WO2025226625A1

WO2025226625A1 - Antimicrobial compositions containing an alkylhydroxamic acid and a glycolipid

Info

Publication number: WO2025226625A1
Application number: PCT/US2025/025678
Authority: WO
Inventors: Ziang LI; Soonjoo Son; Ethan Solomon; Marcelo Filgueira
Original assignee: Lanxess Corp
Current assignee: Lanxess Corp
Priority date: 2024-04-26
Filing date: 2025-04-22
Publication date: 2025-10-30
Anticipated expiration: 2026-10-26

Abstract

Disclosed are antimicrobial compositions containing an alkylhydroxamic acid and a glycolipid, as well as the use of such antimicrobial compositions to preserve or provide antimicrobial activity to product formulations, particularly personal care products, home care products, health care products and other product formulations.

Description

TITLE

Antimicrobial Compositions Containing an Alkylhydroxamic Acid and a Glycolipid

FIELD OF INVENTION

The present invention relates to antimicrobial compositions containing an alkylhydroxamic acid and a glycolipid and the use of such antimicrobial compositions to preserve or provide antimicrobial activity to product formulations, particularly in personal care products, home care products, health care products and other product formulations.

BACKGROUND OF THE INVENTION

Alkylhydroxamic acids, such as caprylhydroxamic acid (CHA), are known and used in various industries, particularly in the personal care, home care and health care industries. Their antimicrobial and chelating properties and naturally-derived production have contributed to their recognition and growth as useful preservative and multifunctional agents. Alkylhydroxamic acids, such as CHA, however, can be difficult to formulate into preservative systems and product formulations as effective antimicrobial and multifunctional agents due to their poor solubility in water and other common solvents.

U.S. Patent No. 11,291,204 discloses an ability to dissolve certain concentrations of an alkylhydroxamic acid (such as CHA) and/or a salt thereof in certain diols, such as caprylyl glycol, glyceryl caprylate and/or methylpropanediol and discloses the use of such diols as solubilizing agents. The reference further discloses using the alkylhydroxamic acid and diol combinations as a preservative composition for preserving cosmetic, toiletry or pharmaceutical formulations. The description and disclosed experiments convey that such diols are required to solubilize the alkylhydroxamic acids or salts thereof for use in a preservative composition to preserve various product formulations.

There is a need in the art for the discovery of additional materials which can sufficiently dissolve or solubilize alkylhydroxamic acids and that are particularly suitable for use in antimicrobial compositions for preserving or providing efficacious antimicrobial activity to personal care, home care, health care and other product formulations.

This need is met by the present disclosure. As disclosed herein, it was discovered that alkylhydroxamic acids are soluble in aqueous compositions comprising glycolipids and that glycolipids are particularly useful solubilizing agents for alkylhydroxamic acids in such compositions. These antimicrobial compositions may be applied to a wide range of product formulations, such as personal care (e.g., cosmetic), home care, health care (e.g., pharmaceutical), and industrial product formulations. The compositions and methods of the present disclosure further benefit from the naturally -derived nature of the glycolipids and their multifunctional properties. It was additionally discovered that N^a-alkanoyl dibasic amino acid ester salts further enhance the solubility or compatibility of the alkylhydroxamic acids in aqueous compositions in the presence of the glycolipids. The compositions and methods of the present disclosure can therefore offer advantageous antimicrobial and preservation solutions, in particular where the active agents may be all, or essentially all, naturally derived.

SUMMARY OF INVENTION

In one aspect, the present disclosure provides an aqueous antimicrobial composition comprising (a) from about 1% to less than 6% by weight of at least one alkylhydroxamic acid (e.g., caprylhydroxamic acid), and (b) from about 10% to about 75% by weight of at least one glycolipid (e.g., at least one sophorolipid), each based on the weight of the composition. The composition optionally further includes (c) at least one N^a-alkanoyl dibasic amino acid ester salt, preferably in an amount up to about 20% by weight of the composition.

In another aspect, the present disclosure provides an aqueous antimicrobial composition comprising (a) from about 1% to about 15%, such as from about 2%, from about 3% or from about 4% to about 15%, to about 13%, or to about 10% by weight, based on the weight of the composition, of at least one alkylhydroxamic acid (e.g., caprylhydroxamic acid), (b) from about l% to about 75% by weight, based on the weight of the composition, of at least one glycolipid (e.g., at least one sophorolipid), and (c) at least one N^a-alkanoyl dibasic amino acid ester salt, preferably in an amount up to about 20% by weight of the composition.

The aqueous antimicrobial composition may consist essentially of, or in further embodiments consist of, (a) at least one alkylhydroxamic acid (e.g., caprylhydroxamic acid), (b) at least one glycolipid (e.g., at least one sophorolipid), optionally (c) at least one N^a-alkanoyl dibasic amino acid ester salt, optionally (d) at least one excipient, and a solvent component comprising water. For example, the aqueous antimicrobial composition may consist essentially of, or in further embodiments consist of, (a) at least one alkylhydroxamic acid (e.g., caprylhydroxamic acid), (b) at least one glycolipid (e.g., at least one sophorolipid), (c) at least one N^a-alkanoyl dibasic amino acid ester salt, optionally (d) at least one excipient, and a solvent component comprising water. The antimicrobial composition may preferably contain amounts of (a) at least one alkylhydroxamic acid (e.g., caprylhydroxamic acid), (b) at least one glycolipid (e.g., at least one sophorolipid), optionally (c) at least one N^a-alkanoyl dibasic amino acid ester salt, and optionally (d) at least one excipient, with the remainder of the antimicrobial composition consisting essentially of, or in further embodiments consisting of, a solvent component comprising water. Preferably, the ratio by weight of the at least one alkylhydroxamic acid to the at least one glycolipid is from about 1:60 to about 1: 1 or more preferably from about 1:40 to about 1: 1.5, from about 1:30 to about 1:2 or from about 1:20 to about 1:5 or to about 1:7.

The present disclosure also includes an aqueous product formulation comprising an antimicrobial effective amount of the aqueous antimicrobial composition according to the present disclosure. Also provided is a personal care, home care, health care or industrial product formulation comprising an antimicrobial effective amount of the aqueous antimicrobial composition according to the present disclosure. Further provided is a method of preparing or formulating the product formulation, comprising adding to the product formulation an antimicrobial effective amount of the aqueous antimicrobial composition of the present disclosure. Also provided is a method of controlling microbial growth in or preserving a personal care, home care, health care or industrial product formulation comprising adding an antimicrobial effective amount of the aqueous antimicrobial composition according to the present disclosure.

The present disclosure also includes a method of formulating or solubilizing at least one alkylhydroxamic acid (e.g., caprylhydroxamic acid) for use as an antimicrobial agent in an aqueous antimicrobial composition, the method comprising combining at least one alkylhydroxamic acid (e.g., caprylhydroxamic acid) with at least one glycolipid (e.g., at least one sophorolipid) in the presence of water. The at least one alkylhydroxamic acid and the at least one glycolipid may be combined in the amounts and ratios as described herein. The method may further comprise combining the at least one alkylhydroxamic acid with at least one N^a-alkanoyl dibasic amino acid ester salt, such as described herein.

DETAILED DESCRIPTION

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

The term “alkylhydroxamic acid” and species thereof as used herein include the free acid form of the compound as well as salts thereof, unless otherwise specifically noted. Examples of such salts include those where the cations of the alkylhydroxamic acid salts are chosen from Li⁺, Na⁺, K⁺, Mg²⁺, Ca²⁺, Al³⁺, NHL, 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. For purposes of calculating the wt% of the at least one alkylhydroxamic acid in the context where a salt of alkylhydroxamic acid is used, the weight associated with the cation of the salt is excluded. In this context, salt forms of the alkylhydroxamic acid are converted by acidification into the protonated form for determining the wt% of alkylhydroxamic acid provided by the salt and can be quantified by well known techniques, such as HPLC or LC-MS. 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.

The term “glycolipid” as used herein means a compound comprising a carbohydrate group having one or more monosaccharide residues (e.g., monosaccharide, disaccharide, oligosaccharide or polysaccharide residues) bound by a glycosidic linkage to a lipid group.

The term “glycosidic bond” or “glycosidic linkage” as used herein refers to a covalent bond linking a monosaccharide or monosaccharide residue of the carbohydrate component to the lipid component.

As used herein, “antimicrobial effective amount” refers to an amount to provide a desired antimicrobial effect or activity. For example, the presently disclosed antimicrobial composition preferably controls gram positive bacteria, gram negative bacteria, and fungi. 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.

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

In general, the alkylhydroxamic acids of the present disclosure have a linear or branched carbon chain preferably having from about two to about twenty -two carbon atoms, more preferably from about six to about twelve carbon atoms. The carbon 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.

Examples of suitable alkylhydroxamic acids include those having an alkyl group of a chain length of from about 2 to about 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 about 6 to about 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.

Preferred alkylhydroxamic acids are of the formula (I) or a salt thereof: wherein R is a linear or branched, substituted or unsubstituted, carbon chain of from about two to about twenty -two carbon atoms, preferably from about six to about twelve 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. R¹ may be hydrogen or R, preferably hydrogen.

The at least one alkylhydroxamic acid preferably comprises caprylhydroxamic acid. While the alkylhydroxamic acid may consist essentially of or consist of one alkylhydroxamic acid (e.g., preferably caprylhydroxamic acid), more than one alkylhydroxamic acid may be used.

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.

The at least one glycolipid of the present disclosure preferably includes a monosaccharide, disaccharide or oligosaccharide moiety. Preferably, the glycolipid includes one, two or three monosaccharide residues. The one or more monosaccharide residues of the glycolipid may be derived, for example, from glucose, sucrose, fructose, xylose, galactose, rhamnose, arabinose, mannose, cellobiose, lactose, galacturonate, sophorose or a mixture thereof. One or more of the hydroxyl groups of the monosaccharide residues may, for example, be acylated (e.g., acetylated) or etherified. Preferably, the lipid component contains a fatty acid moiety or salt thereof having from 6 to 30 carbon atoms (e.g., from 8 to 28 or from 10 to 26 carbon atoms), which may be linear or branched and saturated or unsaturated. The fatty acid chains may be substituted with functional groups, which are not particularly limited, provided that in general the glycolipid is typically water- miscible and/or water soluble. Examples of substituents include, but are not limited to, halogen atoms, hydroxyl, alkyl groups (e.g., Ci-6 alkyl), halo alkyl groups (e.g., halo Ci-6 alkyl), hydroxy alkyl groups (e.g., hydroxy Ci-6 alkyl), halo alkoxy groups (e.g., halo Ci-6 alkoxy), and the like. Further, the lipid component may contain fatty acid residues that are ester linked to one another.

The glycolipid of the present disclosure may have the following general formula (II) wherein L is a lipid group comprising a saturated or unsaturated fatty acid moiety or salt thereof containing from 6 to 30 carbon atoms (e.g., from 8 to 28 or from 10 to 26 carbon atoms), which may be linear or branched and optionally substituted, such as described in the preceding paragraph, and R is a carbohydrate group having from 1 to 5 monosaccharide residues, preferably from 1 to 3 (e.g., 1 or 2) monosaccharide residues, wherein each monosaccharide residue is independently a ring having 5 or 6 ring members, and one or more hydroxyl groups of the monosaccharide residues may be, for example, acylated (e.g., acetylated) or etherified, and wherein the glycolipid may be present in open chain form and/or in the form of a lactone.

The glycolipids of the present disclosure may be obtained commercially or may be produced by techniques known or to be developed in the art, such as by extraction or fermentation processes of natural sources (e.g., natural or modified microorganisms, fungi, etc.) or by chemical synthesis methods.

Preferably, the at least one glycolipid comprises a sophorolipid, a rhamnolipid or a combination thereof, more preferably a sophorolipid.

Sophorolipids are generally composed of the disaccharide sophorose linked to fatty acids via a glycosidic bond. The fatty acid chain length generally varies, such as described herein for the lipid component (preferably, e.g., from 6 to 30, from 8 to 28 or from 10 to 26 carbon atoms) and may be saturated or unsaturated. Sophorolipids are generally known to exist in either of two general forms: acidic form or lactonic form. Sophorolipids according to the present disclosure may be used in their acidic or lactonic forms, often a mixture thereof. Where the at least one glycolipid of the present disclosure comprises a mixture of acidic and lactonic sophorolipids, preferably a majority by weight is in acidic form, such as at least 60%, at least 70%, at least 80%, or at least 90% by weight are in acidic form.

The sophorolipids of the present disclosure in acidic form are preferably of the formula (III) or a salt thereof, and sophorolipids in lactonic form are preferably of the formula (IV).

where R¹ and R¹ independently represent saturated hydrocarbon chains or single or multiple, in particular single, unsaturated hydrocarbon chains having from 8 to 20 carbon atoms, such as from 12 to 18 carbon atoms, in particular 14 to 18 or 14 to 16 carbon atoms, which can be linear or branched and can comprise one or more substituents, including, without limitation, halogen atoms, hydroxyl, lower (Ci-e) alkyl groups, halo lower (Ci-e) alkyl groups, hydroxy lower (Ci-e) alkyl groups, halo lower (Ci-e) alkoxy groups, and the like, R² and R² independently represent a hydrogen atom or a saturated alkyl functional group or a single or multiple, in particular single, unsaturated alkyl functional group having from 1 to 9 carbon atoms, such as from 1 to 4 carbon atoms, which can be linear or branched and can comprise one or more hydroxy groups, and R³, R³ , R⁴ and R⁴ independently represent a hydrogen atom or an acetyl group. In many embodiments, R² and R² represent a methyl group or a hydrogen atom.

The sophorolipids may be obtained commercially or may be produced by techniques known or to be developed in the art, such as by fermentation processes of natural or modified microorganisms, for example, yeasts. Processes for the production of sophorolipids are described, for example, in WO2021183526, including techniques for adjusting the production, such as during fermentation, to control the ratio of acidic to lactonic sophorolipids.

In general, rhamnolipids are composed of one or two rhamnose moieties (mono- or di-rhamnolipid) as the carbohydrate component linked to a fatty acid tail, often a 3-(hydroxyalkanoyloxy)alkanoic acid (HAA) fatty acid tail which may vary in length and degree of branching, such as, e.g., 3- hydroxydecanoic acid.

The rhamnolipids of the present disclosure are preferably of the formula (V) or a salt thereof

(V), where m is 2, 1 or 0, n is 1 (dirhamnolipid) or 0 (monorhamnolipid), R¹ and R² are, independently of one another, the same or a different organic functional group having from 2 to 24 carbon atoms, such as from 5 to 13 carbon atoms, preferably a substituted (e.g., hydroxy-substituted) or unsubstituted, branched or unbranched alkyl functional group, which can also be unsaturated, wherein the alkyl functional group is preferably a linear saturated alkyl functional group having from 8 to 12 carbon atoms, such as a nonyl or a decyl functional group or a mixture thereof.

The rhamnolipids may be obtained commercially or may be produced by techniques known or to be developed in the art.

It shall be understood that the glycolipids may be present at least partially in salt form. For example, the cations of the glycolipid salts may be chosen from Li⁺, Na⁺, K⁺, Mg²⁺, Ca²⁺, Al³⁺, NHT, primary ammonium ions, secondary ammonium ions, tertiary ammonium ions and quaternary ammonium ions. Exemplary representatives of suitable ammonium ions are tetramethylammonium, tetraethylammonium, tetrapropylammonium, tetrabutylammonium and [(2- hydroxyethyl)trimethylammonium] (choline) and also the cations of 2 -aminoethanol (ethanolamine, MEA), diethanolamine (DEA), 2,2',2"-nitrilotriethanol (triethanolamine, TEA), 1 -aminopropan-2-ol (monoisopropanolamine), ethylenediamine, diethylenetriamine, triethylenetetramine, tetraethylenepentamine, 1,4-diethylenediamine (piperazine), aminoethylpiperazine and aminoethylethanolamine. Mixtures of salts, such as of the abovementioned cations, may be used.

In a first aspect, the aqueous antimicrobial composition comprises (a) from about 1% to less than 6% by weight of the at least one alkylhydroxamic acid, such as preferably from about 2% or from about 3% to less than 6%, or from about 1%, from about 2% or from about 3% to about 5.5% or to about 5% by weight of the at least one alkylhydroxamic acid, and (b) from about 10% to about 75% by weight of the at least one glycolipid, such as preferably from about 20% or more preferably from about 30% or from about 40% to about 75%, to about 65% or to about 60% by weight of the at least one glycolipid, each based on the weight of the composition. The composition optionally further includes (c) at least one N^a-alkanoyl dibasic amino acid ester salt, preferably in an amount up to about 20% by weight of the composition, such as from about 1%, from about 3% or from about 5% to about 20%, to about 15% or to about 10%, by weight of the composition. The antimicrobial composition is an aqueous composition and therefore includes a solvent component comprising water. The solvent component constitutes a neutral medium or media for the composition and, in general, typically constitutes at least about 25% by weight of the composition. The solvent component may be present up to an amount such that the sum of the at least one alkylhydroxamic acid (a), the at least one glycolipid (b) and the solvent component is or essentially is 100% by weight of the composition. The solvent component preferably constitutes from about 25% or from about 30% to about 80%, preferably to about 70%, or more preferably to about 60%, to about 50% or to about 40% by weight of the composition. The solvent component may further contain one or more water-miscible solvent materials, but in general typically at least a majority of the solvent is water, such as where the solvent component comprises at least 55%, at least 65%, at least 75%, at least 85%, at least 95%, or higher by weight of water, based on the total amount of solvent. Preferably, the solvent consists essentially of, or in further embodiments consists of, water. Preferably, the aqueous antimicrobial composition comprises from about 25% to about 60% by weight of water, more preferably from about 25% or from about 30% to about 50% by weight of water.

In a second aspect, the aqueous antimicrobial composition comprises (a) from about 1% to about 15%, such as from about 2%, from about 3% or from about 4% to about 15%, to about 13%, to about 10% or to about 8% by weight, based on the weight of the composition, of the at least one alkylhydroxamic acid, (b) from about 1% to about 75%, such as from about 5%, from about 10%, preferably from about 20%, more preferably from about 30% to about 75%, preferably to about 70% or more preferably to about 65%, to about 60% or to about 55%, by weight, based on the weight of the composition, of the at least one glycolipid, and (c) at least one N^a-alkanoyl dibasic amino acid ester salt, preferably in an amount up to about 20% by weight of the composition, such as from about 1%, from about 3% or from about 5% to about 20%, to about 15% or to about 10%, by weight of the composition. The aqueous antimicrobial composition may preferably comprise (a) from about 2%, from about 3% or from about 4% to about 15%, to about 13%, to about 10% or to about 8% by weight of the at least one alkylhydroxamic acid, (b) from about 10% to about 70%, more preferably from about 20%, from about 30% or from about 40% to about 60% or to about 55%, by weight, of the at least one glycolipid, and (c) from about 1%, from about 3%, or from about 5% to about 20%, more preferably from about 2%, from about 3% or from about 5% to about 15%, by weight of the at least one N^a-alkanoyl dibasic amino acid ester salt. In certain embodiments of this second aspect, the amount of alkylhydroxamic acid in the composition in accordance with the weight percentages as described above is provided at least in part by at least one salt thereof, such as a salt as described herein, particularly, for example, where the wt% of alkylhydroxamic acid in the composition is about 6 wt% or higher, such as from about 7 wt%, from about 8 wt%, from about 9 wt% or from about 10 wt% to about 15 wt%, to about 14 wt% or to about 13 wt%. As similarly described above, the antimicrobial composition is an aqueous composition and therefore includes a solvent component comprising water. In this second aspect, the solvent component constitutes a neutral medium or media for the composition and, in general, typically constitutes at least 25% by weight of the composition. The solvent component may be present up to an amount such that the sum of the at least one alkylhydroxamic acid (a), the at least one glycolipid (b), the at least one N^a-alkanoyl dibasic amino acid ester salt (c), and the solvent component is or essentially is 100% by weight of the composition. The solvent component preferably constitutes from about 25% or from about 30% to about 80%, preferably to about 70% or more preferably to about 60%, to about 50% or to about 40% by weight of the composition. The solvent component may further contain one or more water- miscible solvent materials, but in general, typically at least a majority of the solvent is water, such as where the solvent component comprises at least 55%, at least 65%, at least 75%, at least 85%, at least 95%, or higher by weight of water, based on the total amount of solvent. Preferably, the solvent consists essentially of, or in further embodiments consists of, water. Preferably, the aqueous antimicrobial composition comprises from about 25% to about 60% by weight of water, more preferably from about 25% or from about 30% to about 50% by weight of water.

The glycolipid content by weight can be determined according to techniques known in the art, preferably such as by HPLC or HPLC/MS.

In general, the proportion of each component of the aqueous antimicrobial composition can be optimized as desired for the particular application, e.g., based on the desired antimicrobial strength of the composition, the desired physical properties of the composition, and the interactions of the components.

For example, in general, the amount of glycolipid sufficient to solubilize or render compatible the alkylhydroxamic acid in the composition generally increases with increasing amounts of the alkylhydroxamic acid. In turn, a desirable increase in the amount of glycolipid to solubilize or render compatible increasing amounts of the alkylhydroxamic acid is typically balanced against the further objective to maintain the glycolipids in a solution or liquid form in the solvent component, and the amounts of these components can be optimized accordingly, including further with the addition of an N^a-alkanoyl dibasic amino acid ester salt, as described herein, which was found to further enhance the solubility or compatibility of the alkylhydroxamic acid in the presence of the glycolipids.

In general, the ratio by weight of the at least one alkylhydroxamic acid to the at least one glycolipid is preferably from about 1 : 60 to about 1 : 1 or more preferably from about 1 : 40 to about 1: 1.5, from about 1:40, from about 1:30 or from about 1:20 to about 1:2 or from about 1:40, from about 1:30 or from about 1:20 to about 1:5 or to about 1:7.

The aqueous antimicrobial composition of the present disclosure need not contain a diol to solubilize the at least one alkylhydroxamic acid. Accordingly, although one or more diols, such as those described in US 11,291,204, may be included as a water-miscible solvent material in the presently disclosed antimicrobial composition, the composition can be free or substantially free of diols. In this context, “substantially free” means that the antimicrobial composition contains less than 7 wt%, preferably less than 6 wt% or less than 5 wt%, more preferably, less than 3 wt%, less than 2 wt% or less than 1 wt%.

One or more additional antimicrobial agents may, but need not, be present in the aqueous antimicrobial composition.

The aqueous antimicrobial composition of the present disclosure may, but need not, contain at least one excipient as component (d). Excipients, if present, typically constitute a minor amount of the antimicrobial composition. Excipients may be chosen according to their compatibility or suitability for a desired end application or end product formulation, e.g., in a personal care formulation (e.g., a cosmetically acceptable excipient), health care formulation (e.g,. a pharmaceutically acceptable excipient), home care formulation or industrial formulation, as well as according to the desired physical properties of the antimicrobial composition. Examples of excipients include, but are not limited to, dispersants, solubilizers, buffers, viscosity modifiers, stabilizers, etc. The aqueous antimicrobial composition may optionally comprise the at least one excipient in an amount of, for example, from 0 to about 10 wt%, such as from about 0.001 wt%, from about 0.01 wt%, from about 0.05 wt% or from about 0.1 wt% to about 10 wt%, to about 5 wt%, to about 3 wt%, or to about 1 wt%, based on the weight of the antimicrobial composition. For example, the amount of the one or more excipients may range from 0 to about 5 wt%, from 0 to about 3 wt% from about 0.01 to about 5 wt%, from about 0.1 to about 5 wt%, from about 0.01 to about 3 wt%, from about 0.1 to about 3 wt%, from about 0.01 to about 1 wt%, or from about 0.1 to about 1 wt%.

The aqueous antimicrobial composition preferably consists essentially of, or in further embodiments consists of, (a) the at least one alkylhydroxamic acid, (b) the at least one glycolipid, optionally (c) the at least one N^a-alkanoyl dibasic amino acid ester salt, optionally (d) the at least one excipient and the solvent component comprising water. For example, the aqueous antimicrobial composition may consist essentially of, or in further embodiments consist of, (a) the at least one alkylhydroxamic acid, (b) the at least one glycolipid, (c) the at least one N^a-alkanoyl dibasic amino acid ester salt, optionally (d) the at least one excipient and the solvent component comprising water. Preferably, the antimicrobial composition may contain amounts of (a) the at least one alkylhydroxamic acid, (b) the at least one glycolipid, optionally (c) the at least one N^a-alkanoyl dibasic amino acid ester salt, and optionally (d) the at least one excipient, with the remainder of the antimicrobial composition consisting essentially of, or in further embodiments consisting of, the solvent component comprising water. Where the aqueous antimicrobial composition “consists of’ the component (a), the component (b), the solvent component, and optionally the components (c) and (d), the sum of said components total 100 wt% of the composition.

In preferred embodiments, the N^a-alkanoyl dibasic amino acid ester salt is an N^a-alkanoyl dibasic amino acid alkyl ester salt, particularly a N^a-(C6-C2o)alkanoyl dibasic amino acid (Ci-Ce)alkyl ester salt. The N^a-alkanoyl dibasic amino acid ester salt may be derived from a dibasic amino acid ester, such as an alkyl ester, of L-arginine, L-histidine, L-tryptophan, or L-lysine, preferably L-arginine. The N^a-alkanoyl dibasic amino acid ester salt may be derived, for example, from the condensation of fatty acids, such as C6-C20 fatty acids, and esterified dibasic amino acids, such as the amino acids described above. Preferably, the N^a-alkanoyl dibasic amino acid ester salt is derived from N^a-(C6- C2o)alkanoyl -L-arginine (Ci-Ce)alkyl ester, such as N^a-lauroyl -L-arginine (Ci-Ce)alkyl ester, more particularly N^a-lauroyl-L-arginine ethyl ester.

Examples of the anionic component of the N^a-alkanoyl dibasic amino acid ester salt include, but are not limited to, halide, linolenate, laurate, oleoate, nitrate, nitrite, gluconate, and pyroglutamate.

The N^a-alkanoyl dibasic amino acid ester salt is preferably of the formula (VI) where Ri is a straight alkyl chain from a saturated fatty acid or a hydroxy acid having from 6 to 20, preferably from 8 to 14, carbon atoms bonded to the a-amino group through an amidic bond, R2 is a straight or branched alkyl chain having from 1 to 6 carbon atoms, such as from 1 to 4, or from 1 to 2, carbon atoms, or an aromatic group, Rs is selected from where n is from 1 to 6, and

X is Cl", Br or a counter ion derived from an organic or inorganic acid or a phenolic compound. Examples of acids that may be the source of the counter ion X include acetic acid, citric acid, lactic acid, fumaric acid, maleic acid, gluconic acid, propionic acid, sorbic acid, benzoic acid, carbonic acid, glutamic acid, pyroglutamic acid, lauric acid, oleic acid, linoleic acid, phosphoric acid, nitric acid, sulfuric acid, and thiocyanic acid. Examples of phenolic compounds that may be the source of the counter ion X include butylated hydroxyanisole (BHA), butylated hydroxytoluene, tertiary butylhydroquinone, methylparaben, ethylparaben, propylparaben, and butylparaben. More preferably, the N^a-alkanoyl dibasic amino acid ester salt is of the formula (VII) where R2, Rs, n and X are as above in formula (VI), and m is from 6 to 18, preferably from 6 to 12.

A particular example of the N^a-alkanoyl dibasic amino acid ester salt is ethyl lauroyl arginate HC1 (LAE), which may be prepared from L-arginine and lauric acid, in particular, the ethyl ester of the lauramide of arginine monohydrochloride. The chemical structure of LAE is shown in formula (VIII)

Another example of the N^a-alkanoyl dibasic amino acid ester salt contains the N^a-cocoyl-L-arginine ethyl ester cation, such as CAE (pyrrolidone carboxylic acid (PCA) ethyl cocoyl arginate).

The ratio by weight in the aqueous antimicrobial composition of the at least one alkylhydroxamic acid to the at least one N^a-alkanoyl dibasic amino acid ester salt is preferably from about 3: 1, from about 2: 1 or from about 1: 1 to about 1: 15, to about 1: 10 or to about 1:5.

The antimicrobial composition of the present disclosure preferably remains in a liquid form without visible precipitation for at least 2 days, more preferably for at least one week, even more preferably for at least four weeks, at 21 °C.

The present disclosure also includes a method of preparing the aqueous antimicrobial composition comprising mixing the components thereof in the presence of the solvent component comprising water. The method comprises mixing the at least one alkylhydroxamic acid, the at least one glycolipid, optionally the at least one N^a-alkanoyl dibasic amino acid ester salt, and optionally the at least one excipient in the presence of the solvent component comprising water. The present disclosure is not limited to any particular technique for mixing the components of the composition and such composition may be prepared in any suitable manner for combining or mixing the components. For example, the composition can be prepared by mixing the components at an elevated temperature. It shall be understood that the compositional percentages and ratios described herein for the aqueous antimicrobial composition further relate to the presently disclosed methods for preparing the composition, that is, the components may be combined, for example, in accordance with the weight concentrations and ratios described herein.

The present disclosure provides for the use of an antimicrobial effective amount of the presently disclosed aqueous antimicrobial composition in a wide range of product formulations and applications, such as for use in personal care (e.g., cosmetic), home care, health care (e.g., 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, health care or home care product. Examples include, without limitation, household products and cleaners, fabric detergents and softeners, dish detergents, cleansers, soaps, bubble baths, disinfectants, deodorizers, antimicrobial packaging, pharmaceutical products, medical device products, contact lens products, cosmetics, hygiene compositions, infant care products, antimicrobial soaps, hand sanitizers, deodorants, antiperspirants, dental compositions, toothpastes, mouthwashes, lipsticks, medications, athlete's foot treatments, wound care compositions, dermatological compositions, acne treatments, skin conditioners, skin moisturizers, anti-wrinkle formulations, skin whiteners, sunscreens, lotions, hair products, shampoos, shower gels, bubble baths, conditioners, creams, paints, coatings, adhesives, agricultural products, etc. Also included are formulations for providing microbial-resistance to fabrics and apparel, condoms, surgical gowns, hospital equipment, paper products, animal care products, plastics, rubbers or other fabrication materials, appliances with antimicrobial constituents or coatings, etc. Depending on the application, the product formulation may contain numerous and different compatible ingredients. For example, the product formulation may comprise an antimicrobial effective amount of the aqueous 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 (e.g., pharmaceutical), or industrial product formulation.

In one aspect, an aqueous product formulation comprises an antimicrobial effective amount of the aqueous antimicrobial composition of the present disclosure. An aqueous product formulation in this context refers to formulations that include water, such as a solvent or carrier, in the formulation medium or media, such as those in the form of a liquid, solution, lotion, cream, gel, dispersion, suspension, emulsion or microemulsion (e.g., oil-in-water emulsions, water-in-oil emulsions, silicone- in-water emulsions, water-in-silicone emulsions, etc.). Preferably, the aqueous product formulation is a personal care (e.g., cosmetic), home care, health care (e.g., pharmaceutical), or industrial product formulation, particularly a personal care, health care or home care product formulation.

The present disclosure also includes a personal care (e.g., cosmetic), home care, health care (e.g., pharmaceutical) or industrial product formulation comprising an antimicrobial effective amount of the aqueous antimicrobial composition according to the present disclosure.

As a particular example, the aqueous antimicrobial composition of the present disclosure can be incorporated into any number and variety of different personal care products, such as cosmetic products. Accordingly, a personal care product formulation is provided comprising an antimicrobial effective amount of the aqueous antimicrobial composition of the present disclosure and one or more additional ingredients suitable for use in a personal care formulation. The personal care product formulation may be, for example, any formulation for skin care, hair care, cosmetics, personal cleaning, hygiene, sun protection, fragrances 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.

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, gelling agents, colorants, rheology modifiers, conditioners, emollients, skin care or protection ingredients, moisturizers, thickeners, humectants, fillers, antioxidants, other antimicrobial agents or preservatives, active ingredients, such as dermatologically active ingredients typically suited for topical application, fragrances, etc.

As a further example, the aqueous antimicrobial composition of the present disclosure can be incorporated into any number and variety of different home care products, such as fabric care products and cleaning products. Accordingly, a home care formulation is provided comprising an antimicrobial effective amount of the aqueous antimicrobial composition of the present disclosure and one or more additional ingredients suitable for use in a home care formulation. Examples include dish soaps, laundry detergents, fabric care treatments, cleaning wipes, cleaning formulations and other home care applications.

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, other antimicrobial agents or preservatives, UV absorbing compounds, anti -corrosion agents, anti-static agents, ironing aids, odor-preventing compounds, etc.

Examples of the foregoing ingredients and other agents used in personal care and home care product formulations are known in the art.

Also described is an industrial product formulation comprising an antimicrobial effective amount of the aqueous antimicrobial composition of the present disclosure and one or more additional ingredients suitable for use in an industrial product formulation, such as one or more ingredients suitable for use in formulations in the form of paints, coatings, varnishes, stains, adhesives, sealants and liquids associated with wood products, textile production, leather making, ropes, paper processing, pulps, paper boards, sheet rocks, ceiling tiles, and plastics, fuels, petroleum, oils, rubber working fluids, metal working fluids, starches, chalk slurries, mineral slurries, or other industrial applications.

Also provided is a health care (e.g., pharmaceutical) product formulation comprising an antimicrobial effective amount of the aqueous antimicrobial composition of the present disclosure and one or more additional ingredients suitable for use in a health care product formulation. Examples include formulations or dosages in liquid, gel, cream, ointment, semi-solid, topical, spray, drop and other forms. Depending on the application, the health care product formulation may contain, for example, any of solvents, emulsifiers, surfactants, antioxidants, buffers, gelling agents, chelating agents, colorants, flavoring agents, fragrances, emollients, humectants, thickeners, active pharmaceutical ingredients, etc.

The aqueous antimicrobial composition of the present disclosure may be used in product formulations containing other antimicrobial, preservative or booster agents. Examples of such agents include those suitable for use in various industries in which the antimicrobial composition of the present disclosure is beneficial. Examples of such agents include, but are not limited to, 1,3 -butanediol, 1,5 -pentanediol, 1,2-decanediol, 1,2-hexanediol, 1,3 -propanediol, 4-hydroxyacetophenone, amyl cinnamic aldehyde, benzyl alcohol, caprylhydroxamic acid, caprylyl glycol, cinnamic alcohol, cinnamic aldehyde, ethylhexylglycerin, gluconolactone, glyceryl caprate/caprylate, phenethyl alcohol, phenoxyethanol, potassium benzoate, propylene glycol caprylate, p-thymol, salicylic acid, sodium anisate, benzoates, such as sodium benzoate, sodium dehydroacetate, sodium levulinate, sorbic acid, sorbitan caprylate, and combinations thereof.

In general, an antimicrobial effective amount of the aqueous antimicrobial composition is added to a product formulation. An optimized antimicrobial effective amount of the aqueous antimicrobial composition may vary depending, for example, on the particular end use application, the desired level of antimicrobial activity or preservation, the final properties of the product, and the like. As known in the art, antimicrobial efficacy may be demonstrated by various suitable antimicrobial effectiveness tests.

In general, the antimicrobial effective amount of the aqueous antimicrobial composition added to a product formulation, such as a personal care (e.g., cosmetic), home care, health care (e.g., pharmaceutical) or industrial product formulation, is preferably from about 0.05 wt% or from about 0. 1 wt% to about 5 wt%, to about 4 wt% or to about 3 wt%, based on the total weight of the product formulation. The antimicrobial effective amount preferably provides a combined amount of the at least one alkylhydroxamic acid, the at least one glycolipid and optionally (if present) the at least one N^a-alkanoyl dibasic amino acid ester salt of, for example, from about 0.01 wt% or from about 0.05 wt%, more preferably from about 0. 1 wt%, from about 0.2 wt%, from about 0.3 wt%, from about 0.4 wt% or from about 0.5 wt% to about 4 wt%, more preferably to about 3.5 wt%, to about 3 wt%, to about 2.5 wt%, or to about 2 wt%, based on the total weight of the product formulation. For example, the antimicrobial effective amount may provide a combined amount of the at least one alkylhydroxamic acid, the at least one glycolipid and optionally (if present) the at least one N^a- alkanoyl dibasic amino acid ester salt of from about 0.01 to about 3 wt%, from about 0.1 or 0.2 to about 3 wt%, from about 0.1 or 0.2 to about 2 wt%, or from about 0. 1 or 0.2 to about 1 wt%, based on the total weight of the product formulation.

Preferably, the amount of the at least one alkylhydroxamic acid ranges from about 0.002 wt%, from about 0.004 or from about 0.006 wt% to about 0.5 wt% or to about 0.4 wt%, more preferably from about 0.01 wt% or from about 0.05 wt% to about 0.3 wt% or to about 0.2 wt%, based on the total weight of the product formulation. Preferably, the combined amount of the at least one alkylhydroxamic acid and the at least one N^a-alkanoyl dibasic amino acid ester salt is from about 0.004 wt%, from about 0.008 wt% or from about 0.01 wt% to about 1 wt%, to about 0.8 wt% or to about 0.6 wt%, more preferably from about 0.01 wt%, from about 0.05 wt% or from about 0.1 wt% to about 1 wt%, to about 0.8 wt% or to about 0.6 wt%, based on the total weight of the product formulation.

The aqueous antimicrobial composition may be included in product formulations of a variety of different forms, for example, liquids, pastes, serums, hydrogels, creams, emulsions or microemulsions (e.g., oil-in-water, water-in-oil, silicone-in-water, water-in-silicone, etc.), lotions, gels, oils, suspensions, dispersions, solutions (e.g., water-based, aqueous/alcoholic, glycolic, etc.), syrups, wipes, ointments, semi-solid compositions, solids, foams, aerosol sprays and liposome-based formulations. The aqueous antimicrobial composition may be used in a leave-on or rinse-off product formulation. The aqueous antimicrobial composition may be incorporated in formulations used to saturate wipes used 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.

The product formulations of the present disclosure preferably have a pH ranging from about 4.0 to about 8.0. Unless otherwise specified, pH values or ranges refer to pH at room temperature (20-25 °C). The selected pH will vary depending, for example, on the particular end use application.

Further provided is a method of preparing or formulating a product formulation of the present disclosure, preferably a personal care (e.g., cosmetic), home care, health care (e.g., pharmaceutical) or industrial product formulation, comprising adding to the product formulation an antimicrobial effective amount of the aqueous antimicrobial composition of the present disclosure. Also provided is a method of preserving or controlling the growth of microorganisms in a product formulation of the present disclosure, preferably a personal care (e.g., cosmetic), home care, health care (e.g., pharmaceutical) or industrial product formulation, the method comprising adding to the product formulation an antimicrobial effective amount of the aqueous antimicrobial composition according to the present disclosure. The methods may further include the step of preparing the aqueous antimicrobial composition followed by adding the antimicrobial composition to the product formulation.

In a further aspect, a method of controlling microbial growth in or preserving a product formulation, preferably a personal care (e.g., cosmetic), home care, health care (e.g., pharmaceutical) or industrial product formulation, comprises adding to the product formulation an antimicrobial effective amount of an aqueous mixture comprising (a) at least one alkylhydroxamic acid, (b) at least one glycolipid, optionally (c) at least one N^a-alkanoyl dibasic amino acid ester salt, and optionally (d) at least one excipient (such as described herein for each such component). The mixture added to the product formulation is an aqueous mixture and thus includes a solvent component comprising water, such as described herein. The aqueous mixture may consist essentially of, or in further embodiments consist of, (a) at least one alkylhydroxamic acid, (b) at least one glycolipid, optionally (c) at least one N^a- alkanoyl dibasic amino acid ester salt, optionally (d) at least one excipient, and a solvent component comprising water (such as described herein for each such component). For example, the aqueous mixture may consist essentially of, or in further embodiments consist of, (a) at least one alkylhydroxamic acid, (b) at least one glycolipid, (c) at least one N^a-alkanoyl dibasic amino acid ester salt, optionally (d) at least one excipient, and a solvent component comprising water (such as described herein for each such component). Preferably, the aqueous mixture may contain amounts of (a) at least one alkylhydroxamic acid, (b) at least one glycolipid, optionally (c) at least one N^a- alkanoyl dibasic amino acid ester salt, and optionally (d) at least one excipient, with the remainder of the antimicrobial composition consisting essentially of, or in further embodiments consisting of, a solvent component comprising water (such as described herein for each such component). Preferably, the ratio by weight of the at least one alkylhydroxamic acid to the at least one glycolipid in the aqueous mixture is preferably from about 1:60 to about 1: 1 or more preferably from about 1:40 to about 1: 1.5, from about 1:40 or from about 1:30 to about 1:2 or from about 1:40, from about 1:30 or from about 1:20 to about 1:5 or to about 1:7.

In another aspect, the present disclosure also includes a method of formulating or solubilizing at least one alkylhydroxamic acid for use as an antimicrobial agent in an aqueous antimicrobial composition, the method comprising combining at least one alkylhydroxamic acid with at least one glycolipid in the presence of water. The at least one alkylhydroxamic acid and the at least one glycolipid may be combined in the amounts and ratios as described herein. The method may further combining the at least one alkylhydroxamic acid with at least one N^a-alkanoyl dibasic amino acid ester salt, such as described herein.

In a further aspect, an aqueous antimicrobial composition consists essentially of, or in further embodiments consists of, (a) at least one alkylhydroxamic acid, (b) at least one glycolipid, optionally (c) at least one N^a-alkanoyl dibasic amino acid ester salt, optionally (d) at least one excipient, and a solvent component comprising water (such as described herein for each such component). The aqueous antimicrobial composition may consist essentially of, or in further embodiments consist of, (a) at least one alkylhydroxamic acid, (b) at least one glycolipid, optionally (c) at least one N^a- alkanoyl dibasic amino acid ester salt, optionally (d) at least one excipient, and a solvent component comprising water (such as described herein for each such component). For example, the aqueous antimicrobial composition may consist essentially of, or in further embodiments consist of, (a) at least one alkylhydroxamic acid, (b) at least one glycolipid, (c) at least one N^a-alkanoyl dibasic amino acid ester salt, optionally (d) at least one excipient, and a solvent component comprising water (such as described herein for each such component). Preferably, the antimicrobial composition may contain amounts of (a) at least one alkylhydroxamic acid, (b) at least one glycolipid, optionally (c) at least one N^a-alkanoyl dibasic amino acid ester salt, and optionally (d) at least one excipient, with the remainder of the antimicrobial composition consisting essentially of, or in further embodiments consisting of, a solvent component comprising water (such as described herein for each such component). Preferably, the ratio by weight of the at least one alkylhydroxamic acid to the at least one glycolipid in the aqueous antimicrobial composition is preferably from about 1:60 to about 1: 1 or more preferably from about 1:40 to about 1: 1.5, from about 1:40 or from about 1:30 to about 1:2 or from about 1:40, from about 1:30 or from about 1:20 to about 1:5 or to about 1:7.

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.

As used herein, the term “comprising” means the presence of the stated features, integers, steps, or components as referred to in the claims, but that it does not preclude the presence or addition of one or more 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.

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.

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.

When a parameter is given either as a range, preferred range, or a list of upper preferable values and lower preferable 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.

EXAMPLES

Test Materials and Abbreviations:

The glycolipid used in the below examples was a mixture of sophorolipids of Formulas (III) and (IV) herein, where R¹ and R¹ were single unsaturated hydrocarbon chains in the range from 14 to 16 carbon atoms, R² and R² were methyl, and R³, R³ , R⁴ and R⁴ were hydrogen. A majority by weight of the sophorolipids was of the Formula (III) (i.e., the acidic form), except for Samples 6L and 7L in Example 1 in which a majority by weight of the sophorolipids was of the Formula (IV) (i.e., the lactonic form). The glycolipid was present in water.

LAE in the below examples is Ethyl lauroyl arginate HC1.

CHA in the below examples is capryl hydroxamic acid.

Example 1.

Samples having the composition as shown in Table 1 and Table 2 were mixed using sonication and heated at 40°C. The mixtures were cooled to room temperature (approximately 21 °C). The compositions were observed after 7 days to evaluate compatibility. As shown in Table 1, Capryl hydroxamic acid (CHA) is practically insoluble in water (< O.lg/lOO mb water). Surprisingly, the presence of glycolipids significantly enhanced the solubility or compatibility of CHA in water. Furthermore, ethyl lauroyl arginate hydrochloride (LAE) surprisingly further enhanced the solubility or compatibility of CHA. Table 1.

Samples 8 and 9 provided in Table 2 below were prepared using a sodium salt of caprylhydroxamic acid and was observed as described above. As shown in Table 2, the mixtures provided clear solutions.

Table 2.

Example 2.

Preservation activity in representative rinse-off and leave-on formulations was evaluated 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 of Preservation ofNon-Eye Area Water Miscible Cosmetic and Toiletry Formulations: Collaborative Study. J of AO AC International. 84: 1, 101-109).

The evaluation was conducted using a four week, two or three-cycle (i.e., two-cycle for personal care and three-cycle for home care applications) microbial preservative efficacy test (i.e., challenge test) at 25 °C to determine the preservative efficacy of each treatment. Table 3 shows a xanthan-gum -based serum. The serum composition was made by adding the ingredients shown in Table 3 into a beaker and mixing with an overhead mixer and heating to 75-80 °C. The mixture was homogenized and was cooled to room temperature. The pH was adjusted with a sodium hydroxide solution to a pH of 5.5.

Table 3.

After dosing, the samples were divided into two separate aliquots of 5 grams each. One aliquot was inoculated with 50 pl of a diluted bacterial pool, and the second aliquot was inoculated with 50 pl of a diluted fungal pool as described below. Unpreserved product samples were included in the test as a growth control. A mixed bacterial inoculum was prepared using 24-hour cultures of the test bacteria (Table 4) 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 10⁷ to 5 x 10⁸ colony 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 10⁶ to 5 x 10⁷ cfu/ml. The test samples were inoculated with 1% of the mixed fungal inoculum.

Table 4. Mixed Bacterial Inoculum

The samples were subjected to microbial challenge at time zero and inoculated a second time after seven days. 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. Samples were incubated at 25 °C for the test duration of four weeks. Samples were monitored for bacterial and fungal contamination after 2, 7, 14, 21, and 28 days. Samples challenged with bacteria were streak -plated onto Trypticase Soy Agar (TSA) and incubated at 30°C for 24 hours. Samples challenged with fungi were streak-plated onto Potato Dextrose Agar (PDA) and incubated at 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 5 represents the growth score.

Table 5. Growth Score Used to Determine CFU/mL in Test Samples.

Three antimicrobial compositions were prepared according to the compositions shown in Table 6. The prepared mixtures were dosed into the serum formulation of Table 3 at varying dosing levels (as provided in Table 7) and mixed homogeneously using a speed mixer. Small quantities of glycerin were also added to the serum formulation as a rheology modifier.

Table 6.

As shown in Table 7, the serum formulations dosed with the Samples 10, 11 and 12, respectively, provided significant preservation efficacy against both bacteria and fungi.

Table 7.

Claims

What is claimed is:

1. An aqueous antimicrobial composition comprising

(a) from about 1% to less than 6% by weight of caprylhydroxamic acid, and

(b) from about 10% to about 75% by weight of at least one sophorolipid, each based on the weight of the composition, wherein the at least one sophorolipid is a mixture of sophorolipids in acidic and lactonic forms, and a majority by weight of the sophorolipids is in acidic form, preferably wherein at least 70% by weight, or more preferably at least 80% by weight, of the sophorolipids is in acidic form.

2. The aqueous antimicrobial composition according to claim 1, wherein the composition comprises from about 3% to less than 6% by weight of the caprylhydroxamic acid.

3. The aqueous antimicrobial composition according to any preceding claim, wherein the composition comprises from about 30% to about 60% by weight of the at least one sophorolipid.

4. The aqueous antimicrobial composition according to any preceding claim, wherein the ratio by weight of the caprylhydroxamic acid to the at least one sophorolipid is from about 1:30 to about 1:5.

5. The aqueous antimicrobial composition according to any preceding claim, wherein the mixture of sophorolipids comprises at least one acidic sophorolipid of formula (III) and/or a salt thereof and at least one lactonic sophorolipid of formula (IV)

where R¹ and R¹ are each independently an optionally substituted saturated or unsaturated hydrocarbon chain having 8 to 20 carbon atoms, which can be linear or branched,

R² and R² are each independently a hydrogen atom or a saturated or unsaturated alkyl functional group having from 1 to 9 carbon atoms, which can be linear or branched, and is optionally substituted with one or more hydroxy groups, and

R³, R³ , R⁴ and R⁴ are each independently a hydrogen atom or an acetyl group.

6. The aqueous antimicrobial composition according to any preceding claim, further comprising at least one N^a-alkanoyl dibasic amino acid ester salt.

7. The aqueous antimicrobial composition according to claim 6, wherein the at least one N^a-alkanoyl dibasic amino acid ester salt is present in an amount up to about 20% by weight of the composition.

8. The aqueous antimicrobial composition according to claim 7, wherein the composition comprises from about 5% to about 15% by weight of the at least one N^a-alkanoyl dibasic amino acid ester salt.

9. An aqueous antimicrobial composition comprising

(a) from about 1% to about 15% by weight of caprylhydroxamic acid,

(b) from about 1% to about 75% by weight of at least one sophorolipid, each based on the weight of the composition, and

(c) at least one N^a-alkanoyl dibasic amino acid ester salt.

10. The aqueous antimicrobial composition according to claim 9, wherein the at least one N^a-alkanoyl dibasic amino acid ester salt is present in an amount up to about 20% by weight of the composition.

11. The aqueous antimicrobial composition according to claim 9 or 10, wherein the composition comprises from about 3% to about 13% of the caprylhydroxamic acid.

12. The aqueous antimicrobial composition according to any one of claims 9-11, wherein the composition comprises from about 30% to about 60% by weight of the at least one sophorolipid.

13. The aqueous antimicrobial composition according to any one of claims 9-12, wherein the composition comprises from about 5% to about 15% by weight of the at least one N^a-alkanoyl dibasic amino acid ester salt.

14. The aqueous antimicrobial composition according to any one of claims 9-13, wherein the caprylhydroxamic acid constitutes at least 6 wt% of the composition, and the composition comprises the caprylhydroxamic acid at least partially as a salt thereof.

15. The aqueous antimicrobial composition according to any one of claims 9-14, wherein the ratio by weight of the caprylhydroxamic acid to the at least one sophorolipid is from about 1 : 30 to about 1:2.

16. The aqueous antimicrobial composition according to any one of claims 9-15, wherein the at least one sophorolipid comprises at least one acidic sophorolipid of formula (III) and/or a salt thereof (III), or at least one lactonic sophorolipid of formula (IV) or a combination thereof, where R¹ and R¹ are each independently an optionally substituted saturated or unsaturated hydrocarbon chain having 8 to 20 carbon atoms, which can be linear or branched,

17. The aqueous antimicrobial composition according to any one of claims 9-16, wherein the at least one sophorolipid is a mixture of sophorolipids in acidic and lactonic forms, and a majority by weight of the sophorolipids is in acidic form.

18. The aqueous antimicrobial composition according to any one of claims 6-17, wherein the at least one N^a-alkanoyl dibasic amino acid ester salt is at least one N^a-(C6-C2o)alkanoyl dibasic amino acid (Ci-Ce)alkyl ester salt.

19. The aqueous antimicrobial composition according to any one of claims 6-17, wherein the at least one N^a-alkanoyl dibasic amino acid ester salt is of the formula (I) where Ri is a straight alkyl chain from a saturated fatty acid or a hydroxy acid having from 6 to 20 carbon atoms bonded to the a-amino group through an amidic bond,

R2 is a straight or branched alkyl chain from 1 to 6 carbon atoms, or an aromatic group,

Rs is selected from n is from 1 to 6, and

X is Cl", Br or a counter ion derived from an organic or inorganic acid or a phenolic compound.

20. The aqueous antimicrobial composition according to any one of claims 6-17, wherein the at least one N^a-alkanoyl dibasic amino acid ester salt is at least one N^a-(C6-C2o)alkanoyl-L- arginine (Ci-Ce)alkyl ester salt.

21. The aqueous antimicrobial composition according to any one of claims 6-17, wherein the N^a-alkanoyl dibasic amino acid ester salt is ethyl lauroyl arginate HC1 (LAE), pyrrolidone carboxylic acid (PCA) ethyl cocoyl arginate, or a combination thereof.

22. The aqueous antimicrobial composition according to any preceding claim, wherein the antimicrobial composition is free or substantially free of diols.

23. The aqueous antimicrobial composition according to any preceding claim, wherein upon storage at 21 °C the composition remains in a liquid form without visible precipitation for at least one week.

24. The aqueous antimicrobial composition according to claim 23, wherein upon storage at 21 °C the composition remains in a liquid form without visible precipitation for at least four weeks.

25. An aqueous product formulation comprising an antimicrobial effective amount of the aqueous antimicrobial composition according to any preceding claim.

26. The aqueous product formulation according to claim 25, further comprising one or more additional ingredients suitable for use in a personal care, home care or health care product formulation.

27. A personal care, home care, health care or industrial product formulation comprising an antimicrobial effective amount of the aqueous antimicrobial composition according to any one of claims 1-24.

28. A method of controlling microbial growth in or preserving a product formulation, comprising adding to the product formulation an antimicrobial effective amount of the aqueous antimicrobial composition according to any one of claims 1-24.

29. A method of formulating or solubilizing caprylhydroxamic acid for use as an antimicrobial agent in an antimicrobial composition, the method comprising combining caprylhydroxamic acid with at least one sophorolipid in the presence of water, a water-miscible solvent or a combination thereof, wherein a ratio by weight of the caprylhydroxamic acid to the at least one sophorolipid is from about 1:60 to about 1: 1.

30. The method according to claim 29, wherein the ratio by weight of the caprylhydroxamic acid to the at least one sophorolipid is from about 1:30 to about 1:2.

31. A method of controlling microbial growth in or preserving a product formulation, comprising adding to the product formulation an antimicrobial effective amount of an aqueous mixture comprising (a) caprylhydroxamic acid, (b) at least one sophorolipid, optionally (c) at least one N^a-alkanoyl dibasic amino acid ester salt, and optionally (d) at least one excipient.