药用气雾剂抛射剂的替代：从CFC到HFA

药用气雾剂抛射剂CFC（氟里昂）的替代转换已成为国际药剂学研究的热点之一,我国尚未起步。本文就CFC替代的沿革及国际国内的科研和市场现状,简介若干替代方案及其产品,综述了CFC替代过程中面临的诸多影响因素,并提出相应的措施。     

利多卡因氯己定气雾剂抛射剂替代实验

目的采用二甲醚替代氟里昂作为抛射剂,改良利多卡因氯己定气雾剂处方。方法以二甲醚替代原处方中的氟里昂作为抛射剂,保持原处方中的主药利多卡因、醋酸氯己定和苯扎溴铵含量,在新处方中添加水。采用高效液相色谱法测定改良利多卡因氯己定气雾剂中主药利多卡因和醋酸氯己定含量。结果利多卡因和醋酸氯己定的含量均符合原质量标准要求。结论二甲醚可以替代氟里昂作为利多卡因氯己定气雾剂的抛射剂。     

药用气雾剂辅料抛射剂质量标准概述

药用气雾剂是一种特别的药物剂型,在治疗支气管哮喘、慢性阻塞性肺病等呼吸系统疾病方面具有其他剂型不可替代的优势;抛射剂是药用气雾剂中药液雾化的动力,也是溶解或分散药物的介质,作为药用气雾剂中的重要辅料,抛射剂的质量直接影响到药品的安全性和有效性。现对几类常见的药用气雾剂辅料抛射剂国内外质量标准进行概括比较,为我国药用气雾剂辅料抛射剂质量标准的制修订工作提供参考。     

氟代烷烃抛射剂在医用气雾剂中的应用

综述了新的无臭氧层破坏作用的氟代烷烃抛射剂的性状及其在医用气雾剂中的应用。     

氟利昂替代后吸入气雾剂(MDIs)的研究要求和进展Ⅰ.欧美抛射剂替代的MDIs的研发和质量控制

分析了欧美国家近20年吸入气雾剂(MDIs)中抛射剂替代的技术、法规、监管的经验和教训;总结了抛射剂替代后MDIs临床前研究的重点考察项目和成品质控的具体要求;介绍了国外MDIs的分类和单个品种与整个类别的淘汰策略.     

药用抛射剂含氯氟烃代用品的研究进展

气雾剂作为众多药物剂型中的一个分支,具有分布均匀、奏效快、使用方便、剂量小等特点,经过多年来的发展,现已广泛为人们所接受。传统的气雾制品采用含氯氟烃(chlorofluorocarbon,CFC)作为抛射剂。但由于CFC对大气臭氧层的破坏作用,近年来其应用受到了限制,国内外都在积极寻找CFC代用品,相继出现了无氯氟代烷烃如四氟乙烷,七氟丙烷等。由此也促使不含CFC的新型肺部药物传递系统取得了重大发展。本文对药用气雾剂中抛射剂CFC代用品的相关研究进展作一综述。     

新型抛射剂HFA的应用研究

新型抛射剂氢氟烷烃(HFA)不含氯，不破坏大气臭氧层，可代替氯氟烷烃用于药物气雾剂的制备。本文综述HFA的理化性质、生物学性质及作为抛射剂用于药物气雾剂时对药物安全性和药效的影响。     

药用定量吸入气雾剂中氟里昂抛射剂替代的研究进展

氯氟烷烃（CFC）即氟里昂,因对臭氧层的破坏和温室效应而导致禁用,以其为抛射剂的药用吸入气雾剂将于2010年全面退出中国市场.国外对CFC替代的研究已有20年,并有一系列品种上市,而国内在该方面的研究几乎为空白.本文综述TCFC的替代概况、替代抛射剂氢氟烷烃的理化性质、气雾剂处方的影响因素、制剂的疗效和安全性等.     

Alternative propellant aerosol delivery systems

The year 2006 represents the 50th anniversary of the pressurized metered dose inhaler. With most technologies, 50 years represents a significant time span for technology evolution and modification, but with propellant-driven metered dose inhalers, the pace of change has been relatively slow. We are now in the era of alternative propellant aerosol delivery systems, but at this 50-year juncture, what are the characteristics of these systems and what are the prospects for future advances? This review will consider alternative propellant aerosol delivery systems broadly from their inception through future opportunities and challenges.     

布地奈德气雾剂联合特布他林气雾剂治疗婴儿支原体肺炎

目的 观察布地奈德气雾剂联合特布他林气雾剂治疗婴儿支原体肺炎（MP）的临床疗效.方法 以240例MP患儿为研究对象,根据治疗方法不同将240例患儿分为观察组和对照组,各120例,观察组给予布地奈德联合特布他林雾化吸入治疗,对照组给予布地奈德雾化吸入治疗.比较两组免疫学指标免疫球蛋白G（IgG）、免疫球蛋白E（IgE）及TNF-α水平、主要临床症状及疗效.结果 与治疗前比较,两组IgG、IgE、TNF-α水平,IgG明显升高,IgE、TNF-α水平明显降低,差异均具有统计学意义（t=19.965、10.780、3.468、6.002、5.440、4.885,均P＜0.05）,且观察组明显优于对照组（=13.920、4.523、2.729,均P＜0.05）;观察组体温、喘憋、发绀、咳嗽及肺部啰音等临床症状缓解时间均明显短于对照组（t=2.991、6.034、4.623、8.562、7.113,均P＜0.05）,显效率（93.3％）显著高于对照组（79.2％）（x2=8.140,P＜0.05）;两组均无明显不良反应.结论 布地奈德、特布他林雾化吸入治疗婴儿支原体肺炎,临床症状缓解快,疗效好,不良反应少,值得临床推广.     

含有新型抛射剂的硫酸沙丁胺醇气雾剂的制备

目的制备不含氟利昂的硫酸沙丁胺醇气雾剂,并进行处方优化.方法以性状、雾滴(粒)分布、含量等作为评价指标进行处方筛选,并进行加速稳定性考察.结果经处方优化确定的硫酸沙丁胺醇气雾剂其性状、雾滴(粒)分布、含量等指标均符合规定,加速稳定性试验结果显示,本品质量稳定.结论所选处方工艺稳定可靠,适合生产.     

Nanoparticle aerosol generation methods from bulk powders for inhalation exposure studies

Abstract

Inhalation toxicity studies of nanoparticles require production of test aerosols with a number of acceptable characteristics. Five different generation methods for producing a nanoparticle aerosol from the bulk powder were evaluated with the goal of producing an acceptable aerosol that is homogenous, has a consistent concentration over time in which the magnitude may be intentionally varied, and has a size distribution that is both unimodal and has a small geometric mean diameter relative to the primary particle size of the nanoparticle bulk powder. Four types of bulk powders were evaluated including titanium dioxide, silicon dioxide, polymer-coated silver, and single walled carbon nanotubes. A nebulizer was the only tested method able to produce a consistent aerosol of sufficient magnitude. However, the resulting aerosol contains particles derived from the carrier water. Prior sonication of the nanoparticle suspension alone was found to be not useful for deagglomerating nanoparticles.     

Formulation of a protein with propellant HFA 134a for aerosol delivery

The purpose of this study was to investigate the formulation and delivery of a protein in a pressurized metered-dose inhaler (pMDI) containing HFA 134a as the propellant for aerosol delivery. Ethanol and surfactants, including polyoxyethylene 10 oleyl ether (Brij 97), polyoxyethylene 20 oleyl ether (Brij 98), polyoxyethylene sorbitan monooleate (Tween 80) and Aerosol OT (AOT), were investigated as formulation adjuvants to improve the dose delivery characteristics of the model protein (bovine serum albumin) containing pMDI formulations. The aqueous solution of a surfactant and protein was lyophilized to obtain a solid carrier system of the protein. Readily dispersible suspensions were obtained by suspending this solid carrier system in HFA 134a with ethanol as a dispersing aid. The formulations containing Tween 80 resulted in the highest respirable fraction. This study suggested a potential formulation containing a lyophilized complex of surfactant and protein readily dispersible in HFA 134a for delivering a therapeutic protein to the respiratory tract by inhalation.     

Ciclosporin aerosol in lung transplantation

The development of ciclosporin as an aerosol for rejection immunosuppression following lung transplantation started as a research idea at the University of Pittsburgh in 1989. In the 17 subsequent years, the development of the aerosol, testing in animals and several protocols testing the drug in patients have all taken place at the University of Pittsburgh and State University of New York. No other medical advances have displaced the potential of the drug during this time in lung transplantation, which still has a dismal 5-year survival of 50%. Therefore, the recent publication of the double-blind, placebo-controlled study of aerosolised ciclosporin for long-term use to significantly improve patient survival was heralded as a breakthrough by the commentary in the New England Journal of Medicine. Nevertheless, multiple problems may prevent this drug from ever receiving FDA approval and reaching the market. These problems include the need for a multi-centre study, a lack of surrogate markers for chronic rejection in lung transplant patients and a drug formulation that will prevent the expansion of the use of aerosolised ciclosporin for other indications.     

Bricasol气雾剂治疗支气管哮喘临床及即时肺功能研究

目的 研究应用Bricasol气雾剂后肺功能的改善情况及治疗效果。方法 选择支气管哮喘发作期患者32例，其中男16例，女16例，分男、女两组观察。患者到实验室后先休息10～15min，然后吸入Bricasol气雾剂共两喷，间隔半分钟，剂量共0．5mg，观察治疗前和治疗后1、5、15min的肺功能变化。结果 男、女两组吸药后1、5、15minFEV1.0均值；V75吸药后5、15min均值；PEFR女吸药后1、5、15min、男吸药后5、15min均值；FVC女吸药后1、5、15min均值均较吸药前明显增加或极明显增加。所有观察对象均于吸药后5min憋喘症状明显减轻，听诊哮鸣音减少，15min憋喘症状改善最为明显。结论 吸入Bricasol气雾剂后，支气管哮喘患者肺功能明显改善，显效迅速，疗效好，是较理想的支气管舒张剂。