复方盐酸利多卡因巴布膏剂的研制

目的:制备复方盐酸利多卡因巴布膏剂,并考察其黏性和体外释药特性。方法:采用盐酸利多卡因和中药三七组成复方,以水溶性高分子材料为基质制备。采用HPLC法测定制剂中盐酸利多卡因的含量,按2005年版《中华人民共和国药典》方法进行体外释放度、含膏量、赋形性及黏附性的测定,利用改良Franz扩散池研究巴布膏剂中盐酸利多卡因的透皮吸收行为。选择疱疹后神经性疼痛20例,将巴布膏剂贴于皮肤患区最痛处观察临床短期效果和不良反应。结果:复方盐酸利多卡因巴布膏剂中盐酸利多卡因含量为5 mg·cm-2,其体外释放速率为4．128 mg·cm-2·h-1。透皮吸收符合零级动力学过程,盐酸利多卡因渗透速率为0．091 mg·cm-2·h-1。每100 cm2巴布膏剂的含膏量为9．088 g,赋形性良好,初黏力能黏住13号钢球(φ9．525 mm,每个3．55 g)。止痛总有效率达85％,所有病例均未见不良反应。结论:复方盐酸利多卡因巴布膏剂为皮肤控释型透皮给药系统,对于神经性疼痛等具有显著疗效。     

盐酸西替利嗪巴布剂的研制及体外释放特性

目的:制备盐酸西替利嗪(CET)巴布剂并研究其体外释药性能和透皮吸收行为.方法:以水溶性高分子材料为基质制备CET巴布剂,采用HPLC法测定制剂中CET的含量.按2000年版中华人民共和国药典方法进行体外释放度的测定,利用Franz扩散池研究巴布剂的透皮吸收行为.结果:CET巴布剂含量稳定,体外释药符合Higuchi方程,释放速率为0.557 7mg·cm-2·h-1/2.透皮吸收符合零级动力学过程,渗透速率为14.58μg·cm-2·h-1.结论:CET巴布剂为皮肤控释型透皮给药系统,为临床治疗过敏性疾病提供了新的给药途径.     

盐酸格拉司琼凝胶膏剂的研制及其质量评价

目的:研制盐酸格拉司琼凝胶膏剂并对其质量进行评价。方法:以亲水性高分子材料为基质制备盐酸格拉司琼凝胶膏剂。采用HPLC法测定膏剂中药物含量,以体外渗透实验考察不同pH值对盐酸格拉司琼透皮特性的影响,按《中华人民共和国药典》规定的方法测定其体外释放度、含膏量、赋形性和黏附性。结果:溶液pH值(范围3.25~8.35)显著影响盐酸格拉司琼的体外透皮特性,pH 8.35时的渗透速率最大。凝胶膏剂的药物含量为(0.485±0.020)mg/cm2,含膏量为(81.37±1.02)mg/cm2,体外释放速率为0.996 9 mg.cm-2.h-1/2。结论:制备的盐酸格拉司琼凝胶膏剂符合《中华人民共和国药典》的要求,值得进一步开发。     

双藤巴布剂中青藤碱、雷公藤甲素的体外释放与体外透皮机制研究

目的:研究双藤巴布剂中青藤碱、雷公藤甲素的体外释放与体外透皮机制;比较以化学单体入药(青藤碱雷公藤甲素巴布剂,STP)与浸膏入药(双藤巴布剂,STEP)释放速率与透皮速率的差异。方法:通过释放度测定法测定体外释放度;通过Franze扩散池法测定药物的体外透皮性,皮肤为裸鼠背部皮肤。结果:STP与STEP中青藤碱、雷公藤甲素的体外释放以Higuchi方程拟合度较优(STP:r青=0.9955,r甲=0.9958;STEP:r青=0.9920,r甲=0.9963)。经皮渗透较好地拟合了零级动力学方程,青藤碱在STP、STEP中的r分别为0.9951与0.9926,透皮速率分别为21.729μg.cm-2.h-1与20.063μg.cm-2.h-1;雷公藤甲素在STP、STEP中的r分别为0.9942与0.9902,透皮速率分别为0.4783μg.cm-2.h-1与0.4168μg.cm-2.h-1。结论:青藤碱、雷公藤甲素在STP、STEP中的释放速率大于其经皮渗透速率,属于皮肤限速型经皮给药制剂。     

来氟米特贴片的制备及体外释药特性

目的制备来氟米特贴片,研究其体外释药特性和离体透皮吸收行为。方法以聚异丁烯为压敏胶制备来氟米特贴片,采用HPLC法测定制剂中来氟米特的含量,按《中华人民共和国药典》(2000年版)方法进行体外释放度的测定,利用改良Franz扩散池研究贴片的透皮吸收行为。结果该药体外释药特性符合Higuchi方程,释放速率为64.57μg·cm-2·h-1/2。离体透皮吸收行为符合零级动力学过程,渗透速率为5.99μg·cm-2·h-1。结论来氟米特贴片是皮肤控释型透皮给药制剂,为临床治疗类风湿性关节炎提供了新的给药途径。     

氨氯地平贴片的体外释药特性

目的研究氨氯地平贴片体外释药特性和离体透皮吸收行为.方法采用HPLC法测定制剂中氨氯地平的含量,按中国药典方法进行体外释放度的测定,利用改良Franz扩散池研究贴片的透皮吸收行为.结果体外释药特性符合Higuchi方程,释放速率为14.59μg·cm-2·h-1.离体透皮吸收行为符合零级动力学过程,渗透速率为12.73μg·cm-2·h-1.结论氨氯地平贴片是皮肤控释型透皮给药系统,为临床治疗高血压提供了新的给药途径.     

布洛芬巴布剂的制备与体外释放研究

目的 制备布洛芬巴布剂并研究其体外释药性能和透皮吸收行为. 方法 以水溶性高分子材料为基质制备布洛芬巴布剂,采用高效液相色谱(HPLC)法测定制剂中布洛芬的含量. 按《中华人民共和国药典》2010年版二部附录 方法 进行体外释放度的测定,利用Franz扩散池研究巴布剂的透皮吸收行为. 结果 布洛芬巴布剂含量稳定,体外释药符合Higuchi方程,释放速率为1.522 mg.(cm²)^-1.h^-1/2,渗透速率为1.071 mg.(cm²)^-1.h^-1,渗透速率小于释放速率. 结论 布洛芬巴布剂为皮肤控释型透皮给药系统,为临床提供新的给药途径.     

双氯芬酸钠贴片的制备及体外释放、透皮吸收测定

目的:制备双氯芬酸钠贴片,研究其体外释放、透皮吸收性能.方法:制备以聚丙烯酸酯为骨架的双氯芬酸钠贴片,以蛇皮为模型,采用改进Franz扩散池考察药物经皮渗透性能,并按中国药典方法考察了贴片的体外释放性能.结果:双氯芬酸钠贴片体外释放速率为21.98μg·cm-2·h1/2,体外透皮速率为17.97 μg·cm-2·h-1/2.结论:双氯芬酸钠贴片释放度曲线及24 h累计渗透量均符合Higuchi方程,是一种新颖的缓释型外用制剂.     

不同促渗剂对盐酸利多卡因巴布剂透皮的影响

目的：研究促渗剂对盐酸利多卡因巴布剂透皮作用的影响。方法：用紫外分光光度法检测浓度，采用Franz扩散池，用离体小鼠皮肤进行体外透皮扩散试验，计算含不同促渗剂的5％盐酸利多卡因巴布剂的累积渗透量Q及渗透速率是。结果：不同促渗剂对5％盐酸利多卡因巴布剂的累积渗透量Q及渗透速率是的影响大小为：丙二醇〉薄荷脑〉尿素。但只有丙二醇表现出显著性（P〈0．05），尿素和薄荷脑对盐酸利多卡因巴布剂透皮作用基本无影响。5％的丙二醇对其影响最大。结论：提示5％的丙二醇可作为促渗剂在盐酸利多卡因巴布剂中使用。     

不同纯度苦杏仁苷巴布剂的透皮吸收比较研究

目的:比较研究不同纯度的苦杏仁苷提取物制备的巴布剂对小鼠皮肤不同的透过吸收情况,以便确定合适纯度的苦杏仁苷作为经皮制剂给药原料.方法:采用Franz扩散池法,研究各种苦杏仁苷巴布剂中苦杏仁苷的透皮吸收情况;并采用高效液相色谱法检测透过小鼠皮肤的苦杏仁苷的透过量.结果:制得巴布剂中苦杏仁苷的透皮吸收符合Higuchi方程,累积渗透量(Q)与t1/2呈线性关系.纯度为38.7%、61.4%、86.7%的苦杏仁苷巴布剂,累积渗透量分别为2 121.339、1 597.441、1 614.173 μg·cm-2,透皮速率常数(J)分别为969.95、828.26、793.14 μg·cm-2·h-1.结论:苦杏仁苷巴布剂能较好地透过皮肤,且38.7%纯度的透皮效果最好,可以考虑选择该纯度的苦杏仁苷提取物制备巴布剂.     

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.