Antimicrobial composition comprising ethyl maltol preparing the same and method of use thereof

Abstract

The present application provides a synergistic antimicrobial composition comprising: (a) about 0.01 to about 99.9 wt.% of ethyl maltol; and (b) about 0.1 to about 95% wt.% of one or more antimicrobial compounds and method of use thereof. Also, the present application discloses the process for preparing synergistic antimicrobial composition and method of use thereof. Further, the present composition demonstrates Synergy Index (SI) value of the total composition from about 0.0001 to about 1.0; and the Combination Index (CI) value of the total composition is between about 0.0001 and about 0.90.

Description

Docket No.: SCH-2024P00617PCTANTIMICROBIAL COMPOSITION COMPRISING ETHYL MALTOL PREPARING THE SAME AND METHOD OF USE THEREOFFIELD OF THE INVENTION

[0001] The present application relates to an antimicrobial composition, and, more particularly, provides a synergistic antimicrobial composition comprising: (a) about 0.01 to about 99.9 wt.% of ethyl maltol; and (b) about 0.1 to about 95% wt.% of one or more antimicrobial compound. Also disclosed a method of use thereof.BACKGROUND OF THE INVENTION

[0002] Commercial use products are generally designed to have a substantial shelflife. The products need to be manufactured at one site, transported possibly over a considerable distance to a depot or other storage facility prior to further transport to a point of sale. The product may then spend considerable time on a retailer's shelf prior to purchase and further storage by the user whether for individual use or use in, for example, a workplace, institution or the like. Storage typically takes place under uncontrolled conditions including considerable variation in temperature. In order to keep bacterial and fungal growth in such products at an acceptable level, it is conventional practice for the products to contain a preservative. Many preservatives are available. The appropriate preservative needs to be selected based on its efficacy and its acceptability in the product.

[0003] Classic preservatives such as formaldehyde donors, parabens, and isothiazolinones are generally very effective at controlling microorganisms in various personal care products. However, in recent years, many consumers developed unfavorable perception of these chemistries. Current market trends strongly favor safe, non-irritating, natural / nature-identical, and biodegradable actives. As a result of these changes, there is a strong need for the development of novel antimicrobial technologies for personal and home care applications. Chemisties that can boost the antimicrobial performance of known actives are highly desired.

[0004] There are multiple benefits in using a combination of antimicrobials, especially if they act synergistically with one another. Firstly, the use of such combination greatly reduces the risk of microorganisms developing resistance to antimicrobials. Additionally, synergistically acting antimicrobials can be used in lower concentrations thus reducing the cost and improving environmental impact. Finally, a synergistically acting multi-component antimicrobial system is likely to be active versus a broader range of microorganisms, or to provide a faster kill rate,Docket No.: SCH-2024P00617PCTcompared to each component acting individually. For these reasons, identifying synergistic combinations of antimicrobial actives is critical for development of effective preservative systems.

[0005] US Publication 20230240953A1 discloses an antimicrobial composition for use in e.g. cosmetic, toiletry and sanitary products and for inhibiting growth of Staphylococcus aureus, Candida albicans and Mucor racemosus, comprises phenyl butane compound and antimicrobial compound.

[0006] PCT Application 2019171385A1 discloses a preservation of personal care compositions comprising a maltol and at least two cationic surfactants.

[0007] PCT Applications 2023222577A1 and 2023147852A1 discloses an anti-microbial mixture, wherein ethyl maltol is used as an aroma and as physiological warming compound.

[0008] In view of the foregoing, still there is a need for improved antimicrobial compositions for aqueous or non-aqueous based end-user compositions for reducing, inhibiting or preventing microbial growth, comprising suitable and effective amounts of antimicrobial compositions in the desired end-user products.

[0009] Accordingly, it is an objective of the present invention to provide an antimicrobial composition comprising (i) ethyl maltol; and (ii) at least one or more antimicrobial compounds. According to another objective of the present application, there is provided a synergistic antimicrobial composition to kill or inhibit the growth of microorganisms in various aqueous and non-aqueous based end user composition. In view of the foregoing, still there is a need for improved antimicrobial compositions for aqueous or non-aqueous based end-user compositions for reducing, inhibiting or preventing microbial growth, comprising suitable and effective amounts of antimicrobial compositions in the desired end-user products.

[0010] Due to synergistic antimicrobial activity, another objective of the present invention is to provide suitable and effective amounts of antimicrobial combinations which allow lower use of concentration, leading to lower material costs, lower environmental impact (lower quantities of material, which then again need to be transported) and lower toxicity due to reduced exposition. Furthermore, the synergistic combinations cover a broader range of microorganisms compared to the limited spectrum of single ingredients.Docket No.: SCH-2024P00617PCTSUMMARY OF THE INVENTION

[0011] The primary aspect of the present application is to provide an antimicrobial composition comprising: (a) about 0.01 to about 99.9 wt.% of ethyl maltol; and (b) about 0.1 to about 95% wt.% of one or more antimicrobial compounds.

[0012] Another non-limiting aspect of the present application provides an antimicrobial composition comprising process for preparing antimicrobial composition, wherein the process comprising the steps of mixing: (a) about 0.01 to about 99.9 wt.% of ethyl maltol; and (b) about 0.1 to about 95 wt.% of one or more antimicrobial compounds.

[0013] Yet another aspect of the present application discloses that the antimicrobial composition can be an aqueous composition or a non-aqueous composition.

[0014] In another aspect, a method of killing or inhibiting the growth of bacteria and fungi in an aqueous or non-aqueous based end-user product selected from the group consisting of personal care or cosmetic products, toiletry products, oral care products, skin care products, hair care products, household & cleaning products, soap and bath products, industrial and institutional cleaning products, disinfecting products, wound care products, sanitary products, agricultural compositions, textile products, coating products and laundry products that are susceptible to growth of microorganisms comprises incorporating the antimicrobial composition of the present application in an amount ranging from about 0.01 wt. % to 5.0 wt. % into the above desired products.

[0015] In yet another aspect, the present application provides an antimicrobial composition comprising (a) about 0.001 to about 40 wt. % of ethyl maltol; and (b) about 0.1 to about 95 wt. % of one or more antimicrobial compounds selected from the group consisting of phenoxyethanol, 3 -phenylpropanol, 1,2-hexanediol, pentylene glycol (pentanediol), 1,3-propanediol, 4-hydroxyacetophenone, ethylhexylglycerin, glyceryl caprylate and combinations thereof.Docket No.: SCH-2024P00617PCTDETAILED DESCRIPTION OF THE INVENTION

[0016] Before explaining at least one aspect of the disclosed and / or claimed inventive concept(s) in detail, it is to be understood that the disclosed and / or claimed inventive concept(s) is not limited in its application to the details of construction and the arrangement of the components or steps or methodologies set forth in the following description or illustrated in the drawings. The disclosed and / or claimed inventive concept(s) is capable of other aspects or of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.

[0017] As utilized in accordance with the disclosure, the following terms, unless otherwise indicated, shall be understood to have the following meanings.

[0018] Unless otherwise defined herein, technical terms used in connection with the disclosed and / or claimed inventive concept(s) shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include pluralities, and plural terms shall include the singular.

[0019] The singular forms "a," "an," and "the" include plural forms unless the context clearly dictates otherwise specified or clearly implied to the contrary by the context in which the reference is made. The term “Comprising” and “Comprises of’ includes the more restrictive claims such as “Consisting essentially of’ and “Consisting of’.

[0020] For purposes of the following detailed description, other than in any operating examples, or where otherwise indicated, numbers that express, for example, quantities of ingredients used in the specification and claims are to be understood as being modified in all instances by the term "about". The numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties to be obtained in carrying out the invention.

[0021] All percentages, parts, proportions and ratios as used herein, are by weight of the total composition, unless otherwise specified. All such weights as they pertain to listed ingredients are based on the active level and therefore do not include solvents or by-products that may be included in commercially available materials, unless otherwise specified.

[0022] All publications, articles, papers, patents, patent publications, and other references cited herein are hereby incorporated herein in their entirety for all purposes to the extent consistent with the disclosure herein.Docket No.: SCH-2024P00617PCT

[0023] The use of the term “at least one” will be understood to include one as well as any quantity more than one, including but not limited to, 1, 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 100, etc. The term “at least one” may extend up to 100 or 1000 or more depending on the term to which it is attached. In addition, the quantities of 100 / 1000 are not to be considered limiting as lower or higher limits may also produce satisfactory results.

[0024] As used herein, the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.

[0025] In non-limiting embodiment, the present application discloses synergistic antimicrobial composition comprising: (a) about 0.01 to about 99.9 wt.% of ethyl maltol; and (b) about 0.1 to about 95% wt.% of one or more antimicrobial compound.

[0026] As used herein, the terms "antimicrobial” / “preservative” refer to substances capable of killing or inhibiting the growth of microorganisms, including but not limited, to bacteria and fungi.

[0027] As used herein, the term ethyl maltol (2 -Ethyl-3 -hydroxy -4H-pyran-4-one) refers to a cyclic organic compound with the formula C7H8O3 that has the following structural formula:0. This compound has been used as an aroma chemical in the perfume industry and the food industry.

[0028] As used herein, antimicrobial compound(s) not being compounds of ethyl maltol refers to any antimicrobial compound preferably selected from the group including, but not limited to diols, organic acids, glycerin ethers, caprylates, glyceryl esters, aldehydes, terpenes, terpenoids, essential oils, peptides, glucosides, enzymes, amino acids and their esters, sclerolide, and sclareol and other conventional preservatives that are well-known to a person skilled in the pertinent art.

[0029] According to the present application, non-limiting examples of suitable antimicrobial diols useful herein include, but are not limited to, propanediol, butanediol, pentanediol, hexanediol, heptanediol, octanediol, nonanediol, decanediol and dodecanediol.Docket No.: SCH-2024P00617PCT

[0030] In another non-limiting embodiments, it is contemplated to use diols having a carbon chain length of from 3 to 12 atoms, including but not limited to, propane- 1 ,2-diol, propane-1, 3-diol, butane- 1 ,2-diol, butane- 1,3 -diol, butane- 1,4-diol, 2-methylpropane-l,2-diol, 2-methylpropane- 1,3 -diol, pentane- 1,2-diol, pentane-l,3-diol, pentane- 1,4-diol, pentane-1,5-diol, pentane-2,3-diol, pentane-2,4-diol, 2-methyl-pentane-2,4-diol, hexane- 1,2-diol, hexane-1,3-diol, hexane- 1,4-diol, hexane- 1,5-diol, hexane- 1,6-diol, hexane-2,3-diol, hexane-2,4-diol, hexane-2,5-diol, hexane-3,4-diol, heptane- 1,2-diol, heptane-l,3-diol, heptane- 1,4-diol, heptane- 1,5 -diol, heptane- 1,6-diol, heptane- 1,7-diol, heptane-2,3-diol, heptane-2,4-diol, heptane-2,5-diol, heptane-2,6-diol, heptane-3,4-diol, heptane-3,5-diol, octane- 1,2-diol, octane-1,3-diol, octane- 1,4-diol, octane- 1,5-diol, octane- 1,6-diol, octane- 1,7-diol, octane- 1,8 -diol, octane-2, 3-diol, octane-2, 4-diol, octane-2, 5-diol, octane-2, 6-diol, octane-2, 7-diol, octane-3, 4-diol, octane-3, 5-diol, octane-3, 6-diol and octane-4, 5-diol, nonane-1,9 diol, decane- 1,2-diol, decane- 1, 10-diol, hexadecan- l-ol, and dodecane- 1, 12-diol.

[0031] In another non-limiting embodiment, the diols have a length of from 3 to 12 carbon atoms, including but not limited to, pentane- 1,2-diol, hexane- 1,2-diol, and octane- 1,2-diol.

[0032] In another non-limiting embodiment, the organic acids or fatty acids or their salts or esters useful herein can be selected from acids having a carbon chain length of from 2 to 25 atoms. The carboxylic acids or fatty acids can be selected from the group including, but not limited to, propionic acid, acetic acid, benzoic acid, malonic acid, succinic acid, fumaric acid, maleic acid, adipic acid, lactic acid, stearic acid, levulinic acid, anisic acid, cinnamic acid, sorbic acid or tartaric acid, malic acid, gluconic acid, citric acid, caproic acid, perillic acid, phytic acid, salicylic acid, undecylenic acid, and the other acids include ascorbic acid, caprylhydroxamic acid, and sorbohydroxamic acid. These acids recited further enhance antibacterial activity while not negatively affecting the quality of the end-user products in terms of their taste, texture, color and odor in which they are applied or engaged.

[0033] In another non-limiting embodiment, the organic acids or fatty acids or their salts or esters can be selected from carboxylic acids having from 2 to 25 carbon atoms, including but not limited to, citric acid, stearic acid, benzoic acid, anisic acid, cinnamic acid, phytic acid, sorbic acid, levulinic acid and other acids include caprylhydroxamic acid.

[0034] In another non-limiting embodiment, the glycerin ethers useful herein include, but are not limited to, ethylhexylglycerin, butylglycerin, pentylglycerin, hexylglycerin, heptylglycerin, octylglycerin and cyclohexylglycerin.Docket No.: SCH-2024P00617PCT

[0035] In another non-limiting embodiment, the glyceryl esters are selected from the group consisting of glyceryl esters of a C8 to C12 carboxylic acid, glyceryl monostearate.

[0036] In still another non-limiting embodiment, the caprylates useful herein include, but are not limited to, glyceryl mono-di caprylate, propylene mono-di caprylate, glyceryl caprylate, sorbitan caprylate, glyceryl undecylenate and glyceryl caprylate / caprate, isosorbide caprylate / caprate and stearyl caprylate.

[0037] Yet another non-limiting embodiment employ aldehydes, including but not limited to, cinnamaldehyde, salicylaldehyde, veratraldehyde, benzaldehyde, butyraldehyde, propionaldehyde, acetaldehyde, vanillin and pyruvaldehyde.

[0038] In still another non -limiting embodiment, the conventional antimicrobial compounds are mixed with ethyl maltol are selected from the group consisting of phenoxyethanol, hydroxy acetophenone, phenoxy propanol, benzyl alcohol, alkyl parabens, bronopol, formaldehyde, diazolidinyl urea, imidazolidinyl urea, sodium hydroxymethyl glycinate, TMAD, DMDMH, silver, chlorphenesin, nisin, natamycin, triclosan, 2-methyl-4-isothiazolin-3-one (MIT), l,2-benzisothiazolin-3-one (BIT), 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT), 2-octyl-4-isothiazolin-3-one (OIT), 3-iodo-2-propynylbutyl-carbamate (IPBC), 3-iodopropynyl-N-phenyl carbamate (IPPC), zinc pyrithione (ZnPy), quaternary ammonium compounds, hydantoins, sodium pyrithione, phenyl ethanol, phenyl propanol and benzalkonium quaternary ammonium compounds.

[0039] The terpenes and terpenoids useful herein for the purposes of the present application include, but are not limited to, citral, pinene, nerol, b-ionone, geraniol, carvacrol, eugenol, carvone, terpeniol, anethole, camphor, menthol, limonene, nerolidol, farnesol, phytol, carotene, squalene, thymol, tocotrienol, perillyl alcohol, borneol, myrcene, simene, carene, terpenene, tropolone, hinokitiol and linalool.

[0040] The essential oils useful herein include, but are not limited to, anise oil, lemon oil, orange oil, oregano, rosemary oil, wintergreen oil, thyme oil, lavender oil, clove oil, hops, tea tree oil, citronella oil, wheat oil, barley oil, lemongrass oil, cedar leaf oil, cedar wood oil, cinnamon oil, fleagrass oil, geranium oil, sandalwood oil, violet oil, cranberry oil, eucalyptus oil, vervain oil, peppermint oil, gum benzoin, basil oil, fennel oil, fir oil, balsam oil, menthol, ocmea origanum oil, Hydrastis canadensis oil, berberidaceae daceae oil, ratanhia oil, curcuma longa oil, sesame oil, macadamia nut oil, evening primrose oil, Spanish sage oil, Spanish rosemary oil, coriander oil, thyme oil, pimento berries oil, rose oil, bergamot oil, rosewood oil,Docket No.: SCH-2024P00617PCTchamomile oil, sage oil, clary sage oil, cypress oil, sea fennel oil, frankincense oil, ginger oil, grapefruit oil, jasmine oil, juniper oil, lime oil, mandarin oil, marjoram oil, myrrh oil, neroli oil, patchouli oil, pepper oil, black pepper oil, petitgrain oil, pine oil, rose otto oil, spearmint oil, spikenard oil, bitter almond oil, palmarosa oil and vetiver oil.

[0041] As used herein, the conventional preservative compounds for the purposes of the present application are selected from the group including, but not limited to, benzoic acid and its sodium salt such as benzoic acid, sodium benzoate; salts of benzoic acid such as ammonium benzoate, butyl benzoate, calcium benzoate, ethyl benzoate, isobutyl benzoate, isopropyl benzoate, magnesium benzoate, MEA-benzoate, methyl benzoate, phenyl benzoate, potassium benzoate, propyl benzoate; propanoic acid and its salts such as propionic acid, ammonium propionate, calcium propionate, magnesium propionate, potassium propionate, sodium propionate; salicylic acid and its salts such as salicylic acid, calcium salicylate, magnesium salicylate, MEA-salicylate, sodium salicylate, potassium salicylate, TEA-salicylate; hexa-2,4-dienoic acid and its salts such as sorbic acid, calcium sorbate, sodium sorbate, potassium sorbate; biphenyl-2-ol as o-phenylphenol; inorganic sulphites and hydrogen sulphites such as sodium sulfite, ammonium bisulfite, ammonium sulfite, potassium sulfite, potassium hydrogen sulfite, sodium bisulfite, sodium meta bisulfite, potassium meta bisulfite; chlorobutanol; 4-hydroxybenzoic acid and its salts and esters other than the esters of isopropyl, isobutyl, phenyl, benzyl and pentyl such as 4-hydroxybenzoic acid, methylparaben, potassium ethylparaben, potassium paraben, sodium methylparaben, sodium ethylparaben, ethylparaben, sodium paraben, potassium methylparaben, calcium paraben; butyl 4-hydroxybenzoate and its salts and propyl 4-hydroxybenzoate and its salts such as butylparaben, propylparaben, sodium propoylparaben, sodium butylparaben, potassium butylparaben, potassium propylparaben; 3-acetyl-6-methylpyran-2,4(3H)- dione and its salts such as dehydroacetic acid, sodium dehydroacetate; formic acid, sodium formate; 3,3'-dibromo-4,4'-hexamethylene dioxydibenzamidine and its salts (including isethionate) such as dibromohexamidine isethionate; thimerosal; phenylmercuric salts such as phenyl mercuric acetate, phenyl mercuric benzoate; undec- 10-enoic acid and its salts such as undecylenic acid, potassium undecylenate, sodium undecylenate, calcium undecylenate, MEA-undecylenate, TEA-undecylenate; 5-pyrimidinamine l,3-bis(2-ethylhexyl)hexahydro-5-methyl- such as hexetidine; 5-bromo-5-nitro-l,3-dioxane; bronopol such as 2-bromo-2-nitropropane- 1,3 -diol; 2,4-dichlorobenzyl alcohol; l-(4-chlorophenyl)-3-(3,4-dichlorophenyl)urea such as triclocarban; chlorocresol such as p-chloro-m-cresol, 5-chloro-2-(2,4-dichlorophenoxy)phenol such as triclosan;Docket No.: SCH-2024P00617PCTchloroxylenol; N,N"-methylenebis[N'-[3-(hydro xymethyl)-2,5-dioxoimidazolidin-4-yl]urea] such as imidazolidinyl urea; polyhexamethylene biguanide hydrochloride such as polyaminopropyl biguanide; 2-phenoxy ethanol; methenamine;l-(4-chlorophenoxy)-l-(imidazo l-l-yl)-3,3-dimethylbutan-2-one such as climbazole; l,3-bis(hydroxymethyl)-5,5-dim ethylimidazolidine-2, 4-dione such as DMDM hydantoin; benzyl alcohol; l-hydroxy-4-methyl-6-(2,4,4-tri methylpentyl)-2 pyridon and its monoethanolamine salt such as 1 -hydroxy -4-methyl-6-(2,4,4-trimethylpentyl)-2pyridon, piroctone olamine; 2,2'-methylenebis(6-bromo- 4-chlorophenol) such as bromochlorophene; 4-isopropyl-m-cresol as o-cymen-5-ol; mixture of 5-chloro-2-methyl-isothiazol-3(2H)-one and 2-methylisothiazol-3(2H)-one with magnesium chloride and magnesium nitrate as methylchloroisothiazolinone and methylisothiazolinone; 2-chloroacetamide; N,N'-bis(4-chlorophenyl)-3,12-diimino-2,4,ll,13-tetraazatetradeca nediamidine and its digluconate, diacetate and dihydrochloride such as chlorhexidine, chi orhexi dine diacetate, chlorhexidine di gluconate, chlorhexidine dihydrochloride; 1-phenoxypropan-2-ol such as phenoxyisopropanol; alkyl (C12-C22) trimethyl ammonium bromide and chloride such as behentrimonium chloride, cetrimonium bromide, cetrimonium chloride, laurtrimonium bromide, laurtrimonium chloride, steartrimonium bromide, steartrimonium chloride; 4,4-dimethyl-l,3-oxazolidine; N-(hydroxymethyl)-N-(dihydroxymethyl-l,3-dioxo-2,5-imidazolidinyl-4)-N'-(hydroxymethyl)urea such as diazolidinyl urea; benzenecarboximidamide 4,4'-(l,6-hexanediylbis(oxy))bis- and its salts (including isothionate and p-hydroxybenzoate) such as hexamidine, hexamidine diisethionate, hexamidine diparaben, hexamidine paraben; glutaraldehyde (pentane-1, 5-dial) such as glutaral; 5-ethyl-3,7-dioxa-l-azabicyclo[3.3.0] octane such as 7-ethylbicyclooxazolidine; 3-(p-chlorophenoxy)-propane-l, 2-diol such as chlorphenesin; sodium hydroxymethylamino acetate such as sodium hydroxymethylglycinate; silver chloride deposited on titanium dioxide; benzethonium chloride such as benzenemethanaminium,N,N-dimethyl-N-[2-[2-[4-(l, 1,3,3, -tetramethylbutyl)phenoxy]ethoxy]ethyl]-chloride; enzalkonium chloride, benzalkonium bromide, benzalkonium saccharinate; methanol, (phenylmethoxy) such as benzylhemiformal; 3-iodo-2-propynylbutylcarbamate; 2-methyl-2H-isothiazol-3-one; ethyl lauroyl arginate HC1; citric acid (and) silver citrate such as 1,2, 3 -propanetricarboxylic acid, 2-hydroxy-, monohydrate and 1,2, 3 -propanetricarboxylic acid, 2-hydroxy-silver(l+) salt, monohydrate; and 4-(3 -ethoxy -4-hydroxyphenyl)bu-tan-2-one.

[0042] According to the present application, other suitable antimicrobial agents useful herein include peptides, glucosides, enzymes, amino acids and their esters, sclerolide, sclareol,Docket No.: SCH-2024P00617PCTCamellia sinensis and other plant extracts that are capable of killing or inhibiting microorganism and others known to a person skilled in the pertinent art.

[0043] Furthermore, according to the present application, other non-limiting antimicrobial agents useful herein include one or more antimicrobial compounds selected from the group consisting of propane- 1 ,3-diol, pentane- 1 ,2-diol, hexane- 1 ,2-diol, octane-1, 2- diol, hexadecan-l-ol, citric acid, stearic acid, benzoic acid, anisic acid, cinnamic acid, phytic acid, caprylhydroxamic acid, hinokitiol, ethylhexylglycerin, hexyl glycerin, glyceryl caprylate / caprate, veratraldehyde, maltol, ethyl maltol, phenyl propanol, tetradecyl trimethyl ammonium bromide (TTAB), 3-iodo-2-propynylbutyl-carbamate (IPBC), sodium fluoride and combinations thereof.

[0044] In some embodiments, the suitable range of ethyl maltol of the present application can be varied from about 0.001 wt.% to about 0.01 wt.%; or 0.01 wt.% to about 0.1 wt.%; or from 0.1 wt.% to about 1 wt.%; or from about 1 wt.% to about 2.5 wt.%; or from about 2.5 wt.% to about 5 wt.%; or from about 5 wt.% to about 10 wt.%; or 10 wt.% to about 15 wt.%; or from about 15 wt.% to about 20 wt.%; or from about 20 wt.% to about 25 wt.%; or from about 25 wt.% to about 30 wt.%; or from about 30 wt.% to about 35 wt.%; or from about 35 wt.% to about 40 wt.%; or from about 40 wt.% to about 45 wt.%; or from about 45 wt.% to about 50 wt.%; or from about 50 wt.% to about 55 wt.%; or from about 55 wt.% to about 60 wt.%; or from about 60 wt.% to about 65 wt.%; or from about 65 wt.% to about 70 wt.%; or from about 70 wt.% to about 75wt.%; or from about 75 wt.% to about 80 wt.%; or from about 80 wt.% to about 85 wt.%; or from about 85 wt.% to about 90 wt.%; or from about 90 wt.% to about 95 wt.%; or from about 95 wt.% to about 99.9 wt.% based on the total weight of the antimicrobial composition.

[0045] In some embodiments, the suitable range of one or more antimicrobial compounds not being compounds ethyl maltol of the present application can be varied from about 0.001 wt.% to about 0.01 wt.%; or 0.01 wt.% to about 0.1 wt.%; or from 0.1 wt.% to about 1 wt.%; or from about 1 wt.% to about 2.5 wt.%; or from about 2.5 wt.% to about 5 wt.%; or from about 5 wt.% to about 10 wt.%; or 10 wt.% to about 15 wt.%; or from about 15 wt.% to about 20 wt.%; or from about 20 wt.% to about 25 wt.%; or from about 25 wt.% to about 30 wt.%; or from about 30 wt.% to about 35 wt.%; or from about 35 wt.% to about 40 wt.%; or from about 40 wt.% to about 45 wt.%; or from about 45 wt.% to about 50 wt.%; or from about 50 wt.% to about 55 wt.%; or from about 55 wt.% to about 60 wt.%; or from about 60 wt.% to about 65 wt.%; or from about 65 wt.% to about 70 wt.%; or from about 70 wt.% to about 75wt.%; orDocket No.: SCH-2024P00617PCTfrom about 75 wt.% to about 80 wt.%; or from about 80 wt.% to about 85 wt.%; or from about 85 wt.% to about 90 wt.%; or from about 90 wt.% to about 95 wt.% based on the total weight of the antimicrobial composition.

[0046] In some embodiments, the suitable range of mixtures can contain components (a) ethyl maltol; and (b) one or more antimicrobial compounds are in a weight ratio of about 0.1:99.9 to about 99.9:0.1.

[0047] The antimicrobial composition of the present application is useful for inhibiting or killing Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecalis, Haemophilus influenzae, Moraxella species, salmonella species, Campylobacter species, Pseudomonas aeruginosa, Clostridium botulinum, Clostridium perfringens, Corynebacteria species, Diplococci species, Mycobacteria species, Streptomyces species, Escherichia coli, Salmonella typhimurium, Salmonella enteritidis, Vibrio parahaemolyticus, Bacillus anthracis, Bacillus azotoformans, Bacillus cereus, Bacillus coagulans, Bacillus israelensis, Bacillus larvae, Bacillus mycoides, Bacillus polymyxa, Bacillus pumilis, Bacillus stearothormophillus, Bacillus subtilis, Bacillus thuringiensis, Bacillus validus, Bacillus weihenstephanensis, Bacillus pseudomycoides, Burkholderia cepacia, Burkholderia multivorans, Burkholderia cenocepacia, Burkholderia vietnamiensis, Burkholderia stabilis, Burkholderia ambifaria, Burkholderia dolosa, Burkholderia anthina, Burkholderia pyrrocinia, Candida tropicalis, Candida albicans, Hansenula anomala, Saccharomyces cerevisiae, Torulaspora delbreuckii, Zygosaccharomyces bailii, Zygosaccharomyces rouxii, Aspergillus niger, Aspergillus jlavus, Aspergillus brasiliensis, Penicillium islandicum, Penicillium citrinum, Penicillium chrysogenum, Fusarium oxysporum, Fusarium graminearum, Fusarium solani, Alternaria alternata, and / or Mucor racemosus.

[0048] According to a non-limiting embodiment of the present application, the antimicrobial composition is used for killing or inhibiting the growth of Staphylococcus aureus, Escherichia coli, Candida albicans, Pseudomonas aeruginosa, and Aspergillus brasiliensis.

[0049] A different embodiment of the present application contemplates that the antimicrobial composition of the present application can be formulated as an emulsion, microemulsion, nanoemulsion, solution, dispersion, suspension, complex coacervate, or concentrate. The antimicrobial compositions may also include various optional additives. Examples of specific additives include, but are not limited to, colorants, pigments, plasticizers, surfactants, wetting agents, fillers, coloring agents, dispersing agents, thickening agents, rheology modifyingDocket No.: SCH-2024P00617PCTagents, thixotropic agents, anti-freezing agents, co-solvents, pH modifying agents, ultraviolet light stabilizers, antioxidants, algaecides, antimicrobial agents, fragrances, buffers, hydrotropes, anti-soil agents, enzymes, suspending agents, emulsifying agent, anti-foaming agents, organic solvents, VOC-free solvents, solubilizers, and / or water-miscible solvents.

[0050] According to another non-limiting embodiment of the present application, the antimicrobial composition can provide a synergistic effect in various aqueous and non-aqueous based end-user applications, and wherein the synergistic index (SI) value is less than or equal to 1.

[0051] Another non-limiting embodiment of the present application discloses that the antimicrobial composition can advantageously be used in personal care compositions, and wherein, the compositions can be an aqueous or non-aqueous based end-user composition. Aqueous and non-aqueous based end-user applications include, but are not limited to, personal care or cosmetic products, toiletry products, oral care products, skin care products, hair care products, household & cleaning products, soap and bath products, industrial and institutional cleaning products, disinfecting products, wound care products, sanitary products, agricultural compositions, textile products, coating products and laundry products.

[0052] A personal care composition is a composition generally used for hygiene, grooming, and beauty purposes. Some non-limiting examples of personal care compositions are skincare, haircare, oral care, and hygiene compositions. According to another non-limiting embodiment of the present application, the personal care compositions include, but are not limited to, sun care compositions, after-sun compositions, hair care compositions, conditioning compositions, skin care compositions, oral care compositions, face care compositions, lip care compositions, body care compositions, nail care compositions, anti-aging compositions, deodorant compositions, color cosmetic compositions, color-protection compositions, self-tanning compositions, and foot care compositions.

[0053] In other non-limiting embodiments, the present application discloses that suitable ranges of incorporating the above-described antimicrobial composition for killing or inhibiting the growth of bacteria and fungi in aqueous or non-aqueous based end-user products can be varied from about 0.01 wt.% to about 0.1 wt.%, or from about 0.1 wt.% to about 1 wt.%, or from about 1 wt.% to about 2.5 wt.%, or from about 2.5 wt.% to about 5 wt.% or from about 5 wt.% to about 7.5 wt.%, or from about 7.5 wt.% to about 10 wt.% based on the total weight of the aqueous or non-aqueous personal care composition.Docket No.: SCH-2024P00617PCT

[0054] Another embodiment of the present application provides an antimicrobial composition comprising: (a) ethyl maltol; and (b) one or more antimicrobial compound.

[0055] In a non-limiting embodiment, the present application discloses an antimicrobial composition comprising process for preparing synergistic antimicrobial composition, wherein the process comprising the steps of mixing: (a) about 0.01 to about 99.9 wt.% of ethyl maltol; and (b) about 0.1 to about 95 wt.% of one or more antimicrobial compounds.

[0056] Yet another embodiment of the present application discloses a method of killing or inhibiting the growth of bacteria and fungi in aqueous or non-aqueous based end-user products selected from the group consisting of personal care or cosmetic products, toiletry products, oral care products, skin care products, hair care products, household & cleaning products, soap and bath products, industrial and institutional cleaning products, disinfecting products, wound care products, sanitary products, agricultural compositions, textile products, coating products and laundry products that are susceptible to growth of microorganisms comprising incorporating about 0.01 wt. % to 5.0 wt. % of the above-described antimicrobial composition into the desired products.

[0057] Further, certain aspects of the present application are illustrated in detail by way of the following examples. The examples are given herein for illustration of the application and are not intended to be limiting thereof.EXAMPLES

[0058] Examples: quantitative germ count reduction test (qGCR)

[0059] Examples 1-8 (Tables 1 to 8) demonstrate activities and synergies of antimicrobials and combinations of antimicrobials in frame formulations versus five common microbial contaminants: Staphylococcus aureus ATCC 6538, Escherichia coli ATCC11229, Pseudomonas aeruginosa ATCC 15442, Candida albicans ATCC 10231, and Aspergillus brasiliensis ATCC 16404.

[0060] Each antimicrobial and combinations of antimicrobials was formulated into an appropriate frame formulation, which was then distributed into 25g sample containers each. Contaminant suspensions were prepared from 2nd subcultures using Tryptone Sob Broth (TSB) for bacteria at cell counts of 1.5-5x10A8 cfu / ml (colony-forming units per milliliter) . For Fungi, 2nd subcultures were grown on Saboroud-Dextrose Agar (SDA). SDA-plates were rinsed with 0.85% NaCl-solution, filtered through gauze compresses to remove mycelial fragments and finally adjusted to 1.5-5xl0A7 cfu / ml.Docket No.: SCH-2024P00617PCT

[0061] Each sample is inoculated with 0.1ml of contaminant suspension and thoroughly mixed. At specific time points each sample is mixed and then diluted 1:10 with neutralization broth (Tryptone-NaCl + TLSH, which is a mixture of Polysorbate 80, Lecithine, Saponine and Histidine). For this, 1g of each sample is weighed into a new test tube and 9g of of Tryptone-NaCl+TLSH is added. After homogenization, the sample is left neutralized for 5-10 minutes and subsequently the germ count is determined by using the surface or pour plate method or with the help of a spiral plater. With the surface or pour plate method, 0.5 ml of two to three dilution levels are plated on / in TSA (Tryptic Soy Agar) or SDA (Soybean Casein Digest Agar), so that for bacteria and yeast 14-330 CFU are expected and for mould 14-165 CFU are expected.

[0062] By using the spiral plater, an adequate dilution level of the germ suspension is chosen and a logarithmic program with several dilution levels on the plate is used. The aim is to achieve a countable range of CFU with a plate reader. Finally, TSA plates are incubated for 24-48h at 36 ±1°C, SDA plates with brasiliensis are incubated for 48-72h at 25±1°C and SDA plates with C. albicans are incubated for 48h at 30±l°C.

[0063] Assessment of Results: After the incubation time the colonies are counted either manually or with a plate reader. The countable range for bacteria and yeast is between 14-330 CFU and for mould between 14-165 CFU. If the colony count is under the threshold, “<14” should be noted and used for calculation. When the colony count is above the threshold, “>330” or “>165” should be noted and used for calculation. The determined germ count on each plate is then calculated back to the origin sample.

[0064] Calculation of synergism index (SI) was based on Kull's equation:SI = C*D / A + C*E / BSI is the Synergy Index according to KullA is the cfu / ml of substance A;B is the cfu / ml of substance B (ethyl maltol);C is the cfu / ml of mixture fo substances A and B;D is the proportion of the substance A in the mixture; andE is the proportion of substance B (ethyl maltol) in the mixture

[0065] The synergistic effect is indicated if the Synergy Index is below one (SI<1). An additive effect is indicated if the Synergy Index is equal to one (SI=1). An antagonistic effect is indicated if synergy index is greater than one (SI> 1 ). The lower the SI index the greater the synergy.Docket No.: SCH-2024P00617PCT

[0066] Example 1: The synergistic activity of phenoxyethanol and ethyl maltol against the microorganism^. brasiliensis was determined. The results are shown in Table 1.Table 1: Synergistic activity of phenoxyethanol and ethyl maltolA. brasiliensis - 14d SI1g (red. factor)germ count [cfu / ml] (Kull's equation) face cream - pH 5.8 60000 - - 0.8% Phenoxyethanol A 40000 0.2 - 0.2% Ethyl maltol B 120000 0.0 - 0.7% PhenoxyethanolC <100 2.8 0.0023+ 0.1 Ethyl maltolparts Phenoxyethanol in the mix D 0.88parts Ethyl maltol in the mix E 0.13

[0067] The Synergy Index SI for the combination of phenoxyethanol and ethyl maltol against A. brasiliensis, calculated according to Kull’s equation, is 0.0023 indicating a very strong synergism between these two compounds. Furthermore, the logarithm of reduction factor by the combination is significantly exceeding the combined reduction by single antimicrobials.

[0068] Example 2: The synergistic activity of 3 -phenylpropanol and ethyl maltol against the microorganism^, brasiliensis was determined. The results are shown in Table 2.Table 2: Synergistic activity of 3-phenylpropanol and ethyl maltolA. brasiliensis - 14d SI1g (red. factor)germ count [cfu / ml] (Kull's equation) shampoo - pH 6.0 240000 - - 1.3% 3-Phenylpropanol A 82000 0.5 - 0.3% Ethyl maltol B 280000 0.0 - 1.0% 3-PhenylpropanolC 4000 1.8 0.0443+ 0.15% Ethyl maltolparts 3-Phenylpropanol in the mix D 0.87parts Ethyl maltol in the mix E 0.13

[0069] The Synergy Index SI for the combination of 3-phenylpropanol and ethyl maltol against brasiliensis, calculated according to Kull’s equation, is 0.0443, indicating a very strong synergism between these two compounds. Furthermore, the logarithm of reduction factor by the combination is significantly exceeding the combined reduction by single antimicrobials.

[0070] Example 3: The synergistic activity of 1,2-hexanediol and ethyl maltol against the microorganism P. aeruginosa was determined. The results are shown in Table 3.Table 3: Synergistic activity of 1,2-hexanediol and ethyl maltolDocket No.: SCH-2024P00617PCTP. aeruginosa - 14d SI1g (red. factor)germ count [cfu / ml] (Kull's equation) shampoo - pH 6.0 21800000 - - 1.0% 1 ,2 -Hexanediol A 18700000 0.1 - 0.2% Ethyl maltol B 28200000 0.0 - 0.8% 1 ,2 -Hexanediol C 209 5.0 0.0000+ 0.1% Ethyl maltolparts 1 ,2 -Hexanediol in the mix D 0.89parts Ethyl maltol in the mix E 0.11

[0071] The Synergy Index SI for the combination of 1,2-hexanediol and ethyl maltol against P. aeruginosa, calculated according to Kull’s equation, is <0.0001 indicating a very strong synergism between these two compounds. Furthermore, the logarithm of reduction factor by the combination is significantly exceeding the combined reduction by single antimicrobials.

[0072] Example 4: The synergistic activity of pentylene glycol and ethyl maltol against the microorganism E. coli was determined. The results are shown in Table 4.Table 4: Synergistic activity of pentylene glycol and ethyl maltolE. coli - 7d SI1g (red. factor)germ count [cfu / ml] (Kull's equation) face cream - pH 5.8 267000 - - 2.2% Pentylene glycol A 129000 0.3 - 0.2% Ethyl maltol B 480000 0.0 - 2.1% Pentylene glycol C 100 3.4 0.0007+ 0.1% Ethyl maltolparts Pentylene glycol in the mix D 0.95parts Ethyl maltol in the mix E 0.05

[0073] The Synergy Index SI for the combination of pentylene glycol and ethyl maltol against E. coli, calculated according to Kull’s equation, is 0.0007 indicating a very strong synergism between these two compounds. Furthermore, the logarithm of reduction factor by the combination is significantly exceeding the combined reduction by single antimicrobials.

[0074] Example 5: The synergistic activity of 1,3 -propanediol and ethyl maltol against the microorganism E. coli wa determined. The results are shown in Table 5.Table 5: Synergistic activity of 1,3-propanediol and ethyl maltolE. coli - 14d SI1g (red. factor)germ count [cfu / ml] (Kull's equation) face cream - pH 5.8 95500 - - 2.4% 1,3-Propanediol A 457000 0.0 -Docket No.: SCH-2024P00617PCT0.1% Ethyl maltol B 15500 0.8 - 2.3% 1,3-Propanediol C 104 3.0 0.0004+ 0.05% Ethyl maltolparts 1,3-Propanediol in the mix D 0.98parts Ethyl maltol in the mix E 0.02

[0075] The Synergy Index SI for the combination of 1,3 -propanediol and ethyl maltol against E. coli, calculated according to Kull’s equation, is 0,0004, indicating a very strong synergism between these two compounds. Furthermore, the logarithm of reduction factor by the combination is significantly exceeding the combined reduction by single antimicrobials.

[0076] Example 6: The synergistic activity of 1,3 -propanediol and ethyl maltol against the microorganism C. albicans was determined. The results are shown in Table 6.Table 6: Synergistic activity of 1,3-propanediol and ethyl maltolC. albicans - 7d SI1g (red. factor)germ count fcfu / ml] (Kull's equation) shampoo - pEI 6.0 447000 - - 4.2% 1,3-Propanediol A 103000 0.6 - 0.3% Ethyl maltol B 114000 0.6 - 4.0% 1,3-Propanediol C <140 3.5 0.0014+ 0.15% Ethyl maltolparts 1,3-Propanediol in the mix D 0.96parts Ethyl maltol in the mix E 0.04

[0077] The Synergy Index SI for the combination of 1,3-propanediol and ethyl maltol against C. albicans, calculated according to Kull’s equation, is 0.0014 indicating a very strong synergism between these two compounds. Furthermore, the logarithm of reduction factor by the combination is significantly exceeding the combined reduction by single antimicrobials.

[0078] Example 7: The synergistic activity of 4-hydroxyacetophenone and ethyl maltol against the microorganism E. coli was determined. The results are shown in Table 7.Table 7: Synergistic activity of 4-hydroxyacetophenone and ethyl maltol E. coli - 14d SI1g (red. factor)germ count fcfu / ml] (Kull's equation) gel emulsion - pH 5.5 96600000 - - 0.2% 4-Hydroxyacetophenone A 203000 2.7 - 0.05% Ethyl maltol B 57000000 0.2 -Docket No.: SCH-2024P00617PCT0.1% 4-HydroxyacetophenoneC 5230 4.3 0.0172+ 0.05% Ethyl maltolparts 4-EIydroxyacetophenone inD 0.67the mixparts Ethyl maltol in the mix E 0.33

[0079] The Synergy Index SI for the combination of 4-hydroxyacetophenone and ethyl maltol against E. coli, calculated according to Kull’s equation, is 0.0004 indicating a very strong synergism between these two compounds. Furthermore, the logarithm of reduction factor by the combination is significantly exceeding the combined reduction by single antimicrobials.

[0080] Example 8: The synergistic activity of ethylhexylglycerin and ethyl maltol against the microorganism E. coli was determined. The results are shown in Table 8.Table 8: Synergistic activity of ethylhexylglycerin and ethyl maltolE. coli - 14d SI1g (red. factor)germ count [cfu / ml] (Kull's equation) gel emulsion - pEI 5.5 96600000 - - 0.7% Ethylhexylglycerin A 55000000 0.2 - 0.1% Ethyl maltol B 27000000 0.6 - 0.6% EthylhexylglycerinC <140 5.8 0.0000+ 0.1% Ethyl maltolparts Ethylhexylglycerin in theD 0.86mixparts Ethyl maltol in the mix E 0.14

[0081] The Synergy Index SI for the combination of ethylhexylglycerin and ethyl maltol against E. coli, calculated according to Kull’s equation, is <0.0001 indicating a very strong synergism between these two compounds. Furthermore, the logarithm of reduction factor by the combination is significantly exceeding the combined reduction by single antimicrobials.

[0082] Examples: Minimal Inhibitory Concentrations (MICs)

[0083] Examples 9-15 (Tables 9 to 15) demonstrate activities and synergies of antimicrobials and combinations of antimicrobials versus five common microbial contaminants: Staphylococcus aureus ATCC 6538, Escherichia coli k!2 NCTC 10538, Pseudomonas aeruginosa AT CC 15442, Candida albicans ATCC 10231, and Aspergillus brasiliensis ATCC 16404. Briefly, each active was dissolved at 1.25-fold of the highest tested concentration in either Tryptic Soy Broth (TSB) for bacterial testing or Malt Extract Broth (MEL) for fungalDocket No.: SCH-2024P00617PCTtesting. The product test solution was diluted geometrically (dilution factor = 0.5) in a deepwell plate. For each contaminant, 200 pl of the appropriate dilution was transferred to a microtiter plate. Contaminant suspensions were prepared with TSB for bacteria and MEL for fungi at cell counts of 1.5-5xl0A8 cfu / ml (bacteria) or 1.5-5xl0A7 cfu / ml (fungi). Bacterial suspensions are diluted 1:100 with TSB and then again 1:2. Fungal suspensions are diluted 1:10 with MEL and then again 1:2. Each well was supplied with 50pl of the corresponding contaminant suspension and carefully mixed by pipetting. Initial germ counts are determined in each experiment by plating out 0.5ml of 2 of the 3 suspensions on appropriate agar plates. Bacterial plates were incubated for 24-48 hours at 36±1 °C and fungal plates were incubated for 2-3 days at 30±l °C prior to being evaluated. The lowest concentration of each compound to inhibit any visible growth was defined as minimum inhibitory concentration (MIC). In some cases, the highest tested concentration of the active was limited by its solubility in water. Whenever MIC was greater than the highest tested concentration, it was reported as being equal to, or greater than (>) the previous hypothetical dilution.

[0084] The synergistic effect is indicated if the Synergy Index is below one (SI<1). An additive effect is indicated if the Synergy Index is equal to one (81=1). An antagonistic effect is indicated if synergy index is greater than one (SI> 1 ). The lower the SI index the greater the synergy. The synergistic effect is indicated if the Synergy Index of the present synergistic antimicrobial composition has a Synergy Index (SI) value of the total composition from about 0.0001 to about 0.90 and synergistic antimicrobial composition has an effect with a Combination Index (CI) value lower than 1.

[0085] The Minimal Inhibitory Concentration (MIC) of the combination A+B (in different ratios) was then compared to the MICs of the compound A and the B acting alone by calculating the Synergy Index (SI) using formula below.

[0086] Calculation of synergism index (SI) based on Kull's equation:SI = C*D / A + C*E / BSI is the Synergy Index according to KullA is the MIC value of substance A;B is the MIC value of substance B (ethyl maltol);C is the MIC value of the mixture of substances A and B;D is the proportion of the substance A in the mixture; andDocket No.: SCH-2024P00617PCTE is the proportion of substance B in the mixture

[0087] Each ratio C*D / A and C*E / B is sometimes referred to as Fractional Inhibitory Concentrations (FICs) of compounds A and B, respectively, when these two compounds are being used in combination with one another. The sum of FICs constitute the Synergy Index (SI).

[0088] The synergistic effect is indicated if the Synergy Index is below one (SI<1). An additive effect is indicated if the Synergy Index is equal to one (SI=1). An antagonistic effect is indicated if synergy index is greater than one (SI> 1 ). The lower the SI index the greater the synergy.

[0089] Example 9: Synergy index SI of mixtures of Phenoxyethanol and Ethyl maltolTable 9: Synergy index SI of mixtures of Phenoxyethanol and Ethyl maltol against . aureus parts in the mixIngredients MIC (S. aureus) SI D (PE) E (EtMal) Phenoxyethanol (PE) A 1.28%Ethyl maltol (EtMal) B 1.28%Phenoxyethanol / Ethyl maltol 2: 1 C 0.64% 0.67 0.33 0.5 Phenoxyethanol / Ethyl maltol 4: 1 C 0.64% 0.80 0.20 0.5Phenoxyethanol / Ethyl maltol 12: 1 C 0.64% 0.92 0.08 0.5

[0090] Example 10: Synergy index SI of mixtures of 3 -Phenylpropanol and Ethyl maltol Table 10: Synergy index SI of mixtures of 3-Phenylpropanol and Ethyl maltol against S. aureusparts in the mixIngredients MIC (S. aureus) SI D (HAP) E (EtMal)3-Phenylpropanol (3PP) A 0.32%Ethyl maltol (EtMal) B 0.64%3-Phenylpropanol / Ethyl maltolC 0.32% 0.67 0.33 0.832:1

[0091] Example 11: Synergy index SI of mixtures of 1,2-Hexanediol and Ethyl maltol Table 11: Synergy index SI of mixtures of 1,2-Hexanediol and Ethyl maltol against E. coliparts in the mixIngredients MIC (E. coli) SID (HD) E (EtMal)1 ,2-Hexanediol (HD) A 1.28%Ethyl maltol (EtMal) B 0.64%1 ,2-Hexanediol / Ethyl maltol 5: 1 C 0.64% 0.83 0.17 0.58Docket No.: SCH-2024P00617PCT1,2-Hexanediol / Ethyl maltol 8:1 | C | 0.64% | 0.89 | 0.11 | 0.56

[0092] Example 12: Synergy index SI of mixtures of Pentylene glycol and Ethyl maltol Table 12: Synergy index SI of mixtures of Pentylene glycol and Ethyl maltol against P. aeruginosa MIC (S. parts in the mix SI Ingredients aureus)D (HAP) E (EtMal)Pentylene glycol (PE) A 0.0256Ethyl maltol (EtMal) B 0.0032Pentylene glycol / Ethyl maltol 10:1 C 0.0128 0.9090909 0.0909091 0.8181818 Pentylene glycol / Ethyl maltol 20: 1 C 0.0128 0.952381 0.047619 0.6666667

[0093] Example 13: Synergy index SI of mixtures of 1,3 -Propanediol and Ethyl maltol Table 13a: Synergy index SI of mixtures of 1,3-Pi"opanediol and Ethyl maltol against E. coliparts in the mixIngredients MIC (E. coli) SID (PDO) E (EtMal)1,3-Propanediol (PDO) A 5.12%Ethyl maltol (EtMal) B 0.64%1 ,3-Propanediol / Ethyl maltol 8: 1 C 2.56% 0.8888889 0.1111111 0.8888889Table 13b: Synergy index SI of mixtures of 1,3-Pi"opanediol and Ethyl maltol against P. aeruginosaMIC (P. parts in the mixSIIngredients aeruginosa)D (PDO) E (EtMal)1,3-Propanediol (PDO) A 5.12%Ethyl maltol (EtMal) B 0.32%1 ,3-Propanediol / Ethyl maltol 5 : 1 C 1.28% 0.8333333 0.1666667 0.8751 ,3-Propanediol / Ethyl maltol 20: 1 C 2.56% 0.952381 0.047619 0.8571429

[0094] Example 14: Synergy index SI of mixtures of 4-Hydroxy acetophenone and Ethyl maltolTable 14: Synergy index SI of mixtures of 4-Hydroxyacetophenone and Ethyl maltol against S. aureusMIC (S. parts in the mix Ingredients SI aureus) D (HAP) E (EtMal) 1.28% - - -4-Hydroxyacetophenone (HAP) ADocket No.: SCH-2024P00617PCTEthyl maltol (EtMal) B 1.28%4-EIydroxy acetophenone / Ethyl maltol 1 : 1 C 0.64% 0.50 0.50 0.50 4-EIydroxy acetophenone / Ethyl maltol 2: 1 C 0.64% 0.67 0.33 0.504-EIydroxy acetophenone / Ethyl maltol 3: 1 C 0.64% 0.75 0.25 0.50

[0095] Example 15: Synergy index SI of mixtures of Glyceryl caprylate and Ethyl maltol Table 15a: Synergy index SI of mixtures of Glyceryl caprylate and Ethyl maltol against _ _ P. aeruginosa _ _MIC (P. parts in the mixIngredients SI aeruginosa) D (GC) E (EtMal)Glyceryl caprylate (GC) A 1.20%Ethyl maltol (EtMal) B 0.60%Glyeryl caprylate / Ethyl maltol 1 : 1 C 0.60% 0.50 0.50 0.75Glyeryl caprylate / Ethyl maltol 4: 1 C 0.80% 0.80 0.20 0.80Table 15b: Synergy index SI of mixtures of Glyceryl caprylate and Ethyl maltol against (5. _ _ _ aureus) _ _parts in the mixIngredients MIC (S. aureus) SID (GC) E (EtMal)Glyceryl caprylate (GC) A 1.20%Ethyl maltol (EtMal) B 0.40%Glyeryl caprylate / Ethyl maltol 4: 1 C 0.60% 0.80 0.20 0.70Glyeryl caprylate / Ethyl maltol 10: 1 C 0.80% 0.91 0.09 0.79

[0096] Examples: cosmetic challenge tests (CosPET - Cosmetic Preservation Efficacy Test)

[0097] Examples 16 to 20 (Tables 16-20) demonstrate the preservative efficacy of antimicrobial substances and combinations in cosmetic formulations. Each formulation with its respective preservative system is inoculated with a mixed inoculum of either bacteria or fungi and the microbial load is monitored semi-quantitatively over a span of 28 days.

[0098] The bacterial mixed inoculum consists of 8 different bacterial strains, namely: Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Pluralibacter gergoviae ATCC 33028, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas paraeruginosa ATCC 9027, Pseudomonas putida ATCC 12633 and Burkholderia cepacia ATCC 25416. For the preparation of the mixed suspension 2nd subcultures of each bacterial strain is used. The fungal mixed inoculum contains Candida albicans ATCC 10231, and Aspergillus brasiliensis ATCC 16404.Docket No.: SCH-2024P00617PCT

[0099] For each test, two sample containers, each with 25g sample, are prepared and inoculated with a fixed amount of either fungal or bacterial mixed suspension. Additionally, each sample is tested for contamination by streaking a small amount of sample on appropriate growth media plates. After thoroughly mixing each sample, each container is closed and incubated for 2 days, 7 days, 14 days and 28 days, (bacterial inoculum) or 14 days and 28 days (fungal inoculum). At each timepoint a small amount of sample is streaked on growth media plates (Trypton-Soy-Agar for bacteria; Saboraud-Dextrose-Agar for fungi). Additionally, growth plates contain chemical dis-inhibitors to allow for un-inhibited growth of remaining microorganisms. In the following, each plate is incubated assessed for growth of microorganisms.

[0100] Assessment of Results: After the appropriate incubation time each plate is assessed for growth of remaining microorganisms. Assessment is done semi-quantitatively by visually sorting the amount of growth in 6 categories ranging from “completely overgrown” to “no growth”.= free of growth (ca. <10E02 cfu / ml)+ = light growth (ca.10E02 cfu / ml)++ = moderate growth (ca. 10E03 cfu / ml)+++ = heavy growth (ca. 10E04 cfu / ml)++++ = massive growth (ca. 10E05 cfu / ml)C = completely overgrown (ca. 10E06 cfu / ml)

[0101] Following the full assessment at all timepoint, the observed growth is used to categorize each sample according to acceptance following acceptance criteria:Evaluation 2 days 7 days 14 days 28 daysA <+++ <++ NIBacteriaB <++ NIA n.d. n.d. <++ NIFungiB n.d. n.d. +++ NIn.d. not determinedNI no increase

[0102] Example 16: Preservative efficacy of phenoxyethanol alone and in combination with ethyl maltol in a face cream are shown in Table 16.Table 16: Challenge test results for phenoxyethanol with and without ethyl maltolDocket No.: SCH-2024P00617PCTbacteria fungiface cream sterility assess- (o / w) PH control 2d 7d 14d 28d assess1 assess ment ment 4d 28d ment unpreserved 5.8 - C C C C f C C f f + 0.9% phenoxyethnaol 5.8 - C +++ - - B C C f f + 0.9% phenoxyethanol5.8+ 0 - c ++ - - B +++ - B B.05% ethyl maltol

[0103] The combination of phenoxyethanol and ethyl maltol covers a broad range of microbes including bacteria and fungi. Phenoxyethanol alone only showed preservative activity against the bacterial mix but failed against the fungi mix. Addition of ethyl maltol, which alone doesn’t have activity at the used concentration ensured broad activity spectrum against both, mix of bacteria and mix of fungi, passing the cosmetic challenge test with a B-criteria.

[0104] Example 17: Preservative efficacy of benzyl alcohol alone and in combination with ethyl maltol in a shower gel are shown in Table 17.Table 17: Challenge test results for benzyl alcohol with and without ethyl maltol bacteria fungisterility assess- shower gel PH control 2d 7d 14d 28d assessassessme 14d 28d ment nt ment unpreserved 5.5 C C C C f C C f f - ++ ++++ + 1.0% benzyl alcochol 5.5 C B C f f - - - + 1.0% benzyl alcohol ++ 5.5 c B A B - - - - - + 0.2% ethyl maltol

[0105] The combination of benzyl alcohol and ethyl maltol covers a broad range of microbes including bacterial and fungal mix. Benzyl alcohol alone showed insufficient activity against fungi. Addition of ethyl maltol bacterial kill-rate and ensured that the preservative system is effective against both, bacterial and fungal mixes.

[0106] Example 18: Preservative efficacy of caprylyl glycol alone and in combination with ethyl maltol in a lotion is shown in Table 18.Table 18: Challenge test results for caprylyl glycol with and without ethyl maltol bacteria fungiLotion sterility assess- PH assessassess(o / w) control ment 2d 7d 14d 28d 14d 28d ment ment unpreserved 5.8 C C C C f C C f f - + 0.6% caprylyl glycol 5.8 A C f f - - + 0.6% caprylyl glycol + 5.8 A A A - - + 0.05% ethyl maltolDocket No.: SCH-2024P00617PCT

[0107] Caprylyl glycol is effective against bacteria in this formulation but ineffective versus fungi as shown, the kill rate against fungi did not pass the test. Addition of ethyl maltol, which alone doesn’t have activity at the used concentration, ensured quick kill rate also against the fungal mix to ensure sufficient preservative activity to pass the test with an A-criteria.Table 19: Challenge test results for caprylyl glycol with and without ethyl maltol bacteria fungiSulfate-free shampoo sterility assess- (o / w) PH control 2d 7d 14d 28d assessassessment 14d 28d ment ment unpreserved 6.7 - C C C C f C C f f + 1.0% caprylyl glycol 6.7 - C c C C f C C f f + 1.0% caprylyl glycol. % t y 6.7 - c ++ - - B +++ 02 e h l maltol - A A

[0108] Caprylyl glycol is not effective against bacteria or fungi. Addition of ethyl maltol, leads to passing the test with an A-criteria against fungi and B-criteria against bacteria.Table 20: Challenge test results for pentylene glycol with and without ethyl maltol bacteria fungiGel emulsion sterility assess- (o / w) PH control 2d 7d 14d 28d assessassessment 14d 28d ment ment Unpreserved 5.5 C C C C f C C f f - + 3.0% pentylene glycol 5.5 C F C C f f - - - - + 3.0% pentylene glycol ++ ++ 5.5 A A A - - - - - + 0.2% ethyl maltol

[0109] Pentylene glycol alone is not passing the test, however, addition of ethyl maltol leads to sufficient preservation with an A-criterium.

[0110] While the compositions and methods of the disclosed and / or claimed inventive concept(s) have been described in terms of particular aspects, it will be apparent to those of ordinary skill in the art that variations may be applied to the compositions and / or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the disclosed and / or claimed inventive concept(s). All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the disclosed and / or claimed inventive concept(s).

Claims

Docket No.: SCH-2024P00617PCTWe claim:

1. A synergistic antimicrobial composition comprising:(a) about 0.01 to about 99.9 wt.% of ethyl maltol; and(b) about 0.1 to about 95% wt.% of one or more antimicrobial compounds, wherein the wt.% is based on the total weight of (a) and (b).

2. The synergistic antimicrobial composition according to claim 1, wherein the antimicrobial compound selected from the group consisting of diols, organic acids, glycerin ethers, caprylates, glyceryl esters, aldehydes, terpenes, terpenoids, essential oils, peptides, glucosides, enzymes, amino acids and their esters, sclerolide, and sclareol;wherein(i) the diols are selected from the group consisting of propanediol, propylene glycol, butanediol, pentanediol, hexanediol, heptanediol, octanediol, nonanediol, decanediol and dodecanediol;(ii) the organic acids are selected from the group consisting of benzoic acid, sorbic acid, levulinic acid, anisic acid, cinnamic acid, perillic acid, phytic acid, salicylic acid, propionic acid, lactic acid, undecylenic acid, caprylhydroxamic acid and sorbohydroxamic acid;(iii) the glycerin ethers are selected from the group consisting of ethylhexylglycerin, hexyl glycerin, caprylyl glycerine ether, methylheptyl glycerin and cyclohexyl glycerin(iv) wherein the glyceryl esters are selected from the group consisting of glyceryl esters of a C8 to C12 carboxylic acid, glyceryl monostearate;(v) the caprylates are selected from the group consisting of glyceryl mono-di caprylate, propylene mono-di caprylate, glyceryl caprylate, sorbitan caprylate, and glyceryl caprylate;(vi) the aldehydes are selected from the group consisting of cinnamaldehyde, salicylaldehyde, veratraldehyde, vanillin and benzaldehyde; and(vii) the antimicrobial compounds are selected from the group consisting of phenoxyethanol, hydroxy acetophenone, phenoxy propanol, benzyl alcohol, alkyl parabens, bronopol, formaldehyde, diazolidinyl urea, imidazolidinyl urea, sodium hydroxymethyl glycinate, Tetramethylol-acetylen-dihamstoff (TM D), 1,3- dimethylol-5,5-dimethylhydantoin (DMDMH), silver, chlorphenesin, nisin,Docket No.: SCH-2024P00617PCTnatamycin, triclosan, 2-methyl-4-isothiazolin-3-one (MIT), l,2-benzisothiazolin-3- one (BIT), 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT), 2-octyl-4-isothiazolin- 3 -one (OIT), 3-iodo-2-propynylbutyl-carbamate (IPBC), 3-iodopropynyl-N-phenyl carbamate (IPPC), zinc pyrithione (ZnPy), quaternary ammonium compounds, hydantoins, sodium pyrithione, phenyl ethanol, phenyl propanol and benzalkonium quaternary ammonium compounds.

3. The synergistic antimicrobial composition according to claim 1, wherein the composition is used for killing or inhibiting the growth of Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecalis, Haemophilus influenzae, Moraxella species, salmonella species, Campylobacter species, Pseudomonas aeruginosa, Clostridium botulinum, Clostridium perfringens, Corynebacteria species, Diplococci species, Mycobacteria species, Streptomyces species, Escherichia coli, Salmonella typhimurium, Salmonella enteritidis, Vibrio parahaemolyticus, Bacillus anthracis, Bacillus azotoformans, Bacillus cereus, Bacillus coagulans, Bacillus israelensis, Bacillus larvae, Bacillus mycoides, Bacillus polymyxa, Bacillus pumilis, Bacillus stearothormophillus, Bacillus subtilis, Bacillus thuringiensis, Bacillus validus, Bacillus weihenstephanensis, Bacillus pseudomycoides, Burkholderia cepacia, Burkholderia multivorans, Burkholderia cenocepacia, Burkholderia vietnamiensis, Burkholderia stabilis, Burkholderia ambifaria, Burkholderia dolosa, Burkholderia anthina, Burkholderia pyrrocinia, Candida tropicalis, Candida albicans, Hansenula anomala, Saccharomyces cerevisiae, Torulaspora delbreuckii, Zygosaccharomyces bailii, Zygosaccharomyces rouxii, Aspergillus niger, Aspergillus flavus, Aspergillus brasiliensis, Penicillium islandicum, Penicillium citrinum, Penicillium chrysogenum, Fusarium oxysporum, Fusarium graminearum, Fusarium solani, Alternaria alternata and / or Mucor racemosus.

4. The synergistic antimicrobial composition according to claim 1, wherein the composition used for killing or inhibiting the growth of Staphylococcus aureus, Escherichia coli, Candida albicans, Pseudomonas aeruginosa and Aspergillus brasiliensis.

5. The synergistic antimicrobial composition according to claim 1,wherein(i) the composition is aqueous composition or non-aqueous composition;(ii) the composition is formulated as an emulsion, microemulsion, nanoemulsion, solution, dispersion, suspension, complex coacervate, or concentrate; andDocket No.: SCH-2024P00617PCT(iii) the composition is formulated into a spray, a lotion, a mousse, a fluid, a serum, a solution, a suspension, a perm, an emulsion, a gel, a mist, a vesicle, a dispersion, a paste, a cream, a solid stick, a shampoo, a balm, a wipe, a milk, a foam, a jelly and a liquid.

6. The synergistic antimicrobial composition according to claim 5, wherein the amount of the composition employed in an aqueous or non-aqueous based end-user composition is in the range of from about 0.01 wt. % to about 10.0 wt. % of the total composition.

7. The synergistic antimicrobial composition according to claim 1, wherein an aqueous and non-aqueous based end-user applications selected from the group consisting of personal care or cosmetic products, toiletry products, oral care products, skin care products, hair care products, household & cleaning products, soap and bath products, industrial and institutional cleaning products, disinfecting products, wound care products, sanitary products, agricultural compositions, textile products, coating products and laundry products;wherein the personal care or cosmetic composition includes sun care compositions, hair care compositions, conditioning compositions, skin care compositions, oral care compositions, face care compositions, lip care compositions, body care compositions, nail care compositions, anti-aging compositions, deodorant compositions, color cosmetic compositions, colorprotection compositions, self-tanning compositions and foot care compositions.

8. The synergistic antimicrobial composition according to claim 1, wherein the composition can provide synergistic effect having a synergistic index (SI) value is lower than 1.

9. The synergistic antimicrobial composition according to claim 1, wherein(i) the composition has a Synergy Index (SI) value of the total composition from about 0.0001 to about 0.90;(ii) the composition has an effect with a Combination Index (CI) value lower than 1; and(ii) the combination index is between about 0.0001 and about 0.90.

10. A process for preparing synergistic antimicrobial composition according to claim 1, wherein the process comprising the steps of mixing:(a) about 0.01 to about 99.9 wt.% of ethyl maltol; andDocket No.: SCH-2024P00617PCT(b) about 0.1 to about 95 wt.% of one or more antimicrobial compounds, wherein the wt.% is based on the total weight of (a) and (b).

11. A method of killing or inhibiting the growth of bacteria and fungi, in an aqueous or non-aqueous based products selected from the group consisting of personal care or cosmetic products, toiletry products, oral care products, skin care products, hair care products, cleaning products, soap and bath products, household products, industrial and institutional cleaning products, disinfecting products, wound care products, sanitary products, agricultural compositions, textile products, coating products and laundry products that are susceptible to growth of microorganisms comprising incorporating about 0.01 wt. % to 5.0 wt. % of the antimicrobial composition of claim 1 into the products.

12. A synergistic antimicrobial composition comprising:(a) about 0.001 to about 40 wt. % of ethyl maltol; and(b) about 0.1 to about 95 wt. % of one or more antimicrobial compounds, wherein the wt.% is based on the total weight of (a) and (b).

13. The synergistic antimicrobial composition according to claim 12 comprising:(a) about 0.001 to about 40 wt. % of ethyl maltol; and(b) about 0.1 to about 95 wt. % of one or more antimicrobial compounds selected from the group consisting of phenoxyethanol, 3-phenylpropanol,l,2-hexanediol, pentylene glycol (pentanediol), 1,3 -propanediol, benzyl alcohol, 4-hydroxyacetophenone, ethylhexylglycerin, glyceryl caprylate and combinations thereof;wherein,(i) the composition has a Synergy Index (SI) value of the total composition from about 0.0001 to about 1.0; and(ii) the Combination Index (CI) is between about 0.0001 and about 0.90.

14. The synergistic antimicrobial composition according to claim 13, wherein the composition used for killing or inhibiting the growth of Staphylococcus aureus, Escherichia coli, Candida albicans, Pseudomonas aeruginosa and Aspergillus brasiliensis.

15. The synergistic antimicrobial composition according to claim 13, wherein the amount of benzyl alcohol or phenoxyethanol is in the range of less than or equal to 0 1 % of the total composition.

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