Topical Antibacterial Compositions

Abstract

A topical composition is disclosed that includes: (i) an antimicrobial active agent that is at least one of piroctone, caprylhydroxamic acid, benzohydroxamic acid, or piroctone olamine; and (ii) norbrailein. Also disclosed is a non-therapeutic method of providing a topical antimicrobial benefit to a topical surface of the human or animal body, the method comprising applying a safe and effective amount of the topical composition.

Description

[Technical Field]

[0001] The present invention relates to topical antimicrobial compositions, particularly cosmetic compositions, and more particularly to cosmetic compositions containing actives 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 that are useful for cleaning and / or caring for any body part, but are particularly suitable for hair and scalp care, hand hygiene or facial care and cleansing.

[0003] Dandruff is a problem affecting many people worldwide. This condition manifests itself through the shedding of clumps of dead skin cells from the scalp. Dandruff is white and easily visible, resulting in an aesthetically unpleasing appearance. The contributing factor to dandruff is certain members of the Malassezia yeast genus. To combat it, 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 are metal pyrithiones, such as zinc pyrithione (ZPTO), octopirox® (piroctone olamine), azole antibacterial agents (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 usually 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 effects, has been used for mild cases of acne and is thought to prevent further acne formation. In very severe cases of acne, antibiotics such as tetracycline, erythromycin, and clindamycin have been used. Summary of the Invention [Problem to be solved by the invention]

[0006] It is therefore an object of the present invention to provide a topical composition that exhibits synergistic antimicrobial activity compared to the individual components. [Means for solving the problem]

[0007] The inventors have determined that when a specific active substance commonly found in natural plants is formulated with at least one typical antibacterial active substance, which is piroctone, caprylhydroxamic acid, benzohydroxamic acid, or piroctone olamine, 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 antibacterial activity, and can be suitable for use in, for example, shampoos, body and face care.The specific active substance mentioned above is norbrylin.

[0008] Thus, according to the first aspect, (i) an antibacterial active agent that is at least one of piroctone, caprylhydroxamic acid, benzohydroxamic acid, or piroctone olamine; (ii) Norbrylin and A topical composition comprising:

[0009] According to a second aspect, a non-therapeutic method of providing topical antimicrobial benefit 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.

[0010] According to a third aspect, there is disclosed a composition of the first aspect for use in providing an antimicrobial benefit to a topical surface of the human or animal body. DETAILED DESCRIPTION OF THE INVENTION

[0011] The compositions according to the present invention comprise a topically acceptable carrier, vehicle, or diluent, which may 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 causing 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 emulsions. Emulsions can cover 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), and aqueous-based mousse systems. Non-limiting examples of topical carrier systems useful in the present invention are set forth below.

[0012] 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 word "comprising" is intended to mean "including," but not necessarily "consisting of" or "composed of." In other words, the listed steps or options need not be exhaustive. It is noted that the examples provided in the following description are intended to clarify the invention, but are not intended to limit the invention to these examples per se. Similarly, unless otherwise indicated, all percentages and ratios contained herein are weight / weight percentages.

[0013] Except in the examples and comparative examples, or unless expressly indicated otherwise, all numbers in this specification expressing amounts of ingredients or conditions, physical properties of materials and / or use, should be understood to be modified by the word "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. Consequently, 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.

[0014] A topical composition refers to a leave-on or wash-off composition intended for external use to cleanse or disinfect localized areas of mammals, particularly humans, such as the skin and / or hair and / or oral cavity. Such compositions include any product applied to the human body for improving appearance, cleaning, odor control, or general aesthetics. In one embodiment, the topical 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, gel, or toner, or may be applied using a device or via a face mask, pad, or patch. As used herein, "skin" refers to the skin of 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.

[0015] As used herein, "antimicrobial composition" is meant to include compositions 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. When the application time is short, e.g., from a few seconds to a few minutes, and the composition is then rinsed off with water or wiped away, such compositions are known as cleansing or rinse-off compositions. When the composition is applied for a longer period, e.g., from a few minutes to up to 24 hours, and is typically washed off during normal personal cleansing procedures, such compositions are known as leave-on compositions. More preferably, the compositions are used to prevent or alleviate the symptoms of dandruff on the scalp and / or hair, for anti-acne benefits, or to disinfect hands or other parts of the human body.

[0016] 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 bar soaps.When the composition of the present invention is a hair care composition, it is preferably a wash-off composition, particularly a shampoo or conditioner.

[0017] The present invention provides (i) an antibacterial active agent that is at least one of piroctone, caprylhydroxamic acid, benzohydroxamic acid, or piroctone olamine; (ii) Norbrylin and The present invention relates to a topical composition comprising:

[0018] Hydroxamic Acids and Hydroxamic Acid Derivatives Hydroxamic acids are a class of organic compounds that have the functional group RC(O)N(OH)R' (R and R' are organic residues and CO is a carbonyl group).

[0019] The antibacterial active substance according to the present invention is at least one hydroxamic acid or hydroxamic acid derivative. The hydroxamic acid is piroctone, caprylhydroxamic acid, or benzohydroxamic acid, more preferably caprylhydroxamic acid. The hydroxamic acid derivative is piroctone olamine.

[0020] The antibacterial active substance according to the present invention is at least one of piroctone, caprylhydroxamic acid, benzohydroxamic acid, or piroctone olamine. More preferably, the antibacterial active substance according to the present invention is at least one of caprylhydroxamic acid or piroctone olamine. Most preferably, the antibacterial active substance is piroctone olamine.

[0021] 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]

[0022] Caprylhydroxamic acid is an amino acid derived from coconut oil. It is a preservative and a broad-spectrum antifungal agent. Its CAS number is 7377-03-9, and the compound has the following general formula (b): [ka]

[0023] Benzohydroxamic acid is a hydroxamic acid. Its CAS number is 495-18-1 and it has the following general formula (c): [ka]

[0024] Piroctone olamine is the olamine salt of the hydroxamic acid derivative piroctone, a typical antibacterial active substance, commonly known as piroctone ethanolamine under the trade name Octirox®.

[0025] 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 this compound has the following general formula (d): [ka]

[0026] The amount of at least one hydroxamic acid or hydroxamic acid derivative antibacterial active in the compositions of the present invention will depend on the type of topical composition and the exact nature of any other antibacterial actives used. Preferably, the compositions comprise from 0.01 to 10%, more preferably from 0.1 to 5%, and even more preferably from 0.5 to 3% of said antibacterial active by weight of the composition.

[0027] Norbrylin Norbulilin according to the present invention is 6-hydroxy-8,8-dimethylpyrano[2,3-f]chromen-2-one (C14H12O4). Its CAS number is 60796-64-7, and this compound has the following general formula (e): [ka]

[0028] Such norbrilines can also be found in the plants Zanthoxylum nitidum, Toddalia asiatica, and Cedrelopsis grevei.

[0029] The amount of norbulin in the composition of the present invention is preferably 0.01 to 10% by weight, more preferably 0.01 to 5% by weight, and most preferably 0.1 to 2% by weight of the composition.

[0030] Preferably, the composition of the present invention comprises an extract of Zanthoxylum nitidum, or an extract of Toddalia asiatica or Cedrelopsis grevei, which also contain norbraline. The measured amount of the extract is selected so that the required amount of norbraline contained therein is included in the composition.

[0031] Zanthoxylum nitidum extracts containing norbulin are commercially available from a variety of different sources. For example, Zanthoxylum nitidum extracts are available from the Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Alternatively, those skilled in the art can isolate Zanthoxylum nitidum by using any suitable isolation and purification method known in the art. In some embodiments, Zanthoxylum nitidum extracts can be obtained from dried Zanthoxylum nitidum plants or prepared by any means known or developed in the art.

[0032] Typically, plant extracts can be prepared using aqueous solvents containing water and alcohol, or supercritical carbon dioxide, which extracts beneficial plant components. For example, the herbal material is crushed into small pieces and soaked in 10 volumes of deionized water for 30 minutes, followed by reflux extraction for two 30-minute periods. After filtration, the liquid is dried to obtain an extract powder. Alternatively, the herbal material can be crushed into small pieces and soaked in 10 volumes of 95% ethanol for 24 hours. The two filtered solutions are combined and filtered. The solvent in the supernatant is removed by evaporation, yielding an extract powder.

[0033] Since the composition contains an antibacterial active and norbraline, it is preferred that a ratio between the amounts of the active ingredients be maintained for optimal effectiveness. Preferably, the weight ratio of the amount of norbraline to the antibacterial active is 1:10 to 100:1, more preferably 1:2 to 50:1, even more preferably 1:1 to 20:1, particularly preferably 3:1 to 10:1, and most preferably 5:1 to 10:1.

[0034] The sum of fractional inhibitory concentrations (ΣFIC) is widely used in the context of antimicrobial combinations. It is a tool to determine whether antimicrobial components (when used in combination) have a synergistic or antagonistic effect, or neither of the two, i.e., an additive effect. We relied on the ΣFIC test to evaluate the combined effect of antimicrobial active substances and norbraylin against M. furfur.

[0035] Although the antimicrobial active of the present invention and norbrailein are present in the compositions of the present invention, it is believed that the norbrailein compound interacts synergistically with the antimicrobial active, making it more effective.

[0036] The topical compositions of the present invention preferably comprise piroctone olamine and norbraline, wherein the weight ratio of the amount of norbraline to the amount of piroctone olamine is preferably 1:10 to 100:1, alternatively 1:2 to 50:1, or even alternatively 1:1 to 10:1.

[0037] Preferably, the topical compositions of the present invention comprise caprylhydroxamic acid and norbraline, wherein the weight ratio of the amount of norbraline to the amount of caprylhydroxamic acid is preferably 1:10 to 100:1, alternatively 1:2 to 50:1, or even alternatively 1:1 to 10:1.

[0038] Other ingredients The compositions of the present invention preferably comprise a cosmetically acceptable vehicle such that the composition can be formulated as, for example, a shampoo, conditioner, body wash, hand wash, or facial cleanser, cream, lotion, gel, powder, ointment, hand sanitizer, or soap bar, and the remainder of the ingredients will vary accordingly.

[0039] In one embodiment, the topical composition according to the present invention is a hair care composition. Preferably, such composition is a shampoo, hair conditioner, hair serum, or hair oil. Most preferably, the topical composition is an anti-dandruff composition that is effective against at least some Malassezia species.

[0040] When the composition of the present invention is a shampoo, it preferably contains other ingredients typically included in such compositions.

[0041] 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 an ethoxylated alkyl sulfate surfactant. Preferred alkyl sulfates are C 8~18 Alkyl sulfates, more preferably C 12~18 Alkyl sulfates, preferably in the form of salts with solubilizing cations such as sodium, potassium, ammonium or substituted ammonium.

[0042] Particularly preferred alkyl ether sulfates are those of the formula: RO(CHCHO) n SO -3 M, where 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. An 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.

[0043] 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 and 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 and their salts may contain 1 to 20 ethylene oxide or propylene oxide units per molecule.

[0044] 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).

[0045] Mixtures of any of the foregoing anionic cleansing surfactants may also be suitable.The shampoo compositions of the present invention preferably further comprise 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.

[0046] The pH of the composition is preferably 4.0 or higher, more preferably in the range of 5.0 to 10.0.

[0047] 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 efficacy. Suitable zinc compounds are ZPTO, zinc oxide, zinc citrate, zinc malonate, zinc carbonate, or combinations thereof.

[0048] 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, climbazole, or a mixture thereof. The presence of the conazole fungicide is believed to improve deposition of zinc pyrithione (ZPTO).

[0049] The shampoo composition further preferably contains a suspending agent. Suitable suspending agents include polyacrylic acid, crosslinked polymers of acrylic acid, copolymers of acrylic acid and hydrophobic monomers, copolymers of carboxylic acid-containing monomers and acrylic esters, crosslinked copolymers of acrylic acid and acrylic 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 can also be used; they 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.

[0050] Suitable cross-linked polymers of acrylic acid and acrylic acid esters are Pemulen® TR1 and Pemulen® TR2. A suitable heteropolysaccharide gum is xanthan gum, available for example as Kelzan.

[0051] Mixtures of any of the above suspending agents may be used, with mixtures of crosslinked polymers of acrylic acid and crystalline long chain acyl derivatives being preferred.

[0052] If included, the suspending agent is generally present at 0.1 to 10% by weight, preferably 0.5 to 6% by weight.

[0053] The compositions of the present invention may contain other ingredients to enhance performance and / or consumer acceptability, including fragrances, dyes and pigments, pH adjusters, pearlizers or opacifiers, viscosity adjusters, preservatives, and natural hair nutrients (such as botanical and fruit extracts, sugar derivatives, and amino acids).

[0054] The shampoo composition is preferably aqueous based, preferably comprising 70 to 95% water by weight.

[0055] Hair conditioner Alternatively, the topical composition of the present invention is a hair conditioner. When the conditioning benefit is provided 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 substances, such as mineral oil, natural oils, such as triglycerides and silicone polymers. The conditioning benefit is achieved when the oily substance deposits on the hair, resulting in the formation of 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 remain and deposit on the hair after rinsing with water. Suitable silicone oils can include polyalkylsiloxanes, polyarylsiloxanes, polyalkylarylsiloxanes, polyethersiloxane copolymers, and mixtures thereof. Aminosilicones are often formulated in shampoo compositions. Aminosilicones are silicones containing at least one primary amine, secondary amine, tertiary amine, or quaternary ammonium group. High molecular weight silicone rubbers are also available. Another useful type is a crosslinked silicone elastomer, such as dimethicone / vinyl / dimethicone crosspolymer (e.g., Dow Corning 9040 and 9041).

[0056] 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, containing 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.

[0057] The hair conditioner compositions of the present invention may also preferably contain 0.5 to 10% by weight of a fatty alcohol. The use of a fatty alcohol in combination with 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.

[0058] 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.

[0059] Skin cleansing The composition of the present invention can be used for skin care, such as body or face cleansing. The topical composition can further comprise a surfactant. Preferred surfactants are nonionic surfactants.

[0060] For example, in a highly preferred embodiment, the topical composition comprises a surfactant selected from the group of anionic surfactants.

[0061] When a surfactant is present, the topical composition preferably comprises 1 to 90% surfactant by weight of the composition. When a surfactant is used, a particularly preferred surfactant is soap. Soap is a suitable surfactant for personal cleansing applications of the topical compositions of the present invention.

[0062] The soap of the present invention, when present, 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.

[0063] Preferred compositions may contain other known ingredients such as fragrances, pigments, preservatives, emollients, sunscreens, emulsifiers, gelling agents and thickeners. The selection of these ingredients will largely depend on the type of composition.

[0064] Water is a preferred carrier. When present, water is preferably present in an amount of at least 1% by weight of the composition, more preferably at least 2% by weight, and even more preferably at least 5% by weight. 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 skin cleansing, particularly hand washes or face washes. When water is the carrier, preferred solid compositions contain 5 to 30% by weight of water.

[0065] Solid topical compositions are preferably in the form of a molded solid, more preferably a bar.Liquid topical compositions are particularly useful for cleansing the skin, especially as hand washes or face washes.

[0066] According to 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 antibacterial composition is particularly useful as talcum powder for application to the face or body.

[0067] In another aspect of the invention, the compositions of the present invention are suitable for use in personal hygiene wipes.

[0068] 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 antimicrobial benefit to a topical surface of the human or animal body. The present invention also discloses a topical composition for use against at least a portion of Malassezia species on a 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 a topical surface of the human or animal body. Alternatively, the topical composition is an anti-acne composition effective against at least C. acnes. Alternatively, the topical composition is a rinse-off or leave-on composition effective against at least S. aureus. Preferably, the use according to the present invention is for non-therapeutic purposes. Preferably, non-therapeutic purposes refer to cosmetic purposes. Alternatively, the use of the composition according to the present invention is for therapeutic purposes. Those skilled in the art will understand the difference between therapeutic and non-therapeutic uses of a composition.

[0069] According to another aspect, a non-therapeutic method for providing topical antimicrobial benefit to a topical surface of the human or animal body is disclosed, comprising applying a safe and effective amount of the topical 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 format; for example, for a leave-on composition, the amount may be 1-2 ml per application, and for a shampoo, the same amount may be 5-10 ml per application. This method may be used to prevent or treat acne, dandruff, or to maintain general hygiene.

[0070] 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. Alternatively, the topical composition is a rinse-off or leave-on composition effective against at least S. aureus.

[0071] This method is more effective when the weight ratio of norbraylin to antibacterial active substance to Malassezia furfur cells is in the range of 1:10 to 100:1, and even more effective when it is in the range of 3:1 to 100:1.

[0072] According to another aspect, a composition is disclosed for use in providing antimicrobial benefit to a topical surface of the human or animal body.

[0073] 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 S. aureus.

[0074] The invention will now be described in detail with the aid of the following non-limiting examples. [Example]

[0075] [Example 1] The antimicrobial efficacy of exemplary compositions according to the present invention was determined against M. furfur.

[0076] Here we briefly describe the steps involved.

[0077] 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). These 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 x 10 6 This should contain 5 x 10 cells / ml using PB. 5 This is achieved by diluting to 100 cells / ml.

[0078] Preparation of solution A: Modified Dixon Agar (MD) 36g Malt Extract (Oxoid) 6g fungal peptone (Oxoid) 10 Purified agar (Oxoid) 20g ox bile 2ml oleic acid (Sigma) 2ml glycerin (Sigma) 10ml Tween 40 (Sigma) Up to 1000ml of deionized water Dissolve 50 mg (1 vial) in 2 ml of 95% ethanolic chloramphenicol (Oxoid SR078E) (Ensure sufficient stirring, even after autoclaving)

[0079] 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 glycerin Adjust pH to 6.2 After sterilization 0.5ml UHT milk

[0080] Step 2: In vitro susceptibility testing Octopirox® was serially diluted (2-fold) to prepare a range of 60 to 1000 ppm in growth medium. Test norbrilin (stock: 10 mg / ml) was serially diluted 2-fold in DMSO to prepare a range of 5000 to 5 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 strain suspension in PB.

[0081] The final cell density in the test plate was approximately 5*10 4 The final concentrations of each component (in parts per million (ppm)) after 20-fold dilution were as follows: 1000 cells / ml. Each of these concentrations was tested to determine the FIC value of Octopirox® (or any of the broth media) in combination with norbrilin. Broth medium and solvent controls served as negative controls for comparison of results.

[0082] Octopirox® - 6.25, 3.125 and 0 ppm. Norbrylin - 500, 250, 125, 62.5, 31.25, 15.63, 7.8, 3.9, 2.0, 1.0, 0.5 and 0 ppm

[0083] The compound and strain suspensions were mixed using a multichannel pipette. The 96-well plate was then incubated in an incubator. OD600 (start) was read. For M. furfur, OD600 (end) was read after 2 days of incubation. Alamar Blue (10%) was then added and incubated for 8 hours. 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.

[0084] Step 3: Calculation: ΣFIC Test (1) Minimum inhibitory concentration (MIC): The MIC is defined as the absolute lowest concentration of active substance that provides complete microbial growth inhibition, as indicated by the blue color of Alamar Blue, under the test conditions.

[0085] (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 was as follows:

[0086] The different behavior of inhibitory antimicrobial agents alone and in mixtures has been widely investigated using the concepts of fractional concentration (FC) and fractional inhibitory concentration (FIC). The parameters can be defined as: FIC(component a)= MIC (component a tested in the mixture) MIC (ingredient a tested as single active substance)

[0087] (3) Synergistic and additivity Interactions between antimicrobial agents may be additive, synergistic, or antagonistic, depending on whether the effectiveness of the combination is equal to, greater than, or less than that obtained for the same total concentrations of the individual components when tested alone.

[0088] All observations were recorded and tabulated, and the fractional inhibitory concentration (FIC) was calculated.

[0089] The combined effects of inhibitory antimicrobial agents are broadly investigated using the concepts of fractional concentration (FC) and fractional inhibitory concentration (FIC), which are defined as follows: ΣFIC=FIC(component 1)+FIC(component 2)

[0090] Further inferences that can be drawn from ΣFIC values ​​are summarized in the table below. There is no consistent approach in either 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 liberal approach of defining any binary mixture with a ΣFIC<0.9 as showing evidence of synergistic behavior.

[0091] [Table 1]

[0092] The final concentrations (in parts per million (ppm)) of each component after (10-fold dilution) were as follows: Each of these concentrations was tested to determine the FIC value of (either of) Octopirox® in combination with norbraline.

[0093] result: A synergistic effect of Octopirox® and norbraylin against M. furfur was observed (Table 1).

[0094] [Table 2]

[0095] The observations summarized in Table 1 clearly demonstrate that norbrilin interacts synergistically with Octopirox® (the antibacterial active substance according to the present invention), which was evident from the fact that the ΣFIC was less than 0.9.

[0096] A combination of Octopirox® with another known antibacterial active substance, ZPTO, as a negative control. Using an in vitro ΣFIC assay against M. furfur similar to that used above, experiments were conducted to determine whether interactions between Octopirox® and other known antimicrobial actives, such as zinc pyrithione, result in synergistic antimicrobial activity. Experiments were conducted over a range of concentrations of the components as follows: Octopirox® - 50, 25, 12.5, 6, 3 and 0. ZnPT: 50, 25, 12.5, 6.25, 3.13, 1.56, 0.78, 0.39, 0.2, 0.1, 0.05 and 0.

[0097] When a ΣFIC assay was performed, the data showed that Octopirox® was unable to synergistically interact with ZPTO to produce synergistic antibacterial activity. Therefore, it cannot be concluded that the combination of piroctone olamine with any known antibacterial active substance always produces a synergistic effect. Surprisingly, the combination of norbraline and an antibacterial active substance claimed in the present invention exhibits synergistic behavior.

[0098] Example 2: The antimicrobial efficacy of exemplary compositions according to the present invention was determined against M. furfur.

[0099] Preparation of microorganisms: M. furfur (CBS 1878) was maintained on MD agar plates (solution A) and cultured in 20 ml of growth medium Pityrosporum broth (PB, solution B).

[0100] These are then incubated with shaking for 48 hours at 32° C. 1 ml of the first broth culture is then transferred to 9 ml of fresh PB and incubated with shaking at 32° C. for 48 hours.

[0101] The final culture was 2–6 × 10 6 This should contain 5*10 cells / ml using PB. 5 This is achieved by diluting to 100 cells / ml.

[0102] In vitro susceptibility testing Caprylhydroxamic acid (0.5%) was prepared in DMSO and serially diluted two-fold into growth medium to yield a range of 5000 to 78 ppm. 20 μl of the serial dilutions were added to each column of a 96-well plate (Corning-3788).

[0103] Test norbulin compounds (stock: 20 mg / ml in DMSO) were serially diluted 2-fold in growth medium to a range of 20,000 to 20 ppm. 20 µl of the serial dilutions were added to each row of a 96-well working plate (Corning-3788) to create binary combinations with caprylhydroxamic acid.

[0104] The final cell density in the test plate was approximately 5*10^4 cells / ml, and the final concentrations of the active substances in each well of the 96-well plate were as follows: Norbrylin 2000, 1000, 500, 250, 125, 62.5, 31.25, 15.63, 7.8, 3.9, 2.0, 0 ppm. Caprylhydroxamic acid: 500, 250, 125, 62.5, 31.25, 15.63, 7.8, 0 ppm

[0105] After 2 days of incubation, OD600 (end) was read for M. furfur. Alamar Blue (10%) was then added and incubated for 8 hours. The color change from blue to red was recorded, and the fluorescence (530EX nm / 590EM nm) was read.

[0106] It was observed that there was a synergistic effect of caprylhydroxamic acid and norbrilin against M. furfur (Table 2).

[0107] [Table 3]

[0108] The observations summarized in Table 2 indicate that norbrilin interacts synergistically with caprylhydroxamic acid (the antibacterial active substance according to the present invention).

[0109] 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 norbriline—has synergistic, additive, or antagonistic activity relative 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 not appear to be within the range (usually by weight) at which such ingredients are typically used in cosmetic compositions.

[0110] 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 different sets of physical properties and hydrodynamic properties, such as partition coefficient, diffusion rate, convective transport rate and rheological properties.Therefore, the concentration used when formulating 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.

Claims

1. (i) an antibacterial active agent that is at least one of caprylhydroxamic acid or piroctone olamine; (ii) Norbrylin and A topical composition comprising:

2. 2. The composition of claim 1, wherein the weight ratio of the amount of norbrayllin to the amount of the antibacterial active is 1:10 to 100:

1.

3. A compound comprising norbrylin. (i) an extract of Zanthoxylum nitidum, or (ii) extracts of Toddalia asiatica or Cedrelopsis grevei; Including, The composition according to claim 1 or 2.

4. 4. The composition of claim 1, wherein the antibacterial active is at least one of caprylhydroxamic acid or piroctone olamine.

5. The composition according to any one of claims 1 to 4, wherein the amount of norbulin is 0.01 to 10% by weight.

6. A composition according to any one of claims 1 to 5, wherein the amount of the antimicrobial active is from 0.01 to 10% by weight.

7. The composition of claim 1 , wherein the composition comprises a cosmetically acceptable carrier comprising water.

8. The composition of claim 7 , wherein the carrier further comprises a surfactant.

9. 9. The composition of any one of claims 1 to 8, wherein the composition is a wash-off or leave-on hair care composition.

10. 10. A non-therapeutic method of providing topical antimicrobial benefit to a topical surface of the human or animal body, comprising applying a safe and effective amount of a topical composition of any one of claims 1 to 9.

11. 10. A composition according to any one of claims 1 to 9 for use in providing an antimicrobial benefit to a topical surface of the human or animal body.

12. 12. The composition of claim 11 for use against at least some Malassezia species on topical surfaces of the human or animal body.

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