CN101267734A - 包含杀生物酚和角质分离剂的组合的消毒剂 - Google Patents
包含杀生物酚和角质分离剂的组合的消毒剂 Download PDFInfo
- Publication number
- CN101267734A CN101267734A CNA2006800343908A CN200680034390A CN101267734A CN 101267734 A CN101267734 A CN 101267734A CN A2006800343908 A CNA2006800343908 A CN A2006800343908A CN 200680034390 A CN200680034390 A CN 200680034390A CN 101267734 A CN101267734 A CN 101267734A
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- China
- Prior art keywords
- phenol
- disinfectant
- eimeria
- chloro
- chlorination
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 238000005660 chlorination reaction Methods 0.000 claims description 21
- LLEMOWNGBBNAJR-UHFFFAOYSA-N biphenyl-2-ol Chemical compound OC1=CC=CC=C1C1=CC=CC=C1 LLEMOWNGBBNAJR-UHFFFAOYSA-N 0.000 claims description 14
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Abstract
本发明涉及一种消毒剂，其包含杀生物酚，以及视需要的酚衍生物，与角质分离剂的特定组合。该消毒剂特别适用于防治寄生原生动物，包括其的持久型。
Description
本发明涉及一种消毒剂，其包含杀生物酚以及适宜时的酚衍生物与角质分离剂的特定组合。该消毒剂特别适宜于防治寄生原生动物，包括持久型的寄生原生动物。
该杀菌剂例如在防治有益动物的虫球病方面具有特别重要的意义。柔嫩艾美球虫(Eimeria tenella)是能导致禽类虫球病的一种原生动物病原体，虫球病在场地密集饲养的小鸡和母鸡情况下造成严重的经济问题。动物间的传染是在它们接受了形成孢子的卵囊后开始的，所述卵囊是传染性单细胞的子孢子的载体。这些子孢子会植根于肠细胞中，而在其保护下，寄生期能繁殖到其百万倍的数量。虫球病的病状包括带血腹泻，其将会由于母鸡减少了营养摄入和重量减轻而导致严重的经济损失。
目前，为了预防该疾病，每年至少需要消耗价值三亿五千万美元的抗虫球剂。自1970年以来，尤其使用聚醚离子载体莫能菌素、甲基盐霉素、盐霉素以及拉沙里菌素的化学疗法实施。除了对母鸡有严重药物副作用之外，抗药性的增强被认为是化学疗法治疗中最大的问题。抗药性出现的最初表现通常为卵囊排泄物重新增多。
化学疗法治疗虫球病的替代方法是提早消毒禽舍。在这些禽舍中，如被称为卵囊的艾美球虫(Eimeria)的持久阶段(Dauerstadien)产在动物的排泄物中，并与排泄物残渣和饲料成分一起持续分布在地面、墙面上，分布在墙壁的裂缝中和饲养设施上，并且作为恒定的传染源，在很长时间内引发所饲养动物的新疾病。艾美球虫(Eimeria)的卵囊在直到其被排泄一年之后还可以具有传染性。在之一阶段通过人或动物将卵囊传播到邻近的禽舍形成了另外的问题。
柔嫩艾美球虫(Eimeria tenella)卵囊的大小是24.5-18.3mm，且其通过发生在感染动物肠细胞中的无性繁殖循环使其数目增长数百万倍。雌性的雌配子与雄性的雄配子完成受精并形成受精卵，其本身环绕着两层典型的层：平滑的外层在壁形成体WFI(“壁形成体I”)融合之后发育，而内层在壁形成体II(“壁形成体II”)融合之后发育。直到两层都已经完全形成，成熟的卵囊保持在感染肠细胞的寄生泡中，然后才与粪便一起排泄。然后在有氧的情况下开始所谓孢子的形成：由未分化的母孢子通过减数分裂形成每个都含有两个子孢子的四个孢子囊。对于柔嫩艾美球虫(Eimeria tenella)来说，孢子的形成通常持续2-3天。在其完成之后，卵囊才具有传染性。
两层卵囊壁的结构和组成赋予了它们显著的生化和生理抗性，从而使该壁成为确保寄生生物在户外存活的有效保护屏障。外层的卵囊壁由磷脂、长链醇和甘油三酸酯构成，而内层由通过二硫键稳定的糖蛋白组成。大小为12-14kDa的主卵囊壁蛋白包含有丝氨酸、酪氨酸和苏氨酸的氨基酸并结合到碳水化合物上。这些蛋白质使卵囊具有对热或冷的较大结构稳定性。外层中的脂类决定了对化学物质的高抗性。
采用加热、冷冻、干燥或照射的简单物理消毒法仅能非常有限地使用：比如，虽然卵囊在试验室中在60-100℃的温度下几分钟内就会被杀灭，但是在室内热水的消毒效果却通常很小，这是因为水在房间地板上会很快冷却。高压净化在作用时间较短时也仅能实现部分消毒。而且卵囊也具有显著地耐寒性。艾美球虫(Eimeria)卵囊即使在-25℃下深度冷冻14天也仍能存活并保持传染性。虽然干燥能造成一定程度的损害，但该方法对于消毒目的而言仍然不很可靠。
虽然3.5-4.0kGy及更高的γ辐射或电子辐射会使卵囊失去形成孢子的能力，但是由于所需设备的成本较高，则对于农民来说使用该辐射的方法是不切实际的。
大多数对细菌和病毒有效的化学消毒剂对艾美球虫(Eimeria)卵囊不起作用，这是由于后者的壁具有更复杂的化学构造并能阻止化学试剂透入。特别针对寄生虫的消毒剂首先要能穿透含有脂类物质的卵囊外壁，之后侵蚀内壁中的稳定糖蛋白，然后才能破坏含有薄膜的孢子囊和子孢子。
艾美球虫(Eimeria)卵囊对侵蚀性无机物如氢氧化钠(NaOH)水溶液或次氯酸钠(NaOCl)的抗性比细菌强1000倍。卵囊的传染性即使是在＞5％的浓度下接触120分钟也不会丧失。虽然在东欧国家中偶尔有使用氨气(NH3)接触24小时后成功的情况，但是同时充满氨气的空气闻起来也是非常难受的。
乙醇(70-90％)和甲醛对于有抗性的艾美球虫(Eimeria)卵囊没有足够的实际效果。
一些酚衍生物，特别是对氯间甲酚，作为唯一的有机活性化合物容纳在一些商用制剂中(表1)，此外其也与二硫化碳和氯仿组合出现(表1)。这些衍生物在实践中被用来防治空房屋中的禽类虫球病。
表1：经许可的能有效抗艾美球虫(Eimeria)卵囊的消毒剂(
2000)
WO 94/17761中描述了具有杀寄生虫活性的消毒剂，其含有一种或多种苯酚与角质分离剂活性有机酸、乙二醇二烃基醚、和钠或钾的烷基磺酸盐或烷基硫酸盐的组合。
在德国，按照德国兽医协会(DVG)的指南用悬浮试验(溶胞试验)和对小母鸡(Hühnerküken)的传染试验测试了抗寄生虫消毒剂对柔嫩艾美球虫(Eimeria tenella)卵囊的活性。″Houghton″株的柔嫩艾美球虫(Eimeria tenella)卵囊被列为具有特别抗性的，并被推荐作为试验菌。
同时，在实践中防治艾美球虫(Eimeria)种的卵囊尤其麻烦。然而，囊壁的结构与其他原生动物的相似，特别是与球虫以及蠕虫相似。因此，以艾美球虫(Eimeria)种为例的上述描述也可以被应用于这些生物。
当采用该测试系统，我们惊奇地发现，含有不同杀生物酚或酚衍生物，同时利用了角质分离剂的试剂的消毒效果明显优于已有消毒剂。
因此，本发明涉及：
一种消毒剂，其包括：
(a)氯化的杀生物酚；
(b)其它的氯化的或非氯化的杀生物酚；
(c)其它的非氯化的杀生物酚和/或酚衍生物，以及
(d)角质分离剂。
杀生物酚被理解为带有游离的OH基团，并具有杀生物效果的苯酚化合物。这些苯酚可以带有其它的环取代基，例如卤素，特别是氯，C1-6-烷基，C3-6-环烷基，苯基，氯苯基，苯甲基和/或氯苯甲基。
非氯化杀生物酚的例子有：2-甲酚，3-甲酚，4-甲酚，4-乙基苯酚，2，4-二甲苯酚，2，5-二甲苯酚，3，4-二甲苯酚，2，6-二甲苯酚，4-正丙基苯酚，4-正丁基苯酚，4-正戊基苯酚，4-正己基苯酚，百里酚(5-甲基-2-异丙基苯酚)，2-苯基苯酚，4-苯基苯酚和2-苄基苯酚。优选使用2-苯基苯酚作为非氯化杀生物酚。
氯化杀生物酚的例子有：4-氯-3-甲酚(PCMC，对氯间甲酚)，4-氯-3-乙基苯酚，2-正戊基-4-氯苯酚，2-正己基-4-氯苯酚，2-环己基-4-氯苯酚，4-氯-3，5-二甲酚(PCMX，对-氯-间二甲酚)，2，4-二氯-3，5-二甲酚(DCMX，二氯-对二甲酚)，4-氯-2-苯基苯酚，2-苄基-4-氯苯酚，苄基-4-氯-间甲酚以及4-氯苯甲基-二氯-间甲酚。优选氯化的杀生物酚为2-苄基-4-氯苯酚，4-氯-3，5-二甲酚，2，4-二氯-3，5-二甲酚，以及特别是4-氯-3-甲酚。
在此，酚衍生物被理解为由苯酚衍生的化合物，其OH基团是衍生的，因此它们不含有任何游离的OH基团。酚衍生物优选苯酚醚，特别是含有具有1至6个碳原子的脂肪醇的苯酚醚。苯氧基乙醇可作为优选的实例而提及。
根据本发明中的一种实施方案，非氯化苯酚作为杀生物活性成分可与二氯苯酚组合。一个优选的例子是4-氯-3-甲酚、2-苯基苯酚和2-苄基-4-氯苯酚的组合。
还已经发现，将非氯化酚衍生物，特别是苯氧基乙醇，与杀生物酚一起使用通常会导致进一步提高效果。
根据一个优选的实施方案，可以将氯化苯酚、非氯化苯酚和非氯化酚衍生物，特别是苯氧基乙醇，一起用作杀生物活性成分使用。
根据另一个优选的实施方案，也可以将两种不同的氯化苯酚和非氯化酚衍生物，特别是苯氧基乙醇，一起用作杀生物活性成分。
特别优选的是将两种不同的氯化苯酚、非氯化苯酚以及非氯化酚衍生物，特别是苯氧基乙醇，一起作为杀生物活性成分使用。特别优选的例子是将4-氯-3-甲酚、2-苯基苯酚、2-苄基-4氯苯酚和苯氧基乙醇组合使用。
角质分离剂是那些能对角质起作用，而且在极端情况下，能使其变性或分解的物质。针对本发明的试剂作为角质分离剂可以考虑：有机酸，如柠檬酸、蚁酸和水杨酸；此外还有，尿素、间苯二酚、巯基乙酸、硫化物、尿素、5-氟尿嘧啶。根据本发明，水杨酸是优选的。
酚类活性成分和角质分离剂可以以多种方式配成消毒剂，液体或固体的制剂都可以考虑。
可以使用例如以粉末、粉尘、颗粒等形式的固体制剂。其通常含有载体物质和/或辅助物质。活性成分可以与载体物质和/或辅助物质混合或吸附在其上。
然而，优选使用液体制剂，例如以乳液、悬浮液、或特别是溶液的形式。虽然液体制剂可以直接施用，但是优选其是浓缩的，通常在施用前用水稀释至适宜浓度。
乳液既可以是油包水型的也可以是水包油型的。其中将活性成分溶解到疏水相或亲水相中，并借助适当的乳化剂将该相与视需要的其它辅助物质和另一相的溶剂一起均质化，其中视需要的辅助物质如着色剂、防腐剂、抗氧化剂、光稳定剂和粘性增强物质。
所述的疏水相(油剂)有：石蜡油，硅油，天然植物油，例如芝麻油、杏仁油和蓖麻油，合成三酸甘油酯，例如辛酸/葵酸甘油二酯，含有链长为C8-12的植物脂肪酸或其他特别选择的天然脂肪酸的三酸甘油酯混合物，饱和或不饱和、可能还含羟基的脂肪酸的偏甘油酯混合物，C8/C10脂肪酸的甘油单酯和甘油二酯。脂肪酸酯，例如硬脂酸乙酯，己二酸二正丁酰酯，月桂酸己酯，壬酸二丙二酯，中等链长的支链脂肪酸与链长C16-C18的饱和脂肪醇的酯，肉豆蔻酸异丙酯，棕榈酸异丙酯，链长C12-C18的饱和脂肪醇的辛酸/癸酸酯，硬脂酸异丙酯，油酸油酯，油酸癸酯，油酸乙酯，乳酸乙酯，蜡类脂肪酸酯，例如邻苯二甲酸二丁酯和己二酸二异丙酯，后者尤其使用脂肪醇的酯混合物，例如异十三烷基醇，2-辛基十二烷醇，十六十八醇和油醇，以及脂肪酸，例如油酸。以及它们的混合物。
所述的亲水相为：水，醇例如丙二醇，甘油，山梨糖醇，乙醇，1-丙醇，2-丙醇和正丁醇，以及这些溶剂的混合物。
所述的乳化剂为：
非离子表面活性剂，如聚氧乙烯化的蓖麻油，聚氧乙烯化的单油酸脱水山梨糖醇酯，单硬脂酸脱水山梨糖醇酯，单硬脂酸甘油酯，聚氧乙基硬脂酸酯(Polyoxyethylstearat)，和烷基苯酚聚乙二醇醚；
两性表面活性剂例如N-月桂基-β-亚氨基二丙酸二钠或卵磷脂；
阴离子表面活性剂，例如脂肪醇醚硫酸盐，C8-18-烷基磺酸盐或C8-18-烷基硫酸盐，如月桂基硫酸钠或仲烷基磺酸盐(
优选含有15个碳原子的中等烷基链长)，和单/二烷基聚乙二醇醚正磷酸酯单乙醇胺盐；
阳离子表面活性剂，例如氯化十六烷基三甲铵。
所述的其它辅助物质有：增强粘度和乳液稳定性的物质，例如羧甲基纤维素、甲基纤维素及其他纤维素和淀粉衍生物、聚丙烯酸酯、藻朊酸盐、聚乙烯基吡咯烷酮、聚乙烯醇、由甲基乙烯基醚和马来酸酐构成的共聚物、聚乙二醇、蜡和胶状硅酸、或上述物质的混合物。
悬浮液是通过使活性成分悬浮在载液中制备的，视需要向其中添加其它辅助物质如：湿润剂，着色剂，防腐剂，抗氧化剂和光稳定剂。
本文中所提到的所有溶剂和均匀的溶剂混合物均可以考虑作为载液。
上述的表面活性剂也可以被称作湿润剂(分散剂)。
溶液是将活性成分溶解在适宜的溶剂中，并可能添加添加剂，如表面活性剂、增溶剂、酸、碱、缓冲盐、抗氧化剂和防腐剂。
上述的溶剂有：水、醇如具有1至4个碳原子的链烷醇(如乙醇，1-丙醇，2-丙醇，正丁醇)、芳族取代醇，如苯甲醇和苯乙醇；甘油，乙二醇、丙二醇、聚乙二醇、聚丙二醇，酯如乙酸乙酯，乙酸丁酯和苯甲酸苄酯；醚如亚烷基二醇烷基醚，例如二丙二醇单甲醚和二乙二醇单丁醚；酮如丙酮、甲基乙基酮，芳族和/或脂族烃，植物或合成油，二甲基甲酰胺(DMF)，二甲基乙酰胺，N-甲基吡咯烷酮，2-二甲基-4-氧亚甲基-1，3-二氧戊烷，和它们的混合物。
尽管溶液中使用的表面活性剂可以是在乳液情况下已列出的表面活性剂，但是，优选使用阴离子表面活性剂，特别是C8-18烷基磺酸盐或C8-18烷基硫酸盐，例如仲烷基磺酸盐()，优选具有15个碳原子的中等烷基链长的那些。
所述的增溶剂有：那些能够在主溶剂中促进活性成分溶解或防止其沉淀的溶剂。其例子为聚乙烯基吡咯烷酮、聚氧乙烯化的蓖麻油和聚氧乙烯化的脱水山梨糖醇酯。
作为其它辅助物质或添加剂，本发明中的消毒剂还可以包括软化剂和/或腐蚀抑制剂。
作为软化剂可以考虑例如水处理中已知的添加剂，例如膦酸，链状多磷酸盐或低分子量的多元羧酸。
在那些情况下，其中本发明的消毒剂还应稀释使用，各内容物通常以下列的浓度存在：
杀生物酚和视需要的酚衍生物通常的总浓度为：基于消毒剂，按重量计10至90％，优选按重量计10至50％，特别优选按重量计15至40％。
氯化杀生物酚与非氯化杀生物酚或酚衍生物的比例优选在40∶60至90∶10的范围内，优选50∶50至85∶15，特别优选65∶35至82∶18(基于所含的杀生物酚和/或酚衍生物的总重量的重量比，杀生物酚和/或酚衍生物在下文中概括为酚类杀生物剂)。优选的酚类杀生物剂的优选浓度范围例如为(在每种情况下，基于试剂中所含的酚类杀生物剂的总重的重量百分比)：
4-氯-3-甲酚：30％至80％，优选40％至70％，特别优选45％至60％。
2-苄基-4-氯苯酚：5％至50％，优选10％至40％，特别优选15％至30％。
2-苯基苯酚：5％至60％，优选10％至50％，特别优选13％至45％。
苯氧基乙醇：3％至30％，优选5％至25％，特别优选10％至20％。
根据一个特别优选的实施方案，本发明的消毒剂作为杀生物酚包括4-氯-3-甲酚、2-苄基-4-氯苯酚和2-苯基苯酚的组合，其可以视需要和特别优选包括苯氧基乙醇。活性成分的浓度则在上述范围之内。
角质分离剂通常在本发明中的消毒剂中是以与酚类杀生剂的重量比为50∶50至10∶90使用，优选40∶60至15∶85，特别优选30∶70至20∶80。基于消毒剂成品(常为浓缩物)，角质分离剂的浓度通常为以重量计1％至30％，优选以重量计3％至20％，特别优选以重量计5％至18％。
本发明的消毒剂优选包括表面活性剂，通常的浓度是以重量计3％至20％，优选以重量计5％至20％，特别优选以重量计5％至15％。
溶剂的含量可以大幅度变化。在浓缩物情况下，非水溶剂，优选上述的具有1至4个碳原子的链烷醇(如乙醇，1-丙醇，2-丙醇，正丁醇)，通常以重量计15％至65％，优选以重量计20％至60％，特别优选以重量计30％至50％的量使用。此外，所述试剂还优选包括水，其量通常为以重量计0至30％，优选以重量计5至25％，特别优选以重量计5至20％。
如上详细描述的消毒剂通常是浓缩物，其通常需要用水稀释后再使用。即用型溶液通常含有按体积计0.5％至20％，优选按体积计1％至10％，特别优选按体积计1％至5％的消毒剂浓缩物。使用的浓度可以根据使用目的不同而变化。例如当使用高浓度的试剂时，达到令人满意的所需效果的作用时间就会更短。
通常的作用时间是，例如0.5至5小时，优选1-4小时。
本发明的消毒剂适于防治发现于畜牧业和动物育种中生产动物、繁育动物、动物园动物、实验室动物、试验动物和玩赏动物中的寄生原生生物和蠕虫。在该方面。该消毒剂特别对持久阶段(胞外囊孢阶段)有效。
寄生原生生物包括：
肉鞭毛虫亚门(Sarcomastigophora)(根足虫(Rhizopoda))，例如内阿米巴科(Entamoebidae)，如痢疾内变形虫(Entamoeba histolytica)，哈曼属(Hartmanellidae)如棘阿米巴种(Acanthamoeba sp.)，和哈氏虫种(Hartmanella sp.)。
顶复门(Apicomplexa)(孢子虫(Sporozoa))，特别是虫球目(coccidia)，如艾美球虫科(Eimeridae)，如堆型艾美球虫(Eimeriaacervulina)，腺型艾美球虫(E.adenoids)，阿拉巴马艾美球虫(E.alabahmensis)，鸭艾美球虫(E.anatis)，鹅艾美球虫(E.anseris)，阿氏艾美球虫(E.arloingi)，阿萨塔艾美球虫(E.ashata)，奥博艾美球虫(E.auburnensis)，牛艾美球虫(E.bovis)，布氏艾美球虫(E.brunetti)，犬艾美球虫(E.canis)，栗鼠艾美球虫(E.chinchillae)，E.clupearum，鸽艾美球虫(E.columbae)，E.contorta，槌形艾美球虫(E.crandalis)，蒂氏艾美球虫(E.debliecki)，分散艾美球虫(E.dispersa)，E.ellipsoidales，镰形艾美球虫(E.falciformis)，浮氏艾美球虫(E.faurei)，E.flavescens，火鸡孔雀艾美球虫(E.gallopavonis)，哈氏艾美球虫(E.hagani)，肠艾美球虫(E.intestinalis)，E.iroquoina，无余体艾美球虫(E.irresidua)，拉氏艾美球虫(E.labbeana)，E.leucarti，大型艾美球虫(E.magna)，巨型艾美球虫(E.maxima)，中型艾美球虫(E.media)，火鸡艾美球虫(E.meleagridis)，火鸡和缓艾美球虫(E.meleagrimitis)，和缓艾美球虫(E.mitis)，毒害艾美球虫(E.necatrix)，柯雅二氏艾美球虫(E.ninakohlyakimovae)，绵羊艾美球虫(E.ovis)，小型艾美球虫(E.parva)，孔雀艾美球虫(E.pavonis)，穿孔艾美球虫(E.perforans)，E.phasani，E.piriformis，早熟艾美球虫(E.praecox)，E.residua，粗糙艾美球虫(E.scabra)，E.spec.，斯氏艾美球虫(E.stiedai)，猪艾美球虫(E.suis)，柔嫩艾美球虫(E.tenella)，截形艾美球虫(E.truncata)，特鲁特艾美球虫(E.truttae)，邱氏艾美球虫(E.zuernii)，Globidium spec.，贝氏等孢球虫(Isospora belli)，犬等孢球虫(I.canis)，猫等孢球虫(I.felis)，俄亥俄等孢球虫(I.ohioensis)，芮氏等孢球虫(I.rivolta)，I.spec.，猪等孢球虫(I.suis)，犬新孢子虫(Neospara caninum)，囊等孢球虫属(Cystisospora spec.)，隐孢子虫属(Cryptosporidium spec.)，如弓形虫(Toxoplasmadidae)，例如刚地弓形虫(Toxoplasma gondii)，以及肉孢球虫科(Sarcocystidae)，如克氏肉孢球虫(Sarcocystis bovicanis)，牛人肉孢子虫(S.bovihominis)，住肉孢子虫(S.ovicanis)，绵羊巨肉孢子虫(S.ovifelis)，S.spec.和猪人肉孢子虫(S.suihominis)。
鞭毛纲(Mastogophora)(鞭毛虫(Flagellata))，如兰氏贾第球虫(Giardia lamblia)和G.canis。
还有，粘孢子纲(Myxospora)和微孢子门(Microspora)，如格留虫属(Glugea spec.)和微粒子属(Nosema spec.)。
蠕虫(helminth)，包括吸虫(Trematode)、绦虫以及线虫。
吸虫包括，如属于以下族/属的病原体：片形属(Fasciola)，前后盘属(Paramphistomum)，双腔属(Dicrocoelium)和后睾属(Opisthorchis)；
绦虫包括，如属于以下族/属的病原体：莫尼茨属(Moniezia)，大裸头属(Anoplocephala)，裂头属(Diphyllobothrium)，带属(Taenia)，棘球属(Echinococcus)，复孔属(Dipylidium)，瑞列属(Raillietina)，漏斗属(Choanotaenia)和棘结属(Echinuria)；
线虫包括，如属于以下族/属的病原体：Stronglyoides，血矛属(Haemonchus)，奥斯特属(Ostertagia)，毛园属(Trichostrongylus)，古柏属(Cooperia)，细颈属(Nematodirus)，毛首鞭形属(Trichuris)，有齿食道口属(Oesophagostomum)，夏柏特属(Chabertia)，仰口属(Bunostomum)，弓首属(Toxocara vitulorum)，蛔虫属(Ascaris)，副蛔虫属(Parascaris)，蛲虫属(Oxyuris)，Oesophagostumum，球头属(Globocephalus)，猪圆属(Hyostrongylus)，旋尾属(Spirocerca)，狮弓属(Toxascaris)，弓首属(Toxocara)，钩口属(Ancylostoma)，弯口属(Uncinaria)，毛细线虫属(Capillaria)，前殖属(Prosthogonimus)，裂口属(Amidostomum)，毛细线虫属(Capillaria)，蛔虫目(Ascaridia)，异刺属(Heterakis)，比翼属(Syngamus)和棘头动物门(Acanthocephala)。
除了用来对抗原生动物和蠕虫，本发明的消毒剂还可以用于例如防治下列物种：
细菌，如梭状芽孢杆菌(Clostridien)、大肠杆菌(Escherichia coli)、沙门氏属(Salmonella spec.)、假单孢菌属(Pseudomonas spec.)、葡萄球菌属(Staphylococcus spec.)、结核分支杆菌，以及
酵母，如白色念珠菌(Candida albicans)，以及真菌的传染。
此外，本发明的消毒剂还可以用于防治病毒，例如流感病毒。已知的是A型流感病毒和B型流感病毒。这例如对于属于A型的禽类不传染型流感病毒特别重要。作为实例可以提及H5N 1亚型不传染型流感病毒。
生产或繁育动物包括，哺乳动物，如牛、马、羊、猪、山羊、骆驼、水牛、驴、骡、斑马、兔、扁角鹿、驯鹿，毛皮动物，如貂、灰鼠和浣熊，鸟类，如母鸡、鹅、火鸡、鸭、鸽子和野鸡，以及家庭或动物园饲养的鸟类。
实验室或试验动物包括大鼠、小鼠、豚鼠、金黄田鼠、狗和猫。
玩赏动物，包括狗和猫。
本发明中的消毒剂特别适合被用于大规模的畜牧业，特别是，例如用于家禽繁育(例如养鸡业)、养牛业或养猪业。
实施例
I.制剂实施例
一般制备方案
将酚类在搅拌条件下溶解于醇或醇混合物中。在得到的醇溶液中加入水，视需要加入苯氧基乙醇，水杨酸和烷基磺酸盐(W93)并持续搅拌以使其溶解。
生物试验方法中的材料和方法
消毒制剂试验按照德国兽医协会(German Veterinary Society)测试化学消毒剂的指南以及Daugschies等人已经公开(2002)的方法进行。
1.卵囊的获得
试验使用了柔嫩艾美球虫(Eimeria tenella)的″Houghton″菌株(动物健康学会，Compton实验室，Newbury附近，Berks.RG16 ONN，英国)。用由Brinkschulte公司提供的14天大的雄性蛋用型小鸡(LSL菌株)来繁殖和分离卵囊。以1天大的小鸡的方式给动物中心提供动物，并保持其在动物中心不感染球虫，使用不含有球虫抑制剂的、能促进小鸡生长饲料和不限量的水，直到开始试验。感染是将13000个卵囊分散在0.2ml的水中通过管饲法分别接种给动物的。感染7天之后，用二氧化碳无痛地杀死动物，在此之后，将卵囊从盲囊中分离出来，并放入2％的重铬酸钾溶液中4天，而使它们形成孢子。在试验当天，通过3次离心将重铬酸钾从卵囊悬浮液洗出，每次离心均为2000转每分，5分钟，并将小球再悬浮于水中。在第3次离心之后，用Bürker箱将卵囊悬浮液的浓度调节至每ml母液含25000个卵囊。
2.卵囊的消毒(溶胞试验)
在每次试验进行之前立即将待测的消毒剂以使用浓度的两倍浓度在水(重蒸水)中配制。母液被用来制备1％，2％及4％的溶液：
100μl的母液+4900μl的蒸馏水(＝1％，双倍浓度)
200μl的母液+4800μl的蒸馏水(＝2％，双倍浓度)
400μl的母液+4600μl的蒸馏水(＝1％，双倍浓度)
每个制剂在每次试验中测定两次。每组试验中，将0.5ml的卵囊悬浮液(＝12500个卵囊＝100％)和0.5ml的消毒剂溶液混合在两个25ml的玻璃烧杯中。对于试验中的未处理试验对照(KI)是将0.5ml的水与0.5ml的卵囊悬浮液混合。在作用时间内(1h，2h或3h)，将悬浮液保持在轻柔动作的振荡器上。
在各作用时间结束后，将每个烧杯中的全部内容物都转移到2000ml的锥形烧瓶中。随后将烧杯用水漂洗，并用漂洗水补足1500ml。将烧瓶中的内容物混合，并经过室温下24小时的沉淀期，滗析直到只剩100ml。将沉淀物转移到200ml的离心管中，用水补足至200ml，并保持过夜。在第二天，将上清液抽出直到只剩大约30ml，之后将沉淀物转到50ml离心管中，并用水补足至50ml。在翻转混合之后，每个消毒批次，吸取6×200μl至96孔的微量滴定盘的6个孔中。将盘置于4℃的冰箱中，直到其要在显微镜下测试时为止。用倒置显微镜在200倍的放大倍数下对存在的卵囊数计数。只计数完整的、在其外壁上没有任何可辨认的变化的卵囊。
3.计算溶胞率
每个消毒批次从两个微量滴定盘(盘1、盘2，重复测定)再观察到的卵囊数量的算术平均数构成了计算溶胞率的基础。就此而言，各消毒剂批次的回收率(Wiederfindungsrate)(WR)与未处理对照(KI)的回收率的关系为：(rel.WR)：rel.WR[％]＝经消毒卵囊的WR×100/对照(KI)的WR[％]。消毒制剂的活性通过卵囊的“溶胞率”表明，而且其通过与100的差额表示：溶胞率[％]＝100-rel.WR[％]。
4.体内主试验(对小母鸡的传染试验)
为了确定经消毒的卵囊是否被实际杀死并丧失传染性，就必须按照德国兽医协会的(DVG)指南用经消毒的卵囊对小母鸡进行传染试验。
在我们的试验中，使约14天大的LSL蛋生型小鸡感染经消毒的卵囊；为此，将消毒或停止反应之后获得的卵囊悬浮液的密度以相应的对照例确定的稀释倍数稀释至2000/ml的理论剂量。为此，为了确定有多少ml的悬浮液来自含有2000个形成孢子的卵囊的KI 50ml管，使用了计算体外溶胞试验中采用的96孔微量滴定盘的值。为了进行感染，在此情况下测定的体积也从所有其他的消毒批次中取出，而与在该体积中存在的卵囊无关。给每只小鸡施加的体积是0.5ml。除了其中的试验对照以外，将来自原始卵囊悬浮液的传染对照调整至在0.3ml的体积中为2000个卵囊/ml。在传染7天之后，用二氧化碳将动物无痛苦地杀死。
为了评价有效性，我们考虑下述的指标：从试验开始至试验结束时体重的增加，与传染性相关的死亡率，在感染后的第6天和第7天，肉眼对粪便的评价(关于腹泻和排血)，(评级为0至6)，用肉眼对肠黏膜(特别是对于盲囊(评级为0-6))的损伤和卵囊排泄进行评价。排泄物中卵囊的数目用McMaster计数室来测定。计算被发现是与未处理和未感染的对照组有关的个体以及总评级(Haberkorn and Greif1999)。
根据本发明中的制剂所获得的试验结果在下面的表格中举例说明。可以看出新制剂与不是根据本发明的比较制剂相比具有更高的活性，特别是在减少卵囊排泄方面。
在实施例B、E、F和H的表格中，“处理”栏中的说明具有下列含义：
未感染对照＝未感染的对照组
感染对照＝感染对照组
实施例1＝制剂的实施例编号
“死亡”栏给出了死亡动物数/试验用动物数的值。“未感染对照的体重％”栏中给出了处理过的动物体重与未感染对照组体重的比例。“腹泻”、“损伤”和“卵囊”栏中提供有关效果的详细信息。总体评价列入“有效率％”栏中，0％意指无效而100％意指全效。
生物试验方法的结果
生物实施例A
3小时的作用时间后不同消毒制剂(4％)在体外抗柔嫩艾美球虫(Eimeria tenella)的试验
生物实施例B
3小时的作用时间后不同消毒制剂(4％)在小母鸡体内抗柔嫩艾美球虫(Eimeria tenella)的试验
*不是根据本发明的
**商业产品
生物实施例C：
在3小时的作用时间后，不同消毒制剂(1％，2％和4％)在体外抗柔嫩艾美球虫(Eimeria tenella)卵囊的试验
生物实施例D：
在1，2或3小时的作用时间后，不同消毒制剂(4％)在体外抗柔嫩艾美球虫(Eimeria tenella)卵囊的试验
生物实施例E：
在3小时的作用时间后，不同消毒制剂(4％)在小母鸡体内抗柔嫩艾美球虫(Eimeria tenella)卵囊的试验
生物实施例F：
在1小时的作用时间后，不同消毒制剂(4％)在小母鸡体内抗柔嫩艾美球虫(Eimeria tenella)卵囊的试验
生物实施例G：
在1，2和3小时的作用时间后，实施例6的消毒制剂(1％)在体外与Neopredisan(1％)相比的抗柔嫩艾美球虫(Eimeria tenella)卵囊的试验
生物实施例H：
在1小时的作用时间后，实施例6的消毒制剂(1％，4％)在小母鸡体内与Neopredisan(1％，4％)相比的抗柔嫩艾美球虫(Eimeria tenella)卵囊的试验
参者文献
R.(2000)：Liste der nach der Richtlinien der DVG geprüften undals wirksam befundenen Desinfektionsmittel für die Tierhaltung
Deutsches
9/2000.
Daugschies，A.，R.，Marx，J.，Teich，K.，Friedhoff，KT(2002)：Development and application of a standardization assay for chemicaldisinfection of coccidia oocysts.Vet.Parasitol.103(4)：299-308.
Mouafo，A.N.，Richard，F.，Entzeroth，R.(2000)：Observation of suturesin the oocyst wall of Eimeria tenella(Apicomplexa).Parasitol.Res.86：1015-1017.
Eckert，J.(2000)：Parasitenstadien als umwelthygienisches Problem.In：
Parasitologie 94-119.Eds.：Rommel，Eckert，Kutzer，
和Schnieder.Parey Buchverlag Berlin.
Haberkorn，A.，Greif，G.(1999)：Animal Models of Coccidia Infection.In：Handbook of Animal Models of Infection，第99章.Academic Press.
Claims (10)
1、消毒剂，包括：
(a)氯化杀生物酚，
(b)另外的氯化或非氯化的杀生物酚，
(c)非氯化杀生物酚和/或酚衍生物，和
(d)角质分离剂。
2、根据权利要求1中的消毒剂，其包括两种不同的氯化杀生物酚和非氯化杀生物酚。
3、根据权利要求1或2中的消毒剂，其包括非氯化杀生物酚衍生物。
4、根据前述权利要求之一的消毒剂，其中氯化杀生物酚选自下述组：4-氯-3-甲酚(PCMC，对氯间甲酚)，4-氯-3-乙酚，2-正戊基-4-氯苯酚，2-正己基-4-氯苯酚，2-环己基-4-氯苯酚，4-氯-3，5-二甲酚(PCMX，对氯间二甲酚)，2，4-二氯-3，5-二甲酚(DCMX，二氯对二甲酚)，4-氯-2-苯基苯酚，2-苄基-4-氯苯酚，苄基-4-氯-间甲酚和4-氯苄基二氯-间甲酚。
5、根据前述权利要求之一的消毒剂，其中非氯化杀生物酚选自下述组：2-甲酚，3-甲酚，4-甲酚，4-乙酚，2，4-二甲基苯酚，2，5-二甲基苯酚，3，4-二甲基苯酚，2，6-二甲基苯酚，4-正丙基-苯酚，4-正丁基-苯酚，4-正戊基-苯酚，4-正己基-苯酚，百里酚(5-甲基-2-异丙基苯酚)，2-苯基苯酚，4-苯基苯酚和2-苄基苯酚。
6、根据前述权利要求之一的消毒剂，其中非氯化杀生物酚衍生物是苯酚醚，特别是苯氧基乙醇。
7、根据前述权利要求之一的消毒剂，其中角质分离剂选自下述组：有机酸，如柠檬酸、蚁酸和水杨酸；尿素，间苯二酚，巯基乙酸、硫化物、5-氟尿嘧啶。
8、根据权利要求7的消毒剂，其中角质分离剂是水杨酸。
9、根据前述权利要求之一的消毒剂在防治寄生原生动物、蠕虫、细菌和/或酵母中的用途。
10、根据权利要求9的用途，用于防治寄生原生动物和/或蠕虫持久阶段。
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| CN105821665A (zh) * | 2015-12-28 | 2016-08-03 | 福建恒安集团有限公司 | 一种多功能es纤维纺丝油剂 |
| CN105821666A (zh) * | 2015-12-28 | 2016-08-03 | 福建恒安集团有限公司 | 一种多功能es纤维 |
| CN107593719A (zh) * | 2017-10-17 | 2018-01-19 | 赖丰光 | 含银果与氟环唑的农药组合物 |
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| JP5537033B2 (ja) * | 2005-12-19 | 2014-07-02 | ザ ユニヴァーシティー オブ リヴァプール | 無痛覚 |
| CA2685813A1 (en) * | 2007-05-09 | 2008-11-20 | Pharmacofore, Inc. | Therapeutic compounds |
| NZ580752A (en) * | 2007-05-09 | 2012-03-30 | Pharmacofore Inc | Stereoisomers propofol therapeutic compounds |
| DE102008031284A1 (de) | 2008-07-02 | 2010-01-07 | Bayer Schering Pharma Aktiengesellschaft | Neue Bekämpfungsmöglichkeit der Giardiose |
| US9693941B2 (en) | 2011-11-03 | 2017-07-04 | Conopco, Inc. | Liquid personal wash composition |
| JP6040257B2 (ja) | 2011-12-06 | 2016-12-07 | ユニリーバー・ナームローゼ・ベンノートシヤープ | 殺菌薬組成物 |
| BR112014015523A8 (pt) * | 2011-12-22 | 2017-07-04 | Unilever Nv | método de desinfecção, composição microbicida e uso de um ou mais fenóis substituídos para higiene aprimorada |
| RU2640500C1 (ru) * | 2017-06-30 | 2018-01-09 | Федеральное государственное бюджетное научное учреждение Всероссийский научно-исследовательский институт фундаментальной и прикладной паразитологии животных и растений имени К.И. Скрябина (ФГБНУ "ВНИИП им. К.И. Скрябина") | Способ дезинвазии против ооцист кокцидий птиц |
| RU2687487C1 (ru) * | 2018-05-30 | 2019-05-14 | Федеральное государственное бюджетное научное учреждение "Федеральный научный центр - "Всероссийский научно-исследовательский институт экспериментальной ветеринарии имени К.И. Скрябина и Я.Р. Коваленко Российской академии наук" (ФГБНУ ФНЦ ВИЭВ РАН) | Способ дезинвазии против ооцист кокцидий лисиц и песцов |
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| GB872900A (en) * | 1959-01-29 | 1961-07-12 | William Pearson Ltd | Disinfectant compositions |
| DE1202443B (de) * | 1965-01-18 | 1965-10-07 | Chem Fab Marienfelde G M B H | Desinfektionsmittel |
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| US5620655A (en) * | 1993-02-11 | 1997-04-15 | Menno-Chemie-Vertrieb Gmbh | Composition and method for killing parasites and invasive durable forms of said parasites |
| TWI245763B (en) * | 1998-04-02 | 2005-12-21 | Janssen Pharmaceutica Nv | Biocidal benzylbiphenyl derivatives |
| DE10222455A1 (de) * | 2002-05-22 | 2003-12-11 | Ewabo Chemikalien Gmbh | Desinfektionsmittel |
| US7208453B2 (en) * | 2002-09-05 | 2007-04-24 | Menno Chemie-Vertrieb Gmbh | Means for inactivating pathogenic agents on surfaces, instruments and in contaminated fluids |
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| CN105821665A (zh) * | 2015-12-28 | 2016-08-03 | 福建恒安集团有限公司 | 一种多功能es纤维纺丝油剂 |
| CN105821666A (zh) * | 2015-12-28 | 2016-08-03 | 福建恒安集团有限公司 | 一种多功能es纤维 |
| CN107593719A (zh) * | 2017-10-17 | 2018-01-19 | 赖丰光 | 含银果与氟环唑的农药组合物 |
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| JP2013056897A (ja) | 2013-03-28 |
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| CA2615540C (en) | 2013-09-03 |
| CA2615540A1 (en) | 2007-01-25 |
| EP1909569A2 (de) | 2008-04-16 |
| RU2419287C2 (ru) | 2011-05-27 |
| US20110086823A1 (en) | 2011-04-14 |
| KR20080033989A (ko) | 2008-04-17 |
| IL188776A0 (en) | 2008-08-07 |
| BRPI0613682B1 (pt) | 2018-05-22 |
| WO2007009606A3 (de) | 2007-05-24 |
| WO2007009606A2 (de) | 2007-01-25 |
| CR9675A (es) | 2008-06-09 |
| MX2008000778A (es) | 2008-03-06 |
| CN101267734B (zh) | 2012-05-30 |
| DE102005033496A1 (de) | 2007-01-25 |
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| MY157990A (en) | 2016-08-30 |
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| AU2006272087A1 (en) | 2007-01-25 |
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