复方氧氟沙星酮替芬鼻用喷雾剂的制备及质量控制

目的:制备复方氧氟沙星酮替芬鼻用喷雾剂并建立其质量控制方法。方法:以氧氟沙星、富马酸酮替芬、盐酸麻黄碱为主药制备鼻用喷雾剂;采用高效液相色谱法测定其中主药含量。结果:该制剂各项检查均符合鼻用喷雾剂的有关规定;检测浓度氧氟沙星在30～300mg.L-1(r=0.9999)、富马酸酮替芬在20～200mg.L-1(r=0.9998)、盐酸麻黄碱在100～1000mg.L-1(r=0.9998)范围内呈良好的线性关系,平均回收率分别为99.29%(RSD=1.08%)、100.1%(RSD=1.61%)、99.98%(RSD=1.23%)。结论:本制剂制备工艺简单,性质稳定,质量可控。     

复方羟甲唑啉鼻用凝胶的制备及质量控制

目的:制备复方羟甲唑啉鼻用凝胶,并建立其质量控制方法。方法:以盐酸羟甲唑啉与富马酸酮替芬为主要成分,羧甲基纤维素钠为凝胶基质,制备复方羟甲唑啉鼻用凝胶;采用高效液相色谱法同时测定盐酸羟甲唑啉、富马酸酮替芬的含量。结果:该制剂pH及其他检查均符合鼻用凝胶的相关规定,盐酸羟甲唑啉,富马酸酮替芬分别在25～150mg.L-1,75～450mg.L-1范围内,峰面积与其质量浓度线性关系良好,平均回收率分别为100.1%,99.93%;RSD为1.36%,1.34%。结论:该制剂制备工艺简单,质量可控。     

分光光度法测定羟苯乙酯溶液的含量

目的:测定羟苯乙酯溶液中羟苯乙酯的含量.方法:采用紫外分光光度法,羟苯乙酯的测定波长为257.5nm.结果:羟苯乙酯含量为C(mg·L-1)=9.6340A 0.337,r=0.9998.平均回收率为99.06%,RSD为0.50%(n=5).表明浓度2～6 mg·L-1的范围内,吸收度与浓度呈良好的线性关系.结论:该方法简单、快速、准确,适用于该制剂的质量控制.     

毛细管电泳法测定富马酸酮替芬糖浆中富马酸酮替芬的含量

目的:建立毛细管电泳法测定富马酸酮替芬糖浆剂中富马酸酮替芬的含量。方法:以50 mmol·L-1磷酸二氢钾缓冲液为运行缓冲液,运行电压为30 kV,检测波长为301 nm。结果:富马酸酮替芬(以酮替芬计)在16.08～80.40μg·mL-1浓度范围内有良好的线性关系(r=0.9995),回收率为100.1%(n=9)。结论:此方法可用于富马酸酮替芬糖浆剂的含量测定。     

HPLC法测定富马酸酮替芬片的含量

目的:建立富马酸酮替芬片含量测定的HPLC方法.方法:色谱柱:Hypersil ODS C18(5μm,4.6 mm×200mm),流动相:水-甲醇-三乙胺(375:625:0.35),检测波长:300 nnm.结果:富马酸酮替芬在0.01～0.6 mg·ml-1范围内线性关系良好(r=0.999 9,n=5).平均回归率为100.9%,RSD=2.2%.结论:本方法简便,结果准确,重复性好,适用于富马酸酮替芬片的质量控制.     

酮替芬麻黄碱喷鼻剂的制备及质量控制

目的探讨酮替芬麻黄碱喷鼻剂的制备方法及质量标准。方法采用紫外分光光度法测定富马酸酮替芬含量,旋光法测定盐酸麻黄碱含量;以经典恒温加速实验预测该制剂的有效期。结果富马酸酮替芬在7.5~25mg·L-1范围内吸收度与浓度呈良好线性相关,r=0.9999,平均回收率99.99%,RSD为0.41%(n=5);t0.9309d;盐酸麻黄碱t0.9为411d。结论本制剂配制方法简单,质量可控,稳定性较好,有效期暂定为10个月。     

盐酸布替萘芬阴道泡腾片的制备及质量控制

目的制备盐酸布替萘芬阴道泡腾片并进行含量测定.方法用酒石酸、硼酸为酸源,制备盐酸布替萘芬泡腾片,以高效液相色谱法测定盐酸布替萘芬的含量.结果盐酸布替萘芬在60～280 mg·L-1之间线性关系良好(r=0.999 8),平均回收率99.74%,RSD为0.61%,3批样品含量达到99.82%.结论盐酸布替萘芬泡腾片制备工艺简单,所制得盐酸布替萘芬泡腾片的质量符合规定.     

2005年《中华器官移植杂志》征订启事

目的测定羟苯乙酯溶液中羟苯乙酯的含量.方法采用紫外分光光度法,羟苯乙酯的测定波长为257.5nm.结果羟苯乙酯含量为C(mg·L-1)=9.6340A+0.337,r=0.9998.平均回收率为99.06%,RSD为0.50%(n=5).表明浓度2～6 mg·L-1的范围内,吸收度与浓度呈良好的线性关系.结论该方法简单、快速、准确,适用于该制剂的质量控制.     

HPLC法测定富马酸酮替芬片的含量及含量均匀度

目的建立高效液相色谱法测定富马酸酮替芬片的含量及含量均匀度的方法。方法采用Shim-pack VP-ODS C18柱(150mm×4.6mm,5μm);以乙腈-0.04mol.L-1磷酸二氢钾(28∶72)为流动相,磷酸调pH 3.5;流速1mL.min-1;检测波长300nm;柱温为30℃。结果富马酸酮替芬在9.75～97.50μg.mL-1的范围内线性关系良好(r=0.999 6),平均加样回收率为99.3%,RSD为0.4%(n=6)。结论高效液相法简便、快速,重复性良好。     

高效液相色谱法测定盐酸萘替芬的含量

目的:建立非水反相高效液相色谱法测定盐酸萘替芬的含量.方法:采用Phenomenex C18色谱柱(250 mm×4.6mm,5μm),乙腈为流动相,流速1.0 mL·min-1,检测波长254nm.结果:盐酸萘替芬在9.7～29.1 mg·L-1浓度范围内与峰面积线性关系良好,r=0.999 9.平均回收率为100.3%,RSD＜0.78%.结论:本方法简便,快速,准确,可用于盐酸萘替芬的快速含量测定.     

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.     

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.