Cosmetic method, kit of parts and use of skin prebiotic actives in combination with antimicrobial metal salts to provide skin care benefits through remodeling of skin microorganisms

Abstract

The present invention provides cosmetic methods that provide skin care benefits by microbial remodeling of the skin; the method comprises the steps of (i) treating the skin by topical application of an antimicrobial metal salt, followed by (ii) washing the treated skin and treating the washed skin by topical application of a skin prebiotic active. The invention also provides the cosmetic use of a skin prebiotic active in combination with an antimicrobial metal salt for providing skin care benefits by microbial remodeling of the skin.

Description

Technical Field

[0001] The present invention relates to a cosmetic method for providing skin care benefits through the reprofiling of the skin microbiota. Background Art

[0002] The human skin harbors many different microorganisms that colonize the stratum corneum of the epidermis and skin appendages such as sweat glands and hair follicles. The total microorganisms in and on our skin are called the cutaneous microbiota, and the skin microbiome is their collective genome.

[0003] Sequencing studies of different skin sites in healthy adults have shown that the composition of the skin microbiome is mainly determined by body site. Microbial colonization is shaped differently due to the physiological and topological variations of the skin and varies systematically between different skin habitats such as dry, moist, and sebum-secreting skin areas.

[0004] The human axilla (underarm) is covered by scales, hair shafts and follicles, exocrine glands, apocrine glands, and sebaceous glands. The axillary region represents a unique ecological niche characterized by warm, moist, and nutrient-rich conditions. Salts, proteins, squalene, sterols, sterol esters, wax esters, a wide range of lipids, and fatty acids are secreted, thus maintaining one of the highest densities of microorganisms on the body surface.

[0005] The human skin microbiome plays an important role in the production of body odor, especially in the axillary (underarm) region. The main causative molecule of axillary body odor has been identified as 3-methyl-3-mercaptohexan-1-ol (3M3SH) of thiols. 3M3SH is derived from the biotransformation of an odorless dipeptide precursor (Cys-Gly-3M3SH) by certain bacterial species found in the axilla.

[0006] Gram-positive anaerobic cocci (GPAC), such as Anaerococcus octoavius and Peptoniphilus spp., are important components of the axillary microbiome and show a strong correlation with the intensity of axillary body odor at the taxon level. Studies at the species level have shown that Staphylococcus hominis is positively correlated with axillary body odor, while Staphylococcus epidermidis and Cutibacterium acnes are negatively correlated.

[0007] Staphylococcus epidermidis mainly colonizes the axillae, head, and nostrils. Studies have shown that the metabolites of Staphylococcus epidermidis, including organic acids such as lactic acid, improve skin hydration, maintain low acidic conditions on the skin surface, and improve the rough texture of the skin. Staphylococcus epidermidis is also thought to complement the epidermal barrier function and inhibit the colonization of skin pathogens such as Staphylococcus aureus (S. aureus) through factors such as nutrient competition, production of antimicrobial peptides (AMPs), immunomodulatory properties (inhibition of inflammatory cytokine production), and enhanced expression of tight junction proteins.

[0008] Propionibacterium acnes (C. acnes) is another major skin commensal that prevents the colonization and invasion of pathogens by hydrolyzing triglycerides in sebum and releasing fatty acids that are antimicrobial and promote an acidic pH on the skin surface.

[0009] The main intervention strategies for treating axillary malodor are the topical application of deodorants and antiperspirants.

[0010] Although treatments such as deodorants and antiperspirants are undoubtedly effective, they may also deplete or eliminate beneficial commensal microbial strains such as Staphylococcus epidermidis and Propionibacterium acnes. As described above, these microbial strains are thought to play many important beneficial roles in skin health, skin appearance, and skin function.

[0011] The present invention solves this problem.

[0012] An object of the present invention is to provide skin care benefits through microbial remodeling of the skin. Summary of the Invention

[0013] The present invention provides a cosmetic method for providing skin care benefits through microbial remodeling of the skin; the method comprises the steps of: (i) treating the skin by topical application of an antimicrobial metal salt, followed by (ii) washing the treated skin and treating the washed skin by topical application of a skin prebiotic active.

[0014] The present invention also provides the cosmetic use of a combination of a skin prebiotic active and an antimicrobial metal salt for providing skin care benefits through microbial remodeling of the skin. Detailed Description of the Invention

[0016] In the context of the present invention, "skin" should be understood to include its layers, from the uppermost or stratum corneum to the lowermost or subcutaneous tissue, both being included. These layers are composed of different types of cells, such as keratinocytes, fibroblasts, melanocytes, mast cells, neuronal cells, and / or adipocytes, etc.

[0017] As used herein, "skin care" refers to modulating and / or improving the cosmetic quality of the skin. These properties are modulated and / or improved in healthy subjects as well as those subjects having a skin disease or disorder such as psoriasis, lichen planus, folliculitis or atopic dermatitis.

[0018] In the context of the present invention, examples of skin care benefits include reducing and / or preventing skin malodor; providing a smoother, more even texture; improving the elasticity or resilence of the skin; improving the firmness of the skin; reducing the oily, shiny and / or dull appearance of the skin; improving the hydration state or moisture retention of the skin, improving the appearance of fine lines and / or wrinkles; improving skin flaking or desquamation; plumping the skin; improving skin barrier properties; improving skin color; reducing the appearance of redness or skin blotches and improving the brightness, luminosity or translucency of the skin.

[0019] In the context of the present invention, a preferred skin care benefit is reducing and / or preventing skin malodor, particularly axillary malodor.

[0020] As used herein, the term "microbial remodeling of the skin" means selectively supporting the growth, metabolism and / or colonization of desired microbial strains in the human skin microbiome, such as Staphylococcus epidermidis and Propionibacterium acnes, relative to other less desirable microbial strains in the human skin microbiome such as Staphylococcus hominis, Staphylococcus haemolyticus and Staphylococcus lugunensis. Generally, these microbial strains naturally compete for local resources and attach to epithelial sites. Different from generally reducing the microbial load and diversity, the compositions and methods of the present invention provide an ecological change that is more favorable for the growth, metabolism and / or colonization of desired microbial strains relative to less desirable microbial strains.

[0021] Antimicrobial metal salts

[0022] Suitable antimicrobial metal salts for use in the present invention are used to reduce the density of the skin bacterial community.

[0023] Examples of antimicrobial metal salts for use in the present invention include aluminum chlorohydrate (ACH), activated aluminum chlorohydrate (AACH), aluminum sesquichlorohydrate (ASCH), activated aluminum sesquichlorohydrate (AASCH), aluminum bromohydrate, aluminum chloride, aluminum sulfate, potassium alum, sodium aluminum chlorohydroxy lactate, aluminum zirconium chlorohydrate, zinc gluconate, zinc glycerate, zinc acetate, zinc sulfate, zinc oxide, zinc citrate, zinc chloride, zinc pyrrolidone carboxylate, zinc lactate and zinc phenolsulfonate.

[0024] Mixtures of any of the above materials can also be used.

[0025] Preferred examples of the antimicrobial metal salts for use in the present invention are selected from aluminium chlorohydrate (ACH), activated aluminium chlorohydrate (AACH), sesquialuminium chlorohydrate (ASCH), activated sesquialuminium chlorohydrate (AASCH), and mixtures thereof.

[0026] Skin prebiotic actives

[0027] In the context of the present invention, the term "skin prebiotic actives" denotes components that are metabolized by members of the skin microbiome and promote microbial remodelling of the skin (as defined above).

[0028] Examples of skin prebiotic actives suitable for use in the present invention are those that can selectively support the growth, metabolism, and / or colonization of desired microbial strains in the human skin microbiome selected from Staphylococcus epidermidis and / or Propionibacterium acnes strains; while inhibiting or not promoting the growth, metabolism, and / or colonization of less desired microbial strains in the human skin microbiome selected from Staphylococcus hominis, Staphylococcus haemolyticus, and Staphylococcus lugdunensis strains.

[0029] These substances include pimelic acid, pimelic anhydride, sucrose, lactose, ribose, maltose, mannose, sugar isomers, and glycerol.

[0030] Mixtures of any of the above substances can also be used.

[0031] Preferred examples of skin prebiotic actives for use in the present invention are selected from pimelic acid, pimelic anhydride, and mixtures thereof. Pimelic acid is a straight-chain 7-carbon saturated α,ω-dicarboxylic acid (IUPAC name heptanedioic acid).

[0032] In a preferred method according to the present invention, step (i) is carried out on the first day of treatment, step (ii) is carried out on the second day, and is repeated daily for at least two further consecutive days thereafter (e.g., days 2 to 10 thereafter).

[0033] Suitably, the two-part cosmetic system for use in the method of the present invention has a first composition comprising an antimicrobial metal salt and a second composition comprising a skin prebiotic active.

[0034] The first composition for use in the present invention generally contains from about 0.5% to about 30%, preferably from about 5% to 25% of the antimicrobial metal salt (by weight, based on the total weight of the composition). The preferred first composition for use in the present invention generally contains from about 0.5% to about 30%, preferably from about 5% to 25% (by weight, based on the total weight of the composition) of an antimicrobial metal salt selected from: aluminium chlorohydrate (ACH), activated aluminium chlorohydrate (AACH), sesquialuminium chlorohydrate (ASCH), activated sesquialuminium chlorohydrate (AASCH), and mixtures thereof.

[0035] The second composition for use in the present invention typically may contain from about 0.1% to about 15%, preferably from about 1% to 10% of a skin prebiotic active (by weight, based on the total weight of the composition). The preferred second composition for use in the present invention typically contains from about 0.1% to about 15%, preferably from about 1% to 10% (by weight, based on the total weight of the composition) of a skin prebiotic active selected from pimelic acid, pimelic anhydride, and mixtures thereof.

[0036] The compositions for use in the present invention typically include a cosmetically acceptable carrier. The term "cosmetically acceptable" means that the carrier is suitable for topical application to the skin, has good aesthetic properties, is compatible with the antimicrobial metal salt or skin prebiotic active, respectively, and does not cause any safety or toxicity problems. The cosmetically acceptable carriers of the first and second compositions may be the same or different, respectively.

[0037] In the context of the present invention, suitable cosmetically acceptable carriers may include an aqueous phase, an oil phase, an alcohol, a silicone phase, or mixtures thereof, and may be in the form of an emulsion. The emulsion may have a range of consistencies, including thin emulsions (which may also be suitable for spray or aerosol delivery), thick emulsions, light creams, and heavy creams.

[0038] Exemplary emulsions include water-in-oil emulsions, oil-in-water emulsions, water-in-silicone emulsions, silicone-in-water emulsions, silicone-in-polyol emulsions, polyol-in-silicone emulsions, oil-in-polyol emulsions, polyol-in-oil emulsions, water-in-wax emulsions, and water-in-oil-in-water ternary emulsions. Preferred emulsions include oil-in-water emulsions and water-in-oil emulsions.

[0039] Compositions in the form of an emulsion and suitable for use in the present invention typically have an oil phase containing one or more cosmetically acceptable fatty materials, which may be liquid or solid at room temperature (25 °C).

[0040] Suitable cosmetically acceptable fatty materials include oils of natural origin (such as sunflower oil, borage oil, soybean oil, castor oil, olive oil and almond oil); esters of monoalcohols or polyols with mono- or polycarboxylic acids, at least one of said alcohol and / or acid comprising at least one hydrocarbon-based chain containing at least 6 carbon atoms (such as octyl palmitate, isopropyl myristate, isopropyl palmitate, isopropyl isostearate, hexyl laurate, isohexyl laurate, isohexyl palmitate, decyl oleate, isodecyl oleate, cetyl stearate, decyl stearate, dihexyl decyl adipate, lauryl lactate, myristyl lactate, cetyl lactate, oleyl stearate, oleyl oleate, oleyl myristate, lauryl acetate, cetyl propionate, isononyl isononanoate, dipropylene glycol dicaprate, diisopropyl adipate, dibutyl adipate and oleyl adipate); ethers (such as dioctyl ether); fatty alcohols (such as cetyl alcohol, stearyl alcohol and behenyl alcohol); isoparaffins (such as isooctane, isododecane and isocetane); silicone oils (such as dimethicone, cyclic organosilicons and polysiloxanes); and hydrocarbon oils (such as mineral oil, petrolatum and polyisobutene); fatty acids containing from 8 to 30 carbon atoms (such as stearic acid, lauric acid, palmitic acid and oleic acid); vegetable fats (such as cocoa butter, coconut oil, palm oil and shea butter); petroleum-based, natural and synthetic waxes (such as lanolin wax, beeswax, carnauba wax, candelilla wax, paraffin wax, montan wax, microcrystalline wax, ozokerite, ceresin and polyethylene wax); hydrogenated oils which are solid at 25 °C (such as hydrogenated castor oil, hydrogenated jojoba oil, hydrogenated palm oil, hydrogenated beef tallow and hydrogenated coconut oil); and fatty esters which are solid at 25 °C (such as C 20-40 alkyl stearates).

[0041] Compositions in the form of an emulsion and suitable for the present invention generally have an aqueous phase which may also include one or more organic liquids which are miscible with water at room temperature (25 °C). Exemplary water-miscible organic liquids include monoalcohols and polyols and their derivatives, such as C2-C6 alkanols (such as ethanol and isopropanol); C2-C 10 diols and polyols (such as glycerol, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, octylene glycol, dipropylene glycol and diethylene glycol); C3-C 16 diol ethers (such as mono-, di- or tripropylene glycol (C1-C4) alkyl ethers and mono-, di- or triethylene glycol (C1-C4) alkyl ethers) and polyethylene glycols having from 2 to 12 oxyethylene units.

[0042] Compositions in the form of emulsions and suitable for use in the present invention typically contain surface active ingredients such as emulsifiers and solubilizers to enable two or more immiscible components to be combined uniformly and to help stabilize the composition. Emulsifiers that can be used to form O / W or W / O emulsions include sorbitan oleate, sorbitan sesquioleate, sorbitan isostearate, sorbitan trioleate, PEG-20 sorbitan isostearate, polyglyceryl-3-diisostearate, polyglyceryl esters of oleic acid / isostearate, polyglyceryl-6 hexaricinoleate, polyglyceryl-4-oleate, polyglyceryl-4 oleate / PEG-8 propylene glycol cocoate, polyglyceryl-2 dipolyhydroxystearate, PEG-30 dipolyhydroxystearate. Stearate, Oleamide DEA, TEA Myristate, TEA Stearate, Magnesium Stearate, Sodium Stearate, Potassium Laurate, Potassium Ricinoleate, Sodium Cocoate, Sodium Tallowate, Potassium Ricinoleate, Sodium Oleate, Cetyl Phosphate, Diethanolamine Cetyl Phosphate, Potassium Cetyl Phosphate, Glyceryl Sodium Oleate, Dimethicone Copolyol, Cetyl Dimethicone Copolyol, Caprylyl Dimethicone Ethoxyglucoside Copolyol, Dimethicone Copolyol Crosspolymer and Lauryl Methicone Copolyol.

[0043] The compositions for use in the present invention may also be formulated in a single phase carrier such as a hydrophobic or hydrophilic liquid. Suitable hydrophobic liquid carriers include liquid polyorganosiloxanes, mineral oils, hydrogenated polyisobutene, polydecene, paraffins and isoparaffins having at least 10 carbon atoms, aliphatic or aromatic ester oils (e.g., isopropyl myristate, lauryl myristate, isopropyl palmitate, diisopropyl sebacate, diisopropyl adipate and C 12 -C 15 Suitable hydrophilic liquid carriers include water, monohydric or polyhydric aliphatic alcohols (e.g., ethanol and isopropanol) having 2 to 8, preferably 2 or 3 carbon atoms, oligomeric glycol ethers (e.g., dipropylene glycol) having 2 to 5 repeating units, and mixtures thereof.

[0044] Liquid form compositions for use in the present invention may be thickened, for example, using one or more water-soluble or colloidally water-soluble polymer thickeners. Suitable water-soluble or colloidally water-soluble polymer thickeners include hydroxyethylcellulose, methylcellulose, hydroxypropylmethylcellulose, polyquaternium-10, carrageenan, guar gum, hydroxypropyl guar gum, xanthan gum, polyvinyl alcohol, acrylic acid / ethyl acrylate copolymers, carboxyvinyl polymers, cross-linked polyacrylate polymers, and polyacrylamide polymers.

[0045] Solid form compositions for use in the present invention, such as gels and sticks, typically include one or more structuring agents in an amount of from about 1% to about 35% by weight, based on the total weight of the composition, depending on the desired product consistency. Examples of structuring agents include fatty acid gelling agents selected from saturated fatty acids or hydroxy acids having from about 8 to 30 carbon atoms and their salts, esters or amides (such as sodium stearate and potassium stearate, 12-hydroxy stearic acid, esters of 12-hydroxy stearic acid and amides of 12-hydroxy stearic acid); saturated, unsubstituted monohydric fatty alcohols having from about 8 to 30 carbon atoms (such as cetyl alcohol, myristyl alcohol and stearyl alcohol); acyl amino acid derivatives such as N-lauroyl-L-glutamic acid dibutylamide; amide derivatives of di- or tribasic carboxylic acids such as alkyl N,N'dialkyl succinimides; inorganic particulate thickeners selected from siliceous and aluminosiliceous materials (such as pyrogenic silica, bentonite, hectorite, colloidal magnesium aluminum silicate and organoclays such as stearalkonium bentonite, distearyldimethylammonium hectorite, quaternium-90 bentonite), quaternium-18 bentonite and quaternium-18 hectorite); and petroleum-based, natural and synthetic waxes (such as lanolin wax, beeswax, carnauba wax, candelilla wax, castor wax, montan wax, paraffin wax, lignite wax, microcrystalline wax, ozokerite, ceresin, polymethylene wax and polyethylene wax).

[0046] Combinations of any of the above materials or product forms may also be used.

[0047] The compositions for use in the present invention (as described above) may include additional skin care actives for improving the physical and / or aesthetic characteristics of the skin. Examples include vitamins, minerals and / or antioxidants, emollients, humectants, skin brighteners, sunscreens, anti-irritants, exfoliants, herbal extracts (such as pomegranate, birch, green tea, chamomile and licorice extracts) and mixtures thereof.

[0048] The compositions for use in the present invention (as described above) may include additional functional ingredients for improving the physical and / or aesthetic properties of the composition itself. Examples include inorganic pigments (such as titanium oxide, zirconium oxide, cerium oxide, zinc oxide, iron oxide, chromium oxide, manganese violet, ultramarine, chromium hydrate and iron blue); organic pigments (such as carbon black and organic lakes of barium, strontium, calcium or aluminum); pearlescents (such as mica coated with titanium oxide and / or iron oxide); dyes, preservatives (such as disodium EDTA, benzyl alcohol, methyl paraben, phenoxyethanol, propyl paraben, ethyl paraben, butyl paraben and isobutyl paraben); pH adjusters and fragrances (such as essential oils, flower oils, natural extracts of resins, gums, balsams, legumes, mosses and other plants, as well as synthetic aromatics).

[0049] Mixtures of any of the above materials may also be used.

[0050] Packaging

[0051] The compositions (as described above) for use in the present invention can be packaged in suitable containers to suit the viscosity and the intended use by the consumer. For example, liquid compositions can be packaged in bottles or roll-on applicators, or in containers fitted with pumps suitable for finger operation, or in propellant-driven aerosol devices. Gel or cream compositions can be packaged in non-deformable bottles or squeeze containers, such as tubes or capped jars, or in applicators having a dispensing head provided with at least one hole through which the composition can be extruded under gentle pressure. Solid compositions can be shaped into sticks which can be elevated out of a dispensing package and applied directly to the desired skin area.

[0052] The present invention will be further illustrated by the following non-limiting examples. Detailed Description

[0053] Examples

[0054] A two-part cosmetic system according to the present invention is formulated with a first composition and a second composition. The first and second compositions are roll-on emulsions having the ingredients shown in Table 1a and Table 1b, respectively.

[0055] Table 1a

[0056] Ingredients Weight % ACH 12 Steareth-2 2.6 Glycerin 4 Steareth-20 0.6 PPG-15 stearyl ether 4 Water, antioxidants, chelating agents Up to 100

[0057] Table 1b

[0058] Ingredients Weight % Pimelic acid 5 Sunflower seed oil 4 Steareth-2 3 Steareth-20 0.8 Sodium hydroxide 1 Water, antioxidants, preservatives Up to 100

[0059] In vivo human studies were conducted to evaluate the performance of the cosmetic system on axillary malodor and the axillary microbiome.

[0060] The first composition (Table 1a) was applied to both axillae of healthy test subjects after washing on the first day of the study. The second composition (Table 1b) was applied to one axilla of the test subjects after washing in 3 consecutive daily doses (on the 2nd, 3rd and 4th days of the study, respectively), and the other axilla was used as a control (washed but not applied with the second composition).

[0061] The mean malodor score (MMS) of the control and treated axillae was evaluated daily by a team of expert odor assessors, and the results are shown in Table 2.

[0062] Table 2

[0063] MMS Treated Control Difference LSD p-value Day 2 2.411 2.353 -0.058 0.213 0.5799 Day 3 2.287 2.41 0.123 0.25 0.329 Day 4 2.344 2.548 0.204 0.202 0.048

[0064] The results show that, compared to the control, the treatment according to the invention leads to a gradual and significant reduction in the average malodor score.

[0065] Microbial sampling of the control and treated axillae (via swabs) was also performed daily. The results show that, compared to the control, the treatment according to the invention leads to a reshaping of the axillary microbiome, with a selective reduction of odor-related species.

Claims

1. A cosmetic method for providing skin care benefits through microbial remodeling of the skin; the method comprising the steps of: (i) Treating the skin by topical application of an antimicrobial metal salt, followed by (ii) washing the treated skin, and treating the washed skin by topical application of a skin prebiotic active, wherein the antimicrobial metal salt is selected from aluminium chlorohydrate (ACH), activated aluminium chlorohydrate (AACH), sesquialuminium chlorohydrate (ASCH), activated sesquialuminium chlorohydrate (AASCH), and mixtures thereof, and wherein the skin prebiotic active is selected from pimelic acid, pimelic anhydride, and mixtures thereof, and wherein the skin care benefit is reduction and / or prevention of axillary skin malodor.

2. The method according to claim 1, wherein step (i) is carried out on the first day of treatment, step (ii) is carried out on the following day, and repeated daily for at least two further consecutive days thereafter.

3. A two-part cosmetic system for the method according to any one of claims 1 - 2, the system having a first composition and a second composition, the first composition containing 5 to 25% of an antimicrobial metal salt (by weight, based on the total weight of the composition), the second composition containing 1 to 10% of a skin prebiotic active (by weight, based on the total weight of the composition), wherein the first composition contains 5 to 25% (by weight, based on the total weight of the composition) of an antimicrobial metal salt selected from: aluminium chlorohydrate (ACH), activated aluminium chlorohydrate (AACH), sesquialuminium chlorohydrate (ASCH), activated sesquialuminium chlorohydrate (AASCH), and mixtures thereof; and the second composition contains 1 to 10% (by weight, based on the total weight of the composition) of a skin prebiotic active selected from: pimelic acid, pimelic anhydride, and mixtures thereof.

4. The cosmetic use of a skin prebiotic active in combination with an antimicrobial metal salt for providing a skin care benefit by microbial remodeling of the skin, wherein the antimicrobial metal salt is selected from aluminium chlorohydrate (ACH), activated aluminium chlorohydrate (AACH), sesquialuminium chlorohydrate (ASCH), activated sesquialuminium chlorohydrate (AASCH), and mixtures thereof, and wherein the skin prebiotic active is selected from pimelic acid, pimelic anhydride, and mixtures thereof, and wherein the skin care benefit is reduction and / or prevention of axillary skin malodor.