Antibacterial systems having indole alkaloids and phenolic acids and compositions containing same

Abstract

Antimicrobial systems having naturally derived components and compositions containing them are described, the systems having a first component comprising an indole alkaloid and a second naturally derived component comprising a phenolic acid, and the systems and compositions provide superior antimicrobial benefits.

Description

[Technical field]

[0001] The present invention is directed to an antimicrobial system comprising naturally occurring ingredients. More particularly, the present invention relates to indole alkaloids and phenolic acids and / or their salts that constitute an antimicrobial system that can be included in end-use formulations, including cosmetic compositions, pharmaceutical compositions, home care compositions, and cleaning compositions. The ingredients of the antimicrobial system of the present invention are naturally found in fruits and plants, and unexpectedly provide superior synergistic antimicrobial benefits when added to such end-use compositions. End-use compositions comprising the antimicrobial system of the present invention can be formulated to be substantially free of parabens, formaldehyde donors, triclosan, and other conventional antimicrobial ingredients (e.g., sulfated and halogenated antimicrobial ingredients). [Background technology]

[0002] DMDM hydantoin, parabens, methylisothiazolinone and methylchloroisothiazolinone are commonly used preservatives (i.e., antimicrobial ingredients) found in consumer products. Such ingredients have been used for many years and are known to work effectively in maintaining the integrity and stability of certain end-use compositions. Nevertheless, it is desirable to develop antimicrobial systems that contain naturally derived ingredients suitable for performing well across all consumer products. The naturally derived microbial system should be effective in preserving the product, should not be skin sensitizing, and should not adversely affect the sensory properties of the consumer product, especially those that are topically applied.

[0003] In addition to providing excellent antimicrobial benefits, the system must not be harmful to the environment and must be gentle enough for use on the most vulnerable consumers: infants and young children.

[0004] There is an increasing interest in developing effective, non-skin sensitizing, and environmentally sustainable antimicrobial systems. Accordingly, the present invention is directed to antimicrobial systems having naturally derived components and compositions containing the same. The antimicrobial systems include indole alkaloids and phenolic acids and / or their salts. Such systems unexpectedly provide superior synergistic antimicrobial benefits to the end-use compositions in which they are used.

[0005] Additional Information Efforts to produce preservative systems have been disclosed. U.S. Published Patent Application No. 2012 / 0190744A1 describes a preservative system for cosmetic formulations.

[0006] Further efforts to produce a preservative system have been disclosed: US Patent No. 7,754,774 B2 describes a preservative disinfectant using 1,2-octanediol.

[0007] Further efforts to produce preservative systems have been disclosed: US Patent No. 7,582,681 B2 describes antimicrobially active compounds containing 1,2-alkanediols.

[0008] Further efforts to modulate inflammatory responses have been disclosed: in WO 2021 / 202982 A1 compositions are described that contain aqueous or solid fractions of mushroom mycelium and / or fruiting body mixtures for preventing one or more adverse responses caused by, for example, an infection or for ameliorating the symptoms of such adverse responses.

[0009] None of the above additional information describes the antimicrobial systems and end-use compositions containing such systems as described and claimed herein. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] US Patent Application Publication No. 2012 / 0190744A1 [Patent Document 2] U.S. Patent No. 7,754,774B2 [Patent Document 3] U.S. Patent No. 7,582,681B2 [Patent Document 4] International Application No. 2021 / 202982A1 Summary of the Invention

[0011] Summary of the Invention In a first aspect, the present invention provides a method for producing a composition comprising the steps of: (a) a first component comprising an indole alkaloid, an indole alkaloid salt, or both; and (b) a second component comprising a phenolic acid, a phenolate, or both; The present invention relates to antibacterial systems comprising:

[0012] In a second aspect, the present invention provides a method for producing a composition comprising the steps of: (a) a first component comprising an indole alkaloid, an indole alkaloid salt, or both; and (b) a second component comprising a phenolic acid, a phenolate, or both; The present invention is directed to an end-use composition comprising:

[0013] In a third aspect, the present invention is directed to a use or method for preserving a composition having an antimicrobial system with a first component comprising an indole alkaloid, an indole alkaloid salt, or both, and a second component comprising a phenolic acid, a phenolic acid salt, or both.

[0014] In a fourth aspect, the present invention is directed to a use or method for providing an antimicrobial benefit to a consumer by contacting the skin with a composition having a first component comprising an indole alkaloid, an indole alkaloid salt, or both, and a second component comprising a phenolic acid, a phenolic acid salt, or both.

[0015] In a fifth aspect, the present invention is directed to a use or method for providing an antimicrobial benefit to an object (e.g., a table surface) by contacting the object with a composition having a first component comprising an indole alkaloid, an indole alkaloid salt, or both, and a second component comprising a phenolic acid, a phenolic acid salt, or both.

[0016] All other aspects of the present invention will become more readily apparent from the ensuing description and examples.

[0017] "Antimicrobial system" as used herein means at least a two-component natural system suitable for exhibiting synergistic antimicrobial reduction, including antimicrobial benefits as seen with preservatives in the composition and when applied topically to a surface (e.g., skin, or home care surfaces, such as table surfaces). Antimicrobials surprisingly synergistically reduced by the system of the present invention include Enterobacter gergoviae ATCC 33028 or similar bacteria of the family Pluralibacter gergoviae, which is a gram-negative rod-shaped bacterium often resistant to parabens, and Aspergillus brasiliensis ATCC 16404, which is a fungus of the genus Aspergillus. "At least a two-component system" means that it contains at least one component that is an indole alkaloid and at least one component that is a phenolic acid (i.e., it can be sold as a separate additive composition for addition to an end-use composition, or it can be added separately with the components to produce the final desired end-use composition). "Naturally derived" means suitable for recovery (at least in one form) from fruits, plants and / or roots without the need for synthetic production. Naturally derived therefore includes any analogue / derivative of the component ready for use as extracted or isolated from a natural source. For example, in the case of phenolic acids, naturally derived includes components such as syringic acid naturally recovered from fruits such as sea buckthorn fruit and any ether or ester variants made therefrom. Salts as used herein in relation to phenolic acids are meant to have cations such as sodium, potassium, calcium, magnesium and / or ammonium.

[0018] "Skin" as used herein includes the skin of the feet, face, neck, chest, arms (including under the arms), hands, legs, buttocks, back and scalp (including hair). End-use compositions (i.e. compositions that can be used or applied immediately) described herein include creams, lotions, serums, gels, balms, deodorants and antiperspirants, oral care compositions, shampoos, conditioners, bar and liquid cleaning products, and home care compositions such as hard surface cleaners and window cleaners, toilet bowl cleaners and laundry detergents. In one embodiment, the end-use composition of the present invention is a cleaning composition, wash product or leave-on product, such as a cream or lotion applied to the face, body or hands. In another embodiment, the end-use composition is a cosmetic leave-on product suitable for cosmetically improving the attributes of the skin, such as reducing the appearance of wrinkles and / or moisturizing the skin. Such compositions can also be compositions that provide skin with an even color or tone, as well as compositions that provide a reduction in pigmentation spots caused by environmental factors, the aging process, or both.

[0019] Unless expressly indicated otherwise, all ranges described herein are intended to include all ranges subsumed therein. The term "comprise" is intended to encompass the terms "consisting essentially of" and "consisting of." For the avoidance of doubt, a composition comprising a preservative portion having syringic acid and gramine is intended to encompass compositions consisting essentially of syringic acid and gramine and compositions consisting of syringic acid and gramine. Percentages used herein are intended to be by weight unless otherwise indicated. Except in the Examples and Comparative Examples, or unless otherwise expressly indicated, all numbers used herein indicating amounts or proportions of ingredients and / or their use should be understood as modified by the word "about." As used herein, substantially free means less than 1.5% by weight or less than 0.35% by weight based on the total weight of the end-use composition. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] With regard to ingredients containing phenolic acids or their salts suitable for use in the present invention, there are no limitations as to how such ingredients are naturally sourced, except that their recovery is preferably accomplished in the most sustainable manner. Natural sources of ingredients containing phenolic acids are fruits including olives, dates, pumpkins and grapes, as well as spices, acai, honey and red wine. Phenolic acids can be recovered from such sources using art-recognized techniques, including extraction with solvents such as ethanol, methanol, ethyl acetate or ethyl ether, and even extraction with water since phenolic acids are sparingly soluble in water.

[0021] Exemplary phenolic acids suitable for use in the present invention are represented as follows:

[0022] Formula I [ka] Here, R 1 , R 2 and R 3 are each independently hydrogen or C1-C4 alkyl.

[0023] In one embodiment of the present invention, R 1 and R 3 is CH3 and R 2 is H and the acid is 4-hydroxy-3,5-dimethoxybenzoic acid, commonly referred to as syringic acid. 1 , R 2 and R 3 is H, and the acid is 3,4,5-trihydroxybenzoic acid, commonly referred to as gallic acid. 1 , R 2 and R 3 Each of is CH3, and the acid is 3,4,5-trimethoxybenzoic acid, commonly referred to as eudesmic acid. Mixtures of such acids are suitable for use as are the salts thereof. As for derivatives and analogs of the same, these can be prepared by subjecting the naturally occurring acids to art-recognized alkylation and dealkylation process steps.

[0024] There is no particular limit to how the indole alkaloid-containing components used in the present invention are naturally sourced, except that obtaining the same components is preferably accomplished in the most sustainable way. For example, solid phase extraction with water is often the desired technique for recovering such indoles from plants of the Lupinus genus. Indole alkaloids suitable for use in the present invention have also been found and recovered from plants of the grass family, such as Danchiku, Silver Maple, and the Hordeum and Phalaris genera. Another option is to use commercially available mixed-mode polymeric sorbents designed to achieve higher selectivity and sensitivity to extract such compounds with cation exchange groups. For indole alkaloid derivatives, one method used to prepare such derivatives is the Fisher-Indole type process.

[0025] Exemplary indole alkaloids suitable for use in the present invention are represented as follows:

[0026] Formula II [ka] Here, R 4 and R 5 are each independently H or a C1-C2 alkyl group, and R 6 and R 7 are each independently a C1-C2 alkyl group. In a preferred embodiment, R 4 and R 5 is hydrogen, and R 6 and R 7is CH3, and the indole alkaloid is 1-(1H-indol-3-yl)-N,N-dimethylmethanamine, commonly referred to as gramine. It is within the scope of the present invention to include salts of the indole alkaloids (i.e., quaternary ammonium salts or tertiary amine salts), particularly where the pH of the end use composition is between 5 and 7. With regard to ingredients used for suitable counter anions, these are limited only to the extent that they are compatible in end use compositions used by consumers, particularly end use compositions used topically on the skin. Illustrative non-limiting examples of counter anions suitable for use include halogens (e.g., Cl, - ), phosphate anion, sulfate anion, carbonate anion and organic carboxylate anion (e.g., YCOO - , where Y is C1-C 17 The hydrocarbons may be straight chain, branched chain, saturated, unsaturated or substituted.

[0027] The preferred weight ratio of indole alkaloids to phenolic acids is often 0.5:9 to 2:10, preferably 0.6:7 to 4:9, and most preferably 0.75:4 to 5:8 (including any salts thereof).

[0028] In one embodiment of the invention, from 8 to 75% by weight of the antimicrobial system is indole alkaloids, preferably from 10 to 65% by weight, and most preferably from 12 to 50% by weight, based on the total weight of indole alkaloids and phenolic acids (including their salts).

[0029] Typically, end use compositions made with the antimicrobial system of the present invention have a total weight of the antimicrobial system (i.e., indole alkaloids and phenolic acids) of 0.001-12% based on the total weight of the end use composition. In one embodiment of the invention, the composition has 0.01-10% by weight of the antimicrobial system, and in yet another embodiment, 0.1-8% by weight of the antimicrobial system, based on the total weight of the end use composition. In yet another embodiment, the end use composition has 1-6% by weight, or 1.25-6% by weight, or 1.5-5% by weight, or 2-4.5% by weight of the antimicrobial system, based on the total weight of the end use composition.

[0030] There are generally no limitations as to the type of end use composition that may contain the antimicrobial system of the present invention. End use compositions suitable for use with the antimicrobial system of the present invention typically contain a cosmetically acceptable carrier component. Water is the most preferred carrier. The amount of water can range from 1 to 96% by weight, preferably 5 to 90% by weight, most preferably 35 to 80% by weight, and optimally 40 to 75% by weight, based on the total weight of the end use composition. Typically, the end use compositions of the present invention are water and oil emulsions, most preferably oil-in-water emulsions. However, water-in-oil emulsions are also an option, particularly those generally classified as water-in-oil and high internal phase emulsions. Examples of high internal phase emulsions suitable for containing the antimicrobial system of the present invention are described in commonly owned U.S. Patent Application Publication No. 2008 / 0311058 and U.S. Patent No. 8,425,882, the disclosures of which are incorporated herein by reference.

[0031] Other cosmetically acceptable carriers suitable for use in the present invention include mineral oils, silicone oils, synthetic or natural esters, and alcohols. The amount of these materials can range from 0.1 to 50% by weight, preferably from 0.1 to 30% by weight, and most preferably from 1 to 20% by weight of the end use composition, including all ranges subsumed therein. In yet other embodiments, such carriers collectively comprise 1 to 12% or 1 to 8% by weight of the end use composition.

[0032] Silicone oils can be divided into volatile and non-volatile types. The term "volatile" as used herein refers to a material that has a measurable vapor pressure at ambient temperature. Volatile silicone oils are preferably selected from cyclic or linear polydimethylsiloxanes containing 3 to 9, more preferably 4 to 5, silicon atoms.

[0033] Linear volatile silicone materials generally have a viscosity of less than 5 centistokes at 25° C., while cyclic materials typically have a viscosity of less than 10 centistokes (measured on a Brookfield Viscometer, RV No. 3 spindle, 20 RPM, normalized against mineral oil).

[0034] Nonvolatile silicone oils useful as carrier materials include polyalkyl siloxanes, polyalkylaryl siloxanes, and polyether siloxane copolymers. Essentially nonvolatile polyalkyl siloxanes useful herein include, for example, polydimethyl siloxanes (such as dimethicone) having a viscosity of 5 to 100,000 centistokes at 25°C.

[0035] An often preferred silicone source is a solution of cyclopentasiloxane and dimethiconol.

[0036] Suitable esters include: (1) Alkenyl or alkyl esters of fatty acids having 10 to 20 carbon atoms, such as isopropyl palmitate, isopropyl isostearate, isononyl isononanoate, oleyl myristate, isopropyl myristate, oleyl stearate, and oleyl oleate; (2) Ether esters, for example fatty acid esters of ethoxylated fatty alcohols; (3) polyhydric alcohol esters, such as ethylene glycol mono- and di-fatty acid esters, diethylene glycol mono- and di-fatty acid esters, polyethylene glycol (200-6000) mono- and di-fatty acid esters, propylene glycol mono- and di-fatty acid esters, polypropylene glycol 2000 monooleate, polypropylene glycol 2000 monostearate, ethoxylated propylene glycol monostearate, glyceryl mono- and di-fatty acid esters, polyglycerol polyfatty esters, ethoxylated glyceryl monostearate, 1,3-butylene glycol monostearate, 1,3-butylene glycol distearate, polyoxyethylene polyol fatty acid esters, sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters; (4) Wax esters, such as beeswax, spermaceti, myristyl myristate, stearyl stearate; and (5) Sterol esters, such as soybean sterol and cholesterol fatty acid esters.

[0037] An emulsifier (or surfactant) may be present in the end use composition comprising the antimicrobial system of the present invention. The total concentration of emulsifier may range from 0.1 to 30% by weight of the end use composition, preferably from 2 to 20% by weight, most preferably from 1 to 8% by weight. The emulsifier may be selected from the group consisting of anionic, nonionic, cationic and amphoteric components. Particularly preferred nonionic components are C4 condensed with 2 to 100 moles of ethylene oxide or propylene oxide per mole of hydrophobic component. 10 -C 20 Fatty alcohol or acid hydrophobic moiety; C2-C condensed with 2 to 20 moles of alkylene oxide 10 Alkylphenols;Mono- and di-fatty acid esters of ethylene glycol;Fatty acid monoglycerides;Sorbitan, mono- and di-C8-C 20fatty acids; and polyoxyethylene sorbitan, and combinations thereof. Alkyl polyglycosides and saccharide fatty amides (e.g., methyl gluconamide) are also suitable nonionic emulsifiers.

[0038] Suitable anionic emulsifiers that may be used include alkyl ether sulfates and sulfonates, alkyl sulfates and sulfonates, alkyl benzene sulfonates, alkyl and dialkyl sulfosuccinates, C8-C 20 Acyl isethionates, C8-C 20 These include alkyl ether phosphates, alkyl ether carboxylates, and combinations thereof.

[0039] Cationic emulsifiers that may be used include, for example, palmitamidopropyltrimonium chloride, distearyldimonium chloride, and mixtures thereof. Useful amphoteric emulsifiers include cocoamidopropyl betaine, C 12 -C 20 Examples include trialkylbetaines, sodium lauroamphoacetate and sodium laurodiamphoetate or mixtures thereof.

[0040] Other generally preferred emulsifiers include glyceryl stearate, glycol stearate, stearamide AMP, PEG-100 stearate, cetyl alcohol, and emulsifying / thickening additives such as hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer / squalene and mixtures thereof.

[0041] Although not required, conventional preservatives can be optionally incorporated into the end-use compositions containing the antimicrobial system of the present invention to aid in the growth of potentially harmful microorganisms. Conventional preservatives suitable for optional use in the final compositions of the present invention include alkyl esters of parahydroxybenzoic acid. Other preservatives include hydantoin derivatives, propionate salts, and various quaternary ammonium compounds. Often preferred preservatives are sodium benzoate, iodopropynyl butylcarbamate, phenoxyethanol, methylparaben, propylparaben, imidazolidinyl urea, sodium dehydroacetate, and benzyl alcohol. Particularly preferred additives suitable for use with or without conventional preservatives that may be optionally used in the present invention are 1,2-alkanediols (e.g., 1,2-octanediol and 1,2-hexanediol).

[0042] Conventional fragrance ingredients such as eugenol, coumarin, thymol, terpineol, linalyl acetate, citronellal, iris concentrate, terpinyl acetate, pinenes (alpha pinene and beta pinene) and citronellol can optionally be added (either separately from or along with the fragrance in the end use composition).

[0043] If used, conventional preservatives, vicinal diols and / or fragrance ingredients comprise no more than 2% by weight, preferably no more than 1% by weight, and most preferably no more than 0.6% by weight, or even no more than 0.2% by weight, of the end use composition of the present invention. In one embodiment of the present invention, 0.0001 to 0.85% by weight of preservatives, vicinal diols and / or fragrance ingredients, based on the total weight of the end use composition, may be used. Since the end use composition includes the antimicrobial system of the present invention, in a preferred embodiment of the present invention, no conventional preservatives, vicinal diols and / or fragrance ingredients (except as may be provided in the fragrance used in the end use composition) are used in the end use composition. In another embodiment of the present invention, the end use composition is free (0.0% by weight) of parabens, formaldehyde donors and / or phenoxyethanol. In yet another embodiment of the present invention, the end use composition is substantially free of silicone and / or sulfate-containing ingredients (e.g., surfactants or emulsifiers). In yet another embodiment, the end use compositions of the present invention are silicone-free and / or contain no sulfate-containing ingredients (ie, 0.0 wt %).

[0044] The end-use compositions of the present invention may optionally include a thickening agent. Particularly useful are polysaccharides. Examples include citrus fiber, starch, natural / synthetic gums and celluloses. Representative of starches are chemically modified starches such as sodium hydroxypropyl starch phosphate and aluminum starch octenyl succinate. Tapioca starch is often preferred. Suitable gums include xanthan, sclerotium, pectin, karaya, arabic, agar, guar, carrageenan, alginates and combinations thereof. Suitable celluloses include hydroxypropyl cellulose, hydroxypropyl methylcellulose, ethylcellulose and sodium carboxymethylcellulose. Synthetic polymers are yet another class of effective thickening agents. This category includes crosslinked polyacrylates such as Carbomers, polyacrylamides such as Sepigel® 305 and taurate copolymers such as Simulgel EG® and Aristoflex® AVC, which are identified according to their respective INCI nomenclature as sodium acrylate / sodium acryloyldimethyl taurate and acryloyldimethyl taurate / vinylpyrrolidone copolymers. Another preferred synthetic polymer suitable for thickening is the acrylate-based polymer marketed by Seppic and sold under the name Simulgel IN100.

[0045] When a thickener is used, the amount of the thickener may range from 0.001 to 5% by weight, preferably from 0.1 to 2% by weight, and most preferably from 0.2 to 0.5% by weight of the end use composition.

[0046] Perfumes, fixatives and abrasives may optionally be used in end use compositions containing the antimicrobial system of the present invention, each of which may range from 0.05 to 5% by weight, preferably from 0.1 to 3% by weight, and most preferably from 0.2 to 1% by weight, of the total weight of the end use composition.

[0047] Conventional humectants can be used in the end use compositions of the present invention. These are generally polyhydric alcohol type materials. Representative polyhydric alcohols include glycerol (i.e., glycerine or glycerin), propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol, sorbitol, hydroxypropyl sorbitol, hexylene glycol, 1,3-butylene glycol, isoprene glycol, 1,2,6-hexanetriol, ethoxylated glycerin, propoxylated glycerin, and mixtures thereof. Most preferred are glycerin, propylene glycol, or mixtures thereof. The amount of humectant used can range from 0.5 to 20% by weight, preferably from 1 to 15% by weight, and most preferably from 2 to 10% by weight of the end use composition.

[0048] The end use compositions of the present invention may include vitamins. Exemplary vitamins are vitamin A (retinol) and retinol esters (e.g., retinol palmitate and retinol propionate), vitamin B2, vitamin B3 (niacinamide), vitamin B6, vitamin C, vitamin A, vitamin D, vitamin E, vitamin K, folic acid, and biotin. Derivatives of vitamins may also be used. For example, derivatives of vitamin C include ascorbyl tetraisopalmitate, magnesium ascorbyl phosphate, and ascorbyl glycosides. Derivatives of vitamin E include tocopheryl acetate, tocopheryl palmitate, and tocopheryl linoleate. DL-panthenol and its derivatives may also be used. When present, the total amount of vitamins ranges from 0.001 to 10%, preferably from 0.01 to 5%, and optimally from 0.1 to 2% by weight of the end use composition.

[0049] Other optional additives suitable for use in the present invention include resorcinols, such as 4-ethylresorcinol, 4-hexylresorcinol, 4-phenylethylresorcinol, dimethoxytolylpropylresorcinol, 4-cyclopentylresorcinol, 4-cyclohexylresorcinol, α- and / or β-hydroxy acids, petroselinic acid, conjugated linoleic acid, 12-hydroxystearic acid, thiamidol, mixtures thereof, and the like. Still other optional additives, such as ethanol, quaternary ammonium compounds (e.g., cetrimonium chloride, benzalkonium chloride, and the like), and lecithin, may also be included. Such additives, when used, collectively constitute 0.001 to 12% by weight, preferably 0.01 to 6% by weight, and most preferably 0.1 to 4% by weight, of the end-use composition. In one embodiment of the present invention, these optional additives, individually and when used, constitute 0.01 to 1% by weight of the end-use composition. In another embodiment of the present invention, optional additives used in the end use composition include niacinamide, 12-hydroxystearic acid, resorcinol (such as thiamidol) or mixtures thereof.

[0050] In the end use compositions of the present invention, desquamation promoters can be present. Exemplary are α-hydroxycarboxylic acids, β-hydroxycarboxylic acids. The term "acid" does not mean only the free acid, but also its salts and C1-C 30 Alkyl or aryl esters and lactones produced by removal of water to form cyclic or linear lactone structures are also intended to be included. Representative acids are glycolic acid and its derivatives, lactic acid and malic acid. Salicylic acid is representative of the β-hydroxycarboxylic acids. When present, the amounts of these materials may range from 0.001 to 15%, preferably from 0.01 to 6%, and most preferably from 0.1 to 3% by weight of the end use composition.

[0051] The end-use compositions of the present invention may optionally include various herbal extracts. The extracts may be water-soluble or water-insoluble and are carried in a solvent that is hydrophilic or hydrophobic, respectively. Water and ethanol are the preferred extraction solvents. Exemplary extracts include those derived from green tea, yarrow, chamomile, licorice, aloe vera, grape seed, citrus unshiu, willow bark, sage, and rosemary.

[0052] Also optionally suitable for use are materials such as: chelating agents (e.g., EDTA), opacifying agents (e.g., TiO2, particle size 50-1200 nm, preferably 50-350 nm), C 8-22 Fatty acid substituted sugars, lipoic acid, retinoxytrimethylsilane (available from Clariant Corp. under the trade name Silcare 1M-75), dehydroepiandrosterone (DHEA) and combinations thereof. Ceramides (including ceramide 1, ceramide 3, ceramide 3B and ceramide 6) and pseudoceramides can also be optionally included. The amount of these materials, when used, can range from 0.0001 to 8% by weight, preferably from 0.001 to 6% by weight, and most preferably from 0.001 to 3% by weight of the end use composition.

[0053] The end use compositions of the present invention may also optionally include a sunscreen active. Particularly preferred are materials such as p-ethylhexyl methoxycinnamate available as Parsol MCX®, Avobenzene available as Parsol 1789®, and Benzophenone-3, also known as Oxybenzone. Inorganic sunscreen actives may also be used, such as microfine titanium dioxide, zinc oxide, polyethylene and various other polymers. When present, the amount of sunscreen may generally range from 0.1 to 30% by weight, preferably from 0.5 to 20% by weight, optimally from 0.75 to 10% by weight.

[0054] Conventional buffers / pH adjusters can be used. These include commonly used additives such as sodium hydroxide, potassium hydroxide, hydrochloric acid, citric acid, triethanolamine, citrate / citric acid buffer or mixtures thereof. In an embodiment of the invention, the pH of the end-use composition is 4-8, preferably 4.25-7.75, most preferably 5.6-7.5. In another embodiment, the pH of the end-use composition is 5-7.

[0055] In yet another embodiment of the present invention, and when the end use composition is a conventional cleansing or cleaning composition, such a cleansing or cleaning composition often contains 4 to 45 wt. %, or 6 to 28 wt. %, or 8 to 22 wt. % C8-C 20 , preferably C 10 -C 20 Or C 12 -C 18 of fatty acid or fatty acid soap and less than 5% by weight of synthetic surfactant, preferably 1-3% by weight of synthetic surfactant (synthetic detergent). In one embodiment of the invention, the cleansing or washing composition comprises 0-5% by weight, preferably 0.01-4% by weight of 12-hydroxystearic acid (12-HSA) and 0.01-25% by weight of glycerol. In yet another embodiment, the end use composition of the invention comprises 0-6% by weight of a sulfate surfactant (e.g. sodium lauryl sulfate), but preferably is free of sulfate surfactant (0.0% by weight).

[0056] In yet another embodiment of the present invention, and when the end use composition is a cleansing or washing composition, the composition may contain less than 8% by weight of fatty acids and fatty acid soaps. In that case, the synthetic detergents constitute 2-30% by weight, preferably 3-22% by weight, most preferably 4-15% by weight of the end use composition having the antimicrobial system of the present invention. The synthetic detergents used are typically glycinates, glutamates, isethionates, taurates, betaines or mixtures thereof.

[0057] The viscosity of the end use compositions of the present invention is typically 1,000 to 50,000 cps. The wash-off compositions preferably have a viscosity of less than 9,000 cps and the leave-on compositions preferably have a viscosity of 6,000 to 15,000 cps. Viscosity can be measured using an art-recognized instrument such as a Brookfield Viscometer RVT, Model D220, using a T-bar spindle D, at 25° C., 5 RPM, 60 seconds.

[0058] Exemplary end-use compositions that may contain from 0.001 to 12% by weight of the antimicrobial system of the present invention are set forth below.

[0059] [Table 1]

[0060] [Table 2]

[0061] [Table 3]

[0062] [Table 4]

[0063] In preparing such compositions, moderate heating (50-70°C) and stirring at atmospheric pressure are used until a homogenous composition is obtained, preferably involving homogenization. The antimicrobial system can be added to the desired end-use composition as a combined component or as individual components, with water being added to make the balance.

[0064] A wide variety of packaging can be used to store and deliver end use compositions containing the antimicrobial system of the present invention. The packaging often depends on the type of product and its intended use. For example, leave-on-skin lotions and creams, shampoos, conditioners and shower gels generally use plastic containers with an opening at the dispensed end covered with a closure. Metal cans pressurized with a propellant and equipped with a spray nozzle can be used to package mousses and other personal care products (e.g., antiperspirants). Post-consumer resins are often preferred.

[0065] It is also within the scope of the present invention for the antimicrobial system to be included in a concentrate (i.e., a precursor end-use composition), where the consumer obtains such a concentrate and adds water to it to produce the desired end-use composition.

[0066] The following examples are provided to facilitate understanding of the invention and are not intended to limit the scope of the claims.

[0067] The surprising synergistic benefits obtained when using the microbial system of the present invention were confirmed by conducting studies similar to those described below. EXAMPLES

[0068] Indole alkaloids and phenolic acids were combined as shown below to create a natural antibacterial system. Two pools were set up, each containing one species of bacteria. The target strains were Enterobacter gergoviae ATCC 33028 and Aspergillus brasiliensis ATCC 16404, both Gram-negative bacteria of the family Pluralibacter gergoviae. The FIC test range was 16-fold higher than the predicted MIC for each sample. The first and second natural components (Component A and Component B) were combined to create a natural component mixture and antibacterial system, demonstrating unexpected superior results.

[0069] The concepts of fractional concentration and fractional inhibitory concentration (FIC) have been used to widely study the different behavior of inhibitory antimicrobial agents in single and mixtures. See, for example, JRW Lambert and R Lambert, J. Appl. Microbiol 95, 734 (2003), T. Jadavji, CG Prober and R Cheung, Antibacterial Agents and Chemotherapy 26, 91 (1984) and WO 2004 / 006876. MIC is the minimum inhibitory concentration at which an ingredient prevents visible growth of a microorganism. The FC and FIC parameters can be defined as follows: FC(component A) = concentration of component A tested in the mixture / MIC(component A tested as single active agent); FIC(component a)=MIC(component a tested in mixture) / MIC(component a tested as single active agent).

[0070] Interactions between antimicrobial agents may be additive, synergistic, or perhaps antagonistic, depending on whether the efficacy is equal to, greater than, or less than that obtained at the same total concentration of each component when tested alone. These relationships can be expressed mathematically by summing the fractional MIC values ​​for all components present in the mixture to give a "fractional inhibitory index": ΣFIC=FIC (成分1) +FIC (成分2) the result, A ΣFIC greater than 0.5 corresponds to mediocre, additive, or antagonistic activity; A ΣFIC of 0.5 or less corresponds to synergistic activity.

[0071] A comparable method is to calculate the synergy index (SI), which is an industry accepted method described by Kull, FC (Eisman, PC; Sylwestrowicz, HD and Mayer, RL, in Applied Microbiology 9:538-541 (1961)).

[0072] Test Method Liquid broth assays (MIC and checkerboard) were performed to identify the minimum concentrations of the natural preservatives alone and in combination. A modified version of ISO 20776-1:2006 was used to screen as follows: 200uL / cell (or well) of each preservation chemical stock solution and 100uL of broth were made in separate 96-well plates. Each of the two preservation chemical / broth mixtures were then combined in a third 96-well plate at various concentrations and then diluted with 1-5x10 6 The microorganisms were inoculated and incubated at 30 °C for 24 h, after which the OD 600 The optical density at nm was measured and the MIC was defined as the concentration at which less than 25% growth was observed compared to the positive growth control without the preservative chemical.

[0073] Microbial Pool [Table 5]

[0074] A synergistic combination Enterobacter gergoviae Syringic acid and gramine Syringic acid alone showed a minimum inhibitory concentration (MIC) of over 50 mg / mL against Enterobacter gergoviae. Gramine alone showed an MIC of 6.25 mg / mL. The combination of gramine and syringic acid required 0.098 mg / mL of gramine and 0.781 mg / mL of syringic acid to achieve the inhibitory effect, indicating a significant synergistic effect of gramine and syringic acid.

[0075] Aspergillus brasiliensis Syringic acid and gramine Syringic acid alone showed an MIC of over 50 mg / mL against Aspergillus brasiliensis. Gramine alone showed an MIC of 12.5 mg / mL against A. brasiliensis. The combination of gramine and syringic acid required 1,563 mg / mL of gramine and 6.25 mg / mL of syringic acid to achieve the inhibitory effect, indicating a significant synergistic effect of gramine and syringic acid.

[0076] The data provided above surprisingly demonstrates that when natural antimicrobial components are combined in accordance with the present invention, a synergistic benefit against Enterobacter gergoviae and Aspergillus brasiliensis is unexpectedly observed.

Claims

1. An antibacterial system, (a) a first component comprising an indole alkaloid, an indole alkaloid salt, or both; and (b) a second component comprising a phenolic acid, a phenolic acid salt, or both; Contains wherein the phenolic acid has the formula: 【Chemistry 1】 Further, where R １ , R ２ and R ３ are each independently hydrogen or C １ -C ４ is alkyl; and The indole alkaloid has the formula: 【Chemistry 2】 where R ４ and R ５ are each independently H or C １ -C ２ is an alkyl group, and R ６ and R ７ are each independently １ -C ２ is an alkyl group; Where: The phenolic acids include 4-hydroxy-3,5-dimethoxybenzoic acid (syringic acid) and the phenolic acid salts include salts of 4-hydroxy-3,5-dimethoxybenzoic acid; And, The indole alkaloids include 1-(1H-indol-3-yl)-N,N-dimethylmethanamine (gramine), and the indole alkaloid salts include salts of 1-(1H-indol-3-yl)-N,N-dimethylmethanamine; The antibacterial system.

2. 2. The antimicrobial system of claim 1, wherein the antimicrobial system comprises a salt of the phenolic acid and / or the indole alkaloid.

3. The composition further comprises a phenolic acid which is 3,4,5-trihydroxybenzoic acid (wherein R １ , R ２ and R ３ is H) or 3,4,5-trimethoxybenzoic acid, a phenolic acid (where R １ , R ２ and R ３ Each of ３ 13. The antimicrobial system according to any of the preceding claims, comprising:

4. 10. An antibacterial system according to any of the preceding claims, wherein the indole alkaloids and phenolic acids and / or salts thereof are present in a weight ratio of from 0.5:9 to 2:10, preferably from 0.6:7 to 4:9, most preferably from 0.75:4 to 5:

8.

6. 10. An antimicrobial system according to any preceding claim, wherein from 8 to 75% by weight of the antimicrobial system is indole alkaloids or salts thereof, preferably from 10 to 65% by weight, most preferably from 12 to 50% by weight, based on the total weight of indole alkaloids and phenolic acids (including any salts thereof).

7. 1. An end-use composition comprising an antimicrobial system, the antimicrobial system comprising: (a) a first component comprising an indole alkaloid, an indole alkaloid salt, or both; (b) a second component comprising a phenolic acid, a phenolic acid salt, or both; and (c) A cosmetically acceptable carrier. Contains wherein the phenolic acid has the formula: 【Chemistry 3】 Further, where R １ , R ２ and R ３ are each independently hydrogen or C １ -C ４ is alkyl; and The indole alkaloid has the formula: 【Chemistry 4】 where R ４ and R ５ are each independently H or C １ -C ２ is an alkyl group, and R ６ and R ７ are each independently １ -C ２ is an alkyl group; Where: The phenolic acids include 4-hydroxy-3,5-dimethoxybenzoic acid (syringic acid) and the phenolic acid salts include salts of 4-hydroxy-3,5-dimethoxybenzoic acid; And, The indole alkaloids include 1-(1H-indol-3-yl)-N,N-dimethylmethanamine (gramine), and the indole alkaloid salts include salts of 1-(1H-indol-3-yl)-N,N-dimethylmethanamine; The end use composition.

8. 8. The end-use composition of claim 7, wherein said composition comprises a salt of said phenolic acid and / or indole alkaloid.

9. R １ and R ３ is CH ３ and R ２ is H and the acid is 4-hydroxy-3,5-dimethoxybenzoic acid, or R １ , R ２ and R ３ is H and the acid is 3,4,5-trihydroxybenzoic acid, or １ , R ２ and R ３ Each of ３ and the acid is 3,4,5-trimethoxybenzoic acid or a mixture thereof, and R ４ and R ５ is hydrogen, and R ６ and R ７ is CH ３ and said indole alkaloid is 1-(1H-indol-3-yl)-N,N-dimethylmethanamine.

10. 10. End use composition according to claims 7 to 9, wherein said indole alkaloid and phenolic acid or salt thereof are present in a weight ratio of 0.5:9 to 2:10, preferably 0.6:7 to 4:9, most preferably 0.75:4 to 5:

8.

11. The end use composition of claims 7 to 10, wherein the composition is a shampoo, a cream, a lotion, a serum, a gel, a balm, a deodorant, an antiperspirant, an oral care composition, a conditioner, a cleansing bar or a liquid cleaning product.

12. The end use composition of claims 7-11, wherein the composition is substantially free of parabens, formaldehyde donors, phenoxyethanol, silicones, sulfates, or mixtures thereof.

13. The end use composition of claims 7-12, further comprising terpineol, thymol, 12-hydroxystearic acid, niacinamide, retinol, resorcinol or mixtures thereof.

15. 7. Non-therapeutic use of an antimicrobial system according to any of claims 1 to 6 to preserve an end-use composition or to provide an antimicrobial benefit to an object by contacting the object with a composition comprising said antimicrobial system.

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