Antibacterial systems containing beta-carboline alkaloids and phenolic acids and compositions containing them

Abstract

An antimicrobial system containing naturally derived components and compositions containing the same are described, the system having a first component that includes a beta-carboline alkaloid and a second naturally derived component that includes a phenolic acid, and the system and composition provide superior antimicrobial efficacy.

Description

[Technical field]

[0001] The present invention relates to an antimicrobial system comprising naturally occurring components. In particular, the present invention relates to beta-carboline alkaloids and phenolic acids and / or salts thereof comprising an antimicrobial system that can be included in end-use formulations such as cosmetics, pharmaceuticals, home care compositions and cleaning compositions. The components of the antimicrobial system of the present invention are naturally found in fruits and plants and unexpectedly provide excellent synergistic antimicrobial effects when added to such end-use compositions. End-use compositions comprising the antimicrobial system of the present invention can be formulated substantially free of parabens, formaldehyde donors, triclosan, and other conventional antimicrobial components including sulfated and halogenated antimicrobial components. [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 well in maintaining the integrity and stability of certain end-use compositions. Nevertheless, it is desirable to develop new preservative systems, antimicrobial systems that contain natural ingredients suitable for performing well across a full range of consumer products. Natural microbial systems should be effective in preserving products, not skin sensitizing, and not adversely affect the sensory properties of consumer products, especially those that are topically applied.

[0003] In addition to providing superior antimicrobial benefits, the system should not be harmful to the environment and should be gentle enough for use on the most vulnerable consumers, infants. Summary of the Invention [Problem to be solved by the invention]

[0004] There has been an increasing interest in developing effective, non-skin sensitizing, and environmentally sustainable antimicrobial systems. Accordingly, the present invention relates to an antimicrobial system comprising natural ingredients, and compositions comprising the same. The antimicrobial system comprises a beta-carboline alkaloid, and a phenolic acid and / or a salt thereof. Such a system unexpectedly provides excellent synergistic antimicrobial effects in the end-use compositions in which it is used.

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

[0006] Other approaches to creating antiseptic systems have also been disclosed. In U.S. Patent No. 7,754,774 B2, an antiseptic disinfectant containing 1,2-octanediol is described.

[0007] Other approaches to creating preservative systems have also been disclosed: US Patent No. 7,582,681 B2 describes antimicrobially active compounds that include 1,2-alkanediols.

[0008] Further efforts to modulate inflammatory responses have been disclosed: International Application 2021 / 202982A1 describes compositions comprising aqueous or solid fractions of mushroom mycelium and / or fruiting body mixtures for treating, for example, the prevention or amelioration of one or more adverse reactions caused by an infectious disease.

[0009] None of the above additional information describes the antimicrobial systems and end-use compositions comprising such systems as described and claimed herein. [Means for solving the problem]

[0010] In a first aspect, the present invention provides a method for producing a composition comprising the steps of: (a) a first component comprising a beta-carboline alkaloid; and (b) a second component comprising a phenolic acid, a phenolic acid salt, or both; The present invention relates to an antibacterial system comprising:

[0011] In a second aspect, the present invention provides a method for producing a composition comprising the steps of: (a) a first component comprising a beta-carboline alkaloid; and (b) a second component comprising a phenolic acid, a phenolic acid salt, or both; The present invention relates to an end use composition comprising:

[0012] In a third aspect, the present invention relates to a use or method for preserving a composition having an antimicrobial system having a first component comprising a beta-carboline alkaloid and a second component comprising a phenolic acid, a phenolate, or both.

[0013] In a fourth aspect, the present invention relates 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 a beta-carboline alkaloid and a second component comprising a phenolic acid, a phenolate, or both.

[0014] In a fifth aspect, the present invention relates to a use or method of providing an antimicrobial effect to an object, such as a table surface, by contacting the object with a composition having a first component comprising a beta-carboline alkaloid and a second component comprising a phenolic acid, a phenolate, or both.

[0015] All other aspects of the present invention will become more readily apparent from the following description and examples.

[0016] As used herein, antimicrobial system refers to a natural system of at least two components suitable for exhibiting synergistic antimicrobial reduction, such as the antimicrobial effect seen in preservatives in the composition, or when applied topically to surfaces, including home care surfaces such as skin and table surfaces. Antimicrobial agents surprisingly synergistically reduced by the system of the present invention include Enterobacter gergoviae ATCC 33028, a gram-negative bacillus that often exhibits resistance to parabens, or such bacteria, and Aspergillus brasiliensis ATCC 16404, a fungus in the Aspergillus genus. At least two component system means that it includes at least one component that is a beta-carboline 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 the end-use composition, or it can be added separately with the components to make the desired end-use composition). Naturally derived means suitable for recovery (in at least one form) from fruits, plants, and / or roots without the need for synthetic production. Naturally derived therefore includes analogs / derivatives of components that are used immediately as extracted or isolated from natural sources. For example, in the case of phenolic acids, naturally derived includes components such as syringic acid that are naturally recovered from fruits such as sea buckthorn berries, and ether or ester variations made therefrom. Salt as used herein with respect to phenolic acids means having, for example, sodium, potassium, calcium, magnesium, and / or ammonium cations.

[0017] Skin as used herein includes the skin of the feet, face, neck, chest, arms (including underarms), hands, legs, buttocks, back and scalp (including hair). End-use compositions (i.e., ready-to-use or applied compositions) 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 and window cleaners, toilet bowl cleaners and laundry cleaners. In one embodiment, the end-use composition of the present invention is a cleaning composition, cleaning 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 characteristics of the skin, such as reducing the appearance of wrinkles and / or moisturizing the skin. Such compositions can also be compositions that provide for the evening out of skin color or tone and the reduction of pigmentation spots caused by environmental factors, the aging process, or both.

[0018] Unless expressly stated otherwise, all ranges set forth herein are intended to include all ranges subsumed therein. The term comprising is meant to encompass the terms consisting essentially of and consisting of. For the avoidance of doubt, a composition comprising a preservative portion comprising syringic acid and harmol is meant to include compositions consisting essentially of and compositions consisting of. With respect to percentages used herein, they are meant to be on a weight basis unless otherwise stated. Except in the operating and comparative examples, or unless expressly indicated otherwise, all numbers used in this description indicating the amount or proportion of a material or its use should be understood to be modified by the word "about". As used herein, "substantially free" means less than 1.5% by weight or less than 0.35% by weight of the total weight of the end-use composition. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] There are no limitations on how the beta-carboline alkaloid-containing ingredients used in the present invention are naturally sourced, other than that their acquisition is preferably done in the most sustainable way. In many cases, a green extraction process using ethyl acetate and sodium bicarbonate is used instead of the common extraction process, particularly using chloroform. Natural sources of beta-carboline alkaloids used in the present invention are, for example, fruits such as sea buckthorn berries and plants such as the roots of the harmala plant. Alkylation of natural source ingredients is typically achieved by reacting the alkaloids with olefins in the presence of an acid catalyst or by reacting the alkaloids with alkyl groups containing leaving groups (i.e., nucleofuges) in the presence of a base.

[0020] Exemplary beta-carboline alkaloids suitable for use in the present invention are represented as follows: [ka] wherein each R is independently hydrogen or C 1 -C 4 It is an alkyl.

[0021] In one embodiment of the invention, -OR is a hydroxy group, -NR is -NH, and the beta-carboline alkaloid is 1-methyl-9H-pyrido[3,4-b]indol-7-ol, commonly known as harmol.

[0022] Regarding the ingredients containing phenolic acids or their salts suitable for use in the present invention, there are no limitations on how such ingredients are naturally derived, except that their recovery is preferably carried out in the most sustainable manner. Natural sources of ingredients containing phenolic acids are fruits such as olives, dates, pumpkins and grapes, as well as spices, acai, honey and red wine. Phenolic acids can be recovered from such sources by art-recognized techniques, such as extraction with solvents such as ethanol, methanol, ethyl acetate or ethyl ether, and even extraction with water since phenolic acids are slightly soluble in water.

[0023] Illustrative examples of phenolic acids suitable for use in the present invention are represented as follows: [ka]

[0024] In the formula, R 1 , R 2 and R 3 Each of the groups is independently hydrogen or C 1 -C 4 It is an alkyl.

[0025] In one embodiment of the present invention, R 1 and R 3 CH 3 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 the CH 3where the acid is 3,4,5-trimethoxybenzoic acid, commonly referred to as eudesmic acid. Mixtures of such acids are suitable for use as are salts thereof. As for derivatives and analogs thereof, they can be prepared by subjecting the natural acid to art-recognized alkylation and dealkylation process steps.

[0026] The weight ratio of carboline alkaloid to phenolic acid (and / or salts thereof) used in the present invention is often 0.75:8 to 0.75:48, preferably 0.85:4 to 1:44, and most preferably 0.95:3 to 2:40. In one embodiment of the present invention, and where it is desired that the end-use composition be effective against bacteria, the antimicrobial system preferably comprises 0.7 to 5 weight percent carboline alkaloid, preferably 0.8 to 4 weight percent, and most preferably 0.9 to 3 weight percent carboline alkaloid, based on the total weight of the carboline alkaloid and phenolic acid in the antimicrobial system. In another embodiment, and where it is desired that the end-use composition be effective against both bacteria and fungi, the antimicrobial system preferably comprises 45 to 78 weight percent carboline alkaloid, preferably 50 to 75 weight percent, and most preferably 58 to 70 weight percent carboline alkaloid, based on the total weight of the carboline alkaloid and phenolic acid (and / or salts thereof) in the antimicrobial system.

[0027] Typically, end-use compositions made with the antimicrobial system of the present invention have a total weight of antimicrobial system (i.e., carboline alkaloids and phenolic acids) of 0.001-12% by weight based on the total weight of the end-use composition. In one embodiment of the present invention, the composition has 0.01-10% by weight, 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 a total weight of antimicrobial system of 1-6% by weight, or 1.25-6% by weight, or 1.5-5% by weight, or 2-4.5% by weight based on the total weight of the end-use composition.

[0028] There are no limitations regarding 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 include a cosmetically acceptable carrier component. Water is the most preferred carrier. The amount of water may range from 1 to 96%, preferably 5 to 90%, most preferably 35 to 80%, 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-based emulsions, most preferably oil-in-water. However, water-in-oil emulsions are an option, particularly those commonly classified as water-in-oil and high internal phase emulsions. Illustrative 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.

[0029] Other cosmetically acceptable carriers suitable for use in the present invention may include mineral oil, silicone oil, synthetic or natural esters, and alcohols. Amounts of these materials range from 0.1 to 50%, preferably 0.1 to 30%, and most preferably 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.

[0030] Silicone oils can be classified as volatile and non-volatile. The term "volatile" as used herein refers to a substance that has a measurable vapor pressure at room temperature. Volatile silicone oils are preferably selected from cyclic or linear polydimethylsiloxanes containing 3 to 9, preferably 4 to 5, silicon atoms.

[0031] Linear volatile silicone materials usually have viscosities of less than 5 centistokes at 25° C., while cyclic materials typically have viscosities of less than 10 centistokes (measured with a Brookfield viscometer, RV No. 3 spindle at 20 RPM, normalized to mineral oil).

[0032] Non-volatile silicone oils useful as carrier materials include polyalkyl siloxanes, polyalkylaryl siloxanes, and polyether siloxane copolymers. Essentially non-volatile polyalkyl siloxanes useful herein include, for example, polydimethyl siloxanes (such as dimethicone) having a viscosity of 5 to 100,000 centistokes at 25°C.

[0033] An optional silicone source is a solution of cyclopentasiloxane and dimethiconol.

[0034] 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, such as fatty acid esters of ethoxylated fatty alcohols; (3) Polyhydric alcohol esters such as ethylene glycol mono- or di-fatty acid esters, diethylene glycol mono- and di-fatty acid esters, polyethylene glycol (200 to 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, and stearyl stearate; and (5) Sterol esters, such as soybean sterol and cholesterol fatty acid esters. There is.

[0035] 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%, preferably 2 to 20%, most preferably 1 to 8% by weight of the end use composition. The emulsifier may be selected from the group consisting of anionic, nonionic, cationic and amphoteric components. Particularly preferred nonionic components are C6-C10 condensed with 2 to 100 moles of ethylene oxide or propylene oxide per mole of hydrophobe. 10 -C 20 Those with fatty alcohol or acid hydrophobes; C condensed with 2 to 20 moles of alkylene oxide 2 -C 10 Alkylphenols;Mono- and di-fatty acid esters of ethylene glycol;Fatty acid monoglycerides;Sorbitan, mono- and di-C 8 -C 20 fatty acids; and polyoxyethylene sorbitan, and combinations thereof.Alkyl polyglycosides and monosaccharide fatty amides (e.g., methyl gluconamides) are also suitable nonionic emulsifiers.

[0036] Suitable anionic emulsifiers that can be used include alkyl ether sulfates and sulfonates, alkyl sulfates and sulfonates, alkyl benzene sulfonates, alkyl and dialkyl sulfosuccinates, C 8 -C 20and end-use compositions. 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 since such compositions contain the antimicrobial system of the present invention. In another embodiment of the present invention, the end-use composition is completely free (0.0 wt%) 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, such as surfactants or emulsifiers. In yet another embodiment, the end-use composition of the present invention is silicone-free and / or sulfate-containing ingredients (i.e., 0.0 wt%).

[0037] The end-use compositions of the present invention may also include thickening agents. Particularly useful are polysaccharides. Examples include citrus fibers, starches, natural and synthetic gums, and cellulosics. Representative examples 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 cellulosics include hydroxypropyl cellulose, hydroxypropyl methylcellulose, ethyl cellulose, and sodium carboxymethyl cellulose. Synthetic polymers are yet another class of effective thickening agents. This category includes carbomers, polyacrylamides such as Sepigel® 305, and taurate copolymers such as Simulgel EG® and Aristoflex® AVC, which are identified by the INCI nomenclature as Sodium Acrylate / Sodium Acrylol Dimethyl Taurate and Acryloyl Dimethyl Taurate / Vinyl Pyrrolidone Copolymer, respectively. Another preferred synthetic polymer suitable for thickening is an acrylate-based polymer manufactured and sold by Seppic under the name Simulgel INS100.

[0038] If used, the amount of this thickening agent may range from 0.001 to 5%, preferably from 0.1 to 2%, and most preferably from 0.2 to 0.5% by weight of the end use composition.

[0039] Fragrances, fixatives and abrasives may also be used in end-use compositions containing the antimicrobial agent of the present invention. Each of these materials may range from 0.05 to 5%, preferably 0.1 to 3%, and most preferably 0.2 to 1% by weight of the total weight of the end-use composition.

[0040] 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 glycerol, propoxylated glycerol, and mixtures thereof. Glycerin, propylene glycol, or mixtures thereof are most preferred. The amount of humectant used can be anywhere from 0.5 to 20%, preferably 1 to 15%, and most preferably 2 to 10% or even 2 to 4% by weight of the end use composition.

[0041] The end use compositions of the present invention may also include vitamins. Examples of vitamins include vitamin A (retinol) and retinol esters such as retinol palmitate and retinol propionate, vitamin B 2 , Vitamin B 3 (niacinamide), vitamin B 6 , Vitamin C, Vitamin A, Vitamin D, Vitamin E, Vitamin K, folic acid and biotin. Derivatives of vitamins may also be used. For example, Vitamin C derivatives include ascorbyl tetraisopalmitate, magnesium ascorbyl phosphate and ascorbyl glycosides. Derivatives of Vitamin E include tocopheryl acetate, tocopheryl palmitate, tocopheryl linoleate. DL-panthenol and derivatives may also be used. The total amount of vitamins, if present, may range from 0.001 to 10%, preferably 0.01 to 5%, optimally 0.1 to 2% by weight of the end use composition.

[0042] Other optional additives suitable for use in the present invention include resorcinols such as thiamidol, 4-ethylresorcinol, 4-hexylresorcinol, 4-phenylethylresorcinol, dimethoxytolylpropylresorcinol, 4-cyclopentylresorcinol, 4-cyclohexylresorcinol; alpha- and / or beta-hydroxy acids; petroselinic acid; conjugated linoleic acid; 12-hydroxystearic acid; mixtures thereof; and the like. Still other optional additives such as ethanol, quaternary ammonium compounds (such as 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.

[0043] Exfoliation promoters may be present in the end use compositions of the present invention. Examples include alpha-hydroxycarboxylic acids, beta-hydroxycarboxylic acids. The term "acid" refers not only to the free acid but also to its salts, C 1 -C 30 It is also meant to include alkyl or aryl esters, and lactones formed by removal of water to form cyclic or linear lactone structures. Representative acids are glycolic acid and its derivatives, lactic acid, and malic acid. Salicylic acid represents the beta-hydroxy carboxylic acids. The amounts of these materials, when present, can range from 0.001 to 15%, preferably 0.01 to 6%, and most preferably 0.1 to 3% by weight of the end use composition.

[0044] The end-use compositions of the present invention can optionally include various herbal extracts. The extracts can be water-soluble or water-insoluble, in a solvent that is hydrophilic or hydrophobic, respectively. Water and ethanol are the preferred extract solvents. Exemplary extracts include those extracted from green tea, yarrow, chamomile, licorice, aloe vera, grape seed, unshu mandarin, willow bark, sage, and rosemary.

[0045] Also optionally suitable for use are chelating agents (e.g., EDTA), opacifying agents (TiO 2 , particle size 50 to 1200 nm, preferably 50 to 350 nm), C 8-22 Materials such as fatty acid substituted sugars, lipoic acid, retinoxytrimethylsilane (available from Clariant Corp. under the trade name Silcare 1M-75), dehydroepiandrosterone (DHEA) and combinations thereof. Ceramides (such as ceramide 1, ceramide 3, ceramide 3B, and ceramide 6) and pseudoceramides may also be optionally included. When these materials are used, the amount may range from 0.0001 to 8%, preferably 0.001 to 6%, and most preferably 0.001 to 3% by weight of the end use composition.

[0046] The end use compositions of the present invention may also optionally include a sunscreen active. Particularly preferred are materials such as ethylhexyl p-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 particulate titanium dioxide, zinc oxide, polyethylene, and various other polymers. Amounts of sunscreen when present may generally range from 0.1 to 30%, preferably from 0.5 to 20%, optimally from 0.75 to 10% by weight.

[0047] Conventional buffers / pH adjusters can be used, including commonly used additives such as sodium hydroxide, potassium hydroxide, hydrochloric acid, citric acid, triethanolamine, citrate / citric acid buffer or mixtures thereof. In one embodiment of the invention, the pH of the end-use composition is 4-8, and preferably 4.25-7.75, most preferably 5.6-7.5.

[0048] In yet another embodiment of the present invention, and when the end use composition is a conventional cleansing or cleaning composition, the composition often comprises 4 to 45 wt. %, or 6 to 28 wt. %, or 8 to 22 wt. % C. 8 ~C 20 , preferably C 10 ~C 20 , or C 12 ~C 18 It contains a fatty acid or fatty acid soap, as well as less than 5% by weight of a synthetic surfactant, preferably 1-3% by weight of a synthetic surfactant (synthetic detergent). In one embodiment of the invention, the cleansing or washing composition contains 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 contains 0-6% by weight of a sulfate surfactant (e.g. sodium lauryl sulfate), but is preferably free of sulfate surfactants (0.0% by weight).

[0049] 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%, preferably 3-22%, 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.

[0050] The viscosity of the end-use compositions of the present invention is typically 1,000-50,000 cps. Wash-off compositions preferably have a viscosity of 9,000 cps or less, and leave-on compositions preferably have a viscosity of 6,000-15,000 cps. Viscosity can be measured with an industry-recognized instrument such as a Brookfield Viscometer RVT, Model D220, using a T-bar spindle D at 5 RPM and 25°C for 60 seconds.

[0051] Exemplary end-use compositions that may contain from 0.001 to 12% by weight of the antimicrobial system of the present invention are described below.

[0052] Shower body lotion [Table 1]

[0053] Body Lotion [Table 2]

[0054] Shampoo Composition [Table 3]

[0055] Body Wash Composition [Table 4]

[0056] In preparing such compositions, the mixture is stirred at atmospheric pressure over moderate heat (50-70°C) until a homogenous composition is obtained. Homogenization is preferably included. The antimicrobial system can be added to the desired end-use composition as a composite component or as individual components, with water added to volume.

[0057] A variety of packages can be used to store and deliver end use compositions containing the antimicrobial system of the present invention. Packaging often depends on the type of product and its intended use. For example, plastic containers with an opening at the dispenser end covered with a lid are commonly used for leave-on-skin lotions and creams, shampoos, conditioners and shower gels. Metal cans pressurized with a propellant and equipped with a spray nozzle are used to package other personal care products such as mousses and antiperspirants. Used resin is often preferred.

[0058] It is also within the scope of the present invention to include an antimicrobial system in the concentrate (i.e., a precursor end use composition) where a consumer obtains such a concentrate and adds water to it to produce the desired end use composition.

[0059] The following examples are provided to facilitate understanding of the invention and are not intended to limit the scope of the claims.

[0060] The surprising synergistic effect obtained when using the microbial system of the present invention was confirmed by carrying out tests similar to those described below.

[0061] A natural antibacterial system was created by combining beta-carboline alkaloids and phenolic acids as shown below. Two pools were set up, with one microorganism in each pool. The strains involved were Enterobacter gergoviae ATCC33028, gram-negative, of the family Pluralibacter gergoviae, and Aspergillus brasiliensis ATCC16404. The FIC test range was 16-fold higher than the predicted MIC for each sample. Combining the first and second natural components (components A and B) to create a mixture of natural components and antibacterial systems demonstrated unexpected and superior results.

[0062] The different behavior of inhibitory antimicrobial agents alone and in mixtures has been widely studied using the concepts of fractional concentration and fractional inhibitory concentration (FIC). 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 WO2004 / 006876. MIC is the minimum inhibitory concentration at which a component prevents visible growth of a microorganism. The FC and FIC parameters can be defined as follows:

[0063] FC(Component A) = concentration of test component A in the mixture / MIC(Test component A as single active substance) FIC(component a)=MIC(component a in mixture) / MIC(component a as single active substance) Interactions between antimicrobial agents may be additive, synergistic, or in some cases antagonistic, depending on whether the potency of the combination is equal to, greater than, or less than that obtained at the same total concentration when each component is tested alone. These relationships can be expressed mathematically by summing the fractional MIC values ​​for all components present in the mixture to obtain a "fractional inhibition index."

[0064] ΣFIC=FIC (成分1) +FIC (成分2) And so, A ΣFIC of greater than 0.5 corresponds to irrelevant, additive or antagonistic activity.

[0065] A ΣFIC of 0.5 or less corresponds to synergistic activity.

[0066] An equivalent method is the calculation of the synergy index (SI), which is an industry accepted method reported by Kull, FC; Eisman, PC; Sylwestrowicz, HD and Mayer, RL, Applied Microbiology 9:538-541 (1961).

[0067] Test Method Liquid broth assays (MIC and checkerboard) were performed to identify the minimum concentrations of natural preservatives individually and in binary combinations. A modified method of ISO20776-1:2006 was used for screening as follows: 200 μL / cell (or well) of stock solution of each preservative chemical and 100 μL of broth were made in separate 96-well plates. Each of the two preservative chemical / broth mixtures were then combined in a third 96-well plate at various concentrations and diluted to 1–5 × 10. 6 The microorganisms were inoculated and incubated at 30°C for 24 hours, after which the OD 600 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 any preservative chemical.

[0068] Microbial Pool [Table 5]

[0069] Synergistic Combinations Enterobacter gergoviae Harmol and syringic acid Syringic acid alone showed a minimum inhibitory concentration (MIC) of >50 mg / mL against Enterobacter gergoviae. Harmol alone showed an MIC of 0.625 mg / mL. In combination, a combination of 0.156 mg / mL harmol and 3.125 mg / ml syringic acid was required to achieve an inhibitory effect. This indicates a significant synergistic effect of harmol and syringic acid.

[0070] Aspergillus brasiliensis Harmol / Syringic Acid Syringic acid alone demonstrated an MIC of >50 mg / mL against Aspergillus brasiliensis. Harmol alone demonstrated an MIC of 12.5 mg / mL against Aspergillus brasiliensis. In combination, 1.563 mg / mL harmol and 1.563 mg / mL syringic acid were required to achieve inhibitory effects, indicating significant synergy between harmol and syringic acid.

[0071] The data provided above surprisingly demonstrates that the combination of natural antimicrobial components consistent with the present invention exhibits synergistic effects against Enterobacter gergoviae and Aspergillus brasiliensis.

Claims

1. (a) a first component comprising a beta-carboline alkaloid; and (b) a second component comprising a phenolic acid, a phenolic acid salt, or both; and The beta-carboline alkaloid has the formula: 【Chemistry 1】 wherein each R is independently hydrogen or C １ -C ４ and the phenolic acid is represented by the formula: 【Chemistry 2】 Represented by: Furthermore, R １ , R ２ and R ３ each independently represents hydrogen or C １ -C ４ is alkyl, the beta-carboline alkaloid comprises 1-methyl-9H-pyrido[3,4-b]indol-7-ol (harmol); An antibacterial system wherein the phenolic acid comprises 4-hydroxy-3,5-dimethoxybenzoic acid (syringic acid) and the phenolic acid salt comprises a salt of 4-hydroxy-3,5-dimethoxybenzoic acid.

2. 2. The antimicrobial system of claim 1, wherein the antimicrobial system comprises a sodium, calcium, magnesium and / or ammonium salt of the phenolic acid.

3. 3. The antibacterial system according to claim 1 or 2, wherein the ratio of carboline alkaloid to phenolic acid or salt thereof is in a weight ratio of from 0.75:8 to 0.75:48, preferably from 0.85:4 to 1:44, most preferably from 0.95:3 to 2:

40.

4. (a) a first component comprising a beta-carboline alkaloid; and (b) a second component comprising a phenolic acid, a phenolic acid salt, or both; and (c) A cosmetically acceptable carrier 1. An end-use composition comprising an antimicrobial system comprising: The beta-carboline alkaloid has the formula: 【Chemistry 3】 wherein each R is independently hydrogen or C １ -C ４ and the phenolic acid is represented by the formula: 【Chemistry 4】 [In the formula, R １ , R ２ and R ３ Each of the is independently hydrogen or C １ -C ４ is alkyl. an end-use composition wherein the beta-carboline alkaloid comprises 1-methyl-9H-pyrido[3,4-b]indol-7-ol (harmol), the phenolic acid comprises 4-hydroxy-3,5-dimethoxybenzoic acid (syringic acid), and the phenolate comprises a salt of 4-hydroxy-3,5-dimethoxybenzoic acid.

5. 5. The end-use composition of claim 4, wherein said composition further comprises a sodium, potassium, calcium, magnesium and / or ammonium salt of said phenolic acid.

6. 6. The end use composition according to claim 4 or 5, wherein the ratio of carboline alkaloid to phenolic acid or its salt is in a weight ratio of from 0.75:8 to 0.75:48, preferably from 0.85:4 to 1:44, most preferably from 0.95:3 to 2:

40.

7. 7. The end use composition of any one of claims 4 to 6, wherein the composition is a shampoo, cream, lotion, serum, gel, balm, deodorant, antiperspirant, oral care composition, conditioner, bar and liquid cleaning product.

8. 8. The end use composition of any one of claims 4 to 7, wherein the composition is substantially free of parabens, formaldehyde donors, phenoxyethanol, silicones, sulfates, or mixtures thereof, and further comprises terpineol, thymol, niacinamide, 12-hydroxystearic acid, retinol, resorcinol, or mixtures thereof.

9. The end use composition of any one of claims 4 to 8, wherein said antimicrobial system retains said end use composition and is an antimicrobial agent to surfaces with which it comes in contact.

10. 10. The end use composition according to any one of claims 4 to 9, wherein the antimicrobial system comprises 0.7 to 5 wt. %, preferably 0.8 to 4 wt. %, most preferably 0.9 to 3 wt. % carboline alkaloid, based on the total weight of the carboline alkaloid and the phenolic acid or salt thereof in the antimicrobial system, or wherein the antimicrobial system comprises 45 to 78 wt. %, preferably 50 to 75 wt. %, most preferably 58 to 70 wt. % carboline alkaloid, based on the total weight of the carboline alkaloid and the phenolic acid or salt thereof in the antimicrobial system.

11. 4. Non-therapeutic use of an antimicrobial system according to any one of claims 1 to 3 to provide an antimicrobial effect to a subject by holding an end use composition or contacting the subject with a composition comprising said antimicrobial system.

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