Synergistic antimicrobial combinations comprising quaternary ammonium biocides

Abstract

A composition having biocidal properties is disclosed. The composition comprises a first biocide that cooperates with a second biocide to disrupt or inhibit the growth of at least one microorganism. The first biocide comprises a quaternary ammonium salt. In another aspect, the second biocide may comprise a quaternary ammonium compound, an amine, and / or pyridinethiol. The compositions are particularly suitable for disinfecting products and as preservatives.

Description

[0001] This application is a divisional application of Chinese patent application No. 201780050785.5 (PCT / US2017 / 038095), filed on December 28, 2017, and entitled “Synergistic antimicrobial combination comprising quaternary ammonium biocides”.

[0002] Related Applications

[0003] This application is based upon and claims the benefit of U.S. Provisional Patent Application Serial No. 62 / 354,425, filed on June 24, 2016, which is incorporated herein by reference. background

[0005] Disinfectant refers to any chemical agent that can kill, destroy or inhibit the growth of organisms, especially microorganisms. Disinfectant products include hard surface cleaners, hand sanitizers, pre-disinfectant cleaners for instruments, disinfectant and high-level disinfectant compositions, etc.

[0006] Ideally, the disinfectant has a broad spectrum of activity against all types of microorganisms at various pH levels. The disinfectant should also have high potency so that the minimum amount of antimicrobial agent can be used to save costs and avoid or reduce any possible adverse effects caused by the antimicrobial agent. Moreover, it is desirable that the disinfectant is stable to any temperature changes encountered during manufacturing, packaging and transportation, and during storage. In addition, the ideal disinfectant is physically and chemically compatible with the components of different application systems, so that the antimicrobial agent can be appropriately incorporated into a variety of products.

[0007] In the past, various disinfectants have been proposed. For example, disinfectants that have been used in the past include alcohols, such as isopropyl alcohol and ethanol, copper compounds, silver compounds, aldehydes, oxidants such as sodium hypochlorite, etc.

[0008] In addition to the above-mentioned disinfectants, quaternary compounds have also been used in the past. However, quaternary compounds may have a limited spectrum of activity. In addition, in certain applications, it is necessary to use quaternary compounds in relatively high concentrations to obtain the desired efficacy. However, adding relatively high concentrations of quaternary compounds to products may be problematic. For example, not only are quaternary compounds expensive to manufacture and produce, but they may also be subject to various regulatory requirements. Therefore, there is a need for a method for increasing the efficacy spectrum of quaternary compounds while reducing the required concentration of the compound while still maintaining the desired effect. In this regard, the present disclosure relates to improved antimicrobial compositions containing quaternary compounds and methods of using the compositions. SUMMARY OF THE INVENTION

[0010] In general, the present disclosure relates to compositions having biocidal properties. According to the present disclosure, an antimicrobial composition is disclosed, which contains a first biocide and a second biocide in combination. The first biocide includes a salt of a quaternary ammonium cation. The first biocide may include a carbonate salt of a quaternary ammonium cation / a bicarbonate salt, a halide, or a propionate salt of a quaternary ammonium cation. On the other hand, the second biocide is selected according to the desired specific biocide properties so that the second biocide acts synergistically with the first biocide to kill or inhibit the growth of a microorganism or a plurality of different microorganisms. As used herein, a synergistic interaction refers to the fact that the total effect of the two biocides combined together is greater than the biocide properties of only one biocide acting alone. In other words, the first and second biocides of the present disclosure act synergistically together, thereby having greater antimicrobial activity in the presence of each biocide against a certain microorganism, compared to the antimicrobial activity of the first biocide alone or the antimicrobial activity of the second biocide alone at the same concentration. Due to the synergistic effect, the amount of the first biocide present in the composition can be reduced while still producing the desired efficacy.

[0011] In one embodiment, the present disclosure relates to a composition having biocidal properties, comprising a first biocide comprising a salt of a quaternary ammonium cation and a second biocide selected to act synergistically with the first biocide to kill, destroy or inhibit the growth of microorganisms. The second biocide may include an alkyl quaternary ammonium halide, a benzyl ammonium halide, a quaternary ammonium propionate, a tertiary amine or pyrithione (also known as 2-pyridinethiol-N-oxide). The second biocide is present in the composition relative to the first biocide so that the ability of the two biocides to kill or inhibit the growth of microorganisms is greater than if only one biocide is present at the same concentration as the two biocides.

[0012] A variety of different microorganisms can be killed according to the present disclosure. For example, the antimicrobial compositions of the present disclosure can control Gram-positive bacteria, Gram-negative bacteria, fungi, yeasts, spores, viruses, etc. Examples of specific microorganisms that can be controlled according to the present invention include Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, or mixtures thereof.

[0013] In one embodiment, for example, the second biocide may comprise an alkyl quaternary ammonium halide. The alkyl quaternary ammonium halide may comprise a dialkyl dimethyl ammonium chloride, such as a di-C8 to C 12Alkyl dimethyl ammonium chloride. An example of a dialkyl dimethyl ammonium chloride that can be used according to the present disclosure is didecyl dimethyl ammonium chloride. Alternatively, the second biocide can include a benzyl ammonium halide. The benzyl ammonium halide can include a benzyl alkyl dimethyl ammonium chloride, such as benzyl C 12 To C 16 Alkyl dimethyl ammonium chloride. In a particular embodiment, the composition can comprise a second biocide and a third biocide, wherein the second biocide comprises a quaternary ammonium halide and the third biocide comprises a benzyl ammonium halide.

[0014] In another embodiment, the second biocide may comprise a quaternary ammonium propionate. An example of a quaternary ammonium propionate is N,N-didecyl-N-methyl-poly(oxyethyl)ammonium propionate.

[0015] In yet another embodiment, the second biocide may comprise an amine, particularly a tertiary amine.An example of a tertiary amine that may be used according to the present invention is N-3-aminopropyl-N-dodecylpropane-1-3-diamine.

[0016] In yet another embodiment of the present disclosure, the second biocide may comprise pyrithione. For example, a pyrithione salt, such as sodium pyrithione, may be used.

[0017] Typically, the first biocide and the second biocide may be present in the composition in a weight ratio of about 1:20 to about 20:1, such as about 1:5 to about 5:1.

[0018] The antimicrobial compositions of the present disclosure can be used in many different products. For example, the antimicrobial compositions can be incorporated into hard surface cleaners, hand sanitizers, disinfectant solutions for instruments such as medical instruments, or any other suitable disinfectant products. In addition to disinfectants, the antimicrobial compositions of the present disclosure can also be used as preservative compositions and can be included in, for example, cosmetics or sanitary products. The cosmetics or sanitary products can include a base composition and a preservative, wherein the preservative includes a combination of biocides as described above.

[0019] The present disclosure also relates to a method for preparing a disinfectant composition. The method includes combining a first biocide comprising a salt of a quaternary ammonium cation with a second biocide selected to act synergistically with the first biocide to kill or inhibit the growth of microorganisms. The second biocide can be any of the biocides described above.

[0020] Other features and aspects of the disclosure are discussed in more detail below. DETAILED DESCRIPTION OF THE INVENTION

[0022] Those of ordinary skill in the art will appreciate that this discussion is merely a description of exemplary embodiments and is not intended to limit the broader aspects of the present disclosure.

[0023] Generally, the present disclosure relates to compositions having biocidal properties. The compositions have many uses and applications. In one embodiment, the composition may comprise a disinfectant. The disinfectant may be used in any suitable industry or field. For example, the disinfectant may be used in the food and beverage field and may include institutional products, household products, or health care products. For example, the disinfectant may include a hard surface disinfectant, a hand sanitizer, a disinfectant or high-level disinfectant composition, a pre-disinfectant cleaner for instruments, and the like. In an alternative embodiment, the composition may be used as a preservative for a product, such as a personal care product or a hygiene product.

[0024] The composition of the present invention contains a first biocide comprising a salt of a quaternary ammonium cation. The first biocide may comprise a carbonate of a quaternary ammonium cation / a bicarbonate of a quaternary ammonium cation, a halide or a propionate. The first biocide is combined with a second biocide to kill and / or control one or more microorganisms. The first biocide according to the present disclosure and the second biocide act synergistically to kill or inhibit the growth of microorganisms. More specifically, the two biocides combined together according to the present disclosure have a higher efficacy at lower concentrations than if one biocide is present alone in the composition. The use of two different biocides can also enhance the spectrum of activity of the composition against a variety of microorganisms. Therefore, the antimicrobial composition of the present disclosure can be used at lower concentrations and is more effective against a wider range of microorganisms. The selection of the second biocide used in combination with the first biocide can be based on the target microorganism and can be selected using a screening program. Ultimately, the antimicrobial composition can be produced with a relatively low total biocide concentration while still providing strong preservation and / or antimicrobial properties.

[0025] The synergistic combination of biocides combined together according to the present disclosure includes at least the first biocide and the second biocide. In some embodiments, the third biocide and / or the fourth biocide may be present to further enhance the synergistic effect. According to the present disclosure, the first biocide generally comprises a quaternary ammonium salt. Therefore, the present disclosure, in one embodiment, is particularly directed to selecting a second biocide having a synergistic interaction with the quaternary ammonium salt. In this way, the amount of the quaternary ammonium salt included in the composition can be minimized. In addition, due to the synergistic interaction, the amount of the second biocide can also be minimized. In other words, a composition can be prepared according to the present disclosure, which comprises two biocides with synergistic interaction, wherein the two biocides are included in the composition with a total concentration lower than if only one or more quaternary ammonium salts are present in the composition, while still having the same or better efficacy to one or more target microorganisms.

[0026] In one embodiment, the first biocide may comprise a quaternary ammonium carbonate. The quaternary ammonium carbonate may be represented by the formula:

[0027]

[0028] Where R 1 It is C1-C 20 alkyl or aryl-substituted alkyl, and R 2 It is C8-C 20 Alkyl, preferably wherein R 1 With R 2 The same, and R 1 It is C8-C 12 Alkyl, and the composition further comprises a corresponding quaternary ammonium bicarbonate

[0029]

[0030] Where R 1 Same as above, but different from C1-C 20 alkyl or aryl-substituted alkyl, and R 2 Same as above, different C8-C 20 alkyl, but preferably wherein R 1 With R 2 The same, and R 1 It is C8-C 12 alkyl.

[0031] In one embodiment, the first biocide included in the composition comprises a di-C8-C 12 Alkyl ammonium carbonate / di-C8-C 12 Alkyl ammonium bicarbonates. For example, in one particular embodiment, the antimicrobial or preservative composition comprises didecyl dimethyl ammonium carbonate and didecyl dimethyl ammonium bicarbonate.

[0032] However, in other embodiments, the carbonate salt of the quaternary ammonium cation / the bicarbonate salt of the quaternary ammonium cation can be selected from dioctyldimethylammonium carbonate, decyloctyldimethylammonium carbonate, benzalkonium carbonate, benzethonium carbonate, stearalkonium carbonate, cetrimonium carbonate, behentrimonium carbonate, dioctyldimethylammonium bicarbonate, decyloctyldimethylammonium bicarbonate, benzalkonium bicarbonate, benzethonium bicarbonate, stearalkonium bicarbonate, cetrimonium bicarbonate, behentrimonium bicarbonate and mixtures of one or more of such carbonates.

[0033] In another embodiment, the first biocide can include a quaternary ammonium halide. The quaternary ammonium halide can include, for example, an alkyl quaternary ammonium halide or a benzyl ammonium halide.

[0034] Quaternary ammonium compounds, also called "quats", generally contain at least one quaternary ammonium cation with a suitable anion. Quaternary ammonium compounds generally have the general formula (1).

[0035]

[0036] The groups R1, R2, R3 and R4 can vary within wide ranges, and examples of quaternary ammonium compounds having antimicrobial properties are well known to those skilled in the art. Typically, two of R1, R2, R3 and R4 are lower alkyl groups, meaning having 1 to 4 carbon atoms, such as methyl, ethyl, propyl or butyl. Alternatively, two of R1, R2, R3 and R4 are benzyl or long chain alkyl groups having 6 to 24 carbon atoms. - It is a monovalent anion or a monovalent polyvalent anion of an inorganic or organic acid. - Suitable anions are in principle all inorganic or organic anions, in particular halides, for example chlorides or bromides, carboxylates, sulfonates, phosphates or mixtures thereof.

[0037] In one embodiment, the quaternary ammonium compound may have the following R groups: R1 is benzyl or C 6-18 -alkyl, R2 is C 1-18 -alkyl or -[(CH2)2-O] n R5, wherein n=1-20, R3 and R4 are independently C 1-4 -alkyl, R5 is hydrogen or unsubstituted or substituted phenyl, and A - It is a monovalent anion or a monovalent polyvalent anion of an inorganic or organic acid.

[0038] In one embodiment, the quaternary ammonium compound may include a dialkylammonium compound, such as a dimethyldialkylammonium compound. In one embodiment, the dimethyldialkylammonium compound may have from about 8 to about 12 carbon atoms, such as from about 8 to about 10 carbon atoms in each alkyl group.

[0039] Examples of dimethyldialkylammonium compounds that can be used as the first biocide include dimethyldioctylammonium compounds, such as dimethyldioctylammonium chloride, dimethyldidecylammonium compounds, such as dimethyldidecylammonium chloride, and the like. Mixtures of dimethyldialkylammonium compounds can also be used, as can other anions such as those described above. Commercially available dimethyldialkylammonium compounds include, for example, those marketed by Lonza America, Inc as BARDAC TMThe composition is marketed and sold under the trade name ANTIBIOTIC®.

[0040] In an alternative embodiment, the first biocide may comprise a benzyl ammonium compound, such as an alkyl dimethyl benzyl ammonium compound. Typically, the alkyl group may contain from about 10 to about 18 carbon atoms, such as from about 12 to about 16 carbon atoms.

[0041] Examples of alkyl dimethyl benzyl ammonium compounds that can be used as the first biocide include C 12 Alkyl dimethyl benzyl ammonium chloride, C 14 Alkyl dimethyl benzyl ammonium chloride and C 16 Alkyl dimethyl benzyl ammonium chloride. In addition, mixtures of these alkyl dimethyl benzyl ammonium compounds can be used. Commercially available alkyl dimethyl benzyl ammonium compounds include, for example, Lonza America, Inc. These commercially available alkyl dimethyl benzyl ammonium compounds are C 12 , C 14 and C 16 alkyl dimethyl benzyl ammonium chloride. Generally, when the blend contains more than C 16 The higher concentration of alkyl components in C 12 Alkyl and C 14 As the alkyl component, alkyl dimethyl benzyl ammonium compounds are preferred. It should be noted that other anions, including those mentioned above, may also be used.

[0042] In yet another embodiment, the first biocide may comprise a quaternary ammonium propionate. For example, the quaternary ammonium propionate may comprise poly(oxyalkyl)ammonium propionate. In a specific embodiment, for example, the first biocide may comprise N,N-didecyl-N-methyl-poly(oxyethyl)ammonium propionate.

[0043] The first biocide as described above is combined with at least a second biocide according to the present invention. The second biocide is selected to act synergistically with the first biocide to destroy and / or inhibit the growth of one or more target microorganisms. In one embodiment, the second biocide is selected to improve the efficacy of the first biocide to microorganisms so that the total concentration of the biocide in the composition can be reduced compared to a composition containing only one biocide. As will be explained in the following examples, the second biocide can be selected through a screening process to determine a synergistic interaction. Depending on the specific application and the microorganism to be controlled, the second biocide can include a variety of different compounds.

[0044] In one embodiment, the second biocide is selected so that when tested against a target microorganism, the sum of the fractional inhibition concentrations of the first biocide and the second biocide is less than 1. The fractional inhibition concentration of the biocide is calculated as the concentration of the biocide that controls growth in the mixture divided by the amount of the biocide required to control growth when used alone. The fractional inhibition concentration of the biocide can be calculated by dividing the concentration of the biocide attributable to antimicrobial activity in the mixture of the first biocide and the second biocide by the minimum inhibition concentration of the biocide when tested against the target microorganism. According to the present disclosure, when targeting a specific microorganism, the sum of the fractional inhibition concentrations of the first biocide and the second biocide may be less than about 0.9, such as less than about 0.8, such as less than about 0.7. Any value less than 1 indicates a synergistic interaction.

[0045] In one embodiment, for example, the second biocide can include a different quaternary ammonium compound than the first biocide.For example, the second biocide can include an alkyl quaternary ammonium halide, a benzyl ammonium halide, and / or an alkyl quaternary ammonium propionate.

[0046] In one embodiment, the composition of the present disclosure may include a second biocide and a third biocide in combination with a first biocide. For example, in one embodiment, the second biocide may include a dimethyldialkylammonium compound as described above, and the third biocide may include an alkyldimethylbenzylammonium compound as described above.

[0047] In another embodiment of the present disclosure, the second biocide may comprise an amine. For example, amines have been found to have synergistic interactions with quaternary ammonium carbonates in killing and controlling the growth of bacteria, particularly gram-negative bacteria.

[0048] Suitable amines include, but are not limited to, tertiary amines, such as (C8-C 14 ) alkylamine. The term "(C8-C 14 ) alkylamines include (C1-C 14 All amines containing a (C8-C 14 ) alkylamine is N,N-bis(3-aminopropyl)dodecylamine, which can be used as 12.30 and 12.100 were obtained from Lonza, Inc.

[0049] Other exemplary tertiary amines include, for example, N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine, N-(3-aminopropyl)-N-decyl-1,3-propanediamine, N-(3-aminopropyl)-N-tetradecyl-1,3-propanediamine, and acid addition compounds thereof. Other similar tertiary amines may be used.

[0050] In another embodiment, the second biocide present in the antimicrobial or preservative composition may comprise pyrithione. It has been found that the combination of pyrithione and the first biocide has a synergistic interaction when killing and controlling a variety of microorganisms such as bacteria, particularly when controlling Gram-positive bacteria.

[0051] Pyrithione is known by several names, including 2-pyridinethiol-N-oxide; 2-pyridinethiol-1-oxide (CAS Reg. No. 1121-31-9); 1-hydroxypyridine-2-thione and 1-hydroxy-2(1H)-pyridinethione (CAS Reg. No. 1121-30-8). Pyrithione salts are commercially available from Lonza, Inc. as Sodium OMADINE or Zinc OMADINE.

[0052] The pyrithione present in the antimicrobial composition can exist in a water-insoluble form or a water-soluble form. The pyrithione can include sodium pyrithione, zinc pyrithione, barium pyrithione, strontium pyrithione, copper pyrithione, cadmium pyrithione and / or zirconium pyrithione. Other pyrithiones that can be present in the composition include sodium pyrithione, bismuth pyrithione, potassium pyrithione, lithium pyrithione, ammonium pyrithione, calcium pyrithione, magnesium pyrithione, silver pyrithione, gold pyrithione, manganese pyrithione and / or an organic amine pyrithione. A single pyrithione can be present in the composition, or the composition can include any of the above-mentioned combinations.

[0053] The particle size of the pyrithione particles can be such that 100% of the particles have a particle size of less than about 10 microns, and at least 70% of the particles have a particle size of less than 5 microns, such as at least about 50% of the particles can have a particle size of 1 micron or less. The particle size can be measured using a laser scattering particle size analyzer, such as a HORIBA LA 910 particle size analyzer.

[0054] Pyrithione particles can be prepared by reacting pyrithione or a water-soluble salt of pyrithione with a water-soluble multivalent metal salt in a pressurized turbulent flow reactor that generates a pulverizing force. The pulverizing force generated by the pressurized turbulent flow reactor effectively produces micron-sized pyrithione salt particles. The micron-sized pyrithione salt particles prepared by this method have a narrow and uniform particle size distribution and have excellent surface deposition properties due to the large surface area provided by the micron particle group.

[0055] In one embodiment of the present disclosure, the composition of the present disclosure may include didecyl dimethyl ammonium carbonate and didecyl dimethyl ammonium bicarbonate, which are combined with a second biocide, such as didecyl methyl poly (oxyethyl) -ammonium propionate. The composition may further optionally include an alkaline builder, a surfactant, a complexing agent and / or a corrosion inhibitor. In a non-limiting embodiment, the optional alkaline builder is selected from monoethanolamine (MEA), diethanolamine, triethanolamine and mixtures thereof. The optional surfactant is selected from, but not limited to, alkyl polyglucoside, cocamidopropyl betaine, cocamidopropylhydroxylsultaine, alcohol polyglycol ether, ethoxylated amines, fatty alcohol alkoxylates, polyethylene glycol, alcohol PEG-ether and combinations thereof. The optional complexing agent is selected from, but not limited to, trisodium methylglycine diacetate, tetrasodium ethylenediaminetetraacetate and mixtures thereof. The optional corrosion inhibitor is selected from, but not limited to, methyl dihydrogen phosphate, TEA neutralized polycarboxylic acid, and mixtures thereof.

[0056] In the above embodiment, the composition of the present disclosure may contain the first biocide in an amount of 3% to 15% by weight, such as 4% to 10% by weight. The composition may contain the second biocide in an amount of 3% to 15% by weight, such as 6% to 12% by weight.

[0057] In one embodiment, the composition may comprise an alkaline builder in an amount of 0.1% to 8% by weight, such as 1% to 5% by weight.

[0058] In one embodiment, the composition may comprise at least one surfactant in an amount of 0.1% to 8% by weight, such as 0.5% to 6% by weight.

[0059] In one embodiment, the composition may comprise a complexing agent in an amount of 0.1% to 5% by weight, such as 0.25% to 3% by weight.

[0060] In one embodiment, the composition may include a corrosion inhibitor in an amount of 0.1% to 5% by weight, such as 0.25% to 3% by weight.

[0061] In one embodiment, the composition of the present disclosure may include a first biocide, which includes didecyl dimethyl ammonium carbonate and didecyl dimethyl ammonium bicarbonate, didecyl methyl poly (oxyethyl) -ammonium propionate, an alkaline builder, a surfactant, a complexing agent, and a corrosion inhibitor. Didecyl dimethyl ammonium carbonate and didecyl dimethyl ammonium bicarbonate may be present in the composition in an amount of about 3% by weight to about 15% by weight. Didecyl methyl poly (oxyethyl) -ammonium propionate may be present in the composition in an amount of 3% by weight to about 15% by weight. The alkaline builder may be present in the composition in an amount of about 0.1% by weight to about 8% by weight. The surfactant may be present in the composition in an amount of about 0.1% by weight to about 8% by weight. The complexing agent may be present in the composition in an amount of about 0.1% by weight to about 5% by weight. The corrosion inhibitor may be present in the composition in an amount of about 0.1% by weight to about 5% by weight.

[0062] In another embodiment of the present disclosure, the composition of the present disclosure may include didecyl dimethyl ammonium carbonate and didecyl dimethyl ammonium bicarbonate, which is combined with a second biocide such as N, N-bis (3-aminopropyl) dodecylamine. The composition also optionally includes an alkaline builder, a surfactant and / or a complexing agent. In a non-limiting embodiment, the optional alkaline builder is selected from monoethanolamine (MEA), diethanolamine, triethanolamine and mixtures thereof. The optional surfactant is selected from, but not limited to, polyethylene glycol, alcohol PEG-ether and combinations thereof. The optional complexing agent is selected from, but not limited to, trisodium methylglycine diacetate, tetrasodium ethylenediaminetetraacetate and mixtures thereof.

[0063] In the above embodiments, the composition of the present disclosure may include a first biocide in an amount of 5% to 20% by weight, such as 8% to 18% by weight. The composition may include a second biocide in an amount of 1% to 10% by weight, such as 2% to 8% by weight.

[0064] In one embodiment, the composition may comprise an alkaline builder in an amount of 3% to 12% by weight, such as 5% to 10% by weight.

[0065] In one embodiment, the composition may comprise at least one surfactant in an amount of 1% to 8% by weight, such as 3% to 7% by weight.

[0066] In one embodiment, the composition may comprise a complexing agent in an amount of 2% to 10% by weight, such as 3% to 8% by weight.

[0067] In one embodiment, the composition of the present disclosure may include a first biocide, which includes didecyl dimethyl ammonium carbonate and didecyl dimethyl ammonium bicarbonate, N, N-bis (3-aminopropyl) dodecyl amine, an alkaline builder, a surfactant, and a complexing agent. Didecyl dimethyl ammonium carbonate and didecyl dimethyl ammonium bicarbonate may be present in the composition in an amount of about 5% by weight to about 20% by weight. N, N-bis (3-aminopropyl) dodecyl amine may be present in the composition in an amount of about 1% by weight to about 10% by weight. The alkaline builder may be present in the composition in an amount of about 3% by weight to about 12% by weight. The surfactant may be present in the composition in an amount of about 1% by weight to about 8% by weight. The complexing agent may be present in the composition in an amount of about 2% by weight to about 10% by weight.

[0068] The composition of the present invention can first be formulated as a concentrate, which is then diluted and added to the final product. The relative amounts of the different components can vary significantly based on many factors. These factors include the type of biocide used, the end-use application, and the microorganisms that are desired to be controlled. In one embodiment, the first biocide can be present in a weight ratio of about 20:1 to about 1:20 relative to the second biocide, such as about 1:5 to about 5:1.

[0069] As described above, the first and second biocides can be included together in a concentrate and then diluted when used. For example, when producing a disinfectant product, the first and second biocides can be present in the concentrate in an amount greater than about 5% by weight, such as an amount greater than about 10% by weight, such as an amount greater than about 15% by weight, such as an amount greater than about 20% by weight. The concentrate may contain less than about 50% by weight, such as less than about 30% by weight of the first and second biocides. During use, the concentrate can be diluted so that the final product contains an amount of the first and second biocides greater than about 0.01% by weight, such as greater than about 0.1% by weight, such as greater than about 0.5% by weight, such as greater than about 0.75% by weight, such as greater than about 1% by weight, such as greater than about 1.25% by weight, such as greater than about 1.5% by weight. The final product typically contains less than about 5% by weight, such as less than about 3% by weight, such as less than about 2% by weight of the first and second biocides.

[0070] When the first and second biocides are used as preservatives, the preservative in concentrated form may contain greater than about 15% by weight, such as greater than about 20% by weight, such as greater than about 25% by weight, such as greater than about 30% by weight, such as greater than about 35% by weight of the first and second biocides. The concentrated preservative composition generally contains less than about 50% by weight, such as less than about 45% by weight, such as less than about 40% by weight of the first and second biocides. When added to a product as a preservative, the concentrate is then diluted so that the preservative contains greater than about 0.01% by weight, such as greater than about 0.05% by weight, such as greater than about 0.1% by weight, such as greater than about 0.2% by weight, such as greater than about 0.3% by weight, such as greater than about 0.4% by weight, such as greater than about 0.5% by weight of the first and second biocides. When added to a product, the first and second biocides may be included in the preservative in an amount of less than about 2% by weight, such as less than about 1.5% by weight, such as less than about 1% by weight. However, it should be understood that the above ranges are merely exemplary.

[0071] According to the present invention, a variety of different microorganisms can be killed or controlled. For example, the antimicrobial composition of the present disclosure can control Gram-positive bacteria, Gram-positive bacteria, etc. In addition to bacteria, the antimicrobial composition of the present disclosure can also kill and control the growth of a variety of other microorganisms, such as fungi, viruses, spores, yeasts, mycobacteria, etc.Examples of specific microorganisms that can be killed or controlled according to the present disclosure include Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Serratia marcescens, Salmonella enteritidis, Neisseria gonorrhoeae, Escherichia coli, Enterococcus hirae, Acinetobacter baumannii, Listeria monocytogenes, Enterobacter gergoviae, Klebsiella pneumoniae, Burholderia cepacia, Pseudomonas putida, Kocuria rhizophila, Candida albicans, Saccharomyces cerevisiae. cerevisiae, Aspergillus brasiliensis, Penicillium funiculosum, Eupenicillium levitum, Bacillus cereus, Bacillus subtilis, Clostridium difficile, Clostridium perfringens, Mycobacterium tuberculosis, Mycobacterium terrae, Mycobacterium avium, Poliovirus, Adenovirus, Norovirus, Vaccinia virus, Influenza virus, Hepatitis B virus, Human Immunodeficiency virus, Human papilloma virus, or a mixture thereof.

[0072] In addition to the first biocide and the second biocide, the composition can contain various other components and ingredients. For example, the first and second biocides can be combined with various different components depending on whether the biocides are formulated into a disinfectant product or used as a preservative.

[0073] Disinfectant application

[0074] A variety of different disinfectant compositions can be prepared according to the present disclosure. For example, the disinfectant product can be used to clean hard surfaces, pre-clean disinfection or high-level disinfection equipment and / or used as a hand sanitizer. Generally, the first and second biocides can be incorporated into any suitable disinfectant product.

[0075] When used as a hard surface cleaner, the antimicrobial composition can be delivered to the surface to be cleaned, sanitized or disinfected by conventional methods, such as pouring the composition on the surface; spraying it; applying it to the surface by a spraying device, including but not limited to a pump sprayer, a pressurized sprayer, etc.; saturated wipes; rags and buckets; mops and buckets; sponges and buckets; or applying the antimicrobial composition to the surface by automatic cleaning equipment and other similar and conventional methods to sanitize or disinfect the surface.

[0076] In order to use the antimicrobial composition of the present disclosure, the antimicrobial composition is applied on the surface by spraying, pouring, wiping or otherwise treating the surface with a substrate. Once applied to the surface, the antimicrobial composition is allowed to remain on the surface for a period of time. The antimicrobial composition can be applied to the surface and allowed to dry, or can be dried by wiping the surface with a dry wipe or wiping device.

[0077] Available composition disinfection surfaces include but are not limited to those located in dairy industry, family, health institutions, swimming pools, canning plants, food processing plants, restaurants, hospitals, institutions and industries including secondary oil recovery. Hard surfaces, such as glass and polished aluminum are particularly suitable for application. Specific areas for application include hard surfaces in the family, such as kitchen countertops, cabinets, appliances, waste cans, laundry areas, trash cans, bathroom fixtures, toilets, water tanks, faucets, mirrors, dressing tables, bathtubs and showers. Said composition can also be used for disinfecting floors, walls, furniture, mirrors, toilet fixtures, windows and wood surfaces, such as fence railings, porch railings, decks, roofs, sidings, window frames and door frames. Said composition, quaternary ammonium chloride and disinfection active substances are particularly suitable for indirect food contact surfaces, such as cutting boards, cookware, containers, tableware, wash basins, utensils and countertops. Said composition or quaternary ammonium chloride can be used for disinfecting dairy equipment, milking machines, milk barrels, tank trucks etc. Areas in a hospital include beds, gurneys, tables, cans, toilets, trash cans, racks, cabinets, showers, floors, walls, or any other non-porous surface.

[0078] In addition to hard surface cleaners as described above, the antimicrobial composition may also be incorporated into a hand sanitizer, a pre-disinfectant cleaner, or a high-level disinfectant or sanitizer solution.

[0079] Disinfectants

[0080] When included in the disinfectant product, the biocide can be combined with a variety of different components. For example, in one embodiment, a solvent can be present in the product. Typically, the solvent is a polar solvent such as water, or a water-miscible solvent such as alcohol and / or glycol ether. In addition to water, the antimicrobial composition can also include an organic solvent miscible with water. Examples of water-miscible solvents include ethanol, propyl alcohol, benzyl alcohol, phenoxyethanol, isopropyl alcohol, diethylene glycol propyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, ethylene glycol monoisopropyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether, diethylene glycol mono-n-butyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol dibutyl ether, propylene glycol n-butyl ether, tripropylene glycol methyl ether, dipropylene glycol methyl ether, dipropylene glycol butyl ether and combinations thereof.

[0081] In addition to the solvent, the disinfectant product may contain a surfactant. Typically, the surfactant is a nonionic surfactant or a cationic surfactant. The surfactant is present in an amount of about 1% to about 20% by weight of the disinfectant concentrate. Typically, the surfactant comprises 2% to 15% by weight of the concentrate.

[0082] Particularly suitable surfactants are alkoxylated alcohol surfactants, typically having from about 2 to about 8 moles of alkoxylation. Typically, there will be 3 to 6 moles of alkoxylation. A specific example is about 4.5 moles of alkoxylation. In addition to having a degree of alkoxylation, the alcohol as the alkoxylate will be Ce-C 12 Alkyl alcohol. In one embodiment, the alkyl alcohol is a Cs-C10 alkyl alcohol. The alkoxylation may be ethoxylation. Typically, it is desirable that the HLB (hydrophile-lipophile balance) is in the range of 8-14, more typically between 10-12, for example about 11.

[0083] The nonionic surfactants useful in the present invention include, but are not limited to, polyoxyethylene glycol alkyl ethers, octaethylene glycol monododecyl ether, pentaethylene glycol monododecyl ether, polyoxypropylene glycol alkyl ethers, glucoside alkyl ethers, decyl glucoside, dodecyl glucoside, octyl glucoside, polyoxyethylene glycol octylphenol ether, polyoxyethylene glycol alkylphenol ether, glycerol alkyl esters, polyglycerol esters, lauric acid glyceryl esters, polyoxyethylene glycol sorbitan alkyl esters, sorbitan alkyl esters, dodecyl dimethylamine oxide, block copolymers of polyethylene glycol and polypropylene glycol, poloxamer and polyethoxylated tallow amine (POEA) and mixtures thereof. The amount of the nonionic surfactant in the concentrate is about 1 to about 8% w / w% of the preparation. Typically, the concentrate contains 2 to 5 w / w% of the nonionic surfactant. The amount of the nonionic surfactant in the ready-to-use product is about 0.05 to about 3 w / w% of the solution. In another embodiment, the nonionic surfactant in the product is from about 0.05 to about 1.5 w / w % of the solution. Typically, disinfectant products contain 0.06 to 1 w / w % nonionic surfactant.

[0084] In addition, the disinfectant product may contain an optional chelating agent. Chelating agents include, for example, acetic acid derivatives selected from ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), EDTA tetrasodium. The ability of NTA and EDTA to remove metal ions is beneficial to the solution by preventing hardness (calcium) precipitation. Chelating agents can also be used to bind other metal ions that may adversely affect the effectiveness of the disinfecting components in the composition. In addition, chelating agents can also help remove dirt and / or prevent dirt from being redeposited into the disinfecting composition when used. When present in the concentrate, the chelating agent is generally present in an amount of up to about 20% by weight, and is generally present in an amount of about 2 to about 8% by weight.

[0085] The disinfectant product may also contain a pH adjuster. Suitable pH adjusters include sodium hydroxide, sodium citrate and other similar compounds. In the present invention, the pH of the concentrate and the final disinfectant composition is in the range of about 6 to about 13. If the pH is in the range of about 6 to about 8, the disinfectant composition is generally considered to be a neutral disinfectant composition. When the pH is in the range of 8 to about 12, the disinfectant composition will be considered to be an alkaline disinfectant composition.

[0086] The disinfectant product may optionally further contain corrosion inhibitors, complexing agents, adjuvants, preservatives, fragrances, colorants, and the like. Exemplary corrosion inhibitors include, for example, organic phosphorous compounds and blends of organic phosphorous compounds with polymer components. Exemplary adjuvants include, for example, polyethylene glycol or other similar compounds. Colorants and fragrances may be added as long as they do not interfere with the function of the composition and can be used to identify the composition. Typically, the optional other ingredients account for less than about 20% of the composition weight.

[0087] The antimicrobial composition may also include at least one acid or salt thereof. The acid may be an inorganic acid or an organic acid. In a preferred embodiment, the acid is a C1 to C8 carboxylic acid. In a more preferred embodiment, the acid is a monocarboxylic acid, a dicarboxylic acid, a tricarboxylic acid or a mixture thereof. In a further embodiment, the acid is a hydroxy acid, an aromatic acid or a mixture thereof. In another further embodiment, the acid is methanesulfonic acid, phosphoric acid, etidronic acid, phytic acid, phosphoacetic acid, N-(phosphonomethyl)iminodiacetic acid, diethylenetriamine penta(methylphosphonic acid), S,S-ethylenediamine-N'N'-disuccinic acid, their alkaline salts or any mixture thereof.

[0088] In some embodiments, the acid is citric acid, phosphoric acid, succinic acid, lactic acid, S,S-ethylenediamine-N,N′-disuccinic acid, 1-hydroxyethane 1,1-diphosphonic acid (HEDP), dipicolinic acid (DPA), methanesulfonic acid (MSA), basic salts thereof, or any mixture thereof.

[0089] In a preferred embodiment, the acid is a mixture of acids. In some embodiments, the acid comprises one or more of the following organic acids: citric acid, succinic acid, phosphoric acid and lactic acid. In another embodiment, the acid comprises one or more of the following acids: citric acid, succinic acid, phosphoric acid and lactic acid and another acid. For example, citric acid can be used in combination with ethylenediamine-N, N'-disuccinic acid or its alkaline salt, HEDP and / or MSA. As another example, succinic acid can be used in combination with ethylenediamine-N, N'-disuccinic acid or its alkaline salt, HEDP and / or MSA. As another example, phosphoric acid can be used in combination with ethylenediamine-N, N'-disuccinic acid or its alkaline salt, HEDP and / or MSA. As another example, lactic acid can be used in combination with ethylenediamine-N, N'-disuccinic acid or its alkaline salt, HEDP and / or MSA.

[0090] The composition may include about 1% to about 5% by weight of an organic acid, such as citric acid, succinic acid, phosphoric acid, lactic acid, or any mixture thereof, in combination with another acid. In another aspect, the composition may include about 1% to about 5% by weight of an organic acid, such as citric acid, succinic acid, phosphoric acid, lactic acid, or any mixture thereof, in combination with about 0.05% to about 5% by weight of another acid. In another embodiment, the composition may include about 2% to about 4% by weight of an organic acid, such as citric acid, succinic acid, phosphoric acid, lactic acid, or any mixture thereof, in combination with about 0.1% to about 4% by weight of another acid, such as ethylenediamine-N,N′-disuccinic acid or an alkaline salt thereof, HEDP, and / or MSA.

[0091] A particularly useful application method is to impregnate the disinfectant composition to the wipe substrate. In this embodiment, the wipe is a single-use wipe that is impregnated with the disinfectant composition and stored in a container that distributes the wipe to the user. The container with the wipe can contain a single wipe or a plurality of wipes. Suitable containers include pouches containing a single wipe, such as a wet towelette torn open by the user, or can be a pouch with a resealable opening that contains multiple wipes in a stacked manner, rolled up or other suitable form that allows a single wipe to be taken out of the opening at one time. The pouch is usually made of liquid-impermeable material, such as a film, coated paper or foil or other similar liquid-impermeable material. Another method of distributing the wipe of the present invention is to place the wipe in a liquid-impermeable container having an opening to access the wipe in the container. The container can be a molded plastic container having a liquid-impermeable lid. Typically, the lid will have an opening to access the wipe in the container. The wipes in the container can be staggered so that when the wipes are removed from the container, the next wipe is positioned in the opening of the container, ready for the user to remove the next wipe. Alternatively, the wipes can be a continuous material with perforations between the individual wipes of the continuous material. The continuous wipe material with perforations can be in folded form or can be in rolled form. Typically, in rolled form, the wipe material is fed from the center of the rolled material. As with the staggered stacking, when the wipes are removed from the container, the next wipe is positioned in the opening so that the next wipe is removed when needed.

[0092] Disposable wipes offer advantages over other application carriers (e.g., reusable sponges, rags, etc.). Unlike sponges, rags, etc., which are reused, impregnated wipes are used once and discarded. As mentioned above, reusable sponges or rags are problematic because the sponge or rag may carry microorganisms that are not easily killed by the disinfecting composition. In addition, the disinfecting composition is formulated to treat hard surfaces, rather than porous soft surfaces present in sponges or rags.

[0093] The disinfecting composition can be impregnated into the wipe so that the wipe is pre-wetted and, when the wipe passes through the surface to be treated, the disinfecting composition is squeezed or released onto the surface. Typically, the disinfecting composition is saturated into the wipe so that the wipe releases the disinfecting composition onto the surface by the wiping action. Depending on the wiping substrate, typically about 3 parts by weight of the disinfecting composition are used to saturate per 1 part by weight of the wiping substrate. Typically, the disinfecting composition is used in an amount of about 4 to 6 parts by weight of the disinfecting composition per 1 part of the wipe substrate. Within these ranges, complete saturation of the substrate can be achieved. It should be noted that, depending on the specific wiping substrate, the amount of the disinfecting solution can rise or fall to achieve complete saturation of the wiping substrate.

[0094] Suitable wiping substrates include woven and nonwoven materials. Basically any nonwoven web material can be used. Exemplary nonwoven materials may include, but are not limited to, meltblown, co-formed, spunbonded, air-laid, hydraulically entangled nonwoven fabrics, spunlace, bonded carded webs and laminates thereof. Optionally, nonwoven materials may also be laminated with film materials. The fiber used to prepare the wiping substrate may be cellulosic fiber, thermoplastic fiber and mixtures thereof. Fiber may also be long fiber, discontinuous fiber, staple fiber and mixtures thereof. The basis weight of the nonwoven web may be about 12 g / m2 to 200 g / m2 or higher.

[0095] In one embodiment, the wipe is impregnated with a liquid composition containing two active and inert ingredients within the tolerance allowed, and the disinfectant composition squeezed from the wipe contains an active ingredient within the tolerance allowed. Once applied to the surface, the antimicrobial disinfectant composition is allowed to remain on the surface for a period of time. The antimicrobial composition can be applied to the surface and allowed to dry, or it can be dried by wiping the surface with a dry wipe or wiping device, preferably without using this method.

[0096] When the wipe or disinfecting composition of the present invention is used to wipe a surface, disinfection is achieved in less than 4 minutes, typically 3 minutes or less, particularly in 90 seconds or less. It will be appreciated by those of ordinary skill in the art that the antimicrobial disinfecting composition maintains contact with the surface in need of disinfection for a sufficient time to cause disinfection. It has been found that the composition of the present invention is effective for many different microorganisms, including but not limited to.

[0097] In yet another embodiment, the disinfectant composition can be used as a hand sanitizer. When used as a hand sanitizer, the biocide of the present disclosure can be combined with any of the above ingredients. For example, in one embodiment, the biocide can be combined with a solvent, such as water and / or alcohol. In a particular application, a foaming agent can be added that causes the composition to foam when pumped from a dispenser. The foaming agent can include any suitable foaming agent that is compatible with the biocide. For example, in one embodiment, the foaming agent can include dimethicone.

[0098] In one embodiment, the composition of the present disclosure may include a second biocide and a third biocide in combination with the first biocide. For example, in one embodiment, the second biocide may include a dimethyl dialkyl ammonium compound as described above, and the third biocide may include an aromatic dialdehyde. The aromatic dialdehyde is selected from o-phthalaldehyde (OPA), isophthalaldehyde, terephthalaldehyde, or a combination thereof. The structure of the phthalaldehyde isomer is shown below:

[0099]

[0100] In one embodiment, the preferred aromatic dialdehyde is OPA.

[0101] In one embodiment, the disinfectant composition can be used to disinfect instruments, such as pre-cleaning and disinfection of equipment, medical devices or endoscopes or for regular, high-level disinfection. In one embodiment, when handling instruments in a manual process, the disinfectant composition can be applied by immersing the instruments in a disinfectant composition of appropriate concentration. For example, a plastic or metal container, a stainless steel sink or any other suitable container can be used as a container for holding the disinfectant composition. In one embodiment, it may be necessary to fully immerse the instrument or device or endoscope, including spaces, cavities and hollow parts. When used for disinfection of instruments such as endoscopes, the channels of endoscopes and other instruments may need to be rinsed. Typically, after disinfection, the instruments must be cleaned and thoroughly rinsed with water, preferably with a large amount of water.

[0102] In applications involving instruments, the appropriate concentration of the disinfectant composition may be about 500 mg / L to about 25,000 mg / L, such as about 1,000 mg / L to about 23,000 mg / L. For pre-cleaning, the preferred concentration of the disinfectant composition may be about 500 mg / L to about 10,000 mg / L, such as about 1,000 mg / L to about 9,000 mg / L, such as about 2,000 mg / L to about 8,000 mg / L, such as about 3,000 mg / L to about 7,000 mg / L, such as about 4,000 mg / L to about 6,000 mg / L. For high-level disinfection, the preferred concentration of the disinfectant composition may be about 5,000 mg / L to about 25,000 mg / L, such as about 8,000 to about 23,000 mg / L, such as about 10,000 to about 20,000 mg / L. In embodiments where the instrument is immersed in the disinfectant composition, the necessary contact time may be from about 10 minutes to about 60 minutes, preferably from about 15 minutes to about 30 minutes. The necessary contact time may be adjusted based on the target disinfection level. In yet another embodiment, the disinfectant composition may be used for disinfection of instruments in an automatic washer-disinfector.

[0103] preservative

[0104] In addition to disinfectant compositions, biocides of the present invention may also be used as preservatives. When used as preservatives, biocides may be incorporated into any suitable product, such as paints, latex emulsions, polymer emulsions, adhesives, sealants, caulking agents, mineral or pigment slurries, printing inks, pesticide formulations, household products, personal care products, sanitary products, metalworking fluids, etc. In addition, preservatives may be incorporated into building materials. Personal care products that may contain preservatives include cosmetic preparations, such as creams, makeup removers, or mascara. Personal care products may also include shampoo, conditioner, or lotion.

[0105] When used as a preservative, the biocide may be combined with any suitable surfactant. The surfactant may comprise, for example, anionic surfactants.

[0106] Suitable anionic surfactants having a sulfate moiety include sulfates represented by the formula RSO4M, wherein R is a chain having about 10 to about 18 atoms in the backbone of the chain, and M is a cation such as ammonium; an alkanolamine such as triethanolamine; a monovalent metal such as sodium and potassium; and a polyvalent metal such as magnesium and calcium. In one embodiment, the anionic surfactant having a sulfate moiety is an alkyl sulfate, wherein R is an alkyl having 10-18 carbon atoms, preferably 10-16 carbon atoms, more preferably 10-14 carbon atoms. R can be straight or branched. Advantageously, R is a straight chain. In one embodiment, R is an octyl group.

[0107] Exemplary alkyl sulfates include sodium lauryl sulfate, potassium lauryl sulfate, triethylamine lauryl sulfate, triethanolamine lauryl sulfate, monoethanolamine lauryl sulfate, diethanolamine lauryl sulfate, and ammonium lauryl sulfate.

[0108] Suitable anionic surfactants having a sulfonate moiety include sulfonates having the formula RSO3M, wherein R is a straight or branched chain containing 10 to 18 atoms in the backbone of the chain, and M is a cation such as ammonium; an alkanolamine such as triethanolamine; a monovalent metal such as sodium and potassium; and a polyvalent metal such as magnesium and calcium. In one embodiment, R contains a succinate group on the backbone. In another embodiment, R is an alkyl group containing from about 10 to about 18 carbon atoms, preferably from about 10 to about 16 carbon atoms, and more preferably from about 10 to about 14 carbon atoms.

[0109] Exemplary sulfonates suitable for use in the compositions of the present invention include dioctyl sodium sulfosuccinate, and primary and secondary alkyl sulfonates.

[0110] Suitable anionic surfactants (ii) are alkyl aryl sulfonic acids or salts thereof wherein the alkyl portion contains from about 10 to about 18 carbon atoms and the aryl portion contains benzyl or substituted benzyl.

[0111] In one embodiment, the alkyl aryl sulfonic acid is represented by the formula

[0112]

[0113] wherein R is an alkyl group having from about 10 to about 18, preferably from 10 to 16, more preferably from 10 to 14 carbon atoms. 12 alkyl.

[0114] The presence or absence of surfactants may depend on the end-use application of the composition. In this regard, the composition (concentrate or final product) may contain emulsifiers, consistency factors, emollients, thickeners, fillers, lubricants, fragrances, and the like.

[0115] When incorporated into personal care products, the products may contain emulsifiers, consistency factors, emollients and / or active ingredients.

[0116] Suitable emulsifiers are, for example, anionic surfactants such as salts of fatty acids, for example sodium stearate or sodium palmitate, organic soaps such as mono-, di- or tri-ethanolaminoeate, sulfated or sulfonated compounds, for example sodium lauryl sulfate or sodium cetyl sulfonate, saponins, lamepones; cationic surfactants such as quaternary ammonium salts; nonionic surfactants such as fatty alcohols, fatty acid esters with saturated or unsaturated fatty acids, polyoxyethylene esters or polyoxyethylene ethers of fatty acids, polymers from ethylene oxide and propylene oxide or propylene glycol, amphoteric surfactants such as phospholipids, proteins such as gelatin, casein alkylamidobetaines, alkyl betaines and amphoteric glycinates, alkyl phosphates, alkyl polyoxyethylene phosphates or the corresponding acids, silicone derivatives, for example alkyl dimethiconecoplyol.

[0117] Suitable consistency factors are, for example, fatty alcohols or mixtures thereof with fatty acid esters, for example acetylated lanolin alcohol, aluminum stearate, carbomer, cetyl alcohol, glyceryl oleate, glyceryl stearate, glyceryl stearate (and) PEG 100 stearate, magnesium stearate, magnesium sulfate, oleic acid, stearic acid, stearyl alcohol, myristyl myristate, isopropyl palmitate, beeswax and its synthetic equivalents, carbomer, etc. Suitable conditioning agents are, for example, alkylamidoammonium lactylates, cetrimonium chloride and distearoylethyl hydroxyethylmonium methosulfate and cetearyl alcohol, cetyl dimethicone, cetyl ricinoleate, dimethicone, laureth-23, laureth-4, polydecene, retinyl palmitate, quaternized protein hydrolysates, quaternized cellulose and starch derivatives, quaternized copolymers of acrylic acid or methacrylic acid or salts, quaternized silicone derivatives.

[0118] Suitable emollients are, for example, cetearyl isononanoate, cetyl octanoate, decyl oleate, isooctyl stearate, coco-caprylate / caprate, ethylhexyl hydroxystearate, ethylhexyl isononanoate, isopropyl isostearate, isopropyl myristate, oleyl oleate, hexyl laurate, petrolatum, PEG-75 lanolin, PEG-7 glyceryl cocoate, petrolatum, ozokerite, dimethicone, dimethicone copolyol, dicaprylyl ether, shea butter, boxwood, canola, carnauba wax, carnauba, evening primrose, palm oil, sweet almond oil, squalane, corn silk powder, soy bean, sunflower, lanolin, hydrogenated castor oil, hydrogenated coconut oil, hydrogenated polyisobutene, sucrose cocoate, stearyl dimethiconol, lanolin alcohol, isohexadecane.

[0119] The composition may further contain active ingredients such as antimicrobial agents, anti-inflammatory agents, plant extracts, bisabolol, panthenol, tocopherol, active agents for anti-stinging, anti-irritants or anti-dandruff agents, or anti-aging agents such as retinol, melibiose and the like. Other suitable active substances are, for example, Medicago officinalis, kiwi fruit, allantoin, aloe vera, custard apple, white chamomile, peanut, mountain aronia, oats, beta-carotene, bisabolol, borage, butylene glycol, calendula, large leaf tea, camphor, candida, capryloyl glycine, papaya, cornflower, cetylpyridinium chloride, German chamomile, quinoa, chicken tree, crisp wave hornwort, Citrus aurantium dulcis, grapefruit, citrus, coconut, coffee, hawthorn, melon, dichlorophenyl imidazole dioxolane, enteromorpha, horsetail, ethyl diglycol ether, ethyl panthenol, farnesol, ferulic acid, strawberry, gentiana, ginkgo, glycerin, lauric acid glyceryl, licorice, witch hazel, heliotropin, hydrogenated palm glycerides, citrate, hydrolyzed castor oil, hydrolyzed wheat protein, hypericum perforatum, iris vetiver, juniperus chinensis, milk protein, lactose, henna, linalool, flax, lysine, magnesium aspartate, Magnifera indica, mallow, mannitol, melaleuca alternifolia, peppermint, menthol, menthyl lactate, mimosa, white water lily, oraflutol, rice, panthenol, liquid paraffin, PEG-20M, PEG-26 jojoba acid, PEG-26 jojoba alcohol, PEG-35 castor oil, PEG-40 hydrogenated castor oil, PEG-60 hydrogenated castor oil, PEG-8 caprylic / capric acid, persea gratissima oil, petrolatum, potassium aspartate, potassium sorbate, propylene glycol, prunes dulcis, apricot, peach, retinyl palmitate, castor, rosa canina, rosemary, raspberry, salicylic acid, sambucus nigra, sarcosine, saw palmetto, jojoba oil, sodium carboxymethyl beta-glucan, sodium cocoyl amino acids, sodium hyaluronate, sodium palmitoyl proline, stearoxytrimethylsilane, stearyl alcohol, TEA-ricinoleate sulfate, talc, thyme, tilia microphylla, tocopherol, tocopheryl acetate, trideceth-9, wheat germ, tyrosine, undecylenyl glycine, urea, vaccinium myrtillus, valine, zinc oxide, zinc sulfate.

[0120] The present invention may be better understood by reference to the following examples. Example

[0121] Various different biocides were tested for their minimum inhibitory concentrations against various microorganisms. More specifically, MIC tests were performed for quaternary ammonium carbonate / quaternary ammonium bicarbonate and various other biocides. The quaternary ammonium carbonate / quaternary ammonium bicarbonate was then combined with one other biocide and tested for synergistic interactions against various microorganisms. The following results demonstrate the synergistic effect of quaternary ammonium carbonate / quaternary ammonium bicarbonate with other biocides.

[0122] Material

[0123] Obtain sterile 96-well microtiter plates from Fisher scientific.

[0124] Titretek self-adhesive panel sealant was obtained from Fisher scientific.

[0125] 50 ml reservoir obtained from Fisher scientific

[0126] Malt agar, malt broth, nutrient agar, and nutrient broth were obtained from E&O.

[0127] Microbial strains used

[0128] Bacteria Escherichia coli ATCC 1576

[0129] Staphylococcus aureus ATCC 799

[0130] Pseudomonas aeruginosa ATCC 9027

[0131] Maintenance of stock cultures

[0132] Bacteria were maintained on nutrient agar and fungi were maintained on malt agar or in a spore suspension in physiological saline (0.85% (w / v) NaCl).

[0133] Calculation of minimum inhibitory concentration

[0134] The bacteria were grown in nutrient broth until the stationary phase (18 hours) (approximately 10 9 Organisms). 0.1% (V / V) inoculum was used to inoculate fresh medium and 100 μL was added to each well of the microtiter plate, except for the first well which contained 200 μL. Using two-fold dilutions, the concentration of each antimicrobial agent was varied in each well along the ordinate axis. The presence of growth was determined by visual inspection after incubation at 37°C for 24 hours.

[0135] Calculating synergy using microtiter plates

[0136] A simple matrix was constructed in which the two compounds under investigation were present at different concentrations, from 2x MIC (minimum inhibitory concentration) to zero concentration in an 8 x 8 array. After pre-diluting the test materials in deionized water, solutions were prepared in broth at twice the desired final concentration.

[0137] Each solution (100 μl) was added to the plate so that the total volume of each mixture in each well was 200 μl. Nutrient broth was used for E. coli and S. aureus, and malt broth was used for C. albicans. The plates were incubated at 37°C for 16-24 hours for bacteria, 48 hours for yeast, and 40-72 hours for fungi. The presence or absence of growth was recorded by visual inspection.

[0138] result

[0139] The minimum inhibitory concentration (MIC) is the lowest concentration of a biocide that shows growth inhibition when used alone. The results are shown in Table 1.

[0140] Table 1: Minimum inhibitory concentrations

[0141]

[0142] The contribution to microbial inhibition provided by each biocide in the mixture - the fractional inhibition concentration (FIC) - was calculated as the concentration of biocide in the mixture that controlled growth divided by the amount of biocide required to control growth when used alone. FIC values ​​were calculated for all compounds in the study in combination with quaternary ammonium carbonate / bicarbonate.

[0143] FIC = Concentration of biocide A attributable to antimicrobial activity in the mixture / MIC of biocide A

[0144] The sum of these numbers gives an indication of the effect of the two biocides. A value less than 1 indicates a synergistic effect. If the total is equal to 1, the effect is additive or neutral, and if the value is greater than 1, the biocides are antagonistic.

[0145] The result is shown below.

[0146] Synergistic mixture of didecyldimethylammonium carbonate / didecyldimethylammonium bicarbonate against Escherichia coli

[0147] Table 2: Calculated fractional inhibition concentrations for didecyldimethylammonium carbonate / didecyldimethylammonium bicarbonate and N-3-aminopropyl-N-dodecylpropane-1-3-diamine

[0148]

[0149] Table 3: Calculated fractional inhibition concentrations for didecyldimethylammonium carbonate / didecyldimethylammonium bicarbonate and alkyldimethylbenzylammonium chloride

[0150]

[0151] Table 4: Fractional Inhibitory Concentrations Calculated for Didecyldimethylammonium Carbonate / Didecyldimethylammonium Bicarbonate and N,N-Didecyl-N-methyl-Poly(oxyethyl)ammonium Propionate

[0152]

[0153] Synergistic mixture of didecyldimethylammonium carbonate / didecyldimethylammonium bicarbonate against Pseudomonas aeruginosa

[0154] Table 5: Calculated fractional inhibition concentrations for didecyldimethylammonium carbonate / didecyldimethylammonium bicarbonate and N-3-aminopropyl-N-dodecylpropane-1-3-diamine

[0155]

[0156] Table 6: Fractional Inhibitory Concentrations Calculated for Didecyldimethylammonium Carbonate / Didecyldimethylammonium Bicarbonate and Alkyldimethylbenzylammonium Chloride

[0157]

[0158] Table 7: Fractional Inhibitory Concentrations Calculated for Didecyl Dimethyl Ammonium Carbonate / Didecyl Dimethyl Ammonium Bicarbonate and Benzyl C12-16 Alkyl Dimethyl Chloride

[0159]

[0160] Table 8: Calculated fractional inhibition concentrations for didecyldimethylammonium carbonate / didecyldimethylammonium bicarbonate and alkyldimethylbenzylammonium chloride

[0161]

[0162] Table 9: Fractional Inhibitory Concentrations Calculated for Didecyl Dimethyl Ammonium Carbonate / Didecyl Dimethyl Ammonium Bicarbonate and N,N-Didecyl-N-methyl-Poly(oxyethyl)ammonium Propionate

[0163]

[0164] Table 10: Fractional Inhibition Concentrations Calculated for Didecyl Dimethyl Ammonium Carbonate / Didecyl Dimethyl Ammonium Bicarbonate and Di-C8-10 Alkyl Dimethyl Chloride + Benzyl C12-16 Alkyl Dimethyl Chloride

[0165]

[0166] Table 11: Calculated Fractional Inhibitory Concentrations for Didydecyldimethylammonium Carbonate / Didecyldimethylammonium Bicarbonate and Sodium Pyrithione

[0167]

[0168] A synergistic interaction is when the combined effect of two chemicals is greater than their individual effects. For disinfection, this means that a pair of synergistic biocides have greater antimicrobial activity against certain microorganisms in the presence of each other than in the presence of only a single biocide.

[0169] As shown above, significant and unexpected synergy was demonstrated between the quaternary ammonium carbonate / quaternary ammonium bicarbonate biocides tested and other biocides. In fact, as shown above, in many cases, the sum of the fractional inhibition concentrations of the two biocides was less than about 0.9, such as less than about 0.8, such as less than about 0.7. The sum of the fractional inhibition concentrations of the two biocides was typically greater than about 0.4.

[0170] Without departing from the spirit and scope of the present invention, those of ordinary skill in the art may implement these and other modifications and variations of the present invention, which are more specifically set forth in the appended claims. In addition, it should be understood that the various aspects of the various embodiments may be interchangeable in whole or in part. In addition, those of ordinary skill in the art will appreciate that the foregoing description is merely exemplary and is not intended to limit the present invention as further described in the appended claims.

Claims

1. A composition having biocidal properties, comprising: a first biocide comprising a carbonate salt of a quaternary ammonium cation and / or a bicarbonate salt of a quaternary ammonium cation; and The second biocide is selected so as to act synergistically with the first biocide to kill or inhibit the growth of microorganisms, the second biocide comprising alkyl dimethyl benzyl ammonium chloride, N,N-didecyl-N-methyl-poly(oxyethyl) ammonium propionate, di-C8 to C 12 Alkyl dimethyl ammonium chloride, or benzyl C 12 To C 16 alkyldimethylammonium chloride, and wherein the second biocide is present relative to the first biocide such that the ability of both biocides to kill or inhibit the growth of microorganisms is greater than if only one biocide were present at the same concentration with the two biocides together; Wherein the first biocide and the second biocide are present in the composition in a weight ratio of 1:5 to 5:

1.

2. A composition as defined in claim 1, wherein the first biocide has a fractional inhibition concentration against microorganisms in the composition, and the second biocide also has a fractional inhibition concentration against microorganisms in the composition, and wherein the sum of the fractional inhibition concentration of the first biocide and the fractional inhibition concentration of the second biocide is less than 1.

3. A composition as defined in claim 1, wherein the first biocide has a fractional inhibition concentration against microorganisms in the composition, and the second biocide also has a fractional inhibition concentration against microorganisms in the composition, and wherein the sum of the fractional inhibition concentration of the first biocide and the fractional inhibition concentration of the second biocide is less than 0.

9.

4. A composition as defined in claim 3, wherein the sum of the fractional inhibition concentration of the first biocide and the fractional inhibition concentration of the second biocide is less than 0.

8.

5. A composition as defined in claim 4, wherein the sum of the fractional inhibition concentration of the first biocide and the fractional inhibition concentration of the second biocide is less than 0.

7.

6. A composition as defined in any one of claims 1 to 5, wherein the microorganism comprises a Gram-positive bacterium.

7. A composition as defined in any one of claims 1 to 5, wherein the microorganism comprises a Gram-negative bacterium.

8. A composition as defined in any one of claims 1 to 5, wherein the microorganism comprises a fungus, a virus, a yeast, a spore or a mycobacterium.

9. A composition as defined in any one of claims 1 to 5, wherein the carbonate of the quaternary ammonium cation and / or the bicarbonate of the quaternary ammonium cation comprises at least one di-C8 to C 12 Alkyl ammonium carbonate and / or ammonium bicarbonate.

10. A composition as defined in any one of claims 1 to 5, wherein the carbonate salt of the quaternary ammonium cation and / or the bicarbonate salt of the quaternary ammonium cation comprises didecyldimethylammonium carbonate and / or ammonium bicarbonate.

11. A composition as defined in any one of claims 1 to 5, wherein the microorganisms include Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Serratia marcescens, Salmonella enteritidis, Neisseria gonorrhoeae, Escherichia coli, Enterococcus hirae, Acinetobacter baumannii, Listeria monocytogenes, Enterobacter gergoviae, Klebsiella pneumoniae, Burholderia cepacia, Pseudomonas putida, Kocuria rhizophila, rhizophila, Candida albicans, Saccharomyces cerevisiae, Aspergillus brasiliensis, Penicillium funiculosum, Eupenicillium levitum, Bacillus cereus, Bacillus subtilis, Clostridium difficile, Clostridium perfringens, Mycobacterium tuberculosis, Mycobacterium terrae, Mycobacterium avium, poliovirus, adenovirus, norovirus, vaccinia virus, influenza virus, hepatitis B virus, human immunodeficiency virus and / or human papillomavirus.

12. A disinfectant composition comprising: a first biocide comprising a carbonate salt of a quaternary ammonium cation and / or a bicarbonate salt of a quaternary ammonium cation; The second biocide is selected so as to act synergistically with the first biocide to kill or inhibit the growth of microorganisms, the second biocide comprising alkyl dimethyl benzyl ammonium chloride, N,N-didecyl-N-methyl-poly(oxyethyl) ammonium propionate, di-C8 to C 12 Alkyl dimethyl ammonium chloride, or benzyl C 12 To C 16 alkyldimethylammonium chloride, and wherein the second biocide is present relative to the first biocide such that the ability of both biocides to kill or inhibit the growth of microorganisms is greater than if only one biocide were present at the same concentration as the two biocides together; and One or more adjuvants selected from solvents, surfactants, chelating agents, complexing agents, corrosion inhibitors, alkaline synergists, pH adjusters, preservatives, adjuvants, acids, foaming agents, fragrances and colorants; Wherein the first biocide and the second biocide are present in the composition in a weight ratio of 1:5 to 5:

1.

13. A cosmetic or hygiene product comprising: Base formulation; and A preservative comprising a composition as defined in any one of claims 1 to 12.

14. A method for disinfecting adjacent objects for non-therapeutic purposes, comprising: The antimicrobial composition is mixed with one or more adjuvants, the antimicrobial composition comprising a combination of a first biocide and a second biocide, the first biocide comprising a carbonate of a quaternary ammonium cation and / or a bicarbonate of a quaternary ammonium cation, the second biocide being selected to synergistically act with the first biocide to kill or inhibit the growth of microorganisms, the second biocide comprising alkyl dimethyl benzyl ammonium chloride, N,N-didecyl-N-methyl-poly(oxyethyl) ammonium propionate, di-C8 to C 12 Alkyl dimethyl ammonium chloride, or benzyl C 12 To C 16 alkyl dimethyl ammonium chloride, the second biocide being present relative to the first biocide such that the ability of both biocides to kill or inhibit the growth of microorganisms is greater than if only one biocide were present at the same concentration with the two biocides; wherein the one or more auxiliary agents are selected from solvents, surfactants, chelating agents, complexing agents, corrosion inhibitors, alkaline synergists, pH adjusters, preservatives, adjuvants, acids, foaming agents, fragrances and colorants; Wherein the first biocide and the second biocide are present in the composition in a weight ratio of 1:5 to 5:

1.

15. A method for non-therapeutic purposes as defined in claim 14, wherein the microorganism comprises a Gram-positive bacterium.

16. A method for non-therapeutic purposes as defined in claim 14, wherein the microorganisms comprise Gram-negative bacteria.

17. A non-therapeutic method as defined in claim 14, wherein the first biocide has a fractional inhibition concentration against microorganisms in the composition, and the second biocide also has a fractional inhibition concentration against microorganisms in the composition, and wherein the sum of the fractional inhibition concentration of the first biocide and the fractional inhibition concentration of the second biocide is less than 1.

18. A non-therapeutic method as defined in claim 14, wherein the first biocide has a fractional inhibition concentration against microorganisms in the composition, and the second biocide also has a fractional inhibition concentration against microorganisms in the composition, and wherein the sum of the fractional inhibition concentration of the first biocide and the fractional inhibition concentration of the second biocide is less than 0.

9.

19. The non-therapeutic method as defined in claim 18, wherein the sum of the fractional inhibitory concentration of the first biocide and the fractional inhibitory concentration of the second biocide is less than 0.

8.

20. The non-therapeutic method as defined in claim 19, wherein the sum of the fractional inhibitory concentration of the first biocide and the fractional inhibitory concentration of the second biocide is less than 0.7.

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