硫酸沙丁胺空释微丸研究

采秀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，释药速率常数与农膜增重水平的倒数呈线性关系（ｒ＝０．９９２６），在４０℃，ＲＨ７５％的环境中定存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％。     

盐酸地尔硫Zhuo控释微丸的研究

采用包衣法制备衾中速释和缓释两地尔硫Ｚｈｕｏ控释丸。体外溶出试验表明，微丸在最初１ｈ溶出主药２０％之间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％１ｈ。     

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。     

法莫替丁缓释片的研制及体外释药作用

研制了法莫替丁缓释片并测定其体外溶出度。结果表明：该制剂的体外溶出行为符合Ｈｉｇｕｃｈｉ方程，释药速度常数（Ｋ）主要受药物与辅料比例的影响；不同处方的释药速度常数（Ｋ）、释药５０％的时间、释药６３．２％的时间有显著差异（Ｐ＜０．０１）。     

透皮给药动力学的阐述和预测:雌二醇、东莨菪碱和噻吗洛尔

利用动力学模型预测雌二醇、东莨菪碱和噻吗洛尔的血浆药-时曲线,并与最近报道的这三种药物的体内数据进行比较,结果相一致。在动力学模型中,药物从透皮给药制剂中释药的速度常数为K_1,它是通过控释膜的零级速度常数K~0与从紧贴皮肤的胶粘剂中释药的一级速率常数K_1之和。对     

头孢氨苄口腔粘膜粘附片的研究

研制的头孢氨苄口腔粘膜粘附片的体外溶出速率常数K_r=0.2368/h、T_d为3.17h,其重量比溶胀速率常数K_(sw)=5.4088、体积比溶胀速率常数K_(sw)=1.5134,生物粘附强度为1.183±0.009N/cm~2。8名正常受试者颊部使用本品,其释药呈一级动力学过程,K_r=0.7844/h,可缓慢释药3h以上。     

岩白菜素包合物渗透泵片体外释药机制研究

目的探索岩白菜素β-环糊精(β-CD)包合物渗透泵片的体外释药机制。方法通过考察可能影响药物释放的3个因素(包衣膜、片芯和释药孔),探讨其主要的释药动力和零级释药机制。结果水透膜的速率远小于片芯中药物的溶出速率及岩白菜素渗透泵片的释药速率;扩散与溶蚀机制对渗透泵片释药有影响。结论岩白菜素包合物渗透泵片的释药受多种机制共同影响;片芯的渗透压主要由岩白菜素包合物产生;体外释药的限速步骤为水透膜速率,因此渗透泵系统呈现出零级释放。     

双氯芬酸钠控释片剂的初步研究

采用正交设计，以一种进口缓释片为对照，研制了双氯芬酸钠控释包衣片剂。其体外溶出符合零级速率方程，释药速率为３ｍｇ／ｈ，与对照制剂相当，其释药受ｐＨ及转速的影响，衣膜增重百分比的倒数与释药速率成较好的线性关系（ｒ＝０．９９８８），批内及批间释药重现性良好。     

东莨菪碱EVA控释膜的物理化学性质与释药速率关系的研究

考察了东莨菪碱透皮控释膜剂制膜工艺、温度、增塑剂含量、膜厚度等对释药速率的影响。探讨了高分子膜的渗透参数与释药速率的关系,并进行了膜微观结构和热性质的研究。结果显示制膜工艺不同,高分子膜的孔隙率和结晶度有较大差别,可影响药物在膜中的溶解度、渗透参数以及影响控释膜的释药速率。     

曲尼司特缓释片的制备及其释药影响因素研究

目的 制备了曲尼司特凝胶骨架片。方法 采用HPMC K4M、K15M为凝胶骨架材料，进行了处方研究；通过测定制剂体外释放度，评价了该缓释片处方。结果 曲尼司特缓释片体外释药符合Higuchi方程，其释药速率常数Kr为0．193h^1/2。影响缓释片体外释药的因素有骨架材料的种类、用量、粘合剂的种类和释药介质的pH等。结论 缓释片具有明显的缓释作用，可缓慢释药12h。     

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.     

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.