HPLC同时测定参坤养血颗粒中的毛蕊异黄酮葡萄糖苷、黄芪甲苷、丹参素和党参炔苷

目的：采用HPLC梯度洗脱法同时测定参坤养血颗粒中毛蕊异黄酮葡萄糖苷、黄芪甲苷、丹参素和党参炔苷的含量.方法：Hypersil C18色谱柱（250 mm×4.6 mm,5μm）;流速1.0ml·min-1;流动相A为甲醇-乙腈（3∶2）,流动相B为0.2％甲酸溶液;检测波长λ1=260 nm（检测毛蕊异黄酮葡萄糖苷）,检测波长λ2=210 nm（检测黄芪甲苷）,检测波长λ3=280 nm（检测丹参素和党参炔苷）.结果：毛蕊异黄酮葡萄糖苷、黄芪甲苷、丹参素和党参炔苷分别在0.012 8 ～0.256 0 μg（r =0.999 3）、0.015 2～0.304 0 μg（r =0.999 6）、0.039 4 ～0.788 0 μg（r =0.999 4）、0.100 6～2.012 0 μg（r =0.999 9）范围内进样量与峰面积呈良好的线性关系,平均加样回收率分别为98.19％、97.92％、98.13％、97.80％,RSD（n =6）分别为1.76％、1.41％、1.12％、1.19％.结论：该含量测定方法简便、准确、灵敏、重复性好,可作为参坤养血颗粒的含量控制方法.     

牙周康胶囊的质量标准

目的：建立牙周康胶囊的质量控制方法.方法：采用薄层色谱法（TLC）对牙周康胶囊中的制首乌、赤芍、当归进行鉴别,采用高效液相色谱法测定牙周康胶囊中二苯乙烯苷的含量.结果：TLC斑点清晰,具较好专属性,二苯乙烯苷在0.05～0.43μg范围内呈良好的线性关系（r=0.999 8） 平均回收率为98.51%,RSD=1.71%（n=6）.结论：所建立的方法可用于牙周康胶囊的质量控制.     

肝肾颗粒的制备、质量标准及指纹图谱研究

目的:制备肝肾颗粒,并初步拟定其质量标准,建立其高效液相色谱(HPLC)指纹图谱。方法:以送料速度、压辊速度、压辊压力、压辊间隙为考察因素,颗粒成型率为评价指标,采用单因素试验及正交试验优化肝肾颗粒干法制粒工艺。根据2015年版《中国药典》(四部)(以下简称"药典")对其水分、粒度、溶化性进行测定;采用薄层色谱定性鉴别肝肾颗粒中的枸杞子、黄芪、党参;采用HPLC法定量测定肝肾颗粒中甜菜碱、毛蕊异黄酮葡萄糖苷、党参炔苷的含量,并绘制10批肝肾颗粒的指纹图谱。结果:肝肾颗粒干法制粒的最优工艺为送料速度25 r/min、压辊转速8 r/min、压辊压力7 MPa、压辊间隙1.1 mm,所制颗粒成型率为85.53%。肝肾颗粒的水分、粒度、溶化性均符合药典标准;枸杞子、黄芪、党参供试品薄层色谱在对照品色谱相应的位置上显相同颜色的斑点;甜菜碱的进样量线性范围为4.32～8.64μg,毛蕊异黄酮葡萄糖苷、党参炔苷的检测质量浓度线性范围分别为5～30、10～60μg/mL,精密度、重复性、稳定性(24 h)试验的RSD均<2.0%(n=5),平均回收率分别为97.02%、99.25%、101.04%(RSD均<1.7%,n=6或9),含量分别为4.298、0.054、0.025 mg/g;10批肝肾颗粒样品HPLC指纹图谱与对照指纹图谱相似度均>0.95。结论:优化后的肝肾颗粒制粒工艺稳定、可行,所建立的质量标准及HPLC指纹图谱可为肝肾颗粒的质量控制提供依据。     

UPLC-MS/MS法同时检测大鼠血浆中参芪扶正注射液主要成分的含量及其药动学

目的：建立超高效液相-三重四极杆质谱联用（UPLC-MS/MS）法同时测定大鼠血浆中黄芪甲苷、毛蕊异黄酮-7-O-β-D葡萄糖苷和党参炔苷的浓度,研究参芪扶正注射液在大鼠体内的药动学。方法：血浆样品加入适量内标,50%甲醇-乙腈沉淀蛋白,离心后取上清进样。采用ACE Excel 1.7 C₁₈柱（50 mm×2.1 mm,2.1 μm）,柱温：40℃,流速：0.6 mL·min^-1,流动相由0.1%甲酸水和0.1%甲酸-乙腈组成,采用梯度洗脱,分析时间2.5 min。质谱采用ESI源,正离子检测。大鼠尾静脉注射参芪扶正注射液浓缩液,眼眶采血测定血浆中药物浓度,药动学参数以DAS 3.0软件处理。结果：黄芪甲苷、毛蕊异黄酮-7-O-β-D葡萄糖苷、党参炔苷的浓度分别在5~2 000 ng·mL^-1、2~800 ng·mL^-1、10~4 000 ng·mL^-1内均呈良好线性关系（R ≥ 0.991 5）;日内、日间精密度良好,RSD均小于13.3%（n=6）;提取回收率均在79.0%~97.1%之间,RSD均小于11.4%（n=6）。药动学结果表明,黄芪甲苷、党参炔苷和毛蕊异黄酮-7-O-β-D葡萄糖苷在大鼠体内的AUC_0-t分别为（38.84±17.20）、（23.11±6.84）、（5.32±0.36）μg·min·L^-1,t_1/2分别为（56.44±28.25）、（47.48±9.54）、（10.01±4.42）min,CL分别为（0.15±0.06）、（1.18±0.47）、（0.47±0.11）mL·min^-1·kg^-1。结论：本法简便、快速、灵敏度高、专属性好,可用于参芪扶正口服液大鼠血浆中黄芪甲苷、毛蕊异黄酮-7-O-β-D葡萄糖苷和党参炔苷的含量测定及药动学研究。     

妇康颗粒的质量控制

目的 建立妇康颗粒的质量标准. 方法 对制剂中的黄芪、川芎、牡丹皮、赤芍进行了薄层鉴别;采用薄层扫描法测定了妇康颗粒中黄芪甲苷的含量. 结果 薄层图谱斑点清晰, 分离度好, 易于分辩;黄芪甲苷平均加样回收率为97.9%, RSD为1.2%;结论 该法操作简便, 准确可靠, 可用于妇康颗粒的质量控制.     

参芪肝康片质量标准研究

目的探讨参芪肝康片质量标准。方法采用薄层色谱法鉴别制剂中的当归、五味子、菌陈和黄芪，用高效液相色谱法测定制剂中绿原酸含量。结果绿原酸进样量在65～650ng范围内与峰面积线性关系良好（r=0.99995），平均回收率为98.45％，RSD为0.99％（n=9）。结论所建立的方法简便、快捷、准确，能很好地控制参芪肝康片的质量。     

益肝康口服液的制备及质量标准研究

目的:制备益肝康口服液并建立其质量标准。方法:采用薄层色谱(TLC)法对方中黄芪、党参、丹参进行定性鉴别;采用高效液相色谱(HPLC)法对党参炔苷进行含量测定。结果:TLC中特征斑点明显;党参炔苷检测浓度在0.036~1.317mg·mL-1范围内与峰面积积分值呈良好线性关系(r=0.9999);平均加样回收率为100.10%,RSD=1.70%(n=6)。结论:制备方法简便、可靠;所建标准可用于益肝康口服液的质量控制。     

康瘫丸的质量标准

目的：建立康瘫丸的质量标准。方法：用薄层色谱法对康瘫丸中的黄芪、赤芍、羌活、当归进行定性鉴别;HPLC法测定制剂中芍药苷含量;检测波长230nm,流速1．0ml·min^-1。结果：薄层色谱斑点清晰,芍药苷在21．6～216．0μg·ml^-1浓度范围内线性关系良好（r=0．9999）,平均回收率为99．5％,RSD为1．15％（n=6）。结论：本方法简便、准确,可控制该制剂的质量。     

乳核分散片质量标准的建立

目的：建立乳核分散片质量标准,以更好地控制其质量.方法：采用薄层色谱法鉴别处方中三棱、香附、当归、郁金、蒲公英等药味,运用高效液相色谱法测定制剂中芍药苷、橙皮苷含量.结果：TLC色谱斑点清晰.芍药苷在0.098～0.343 mg·ml-1范围内呈良好线性关系（r=0.999 3）,平均回收率98.48%,RSD=1.80%（n=6）;橙皮苷在0.032～0.112 mg·ml-1范围内线性关系良好（r=0.999 0）,平均回收率98.15%,RSD=1.70%（n=6）.结论：该方法准确、可靠,可用于乳核分散片的质量控制.     

一测多评法测定升提颗粒中8种成分的含量

目的 建立同时测定升提颗粒中党参炔苷、紫丁香苷、毛蕊异黄酮葡萄糖苷、芒柄花素、芸香柚皮苷、柚皮苷、橙皮苷和新橙皮苷含量的一测多评法(quantitative analysis of multi-components with single-marker, QAMS)。方法 该药物甲醇提取液的分析采用Agilent HC-C_(18)色谱柱(4.6 mm×250 mm, 5μm);柱温为30℃;流动相为乙腈(A)-1 mL·L^(-1)甲酸溶液(B);流速为1.0 mL·min(-1)甲酸溶液(B);流速为1.0 mL·min^(-1);梯度洗脱;检测波长为254 nm(检测党参炔苷、紫丁香苷、毛蕊异黄酮葡萄糖苷和芒柄花素)和283 nm(检测芸香柚皮苷、柚皮苷、橙皮苷和新橙皮苷)。以毛蕊异黄酮葡萄糖苷为内参物,建立与其他7种成分的相对校正因子,检测各成分的含量。结果 党参炔苷、紫丁香苷、毛蕊异黄酮葡萄糖苷、芒柄花素、芸香柚皮苷、柚皮苷、橙皮苷和新橙皮苷的质量浓度分别在2.99～74.75、0.53～13.25、1.36～34.00、2.09～52.25、4.87～121.75、24.45～611.25、1.81～45.25、12.54～313.50μg·mL(-1);梯度洗脱;检测波长为254 nm(检测党参炔苷、紫丁香苷、毛蕊异黄酮葡萄糖苷和芒柄花素)和283 nm(检测芸香柚皮苷、柚皮苷、橙皮苷和新橙皮苷)。以毛蕊异黄酮葡萄糖苷为内参物,建立与其他7种成分的相对校正因子,检测各成分的含量。结果 党参炔苷、紫丁香苷、毛蕊异黄酮葡萄糖苷、芒柄花素、芸香柚皮苷、柚皮苷、橙皮苷和新橙皮苷的质量浓度分别在2.99～74.75、0.53～13.25、1.36～34.00、2.09～52.25、4.87～121.75、24.45～611.25、1.81～45.25、12.54～313.50μg·mL^(-1)范围内有较好的线性关系(r≥0.999 1);平均加样回收率(RSD%)分别为99.02%(0.58%)、98.13%(1.46%)、99.35%(1.51%)、96.78%(1.40%)、99.39%(0.76%)、100.08%(0.62%)、97.71%(1.27%)、99.36%(0.85%);QAMS计算结果与外标法(external standard method, ESM)实测值无明显差异。结论 建立的方法易操作,结果准确,能用于升提颗粒中党参炔苷、紫丁香苷、毛蕊异黄酮葡萄糖苷、芒柄花素、芸香柚皮苷、柚皮苷、橙皮苷和新橙皮苷含量的测定。     

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.