青风藤总生物碱聚乳酸微球的制备

聚乳酸(PLA)及其共聚物具有良好的生物相容性和生物降解性,在人体内无积聚,最终可完全降解为二氧化碳和水.PLA微球可用于制备生物降解型缓释或定向给药体系[1,3],具有广泛的应用前景.     

聚乳酸乙醇酸的生物降解和安全性研究进展

聚乳酸乙醇酸(PLGA)的降解主要是通过酯键水解,自催化作用和巨噬细胞吞噬;水解产物为乳酸和乙醇酸,均可代谢分解生成二氧化碳和水,分别通过肺和肾排出体外,仅有微量的原型聚合物经尿液排出,体内没有蓄积现象.PLGA具有良好的生物相容性和可生物降解性,作为组织工程支架和药物控释系统材料是安全的.美国食品药品管理局(FDA)已经批准将PLGA作为组织工程细胞支架和药物载体,在美国、日本市场应用多年,未见严重的不良反应报道.目前国产PLGA的质量和控释微球药品的开发研究仍需要提高,尤其是制剂的载药量、控释技术以及稳定性技术.介绍PLGA的生物降解与安全性研究进展,为开发PLGA控释系统提供参考.     

聚乳酸载药微球的制备及应用研究进展

目的介绍聚乳酸载药微球的研究情况。方法查阅数据库相关文献,较全面介绍了聚乳酸载药微球的制备方法及应用现状。结果聚乳酸载药微球具有良好的生物相容性、生物降解性、靶向性和控释性,在目前应用中还存在一些问题。结论聚乳酸载药微球在药学领域有着广阔的发展前景。     

聚乳酸-羟基乙酸载药微球控制体外释放因素的研究进展

体外释放行为研究是为了能够更好地反映微球在体内的释药状况,有利于筛选出更理想的处方及工艺.体外释放度试验是微球制剂释药速度的体外评价方法,可以了解制剂的生物药剂学特点和预测药物在体内的释放和吸收,使体外释放获得的数据能与体内数据具有相关性.体外释放度实验是常用的微球制剂体外释药速度的评价方法.建立体内外相关性后就能以体外实验代替体内实验来测定生物利用度和生物等效性.根据药物的性质、给药途径和释药时间,选用不同的聚乳酸-羟基乙酸(PLGA)采用相应的制备工艺;通过调整PLGA的组成、分子量、载药量及粒径的大小等因素,能控制药物达到不同的释放速度或程度.     

影响聚酯微球中药物释放的因素

聚酯材料因其原料易得、容易加工、生物相容性好、具有可生物降解性等优点,已经成为当今药物载体材料中的一大研究热点。现综合国内外的有关报道对可生物降解聚酯材料作为药物载体制备微球制剂的研究进展进行了综述。针对目前限制聚酯材料微球制剂临床应用存在的问题,从聚合物、药物、制备工艺、附加剂、辐射灭菌5个方面对影响聚乳酸(PLA)和聚乳酸乙醇酸共聚物(PLGA)缓释微球中药物释放的因素进行了重点介绍,为研究聚酯微球中药物的释放提供思路。     

聚乳酸微球生物降解机制和生物相容性研究进展

介绍了人工合成高分子材料聚乳酸（PLA）的性质，综述了PLA和乳酸／羟基乙酸共聚物（PLGA）微球的生物降解性和生物相容性。其生物降解为均匀降解，材料相对分子质量及其分布对降解行为有很大影响。注射微球的组织反应分为3个阶段，做组织相容性考察时应注意药物或生物活性物质的细胞毒性、抗原性和愈合作用对组织反应的影响。     

抗癌药物白蛋白微球的研究进展

为提高抗癌药物对癌细胞或组织的靶向性,增强疗效,降低其全身毒副作用,以不同材料作载体的抗癌药物微球相继研制成功:不可生物降解的乙基纤维素微球,可生物降解的白蛋白微球、淀粉微球、明胶微球、聚乳酸微球,以及近年来问世的磁性微球、毫微球等。白蛋白微球以其良好的生物相容性和可降解性被广泛用于抗癌药靶向给药系统。 白蛋白微球最初用于动物及人的肺部扫描和循环系统研究,自1974年首次作为抗癌药物载体以来,相继用作诊断试剂及靶向给药、化学栓塞治疗的载体。1 抗癌药物动脉栓塞白蛋白微球 肿瘤动脉栓塞疗法是将抗癌药物制剂选择性注入支配     

聚乳酸载药微球的制备及修饰研究进展

聚乳酸(PLA)是一种新型的高分子聚合物,不溶于水、乙醇,可溶于二氯甲烷(DCM)、丙酮等.PLA无免疫原性,它以玉米为主要原料,合成及改性技术已经趋于成熟[1].PLA和乳酸-羟基乙酸共聚物(PLGA)都具有良好的生物相容性,在体内最终代谢为二氧化碳和水,是可用于人体的生物降解材料.PLA有良好的力学性能[2],也有亲水性不足等缺点,为改善药物的靶向性及释药速度,常需要对其进行修饰.与其他靶向释药系统相比,微球具有制备较简单、稳定性好、成本低等特点,为近年来研究的热点[3].不过有些PLA微球的包封率和载药量低,突释及体内生物降解而造成药物难以在最恰当的时间内释放,以至于有些制剂尚难以应用于临床.本文从制备和修饰方面综述近几年PLA微球的研究进展.     

局部应用环孢素A聚乳酸微球的性状及释药研究

目的对局部应用环孢素A聚乳酸微球的性状及其在体外、体内释放进行研究。方法通过采用O/W型乳化-溶剂挥发法制备环孢素A聚乳酸微球。观察微球分散度、粒径及外观形态及体外释药特性,对比全身与局部给药后全血中及气管组织中的环孢素A药物浓度。结果环孢素A聚乳酸微球的形态圆整,平均粒径18.234μm,跨距:1.131,粒径在9.525～32.400μm者占总数的80%以上。包封率为(86.1±0.8)%,载药量为(34.5±0.6)%。环孢素A聚乳酸微球的体外释药情况:30d的累积释药量为40.8%,采用局部埋植微球后前2周可以维持较高的血药浓度,2周后也可以维持在200ng/ml的药物浓度。结论环孢素A聚乳酸微球具有较好的缓释性能。局部应用可获得有效的血药浓度,在局部气管组织中的药物浓度高于全身用药组。     

阿霉素聚乳酸微球的制备及体外释药特性研究

目的:对阿霉素聚乳酸微球的制备工艺、含量测定及体外释药特性进行初步研究.方法:以人工合成可生物降解聚合物聚乳酸为载体,采用乳化-溶剂挥发法制备阿霉素聚乳酸微球,用UV-260紫外分光光度计测定其药物含量和体外释药量.结果:所制备的阿霉素聚乳酸微球外形圆整,算术平均球径为55.2 μm,载药量为30.21 μg*mg-1,12 h体外累积释药量36%.结论:聚乳酸微球具有很好的控释能力,使用前景广阔.     

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.