注射用盐酸米诺环素在健康人体的药物动力学

目的：研究注射用盐酸米诺环素在健康人体内的药物动力学。方法：10名健康志愿者单剂量静脉滴注200mg注射用盐酸米诺环素,采用HPLC测定血浆中米诺环素浓度,计算药动学参数。结果：10例健康受试者单剂量静脉滴注200mg盐酸米诺环素,主要药动学参数t1/2为（18．1±4．07）h;Cmax为（4．744±0．887）mg／L;tmax为2．0h;AUC0→72h为（75．71±10．68）mg·h／L;AUC0→∞为（79．90±12．81）mg·h／L。结论：受试制剂注射用盐酸米诺环素在人体内的药代动力学特征与文献报道一致。     

反相高效液相色谱法测定注射用盐酸米诺环素含量

目的：测定注射用盐酸米诺环素中米诺环素的含量，并对其色谱条件进行筛选。方法：采用反相高效液相色谱法，检测波长为280nm。结果：平均加样回收率为99．9％，RSD为0．95％。结论：可采用此方法测定注射用盐酸米诺环素中米诺环素的含量。     

浊度法测定盐酸米诺环素胶囊的效价

目的建立浊度法测定盐酸米诺环素胶囊的效价。方法以金黄色葡萄球菌为试验菌，加菌量为0．5％～1．0％（V／V），于（37±0．5）℃培养约4h后测定。结果抗生素线性质量浓度为0．03～0．10U／mL，二剂量法的平均回收率为99．77％，RSD为2．2％（n=9）。结论该方法灵敏、快速，影响因素较少，可作为盐酸米诺环素胶囊效价的测定方法。     

盐酸米诺环素HPLC的流动相探讨

目的：建立新的HPLC流动相分析方法，使米诺环素与甲基米诺环素达到有效的分离，测定准确的米诺环素含量。方法：流动相为醋酸铵缓冲溶液(pH6.55)：乙腈：甲醇-830：185：5，检测波长为280nm，流速为1．0ml／min，进样量为2μl。结果：米诺环素与甲基米诺环素的分离度大于2．3，线性范围在0．2mg／ml-2mg／m1，r=0．9999；回收率为99．22％，95％可信限范围为99．22 0．52％(n=9)，RSD=1．14％。     

不同厂家盐酸多西环素有关物质含量比较

目的比较不同厂家盐酸多西环素原料的含量及有关物质，并分析样品稳定性变化趋势。方法采用改良的反相高效液相色谱法，以C18色谱柱，在药典使用的流动相中加入甲醇[0．05mol／L草酸铵溶液：二甲基甲酰铵：0．2mol／L磷酸氢二铵：甲醇（50：36：4：10）]为流动相，检测波长280nm，流速0．9ml／min，柱温35℃。结果多西环素在2．500～249．956μg／ml浓度内线性关系良好。r=1．000（n=8）；日内以及日间的精密度（RSD）分别为0．79％、0.73％；回收率为98．0％（RSD=1．04％）。各原料有关物质总量在1．5％～2．7％之间，苛刻条件下放置过程中多西环紊可转变成美他环素使有关物质明显增加。结论改良后的溶剂系统检测有关物质灵敏度和准确性高。不同厂家原料质量存在明显差异，虽然都符合中国药典，但应加强内部质量控制。     

HPLC法测定注射用氟氯西林钠氨苄西林钠的含量及有关物质

目的 建立注射用氟氯西林钠氨苄西林钠含量的HPLC测定方法。方法 使用C18柱。以磷酸二氢钾（0．1mol／L）：十二烷基硫酸钠（0．012mol／L）：甲醇：乙腈（280：300：200：220）（用磷酸调pH值至2．8）为流动相，检测波长为225nm。结果 氟氯西林钠与氨苄西林钠的线性范围均为0．03～0．60mg／ml。r均为0．9999。氟氯西林平均加样回收率为99．9％，RSD为0．6％（n=9）；氨苄西林钠平均加样回收率为99．9％，RSD为1．2％（n=9）。结论 该方法简便、准确、灵敏度高。同时对产品中的有关物质能进行准确控制。     

高效液相色谱法测定盐酸米诺环素的含量及有关物质

目的本文建立了盐酸米诺环素含量及有关物质的HPLC测定方法,并同时考察了全国数批盐酸米诺环素原料的含量及有关物质。方法使用C8柱,以0.2mol/L醋酸铵-N,N二甲基甲酰胺-四氢呋喃(600∶398∶2,内含0.01mol/L乙二胺四乙酸二钠)为流动相,检测波长为280nm。结果盐酸米诺环素的线性范围为0.1 mg/m l~2.0 mg/m l,r为0.9999,盐酸米诺环素的平均加样回收率为100.7%,RSD为0.5%(n=9)。结论方法准确、灵敏度高,本方法可有效地控制药品质量。     

高效液相色谱法测定盐酸米诺环素胶囊及片剂的溶出度

目的:建立测定盐酸米诺环素胶囊及片剂溶出度的高效液相色谱法.方法:采用桨法,以水为溶剂,转速为50r/min,45 min取样滤过,进样.Kromasil C8柱(4.6 mm×250 mm,5μm),以0.2 mol/L醋酸铵:N,N-二甲基甲酰胺:四氢呋喃(600:398:2,内含0.01 mol/L乙二胺四乙酸二钠)为流动相,检测波长为280 nm.结果:盐酸米诺环素线性范围是0.10～2.00mg/mL,r=0.999 9.平均回收率盐酸米诺环素胶囊为98.6%,RSD为1.4%(n=9),盐酸米诺环素片剂为98.8%,RSD为1.2%(n=9).结论:该方法简便、准确、灵敏度高,能有效控制产品质量.     

HPLC法测定清热通淋合剂中盐酸小檗碱的含量

目的：建立HPLC法测定清热通淋合剂中盐酸小檗碱含量的方法。方法：采用Diamonsil ODS（4．6hm×150nm×5μm）色谱柱，检测波长（2）=346 nm，流动相：妒（磷酸二氢钾）=0．05mol／L（三乙胺调至pH7．5）-乙腈（75：25）。结果：盐酸小檗碱在9．2-46．0mg／L浓度范围内，线性关系良好（r=0．9996），平均回收率为98．40％，RDS=1．48％（n=5）。结论：该法操作简便，结果正确，重现性良好，可作为测定清热通淋合剂中盐酸小檗碱含量，以控制该制剂质量。     

高效液相色谱法测定茶碱麻黄碱片中茶碱与盐酸麻黄碱含量

目的用高效液相色谱（HPLC）法测定茶碱麻黄碱片中茶碱与盐酸麻黄碱的含量。方法采用Kromasil C18柱（150mm×4．6mm，5μm），流动相为0．05mol／L磷酸二氢钾溶液-甲醇-三乙胺（72：28：0．2），检测波长为215nm，流速为1．0mL／min，柱温为42℃。结果茶碱质量浓度的线性范围为22．34～111．7μg／mL，r=0．9999（n=6），平均回收率为99．85％，RSD为0．14％（n=9）；盐酸麻黄碱质量浓度的线性范围为5．17～25．86μg／mL，r=0．9997（n=6），平均回收率为99．25％，RSD为0．39％（n=9）。结论HPLC法简便易行，结果准确，重现性好。     

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.

---

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.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.