稳定的次氯酸(HOCl)作为一种非常有效的环境消毒剂正在迅速崛起。这种发展迎合了人们对环境友好型合成化学品的日益关注,以及新出现的疾病的抗微生物趋势(Choffnes、Relman, and Mack,2010年;Coates,2012年;Gualerzi、Brandi、Fabbretti and Pon,2014年;Ventola,2015年)。
在病人护理、环境卫生和畜禽饲料添加剂中过度使用抗菌剂,有可能使药物回到抗生素之前的时代(Drlica and Perlin,2011;Fong and Drlica,2008;Kon and Rai,2016)。如今,各类病原体对传统消毒剂、抗菌剂和疗法的抗性逐渐增加,使用新的抗感染制剂已成为安全和成功管理住院患者的关键(Bhardwaj、Zeigler and Palmer,2016;Yazdankha et al,2006)。
美国FDA(食品及药物管理局)认为HOCl是“对多种微生物具有最高杀菌活性的游离氯”(US FDA,2015年),但在传统观念中HClO因会迅速降解而无效,其使用受到诸多限制(Lister,1952年)。近年来,HClO因其在哺乳动物和多数脊椎动物(包括鱼类)自然防御系统中作为“第一反应者”的作用而被认知,从广义上而言,HClO为感染控制提供了一个新的机遇(Klebanoff,1975;Albrich et al,1986;Black and Pickering,1998;Marcinkiewicz et al,2000)。此外,电解技术的进步克服了HOCl原有不稳定性带来的技术挑战,实现了稳定和高纯度HClO的大规模生产(Terry and Williams,2016)。
游离氯:以次氯酸、次氯酸根离子或溶解的单质氯形式存在的氯。
大量的测试和应用实践表明,稳定的HOCl是一种有效和安全的化合物,可满足不同领域的应用需求(Al-Haq、Sugiyama and Isobe,2005;Thorn et al,2012)。在pH 3或以下时,HOCl存在于盐酸和氯(分别为HCl和Cl2)的溶液中。在pH值为7.5或更高的溶液中,HOCl溶液含有更多的次氯酸盐(OCl-)。活性氯最终还原为氯离子(Cl-),导致传统方法制备的HOCl溶液的抗菌活性随时间而降低,并被描述为“高度不稳定”(USDA-AMS,2015年8月)。HOCl没有有毒物质的处理要求,OSHA认为HClO在使用后不属于危险废弃物,这为HOCl的使用提供了一个有力条件。HOCl可以使蛋白质变性而失去活性,特别是其对朊蛋白的灭活作用,为医疗机构疾病控制方案的设计和实施提供了新的机会(Hughson et al,2016)。朊病毒感染性尤其值得关注,因为已知朊病毒普遍存在,而且极难灭活(Abbott,2015)。
译者注:OSHA,即职业安全与健康管理局。
因此,HOCl可以在必要时为患者护理提供可行的帮助。随着抗药性微生物的出现,从外来黄病毒到高侵袭性念珠菌、酵母菌,HOCl的重要性正在增加(Sherry et al,2017年;Clancy和Nguyen,2017年)。HClO作为一种暂未被广泛应用的感控产品,在环境卫生、消毒、食品安全和卫生领域都可能具有较大作为。
150多年前,次氯酸被认作为一种独特的化学物质(Cordova,1916)。在第一次世界大战中,次氯酸因其抗感染特性被广泛用作创伤伤口的抗菌剂(Smith,Drennan,Rettie and Campbell,1915),随后其应用逐渐扩展至环境卫生和治疗坏疽、白喉和猩红热(Beattie,Lewis and Gee,1917年)。到了20世纪40年代,伦敦医院已将酸化次氯酸盐得到的HClO溶液雾化用作防止病原体在空气中扩散的感染控制措施(Elford and van den Ende,1945)。
在过去的20年里,有超过100份文献报道了HOCl在园艺、乳制品设施、动物产房、护理机构和医院中的应用表现,有力地证明了HOCl是不同行业中可靠、安全、高水平消毒的选择之一(Al Haq etal. 2012, Thorn etal., 2012)。HOCl作为一种化学消毒剂,对关键指示微生物(如孢子)展示良好的杀灭效果(Loshon,Melly,Setlow and Setlow,2001)。这些用途申请已在美国和欧盟已获得批准,包括美国农业部批准使用现场生产的HOCl作为各种农产品的安全清洗剂(美国农业部食品安全检验局,2017年)。
近几年,几份关于医疗保健方面的文献报道也值得重点关注。Fertelli等人(2013年)使用现场电解盐水制备的HOCl喷雾来净化接种了艰难梭菌孢子的病房表面。报告指出,与对照组相比,在使用HClO处理后,血压计、血氧计、床边便桶和药物泵等设备表面艰难梭菌减少了约105。Park等人(2007年)采用了类似的方法来测试HOCl对诺如病毒接种表面(陶瓷、不锈钢)的杀菌效果,结果表明在接触10分钟后杀菌效果大于99.9%。在费拉拉大学(意大利)进行了8周的研究后表明,暴露于低水平(<1ppm)的现场产生的HOCl后,医院水系统中军团菌显著下降,因此建议在其机构中使用HClO进行清洁干预和预防(Migliarina and Ferro,2014)。
在Hakim等人的一篇论文中,通过将HOCl进行喷雾,禽流感(H5N1)病毒在10秒或更短时间内被灭活(2015),因此考虑可将其用于病毒控制中。现场电解生成的HOCl气溶胶用于手术设施的卫生控制试验中,在研究期间对暴露于HClO气溶胶中的各种电子设备未检测到不良影响(Rainina et al.,2012)。这些研究报告为HOCl制剂的有效性和可靠性建立了信心,证明了其在医疗感染防控中的实际潜力。
次氯酸的稳定性
尽管有证据表明HOCl是一种卫生资源,但其商业化进展缓慢。精确控制次氯酸盐溶液的pH值,使反应平衡向以HOCl为主的方向转变(Wang et al,2007)。然而,事实证明,要在不受分子氯(Cl2)、三氯化碳、次氯酸盐或氯酸盐/亚氯酸盐离子混杂的情况下生产出一致的产品是很困难的。此外,以这种方式制备的HClO溶液如果没有做好原料管控和制程管理(如Wang等人所述),通常显示出不稳定性,无法体现出HOCl的优势(Soo Voon等人,2002)。
通过电解氯化钠水溶液产生HClO,已经可以实现的商业化运行。电解过程中分别在阳极和阴极产生HClO和氢氧化钠。阳极区产生的富含HOCl的溶液,但容易迅速转变为氯酸盐/亚氯酸盐和次氯酸盐的混合物(Eryilmaz and Palabiyik,2013年,Lister,1952年)。
HClO溶液
如果不依赖稳定性添加剂来抑制HClO的衰减,电解制备稳定的HOCl溶液并不容易(Wang et al,2007)。然而,美国一家叫Briotech的公司通过精细控制工艺条件实现了稳定性HClO的生产。Briotech HOCLTM是一种等渗溶液,含有约9000 ppm的Cl-和200ppm HOCl。因此,随着时间的推移,一部分HOCl最终转化为Cl-不会严重影响溶液的总Cl-含量,并且它保持在等渗浓度范围内。
Brio HOCLTM在标准温度和压力下展示出了对传染性朊病毒的灭活能力(Hughson et al.,2016)。朊病毒是一种具有传染性的非活性畸形蛋白,可导致一系列的人类和动物致命性疾病,包括疯牛病和人类的克雅氏病。有证据表明,阿尔茨海默症具有朊病毒传播的传染性成分(Abbott,2015)。如引文中所述,已知朊病毒能够抵抗所有传统的灭菌方法,相比之下,这些方法都需要苛刻的条件,但是当它们暴露在含有160ppm有效氯浓度的Brio-HOCLTM溶液中(朊病毒在5分钟内减少99.9%;1小时后超过99.999%)时,它们被迅速破坏。此外,HClO对细菌孢子也具有杀灭作用,因此HClO制剂具有对医疗器械和外科器械进行高水平消毒的潜力(Russell,1990;Fertelli et al.,2013)。
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