咳喘凝胶贴膏皮肤安全性考察

摘要：目的:制备咳喘凝胶贴膏,并进行皮肤安全性评价。方法:将处方药材经水煎煮提取、浓缩制成一定比例的药液加入凝胶贴膏基质并快速涂抹,制成凝胶贴膏;分别进行大鼠皮肤急性毒性、家兔皮肤刺激性、豚鼠皮肤过敏性试验,观察咳喘凝胶贴膏对动物经皮给药的急毒性、刺激性和过敏性。结果:皮肤急性毒性试验中,大鼠完整皮肤及破损皮肤均未出现红斑及水肿;皮肤刺激性试验中,家兔完整及破损皮肤组未出现异常情况;豚鼠皮肤过敏性试验中,咳喘凝胶贴膏低剂量及高剂量组均无过敏反应。结论:咳喘凝胶贴膏临床剂量用于大鼠、家兔及豚鼠皮肤安全、可靠。     

碳糊电极阳极吸附伏安法测定雷贝拉唑

目的:考察乳癖消巴布膏皮肤用药的安全性.方法:用健康家兔分别进行完整与破损皮肤的皮肤刺激性试验;用健康豚鼠进行皮肤过敏试验;用健康大鼠进行慢性经皮毒性试验.结果与结论:乳癖消巴布膏对家兔无皮肤刺激性.对豚鼠无致敏性,对大鼠无经皮毒性.     

热熔压敏胶制备的伤科贴膏皮肤用药安全性研究

目的通过动物试验探讨伤科贴膏皮肤用药的安全性。方法采用小鼠进行急性毒性试验,采用家兔同体左右侧自身比较法进行皮肤刺激性试验,采用豚鼠进行过敏性试验。结果伤科贴膏对小鼠完整皮肤无急性毒性反应,对家兔完整皮肤无刺激性,对豚鼠皮肤无过敏反应。结论伤科贴膏是较安全、使用方便的新型外用药。     

安喘颗粒对实验性哮喘豚鼠的平喘作用及其机制探讨

目的 观察安喘颗粒(AG)对实验性哮喘豚鼠的平喘作用,并探讨其作用机制.方法 60只豚鼠均分为五组,采用腹腔注射10％卵蛋白(OVA)建立豚鼠哮喘模型;另取10只豚鼠作为空白对照(BC)组.哮喘模型豚鼠中,A组不用药作为模型对照,B组给予氨茶碱11 mg/kg灌胃,C、D和E组分别用AG 1.53、0.77和0.38 g/kg 3个剂量灌胃.观察动物哮喘潜伏期、外周血嗜酸性粒细胞(EOS)计数、血清白三烯E4(LTE4)、环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)的变化.采用离体豚鼠气管环体外试验,观察AG对磷酸组胺引起的豚鼠离体气管平滑肌收缩的影响.结果 3个AG剂量组的哮喘潜伏期均延长,C组潜伏期长于A组(P＜0.05).与A组比较,C、D组外周血中EOS计数均明显减少、血清LTE4升高(P＜0.05),cAMP/cGMP恢复至正常值,并有磷酸组胺所致离体气管平滑肌痉挛性收缩明显抑制(P＜0.05).结论 AG对实验性哮喘模型豚鼠有良好治疗作用.其作用机制与预防和缓解气管平滑肌痉挛、降低模型豚鼠外周血中EOS计数和LTE4的含量及恢复cAMP/cGMP比值有关.     

喘可治注射液质量标准中药效学检查项目的研究

目的 研究喘町治注射液质量标准中设立药效学检查项目的 可行性.方法 从氨水和SO2引咳小鼠、组胺引喘豚鼠与离体豚鼠气管条收缩等药理学实验中筛选能够反映有效性指标的评价方法.结果 喘可治注射液能明显延长氨水和SO2诱导的小鼠咳嗽潜伏期,并减少咳嗽次数;明显延长组胺引发的豚鼠哮喘潜伏期,减少哮喘次数;明显抑制组胺引起的离体豚鼠气管条收缩;不同批号的喘可治注射液能明显抑制组胺引起的离体豚鼠气管条收缩.结论 喘可治注射液的质量标准中设立药效学检查项目是可行的.     

合郎喘必消冲剂的药理学研究

本文通过对小鼠急性实验、抗炎实验、对胸腺脾脏的影响及对豚鼠在体、离体气管平滑肌作用实验,观察了合郎喘必消冲剂的药理学效应。结果表明,该制剂无明显毒性,最大耐受量为1000g/(kg·d)。它有明显的对抗二甲苯致小鼠耳炎及延长组胺诱发哮喘发作潜伏期的作用,对豚鼠离体气管平滑肌无松弛作用, 对小鼠胸胨和脾脏有使其重量减小的趋势,但与对照组比较无显著性差异。     

固本喘嗽康颗粒的镇咳、祛痰、平喘实验研究

目的观察固本喘嗽康颗粒对哮喘的药效作用。方法通过动物模型引咳、祛痰和引喘实验来观察其镇咳、祛痰、平喘效果。结果高、中、低剂量的固本喘嗽康颗粒均能显著地抑制浓氨水所致小鼠咳嗽潜伏期和咳嗽次数;能增加小鼠呼吸道的酚红排泌量;还能显著地延长豚鼠哮喘潜伏期,对豚鼠离体气管平滑肌痉挛具有明显的松弛作用。结论固本喘嗽康颗粒具有明显的镇咳、祛痰、平喘作用。     

消疣液的毒理学研究

目的：观察消疣液的安全性。方法：①大鼠20只，随机分2组，观察消疣液对大鼠灌胃后产生的急性毒性反应。②家兔10只，观察消疣液对家兔完整及破损皮肤的刺激反应。③豚鼠30只，随机分3组，观察消疣液的皮肤过敏反应。④家兔18只，随机分3组，观察消疣液高、低剂量组的皮肤长期毒性。结果：消疣液经口给药大鼠的LD50＞35g·kg^-1，对家兔完整皮肤无明显刺激性，破损皮肤24h内为轻度刺激性。对豚鼠皮肤无明显致敏作用，家兔外涂消疣液4周，未见明显毒性反应。结论：消疣液外用安全低毒、刺激性小、无过敏性，可在临床推广使用。     

喘平滴丸对卵白蛋白诱发哮喘结合寒饮蕴肺证豚鼠的药效学初步研究

目的：探讨新药喘平滴丸对卵白蛋白诱发哮喘结合寒饮蕴肺证豚鼠的药效。方法：采用卵白蛋白诱发哮喘,同时结合寒饮蕴肺证法。结果：喘平滴丸明显降低卵白蛋白诱发哮喘结合寒饮蕴肺证豚鼠哮喘的反应级,明显延长卵白蛋白诱发哮喘结合寒饮蕴肺证豚鼠哮喘反应的潜伏期。结论：喘平滴丸治疗寒饮蕴肺证哮喘有平喘功效。     

双喘通药理作用的研究

本文比较了双喘通与喘通的平喘作用。二者弛张豚鼠离体气管平滑肌作用和对抗组织胺收缩豚鼠离体气管平滑肌作用,在低浓度时相近,在较高浓度时双喘通强于喘通。延长组织胺气雾对豚鼠致喘时间的作用,喘通强于双喘通。心得安不能阻断双喘通对离体气管和离体子宫平滑肌的弛张作用,但能阻断喘通的作用。双喘通可拮抗 Ach 和 BaCl_2对离体气管和离体肠管平滑肌的收缩作用。双喘通对豚鼠离体回肠具有弛张作用和解痉作用。双喘通给小鼠静脉注射 LD_(50)为10.0±0.2mg/kg,灌胃给药 LD_(50)为64.0±8.6mg/kg。     

Role of glutathione in reduction of arsenate and of gamma-glutamyltranspeptidase in disposition of arsenite in rats

Arsenate (AsV), the environmentally prevalent form of arsenic, is converted sequentially in the body to arsenite (AsIII), monomethylarsonic acid (MMAsV), monomethylarsonous acid (MMAsIII), and dimethylarsinic acid (DMAsV) and some trimethylated metabolites. Although the biliary excretion of arsenic in rats is known to be glutathione (GSH)-dependent, involving transport of arsenic-GSH conjugates, the role of GSH in the reduction of AsV to the more toxic AsIII in vivo has not been defined. Therefore, we studied how the fate of AsV is influenced by buthionine sulfoximine (BSO), which depletes GSH in tissues. Control and BSO-treated rats were given AsV (50 micromol/kg, i.v.) and arsenic metabolites in bile, urine, blood and tissues were analysed by HPLC-HG-AFS. BSO increased retention of AsV in blood and tissues and decreased appearance of AsIII in blood, bile (by 96%) and urine (by 63%). The biliary excretion of MMAsIII was also nearly abolished, the appearance of MMAsIII and MMAsV in the blood was delayed and the renal concentrations of these monomethylated arsenicals were decreased by BSO. Interestingly, appearance of DMAsV in blood and urine remained unchanged and the concentrations of this metabolite in the kidneys and muscle were even increased in response to BSO. To test the role of gamma-glutamyltranspeptidase (GGT) in arsenic disposition, the effect of the of the GGT inhibitor acivicin was investigated in rats injected with AsIII (50 micromol/kg, i.v.). Acivicin lowered the hepatic and renal GGT activities and increased the biliary as well as urinary excretion of GSH, but failed to alter the disposition (i.e. blood and tissue concentrations, biliary and urinary excretion) of AsIII and its metabolites. In conclusion, shortage of GSH decreases not only the hepatobiliary transport of arsenic, but also reduction of AsV and the formation of monomethylated arsenic, while not hindering the production of dimethylated arsenic. While GSH plays an important role in the disposition and toxicity of arsenic, GGT, which hydrolyses GSH and GSH conjugates, apparently does not influence the fate of the GSH-reactive trivalent arsenicals in rats.     

2009年某院住院患者抗真菌药用药调查

目的:分析讨论某院抗真菌药使用的合理性,为临床安全有效地使用抗真菌药提供参考。方法:回顾性统计分析某院2009年住院患者抗真菌药用药信息。结果:2009年某院住院患者抗真菌药DDDs排名前3名分别为:氟康唑、制霉菌素和伊曲康唑;使用金额排名前3名分别为:氟康唑、米卡芬净及卡泊芬净;更换一种抗真菌药进行治疗的患者数为176人,在全部患者中占13.4%。结论:应进一步强化用药指征的意识,提高标本送检率,同时改善某些抗真菌用药不合理更换的现象,以避免耐药性发生,从而更好更长远地体现抗真菌药的治疗价值。     

Role of desacetylation in the detoxification of cephalothin in renal cells in culture

The toxicity of three cephalosporin antibiotics to rabbit kidney cells in culture was compared to their known nephrotoxic potential in vivo (cephaloridine greater than cefazolin greater than cephalothin). While cephalothin is considered to be a relatively nonnephrotoxic cephalosporin when administered to many species including humans and rabbits, in several in vitro systems involving rabbit renal tissue, cephalothin was comparatively more toxic than anticipated based on in vivo data. Cephalothin is extensively desacetylated in rabbits to a less microbiologically active metabolite, desacetylcephalothin. When a microsomal S9 fraction from rabbit kidney was added to the in vitro assay in cultured rabbit renal cells, cephalothin was desacetylated and its toxicity to kidney cells was reduced. The addition of S9 in vitro provided a toxicity ranking of the cephalosporins that correlated with their known in vivo nephrotoxic potentials (cephaloridine greater than cefazolin greater than cephalothin). The in vitro detoxification of cephalothin by S9 was blocked by the coadministration of the esterase inhibitor, aminocarb. Desacetylcephalothin was relatively nontoxic to rabbit renal tissue in vitro. These results suggest that the desacetylation of cephalothin in vivo represents a previously unrecognized mechanism of detoxification of this cephalosporin antibiotic. Furthermore, this mechanism of detoxification may be applicable to other acetylated cephalosporins.     

应用PASS系统对我院2008年住院医嘱的分析

目的监测分析2008年我院住院患者用药情况。方法将PASS系统嵌入医生工作站、临床药学工作站等子系统,构建合理用药计算机网络系统,对住院医嘱进行及时监测,将监测结果向医生反馈,并对其进行统计、分析。结果2008年共监测医嘱3 620 241条,不合理医嘱908条,占0.02%。不合理医嘱中,配伍禁忌(381条)占41.96%,用法用量(381条)占41.96%,药物相互作用(108条)占11.89%,儿童用药(38条)占4.19%。经与医生沟通后,更改不合理医嘱856条,占94.27%。结论PASS系统可有效监测医嘱中的不合理用药,通过与医生交流,大大减少药物不良事件的发生,值得临床推广应用,也为临床药师开展工作带来了极大的便利。但PASS系统尚存在局限性,有待进一步完善。     

微透析取样技术在中药体内分析中的应用研究进展

本文综述了微透析取样技术在中药体内分析中的应用,介绍微透析取样技术的原理、组成、探针类型、特点,重点阐述了微透析取样技术在测定脑、血液、皮肤等组织器官中中药有效成分浓度的应用实例。表明微透析取样技术在中药药效研究中具有广阔的前景。     

Kinetics of in vitro metabolism of methoxyphenamine in rats

1. Methoxyphenamine (MP) was metabolized in vitro by rat liver preparations to O-desmethylmethoxyphenamine (O-desmethyl-MP), N-desmethylmethoxyphenamine (N-desmethyl-MP) and 5-hydroxymethoxyphenamine (5-hydroxy-MP). These metabolic pathways were inhibited by SKF 525-A and carbon monoxide, which indicates that these reactions were mediated at least partly by an NADPH-dependent cytochrome P-450 system. 2. Strain differences in the metabolism of this drug in vitro were observed in female Lewis and Dark Agouti (DA) rats, which are proposed models for human debrisoquine phenotypes. Methoxyphenamine O-demethylase and 5-hydroxylase activity in DA rats were lower than those in Lewis rats. 3. The metabolic transformation of methoxyphenamine in vitro to O-desmethyl-MP was inhibited competitively by debrisoquine and sparteine. This indicates that the cytochrome P-450 isoenzyme mediating the metabolism of MP to O-desmethyl-MP is similar to that mediating metabolism of debrisoquine and sparteine. However, no inhibition was observed with methenytoin.     

应用PASS系统分析我院2010年住院医嘱

目的:了解我院2010年住院患者的合理用药情况,探讨如何利用合理用药监测系统( PASS)提高合理用药水平.方法:利用PASS对我院2010年15 966例住院患者的1 184 997条用药医嘱进行监测,以黑色警示医嘱为依据,收集不合理用药信息,并对监测结果进行统计、分析.结果:不合理用药医嘱50 261条,发生率为4.24％.绝对禁止黑色医嘱5441条,主要为药物相互作用(66.54％)、注射液体外配伍(17.86％)、用法用量(15.46％)、儿童警告(1.14％).结论:应用PASS系统能有效监测医嘱中的不合理用药情况,有利于提高临床合理用药水平,但PASS系统尚存在局限性,有待进一步完善.     

Changes in levels of dependency and predictors of mortality in elderly people in institutional care in Dunedin

The 1983 study of dependency of subjects in institutional care in Dunedin was repeated two years later. A significant increase in levels of dependency in residential homes, particularly in the Religious and Welfare sector was found. In 1983 there were 29 high dependency residents and 73 medium dependency residents in residential homes. In 1985 these numbers had increased to 55 and 86 respectively. There was no change in the number of low dependency residents. In 1983, 6 high dependency residents had been admitted to residential home care in the year prior to the study. In 1985 the number of high dependency residents recently admitted had increased to 23. There had also been a significant increase in the dependency of patients in Religious and Welfare continuing care hospitals. Of the 933 subjects in institutional care in 1983 who were able to be followed, 354 (37.9%) died in the following 2 years. Mortality rate was higher for those in hospital care (48.1%) than for those in residential home care (29.6%). Mortality rates were higher in more dependent subjects and this was evident for each measure of dependency.     

Chondroprotective Effects of Wogonin in Experimental Models of Osteoarthritis in vitro and in vivo

We evaluated the chondroprotective effects of wogonin by investigating its effects on the gene expression and production of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as on production of MMP-3 in the rat knee. Rabbit articular chondrocytes were cultured in a monolayer, and RT-PCR was used to measure interleukin-1β (IL-1β)-induced expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), and type II collagen. In rabbit articular chondrocytes, the effects of wogonin on IL-1β-induced production and proteolytic activity of MMP-3 were investigated using western blot analysis and casein zymography, respectively. The effect of wogonin on MMP-3 protein production was also examined in vivo. In rabbit articular chondrocytes, wogonin inhibited the expression of MMP-3, MMP-1, MMP-13, and ADAMTS-4, but increased expression of type II collagen. Furthermore, wogonin inhibited the production and proteolytic activity of MMP-3 in vitro, and inhibited production of MMP-3 protein in vivo. These results suggest that wogonin can regulate the gene expression and production of MMP-3, by directly acting on articular chondrocytes.