Antibacterial systems containing beta-carboline and indole alkaloids and compositions containing them - Patents.com

Abstract

Antimicrobial systems containing naturally derived components and compositions containing them are described, the systems having a first component that includes an indole alkaloid and a second naturally derived component that includes a beta-carboline alkaloid, and the systems and compositions provide superior antimicrobial efficacy.

Description

[Technical field]

[0001] The present invention relates to an antimicrobial system comprising naturally occurring ingredients. In particular, the present invention relates to a beta-carboline alkaloid and indole alkaloid comprising antimicrobial system that can be included in end-use formulations such as cosmetics, pharmaceuticals, 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 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 ingredients including 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 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 an effective, non-skin sensitizing, and environmentally sustainable antimicrobial system. 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 an indole alkaloid. 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 an indole alkaloid and / or a salt thereof; and (b) a second component containing a beta-carboline alkaloid 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 an indole alkaloid and / or a salt thereof; and (b) a second component containing a beta-carboline alkaloid 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 an indole alkaloid and / or a salt thereof and a second component comprising a beta-carboline alkaloid.

[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 an indole alkaloid and / or a salt thereof and a second component comprising a beta-carboline alkaloid.

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

[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 found in preservatives in compositions and 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 ATCC33028 of the family Pluralibacter gergoviae, a gram-negative rod that often exhibits resistance to parabens, or such bacteria and Aspergillus brasiliensis ATCC16404, a fungus of the genus Aspergillus. At least two component systems means that they include at least one component that is an indole alkaloid and at least one component that is a beta carboline alkaloid (i.e., they can be sold as separate additive compositions for addition to end-use compositions or can be added separately with the components to make the desired end-use composition). Naturally derived means that they do not require synthetic production and are suitable for recovery (in at least one form) from fruits, plants, and / or roots. Thus, naturally derived includes analogs / derivatives of the components that are used immediately as extracted or isolated from the natural source. For example, in the case of indole alkaloids, naturally derived includes components such as gramine that are naturally recovered from plants by commercially known extraction methods and derivatives thereof are made by art recognized techniques used to make alkaloid heterocycles.

[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, compositions comprising preservative portions including harmol and gramine are 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. Often, a green extraction process using ethyl acetate and sodium bicarbonate is used instead of the common extraction process, particularly using chloroform. Natural sources of the beta-carboline alkaloids used in the present invention are fruits such as sea buckthorn berries and plants such as the roots of the harmala plant. Alkylation of the naturally 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]

[0021] wherein each R is independently hydrogen or C1-C4 alkyl.

[0022] 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.

[0023] There are no limitations on how the indole alkaloid-containing components used in the present invention are naturally derived, except that the acquisition is preferably done in the most sustainable way. For example, solid phase extraction with water is often a desirable 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 reed trees, European maples, and grasses such as Hordeum vulgare and Phragmites canaryense. Commercially available mixed-mode polymeric sorbents designed to enhance selectivity and sensitivity for the extraction of such compounds using cation exchange groups are also an option for use. With regard to indole alkaloid derivatives, one method used to produce such derivatives is the Fischer-indole type process.

[0024] Exemplary indole alkaloids suitable for use in the present invention are represented as follows: [ka]

[0025] In the formula, R 1 and R 2 are each independently H or a C1-C2 alkyl group; R 3 and R 4 are each independently a C1-C2 alkyl group. In a preferred embodiment, R 1 and R 2 is hydrogen, and R 3 and R 4 is 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 when the pH of the end-use composition is between 5 and 7. With regard to ingredients used for suitable counter anions, they are limited only to the extent that they are compatible in the end-use composition to be used by the consumer, particularly topically on the skin. Illustrative non-limiting examples of counter anions suitable for use include halogens (e.g., Cl,- ), phosphate ion, sulfate ion, carbonate ion and organic carboxylate ion (e.g., YCOO - ;Y is C1-C 17 It can be a straight chain, branched, saturated, unsaturated or substituted hydrocarbon.

[0026] The weight ratio of indole alkaloids to beta-carboline alkaloids used herein is often from 0.5:9 to 3:10, preferably from 0.65:7 to 4:9, and most preferably from 0.75:4 to 5:8.

[0027] In one embodiment of the invention, 1 to 80% by weight, preferably 10 to 75% by weight, and most preferably 30 to 75% by weight, of the antibacterial system is an indole alkaloid, based on the total weight of the indole alkaloids and beta-carboline alkaloids, including salts.

[0028] Typically, end-use compositions made with the antimicrobial system of the present invention have a total weight of antimicrobial system (i.e., indole alkaloids and beta-carboline alkaloids) 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.

[0029] 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.

[0030] 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.

[0031] 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.

[0032] 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).

[0033] 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.

[0034] An often preferred silicone source is a solution of cyclopentasiloxane and dimethiconol.

[0035] 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.

[0036] 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 With fatty alcohol or acid hydrophobe; 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 20 fatty acids; and polyoxyethylene sorbitan, and combinations thereof.Alkyl polyglycosides and monosaccharide fatty amides (e.g., methyl gluconamides) are also suitable nonionic emulsifiers.

[0037] Suitable anionic emulsifiers that can be used include alkyl ether sulfates and sulfonates, alkyl sulfates and sulfonates, alkyl benzene sulfonates, alkyl and dialkyl sulfosuccinates, C8-C 20 Acylisethionate, C8-C 20 These include alkyl ether phosphates, alkyl ether carboxylates, and combinations thereof.

[0038] Cationic emulsifiers that can 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.

[0039] Other currently preferred emulsifiers include glyceryl stearate, glycol stearate, stearamide AMP, PEG-100 stearate, cetyl alcohol and emulsifying / thickening additives such as hydroxyethyl acrylate / sodium acryloyldimethyltaurate copolymer / squalene and mixtures thereof.

[0040] Although not required, preservatives may be incorporated into end-use compositions containing the antimicrobial system of the present invention to help prevent the growth of potentially harmful microorganisms. Conventional preservatives suitable for optional use in the end-use compositions of the present invention include alkyl esters of para-hydroxybenzoic 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 used in the present invention are 1,2-alkanediols, such as 1,2-octanediol and 1,2 hexanediol.

[0041] Conventional fragrance ingredients (added separately or together with the fragrance in the end use composition) such as eugenol, coumarin, thymol, terpineol, linalyl acetate, citronellal, iris concentrate, terpinyl acetate, pinenes (alpha and beta pinene) and citronellol may also be added.

[0042] If used, conventional preservatives, vicinal diols and / or fragrance ingredients will comprise no more than 2 wt. %, preferably no more than 1 wt. %, and most preferably no more than 0.6 wt. % or no more than 0.2 wt. % of the end-use composition of the present invention. In one embodiment of the present invention, 0.0001 to 0.85 wt. % of any preservative, vicinal diol and / or fragrance ingredient is used, based on the total weight of the end-use composition. 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 include 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 compositions of the present invention are silicone-free and / or free of sulfate-containing components (ie, 0.0 wt %).

[0043] 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.

[0044] 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.

[0045] Fragrances, fixatives and abrasives may also be used in end use compositions containing the antimicrobial system 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.

[0046] 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% by weight of the end use composition.

[0047] Vitamins may also be included in the end use compositions of the present invention. Examples of vitamins include vitamin A (retinol) and retinol esters such as 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, vitamin C derivatives include ascorbyl tetraisopalmitate, magnesium ascorbyl phosphate and ascorbyl glycosides. Derivatives of vitamin E include tocopheryl acetate, tocopheryl palmitate, tocopheryl linoleate and the like. 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.

[0048] 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; alpha- and / or beta-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 (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. 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.

[0049] 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 to the free acid as well as its salts, C1-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.

[0050] 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.

[0051] Also suitable for use are optional chelating agents (e.g., EDTA), opacifiers (TiO2, particle size 50-1200 nm, preferably 50-350 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.

[0052] 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.

[0053] 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.

[0054] In yet another embodiment of the present invention, and when the end use composition is a conventional cleansing or cleaning composition, the 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 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).

[0055] 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.

[0056] 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.

[0057] 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. [Table 1] [Table 2] [Table 3] [Table 4]

[0058] 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.

[0059] 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.

[0060] 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.

[0061] The following examples are provided to facilitate understanding of the invention and are not intended to limit the scope of the claims.

[0062] 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.

[0063] A natural antibacterial system was created by combining indole alkaloids and beta-carboline alkaloids 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.

[0064] 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:

[0065] 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."

[0066] 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.

[0067] A ΣFIC of 0.5 or less corresponds to synergistic activity.

[0068] 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).

[0069] 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. [Table 5]

[0070] Synergistic Combinations Enterobacter gergoviae Grameen and Halmor Gramine alone showed a minimum inhibitory concentration (MIC) of 6.25 mg / mL against Enterobacter gergoviae. Harmol alone showed an MIC of 0.313 mg / mL against Enterobacter gergoviae. In combination, a combination of 0.098 mg / mL of gramine and 0.020 mg / mL of harmol was required to achieve an inhibitory effect. This indicates a significant synergistic effect of gramine and harmol.

[0071] Aspergillus brasiliensis Grameen / Halmor Gramine alone showed an MIC of 6.25 mg / mL against Aspergillus brasiliensis. Harmol alone showed an MIC of 6.25 mg / mL against Aspergillus brasiliensis. In combination, 1.563 mg / mL of gramine and 1.56 mg / mL of harmol were required to achieve an inhibitory effect, indicating a significant synergistic effect of gramine and harmol.

[0072] The data provided above surprisingly demonstrates that the combination of natural antimicrobial components consistent with the present invention unexpectedly exhibits synergistic effects against Enterobacter gergoviae and Aspergillus brasiliensis.

Claims

1. (a) a first component comprising an indole alkaloid, a salt thereof, or both; and (b) a second component comprising a beta-carboline alkaloid or a salt thereof. An antibacterial system comprising: The beta-carboline alkaloid has the formula: 【Chemistry 1】 wherein each R is independently hydrogen or C １ -C ４ wherein the indole alkaloid is represented by the formula: 【Chemistry 2】 [In the formula, R １ and R ２ are each independently H or C １ -C ２ is an alkyl group, R ３ and R ４ are each independently C １ -C ２ is an alkyl group. the indole alkaloid comprises 1-(1H-indol-3-yl)-N,N-dimethylmethanamine (gramin); An antibacterial system wherein the beta-carboline alkaloid comprises 1-methyl-9H-pyrido[3,4-b]indol-7-ol (harmol).

2. 10. The antimicrobial system of claim 1, wherein the antimicrobial system further comprises terpineol, thymol, 12-hydroxystearic acid, resorcinol, retinol, niacinamide, or mixtures thereof.

3. -OR is a hydroxyl group, -NR is -NH, the beta-carboline alkaloid is 1-methyl-9H-pyrido[3,4-b]indol-7-ol, and R １ and R ２ is hydrogen, R ３ and R ４ CH ３ 3. The antibacterial system according to claim 1 or 2, wherein the indole alkaloid is 1-(1H-indol-3-yl)-N,N-dimethylmethanamine.

4. 10. An antibacterial system according to any one of the preceding claims, wherein the weight ratio of indole alkaloid to beta-carboline alkaloid is from 0.5:9 to 3:10, preferably from 0.65:7 to 4:9, most preferably from 0.75:4 to 5:

8.

5. 10. An antibacterial system according to any one of the preceding claims, wherein 1 to 80% by weight, preferably 10 to 75% by weight, most preferably 30 to 75% by weight of the antibacterial system is indole alkaloids, based on the total weight of indole alkaloids and beta-carboline alkaloids, including salts.

6. (a) a first component comprising an indole alkaloid, a salt thereof, or both; and (b) a second component comprising a beta-carboline alkaloid, a salt thereof, 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 wherein the indole alkaloid is represented by the formula: 【Chemistry 4】 [In the formula, R １ and R ２ are each independently H or C １ -C ２ is an alkyl group, R ３ and R ４ are each independently C １ -C ２ is an alkyl group. the indole alkaloid comprises 1-(1H-indol-3-yl)-N,N-dimethylmethanamine (gramin); The end-use composition wherein the beta-carboline alkaloid comprises 1-methyl-9H-pyrido[3,4-b]indol-7-ol (harmol).

7. 7. The end use composition of claim 6, wherein said composition further comprises terpineol, thymol, 12-hydroxystearic acid, resorcinol, retinol, niacinamide, or mixtures thereof.

8. -OR is a hydroxyl group, -NR is -NH, the beta-carboline alkaloid is 1-methyl-9H-pyrido[3,4-b]indol-7-ol, and R １ and R ２ is hydrogen, R ３ and R ４ CH ３ 8. The end use composition of claim 6 or 7, wherein said indole alkaloid is 1-(1H-indol-3-yl)-N,N-dimethylmethanamine.

9. 9. The end use composition according to any one of claims 6 to 8, wherein the indole alkaloid:beta-carboline alkaloid is in a weight ratio of from 1:15 to 5:1, preferably from 1:12 to 4:1, most preferably from 1:11 to 3.25:

1.

10. 10. The end use composition according to any one of claims 6 to 9, wherein the weight ratio of indole alkaloids to beta-carboline alkaloids is from 0.5:9 to 3:10, preferably from 0.65:7 to 4:9, most preferably from 0.75:4 to 5:

8.

11. 11. The end use composition of any one of claims 6 to 10, wherein the composition is substantially free of parabens, formaldehyde donors, phenoxyethanol, silicones, sulfates or mixtures thereof, and further wherein the composition is a shampoo, cream, lotion, serum, gel, balm, deodorant, antiperspirant, oral care composition, conditioner, cleansing bar or liquid cleaning product, and wherein the composition optionally comprises thiamidol.

12. The end use composition of any one of claims 6 to 11, wherein the antimicrobial system preserves the end use composition and is an antimicrobial agent for surfaces it comes in contact with.

13. 6. Non-therapeutic use of an antimicrobial system according to any one of claims 1 to 5 for preserving an end-use composition or for providing an antimicrobial effect to a subject by contacting the subject with a composition comprising said antimicrobial system.

Images