肝动脉栓塞米托蒽醌乙基纤维素微球的研究

利用正交实验设计法,优选适用于肝动脉栓塞的米托蒽醌乙基纤维素微球制备条件和工艺;采用动态透析法研究了该微球的体外释药规律;根据混悬液的稳定性理论,优选并制备了适于临床肝动脉介导栓塞使用的米托蒽醌乙基纤维素微球混悬注射液。结果表明∶在优化工艺条件下制得的米托蒽醌乙基纤维素微球外形圆整,球径在40～200μm范围内的占总数的91.9%,平均球径为110.24±38.19μm;包封率为55.6%;载药量为12.5%;体外释药符合单指数模型,释药方程为lg(Y_∞-Y)=-0.116t-1.198×10^-3(γ=0.9992,t₅₀=2.6h);其混悬液适于临床应用。用狗进行的实验表明肝血药浓度高,平均驻留时间比注射剂长2.45倍。     

联糖米托蒽醌白蛋白微球的制备及其性质研究

以米托蒽醌为模型药物，用乳化热固化法制备了米托蒽醌白蛋白微球。以Ｄ－半乳糖为原料，经溴代、缩合、转换、加成等反应合成了２－亚氨基－２－甲氧基乙基－１－硫化β－Ｄ半乳吡喃糖苷（ＩＭＥ－ｔｈｉｐｇａｌａｃｔｏｓｅ）。以此为中间体与米托蒽醌白蛋白微球在室温下反应制备了联糖米托蒽醌白蛋白微球及其冻干剂，并对冻干剂的形态，球径及其分布、再分散性、糖精密、载药量、体外释药特性进行了研究，为白蛋白微球与联糖白蛋     

均匀设计法优选米托蒽醌毫微球的制备工艺

采用单因素试验法初选，均匀设计方案精选的方法，优选了制备米托蒽醌聚氰基丙烯酸正丁酯毫微球的优化条件和工艺。使其制备工艺快速、简单，适于工业化生产。制得的米托蒽醌毫微球包封率为８４％，载药量为５１％，平均球径为５５．１１±１０．１３ｎｍ。     

米托蒽醌肝动脉栓塞羧甲基淀粉微球的研究

为进一步研究栓塞微球的制备工艺、体外释药规律及药动学与药效学之间的关系,以米托蒽醌为模型药物、羧甲基淀粉钠为载体材料、对苯二甲酰氯为交联剂,经均匀设计法优化了制备空白羧甲基淀粉微球的工艺,用吸附法制备了米托蒽醌载药羧甲基淀粉微球。对载药微球的理化性质进行了研究。并以家兔为模型动物研究了载药微球经肝动脉栓塞给药后的药代动力学情况。结果表明:载药微球的平均算术粒径为75.71μm,含药量为13.21%,吸水膨胀率为71.94%,体外释药符合单指数模型。药动学研究表明,米托蒽醌制成微球经肝动脉栓塞给药后可延长药物驻留于靶位的时间,提示有利于肝癌的治疗。     

米托蒽醌白蛋白微球和糖蛋白微球的体外释药规律

目的：考察米托蒽醌白蛋白微球和米托蒽醌联糖白蛋白球的体外释药规律。方法：采用动脉透析法释药,分光光度法测定米托蒽酯含量。结果：二者在体外释药符合双指数双相动力学规律,但后者达释药平衡快（约6小时）,累积释放量几科比前者小一倍。结论：两种微球的累积药分数经单因数经单因数经方差分析,具有显著差异。     

乳化-溶剂扩散法制备布洛芬乙基纤维素微球

目的制备布洛芬乙基纤维素微球。方法采用乳化-溶剂扩散法制备布洛芬乙基纤维素微球，通过正交试验优选制备工艺；并对所得微球的外形、粒度分布、包封率及释放度等进行了研究。结果该法所制微球呈球形，外观圆整流动性好，粒度分布为80-120μm，包封率可达88％。结论该成球方法重现性好，简单易行，体外释药试验表明所得布洛芬微球有明显的缓释作用。     

阿莫西林—乙基纤维素微型胶囊的研制及缓释性的研究

阿莫西林（羟氨苄青霉素Amokicillin）为常用广谱抗菌药，毒副作用低，但半衰期短；体内仅为1．2h[2]。为延缓释药速度，我们以乙基纤维素为爱材，用液中干燥法[3]将其制成微囊，体外溶出度试验表明【‘1，该微囊和口服国产胶囊相比，具有明显的缓释作用。l材料与仪器阿莫西林原料药（重庆制药六厂）；乙基纤维素40Cpe（江苏昆山年沙助剂厂）；阿莫西林胶囊（重庆制药六厂，批号970207，规格D．259／粒）；JJ－1型定时电动搅拌器（江苏中大仪器厂）；ru－650紫外分光光度仪（美国贝克曼公司）。2方法与结果21微爱的制备：将乙某纤维素‘．…     

载舒尼替尼栓塞微球的制备及体外性质研究

近年来载药微球在栓塞治疗中引起了广泛关注。本研究采用反相悬浮聚合法制备了用于栓塞的聚乙烯醇／丙烯酸微球,首先筛分出粒径在100—1000μm范围的微球,并以舒尼替尼为模型药物,根据离子交换原理制备出载药微球：系统地评价了空白微球（B-Ms）和载药微球（su—Ms）的理化性质：微球的形态、粒径及其分布、平衡含水量、弹性性质等,考察了微球的载药和体外释药的规律。结果显示：微球外观圆整,载药前后微球的粒径均适用于栓塞,载药后微球平衡含水量下降,刚性增加,载药前后微球的弹性均适于栓塞;微球载药量和包封率主要受药液浓度的影响,载药微球在磷酸盐缓冲液（PBS）中缓慢释药,因此,舒尼替尼载药微球具有动脉栓塞治疗的潜在应用价值。     

盐酸维拉帕米脉冲控释微丸的研制

采用流化床包衣法制备盐鞍维拉帕米脉冲控释微丸，并考察了羧甲淀粉钠、经丙甲纤维素和乙基纤维素—聚乙烯砒咯烷酮(4：1，ω／ω)的用量对微丸体外释药的影响。结果表明，该包衣微丸可脉冲释药，其中经丙甲纤维素和乙基纤维素—聚乙烯砒咯烷酮(4：1，ω／ω)用量增加，可延长时滞；羧甲淀粉钠用量增加，释药加快；乙基纤维素—聚乙烯毗咯烷酮(4：1，ω／ω)用量增加，释药减慢。     

氟脲嘧啶微球的研制

报道了氟脲嘧啶明胶微球及其乙基纤维素微球的制备，体外释药及６０Ｃｏ辐射灭菌对药物稳定性的影响。     

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.