复方氯唑沙宗的药理和临床应用

复方氯唑沙宗片是由氯唑沙宗和对乙酰氨基酚组成的中枢骨骼肌松弛剂,已被列入美国21版药典。氯唑沙宗和对乙酰氨基酚有镇痛协同作用。临床验证表明:复方氯唑沙宗片疗效优于氯唑沙宗片。 1 药理作用研究 1.1 肌肉松弛作用:以小鼠攀网法肌松作用比较,复方氯唑沙宗片与氯唑沙宗片都具有肌肉松弛作用,且呈剂量依赖性,ED_(50)复方氯唑沙宗片为195.72±37.83mg/kg,氯唑沙宗片为187.50±34.40mg/kg,若将复方制剂的ED_(50)以其中所含氯唑沙宗的剂量计算,其ED_(50)仅88.97mg/kg,低于单方应用氯唑沙宗。     

复方氯唑沙宗胶囊人体生物等效性研究

目的:比较复方氯唑沙宗胶囊与片剂的生物等效性。方法:20名男性健康志愿者,双交叉于试验当日晨空腹一次口服试验制剂复方氯唑沙宗胶囊、参比制剂复方氯唑沙宗片各2粒/片,于给药前及给药后0.25、0.5、0.75、1.0、1.5、2.0、2.5、3.0、4.0、5.0、6.0、8.0、10.0、12.01、5.0 h取肘静脉血,剂间间隔为1周。高效液相色谱法同时测定复方氯唑沙宗中氯唑沙宗和对乙酰氨基酚的血药浓度。血药浓度-时间数据经DAS 2.0处理,对主要药动学参数进行方差分析、双单侧t检验和(1-2α)置信区间分析,并计算相对生物利用度评价两种制剂的生物等效性。结果:复方氯唑沙宗胶囊中的对乙酰氨基酚和氯唑沙宗与片剂中同种成分的相对生物利用度分别为(109.1±30.9)%和(114.0±50.5)%。结论:复方氯唑沙宗胶囊与片剂为生物等效制剂。     

HPLC 法测定氯唑沙宗胶囊含量

用ＯＤＳ柱、甲醇∶水（４∶６）为流动相，以非那西丁为内标，测定氯唑沙宗胶囊中氯唑沙宗和扑热息痛的含量．结果为氯唑沙宗和扑热息痛线性范围分别是０．１２～０．６０ｍｇ，０．１０～０．５０ｍｇ；回收率分别为９７．１％，９６．４％，标准差为１．３％，１．２％．     

氯唑沙宗的合成

氯唑沙宗(chlorzoxazone,1),化学名5-氯-2(3H)-苯并(口恶)唑酮,为一强效肌肉松弛药,工业上是以邻氨基对氯苯酚(2)与脲环合而成,可使用60%硫酸的熔融法(本刊1987,18:49)和使用乙酸丁酯的溶剂法(本刊1988,     

系数倍率法测定复方氯唑沙宗片的含量

不经任何分离,应用系数倍率法可同时测定复方氯唑沙宗片中两种组分的含量,方法可靠易行。     

氯唑沙宗片治疗肌肉痉挛疼痛的临床观察

氯唑沙宗片治疗60例各种软组织损伤患者,总有效率为93.5％,并以安定为对照组,观察服药前后不同时间,症状减轻程度和活动改善情况,结果显示氯唑沙宗疗效,较安定为好,且不良反应小。     

HPLC法测定氯唑沙宗片含量

本文采用HPLC测定氯唑沙宗片中氯唑沙宗含量。以甲醇:水(50:50)为流动相,非那西丁为内标,在280nm处检测。其平均回收率为99.93％,RSD=0.55％,方法简便、准确。     

复方氯唑沙宗胶囊人体药物动力学研究

目的建立同时测定复方氯唑沙宗胶囊中两种成分血药浓度的方法,并进行其在健康人体药物动力学研究。方法20名男性健康志愿者单剂量口服复方氯唑沙宗胶囊2粒,高效液相色谱法同时测定复方氯唑沙宗中氯唑沙宗和对乙酰氨基酚的血药浓度。结果和结论复方氯唑沙宗胶囊中的氯唑沙宗和对乙酰氨基酚主要药物动力学参数分别为:t1/21.629±2.218 h和3.82±1.222 h;Tm ax1.333±0.636 h和0.958±0.724 h;Cm ax4.995±2.11 mg.L-1和1.85±0.409 mg.L-1;AUC0~15 h12.16±4.192 mg.h-1.L-1和8.661±2.844 mg.h-1.L-1;AUC0~∞12.34±4.328和9.927±3.644 mg.h-1.L-1。     

氯唑沙宗及其代谢物的HPLC测定方法和药代动力学研究

目的旨在建立氯唑沙宗及其代谢物的方法。应用高效液相色谱法,内标物为5-fluorobenzoxazolone,经乙酸乙酯提取,紫外检测波长为287nm。结果表明,6-羟氯唑沙宗、内标物及氯唑沙宗的保留时间分别为6.12,10.47和18.65min。6-羟氯唑沙宗及氯唑沙宗在0.5～20μg·ml^-1血浆浓度范围内线性关系良好,回收率均在82.80%～100.76%之间,当日及日间相对标准差分别小于8%和11%。两药的最低检测浓度分别为0.2和0.5μg·ml^-1。多种常用药物对样品的色谱峰无干扰。曾对8名健康受试者单次口服氯唑沙宗400mg的药代动力学进行了观察。提示此方法可用于氯唑沙宗的体内氧化代谢研究。     

紫外分光光度法测定复方氯唑沙宗片中扑热息痛的含量

本文采用紫外分光光度法测定复方氯唑沙宗片中扑热息病的含量,较现行标准的方法为简单,结果较为满意。     

Regeneration of injured airway epithelium

The airway surface epithelium is frequently injured by microorganisms and viruses due to its permanent contact with the external medium. Following injury, the epithelium is able to repair itself and regenerate through several mechanisms including spreading and migration of basal cells, cell proliferation and differentiation. The cellular and molecular factors involved in wound repair and epithelial regeneration interact closely, implying the participation of cytoskeleton proteins and integrins receptors, matrix metalloproteinases and their inhibitors as well as cytokines and growth factors secreted by airway epithelial and mesenchymal cells. The spatio-temporal modulation of the pro-inflammatory cytokines such as IL-8, and MMPs (MMP-9 and -7) during the different steps of regeneration suggests that the matrix and secretory environment are markedly involved in these mechanisms and that their dysregulation may induce remodeling of the airway mucosa. A better knowledge of the mechanisms involved in airway epithelium regeneration may pave the way to regenerative therapeutics allowing the reconstitution of a functional airway mucosa in numerous respiratory diseases such as cystic fibrosis, chronic obstructive pulmonary diseases and bronchiolitis.     

Multigeneration assessment of nonylphenol and endosulfan using a model Australian freshwater fish, Melanotaenia fluviatilis

Changes over two generations in offspring and reproductive ability were recorded in crimson-spotted rainbowfish (Melanotaenia fluviatilis), a model Australasian freshwater fish, following a 24 h exposure to nominal nonylphenol concentrations of 50, 100, 500, 1000, 2250, and 5000 microg/L and following a 4 h exposure to nominal endosulfan concentrations of 1.0, 5.0, 10, 22, 33, and 50 microg/L. There were also four replicated control treatments: control 1 and 2 and solvent control 1 and 2, as well as "positive" female and male controls: 1 microg/L estradiol 1 and 2 and 1 microg/L testosterone 1 and 2. Results suggested that there may be some parental transfer of toxicants to embryos even over this short exposure period. Fertility of M. fluviatilis was reduced by a 24 h pulse exposure of adults to 100 microg/L nonylphenol and a 4 h exposure to 1.0 microg/L endosulfan. Hatch rates were significantly reduced after exposure to nonylphenol, endosulfan, and estradiol control but not in solvent controls and testosterone control. Significant correlations were found between reproductive and physiological parameters for nonylphenol and endosulfan exposed F0 adult rainbowfish. The major reproductive effects were on hatchability of the F1 generation and the gonadosomatic indices of male F1. The respective nominal NOEC and LOEC's for nonylphenol were 50 and 100 microg/L, and for endosulfan were <1.0 and 1 microg/L. These observed effects have the potential to significantly impact exposed rainbowfish populations through the observed approximately 45% reduction of hatchability and thus larval production.     

舒芬太尼复合咪达唑仑在乳腺癌手术麻醉苏醒中的应用

目的研究舒芬太尼+咪达唑仑在乳腺癌手术麻醉复苏中的应用,术后麻醉苏醒情况及拔管时血流动力学变化。方法选取ASAⅠ级,临床诊断为乳腺癌,拟行乳腺癌改良根治术患者60例,随机分为三组,每组20例,三组均采用气管内插管全身麻醉方式,以维库溴铵诱导插管,1组(F)以芬太尼+异丙酚+咪达唑仑维持麻醉,2组(S)以舒芬太尼+丙泊酚+咪达唑仑维持麻醉,3组(T)以舒芬太尼+丙泊酚+咪达唑仑维持麻醉,于术毕前10min停止丙泊酚输注,追加舒芬太尼+咪达唑仑,观察记录手术结束,取吸痰时,拔管时及拔管后MAP,HR,与基础值进行比较,记录呼患者睁眼时间,拔除气管导管时间和OAA/S评分。结果与术毕时比,F组和S组的MAP和HR在吸痰、拔管时均明显增高(P<0.05)。在睁眼时间、拔管时间两项观察指标中,各组之间差异有统计学意义,T组患者睁眼时间及拔管时间最短,S组次之,F组最慢,OAA/S评分T组评分较F组和S组明显升高(P<0.05)。结论舒芬太尼联合咪达唑仑用于乳腺癌手术患者,能保证很好的麻醉深度,术毕前10min追加舒芬太尼+咪达唑仑,拔管时心血管反应轻,术毕苏醒时间快,清醒状况良好,值得临床推广。     

Caspofungin: pharmacology,safety and therapeutic potential in superficial and invasive fungal infections

Invasive fungal infections are important causes of morbidity and mortality in hospitalised patients. Current therapy with amphotericin B and antifungal triazoles has overlapping targets and is limited by toxicity and resistance. The echinocandin lipopeptide caspofungin is the first of a new class of antifungal compounds that inhibit the synthesis of 1,3-β-D-glucan. This homopolysaccharide is a major component of the cell wall of many pathogenic fungi and yet is absent in mammalian cells. It provides osmotic stability and is important for cell growth and cell division. In vitro, caspofungin has broad-spectrum antifungal activity against Candida and Aspergillus spp. without cross-resistance to existing agents. The compound exerts prolonged post-antifungal effects and fungicidal activity against Candida spp. and causes severe damage of Aspergillus fumigatus at the sites of hyphal growth. Animal models have demonstrated efficacy against disseminated candidiasis and disseminated and pulmonary aspergillosis, both in normal and in immunocompromised animals. Caspofungin possesses favourable pharmacokinetic properties and is not metabolised through the cytochrome P450 (CYP) enzyme system. It showed highly promising antifungal efficacy in Phase II and III clinical trials in immunocompromised patients with oesophageal candidiasis. Caspofungin was effective in patients with invasive aspergillosis intolerant or refractory to standard therapies. Based on its documented antifungal efficacy and an excellent safety profile, caspofungin has been approved recently by the US Food and Drug Administration for the treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies (i.e., amphotericin B, lipid formulations of amphotericin B, and/or itraconazole). Phase III clinical trials in patients with candidaemia and in persistently febrile neutropenic patients requiring empirical antifungal therapy are ongoing. This paper reviews the preclinical and clinical pharmacology of caspofungin and its potential role for treatment of invasive and superficial fungal infections in patients.     

Strain and sex alter effects of stress and nicotine on feeding, body weight, and HPA axis hormones

Gender and genotype result in differential sensitivity to stress and to nicotine. Male and female Sprague–Dawley and Long–Evans rats exhibit different behavioral responses to immobilization stress and to chronically-administered nicotine, suggesting that these animals may be useful to model human variability in stress and nicotine sensitivity. It is possible that differences in sensitivity of the hypothalamo–pituitary–adrenocortical (HPA) axis might account for these sex and strain differences. This experiment examined corticosterone (CORT) and adrenocorticotropin hormone (ACTH) responses of male and female Sprague–Dawley (n=117) and Long–Evans (n=120) rats administered 0, 6, or 12 mg/kg/day nicotine for 14 days; half of each treatment group was exposed to immobilization stress (20 min/day). Feeding and body weight also were measured. Nicotine increased CORT and ACTH levels of Sprague–Dawley females only. Stress increased CORT and ACTH levels of all groups except for Long–Evans females. Nicotine and stress decreased feeding and body weight with greatest effects in Long–Evans females. CORT, feeding, and body weight were positively correlated among stressed females. These findings suggest that strain differences in HPA axis, body weight, and feeding responses to nicotine and to stress are robust among females but not among males. CORT reactivity and female sex hormones may explain these differences.     

Drugs for insomnia

Introduction: Sleep is a vital neurochemical process involving sleep-promoting and arousal centers in the brain. Insomnia is a pervasive disorder characterized by difficulties in initiating or maintaining or non-refreshing (poor quality) sleep and clinically significant daytime distress. Insomnia is more prevalent in women and old age and puts sufferers at significant physical and mental health risks. This review summarizes published data on the current and emerging insomnia drug classes, rationale for development and associated risks/benefits. (Summary of Product Characteristics and Medline search on "hypnotic" or specific drug names and "Insomnia").

Areas covered: GABA_A receptor modulators facilitate sleep onset and some improve maintenance but increase risk of dependence, memory, cognitive and psychomotor impairments, falls, accidents and mortality. Melatonin receptor agonists improve quality of sleep and/or sleep onset but response may develop over several days. They have more benign safety profiles and are indicated for milder insomnia, longer usage and (prolonged release melatonin) older patients. Histamine H-1 receptor antagonists improve sleep maintenance but their effects on cognition, memory and falls remain to be demonstrated. Late-stage pipeline orexin OX1/OX2 and serotonin 5HT2A receptor antagonists may hold the potential to address several unmet needs in insomnia pharmacotherapy but safety issues cast some doubts over their future.

Expert opinion: Current and new insomnia drugs in the pipeline target different sleep regulating mechanisms and symptoms and have different tolerability profiles. Drug selection would ideally be based on improvement in the quality of patients' sleep, overall quality of life and functional status weighed against risk to the individual and public health.     

Some observations on the effects of bioprocessing on biopolymer stability

A short review is given of some of the effects of the stresses encountered during bioprocessing of protein and carbohydrate-based macromolecular systems. This is of relevance to the effectiveness and safety of protein or peptide drugs themselves (such as insulin and monoclonal antibodies) and for the integrity of delivery systems (such as various carbohydrate-based hydrogel or mucoadhesive polymers). Some carbohydrate polymers are themselves bioactive or immunostimulatory and particular use is being made of polysaccharide and glycoconjugate vaccines whose effectiveness can be severely effected by chain degradation. Stability criteria include molecular weight and conformation and techniques ranging from simple viscomery measurements to sophisticated analytical ultracentrifuge and multi-angle light scattering coupled to size exclusion chromatography and precision viscometry measurements have been useful in this regard. We focus on some recent work on the degradation and aggregation of immunoglobulin G4-based monoclonal antibodies in response to repeated freezing and thawing and long-term storage, looking at the possible connection between conformation change and aggregation, the effects of storage conditions on the stability of chitosan mucoadhesive systems used for nasal and oral delivery. We look at the effects of sterilization conditions (thermal and irradiation) on the stability of a variety of other polysaccharides such as starches, κ-carrageenan, carboxymethylcellulose, alginate, low- and high-methoxy pectins, guar, and xyloglucans and consider the use of a relatively new method for the evaluation of the molecular weight distribution of glycoconjugate vaccines with molecular weights as high as 100?×?10⁶ g/mol.     

脂蟾毒配基PLGA-TPGS纳米粒的质量评价

目的：以自制材料乙交酯丙交酯共聚物-维生素E聚乙二醇1000琥珀酸酯（polylactide-co-glycolide-D-α-tocopheryl polyethylene glycol 1000 succinate,PLGA-TPGS）为载体制备脂蟾毒配基PLGA-TPGS纳米粒（Resibufogenin-loaded PLGA-TPGS nanoparticles,RPTN）,并以市售材料乙交酯丙交酯共聚物（PLGA）为载体制备脂蟾毒配基PLGA纳米粒（RBG-loaded PLGA nanoparticles,RPN）,体外评价和比较2种纳米粒的质量。方法：采用超声乳化-溶剂挥发法制备RPTN和RPN,用透射电子显微镜和激光粒度仪分别测定二者的外观、粒径、表面电荷。采用反相高效液相色谱法,色谱柱为Hypersil C₁₈（4.6 mm×250 mm,5 μm）,甲醇和0.05%冰醋酸溶液（9∶1）为流动相,检测波长为298 nm,测定RBG在RPTN和RPN中的载药量、包封率和体外释放度。结果：RPTN和RPN的粒径分别为152.3 nm和331.7 nm,载药量和包封率分别为18.4%、79.3%和15.1%、68.6%。体外药物释放30 d时RPTN和RPN的体外累积释放率分别为86.7%和72.3%,RPTN释放较完全。结论：自制载体制备的RPTN比RPN粒径更小,载药量和包封率更大,体外有明显的缓释作用,释放更完全。     

Tannins medical / pharmacological and related applications: A critical review

Tannins are natural phenolic compounds that are widespread and almost ubiquitous in the vegetal world. They can be found in fruit, wood and bark of trees, and many types of wild herbs and plants or from sustainable agriculture and forestry. Their traditional use for leather has been doubled for centuries in the popular medical and pharmacological lore by their use to cure or alleviate a variety of infections and diseases. This has indicated to modern researchers that these materials possess a great potential for the use in modern medicine and pharmacy. This review, after an introduction on tannins their structures and their basic chemistry describe what modern researchers have been able to glean and demonstrate of their real, identified and quantified effects on various diseases, from their bactericidal, anticancer and antinflammatory actions to the many other effects that putsnow in more close focus in pharmacology.     

甲基黄酮醇胺盐对大鼠学习记忆的促进作用与其抗氧化作用的关系

目的研究甲基黄酮醇胺盐对大鼠学习记忆的影响，分析该药影响学习记忆与其影响脑内自由基反应的关系。方法ｉｐ甲基黄酮醇胺盐５，１０ｍｇ·ｋｇ－１共７ｄ后，采用Ｍｏｒ－ｒｉｓ水迷宫测试大鼠的学习记忆能力，同时测定训练ｄ５和休息３０ｄ后大鼠脑内过氧化脂质（ＬＰＯ）含量和超氧化歧化酶（ＳＯＤ）活性。结果甲基黄酮醇胺盐两种剂量均可提高大鼠获取空间定位信息能力和信息贮存能力并增强记忆保持和再现过程。用药大鼠脑内ＬＰＯ含量明显低于对照组，与其记忆成绩呈正相关性。而脑内ＳＯＤ活性则高于对照组，与其记忆成绩呈负相关性。结论甲基黄酮醇胺盐对大鼠的学习记忆机能具有促进作用，而它的抗氧化作用可能为其促进学习记忆的作用机制。