Antimicrobial compositions, stabilized compositions thereof, and applications thereof in product formulations

Abstract

The present disclosure provides antimicrobial compositions containing at least one saturated straight-chain fatty acid having a carbon chain length of from 6 to 12 carbon atoms and / or a salt thereof, at least one alkylhydroxamic acid and / or a salt thereof, and an organic solvent each in the amounts described herein. The present disclosure further relates to stabilized antimicrobial compositions containing such materials, as well as to the application of the presently disclosed antimicrobial compositions in product formulations.

Description

[0001] Docket No.: P003 00091-WQ-PCT

[0002] TITLE

[0003] Antimicrobial Compositions, Stabilized Compositions Thereof, and Applications Thereof in Product Formulations

[0004] FIELD OF INVENTION

[0005] The present invention relates to antimicrobial compositions containing a combination of certain fatty acids and alkylhydroxamic acids and the application of such antimicrobial compositions to product formulations, and further relates to stabilized antimicrobial compositions containing the fatty acid and alkylhydroxamic acid materials.

[0006] BACKGROUND OF THE INVENTION

[0007] Preservation against microbial contamination of product formulations, such as personal care products (e.g., cosmetic products) and home care products, plays a pivotal role in consumer safety, product stability, integrity, and quality, sustainability, among others. There is increasing consumer demand and a need for antimicrobial or preservative systems that can reduce reliance on traditional preservatives in favor of naturally -derived ingredients, particularly ingredients that can provide multifunctional benefits to end product formulations.

[0008] SUMMARY OF INVENTION

[0009] In accordance with the present disclosure, it has been discovered that an antimicrobial composition containing, in the amounts described herein, a combination of at least one alkylhydroxamic acid and / or a salt thereof and at least one saturated straight-chain fatty acid having a carbon chain length of from 6 to 12 carbon atoms and / or a salt thereof in an organic solvent can provide multifunctional benefits to product formulations, including surprisingly effective antimicrobial properties even in the absence of conventional preservatives (such as phenoxyethanol).

[0010] The present disclosure provides an antimicrobial composition comprising (a) from about 2 to about 15 wt% of at least one alkylhydroxamic acid and / or a salt thereof; (b) from about 20 to about 70 wt% of at least one saturated straight-chain fatty acid having a carbon chain length of from 6 to 12 carbon atoms and / or a salt thereof; and (c) from about 20 to about 70 wt% of at least one organic solvent. Also provided is a method of preparing an antimicrobial composition comprising combining (a) at least one alkylhydroxamic acid and / or a salt thereof in an amount of from about 2 to about 15 wt%; (b) at least one saturated straight-chain fatty acid having a carbon chain length of from 6 to 12 carbon atoms and / or a salt thereof in an amount of from about 20 to about 70 wt%; and (c) at least one organic solvent in an amount of from about 20 to about 70 wt%. The method preferably further comprises combining the components (a), (b), and (c) with water and / or at least one alkaline stabilizer, preferably in an amount of from about 2 to about 20 wt%.Docket No.: P003 00091-WQ-PCT

[0011] Also provided is an aqueous product formulation comprising an antimicrobial effective amount of an antimicrobial composition in accordance with the present disclosure.

[0012] Further provided is a personal care or home care product formulation comprising an antimicrobial effective amount of an antimicrobial composition in accordance with the present disclosure.

[0013] In addition, the present disclosure includes a method of controlling microbial growth in or preserving a product formulation, comprising adding to the product formulation an antimicrobial effective amount of the antimicrobial composition according to the present disclosure.

[0014] DETAILED DESCRIPTION

[0015] Unless otherwise specified, the following terms are defined as follows:

[0016] As used herein, “formulation” refers to a preparation that is to be preserved or provided with antimicrobial activity using the antimicrobial composition of the present disclosure.

[0017] As used herein, an “antimicrobial effective amount” means an amount to provide a desired antimicrobial effect or activity, such as a desired preservative, antibacterial and / or antifungal effect. As used herein, “microorganism” includes, for example, bacteria and fungi, including yeast and mold. pH values or ranges as provided herein refer to pH at room temperature (approximately 25 °C), unless otherwise specified.

[0018] All weight percentages (wt%) disclosed herein are based on the total weight of the composition or formulation, unless otherwise indicated.

[0019] The antimicrobial composition of the present disclosure comprises (a) from about 2 to about 15 wt%, preferably from about 3.5 to about 13 wt%, more preferably from about 4.5 wt% or from about 5 wt% to about 12.5 wt% or to about 10 wt%, of at least one alkylhydroxamic acid and / or a salt thereof; (b) from about 20 to about 70 wt%, preferably from about 30 to about 65 wt%, more preferably from about 35 wt% or from about 40 wt% to about 60 wt%, to about 55 wt%, or to about 50 wt%, of at least one saturated straight-chain fatty acid having a carbon chain length of from 6 to 12 carbon atoms and / or a salt thereof; and (c) from about 20 to about 70 wt%, preferably from about 25 to about 60 wt%, more preferably from about 25 wt% or from about 30 wt% to about 55 wt%, to about 50 wt%, to about 45 wt% or to about 40 wt%, of at least one organic solvent. Preferably, the antimicrobial composition comprises the at least one alkylhydroxamic acid and / or a salt thereof (a) and the at least one saturated straight-chain fatty acid and / or a salt thereof (b) in a weight ratio of (a) to (b) of from about 1: 1.5 to about 1:15, preferably from about 1:2 to about 1: 12, more preferably from about 1:2.5, from about 1:3 or from about 1:4 to about 1:10, to about l:8 or to about 1:6.

[0020] In general, the alkylhydroxamic acids of the present disclosure have a linear or branched carbon chain preferably having from 2 to 22 carbon atoms, more preferably from 6 to 12 carbon atoms. The carbonDocket No.: P003 00091-WQ-PCT

[0021] chains may include double bonds, i.e., areas of unsaturation and may also have functionality using substituted groups (e.g., hydroxyl group(s)) depending on the desired end use and properties. The antimicrobial composition may comprise one or more salts of alkylhydroxamic acids, such as those where the cations of the alkylhydroxamic acid salts are chosen from Li+, Na+, K+, Mg2+, Ca2+, Al3+, NH?, primary ammonium ions, secondary ammonium ions, tertiary ammonium ions and quaternary ammonium ions, e.g., caprylhydroxamic acid sodium salt, caprylhydroxamic acid potassium salt, caprylhydroxamic acid ammonium salt, etc.

[0022] Preferred alkylhydroxamic acids include those having an alkyl group of a chain length of from 2 to 22 carbon atoms, which may be branched or linear in structure, substituted (e.g., hydroxy, alkoxy and the like) or unsubstituted, and saturated or unsaturated (e.g., alkenyl, alkenoxy, alkynyl, alkynoxy and the like). For example, the carbon chains may be interrupted by one or more oxygen atoms and / or may contain one or more side- and / or terminal -hydroxyl group substituents. Other functional groups, particularly groups compatible with or suggested for use in personal care (e.g., cosmetics), health care (e.g., pharmaceutical) or home care formulations, may be used. Preferably, the alkylhydroxamic acid contains an alkyl group having a chain length of 6 to 12 carbon atoms. Examples of suitable alkylhydroxamic acids include hexanohydroxamic acid (six-carbon chain), caprylhydroxamic acid (eight-carbon chain), decanohydroxamic acid (10-carbon chain), laurohydroxamic acid (12-carbon chain) and combinations thereof.

[0023] Preferred alkylhydroxamic acids are of the formula (I) or a salt thereof:

[0024] O R?

[0025] R - £ - - Q ; >

[0026]

[0027] (I)

[0028] wherein R is a linear or branched, substituted or unsubstituted, carbon chain of from 2 to 22 carbon atoms, preferably from 6 to 12 carbon atoms, which chain may be interrupted by one or more oxygen atoms, and may include saturated or unsaturated carbon bonds. R groups may include, for example, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy and similar groups, are branched or linear, and which groups may be further functionalized using substituted groups, including hydroxy or other groups, such as acceptable for personal care (e.g., cosmetically acceptable), health care (e.g., pharmaceutically acceptable) or home care formulations and compatible with such end applications. R1may be hydrogen or R, preferably hydrogen.

[0029] The at least one alkylhydroxamic acid more preferably comprises caprylhydroxamic acid. While the alkylhydroxamic acid may consist essentially of or consist of one alkylhydroxamic acid (e.g., caprylhydroxamic acid), more than one alkylhydroxamic acid may be used.Docket No.: P003 00091-WQ-PCT

[0030] The alkylhydroxamic acids may be derived, e.g., from natural oils and are commercially available or may be synthesized by techniques known or to be developed in the art.

[0031] Fatty acids of the present disclosure are known to occur naturally and can be derived from plant oils, among other extraction or production processes. Preferably, the at least one fatty acid (and / or salt thereof) has a carbon chain length of from 8 to 10 carbon atoms. The fatty acid (and / or salt thereof) of the present disclosure can be essentially a single saturated, straight-chain fatty acid (and / or salt thereof) having a carbon chain length of from 6 to 12, preferably from 8 to 10, carbon atoms or can be any mixture of saturated straight-chain fatty acids (and / or salts thereof) having carbon chain lengths within the range of from 6 to 12, preferably from 8 to 10, carbon atoms. For example, the at least one fatty acid and / or salt thereof may comprise caproic acid and / or a salt thereof, heptanoic acid and / or a salt thereof, caprylic acid and / or a salt thereof, pelargonic acid and / or a salt thereof, capric acid and / or a salt thereof or any combination thereof. More preferably, the fatty acid and / or salt thereof comprises caprylic acid and / or a salt thereof, pelargonic acid and / or a salt thereof, capric acid and / or a salt thereof, or any combination thereof. In preferred embodiments, the fatty acid and / or salt thereof comprises caprylic acid and / or a salt thereof, pelargonic acid and / or a salt thereof, or any combination thereof. Examples of suitable salts of the fatty acids include, but are not limited to, alkali salts, such as sodium and potassium, and ammonium salts.

[0032] The organic solvent component (c) provides a liquid medium or carrier for the antimicrobial composition and, in general, may be chosen to achieve desired physical properties and / or stability of the composition. The organic solvent may also be chosen according to its compatibility or suitability for a desired end application or end product formulation, e.g., in a personal care formulation (e.g., a cosmetically acceptable solvent), health care formulation (e.g., pharmaceutically acceptable solvent) or a home care formulation. Suitable organic solvents include, but are not limited to, alcohols, ethers, esters, and combinations thereof. The alcohols are preferably diols (e.g., glycols) or triols.

[0033] Preferably, the ethers are hydroxyl -containing ethers, such as glyceryl ethers, more preferably glyceryl monoethers. The esters are preferably hydroxyl -containing esters, such as glyceryl esters, more preferably glyceryl monoesters. In further preferred embodiments, the organic solvent comprises a citrate triester (e.g., a trialkyl citrate).

[0034] Examples of the foregoing solvents include, but are not limited to, ethylhexylglycerin, 1,3-propanediol, 2-methyl-l,3-propanediol, 1,2-hexanediol, 1,2-pentanediol, 1,2-decanediol, caprylyl glyceryl ether, caprylyl glycol (1,2-octanediol), propylene glycol (1,2-propanediol), butylene glycol (1,3 -butanediol), pentylene glycol (1,2-pentanediol), hexylene glycol (2-methyl-2,4-pentanediol), glycerol, phytantriol, 1,2, 3 -hexanetriol, 1,2,6-hexanetriol, 2,5-dimethyl-l,2,6-hexanetriol, 1,2,4-hexanetriol, glyceryl monolaurate, glyceryl monocaprate, glyceryl monocaprylate, triethyl citrate, tributyl citrate, trihexyl citrate, triethylhexyl citrate, trioctyl citrate, acetyl triethyl citrate, acetylDocket No.: P003 00091-WQ-PCT

[0035] tributyl citrate, acetyl trihexyl citrate, acetyl triethylhexyl citrate, acetyl trioctyl citrate, and combinations thereof.

[0036] Suitable diols preferably contain from 2 to 24 carbon atoms, more preferably from 2 to 12 carbon atoms, still more preferably from 2 carbon atoms or 3 carbon atoms to 8 carbon atoms or to 6 carbon atoms, such as exemplary species described herein. In many preferred embodiments, the diol comprises or is chosen from pentylene glycol, hexylene glycol, or combinations thereof. Suitable triols preferably contain from 3 to 30 carbon atoms, more preferably from 3 to 24 carbon atoms (e.g., phytantriol), still more preferably from 3 carbon atoms to 12 carbon atoms or to 8 carbon atoms, such as glycerol, 1,2,6-hexanetriol, 2,5-Dimethyl-l,2,6-hexanetriol, 1,2,3-Hexanetriol, 1,2,4-hexanetriol, and combinations thereof. Suitable triester citrates preferably include tri(Ci-Cis)alkyl citrates or tri(C2-Cis)alkenyl citrates, more preferably tri(Ci-Ci2)alkyl citrates or tri(C2-Ci2)alkenyl citrates, still more preferably tri(Ci-Cs)alkyl, tri(C2-Cs)alkyl citrates, or tri(C2-Cs)alkenyl citrates, often trialkyl citrates, such as exemplary species described herein. It will be understood that carbon chains within the foregoing classes of solvents may be linear or branched as suitable to provide solvents that are liquid at room temperature (about 25 °C).

[0037] In preferred embodiments, the organic solvent may comprise a citrate triester of the formula (II): R2OOC-CH2-C(OR5)(COOR3)-CH2-COOR4(II)

[0038] wherein each of R2, R3, and R4is independently a Ci-Cis hydrocarbyl group, preferably a C1-C12 or Ci-Cs hydrocarbyl group, optionally substituted and optionally containing one or more unsaturations, and R5is hydrogen, a Ci-Cs acyl group, or a Ci-Cs alkyl group, preferably hydrogen or a Ci-Cs acyl group, and provided that the triester citrate is a liquid at room temperature (about 25 °C). Preferably, each of R2, R3, and R4is independently an optionally substituted C1-C12 linear or branched alkyl group or an optionally substituted C2-C12 linear or branched alkenyl group. More preferably, each of R2, R3, and R4is independently an optionally substituted Ci-Cs or C2-C8 linear or branched alkyl group or an optionally substituted C2-C8 linear or branched alkenyl group, often an alkyl group, such as ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-hexyl, 2-ethylhexyl, or n-octyl.

[0039] Preferably, R5is hydrogen or a C2-C4 acyl group (e.g., acetyl), more preferably hydrogen.

[0040] The antimicrobial composition may optionally further comprise water in an amount of from 0 to about 20 wt%, preferably in an amount of from about 2 wt% or from about 5 wt% to about 20 wt%, more preferably from about 5 wt%, from about 7.5 wt% or from about 10 wt% to about 17.5 wt% or to about 15 wt%. The antimicrobial composition may optionally comprise water and / or at least one alkaline stabilizer in a total amount of from 0 to about 20 wt%, preferably in an amount of from about 2 wt% or from about 5 wt% to about 20 wt%, more preferably from about 5 wt%, from about 7.5 wt% or from about 10 wt% to about 17.5 wt% or to about 15 wt%. In embodiments of the antimicrobial composition prepared with at least one alkaline stabilizer, the antimicrobial composition preferablyDocket No.: P003 00091-WQ-PCT

[0041] has a pH of from about 5 to about 7.5, such as from about 5.5 or from about 6.0 to about 7.5, to about 7.0 or to about 6.5. The alkaline stabilizer comprises a base preferably chosen from a metal (preferably an alkali metal or alkaline earth metal) hydroxide, oxide, carbonate, bicarbonate, phosphate, or hydride, an amine base or a combination thereof, more preferably a metal hydroxide. The metals are preferably chosen from sodium, potassium, magnesium and calcium. In many preferred embodiments, the alkaline stabilizer comprises sodium hydroxide, potassium hydroxide or a combination thereof. In particular, the alkaline stabilizer may be chosen to ensure compatibility or suitability for a desired end application or end product formulation (e.g., cosmetically or pharmaceutically acceptable). The antimicrobial composition may comprise the base of the alkaline stabilizer in an amount, for example, of from about 0.1 wt%, from about 0.3 wt%, preferably from about 0.5 wt%, more preferably from about 1 wt% or from about 2 wt% to about 10 wt%, preferably to about 8 wt%, to about 6 wt%, or to about 4.5 wt%, based on the total weight of the antimicrobial composition. Typically, the alkaline stabilizer is in the form of an alkaline aqueous solution. For example, the alkaline stabilizer may be an alkaline aqueous solution, such as a metal hydroxide aqueous solution (e.g., where the metal hydroxide is potassium hydroxide, sodium hydroxide or a combination thereof), and may have a strength of the base component in the solution of from about 1% to about 90%, to about 80%, to about 70% or to about 60% (w / w), preferably from about 10%, from about 20% or from about 30% to about 70%, to about 60% or to about 50% (w / w). Higher strength alkaline solutions may also be used. Preferably, the alkaline stabilizer has a pH ranging from about 9.0, more preferably from about 10.0 to about 14.0, such as from about 11.0 or from about 12.0 to about 14.0 orto about 13.0.

[0042] In many preferred embodiments, the antimicrobial composition comprises from about 2 to about 20 wt% of water, more preferably from about 2 wt% or from about 5 wt% to about 15 wt% of water, and the at least one organic solvent comprises or is a diol (e.g., pentylene glycol, hexylene glycol), triol (e.g., glycerol, phytantriol, 1,2,6-hexanetriol), citrate triester (e.g., trialkyl citrate, such as triethyl citrate), or combination thereof.

[0043] Preferably, the antimicrobial composition is free or substantially free of parabens. Preferably, the antimicrobial composition is free or substantially free of formaldehyde donors. Preferably, the antimicrobial composition is free or substantially free of isothiazolinones. Preferably, the antimicrobial composition is free or substantially free of iodopropynyl butyl carbamate (IPBC). Preferably, the antimicrobial composition is free or substantially free of phenoxyethanol. Preferably, the antimicrobial composition is free or substantially free of benzyl alcohol. Preferably, the antimicrobial composition is free or substantially free of benzoic acid and salts thereof, such as sodium benzoate. Preferably, the antimicrobial composition is free or substantially free of parabens, formaldehyde donors, isothiazolinones, IPBC, phenoxyethanol, benzyl alcohol and benzoic acid and salts of benzoic acid (such as sodium benzoate). Preferably, the antimicrobial composition is free orDocket No.: P003 00091-WQ-PCT

[0044] substantially free of conventional preservative materials. In preferred embodiments, the antimicrobial composition is free or substantially free of any additional antimicrobial materials. In general, “substantially free” in the above context means less than 1 wt%, preferably less than 0.75 wt%, more preferably less than 0.5 wt%, even more preferably less than 0.2 wt%, less than 0.1 wt%, less than 0.05 wt%, or less than 0.01 wt%. In the case of isothiazolinones, “substantially free” preferably means less than 0.1 wt%, more preferably less than 0.05 wt% or even more preferably less than 0.01 wt%.

[0045] The antimicrobial composition may further comprise one or more excipients or additives, typically in minor quantities, such as up to about 10 wt% or up to about 5 wt%. Such excipients or additives may be chosen according to their compatibility or suitability for a desired end application or end product formulation (e.g., a cosmetically or pharmaceutically acceptable excipient). Examples include, but are not limited to, dispersants, solubilizers, buffers, fragrances, and / or stabilizers (other than the at least one alkaline stabilizer).

[0046] In many embodiments, the antimicrobial composition consists essentially of, or in further embodiments consists of, the at least one alkylhydroxamic acid and / or salt thereof (a), the at least one fatty acid and / or salt thereof (b), the at least one organic solvent (c), and optionally water and / or the at least one alkaline stabilizer. In further embodiments, the antimicrobial composition consists essentially of, or in further embodiments consists of, the at least one alkylhydroxamic acid and / or salt thereof (a), the at least one fatty acid and / or salt thereof (b), the at least one organic solvent (c), optionally water and / or the at least one alkaline stabilizer, and optionally at least one excipient or additive. In further embodiments, the antimicrobial composition consists essentially of, or in further embodiments consists of, the at least one alkylhydroxamic acid and / or salt thereof (a), the at least one fatty acid and / or salt thereof (b), the at least one organic solvent (c), optionally water and / or the at least one alkaline stabilizer, optionally at least one additional antimicrobial material and optionally at least one excipient or additive.

[0047] Also disclosed is a method of preparing an antimicrobial composition comprising combining (a) at least one alkylhydroxamic acid and / or a salt thereof in an amount of from about 2 to about 15 wt%, preferably from about 3.5 to about 13 wt%, more preferably from about 4.5 wt% or from about 5 wt% to about 12.5 wt% or to about 10 wt%; (b) at least one saturated straight-chain fatty acid having a carbon chain length of from 6 to 12 carbon atoms and / or a salt thereof in an amount of from about 20 to about 70 wt%, preferably from about 30 to about 65 wt%, more preferably from about 35 wt% or from about 40 wt% to about 60 wt%, to about 55 wt%, to about 50 wt% or to about 45 wt%; and (c) at least one organic solvent in an amount of from about 20 to about 70 wt%, preferably from about 25 to about 60 wt%, more preferably from about 25 wt% or from about 30 wt% to about 55 wt%, to about 50 wt%, to about 45 wt% or to about 40 wt%, and, optionally, (d) water and / or an alkaline stabilizer in a total amount of from 0 to about 20 wt%, wherein the weight percentages are based on the totalDocket No.: P003 00091-WQ-PCT

[0048] weight of the antimicrobial composition. The method of preparing the antimicrobial composition preferably comprises combining the components (a), (b), and (c) with water and / or at least one alkaline stabilizer. The total amount of water and / or the at least one alkaline stabilizer which is combined with the components (a), (b), and (c) is preferably from about 2 wt% or from about 5 wt% to about 20 wt%, more preferably from about 5 wt%, from about 7.5 wt% or from about 10 wt% to about 17.5 wt% or to about 15 wt%, based on the total weight of the antimicrobial composition. As described above, the alkaline stabilizer is often in the form of an alkaline aqueous solution (and therefore itself contains water). Nonetheless, the components (a), (b), and (c) may also be combined with water that is added separately from the alkaline aqueous solution, preferably wherein, as described above, the total amount of water and the alkaline stabilizer which is combined with the components (a), (b), and (c) is from about 2 wt% or from about 5 wt% to about 20 wt%, more preferably from about 5 wt%, from about 7.5 wt% or from about 10 wt%to about 17.5 wt% or to about 15 wt%, based on the total weight of the antimicrobial composition. In other embodiments, water is combined with the components (a), (b), and (c) without any addition of an alkaline stabilizer. In embodiments where the antimicrobial composition is prepared with an alkaline stabilizer, the antimicrobial composition preferably has a pH of from about 5.0 to about 7.5, such as from about 5.5 or from about 6.0 to about 7.5, to about 7.0 or to about 6.5. Preferably, the at least one alkylhydroxamic acid and / or a salt thereof (a) and the at least one saturated straight-chain fatty acid and / or a salt thereof (b) are combined in a weight ratio of (a) to (b) of from about 1 : 1.5 to about 1:15, preferably from about 1:2 to about 1: 12, more preferably from about 1:2.5, from about 1:3 or from about 1:4 to about 1: 10, to about 1:8 or to about 1:6. Exemplary embodiments of the at least one alkylhydroxamic acid and / or salt thereof, the at least one saturated straight-chain fatty acid, the at least one organic solvent, and the at least one alkaline stabilizer for the presently disclosed methods are as described above.

[0049] The present disclosure is not limited to any particular technique for preparing the antimicrobial composition and such composition may be prepared in any suitable manner for combining or mixing the components described herein.

[0050] In certain preferred embodiments, the method of preparing an antimicrobial composition comprises combining the components (a), (b), and (c) with an alkaline stabilizer in an amount of the alkaline stabilizer of from about 2 to about 20 wt% (preferably in an amount from about 2 wt% or from about 5 wt% to about 20 wt%, more preferably from about 5 wt%, from about 7.5 wt% or from about 10 wt% to about 17.5 wt% or to about 15 wt%), based on the total weight of the antimicrobial composition, and where the alkaline stabilizer is in the form of an alkaline aqueous solution, and the at least one solvent comprises or is a diol (e.g., pentylene glycol, hexylene glycol), triol (e.g., glycerol, phytantriol, 1,2,6-hexanetriol), citrate triester (e.g., trialkyl citrate, such as triethyl citrate), or combination thereof.Docket No.: P003 00091-WQ-PCT

[0051] The present disclosure further provides for the use of an antimicrobial effective amount of the presently disclosed antimicrobial compositions in a wide range of product formulations and applications, such as for use in personal care (e.g., cosmetic), home care, health care (such as pharmaceutical (i.e., having at least one active pharmaceutical ingredient) or other health care products) or industrial product formulations, particularly formulations for use as a personal care or home care product. Examples include, without limitation, household products and cleaners, fabric detergents, dish detergents, cleansers, soaps, bubble baths, disinfectants, deodorizers, pharmaceutical products, cosmetics, hygiene compositions, infant care products, antimicrobial soaps, hand sanitizers, deodorants, antiperspirants, anti-microbial coatings, wound care compositions, dermatological compositions, skin conditioners, skin moisturizers, anti-wrinkle formulations, sunscreens, tanning lotions, hair products, shampoos, shower gels, bubble baths, conditioners, shaving creams, etc.

[0052] Depending on the application, the product formulation may contain numerous and different compatible ingredients. In many embodiments, the product formulation comprises an antimicrobial effective amount of the antimicrobial composition of the present disclosure and one or more additional ingredients suitable for use in a personal care (e.g., cosmetic), home care, health care, or industrial product formulation, particularly a personal care or home care formulation.

[0053] In one aspect, an aqueous product formulation comprises an antimicrobial effective amount of the antimicrobial composition of the present disclosure. Preferably, the aqueous product formulation is a personal care (e.g., cosmetic), home care, health care, or industrial product formulation, particularly a personal care or home care formulation.

[0054] The aqueous product formulation may have a pH, for example, of from about 3 to about 10, preferably from about 3.5 to about 7.5, more preferably from about 5.0 to about 7.5.

[0055] In a further aspect of the present disclosure, a personal care or home care product formulation comprises an antimicrobial effective amount of the antimicrobial composition of the present disclosure and one or more additional ingredients suitable for use in a personal care or home care product formulation.

[0056] In general, the antimicrobial effective amount of the antimicrobial composition in the product formulation ranges from about 0.1 wt% to about 3 wt%, preferably from about 0.3 wt% to about 2 wt%, more preferably from about 0.3 wt% or from about 0.5 wt%to about 1.5 wt% or to about 1.0 wt%.

[0057] In general, the antimicrobial effective amount of the antimicrobial composition provides from about 0.05 wt%, preferably from about 0.1 wt%, more preferably from about 0.2 wt% or from about 0.3 wt% to about 1.5 wt%, preferably to about 1.2 wt%, or more preferably to about 1.0 wt% or to about 0.8 wt%, of the alkylhydroxamic acid and / or salt thereof (a) and the fatty acid and / or salt thereof (b) combined in the product formulation.Docket No.: P003 00091-WQ-PCT

[0058] In a further aspect, a method of controlling microbial growth in or preserving a product formulation comprises adding to the product formulation an antimicrobial effective amount of the antimicrobial composition of the present disclosure. The antimicrobial composition preferably controls gram positive bacteria, gram negative bacteria, and fungi, among other microorganisms. Non-limiting examples include Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli, Enterohacter gergoviae, Klebsiella pneumoniae, Burholderia cepacia, Pseudomonas putida, Candida albicans, Aspergillus brasiliensis, and mixtures thereof.

[0059] As a particular example, the product formulation may be any number and variety of different personal care products, such as cosmetic products. The personal care formulation may be, for example, any formulation for skin care, hair care, cosmetics, personal cleaning, hygiene, sun protection and other personal care applications. Examples of such products include, without limitation, skin toners, skin cleansers, night creams, skin creams, shaving creams, skin lotions, makeup, mascara, lipstick, blush, gloss, eye-liner, makeup removers, sunscreens, lip balms, fragrances, massage oils, shampoos, conditioners, hair styling gels, hair reparatives, hair tonics, hair fixatives, hair mousses, bath and shower gels, liquid soaps, moisturizing sprays, bath additives, ophthalmic preparations, foaming soaps and body washes, liquids for any personal care wet wipe application, etc.

[0060] Depending on the application, the personal care product formulation may contain numerous and different compatible ingredients. A personal care formulation may contain, for example, any of solvents, surfactants, emulsifiers, chelating agents, oxidizing agents, colorants, rheology modifiers, conditioners, emollients, skin care ingredients, moisturizers, thickeners, humectants, fillers, antioxidants, active ingredients, such as dermatologically active ingredients typically suited for topical application, fragrances, etc.

[0061] As a further example, the product formulation may be any number and variety of different home care products, such as fabric care products and cleaning products. Examples include dish soaps, laundry detergents, cleaning wipes, cleaning formulations and other home care applications.

[0062] Depending on the application, the home care product formulation may contain, for example, any of cleaning agents, detergents, emulsifiers, surfactants, thickeners, gelling agents, bleaches, whiteners, deodorizers, enzymes, stabilizers, fragrances, soil-release agents, anti-shrinking agents, anti-wrinkle agents, anti-spotting agents, antioxidants, UV absorbing compounds, anti -corrosion agents, anti-static agents, ironing aids, odor-preventing compounds, etc.

[0063] Examples of the foregoing ingredients and other agents used in personal care and home care product compositions are known in the art.

[0064] The product formulations of the present disclosure may be of a variety of different forms, for example, liquids, pastes, serums, hydrogels, creams, emulsions, lotions, gels, oils, wipes, ointments, semi-solid compositions, foams and aerosol sprays. The product formulations may be leave-on orDocket No.: P003 00091-WQ-PCT

[0065] rinse-off formulations. The product formulations may be hair care products, such as shampoos, hair conditioners, hair dyes, hair tonic, hair gel, hair dressings, hair grooming aids and other hair care preparations; products for shaving applications such as shaving cream, aftershave lotions, and other shaving applications; personal cleaners for the body and hands, such as liquid bath soaps and detergents; fragrance preparations, such as perfumes, after bath splashes, and other similar fragrant preparations, skin care products, such as moisturizers, creams, and lotions and other similar skin care products, make-up products, such as mascara, base foundations and the like; make-up removal products, sun care products, indoor tanning products and other similar personal care products. The product formulations may be liquids used to saturate wipes for personal cleaning and hygiene, for example baby wipes, wet toilet wipes, make-up removal wipes and exfoliating wipes the like, or wet wipe formulations for home care.

[0066] The product formulations may further comprise one or more conventional preservatives (in particular, e.g., phenoxyethanol, benzyl alcohol, benzoic acid and / or a salt of benzoic acid, such as sodium benzoate), but preferably in an amount no greater than 0.8 wt%, more preferably no greater than 0.6 wt% or 0.5 wt%, most preferably no greater than 0.4 wt%. Preferably, the product formulation is free or substantially free of parabens. Preferably, the product formulation is free or substantially free of formaldehyde donors. Preferably, the product formulation is free or substantially free of isothiazolinones. Preferably, the product formulation is free or substantially free of iodopropynyl butyl carbamate (IPBC). Preferably, the product formulation is free or substantially free of phenoxyethanol. Preferably, the product formulation is free or substantially free of benzyl alcohol. Preferably, the product formulation is free or substantially free of benzoic acid and salts thereof, such as sodium benzoate. Preferably, the product formulation is free or substantially free of parabens, formaldehyde donors, isothiazolinones, IPBC, phenoxyethanol, benzyl alcohol and benzoic acid and salts of benzoic acid (such as sodium benzoate). In general, “substantially free” in the above context of a product formulation means less than 0.1 wt%, preferably less than 0.05 wt%, more preferably less than 0.01 wt%, even more preferably less than 0.005 wt%, less than 0.0025 wt%, or less than 0.001 wt%. In the case of isothiazolinones, “substantially free” preferably means less than 0.005 wt%, more preferably less than 0.0025 wt%, even more preferably less than 0.001 wt% or less than 0.00075 wt%. As used herein, the articles “a”, “an”, and “the” preceding an element or component of the invention are intended to be nonrestrictive regarding the number of instances (i.e., occurrences) of the element or component. Therefore “a”, “an”, and “the” should be read to include one or at least one, and the singular word form of the element or component also includes the plural unless the number is obviously meant to be singular.

[0067] As used herein, the term “comprising” means the presence of the stated features, integers, steps, or components and does not preclude the presence or addition of one or more other features, integers, steps, components or groups thereof. That is, the stated features, integers, steps, or components mayDocket No.: P003 00091-WQ-PCT

[0068] include other features, integers, steps, components or groups thereof. The term “comprising” is intended to include embodiments encompassed by the terms “consisting essentially of’ and “consisting of,” unless the context dictates otherwise.

[0069] The phrase “consisting of’ limits the scope to which the phrase applies to the stated elements, steps, or ingredients, precluding the inclusion of other elements or materials, except for impurities ordinarily associated therewith. For example, in the context of the fatty acids of the present disclosure, such impurities may include, for example, unsaturation, branching, and / or varying chain lengths above or below the stated ranges for chain-length.

[0070] The phrase “consisting essentially of’ limits the scope to which the phrase applies to the stated elements, steps, or ingredients and those that do not materially affect the basic and novel characteristic(s) of the claimed invention. “Consisting essentially of’ occupies a middle ground between a closed scope that is written in a “consisting of’ format and an open scope that is written in a “comprising” format.

[0071] As used herein, the term “about” modifying the quantity of an ingredient employed refers to variation in the numerical quantity that can occur, for example, through typical measuring and handling procedures used for making concentrates or use solutions in the real world; through inadvertent error in these procedures; through differences in the manufacture, source, or purity of the ingredients employed to make the compositions or carry out the methods; and the like.

[0072] Where present, all ranges are inclusive and combinable. For example, when a range of “1 to 5” is recited, the recited range should be construed as including ranges “1 to 4”, “1 to 3”, “1-2”, “1-2 & 4-5”, “1-3 & 5”, and the like.

[0073] When a parameter is given either as a range, preferred range, or a list of upper values and lower values, this is to be understood as specifically disclosing all ranges formed from any pair of any upper range limit or preferred value and any lower range limit or preferred value, regardless of whether ranges are separately disclosed. Where a range of numerical values is recited herein, unless otherwise stated, the range is intended to include the endpoints thereof, and all integers and fractions within the range.

[0074] EXAMPLES

[0075] Antimicrobial or preservative activity of representative antimicrobial compositions of the present disclosure and various comparative materials was evaluated via challenge testing conducted using a modification of the Personal Care Products Council (PCPC - formerly the Cosmetic, Toiletry and Fragrance Association) protocol (Machtiger, et al. 2001. Determination of the Efficacy ofDocket No.: P003 00091-WO-PCT

[0076] Preservation ofNon-Eye Area Water Miscible Cosmetic and Toiletry Formulations: Collaborative Study. J of AO AC International. 84:1, 101-109).

[0077] The evaluations were carried out using a four week, two-cycle efficacy test at 25°C. The antimicrobial compositions representative of the present disclosure and various comparative materials were each dosed (at the dosing concentrations specified in the following Examples) and mixed thoroughly at room temperature into separate samples of a personal care formulation as provided in Table 1. The pH of the final formulation was readjusted to match the pH of the original formulation prior to dosing using a sodium hydroxide solution.

[0078] In particular, Table 1 shows an exemplary xanthan-gum-based serum. The serum formulation was made by adding all of the listed ingredients into a beaker and mixing with an overhead mixer and heating to 75-80 °C. The mixture was homogenized and cooled to room temperature. The pH was adjusted with a sodium hydroxide solution to pH ~5.5.

[0079] Table 1. Representative serum composition with xanthan gum.

[0080] Ingredients INCI Name WT %

[0081] Water Water 82.40

[0082] Xanthan gum Xanthan gum 0.20

[0083] Aristoflex AVC Ammonium 0.20

[0084] acryloyldimethyltaurate /

[0085] vinylpyrrolidone

[0086] copolymer

[0087] Hyaluronic acid Hyaluronic acid 0.15

[0088] Propylene glycol Propylene glycol 4.00

[0089] Glycerin Glycerin 5.00

[0090] Disodium EDTA Disodium EDTA 0.05

[0091] Genencare OSMS Pro Aqua (water), betaine, 3.00

[0092] proline, inositol, serine

[0093] Cremophor RH 40 PEG-40 Hydrogenated 3.00

[0094] Castor oil

[0095] XIAMETER PMX-200 Dimethicone 2.00

[0096] Silicone Fluid 100 cSt

[0097]

[0098] After dosing, the sample product formulations were divided into two separate five gram aliquots. One aliquot was inoculated with 50 pl of a diluted bacterial pool, and the second aliquot was inoculatedDocket No.: P003 00091-WQ-PCT

[0099] with 50 pl of a diluted fungal pool, as described below. Unpreserved product samples were included as a growth control.

[0100] A mixed bacterial inoculum was prepared using 24-hour cultures of the test bacteria (Table 2) grown in trypticase soy broth (TSB). Equal volumes of the bacterial test strains were combined and diluted one to ten in phosphate buffer to obtain an inoculum of approximately 5 x 107to 5 x 108colony forming units per ml (cfu / ml). The test samples were inoculated with 1% of the mixed bacterial inoculum. A mixed fungal inoculum was prepared using cell suspensions of the yeast Candida albicans ATCC # 10231 and the mold Aspergillus brasiliensis ATCC #16404 in phosphate buffer. Equal volumes of the fungal test strains were combined and diluted one to ten with phosphate buffer to obtain an inoculum of approximately 5 x 106to 5 x 107cfu / ml. The test product samples were inoculated with 1% of the mixed fungal inoculum.

[0101] Table 2. Mixed Bacterial Inoculum

[0102] Microorganism ATCC Type

[0103] Number

[0104] Burkholderia cepacia 25416 Gram-Negative Non-fermenter Enterobacter gergoviae 33028 Gram-Negative Fermenter Escherichia coli 8739 Gram-Negative Fermenter Klebsiella pneumoniae 13883 Gram-Negative Fermenter Pseudomonas aeruginosa 9027 Gram-Negative Non-fermenter Pseudomonas aeruginosa 15442 Gram-Negative Non-fermenter Pseudomonas putida 49128 Gram-Negative Non-fermenter Staphylococcus aureus 6538 Gram-Positive Staphylococcus epidermidis 12228 Gram-Positive

[0105]

[0106] The sample products were subjected to three microbial challenges at time zero, and inoculated a second and third time after seven and fourteen days, respectively. The number of microorganisms added to each sample was determined by a standard Most Probable Number (MPN) determination in Trypticase Soy Broth (TSB) for bacteria and Potato Dextrose Broth (PDB) for fungi. The sample product formulations were incubated at 25 °C for the test duration of four weeks and were monitored for bacterial and fungal contamination after 2, 7, 14, 21, and 28 days. The samples challenged with bacteria were streak-plated onto Trypticase Soy Agar (TSA) and incubated at 30°C for 24 hours, and those challenged with fungi were streak-plated onto Potato Dextrose Agar (PDA) and incubated atDocket No.: P003 00091-WQ-PCT

[0107] 25 °C for 7 days. After incubation, plates were given a Growth Rating to determine the colony forming units per gram (CFU / g) present in each test sample at the testing time point. Table 3 represents the growth scoring system.

[0108] Table 3. Growth score used to determine CFU / mL in test samples.

[0109] Growth

[0110] Description of Microbial Growth Plating Results Approximate cfu / g Rating

[0111] No detectable

[0112] 0 No contamination < 10

[0113] growth

[0114] 1 Trace contamination 1 to 9 colonies l x lO’ to O x 1012 Light contamination 10 to 99 colonies 1 x 102to 9.9 x 102

[0115] 100 to 1,000

[0116] 3 Moderate contamination

[0117] colonies 1 x 103to 9.9 x 1034 Heavy contamination > 1,000 or smear > 1 x 104

[0118]

[0119] Example 1

[0120] A series of antimicrobial compositions containing caprylic acid, caprylhydroxamic acid, an organic solvent, and an alkaline stabilizer (aqueous solution of potassium hydroxide) were prepared according to the amounts shown in Table 4. Caprylic acid, caprylhydroxamic acid, and hexylene glycol solvent were first mixed to form a homogenous clear solution. Potassium hydroxide (KOH) was added to water to form an alkaline solution as the alkaline stabilizer. The alkaline solution was then slowly added to the homogenous clear solution to produce the antimicrobial compositions (Samples 1-3).

[0121] Table 4.

[0122] Caprylhydroxamic Hexylene Alkaline stabilizer Composition Caprylic acid acid glycol (KOH / water 30 / 70 w / w) Sample 1 45 wt% 10 wt% 30 wt% 15 wt%

[0123] Sample 2 40 wt% 10 wt% 40 wt% 10 wt%

[0124] Sample 3 45 wt% 5 wt% 40 wt% 10 wt%

[0125]

[0126] Samples 1-3 were dosed into respective samples of the serum product formulation made according to Table 1 above. Serum formulations according to the Table 1 were also dosed respectively with phenoxyethanol (POE), a combination of POE and hydroxyacetophenone (HAP), a combination of POE and ethylhexylglycerin, and a combination of HAP and 1,2 -hexanediol. All the dosed serum formulations were adjusted to the same pH value of 5.5. As shown in Table 5, POE dosed alone into the serum formulations at 0.8% did not show significant efficacy in controlling microbial growth in the challenge testing, particularly against bacteria. The benchmark comparisons of POE + HAP (tested at 0.8% combined), HAP + 1,2 hexanediol (tested at 0.8% combined), and POE + ethylhexylglycerinDocket No.: P003 00091-WO-PCT

[0127] (tested at both 0.8% combined and 1.0% combined) also struggled to control microbial growth in the challenge testing, particularly against bacteria. In contrast, Sample Compositions 1-3 from Table 4, when dosed into respective samples of the serum formulation, surprisingly showed superior antimicrobial efficacy compared to phenoxyethanol, as well as compared to each of the tested benchmark combinations, at the same total dosing levels.

[0128] Table 5. Challenge test data - xanthan gum based serum formulation.

[0129] Bacteria growth rating Fungi growth rating

[0130] Sample and Dosing

[0131] D21 D28 D21 D28

[0132] (wt%)

[0133] Serum Blank 4 4 4 4

[0134] Phenoxyethanol (POE)

[0135] (0.8%) 4 4 2 0

[0136] POE (0.4%) +

[0137] hydroxyacetophenone

[0138] (HAP) (0.4%) 4 3 0 0

[0139] HAP (0.4%) + 1,2

[0140] hexanediol (0.4%) 4 3 0 0

[0141] POE / ethylhexylglycerin

[0142] (90 / 10 w / w) (0.8%) 4 3 2 0

[0143] POE / ethylhexylglycerin

[0144] (90 / 10 w / w) (1.0%) 4 3 1 0

[0145] Sample 1 (0.8%) 1 0 0 0

[0146] Sample 1 (1.0 %) 0 0 0 0

[0147] Sample 2 (0.8%) 1 0 0 0

[0148] Sample 2 (1.0 %) 0 0 0 0

[0149] Sample 3 (0.8%) 2 0 0 0

[0150] Sample 3 (1.0 %) 1 0 0 0

[0151]

[0152] Example 2

[0153] A series of antimicrobial compositions containing caprylic acid, caprylhydroxamic acid, an organic solvent, and water or an alkaline stabilizer (an aqueous solution of potassium hydroxide) were prepared according to the amounts shown in Table 6. Caprylic acid, caprylhydroxamic acid, and the solvent were first mixed to form a homogenous clear solution. Potassium hydroxide (KOH) was added to water to form an alkaline solution as the alkaline stabilizer. The alkaline solution or water alone was then slowly added to the homogenous clear solution to produce the antimicrobial compositions (Samples 4-7 in Table 6).Docket No.: P003 00091-WQ-PCT

[0154] Table 6.

[0155] Caprylhydroxamic Water or Composition Caprylic acid Solvent

[0156] acid Alkaline stabilizer Alkaline stabilizer Propylene glycol

[0157] Sample 4 45 wt% 10 wt% (KOH / water 30 / 70 w / w)

[0158] 30 wt%

[0159] 15 wt% Alkaline stabilizer Pentylene Glycol

[0160] Sample 5 45 wt% 10 wt% (KOH / water 30 / 70 w / w)

[0161] 30 wt%

[0162] 15 wt% Alkaline stabilizer 1,2-hexanediol

[0163] Sample 6 45 wt% 10 wt% (KOH / water 30 / 70 w / w)

[0164] 30 wt%

[0165] 15 wt% Pentylene Glycol Water only Sample 7 45 wt% 10 wt%

[0166] 30 wt% 15 wt%

[0167]

[0168] Samples 4-7 were dosed into respective samples of the serum formulation made according to Table 1 above. Serum formulations according to the Table 1 were also dosed respectively with phenoxyethanol (POE) alone and a combination of POE and each of the respective Samples 4-7. All the dosed serum formulations were adjusted to the same pH value of 5.5. As shown in Table 7, POE dosed alone into the serum formulations at 0.4% and 0.8% did not show significant efficacy in controlling microbial growth in the challenge testing, particularly against bacteria. In contrast, Sample Compositions 4-7 from Table 6, when dosed into respective samples of the serum formulation, surprisingly showed superior antimicrobial efficacy compared to phenoxyethanol at the same total dosing levels. When the serum formulations were formulated with both phenoxyethanol (at a reduced concentration of 0.4%) and the respective Samples 4-7 (at 0.6 %), the Samples 4-7 improved the antimicrobial efficacy of phenoxyethanol, and the serum formulations were robustly protected from microbial contamination despite the low concentration of preservative (phenoxyethanol).

[0169] Table 7. Challenge test data - xanthan gum based serum formulation.

[0170] Bacteria growth rating Fungi growth rating Sample and Dosing (wt%) D21 D28 D21 D28 Serum Blank 4 4 4 4 Phenoxyethanol (POE) (0.4%) 4 4 3 3 POE (0.8%) 4 4 2 0 Sample 4 (0.8 %) 2 0 0 0 Sample 5 (0.8%) 1 0 0 0 Sample 6 (0.8%) 1 0 0 0 Sample 7 (0.8%) 1 0 0 0

[0171]

[0172] Docket No.: P003 00091-WQ-PCT

[0173] POE (0.4%) + Sample 4 (0.6%) 0 0 0 0 POE (0.4%) + Sample 5 (0.6%) 0 0 0 0 POE (0.4%) + Sample 6 (0.6%) 0 0 0 0 POE (0.4%) + Sample 7 (0.6%) 0 0 0 0

[0174]

[0175] Example 3

[0176] A series of antimicrobial compositions containing fatty acids with different chain length, caprylhydroxamic acid, an organic solvent, and alkaline stabilizer (an aqueous solution of potassium hydroxide) were prepared according to the amounts shown in Table 8. The respective fatty acid, caprylhydroxamic acid, and hexylene glycol solvent were first mixed to form a homogenous clear solution. Potassium hydroxide (KOH) was added to water to form an alkaline solution as the alkaline stabilizer. The alkaline solution was then slowly added to the homogenous clear solution to produce the antimicrobial compositions (Samples 8-11).

[0177] Table 8.

[0178] Caprylhydroxamic Hexylene Alkaline stabilizer Composition Fatty acid acid glycol (KOH / water 30 / 70 w / w) Sample 8 Caproic acid, 40 wt% 10 wt% 40 wt% 10 wt% Sample 9 Caprylic acid, 40 wt% 10 wt% 40 wt% 10 wt% Sample 10 Pelargonic acid, 40 wt% 10 wt% 40 wt% 10 wt% Sample 11 Capric acid, 40 wt% 10 wt% 40 wt% 10 wt%

[0179]

[0180] Samples 8-11 were dosed into respective samples of the serum formulation according to Table 1. All of the dosed serum formulations were adjusted to the same pH value of 5.5. As shown in Table 9, Samples 8-11 surprisingly showed highly effective antimicrobial efficacy, against both bacteria and fungi.

[0181] Table 9. Challenge test data - xanthan gum based serum formulation.

[0182] Bacteria growth rating Fungi growth rating Sample and Dosing (wt%) D21 D28 D21 D28 Serum Blank 4 4 3 4 Sample 8 (0.8%) 0 0 0 0 Sample 8 (1.0%) 0 0 0 0 Sample 9 (0.8%) 0 0 0 0 Sample 9 (1.0%) 0 0 0 0 Sample 10 (0.8%) 0 0 0 0

[0183]

[0184] Docket No.: P003 00091-WQ-PCT

[0185] Sample 10 (1.0%) 0 0 0 0 Sample 11 (0.8%) 0 0 1 1 Sample 11 (1.0%) 0 0 0 0

[0186]

[0187] Example 4

[0188] A series of antimicrobial compositions containing fatty acids with different chain length, caprylhydroxamic acid, an organic solvent, and optionally an alkaline stabilizer (an aqueous solution of potassium hydroxide) were prepared according to the amounts shown in Tables 10 and 11. Two comparative compositions were prepared according to Table 12.

[0189] Table 10.

[0190] Caprylhydroxamic Hexylene Alkaline stabilizer pH Composition Fatty acid acid glycol (KOH / water 30 / 70 w / w)

[0191] Caprylic acid 5.3

[0192] 10 wt% 30 wt% 10 wt%

[0193] Sample 12 50 wt%

[0194] Pelargonic acid 5.4

[0195] 10 wt% 30 wt% 10 wt%

[0196] Sample 13 50 wt%

[0197]

[0198] Table 11.

[0199] Caprylhydroxamic Hexylene

[0200] Composition Fatty acid acid glycol

[0201] Sample 14 Caprylic acid, 40 wt% 10 wt% 50 wt%

[0202] Sample 15 Pelargonic acid, 40 wt% 10 wt% 50 wt%

[0203]

[0204] Table 12.

[0205] 50 wt% 25 wt% 25 wt% Comparative A caprylic acid lauric acid 1,3 propanediol 40 wt% 10 wt% 50 wt% Comparative B benzyl alcohol Caprylhydroxamic acid 1,3 propanediol

[0206]

[0207] Sample Compositions 12-15 and Comparative Compositions A and B were dosed into respective samples of the serum product formulation according to Table 1. All of the dosed serum formulations were adjusted to the same pH value of 5.5. As shown in Table 13, Sample Compositions 12-15 exhibited robust protection in the product formulation against both bacteria and fungi, providing superior antimicrobial efficacy as compared to the Comparative Compositions A and B.

[0208] Table 13.

[0209] Bacteria growth Fungi growth

[0210] Sample and Dosing (wt%)

[0211] rating rating

[0212]

[0213] Docket No.: P003 00091-WQ-PCT

[0214] D21 D28 D21 D28

[0215] Serum Blank 4 4 4 4

[0216] Sample 12 (0.6%) 0 0 0 0

[0217] Sample 12 (0.8%) 0 0 0 0

[0218] Sample 13 (0.6%) 1 0 1 1

[0219] Sample 13 (0.8%) 0 0 0 0

[0220] Sample 14 (0.6%) 0 0 0 0

[0221] Sample 14 (0.8%) 0 0 0 0

[0222] Sample 15 (0.6%) 0 0 1 1

[0223] Sample 15 (0.8%) 0 0 0 0

[0224] Comparative A (0.6%) 0 0 3 3

[0225] Comparative A (0.8%) 0 0 2 2

[0226] Comparative B (0.6%) 3 1 1 0

[0227] Comparative B (0.8%) 3 1 0 0

[0228]

[0229] Example 5

[0230] The chelating activity of Sample Compositions 8-11 from Table 8 above was measured by using the ZenBio Cupric Ion Chelating (CIC) Assay (Cat# AOX-16). The assay measured the capacity of the Samples to chelate free cupric ions in solution, thereby inhibiting Cu(II) binding to pyrocatechol violet (PV) for generating a highly colored complex. The absorbance of the Cupric -PV complex was measured at a wavelength of 632 nm. The cupric ion chelating activity was determined as the percent of total PV over the Cu(II) binding. Ethylenediaminetetraacetic acid (EDTA), a well-known chelating agent, was used as a positive control. A series of EDTA with 7 different concentrations from 0 to 1000 pM were prepared and their corresponding absorbance measured and used as the calibration curve (Cupric ion chelating (%) vs. EDTA concentration). Percent cupric ion chelating was determined following the following calculations and Equation 1. The background absorbance value by averaging the absorbance values of the three background wells (no CuSO4 or sample). The average background absorbance was then subtracted from all the sample absorbance values. The maximal absorbance value (Absmax) was determined by averaging the absorbance values of the three wells containing CuSO4, PV and assay buffer. Abstest in Equation 1 is the absorbance of the test sample. Cupric ion chelating (%) = 100 x (Absmax - Abstest) / Absmax (Equation 1)Docket No.: P003 00091-WQ-PCT

[0231] The calibration curve (Cupric ion chelating (%) vs. EDTA concentration) was fit by using a polynomial curve after log 10 transforming the concentrations (R2>0.99).

[0232] As shown in Table 14, each of the Samples 8-11 showed chelating activity that was superior (i.e., higher EDTA equivalent) than the ascorbic acid, a well-known chelating agent that complexes with metal ions. Table 14. EDTA equivalent (calculated from a EDTA calibration curve).

[0233] Sample Calculated EDTA

[0234] equivalent (pM)

[0235] Sample 8 578 ± 33

[0236] Sample 9 614 ± 45

[0237] Sample 10 647 ± 52

[0238] Sample 11 669 ± 56

[0239] Ascorbic Acid 493 ± 12

[0240]

[0241] Example 6

[0242] Additional representative compositions of the present disclosure were prepared using triol and triester citrate solvents, respectively, as shown in Table 15. The respective components were combined in the amounts by weight (wt%) provided in Table 15, based on the total weight of each sample composition. In particular, Sample 16 was prepared by mixing pelargonic acid and 1,2,6-hexanetriol, followed by adding caprylhydroxamic acid. Sample 17 was prepared by mixing pelargonic acid and 1,2,6-hexanetriol, followed by adding caprylhydroxamic acid and, finally, water. Samples 18 and 19 were prepared as follows: potassium hydroxide (KOH) was dissolved in water to prepare the alkaline stabilizer in the form of an alkaline aqueous solution. The alkaline stabilizer was added gradually to pelargonic acid under continuous mixing. Solvent as shown in Table 15 for the respective Samples 18 and 19 was subsequently added, followed by the addition of caprylhydroxamic acid. For each sample composition, the resulting mixture was a homogenous and clear liquid.

[0243] As with the preceding examples, the prepared compositions are expected to exhibit multifunctional properties, including highly effective antimicrobial properties even in the absence of conventional preservatives. Additionally, the ability to formulate the present compositions using a variety of solvents, such as triethyl citrate, expands the options for preparing compositions that contain caprylhydroxamic acid and for applying such compositions to product formulations.Docket No.: P003 00091-WQ-PCT

[0244] Table 15.

[0245] Pelargonic Caprylhydroxamic Water or Composition acid acid Solvent Alkaline stabilizer 1 ,2,6-Hexanetriol

[0246] Sample 16 51 wt% 10 wt% - 39 wt%

[0247] 1 ,2,6-Hexanetri Water only Sample 17 51 wt% 10 wt% ol

[0248] 29 wt% 10 wt%

[0249] Alkaline stabilizer 51 wt% 10 wt% 1 ,2,6-Hexanetriol

[0250] (KOH / water 30 / 70 w / w) Sample 18 29 wt%

[0251] 10 wt% Alkaline stabilizer 51 wt% 10 wt% Triethyl citrate

[0252] (KOH / water 30 / 70 w / w) Sample 19 29 wt%

[0253]

[0254] 10 wt%

Claims

Docket No.: P003 00091-WQ-PCTWhat is claimed is:

1. An antimicrobial composition comprising(a) from about 2 to about 15 wt% of caprylhydroxamic acid and / or a salt thereof;(b) from about 20 to about 70 wt% of at least one saturated straight-chain fatty acid having a carbon chain length of from 6 to 12 carbon atoms and / or a salt thereof;(c) from about 20 to about 70 wt% of at least one organic solvent; and optionally(d) from 0 to about 20 wt% of water,wherein the weight percentages are based on the total weight of the antimicrobial composition, and wherein the antimicrobial composition is free or substantially free of parabens, formaldehyde donors, isothiazolinones, iodopropynyl butyl carbamate (IPBC), phenoxyethanol, benzyl alcohol, and benzoic acid and salts of benzoic acid.

2. The antimicrobial composition of claim 1, wherein the at least one fatty acid is caprylic acid and / or a salt thereof, pelargonic acid and / or a salt thereof, capric acid and / or a salt thereof, or any combination thereof.

3. The antimicrobial composition of any preceding claim, wherein the at least one solvent is chosen from alcohols, ethers, esters or combinations thereof, preferably wherein the at least one solvent is chosen from diols, triols, glyceryl ethers, glyceryl esters, citrate triesters, or combinations thereof.

4. The antimicrobial composition of any preceding claim, wherein the antimicrobial composition is free of parabens, formaldehyde donors, isothiazolinones, iodopropynyl butyl carbamate (IPBC), phenoxyethanol, benzyl alcohol, and benzoic acid and salts of benzoic acid.

5. The antimicrobial composition of any preceding claim, wherein the antimicrobial composition comprises from about 2 to about 20 wt% of water.

6. The antimicrobial composition of any one of claims 1-5, wherein the at least one solvent comprises a Cs to Cs diol.

7. The antimicrobial composition of claim 5, wherein the at least one solvent comprises a citrate triester.

8. The antimicrobial composition of claim 7, wherein the citrate triester is triethyl citrate.

9. A method of preparing an antimicrobial composition, comprising combining (a) caprylhydroxamic acid and / or salt thereof in an amount of from about 2 to about 15 wt%; (b) at least one saturated straight-chain fatty acid having a carbon chain length of from 6 to 12 carbon atoms and / or a salt thereof in an amount of from about 20 to about 70 wt%; (c) at least one organic solvent in an amount of from about 20 to about 70 wt%; and optionally (d) water and / or an alkaline aqueous solution in a total amount of from 0 to about 20 wt%, wherein the weight percentages are based on the total weight of the antimicrobial composition, and wherein the antimicrobial composition is free or substantially free of parabens, formaldehyde donors, isothiazolinones, iodopropynyl butyl carbamate (IPBC), phenoxyethanol, benzyl alcohol, and benzoic acid and salts of benzoic acid.Docket No.: P003 00091-WQ-PCT10. The method of claim 9, wherein water and / or the alkaline aqueous solution is combined with the components (a), (b), and (c) in a total amount of water and / or the alkaline aqueous solution from about 2 to about 20 wt%, based on the total weight of the antimicrobial composition.

11. The method of claim 9 or 10, wherein the at least one fatty acid is caprylic acid and / or a salt thereof, pelargonic acid and / or a salt thereof, capric acid and / or a salt thereof, or any combination thereof.

12. The method of any one of claims 9-11, wherein the at least one solvent is chosen from alcohols, ethers, esters or combinations thereof, preferably wherein the at least one solvent is chosen from diols, triols, glyceryl ethers, glyceryl esters, citrate triesters, or combinations thereof.

13. The method of any one of claims 9-12, wherein the antimicrobial composition is free of parabens, formaldehyde donors, isothiazolinones, iodopropynyl butyl carbamate (IPBC), phenoxyethanol, benzyl alcohol, and benzoic acid and salts of benzoic acid.

14. The method of any one of claims 9-13, wherein the alkaline aqueous solution is combined with the components (a), (b), and (c) in an amount of from about 2 to about 20 wt%, based on the total weight of the antimicrobial composition.

15. The method of any one of claims 9-14, wherein the alkaline aqueous solution comprises a base that is a metal hydroxide.

16. The method of claim 15, wherein the metal hydroxide is chosen from sodium hydroxide, potassium hydroxide or a combination thereof.

17. The method of any one of claims 9-16, wherein the at least one solvent comprises a Cs to Cs diol.

18. The method of any one of claims 14-16, wherein the at least one solvent comprises a citrate triester.

19. The method of claim 18, wherein the citrate triester is triethyl citrate.

20. The method of any one of claims 14-16, wherein the antimicrobial composition has a pH of from about 5.0 to about 7.5.

21. A method for controlling microbial growth in or preserving a product formulation, comprising adding to the product formulation an antimicrobial effective amount of the antimicrobial composition according to any one of claims 1-8.

22. A method for controlling microbial growth in or preserving a product formulation, comprising adding to the product formulation an antimicrobial effective amount of the antimicrobial composition prepared according to any one of claims 9-20.

23. The method of claim 21 or 22, wherein the product formulation is free or substantially free of parabens, formaldehyde donors, isothiazolinones, iodopropynyl butyl carbamate (IPBC), phenoxyethanol, benzyl alcohol, and benzoic acid and salts of benzoic acid.

Images