺醛阴道栓的含量

目的：建立HPLC法测定聚甲酚磺醛阴道栓中聚甲酚磺醛含量的方法。方法：采用PhenomexexLuna-C18色谱柱（150mm×4.6mm,5μm）,以0.5%四甲基氢氧化铵溶液（用磷酸调节pH至4.0）-甲醇（30∶70）为流动相;流速为1.0ml·min-1;检测波长为280nm;柱温为35℃,进样量为20μl。结果：聚甲酚磺醛在10～160g·ml-1范围内峰面积与浓度呈良好的线性关系（r=0.9999）;平均加样回收率为99.35%,RSD=0.92%（n=9）。结论：本方法操作简便,结果准确,可用于该制剂中聚甲酚磺醛的含量测定。     

超临界流体色谱法快速测定甲酚皂溶液中3个甲酚异构体含量

目的:建立超临界流体色谱方法同时测定甲酚皂溶液中3个甲酚异构体的含量。方法:采用ACQUITY UPC~2 Trefoil^TM CEL1(150 mm×3.0 mm, 2.5μm)色谱柱,流动相为二氧化碳-甲醇,梯度洗脱,流速2 mL·min^-1,柱温30℃,样品室温15℃,背压11.7 MPa,检测波长278 nm,进样量1μL。结果:甲酚皂溶液中邻甲酚、间甲酚和对甲酚在3 min内实现分离,相邻主峰间的分离度分别为5.8和7.4。邻甲酚、间甲酚和对甲酚的检测限均为0.8μg·mL^-1,定量限均为2.0μg·mL^-1,线性范围均为4～200μg·mL^-1(r=0.999 9,n=6),平均加标回收率分别为99.0%(n=9),97.5%(n=9)和98.4%(n=9),3批甲酚皂溶液中含甲酚分别为86.8%、86.9%和87.2%。结论:建立的超临界流体色谱方法能快速分离甲酚的3个异构体,操作简单,且极大幅度减少有机溶剂使用量,绿色环保,准确度高,重现性好,可用于甲酚皂溶液中...     

聚甲酚磺醛溶液对家兔阴道黏膜和皮肤刺激性的评估研究

目的:研究聚甲酚磺醛溶液的局部刺激性,以期为临床合理用药提供依据。方法:本实验通过肉眼及病理组织学观察,研究给药期及恢复期聚甲酚磺醛溶液多次给药对完整和家兔破损阴道黏膜及皮肤的刺激性。结果:聚甲酚磺醛溶液对家兔完整及破损阴道黏膜有轻度刺激反应,但无病理性损害;对完整皮肤无刺激反应,对破损皮肤有轻度刺激反应。结论:聚甲酚磺醛溶液具有选择性的凝固作用,对坏死或病变组织可致蛋白质坏死变性脱落,对物理屏障完整的组织则无明显刺激作用;其对屏障损坏后的皮下组织的轻度刺激属药物效应的固有体现,而非不良反应。     

聚甲酚磺醛不同给药方法治疗宫颈糜烂疗效观察

目的探讨聚甲酚磺醛不同给药方法治疗宫颈糜烂的临床疗效。方法对180例宫颈糜烂患者随机分为3组,A组（60例）采用聚甲酚磺醛溶液＋聚甲酚磺醛栓治疗,B组（60例）单用聚甲酚磺醛栓治疗,以C组（60例）为对照组,采用复方莪术油栓治疗。比较3组临床疗效。结果A、B、C组治愈率分别为71．7％、38．3％、6．7％,总有效率分别为100．0％、95．0％、66．7％。3组临床疗效经统计学处理,差异有统计学意义（χ^2=75．38,P〈0．01）,A、B2组临床疗效均优于对照组,且以A组疗效更佳。结论聚甲酚磺醛不同给药方法治疗宫颈糜其疗效不同,其中以聚甲酚磺醛溶液与栓剂联合应用较为合理。     

聚甲酚磺醛治疗宫颈糜烂102例

目的:评价聚甲酚磺醛局部治疗宫颈糜烂的临床疗效.方法:对102例临床诊断为宫颈糜烂的患者用聚甲酚磺醛浓缩液清洗宫颈及阴道,后用稍大于糜烂面的棉块湿以浓缩液贴敷糜烂面3～4 min,qod,共2次,重度糜烂者可用3次.然后嘱咐患者自行隔日上聚甲酚磺醛栓1枚,共6枚.禁止性生活及盆浴2个月.结果:总有效率100.0%,治愈率72.5%.结论:聚甲酚磺醛治疗宫颈糜烂疗效可靠,使用方便,副作用少,有临床使用价值.     

爱宝疗治疗宫颈糜烂50例临床观察

目的:观察聚甲酚磺醛治疗宫颈糜烂的临床疗效。方法:对100例宫颈糜烂患者随机分两组,治疗组用聚甲酚磺醛液和聚甲酚磺醛栓,对照组用康妇特栓塞阴道,治疗前均行宫颈刮片和白带常规检查。结果:两组治疗前后症状比较及两种方法疗效比较均存在显著性差异(P<0.01)。结论:聚甲酚磺醛治疗宫颈糜烂疗效确切,副作用轻微,安全性好。     

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.