盐酸川丁特罗的合成工艺研究

目的合成抗哮喘药盐酸川丁特罗。方法以2-三氟甲基苯胺为起始原料,经碘代、酰化、取代、Stephen还原、水解、氯代、Wittig反应、环氧化、胺化和成盐10步反应制得盐酸川丁特罗。结果与结论目标化合物的总收率为5.71%,其结构经质谱、1H-NMR谱确证。改进后的合成工艺缩短了步骤、简化了操作、降低了合成成本,适合工业化生产。     

万托林雾化吸入治疗支气管哮喘不良反应

我科1999年12月~2003年12月期间利用空气压缩泵或氧气作动力,雾化吸入β2受体激动剂万托林治疗哮喘急性发作629例次,其中55例在首次雾化吸入时出现明显不良反应,现总结如下:1对象与方法1.1对象1999年12月~2003年12月就诊于我科的急性哮喘发作患者629例次,其中男性340例,女性289     

盐酸川丁特罗代谢物的合成

目的研究新药盐酸川丁特罗进入大鼠体内后经独特的代谢途径生成特殊代谢产物的合成方法。方法以4-氨基-3-三氟甲基苯甲酸为起始原料,经氯代、甲基化、碘代、甲磺酰基化、溴代、还原、胺化得到目标化合物。结果经7步反应合成目标化合物,总收率为3%,目标化合物结构经1 H-NMR和MS确证。结论该化合物为盐酸川丁特罗代谢物研究提供物质支持。     

舒利迭治疗支气管哮喘40例分析

目的观察并探讨舒利迭（沙美特罗/丙酸氟替卡松）治疗支气管哮喘的临床疗效。方法对40例确诊支气管哮喘的患者,随机分为治疗组20例和对照组20例,对照组吸入长效β2受体激动剂和糖皮质激素的复方制剂舒利迭（沙美特罗/丙酸氟替卡松）,对照组吸入糖皮质激素（必可酮）。结果治疗组有效率为95%,对照组有效率为65%,治疗组用舒利迭治疗后临床疗效和肺功能恢复情况明显优于对照组。结论舒利迭在治疗支气管哮喘方面临床疗效明显,能更好控制及改善支气管哮喘症状。     

抗哮喘药的药物基因组学研究进展

目的:综述三类常用抗哮喘药的药物基因组学研究进展。方法:通过对近年来的研究文献进行分析、整理和归纳,较为全面地概况了β2受体激动剂,白三烯调节剂和糖皮质激素三类常用抗哮喘药物基因组学的研究现状。结果:ADRB2、LTC4S、ALOX5和NR3C1等基因的多态性能够影响三类常用抗哮喘药物的治疗反应。结论:了解抗哮喘药物治疗反应和基因多态性的关系,可以用于指导用药前的预测试验,以减少不良反应的发生,增强疗效。     

糖皮质激素治疗支气管哮喘

支气管哮喘为慢性炎症性疾病,糖皮质激素(GCS)仍然为临床哮喘包括慢性哮喘和哮喘急性发作最有效的治疗药物.吸入型糖皮质激素(ICS)可考虑用作慢性持续性哮喘的一线治疗.ICS联合长效β2受体激动剂(LABA)控制哮喘的效果优于单纯增加ICS剂量.本文阐述ICS和ICS/LABA在轻、中度持续性哮喘治疗中的临床地位,以及哮喘急性发作时全身用GCS的效果.     

β2受体激动剂治疗支气管哮喘的临床观察

目的探讨β2受体激动剂治疗支气管哮喘的疗效。方法对60例确诊支气管哮喘的患者,采用长效β2受体激动剂治疗。结果β2受体激动剂治疗后临床疗效和肺功能改善方面明显优于。结论β2受体激动剂在治疗支气管哮喘方面改善临床症状和肺功能明显。     

沙美特罗替卡松干粉吸入剂治疗支气管哮喘的疗效观察

目的:比较沙美特罗替卡松干粉剂(SM/FP)与单独吸入丙酸氟的卡松(FP)治疗中度持续哮喘的疗效。方法:74例中度持续哮喘患者分为两组,治疗组(38例)吸入SM/FP50/100μg,每日早晚各1次,对照组(36例)吸入FP125μg每日早晚各1次。两组均治疗12周。观察晨间最大呼气峰流速值(PEFam)、晚间最大呼气峰流速值(PEFpm)、昼夜间哮喘症状、吸入沙丁胺醇气雾剂次数及FEV1变化。结果:治疗前昼夜间哮喘症状、吸入沙丁胺醇气雾剂次数、PEFam、PEFpm及FEV1差异无显著性,吸入SFC治疗后第2周上述观察指标有明显改善,治疗组和对照组比较差异有显著性(P<0.01),在随后的观察期第4,6,8,12周,上述指标持续好转(P<0.01)。两组患者耐受性均较好,不良反应发生率低,症状轻微,差异无显著性(P>0.05)。结论:对于改善中度持续支气管哮喘患者症状和肺功能,联合吸入糖皮质激素和长效β2受体激动剂较单一吸入糖皮质激素效果更佳。     

舒利迭治疗支气管哮喘的临床观察

目的观察舒利迭（沙美特罗/氟替卡松）治疗支气管哮喘的疗效。方法对120例确诊支气管哮喘的患者,分为吸入糖皮质激素和长效β2受体激动剂的复方制剂舒利迭（沙美特罗/氟替卡松）治疗组60例,吸入糖皮质激素（丙酸氟替卡松）对照组60例。治疗后对临床疗效、肺功能指标进行比较及统计学分析。结果舒利迭治疗组用药后临床疗效和肺功能改善方面明显优于对照组。结论舒利迭在治疗支气管哮喘改善临床症状和肺功能明显,较单纯吸入糖皮质激素能更好控制及改善的哮喘症状。     

糖皮质激素与长效β_2受体激动剂联合吸入治疗小儿支气管哮喘的临床疗效观察

目的探讨糖皮质激素与长效β_2受体激动剂联合吸入治疗小儿支气管哮喘的临床疗效。方法选取2015年1月至2015年12月我院收治的70例小儿支气管哮喘患者,根据随机原则将患者分为对照组和观察组各35例,对照组予以单纯糖皮质激素吸入治疗,观察组予以糖皮质激素与长效β_2受体激动剂联合吸入治疗,比较2组患者的临床疗效。结果对照组无效5例,好转4例,显效12例,临床控制14例,总有效率为85.71%;观察组无效2例,好转5例,显效13例,临床控制15例,总有效率为94.29%;经χ~2检验,观察组的总有效率明显高于对照组,P<0.05。结论与单用糖皮质激素吸入治疗相比,采用糖皮质激素与β_2受体激动剂联合吸入治疗,可有效改善患者的临床症状,提高临床疗效,具有重要的临床意义。     

特非那定对成人哮喘者呼气流速的作用

目的：研究特非那定对成人哮喘的作用。方法：采用随机、单盲、交叉对照法，以呼气峰流速仪监测２０例稳定期或轻度发作期成年哮喘病人口服特非那定（６０ｍｇ，ｂｉｄ×２ｗｋ）时的呼气峰流速（ＰＥＦ）及其变异率（ＰＥＦＲＶ）。结果：口服特非那定时ＰＥ ＦＲＶ和ＰＥＦ分别为１３％±ｓ１０％和２９２±８９Ｌ／ｍｉｎ，不用特非那定时分别为１９％±７％和２８１±１０４Ｌ／ｍｉｎ。胸闷、气急、咳嗽、咯痰及喘鸣有效率分别为７９％，８２％，８４％，５０％和３８％。对过敏性鼻炎症状（鼻痒、流涕、打喷嚏等）的改善更明显     

Effect of neutral endopeptidase inhibitor on airway function and bronchial responsiveness in asthmatic subjects

Summary We determined the effect of an inhibitor of neutral endopeptidase, acetorphan, on the skin responses to substance P and on the bronchostrictor effects of sodium metabisulphite aerosol in asthmatic subjects. One hour following ingestion of acetorphan (200 mg) or placebo tablets, cutaneous responses to substance P were performed in four subjects. In seven subjects, bronchial challenge with increasing concentrations of sodium metabisulphite solutions was performed and the concentration required to cause a 20% fall in baseline FEV₁ determined (PC₂₀).On the acetorphan day, there was a significant increase in the wheal and flare responses to substance P and to the diluent (0.9% NaCl) alone. However, there was no significant effect of acetorphan on the PC₂₀ metabisulphite.We conclude that metabisulphite airway challenge in vivo may not invoke the release of endogenous neuropeptides. However, the degree of inhibition of neuropeptide breakdown by the oral dose of acetorphan used may not have been optimal.     

Effect of cold exposure on drug action and hepatic drug metabolism in the rat

Exposure of male rats to a temperature of 4°C for 4 days decreased the sleeping time response to hexobarbital and meprobamate, but not to barbital. Plasma concentrations of these drugs present at the time the righting reflex was regained were lower in the cold-exposed rats, indicating that the observed decrease in sleeping time was not due to decreased central nervous system sensitivity to these agents. The onset time of hexobarbital, meprobamate and barbital hypnosis was similar in cold-exposed and control rats, suggesting that altered drug absorption is not responsible for the observed differences in duration of drug response. The decline of brain and plasma concentrations of zoxazolamine was more rapid in the cold-exposed animal. The metabolism of hexobarbital and aminopyrine was significantly elevated in isolated perfused livers from cold-exposed rats. Hepatic microsomal N-demethylase activity, hexobarbital and meprobamate oxidation, CO-binding pigment, and NADPH-cytochrome c reductase activity were increased in the cold-exposed rat. Experiments with 2-¹⁴C-glycine indicated that the in vivo incorporation of this isotope into hepatic microsomes was increased significantly in the cold-exposed rat. These results indicate that cold exposure stimulates hepatic drug metabolism and suggest that this stimulation is mediated via an accelerated synthesis of the hepatic drug-metabolizing system.     

Effect of route of administration and distribution on drug action

The extent and time course of drug action can be markedly affected by the route of drug administration into the patient as well as the pattern of drug distribution within the patient. Drugs which are rapidly cleared by hepatic processes will show a decreased extent of availability following oral administration due to metabolism of drug on its first pass through the liver. The magnitude of this first pass will depend on the blood flow to the liver and the intrinsic clearing ability of the liver (i.e., the ability of the organ to eliminate the drug independent of the rate at which drug is brought to the organ). Drug distribution in the patient will depend on the blood flow to various sites in the body as well as the partition coefficient of the drug between the blood and the distributive organs. Protein binding both in the plasma and in the tissues will markedly affect this distribution. However, free drug concentrations are generally believed to be the effective determinant in drug therapy. Often a redistribution due to changes in protein binding will have little effect on the therapeutic efficacy since, although total drug distribution changes, free concentrations in the plasma remain essentially similar.This article is extracted from the forthcoming bookModern Pharmaceutics: Drug Product Design and Evaluation, edited by Gilbert S. Banker and Christopher T. Rhodes, copyright 1978, Marcel Dekker, Inc. Published with permission.     

昂立品山抑瘤口服液抗小鼠肿瘤实验研究

目的：评价昂立品山抑瘤口服液对小鼠H22肝癌和S180肉瘤的抑瘤作用。方法：小鼠预先给予昂立品山抑瘤口服液每天10，20，30ml/kg，连用21天，然后皮下接种肿瘤，继续给予口服液7天。疗效评价采用瘤体称重法。结果：昂立品山抑瘤口服液能够明显抑制以上肿瘤的生长，它对小鼠H22肝癌和S180肉瘤的抑制率分别达到41％和44％（30ml/kg)，并增加小鼠体重。结论：在本试验条件下，昂立品山抑瘤口服液能够明显抑制小鼠H22肝癌和S180肉瘤的生长，改善小鼠的营养状态。     

妥洛特罗贴剂经皮给药治疗小儿支气管哮喘的疗效

目的监测小儿支气管哮喘患者在综合治疗过程中经皮给予妥洛特罗贴剂后病情的缓解及症状的改善。方法将104例轻中度小儿支气管哮喘患者分为2组:对照组50例,给予综合治疗,抗感染、抗病毒、止咳、化痰等常规治疗;治疗组54例,除综合治疗外,根据年龄的不同,给予妥洛特罗贴剂0.5mg或1mg,观察两组咳嗽时限及痰液排出时间。结果治疗组咳嗽及排痰时限均短于对照组,差异有统计学意义(P<0.05)。结论妥洛特罗经皮给药治疗小儿支气管哮喘,能缩短咳嗽、排痰时限,达到缩短病程的效果。