Antimicrobial compositions comprising nonanoic acid

Abstract

The present disclosure provides antimicrobial compositions comprising phenoxyethanol, benzyl alcohol, or a combination thereof, and nonanoic acid and / or a salt thereof as antimicrobial agents, and further provides uses and uses of the antimicrobial compositions of the present disclosure in product formulations, particularly personal care formulations and home care formulations.

Description

Antimicrobial compositions containing nonanoic acid Technical Field

[0001] This invention relates to the synergistic enhancement of the antimicrobial activity of certain antimicrobial agents that can be used in a wide range of product formulations, particularly personal care and home care formulations. Background Technology

[0002] Protective protection against microbial contamination in product formulations such as personal care products (e.g., cosmetics) and household care products plays a central role in consumer safety, product stability, integrity, quality assurance, regulatory compliance, sustainability, and other factors. Traditional preservatives, such as isothiazolinones, formaldehyde releasers, parabens, and IPBCs, are under increasing scrutiny regarding their potential health and environmental impacts. This, along with consumer preferences, has led to a growing demand for alternative preservatives that are both effective and aligned with contemporary expectations. While many product formulators have turned to “soft” preservatives, such as phenoxyethanol and benzyl alcohol, these agents alone, especially at desired dosage levels, often do not provide the full-spectrum antimicrobial efficacy necessary for robust protection, potentially complicating their use in product formulations and / or requiring undesirable high dosage levels.

[0003] Therefore, there is an urgent need to address the efficacy gaps of certain soft preservatives while meeting consumers' growing demand for natural and sustainable products.

[0004] This disclosure, which is further described herein, satisfies this and other needs. Summary of the Invention

[0005] This disclosure provides an antimicrobial composition comprising (a) an antimicrobial agent selected from the group consisting of phenoxyethanol, benzyl alcohol, and combinations thereof, and (b) nonanoic acid and / or a salt thereof, wherein the weight ratio of the antimicrobial agent (a) to nonanoic acid (b) is from about 40:1 to about 1:5, preferably from about 40:1 or from about 20:1 to about 1:2.5.

[0006] Aqueous product formulations, such as personal care or home care product formulations, are also provided, which contain an effective amount of the antimicrobial composition of this disclosure.

[0007] A further method for controlling or inhibiting microbial growth in a product formulation (such as a personal care or home care formulation) is provided, comprising adding to the formulation (a) an antimicrobial agent selected from the group consisting of phenoxyethanol, benzyl alcohol, and combinations thereof, and (b) nonanoic acid and / or a salt thereof, wherein the weight ratio of the antimicrobial agent (a) to the nonanoic acid and / or its salt (b) is from about 40:1 to about 1:5, preferably from about 40:1 or from about 20:1 to about 1:2.5, and adding the antimicrobial agent (a) and the nonanoic acid and / or its salt (b) in an antimicrobially effective amount.

[0008] In another aspect, this disclosure includes a method for enhancing the antimicrobial efficacy of an antimicrobial agent selected from the group consisting of phenoxyethanol, benzyl alcohol, and combinations thereof, the method comprising combining or mixing nonanoic acid and / or its salts with the antimicrobial agent in a weight ratio of antimicrobial agent to nonanoic acid of about 40:1 to about 1:5, preferably about 40:1 or about 20:1 to about 1:2.5.

[0009] It also provides the use of nonanoic acid and / or its salts for enhancing the antimicrobial efficacy of an antimicrobial agent selected from the group consisting of phenoxyethanol, benzyl alcohol, and combinations thereof, wherein the weight ratio of the antimicrobial agent to nonanoic acid and / or its salt is from about 40:1 to about 1:5, preferably from about 40:1 or from about 20:1 to about 1:2.5.

[0010] Another method is provided for reducing the minimum amount of antimicrobial preservative required for preservative activity in a product formulation (such as a personal care or home care formulation), comprising combining or mixing nonanoic acid and / or its salts with an antimicrobial agent in the product formulation, wherein the antimicrobial agent is selected from the group consisting of phenoxyethanol, benzyl alcohol and combinations thereof, and the weight ratio of the antimicrobial agent to nonanoic acid and / or its salts is from about 40:1 to about 1:5, preferably from about 40:1 or from about 20:1 to about 1:2.5. Detailed Implementation

[0011] According to this disclosure, it has been unexpectedly found that nonanoic acid and / or its salts, when combined with an antimicrobial agent selected from phenoxyethanol, benzyl alcohol, and combinations thereof in the ratios described herein, synergistically enhance the antimicrobial activity of the antimicrobial agent. Furthermore, as demonstrated in this disclosure, it has been further unexpectedly found that when the antimicrobial agent is combined with nonanoic acid and / or its salts, enhanced antimicrobial activity is achieved in product formulations having a pH higher than (even significantly higher than) that of nonanoic acid (pKa 4.95 at 25°C), such as in formulations having a pH of at least 6.0, at least 6.5, at least 7.0, or higher as described herein. Therefore, the combinations of this disclosure with nonanoic acid are advantageously applicable to a wide range of product formulations, while also allowing for a reduction in the amount of antimicrobial agent typically required to achieve sufficient antimicrobial performance. Furthermore, nonanoic acid and / or its salts, along with antimicrobial agents selected from phenoxyethanol, benzyl alcohol, and combinations thereof, can be incorporated into antimicrobial compositions, for example, to inhibit microbial growth in the final product formulation or to preserve the final product formulation, without the need for an added solvent in the antimicrobial composition. According to this disclosure, it has been further found that additional antimicrobial agents, such as alkyl hydroxamic acids, can be used, typically in small amounts relative to the combined amount of the antimicrobial agent (a) with nonanoic acid and / or its salts (b), to increase the antimicrobial properties of the composition at the same total load level. As demonstrated herein, nonanoic acid and / or its salts exhibit a superior enhancement of the antimicrobial activity of the antimicrobial agent compared to two commercial multifunctional synergist benchmarks, 2-ethylhexylglycerol and 1,2-hexanediol, at the same dosage level.

[0012] Furthermore, according to the present invention, it has been found that the stability of an antimicrobial composition comprising (a) an antimicrobial agent and (b) nonanoic acid and / or its salts over time can be significantly improved by comprising at least one alkaline stabilizer selected from the group consisting of phenoxyethanol, benzyl alcohol and combinations thereof.

[0013] Unless otherwise stated, the following terms are defined as follows: As used herein, "formulation" means a preparation which is preserved or provided with antimicrobial activity by employing an antimicrobial agent (a) of this disclosure in combination with nonanoic acid and / or its salts (b).

[0014] As used herein, “antimicrobial effective amount” refers to the amount that provides the desired antimicrobial effect or activity, such as the desired preservative, antibacterial and / or antifungal effect.

[0015] As used herein, "synergistic" means that the combined antimicrobial effect (e.g., antibacterial and / or antifungal effect) is greater than the sum of the effects of each component.

[0016] As used herein, “microorganism” includes, for example, bacteria and fungi (such as yeast and mold).

[0017] Unless otherwise stated, pH value or its range refers to pH at room temperature (20-25°C).

[0018] The antimicrobial composition disclosed herein comprises (a) an antimicrobial agent selected from the group consisting of phenoxyethanol (2-phenoxyethyl-1-ol), benzyl alcohol, and combinations thereof, and (b) nonanoic acid and / or a salt thereof, wherein the weight ratio of the antimicrobial agent (a) to nonanoic acid or a salt thereof is from about 40:1 to about 1:5, preferably from about 40:1 or from about 20:1 to about 1:2.5. Nonanoic acid (also known as pelargonic acid) is a naturally occurring fatty acid having a saturated nine-carbon straight chain and which can be naturally derived from vegetable oils, except through other extraction or production processes. Examples of suitable salts of nonanoic acid include, but are not limited to, alkali metal salts such as sodium and potassium salts (i.e., sodium nonanoate, potassium nonanoate) and ammonium salts (i.e., ammonium nonanoate).

[0019] In many embodiments, the antimicrobial agent (a) is phenoxyethanol. In many other embodiments, the antimicrobial agent (a) is benzyl alcohol. In still other embodiments, the antimicrobial agent (a) is any combination of phenoxyethanol and benzyl alcohol.

[0020] Preferably, the weight ratio of the antimicrobial agent (a) to nonanoic acid and / or its salt (b) is about 40:1 or about 20:1 to about 1:2.5, for example about 20:1, preferably about 15:1, more preferably about 10:1, even more preferably about 5:1 or about 3:1 to about 1:2, preferably about 1:1.5, about 1:1.25, about 1:1.2, about 1:1.15, about 1:1.1, about 1:1.05, or more preferably about 1:1. In particular, this ratio is preferably about 15:1 to about 1:1.5, more preferably about 10:1, even more preferably about 5:1 or about 3:1 to about 1:1.25, about 1:1.2, about 1:1.1, or more preferably about 1:1. The optimized amount and ratio can vary depending on, for example, the application, the desired performance of the product, etc. As demonstrated herein, the antimicrobial activity (e.g., antibacterial and / or antifungal effects) of antimicrobial agents (a) is synergistically enhanced against a wide range of microorganisms, including bacteria and fungi. For example, among other microorganisms, the combinations disclosed herein preferably control Gram-positive bacteria, Gram-negative bacteria, and fungi. Non-limiting embodiments include Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli, Enterobacter gergoviae, Klebsiella pneumoniae, Burholderia cepacia, Pseudomonas putida, Candida albicans, Aspergillus brasiliensis, and mixtures thereof.

[0021] The antimicrobial agent (a) and nonanoic acid and / or its salt (b) typically constitute 50 to 100 wt% of the active ingredient in the antimicrobial composition, typically the majority (>50 wt%) of the active ingredient, for example at least 60 wt% or at least 70 wt%, more preferably at least 80 wt%, even more preferably at least 85 wt%, at least 90 wt%, at least 95 wt%, at least 96 wt%, at least 97 wt%, at least 98 wt%, or at least 99 wt%, based on the total weight of the active ingredient in the antimicrobial composition. The antimicrobial composition typically contains about 60 to 100 wt%, preferably about 65 to 100 wt%, about 70 to 100 wt%, about 75 to 100 wt%, about 80 to 100 wt%, about 85 to 100 wt%, about 90 to 100 wt%, or about 95 or about 97 to 100 wt% of the combination of the antimicrobial agent (a) and nonanoic acid and / or its salt (b), based on the total weight of the active ingredient in the antimicrobial composition. In many embodiments, the antimicrobial composition comprises essentially an antimicrobial agent (a) with nonanoic acid and / or its salt (b), or in other embodiments, an active ingredient comprising an antimicrobial agent (a) with nonanoic acid and / or its salt (b).

[0022] One or more other antimicrobial agents (c), such as antimicrobial agents suitable for personal care or home care preparations, may be present in the antimicrobial composition, and, if present, preferably constitute no more than 50 wt% of the active ingredient in the antimicrobial composition based on the total weight of the active ingredient, typically a small number (<50 wt%) of the active ingredient, for example no more than 40 wt% or no more than 30 wt%, more preferably no more than 25 wt%, no more than 20 wt%, even more preferably no more than 15 wt%, no more than 10 wt%, no more than 5 wt%, or no more than 3 wt%.

[0023] Preferably, based on the total weight of the active ingredients in the antimicrobial composition, the antimicrobial composition comprises about 70 to 100 wt%, about 75 to 100 wt%, about 80 to 100 wt%, about 85 to 100 wt%, about 90 to 100 wt%, or about 95 or about 97 to 100 wt% of a combination of antimicrobial agent (a), nonanoic acid and / or its salt (b), and one or more additional antimicrobial agents (c). Preferably, the antimicrobial agent (a), nonanoic acid and / or its salt (b), and one or more additional antimicrobial agents (c) constitute all or substantially all of the active ingredients in the antimicrobial composition. In many embodiments, the antimicrobial composition comprises substantially the antimicrobial agent (a), nonanoic acid and / or its salt (b), and one or more additional antimicrobial agents (c), or in other embodiments comprises the active ingredient consisting of the antimicrobial agent (a), nonanoic acid and / or its salt (b), and one or more additional antimicrobial agents (c).

[0024] Based on the total weight of the antimicrobial composition, the antimicrobial agent (a) and nonanoic acid and / or its salt (b) generally constitute about 50 to about 100 wt% of the total weight of the antimicrobial composition, generally constitute the majority (>50 wt%) of the total weight of the antimicrobial composition, such as at least 60 wt%, preferably at least 70 wt%, more preferably at least 75 wt%, at least 80 wt%, even more preferably at least 85 wt% or at least 90 wt%. Based on the total weight of the antimicrobial composition, the antimicrobial composition typically contains about 60-100 wt%, preferably about 70-100 wt%, about 75 wt% to 100 wt%, about 80 wt% to 100 wt%, more preferably about 85 wt% to 100 wt%, or about 90 wt% to 100 wt%, or about 60 wt%, preferably about 70 wt%, more preferably about 75 wt%, about 80 wt%, or about 85 wt% to about 99 wt%, about 97 wt%, about 95 wt%, or about 92 wt% of a combined amount of antimicrobial agent (a) and nonanoic acid and / or its salt (b). In many embodiments, the antimicrobial composition consists essentially of antimicrobial agent (a) and nonanoic acid and / or its salt (b), or in other embodiments, it consists of antimicrobial agent (a) and nonanoic acid and / or its salt (b).

[0025] When the antimicrobial composition contains one or more additional antimicrobial agents (c), the one or more additional antimicrobial agents (c) preferably constitute no more than 50 wt% of the total weight of the antimicrobial composition. Typically, a small number (<50 wt%) of the antimicrobial composition or a small number by weight relative to the amount of the combination of the antimicrobial agent (a) with nonanoic acid and / or its salt (b) is, for example, no more than 40 wt% or no more than 30 wt% of the total weight of the antimicrobial composition, more preferably no more than 25 wt%, no more than 20 wt%, even more preferably no more than 15 wt%, no more than 10 wt%, no more than 5 wt%, or no more than 3 wt%.

[0026] Based on the total weight of the antimicrobial composition, the antimicrobial composition may preferably contain about 70-100 wt%, about 75-100 wt%, about 80-100 wt%, about 85-100 wt%, or about 90 to 100 wt%, or preferably about 70 wt%, more preferably about 75 wt%, about 80 wt%, or about 85 wt% to about 99 wt%, about 97 wt%, about 95 wt%, or about 92 wt% of a combination of antimicrobial agent (a), nonanoic acid and / or its salts (b), and one or more additional antimicrobial agents (c). The antimicrobial agent (a), nonanoic acid and / or its salts (b), and one or more additional antimicrobial agents (c) may constitute all or substantially all of the components of the antimicrobial composition. In many embodiments, the antimicrobial composition consists essentially of an antimicrobial agent (a), nonanoic acid and / or its salts (b) and one or more additional antimicrobial agents (c), or in other embodiments, it consists of an antimicrobial agent (a), nonanoic acid and / or its salts (b) and one or more additional antimicrobial agents (c).

[0027] The weight ratio of the combined amount of (a) and (b) to the amount of one or more other antimicrobial agents (c) is generally from about 1:1 to about 150:1, for example, about 1.1:1, about 1.2:1, about 1.5:1, about 2:1, about 3:1, about 4:1, preferably about 5:1, about 9:1, more preferably about 12:1, about 16:1, even more preferably about 20:1 to about 150:1, preferably about 100:1, more preferably about 75:1 or about 50:1.

[0028] The antimicrobial compositions of this disclosure may, but do not necessarily, contain an added solvent (d). One advantage of combining the antimicrobial agent (a) of this disclosure with nonanoic acid and / or its salt (b) is that these materials can be combined without the need for the addition of a solvent. Therefore, in many embodiments, the antimicrobial compositions are solvent-free or substantially solvent-free. Preferably, the amount of nonanoic acid and / or its salt (b) does not exceed a ratio of 1:2.5 of the antimicrobial agent (a) to nonanoic acid and / or its salt (b), for example, not exceeding 1:2, 1:1.5, or 1:1.25.

[0029] If present, based on the total weight of the antimicrobial composition, one or more solvents (d) typically constitute about 10 wt%, about 20 wt%, or about 30 wt% to about 90 wt%, about 85 wt%, about 80 wt%, about 70 wt%, about 60 wt%, or about 50 wt%. Solvents may be selected based on their compatibility or suitability for the desired end application or final product formulation, for example, in a personal care formulation (e.g., a cosmetically acceptable solvent) or a household care formulation. Suitable solvents include, but are not limited to, water, C1-C4 alcohols, C1-C4 diols (e.g., glycols), glycerin, etc.

[0030] Antimicrobial compositions may, but do not necessarily, contain one or more excipients (e). Excipients may be selected similarly based on their compatibility or suitability for the desired end application or final product formulation, such as in personal care formulations (e.g., cosmetically acceptable excipients) or home care formulations. Examples of excipients include, but are not limited to, dispersants, solubilizers, buffers, and / or stabilizers. As similarly described above regarding solvents, one advantage of the combination of the antimicrobial agent (a) of this disclosure with nonanoic acid and / or its salts (b) is that these materials can be combined without requiring solubilizers or miscibility agents. Thus, in many embodiments, the antimicrobial composition contains no or substantially no solubilizers or miscibility agents. Preferably, the amount of nonanoic acid and / or its salts (b) does not exceed a ratio of 1:2.5 of the antimicrobial agent (a) to nonanoic acid and / or its salts (b), for example, not exceeding 1:2, 1:1.5, or 1:1.25.

[0031] The antimicrobial composition may contain one or more excipients (e), for example, from 0 to 25 wt% based on the total weight of the antimicrobial composition, such as from about 0.001 wt%, about 0.01 wt%, about 0.05 wt%, or about 0.1 wt% to about 20 wt%, about 15 wt%, about 10 wt%, about 5 wt%, about 3 wt%, or about 1 wt%. For example, component (e) may be 0 to about 20 wt%, 0 to about 15 wt%, 0 to about 10 wt%, 0 to about 5 wt%, or 0 to about 3 wt%, or about 0.01 wt% to about 25 wt%, about 20 wt%, about 15 wt%, about 10 wt%, or about 5 wt%, about 0.1 wt% to about 25 wt%, about 20 wt%, about 15 wt%, about 10 wt%, or about 5 wt%, about 0.01 to about 3 wt%, about 0.1 wt% to about 3 wt%, about 0.01 wt% to about 1 wt%, or about 0.1 wt% to about 1 wt%.

[0032] According to this disclosure, it has been found that the stability of the antimicrobial compositions of this disclosure over time can be significantly enhanced by including an alkaline stabilizer in the composition. Therefore, preferably, at least one excipient (e) comprises at least one alkaline stabilizer. The alkaline stabilizer comprises a base, preferably selected from metal (preferably alkali metal or alkaline earth metal) hydroxides, oxides, carbonates, bicarbonates, phosphates or hydrides, amine bases, or combinations thereof, more preferably metal hydroxides. The metal is preferably selected from sodium, potassium, magnesium, and calcium. In many preferred embodiments, the alkaline stabilizer comprises sodium hydroxide, potassium hydroxide, or combinations thereof. In particular, the alkaline stabilizer can be selected to ensure compatibility or suitability for the desired final application or final product formulation, for example, in personal care formulations (e.g., cosmetically acceptable alkaline stabilizers) or home care formulations. Based on the total weight of the antimicrobial composition, the alkali in the alkaline stabilizer may be present, for example, in an amount of about 0.1 wt%, about 0.3 wt%, preferably about 0.5 wt%, more preferably about 1 wt%, or about 3 wt% to about 10 wt%, preferably about 8 wt%, or about 6 wt%. Typically, the alkaline stabilizer is in the form of an alkaline solution, preferably an alkaline aqueous solution. For example, the alkaline solution, such as a metal hydroxide solution (e.g., wherein the metal hydroxide comprises potassium hydroxide, sodium hydroxide, or a combination thereof), may have an alkaline component strength of about 1% to about 90%, about 80%, about 70%, or about 60% (w / w), preferably about 10%, about 20%, or about 30% to about 70%, about 60%, or about 50% (w / w). Alkaline solutions of higher strength may also be used. Preferably, the pH range of the alkaline stabilizer is about 9.0, more preferably about 10.0 to about 14.0, such as about 11.0 or about 12.0 to about 14.0 or about 13.0. When an alkaline stabilizer is included, the pH of the antimicrobial composition is preferably about 5.0 to about 7.5, more preferably about 5.5 or about 6.0 to about 7.5, about 7.0 or about 6.5. If included, the alkaline stabilizer typically constitutes about 0.2 wt%, about 0.5 wt%, or about 1 wt% to about 25 wt% of the total weight of the antimicrobial composition, preferably about 1 wt%, more preferably about 3 wt% or about 5 wt% to about 20 wt% or about 15 wt%, for example about 5 wt% or about 8 wt% to about 15 wt% or about 12 wt%. As shown in the Examples section, when stored at 55°C for 2 weeks, the stabilized antimicrobial composition preferably exhibits a loss of ≤5 wt% of the combined antimicrobial agent (a) and nonanoic acid (and / or its salt) (b).As further shown in the Examples section, when stored at 55°C for 5 weeks, the stabilized antimicrobial composition preferably exhibits a loss of ≤15 wt% of the combined antimicrobial agent (a) and nonanoic acid (and / or its salt) (b), more preferably ≤10 wt%, and even more preferably ≤5 wt%.

[0033] In general, the antimicrobial composition may comprise from about 10 wt% to 100 wt% of an antimicrobial agent (a) in combination with nonanoic acid and / or its salts (b), for example, from about 15 wt% or about 20 wt%, about 30 wt%, about 40 wt%, about 50 wt% or about 60 wt% to about 100 wt%, based on the total weight of the antimicrobial composition, to about 99 wt%, to about 97 wt%, to about 95 wt%, to about 92 wt%, to about 85 wt%, to about 80 wt%, or to about 70 wt%; optionally, one or more additional antimicrobial agents (c), typically in the weight ratio of the combination of (a) and (b) as described herein to the amount of (c); optionally, one or more solvents (d), in an amount from 0 to about 90 wt%, for example, from about 10 wt%, about 20 wt% or about 30 wt% to about 90 wt%, to about 85 wt%, to about 80 wt%, to about 70 wt%, to about 60 wt%, to about 50 wt%. wt% or up to 40 wt%, based on the total weight of the antimicrobial composition; and optionally one or more excipients (e) in an amount of about 0 to about 25 wt%, about 20 wt%, about 15 wt%, or about 10 wt%, for example about 0.001 wt%, about 0.01 wt%, about 0.05 wt%, or about 0.1 wt% to about 20 wt%, about 15 wt%, about 10 wt%, about 5 wt%, about 3 wt%, or about 1 wt%, or particularly in the case of basic stabilizer excipients, about 0.2, about 0.5, or about 1 wt% to about 25 wt%, preferably about 3 wt%, more preferably about 5 wt% to about 20 wt%, such as about 5 wt% or about 8 wt% to about 15 wt% or about 12 wt%, based on the total weight of the antimicrobial composition.

[0034] In many embodiments, the antimicrobial composition comprises essentially the following, or in other embodiments, the following: an antimicrobial agent (a), nonanoic acid and / or its salts (b), one or more additional antimicrobial agents (c), one or more solvents (d), and one or more excipients (e). In many embodiments, the antimicrobial composition comprises essentially the following, or in other embodiments, the following: an antimicrobial agent (a), nonanoic acid and / or its salts (b), one or more additional antimicrobial agents (c), one or more solvents (d), and one or more excipients (e). In other embodiments, the stabilized antimicrobial composition comprises essentially the following, or in other embodiments, the following: an antimicrobial agent (a), nonanoic acid and / or its salts (b), one or more excipients (e) (including an alkaline stabilizer), one or more additional antimicrobial agents (c), and one or more solvents (d). In another embodiment, the stabilized antimicrobial composition consists essentially of the following, or in other embodiments, of the following: an antimicrobial agent (a), nonanoic acid and / or its salts (b), one or more additional antimicrobial agents (c), one or more excipients containing an alkaline stabilizer (e), and optionally one or more solvents (d).

[0035] One or more additional antimicrobial agents (c) of this disclosure may be selected based on their suitability for the intended application (e.g., in personal care or home care formulations), and preferably suitably selected to be sufficiently soluble in combination with antimicrobial agent (a) and nonanoic acid (b) in the absence of any added solvent or in a solvent selected for the antimicrobial composition.

[0036] Examples of other antimicrobial agents (c) include, but are not limited to, alkyl hydroxamic acids and / or their salts, aromatic aldehydes (e.g., cinnamaldehyde), aromatic alcohols (e.g., cinnamyl alcohol), dichlorobenzyl alcohol, phenolic compounds such as hydroxyacetophenone), diols (e.g., diols such as 1,2-propanediol, 1,2-butanediol, 1,2-pentanediol, 1,2-hexanediol, 1,2-heptanediol, and 1,2-octanediol (i.e., octanoyl diol), bromonitrobenzyl glycol), glycerol ethers (e.g., ethylhexylglycerol, chlorophenylglycerol ether), isothiazolinones (e.g., methylisothiazolinone, chloromethylisothiazolinone, benzisothiazolinone), fatty acids other than nonanoic acid and its salts and / or their salts (e.g., fatty acids and their salts having up to 24 carbon atoms, such as up to 20, up to 16, or up to 12 carbon atoms, especially C6-C8 and C4-C5). 10 -C 12Fatty acids and their salts), pyrithiones (e.g., zinc pyrithione, sodium pyrithione), and combinations thereof. It should be understood that the scope of one or more additional antimicrobial agents (c) does not include antimicrobial agents (a) or nonanoic acid and / or their salts (b).

[0037] Examples of suitable alkyl hydroxamic acids and their salts include those having at least one alkyl group with a chain length of about 2 to about 22 carbon atoms, which may be structurally branched or linear, substituted (e.g., alkoxy, etc.) or unsubstituted, and saturated or unsaturated (e.g., alkenyl, alkynyl, alkenoxy, alkynoxy, etc.). For example, the carbon chain may be interrupted by one or more oxygen atoms and / or may contain one or more side hydroxyl groups and / or terminal hydroxyl groups as substituents. Other functional groups may be used, particularly those compatible with or recommended for use in personal care or home care formulations. Preferably, the alkyl hydroxamic acid and / or its salts comprise an alkyl group with a chain length of about 6 to about 12 carbon atoms (typically linear). Examples of suitable alkyl hydroxamic acids and their salts include hexanohydroxyxamic acid, octanoyl hydroxamic acid, decanoyl hydrofluoric acid, lauroyl hydrofluoric acid and their salts and combinations thereof, preferably octanoyl hydroxamic acid and / or its salts. More than one alkyl hydroxamic acid and / or its salt can be used.

[0038] One or more additional antimicrobial agents (c) preferably comprise alkyl hydroxamic acids and / or their salts (more preferably, hexanohydroxamic acid, capryloyl hydroxamic acid, decanoyl hydrofluoric acid, lauroyl hydrofluoric acid and / or their salts or combinations thereof, particularly capryloyl hydroxamic acid and / or their salts), hydroxyacetophenone, dichlorobenzyl alcohol, cinnamaldehyde, cinnamyl alcohol, 1,2-propanediol, 1,2-butanediol, 1,2-pentanediol, 1,2-hexanediol, 1,2-heptanediol, 1,2-octanediol (i.e., capryloyldiol), bromonitrobenzene glycol, ethylhexylglycerol, chlorophenylglycerol ether, methylisothiazolinone, chloromethylisothiazolinone, benzisothiazolinone, fatty acids and / or their salts (e.g., C6 to C8 or C4). 10 To C 12 Fatty acids and / or their salts, preferably C6, C7, C8 or C4, are preferred. 10 Especially C8 or C 10 Fatty acids and / or their salts or combinations thereof), zinc pyrithione, sodium pyrithione or combinations thereof.

[0039] More preferably, one or more additional antimicrobial agents (c) comprise an alkyl hydroxamic acid and / or its salt (e.g., any exemplary alkyl hydroxamic acid and / or its salt as described herein, particularly octanoyl hydroxamic acid and / or its salt), cinnamaldehyde, C6 to C8 or C4 hydroxylamine, C6 to C8 ...9 hydroxylamine, C9 to C9 hydroxy 10 To C 12 Fatty acids and / or their salts, zinc pyrithione, sodium pyrithione, or combinations thereof.

[0040] In a particularly preferred embodiment, one or more additional antimicrobial agents (c) comprise or contain alkyl hydroxamic acids and / or their salts, such as any of the exemplary alkyl hydroxamic acids and / or their salts described herein, preferably octanoyl hydroxamic acids and / or their salts.

[0041] In another aspect, the antimicrobial composition, such as any embodiment of the antimicrobial composition disclosed herein, is free from or substantially free from any dicarboxylic acid or its salts. In another aspect, the antimicrobial composition, such as any embodiment of the antimicrobial composition disclosed herein, is free from or substantially free from glutaric acid, adipic acid, pimelic acid, or its salts. In another aspect, the antimicrobial composition, such as any embodiment of the antimicrobial composition disclosed herein, is free from or substantially free from any aromatic carboxylic acid or its salts. In another aspect, the antimicrobial composition, such as any embodiment of the antimicrobial composition disclosed herein, is free from or substantially free from benzoic acid, p-hydroxybenzoic acid, p-methoxybenzoic acid, salicylic acid, cinnamic acid, gentian acid, caffeic acid, or its salts.

[0042] This disclosure is not limited to any particular technique for preparing antimicrobial compositions, and such compositions can be prepared in any suitable manner for combining or mixing the components described herein.

[0043] This disclosure provides the use of antimicrobial compositions of this disclosure in a wide range of product formulations and applications, such as for personal care (e.g., cosmetics), home care, health care (e.g., pharmaceuticals (i.e., having at least one active pharmaceutical ingredient) or other health care products), or industrial product formulations, particularly for formulations used as personal care or home care products. Examples include, but are not limited to, household products and cleaners, fabric detergents, dishwashing liquids, cleaning agents, soaps, bubble baths, disinfectants, deodorants, pharmaceutical products, cosmetics, hygiene compositions, baby care products, antimicrobial soaps, hand sanitizers, deodorants, antiperspirants, antimicrobial coatings, wound care compositions, skin compositions, skin conditioning agents, skin moisturizers, anti-wrinkle preparations, sunscreens, tanning washes, hair products, shampoos, shower gels, bubble baths, conditioning agents, shaving creams, etc. Depending on the application, product formulations may contain many and different compatible ingredients. In many embodiments, the product formulation comprises an antimicrobially effective amount of the antimicrobial composition of this disclosure, as well as one or more additional ingredients suitable for use in personal care (e.g., cosmetics), home care, health care, or industrial product formulations (particularly personal or home care formulations).

[0044] In one aspect, the aqueous product formulation comprises an antimicrobially effective amount of the antimicrobial composition of this disclosure. Preferably, the aqueous product formulation is a personal care (e.g., cosmetic), household care, health care, or industrial product formulation, particularly a personal care or household care product formulation.

[0045] This aqueous product formulation typically has a pH range of about 3.0, about 4.0, about 5.0, about 5.5, about 6.0 or about 6.5 to about 12 or about 11, such as about 3.0 to about 10, about 3.0 to about 8.5, about 4.0 to about 8.5, about 3.0 to about 8.0, about 4.0 to about 8.0, about 3.0 to about 7.5, about 4.0 to about 7.5 or about 5.0 to about 7.5. Unless otherwise stated, as provided herein, pH values ​​or ranges refer to pH at room temperature (20-25°C). The selected pH will vary depending on, for example, the specific end-use application (e.g., home care or personal care application).

[0046] As demonstrated in this disclosure, it has been unexpectedly found that when combined with nonanoic acid and / or its salts (b), enhanced antimicrobial activity of the antimicrobial agent (a) is achieved in product formulations having a pKa higher than (even significantly higher than) that of nonanoic acid (4.95 pKa at 25°C). Therefore, in many embodiments, the aqueous product formulation has a pH range of about 5.0, about 5.1, about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3, about 6.4 or about 6.5 to about 12, about 11, about 10, about 9.5, about 9.0, about 8.5, about 8.4, about 8.3, about 8.2, about 8.1, about 8.0, about 7.9, about 7.8, about 7.7, about 7.6 or about 7.5. The pH can be in the range of, for example, about 5.0, about 5.5, about 6.0 or about 6.5 to about 12, about 11, about 10, about 9.0, about 8.5, about 8.0 or about 7.5. In many embodiments, the pH is higher than 5.0, higher than 5.5, higher than 6.0 or higher than 6.5, preferably at most about 11, at most about 10, at most about 9.0, at most about 8.5, at most about 8.0 or at most about 7.5.

[0047] The pH of the aqueous product formulation is more preferably at least 6.0, or even more preferably higher than 6.0, for example, at least 6.1, at least 6.3, most preferably at least 6.5, at least 6.7, at least 6.9, at least 7.0, at least 7.1, at least 7.2, at least 7.3, at least 7.4, or at least 7.5. The pH of the aquatic product formulation may be at most about 12, preferably at most about 11 or at most about 10.

[0048] As a specific embodiment, the antimicrobial compositions of this disclosure can be incorporated into any number and variety of different personal care products (such as cosmetic products). Therefore, a personal care formulation is provided comprising an antimicrobially effective amount of an antimicrobial agent (a), nonanoic acid and / or its salts (b), and optionally one or more additional antimicrobial agents (c), and further comprising one or more additional ingredients suitable for use in a personal care formulation. This personal care formulation can be, for example, any formulation for skin care, hair care, cosmetics, personal hygiene, sanitation, sun protection, and other personal care applications. Examples of such products include, but are not limited to: toners, facial cleansers, night creams, face creams, shaving creams, body lotions, makeup, mascaras, lipsticks, blushes, lip glosses, eyeliners, makeup removers, sunscreens, lip balms, perfumes, massage oils, shampoos, conditioners, hair styling gels, hair repair products, hair serums, hair setting products, hair mousses, shower gels, liquid soaps, moisturizing sprays, bath additives, eye care preparations, foaming soaps and shower gels, and special care solutions for personal care wipes.

[0049] Depending on the application, personal care product formulations can contain many and different compatible ingredients. Personal care formulations can contain any of the following, such as solvents, surfactants, emulsifiers, chelating agents, oxidizing agents, colorants, rheology modifiers, conditioning agents, emollients, skin care ingredients, moisturizers, thickeners, humectants, fillers, antioxidants, active ingredients (such as dermatologically active ingredients typically suitable for topical application), fragrances, etc.

[0050] Personal care formulations preferably have a pH range of about 3.0 or about 4.0 to about 8.0, for example, from about 3.0 or about 4.0 to about 7.5. The pH can be in the range of, for example, from about 5.0, about 5.5, about 6.0 or about 6.5 to about 8.0, about 7.5 or about 7.0. The pH of the personal care product formulation is more preferably at least 6.0, even more preferably higher than 6.0, for example, at least 6.1, at least 6.3, most preferably at least 6.5, at least 6.7, at least 6.9, at least 7.0, at least 7.1, at least 7.2, at least 7.3, at least 7.4 or at least 7.5. The pH of the personal care formulation is preferably at most about 8.0.

[0051] As a further embodiment, the antimicrobial compositions of this disclosure can be incorporated into any number and variety of different household care products, such as fabric care products and cleaning products. Therefore, a household care formulation is provided comprising an antimicrobially effective amount of an antimicrobial agent (a), nonanoic acid and / or its salts (b), and optionally one or more additional antimicrobial agents (c), and the formulation further comprises one or more additional ingredients suitable for use in household care formulations. Examples include dish soaps, laundry detergents, cleaning wipes, cleaning formulations, and other household care applications.

[0052] Depending on the application, home care product formulations may contain any of the following: detergents, washes, emulsifiers, surfactants, thickeners, gelling agents, bleaching agents, brighteners, deodorizers, enzymes, stabilizers, fragrances, stain removers, anti-shrinkage agents, anti-wrinkle agents, anti-staining agents, antioxidants, UV-absorbing compounds, corrosion inhibitors, antistatic agents, ironing aids, odor-preventing compounds, etc.

[0053] Home care formulations preferably have a pH range of about 3.0 to about 11, for example, about 3.0 or about 4.0 to about 10. The pH can be in the range of about 5.0, about 5.5, about 6.0, about 6.5, or about 7.0 to about 11, about 10, about 9.0, about 8.5, about 8.0, or about 7.5. The pH of the home care product formulation is more preferably at least 6.0, even more preferably higher than 6.0, for example, at least 6.1, at least 6.3, most preferably at least 6.5, at least 6.7, at least 6.9, at least 7.0, at least 7.1, at least 7.2, at least 7.3, at least 7.4, or at least 7.5. The pH of the home care formulation can preferably be at most about 12 or at most about 11.

[0054] Examples of the above-mentioned ingredients and other reagents used in personal care and home care product compositions are known in the art.

[0055] The antimicrobial compositions disclosed herein can be included in a variety of different forms of product formulations, such as liquids, pastes, slurries, hydrogels, creams, lotions, lotions, gels, oils, wipes, ointments, semi-solid compositions, foams, and aerosol sprays. The antimicrobial compositions can be used in indwelling or rinsing product formulations. The antimicrobial compositions can be used in hair care products such as shampoos, hair conditioners, hair dyes, hair tonics, hair gels, hair flavorings, hair combing aids, and other hair care formulations; shaving applications such as shaving creams, aftershaves, and other shaving applications; personal cleansers for the body and hands, such as liquid bath soaps and detergents; fragrance formulations such as fragrances, aftershave sprays, and other similar aromatic formulations; skin care products such as moisturizers, creams, and lotions, and other similar skin care products; cosmetic products such as mascaras, foundations, etc.; makeup removal products, sun care products, indoor tanning products, and other similar personal care products. Antimicrobial compositions can be incorporated into formulations used to saturate wipes for personal cleaning and hygiene purposes, such as baby wipes, wet toilet wipes, cosmetic removal wipes, and peel-off wipes, or wet wipe formulations for home care.

[0056] The optimal ratio of antimicrobial agent (a) to nonanoic acid and / or its salt (b), the optimal ratio of the amounts of components (a) and (b) to the amount of one or more additional antimicrobial agents (c) (if used), and the optimal antimicrobial effective amount of the antimicrobial composition can vary depending on, for example, the specific components selected, the end-use application, the desired level of antimicrobial activity, the final characteristics of the product, etc. As is known in the art, antimicrobial activity can be demonstrated by a variety of suitable antimicrobial effectiveness tests. Preferably, when added to a product formulation, the antimicrobial composition provides antimicrobial activity according to the challenge test procedure in the examples below, thereby achieving a qualified growth grade according to the standards associated with Table 8 and the relevant description herein.

[0057] Typically, based on the total weight of the formulation, the antimicrobial effective amount of the antimicrobial composition provides about 0.05 wt%, preferably about 0.1 wt%, more preferably about 0.2 wt%, about 0.3 wt%, about 0.4 wt%, or about 0.5 wt% to about 5 wt%, about 4 wt%, preferably about 3 wt%, about 2.5 wt%, more preferably about 2 wt% combined with about 1.5 wt% or about 1 wt% of antimicrobial agent (a) and nonanoic acid and / or its salt (b), and the formulation may optionally include one or more additional antimicrobial agents (c), preferably in a weight ratio of the combined amount of (a) and (b) as described herein to the amount of (c). If optional component (c) is included (preferably in a weight ratio of the combined amount of (a) and (b) described herein to the amount of (c),), an antimicrobial effective amount may be provided, for example, about 0.2 wt%, about 0.3 wt%, about 0.4 wt%, or about 0.5 wt% to about 6 wt%, or about 5 wt%, based on the total weight of the formulation, in a combined amount of about 4 wt%, preferably about 3 wt%, more preferably about 2 wt%, or about 1 wt% of components (a), (b), and (c). Typically, based on the total weight of the formulation, the antimicrobial agent (a) and nonanoic acid and / or its salt (b) are each present in the product formulation in an amount not exceeding 3 wt%, preferably not exceeding 2 wt%, not exceeding 1.5 wt%, or not exceeding 1 wt%. Typically, each is present at less than 1 wt%. Preferably, the combined amount of the antimicrobial agent (a), nonanoic acid and / or its salt (b), and, if used, one or more optional additional antimicrobial agents (c) is about 2 wt% or less (e.g., 2 wt% or less). The dosage is approximately 0.1 wt%, approximately 0.2 wt%, or approximately 0.3 wt% to approximately 2 wt%, approximately 1.5 wt% or less (e.g., approximately 0.1 wt%, approximately 0.2 wt%, or approximately 0.3 wt% to approximately 1.5 wt%), approximately 1.2 wt% or less (e.g., approximately 0.1 wt%, approximately 0.2 wt%, or approximately 0.3 wt% to approximately 1.2 wt%), or approximately 1 wt% or less (e.g., approximately 0.1 wt%, approximately 0.2 wt% or approximately 0.3 wt% to approximately 1 wt% based on the total weight of the formulation). In many embodiments, the formulation comprises no more than 1.5 wt%, preferably no more than 1 wt%, no more than 0.9 wt%, no more than 0.8 wt%, no more than 0.7 wt%, no more than 0.6 wt%, more preferably no more than 0.5 wt%, no more than 0.4 wt%, or no more than 0.3 wt% of an antimicrobial agent (a).Preferably, the formulation comprises no more than 0.5 wt%, no more than 0.4 wt%, no more than 0.3 wt%, more preferably no more than 0.2 wt%, even more preferably no more than 0.1 wt% or no more than 0.05 wt% of one or more other antimicrobial agents (c).

[0058] The product formulation may include, for example, an antimicrobial effective amount of an antimicrobial agent (a) and nonanoic acid and / or its salt (b) in combination of about 0.2 wt%, about 0.3 wt%, about 0.4 wt%, or about 0.5 wt% to about 5 wt%, preferably about 3 wt%, more preferably about 2 wt%, about 1.5 wt%, or about 1 wt% based on the total weight of the formulation, and further includes one or more additional antimicrobial agents (c), wherein the weight ratio of the combined amount of (a) and (b) to the amount of (c) ranges from about 1:1 to about 150:1, for example, about 1.1:1, about 1.2:1, about 1.5:1, about 2:1, about 3:1, about 4:1, preferably about 5:1, about 9:1, more preferably about 12:1, about 16:1, particularly preferably about 20:1 to about 150:1, preferably about 100:1, more preferably about 75:1 or about 50:1. Preferably, one or more additional antimicrobial agents (c) comprise or contain at least one alkyl hydroxamic acid and / or its salt as described herein, more preferably octanoyl hydroxamic acid and / or its salt.

[0059] The product formulation may comprise, for example, about 0.2 wt% of a combined antimicrobial effective amount of an antimicrobial agent (a) and nonanoic acid and / or its salt (b), about 0.3 wt%, about 0.4 wt%, or about 0.5 wt% to about 5 wt%, preferably to about 3 wt%, more preferably to about 2 wt%, to about 1.5 wt%, or about 1 wt%, and further comprise, in an amount less than or equal to about 0.2 wt%, for example, not more than 0.15 wt%, not more than 0.1 wt%, or not more than 0.05 wt%, each based on the total weight of the formulation. Preferably, the one or more additional antimicrobial agent (c) comprises or at least one alkyl hydroxamic acid and / or its salt as described herein, more preferably octanoyl hydroxamic acid and / or its salt.

[0060] This disclosure is not limited to any specific technique for preparing product formulations, and the antimicrobial compositions of this disclosure can be added to the product formulation in any suitable manner. For example, antimicrobial agents (a) as described herein, nonanoic acid and / or salts thereof (b), one or more alternative antimicrobial agents (c) and other components may be applied to the product formulation as a mixture or applied to the formulation simultaneously or individually in any order.

[0061] This disclosure further includes a method for controlling or inhibiting microbial growth in a product formulation (such as any formulation described herein). Methods for preserving product formulations (such as any formulation described herein) are also disclosed. These methods include adding an antimicrobially effective amount of an antimicrobial composition, as described herein, to the formulation.

[0062] In another aspect, this disclosure includes a method for enhancing the antimicrobial efficacy of an antimicrobial agent selected from the group consisting of phenoxyethanol, benzyl alcohol, and combinations thereof, the method comprising combining or mixing nonanoic acid and / or its salts with the antimicrobial agent in the weight ratios as described herein. The method may include combining or mixing nonanoic acid and / or its salts with the antimicrobial agent in a product formulation (such as any formulation described herein).

[0063] It is also provided that nonanoic acid and / or its salts are used to enhance the antimicrobial efficacy of antimicrobial agents selected from the group consisting of phenoxyethanol, benzyl alcohol, and combinations thereof, wherein the weight ratio of the antimicrobial agent to nonanoic acid and / or its salts is as described herein.

[0064] Another method is provided for reducing the minimum amount of antimicrobial agent required to preserve activity in a product formulation (such as any formulation described herein), comprising combining or mixing nonanoic acid and / or its salts with an antimicrobial agent in the product formulation, wherein the antimicrobial agent is selected from the group consisting of phenoxyethanol, benzyl alcohol, and combinations thereof, and the weight of the antimicrobial agent with nonanoic acid and / or its salts is as described herein.

[0065] This disclosure further includes, but is not limited to, the following exemplary embodiments.

[0066] Implementation 1: An antimicrobial composition comprising (a) an antimicrobial agent selected from the group consisting of phenoxyethanol, benzyl alcohol and combinations thereof, and (b) nonanoic acid and / or a salt thereof, wherein the weight ratio of the antimicrobial agent (a) to nonanoic acid and / or a salt thereof (b) is from about 40:1 to about 1:5, preferably from about 40:1 or from about 20:1 to about 1:2.5.

[0067] Implementation Method 2: The antimicrobial composition according to Implementation Method 1, wherein the antimicrobial agent (a) is phenoxyethanol.

[0068] Implementation Method 3: The antimicrobial composition according to Implementation Method 1, wherein the antimicrobial agent (a) is benzyl alcohol.

[0069] Embodiment 4: The antimicrobial composition according to Embodiment 1, wherein the antimicrobial agent is a combination of phenoxyethanol and benzyl alcohol.

[0070] Example 5: An antimicrobial composition according to any one of Examples 1-4, wherein component (b) is nonanoic acid.

[0071] Embodiment 6: An antimicrobial composition according to any one of Embodiments 1 to 5, wherein, based on the total weight of the active ingredients in the antimicrobial composition, the antimicrobial composition comprises more than or equal to about 50 wt% of a combination of an antimicrobial agent (a) and nonanoic acid and / or its salt (b), preferably, based on the total weight of the active ingredients in the antimicrobial composition, about 60 to 100 wt%, about 70 to 100 wt%, about 75 to 100 wt%, about 80 to 100 wt%, about 85 to 100 wt%, about 90 wt% to 100 wt%, or about 95 wt% or about 97 wt% to 100 wt% of a combination of an antimicrobial agent (a) and nonanoic acid and / or its salt (b).

[0072] Embodiment 7: An antimicrobial composition according to any one of Embodiments 1 to 5, wherein the antimicrobial composition comprises an active ingredient, said active ingredient being substantially composed of an antimicrobial agent (a) and nonanoic acid and / or its salt (b), or in other embodiments, composed of an antimicrobial agent (a) and nonanoic acid and / or its salt (b).

[0073] Embodiment 8: An antimicrobial composition according to any one of Embodiments 1 to 5, wherein, based on the total weight of the antimicrobial composition, the antimicrobial composition comprises more than or equal to about 50 wt% of a combination of an antimicrobial agent (a) and nonanoic acid and / or its salt (b), preferably about 60 to 100 wt%, about 70 to 100 wt%, about 75 to 100 wt%, about 80 to 100 wt%, about 85 to 100 wt%, or about 90 to 100 wt% or about 60 wt% based on the total weight of the composition, more preferably about 70 wt%, more preferably about 75 wt%, about 80 wt% or about 85 wt% to about 99 wt%, about 97 wt%, about 95 wt%, or about 92 wt% of a combination of an antimicrobial agent (a) and nonanoic acid and / or its salt (b).

[0074] Embodiment 9: An antimicrobial composition according to any one of Embodiments 1 to 5, wherein the composition is substantially composed of the following, or in other embodiments, the following: an antimicrobial agent (a), nonanoic acid and / or its salt (b), one or more solvents (d), and one or more excipients (e).

[0075] Embodiment 10: The antimicrobial composition according to Embodiment 6, wherein the antimicrobial composition further comprises one or more additional antimicrobial agents (c) in amounts not greater than 50 wt%, preferably not greater than 40 wt%, not greater than 25 wt%, not greater than 20 wt%, not greater than 15 wt%, not greater than 10 wt%, or not greater than 5 wt%, based on the total weight of the active ingredients in the antimicrobial composition. Preferably, one or more additional antimicrobial agents (c) include alkyl hydroxamic acids and / or their salts, aromatic aldehydes (e.g., cinnamaldehyde), aromatic alcohols (e.g., cinnamyl alcohol, dichlorobenzyl alcohol, phenolic compounds, such as hydroxyacetophenone), diols (e.g., diols such as 1,2-propanediol, 1,2-butanediol, 1,2-pentanediol, ... 1,2-Hexanediol, 1,2-Heptanediol or 1,2-Octandiol (i.e., octanoyldiol), bromonitrobenzyldiol), glyceryl ethers (e.g., ethylhexylglycerol, chlorophenylglycerol ether), isothiazolinones (e.g., methylisothiazolinone, chloromethylisothiazolinone, benzisothiazolinone), fatty acids and / or their salts (e.g., fatty acids and / or their salts having up to 24 carbon atoms, such as up to 20, up to 16 or up to 12 carbon atoms, particularly, for example, C6-C8 or C4-C5). 10 -C 12 Fatty acids and / or their salts), pyrithiones (e.g., zinc pyrithione, sodium pyrithione), or combinations thereof.

[0076] Embodiment 11: The antimicrobial composition according to Embodiment 8, wherein the antimicrobial composition further comprises one or more additional antimicrobial agents (c) in an amount of no more than 50 wt%, preferably no more than 40 wt%, no more than 25 wt%, no more than 20 wt%, no more than 15 wt%, no more than 10 wt%, or no more than 5 wt%, based on the total weight of the antimicrobial composition, preferably, wherein one or more additional antimicrobial agents (c) are as described in Embodiment 10 above.

[0077] Embodiment 12: An antimicrobial composition according to any one of Embodiments 1 to 5, wherein the antimicrobial composition comprises an active ingredient, the active ingredient being substantially composed of an antimicrobial agent (a), nonanoic acid and / or its salt (b), and one or more additional antimicrobial agents (c), or in other embodiments, composed of an antimicrobial agent (a), nonanoic acid and / or its salt (b), and one or more additional antimicrobial agents (c), wherein one or more additional antimicrobial agents (c) are present in small amounts relative to the combined amount of the antimicrobial agent (a) and nonanoic acid and / or its salt (b), preferably wherein one or more additional antimicrobial agents (c) are as described in Embodiment 10 above.

[0078] Embodiment 13: An antimicrobial composition according to any one of Embodiments 10 to 12, wherein the weight ratio of the combined amount of (a) and (b) to the amount of one or more other antimicrobial agents (c) ranges from about 1.5:1 to about 150:1, for example about 2:1, about 3:1, about 4:1, preferably about 5:1, about 9:1, more preferably about 12:1, about 16:1, particularly preferably about 20:1 to about 150:1, preferably about 100:1, more preferably about 75:1 or about 50:1.

[0079] Embodiment 14: The antimicrobial composition according to Embodiment 6, wherein the antimicrobial composition comprises an active ingredient, the active ingredient being substantially composed of an antimicrobial agent (a), nonanoic acid and / or its salt (b), and optionally one or more additional antimicrobial agents (c), or in other embodiments, composed of an antimicrobial agent (a), nonanoic acid and / or its salt (b), and optionally one or more additional antimicrobial agents (c), wherein, based on the total weight of the active ingredient in the antimicrobial composition, approximately 60 to 100 wt%, preferably approximately 70 to 100 wt%, approximately 75 to 100 wt%, approximately 80 to 100 wt%, approximately 85 to 100 wt%, approximately 90 to 100 wt%, or approximately 95 or approximately 97 to 100 wt% of the combination of antimicrobial agent (a) and nonanoic acid and / or its salt (b), preferably one or more additional antimicrobial agents (c) are as described in Embodiment 10 above.

[0080] Embodiment 15: An antimicrobial composition according to any one of Embodiments 1 to 5, wherein the antimicrobial composition is substantially composed of the following, or in other embodiments, the following: an antimicrobial agent (a), nonanoic acid and / or its salt (b), one or more additional antimicrobial agents (c), optionally one or more solvents (d), and optionally one or more excipients (e), wherein one or more additional antimicrobial agents (c) are present in a small amount relative to the combined amount of the antimicrobial agent (a) and nonanoic acid and / or its salt (b), preferably wherein one or more additional antimicrobial agents (c) are as described in Embodiment 10 above.

[0081] Embodiment 16: An antimicrobial composition according to Embodiment 14 or 15, wherein the weight ratio of the combined amount of (a) and (b) to the amount of one or more other antimicrobial agents (c) ranges from about 1.5:1 to about 150:1, for example about 2:1, about 3:1, about 4:1, preferably about 5:1, about 9:1, more preferably about 12:1, about 16:1, particularly preferably about 20:1 to about 150:1, preferably about 100:1, more preferably about 75:1 or about 50:1.

[0082] Embodiment 17: An antimicrobial composition according to any one of Embodiments 1 to 5, wherein, based on the total weight of the composition, the antimicrobial composition comprises about 70 to 100 wt%, about 75 to 100 wt%, about 80 to 100 wt%, about 85 to 100 wt%, or about 90 to 100 wt%, or preferably about 70 wt%, more preferably about 75 wt%, about 80 wt%, or about 85 wt% to about 99 wt%, about 97 wt%, about 95 wt%, or about 92 wt% of an antimicrobial agent (a), and nonanoic acid and / or its salts (b) and one or more additional antimicrobial agents (c), preferably one or more additional antimicrobial agents (c) as described in Embodiment 10 above.

[0083] Embodiment 18: An antimicrobial composition according to any one of Embodiments 10 to 17, wherein one or more additional antimicrobial agents (c) comprise alkyl hydroxamic acid and / or its salt, wherein the alkyl hydroxamic acid and / or its salt contains at least one alkyl group having a chain length of about 2 to about 22 carbon atoms, preferably about 6 to about 12 carbon atoms, which may be branched or linear, preferably linear, substituted or unsubstituted, and saturated or unsaturated.

[0084] Example 19: The antimicrobial composition according to Example 18, wherein the alkyl hydroxamic acid and / or its salt is hexanohydroxyxamic acid, octanohydroxyxamic acid, decanoyl hydrofluoric acid, lauroyl hydrofluoric acid or its salt or a combination thereof, preferably octanohydroxyxamic acid and / or its salt.

[0085] Embodiment 20: An antimicrobial composition according to any one of Embodiments 1 to 19, wherein the weight ratio of the antimicrobial agent (a) to nonanoic acid and / or its salt (b) is about 15:1 to about 1:1.5, more preferably about 10:1, even more preferably about 5:1 or about 3:1 to about 1:1.25, to about 1:1.2, to about 1:1.1 or more preferably about 1:1.

[0086] Embodiment 21: Any of the antimicrobial compositions of the foregoing embodiments further comprises one or more excipients (e), including at least one alkaline stabilizer.

[0087] Example 22: An antimicrobial composition according to Example 21, wherein the antimicrobial composition has a pH of about 5.0 to about 7.5, preferably about 5.5 or about 6.0 to about 7.5, about 7.0 or about 6.5.

[0088] Embodiment 23: The antimicrobial composition according to Embodiment 21 or 22, wherein at least one alkaline stabilizer comprises a base selected from metal (preferably alkali metal or alkaline earth metal) hydroxides, oxides, carbonates, bicarbonates, phosphates or hydrides, amine bases or combinations thereof, preferably metal hydroxides, and preferably wherein the metal is sodium, potassium, magnesium or calcium, and more preferably wherein the base of the alkaline stabilizer is present in an amount of about 0.1 wt%, about 0.3 wt%, more preferably about 0.5 wt%, even more preferably about 1 wt% or about 3 wt% to about 10 wt%, preferably about 8 wt% or about 6 wt%, based on the total weight of the antimicrobial composition.

[0089] Embodiment 24: The antimicrobial composition according to Embodiment 23, wherein the base is a metal hydroxide, preferably sodium hydroxide, potassium hydroxide or a combination thereof.

[0090] Example 25: An antimicrobial composition according to any one of Examples 21 to 24, wherein when stored at 55°C for 2 weeks, the antimicrobial composition exhibits a loss of ≤ 5 wt% of the combined antimicrobial agent (a) and nonanoic acid and / or its salt (b), more preferably, wherein when stored at 55°C for 5 weeks, the antimicrobial composition exhibits a loss of ≤ 15 wt% of the combined antimicrobial agent (a) and nonanoic acid and / or its salt (b), more preferably ≤ 10 wt% or even more preferably ≤ 5 wt%.

[0091] Implementation Method 26: An aqueous product formulation comprising an antimicrobial effective amount of an antimicrobial composition according to any one of Implementation Methods 1 to 25.

[0092] Embodiment 27: The aqueous product formulation according to Embodiment 26, wherein the aqueous product formulation has a pH range of about 5.0, about 5.5, about 6.0 or about 6.5 to about 12, about 11, about 10, about 9.5, about 9.0, about 8.5, about 8.0 or about 7.5, or wherein the aqueous product formulation has a pH higher than 5.0, higher than 5.5, higher than 6.0 or higher than 6.5, preferably up to about 12, up to about 11, up to about 10, up to about 9, up to about 8.5, up to about 8.0 or up to about 7.5, or more preferably wherein the aqueous product formulation has a pH of at least 6.0, even more preferably higher than 6.0, such as at least 6.1, at least 6.3, most preferably at least 6.5, at least 6.7, at least 6.9, at least 7.0, at least 7.1, at least 7.2, at least 7.3, at least 7.4 or at least 7.5.

[0093] Implementation method 28: Aqueous product formulations according to implementation method 26 or 27, which are in the form of personal care (e.g., cosmetics), home care, health care or industrial product formulations, preferably in the form of personal care or home care formulations.

[0094] Embodiment 29: A personal care preparation comprising an antimicrobial effective amount of an antimicrobial composition according to any one of Embodiments 1 to 25, and one or more additional ingredients suitable for personal care preparations.

[0095] Embodiment 30: A home care preparation comprising an antimicrobial effective amount of an antimicrobial composition according to any one of Embodiments 1 to 25 and one or more additional ingredients suitable for home care preparations.

[0096] Implementation Method 31: A method for controlling or inhibiting microbial growth in a product formulation, comprising adding an antimicrobially effective amount of an antimicrobial composition according to any one of Implementation Methods 1 to 25 to the formulation, preferably wherein the formulation is a personal care (e.g., cosmetic), home care, health care, or industrial product formulation, more preferably wherein the formulation is a personal care (e.g., cosmetic) or home care formulation.

[0097] Implementation Method 32: A formulation or method according to any one of Implementation Methods 26 to 31, wherein, based on the total weight of the formulation, the antimicrobial effective amount of the antimicrobial composition provides an amount of about 0.1 wt%, about 0.3 wt%, or about 0.5 wt% to about 5 wt%, preferably about 3 wt%, more preferably about 2 wt%, about 1.5 wt%, or about 1 wt% of an antimicrobial agent (a), nonanoic acid and / or its salts (b), and optionally one or more additional antimicrobial agents (c), preferably one or more additional antimicrobial agents (c) as described in Implementation Method 10 above.

[0098] Implementation method 33: The formulation or method according to implementation method 32, wherein the formulation contains no more than 1 wt%, preferably no more than 0.8 wt% or 0.7 wt%, more preferably no more than 0.6 wt%, no more than 0.5 wt%, no more than 0.4 wt% or no more than 0.3 wt% of an antimicrobial agent (a).

[0099] Embodiment 34: A method for enhancing the antimicrobial efficacy of an antimicrobial agent selected from the group consisting of phenoxyethanol, benzyl alcohol, and combinations thereof, the method comprising combining or mixing nonanoic acid and / or its salts with the antimicrobial agent in a weight ratio of antimicrobial agent to nonanoic acid of about 40:1 to about 1:5, preferably about 40:1 or about 20:1 to about 1:2.5, more preferably as described in Embodiment 20.

[0100] Embodiment 35: The method according to Embodiment 34, wherein the antimicrobial agent is used in personal care (e.g., cosmetics), home care, health care or industrial product formulations, preferably personal care or home care formulations, and preferably wherein the formulation has a pH as described in Embodiment 27.

[0101] Embodiment 36: Use of nonanoic acid for enhancing the antimicrobial efficacy of an antimicrobial agent selected from the group consisting of phenoxyethanol, benzyl alcohol, and combinations thereof, wherein the weight ratio of the antimicrobial agent to nonanoic acid is about 40:1 to about 1:5, preferably about 40:1 or about 20:1 to about 1:2.5, more preferably the weight ratio described in Embodiment 20.

[0102] Embodiment 37: According to the use of Embodiment 36, the antimicrobial agent is used in personal care (e.g., cosmetics), home care, health care or industrial product formulations, preferably personal care or home care formulations, preferably wherein the formulation has a pH as described in Embodiment 27.

[0103] Embodiment 38: A method for reducing the minimum amount of antimicrobial preservative required for preservative activity in a product formulation, preferably a personal care or home care formulation, comprising combining or mixing nonanoic acid and / or its salt with an antimicrobial agent in the product formulation, wherein the antimicrobial agent is selected from the group consisting of phenoxyethanol, benzyl alcohol and combinations thereof, and the weight ratio of the antimicrobial agent to nonanoic acid and / or its salt is from about 40:1 to about 1:5, preferably from about 40:1 or from about 20:1 to about 1:2.5, more preferably the weight ratio described in Embodiment 20.

[0104] Implementation 39: The method according to Implementation 38, wherein the product formulation has a pH as described in Implementation 27.

[0105] As used herein, the articles “a,” “an,” and “the” preceding an element or component of the invention are intended to be non-limiting in terms of the number of embodiments (i.e., occurrences) of that element or component. Thus, “a,” “an,” and “the” should be understood to include one or at least one, and the singular form of an element or component also includes the plural, unless the number clearly indicates the singular.

[0106] As used herein, the term "comprising" means the presence of the stated feature, integral, step, or component, and does not exclude the presence or addition of one or more other features, integrals, steps, components, or combinations thereof. That is, the stated feature, integral, step, or component may include other features, integrals, steps, components, or combinations thereof. The term "comprising" is intended to include embodiments covered by the terms "substantially constitutes" and "consisting of," unless the context otherwise requires.

[0107] The phrase “composed of” limits the scope of the phrase to the element, step, or component, excluding other elements or materials, except for impurities typically associated with them. For example, in the context of nonanoic acid of this disclosure, such impurities may include, for example, unsaturation, branching, and / or chain length varying above or below nine carbons.

[0108] The phrase “consistently composed of” limits its application to the stated elements, steps, or components, as well as those that do not substantially affect one or more essential and novel features of the claimed invention. “Consistently composed of” occupies an intermediate position between the closed scope written in the “consistent with” format and the open scope written in the “including” format.

[0109] As used herein, the term “about” for the amount of an ingredient used in a modification refers to, for example, a change in numerical quantity that can occur through typical measurement and processing procedures used to manufacture concentrates or to use solutions in the real world; through unintentional errors in these processes; through differences in the manufacture, origin, or purity of the ingredients used to prepare the composition or to carry out the methods; and so on.

[0110] When present, all ranges are inclusive and composable. For example, when stating the range "1 to 5", the range should be interpreted as including the ranges "1 to 4", "1 to 3", "1-2", "1-2 and 4-5", "1-3 and 5", etc.

[0111] When parameters are given as ranges, preferred ranges, or lists of upper and lower limits, this should be understood as specifically disclosing all ranges formed by any pair of any upper or preferred range value and any lower or preferred range value, regardless of whether the range is disclosed individually. In the case of ranges of numerical values ​​described herein, unless otherwise stated, the range is intended to include its endpoints and all integers and fractions within that range.

[0112] Example

[0113] The following examples demonstrate a surprising and synergistic enhancement of the antimicrobial activity of phenoxyethanol and benzyl alcohol when combined with nonanoic acid, and this synergistic enhancement can be further improved by including additional antimicrobial agents. These examples further illustrate this unexpected enhancement in product formulations with pH values ​​even higher than those of nonanoic acid. Nonanoic acid also exhibits chelating activity as a multifunctional property, in contrast to 2-ethylhexylglycerol, which does not exhibit this activity.

[0114] Example 1. Challenge test demonstrating the antimicrobial enhancement of phenoxyethanol and benzyl alcohol when combined with nonanoic acid.

[0115] Using the improvement approach of the Personal Care Products Council (PCPC – formerly the Cosmetic, Toiletries and Fragrance Association) program, the preservative activity in representative rinse-off and leave-on formulations was evaluated (Machtiger, et al. 2001. Determination of the Efficacy of Preservation of Non-Eye Area Water Miscible Cosmetic and Toiletry Formulations: Collaborative Study. J of AOAC International. 84:1, 101-109).

[0116] This assessment was conducted at 25°C using a four-week, two- or three-cycle (i.e., two cycles for personal care applications and three cycles for home care applications) microbial preservative efficacy test (i.e., challenge test) to determine the preservative efficacy of each treatment. Phenoxyethanol, benzyl alcohol, and nonanoic acid were tested individually and in various combinations. Nonanoic acid used in the tests was purchased from Sigma-Aldrich. Combinations of phenoxyethanol or benzyl alcohol with benchmark multifunctional synergist compounds were also tested for comparison. The preservative and synergist components were administered at room temperature and thoroughly mixed into various formulations, specifically different personal care formulations including lotions (no-rinse, Table 1), micellar water (rinse, Table 2), and shower gel formulations (rinse, Table 3), and different home care formulations including manual dishwashing formulations (Table 4) and liquid laundry detergent formulations (Table 5). In all cases after administration, the pH of the final formulation was readjusted to match the pH of the original formulation prior to administration using citric acid, triethanolamine, or diluted sodium hydroxide.

[0117] Table 1 shows exemplary formulations of carbomer-based lotion compositions. Carbomer is a commonly used synthetic rheology modifier in personal care products. The following formulations were prepared by heating the aqueous phase (A) and oil phase (B) to 75-80°C, respectively. The oil phase was then poured into the aqueous phase and mixed via a homogenizer at approximately 45°C. The resulting oil-in-water emulsion was cooled to room temperature. The final pH was adjusted to 6.3 or 6.5 using triethanolamine and / or diluted sodium hydroxide (as shown in the examples below).

[0118] Table 1. Representative emulsion formulations containing carbomer

[0119] Table 2 shows representative micellar water formulations. The micellar water compositions were prepared by adding all components to a beaker and heating the mixture to 75–80°C. The final product was cooled to room temperature and the pH was adjusted to 6.0 with citric acid solution (unless otherwise stated in the examples below).

[0120] Table 2. Representative micellar water compositions

[0121] Table 3 shows representative shower gel formulations. The composition was prepared by mixing ACULYN 88 and water in a beaker and then adding STEOL 230 and AMPHOSOL CA. The solution was mixed using an overhead mixer. The final pH was adjusted to 6.5 using triethanolamine (unless otherwise stated in the examples below).

[0122] Table 3. Representative Shower Gel Formulations

[0123] Table 4 shows representative manual dishwashing formulations. The manual dishwashing formulation compositions were prepared by adding all ingredients to a beaker and heating the mixture to 60°C. The final product was cooled to room temperature and the pH was adjusted to 5.5 with citric acid solution (unless otherwise stated in the examples below).

[0124] Table 4. Representative manual dishwashing preparations

[0125] Table 5 shows representative liquid laundry detergent formulations. The liquid laundry detergent compositions were prepared by adding all ingredients to a beaker and heating the mixture to 40°C. The final product was cooled to room temperature and the pH was adjusted to 7.5 with citric acid solution (unless otherwise stated in the examples below).

[0126] Table 5. Liquid Laundry Detergent Formulations

[0127] Following administration, the sample was divided into two separate 5-gram aliquots. One aliquot was inoculated with a 50 µl diluted bacterial solution, and the second aliquot was inoculated with a 50 µl diluted fungal solution, as described below. An unpreserved product sample was included as a growth control.

[0128] For personal care products, a mixed bacterial inoculum is prepared using a 24-hour culture of test bacteria grown in trypsin-soy liquid medium (TSB) (Table 6). For home care products, a mixed bacterial inoculum is prepared using a 24-hour culture of test bacteria from Table 6 (whole pool) or Table 7 (simplified pool) grown in trypsin-soy liquid medium (TSB). Details are disclosed in the following home care examples. Equal volumes of bacterial test strains are combined and diluted 1 to 10 times in phosphate buffer to obtain approximately 5 x 10⁻⁶ cells / mL. 7 Up to 5x10 8 Inoculum at colony-forming units / ml (cfu / ml). Inoculate test samples with a 1% mixed bacterial inoculum. For personal and home care products, prepare a mixed fungal inoculum using a yeast cell suspension of *Candida albicans* ATCC#10231 and *Aspergillus brasiliensis* ATCC#16404 in phosphate-buffered saline. Combine equal volumes of the fungal test strains and dilute 1 to 10 times with phosphate-buffered saline to obtain approximately 5 x 10⁻⁶ cells / ml. 6 Up to 5 x 10 7 Inoculum of cfu / ml. Inoculate test samples with 1% mixed fungal inoculum.

[0129] Table 6. Mixed bacterial inoculants for personal care and / or home care

[0130] Table 7. Mixed bacterial inoculants for home care

[0131] For personal care products, samples were subjected to two microbial challenges at time 0 and a second inoculation 7 days later. For home care products, samples were subjected to three microbial challenges at time 0 and a second and third inoculation 7 and 14 days later, respectively. The number of microorganisms added to each sample was determined by standard most probable number (MPN) assays in tryptone soy broth (TSB) for bacteria and potato dextrose broth (PDB) for fungi. Samples were incubated at 25°C for four weeks as the test duration. Bacterial and fungal contamination of samples was monitored at 2, 7, 14, 21, and 28 days. Samples challenged with bacteria were streaked onto tryptone soy agar (TSA) and incubated at 30°C for 24 hours. Samples challenged with fungi were streaked onto potato dextrose agar (PDA) and incubated at 25°C for 7 days. After incubation, the plates were assigned a growth grade to determine the colony-forming units (CFU / g) present in each test sample at the test time point.

[0132] Table 8 shows the growth scores. As used in various challenge testing methods, the passing standard is more stringent for bacteria than for fungi. A rating of 2, 3, or 4 at 21 and / or 28 days is considered a failure for bacteria. For fungi, a rating of 2 at 21 and / or 28 days is sufficient and therefore acceptable.

[0133] Table 8. Growth score is used to determine CFU / mL in the test sample.

[0134]

[0135] For the bacterial challenge test, if the composition receives a growth rating score of 1 or less due to bacteria during days 21-28 of the test period, the composition is rated "pass"; and if the composition receives a growth rating score of 2 or greater due to bacteria during days 21-28 of the test period, the composition is rated "fail".

[0136] For the fungal challenge test, if the composition obtains a growth rating score of 2 or less for fungal growth during days 21-28 of the test period, the composition is rated as “acceptable”, and if the composition obtains a growth rating score of more than 2 for fungal growth during days 21-28 of the test period, the composition is rated as “unacceptable”.

[0137] The "qualified" grade of the dosage formulation also depends on the unpreserved sample that has a "unqualified" grade.

[0138] Example 1A

[0139] Representative no-rinse emulsion formulations (pH 6.3) were prepared according to Table 1. As shown in Table 9, although the emulsion formulations with 0.4 wt% of the preservatives phenoxyethanol or benzyl alcohol alone showed some antimicrobial activity compared to the unpreserved wash (blank), the formulations fell far short of the challenge test criteria. Formulations administered with nonanoic acid alone also failed the challenge test criteria. However, when the same doses of phenoxyethanol or benzyl alcohol were combined with nonanoic acid, these emulsion formulations unexpectedly showed significantly enhanced antimicrobial properties against both bacteria and fungi (i.e., an enhanced reduction of ≥3 logarithmic colony-forming units / g (CFU / g) for bacteria at day 21 or 28, and an enhanced reduction of ≥1 logarithmic colony-forming units / g for fungi at day 21 or 28), each achieving a pass rating in the challenge test. This example demonstrates that nonanoic acid surprisingly enhances the potency of phenoxyethanol and benzyl alcohol, and advantageously enables effective broad-spectrum antimicrobial activity even at low dose levels of phenoxyethanol and benzyl alcohol (e.g., at 0.4 wt%).

[0140] Table 9. Challenge Test Data - Emulsion Formulations Containing Carbomer

[0141] Example 1B

[0142] Representative micelle water formulations (pH 6.0) were prepared according to Table 2. As shown in Table 10, the micelle water formulations passed the challenge test against bacteria when administered alone with phenoxyethanol (POE) or benzyl alcohol (BA), but neither phenoxyethanol nor benzyl alcohol was sufficient to protect the micelle water formulations from fungal growth. The micelle water formulations also failed the challenge test when administered alone with nonanoic acid or with the commercial multifunctional synergist 2-ethylhexylglycerol or 1,2-hexanediol.

[0143] In contrast, when the same doses of phenoxyethanol or benzyl alcohol are combined with nonanoic acid, the micellar aqueous formulation unexpectedly exhibits significantly enhanced antimicrobial properties, particularly against fungi in this example. Furthermore, the combination with nonanoic acid demonstrates superior antimicrobial performance compared to combinations of two commercially available multifunctional benchmarks, 2-ethylhexylglycerol (EHG) and 1,2-hexanediol. This example further demonstrates that nonanoic acid enhances the antimicrobial activity of phenoxyethanol and benzyl alcohol, and advantageously enables effective broad-spectrum antimicrobial activity at reduced dose levels of phenoxyethanol and benzyl alcohol (e.g., at 0.3 wt%).

[0144] Table 10. Challenge Test Data - Micellar Water Formulation

[0145] Example 1C

[0146] Representative micelle aqueous formulations (pH 6.0) were prepared according to Table 2. In this example, approximately 10 [units of measurement] were used, compared to [units of measurement] in Example 1B. 7 Compared to an inoculation intensity of CFU / ml, the inoculation intensity of the bacterial pool is approximately 10. 8 The cfu / ml level was high. As shown in Table 11, according to the challenge test criteria, neither phenoxyethanol nor benzyl alcohol alone at a dose level of 0.3 wt% was sufficient to protect the micelle aqueous formulation against bacterial or fungal growth. As expected, the formulation administered with nonanoic acid alone (0.3 wt%) failed the challenge test. However, when the same dose of phenoxyethanol or benzyl alcohol was combined with nonanoic acid, the formulation unexpectedly showed a significant enhancement in antimicrobial activity to protect the formulation from both bacteria and fungi (“pass” overall result). This example further demonstrates that nonanoic acid unexpectedly enhances the antimicrobial efficacy of phenoxyethanol and benzyl alcohol, enabling effective broad-spectrum antimicrobial activity at reduced dose levels of phenoxyethanol and benzyl alcohol (e.g., at 0.3 wt%).

[0147] Table 11. Challenge Test Data - Micellar Water Formulation

[0148] Example 1D

[0149] Additional representative no-rinse emulsion formulations (pH 6.3) were prepared according to Table 1. Phenoxyethanol, benzyl alcohol, and / or nonanoic acid were administered as shown in Table 12, and antibacterial challenge tests were performed. Growth ratings on days 2, 7, 14, 21, and 28 are provided in Table 12. As shown, when phenoxyethanol (POE, 0.4 wt%) or benzyl alcohol (BA, 0.4 wt%) was added alone, the emulsion formulations failed the antibacterial challenge test. However, when the same dose of phenoxyethanol or benzyl alcohol was combined with nonanoic acid (0.4 wt%), these formulations passed the antibacterial challenge test. Furthermore, the combination of 0.4% BA + 0.4% nonanoic acid unexpectedly showed superior antibacterial efficacy compared to 0.8 wt% benzyl alcohol alone (e.g., a 2-log reduction improvement on days 14 and 21). This example further demonstrates the synergistic enhancement of the antimicrobial activity of benzyl alcohol when combined with nonanoic acid.

[0150] Furthermore, the combination of 0.4% POE + 0.4% nonanoic acid unexpectedly showed superior antimicrobial efficacy compared to 0.8 wt% phenoxyethanol alone (e.g., a 1-log reduction improvement on day 2 and a 3-log reduction improvement on day 7). This example further demonstrates the synergistic enhancement of antimicrobial activity when phenoxyethanol is combined with nonanoic acid.

[0151] Table 12. Challenge Test Data - Emulsion Formulations Containing Carbomer

[0152] Example 1E

[0153] Representative shower gels (pH 6.5) were prepared according to Table 3. As shown in Table 13, the unpreserved shower gel formulation (blank) passed the challenge criterion against fungi but failed against bacteria. Formulations administered alone with benzyl alcohol (0.5 wt%) or nonanoic acid (0.5 wt%) also failed to resist bacteria. However, the shower gel formulation administered with both benzyl alcohol (0.5 wt%) and nonanoic acid (0.5 wt%) unexpectedly showed a significant improvement in antimicrobial activity through the challenge test. In direct comparison, the combination of benzyl alcohol (0.5 wt%) and the baseline multifunctional synergist ethylhexylglycerin (0.5 wt%) failed the challenge test and showed no improvement compared to the unpreserved shower gel blank.

[0154] Table 13. Challenge Test Data - Shower Gel

[0155] Example 1F

[0156] Representative manual dishwashing formulations (pH = 5.5) were prepared according to Table 4. A simplified bacterial library (i.e., Table 7) was used in this example. As shown in Table 14, phenoxyethanol alone at a dose of 1.0 wt% failed the challenge test. As expected, nonanoic acid alone at a dose of 1.0 wt% also failed the challenge test. However, at the same total dosage level (1 wt%), the combination of phenoxyethanol and nonanoic acid at 50 / 50 (w / w) and 60 / 40 (w / w) ratios showed a significant improvement in antimicrobial efficacy (i.e., a 4-log reduction on day 21 compared to phenoxyethanol alone, and a 4-log reduction on days 21 and 28 compared to nonanoic acid alone). The combination also showed improved antifungal efficacy and was sufficient to pass the challenge test. This further demonstrates the synergistic enhancement of antimicrobial activity of phenoxyethanol when combined with nonanoic acid. Furthermore, compared to the two-component combination, at the same total dose level (1 wt%), the three-component combination with phenoxyethanol, nonanoic acid, and capryloyl hydroxamic acid (i.e., 49 / 49 / 2 and 59 / 39 / 2 w / w / w) showed further improvement. In these three-component combinations, a dose level of only 0.02 wt% capryloyl hydroxamic acid was sufficient to provide a 1–2 log reduction improvement in fungal activity by day 28 compared to the two-component combination.

[0157] Table 14. Challenge Test Data - Manual Dishwashing

[0158] Example 1G

[0159] Representative liquid laundry detergent formulations (pH = 7.5) were prepared according to Table 5. A simplified bacterial library (i.e., Table 7) was used in this example. As shown in Table 15, phenoxyethanol alone at 0.5% or 1.0% dosage levels was insufficient to pass the challenge test due to lack of antifungal efficacy, and nonanoic acid alone at 1.0% dosage level failed to pass the challenge criteria for both bacteria and fungi. However, the combination of phenoxyethanol and nonanoic acid synergistically enhanced antimicrobial properties at the same total dose level of 1.0% with 50 / 50 (w / w) and 60 / 40 (w / w) dosage levels. The combination of phenoxyethanol and nonanoic acid showed a significant improvement in antifungal efficacy at 1% compared to phenoxyethanol or nonanoic acid alone. Furthermore, the 3-component combination of phenoxyethanol, nonanoic acid, and capryloyl hydroxamic acid (49 / 49 / 2 and 59 / 39 / 2 w / w / w) showed additional unexpected synergy and further improvement at a total dose level of 1% compared to each component alone or in a 2-component combination. Compared to the two-component combination, the loading level of only 0.02% capryloyl hydroxamic acid in these three-component combinations was sufficient to provide a 1-log reduction improvement against fungi by day 28.

[0160] Table 15. Challenge Test Data - Liquid Washing

[0161] Example 1H

[0162] Representative liquid laundry detergent formulations (pH = 7.5) were prepared according to Table 5. A full bacterial pool (i.e., Table 6) was used in this example (compared to the simplified pool in Example 1G). As shown in Table 16, phenoxyethanol alone at dose levels of 0.5% or 1.0% was insufficient to pass the challenge test due to a lack of antifungal efficacy. For the full bacterial pool (i.e., Table 6), 0.5% phenoxyethanol alone also failed against bacteria. A 1.0% dose level of nonanoic acid alone failed the challenge criteria against both bacteria and fungi. However, the combination of phenoxyethanol and nonanoic acid synergistically enhanced antimicrobial performance at the same total dose level of 1.0% with 60 / 40 (w / w) and 70 / 30 (w / w) rates. Furthermore, the three-component combination of phenoxyethanol, nonanoic acid, and capryloyl hydroxamic acid (59 / 39 / 2 and 69 / 29 / 2 w / w / w) showed additional unexpected synergy and further improvement at a total dose level of 1% compared to each component alone or in a two-component combination. Compared to the two-component combination, the loading level of only 0.02% capryloyl hydroxamic acid in these three-component combinations was sufficient to provide a 1-log reduction improvement in fungi by day 21.

[0163] Table 16. Challenge Test Data - Liquid Washing

[0164] Example 1I

[0165] Representative no-rinse emulsion formulations (pH=6.5) were prepared according to Table 1. As shown in Table 17, 0.4 wt% phenoxyethanol and 0.8 wt% nonanoic acid alone did not pass the challenge criteria against bacteria and fungi. At a total dose level of 0.8 wt%, the combination of phenoxyethanol and nonanoic acid at different ratios (50 / 50, 60 / 40, 70 / 30, 80 / 20, 90 / 10 w / w) showed superior antifungal properties (e.g., a logarithmic difference in fungal growth rating) compared to 0.8 wt% phenoxyethanol on day 2. The combination of phenoxyethanol and nonanoic acid showed an additional significant improvement in antimicrobial properties compared to 0.4 wt% phenoxyethanol, as particularly demonstrated by the combination of phenoxyethanol and nonanoic acid at 50 / 50 w / w, which also applied phenoxyethanol at 0.4 wt%. The unexpected performance improvement of this combination is attributed to the synergistic effect between phenoxyethanol and nonanoic acid, although nonanoic acid showed little to no antimicrobial efficacy when used alone at the applied dose levels. Furthermore, the three-component combinations of phenoxyethanol, nonanoic acid, and capryloyl hydroxamic acid (at 49 / 49 / 2, 69 / 29 / 2, and 69 / 29 / 2 w / w / w) showed additional unexpected synergistic effects and further improvements against both bacteria and fungi at a total dose level of 0.8%, compared to the two-component combinations or each component alone. In these three-component combinations, a loading level of only 0.016% capryloyl hydroxamic acid was sufficient to provide at least one log reduction improvement against fungi (days 2, 21, and 28) and at least one log reduction improvement against bacteria (day 2), compared to the two-component combinations.

[0166] Table 17. Challenge Test Data - Emulsion Formulations Containing Carbomer

[0167] Example 2

[0168] The chelating properties of nonanoic acid were measured using the ZenBio Cupric Ion Chelating (CIC) assay (catalog number AOX-16). This assay measures the ability of nonanoic acid to chelate free divalent copper ions in a solution, thereby inhibiting Cu(II) binding to catechol violet (PV) to produce a highly colored complex. The absorbance of the divalent copper-PV (Cupric-PV) complex was measured at a wavelength of 632 nm. The divalent copper ion chelating activity was determined as the percentage of total PV relative to Cu(II) binding. Ethylenediaminetetraacetic acid (EDTA), a well-known chelating agent, was used as a positive control. A series of EDTA concentrations of seven different concentrations from 0 to 1000 µM were prepared and their corresponding absorbances were measured and used as calibration curves (divalent copper ion chelation (%) versus EDTA concentration). The percentage of divalent copper ion chelation was determined according to the following calculations and Equation 1. The background absorbance value was calculated by averaging the absorbance values ​​of three background wells (without CuSO4 or sample). Then, the average background absorbance is subtracted from the absorbance values ​​of all samples. The maximum absorbance value (Absmax) is determined by averaging the absorbance values ​​of the three wells containing CuSO4, PV, and assay buffer. In Equation 1, Abstest is the absorbance of the test sample.

[0169] The percentage of divalent copper ion chelation is calculated as follows: 100 × (Absmax – Abstest) / Absmax (Equation 1)

[0170] Calibration curves (the percentage of divalent copper ion chelation was fitted to the EDTA concentration using a polynomial curve after the Log10 conversion concentration (R2>0.98)).

[0171] As shown in Table 18, nonanoic acid (775 μM) exhibited chelating activity equivalent to 667 μM EDTA. In contrast, ethylhexylglycerol (a multifunctional compound) and phenoxyethanol (a preservative) did not show chelating properties from the same assay (i.e., approximately 0 μM EDTA equivalents).

[0172] Table 18. EDTA Equivalent (Calculated from EDTA Calibration Curve)

[0173] Example 3

[0174] A series of preservative compositions with alkaline stabilizers were prepared according to Table 19. First, phenoxyethanol and nonanoic acid were mixed to form a homogeneous, clear solution. Sodium hydroxide (NaOH) or potassium hydroxide (KOH) was added to water to form an alkaline solution as an alkaline stabilizer. Then, the alkaline solution was slowly added to the homogeneous, clear solution. The pH value of the final composition was measured (Table 19).

[0175] Table 19. Preservative compositions containing alkaline stabilizers

[0176] All preservative compositions were stored in an oven at 55°C. Gas chromatography (GC) was used to measure the wt% loss of the combined phenoxyethanol (POE) and nonanoic acid (PA) after 2 and 5 weeks. As shown in Table 20, the addition of an alkaline solution stabilized the compositions over time at elevated temperatures (i.e., these compositions showed much lower wt% loss over time). Specifically, samples 2 and 4 showed excellent shelf-life stability, with a loss of less than 4.0 wt% of the combined phenoxyethanol and nonanoic acid when stored at 55°C for 5 weeks.

[0177] Table 20. Stability of preservative compositions containing alkaline stabilizers

[0178] Example 4

[0179] Representative no-rinse emulsion formulations were prepared according to Table 1 (pH 6.5). As shown in Table 21, the preservative composition containing phenoxyethanol (POE), nonanoic acid (PA), and an alkaline stabilizer (an alkaline solution of potassium hydroxide (KOH+H2O)) showed better antifungal efficacy compared to phenoxyethanol alone (the preservative composition also used 40% less POE compared to the sample administered with POE alone). Furthermore, as shown in Table 21, the preservative composition containing POE, PA, an alkaline stabilizer, and octylhydroxamic acid (CHA) showed additional synergistic effects and improvements at the same total dose level (0.8%) compared to phenoxyethanol alone, even when the CHA loading level was as low as 0.016% in the emulsion formulation.

[0180] Table 21. Challenge Test Data - Emulsion Formulations

[0181] Representative manual dishwashing formulations were prepared according to Table 4 (pH 6.5). Phenoxyethanol (POE) was administered alone to the dishwashing formulation at a loading level of 0.8 wt%, and separately, the same preservative composition as shown in Table 21 above was administered to the dishwashing formulation at a total loading level of 0.8 wt%. As shown in Table 22, the preservative compositions of this disclosure exhibited better antifungal efficacy compared to phenoxyethanol alone. The manual dishwashing formulations given the preservative blends passed the antifungal challenge test with significant efficacy improvements (e.g., improvements greater than 2 logarithmic levels at days 21 and 28).

[0182] Table 22. Challenge Test Data - Manual Dishwashing Agents 。

Claims

1. An antimicrobial composition comprising (a) an antimicrobial agent selected from the group consisting of phenoxyethanol, benzyl alcohol, and combinations thereof, and (b) nonanoic acid and / or a salt thereof, wherein the antimicrobial agent (a) and the nonanoic acid and / or a salt thereof are present in a combined amount of at least 50 wt% based on the total weight of the composition, and the weight ratio of the antimicrobial agent (a) to the nonanoic acid and / or a salt thereof (b) is from about 20:1 to about 1:2.5, and wherein, Based on the total weight of the composition, the composition further comprises about 0.2 wt% to about 25 wt% of an alkaline stabilizer, and wherein the composition has a pH of about 5.0 to about 7.

5.

2. The composition according to claim 1, wherein, Based on the total weight of the composition, the composition comprises at least 75 wt% of the combined amount of the antimicrobial agent (a) and the nonanoic acid and / or its salt (b).

3. The composition according to claim 2, wherein, The composition comprises an antimicrobial agent (a) in an amount of at least 85 wt% combined with the nonanoic acid and / or its salt (b) and an alkaline stabilizer in an amount of about 1 wt% to about 15 wt%, each based on the total weight of the composition.

4. The antimicrobial composition according to claim 1, wherein, The antimicrobial agent (a) is phenoxyethanol.

5. The antimicrobial composition according to claim 1, wherein, The antimicrobial agent (a) is benzyl alcohol.

6. The antimicrobial composition according to any one of the preceding claims, wherein, The component (b) is nonanoic acid.

7. The antimicrobial composition according to any one of the preceding claims, wherein, The antimicrobial composition further comprises one or more additional antimicrobial agents (c).

8. The antimicrobial composition according to claim 7, wherein, The weight ratio of the combined amount of (a) and (b) to the amount of (c) ranges from about 5:1 to about 150:

1.

9. The antimicrobial composition according to claim 7 or 8, wherein, Based on the total weight of the antimicrobial composition, the antimicrobial composition contains no more than 10 wt% of the amount of one or more other antimicrobial agents (c).

10. The antimicrobial composition according to claim 7, wherein, The weight ratio of the combined amount of (a) and (b) to the amount of (c) ranges from about 12:1 to about 100:

1.

11. The antimicrobial composition according to claim 7 or 10, wherein, Based on the total weight of the antimicrobial composition, the antimicrobial composition contains one or more of the other antimicrobial agents (c) in an amount not exceeding 5 wt%.

12. The antimicrobial composition according to any one of claims 7 to 11, wherein, The one or more additional antimicrobial agents (c) include alkyl hydroxamic acids and / or their salts.

13. The antimicrobial composition according to claim 12, wherein, The alkyl hydroxamic acid and / or its salt is octanoyl hydroxamic acid and / or its salt.

14. The antimicrobial composition according to any one of the preceding claims, wherein, The weight ratio of the antimicrobial agent (a) to the nonanoic acid and / or its salt (b) is about 5:1 to about 1:1.

5.

15. The antimicrobial composition according to any one of the preceding claims, wherein, The at least one alkaline stabilizer includes a base selected from metal hydroxides, oxides, carbonates, bicarbonates, phosphates or hydrides, amine bases, or combinations thereof.

16. The antimicrobial composition according to claim 15, wherein, The base is selected from sodium hydroxide, potassium hydroxide, or a combination thereof.

17. The antimicrobial composition according to any one of the preceding claims, wherein, When stored at 55°C for two weeks, the composition exhibits a loss of ≤5 wt% of the combined antimicrobial agent (a) and the nonanoic acid and / or its salt (b).

18. The antimicrobial composition according to any one of the preceding claims, wherein, When stored at 55°C for five weeks, the composition exhibits a loss of ≤10 wt% of the combined antimicrobial agent (a) and the nonanoic acid and / or its salt (b).

19. An aqueous product formulation comprising an antimicrobially effective amount of the antimicrobial composition according to any one of the preceding claims.

20. The aqueous product formulation according to claim 19, wherein, The formulation is in the form of a personal care or home care product formulation.

21. The aqueous product formulation according to claim 19 or 20, wherein, The formulation has a pH of at least 6.

0.

22. The aqueous product formulation according to claim 19 or 20, wherein, The formulation has a pH of at least 6.

5.

23. The aqueous product formulation according to claim 19 or 20, wherein, The formulation has a pH of at least 7.

0.

24. The aqueous product formulation according to claim 19 or 20, wherein, The formulation has a pH of at least 7.

5.

25. A personal care or home care product formulation comprising an antimicrobially effective amount of (a) an antimicrobial agent and (b) nonanoic acid and / or a salt thereof, said antimicrobial agent being selected from the group consisting of phenoxyethanol, benzyl alcohol and combinations thereof, and one or more additional ingredients suitable for use in the personal care or home care formulation, wherein, The antimicrobial agent (a) is in a weight ratio of about 40:1 to about 1:5 to the nonanoic acid and / or its salt (b), and the product formulation has a pH of at least 6.

0.

26. A method for controlling microbial growth in a product formulation or for preserving a product formulation, comprising adding to the product formulation (a) an antimicrobial agent selected from the group consisting of phenoxyethanol, benzyl alcohol, and combinations thereof, and (b) nonanoic acid and / or a salt thereof, wherein, The antimicrobial agent (a) and the nonanoic acid and / or its salt (b) are present in the formulation in a combined antimicrobial effective amount, the weight ratio of the antimicrobial agent (a) to the nonanoic acid and / or its salt (b) being about 40:1 to about 1:5, and the product formulation having a pH of at least 6.

0.

27. The formulation or method according to claim 25 or 26, wherein, The weight ratio of the antimicrobial agent (a) to the nonanoic acid and / or its salt (b) is about 20:1 to about 1:2.

5.

28. The formulation or method according to claim 27, wherein, The weight ratio of the antimicrobial agent (a) to the nonanoic acid and / or its salt (b) is from about 10:1 to about 1:1.

5.

29. The formulation or method according to any one of claims 25 to 28, wherein, The formulation has a pH of at least 6.

5.

30. The formulation or method according to any one of claims 25 to 28, wherein, The formulation has a pH of at least 7.

0.

31. The formulation or method according to any one of claims 25 to 28, wherein, The formulation has a pH of at least 7.

5.

32. The formulation or method according to any one of claims 25 to 31, wherein, Based on the total weight of the formulation, the antimicrobial agent (a) constitutes no more than 0.7 wt%.

33. The formulation or method according to claim 32, wherein, Based on the total weight of the formulation, the antimicrobial agent (a) constitutes no more than 0.5 wt%.

34. A personal care or home care product formulation comprising, based on the total weight of the formulation, about 0.2 wt% to about 3 wt% of an antimicrobially effective amount of (a) an antimicrobial agent and (b) nonanoic acid and / or a salt thereof, said antimicrobial agent being selected from the group consisting of phenoxyethanol, benzyl alcohol and combinations thereof, (c) alkyl hydroxamic acid and / or a salt thereof, and one or more additional ingredients suitable for use in the personal care or home care formulation, wherein, The antimicrobial agent (a) is in a weight ratio of about 40:1 to about 1:5 to the nonanoic acid and / or its salt (b), and the combined amount of (a) and (b) is in a weight ratio of about 5:1 to about 150:1 to the amount of the alkyl hydroxamic acid and / or its salt (c).

35. A method for controlling microbial growth in a product formulation or for preserving a product formulation, comprising adding to the product formulation (a) an antimicrobial agent selected from the group consisting of phenoxyethanol, benzyl alcohol, and combinations thereof, (b) nonanoic acid and / or its salts, and (c) alkyl hydroxamic acid and / or its salts, wherein, Based on the total weight of the formulation, the antimicrobial agent (a) and the nonanoic acid and / or its salt (b) are present in the formulation in an antimicrobial effective amount in combination of about 0.2 wt% to about 3 wt%, and wherein the weight ratio of the antimicrobial agent (a) to the nonanoic acid and / or its salt (b) is about 40:1 to about 1:5, and the weight ratio of the combined amount of (a) and (b) to the amount of the alkyl hydroxamic acid and / or its salt (c) is about 5:1 to about 150:

1.

36. The formulation or method according to claim 34 or 35, wherein, The weight ratio of the antimicrobial agent (a) to the nonanoic acid and / or its salt (b) is about 20:1 to about 1:2.

5.

37. The formulation or method according to claim 36, wherein, The weight ratio of the antimicrobial agent (a) to the nonanoic acid and / or its salt (b) is from about 10:1 to about 1:1.

5.

38. The formulation or method according to any one of claims 34 to 37, wherein, The alkyl hydroxamic acid and / or its salt (c) are present in an amount not exceeding 0.1 wt%.

39. The formulation or method according to any one of claims 34 to 38, wherein, The weight ratio of the combined amount of (a) and (b) to the amount of (c) ranges from about 12:1 to about 100:

1.

40. The formulation or method according to any one of claims 34 to 39, wherein, The alkyl hydroxamic acid and / or its salt is octanoyl hydroxamic acid and / or its salt.

41. The formulation or method according to any one of claims 34 to 40, wherein, The formulation has a pH of at least 6.

0.

42. The formulation or method according to any one of claims 34 to 40, wherein, The formulation has a pH of at least 6.

5.

43. The formulation or method according to any one of claims 34 to 40, wherein, The formulation has a pH of at least 7.

0.

44. The formulation or method according to any one of claims 34 to 40, wherein, The formulation has a pH of at least 7.5.

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