Methods to increase the propagation of Staphylococcus epidermidis

Abstract

To provide a method of increasing the growth of Staphylococcus epidermidis.SOLUTION: The method comprises bringing Staphylococcus epidermidis into contact with an aqueous solution containing an extract of Pichia anomala and glycerin under aerobic conditions. Preferably, in the aqueous solution, the content of the extract of Pichia anomala is 0.13 wt.% and the content of glycerin is 3 wt.%. Preferably, in the method, Staphylococcus epidermidis is brought into contact with the aqueous solution in an aerobic bottle.SELECTED DRAWING: None

Description

Technical Field

[0001] (Cross-Reference to Related Applications) This application is a divisional continuation-in-part application of U.S. Patent Application No. 15 / 799,350, filed on October 31, 2017, which claims priority to U.S. Provisional Patent Application No. 62 / 432,945, filed on December 12, 2016. The entire disclosures of these patent applications are incorporated herein by reference for all purposes.

[0002] (Field of the Invention) The present invention provides a topically applied composition comprising (a) 0.5 to 25 weight percent of glycerin, (b) 0.1 to 5 weight percent of cetearyl olivate, (c) 0.1 to 5 weight percent of sorbitan olivate, and (d) 0.01 to 1 weight percent of Pichia anomala extract, wherein the topically applied composition is substantially free of aliphatic alcohols and is in the form of a gel cream. The composition is also a prebiotic.

Background Art

[0003] Gel creams are a desirable form of topically applied skin care compositions. The cosmetic properties of gel creams are characterized by a watery break, a translucent appearance and a light feel upon use.

[0004] NEUTROGENA Hydro Boost Gel Cream, commercially available from Johnson & Johnson Consumer Inc., is a gel cream that provides a long-lasting moisturizing effect. It is rapidly absorbed into the skin like a gel, yet has the long-lasting, powerful moisturizing power of a cream. It contains hyaluronic acid in addition to glycerin, cetearyl olivate and sorbitan olivate.

[0005] U.S. Patent No. 6,620,420 discloses an oil-in-water cosmetic or dermal gel cream (ARISTOFLEX® AVC, marketed by Clariant GmbH) comprising (i) an aqueous phase of 90% by weight or less, (ii) a lipid phase of 20% by weight or less based on the total weight of the formulation, (iii) one or more emulsifiers in 5% by weight or less, and (iv) one or more ammonium acryloyldimethyltaurate / vinylpyrrolidone copolymers in 5% by weight or less.

[0006] The genus Pichia is a genus of yeast belonging to the family Saccharomycetaceae. More than 100 species of this genus are known. Particularly well-known species include Pichia anomala, Pichia guilliermondii, Pichia norvegensis, and Pichia ohmeri.

[0007] Pichia anomala (formerly known as Hansenula anomala) can be found in raw milk and cheese. Extracts of Pichia yeast are rich in mannan, a polysaccharide composed of mannose monomers. Pichia anomala and mannan are known to be used in the treatment of aging skin. See, for example, French Patent Nos. 2938768, 2906719, 2897266, and 2976490.

[0008] PRO-LIPISKIN® is a commercially available cosmetic ingredient containing an extract of Pichia anomara. It is produced from a Pichia strain isolated from sugarcane. It is available from Silab-France.

[0009] A gel cream formula with improved anti-aging effects is needed.

[0010] The applicants found that compositions containing glycerin and yeast extracts, when administered topically, increase the concentration of glycosaminoglycans (GAGs) produced by skin that needs treatment for signs of skin aging. Specifically, these compositions contain glycerin, cetearyl olive, sorbitan olive, and Pichia anomala extract, but are substantially free of aliphatic alcohols, particularly cetyl alcohol and behenyl alcohol.

[0011] Glycosaminoglycans (GAGs), such as hyaluronic acid and chondroitin sulfate, are primarily synthesized by fibroblasts. The skin aging process is known to reduce the metabolic activity of these GAGs, resulting in a decrease in GAGs in the extracellular matrix of the dermis, reduced cell proliferation, and consequently, detrimental changes in the mechanical properties of the skin, specifically its firmness, elasticity, tensile strength, and / or flexibility.

[0012] The applicants found that in skin treated topically with the composition of the present invention, the composition of the present invention increases the amounts of hyaluronic acid and chondroitin sulfate.

[0013] The applicants also discovered that a composition containing glycerin and yeast extract acts as a prebiotic composition, increasing the concentration of Staphylococcus epidermidis on the skin. Staphylococcus epidermidis is one of the most abundant bacterial species in the skin microbiome. This bacterium constitutes 90% of the aerobic commensal bacteria and is a symbiotic, Gram-positive, facultative anaerobic bacterium associated with skin health. (Baviera G, Leoni MC, Capra L, et al. Microbiota in healthy skin and in atopic eczema. Biomed Res Int 2014;2014:436921.) [Overview of the Initiative] [Means for solving the problem]

[0014] The present invention provides a topical application composition comprising (a) 0.5 to 25 weight percent glycerin, (b) 0.1 to 5 weight percent cetearyl olive, (c) 0.1 to 5 weight percent sorbitan olive, and (d) 0.01 to 1 weight percent Pichia anomara extract, which is substantially free of aliphatic alcohols and is in the form of a gel cream.

[0015] The present invention also provides a method for increasing the proliferation of Staphylococcus epidermidis on the skin, comprising topically applying a composition comprising an extract of Pichia anomara and glycerin to skin requiring treatment for microbiome dysbiosis. [Modes for carrying out the invention]

[0016] Those skilled in the art will likely be able to make the most of the use of the present invention based on the description herein. The following specific embodiments should be interpreted as illustrative only and should not be interpreted as limiting the following disclosure in any way.

[0017] Unless otherwise specified, all scientific and technical terms used herein have the same meaning as those generally interpreted by those skilled in the art in the field to which this invention pertains. Furthermore, all publications, patent applications, patents, and other references mentioned herein are incorporated by reference only. Unless otherwise specified, percentages used to express the quantity of a component are weight percentages (i.e., %(W / W)). Similarly, weight ratios used to express the relative proportion of a component are also determined using weight percentages (i.e., weight ratios are calculated by dividing the weight percentage of one component by the weight percentage of another component). Unless otherwise specified, all ranges include both endpoints; for example, "4-9" includes both endpoints 4 and 9.

[0018] As used herein, “product” optionally refers to a finished packaged form. In one embodiment, the package is a container such as a plastic, metal, or glass tube or jar containing the composition. The product may further include additional packaging such as a plastic or cardboard box for storing such a container. In one embodiment, the product comprises the composition of the present invention and includes instructions instructing the user to apply the composition to skin or hair.

[0019] As used herein, “topical application” means applying or spreading directly onto the skin, scalp, or hair, for example, by hand, or by using an applicator such as a wipe, roller, or spray.

[0020] As used herein, “cosmetics” specifically refers to cosmetic substances or preparations that, in the case of the appearance of tissues or skin, maintain, restore, give, adorn or enhance a physically beautiful appearance, or make a person appear more beautiful or youthful.

[0021] When used in the present invention, "suitable for cosmetic use" means that the ingredients described by this term are suitable for use in contact with tissues (e.g., skin or hair) without excessive toxicity, maladaptation, instability, irritation, or allergic reactions.

[0022] In certain embodiments, the compositions of the present invention are suitable for treating signs of skin aging. As used herein, “signs of skin aging” includes the presence of fine lines and wrinkles, loss of elasticity, mottled skin, and age spots. In particularly preferred embodiments, the signs of aging are the presence of fine lines and wrinkles and / or loss of elasticity.

[0023] When used in the present invention, "treatment of signs of skin aging" refers to the alleviation, reduction, prevention, improvement, or elimination of the presence or signs of skin aging described above.

[0024] As used herein, "wrinkles" include fine lines, fine wrinkles, and coarse wrinkles. Examples of wrinkles include, but are not limited to, fine lines around the eyes (e.g., "crow's feet"), wrinkles on the forehead and cheeks, fine lines between the eyebrows, and laugh lines around the mouth.

[0025] As used herein, "loss of elasticity" includes loss of elasticity or structural integrity of skin or tissue, including but not limited to sagging, flaccidity, and lax tissue. Loss of elasticity or structural integrity of tissue may result from numerous factors, including but not limited to disease, aging, hormonal changes, mechanical trauma, environmental damage, or application of products such as cosmetics or pharmaceuticals to tissue.

[0026] As used herein, "mottled skin" refers to a skin condition associated with diffuse or spotted pigmentation that can be classified as hyperpigmentation, such as post-inflammatory hyperpigmentation.

[0027] As used herein, "spots" refers to a skin condition associated with redness or erythema.

[0028] As used herein, "improving skin firmness" means enhancing skin firmness or elasticity, preventing loss of skin firmness or elasticity, or preventing or treating sagging, flaccidity, and lax skin. Skin firmness or elasticity can be measured using a cutometer. See Handbook Of Non-Invasive Methods And The Skin, eds. J. Serup, G. Jemec & G. Grove, Chapter 66.1 (2006). Loss of skin elasticity or firmness may result from numerous factors, including but not limited to aging, environmental damage, or application of cosmetics to the skin.

[0029] As used herein, "improving skin texture" means smoothing the skin surface to remove either raised areas or crevices on the skin surface.

[0030] As used herein, “improvement of the appearance of wrinkles in the skin” means blocking, delaying, stopping, or reversing the process of wrinkle and fine line formation in the skin.

[0031] As used herein, the term “safe and effective amount” means an amount sufficient to induce the desired effect but small enough to avoid serious side effects. The safe and effective amount of a compound, extract, or composition will vary depending, for example, the age of the end user, their health and environmental exposure, the duration and nature of the treatment, the specific extract, component, or composition used, the specific carrier used, and similar factors.

[0032] As used herein, the term "gel cream" refers to a formulation in which low concentrations of oil droplets are suspended in an aqueous gel matrix.

[0033] In certain embodiments, the compositions of the present invention are suitable for treating skin that requires improvement of the skin's barrier function and moisturization. When used in the present invention, "skin that requires improvement of the skin's barrier function and moisturization" means skin that is dehydrated,.

[0034] As used herein, “prebiotics” means that which selectively promote the growth of beneficial bacteria or are used as a substrate for producing beneficial metabolites on the skin. In one embodiment, the beneficial bacteria is Staphylococcus epidermidis.

[0035] As used herein, “microbiome dysbiosis” means any change in the composition of the commensal microorganisms on or within the skin of a healthy individual, i.e., an imbalance between normally dominant and normally recessive microbial species on or within the skin.

[0036] As used herein, “acne” refers to a condition resulting from the action of hormones and other substances in the sebaceous glands and hair follicles, typically resulting in clogged pores and the formation of inflammatory or non-inflammatory lesions on the skin. In particular, this relates to blemishes, lesions, or pimples, pre-germinating pimples, blackheads, and / or whiteheads. As used herein, “pre-germinating pimples” refers to inflammatory vesicles that are not visually apparent to the naked eye on the surface of the skin (e.g., as lesions).

[0037] As used herein, "rosacea" means skin having persistent erythema with or without papules, pustules, or nodules.

[0038] As used herein, “eczema” refers to a chronic skin disease involving inflammation of the epidermis, often presenting as a scaly and itchy rash. As used herein, “atopic dermatitis” refers to a type of chronic, recurrent, non-contagious, and itchy eczematous disease. As used herein, “psoriasis” refers to a chronic, non-infectious disease that often presents as red, scaly patches or plaques of excessive inflammation or excess skin growth on the extensor surfaces, such as the knees and elbows.

[0039] As described herein, the applicants have discovered a topical composition comprising (a) 0.5 to 25 weight percent glycerin, (b) 0.1 to 5 weight percent cetearyl olive, (c) 0.1 to 5 weight percent sorbitan olive, and (d) 0.01 to 1 weight percent Pichia anomara extract, which is substantially free of aliphatic alcohols and is in the form of a gel cream.

[0040] Glycerin The above composition contains 0.5 to 25 weight percent of glycerin. In one embodiment, the above composition contains 1 to 6 weight percent of glycerin.

[0041] In another embodiment, the composition is a prebiotic and contains about 3 weight percent glycerin.

[0042] Cetearyl olive and sorbitan olive The above composition contains 0.1 to 5 weight percent of cetearyl olivate. In one embodiment, the above composition contains 0.1 to 2 weight percent of cetearyl olivate.

[0043] Furthermore, the above composition contains 0.1 to 5 weight percent of sorbitan olivete. In one embodiment, the above composition contains 0.1 to 2 weight percent of glycerin olivete.

[0044] A convenient source of cetearyl olive and sorbitan olive is Olivem® 1000, commercially available from Hallstar.

[0045] yeast extract The topical composition contains one or more extracts of Pichia anomala. Pichia is a genus of yeast in the Saccharomycesaceae family. More than 100 species of this genus are known. Particularly well known species include Pichia anomala, Pichia guilermonzi, Pichia norbegensis, and Pichia omerii. Pichia anomala (formerly named Hanzenula anomala) can be found in raw milk and cheese. Extracts of Pichia yeasts are rich in mannan, a polysaccharide composed of mannose monomers. Pichia anomala and mannan are known to be used in the treatment of aging skin. See, for example, French Patent Nos. 2938768, 2906719, 2897266, and 2976490.

[0046] Specifically, such extracts may be extracts produced using one of various strains of Pichia anomara isolated from the fruit or other aerial parts of the plant. Any cosmetically acceptable extract of Pichia anomara may be used.

[0047] One example of a suitable extract from Pichia anomara is PRO-LIPISKIN, commercially available from Silab-France. This is produced from a strain of Pichia anomara found in sugarcane.

[0048] Another example of a suitable extract from Pichia anomara is produced from the Pichia anomara strain found in the fruits or leaves of the kiwi plant.

[0049] All of the aforementioned can be provided as aqueous solutions containing approximately 20%, more specifically 2-10%, and most specifically 3-7% of the dry matter. Thus, the above compositions may contain 0.01-1 weight percent of Pichia anomara extract.

[0050] PRO-LIPISKIN® is a commercially available cosmetic ingredient containing an extract of Pichia anomara. It is produced from a Pichia strain isolated from sugarcane. It is available from Silab-France.

[0051] In one embodiment, the above composition is substantially free of aliphatic alcohols. Specifically, the above composition is substantially free of cetyl alcohol and behenyl alcohol. As used herein, the phrase "substantially free" means that the component is present in less than 0.1 weight percent, less than 0.01 weight percent, or not present at all. In one embodiment of the present invention, the above composition is free of both cetyl alcohol and behenyl alcohol. In another embodiment of the present invention, the above composition is free of aliphatic alcohols.

[0052] In another embodiment, the above composition has a pH of less than 7.

[0053] Additional cosmetic surfactants The compositions of the present invention may further contain any variety of additional cosmetic surfactants. Examples of suitable additional surfactants include skin whitening agents, darkening agents, additional anti-aging agents, tropoelastin promoters, collagen promoters, anti-acne agents, gloss modifiers, antimicrobial agents (e.g., anti-yeast agents, antifungal agents and antibacterial agents), anti-inflammatory agents, antiparasitic agents, topical analgesics, sunscreens, photoprotective agents, antioxidants, keratolytic agents, detergents / surfactants, moisturizers, nutrients, vitamins, energy enhancers, antiperspirants, astringents, deodorants, hair removal agents, hair growth enhancers, hair growth retardants, stabilizers, hydration enhancers, efficacy enhancers, anti-callus agents, skin conditioning agents, anti-cellulite agents, odor inhibitors (e.g., odor masking agents), or pH modifiers.

[0054] Examples of various suitable additional cosmetic-grade active substances include the following: Hydroxy acids, benzoyl peroxide, D-panthenol, UV filters [Avobenzone (Parsol 1789), bis-disulizole disodium (Neo Heliopan AP), diethylamino hydroxybenzoyl hexyl benzoate (Uvinul A Plus), ecumsul (Mexoryl SX), methyl anthranilate, 4-aminobenzoic acid (PABA), cinoxate, ethylhexyl triazone (Uvinul T150), homosalate, 4-methylbenzylidene camphor (Parsol 5000), octyl methoxycinnamate (Octinoxate), octyl salicylate (Octisalate), padimate O (Escalol 507), phenylbenzimidazole sulfonic acid (Ensulizole), polysilicone-15 (Parsol SLX), torosamine salicylate, bemotoridinol (Tinosorb Examples of S) include, but are not limited to, benzophenone 1-12, dioxybenzone, drometrizole trisiloxane (Mexoryl XL), isocotridinol (Uvasorb HEB), octocrylene, oxybenzone (Eusolex 4360), sulisobenzone, bisoctrizole (Tinosorb M), titanium dioxide, and zinc oxide. ], carotenoids, free radical scavengers, spin traps, retinoids and retinoid precursors (e.g., retinol, retinoic acid and retinyl palmitate), ceramides, polyunsaturated fatty acids, essential fatty acids, enzymes; enzyme inhibitors; minerals; hormones (e.g., estrogen), steroids (e.g., hydrocortisone, 2-dimethylaminoethanol), copper salts (e.g., copper chloride), copper-containing peptides, coenzyme Q10, amino acids (e.g., proline), vitamins; lactobionic acid, acetyl-coenzyme A, niacin, riboflavin, thiamine, ribose, electron transporters (e.g., NADH and FADH2), and other plant extracts (e.g., extracts of oats, aloe vera, feverfew, soybeans, shiitake mushrooms), and derivatives and mixtures thereof.

[0055] In certain preferred embodiments, the above composition comprises at least one additional skin moisturizing agent.

[0056] In certain preferred embodiments, the composition comprises at least one additional agent for improving the appearance of at least one sign of skin aging. Examples of preferred additives for improving the appearance of at least one sign of skin aging include, but are not limited to, tropoelastin promoters, collagen promoters, retinoids, dimethylaminoethanol, N,N,N',N'-tetrakis(2-hydroxypropyl)ethylenediamine, alpha hydroxy acids, polyhydroxy acids, sugar amines, and two or more combinations thereof.

[0057] "Tropoelastin promoter" as used herein refers to a classification of compounds that have biological activity to enhance tropoelastin production. The tropoelastin promoters according to the present invention include all natural or synthetic compounds that can enhance tropoelastin production in the human body.

[0058] Examples of suitable tropoelastin promoters include, but are not limited to, blackberry extract, sedge extract, feverfew extract, and dimetallic complexes having copper and / or zinc components. Dimetallic complexes having copper and / or zinc components may be, for example, copper-zinc citrate, copper-zinc oxalate, copper-zinc tartrate, copper-zinc malate, copper-zinc succinate, copper-zinc malonate, copper-zinc maleate, copper-zinc aspartate, copper-zinc glutamate, copper-zinc glutarate, copper-zinc fumarate, copper-zinc glucarate, copper-zinc polyacrylate, copper-zinc adipate, copper-zinc pimelate, copper-zinc suberate, copper-zinc azelaate, copper-zinc sebacate, copper-zinc dodecanoate, or combinations thereof. In preferred embodiments, the tropoelastin promoter is selected from blackberry extract, sedge extract, feverfew extract, and combinations thereof. In a particularly preferred embodiment, the tropoelastin promoter is selected from blackberry extract, feverfew extract, and combinations thereof.

[0059] "Blackberry extract" means a blend of compounds isolated from plants of the genus Rubus, preferably from Rubus parvifolius. In one embodiment, the above compounds are isolated from the flowers of the plant. In a further embodiment, the above compounds are isolated from dried flowers of the plant. Such compounds may be isolated from one or more parts of the plant (e.g., the whole plant, the flowers, seeds, roots, rhizomes, stems, fruits and / or leaves). In a preferred embodiment, the blackberry extract is a blackberry leaf extract. One particularly preferred blackberry extract is produced by extracting Rubus parvifolius leaves with a mixture of water and ethanol formulated to have an activity of about 5% to about 10% using a maltodextrin matrix, and is commercially available from Symrise Inc. (Teterboro, NJ) under the trademark name SymMatrix.

[0060] The compositions of the present invention may contain one or more tropoelastin promoters (e.g., those described above) in amounts effective for cosmetic use. Based on the active substance, the compositions preferably contain about 0.1% to about 10% of tropoelastin promoters, more preferably about 0.5% to about 5% of tropoelastin promoters, and most preferably about 0.5% to about 2% of tropoelastin promoters.

[0061] "Collagen promoter" as used herein refers to a bioactive compound that enhances collagen production. "Non-retinoid collagen promoter" according to the present invention includes all natural or synthetic compounds that are neither retinoids nor derived from retinoids, and that can enhance collagen production in the human body.

[0062] Suitable collagen promoters include, but are not limited to, retinoids including retinol, retinaldehyde and retinoic acid, extracts of feverfew (Tanacetum parthenium), extracts of centella asiatica and Siegesbeckia orientalis, soybean extracts, collagen-promoting peptides, ursolic acid, and asiaticosides.

[0063] Centella asiatica, also known as Violette marronne on Réunion Island, Gotu Kola or Indian Centella asiatica in India, Centella repanda in North America, and Talapetraka in Madagascar, is a pleomorphic herbaceous plant belonging to the Apiaceae family, particularly the Hydrocotyleioideae subfamily. It is native to the tropics and prefers humid, shady areas at altitudes of approximately 600-1200 meters above sea level. Centella asiatica has three varieties: Typica, Abyssinica, and Floridana. This herbaceous plant is well-known and used for its healing, sedative, analgesic, antidepressant, antiviral, and antimicrobial properties. The bioactivity of this herbaceous plant is thought to be due to the presence of triterpene molecules within the plant. A suitable Centella asiatica extract is available as TECA from Bayer Consumer HealthCare (Basel, Switzerland).

[0064] "Menamomi extract" refers to any of the various extracts of the Menamomi plant that contain darutoside, available from Sederma (Croda International Group (Edison, NJ)).

[0065] Suitable collagen-promoting peptides include matricine peptides (i.e., peptides derived from the degradation of extracellular matrix proteins—collagen, elastin, or proteoglycans), which include palmitoyl pentapeptides [e.g., MATRIXYL from Sederma (Croda International Group (Edison, NJ))], GHK copper peptide available as PROCYTE from Photomedex (Montgomeryville, PA), palmitoyl GHK peptide available as Biopoeptide CL from Sederma (Croda International Group (Edison, NJ)), biomimetic tetrapeptides such as those available as Chronoline Tri Peptide from Unipex (Quebec, Canada), and palmitoyl tripeptides available as Syn-Coll from DSM (Basel, Switzerland).

[0066] Ursolic acid is also known as pentacyclic triterpenic acid, Prunol, Malol, Urson, beta-ursolic acid, and 3-beta-hydroxy-ursa-12-eno-28-acid. It is commercially available, for example, from Sigma-Aldrich (St. Louis, MO).

[0067] Asiaticoside, also chemically known as [6-[[3,4-dihydroxy-6-(hydroxymethyl)-5-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxymethyl]-3,4,5-trihydroxyoxan-2-yl]10,11-dihydroxy-9-(hydroxymethyl)-1,2,6a,6b,9,12a-hexamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picen-4a-carboxylate), is commercially available, for example, from Bayer Sante Familiale Division Serdex, 69, Boulevard Victor Hugo 93400 SAINT-OUEN France.

[0068] The composition of the present invention may contain one or more collagen promoters in an amount effective for cosmetic use. The above composition preferably contains about 0.1% to about 10% collagen promoter, more preferably about 0.5% to about 5% collagen promoter, and most preferably about 0.5% to about 2% collagen promoter, based on the active substance.

[0069] The composition of the present invention may further contain at least one skin whitening activator. Examples of suitable skin whitening activators include, but are not limited to, tyrosinase inhibitors, melanin degrading agents, melanosome transport inhibitors (including PAR-2 ​​antagonists), exfoliating agents, sunscreens, retinoids, antioxidants, tranexamic acid, cetyl tranexamate hydrochloride, skin whitening agents, linoleic acid, adenosine monophosphate disodium salt, chamomile extract, allantoin, opacifiers, talc and silica, zinc salts, and other agents as described in Solano et al. Pigment Cell Res. 19 (550-571) and Ando et al. Int J Mol Sci 11 (2566-2575).

[0070] Suitable tyrosinase inhibitors include, but are not limited to, vitamin C and its derivatives, vitamin E and its derivatives, kojic acid, arbutin, resorcinol, hydroquinone, flavonoids (e.g., licorice flavanoids, licorice root extract, mulberry root extract, Dioscorea coposita root extract, Saxifragaceae extract, etc.), ellagic acid, salicylates and derivatives, glucosamine and its derivatives, fullerene, hinokitiol, diacitol, acetylglucosamine, 5,5'-dipropyl-biphenyl-2,2'-diol (Magnolignan), 4-(4-hydroxyphenyl)-2-butanol (4-HPB), and combinations of two or more of these. Examples of vitamin C derivatives, but not limited to these, include ascorbic acid and its salts, ascorbic acid-2-glucoside, sodium ascorbic acid phosphate, magnesium ascorbic acid phosphate, and concentrated natural extracts of vitamin C. Examples of vitamin E derivatives, but not limited to these, include α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, α-tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol, and mixtures thereof, tocopherol acetate, tocopherol phosphate, and concentrated natural extracts of vitamin E derivatives. Examples of resorcinol derivatives include, but are not limited to, resorcinol, 4-substituted resorcinols [e.g., 4-butylresorcinol (Lucinol), 4-hexylresorcinol (Synovea HR, Sytheon), phenylethylresorcinol (Symwhite, Symrise), 1-(2,4-dihydroxyphenyl)-3-(2,4-dimethoxy-3-methylphenyl)-propane (Nibitol, Unigen), and other 4-alkylresorcinols], and natural extracts rich in resorcinol. Examples of salicylates include, but are not limited to, 4-methoxypotassium salicylate, salicylic acid, acetylsalicylic acid, 4-methoxysalicylic acid, and salts thereof.In certain preferred embodiments, the tyrosinase inhibitor may be a 4-substituted resorcinol, a vitamin C derivative, or a vitamin E derivative. In more preferred embodiments, the tyrosinase inhibitor may include phenylethyl resorcinol, 4-hexyl resorcinol, or ascorbyl-2-glucoside.

[0071] Examples of suitable melanin-degrading agents include, but are not limited to, peroxides and enzymes (e.g., peroxidases and ligninases). In certain preferred embodiments, melanin inhibitors include peroxides and ligninases.

[0072] Examples of suitable melanosome transport inhibitors include PAR-2 ​​antagonists (e.g., soy trypsin inhibitors or Bowman-Burk inhibitors), vitamin B3 and its derivatives (e.g., niacinamide), essential soy, whole soy, and soy extracts. In certain preferred embodiments, the melanosome transport inhibitor may be soy extract or niacinamide.

[0073] Examples of release agents include, but are not limited to, alpha-hydroxy acids (e.g., lactic acid, glycolic acid, malic acid, tartaric acid, citric acid, or any combination thereof), beta-hydroxy acids (e.g., salicylic acid, polyhydroxy acids, e.g., lactobionic acid and gluconic acid), and mechanical release agents (e.g., micro-skin abrasives). In certain preferred embodiments, glycolic acid or salicylic acid may be used as the release agent.

[0074] Examples of retinoids include, but are not limited to, retinol (vitamin A alcohol), retinal (vitamin A aldehyde), retinyl acetate, retinyl propionate, retinyl linoleate, retinoic acid, retinyl palmitate, isotretinoin, tazarotene, bexarotene, adapalene, and combinations of two or more of these. In certain preferred embodiments, the retinoid is selected from the group consisting of retinol, retinal, retinyl acetate, retinyl propionate, retinyl linoleate, and combinations of two or more of these. In certain more preferred embodiments, the retinoid is retinol.

[0075] Examples of antioxidants include, but are not limited to, sulfhydryl compounds and their derivatives (e.g., sodium metabisulfite and N-acetyl-cysteine, glutathione), lipoic acid and dihydrolipoic acid, stilbenoides (e.g., resveratrol and its derivatives), lactoferrin, iron and copper chelating agents, and water-soluble antioxidants such as ascorbic acid and ascorbic acid derivatives (e.g., ascorbyl-2-glucoside, ascorbyl palmitate, and ascorbyl polypeptide). Suitable oil-soluble antioxidants for use in the compositions of the present invention include, but are not limited to, butylated hydroxytoluene, retinoids (e.g., retinol and retinyl palmitate), tocopherol (e.g., tocopherol acetate), tocotrienol, and ubiquinone. Suitable natural extracts containing antioxidants for use in the compositions of the present invention include, but are not limited to, extracts containing flavonoids and isoflavonoids and their derivatives (e.g., genistein and daidzein), and extracts containing resveratrol. Examples of such natural extracts include grape seeds, green tea, black tea, white tea, pine bark, feverfew, feverfew without parthenolide, oat extract, blackberry extract, sedge extract, soybean extract, grapefruit extract, wheat germ extract, hesperezin, grape extract, purslane extract, lycochalcone, chalcone, 2,2'-dihydroxychalcone, primrose extract, and propolis.

[0076] The composition of the present invention may contain one or more anti-inflammatory compounds in an amount effective for cosmetic use.

[0077] Examples of suitable anti-inflammatory compounds include substituted resorcinols, (E)-3-(4-methylphenylsulfonyl)-2-propennitrile (e.g., "Bay11-7082" commercially available from Sigma-Aldrich (St. Louis, Missouri)), tetrahydrocurcuminoids (e.g., Tetrahydrocurcuminoid CG available from Sabinsa Corporation (Piscataway, NJ)), and extracts and substances derived from the following: Phellodendron amurense peel extract (PCE), undenatured soybean (Glycine max), feverfew (Tanacetum parthenium), ginger (Zingiber officinale), ginkgo biloba, madecassoside (Centella asiatica extract component), Cotinus coggygria, butterbur extract (Petasites hybridus), and goji berry (Lycium verum). Examples include barbarum, milk thistle extract (Silybum marianum), honeysuckle (Lonicera japonica), Peruvian balsam (Myroxylon pereirae), sage (Salvia officinalis), cranberry extract (Vaccinium oxycoccos), amaranth oil (Amaranthus cruentus), pomegranate (Punica granatum), yerba mate (Ilex paraguariensis leaf extract), white lily flower extract (Lilium candidum), olive leaf extract (Olea europaea), phloretin (apple extract), oat flour (Aveena sativa), Lifenol (hops, Humulus lupulus) extract, Bugrane P (Ononis spinosa), licochalcone (licorice, Glycyrrhiza inflate extract component), Symrelief (bisabolol and ginger extract), and combinations of two or more of these.

[0078] In one embodiment, the anti-inflammatory agent is resorcinol. Particularly preferred substituted resorcinols are 4-hexylresorcinol and 4-octylresorcinol, especially 4-hexylresorcinol. 4-hexylresorcinol is commercially available from Sytheon (Lincoln Park, NJ) as SYNOVEA HR. 4-octylresorcinol is commercially available from City Chemical LLC (West Haven, Connecticut).

[0079] "Feverfew extract" means, for example, an extract of the plant "Tanacetum parthenium" that can be produced according to the details described in U.S. Patent Publication No. 2007 / 0196523, entitled "PARTHENOLIDE FREE BIOACTIVE INGREDIENTS FROM FEVERFEW (TANACETUM PARTHENIUM) AND PROCESSES FOR THEIR PRODUCTION." A particularly preferred feverfew extract is commercially available from Integrated Botanical Technologies (Ossining, NY) as approximately 20% active feverfew.

[0080] In one embodiment, the topical application composition contains hyaluronic acid. The hyaluronic acid may be linear hyaluronic acid, cross-linked hyaluronic acid, or a mixture of linear and cross-linked hyaluronic acid. It may also be in salt form, for example, sodium hyaluronate. The molecular weight of the hyaluronic acid can be varied as desired, from very low to very high molecular weight.

[0081] A commercially available cross-linked hyaluronic acid useful in this invention is HyaCare® Filler CL, manufactured by Evonik Industries AG. HyaCare® Filler CL is a high-purity, fermentation-derived, high-quality biopolysaccharide obtained by a solvent-free process. It is a skin-like hyaluronic acid with an intermediate molecular weight of 700 kDa.

[0082] Another commercially available cross-linked hyaluronic acid useful in the present invention is Hylasome® EG10, sold by Vantage Specialty Ingredients.

[0083] Crosslinked hyaluronic acid can be prepared as is known in the art. For example, natural or synthetic sources of linear hyaluronic acid can be crosslinked using a variety of crosslinking agents, including divinyl sulfone (DVS), formaldehyde, polyanhydride, polyaldehyde, polyhydric alcohol, carbodiimide, epichlorohydrin, ethylene glycol diglycidyl ether, butanediol diglycidyl ether, polyglycerol polyglycidyl ether, polyethylene glycol, polypropylene glycol diglycidyl ether, bis- or poly-epoxy crosslinking agents [such as 1,2,3,4-diepoxybutane or 1,2,7,8-diepoxyoctane], or other crosslinking agents known in the art. The degree of crosslinking can also be adjusted as is known in the art.

[0084] In another embodiment, the composition includes a citrus fruit extract, such as lemon peel extract.

[0085] Other ingredients The compositions of the present invention are applied topically to human skin or hair. Therefore, the compositions may further contain topically applicable ingredients known in the personal care field for use in oil-in-water emulsion-type gel cream formulations.

[0086] In certain preferred embodiments, the composition comprises one or more topical application components selected from the group consisting of surfactants, chelating agents, additional emollients, moisturizers, conditioners, preservatives, emulsions, fragrances, and the like.

[0087] Additional emollients include compounds that help maintain the soft, smooth, and supple appearance of the skin (for example, by remaining on the surface or stratum corneum of the skin to act as a lubricant). Examples of suitable emollients can be found in Chapter 35, pages 399-415 (Skin Feel Agents, by G. Zocchi) of the Handbook of Cosmetic Science and Technology (edited by A. Barel, M. Paye, and H. Maibach, published in 2001 by Marcel Dekker, Inc. New York, NY), and include, but are not limited to, petrolatum, hexyldecyl stearate, and plant, nut, and vegetable oils (e.g., macadamia nut oil, rice bran oil, grape seed oil, palm oil, primrose oil, hydrogenated peanut oil, and avocado oil).

[0088] A humectant is a compound intended to increase the water content of the outermost layer of skin (e.g., a hygroscopic compound). Examples of suitable humectants can be found in Chapter 35, pages 399-415 (Skin Feel Agents, by G. Zocchi) of the Handbook of Cosmetic Science and Technology (edited by A. Barel, M. Paye, and H. Maibach, published in 2001 by Marcel Dekker, Inc. New York, NY), and include, but are not limited to, glycerin, sorbitol, or trehalose (e.g., α,α-trehalose, β,β-trehalose, α,β-trehalose) or their salts or esters (e.g., trehalose-6-phosphate).

[0089] A surfactant refers to a surface-active agent intended for cleaning or emulsifying. Suitable examples of surfactants can be found in Chapter 37, pages 431-450 (Classification of surfactants, by L. Oldenhove de Guertechin) of the Handbook of Cosmetic Science and Technology (edited by A. Barel, M. Paye, and H. Maibach, published in 2001 by Marcel Dekker, Inc., New York, NY), and include, but are not limited to, anionic surfactants such as sulfates, cationic surfactants such as betaine, amphoteric surfactants such as sodium cocoglycinate, and nonionic surfactants such as alkyl polyglucosides.

[0090] Examples of suitable chelating agents include those that can protect and preserve the composition of the present invention. Preferably, the chelating agent is ethylenediaminetetraacetic acid ("EDTA"), and more preferably, tetrasodium EDTA, which is commercially available from Dow Chemical Company (Midland, Michigan) under the trademark name VERSENE 100XL.

[0091] Suitable preservatives include, for example, parabens, quaternary ammonium species, phenoxyethanol, benzoate, DMDM ​​hydantoin, and organic acids, which are present in the composition in an amount of about 0 to about 1% or about 0.05% to about 0.5% based on the total weight of the composition.

[0092] Any conditioner that imparts additional attributes to hair, such as shine, is suitable for use in the present invention. Examples include, but are not limited to, volatile silicone conditioning agents having an atmospheric pressure boiling point of less than approximately 220°C. Suitable examples of volatile silicones include, non-exclusively, cyclomethicone fluids such as polydimethylsiloxane, polydimethylcyclosiloxane, hexamethyldisiloxane, and polydimethylcyclosiloxane, which is commercially available from Dow Corning Corporation (Midland, Michigan) under the trade name "DC-345," and mixtures thereof, with cyclomethicone fluid being preferred. Other suitable conditioners include cationic polymers, such as polyquaternium and cationic guar.

[0093] Various commercially available pearlescent or opacifying agents are suitable for use in compositions. Examples of suitable pearlescent or opacifying agents include, but are not limited to, the following: (a) fatty acids having about 16 to about 22 carbon atoms and (b) mono or diester of either ethylene or propylene glycol, (a) fatty acids having about 16 to about 22 carbon atoms, (b) formula HO-(JO) a Mono or diesters of polyalkylene glycols of -H (wherein J is an alkylene group having about 2 to about 3 carbon atoms, and a is 2 or 3), aliphatic alcohols containing about 16 to about 22 carbon atoms, aliphatic esters of formula:KCOOCH2L (wherein K and L independently contain about 15 to about 21 carbon atoms), inorganic solids insoluble in shampoo compositions, and mixtures thereof.

[0094] Any fragrance composition suitable for use on the skin may be used in accordance with the present invention.

[0095] The above composition may contain a thickening agent such as hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer. Such an agent is commercially available from Seppic as Sepimax® C. In one embodiment, the above composition contains about 0.1 to about 10 weight percent or about 1 to about 8 weight percent of the thickening agent.

[0096] By adjusting the amount and selection of the thickening agent, the gel cream can be stabilized while maintaining its appearance and texture.

[0097] The above compositions may contain, for example, natural rubber, acrylic acid and acrylate polymers and copolymers, and suitable gelling agents such as cellulose derivatives (e.g., hydroxymethylcellulose and hydroxypropylcellulose). Suitable gelling agents for oils (such as mineral oils) include, but are not limited to, hydrogenated butylene / ethylene / styrene copolymers and hydrogenated ethylene / propylene / styrene copolymers. Such gels typically contain about 0.1% to 5% by weight of such gelling agents.

[0098] Additional cosmetic surfactants may be present in the composition in any preferred amount, for example, about 0.0001% to about 20% by weight of the composition, for example, about 0.001% to about 10% by weight, for example, about 0.01% to about 5% by weight. In certain preferred embodiments, the amount is 0.1% to 5%, and in other preferred embodiments, it is 1% to 2%.

[0099] Compositions, as well as formulations and products containing such compositions, can be prepared using methods known to those skilled in the art.

[0100] In one embodiment, the above composition comprises dimethicone, carbomer, glycerin, beeswax, polyacrylamide, laureth-7, C13-14 isoparaffin, water, chlorphenesin, ethylhexylglycerin, phenoxyethanol, cetearyl olivine, sorbitan olivine, dimethicone, dimethicone crosspolymer, sodium hydroxide, dimethiconol, vinyl dimethicone crosspolymer, C12-14 pareth-12, sodium hyaluronate, and an extract of Pichia anomala.

[0101] method The present invention further includes a method for improving the barrier function of skin and moisturizing skin by applying the composition of the present invention to skin that requires improvement of the skin barrier function and moisturizing. The above method includes, for example, topical application of the above composition to skin that requires improvement of the skin barrier function and moisturizing. Such topical application may be performed on any skin of the body that requires treatment, such as the face, lips, neck, chest, back, arms, armpits, hands, feet and / or legs.

[0102] The present invention further includes a method for improving the appearance of at least one sign of skin aging by applying the composition of the present invention to skin that requires improvement in the appearance of at least one sign of skin aging. The above method includes, for example, topical application of the above composition to skin that requires treatment for at least one sign of skin aging. Such topical application may be performed on any skin of the body that requires treatment, such as the face, lips, neck, chest, back, arms, armpits, hands, feet and / or legs.

[0103] The present invention also provides a method for increasing the proliferation of Staphylococcus epidermidis on the skin, comprising topically applying a composition comprising an extract of Pichia anomara and glycerin to skin requiring treatment for microbiome dysbiosis. In one embodiment, the composition comprises about 0.13 weight percent of Pichia anomara extract and about 3 weight percent of glycerin.

[0104] In certain embodiments, microbiome dysbiosis is accompanied by eczema.

[0105] In certain embodiments, the microbiome dysbiosis is accompanied by acne or rosacea.

[0106] In certain embodiments, microbiome dysbiosis is accompanied by a decrease in the skin's barrier function or moisture retention, such as skin that is dehydrated, lacks sebum, cracked, dry, itchy, scaly, xerotic, dehydrated, lacking flexibility, lacking radiance, dull, or lacking in lipids.

[0107] The applicants discovered that a combination of Pichia anomala extract and glycerin surprisingly enhances the growth of beneficial S. epidermis.

[0108] Any preferred method may be used to apply the composition to the skin in need. For example, the composition may be applied directly from the package to the skin in need, applied by hand to the skin in need, transferred from a base material such as a wipe or mask, or a combination of two or three of these. In other embodiments, the composition may be applied via a dropper, tube, roller, spray and patch, or added to a bath or water otherwise applied to the skin. The above compositions may be applied in a variety of ways / forms, including but not limited to leave-on creams, masks and / or serums.

[0109] The following non-limiting embodiments further illustrate the present invention. [Examples]

[0110] (Example 1) A topical gel cream composition according to the present invention was prepared, having the following components.

[0111] [Table 1]

[0112] (Example 2) A topical gel cream composition according to the present invention was prepared, having the following components.

[0113] [Table 2]

[0114] (Example 3) The ability of four test materials to grow S. epidermis (ATCC 12228) under aerobic conditions was investigated. The materials were: 1) sterile filtered water for injection (WFI), 2) WFI containing 5% aqueous solution containing 0.13 wt percent extract of Pichia anomara grown on kiwi, 3) WFI containing 3% glycerol, and 4) WFI containing both 5% aqueous solution containing 0.13 wt percent extract of Pichia anomara grown on kiwi and 3% glycerol.

[0115] The detection time ("TTD") of S. epidermidis was measured using the BacT / Alert 3D system (BioMerieux Inc.) according to the manufacturer's instructions. S. epidermidis was inoculated into standard BacT / ALERT aerobic vials (BioMerieux Inc.) at a population size of approximately 1000 colony-forming units (CFU) / mL. The test material was prepared with WFI and injected into standard aerobic vials in 1 mL volumes at the indicated population size. Standard aerobic vials inoculated with S. epidermidis alone and 10 mL of WFI were used as controls. The vials were then inserted into the BacT / Alert 3D system until the steady growth phase. The TTD value was automatically calculated by the BacT / Alert 3D according to the system's growth detection algorithm. Three samples were tested for each test material, and the results were averaged. The relative detection time (RTTD) was calculated as (TTD treatment) / TTD control × 100.

[0116] The results are shown in Table 3.

[0117] [Table 3]

[0118] The round-to-the-minute (RTTD) of the Pichia anomala extract combined with glycerol was remarkably lower than that of either test material alone.

[0119] [Implementation Method] (1) A method for increasing the proliferation of Staphylococcus epidermidis on the skin, comprising topically applying a composition comprising an extract of Pichia anomala and glycerin to skin requiring treatment for microbiota dysbiosis. (2) The method according to Embodiment 1, wherein the composition comprises about 0.13 weight percent of Pichia anomara extract and about 3 weight percent of glycerin. (3) The method according to Embodiment 1, wherein the composition is substantially free of aliphatic alcohols and is in the form of a gel cream. (4) The method according to Embodiment 1, wherein the composition has a pH of less than about 7. (5) The method according to Embodiment 1, wherein the Pichia anomara extract is prepared from a strain of Pichia anomara found in the fruit or leaves of a kiwi.

[0120] (6) The method according to Embodiment 1, wherein the extract of Pichia anomara is prepared from a strain of Pichia anomara found on sugarcane. (7) The method according to Embodiment 1, wherein the microbial dysbiosis is accompanied by eczema. (8) The method according to Embodiment 1, wherein the microbial dysbiosis is accompanied by acne or rosacea. (9) The method according to Embodiment 1, wherein the microbial dysbiosis is accompanied by a decrease in the skin's barrier function or moisture retention.

Claims

1. A method for increasing the growth of Staphylococcus epidermidis on skin, comprising topically applying a composition comprising (i) an aqueous solution containing an extract of Pichia anomala and (ii) glycerin to the skin requiring treatment for microbiome dysbiosis under aerobic conditions, thereby bringing Staphylococcus epidermidis into contact with the composition. The composition comprises 0.01 to 1 weight percent of Pichia anomara extract and 1 to 6 weight percent of glycerin. Regarding the decrease in relative detection time (RTTD) of Staphylococcus epidermidis compared to water as a control, (a) is the reduction value of a first similar composition that includes (i) but does not include (ii), (b) is the reduction value of a second similar composition which includes (ii) but does not include (i), (c) is the reduction value of the composition containing both (i) and (ii), The sum of (a) and (b) is less than (c) in terms of methods (excluding medical procedures performed on humans).

2. The method according to claim 1, wherein the sum of (a) and (b) is 0.481 times or less of (c).

3. The method according to claim 1, wherein the composition comprises 0.13 weight percent of Pichia anomara extract and 3 weight percent of glycerin.

4. The method according to claim 3, wherein the sum of (a) and (b) is 0.481 times or less of (c).

5. The method according to any one of claims 1 to 4, wherein the Pichia anomara extract is prepared from a strain of Pichia anomara found in the fruit or leaves of a kiwi.

6. The composition comprises 0.13 weight percent of Pichia anomara extract and 3 weight percent of glycerin. The method according to claim 5, wherein the sum of (a) and (b) is 0.481 times or less of (c).

7. The method according to claim 1, wherein the composition has a pH of less than 7.

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