口服胸腺肽微球的研究

目的：制备胸腺肽微球,并研究其性质。方法：以邻苯二甲酸醋酸纤维素为成球材料,胸腺肽为球心物,制备工艺经均匀设计优化。结果：得到白色粉末状微球。微球载药量３１．２±１．４％。平均粒径１５．６ｍ。微球在ＨＭ胃液中２ｈ释药不超过１０％,在人工肠液中２ｈ释药１００％。微球给大鼠灌胃后,ＨＰＬＣ测得大鼠血中胸腺肽浓度在２～３ｈ最高。结论：制备的胸腺肽微球可口服吸收。     

促肝细胞生长素口服肠溶微球的制备

以促肝细胞生长素为多肽大分子模型药物，利用能在结肠ｐＨ值较高的环境下溶解的邻苯二甲酸醋酸纤维素为材料，经优化工艺制备口服结肠释放微球。粒径５～１５μｍ者占总数７７．８％，平均粒径１２．７μｍ，建立了微球中载药量的测定方法，测得为２９．７±２．５％。微球在人工胃液中２ｈ释药未超过１０％，而在ｐＨ７．２的磷酸盐缓冲液中１ｈ释药达９８％。     

Influence of Preparation Factors on the Sustained Release of Nifedipine from Eudragit RL/RS Microspheres

用乳剂—溶剂挥发法制备硝苯地平的丙烯酸树脂缓释微球。微球中药物的释放速度随丙烯酸树脂ＥｕｄｒａｇｉｔＲＬ／ＲＳ比率的增加以及制备时搅拌速率的增加而增大，随内相聚合物浓度的增加及微球粒径的增加而减小，释药５０％所需时间与微球粒径呈良好线性。微球的释药速率也随药物含量的增加（从４．２％到１６．７％）而增大，并快于药物结晶的溶解速率，但药物含量达２６．６％时，微球释药速率明显下降并低于药物结晶的溶解速率。用差热分析和Ｘ射线衍射分析证明，药物含量为４．２，９．４和１６．７％的微球中药物完全是以非晶态分散的，而含药２６．６％的微球中有药物结晶存在。不同微球释药低于７０％时，释放方式均符合Ｈｉｇｕｃｈｉ时间平方根方程。     

口服促肝细胞生长素微球的研究

以邻苯二甲酸醋酸纤维素为成球材料、促肝细胞生长素为球心物，制备工艺经均匀设计优化，制得类白色粉末状微球。高效液相色谱（HPLC）测得微球包封的药物图谱与促肝细胞生长素的HPLC图谱一致。微球载药量量29．7±2．5％，平均粒径127um。微球在人工胃液中2h释药不超过10％，在人工肠液中2h，释药100％。微球给大鼠灌胃后，HPLC测得大鼠血中促肝细胞生长素浓度在2．5h最高。     

盐酸川芎嗪肺靶向微球理化性质的研究

考察了盐酸川芎嗪肺靶向微球的微粉学性质、热解稳定性、载药量和体外释药模式。结果表明，微球为类白色圆球状粉末，平均算术粒径为１２．６５μｍ，５～２４．９μｍ，粒径范围的微球数占总数的８７．５％，平均堆密度为０．５９ｇ／ｍｌ，休止角为６８．６３°，临界相对湿度为５６％，热解活化能为８１．６ｋＪ／ｍｏｌ，反应级数为１。用ＵＶ法测得微球载药量为１７．０％，微球体外释药符合一级动力学规律。微球粒径符合肺靶向要求     

硫酸沙丁胺醇控释微丸研究

采用膜控法制备沙丁胺醇控释微丸。体外释放试验表明,其释药速度符合零级动力学过程,释药速率常数为９．７１％／ｈ。在一定膜厚范围内,释药速率常数与衣膜增重水平的倒数呈线性关系（ｒ＝０．９９２６）;在４０°Ｃ、ＲＨ７５％的环境中贮存３个月,质量稳定。健康志愿者服用后,血药浓度较为平缓,达峰时间、半衰期明显延长,具有缓释效果。其平均相对生物利用度为普通片的９６．２％。     

心脏靶向超声造影剂空气白蛋白微球的研究(1)

按正交设计筛选了用发射超声能量合成白蛋白空气微球的较佳制备工艺,并对微球的形态、粒径与粒径分布、稳定性、安全性和显影效果进行了系统研究。结果表明：微球的平均直径为 ４．２±０． ２ μｍ,平均浓度为（３．５±１．２）×１０８／ｍｌ。９２．５％的微球直径小于１０μｍ,微球在２℃～５℃条件下能稳定储存１２个月,经兔外用静脉注射后能顺利通过肺微循环到达左心室致使左心室靶向超声显影。     

肝动脉栓塞米托蒽醌乙基纤维素微球的制剂学研究

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，采用动态透析法模拟体内情况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观圆整，球径在４０～１５０μｍ范围内的占总数的８６．５％，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ｌｏｇ（Ｙ∞－Ｙ）＝－０．１１６ｔ－１．１９８×１０（－３）（ｒ＝０．９９９２，ｔ（５０）＝２．６ｈ）；其混悬注射液理化性质稳定，可适于临床应用。     

胺碘酮治疗风湿性心脏病合并慢性心房颤动20例临床观察

随机选择风湿性心脏病二尖瓣狭窄合并慢性房颤共２０例,门诊１８例,住院２例现分析报告如下。１临床资料与方法１． １病例选择男 ９例,女 １１例;年龄 ２１～ ４０（平均 ３ ０．５）岁;病程２～１０（平均７．５）年;房颤时间６个月～２（平均１．３）年;心功能：Ⅱ级１５例,Ⅲ级５例。２０例均未做过其它复律治疗。１．２治疗与观察方法口服第１周０．２ｇ,１日３次;第２,３周０．２ｇ,１日２次,第４周以后,０．２ｇ／ｄ·次,个别０．１ｇ／ｄ·次。复律成功者继续服此药０．１ｇ／ｄ维持,服药前后除询问病史和体查外,…     

盐酸地尔硫卓控释微丸的研究

采用包衣法制备含有速释和缓释两部分的地尔硫控释微丸。体外溶出试验表明，微丸在最初１ｈ溶出主药２０％之后以缓慢平稳的速度持续释药，其释药曲线与对照制剂恬尔心缓释胶囊接近，零级释药速率常数为７．２５％／ｈ。其释药速度受介质ｐＨ的影响，但受转速的影响较小。控释微丸在４０℃、相对湿度７５％时贮存３个月，质量稳定。     

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.     

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.     

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.     

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.