灯盏花素亚微乳的制备及大鼠体内药动学

以高速分散-超声法制备了灯盏花素亚微乳,所得制品在透射电镜下呈圆形或椭圆形,平均粒径为(225.0±7.5)nm,?电位为(-42.7±1.3)mV.以灯盏花素注射剂为参比制剂,考察了灯盏花素亚微乳在大鼠体内的药动学.结果显示,灯盏花素亚微乳及其注射剂的体内过程均符合三室模型,t_1/2β为214.1和47.6 min,AUC为294.8和123.7 μg-ml~-1-min,ART为32.5和10.3 min.表明灯盏花素亚微乳能改变灯盏花素的体内消除行为,延长体内滞留时间.     

灯盏细辛注射液生物活性限度测定方法适用性研究

目的：探讨灯盏细辛注射液生物活性测定方法的适用性。方法：经预试验,采用小鼠体内血栓形成试验和急性脑缺血试验、大鼠体内和体外血小板聚集试验,观察不同批号灯盏细辛注射液的药理作用,作为生物活性测定方法和限值确定依据。结果：3批样品中有2批样品小鼠30mL·kg^-1可明显增加血栓形成试验偏瘫恢复数,明显延长急性脑缺血试验小鼠存活时间;大鼠10mL·kg^-1可降低体内血小板最大聚集率,另一批反应较弱。3批样品对ADP诱导大鼠体外血小板聚集率有明显抑制作用,体内体外结果作用趋势相近。结论：灯盏细辛注射液三批样品对不同药理模型呈现不同的活性作用差别,考虑均可作为生物活性测定方法。建议选用其中之1～2种方法和10～30mL·kg^-1限值剂量对产品进行质量内部控制,积累数据,为制定正式标准提供依据。     

灯盏细辛注射液的抗氧化作用

目的探讨灯盏细辛注射液的抗氧化作用。方法对比50例门诊患者（存在胸闷、胸痛、头晕、肢体麻木、言语謇涩、中风偏瘫等症状）接受灯盏细辛注射液治疗前后血浆中的丙二醛,髓过氧化物酶和还原型谷胱甘肽浓度的差异。结果患者静脉滴注灯盏细辛注射液治疗90min后,血浆丙二醛、髓过氧化物酶明显降低[（1．2±0．3）±μmol／L比（1．5±0．3）μmol／L,P=0．0235;（200±48）μg／L比（223±43）μg/L,P=0．0132],还原型符胱甘肽浓度升高[（4．3±2．7）μmol／L比（3．4±1．7）±mol／L,P=0．0489]。结论灯盏细辛注射液可抑制体内氧自由基,升高还原物质含量,发挥抗氧化作用。     

冰片对灯盏花素在大鼠体内药动学的影响

目的:观察冰片对灯盏花素在大鼠体内药动学的影响。方法:建立高效液相色谱(HPLC)方法测定大鼠血浆中灯盏乙素的浓度。大鼠尾静脉注射灯盏花素注射液(灯盏乙素24 mg.kg-1)及灯盏花素冰片注射液(灯盏乙素24 mg.kg-1 冰片0.96 mg.kg-1),用HPLC法测定大鼠给药后不同时间血浆灯盏乙素的浓度,BAPP数据处理软件计算药动学参数。结果:灯盏乙素在0.05~60μg.mL-1范围内线性良好(r=0.999 4)。灯盏花素与冰片配伍给药可使灯盏花素中灯盏乙素的药动学参数t1/2α,t1/2β和t1/2γ较单独给药时明显减小[t1/2α:(1.87±0.14)vs(3.46±0.45),P<0.01;t1/2β:(11.18±2.07)vs(14.74±2.89),P<0.05;t1/2γ:(53.31±8.21)vs(161.16±15.48),P<0.01],而K12较单独给药时明显增大[(0.120±0.042)vs(0.039±0.037),P<0.05]。结论:冰片可加快灯盏花素在大鼠体内的分布与消除。     

灯盏细辛注射液的临床应用

灯盏细辛注射液主要成分为黄酮、黄芩苷、灯盏花乙素,具有活血化淤、通络止痛的功能。近年来在临床广泛应用,现综述如下。1高血压脑出血侯电波等〔1〕采用灯盏细辛注射液治疗高血压脑出血36例,并与常规治疗者36例作对照,结果显示治疗组有效率高于对照组,治疗组血肿吸收时间明显     

灯盏花素在小鼠体内药物动力学研究

目的:研究灯盏花素在小鼠体内的药物动力学和绝对生物利用度。方法:采用固相萃取 高效液相色谱(SPE HPLC)法,测定小鼠静脉注射灯盏花素5 0mg·kg-1和灌胃15 0mg·kg-1后血浆灯盏乙素浓度,3p97程序处理数据。结果:小鼠静注灯盏花素后灯盏乙素的血浓 时间变化符合三房室模型,AUC、C0 和T1 2 β分别为12 .97±3.5 5mg·L-1·h、132 .2 3±39.90mg·L-1和4 .0 4±1.2 9h。灌胃后药物吸收很快,但血浓低。采用非房室模型法计算AUC为1.97±0 .5 3mg·L-1·h ,T1 2Ke 为3.4 1±1.2 3h。绝对生物利用度为5 .0 5 %。结论:灯盏花素经静注在小鼠体内的药代动力学符合三室模型。灌胃给药吸收快,但吸收差,绝对生物利用度低,且药时曲线变化不规则。     

HPLC测定兔血浆中的藁本内酯

目的 采用HPLC测定兔血浆中藁本内酯的浓度.方法 样品经正己烷萃取后进样分析.色谱柱为Kromasil C18(150mm×4.6 mm,5 μm),流动相为甲醇-水(75:25),流速1.0 ml·min-1,检测波长328 nm,测定兔灌胃100 mg·kg-1当归挥发油有效部位后的血药浓度变化.结果 藁本内酯在血浆中的线性范围为0.2～6.4 μg·ml-1,最低检测浓度为0.1 μg·ml-1,日内和日间RSD均小于8%,平均回收率分别为97.18%、93.91%.兔灌胃后,Tpeak=1.28±0.12 h,Cmax=3.86±0.24 μg·ml-1,t1/2α=2.04±0.20 h.结论 所建方法符合生物样品的测定要求,可用于兔血浆中藁本内酯的测定和药物动力学研究.     

HPLC法测定灯盏花素片含量

目的测定灯盏花素片的含量.方法采用高效液相色谱法.色谱柱为C18柱.(10μm,4.6mm×250mm);流动相为甲醇:水(80∶20);流速0.9ml*min-1,检测波长335nm;柱温:室温. 结果灯盏花素片在20μg～80μg*ml-1范围内,线性关系良好,平均回收率为100.2%,RSD为1.53%.结论该法可用于灯盏花素片中灯盏花乙素的含量测定.     

灯盏花乙素苷元对大鼠血栓形成和血液流变学的影响

目的:研究灯盏花乙素苷元对大鼠血栓形成、血小板聚集和血液流变学的影响。方法:大鼠连续灌胃灯盏花乙素苷元(100,50,25 mg.kg-1)7 d。电刺激大鼠颈动脉复制动脉血栓模型,记录血栓形成时间;结扎大鼠下腔静脉复制静脉血栓模型,记录血栓湿重和干重;采用0.5×10-4mol.L-1的二磷酸腺苷(adenosine d iphosphate,ADP)诱导血小板聚集,测定最大聚集率;大鼠皮下注射肾上腺素复制血瘀模型,测定红细胞沉降率、全血表观黏度和血浆黏度。同时设灯盏花乙素(100 mg.kg-1)阳性对照。结果:灯盏花乙素苷元能够明显延缓大鼠动脉血栓形成时间,抑制静脉血栓形成,抑制ADP诱导血小板聚集,降低血瘀模型大鼠的红细胞沉降率和血黏度。结论:灯盏花乙素苷元具有抗血栓形成、抗血小板聚集、改善血液流变学指标的作用,疗效优于灯盏花乙素。     

灯盏细辛注射液连续应用致过敏性休克1例

1 临床资料 患者男,54岁,2003年9月4日因冠心病入院.遵医嘱给予灯盏细辛注射液20 mL(云南生物谷灯盏花药业有限公司,批号:20030508),用0.9%氯化钠注射液250mL稀释后缓慢滴注,1次/d,第1天～2天,均无不良反应且症状减轻,第3天继续应用,当输液进行到5 min时,患者突然出现烦躁不安、面色苍白、呼吸困难、口唇紫绀、四肢冰凉,血压为0,心率为40次/min,心音低钝.考虑系灯盏细辛所致过敏性休克,立即停用灯盏细辛,给予肾上腺素、异丙嗪肌肉注射,并静脉注射地塞米松和参麦注射液,吸氧,行心电图监护、保暖.30 min后,患者呼吸趋于平稳,症状减轻,血压开始回升,60 min后症状完全缓解,呼吸正常,血压升至12/8 kPa.     

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.     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.