盐酸阿比朵尔微乳的制备及其质量评价

目的:研制阿比朵尔微乳并对其质量进行评价。方法:选用肉豆蔻酸异丙酯作为油相,蓖麻油聚氧乙烯醚-40、聚山梨酯-20和聚山梨酯80-司班20(质量比为49∶51)分别作为表面活性剂,乙醇、正丁醇和异丙醇作为助表面活性剂。再通过滴定法制备伪三元相图的基础上,根据相图优选处方,分别考察微乳制剂的稳定性、形态粒径;用高效液相色谱(HPLC)法测定微乳中阿比朵尔的含量。结果:以蓖麻油聚氧乙烯醚-40为表面活性剂和乙醇作为助表面活性剂形成微乳系统。阿比朵尔微乳稳定,透射电镜下呈圆球形,分布均匀,平均粒径为28.4nm,呈Gauss分布。用RP-HPLC法测定回收率为100.18%,RSD为0.51%(n=6)。结论:采用微乳作为药物载体制备口服阿比朵尔微乳,为开发阿比朵尔微乳新型口服制剂提供了依据;HPLC检测方法可靠,重复性好。     

杨梅素微乳的制备及质量评价

目的制备杨梅素微乳,并评价其质量。方法选择适宜的油相、表面活性剂和助表面活性剂,利用伪三元相图筛选微乳处方,研制出适合经口给药的微乳制剂;采用HPLC法测定杨梅素的含量,并对微乳的类型、载药量、体外释放等进行考察。结果优选处方为聚山梨酯80-聚山梨酯20-乙醇-油酸-pH 6.5磷酸缓冲液的质量比20∶10∶15∶5∶50,杨梅素质量分数为2%。所制微乳外观透明,平均粒径为(56.3±8.7)nm,zeta电位为-2.73 mV,电导率为13.27 mS.m-1。载药微乳在不同pH值环境下对药物有良好的释放效果。结论通过优化处方制备的杨梅素微乳具有较稳定的理化性质,HPLC法可以有效、准确的测定杨梅素微乳的含量,并且微乳载药系统有良好的释药效果。     

两种硝酸异山梨醇酯缓释胶囊的人体药动学比较

目的 :选择 12名男性健康志愿者 ,进行单剂量口服硝酸异山梨醇酯缓释胶囊的人体药动学研究。方法 :采用毛细管气相色谱法 ,测定单剂量口服 4 0mg国产与进口硝酸异山梨醇酯缓释胶囊在健康人体内的硝酸异山梨醇酯浓度。结果 :硝酸异山梨醇酯缓释胶囊的体内动态过程呈一级吸收的二房室开放模型 ,国产与进口缓释胶囊的Cmax分别为 (2 3.6± 6 .2 ) μg·L-1和 (2 3.7± 5 .1) μg·L-1,tmax分别为 (3.3± 0 .6 )h和 (3.8± 0 .6 )h ,MRT分别为 (9.1± 0 .8)h和 (9.1± 0 .7)h ,t1/ 2 分别为 (8.2± 1.0 )h和 (8.1± 0 .9)h ,AUC0～ 2 4分别为 (12 6 .3± 15 .4 ) μg·h·L-1和 (12 4 .0± 14 .1) μg·h·L-1,AUC0→∞ 分别为 (139.4±14 .8) μg·h·L-1和 (136 .7± 13.8) μg·h·L-1。结论 :国产与进口硝酸异山梨醇酯缓释胶囊具有相似的人体药动学特征     

复方单硝酸异山梨醇酯缓释片人体生物等效性研究

目的 :评价试验制剂复方单硝酸异山梨醇酯缓释片 (T)与参比制剂单硝酸异山梨醇酯缓释片和阿司匹林肠溶片 (R)的生物等效性 ,以及缓释制剂释放特点、稳态血浓度和波动度。方法 :采用高效液相色谱法分别测定单剂和多剂交叉给药单硝酸异山梨醇酯和阿司匹林代谢物水杨酸经时血浓度 ,计算药物动力学参数 ,并进行方差分析和双单侧t检验。结果 :单剂给药试验制剂和参比制剂单硝酸异山梨醇酯半衰期 (t1 2 )分别为 8.3± 0 .6、8.2± 0 .6h ,血浓度峰值 (Cmax)分别为 0 .5 1± 0 .0 9、 0 .5 3±0 .0 9mg·L-1,达峰时间 (tmax)分别为 4 .8± 0 .4、4 .6± 0 .3h ,药时曲线下面积 (AUC0 -t)分别为 4 .90±0 .6 1、5 .2± 0 .8mg·h-1·L-1,相对生物利用度 (F)为(96 .1± 10 .8) % ;试验制剂和参比制剂阿司匹林代谢物水杨酸t1 2 分别为 2 .4± 0 .3、2 .5± 0 .3h ,Cmax分别为 3.4± 0 .5、3.0± 0 .4mg·L-1,tmax分别为 1.7±0 .2h和 4 .9± 0 .3h ,AUC0 -t分别为 13.4± 2 .5和13.0± 2 .5mg·h-1·L-1,以水杨酸计阿司匹林F为(10 3.6± 9.6 ) %。多剂给药试验制剂和参比制剂单硝酸异山梨醇酯Cmax 分别为 0 .6 8± 0 .14、0 .6 7±0 .13mg·L-1,Cmin 分别为 0 .17± 0 .0 3、 0 .17±0 .0 4mg·L-1,波动系数 (DF)     

醛糖还原酶抑制剂依帕司他胶囊和片剂的人体生物等效性

目的 :评价依帕司他胶囊和片剂的人体生物等效性。方法 :2 0名健康男性受试者 ,随机分为 2组 ,分别于早晨空腹一次口服依帕司他胶囊或片剂5 0mg。 1wk后再交叉服药。用HPLC法测定依帕司他血药浓度。结果 :依帕司他胶囊和片剂的主要药动学参数 ,Tmax为 (1.7±s 0 .4 )h和 (1.6± 0 .6 )h ,Cmax为 (4 .0± 0 .9)mg·L- 1和 (4 .3± 1.1)mg·L- 1,MRT为 (1.6± 0 .3)h和 (1.6± 0 .4 )h ,T1/2 为(1.7± 0 .6 )h和 (1.4± 0 .3)h ,AUC0 8为 (10 .9±2 .1)mg·h·L- 1和 (11.4± 2 .8)mg·h·L- 1,AUC0 ∞为 (11.1± 2 .2 )mg·h·L- 1和 (11.5± 2 .8)mg·h·L- 1。依帕司他胶囊相对生物利用度为 (10 0±2 2 ) %。结论 :依帕司他胶囊与片剂具有生物等效性     

国产与进口去氧氟尿苷胶囊在肿瘤病人体内药动学与生物等效性比较

目的 :以进口去氧氟尿苷胶囊为对照 ,考察国产去氧氟尿苷胶囊的药动学及 2种制剂的生物等效性。方法 :10名肿瘤病人随机双交叉口服 2种胶囊 80 0mg ,采用HPLC法测定药物的血药浓度。结果 :进口和国产去氧氟尿苷胶囊的药动学参数———Cmax分别为 (5 .1± 1.4 )mg·L- 1,(4.6± 1.2 )mg·L- 1;Tmax分别为 (1.0± 0 .4 )h ,(0 .8± 0 .4 )h ;AUC分别为 (6 .5± 1.7)mg·h·L- 1,(6 .0± 1.6 )mg·h·L- 1。国产去氧氟尿苷胶囊相对生物利用度为 (95± 12 ) %。结论 :2种制剂生物等效     

头孢他美酯片人体相对生物利用度研究

目的比较南京海光应用化学研究所研制的头孢他美酯片与意大利罗氏药厂生产的头孢他美酯片的人体相对生物利用度.方法20名健康成年男子,采用随机分组自身交叉对照试验设计方法,分别单剂量口服500mg国产和进口头孢他美酯片剂.用HPLC法测定头孢他美的血药浓度.结果参比药和试验药的主要药动学参数分别为T1/21.96±0.29和1.96±0.29hTmax2.55±0.74和2.45±0.67h;Cmax3.72±0.94和3.56±0.89mg·L-1;AUC0-120.06±5.04和19.29±4.94mg·h·L-1;试验药头孢他美酯的相对生物利用度为96.75±12.18%.结论经统计分析,两种制剂为生物等效制剂.     

液质联用研究5—单硝酸异山梨醇酯缓释胶囊人体生物等效性

目的评价国产和进口5-单硝酸异山梨醇酯缓释胶囊在人体生物等效性研究.方法18名健康受试者随机交叉给药,分别单次(40mg)及多次口服进行人体生物等效性研究,用液相色谱/质谱联用测定血浆中5-单硝酸异山梨醇酯的浓度.结果经数据处理,单次口服国产和进口5-单硝酸异山梨醇酯缓释胶囊的AU0-36分别为7490±1144μg·h·L和7355±1007μg·h·L-1,tpeak分别为4.92±1,31h和4.67±0.79h,Cmax分别为519.15±60.53μg·L-1和523.67±68.99μg·L-1;多次口服达稳态时AUC0-36分别为8514±1318μg·h·L-1和8586±836μg·h·L-1,tpeak分别为4.83±0.94h和4.75±1.14h,Cmax分别为570.44±78.89μg·L-1和580.43±64.04 μ g·L-1,波动系数FI分别为135.10±15.53%和134.82±9.71%.国产5-单硝酸异山梨醇酯缓释胶囊单次给药及多次给药稳态时的相对生物利用度分别为101.9±7.3%和99.1±11.9%.结论单次及多次给药所得梯形法计算的两者的AUC0-36、Cmax、tpeak进行方差分析和双单侧检验结果表明两者具有生物等效性.     

高效液相色谱法测定比格犬血浆中伏立康唑及其药物动力学研究

目的 建立高效液相色谱法(HPLC)测定Beagle犬血浆中伏立康唑(咪唑类抗真菌药)的方法 ,并比较伏立康唑冻干粉针(参比制剂)和伏立康唑亚微乳(受试制剂)的药动学特点.方法 采用Diamonsil C18柱(250 mm×4.6 mm,5 μm),流动相为乙腈-水-乙酸 (55∶45∶0.25,v/v/v),流速为1.0 mL·min-1,外标法测定.结果 在选定的HPLC条件下伏立康唑与血浆杂质分离良好,伏立康唑的线性范围为0.2~50.0 mg·L-1,定量下限为0.2 mg·L-1.提取回收率为97.37%~110.00%,日内和日间RSD均小于10%,Beagle犬静脉滴注伏立康唑亚微乳及冻干粉针后的平均血药浓度-时间曲线符合二室模型,主要药动学参数:t1/2分别为(6.88±1.16) h和(6.82±1.73) h,Ke分别为(0.107±0.025) h-1和(0.109±0.031) h-1,AUC(0~∞)为(136±47.5) mg·h-1·L-1和(179±48.3) mg·h-1·L-1,MRT0~∞为(9.51±1.83) h和(9.35±2.75) h,消除率为(1.01±0.45) mL·min-1·kg-1和(0.68±0.21) mL·min-1·kg-1.结论 该方法 灵敏度高,无杂质干扰,结果 准确.两种制剂具有类似的药动学行为,可为伏立康唑亚微乳临床研究提供科学依据.     

国产和进口单硝酸异山梨酯缓释胶囊单次和多次给药的人体药动学(英文)

目的 :比较国产和进口单硝酸异山梨酯缓释胶囊的人体药动学和相对生物利用度。方法 :采用单次和多次给药的 4周期双交叉设计 ,气相色谱 电子捕获检测法 (GC ECD)测定 2 2名健康男性志愿者血浆中单硝酸异山梨酯的浓度。结果 :单次 (2 5mg)口服国产和进口单硝酸异山梨酯缓释胶囊后的药动学参数分别为 :Tmax为 (5 .7±s 0 .5 )h和 (5 .8±1 .0 )h ,Cmax为 (2 3 6± 62 ) μg·L-1和 (2 42± 62 )μg·L-1,T1/ 2 为 (8.3± 1 .6)h和 (8.4± 2 .1 )h ,AUC0 3 6为 (3 .7± 0 .9)mg·h·L-1和 (3 .6±0 .9)mg·h·L-1,AUC0 ∞ 为 (4 .0± 0 .9)mg·h·L-1和 (3 .8± 0 .8)mg·h·L-1,平均滞留时间MRT为 (1 1 .5±0 .8)h和 (1 1 .4± 0 .7)h。多次 (2 5mg,6d)口服国产和进口单硝酸异山梨酯缓释胶囊后的稳态药动学参数分别为 :Tmax 为 (5 .2± 0 .7)h和 (5 .4±0 .9)h,Cmax为(3 1 4± 67) μg·L-1和 (3 1 0± 5 8) μg·L-1,Cmin为(63± 1 4) μg·L-1和 (65± 1 6) μg·L-1,稳态血药浓度均值Cav为 (1 87± 3 8) μg·L-1和 (1 83± 3 8) μg·L-1,AUC0 3 6h为 (5 .0± 1 .0 )mg·h·L-1和 (4 .9± 1 .0 )mg·h·L-1,波动度DF为 (1 3 4± 2 0 )%和 (1 3 4± 1 8) %。单次和多次口服国产与进口单硝酸异山梨酯     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.