Topical Compositions Comprising Hydroxamic Acids and Atractylenolides

Abstract

Disclosed is a topical composition comprising (i) an antimicrobial active, which is at least one of a hydroxamic acid or a hydroxamic acid derivative, and (ii) an atractylenolide compound, wherein the weight ratio of the amount of the atractylenolide compound to the amount of the antimicrobial active is at least 5: 1. Also disclosed is a non-therapeutic method of providing a local antimicrobial effect to a topical surface of the human or animal body, comprising applying a safe and effective amount of the topical antimicrobial composition.

Description

[Technical Field]

[0001] The present invention relates to topical antimicrobial compositions, particularly cosmetic compositions, and more particularly to cosmetic compositions containing active agents that interact to provide a synergistic antimicrobial effect and are useful against at least some microorganisms associated with cosmetically relevant conditions, such as dandruff and acne. [Background technology]

[0002] The present invention relates to antimicrobial compositions useful for cleansing and / or caring for any body part, but particularly suitable for hair and scalp care, hand hygiene, or facial care and cleansing.

[0003] Dandruff is a problem affecting many people worldwide. The condition manifests itself as the shedding of clumps of dead skin cells from the scalp. These are white and easily visible, resulting in an aesthetically unpleasing appearance. One factor contributing to dandruff is certain members of the Malassezia yeast family. To combat them, various anti-dandruff compositions, such as shampoos, are available. Typically, such shampoos contain a surfactant and one or more anti-dandruff agents. Typical anti-dandruff agents include metal pyrithiones, e.g., zinc pyrithione (ZPTO), octopirox (piroctone olamine), azole antimicrobials (e.g., climbazole), selenium sulfide, and combinations thereof.

[0004] Although the problem of dandruff is significantly reduced by the use of the above actives in such shampoos, there is a need for more effective compositions.

[0005] Acne, also known as acne vulgaris, is a common skin condition affecting nearly all adolescents and adults. It has a complex etiology involving abnormal keratinization and excessive sebum production. Acne typically occurs in areas rich in sebaceous glands, such as the face, neck, and back. The bacterium Cutibacterium acnes (C. acnes, formerly known as Propionibacterium acnes or P. acnes) has also been implicated in the development of acne. Acne has been treated in many ways. Most treatments require weeks to months before noticeable changes are seen. Benzoyl peroxide, which has antibacterial properties, has been used in cases of mild acne and is thought to prevent further acne formation. Antibiotics such as tetracycline, erythromycin, and clindamycin have been used in cases of very severe acne.

[0006] XP055720751 (Mingchen Cosmetics) discloses a premium treatment shampoo containing piroctone olamine and Atractylodes lancea root extract, although the weight ratio of piroctone olamine to Atractylodes lancea root extract is not disclosed.

[0007] Chinese Patent No. 110693751 (Zhou Le) discloses a beauty cream containing (i) caprylhydroxamic acid and (ii) Atractylodes root powder and Atractylodes chinensis extract or Atractylodes sanguinea extract, although the weight ratio of caprylhydroxamic acid to the root powder and Atractylodes chinensis extract or Atractylodes sanguinea extract is not disclosed.

[0008] Chinese Patent No. 110787069 (Luo Xianyi) discloses a face mask containing (i) an extract of Atractylodes macrocephalae and (ii) capryloyl hydroxamic acid or octanoyl hydroxamic acid, although the weight ratio of (i) to (ii) is not disclosed.

[0009] Chinese Patent No. 109700733 (Zhangjiajie Chakunyuan Biotechnology Dev Co Ltd) discloses a face mask containing (i) Atractylodes macrocephalae extract (as part of Ecommia seed plant extract) and (ii) caprylic / octyl / octanoyl hydroxamic acid, although the weight ratio of (i) to (ii) is not disclosed. It is therefore an object of the present invention to provide a topical composition that exhibits synergistic antimicrobial activity compared to the individual components. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] XP055720751 [Patent Document 2] Chinese Patent No. 110693751 [Patent Document 3] Chinese Patent No. 110787069 [Patent Document 4] Chinese Patent No. 109700733 Summary of the Invention [Problem to be solved by the invention]

[0011] The present inventors have found that when a specific active substance that is normally found in natural plants is formulated with a typical antimicrobial active substance that is a hydroxamic acid or a hydroxamic acid derivative, the combination is highly effective against some microorganisms associated with conditions such as dandruff and acne.This has led to the inference that a composition comprising the above combination can have anti-dandruff, anti-acne and general antimicrobial activity, and can be suitable for use in, for example, shampoo, body care and face care.The specific active substance referred to above is atractylenolide compound. [Means for solving the problem]

[0012] Thus, according to the first aspect, (i) an antimicrobial active agent that is at least one of a hydroxamic acid or a hydroxamic acid derivative; (ii) a topical composition comprising an atractylenolide compound, wherein the weight ratio of the amount of the atractylenolide compound to the amount of the antimicrobial active is at least 5:1.

[0013] According to a second aspect, a topical composition of the first aspect is disclosed for use in providing an antimicrobial effect to a topical surface of the human or animal body.

[0014] According to a third aspect, a non-therapeutic method of providing a topical antimicrobial effect to a topical surface of the human or animal body is disclosed, comprising applying a safe and effective amount of the topical antimicrobial composition of the first aspect. DETAILED DESCRIPTION OF THE INVENTION

[0015] The compositions according to the present invention comprise a topically acceptable carrier, vehicle, or diluent, which can have a variety of different forms. A topically acceptable carrier should preferably be non-irritating. Thus, "topically acceptable" means that the carrier is suitable for topical application to the skin without raising any adverse safety or toxicity concerns. In other words, these carriers are suitable for use on mammalian skin. Typical carriers can be in the form of water-alcohol systems (e.g., liquids and gels), anhydrous oil or silicone systems, or emulsion systems, including, but not limited to, oil-in-water, water-in-oil, water-in-oil-in-water, and oil-in-water-in-silicone systems. Emulsions can encompass a wide range of consistencies, including thin lotions (which may also be suitable for spray or aerosol delivery), creamy lotions, light creams, and heavy creams. Emulsions can also include microemulsion systems. Other suitable topical carriers include anhydrous solids and semisolids (such as gels and sticks), as well as aqueous-based mousse systems. Non-limiting examples of topical carrier systems useful in the present invention are described below.

[0016] These and other aspects, features, and advantages will become apparent to those skilled in the art upon reading the following detailed description and the appended claims. For the avoidance of doubt, any feature of one aspect of the present invention may be utilized in any other aspect of the present invention. The term "comprising" is intended to mean "including," but does not necessarily mean "consisting of" or "composed of." In other words, the listed steps or options need not be exhaustive. It should be noted that the examples set forth in the following description are intended to clarify the invention, but are not intended to limit the invention to those examples themselves. Similarly, all percentages and ratios contained herein are weight / weight percentages unless otherwise indicated.

[0017] Except in the operating and comparative examples, or where otherwise expressly stated, all numbers in this specification expressing amounts of materials or reaction conditions, physical properties of materials and / or uses, should be understood to be modified by the term "about." Unless otherwise specified, numerical ranges expressed in the format "x to y" are understood to include x and y. When multiple preferred ranges for a particular feature are described in the format "x to y," it is understood that all ranges combining the different endpoints are also contemplated. Various features of the invention referred to in individual sections above apply mutatis mutandis to other sections, as appropriate. Thus, features specified in one section can be combined with features specified in other sections, as appropriate. Any section headings are added for convenience only and are not intended to limit the disclosure in any way.

[0018] A topical composition refers to a leave-on or wash-off composition intended for external use on mammals, particularly humans, for example, for cleaning or disinfecting localized areas such as the skin and / or hair and / or oral cavity. Such compositions include any product applied to the human body to improve appearance, cleansing, odor control, or general aesthetics. In one embodiment, the compositions according to the present invention are rinse-off compositions. Alternatively, they are leave-on compositions. The compositions of the present invention may be in the form of a liquid, lotion, cream, foam or gel, or toner, or may be applied with a device or via a face mask, pad, or patch. As used herein, "skin" refers to the skin on the face and body (e.g., neck, chest, back, arms, armpits, hands, legs, buttocks, and scalp). The compositions of the present invention also relate to application to any other external substrate of the human body other than the skin, such as hair.

[0019] As used herein, the term "antimicrobial composition" refers to a composition for topical application to the skin, hair, and / or scalp of mammals, particularly humans. Such compositions are generally applied to the desired topical surface of the body for a period of from a few seconds to up to 24 hours. For example, if the application time is short, from a few seconds to a few minutes, and the composition is then rinsed off with water or wiped away, such a composition is known as a cleansing or rinse-off composition. If the composition is applied for a longer period of time, from about a few minutes to 24 hours, and is typically washed off during normal personal cleansing procedures, such a composition is known as a leave-on composition. The composition is more preferably used to prevent or alleviate dandruff symptoms on the scalp and / or hair, for anti-acne effects, or to disinfect hands or other parts of the human body.

[0020] As used herein, "hair care composition" refers to the composition for topical application to hair.Non-limiting examples of such compositions include leave-on hair lotions, creams, and wash-off shampoos, conditioners, shower gels, or toilet bars.When the composition of the present invention is a hair care composition, it is preferably a wash-off composition, particularly a shampoo or conditioner.

[0021] The present invention provides (i) an antimicrobial active agent that is at least one of a hydroxamic acid or a hydroxamic acid derivative; (ii) a topical composition comprising an atractylenolide compound, wherein the weight ratio of the amount of the atractylenolide compound to the amount of the antimicrobial active is at least 5:1.

[0022] Hydroxamic Acids and Hydroxamic Acid Derivatives Hydroxamic acids are a class of organic compounds that have the functional group RC(O)N(OH)R' with R and R' as the organic residues and CO as the carbonyl group.

[0023] The hydroxamic acid derivative of the present invention refers to a class of organic compounds having a functional group RC(O)N(O)R' with R and R' as the organic residue. Preferably, the hydroxamic acid derivative is a salt of hydroxamic acid. More preferably, the hydroxamic acid derivative is an olamine salt of hydroxamic acid.

[0024] The antimicrobial active substance according to the present invention is at least one hydroxamic acid or hydroxamic acid derivative. The hydroxamic acid is preferably piroctone, caprylhydroxamic acid, or benzohydroxamic acid, more preferably caprylhydroxamic acid. The hydroxamic acid derivative is preferably piroctone olamine.

[0025] Thus, the antimicrobial active substance according to the present invention is preferably at least one of piroctone, caprylhydroxamic acid, benzohydroxamic acid, or piroctone olamine. More preferably, the antimicrobial active substance according to the present invention is at least one of caprylhydroxamic acid or piroctone olamine. Most preferably, the antimicrobial active substance is piroctone olamine.

[0026] Piroctone is a cyclic hydroxamic acid consisting of 1-hydroxypyridin-2-one with methyl and 2,4,4-trimethylpentyl substituents at positions 4 and 6, respectively. Its CAS number is 50650-76-5, and the compound has the following general formula (a): [ka]

[0027] Caprylhydroxamic acid is an amino acid derived from coconut oil. Caprylhydroxamic acid is an antiseptic and broad-spectrum antifungal agent. Its CAS number is 7377-03-9, and the compound has the following general formula (b): [ka]

[0028] Benzohydroxamic acid is a hydroxamic acid. Its CAS number is 495-18-1, and the compound has the following general formula (c): [ka]

[0029] Piroctone olamine is the olamine salt of the hydroxamic acid derivative piroctone, a typical antimicrobial active substance. Piroctone olamine is commonly known as piroctone ethanolamine, which has the trade name Octirox®.

[0030] Piroctone olamine according to the present invention is a 1:1 compound of 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridinone and 2-aminoethanol, also known as 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)pyridinone monoethanolamine salt, CAS number 68890-66-4, and the compound has the following general formula (d): [ka]

[0031] The amount of at least one antimicrobial active, which is a hydroxamic acid or hydroxamic acid derivative, in the compositions of the present invention will depend on the type of topical composition and the exact nature of any other antimicrobial actives used. Preferably, the compositions comprise 0.01 to 10% by weight of the composition of said antimicrobial active, more preferably 0.1 to 5% by weight, and even more preferably 0.5 to 3% by weight.

[0032] Atractylenolide compounds The compositions of the present invention contain atractylenolide compounds. The atractylenolide compounds are eudesmane-type sesquiterpenoid lactones that can be found in Atractylodes, including atractylenolide I, atractylenolide II, atractylenolide III, atractylenolide IV, and 4(R),15-epoxy-8β-hydroxyatractylenolide II. The term "atractylenolide compounds" is used to indicate the presence of one or more compounds belonging to a generalized class of compounds having the basic structural formula of eudesmane-type sesquiterpenoid lactones that can be found in Atractylodes. Such atractylenolide compounds can also be found in the plants Sarcandra glabra or Chloranthus serratus.

[0033] The amount of atractylenolide compound in the composition of the present invention is preferably 0.01 to 10% by weight. More preferably, the amount is 0.01 to 5%, and most preferably 0.1 to 2% by weight of the composition. When two or more atractylenolide compounds are present in the composition of the present invention, their total amount is as disclosed above.

[0034] The atractylenolide compound according to the present invention is preferably at least one of atractylenolide I (CAS 73069-13-3), atractylenolide II (CAS 73069-14-4), or atractylenolide III (CAS 73030-71-4). Atractylenolide compounds I, II, and III have the following corresponding general formulas (I, II, and III): [ka]

[0035] It is particularly preferred that the atractylenolide compound according to the present invention is at least one of atractylenolide I and atractylenolide II. Alternatively, and more preferably, the composition comprises atractylenolide I and atractylenolide II. When the composition comprises both atractylenolide I and atractylenolide II, the composition preferably comprises 0.01 to 10% by weight of the atractylenolide I or 0.01 to 10% by weight of the atractylenolide II, provided that the combined amount of both compounds is 0.01 to 10% by weight of the composition.

[0036] Preferably, the compositions of the present invention comprise an extract of Atractylodes species, or an extract of Sarcandra chinensis or Shizuka Misao, containing the atractylenolide compounds described above, wherein the measured amount of the extract is selected so as to include the required amount of the atractylenolide compounds contained therein in the composition.

[0037] Generally, Atractylodes is a genus in the botanical family Asteraceae. Extracts of Atractylodes can be obtained from species within the genus Atractylodes. Non-limiting examples of these species include Atractylodes amurensis, Atractylodes serrata, Atractylodes carlinoides, Atractylodes macrocephala, Atractylodes japonica, Atractylodes koreana, Atractylodes ovata, and Atractylodes chinensis.

[0038] Atractylodes extracts containing atractylenolide compounds are commercially available from a variety of different sources. For example, an extract of Atractylodes macrocephala root containing both atractylenolide I and atractylenolide II is available from Hangzhou Liaoyuan. Individual atractylenolides I and II are available from MCE. Alternatively, one skilled in the art could isolate an Atractylodes extract from Atractylodes root using any suitable isolation and purification method known in the art. In some embodiments, an Atractylodes extract may be obtained from dried Atractylodes plant root and prepared by any means known or developed in the art.

[0039] Because the composition contains piroctone olamine and an atractylenolide compound, a ratio between the amounts of the active ingredients is maintained to achieve efficacy. The weight ratio of the atractylenolide compound to the antimicrobial active substance is at least 5:1. Preferably, the weight ratio of the atractylenolide compound to the antimicrobial active substance is 5:1 to 1280:1, more preferably 5:1 to 100:1, even more preferably 5:1 to 50:1, even more preferably 5:1 to 40:1, even more preferably 5:1 to 20:1, and particularly preferably 5:1 to 10:1.

[0040] In the context of combinations of antimicrobial ingredients, the sum of fractional inhibitory concentrations (ΣFIC) is widely used. It is a means of determining whether antimicrobial ingredients (when used in combination) have a synergistic or antagonistic effect, or neither of the two, i.e., an additive effect. We used the ΣFIC test to evaluate the combined effects of antimicrobial actives with atractylenolide I or atractylenolide II against M. furfur.

[0041] It is believed that during the presence of an antimicrobial active according to the present invention and an atractylenolide compound in the compositions of the present invention, the atractylenolide compound interacts synergistically with the antimicrobial active to become more effective.

[0042] The topical compositions of the present invention preferably comprise piroctone olamine and atractylenolide I. In this case, the weight ratio of the amount of atractylenolide I to the amount of piroctone olamine is at least 5:1. In this case, the weight ratio of the amount of atractylenolide I to the amount of piroctone olamine is preferably from 5:1 to 1280:1, alternatively from 5:1 to 100:1, alternatively from 5:1 to 50:1, alternatively from 5:1 to 40:1, and further alternatively from 5:1 to 10:1.

[0043] Alternatively, the composition comprises piroctone olamine and atractylenolide II, wherein the weight ratio of the amount of atractylenolide II to the amount of piroctone olamine is at least 5:1. Preferably, the weight ratio of the amount of atractylenolide II to the amount of piroctone olamine is 5:1 to 2560:1, alternatively 5:1 to 100:1, alternatively 5:1 to 80:1, alternatively 5:1 to 50:1, and further alternatively 5:1 to 10:1.

[0044] The topical compositions of the present invention preferably comprise caprylhydroxamic acid and atractylenolide I. In this case, the weight ratio of the amount of atractylenolide I to the amount of caprylhydroxamic acid is at least 5:1. In this case, the weight ratio of the amount of atractylenolide I to the amount of caprylhydroxamic acid is preferably from 5:1 to 1280:1, alternatively from 5:1 to 100:1, alternatively from 5:1 to 50:1, alternatively from 5:1 to 40:1, and further alternatively from 5:1 to 10:1.

[0045] Alternatively, the composition comprises caprylhydroxamic acid and atractylenolide II, wherein the weight ratio of the amount of atractylenolide II to the amount of caprylhydroxamic acid is at least 5:1. In this case, the weight ratio of the amount of atractylenolide II to the amount of caprylhydroxamic acid is preferably 5:1 to 2560:1, alternatively 5:1 to 100:1, alternatively 5:1 to 80:1, alternatively 5:1 to 50:1, and further alternatively 5:1 to 10:1.

[0046] Other ingredients Preferably, the compositions of the present invention further comprise a cosmetically acceptable vehicle such that the composition may be formulated as, for example, a shampoo, conditioner, body wash, hand or face wash, cream, lotion, gel, powder, ointment, hand sanitizer, or soap bar, with the remaining ingredients varying accordingly.

[0047] In one aspect, the topical composition according to the present invention is a hair care composition. Preferably, such a composition is a shampoo, a hair conditioner, a hair serum, or a hair oil. Most preferably, the topical composition is an anti-dandruff composition that is effective against at least some Malassezia species.

[0048] When the composition of the present invention is a shampoo, it preferably includes other ingredients typically included in such compositions.

[0049] The shampoo preferably comprises 1 to 20% by weight, more preferably 2 to 16% by weight, and even more preferably 3 to 16% by weight of an anionic surfactant, such as an alkyl sulfate and / or ethoxylated alkyl sulfate surfactant. Preferred alkyl sulfates are C alkyl sulfates, preferably in the form of a salt with a solubilizing cation such as sodium, potassium, ammonium or substituted ammonium. 8~18 Alkyl sulfates, more preferably C 12~18 It is an alkyl sulfate.

[0050] Particularly preferred alkyl ether sulfates are those of the formula: RO(CH2CH2O) n SO -3 wherein R is alkyl or alkenyl having 8 to 18 (preferably 12 to 18) carbon atoms, n is a number at least greater than 0.5, preferably having an average value of 1 to 3, more preferably 2 to 3, and M is a solubilizing cation such as sodium, potassium, ammonium, or substituted ammonium. One example is sodium lauryl ether sulfate (SLES). SLES having an average degree of ethoxylation of 0.5 to 3, preferably 1 to 3, is particularly preferred.

[0051] The shampoo composition according to the present invention may contain one or more additional anionic cleansing surfactants that are cosmetically acceptable and suitable for topical application to hair. Examples include alkaryl sulfonates, alkyl succinates, alkyl sulfosuccinates, alkyl ether sulfosuccinates, N-alkyl sarcosinates, alkyl phosphates, alkyl ether phosphates, and alkyl ether carboxylic acids, as well as their salts, particularly their sodium, magnesium, ammonium, and mono-, di-, and triethanolamine salts. The alkyl and acyl groups generally contain 8 to 18, preferably 10 to 16, carbon atoms and may be unsaturated. The alkyl ether sulfosuccinates, alkyl ether phosphates, and alkyl ether carboxylic acids, as well as their salts, may contain 1 to 20 ethylene oxide or propylene oxide units per molecule.

[0052] Typically, suitable anionic surfactants include sodium oleyl succinate, ammonium lauryl sulfosuccinate, sodium lauryl ether sulfosuccinate, sodium dodecylbenzene sulfonate, triethanolamine dodecylbenzene sulfonate, lauryl ether carboxylic acid, and sodium N-lauryl sarcosinate. Suitable and preferred additional anionic cleansing surfactants are sodium lauryl ether sulfosuccinate (n)EO (n is 1 to 3), lauryl ether carboxylic acid (n)EO (n is 10 to 20).

[0053] Mixtures of any of the foregoing anionic cleansing surfactants may also be suitable.

[0054] The shampoo composition of the present invention preferably further comprises 0.1 to 10% by weight, more preferably 0.5 to 8% by weight, of an amphoteric surfactant, preferably a betaine surfactant such as an alkylamidopropyl betaine surfactant, for example cocoamidopropyl betaine.

[0055] The pH of the composition is preferably 4.0 or higher, and more preferably within the range of 5.0 to 10.0.

[0056] Preferably, the shampoo composition further comprises 0.1 to 3 wt. %, more preferably 0.1 to 1.5 wt. % of a zinc compound. The presence of zinc in the composition is believed to improve anti-dandruff benefits. Suitable zinc compounds are ZPTO, zinc oxide, zinc citrate, zinc malonate, zinc carbonate, or combinations thereof.

[0057] Preferably, the shampoo composition further comprises 0.01 to 2% by weight, more preferably 0.025 to 0.75% by weight, of a conazole fungicide. Preferably, the conazole fungicide is ketoconazole or climbazole or a mixture thereof. The presence of the conazole fungicide is believed to improve deposition of zinc pyrithione (ZPTO).

[0058] The shampoo composition further preferably contains a suspending agent. Suitable suspending agents are polyacrylic acid, crosslinked polymers of acrylic acid, copolymers of acrylic acid and hydrophobic monomers, copolymers of carboxylic acid-containing monomers and acrylic acid esters, crosslinked copolymers of acrylic acid and acrylate esters, heteropolysaccharide gums, and crystalline long-chain acyl derivatives. The long-chain acyl derivative is preferably selected from ethylene glycol stearate, alkanolamides of fatty acids having 16 to 22 carbon atoms, and mixtures thereof. Ethylene glycol distearate and polyethylene glycol distearate are preferred long-chain acyl derivatives because they impart a pearlescent appearance to the composition. Polyacrylic acid is commercially available as Carbopol® 420, Carbopol® 488, or Carbopol® 493. Polymers of acrylic acid crosslinked with polyfunctional agents may also be used. These are commercially available as Carbopol® 910, Carbopol® 934, Carbopol® 941, and Carbopol® 980. An example of a suitable copolymer of a carboxylic acid-containing monomer and an acrylic acid ester is Carbopol® 1342. All Carbopol™ materials are available from Goodrich.

[0059] A suitable crosslinked polymer of acrylic acid and acrylate ester is Pemulen® TR1 or Pemulen® TR2. A suitable heteropolysaccharide gum is xanthan gum, such as that available as Kelzan.

[0060] Mixtures of any of the above suspending agents may be used. Mixtures of crosslinked polymers of acrylic acid and crystalline long chain acyl derivatives are preferred.

[0061] When included, suspending agents are generally present at 0.1 to 10% by weight, preferably 0.5 to 6% by weight.

[0062] The compositions of the present invention may contain other ingredients to enhance performance and / or consumer acceptance, including fragrances, dyes and pigments, pH adjusters, pearlizing or opacifying agents, viscosity adjusters, preservatives, and natural hair nutrients such as botanicals, fruit extracts, sugar derivatives, and amino acids.

[0063] The shampoo composition is preferably aqueous based, preferably comprising 70 to 95% water by weight.

[0064] Hair conditioner Alternatively, the topical composition of the present invention is a hair conditioner.

[0065] When the conditioning effect is achieved through the composition of the present invention, the composition is called a hair conditioner. Typically, the most common conditioning agents used in hair care compositions are water-insoluble oily materials such as mineral oil, naturally occurring oils such as triglycerides and silicone polymers. The conditioning effect is achieved by the oily materials being deposited on the hair to form a film, which makes the hair easier to comb when wet and easier to manage when dry. A particularly useful conditioning agent is silicone, preferably non-volatile silicone. Advantageously, the composition herein can contain one or more silicones. Silicones are conditioning agents found in dispersed or suspended particulate form. They are intended to be deposited on the hair and remain after rinsing the hair with water. Suitable silicone oils can include polyalkylsiloxanes, polyarylsiloxanes, polyalkylarylsiloxanes, polyethersiloxane copolymers, and mixtures thereof. Aminosilicones are often incorporated into shampoo compositions. Aminosilicones are silicones containing at least one primary amine group, secondary amine group, tertiary amine group, or quaternary ammonium group. High molecular weight silicone gums can also be used. Another useful type is crosslinked silicone elastomers, such as dimethicone / vinyl / dimethicone crosspolymers (e.g., Dow Corning 9040 and 9041).

[0066] The hair conditioner composition of the present invention preferably contains 0.1 to 10% by weight of silicone, more preferably about 0.1 to about 8% by weight. Alternatively, the hair conditioner is silicone-free or contains 1% or less by weight of silicone. The pH of the composition is preferably greater than 4.0, more preferably 5.0 to 7.0.

[0067] The hair conditioner compositions of the present invention may also preferably contain 0.5 to 10% by weight of a fatty alcohol. The combination of a fatty alcohol and a cationic surfactant in the conditioning composition is believed to be particularly advantageous as it results in the formation of a lamellar phase in which the cationic surfactant is dispersed.

[0068] Representative fatty alcohols contain 8 to 22 carbon atoms, more preferably 16 to 22 carbon atoms. Fatty alcohols are typically compounds containing a straight-chain alkyl group. Examples of suitable fatty alcohols include cetyl alcohol, stearyl alcohol, and mixtures thereof. The use of these materials is also advantageous in that they contribute to the overall conditioning properties of the compositions of the present invention.

[0069] Skin cleansing The composition of the present invention can be used for skin care, for example, for cleansing the body or face. The topical composition can further comprise a surfactant. Preferred surfactants are nonionic surfactants.

[0070] Therefore, in a highly preferred embodiment, the topical composition comprises a surfactant selected from the group of anionic surfactants.

[0071] If a surfactant is present, the topical composition preferably comprises 1 to 90% surfactant by weight of the composition.

[0072] When a surfactant is used, a particularly preferred surfactant is soap, which is a suitable surfactant for personal washing applications of the topical compositions of the present invention.

[0073] When present, the soap of the present invention is preferably present in an amount of from 1 to 90%, preferably from 10 to 85%, more preferably from 25 to 75% by weight of the composition.

[0074] Preferred compositions may contain other known ingredients such as fragrances, pigments, preservatives, emollients, sunscreens, emulsifiers, gelling agents, thickeners, etc. The selection of these ingredients will largely depend on the form of the composition.

[0075] Water is a preferred carrier. When present, water is preferably present in an amount of at least 1%, more preferably at least 2%, and even more preferably at least 5% by weight of the composition. When water is the carrier, preferred liquid compositions contain 10 to 99.8% by weight of water. Liquid topical compositions are useful as skin disinfectants for cleansing the skin, particularly for hand or face washing. When water is the carrier, preferred solid compositions contain 5 to 30% by weight of water.

[0076] The solid topical composition is preferably in the form of a molded solid, more preferably a bar. Solid topical compositions are particularly useful for cleansing the skin, especially for hand or face washing.

[0077] In another embodiment, inorganic particulate materials are also suitable carriers.When inorganic particulate materials are the carrier, the topical composition is in solid form.Preferably, the inorganic particulate material is talc.When the inorganic particulate material is talc, the solid antimicrobial composition is particularly useful as a talcum powder for application to the face or body.

[0078] In another aspect of the invention, the compositions of the present invention are suitable for use in personal hygiene wipes.

[0079] Uses and methods according to the present invention According to a second aspect, the topical composition of the first aspect is disclosed for use in providing an antimicrobial effect to a topical surface of the human or animal body. Also disclosed is a topical composition for use against at least a portion of Malassezia species on the topical surface of the human or animal body. Preferably, the topical composition is an anti-dandruff composition effective against at least a portion of Malassezia species on the topical surface of the human or animal body. Alternatively, the topical composition is an anti-acne composition effective against at least C. acnes on the topical surface of the human or animal body. Alternatively, the topical composition is a rinse-off or leave-on composition effective against at least Staphylococcus aureus (S. aureus).

[0080] According to another aspect, a non-therapeutic method for providing a topical antimicrobial effect to a topical surface of the human or animal body is disclosed, comprising applying a safe and effective amount of the topical antimicrobial composition of the first aspect. The term safe and effective amount is well known to those skilled in the art, and such amount may vary depending on the product form; for example, for a leave-on composition, the amount may be 1-2 ml for each application, whereas for a shampoo, the same amount may be 5-10 ml for each application. The method is effective for preventing or alleviating acne, dandruff, or treatment It may be used for cleaning, cleaning the skin, or for maintaining general hygiene.

[0081] Preferably, the topical composition is an anti-dandruff composition effective against at least some Malassezia species. Alternatively, the topical composition is an anti-acne composition effective against at least C. acnes. Still alternatively, the topical composition is a rinse-off or leave-on composition effective against at least S. aureus.

[0082] When the atractylenolide compound is atractylenolide I or II, the method is more effective if the weight ratio of the atractylenolide compound to the antimicrobial active substance relative to the Malassezia furfur cells is within the range of 5:1 to 1280:1, and even more effective if the weight ratio is within the range of 40:1 to 100:1.

[0083] According to another aspect, a topical composition is disclosed for use as an anti-dandruff composition effective against at least some Malassezia species. According to yet another aspect, a topical composition is disclosed for use as an anti-acne composition effective against at least C. acnes. According to yet another aspect, a rinse-off or leave-on composition is disclosed that is effective against at least Staphylococcus aureus.

[0084] The invention will now be described in detail with the aid of the following non-limiting examples.

[0085] [Example] The antimicrobial efficacy of exemplary compositions according to the present invention against M. furfur was determined.

[0086] We will now briefly describe the steps involved.

[0087] Method 1: ΣFIC assay for M. furfur. Step 1: Cultivation and preparation of microorganisms M. furfur (CBS1878) was maintained on MD agar plates (solution A) and cultured in 20 ml of growth medium Pityrosporum broth (PB, solution B). They were then incubated at 32°C for 48 hours with shaking. 1 ml of the first broth culture was then transferred to 9 ml of fresh PB and incubated at 32°C for 48 hours with shaking. The final culture contained 2–6 × 10 6 This should contain 5 x 10 cells / ml using PB. 5 This is achieved by diluting to 100 cells / ml.

[0088] Preparation of solution A: Modified Dixon Agar (MD) 36g malt extract (Oxoid) 6g fungal peptone (Oxoid) 10 Purified agar (Oxoid) 20g Ox Bile (Oxoid) 2ml oleic acid (Sigma) 2ml glycerol (Sigma) 10ml Tween 40 (Sigma) Up to 1000ml of deionized water Dissolve 50 mg (1 vial) in 2 ml of 95% ethanol Chloramphenicol (Oxoid SR078E) (Stir thoroughly, including after autoclaving)

[0089] Preparation of solution B: Pityrosporum bros (PB) 10g Bacterial Peptone 0.1g yeast extract 10g ox bile 2.5g taurocholic acid 10g glucose 1L deionized water 0.5ml Tween 60 1ml glycerol Adjust pH to 6.2 After sterilization 0.5 ml UHT milk

[0090] Step 2: In vitro susceptibility testing Octopirox® was serially diluted (2-fold) to a range of 60 to 1,000 ppm in growth medium. Test atractylenolide compounds (stock: 4 mg / ml) were serially diluted 2-fold in DMSO to a range of 40,000 to 10 ppm. Binary combinations of octopirox and test compounds were prepared in 96-well plates by mixing 10 μl of octopirox solution with 10 μl of test compound. The solution in each well was further mixed with 180 μl of M. furfur suspension in PB.

[0091] The final cell density in the test plate was approximately 5 x 10 4The final concentrations (ppm) (parts per million) of each component after (20-fold dilution) were as follows: Each of these concentrations was tested to determine the FIC value of Octopirox® in combination with one atractylenolide compound. Broth medium and solvent controls served as negative controls for comparison of results.

[0092] Octopirox® - 50, 25, 12.5, 6, 3 and 0.

[0093] Atractylenolide I - 2000, 1000, 500, 250, 125, 62.5, 31.25, 15.63, 7.8, 3.9, 2.0, 1.0, 0.5 and 0.

[0094] Atractylenolide II - 2000, 1000, 500, 250, 125, 62.5, 31.25, 15.63, 7.8, 3.9, 2.0, 1.0, 0.5 and 0.

[0095] The compound and strain suspensions were mixed using a multichannel pipette. The 96-well plate was then incubated in an incubator. M. furfur was incubated aerobically at 32°C for 1 day according to the following test protocol. Then, 20 μl of Alamar Blue (0.1%) was dispensed into each well, and the incubation procedure (as described above) was repeated. Finally, the color change of the indicator was monitored to confirm visible signs of microbial growth or growth inhibition. A color change to red indicated growth, while blue indicated no growth or growth inhibition.

[0096] Step 3: Calculation: ΣFIC test (1) Minimum inhibitory concentration (MIC): The MIC is defined as the absolute lowest concentration of active substance that results in complete microbial growth inhibition, as indicated by the blue color of Alamar Blue, under the test conditions.

[0097] (2) Fractional Inhibitory Concentration (FIC): The ΣFIC test was performed based on the principles previously described in Hall MJ, Middleton RF, & Westmacott D (1983), The fractional inhibitory concentration (FIC) index as a measure of synergy. Journal of Antimicrobial Chemotherapy 11(5):427-433. The procedure is as follows:

[0098] The different behaviors of inhibitory antimicrobial agents, alone and in mixtures, have been extensively studied using the concepts of fractional concentration (FC) and fractional inhibitory concentration (FIC). The parameters can be defined as: FIC(component a)= MIC (tested component a in the mixture) MIC (component tested as single active substance a)

[0099] (3) Synergistic and additivity Interactions between antimicrobial agents may be additive, synergistic, or antagonistic, depending on whether the effect of the combination is similar to, greater than, or less than that obtained for the same total concentrations of the individual components when tested alone.

[0100] All observations were recorded and tabulated, and the fractional inhibitory concentration (FIC) was calculated.

[0101] The combined effects of inhibitory antimicrobial agents have been widely studied using the concepts of fractional concentration (FC) and fractional inhibitory concentration (FIC). This parameter is defined as follows: ΣFIC=FIC(component 1)+FIC(component 2)

[0102] Further inferences that can be drawn from ΣFIC values ​​are summarized in the table below. There is no consistent approach in the academic or patent literature to defining the precise limiting ΣFIC value that distinguishes synergy from additivity or antagonism. In this study, we took the progressive approach of defining any binary mixture with a ΣFIC<0.9 as showing evidence of synergistic behavior.

[0103] [Table 1]

[0104] The final concentrations (ppm) (parts per million) of each component after (10-fold dilution) were as follows: Each of these concentrations was tested to determine the FIC value of octopirox (either) in combination with one atractylenolide compound.

[0105] result: It was observed that there was a synergistic effect between octopirox and atractylenolide compounds against M. furfur (Table 1).

[0106] [Table 2]

[0107] The data demonstrate a remarkably wide range of concentrations of relevant atractylenolide compounds at the disposal of formulation scientists that can be used to advantage. The fact that the ΣFIC was less than 0.9 across a wide range of atractylenolide compounds when used in combination with octopirox means that it is possible to formulate highly effective antimicrobial compositions containing the two active ingredients, even taking into account the fact that the experiments were conducted under test conditions and the amounts of the ingredients may not match or reflect the actual amounts under in-use conditions, i.e., in compositions such as shampoos or skin care creams.

[0108] Thus, in summary, the observations summarized in Table 1 clearly demonstrate that atractylenolide compounds interact synergistically with the antimicrobial actives of the present invention. The interaction was found to be synergistic over a wide range of concentrations, and the synergistic interaction was evident from the fact that the ΣFIC was less than 0.9.

[0109] Method 2: Zone off Inhibition (ZOI) assay Atractylodes macrocephala (AM) root water extract (purchased from Huzhou Liaoyuan, China) was prepared at concentrations of 0.75% and 1.5% in 50% water / DMSO. Octopirox (OCT) was prepared at concentrations of 0.1% and 0.2% in DMSO. Malassezia growth agar plates were prepared, and then 200 μL of M. furfur (10 6 CFU (CBS 1878) were spread on the agar. Several sterile filter papers (diameter = 6 mm) were placed on the agar plates. 10 μL of compound solution was added onto the filter paper. The plates were incubated at 32°C for 2 days. Clear zones of growth inhibition were recorded.

[0110] Calculation formula: Synergistic antimicrobial activity: Inhibitory distance for the combination of compound 1 + compound 2 > inhibitory distance for compound 1 alone + inhibitory distance for compound 2 alone

[0111] result: It was observed that there was a synergistic effect between Octopirox and Atractylodes macrocephala (AM) root aqueous extract against M. furfur (Table 2).

[0112] [Table 3]

[0113] The observations summarized in Table 2 clearly show that the atractylenolide compound in the form of an aqueous extract of Atractylodes macrocephala root interacts synergistically with octopirox, indicating that the atractylenolide compound interacts synergistically with the antimicrobial active substance according to the present invention.

[0114] Combination of Octopirox® with another known antimicrobial active substance, ZPTO.

[0115] Using an in vitro ΣFIC assay against M. furfur similar to that used above, experiments were conducted to determine whether the interaction of Octopirox® with other known antimicrobial actives, such as zinc pyrithione, would result in synergistic antimicrobial activity. Experiments were conducted over a range of concentrations of the components, including:

[0116] Octopirox® - 50, 25, 12.5, 6, 3 and 0.

[0117] ZnPT: 50, 25, 12.5, 6.25, 3.13, 1.56, 0.78, 0.39, 0.2, 0.1, 0.05 and 0.

[0118] When a ΣFIC assay was performed, the data showed that Octopirox® was unable to synergistically interact with ZPTO to produce synergistic antimicrobial activity. Therefore, it cannot be concluded that the combination of piroctone olamine with any known antimicrobial active substance always produces a synergistic effect. Surprisingly, the combination of atractylenolide compounds with the antimicrobial active substances claimed in this invention exhibits synergistic behavior.

[0119] All of the experiments disclosed above were conducted under in vitro conditions to determine whether the combination of specific antimicrobial active substances—piroctone olamine and atractylenolide compounds—is synergistic, additive, or antagonistic with respect to their individual activities against the relevant microorganisms. As far as the experiments are concerned, the concentrations of the components were selected to fall within the acceptable limits allowed by the relevant tests, allowing for the recording of technical effects. Therefore, the concentrations tested may appear to fall outside the range (usually in weight percent) at which such components are typically used in cosmetic compositions.

[0120] The composition of the present invention can be formulated as emulsion or gel, which can contain other common components that can affect the concentration of desired active substance in oil phase and water phase.Such composition can also have a series of different physical properties and hydrodynamic properties, such as partition coefficient, diffusion rate, convective transport rate and rheological properties.Therefore, the concentration used when formulated as composition can be different from the concentration at the cellular level in which experiment is carried out, and it is expected that the concentration in use will usually be several orders of magnitude higher.

[0121] Influence of the ratio of Octirox® to atractylenolide compounds on the inhibitory effect. A composition containing Octopirox® and atractylenolide compound was prepared as shown in Tables 3 and 4. This solution was diluted 8-fold with culture growth medium and further mixed with 9 volumes of a suspension of M. furfur in PB to observe the differential growth of Malassezia as assay requirements. The same assay as above was used. The mixture was incubated at 32°C for 48 hours, and the growth of Malassezia was monitored. The observed results are summarized in Tables 3 and 4. Because FIC is defined as the fractional inhibitory concentration, ΣFIC is reported here for compositions that inhibited the growth of Malassezia, but ΣFIC for compositions without inhibitory effect is not valid.

[0122] [Table 4]

[0123] The observations summarized in Table 3 clearly demonstrate that atractylenolide I interacts synergistically with piroctone olamine to inhibit the growth of M. furfur (ΣFIC<0.9) only when the weight ratio of atractylenolide I to piroctone olamine is at least 5:1 (Examples 1-3).

[0124] [Table 5]

[0125] The observations summarized in Table 4 clearly demonstrate that atractylenolide II interacts synergistically with piroctone olamine to inhibit the growth of M. furfur (ΣFIC<0.9) only when the weight ratio of atractylenolide II to piroctone olamine is at least 5:1 (Examples 4-6).

Claims

1. (i) an antimicrobial active agent that is at least one of caprylhydroxamic acid or piroctone olamine; (ii) an atractylenolide compound that is atractylenolide I or II, wherein the weight ratio of the amount of the atractylenolide compound to the amount of the antimicrobial active is from 5:1 to 1280:

1.

2. 2. The composition of claim 1, comprising an extract of Atractylodes species, or an extract of Sarcandra chinensis or Shizuka buddha, which contains the atractylenolide compound.

3. 3. The composition according to claim 1, wherein the amount of the atractylenolide compound is 0.01 to 10% by weight.

4. The composition according to any one of claims 1 to 3, wherein the amount of the antimicrobial active substance is from 0.01 to 10% by weight.

5. 5. The composition of claim 1, further comprising a cosmetically acceptable carrier comprising water.

6. The composition of claim 5 , wherein the carrier further comprises a surfactant.

7. 7. The composition of claim 1, which is a wash-off or leave-on hair care composition.

8. 8. A topical composition according to any one of claims 1 to 7 for use in providing an antimicrobial effect to a topical surface of the human or animal body.

9. 9. The topical composition of claim 8 for use against at least some Malassezia species on a topical surface of the human or animal body.

10. 8. A non-therapeutic method of providing a topical antimicrobial effect to a topical surface of the human or animal body comprising applying a safe and effective amount of the topical composition of any one of claims 1 to 7.

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