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CN115245174A - A kind of water-soluble compound potassium hydrogen persulfate disinfectant and preparation method thereof - Google Patents

A kind of water-soluble compound potassium hydrogen persulfate disinfectant and preparation method thereof Download PDF

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CN115245174A
CN115245174A CN202210972643.7A CN202210972643A CN115245174A CN 115245174 A CN115245174 A CN 115245174A CN 202210972643 A CN202210972643 A CN 202210972643A CN 115245174 A CN115245174 A CN 115245174A
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disinfectant
potassium hydrogen
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hydrogen persulfate
ethanol
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CN115245174B (en
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周燕霞
刘肖肖
姜慧凝
吕玮
杨婷婷
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Shandong University
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    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
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    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N33/00Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
    • A01N33/02Amines; Quaternary ammonium compounds
    • A01N33/12Quaternary ammonium compounds
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
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    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01PBIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00Disinfectants; Antimicrobial compounds or mixtures thereof
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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Abstract

The invention relates to a water-soluble compound potassium hydrogen persulfate disinfectant, which comprises the following components in percentage by mass: 91-92.3% of oxidant and 7.7-9% of quaternary ammonium salt; the concentration of the aqueous solution of the compound disinfectant is 0.54-0.70% (W/V). The potassium hydrogen persulfate composite salt and the quaternary ammonium salt are compounded to have a synergistic effect, so that the ethanol-resistant microorganisms can be quickly and efficiently killed. By compounding the disinfectant, ethanol-resistant microorganisms can be effectively killed, the microbial control of the pharmaceutical environment is facilitated to be enhanced, and the pollution risk of the pharmaceutical environment is reduced.

Description

一种水溶性复方过硫酸氢钾消毒剂及其制备方法A kind of water-soluble compound potassium hydrogen persulfate disinfectant and preparation method thereof

技术领域technical field

本发明涉及一种水溶性复方过硫酸氢钾消毒剂及其制备方法,属于消毒剂技术领域。The invention relates to a water-soluble compound potassium hydrogen persulfate disinfectant and a preparation method thereof, belonging to the technical field of disinfectants.

背景技术Background technique

消毒剂一般是化学制品,它能够杀灭潜在的致病微生物。消毒剂按化学成分通常可分为过氧化物类消毒剂、胍类消毒剂、醇类消毒剂、酚类消毒剂、含碘消毒剂、含氯消毒剂、季铵盐类消毒剂以及醛类消毒剂等类别。Disinfectants are generally chemicals that kill potentially disease-causing microorganisms. Disinfectants can usually be divided into peroxide disinfectants, guanidine disinfectants, alcohol disinfectants, phenol disinfectants, iodine-containing disinfectants, chlorine-containing disinfectants, quaternary ammonium salt disinfectants and aldehydes according to their chemical composition. Disinfectants etc.

目前制药企业常用的消毒剂主要有含氯消毒剂、季铵盐类消毒剂、酚类消毒剂、醇类消毒剂和过氧化物类消毒剂。含氯消毒剂代表产品有84消毒液和杀孢子剂,对各类病原微生物都有极强的杀灭作用,但是有机物存在会影响其效果,易受还原剂和环境的影响,而且对呼吸道有刺激性。季铵盐类消毒剂的代表产品为新洁儿灭;它的优点是杀菌浓度低、毒性与刺激性低、溶液无色、无腐蚀性、气味小、水溶性好、表面活性强、性质稳定;但对无囊膜病毒效果不好,配伍禁忌较多,对芽胞无效,属于中效消毒剂。酚类消毒剂的代表产品为酸性苯酚、碱性苯酚等。它们的稀释浓底低、适应面较窄、气味大、毒性大,它们不易分解,使用后容易造成环境的污染。醇类消毒剂主要有乙醇和异丙醇;其中75%乙醇组分简单、成分明确、无腐蚀性、无残留毒性,可用于洁净环境的消毒,成为制药企业中最普遍使用的中效消毒剂;但其对芽孢和耐乙醇微生物的杀灭率较低。过氧化物类消毒剂是一种高效强氧化型消毒剂,制药企业主要使用过氧化氢;此类消毒剂效果好,但腐蚀性极强、皮肤刺激性较大,稳定性差。在制药企业中,醇类消毒剂和过氧化物类消毒剂常交替使用,确保消杀效果。At present, the commonly used disinfectants in pharmaceutical companies mainly include chlorine-containing disinfectants, quaternary ammonium salt disinfectants, phenol disinfectants, alcohol disinfectants and peroxide disinfectants. Representative products of chlorine-containing disinfectants include 84 disinfectant and sporicide, which have a strong killing effect on various pathogenic microorganisms, but the presence of organic matter will affect its effect, and it is easily affected by reducing agents and the environment, and it is harmful to the respiratory tract. irritating. The representative product of quaternary ammonium salt disinfectant is Xinjieermi; its advantages are low bactericidal concentration, low toxicity and irritation, colorless solution, non-corrosiveness, low odor, good water solubility, strong surface activity and stable properties ; But the effect on non-enveloped virus is not good, and there are many incompatibility, and it is invalid to spores, which belongs to the middle-effect disinfectant. Representative products of phenolic disinfectants are acidic phenol, basic phenol, etc. They have low dilution concentration, narrow adaptability, strong odor, and high toxicity. They are not easy to decompose, and they are easy to cause environmental pollution after use. Alcohol disinfectants mainly include ethanol and isopropanol; among them, 75% ethanol has simple components, clear ingredients, non-corrosiveness, and no residual toxicity. It can be used for disinfection in clean environments and has become the most commonly used medium-efficiency disinfectant in pharmaceutical companies ; but its killing rate of spores and ethanol-resistant microorganisms is low. Peroxide disinfectant is a highly efficient and strong oxidizing disinfectant, and pharmaceutical companies mainly use hydrogen peroxide; this kind of disinfectant is effective, but it is extremely corrosive, skin irritating, and poor in stability. In pharmaceutical companies, alcohol disinfectants and peroxide disinfectants are often used alternately to ensure the disinfecting effect.

过硫酸氢钾相较于其他过氧化物,不仅能够快速有效的杀死各种病原微生物,而且具有低毒、环保的优点,对人体、动物无害而且不会污染环境。目前,现有的过硫酸氢钾复合盐消毒剂通常是由过硫酸氢钾、氯化钠、色素等组成。其杀菌机理为:氧化作用释放出次氯酸,次氯酸分解成新生态氧及游离氯,通过氧化起到杀菌作用。中国专利CN1545883A水溶性复合过硫酸氢钾粉消毒剂、CN101836659A复方过硫酸氢钾消毒剂和CN102265904A复合过硫酸氢钾消毒剂及其制造工艺,均是以过硫酸氢钾为主要的消毒剂。Compared with other peroxides, potassium persulfate can not only quickly and effectively kill various pathogenic microorganisms, but also has the advantages of low toxicity and environmental protection. It is harmless to humans and animals and will not pollute the environment. At present, the existing potassium persulfate compound salt disinfectant is usually composed of potassium persulfate, sodium chloride, pigments and the like. Its bactericidal mechanism is as follows: oxidation releases hypochlorous acid, which decomposes into new ecological oxygen and free chlorine, and sterilizes through oxidation. Chinese patent CN1545883A water-soluble compound potassium hydrogen persulfate powder disinfectant, CN101836659A compound potassium hydrogen persulfate disinfectant and CN102265904A compound potassium hydrogen persulfate disinfectant and manufacturing process thereof all take potassium hydrogen persulfate as the main disinfectant.

与季铵盐类消毒剂复配的过氧化物类消毒剂包括过氧化氢、过氧乙酸、臭氧和次氯酸钠等。中国专利CN112932995A一种表面清洗擦拭巾及生产方法、CN104206415A一种用于清洗CT机的消毒水及其制备方法、CN107396940A一种高效无残留的消毒剂和CN104094969A一种蚕室蚕具消毒剂的配制方法,均是季铵盐与过氧化物复配形成的消毒剂。Peroxide disinfectants compounded with quaternary ammonium salt disinfectants include hydrogen peroxide, peracetic acid, ozone and sodium hypochlorite. Chinese patent CN112932995A a surface cleaning wipe and its production method, CN104206415A a kind of disinfectant water for cleaning CT machine and its preparation method, CN107396940A a kind of high-efficiency non-residue disinfectant and CN104094969A a preparation method of silkworm tool disinfectant , are all disinfectants formed by compounding quaternary ammonium salts and peroxides.

传统消毒剂为单一成分,使用时常会伴随有抑菌效果单一、易产生耐受性等缺点,并且对于细菌孢子和耐乙醇微生物的杀灭效率不高。制药企业常使用乙醇和过氧化物消毒剂轮流消毒,作为中效消毒剂,乙醇在制药企业中使用最为普遍,与其他消毒剂交替应用,使用频次非常高,导致制药环境易产生耐乙醇菌;而且其他消毒剂,如过氧化物高效消毒剂,对乙醇耐受菌无法彻底消杀,所以耐乙醇菌成为主要的微生物污染风险。本发明将过氧化物消毒剂进行复配,提供了一种对耐乙醇菌消杀效果好的消毒剂。The traditional disinfectant is a single component, which is often accompanied by the disadvantages of single antibacterial effect and easy tolerance, and the killing efficiency of bacterial spores and ethanol-resistant microorganisms is not high. Pharmaceutical companies often use ethanol and peroxide disinfectants to disinfect in turn. As a medium-effect disinfectant, ethanol is the most commonly used in pharmaceutical companies. It is used alternately with other disinfectants and the frequency of use is very high, which leads to the production of ethanol-resistant bacteria in the pharmaceutical environment; Moreover, other disinfectants, such as high-efficiency peroxide disinfectants, cannot completely disinfect ethanol-resistant bacteria, so ethanol-resistant bacteria have become the main risk of microbial contamination. The invention compound the peroxide disinfectant to provide a disinfectant with good disinfecting effect on ethanol-resistant bacteria.

发明内容SUMMARY OF THE INVENTION

本发明的目的在于克服上述现有技术的不足之处而提供一种水溶性复方过硫酸氢钾消毒剂及其制备方法,该水溶性复方过硫酸氢钾消毒剂对耐乙醇菌的消杀效果稳定。The object of the present invention is to overcome above-mentioned weak point of prior art and provide a kind of water-soluble compound potassium hydrogen persulfate disinfectant and preparation method thereof, the disinfecting effect of this water-soluble compound potassium hydrogen persulfate disinfectant to ethanol-resistant bacteria Stablize.

为实现上述目的,本发明采取的技术方案为:一种水溶性复方过硫酸氢钾消毒剂,所述消毒剂包括如下质量百分比的组分:氧化剂71.4%~92.3%、季铵盐类7.7%~28.6%。In order to achieve the above object, the technical solution adopted by the present invention is: a water-soluble compound potassium hydrogen persulfate disinfectant, said disinfectant comprising the following components in mass percentage: oxidant 71.4%~92.3%, quaternary ammonium salts 7.7% ~28.6%.

作为本发明所述消毒剂的优选实施方式,所述消毒剂包括如下质量百分比的组分:氧化剂91%~92.3%、季铵盐类7.7%~9%。As a preferred embodiment of the disinfectant of the present invention, the disinfectant includes the following components in mass percentage: 91%-92.3% of oxidizing agent, and 7.7%-9% of quaternary ammonium salts.

作为本发明所述消毒剂的优选实施方式,所述氧化剂为过硫酸氢钾复合盐。As a preferred embodiment of the disinfectant of the present invention, the oxidizing agent is potassium persulfate complex salt.

作为本发明所述消毒剂的优选实施方式,所述季铵盐类为十二烷基二甲基苄基氯化铵。As a preferred embodiment of the disinfectant of the present invention, the quaternary ammonium salt is dodecyldimethylbenzyl ammonium chloride.

过硫酸氢钾复合盐在水中可发生链式反应释放出自由基及新生态氧[O]等活性物质,这些物质具有穿透力强、体积小等特点,可快速扩散到病原体细胞表面,使细胞膜上运输等功能相关的酶失活导致内容物流出,也可以进入细胞内部,将蛋白质变性、与核酸中的金属离子结合、使磷酸二酯键断裂,干扰DNA和RNA的结合等。Potassium persulfate compound salt can undergo a chain reaction in water to release active substances such as free radicals and nascent oxygen [O]. These substances have the characteristics of strong penetrating power and small size, and can quickly diffuse to the surface of pathogen cells, making them The inactivation of functionally related enzymes such as transport on the cell membrane causes the content to flow out, and can also enter the cell interior, denature proteins, combine with metal ions in nucleic acids, break phosphodiester bonds, and interfere with the binding of DNA and RNA.

季铵盐类的作用靶标为细胞膜和凝结物,其亲和性高可吸附到菌体表面,疏水基插入类脂层,破坏细胞壁、细胞膜通透性屏障,促进胞内物质泄漏,增强过硫酸氢钾对细胞膜和胞内大分子如酶、核酸和核糖体的破坏作用。The target of quaternary ammonium salts is the cell membrane and condensate. Its high affinity can be adsorbed to the surface of the bacteria, and the hydrophobic base can be inserted into the lipid layer, destroying the cell wall and cell membrane permeability barrier, promoting the leakage of intracellular substances, and enhancing the persulfate concentration. Potassium hydrogen has a destructive effect on cell membranes and intracellular macromolecules such as enzymes, nucleic acids and ribosomes.

过硫酸氢钾复合盐和季铵盐类的作用靶标不同,可发挥良好的协同作用。季铵盐中存在的氯离子可被过硫酸氢钾复合盐释放出的自由基氧化成氯气,氯气进一步水解生成次氯酸和次氯酸根,增强了本发明的杀菌能力。Potassium hydrogen persulfate compound salts and quaternary ammonium salts have different targets and can play a good synergistic effect. Chloride ions present in the quaternary ammonium salt can be oxidized into chlorine gas by the free radicals released by the potassium persulfate compound salt, and the chlorine gas is further hydrolyzed to generate hypochlorous acid and hypochlorite, which enhances the bactericidal ability of the present invention.

作为本发明所述消毒剂的优选实施方式,所述消毒剂配成0.54-0.70%(W/V)的水溶液使用。As a preferred embodiment of the disinfectant of the present invention, the disinfectant is used in the form of a 0.54-0.70% (W/V) aqueous solution.

作为本发明所述消毒剂的优选实施方式,所述消毒剂配成0.54%(W/V)的水溶液使用。As a preferred embodiment of the disinfectant of the present invention, the disinfectant is used in the form of a 0.54% (W/V) aqueous solution.

第二方面,本发明还提供了上述消毒剂的制备方法,所述制备方法为将氧化剂与季铵盐类按配比混合得到。In the second aspect, the present invention also provides a preparation method of the above-mentioned disinfectant, which is obtained by mixing the oxidizing agent and the quaternary ammonium salt according to the ratio.

本发明的水溶性复方过硫酸氢钾消毒剂(所述消毒剂包括如下质量百分比的组分:氧化剂92.3%,季铵盐类7.7%),在复方消毒剂水溶液浓度为0.54%(W/V)时,即过硫酸氢钾复合盐和季铵盐的终浓度分别为0.503%和0.042%(W/V),可在3分钟内对耐乙醇芽孢杆菌的杀灭率达到99.999%以上,快速和高效方面优于单过硫酸氢钾复合盐为主的消毒剂,如CN107624785A一种低腐蚀性单过硫酸氢钾复合盐消毒剂(该消毒剂需在5%浓度下消杀15分钟)、CN1545883A水溶性复合过硫酸氢钾粉消毒剂(该消毒剂需在0.5%浓度下消杀5分钟)和CN102265904A复合过硫酸氢钾消毒剂及其制造工艺(该消毒剂需在1%浓度下消杀10分钟),也优于季铵盐类消毒剂,如CN104094969A一种蚕室蚕具消毒剂的配制方法(该消毒剂需在季铵盐0.3%浓度下消杀3小时)和CN104206415A一种用于清洗CT机的消毒水及其制备方法(该消毒剂需季铵盐浓度为5.0%)。Water-soluble compound potassium hydrogen persulfate disinfectant of the present invention (described disinfectant comprises the component of following mass percent: oxidizing agent 92.3%, quaternary ammonium salt 7.7%), is 0.54% (W/V) in compound disinfectant aqueous solution concentration ), that is, the final concentrations of potassium persulfate compound salt and quaternary ammonium salt are 0.503% and 0.042% (W/V) respectively, and the killing rate of ethanol-resistant bacillus can reach more than 99.999% within 3 minutes, which is fast And efficient aspect is superior to the disinfectant based on potassium monopersulfate compound salt, as CN107624785A a kind of low corrosivity potassium monopersulfate compound salt disinfectant (this disinfectant needs to kill 15 minutes under 5% concentration), CN1545883A water-soluble compound potassium hydrogen persulfate powder disinfectant (this disinfectant needs to be eliminated at 0.5% concentration for 5 minutes) and CN102265904A compound potassium hydrogen persulfate disinfectant and its manufacturing process (this disinfectant needs to be eliminated at 1% concentration) Kill 10 minutes), also be better than quaternary ammonium salt disinfectant, as CN104094969A a kind of preparation method of silkworm silkworm tool disinfectant (this disinfectant needs to kill 3 hours under 0.3% concentration of quaternary ammonium salt) and CN104206415A a kind of use Disinfectant water for cleaning CT machines and its preparation method (the disinfectant needs quaternary ammonium salt concentration of 5.0%).

与现有技术相比,本发明的有益效果为:本发明水溶性复方过硫酸氢钾消毒剂首次将过硫酸氢钾复合盐与季铵盐类进行复配,通过各组分的协同作用,可迅速有效杀灭耐乙醇微生物,保障了制药环境良好的微生物控制,不仅可以降低消毒剂成分浓度,还可以提高消毒效率和广谱性;在3分钟内对耐乙醇菌的消杀对数可达到5以上;在有机物干扰和较高温度下,对耐乙醇菌的消杀效果稳定;本发明的过硫酸氢钾复合盐溶于水后产的自由基具有较强的氧化消毒作用,可氧化季铵盐中的氯离子生成次氯酸,增强了本发明的消毒效果,延长了本发明的消毒时间。本发明组分少、制备简单、使用方便。Compared with the prior art, the beneficial effects of the present invention are: the water-soluble compound potassium hydrogen persulfate disinfectant of the present invention first compounded potassium hydrogen persulfate compound salt and quaternary ammonium salts, and through the synergistic effect of each component, It can quickly and effectively kill ethanol-resistant microorganisms, ensuring good microbial control in the pharmaceutical environment. It can not only reduce the concentration of disinfectant components, but also improve disinfection efficiency and broad-spectrum; the logarithm of killing ethanol-resistant bacteria within 3 minutes can be reduced Reach more than 5; under the interference of organic matter and higher temperature, the disinfecting effect on ethanol-resistant bacteria is stable; the free radical produced after the potassium persulfate compound salt of the present invention is dissolved in water has stronger oxidative disinfection effect, and can oxidize Chloride ions in the quaternary ammonium salt generate hypochlorous acid, which enhances the disinfection effect of the present invention and prolongs the disinfection time of the present invention. The invention has few components, simple preparation and convenient use.

附图说明Description of drawings

图1为消毒剂中十二烷基二甲基苄基氯化铵质量百分比的考察图。Fig. 1 is the investigation figure of dodecyl dimethyl benzyl ammonium chloride mass percentage in disinfectant.

图2为复方消毒剂水溶液浓度的考察图。Fig. 2 is the investigation diagram of compound disinfectant aqueous solution concentration.

图3为实施例6中杀菌时间试验的结果图。Fig. 3 is the result chart of sterilization time test in embodiment 6.

图4为实施例6中有机干扰物试验的结果图。Fig. 4 is the result chart of organic interfering substance test in embodiment 6.

图5为实施例6中温度试验的结果图。FIG. 5 is a graph showing the results of the temperature test in Example 6.

具体实施方式Detailed ways

为更好地说明本发明的目的、技术方案和优点,下面将结合附图和具体实施例对本发明作进一步说明。In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with the accompanying drawings and specific embodiments.

实施例1Example 1

一种水溶性复方过硫酸氢钾消毒剂,包括如下质量百分比的组分:过硫酸氢钾复合盐71.4%、十二烷基二甲基苄基氯化铵28.6%。配成0.70%(W/V)的水溶液使用,在3分钟内对耐乙醇芽孢杆菌的消杀对数为5.70。A water-soluble compound potassium hydrogen persulfate disinfectant comprises the following components in mass percentage: 71.4% of potassium hydrogen persulfate compound salt and 28.6% of dodecyl dimethyl benzyl ammonium chloride. It is used as an aqueous solution of 0.70% (W/V), and the logarithm of disinfecting ethanol-resistant bacillus within 3 minutes is 5.70.

实施例2Example 2

一种水溶性复方过硫酸氢钾消毒剂,包括如下质量百分比的组分:过硫酸氢钾复合盐92.3%、十二烷基二甲基苄基氯化7.70%。配成0.60%(W/V)的水溶液使用,在3分钟内对耐乙醇芽孢杆菌的消杀对数为5.83。A water-soluble compound potassium hydrogen persulfate disinfectant comprises the following components in mass percentage: 92.3% of potassium hydrogen persulfate compound salt and 7.70% of dodecyl dimethyl benzyl chloride. It is used as an aqueous solution of 0.60% (W/V), and the logarithm of disinfecting ethanol-resistant bacillus within 3 minutes is 5.83.

实施例3Example 3

一种水溶性复方过硫酸氢钾消毒剂,包括如下质量百分比的组分:过硫酸氢钾复合盐76.9%、十二烷基二甲基苄基氯化23.1%。配成0.65%(W/V)的水溶液使用,在3分钟内对耐乙醇芽孢杆菌的消杀对数为5.47。A water-soluble compound potassium hydrogen persulfate disinfectant comprises the following components in mass percentage: 76.9% of potassium hydrogen persulfate compound salt and 23.1% of dodecyl dimethyl benzyl chloride. It is used as an aqueous solution of 0.65% (W/V), and the logarithm of disinfecting ethanol-resistant bacillus within 3 minutes is 5.47.

实施例4Example 4

一种水溶性复方过硫酸氢钾消毒剂,包括如下质量百分比的组分:过硫酸氢钾复合盐91.24%、十二烷基二甲基苄基氯化8.76%。配成0.55%(W/V)的水溶液使用,在3分钟内对耐乙醇芽孢杆菌的消杀对数为5.61。A water-soluble compound potassium hydrogen persulfate disinfectant comprises the following components in mass percentage: 91.24% of potassium hydrogen persulfate compound salt and 8.76% of dodecyl dimethyl benzyl chloride. It is used as an aqueous solution of 0.55% (W/V), and the logarithm of disinfecting ethanol-resistant bacillus within 3 minutes is 5.61.

实施例5Example 5

一种水溶性复方过硫酸氢钾消毒剂,包括如下质量百分比的组分:过硫酸氢钾复合盐92.3%、十二烷基二甲基苄基氯化7.7%。配成0.54%(W/V)的水溶液使用,在3分钟内对耐乙醇芽孢杆菌的消杀对数为5.61。A water-soluble compound potassium hydrogen persulfate disinfectant comprises the following components in mass percentage: 92.3% of potassium hydrogen persulfate compound salt and 7.7% of dodecyl dimethyl benzyl chloride. It is used as an aqueous solution of 0.54% (W/V), and the logarithm of disinfecting ethanol-resistant bacillus within 3 minutes is 5.61.

对耐乙醇菌的消杀效果为单组份过硫酸氢钾复合盐的3.7倍,对耐乙醇菌的消杀效果为单组份季铵盐的3.4倍,对耐乙醇菌的消杀效果为75%乙醇的6.4倍。本发明对耐乙醇菌的消杀效果优于季铵盐与其他过氧化物复配。The disinfecting effect on ethanol-resistant bacteria is 3.7 times that of single-component potassium hydrogen persulfate compound salt, the disinfecting effect on ethanol-resistant bacteria is 3.4 times that of single-component quaternary ammonium salt, and the disinfecting effect on ethanol-resistant bacteria is 6.4 times that of 75% ethanol. The disinfecting effect of the invention on ethanol-resistant bacteria is better than that of compounding of quaternary ammonium salt and other peroxides.

实施例6Example 6

(1)菌悬液的制备(1) Preparation of bacterial suspension

用TPS液体培养基润湿无菌棉签,刮取菌苔转移至含灭菌TPS培养基的锥形瓶中,震荡20s使其分散均匀,测定其OD600值,根据公式1计算,使其含菌量为108cfu/mL—5×108cfu/mL。Wet a sterile cotton swab with TPS liquid medium, scrape the bacterial lawn and transfer it to an Erlenmeyer flask containing sterilized TPS medium, shake it for 20s to make it evenly dispersed, measure its OD600 value, and calculate it according to formula 1 to make it contain bacteria The amount is 10 8 cfu/mL-5×10 8 cfu/mL.

y=60.965x-10.333,r2=0.9908 公式1y=60.965x-10.333, r 2 =0.9908 Formula 1

(2)消毒剂配方的优化(2) Optimization of disinfectant formula

配制不同质量百分比的十二烷基二甲基苄基氯化铵和过硫酸氢钾复合盐的混合消毒剂粉末,然后配置成消毒剂水溶液。The mixed disinfectant powder of lauryl dimethyl benzyl ammonium chloride and potassium hydrogen persulfate compound salt of different mass percentages is prepared, and then configured into disinfectant aqueous solution.

在5mL EP管中分别加入0.5mL菌悬液和2mL消毒剂水溶液,混匀,作用3分钟后,吸取0.25mL试液加入2.25mL D/E肉汤中和剂中,混匀,作用10分钟。Add 0.5mL of bacterial suspension and 2mL of disinfectant aqueous solution into 5mL EP tube respectively, mix well, and act for 3 minutes, absorb 0.25mL test solution and add it to 2.25mL D/E broth neutralizer, mix well, and act for 10 minutes .

梯度稀释至适宜浓度,进行活菌培养计数,计算消杀对数和杀灭率。Gradually dilute to an appropriate concentration, count viable bacteria, and calculate the kill logarithm and kill rate.

分别配置复方消毒剂粉末中氧化剂十二烷基二甲基苄基氯化铵质量百分比为0%、1.96%、3.85%、5.66%、7.41%、7.70%、9.09%、16.7%、23.08%、28.57%的复方消毒剂粉末,然后配置成0.50%(W/V)水溶液,按上述试验操作测定各浓度消杀对数和杀灭率,考察十二烷基二甲基苄基氯化铵最适质量百分比。The mass percentages of oxidant dodecyldimethylbenzyl ammonium chloride in the compound disinfectant powder are respectively configured as 0%, 1.96%, 3.85%, 5.66%, 7.41%, 7.70%, 9.09%, 16.7%, 23.08%, 28.57% compound disinfectant powder, then configured into 0.50% (W/V) aqueous solution, measure the kill logarithm and killing rate of each concentration according to the above-mentioned test operation, investigate the most effective effect of dodecyl dimethyl benzyl ammonium chloride Appropriate mass percentage.

按照十二烷基二甲基苄基氯化铵最适质量百分比配置复方消毒剂粉末,然后配置成不同浓度的水溶液,以消杀对数和杀灭率为评价指标,筛选复方消毒剂水溶液最适浓度。According to the optimum mass percentage of lauryl dimethyl benzyl ammonium chloride, the compound disinfectant powder is configured, and then it is configured into aqueous solutions of different concentrations, and the optimal compound disinfectant aqueous solution is screened with the evaluation index of killing logarithm and killing rate. Appropriate concentration.

试验结果如图1所示,复方消毒剂水溶液中十二烷基二甲基苄基氯化铵质量百分比7.7%及以上时,复方消毒剂水溶液消杀对数均大于5,因十二烷基二甲基苄基氯化铵的毒性随浓度增加而增大,所以复方消毒剂粉末中十二烷基二甲基苄基氯化铵的最适质量百分比为7.7%(相对应地,过硫酸氢钾复合盐最适质量百分比为92.3%),该消毒剂粉末配成0.60%(W/V)的水溶液使用。如图2所示,复方消毒剂水溶液浓度达到0.54%(W/V)时消杀指数达到5.0以上,故该复方消毒剂粉末配成0.54%(W/V)的水溶液使用。Test result as shown in Figure 1, when dodecyl dimethyl benzyl ammonium chloride mass percentage is 7.7% and above in compound disinfectant aqueous solution, compound disinfectant aqueous solution kills logarithm all greater than 5, because dodecyl The toxicity of dimethyl benzyl ammonium chloride increases with concentration, so the optimum mass percentage of dodecyl dimethyl benzyl ammonium chloride is 7.7% (correspondingly, persulfate The optimum mass percentage of hydrogen potassium compound salt is 92.3%), and this disinfectant powder is made into the aqueous solution of 0.60% (W/V) to use. As shown in Figure 2, when compound disinfectant aqueous solution concentration reaches 0.54% (W/V), disinfecting index reaches more than 5.0, so this compound disinfectant powder is made into the aqueous solution of 0.54% (W/V) and uses.

(3)杀菌效果试验(3) Bactericidal effect test

制备菌悬液,按实施例5中的方法配制复方消毒剂水溶液,使用单组份过硫酸氢钾复合盐的0.54%(W/V)的水溶液、单组份十二烷基二甲基苄基氯化铵的0.54%(W/V)的水溶液为对照,另外增加制药环境中常用消毒剂75%乙醇作为对照,进行杀菌效果比较研究。Prepare bacterium suspension, prepare compound disinfectant aqueous solution by the method in embodiment 5, use the aqueous solution of 0.54% (W/V) of one-component potassium hydrogen persulfate compound salt, one-component dodecyl dimethyl benzyl The 0.54% (W/V) aqueous solution of ammonium chloride was used as a control, and 75% ethanol, a commonly used disinfectant in the pharmaceutical environment, was added as a control to conduct a comparative study on the bactericidal effect.

在4个5mL EP管中分别加入0.5mL菌悬液和2mL初浓度消毒剂,使混合后溶液中消毒剂达到终浓度,分别作用3min。Add 0.5mL of bacterial suspension and 2mL of initial concentration disinfectant to four 5mL EP tubes, so that the disinfectant in the mixed solution reaches the final concentration, and act for 3 minutes respectively.

吸取0.25mL各作用时间的样液加入2.25mL D/E肉汤中和剂中,混匀,作用10min。Take 0.25mL of the sample solution of each action time and add it to 2.25mL D/E broth neutralizer, mix well, and act for 10min.

吸取0.5mL样液,稀释至适宜浓度,进行活菌培养计数。Draw 0.5mL sample solution, dilute to an appropriate concentration, and count viable bacteria.

同时用稀释液代替消毒剂作为对照组,进行平行试验,试验结果如表1所示。At the same time, the diluted solution was used instead of the disinfectant as the control group, and a parallel test was carried out. The test results are shown in Table 1.

表1Table 1

组别group 消杀对数disinfect logarithm 杀灭率kill rate 单组份过硫酸氢钾复合盐One-component potassium hydrogen persulfate compound salt 1.511.51 96.909%96.909% 单组份十二烷基二甲基苄基氯化铵One-component dodecyl dimethyl benzyl ammonium chloride 1.651.65 97.761%97.761% 75%乙醇75% ethanol 0.870.87 86.510%86.510% 复方过硫酸氢钾复合盐Compound potassium hydrogen persulfate compound salt 5.615.61 99.999%99.999%

由表1可知,单组份的过硫酸氢钾复合盐、单组份的十二烷基二甲基苄基氯化铵以及75%乙醇对于耐乙醇菌的消杀对数远远低于5.0。与同浓度的单组份相比,本发明的复方过硫酸氢钾消毒剂的消杀对数最高,且杀灭率高达99.999%,能高效消杀耐乙醇菌。As can be seen from Table 1, the single-component potassium hydrogen persulfate compound salt, the single-component dodecyl dimethyl benzyl ammonium chloride and 75% ethanol are far below 5.0 for the disinfect logarithm of ethanol-resistant bacteria . Compared with the single component of the same concentration, the compound potassium hydrogen persulfate disinfectant of the present invention has the highest killing logarithm, and the killing rate is as high as 99.999%, and can efficiently kill ethanol-resistant bacteria.

(4)杀菌时间试验(4) Sterilization time test

制备菌悬液,按实施例5的方法配制消毒剂。Prepare bacterial suspension, prepare disinfectant by the method for embodiment 5.

在4个5mL EP管中加入0.5mL菌悬液和2mL初浓度消毒剂,使混合后溶液中消毒剂达到终浓度,分别作用1min、2min、3min。Add 0.5mL bacterial suspension and 2mL initial concentration of disinfectant to four 5mL EP tubes to make the disinfectant in the mixed solution reach the final concentration, and act for 1min, 2min, and 3min respectively.

吸取0.25mL各作用时间的样液加入2.25mL D/E肉汤中和剂中,混匀,作用10min。Take 0.25mL of the sample solution of each action time and add it to 2.25mL D/E broth neutralizer, mix well, and act for 10min.

吸取0.5mL样液,稀释至适宜浓度,进行活菌培养计数。Draw 0.5mL sample solution, dilute to an appropriate concentration, and count viable bacteria.

同时用稀释液代替消毒剂作为对照组,进行平行试验。At the same time, the diluted solution was used instead of the disinfectant as a control group for parallel experiments.

如图3所示,杀菌时间2min和3min消杀对数达到5.0以上,故选择灭菌时间为2-3min,该复方消毒剂作用时间低于消毒剂规范要求5min,能快速消杀耐乙醇菌。As shown in Figure 3, the kill logarithm of 2 minutes and 3 minutes of sterilization time reaches more than 5.0, so the sterilization time is selected as 2-3 minutes. The action time of this compound disinfectant is lower than the disinfectant specification requirement of 5 minutes, which can quickly disinfect ethanol-resistant bacteria .

(5)有机干扰物试验(5) Test of organic interfering substances

按上述方法配制消毒剂、菌悬液,将无菌牛奶、菌悬液、消毒剂置于(20±2)℃的恒温水浴锅中,静置5min。Prepare disinfectant and bacterial suspension according to the above method, put sterile milk, bacterial suspension and disinfectant in a constant temperature water bath at (20±2)°C, and let it stand for 5 minutes.

试验组:5mL EP管中加入0.25mL菌悬液和0.25mL无菌牛奶,混匀,制成含50%有机干扰物的菌悬液。再加入2mL实施例5的消毒剂,混匀,根据杀菌试验结果,作用时间为3分钟。吸取0.25mL上述液体加入含2.25mL中和剂的5mL EP管中,作用10分钟。Test group: Add 0.25mL of bacterial suspension and 0.25mL of sterile milk into a 5mL EP tube, mix well, and make a bacterial suspension containing 50% organic interfering substances. Then add 2mL of the disinfectant of Example 5, mix evenly, and according to the bactericidal test result, the action time is 3 minutes. Draw 0.25mL of the above liquid into a 5mL EP tube containing 2.25mL of neutralizing agent, and act for 10 minutes.

阳性对照组:5mL EP管中加入0.5mL菌悬液和2mL实施例5的消毒剂,混匀,作用3分钟后,吸取0.25mL上述液体加入含2.25mL中和剂的5mL EP管中,作用10分钟。Positive control group: Add 0.5mL of bacterial suspension and 2mL of the disinfectant of Example 5 to a 5mL EP tube, mix well, and after 3 minutes of action, absorb 0.25mL of the above liquid and add it to a 5mL EP tube containing 2.25mL of neutralizing agent. 10 minutes.

阴性对照组:5mL EP管中加入0.5mL菌悬液和2mL TPS稀释液,混匀,作用3分钟后,吸取0.25mL上述液体加入含2.25mL中和剂的5mL EP管中,作用10分钟。Negative control group: add 0.5mL bacterial suspension and 2mL TPS diluent to a 5mL EP tube, mix well, and act for 3 minutes, then draw 0.25mL of the above liquid into a 5mL EP tube containing 2.25mL neutralizer, and act for 10 minutes.

吸取上述三组样液进行梯度稀释涂布,于37℃培养24小时,统计菌落数目,计算杀灭率和杀灭对数值。The above-mentioned three groups of sample liquids were taken for gradient dilution and coating, cultured at 37°C for 24 hours, the number of colonies was counted, and the killing rate and logarithmic value of killing were calculated.

将试验组中50%有机干扰物菌悬液替换为25%有机干扰物菌悬液再进行上述试验。In the test group, the 50% organic interfering substance bacterial suspension was replaced with 25% organic interfering substance bacterial suspension, and then the above test was carried out.

如图4所示,50%和25%牛奶作用时复方消毒剂的消杀对数均大于5.0,根据显著性分析,P大于0.01,故有机物干扰作用不显著。As shown in Figure 4, the disinfect logarithm of the compound disinfectant was greater than 5.0 when 50% and 25% milk acted. According to the significance analysis, P was greater than 0.01, so the organic matter interference was not significant.

(6)温度试验(6) Temperature test

按上述方法配制菌悬液和消毒剂。Prepare bacterial suspension and disinfectant as above.

取两个5mL EP管,分别加入2mL实施例5的消毒剂和2mL TPS溶液作为试验组和对照组,再分别加入2.25mL中和剂于上述EP管中。Take two 5mL EP tubes, add 2mL of the disinfectant of Example 5 and 2mL of TPS solution respectively as test group and control group, and then add 2.25mL neutralizer into the above-mentioned EP tubes respectively.

将EP管置于(40±1)℃恒温水浴锅中,静置3min。Place the EP tube in a constant temperature water bath at (40±1)°C and let it stand for 3 minutes.

按照悬液定量法进行杀菌试验,稀释至适宜梯度,进行活菌培养计数,统计试验结果,计算平均杀灭对数值和杀灭率。Carry out the bactericidal test according to the suspension quantitative method, dilute to a suitable gradient, carry out the counting of live bacteria culture, count the test results, and calculate the average killing logarithm value and killing rate.

每个温度进行一次平行试验,并在(30±1)℃重复如上试验。Carry out a parallel test at each temperature, and repeat the above test at (30±1)°C.

如图5所示,在较高温度30℃和40℃下,复方消毒剂的消杀对数仍能保持5.0以上,且无显著性变化(P>0.01),故较高温度下复方消毒剂的杀菌效果较为稳定。As shown in Figure 5, at higher temperatures of 30°C and 40°C, the disinfect logarithm of the compound disinfectant can still maintain more than 5.0, and there is no significant change (P>0.01), so the compound disinfectant at higher temperatures The bactericidal effect is more stable.

(7)复方组分联用效果考察(7) Investigation on the combined effect of compound components

为考察复方消毒剂中两组分联用是否具有协同效果,按照所优选的消毒剂粉末配方比例,分别配制0.54%(W/V)复方消毒剂水溶液,及其相同浓度的单组份水溶液(0.042%(W/V)十二烷基二甲基苄基氯化铵水溶液和0.503%(W/V)过硫酸氢钾复合盐水溶液),并采用二倍稀释法进行梯度稀释后分别测定单组份水溶液最小抑菌浓度(MIC)和联用时的分级抑菌浓度(FIC)。In order to investigate whether the combination of two components in the compound disinfectant has a synergistic effect, according to the preferred disinfectant powder formula ratio, prepare 0.54% (W/V) compound disinfectant aqueous solution and a single-component aqueous solution of the same concentration ( 0.042% (W/V) dodecyl dimethyl benzyl ammonium chloride aqueous solution and 0.503% (W/V) potassium hydrogen persulfate complex salt solution), and adopt the two-fold dilution method to measure the single The minimum inhibitory concentration (MIC) of the component aqueous solution and the fractional inhibitory concentration (FIC) when used in combination.

分别取10mL不同浓度上述抗菌液加入无菌培养皿中,再取10mL TSA培养基加入上述培养皿中,边加边轻轻摇晃平板,使抗菌液与培养基混合均匀,待其完全凝固后备用。Take 10mL of the above-mentioned antibacterial solution of different concentrations and add it to a sterile petri dish, then take 10mL of TSA medium and add it to the above-mentioned petri dish, shake the plate gently while adding, so that the antibacterial solution and the medium are evenly mixed, and wait for it to completely solidify before use .

取200μL菌悬液加入凝固后的培养基中,用三角涂布器将菌悬液涂布均匀,置于37℃培养箱中培养24h。培养完成后观察细菌生长情况,培养基中完全无菌存在的最小相应浓度即为该抗菌药物的最小抑菌浓度(MIC)。Take 200 μL of the bacterial suspension and add it to the solidified medium, spread the bacterial suspension evenly with a triangular spreader, and place it in a 37°C incubator for 24 hours. After the culture is completed, the growth of the bacteria is observed, and the minimum corresponding concentration in the culture medium that is completely sterile is the minimum inhibitory concentration (MIC) of the antibacterial drug.

以上述试验测定的两种抗菌物质的MIC为基础,首先配制4MIC的两种抗菌液,接着采用二倍稀释法分别配制2MIC、1MIC、1/2MIC、1/4MIC的抗菌液,将各浓度的两种抗菌液两两联合使用,即分别取5mL两种抗菌液和10mL TSA培养基加入无菌培养皿中,摇匀,凝固后接种X2菌,于37℃培养箱中培养24小时,观察其生长状况,无菌生长的最小相应浓度即为联合作用的MIC大小。Based on the MICs of the two kinds of antibacterial substances measured in the above test, two kinds of antibacterial solutions of 4MIC were first prepared, and then antibacterial solutions of 2MIC, 1MIC, 1/2MIC, and 1/4MIC were prepared respectively by the double dilution method, and the concentrations of each The two antibacterial solutions are used in combination, that is, take 5mL of the two antibacterial solutions and 10mL TSA medium respectively and add them to a sterile petri dish, shake well, inoculate X2 bacteria after solidification, and cultivate them in a 37°C incubator for 24 hours, and observe the Growth status, the minimum corresponding concentration of sterile growth is the MIC size of the combined effect.

分级抑菌浓度计算公式见公式2。See formula 2 for the calculation formula of graded inhibitory concentration.

Figure BDA0003797316500000101
Figure BDA0003797316500000101

FIC的判定标准如下:FIC≤0.5时,联合使用的两种抗菌药物发挥协同作用;0.5<FIC≤1.0时则起相加效果;1.0<FIC≤2.0则无相关作用;FIC>2.0时表现为拮抗作用。试验结果如表2所示。The criteria for judging FIC are as follows: when FIC≤0.5, the two antibacterial drugs used in combination exert synergistic effect; when 0.5<FIC≤1.0, there is an additive effect; antagonism. The test results are shown in Table 2.

表2Table 2

Figure BDA0003797316500000102
Figure BDA0003797316500000102

注:“-”代表无菌生长,“+”代表有菌生长Note: "-" stands for sterile growth, "+" stands for bacterial growth

最小抑菌浓度试验测得十二烷基二甲基苄基氯化铵与过硫酸氢钾复合盐的最小抑菌浓度分别为0.0525g/L、2.52g/L。联用效果试验结果见表2,其中MICA和MICB分别为过硫酸氢钾复合盐和十二烷基二甲基苄基氯化铵的MIC值,由表2得,对于耐乙醇微生物来说,过硫酸氢钾复合盐和十二烷基二甲基苄基氯化铵联合作用的MIC值为1/8MICA+1/4MICB,分别为其单用时MIC值的1/8和1/4,由此可计算出两者复配后的FIC值为0.375,并根据判定标准,得过硫酸氢钾复合盐和十二烷基二甲基苄基氯化铵联用后,对耐乙醇微生物表现出协同作用。The minimum inhibitory concentrations of dodecyl dimethyl benzyl ammonium chloride and potassium hydrogen persulfate compound salt were measured to be 0.0525g/L and 2.52g/L respectively. The combination effect test results are shown in Table 2, wherein MIC A and MIC B are respectively the MIC values of potassium hydrogen persulfate compound salt and dodecyl dimethyl benzyl ammonium chloride, obtained from Table 2, for ethanol-resistant microorganisms In other words, the MIC value of the joint action of potassium persulfate compound salt and dodecyl dimethyl benzyl ammonium chloride is 1/8MIC A + 1/4MIC B , which are 1/8 and 1/8 of the MIC value when used alone. /4, thus the FIC value after the two can be calculated is 0.375, and according to the judgment standard, after potassium persulfate compound salt and dodecyl dimethyl benzyl ammonium chloride are used in combination, the resistance to Ethanol microbes exhibit synergy.

最后所应当说明的是,以上实施例仅用以说明本发明的技术方案而非对本发明保护范围的限制,尽管参照较佳实施例对本发明作了详细说明,本领域的普通技术人员应当理解,可以对本发明的技术方案进行修改或者等同替换,而不脱离本发明技术方案的实质和范围。Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than limit the protection scope of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that The technical solution of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solution of the present invention.

Claims (7)

1. The water-soluble compound potassium hydrogen persulfate disinfectant is characterized by comprising the following components in percentage by mass: 71.4 to 92.3 percent of oxidant and 7.7 to 28.6 percent of quaternary ammonium salt.
2. The disinfectant as set forth in claim 1, wherein the disinfectant comprises the following components in percentage by mass: 91 to 92.3 percent of oxidant and 7.7 to 9 percent of quaternary ammonium salt.
3. The disinfectant of claim 1 or 2 wherein said oxidizing agent is oxone complex salt.
4. The disinfectant of claim 1 or 2, wherein said quaternary ammonium salt is dodecyl dimethyl benzyl ammonium chloride.
5. Disinfectant according to claim 1 or 2, characterized in that it is formulated for use as an aqueous solution of 0.54-0.70% (W/V).
6. The disinfectant of claim 5, wherein said disinfectant is formulated for use as a 0.54% (W/V) aqueous solution.
7. The disinfectant according to claims 1 to 6, wherein said disinfectant is prepared by mixing an oxidant and a quaternary ammonium salt in a ratio.
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Citations (2)

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Publication number Priority date Publication date Assignee Title
CN102017996A (en) * 2009-09-11 2011-04-20 上海家化联合股份有限公司 Curing agent for sewer pipeline
CN108477209A (en) * 2018-05-30 2018-09-04 军事科学院系统工程研究院卫勤保障技术研究所 A kind of thimerosal and preparation method thereof

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102017996A (en) * 2009-09-11 2011-04-20 上海家化联合股份有限公司 Curing agent for sewer pipeline
CN108477209A (en) * 2018-05-30 2018-09-04 军事科学院系统工程研究院卫勤保障技术研究所 A kind of thimerosal and preparation method thereof

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