CN111225660A - 氯己定碱的增溶、抗菌组合物和消毒组合物 - Google Patents
氯己定碱的增溶、抗菌组合物和消毒组合物 Download PDFInfo
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Abstract
本发明涉及一种氯己定碱并且涉及在氧化胺存在下产生含有氯己定碱氨基酸的增溶形式。本发明涉及医学和制药工业,特别是涉及对结核分枝杆菌(包括多重耐药MDR、极度耐药XDR和泛耐药PDR的菌株)、细菌孢子和真菌具有活性的新型抗菌组合物和消毒组合物;并且所述组合物具有杀病毒活性。
Description
技术领域
本发明涉及氯己定碱,在氧化胺存在下制备含有氯己定碱和氨基酸的增溶形式。本发明涉及医学和制药工业,特别是涉及对结核分枝杆菌(包括多重耐药MDR菌株、极度耐药XDR菌株和泛耐药PDR菌株)、细菌孢子、真菌具有活性并且具有杀病毒活性的新型抗菌组合物和消毒组合物。
背景技术
氯己定碱属于双胍类。在化学上,氯己定碱是1,1’-六亚甲基双-[5-(4-氯苯基)双胍]。下面以结构式的形式呈现了氯己定分子C22H30CL2N10的式。
氯己定碱是白色结晶粉末,几乎不溶于水和醇。
通常,鉴于氯己定碱的溶解性差,将氯己定以盐,主要是piazetta、二葡萄糖酸盐、二盐酸盐的形式使用[Ruppert М.,Schlagenhauf U.La clorhexidina enOdontologia.Aspectos generales.Quintessence(Ed.Espanola)2005;18:12-23;FranchM.,Pascual A.,Santos A.Colutorios en periodon-cia.Parte II.ArchOdontoestomatologia 2005;21:471-87]。二葡萄糖酸盐最可溶于水和醇,因此该形式在用于口腔清洗剂、凝胶和清漆的液体中使用[Arevalo J.M.,Arribas J.L.,Calbo L.,Hernandez M.J.,Lizan M.,Herruzco R.Guia del grupo de trabajo sobredesinfectantes у antisepticos.Revision 1998.Medicina Preventiva 1998;4:38-43.]。此外,因为生理pH值释放具有阳离子电荷的活性成分,所以该形式具有附加优点[Albertos J.M.,Junquera L.M.,AlbertosМ.Т.,Olay S.,Lopez-Arranz E.Laclorhexidina.Perspectiva actual.Ann Odontoestomatologia 1996;5:217-23.]。
氯己定在细胞膜的水平上起作用,从而增加了其渗透性[Hugo W.B.Disinfectionmechanisms.In:Russell A.D.,Hugo W.B.,Ayliffe G.A.J.,eds.Principles andPractice of Disinfection,Preservation and Sterilization.Oxford:Blackwell;1992:187-210]。
氯己定作用的第一阶段是其由于存在连接到六亚甲基的亲脂性链上的两个主要且对称的氯苯基胍的基团而在微生物壁上的快速吸附,这形成了与细菌表面相互作用的双阳离子分子[Musteata F.M.,Pawliszyn J.Assay of stability,free and totalconcentration of chlorhexidine in saliva by solid phase microextraction.JPharm Biomedical Analysis 2005;37:1015-24]。在中性或弱碱性pH中的条件对于它们的结合是最有利的;氯己定的吸附量取决于试剂的浓度。细菌细胞壁的外层带有负电荷,其通常在阳离子(诸如Mg2+和Ca2+)的存在下稳定化;这是对细菌细胞壁具有高亲和力的大多数阳离子抗菌剂(包括氯己定)的作用基础[Gilbert P.,Moore L.E.Cationic antiseptics:diversity of action under a common epithet.J Appl Microbiol 2005;99:703-15]。
氯己定的盐,特别是双葡萄糖酸盐是具有杀菌和杀真菌作用的抗菌剂。尽管它不被认为是杀病毒剂,但注意到与病毒,诸如HIV、1型疱疹和2型疱疹、甲型流感病毒的脂膜有关的一些轻微活性[Bemimoulin J.P.Recent concepts in plaque formation.J ClinPeriodontology 2003;30:7-9.]。氯己定双葡萄糖酸盐可以抑制孢子的生长,并且对某些细菌产生抑菌作用,但对耐酸细菌没有作用[Junco-Lafuente М.Р,Baca-Garcia Р.,Mesa-Aguado F.L.Utilizacion de la clorhexidina en la prevencion oral depacientes de la tercera edad.Revista del Ilustre Consejo General de Colegiosde Odontologos у Estomatologos de Espana 2001;6:81-9]。
在低浓度下,氯己定双葡萄糖酸盐是抑菌剂,但是,当将它从环境中移出时,细菌细胞的功能恢复[FardalО.,Turnbull R.S.A review of the literature on use ofchlorhexidine in dentistry.J American Dental Association 1986;112:863-9]。
氯己定盐作为抗菌剂和消毒剂已在许多领域中得到应用。
注册并生产了数十种具有氯己定盐的抗菌组合物和消毒组合物。作为活性组分的氯己定双葡萄糖酸盐是法国公司“PIERRE-FABRE MED”生产的药物Citeal(氯己定双葡萄糖酸盐和己脒定以及氯甲酚)的一部分,并且存在于由克罗地亚公司“PLIVA”生产的以含有氯己定葡萄糖酸盐的乳液形式的药物“Plivasept”的组合物中。
7项专利致力于制备和应用氯己定衍生物和基于它的组合物[专利WO 95/12395-公司“Calgon Vestal Lab”(美国);专利EP 306455-公司“Warner Lambert Co”(美国);专利WO 93/9770-公司“Pierre Fabre”(法国);专利EP 200607-公司“P.F.Cosmetique”(法国)等],公司“Ivoclar AG”(德国)提出了在牙膏中与HF一起使用氯己定(专利de 415397、EP 539811、US 5393516)。
氯己定的苯基衍生物和氰基衍生物已被认为是潜在的高活性杀真菌剂。公司“Bayer”(德国)基于苯基-胍-咪唑和四氢嘧啶的衍生物的组合物(专利EP 279343)开发了驱虫剂。BASF(德国)(专利2812945、3922232)、公司“American Cyanamid Co”(美国)(专利EP 406699、EP534501、US 5449809)、公司“Coro Jokko K.K.”(日本)(日本专利61-25706、61-027)、公司“Hakko Chemical”(印度)(美国专利5116838)开发了新型生物杀灭剂。然而,由于高环境要求以及对含酚和氰化物的废物的处理困难,它们的工业前景很小。
可以通过将碘化合物(专利EP 473320)或丁子香酚化合物(专利WP 93/9770)引入到组合物中来增强氯己定的生物杀灭特性。
基于胍-聚六亚甲基双胍及其衍生物的有前途的一批生物杀灭药物在以下专利中提出:俄国专利No.2351365“Antiseptic composition“CHLORDIX”,其含有已知的、可公开获得且廉价的抗菌剂氯己定双葡萄糖酸盐和双氧化物(dioxidine)的组合;RU No.2147032“Bactericidal-detergent”,其中主要活性物质是氯己定双葡萄糖酸盐或氯己定葡萄糖酸盐、或氯己定盐。在根据专利No.2351365的组合物中注意到对耐酸形式的细菌诸如幽门螺杆菌和结核分枝杆菌的作用活性。
然而,所述描述并未具体说明具有什么程度的耐药性、哪种类型的结核分枝杆菌菌株参与研究。我们可以假设,使用了对抗菌药物敏感的菌株。基于氯己定盐的所有已知和描述的产品对***和革兰氏阴性细菌具有广泛的活性、快速和强力杀菌作用,它们具有杀***活性、对耐酸形式细菌的活性。
每种已知的含有氯己定盐的制剂都通过一种或另外的物质(例如烷基二甲基苄基氯化铵(katamine AB)或二癸基二甲基氯化铵、非离子表面活性物质、季铵盐、基于丙烯三聚物的水溶性的氧乙基化单烷基酚等)来增强以提高消费质量,对某些类型的细菌起作用,但对耐药的结核分枝杆菌、细菌孢子、真菌无效并且具有较低的杀病毒活性。
鉴于许多抗菌组合物和消毒组合物已对微生物形成耐药性,氯己定对微生物细胞的作用机理和氯己定碱的潜力使我们寻找获得可溶于水和醇的其他氯己定碱形式的方法。
一种方法是获得氯己定碱增溶剂。
在报告“Associations based on chlorhexidine and a synergistic effect”中,G.Kardash等人//Materials of the VIII All-Russian Congress ofEpidemiologists,Microbiologists and Parasitologists:v.4.Moscow.Rosineks,2002.-P.21-22概述了一种通过形成氯己定碱和甘氨酸结合物,将氯己定碱转化为可溶形式以协同提高生物杀灭活性的方法。该报告提供了有关氯己定碱和甘氨酸结合物的生物杀灭活性的比较数据,显示了对Gr+(金黄色葡萄球菌)、Gr+(肺炎克雷伯氏菌)和铜绿假单胞菌的试验培养物具有协同作用。然而,氯己定碱和甘氨酸的结合很快失去稳定性。
在报告“Solubilization of chlorhexidine in aqueous micellar solutionsof nonionic surfactants,”//Abstracts of the XXIII All-Russian Conference“Structure and Dynamics of Molecular Systems”,Moscow,2016.-P.74-74中描述了氯己定碱可溶形式的制备方法。
在这项工作中,通过紫外光谱法、折光法和动态光散射研究了用非离子表面活性剂胶束固定氯己定的方法。表明,氯己定在胶束水溶液中的平衡溶解度随非离子表面活性剂浓度的增加而线性增加。确定了胶束对氯己定的增溶能力,其表征了胶束中氯己定分子和非离子表面活性剂的量之比。随着非离子表面活性剂分子中羟乙基单元量的增加,增溶能力的值按顺序增加:Lutensol XL-79、Neonol 9-10、Tween80。计算了标准的增溶吉布斯能,并且计算了增溶氯己定对非离子表面活性剂胶束尺寸的影响。发现氯己定位于胶束的氧乙基层中,而不位于烃核中。在所有情况下,pH值都在6-8的范围内,这对于氯己定的最大杀菌活性表现是最佳的。然而,尚未证明使用非离子表面活性剂获得的增溶的氯己定碱实际上显示出最大的杀菌活性和其他类型的活性。
然而,未显示所获得的增溶形式的氯己定碱的实际杀菌活性。
发明内容
本发明的目的-产生氯己定碱的可溶性良好的增溶物,基于氯己定碱的增溶形式产生抗菌组合物和消毒组合物,所述组合物对结核分枝杆菌(包括多重耐药MDR菌株、极度耐药XDR菌株和泛耐药PDR菌株)、细菌孢子、真菌具有活性并且具有杀病毒活性、高安全性和可购性。
在本发明的第一方面,发现在氧化胺存在下氯己定碱和氨基酸(丙氨酸、谷氨酸、谷氨酰胺、赖氨酸、精氨酸、组氨酸、半胱氨酸、蛋氨酸、甘氨酸、天冬氨酸、天冬酰胺等)的结合物形成良好地溶解于水和醇中的形态结构-胶束和层状类型的增溶物。
据发现,在氧化胺存在下的氯己定碱和氨基酸增溶形式构成胶束和层状类型的平滑层状形成物-液晶。
来自UV和NMR光谱EPR的数据显示,当在层状胶束中的增溶过程期间,氯己定碱进入内部胶束中、位于烃端之间,从而推开了分子链的层,形成了树状晶体或液晶。形成了新的液晶形态结构,这与氯己定碱和氨基酸(甘氨酸)的初始组分的形态截然不同。在出现新的晶体修饰之前,溶液中的分子在静电和氢分子间键的情况下处于有序状态,这导致在低浓度组分(0.1%-1%)下出现异常高的粘度。
新的形态结构显示出对微生物(包括结核分枝杆菌的多重耐药MDR菌株、极度耐药XDR和泛耐药PDR菌株,细菌孢子,真菌)的协同生物杀灭活性和杀病毒活性。
为了理解协同作用机理,使用各种物理化学方法进行了研究,所述研究显示出氯己定分子的亚氨基的质子化以及存在氯己定碱和氨基酸(甘氨酸)的稀溶液中液晶的新形态结构。
氯己定碱、氯己定-甘氨酸增溶物、氧化胺的固体样品的IR光谱是在M-40仪器(德国)上以用EHF压制的粉末的形式获得的。分析IR光谱,可以认为甘氨酸的羧基为带电形式-COO-。
在1700cm-1处的-COOH基团的吸收区域中,在甘氨酸的光谱中、在甘氨酸与氯己定碱的混合物的光谱中均未发现谱带。同时,在1600cm-1和1400cm-1处的COO吸收基团区域中,两个光谱上均有强的谱带。这些数据证明了氯己定碱增溶物在水性溶液中的溶解机理,这是通过氯己定碱的质子化而发生的。
通过UV分光光度计M-80(德国)获得的氯己定增溶物的UV光谱确认了IR光谱数据关于在氧化胺存在下氯己定碱在氨基酸(甘氨酸)溶液中的溶解原因的结论,所述溶解是由于质子从氨基酸(甘氨酸)转移到氯己定碱。
在本发明的第二方面,使用氯己定碱的增溶物和助剂获得了抗菌组合物和消毒组合物,所述组合物对结核分枝杆菌(包括多重耐药MDR菌株、极度耐药XDR菌株和泛耐药PDR菌株)具有活性。
呈浓缩物形式的一种抗菌组合物模型以下述比例(质量%)含有氯己定碱、氨基酸、氧化胺、赋形剂:
氯己定碱为0.1%-1.0%
氧化胺为0.2%-5.0%
氨基酸为0.05%-2.0%
甘油为0.0%-5.0%
染料为0.01%-0.1%
水补足至100%
作为氨基酸,使用亮氨酸、酪氨酸、丝氨酸、谷氨酰胺、天冬酰胺、苯丙氨酸、丙氨酸、赖氨酸、精氨酸、组氨酸、甘氨酸、半胱氨酸、缬氨酸、脯氨酸、蛋氨酸、苏氨酸、羟赖氨酸。
作为氧化胺,使用N-月桂基-N,N-二甲基氧化胺(Barlox-12)(“Lonza”公司的目录)。
作为染料,使用蒽醌染料、偶氮玉红(E122)或三芳基甲烷染料(E133)。
根据本发明的抗菌组合物具有抗菌作用(包括对结核分枝杆菌的作用)、杀真菌活性、杀病毒活性和杀孢子活性,并且旨在用于无菌手部处理、医学装置(包括柔性内窥镜和仪器)的预灭菌并且还用于患者护理物品的消毒、医务人员的卫生和家用目的,不会引起金属产品的腐蚀。
附图说明
图1氯己定碱、氯己定-甘氨酸增溶物和氧化胺的固体样品的IR光谱。
具体实施方式
实施例1.为了获得100ml呈浓缩物形式的抗菌组合物,在室温,将1ml氧化胺Barlox-12(Lonza公司的目录)溶解于100ml水中,添加0.15g氯己定碱、0.05g甘氨酸、0.01g染料E133。所获得的具有pH 7.5-8的组合物是抗菌浓缩物。
实施例2.与实施例1类似地进行,但组合物包含0.5g氯己定碱、3.5ml Barlox 12、1.5g丙氨酸、2ml甘油、0.05g酸性红(E122)。
实施例3.与实施例1类似地进行,但组合物包含1g氯己定碱、5ml Barlox12、2.0g谷氨酰胺、2ml甘油、0.05g蒽醌染料。
进行一系列实验以确认抗菌组合物对结核分枝杆菌、MDR多重耐药菌株和极度耐药XDR(其对第1类、第2类和第3类抗菌药物不敏感)以及泛耐药PDR(其对所有已知的所有种类的抗菌药物不敏感)的高活性。将结核分枝杆菌H37Rv的实验室菌株和从在俄罗斯医学科学院(Russian Academy of medical Sciences)(RAMS)的中央结核病研究所的医院中治疗的肺结核患者的诊断材料分离的临床(野生)MDR、XDR和PDR菌株用作生物测试品。考虑到在敏感时抗TB药物对它们的作用,对两种临床菌株进行表征,并且将其标记为FEEL-1和FEEL-2。将具有不同程度耐药性的三种其他菌株标记为MDR、XDR和PDR菌株。
根据工作计划,使选定的结核分枝杆菌菌株的培养物在致密营养培养基Levenstein-Jensen(国际标准)中生长21天。从生长培养物至制备细菌悬浮液,其初始浓度为5·108,即在1ml溶液中含有5亿个微生物体。测试物质是即用型溶液。对结核分枝杆菌培养物的暴露时间是30分钟和60分钟。
使用修改的浸入法进行实验。结核分枝杆菌悬浮液与根据实施例2的抗菌组合物(以1ml浓缩物/100ml水的比率稀释)的比率是1:1,即将2ml各种菌株的结核分枝杆菌悬浮液和2ml抗菌组合物浓缩物溶液倒入测试管中。因此,工作中使用的细菌悬浮液的浓度是5·104。
悬浮液中微生物体的该浓度与用于通过Ziehl-Nielsen方法(光学显微镜法)检测染色涂片处的诊断材料中的分枝杆菌所需的分枝杆菌数目对应。在给定暴露下,将混合物以3000rpm离心15分钟。将所得沉淀物用蒸馏水洗涤两次。每个具有Finn-2固体营养培养基的测试管的接种剂量为0.5ml沉淀物,并且每个具有Middlebrook 7N9液体营养培养基的测试管的接种剂量为0.5ml沉淀物。使用对照管,在其中接种所用测试菌株的分枝杆菌的悬浮液,并且不用组合物的物质对其进行处理。将致密培养基上的作物在温度为37℃的恒温器中温育;将在液体培养基上的作物-在自动化***Bactec MGIT-960中温育。从播种时间开始在28天、42天和70天收集致密营养培养基上的所得物。在Bartec MGIT-960设备上记录关于液体营养培养基的结果。
表1示出了培养研究抗菌组合物的结果。在俄罗斯医学科学院(RAMS)的中央结核病研究所中对所述组合物针对结核分枝杆菌(包括关于多重耐药MDR菌株和极度耐药XDR菌株(对第1类、第2类和第3类抗菌药物不敏感)和关于泛耐药PDR菌株(对所有已知的所有种类的抗菌药物不敏感))的杀菌活性的微生物研究是根据标准技术文件,俄罗斯联邦No.109dd.21.03.2003,附录No.1,卫生规则SP 1.2.731-99的***指令进行的。
表1对含有氯己定碱的抗菌组合物的作用的培养研究结果
其中:(>100)-结核分枝杆菌的菌落在致密培养基和液体营养培养基上生长;
(–)–结核分枝杆菌的菌落在致密培养基和液体营养培养基上没有生长;
进行的研究结果显示,对于具有不同程度的耐药性的结核分枝杆菌的毒性临床菌株的活性高且稳定。
从播种开始的第70天或更长时间,未检测到多重耐药MDR菌株、极度耐药XDR和泛耐药PDR的菌落的生长。
本发明的实施方式的选项
消毒浓缩物组合物的形式以下述质量分数%的组分比含有氯己定碱、氧化胺、季铵化合物(QAC)、酸度调节剂、防腐蚀添加剂、增稠剂、助剂:
选项1
氯己定碱为1.0%-2.0%
氧化胺为1.0%-15.0%
季铵化合物(QAC)为5.0%-10.0%
酸度调节剂为0.1%-1.0%
防腐蚀添加剂为0.1%-1.0%
染料为0.01%-0.1%
水补足至100%
优选的是,使用烷基二甲基苄基氯化铵(Katamin A或B)作为QAC。优选地,使用三乙醇胺、Trilon A、Trilon B或Trilon C作为防腐蚀添加剂。优选地,使用苹果酸作为酸度调节剂。优选的是,使用的染料是染料E133。
选项2-浓缩物消毒组合物以下述质量分数%的组分比含有氯己定碱、氨基酸、氧化胺、赋形剂:
氯己定碱为0.5%-5.0%
氧化胺为5.0%-30.0%
聚乙二醇为0.2%-3.0%
氨基酸为0.0%-2.0%
染料为0.01%-0.1%
水为直至100%
作为氨基酸,使用亮氨酸、酪氨酸、丝氨酸、谷氨酰胺、天冬酰胺、苯丙氨酸、丙氨酸、赖氨酸、精氨酸、组氨酸、甘氨酸、半胱氨酸、缬氨酸、脯氨酸、蛋氨酸、苏氨酸、羟赖氨酸。作为氧化胺,使用N-月桂基-N,N-二甲基胺(Barlox-12)(Lonza公司的目录)。使用三芳基甲烷染料(E133)作为染料。
选项3-浓缩物消毒组合物以下述质量分数%的组分比含有氯己定碱、氨基酸、氧化胺、赋形剂:
氯己定碱为0.5%-65.0%
氨基酸为0.1%-2.0%
氧化胺为0.2%-5.0%
染料为0.01%-0.1%
醇为10.0%-30.0%
作为氨基酸,使用亮氨酸、酪氨酸、丝氨酸(terine)、谷氨酰胺、天冬酰胺、苯丙氨酸、丙氨酸、赖氨酸、精氨酸、组氨酸、甘氨酸、半胱氨酸、缬氨酸、脯氨酸、蛋氨酸、苏氨酸、羟赖氨酸。作为氧化胺,使用N-月桂基-N,N-二甲基胺(Barlox-12)(Lonza公司的目录)。使用三芳基甲烷染料(E133)作为染料。使用乙醇、丙醇、甲醇作为醇。
通过在室温以指定比例的活性物质混合组分,类似于实施例1地进行变型1、2和3的消毒组合物的浓缩物的制备。
工业应用
为了研究对结核分枝杆菌菌株、革兰氏阴性细菌或***、真菌的消毒活性,将根据变型1、2和3的消毒组合物的浓缩物以1:100的比率稀释于水中。
将在外科手术实践中经常发现的细菌剂,诸如肠杆菌属物种、柠檬酸杆菌属物种(Citobacter spp.)、克雷伯氏菌属、大肠杆菌、铜绿假单胞菌、金黄色葡萄球菌、脊髓灰质炎类、念珠菌属通过普遍接受的方法播种在营养培养基上并根据以下文件的要求进行了评估:标准文件(ND)“Methods of laboratory researches and tests of disinfectantsfor an assessment of their efficiency and safety”(P 4.2.2643-10)和标准文件“Normative indicators of safety and effectiveness of disinfectants,subject tocontrol during the mandatory certification”,No.01-12/75-97。
所述研究在RF的公益监督局的消毒学科学研究所(the Scientific ResearchInstitute of Disinfectology of Rospotrebnadzor of RF)中进行。
消毒活性的数据在表2中给出。
表2
因此,本发明的抗菌组合物对结核分枝杆菌(包括多重耐药MDR菌株、极度耐药XDR)(其对第1类、第2类和第3类抗生素不敏感)以及泛耐药PDR(其对所有已知的所有种类的抗生素不敏感)具有独特的杀菌活性。
消毒组合物的变型具有增加的品质:对宽范围的细菌-土地分枝杆菌、肠杆菌属物种、柠檬酸杆菌属物种、克雷伯氏菌属、大肠杆菌、铜绿假单胞菌、金黄色葡萄球菌、脊髓灰质炎类、念珠菌属起作用,具有低成本,这是由于氯己定碱的使用,所述氯己定碱是生产该化合物的盐和衍生物中的半成品并且易于制备。
Claims (9)
1.一种氯己定碱增溶方法,所述方法包括在氨基酸和氧化胺存在下对氯己定碱进行胶束和层状微胶囊化。
2.根据权利要求1所述的方法,其中将N-月桂基-N,N-二甲基氧化胺用作氧化胺,并且将亮氨酸、酪氨酸、丝氨酸、谷氨酰胺、天冬酰胺、苯丙氨酸、丙氨酸、赖氨酸、精氨酸、组氨酸、甘氨酸、半胱氨酸、缬氨酸、脯氨酸、蛋氨酸、苏氨酸、羟赖氨酸用作氨基酸。
3.一种呈浓缩物形式的抗菌组合物,所述抗菌组合物以下述质量分数%的比例含有氯己定碱、氨基酸、氧化胺、甘油、染料和水:
氯己定碱为0.1%-1.0%,
氧化胺为0.2%-5.0%,
氨基酸为0.05%-2.0%,
甘油为0.0%-5.0%,
染料为0.01%-0.1%,
水补足至100%。
4.根据权利要求3所述的抗菌组合物,其中将N-月桂基-N,N-二甲基氧化胺用作氧化胺;将亮氨酸、酪氨酸、丝氨酸、谷氨酰胺、天冬酰胺、苯丙氨酸、丙氨酸、赖氨酸、精氨酸、组氨酸、甘氨酸、半胱氨酸、缬氨酸、脯氨酸、蛋氨酸、苏氨酸、羟赖氨酸用作氨基酸;并且将蒽醌染料、酸性红(E122)或三芳基甲烷染料(E133)用作染料。
5.根据权利要求3所述的抗菌组合物,其中所述抗菌组合物旨在用于针对结核分枝杆菌的多重耐药MDR菌株、极度耐药XDR菌株和泛耐药PDR菌株的治疗性或非治疗性用途。
6.一种呈浓缩物形式的消毒组合物,所述消毒组合物以下述质量分数%的比例含有氯己定碱、氧化胺、季铵化合物、酸度调节剂、防腐蚀添加剂、染料和水:
氯己定碱为1.0-2.0%
氧化胺为1.0%-15.0%
季铵化合物为5.0%-10.0%
酸度调节剂为0.1%-1.0%
防腐蚀抑制剂为0.1%-1.0%
染料为0.01%-0.1%
水补足至100%。
7.一种呈浓缩物形式的消毒组合物,所述消毒组合物以下述质量分数%的比例含有氯己定碱、氨基酸、氧化胺、聚乙二醇、染料和水:
氯己定碱为0.5%-5.0%,
氧化胺为5.0%-30.0%,
聚乙二醇为0.2%-3.0%,
氨基酸为0.0%-2.0%,
染料为0.01%-0.1%,
水补足至100%。
8.一种呈浓缩物形式的消毒组合物,所述消毒组合物以下述质量分数%的比例含有氯己定碱、氨基酸、氧化胺、染料和醇:
氯己定碱为0.5%-65.0%,
氨基酸为0.1%-2.0%,
氧化胺为0.2%-5.0%,
染料为0.01%-0,1%,
醇为10.0%-30.0%。
9.根据权利要求6-8中任一项所述的消毒组合物的浓缩物,其中N-月桂基-N,N-二甲基氧化胺用作氧化胺;将烷基二甲基二甲基苄基氯化铵(Catamine A或B)用作季铵化合物;将三乙醇胺、Trilon A、Trilon B用作防腐蚀添加剂;将苹果酸用作酸度调节剂;并将染料E133用作染料。
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PCT/RU2018/000146 WO2019083397A1 (ru) | 2017-10-23 | 2018-03-07 | Солюбилизация хлоргексидина основания, антисептическая и дезинфицирующая композиции |
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EP (1) | EP3701942A4 (zh) |
JP (1) | JP7035206B2 (zh) |
KR (1) | KR20200089678A (zh) |
CN (1) | CN111225660A (zh) |
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WO2021206757A1 (en) * | 2020-04-07 | 2021-10-14 | S.Y. Calimero Entrepreneurship Ltd | A dissolving capsule for hand sanitization |
CN112022843B (zh) * | 2020-10-20 | 2021-11-23 | 中国医科大学附属口腔医院 | D-亮氨酸和氯己定组合物的应用 |
RU2750598C1 (ru) * | 2021-03-05 | 2021-06-29 | Общество с ограниченной ответственностью "РЕМЕДИУМ" | Лиотропный жидкий кристалл хлоргексидина основания, антисептическая и дезинфицирующая композиции |
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RU2017133879A3 (zh) | 2019-04-23 |
KR20200089678A (ko) | 2020-07-27 |
RU2017133879A (ru) | 2019-04-23 |
RU2696259C2 (ru) | 2019-08-01 |
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