CN107466207A - Antimicrobial compositions - Google Patents
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Abstract
Description
本发明涉及抗微生物组合物并且涉及包括抗微生物组合物的配制物。具体来说,本发明涉及可在皮肤上使用的抗微生物组合物。The present invention relates to antimicrobial compositions and to formulations comprising antimicrobial compositions. In particular, the present invention relates to antimicrobial compositions for use on the skin.
众所周知微生物,如细菌和病毒,例如诺如病毒、脊髓灰质炎病毒和腺病毒由于感染或污染而存在健康危害。连同真菌、酵母菌和其它微生物,它们还可引起物品,如食品、服装的腐败并且产生令人不愉快的气味。当微生物存在于基材,如皮肤的表面上时,它们可快速复制以形成菌落。Microorganisms such as bacteria and viruses such as norovirus, poliovirus and adenovirus are well known to present health hazards due to infection or contamination. Together with fungi, yeasts and other microorganisms, they can also cause spoilage of items such as food, clothing and produce unpleasant odours. When microorganisms are present on the surface of a substrate, such as skin, they can replicate rapidly to form colonies.
许多抗微生物剂可毁坏在各种环境中存在的微生物。举例来说,可用于医学、工业、市售、国内和海洋环境的抗微生物剂为已知的。许多已知抗微生物剂此前已包括在用于多种应用的这些环境中的组合物中。Many antimicrobial agents can destroy microorganisms present in various environments. For example, antimicrobial agents that are useful in medical, industrial, commercial, domestic and marine environments are known. Many known antimicrobial agents have previously been included in compositions in these environments for a variety of applications.
已知抗微生物剂和含有这些抗微生物剂的组合物经由多种不同机理起作用。Antimicrobial agents and compositions containing these antimicrobial agents are known to act via a number of different mechanisms.
举例来说,许多抗微生物剂对微生物有毒,并且因此,毁坏与其接触的微生物。这种类型的抗微生物剂的实例包括次氯酸盐(漂白剂)、酚及其化合物,和铜、锡和砷的盐。For example, many antimicrobial agents are toxic to microorganisms and, therefore, destroy microorganisms with which they come into contact. Examples of antimicrobial agents of this type include hypochlorite (bleach), phenols and their compounds, and salts of copper, tin, and arsenic.
然而,尽管许多这些抗微生物剂对微生物有效并且适合于某些环境,但是其机理可使其由于其对人体健康或皮肤条件的不利影响而不适于或不利于局部施用到人类皮肤。举例来说,次氯酸盐漂白剂在固体表面上杀灭微生物非常有效,但是由于其腐蚀特性不适合于施用到皮肤。另外,这些材料趋于在潮湿环境中对于灭菌并且洁净有效,但是在干燥之后不久停止起作用。However, while many of these antimicrobial agents are effective against microorganisms and suitable in certain circumstances, their mechanisms may make them unsuitable or disadvantageous for topical application to human skin due to their adverse effects on human health or skin condition. For example, hypochlorite bleach is very effective at killing microorganisms on solid surfaces, but is not suitable for application to the skin due to its caustic properties. Additionally, these materials tend to be effective for sterilization and cleansing in wet environments, but cease to function shortly after drying.
许多皮肤消毒剂为乙醇类。这些通常为被设计成用于施用到手部用于降低在手部上活的微生物的数目的含乙醇制备。这类制备通常含有60%到95%乙醇或异丙醇。然而,虽然异丙醇具有确定的抗菌特性,但是其具有当有规律地使用时可引起干燥和皮肤刺激的缺点。因此一些人可不愿意使用这类乳霜、肥皂和包含显著水平的异丙醇的其它组合物。Many skin antiseptics are alcohols. These are generally ethanol-containing preparations designed for application to the hands for reducing the number of viable microorganisms on the hands. Such preparations typically contain 60% to 95% ethanol or isopropanol. However, while isopropyl alcohol has established antimicrobial properties, it has the disadvantage of causing dryness and skin irritation when used regularly. Some people may therefore be reluctant to use such creams, soaps, and other compositions that contain significant levels of isopropyl alcohol.
一些抗微生物剂对人类和动物高度有毒并且处理危险。因此需要专业处理、治疗和设备以便安全地处理它们。因此,包含这种类型的抗微生物剂的组合物的制造和处置可成问题。还可存在与使用含有这种类型的抗微生物剂的组合物相关联的问题,具体地说在其中难以确保其用于指示目的的消费品材料中。Some antimicrobials are highly toxic to humans and animals and dangerous to handle. Professional handling, therapy and equipment are therefore required in order to handle them safely. Therefore, the manufacture and disposal of compositions containing this type of antimicrobial agent can be problematic. There can also be problems associated with the use of compositions containing this type of antimicrobial agent, particularly in consumer product materials where it is difficult to secure their use for indicated purposes.
除非上下文另外指示,否则本文“毒性”旨在是指对复杂生物如哺乳动物的毒性。提及“有毒”将因此理解。"Toxicity" herein is intended to mean toxicity to complex organisms, such as mammals, unless the context indicates otherwise. References to "toxic" will be understood accordingly.
化学品环境认证的增加审查另外限定不恰好用于局部施用在皮肤上但是用于通用的抗微生物剂的用法。举例来说,一些抗微生物剂一旦进入环境就可损害其它生物。它们还可长时间段非常稳定并且存留在环境中致使围绕积累和残余水平的担忧。Increased scrutiny of environmental certification of chemicals additionally defines the use of antimicrobials not just for topical application on the skin but for general use. For example, some antimicrobial agents can harm other organisms once they enter the environment. They can also be very stable over long periods of time and persist in the environment causing concerns around accumulation and residual levels.
由于这些因素,有效和可获得的抗微生物剂(具体地说用于皮肤上)的列表变得更加受限制并且登记新型抗微生物剂的负荷更受抑制。同时,公众变得越来越关注在医院中爆发如MRSA之后个人和财产两者的消毒。Due to these factors, the list of effective and available antimicrobial agents, particularly for use on the skin, has become more restricted and the burden of registering new antimicrobial agents has been more inhibited. At the same time, the public has become increasingly concerned about the disinfection of both individuals and property following outbreaks such as MRSA in hospitals.
需要提供用于多种应用和用途的组合物,如用于皮肤上的组合物,例如手部消毒试剂,其具有抗微生物特性并且解决上文陈述的问题中的一个或多个。然而,不能直接这样做。存在法规,如杀菌产品法规(指令98/8/EC),其根据给定的可使用的抗微生物剂的性质和量两者调控抗微生物剂的使用。此外,一旦在组合物中,抗微生物剂的潜在反应性为重要的,因为一些抗微生物剂通过化学反应显现惰性。甚至其中抗微生物剂不是通过化学反应去活的,它可具有通过组合物的其它组分遏制的其活性。There is a need to provide compositions for various applications and uses, such as compositions for use on the skin, such as hand sanitizers, which have antimicrobial properties and which address one or more of the problems stated above. However, this cannot be done directly. There are regulations, such as the Biocidal Products Regulation (Directive 98/8/EC), which regulate the use of antimicrobial agents according to both the nature and the amount of a given usable antimicrobial agent. Furthermore, the potential reactivity of the antimicrobial agent once in the composition is important since some antimicrobial agents appear inert through chemical reactions. Even where the antimicrobial agent is not chemically deactivated, it may have its activity suppressed by other components of the composition.
本发明人已出人意料地发现上述不足可通过组分的某些组合克服。此外已发现含有组分的这些组合的组合物可具有一些出人意料并且非预期的特性。The present inventors have surprisingly found that the above mentioned deficiencies can be overcome by certain combinations of components. It has also been discovered that compositions containing these combinations of components can have some surprising and unexpected properties.
在本说明书中对明显先前已出版文献的列举或论述不应视为承认所述文献是目前先进技术的一部分或是公共常识。The listing or discussion of apparently previously published documents in this specification should not be taken as an acknowledgment that said documents are part of the state of the art or are common general knowledge.
本发明提供抗微生物组合物,包含:The present invention provides antimicrobial compositions comprising:
(i)氨基酸、氨基酸的衍生物、氨基酸的盐,或氨基酸的衍生物的盐或其混合物;(i) amino acids, derivatives of amino acids, salts of amino acids, or salts of derivatives of amino acids or mixtures thereof;
(ii)包含两种或更多种抗微生物季铵化合物或至少一种抗微生物季铵化合物和氯己定或氯己定盐的抗微生物组分;和(ii) an antimicrobial component comprising two or more antimicrobial quaternary ammonium compounds or at least one antimicrobial quaternary ammonium compound and chlorhexidine or a chlorhexidine salt; and
(iii)极性溶剂。(iii) Polar solvents.
氨基酸为生命必需的众所周知的有机化合物。其特征为具有附接到与羧酸(CO2H)官能团相邻的碳的胺(NH2)官能团,以及特定于氨基酸的侧链。氨基酸具有下文示出的通式。Amino acids are well known organic compounds essential to life. It is characterized by having an amine ( NH2 ) functional group attached to a carbon adjacent to the carboxylic acid ( CO2H ) functional group, and a side chain specific to the amino acid. Amino acids have the general formula shown below.
因为氨基酸具有胺基和羧酸基两者,所以其可充当碱和酸两者。在低pH下,主要形式将具有中性羧酸基和正铵离子(净电荷+1)。在高pH下,它将具有负甲酸酯和中性氨基(净电荷-1)。在中等pH下,氨基酸将通常含有负甲酸酯和正铵基团两者,因此具有净零电荷。Because amino acids have both amine and carboxylic acid groups, they can act as both bases and acids. At low pH, the predominant form will have a neutral carboxylic acid group and a positive ammonium ion (net charge +1). At high pH it will have negative formate and neutral amino groups (net charge -1). At intermediate pH, amino acids will generally contain both negative formate and positive ammonium groups and thus have a net zero charge.
精氨酸为最常见的氨基酸中的一种并且在下文示出。Arginine is one of the most common amino acids and is shown below.
常见的氨基酸的一些另外实例为甘氨酸、赖氨酸、谷氨酸、谷氨酰胺、天冬氨酸、天冬酰胺、组氨酸、脯氨酸、甲硫氨酸、半胱氨酸、丝氨酸、苏氨酸、异亮氨酸、苯丙氨酸、酪氨酸、色氨酸、缬氨酸和亮氨酸。这些氨基酸的结构为充分研究的。Some additional examples of common amino acids are glycine, lysine, glutamic acid, glutamine, aspartic acid, asparagine, histidine, proline, methionine, cysteine, serine , threonine, isoleucine, phenylalanine, tyrosine, tryptophan, valine and leucine. The structures of these amino acids are well studied.
术语“氨基酸”此外包括氨基酸的链,如肽和多肽。当单个氨基酸经由通过一个氨基酸的胺基与另一个氨基酸的羧基的反应形成的肽(酰胺)键连接在一起时形成肽。最短的肽为由通过单个肽键接合的两个氨基酸构成的二肽,随后三肽、四肽等。多肽为长、连续并且未分支的肽链。The term "amino acid" also includes chains of amino acids, such as peptides and polypeptides. Peptides are formed when individual amino acids are linked together via peptide (amide) bonds formed by the reaction of the amine group of one amino acid with the carboxyl group of another amino acid. The shortest peptides are dipeptides consisting of two amino acids joined by a single peptide bond, followed by tripeptides, tetrapeptides, etc. Polypeptides are long, continuous and unbranched peptide chains.
术语“氨基酸的衍生物”意指其中α-氨基和/或羧基官能团被替代的有机基团取代的氨基酸,或其中在氨基酸的侧链中的官能团被替代的有机基团取代的氨基酸,或其中α-氨基和/或羧基官能团被替代的有机基团取代的和/或在其侧链中的官能团此外被替代的有机基团取代的氨基酸。替代的有机基团包括(但不限于)烯基、苯基、酰胺、酯、醇和醚基或其组合。氨基酸的衍生物的实例为N-月桂酰基-L-精氨酸乙酯,其结构在下文示出。The term "derivative of an amino acid" means an amino acid in which the α-amino and/or carboxyl functional groups are substituted by a substituted organic group, or an amino acid in which a functional group in the side chain of the amino acid is substituted by a substituted organic group, or wherein Amino acids in which the α-amino and/or carboxyl functional groups are substituted by substituted organic groups and/or functional groups in their side chains are additionally substituted by substituted organic groups. Alternative organic groups include, but are not limited to, alkenyl, phenyl, amide, ester, alcohol, and ether groups or combinations thereof. An example of a derivative of an amino acid is N-lauroyl-L-arginine ethyl ester, the structure of which is shown below.
术语“氨基酸的盐”意指与抗衡离子(其为相反电荷的离子)组合的氨基酸的阳离子或阴离子形式。氨基酸的阳离子形式通过在氨基酸中将带正电氢离子从酸转移到氨基形成。抗衡离子衍生自氢离子从其转移的酸。氨基酸的阴离子形式通过在氨基酸中从羧酸基损失带正电氢离子形成。在这种情况下,抗衡离子衍生自氢离子转移到的碱。氨基酸盐的实例为精氨酸乳酸酯,其可以AH Care L65商购。AH Care L65由乳酸;精氨酸混合物构成。精氨酸乳酸酯的结构在下文示出。The term "salt of an amino acid" means the cationic or anionic form of an amino acid in combination with a counterion (which is an ion of opposite charge). The cationic form of an amino acid is formed by transferring a positively charged hydrogen ion from the acid to the amino group in the amino acid. The counterion is derived from the acid from which the hydrogen ion is transferred. The anionic form of an amino acid is formed by the loss of a positively charged hydrogen ion from a carboxylic acid group in the amino acid. In this case, the counterion is derived from the base to which the hydrogen ion is transferred. An example of an amino acid salt is arginine lactate, which is commercially available as AH Care L65. AH Care L65 is composed of lactic acid; arginine mixture. The structure of arginine lactate is shown below.
术语“氨基酸的衍生物的盐”意指如上定义的与抗衡离子(其为相反电荷的离子)组合的氨基酸衍生物的阳离子或阴离子形式。氨基酸的阳离子形式通过在氨基酸衍生物中将带正电氢离子从酸转移到氨基形成。抗衡离子衍生自氢离子从其转移的酸。氨基酸衍生物的阴离子形式通过在氨基酸衍生物中从羧酸基损失带正电氢离子形成。在这种情况下,抗衡离子衍生自氢离子转移到的碱。氨基酸的衍生物的盐的实例为N-月桂酰基-L-精氨酸乙酯单-盐酸盐,其可以其结构在下文示出的Aminat G商购。The term "salt of a derivative of an amino acid" means a cationic or anionic form of an amino acid derivative as defined above in combination with a counterion (which is an ion of opposite charge). The cationic form of an amino acid is formed by transferring a positively charged hydrogen ion from the acid to the amino group in an amino acid derivative. The counterion is derived from the acid from which the hydrogen ion is transferred. The anionic form of the amino acid derivative is formed by the loss of positively charged hydrogen ions from the carboxylic acid group in the amino acid derivative. In this case, the counterion is derived from the base to which the hydrogen ion is transferred. An example of a salt of a derivative of an amino acid is N-lauroyl-L-arginine ethyl ester mono-hydrochloride, which is commercially available as Aminat G whose structure is shown below.
用于本发明的氨基酸或氨基酸衍生物的盐包括(但不限于)盐酸盐、酒石酸盐、丙二酸盐、丁二酸盐、琥珀酰胺酸盐、苹果酸盐、谷氨酸盐、焦谷氨酸盐和天冬氨酸盐。在一个方面中,氨基酸或氨基酸衍生物的盐不是膦酸盐或含磷盐,如单烷基磷酸根离子、单烯基磷酸根离子、单烷基膦酸根离子,或单烯基膦酸根离子,如具有带有8到20个碳原子的直链或分支链烷基或烯基的那些。Salts of amino acids or amino acid derivatives useful in the present invention include, but are not limited to, hydrochloride, tartrate, malonate, succinate, succinamate, malate, glutamate, pyro Glutamate and Aspartate. In one aspect, the salt of an amino acid or amino acid derivative is not a phosphonate or phosphorus-containing salt, such as a monoalkylphosphate ion, a monoalkenylphosphate ion, a monoalkylphosphonate ion, or a monoalkenylphosphonate ion , such as those having straight or branched chain alkyl or alkenyl groups with 8 to 20 carbon atoms.
组分(i)可包含亲水性氨基酸或这类氨基酸的盐或衍生物或这类衍生物的盐。亲水性氨基酸可具有亲水性侧链或可带正电或带负电具有亲水性侧链。Component (i) may comprise hydrophilic amino acids or salts or derivatives of such amino acids or salts of such derivatives. A hydrophilic amino acid can have a hydrophilic side chain or can be positively or negatively charged with a hydrophilic side chain.
举例来说,组分(i)可包含带正电氨基酸或这类氨基酸的盐或衍生物或这类衍生物的盐。For example, component (i) may comprise positively charged amino acids or salts or derivatives of such amino acids or salts of such derivatives.
氨基酸的衍生物可由于对氨基酸进行的改性而为亲水性的。举例来说,氨基酸可被改性使得其带正电或带负电。Derivatives of amino acids may be hydrophilic due to modifications made to the amino acids. For example, amino acids can be modified so that they are positively or negatively charged.
如上定义的亲水性氨基酸通常为水溶性的。A hydrophilic amino acid as defined above is generally water soluble.
水溶性意指氨基酸或这类氨基酸的盐或衍生物或这类衍生物的盐通常在25℃下在水中溶解度为每kg的水至少约0.5g。举例来说,每kg的水至少约1g,例如每kg的水至少约10g,或每kg的水至少约50g。Water-soluble means that the amino acid or a salt or derivative of such an amino acid or a salt of such a derivative generally has a solubility in water of at least about 0.5 g per kg of water at 25°C. For example, at least about 1 g per kg of water, such as at least about 10 g per kg of water, or at least about 50 g per kg of water.
适合用于本发明中的氨基酸的盐和衍生物和这类衍生物的盐通常为水溶性的。Salts and derivatives of amino acids suitable for use in the present invention and salts of such derivatives are generally water soluble.
适合用于本发明中的氨基酸还可通过其水性指数分类。此指数在例如Kyte,J.和Doolittle,R.,1982,“一种用于显示蛋白的亲水特征的简单方法(A simple method fordisplaying the hydropathic character of a protein)”《分子生物学杂志(Jmol.Biol.)》157:105-132中描述。如有经验的读者将理解,水性指数的正值越大,氨基酸的疏水性越大。用于本发明的合适的氨基酸包括水性指数值为0(零)或更小,如-2或更小的氨基酸。这类氨基酸的盐和衍生物和这类衍生物的盐适合用于本发明中。精氨酸及其盐和衍生物以及这类衍生物的盐适合用于本发明中。精氨酸的水性指数值为-4.5。Amino acids suitable for use in the present invention can also be classified by their wateriness index. This index is described in, for example, Kyte, J. and Doolittle, R., 1982, "A simple method for displaying the hydropathic character of a protein" in the Journal of Molecular Biology (Jmol Biol.) "157:105-132 described. As the experienced reader will understand, the more positive the value of the wateriness index, the more hydrophobic the amino acid. Suitable amino acids for use in the present invention include amino acids having a water index value of 0 (zero) or less, such as -2 or less. Salts and derivatives of such amino acids and salts of such derivatives are suitable for use in the present invention. Arginine and its salts and derivatives and salts of such derivatives are suitable for use in the present invention. Arginine has a water index value of -4.5.
可替代地或另外,适合用于本发明中的氨基酸可通过其等电点(pl)分类;其为氨基酸上的净电荷为零的pH。在低于其等电点的pH下,氨基酸将带正电。在本发明的某些组合物中,优选的是氨基酸带正电。在此方面中,使用具有大于组合物的pH的pl的氨基酸。Alternatively or additionally, amino acids suitable for use in the invention can be classified by their isoelectric point (pi); this is the pH at which the net charge on the amino acid is zero. At a pH below its isoelectric point, an amino acid will be positively charged. In certain compositions of the invention, it is preferred that the amino acid be positively charged. In this aspect, amino acids having a pl greater than the pH of the composition are used.
适合用于本发明中的氨基酸包括pl为5或更大,如6或6.25或更大;或8或10或更大的那些。这类氨基酸的盐和衍生物和这类衍生物的盐适合用于本发明中。精氨酸及其盐和衍生物以及这类衍生物的盐适合用于本发明中。精氨酸的pl为10.76。Amino acids suitable for use in the present invention include those with a pI of 5 or greater, such as 6 or 6.25 or greater; or 8 or 10 or greater. Salts and derivatives of such amino acids and salts of such derivatives are suitable for use in the present invention. Arginine and its salts and derivatives and salts of such derivatives are suitable for use in the present invention. The pl of arginine is 10.76.
特别适合用于本发明中的氨基酸包括水性指数值为0(零)或更小,如-2或更小并且pl为6或更大,6.25或更大或8或更大或10或更大的那些。这些氨基酸的盐和衍生物和这类衍生物的盐此外特别适合用于本发明中。Amino acids particularly suitable for use in the present invention include water index values of 0 (zero) or less, such as -2 or less and a pI of 6 or greater, 6.25 or greater or 8 or greater or 10 or greater of those. Salts and derivatives of these amino acids and salts of such derivatives are moreover particularly suitable for use in the present invention.
本发明的组合物包含氯己定或氯己定盐。合适的氯己定盐的实例包括氯己定的乙酸盐、甲酸盐、葡糖酸盐、盐酸盐、异乙二磺酸盐、乳酸盐和琥珀酰胺酸盐。举例来说,合适的盐包括(但不限于)氯己定二苯磷酸盐、氯己定二葡糖酸盐、氯己定二乙酸盐、氯己定二盐酸盐、氯己定二氯化物、氯己定二氢碘酸盐、氯己定二高氯酸盐、氯己定二硝酸盐、氯己定硫酸盐、氯己定亚硫酸盐、氯己定硫代硫酸盐、氯己定二酸式磷酸盐、氯己定二氟磷酸盐、氯己定二甲酸盐、氯己定二丙酸盐、氯己定二碘代丁酸盐、氯己定二-正戊酸盐、氯己定二己酸盐、氯己定丙二酸盐、氯己定丁二酸酯盐、氯己定琥珀酰胺酸盐、氯己定苹果酸盐、氯己定酒石酸盐、氯己定二单羟乙酸盐、氯己定单二羟乙酸盐、氯己定二乳酸盐、氯己定二α-羟基异丁酸盐、氯己定二葡庚糖酸盐、氯己定二羟乙磺酸盐、氯己定二苯甲酸盐、氯己定二肉桂酸盐、氯己定二扁桃酸盐、氯己定二间苯二甲酸盐、氯己定异乙二磺酸盐、氯己定二-2-羟基-萘甲酸盐和氯己定恩波酸盐。The compositions of the present invention comprise chlorhexidine or a salt of chlorhexidine. Examples of suitable chlorhexidine salts include the acetate, formate, gluconate, hydrochloride, isoethanedisulfonate, lactate and succinamate salts of chlorhexidine. For example, suitable salts include, but are not limited to, chlorhexidine diphenylphosphate, chlorhexidine digluconate, chlorhexidine diacetate, chlorhexidine dihydrochloride, chlorhexidine dihydrochloride, Chlorhexidine, Chlorhexidine Dihydroiodide, Chlorhexidine Diperchlorate, Chlorhexidine Dinitrate, Chlorhexidine Sulfate, Chlorhexidine Sulfite, Chlorhexidine Thiosulfate, Chlorhexidine Chlorhexidine diacid phosphate, chlorhexidine difluorophosphate, chlorhexidine dicarboxylate, chlorhexidine dipropionate, chlorhexidine diiodobutyrate, chlorhexidine di-n-valeric acid Salt, Chlorhexidine Dicaproate, Chlorhexidine Malonate, Chlorhexidine Succinate, Chlorhexidine Succinamate, Chlorhexidine Malate, Chlorhexidine Tartrate, Chlorhexidine Chlorhexidine di-monoglycolate, Chlorhexidine monoglycolate, Chlorhexidine di-lactate, Chlorhexidine di-alpha-hydroxyisobutyrate, Chlorhexidine diglucoheptonate, Chlorhexidine Diisethionate, Chlorhexidine Dibenzoate, Chlorhexidine Dicinnamate, Chlorhexidine Dimandelate, Chlorhexidine Diisophthalate, Chlorhexidine Isoethanedisulfonate chlorhexidine di-2-hydroxy-naphthoate and chlorhexidine embolate.
可用于本发明的组合物的氯己定盐的具体实例为氯己定二葡糖酸盐。A specific example of a chlorhexidine salt useful in the compositions of the present invention is chlorhexidine digluconate.
用于本发明的(一种或多种)季铵抗微生物剂通常在室温和压力下为水溶性的。The quaternary ammonium antimicrobial agent(s) used in the present invention are generally water soluble at room temperature and pressure.
合适的抗微生物季铵化合物包括下文所示式(A)的化合物。Suitable antimicrobial quaternary ammonium compounds include compounds of formula (A) shown below.
其中R1和R2各自独立地为直链、未经取代的和不间断的C8-12烷基。在一个方面中,基团R1和R2含有相同数目的碳原子,但是这不是必须的,并且可使用其中R1和R2含有不同数目的碳原子的化合物。X-为卤素阴离子,如氯离子、溴离子、氟离子、碘离子或磺酸根、糖精根、碳酸根或碳酸氢根。Wherein R 1 and R 2 are each independently a linear, unsubstituted and uninterrupted C 8-12 alkyl group. In one aspect, the groups R1 and R2 contain the same number of carbon atoms, but this is not required and compounds in which R1 and R2 contain different numbers of carbon atoms can be used. X - is a halogen anion such as chloride, bromide, fluoride, iodide or sulfonate, saccharinate, carbonate or bicarbonate.
在一个方面中,X-不是膦酸盐或含磷盐,如单烷基磷酸根离子、单烯基磷酸根离子、单烷基膦酸根离子,或单烯基膦酸根离子,如具有带有8到20个碳原子的直链或分支链烷基或烯基的那些。In one aspect, X - is not a phosphonate or phosphorous salt, such as a monoalkylphosphate ion, a monoalkenylphosphate ion, a monoalkylphosphonate ion, or a monoalkenylphosphonate ion, such as with Those of straight or branched chain alkyl or alkenyl groups of 8 to 20 carbon atoms.
合适的抗微生物季铵化合物此外包括具有下文所示式(B)的苯甲烃铵化合物。Suitable antimicrobial quaternary ammonium compounds further include benzalkonium compounds having the formula (B) shown below.
其中m为8到18,并且X-为卤素阴离子,如氯离子、溴离子、氟离子、碘离子、磺酸根、糖精根、碳酸根或碳酸氢根。式(B)的化合物一般被称作苯甲烃铵化合物。提供苯扎氯铵和/或其用作C8-18烷基的混合物,具体来说直链、未经取代的并且不间断的烷基正C8H17到正C18H37,主要正C12H25(十二烷基)、正C14H29(十四基)和正C16H33(十六基)的混合物。优选地,m为8、10、12、14和/或16。最优选地,m为8到12,例如8、10和/或12或12到16,例如12、14和/或16。wherein m is 8 to 18, and X − is a halogen anion such as chloride, bromide, fluoride, iodide, sulfonate, saccharinate, carbonate or bicarbonate. Compounds of formula (B) are generally referred to as benzalkonium compounds. Provides benzalkonium chloride and/or mixtures thereof for use as C 8-18 alkyl, specifically linear, unsubstituted and uninterrupted alkyl n-C 8 H 17 to n-C 18 H 37 , mainly n- Mixture of C 12 H 25 (dodecyl), n-C 14 H 29 (tetradecyl) and n-C 16 H 33 (hexadecyl). Preferably, m is 8, 10, 12, 14 and/or 16. Most preferably, m is 8 to 12, such as 8, 10 and/or 12 or 12 to 16, such as 12, 14 and/or 16.
在式(A)的化合物中,每个基团R1和R2独立地为直链、未经取代的、不间断的C8-12烷基,例如含有8、9、10、11或12个碳原子的烷基。R1和R2可相同,例如R1和R2可均为含有8、9、10、11或12个碳原子的烷基。In the compound of formula (A), each group R 1 and R 2 is independently a linear, unsubstituted, uninterrupted C 8-12 alkyl group, for example containing 8, 9, 10, 11 or 12 an alkyl group of carbon atoms. R 1 and R 2 may be the same, eg R 1 and R 2 may both be alkyl groups containing 8, 9, 10, 11 or 12 carbon atoms.
苯甲烃铵化合物此外包括苯甲烃铵化合物的衍生物,由此下文所示烷基CmH2m+1可被另一个有机基团取代。这类有机基团包括(但不限于)烯基、苯基、酰胺、酯、醇和醚基或其组合。The benzalkonium compounds furthermore include derivatives of the benzalkonium compounds, whereby the alkyl C m H 2m+1 indicated below may be substituted by another organic group. Such organic groups include, but are not limited to, alkenyl, phenyl, amide, ester, alcohol, and ether groups or combinations thereof.
苯甲烃铵化合物的这类衍生物的实例为二异丁基苯氧基乙氧基乙基-二甲苯甲基氯化铵,其INCI名称为苄索氯铵(通常简称为BENZ)。苄索氯铵的结构在下文示出。An example of such a derivative of a benzalkonium compound is diisobutylphenoxyethoxyethyl-xylyl ammonium chloride, which has the INCI name benzethonium chloride (often abbreviated as BENZ). The structure of benzethonium chloride is shown below.
在本发明的组合物中的每种季铵化合物的阴离子可相同或不同。举例来说,式(A)化合物的阴离子可与式(B)化合物的阴离子相同或不同。在一个方面中,对于每种化合物的阴离子为氯离子。The anions of each quaternary ammonium compound in the compositions of the present invention may be the same or different. For example, the anion of the compound of formula (A) may be the same or different from the anion of the compound of formula (B). In one aspect, the anion for each compound is chloride.
在本发明的一方面中,其中组合物包含两种或更多种抗微生物季铵化合物,可存在式(A)化合物和式(B)化合物,或组合物可包含多于一种式(A)化合物或多于一种式(B)化合物。In one aspect of the invention, wherein the composition comprises two or more antimicrobial quaternary ammonium compounds, a compound of formula (A) and a compound of formula (B) may be present, or the composition may comprise more than one compound of formula (A) ) compound or more than one compound of formula (B).
式(A)的季铵化合物的实例包括二-正癸基二甲基氯化铵、辛基癸基二甲基氯化铵和二辛基二甲基氯化铵。Examples of the quaternary ammonium compound of formula (A) include di-n-decyldimethylammonium chloride, octyldecyldimethylammonium chloride, and dioctyldimethylammonium chloride.
可商购的式(A)化合物的实例包括来自索尔(Thor)的Acticide DDQ 40、来自龙沙(Lonza)的Bardac 2240、来自龙沙的Bardac 2280和来自美国梅森化学公司(MasonChemical Company,USA)的Maquat 4480E。Examples of compounds of formula (A) that are commercially available include Acticide DDQ 40 from Thor, Bardac 2240 from Lonza, Bardac 2280 from Lonza, and Bardac 2280 from Mason Chemical Company, USA. ) Maquat 4480E.
式(B)的季铵化合物的实例包括N,N-苯甲基二甲基辛基氯化铵、N,N-苯甲基二甲基癸基氯化铵、N-十二烷基-N-苯甲基-N,N-二甲基氯化铵、N-十四基-N-苯甲基-N,N-二甲基氯化铵、N-十六基-N,N-二甲基-N-苯甲基氯化铵、N,N-二甲基N-苯甲基N-十八基氯化铵及其混合物。Examples of quaternary ammonium compounds of formula (B) include N,N-benzyl dimethyl octyl ammonium chloride, N,N-benzyl dimethyl decyl ammonium chloride, N-dodecyl- N-benzyl-N,N-dimethylammonium chloride, N-tetradecyl-N-benzyl-N,N-dimethylammonium chloride, N-hexadecyl-N,N- Dimethyl-N-benzyl ammonium chloride, N,N-dimethyl N-benzyl N-octadecyl ammonium chloride and mixtures thereof.
应了解单个CAS号通常是指多于一种共混物或混合物。用于市售制备的CAS分类通常涵盖包含以在所定义范围内的量的指定化合物的共混物。具有上文引用的CAS号的组合物仅为具有可用于本发明的给定CAS号的组合物的实例。It should be understood that a single CAS number generally refers to more than one blend or mixture. CAS classifications for commercial preparations generally cover blends containing the specified compounds in amounts within defined ranges. Compositions with CAS numbers cited above are only examples of compositions with a given CAS number that can be used in the present invention.
在本发明的组合物中,抗微生物季铵化合物通常不聚合。In the compositions of the present invention, the antimicrobial quaternary ammonium compound is generally not polymerized.
可商购的式(B)的化合物的实例包括来自索尔的Acticide BAC 50M、来自龙沙的Barquat MB50/80、来自龙沙的Lonzagard苄索氯铵USP。Examples of commercially available compounds of formula (B) include Acticide BAC 50M ex Sol, Barquat MB50/80 ex Lonza, Lonzagard benzethonium chloride USP ex Lonza.
通常,用于本发明的组合物的一种或多种抗微生物季铵化合物选自由以下组成的组:二-正癸基二甲基氯化铵(DDAC(CAS号7173-51-5))、苯扎氯铵(BAC),如上文式(B)的苯扎氯铵,其中m为8。此苯扎氯铵具有CAS号68424-85-1,和苄索氯铵(BENZ)。Typically, the one or more antimicrobial quaternary ammonium compounds used in the compositions of the present invention are selected from the group consisting of: Di-n-decyldimethylammonium chloride (DDAC (CAS No. 7173-51-5)) . Benzalkonium chloride (BAC), such as benzalkonium chloride of formula (B) above, wherein m is 8. This benzalkonium chloride has CAS number 68424-85-1, and benzethonium chloride (BENZ).
存在于本发明的组合物中的组分(i)和抗微生物组分(ii)的量将根据多种因素变化,如组合物的既定用途和使用的(一种或多种)特定化合物。The amount of component (i) and antimicrobial component (ii) present in the compositions of the invention will vary depending on factors such as the intended use of the composition and the particular compound(s) employed.
举例来说,如本领域的技术人员将了解,可需要较高浓度的(i)和/或(ii)以便提供相较于提供清洁或消毒的灭菌。For example, higher concentrations of (i) and/or (ii) may be required in order to provide sterilization than to provide cleaning or disinfection, as will be appreciated by those skilled in the art.
抗微生物组分(ii)可基本上由至少一种抗微生物季铵化合物和氯己定或氯己定盐组成。The antimicrobial component (ii) may consist essentially of at least one antimicrobial quaternary ammonium compound and chlorhexidine or a chlorhexidine salt.
抗微生物组分(ii)可由至少一种抗微生物季铵化合物和氯己定或氯己定盐组成。The antimicrobial component (ii) may consist of at least one antimicrobial quaternary ammonium compound and chlorhexidine or a chlorhexidine salt.
替代抗微生物组分(ii)可基本上由两种或更多种抗微生物季铵化合物组成,而无氯己定。The alternative antimicrobial component (ii) may consist essentially of two or more antimicrobial quaternary ammonium compounds without chlorhexidine.
本发明的组合物可含有两种或更多种抗微生物季铵化合物或至少一种抗微生物季铵化合物和氯己定,或氯己定盐作为在组合物中唯一抗微生物化合物。替代地,本发明的组合物可包含其它合适的(一种或多种)抗微生物剂(b),如在美国环境保护局(UnitedStates Environmental Protection Agency)(EPA)中列表和EC杀生物剂指令的附件I和附件3描述的那些。The compositions of the present invention may contain two or more antimicrobial quaternary ammonium compounds or at least one antimicrobial quaternary ammonium compound and chlorhexidine, or a salt of chlorhexidine, as the only antimicrobial compound in the composition. Alternatively, the compositions of the present invention may comprise other suitable (one or more) antimicrobial agents (b) as listed in the United States Environmental Protection Agency (EPA) and the EC Biocides Directive Those described in Annex I and Annex 3.
通常,包括在抗微生物组分(ii)中的化合物为适合于施用到皮肤的那些。举例来说,满足人类卫生的必需法规批准的化合物,如通过欧洲委员会批准的那些化合物,当用于产品型1的产品时,如在2014年8月4日欧洲委员会授权法规(EU)第1062/2014号的附件II中列出和/或通过食品和药物投予(FDA)批准的那些。Typically, the compounds included in the antimicrobial component (ii) are those suitable for application to the skin. For example, compounds meeting the necessary regulatory approvals for human health, such as those approved by the European Commission, when used in products of product type 1, as specified in Commission Delegated Regulation (EU) No. 1062 of 4 August 2014 Those listed in Annex II of No./2014 and/or approved by Food and Drug Administration (FDA).
可包括在抗微生物组分(ii)中的合适的抗微生物剂(b)包括不为季铵化合物的抗微生物剂。优选地,一种或多种这些附加抗微生物剂在室温和压力下为水溶性的。Suitable antimicrobial agents (b) that may be included in antimicrobial component (ii) include antimicrobial agents that are not quaternary ammonium compounds. Preferably, one or more of these additional antimicrobial agents are water soluble at room temperature and pressure.
合适的附加抗微生物剂的实例包括(但不限于)聚合双胍类化合物(例如聚六亚甲基双胍类化合物(PHMB))、乳酸、银、银的盐,例如氯化银、碳酸银、柠檬酸银、二氢柠檬酸银、奥替尼啶HCl、两性化合物、碘附、酚类化合物、胺抗微生物剂和氮类杂环化合物、邻苯基酚(OPP)和硝基溴丙烷(例如溴硝丙二醇(INN)、2-溴-2-硝基丙烷-1,3-二醇)、天然衍生杀菌化合物(例如蜂蜜和蜂蜜的提取物,如包含甲基乙二醛那些)、黄酮类抗菌剂和精油。Examples of suitable additional antimicrobial agents include, but are not limited to, polymeric biguanides such as polyhexamethylene biguanide (PHMB), lactic acid, silver, silver salts such as silver chloride, silver carbonate, lemon silver acid, silver dihydrocitrate, octenidine HCl, amphoteric compounds, iodophor, phenolic compounds, amine antimicrobials and nitrogen heterocyclic compounds, o-phenylphenol (OPP) and nitrobromopropane (e.g. bronopol (INN), 2-bromo-2-nitropropane-1,3-diol), naturally derived antiseptic compounds (such as honey and honey extracts such as those containing methylglyoxal), flavonoids Antiseptics and essential oils.
在一个方面中,本发明的组合物不含如包含银的那些的无机抗微生物剂。在此方面中,任何附加抗微生物剂为有机抗微生物剂。In one aspect, the compositions of the invention are free of inorganic antimicrobial agents such as those comprising silver. In this aspect, any additional antimicrobial agent is an organic antimicrobial agent.
在一个方面中,本发明的组合物不包含PHMB或其可不含聚合双胍。举例来说,其除了氯己定之外不含有双胍。In one aspect, the composition of the invention does not comprise PHMB or it may be free of polymeric biguanides. For example, it contains no biguanides other than chlorhexidine.
在本发明的一个方面中,抗微生物组合物不包含任何异噻唑酮和/或任何硝基溴丙烷如溴硝丙二醇和/或任何次氯酸盐。In one aspect of the invention, the antimicrobial composition does not comprise any isothiazolones and/or any nitrobromopropanes such as bronopol and/or any hypochlorite.
在本发明的一个方面中,抗微生物组合物不含难溶性于水中的抗微生物化合物,如酚类化合物。In one aspect of the invention, the antimicrobial composition is free of poorly water-soluble antimicrobial compounds, such as phenolic compounds.
通常,当配制为即用组合物时,组分(i)的量可为约0.0005重量%到10重量%的组合物,例如约0.005重量%到约5重量%的组合物,如约0.01重量%到约1重量%的组合物。这些组合物可含有约0.5重量%的组合物或更少的组分(i),如0.02重量%到0.3重量%的组合物,如约0.2重量%或0.1重量%。Typically, when formulated as a ready-to-use composition, the amount of component (i) may range from about 0.0005% to 10% by weight of the composition, for example from about 0.005% to about 5% by weight of the composition, such as about 0.01% by weight to about 1% by weight of the composition. These compositions may contain about 0.5% by weight of the composition or less of component (i), such as 0.02% to 0.3% by weight of the composition, such as about 0.2% or 0.1% by weight.
通常,当配制为即用组合物时,抗微生物组分(ii)和组分(b)(如果存在)的总量(即抗微生物季铵化合物和氯己定或其盐和任何附加抗微生物组分(b)的组合量),可为约0.001重量%到约10重量%的组合物,例如约0.005重量%到约5重量%的组合物,如约0.01重量%到约1重量%的组合物。Typically, when formulated as a ready-to-use composition, the total amount of antimicrobial component (ii) and component (b) (if present) (i.e. antimicrobial quaternary ammonium compound and chlorhexidine or its salt and any additional antimicrobial The combined amount of component (b)) may be from about 0.001% to about 10% by weight of the composition, such as from about 0.005% to about 5% by weight of the composition, such as from about 0.01% to about 1% by weight of the combination thing.
当本发明的组合物配制适用作手部消毒剂时,抗微生物组分(ii)的量可为0.05重量%到约0.5重量%。When the composition of the present invention is formulated for use as a hand sanitizer, the amount of antimicrobial component (ii) may range from 0.05% to about 0.5% by weight.
抗微生物组分(ii)可包含等量的季铵化合物和氯己定或其盐。举例来说,如果抗微生物组分的总量为约0.2重量%的组合物,那么季铵化合物的量将为约0.1%,并且氯己定或其盐的量将为约0.1%。The antimicrobial component (ii) may comprise equal amounts of a quaternary ammonium compound and chlorhexidine or a salt thereof. For example, if the total amount of antimicrobial component is about 0.2% by weight of the composition, then the amount of quaternary ammonium compound will be about 0.1%, and the amount of chlorhexidine or a salt thereof will be about 0.1%.
替代地,抗微生物组分可包含不同量的季铵化合物和氯己定。Alternatively, the antimicrobial component may contain varying amounts of quaternary ammonium compounds and chlorhexidine.
通常,在本发明的组合物中,组分(i)与抗微生物组分(ii)的比率在10:1到1:10的范围内。Typically, in the compositions of the invention, the ratio of component (i) to antimicrobial component (ii) is in the range of 10:1 to 1:10.
本发明的组合物包含极性溶剂(iii)。合适的极性溶剂包括(但不限于)水、醇、二醇醚及其混合物。The composition of the invention comprises a polar solvent (iii). Suitable polar solvents include, but are not limited to, water, alcohols, glycol ethers, and mixtures thereof.
合适的醇包括(但不限于)直链或分支链C1到C5醇,如甲醇、乙醇、正丙醇、异丙醇、丙醇异构体的混合物、正丁醇、仲丁醇、叔丁醇、异丁醇、丁醇异构体的混合物、2-甲基-1-丁醇、正戊醇、戊醇(pentanol)异构体的混合物和戊醇(amyl alcohol)(异构体的混合物)及其混合物。Suitable alcohols include, but are not limited to, straight chain or branched C1 to C5 alcohols such as methanol, ethanol, n-propanol, isopropanol, mixtures of propanol isomers, n-butanol, sec-butanol, tert-butanol, isobutanol, mixtures of butanol isomers, 2-methyl-1-butanol, n-pentanol, mixtures of pentanol isomers and amyl alcohol (amyl alcohol) body mixtures) and mixtures thereof.
用于本发明的组合物的优选的极性溶剂包括(但不限于)水、乙醇、异戊二醇、单丙二醇、己二醇、3-甲氧基-3-甲基-1-丁醇(MMB)、正丙醇、异丙醇、乙二醇醚、丙二醇醚、丁基二甘醇(BDG)及其混合物。在一个方面中,组合物包含水或水和选自上文所述醇的一种或多种醇的混合物。在这类混合物中,水优选地为主要组分。极性溶剂可基本上由水组成或由水组成。Preferred polar solvents for use in compositions of the present invention include, but are not limited to, water, ethanol, isopentyl glycol, monopropylene glycol, hexylene glycol, 3-methoxy-3-methyl-1-butanol (MMB), n-propanol, isopropanol, glycol ethers, propylene glycol ethers, butyldiglycol (BDG) and mixtures thereof. In one aspect, the composition comprises water or a mixture of water and one or more alcohols selected from the alcohols mentioned above. In such mixtures, water is preferably the main component. The polar solvent can consist essentially of or consist of water.
如果本发明的组合物包含醇,那么醇通常以低于提供抗微生物作用的醇必需的量的量存在,但是在被认为改善组合物在皮肤上的干燥的水平下。举例来说,本发明的组合物可包含高达约30重量%的醇,如在20重量%和30重量%之间的醇或小于约20重量%的醇,如约15重量%到约20重量%的醇。If the composition of the invention includes alcohol, the alcohol is generally present in an amount lower than that necessary to provide an antimicrobial effect, but at a level believed to improve dryness of the composition on the skin. For example, the compositions of the present invention may comprise up to about 30% by weight alcohol, such as between 20% and 30% by weight alcohol or less than about 20% by weight alcohol, such as from about 15% to about 20% by weight alcohol.
应了解,醇的百分比可取决于组合物的用途。举例来说,当在拭纸上使用时,本发明的组合物可包含高达20%的醇。It will be appreciated that the percentage of alcohol may depend on the use of the composition. For example, when used on wipes, the compositions of the present invention may contain up to 20% alcohol.
在一个方面中,本发明的组合物大体上不含醇。举例来说,组合物可含有1重量%或更少的醇。举例来说,组合物可含有少于1重量%或少于0.5重量%或0.1重量%或更少的醇,如异丙醇。作为一个实例,本发明的组合物可不包含异丙醇或可不包含醇。In one aspect, the compositions of the invention are substantially free of alcohol. For example, the composition may contain 1% by weight or less alcohol. For example, the composition may contain less than 1% by weight, or less than 0.5% by weight, or 0.1% by weight or less of an alcohol, such as isopropanol. As an example, compositions of the present invention may contain no isopropanol or may contain no alcohol.
在另一个方面中,本发明的组合物可包含高达70重量%,例如高达约50重量%的水平的醇。In another aspect, the composition of the invention may comprise alcohol at a level of up to 70% by weight, for example up to about 50% by weight.
组合物可包含水或水和选自上文所述醇的一种或多种醇的混合物。在这类混合物中,水优选地为主要组分。The composition may comprise water or a mixture of water and one or more alcohols selected from the alcohols mentioned above. In such mixtures, water is preferably the main component.
举例来说,极性溶剂可由水组成或基本上由水组成。作为另一个实例,极性溶剂可为水并且为约0重量%到约20重量%,如约15重量%到约20重量%的醇,例如乙醇或异丙醇。For example, a polar solvent can consist or consist essentially of water. As another example, the polar solvent can be water and from about 0% to about 20%, such as from about 15% to about 20%, by weight of an alcohol, such as ethanol or isopropanol.
本发明的组合物可以浓缩形式提供用于在使用之前稀释或以即用形式提供。优选的是,本发明的组合物以即用形式提供,并且除非另行说明,否则在本文档中提供的关于量的信息(如重量%或ppm)涉及即用组合物。The compositions of the invention may be provided in concentrated form for dilution prior to use or in ready-to-use form. Preferably, the compositions of the invention are provided in ready-to-use form and, unless otherwise stated, information provided in this document regarding amounts (eg % by weight or ppm) relate to ready-to-use compositions.
通常提供浓缩物,使得当稀释时,浓缩物为5重量%到30重量%例如10重量%或20重量%的所得稀释产品。Typically the concentrate is provided such that when diluted the concentrate is 5% to 30% by weight, eg 10% or 20% by weight of the resulting diluted product.
通常,但不是基本上,本发明的组合物具有约0.0005重量%到约10重量%,如约0.005重量%到约5重量%,或0.01重量%到1.0重量%的氨基酸组分(i)的浓度和约0.001重量%到约10重量%,如约0.005重量%到约5.0重量%,或0.01重量%到1重量%的抗微生物组分(ii)的浓度。这些组合物可含有约0.5重量%的组合物或更少的组分(i),如0.02重量%到0.3重量%的组合物,如约0.2重量%或0.1重量%。Typically, but not substantially, the compositions of the present invention have a concentration of amino acid component (i) of from about 0.0005% to about 10% by weight, such as from about 0.005% to about 5% by weight, or from 0.01% to 1.0% by weight and a concentration of the antimicrobial component (ii) of about 0.001% to about 10% by weight, such as about 0.005% to about 5.0% by weight, or 0.01% to 1% by weight. These compositions may contain about 0.5% by weight of the composition or less of component (i), such as 0.02% to 0.3% by weight of the composition, such as about 0.2% or 0.1% by weight.
使用的组合物和配制物的pH可在宽范围内变化,例如约pH 2到约pH 12,更优选地约pH 3到约pH 10或约pH 4.5到8。用于本发明的配制物的pH可类似于旨在用于相同目的或类似目的的已知配制物的pH。举例来说,旨在与皮肤接触的配制物如个人护理或第一辅助配制物将通常具有将不刺激皮肤的pH,例如约pH 3到约pH 8,如约pH 4.5到约pH 7.5或约pH 5到约pH 6。The pH of the compositions and formulations used may vary within wide ranges, for example from about pH 2 to about pH 12, more preferably from about pH 3 to about pH 10 or from about pH 4.5 to 8. The pH of the formulations used in the present invention may be similar to the pH of known formulations intended for the same purpose or a similar purpose. For example, formulations intended to come into contact with the skin, such as personal care or primary adjunct formulations, will generally have a pH that will not irritate the skin, for example about pH 3 to about pH 8, such as about pH 4.5 to about pH 7.5 or about pH 5 to about pH 6.
当用作手部消毒剂时,本发明的组合物的pH通常为约5到约6。When used as a hand sanitizer, the compositions of the present invention generally have a pH of from about 5 to about 6.
应了解,本发明的组合物可包含在本领域中常用的其它成分。使用的任何其它成分的性质将取决于组合物的性质和预期目的。本领域的普通技术人员将知道哪些附加成分适合在用于不同应用的组合物中使用。It will be appreciated that the compositions of the present invention may contain other ingredients commonly used in the art. The nature of any other ingredients employed will depend on the nature and intended purpose of the composition. Those of ordinary skill in the art will know which additional ingredients are suitable for use in compositions for different applications.
本发明的组合物可包含附加材料,如表面活性剂、络合剂、缓冲剂、增稠剂、皮肤护理化合物、极性溶剂和芳香剂。The compositions of the present invention may contain additional materials such as surfactants, complexing agents, buffers, thickeners, skin care compounds, polar solvents and fragrances.
选择表面活性剂将取决于组合物的性质和预期目的。旨在用于不同目的的用于配制物的合适的表面活性剂将在本领域的普通技术人员的知识内。同样地,选择合适的量的表面活性剂将在本领域的普通技术人员的知识内。合适的表面活性剂可选自非离子、阳离子或两性及其混合物。The choice of surfactant will depend on the nature and intended purpose of the composition. Suitable surfactants for formulations intended for different purposes will be within the knowledge of a person of ordinary skill in the art. Likewise, selection of an appropriate amount of surfactant will be within the knowledge of one of ordinary skill in the art. Suitable surfactants may be selected from nonionic, cationic or amphoteric and mixtures thereof.
本发明的一些组合物可包含非离子表面活性剂。合适的非离子表面活性剂包括(但不限于)胺氧化物、烷基多糖苷、线性和分支1°和2°醇乙氧基化物和乙氧基化/丙氧基化(EOPO)嵌段聚合物。Some compositions of the present invention may contain nonionic surfactants. Suitable nonionic surfactants include, but are not limited to, amine oxides, alkyl polyglycosides, linear and branched 1° and 2° alcohol ethoxylates and ethoxylated/propoxylated (EOPO) blocks polymer.
在一个方面中,组合物大体上不含或不含阴离子表面活性剂。在另一个方面中,本发明的组合物不包含两性表面活性剂。In one aspect, the composition is substantially free or free of anionic surfactants. In another aspect, the compositions of the invention do not contain amphoteric surfactants.
本发明的一些组合物可包含两性表面活性剂。合适的两性表面活性剂包括但不限于C6到C20烷基两性乙酸盐或两性二乙酸盐(如椰油两性乙酸盐)、C10到C18烷基二甲基甜菜碱、C10到C18烷基酰氨基丙基二甲基甜菜碱。实例包括但不限于椰子两性表面活性剂椰油酰胺丙基甜菜碱(CAPB)(Surfac B4、CAS 61789-40-9)、椰油基咪唑啉甜菜碱、油酰胺基丙基甜菜碱和松油咪唑啉。Some compositions of the present invention may contain amphoteric surfactants. Suitable amphoteric surfactants include, but are not limited to, C6 to C20 alkyl amphoacetates or amphodiacetates (such as cocoamphoacetates), C10 to C18 alkyl dimethyl betaines, C 10 to C 18 alkyl amidopropyl dimethyl betaine. Examples include, but are not limited to, the coconut amphoteric surfactant cocamidopropyl betaine (CAPB) (Surfac B4, CAS 61789-40-9), cocoimidazoline betaine, oleamidopropyl betaine, and pine oil imidazoline.
本发明的一些组合物可包含阳离子表面活性剂。合适的阳离子表面活性剂包括但不限于十一烷基烯酰胺基丙基三甲铵甲硫酸盐和西曲氯铵。Some compositions of the present invention may contain cationic surfactants. Suitable cationic surfactants include, but are not limited to, undecylenamidopropyltrimethylammonium methosulfate and cetrimonium chloride.
通常,存在于本发明的组合物中的表面活性剂的量为约0.01重量%到20重量%的量。表面活性剂的量取决于多种因素,如组合物的pH和组合物的既定用途。Typically, surfactants are present in the compositions of the present invention in amounts ranging from about 0.01% to 20% by weight. The amount of surfactant will depend on factors such as the pH of the composition and the intended use of the composition.
本发明的组合物可包含络合剂。术语螯合剂或螯合物有时与术语络合剂互换使用。出于描述本发明的目的,术语络合剂包括螯合剂和螯合物两者。甚至当本发明的组合物与硬水一起使用时,络合剂可用于帮助提供透明组合物。合适的络合剂的实例包括但不限于乙二胺四乙酸(EDTA)、葡糖酸盐、谷氨酸二乙酸(GLDA)-商品名Dissolvine GL、乙二胺-N,N'-二丁二酸(EDDS)、柠檬酸盐和葡糖酸盐或戊二酸、己二酸和丁二酸的盐及其混合物。如果络合剂含有抗衡离子,那么抗衡离子优选地为金属。合适的金属抗衡离子包括但不限于Na、Ca、Fe、K、Zn、Mg和Mn。The compositions of the present invention may contain complexing agents. The term chelating agent or chelate is sometimes used interchangeably with the term complexing agent. For purposes of describing the present invention, the term complexing agent includes both chelating agents and chelates. Complexing agents can be used to help provide clear compositions even when the compositions of the present invention are used with hard water. Examples of suitable complexing agents include, but are not limited to, ethylenediaminetetraacetic acid (EDTA), gluconate, glutamic acid diacetic acid (GLDA) - trade name Dissolvine GL, ethylenediamine-N,N'-dibutyl Salts of diacids (EDDS), citrates and gluconates or glutaric, adipic and succinic acids and mixtures thereof. If the complexing agent contains a counterion, the counterion is preferably a metal. Suitable metal counterions include, but are not limited to, Na, Ca, Fe, K, Zn, Mg, and Mn.
优选的络合剂为GLDA(Dissolvine)和EDTA。Preferred complexing agents are GLDA (Dissolvine) and EDTA.
络合剂通常存在量为约100到10,000ppm,优选地约400到3,000ppm,例如约500到2000ppm。Complexing agents are typically present in an amount of about 100 to 10,000 ppm, preferably about 400 to 3,000 ppm, for example about 500 to 2000 ppm.
可包括缓冲剂以将组合物的pH调节到必需值并且将其维持在贮存和使用期间的pH值下或接近所述pH值。Buffering agents can be included to adjust the pH of the composition to the necessary value and maintain it at or near the pH during storage and use.
合适的pH改性剂包括但不限于酸,如柠檬酸、氨基磺酸、盐酸、磷酸、硝酸、乳酸、甲酸、乙酸乙醇酸或葡萄糖酸,或其它矿物或有机酸或碱,如氢氧化钠或氢氧化钾、三乙醇胺和碳酸酯及其混合物。Suitable pH modifiers include, but are not limited to, acids such as citric acid, sulfamic acid, hydrochloric acid, phosphoric acid, nitric acid, lactic acid, formic acid, acetic acid glycolic acid, or gluconic acid, or other mineral or organic acids or bases, such as sodium hydroxide Or potassium hydroxide, triethanolamine and carbonates and mixtures thereof.
可包括增稠剂以将组合物的粘度调节到用于这类目的的必需值,以便使组合物更稳定;促进组合物的施用;或用于美学益处。增稠剂的实例包括但不限于由大同化学公司(Daido chemical corporation)以商品名Sangelose 90供应市售的羟基丙基甲基纤维素硬脂氧基醚,和由里欧实验室(Rheo Lab)以商品名Kleasol 200ST供应的聚季铵盐37。Thickeners may be included to adjust the viscosity of the composition to the value necessary for such purposes, to make the composition more stable; to facilitate application of the composition; or for aesthetic benefit. Examples of thickeners include, but are not limited to, hydroxypropyl methylcellulose stearyl ether commercially available under the trade name Sangelose 90 from Daido chemical corporation, and hydroxypropyl methylcellulose stearyl ether from Rheo Lab. Polyquaternium 37 available under the tradename Kleasol 200ST.
本发明的组合物可含有皮肤护理化合物。合适的皮肤护理化合物包括(但不限于)泛醇、生育酚、乙酸盐、丙三醇、聚季铵盐化合物、PEG-7-甘油基椰油酸盐和硅氧烷及其混合物。通常,本发明的组合物不包含粘多糖。Compositions of the present invention may contain skin care compounds. Suitable skin care compounds include, but are not limited to, panthenol, tocopherol, acetates, glycerol, polyquaternium compounds, PEG-7-glyceryl cocoate, and silicones and mixtures thereof. Typically, the compositions of the invention do not contain mucopolysaccharides.
本发明的组合物可可替代地或另外含有盐,如碱金属或碱土金属的卤化物,例如NaCl或KCl。在一些情况下,使用盐可促进形成稳定组合物。The compositions of the invention may alternatively or additionally contain salts, such as halides of alkali or alkaline earth metals, eg NaCl or KCl. In some cases, the use of salts can facilitate the formation of stable compositions.
本发明的组合物还可含有在本领域中为标准的其它成分,如着色剂、芳香剂、润肤剂、抗氧化剂及其混合物。The compositions of the present invention may also contain other ingredients that are standard in the art, such as colorants, fragrances, emollients, antioxidants, and mixtures thereof.
本发明的组合物可不含阴离子材料。在阴离子材料的含义内不包括可用于存在于用于本发明的成分中的任一种的抗衡离子,如与季铵化合物相关联的抗衡离子。本发明的组合物可例如不含阴离子聚电解质,如高分子量阴离子类粘液聚合物、聚苯乙烯磺酸聚合物和阳离子交换树脂。The compositions of the present invention may be free of anionic materials. Counterions that may be present in any of the ingredients used in the present invention, such as those associated with quaternary ammonium compounds, are not included within the meaning of anionic materials. The compositions of the invention may, for example, be free of anionic polyelectrolytes, such as high molecular weight anionic mucoid polymers, polystyrene sulfonic acid polymers and cation exchange resins.
已发现,在使用时本发明的组合物具有有利的抗微生物效果,并且具体来说当施用到皮肤的表面时。举例来说,当初始施用到表面时,这类组合物具有抗微生物作用(所谓的“湿杀灭”),并且其还可具有在其控制内的残余抗微生物作用,减少或防止在表面处形成新型微生物菌落(所谓的“干杀灭”),这可另外导致形成更持久的生物膜。It has been found that the compositions of the present invention have an advantageous antimicrobial effect when in use, and in particular when applied to the surface of the skin. For example, such compositions have an antimicrobial effect when initially applied to a surface (so-called "wet kill"), and they may also have a residual antimicrobial effect within their control, reducing or preventing Formation of new microbial colonies (so-called "dry kill") can additionally lead to the formation of more persistent biofilms.
本发明的组合物此外抗用水洗涤和擦拭。这意指甚至当已处理的表面随后用水擦拭和/或洗涤或冲洗时,本发明的组合物提供残余抗微生物作用。The compositions of the invention are moreover resistant to washing and wiping with water. This means that the composition of the invention provides a residual antimicrobial effect even when the treated surface is subsequently wiped and/or washed or rinsed with water.
本发明的组合物具体来说适用作皮肤或手部消毒剂或在其它表面上。一些组合物适合用于其它表面上。本发明的组合物通常提供残余抗微生物效果。The compositions of the invention are particularly suitable for use as skin or hand sanitizers or on other surfaces. Some compositions are suitable for use on other surfaces. Compositions of the invention generally provide residual antimicrobial effect.
这类组合物可在广泛多种形式中和出于皮肤消毒的目的应用中使用。举例来说,本发明的组合物具体来说适合于配制成待用于身体或皮肤消毒的到摩丝、凝胶、乳霜、乳液、液体、喷雾和拭纸,如手部消毒剂。Such compositions can be used in a wide variety of forms and applications for the purpose of skin antiseptics. For example, the compositions of the present invention are particularly suitable for formulation into mousses, gels, creams, lotions, liquids, sprays and wipes to be used for body or skin disinfection, such as hand sanitizers.
当以拭纸形式使用时,用于制备拭纸的基材可由任何合适的织造或非织造材料制成。合适的拭纸材料包括(但不限于)非织造纤维片材材料和由来自天然来源的纤维(如木浆)和人造丝或其它纤维素基材料、真丝纤维和角蛋白纤维制成的那些。材料包含1重量%到100重量%的纤维素材料。举例来说,可使用100%纤维素材料,如人造丝或木浆。其它优选的材料包括纤维素和非纤维素材料的共混物,如人造丝与合成基材(如聚酯或聚丙烯)的共混物。共混材料可包含1重量%到99.9重量%纤维素材料,如人造丝,例如20重量%到80重量%或30重量%到70重量%的纤维素材料,如人造丝。When used in the form of a wipe, the substrate used to make the wipe may be made from any suitable woven or nonwoven material. Suitable wipe materials include, but are not limited to, nonwoven fibrous sheet materials and those made from fibers from natural sources such as wood pulp, and rayon or other cellulose-based materials, silk fibers, and keratin fibers. The material comprises from 1% to 100% by weight cellulosic material. For example, 100% cellulosic materials such as rayon or wood pulp may be used. Other preferred materials include blends of cellulosic and non-cellulosic materials, such as blends of rayon and synthetic substrates such as polyester or polypropylene. The blend material may comprise from 1% to 99.9% by weight of a cellulosic material, such as rayon, eg, from 20% to 80% or from 30% to 70% by weight of a cellulosic material, such as rayon.
出于治疗和非治疗目的,本发明的组合物可用于人类和动物。用于非治疗用途的产品的实例包括个人护理和个人卫生产品。出于治疗目的的产品的实例包括第一辅助和皮肤护理产品。The compositions of the invention can be used in humans and animals for both therapeutic and non-therapeutic purposes. Examples of products for non-therapeutic use include personal care and personal hygiene products. Examples of products for therapeutic purposes include first aids and skin care products.
本发明的组合物还可呈液体的形式并且封装到合适的分配器中以在使用时提供泡沫、摩丝或喷雾。本发明的组合物可用于足部卫生产品,包括直接在足部上使用的那些和用于鞋类(具体来说运动鞋类)的处理/脱臭的那些。本发明的组合物还可用在用于直接施用在皮肤或毛发上的其它个人护理产品中,例如肥皂、淋浴产品、毛发护理产品,包括洗发剂和抗头皮屑洗发剂、护发素毛发定型产品,如头发摩丝、凝胶和喷雾,护肤产品,如剃须产品、化妆品和用于毛发去除的产品、除臭剂和止汗剂产品、婴儿产品,包括婴儿清洁和洁净产品,如婴儿浴液、肥皂、拭纸、保湿剂、尿布疹乳膏、用于清洁具有常规和高发生率的婴儿和幼儿接触的表面的产品。The compositions of the invention may also be in liquid form and packaged in suitable dispensers to provide a foam, mousse or spray at the time of use. The compositions of the present invention are useful in foot hygiene products, including those used directly on the feet and those used in the treatment/deodorization of footwear, in particular athletic footwear. The compositions of the present invention can also be used in other personal care products for direct application to the skin or hair, such as soaps, shower products, hair care products including shampoos and anti-dandruff shampoos, conditioners hair Styling products such as hair mousses, gels and sprays, skin care products such as shaving products, make-up and products for hair removal, deodorant and antiperspirant products, baby products including baby cleansing and cleansing products such as Baby washes, soaps, wipes, moisturizers, diaper rash creams, products for cleaning surfaces that babies and young children touch with routine and high incidence.
出于清除或抑制可另外对动物的健康、幸福或清洁度具有不利影响的微生物的目的,本发明的组合物可用作在用于直接施用到动物或其皮毛或毛皮的皮肤表面的宠物产品中的卫生清洁剂。这类组合物还可施用到如与动物接触的表面的材料和可从动物转移的微生物。这类应用的益处此外消除或抑制这类微生物,其另外可转移到另一个动物或人,并且还控制或去除这类生物可生成的副产物,如恶臭。这类宠物应用可包括但不限于染色和臭味去除喷雾、杀菌剂喷雾和拭纸、户外箱清洁剂、罩笼清洁剂、抗菌猫砂喷雾和拭纸、狗洗发剂和喷雾(spritzers)和狗耳清洁拭纸。The compositions of the present invention are useful as pet products for direct application to the skin surface of an animal or its coat or fur for the purpose of removing or inhibiting microorganisms that could otherwise have an adverse effect on the health, well-being or cleanliness of the animal sanitation cleaners. Such compositions can also be applied to materials such as surfaces that come into contact with animals and microorganisms that can be transferred from animals. The benefits of such applications are in addition to eliminating or inhibiting such microorganisms, which could otherwise be transferred to another animal or human, and also controlling or removing by-products, such as malodor, that such organisms may generate. Such pet applications may include, but are not limited to, stain and odor removal sprays, germicide sprays and wipes, outdoor box cleaners, cage cleaners, antibacterial cat litter sprays and wipes, dog shampoos and spritzers and dog ear cleaning wipes.
本发明的组合物可用于第一辅助局部施用到皮肤以给在皮肤的表面上的擦伤或伤口消毒以防止或阻止感染,或防止轻微感染,如运动员的足部、疣、瘊子、斑点/痤疮预防/处理产品。因此,本发明提供用于这些用途,如伤口护理的产品或包含本发明的组合物的第一辅助产品。The compositions of the present invention may be used as a first adjunct to topical application to the skin to disinfect abrasions or wounds on the surface of the skin to prevent or arrest infection, or to prevent minor infections such as athlete's foot, warts, warts, spots /Acne Prevention/Treatment Products. Accordingly, the present invention provides a product for such uses, such as wound care or a first adjunct product comprising a composition of the invention.
本发明的组合物还可用于医学应用,如导管、透析和其它医学设备的灭菌;抑制或清除病毒,例如诺如病毒、脊髓灰质炎病毒或腺病毒;和预防或消除持久的生物膜。The compositions of the invention are also useful in medical applications such as the sterilization of catheters, dialysis and other medical equipment; inhibition or elimination of viruses such as norovirus, poliovirus or adenovirus; and prevention or elimination of persistent biofilms.
本发明的组合物还可在除皮肤之外的表面上使用。本发明的施用到除皮肤之外的表面的实例包括但不限于:表面清洁剂,如旨在用于在盥洗室、厨房、生活区域中使用的那些;硬地板清洁剂;地毯清洁剂;家具清洁剂;玻璃/镜子清洁剂;厕所护理产品,包括固体厕所清洁剂,如轮缘装置和被设计成放置于水箱中的那些;液体厕所清洁剂,不包括包含次氯酸盐漂白剂的那些;餐具清洗产品,如洗涤液体和由餐具清洗机器制备,如餐具清洗固体(呈粉末或片剂形式)和液体;洗衣产品,如固体去垢剂(呈粉末或片剂形式);液体去垢剂;织物调节剂和包含去垢剂和织物调节剂的“2合1”产品;旨在用于在室外使用的清洁产品,如用于清洁木材、石头、混凝土或塑料的那些,例如院子清洁剂、花园家具清洁剂/处理剂、BBQ清洁剂、墙面和围栏清洁剂/处理剂;植物喷雾如旨在去除昆虫如来自植物的蚜虫的那些;食品喷雾,如适合用于食品防腐中的那些。The compositions of the present invention may also be used on surfaces other than the skin. Examples of application of the present invention to surfaces other than skin include, but are not limited to: surface cleaners, such as those intended for use in bathrooms, kitchens, living areas; hard floor cleaners; carpet cleaners; furniture Cleaners; glass/mirror cleaners; toilet care products, including solid toilet cleaners, such as rim units and those designed to be placed in tanks; liquid toilet cleaners, excluding those containing hypochlorite bleach ; dishwashing products, such as washing liquids and prepared by dishwashing machines, such as dishwashing solids (in powder or tablet form) and liquids; laundry products, such as solid detergents (in powder or tablet form); liquid detergents detergents; fabric conditioners and "2-in-1" products containing detergent and fabric conditioner; cleaning products intended for use outside, such as those used to clean wood, stone, concrete or plastic, such as yard cleaning cleaners/treatments for garden furniture, BBQ cleaners, wall and fence cleaners/treatments; plant sprays such as those intended to remove insects such as aphids from plants; food sprays such as those suitable for use in food preservation Those ones.
为了避免怀疑,在本说明书中当使用术语“包含(comprising或comprises)”时意指描述的组合物或配制物或组分必须含有列出的一种或多种成分,但是可任选地含有附加成分。当使用术语“基本上由……组成(consisting essentially of或consistsessentially of)”时意指描述的组合物或配制物或组分必须含有列出的一种或多种成分并且还可含有少量(例如高达5重量%,或高达1重量%或0.1重量%)的其它成分,其条件是任何附加成分不影响组合物、配制物或组分的基本特性。当使用术语“由……组成”时意指描述的组合物或配制物或组分必须仅含有列出的一种或多种成分。这些术语可以类似方式应用到工艺、方法和用途。For the avoidance of doubt, in this specification when the term "comprising or comprises" is used, it is meant that the described composition or formulation or component must contain one or more of the listed ingredients, but may optionally contain Additional ingredients. When the term "consisting essentially of or consists essentially of" is used, it is meant that the composition or formulation or component being described must contain one or more of the listed ingredients and may also contain minor amounts such as up to 5% by weight, or up to 1% or 0.1% by weight) of other ingredients, provided that any additional ingredients do not affect the essential properties of the composition, formulation or component. When the term "consisting" is used it is meant that the composition or formulation or component being described must contain only one or more of the listed ingredients. These terms apply in a similar manner to processes, methods and uses.
“大体上不含”意指描述的组合物或配制物或组分含有少于3重量%,优选地少于1重量%,更优选地0.1重量%或更少的陈述成分。举例来说,大体上不含醇的本发明的组合物含有少于3重量%的醇,优选地少于1重量%的醇,更优选地0.1%或更少的醇。"Substantially free" means that the described composition or formulation or component contains less than 3% by weight, preferably less than 1% by weight, more preferably 0.1% by weight or less of the stated ingredient. For example, substantially alcohol-free compositions of the invention contain less than 3% by weight alcohol, preferably less than 1% by weight alcohol, more preferably 0.1% or less alcohol.
术语“抗微生物”意指杀灭和/或抑制微生物(microbes,microorganisms)生长的化合物或组合物。术语“杀微生物”用于是指杀灭微生物的化合物或组合物。本发明的组合物为抗微生物和/或杀微生物的。The term "antimicrobial" means a compound or composition that kills and/or inhibits the growth of microorganisms (microbes, microorganisms). The term "microbicide" is used to refer to a compound or composition that kills microorganisms. The compositions of the invention are antimicrobial and/or microbicidal.
术语“消毒”或“消毒剂”意指降低在表面上的微生物的总数。The term "disinfectant" or "disinfectant" means to reduce the population of microorganisms on a surface.
术语“灭菌”意指消除微生物的生物以实现无菌(灭菌的微生物环境)。The term "sterilize" means to eliminate the organisms of microorganisms to achieve sterility (sterilized microbial environment).
微生物(microbes或microorganisms)为微小的(太小以至于人类眼睛看不到)的生物。微生物的实例包括细菌、真菌、酵母菌、霉菌、分枝杆菌、藻类孢子、古细菌和原生生物。微生物一般为单细胞(singlecelled或unicellular)生物。然而,如本文所用,术语“微生物”还包括病毒。Microbes or microorganisms are tiny (too small to be seen by the human eye) living things. Examples of microorganisms include bacteria, fungi, yeasts, molds, mycobacteria, algal spores, archaea, and protists. Microorganisms are generally single-celled or unicellular organisms. However, as used herein, the term "microorganism" also includes viruses.
本发明的组合物可抗细菌、抗真菌、抗藻类、抗孢子、抗病毒抗酵母菌和/或抗霉菌。The compositions of the present invention are antibacterial, antifungal, antialgal, antispore, antiviral, antiyeast and/or antimold.
本发明的组合物具体来说适合用于抵抗细菌,如大肠杆菌。The compositions of the invention are particularly suitable for use against bacteria, such as E. coli.
如本文所用,术语抗细菌、抗真菌、抗藻类、抗病毒、抗酵母菌和抗霉菌试剂旨在是指抑制相应的微生物的生长但是不必杀灭微生物的试剂和杀灭相应的微生物的试剂。因此,例如在术语抗细菌内包括抑制细菌的生长但是可不必杀灭细菌的试剂和确实杀灭细菌的杀细菌试剂。As used herein, the terms antibacterial, antifungal, antialgal, antiviral, antiyeast and antimycotic agents are intended to mean agents that inhibit the growth of, but not necessarily kill, the corresponding microorganisms, and agents that kill the corresponding microorganisms. Thus, for example, agents that inhibit the growth of bacteria, but may not necessarily kill bacteria, and bactericidal agents that do kill bacteria are included within the term antibacterial.
抗细菌剂的实例包括myobactericides和杀结核菌剂(tuberculocides)。优选地,本发明的组合物包含选自抗细菌、抗真菌、抗藻类、抗孢子、抗病毒、抗酵母菌和抗霉菌试剂及其混合物中的至少一种试剂。更优选地,本发明的组合物包含至少一种抗细菌、抗病毒、抗真菌和/或抗霉菌试剂。Examples of antibacterial agents include myobactericides and tuberculocides. Preferably, the composition of the present invention comprises at least one agent selected from the group consisting of antibacterial, antifungal, antialgal, antispore, antiviral, antiyeast and antimycotic agents and mixtures thereof. More preferably, the composition of the invention comprises at least one antibacterial, antiviral, antifungal and/or antimycotic agent.
本发明的组合物可有效抵抗各种生物,包括革兰氏阴性和革兰氏阳性细菌、真菌、酵母菌、病毒和形成细菌的一些孢子The compositions of the present invention are effective against a variety of organisms, including Gram-negative and Gram-positive bacteria, fungi, yeasts, viruses and some spore-forming bacteria
本发明的优点在于有可能防止广泛范围的微生物粘附和附接到表面,并且因此,防止形成生物膜。此外大体上防止大量菌落形成。因此,大体上减小或甚至防止菌落生长的能力。本发明因此一般在微生物的控制中。An advantage of the present invention is that it is possible to prevent a wide range of microorganisms from adhering and attaching to surfaces, and thus, preventing the formation of biofilms. Furthermore, massive colony formation is substantially prevented. Thus, the ability to grow colonies is substantially reduced or even prevented. The present invention is thus generally in the control of microorganisms.
在本发明的一方面中,组合物可用于降低或控制生物膜的形成。In one aspect of the invention, the compositions are useful for reducing or controlling biofilm formation.
如先前所描述,本发明的组合物有利地提供残余抗微生物作用,由此在组合物的初始施用之后抗微生物作用继续相当长时间段。As previously described, the compositions of the present invention advantageously provide a residual antimicrobial effect whereby the antimicrobial effect continues for a substantial period of time after the initial application of the composition.
通常,本发明的组合物不需要含有对哺乳动物高度有毒的材料。用于抗微生物组合物的抗微生物剂通常为众所周知并且广泛了解和测试的抗微生物剂。已知抗微生物剂的功效在本发明的配制物中放大。因此,具有低毒性的抗微生物剂可用于抗微生物组合物中。相比之下,用于已知消毒技术的许多“新型”抗微生物剂使用“更强”、更有毒和/或极少测试的材料。In general, the compositions of the present invention need not contain materials that are highly toxic to mammals. Antimicrobial agents used in antimicrobial compositions are generally well known and widely understood and tested antimicrobial agents. The efficacy of known antimicrobial agents is amplified in the formulations of the present invention. Therefore, antimicrobial agents with low toxicity can be used in antimicrobial compositions. In contrast, many "new" antimicrobials for known disinfection technologies use "stronger", more toxic and/or minimally tested materials.
本发明的抗微生物组合物不含有生成高度持久的残基或冲洗液或含有重金属和其盐的产品的材料。因此,长期危害的风险大大降低。The antimicrobial compositions of the present invention are free of materials that create highly persistent residues or rinses or products containing heavy metals and their salts. Therefore, the risk of long-term harm is greatly reduced.
本发明的抗微生物组合物不干扰其控制的微生物的生物化学繁殖路径。因此,耐药积聚和产生抗性菌株的风险低。The antimicrobial compositions of the present invention do not interfere with the biochemical propagation pathways of the microorganisms they control. Therefore, the risk of resistance accumulation and development of resistant strains is low.
本发明的抗微生物组合物可具有双重作用,因为其不仅在使用时提供抗微生物作用,而且还可对组合物具有防腐作用。这意指在本发明的配制物中通常不必包括附加防腐剂。The antimicrobial composition of the present invention can be dual-purpose, since it not only provides an antimicrobial effect when used, but also has a preservative effect on the composition. This means that it is generally not necessary to include additional preservatives in the formulations of the invention.
本发明的组合物通常不使其施用的表面产生油滑感觉。The compositions of the present invention generally do not impart a greasy feel to the surface to which they are applied.
根据本发明的另一方面,提供本发明的组合物的用途以控制、减少或防止在提供其的表面上形成微生物的菌落。According to a further aspect of the invention there is provided the use of a composition of the invention to control, reduce or prevent the formation of colonies of microorganisms on a surface on which it is provided.
本发明提供用于为如硬表面或皮肤的表面提供残余抗微生物益处的方法,所述方法包含将如本文所定义的组合物施用到表面或皮肤。组合物可例如通过将组合物喷洒在表面上或将组合物擦拭到表面或皮肤上施用于表面或皮肤。在本发明的一个方法中,对于方法不必包括除了将组合物简单地施用到表面之外的任何步骤。因此,提供基本上由或由将组合物施用到表面或皮肤组成组成的方法。The present invention provides a method for providing a residual antimicrobial benefit to a surface such as a hard surface or skin, the method comprising applying a composition as defined herein to the surface or skin. The composition can be applied to the surface or skin, for example, by spraying the composition on the surface or wiping the composition onto the surface or skin. In one method of the invention, it is not necessary for the method to include any steps other than simply applying the composition to a surface. Accordingly, methods are provided that consist essentially of or consist of applying the composition to a surface or skin.
在本发明的一方面中,本发明的组合物施用到的表面为身体的表面,如皮肤。In one aspect of the invention, the surface to which the composition of the invention is applied is a surface of the body, such as the skin.
本发明的抗微生物组合物当浸没在水中时通常可降解,以提供低毒性的冲洗液/浸出液并且其在环境中具有短滞留时间。The antimicrobial composition of the present invention is generally degradable when submerged in water to provide a rinse/leach solution of low toxicity and which has a short residence time in the environment.
根据本发明的另一方面,提供本发明的抗微生物组合物的用途,以降低或防止在其提供的表面(如皮肤)上形成微生物的菌落。According to another aspect of the present invention, there is provided the use of an antimicrobial composition of the present invention to reduce or prevent the formation of colonies of microorganisms on a surface provided therefor, such as the skin.
本发明的抗微生物组合物通常通过如下所述的方法制备。The antimicrobial compositions of the present invention are generally prepared by the methods described below.
用于制备如本文中所述的抗微生物组合物的方法包含:The method for preparing the antimicrobial composition as described herein comprises:
(i)在搅拌下将组分(iii)和组分(ii)组合;和(i) combining component (iii) and component (ii) under stirring; and
(ii)将组分(i)添加到组分(iii)和(ii)。(ii) Adding component (i) to components (iii) and (ii).
在一些方面中,可需要调节在步骤(ii)之后获得的溶液的pH。因此,本发明此外描述其中(iii)在步骤(ii)之后调节溶液的pH的方法。In some aspects it may be necessary to adjust the pH of the solution obtained after step (ii). Accordingly, the present invention furthermore describes a process wherein (iii) the pH of the solution is adjusted after step (ii).
除非上下文另外指示,否则对于本发明的给定方面、特征或参数的偏好和选项应被视为已与本发明的所有其它方面、特征和参数的任何和所有偏好和选项组合公开。Unless the context dictates otherwise, preferences and options for a given aspect, feature or parameter of the invention should be considered disclosed in combination with any and all preferences and options for all other aspects, features and parameters of the invention.
现将通过以下非限制性实例说明本发明。The invention will now be illustrated by the following non-limiting examples.
实例1-制备测试样品和对照物Example 1 - Preparation of Test Samples and Controls
使用实例1的方法制备如描述于表1中的组合物。用于组合物的可商购的化合物在下文列出。Compositions as described in Table 1 were prepared using the method of Example 1. Commercially available compounds useful in the compositions are listed below.
Aminat G为N-月桂酰基-L-精氨酸乙酯单盐酸盐于丙三醇中的20%溶液,由赛比克(Seppic)供应。其主要组分为氨基酸L-精氨酸的衍生物的盐。Aminat G is a 20% solution of N-lauroyl-L-arginine ethyl ester monohydrochloride in glycerol supplied by Seppic. Its main component is a salt of a derivative of the amino acid L-arginine.
AH Care L65为含有氨基酸、精氨酸和乳酸的两性羟基络合物。其由巴斯夫(BASF)供应。Aminat G和AH Care L65均为含有本发明的组分(i)的市售实例。AH Care L65 is an amphoteric hydroxyl complex containing amino acids, arginine and lactic acid. It is supplied by BASF. Aminat G and AH Care L65 are both commercially available examples containing component (i) of the present invention.
由索尔供应的Acticide DDQ 40含有40%二-正癸基二甲基氯化铵(DDAC)。这为本发明的组分(ii)的实例,具有式A型。Acticide DDQ 40 supplied by Sol contains 40% di-n-decyldimethylammonium chloride (DDAC). This is an example of component (ii) of the present invention, having formula A type.
由索尔供应的Acticide BAC 50M含有50%苯扎氯铵(BAC),也为本发明的组分(ii)的实例,具有式B型。Acticide BAC 50M supplied by Sol contains 50% benzalkonium chloride (BAC) and is also an example of component (ii) of the present invention, having formula B.
由赢创(Evonik)供应的为20%溶液的氯己定二葡糖酸盐(CHDG)为本发明的组分(ii)的另一实例。Chlorhexidine digluconate (CHDG) supplied by Evonik as a 20% solution is another example of component (ii) of the present invention.
由龙沙供应的Lonzagard苄索氯铵USP为苯甲烃铵衍生物并且含有100%二异丁基苯氧基乙氧基乙基-二甲苯甲基氯化铵(BENZ),另外被称为苄索氯铵。其为本发明的组分(ii)的另一实例。Lonzagard Benzethonium Chloride USP supplied by Lonza is a benzalkonium derivative and contains 100% diisobutylphenoxyethoxyethyl-xylyl ammonium chloride (BENZ), otherwise known as Benzethonium Chloride. It is another example of component (ii) of the present invention.
将极性溶剂(组分(iii))放置于适当大小的容器中(通常1升容量)。保留少量的极性溶剂以允许最终重量调节。随后将必需量的一种或多种杀生物剂(组分(ii))添加到容器,其中在添加下一种杀生物剂之前容器在添加每种杀生物剂之后搅拌5分钟。随后添加必需量的氨基酸、衍生物或盐(组分(i))并且容器再搅拌5分钟。检查pH并且如果需要那么使用乳酸或氢氧化钠溶液调节。随后溶液通过添加保留的极性溶剂组成100重量%并且搅拌最后10分钟。The polar solvent (component (iii)) is placed in an appropriately sized container (typically 1 liter capacity). A small amount of polar solvent was reserved to allow for final weight adjustment. The requisite amount of one or more biocides (component (ii)) is then added to the container with the container agitated for 5 minutes after the addition of each biocide before adding the next biocide. The necessary amount of amino acid, derivative or salt (component (i)) is then added and the vessel is stirred for a further 5 minutes. Check the pH and adjust if necessary with lactic acid or sodium hydroxide solution. The solution was then made up to 100% by weight by addition of the remaining polar solvent and stirred for the final 10 minutes.
对照样品按照相同方法制备,但是省去一种或多种本发明的组分(i)、(ii)或(iii)。Control samples were prepared in the same manner, but omitting one or more components (i), (ii) or (iii) of the invention.
在表1中,本发明的组合组分(i)、Aminat G和AH Care L65的重量%是指可商购的材料的量并且本发明的组分(ii)的重量%是指活性化学组分,即DDAC-二-正癸基二甲基氯化铵、CHDG-氯己定二葡糖酸盐;BEHZ-苄索氯铵;或BAC-苯扎氯铵的量。In Table 1, the weight % of the combined component (i), Aminat G and AH Care L65 of the present invention refers to the amount of commercially available materials and the weight % of the component (ii) of the present invention refers to the active chemical group DDAC-di-decyldimethylammonium chloride, CHDG-chlorhexidine digluconate; BEHZ-benzethonium chloride; or the amount of BAC-benzalkonium chloride.
表1Table 1
实例2-评估测试样品的残余抗微生物功效Example 2 - Evaluation of Residual Antimicrobial Efficacy of Test Samples
25微升(0.025ml)的测试样品施用到活体外皮肤的2cm×2cm部分(如由IMS公司供应),在皮氏培养皿中重复两次。测试样品在表面上扩散,其中灭菌的接种环管确保距边缘大约0.5cm周边保持未处理。在20℃下在烘箱中使测试样品在 *2上干燥,其中皮氏培养皿盖子保持关闭一小时。随后从烘箱取出皮氏培养皿,并且使一条聚丙烯拭纸用放置在内部的灭菌的胰蛋白胨/盐水溶液饱和。关闭盖子并且随后放回烘箱中在20℃下维持4小时。此后,从烘箱取出皮氏培养皿,并且将在胰蛋白胨/盐水溶液中制备的大肠杆菌K12*1的10ul的1到1.5×10^8cfu/ml悬浮液添加到含有测试样品并且扩散的的表面,其中灭菌的接种环管确保悬浮液保持在活体外皮肤的处理区域内。细菌悬浮液保持与活体外皮肤接触5分钟。此后,从皮氏培养皿取出并且放置于含有10ml的中和溶液的试管中。温和地摇晃试管并且在管涡流混合1分钟之后再保持5分钟以从活体外皮肤的表面回收细菌。随后用胰蛋白胨大豆琼脂镀覆1ml的此悬浮液样品并且在37℃下培育48小时。此后,与水处理的对照物相比较,计算大肠杆菌K12的对数下降值。25 microliters (0.025 ml) of test samples were applied to 2 cm x 2 cm sections of skin ex vivo (as supplied by IMS Corporation) in duplicate in petri dishes. Test samples in Spread over the surface with a sterile inoculation loop ensuring that the perimeter approximately 0.5 cm from the edge remains untreated. In an oven at 20°C, the test samples were * 2 on drying, with the petri dish lid kept closed for one hour. The petri dish was then removed from the oven, and a strip of polypropylene swab was saturated with sterile tryptone/saline solution placed inside. The lid was closed and then placed back in the oven at 20°C for 4 hours. Thereafter, the petri dish was removed from the oven, and 10 ul of a 1 to 1.5 x 10^8 cfu/ml suspension of E. coli K12* 1 prepared in tryptone/saline solution was added to the pan containing the test sample and diffused. The surface where the sterile inoculation loop ensures that the suspension remains within the treated area of ex vivo skin. The bacterial suspension was kept in contact with the ex vivo skin for 5 minutes. Thereafter, remove from the petri dish And placed in a test tube containing 10ml of neutralizing solution. The tubes were shaken gently and the tubes were vortexed for 1 minute followed by an additional 5 minutes to recover bacteria from the surface of the ex vivo skin. A 1 ml sample of this suspension was then plated with tryptone soy agar and incubated at 37°C for 48 hours. Thereafter, the log reduction of E. coli K12 was calculated compared to the water-treated control.
*1NB.大肠杆菌K12悬浮液由在37℃下在胰蛋白胨大豆琼脂上生长24小时的‘2a’培养液制备,如描述于BSEN微生物学标准中例如EN1276:2009)*2 为模仿人类皮肤的表面特性的测试基材。其为已配制具有类似于人类皮肤的形貌、pH、关键表面张力和离子强度的合成非生物产品。对于在本领域中经训练的那些其为众所周知的和使用基材,以评估皮肤护理产品对皮肤的拓扑应用的益处,其包括评估施用到皮肤的活性剂的杀菌功效。对活体外皮肤起作用公布的同行审查的实例包括US 20090202463A1,其描述用于评估提供提高对皮肤的表面的即时和残余抗病毒和抗细菌功效的抗微生物组合物的方法;如描述于《抗微生物剂和化学治疗杂志(Journal of Antimicrobial Agents andChemotherapy)》;48(7);2004年7月;2595-2598中的评估在用于预防鼻病毒感染的手部清洁剂中的有机酸的功效;US 20120141396 A1,其描述为多种表面(包括皮肤)提供长期抗微生物特性杀菌剂组合物,使用活体外皮肤进行评估。* 1 NB. E. coli K12 suspension was prepared from '2a' broth grown on Tryptone Soy Agar for 24 hours at 37°C as described in BSEN Microbiology Standards eg EN1276:2009)* 2 A test substrate that mimics the surface properties of human skin. It is a synthetic non-biological product that has been formulated to have topography, pH, critical surface tension and ionic strength similar to human skin. It is well known to those trained in the art and uses substrates to assess the benefits of topological application of skin care products to the skin, which includes assessing the germicidal efficacy of active agents applied to the skin. Peer-reviewed examples of publications acting on skin in vitro include US 20090202463A1, which describes methods for evaluating antimicrobial compositions that provide enhanced immediate and residual antiviral and antibacterial efficacy on the surface of the skin; as described in Antibiotic Evaluation of the efficacy of organic acids in hand sanitizers for the prevention of rhinovirus infection in Journal of Antimicrobial Agents and Chemotherapy; 48(7); July 2004; 2595-2598; US 20120141396 A1, which describes antimicrobial compositions providing long-term antimicrobial properties to various surfaces, including skin, was evaluated using skin in vitro.
实例2的结果Results of Example 2
配制物1Formulation 1
配制物1和对照样品1、2、3、6、8和9根据在实例1中所述的方法制备在表1中所述的组合物。配制物1的样品和对照样品随后使用在实例2中所述的方法测试抗微生物功效。这些测试的结果在下表2中示出。Formulation 1 and Control Samples 1, 2, 3, 6, 8 and 9 The compositions described in Table 1 were prepared according to the method described in Example 1. Samples of Formulation 1 and control samples were then tested for antimicrobial efficacy using the method described in Example 2. The results of these tests are shown in Table 2 below.
表2Table 2
*Tntc=太多无法计数*Tntc=too many to count
相较于不具有Aminat G(本发明的组分(i))的对照物3,在表2中的结果示出本发明的组合物,即与CHDG和Aminat G组合的DDAC具有优异抗微生物性能。The results in Table 2 show that the composition of the invention, DDAC in combination with CHDG and Aminat G, has superior antimicrobial properties compared to Control 3 without Aminat G (component (i) of the invention) .
相较于在具有Aminat G的情况下分别单独使用DDAC和CHDG的对照物6和9和在无Aminat G的情况下分别单独使用DDAC和CHDG的对照物1和8,配制物1也具有优异抗微生物性能。Formulation 1 also had superior resistance to Microbial performance.
对照物2示出Aminat G无抗微生物活性。Control 2 shows no antimicrobial activity of Aminat G.
配制物2Formulation 2
配制物2和对照样品1、2、4、6和7按照在实例1中所述的方法制备在表1中所述的组合物。配制物2的样品和对照样品随后按照在实例2中所述的方法测试抗微生物功效。这些测试的结果在下表3中示出。Formulation 2 and Control Samples 1, 2, 4, 6 and 7 The compositions described in Table 1 were prepared as described in Example 1. Samples of Formulation 2 and control samples were then tested for antimicrobial efficacy as described in Example 2. The results of these tests are shown in Table 3 below.
表3table 3
*Tntc=太多无法计数*Tntc=too many to count
相较于不具有Aminat G(本发明的组分(i))的对照物4,在表3中的结果示出本发明的组合物,即与BAC和Aminat G组合的DDAC具有优异抗微生物性能。The results in Table 3 show that the composition of the invention, DDAC in combination with BAC and Aminat G, has superior antimicrobial properties compared to Control 4 without Aminat G (component (i) of the invention) .
相较于在具有Aminat G的情况下分别单独使用DDAC和BAC的对照物6和7和在无Aminat G的情况下单独使用DDAC的对照物1,配制物2也具有优异抗微生物性能。Formulation 2 also had superior antimicrobial properties compared to Controls 6 and 7, which used DDAC and BAC alone, respectively, with Aminat G, and Control 1, which used DDAC alone without Aminat G.
对照物2示出Aminat G无抗微生物活性。Control 2 shows no antimicrobial activity of Aminat G.
配制物3Formulation 3
配制物3和对照样品5、10、11和12按照在实例1中所述的方法制备在表1中所述的组合物。配制物3的样品和对照样品随后按照在实例2中所述的方法测试抗微生物功效。这些测试的结果在下表4中示出。Formulation 3 and Control Samples 5, 10, 11 and 12 The compositions described in Table 1 were prepared as described in Example 1. Samples of Formulation 3 and control samples were then tested for antimicrobial efficacy as described in Example 2. The results of these tests are shown in Table 4 below.
表4Table 4
*Tntc=太多无法计数*Tntc=too many to count
相较于不具有AH Care L65(本发明的组分(i))的对照物12,在表4中的结果示出本发明的组合物,即与CHDG和AH Care L65组合的DDAC具有优异抗微生物性能。Compared to control 12 without AH Care L65 (component (i) of the invention), the results in Table 4 show that the composition of the invention, DDAC combined with CHDG and AH Care L65, has excellent resistance to Microbial performance.
相较于在具有AH Care L65的情况下分别单独使用DDAC和CHDG的对照物10和11,配制物3也具有优异抗微生物性能。Formulation 3 also had superior antimicrobial performance compared to controls 10 and 11 where DDAC and CHDG were used alone, respectively, with AH Care L65.
对照物5示出AH Care L65无抗微生物活性。Control 5 showed no antimicrobial activity of AH Care L65.
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CN201680020804.5A Pending CN107466207A (en) | 2015-04-02 | 2016-04-01 | Antimicrobial compositions |
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EP (1) | EP3277086A2 (en) |
JP (1) | JP6785789B2 (en) |
CN (1) | CN107466207A (en) |
BR (1) | BR112017021002B8 (en) |
GB (2) | GB201505701D0 (en) |
HK (1) | HK1246088A1 (en) |
MY (1) | MY178425A (en) |
SG (1) | SG11201707755QA (en) |
TW (1) | TWI626006B (en) |
WO (1) | WO2016156869A2 (en) |
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CN115119841A (en) * | 2022-07-29 | 2022-09-30 | 厦门兴勒贸易有限公司 | Novel chitosan composite cationic disinfectant suitable for high-power dilution |
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- 2016-04-01 BR BR112017021002A patent/BR112017021002B8/en not_active IP Right Cessation
- 2016-04-01 SG SG11201707755QA patent/SG11201707755QA/en unknown
- 2016-04-01 CN CN201680020804.5A patent/CN107466207A/en active Pending
- 2016-04-01 TW TW105110531A patent/TWI626006B/en not_active IP Right Cessation
- 2016-04-01 MY MYPI2017703704A patent/MY178425A/en unknown
- 2016-04-01 EP EP16719113.9A patent/EP3277086A2/en not_active Withdrawn
- 2016-04-01 WO PCT/GB2016/050932 patent/WO2016156869A2/en active Application Filing
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Cited By (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112105265A (en) * | 2018-04-09 | 2020-12-18 | 罗地亚经营管理公司 | Compositions and methods for durable disinfection |
CN112261873A (en) * | 2018-04-19 | 2021-01-22 | 优卡健康有限公司 | Antimicrobial properties of surfaces, air, fabrics, paints, plastics, silicone and wood, polyethylene; metals and derivatives |
CN112899087A (en) * | 2018-06-22 | 2021-06-04 | 华东师范大学 | Natural environment-friendly nontoxic kitchen oil stain cleaning agent |
CN112899087B (en) * | 2018-06-22 | 2022-07-08 | 华东师范大学 | Kitchen oil stain cleaning agent |
CN109169653B (en) * | 2018-10-24 | 2020-09-29 | 湖北荷普药业股份有限公司 | Cation composite disinfectant and application thereof |
CN109169653A (en) * | 2018-10-24 | 2019-01-11 | 湖北荷普药业股份有限公司 | A kind of cation composite disinfectant and its application |
CN113395961A (en) * | 2018-11-30 | 2021-09-14 | 优卡健康有限公司 | Woven, nonwoven, cotton, blended nonwoven-cotton, polyethylene and polypropylene and polystyrene masks with antimicrobial properties, wound dressings, underpants, brassieres, handkerchiefs, pads, scrubbing pads, disposable surgical gowns, disposable sheets |
CN111616148A (en) * | 2020-05-28 | 2020-09-04 | 江苏雪豹日化有限公司 | High-efficiency disinfectant |
CN112294789A (en) * | 2020-10-15 | 2021-02-02 | 郑涛 | Compound preparation for preventing and treating respiratory tract infection and application thereof |
CN112294789B (en) * | 2020-10-15 | 2022-06-07 | 郑涛 | Compound preparation for preventing and treating respiratory tract infection and application thereof |
CN113100085A (en) * | 2021-04-21 | 2021-07-13 | 铜陵博锋实业有限公司 | Transparent and high-water-absorption-degree starch cat litter and preparation process thereof |
CN113100085B (en) * | 2021-04-21 | 2023-12-22 | 铜陵博锋实业有限公司 | Transparent high-water-absorptivity starch cat litter and preparation process thereof |
CN115299437A (en) * | 2021-05-06 | 2022-11-08 | 南顺商标有限公司 | Antimicrobial compositions and methods of making the same |
CN115119841A (en) * | 2022-07-29 | 2022-09-30 | 厦门兴勒贸易有限公司 | Novel chitosan composite cationic disinfectant suitable for high-power dilution |
Also Published As
Publication number | Publication date |
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TW201709819A (en) | 2017-03-16 |
GB201505701D0 (en) | 2015-05-20 |
JP6785789B2 (en) | 2020-11-18 |
BR112017021002A2 (en) | 2018-07-03 |
BR112017021002B1 (en) | 2020-05-26 |
JP2018511607A (en) | 2018-04-26 |
HK1246088A1 (en) | 2018-09-07 |
GB2533527A (en) | 2016-06-22 |
WO2016156869A3 (en) | 2016-11-10 |
MY178425A (en) | 2020-10-13 |
EP3277086A2 (en) | 2018-02-07 |
BR112017021002B8 (en) | 2020-06-16 |
TWI626006B (en) | 2018-06-11 |
GB2533527B (en) | 2018-10-17 |
WO2016156869A2 (en) | 2016-10-06 |
SG11201707755QA (en) | 2017-10-30 |
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