HPLC法检查氟马西尼的有关物质

目的建立氟马西尼的有关物质检查方法。方法采用HPLC法,色谱柱为极限AQ-C18,以0.1%柠檬酸溶液-乙腈（68∶32）为流动相,流速为0.80mL.min-1,检测波长为230nm,进样量为20μL。结果氟马西尼在0.0032688-4.086μg范围内线性关系良好;样品溶液在11h内稳定（RSD=0.73%）,最低检测限为8pg。结论与《欧州药典》方法比较,本方法简便快速,结果准确可靠,重现性好,可用于氟马西尼的有关物质检查。     

氟马西尼治疗急性重度苯二氮类药物中毒的临床研究

目的探讨氟马西尼治疗急性重度苯二氮类药物(BZDs)中毒的临床价值.方法将急性重度BZDs中毒患者40例随机分为两组,氟马西尼组20例,常规治疗组20例.疗效评判采用Glasgow～Pittsburgh昏迷深度评定方法和观察者对患者机敏力/镇静程度评判量表(0AA/S)指标.结果治疗组经氟马西尼治疗后昏迷深度显著改善(除5分钟P＜0.05外,其余P＜0.01).以OAA/S指标比较两组疗效差异亦具有显著意义(P＜0.01).结论氟马西尼可作为治疗急性重度BZDs中毒的特效解毒药,且疗效稳定,无明显毒副反应.     

氟马西尼治疗急性重度苯二氮类药物中毒的临床研究

目的探讨氟马西尼治疗急性重度苯二氮艹卓 类药物 (BZDs)中毒的临床价值。方法将急性重度BZDs中毒患者 4 0例随机分为两组 ,氟马西尼组 2 0例 ,常规治疗组 2 0例。疗效评判采用Glasgow～Pittsburgh昏迷深度评定方法和观察者对患者机敏力 /镇静程度评判量表 (OAA/S)指标。结果治疗组经氟马西尼治疗后昏迷深度显著改善 (除 5分钟P <0 0 5外 ,其余P <0 0 1)。以OAA/S指标比较两组疗效差异亦具有显著意义 (P <0 0 1)。结论氟马西尼可作为治疗急性重度BZDs中毒的特效解毒药 ,且疗效稳定 ,无明显毒副反应。     

氟马西尼对抗丙泊酚减弱小鼠学习记忆功能的影响

目的:考察苯二氮受体拮抗剂氟马西尼对丙泊酚所致学习记忆功能减弱的影响。方法:昆明种小鼠40只,随机分为对照组、丙泊酚组、氟马西尼组和氟马西尼+丙泊酚组。训练前20 min皮下注射氟马西尼或生理盐水,训练前10 min腹腔注射脂肪乳或丙泊酚。在跳台实验和避暗实验中观察氟马西尼对丙泊酚导致健忘小鼠错误次数、跳台潜伏期和步入潜伏期的影响。结果:氟马西尼可减少丙泊酚所致健忘小鼠的错误次数,延长跳台潜伏期和步入潜伏期。结论:苯二氮类受体可能是丙泊酚致小鼠学习记忆功能减弱的重要靶位之一。     

硫酸沙丁胺醇有关物质的合成

文章首次将Suzuki-Miyaura偶联反应应用到硫酸沙丁胺醇有关物质的合成中。分别以5-溴-2-羟基苯甲醇、对溴苯酚为起始原料，经苄基保护、Suzuki-Miyaura偶联反应、双键加成、亲核取代、钯炭还原等反应高效合成3个有关物质4-[2-(叔丁基氨基)-1-羟乙基]苯酚(有关物质B)、2,2’-二羟基-4,4’-双-(1-羟基-2-叔丁基氨基乙基)二苯甲醚(有关物质F)和4-[2-(叔丁基氨基)-1-羟乙基]-2-(甲氧基甲基)苯酚(有关物质M)。该合成方法具有通用性和高效性。有关物质B、F和M的结构经高分辨质谱和核磁共振氢谱、碳谱确证。     

比较氟马西尼和纳洛酮在急性苯二氮卓类药物中毒治疗中的疗效观察

目的:研究比较苯二氮卓类受体拮抗剂氟马西尼和阿片受体拮抗剂纳洛酮在急性苯二氮卓类(BZDs)药物中毒患者中的治疗作用。方法随机将60例急性BZDs中毒患者分为氟马西尼组,纳洛酮组和常规治疗组,每组均为20例。疗效分析采用Glasgow—Pittsburgh昏迷观察量表(G—PCS评分)。结果氟马西尼组治疗后1、3和8小时G—PCS得分较治疗前分别增加4．7 7．05 10．05纳洛酮组G—PCS得分分别增加1．45 3．05 9．6常规治疗组G—PCS得分分别增加0．8 2．15 3．8差异具有显著性。结论氟马西尼和纳洛酮治疗急性BZDs中毒均有明显疗效,二者8小时后症状改善无明显差异,但氟马西尼在催醒方面明显优于纳洛酮。     

氟马西尼对苯二氮（艹卓）类药物的拮抗作用观察

氟马西尼化学名为8-氟-5,6-二氢-5-甲基-6-氧代-4 H-咪唑并-［1,5-α］［1,4］苯并二氮（艹卓）-3-甲酸乙酯。氟马西尼对苯二氮（艹卓）类类（ BDZ）受体有很强的亲和力,可竞争性地拮抗BDZ与受体结合,从而消除BDZ的药理作用［1］。笔者对地西泮（安定）或咪达唑仑（咪唑安定）复合静脉全麻术后的4例患者运用氟马西尼拮抗其麻醉苏醒延迟,观察其效果,现报道如下。     

氟马西尼的药理、药效和剂型应用进展

氟马西尼作为苯二氮GFDA1（BDZ）受体拮抗剂,能特异性结合中枢BDZ受体,减少γ-氨基丁酸（GABA）的释放,从而拮抗BDZ类、非BDZ类药物引起的抗焦虑、镇静催眠、麻醉等作用。根据其作用靶点和方式,就目前氟马西尼在临床、科研上的应用和剂型进展做一综述。     

氟马西尼治疗急性苯二氮(艹卓)类药物中毒的疗效观察

目的 探讨苯二氮[艹卓]受体拮抗剂——氟马西尼治疗昏迷的临床价值。方法 随机将61例急性苯二氮[艹卓]类药物（BZDs）中毒患者分为氟马西尼治疗组和对照组、其中对照组30例，用一般治疗和酌情加用呼吸兴奋剂、纳洛酮；治疗组31例，在对照组治疗基础上加用氟马西尼静脉注射。采用Glasgow—Pattoburgh评分量表和观察者对患者机敏力／镇静程度评判量表（OAA／S）进行疗效判断。结果31例BZDs中毒患者经氟马西尼治疗后，5、15、30、60、120和180min Glasgow—Pattoburgh得分较治疗前分别增加了：2．1、5．2、7．3、8．1、8．4、7．3，与对照组各时段比较Glasgow—Pattoburgh得分分别增加了：1．8、4．4、6．4、6．7、6．7、5．4，差异均有统计学意义（P〈0．01）．以OAA／S比较两组疗效．治疗组治疗后平均得分增加2．0，与对照组比较差异也有统计学意义（P〈0．01）。结论 氟马西尼治疗急性BZDs中毒有明显的症状逆转作用，且无严重不良反应。     

氟马西尼治疗苯二氮Zhuo类药物中毒30例

目的：观察氟马西尼治疗苯二氮Zhuo类药物中毒的疗效。方法：将急性苯二氮Zhuo类药物中毒58例随机分为治疗组和对照组，治疗组28例静脉用氟马西尼，对照组30例静脉用醒脑静，两组患者均给予洗胃、导泻、吸氧等一般治疗，并观察患者神志变化、记录催醒时间：结果：治疗组催醒时间明显短于对照组。结论：氟马西尼治疗苯二氮Zhuo类药物中毒疗效好，无严重不良反应。     

Harzianums A and B produced by a fungal strain, Hypocrea sp. F000527, and their cytotoxicity against tumor cell lines

A new compound, harzianum B (1), was isolated from the culture broth of a fungal strain, Hypocrea sp. F000527, together with a known trichothecene, harzianum A (2). Its structure was determined by spectroscopic analyses including HRFAB-MS and various ¹H NMR and ¹³C NMR spectral data. Harzianum B (1) was characterised as (E,Z,E)-2', 4', 6'-octatriendioic acid esterified on the 4β-hydroxyl group of trichodermol. Harzianums A (2) and B (1) showed cytotoxicity against several human cancer cell lines.     

Two new iridoid glucosides from Picrorhiza scrophulariiflora

Two new iridoid glucosides with 3,4-dihydrocatalpol skeleton, piscrosides A (1) and B (2) together with nine known iridoid glucosides and three known cucurbitacin glucosides, were isolated from the stems of Picrorhiza scrophulariiflora. Their structures were established by MS, ¹H NMR, ¹³C NMR and 2D NMR methods (including HSQC, HMBC and NOESY experiments).     

Stilbenoids from Stemona sessilifolia

Two new dihydrostilbenes, stilbostemins H (1), I (2), and a new dihydrophenanthrene, stemanthrene E (3), were isolated and identified from the roots of Stemona sessilifolia, together with known stilbostemins B, D and G, and stemanthrenes A and C (4-8). Structures of new stilbenoids were established by 1D and 2D ¹H NMR and ¹³C NMR spectroscopic analyses.     

氟马西尼注射液细菌内毒素检查方法的建立

目的:建立氟马西尼注射液细菌内毒素的检查方法。方法:按照2010年版《中国药典》(二部)附录细菌内毒素检查法的要求,采用2个不同厂家的鲎试剂对3批氟马西尼注射液进行干扰预试验和干扰试验。结果:供试品溶液质量浓度为0.02 mg/ml及以下时对鲎试剂与细菌内毒素之间的凝集反应无干扰;样品的细菌内毒素限值确定为25 EU/mg。结论:建立的方法可行,可用于氟马西尼注射液的细菌内毒素检查。     

O-methyl nakafuran-8 lactone, a new sesquiterpenoid from a hainan marine sponge Dysidea sp

A new sesquiterpenoid, O-methyl nakafuran-8 lactone (1) has been isolated from a Hainan sponge Dysidea sp. and the structure of the new compound proposed by spectral data, was confirmed by X-ray diffraction analysis. The complete ¹H- and ¹³C-NMR assignments were made on the basis of detailed 2D NMR spectral analysis.

Compound 1 showed strong inhibitory bioactivity against PTP1B with IC₅₀ value of 1.58 μM.     

Cytochalasin D from Hypocrella Bambusae

Cytochalasin D which shows marked cytotoxic effects on multi-tumor cells was newly isolated at high content(5.28 mg/g, dry weight) from Fungus Hypocrella bambusae(B.et Br.) Sacc. Its structure was elucidated by spectroscopic methods. Two-dimensional NMR techniques were applied to make complete assignment for the ¹H- and ¹³C-NMR chemical shifts of this compound.     

Cytotoxic sesquiterpene lactones from Eupatorium lindleyanum

Three new germacrane sesquiterpenes, eupalinolides C-E (1-3), along with three known germacrane sesquiterpenes, eupalinolide A (4), eupalinolide B (5), and 3β-acetoxy-8β-(4'-hydroxytigloyloxy)-14-hydroxycostunolide (6), were isolated from Eupatorium lindleyanum. They were tested for cytotoxicity against A-549, BGC-823, SMMC-7721, and HL-60 tumour cell lines. The results showed that these compounds demonstrated potent cytotoxicity. The structures of the compounds were elucidated by means of ¹H and ¹³C NMR spectroscopic analysis, including 2D NMR experiments.     

Fluorine-19 or phosphorus-31 NMR spectroscopy: a suitable analytical technique for quantitative in vitro metabolic studies of fluorinated or phosphorylated drugs

Fluorine-19 or phosphorus-31 NMR (¹⁹F NMR or ³¹P NMR) spectroscopy provides a highly specific tool for identification of fluorine- or phosphorus-containing drugs and their metabolites in biological media as well as a suitable analytical technique for their absolute quantification. This article focuses on the application of in vitro ¹⁹F or ³¹P NMR to the quantitative metabolic studies of some fluoropyrimidine or oxazaphosphorine drugs in clinical use. The first part presents an overview of the advantages (non-destructive and non-selective direct quantitative study of the biological matrices) and limitations (expensive cost of the spectrometers, limited mass or concentration sensitivity) of NMR spectroscopy. The second part deals with the criteria to be considered for successful quantification by NMR (uniform excitation over the entire spectral width of the spectrum, resonance signals properly characterised by taking into account T₁ values and avoiding NOE enhancements, optimisation of the data processing, choice of a suitable standard reference). The third and fourth parts report some examples of quantification of 5-fluorouracil, its prodrug capecitabine, 5-fluorocytosine and their metabolites in bulk solutions (biofluids, tissue extracts, perfusates and culture media) and heterogeneous media (excised tissues and packed intact cells) as well as cyclophosphamide and ifosfamide in biofluids. These two parts emphasise the high potential of in vitro ¹⁹F or ³¹P NMR for absolute quantification, in a single run, of all the fluorine- or phosphorus-containing species in the matrices analysed. The limit of quantification in bulk solutions is 1–3 μM for ¹⁹F NMR and approximately 10 μM for ³¹P NMR. In heterogeneous media analysed with ¹⁹F NMR, it is 2–5 nmol in excised tissues and cell pellets.     

正电子放射性示踪剂—[~(11)C]氟马西尼注射剂的质量控制研究

目的研究电子放射性示踪药物—[11C]氟马西尼([11C]Flumazenil)的质量控制方法,保证临床用药安全。方法应用高效液相色谱法(HPLC)对[11C]Flumazenil注射剂的化学纯度和放射化学纯度进行检测,并按药典规定对无菌及细菌内毒素等项检查进行测定。结果[11C]Flumazenil注射剂的化学纯度和放射化学纯度分别大于97%和99%,其它各项检测指标也全部合格。结论[11C]Flumazenil注射液的质量符合药用要求,可满足临床安全使用的要求。     

Neolignan and lignan glycosides from branch bark of Davidia involucrata

Two new neolignan glycosides, davidioside A (1) and davidioside B (2), have been isolated along with six known compounds from the branch bark of Davidia involucrata. Identification of their structures was achieved by 1D and 2D NMR experiments, including ¹H-¹H COSY, NOESY, HMQC, and HMBC methods as well as FAB mass spectral data.