TOPICAL COMPOSITION AND ITS USES

Abstract

The invention relates to methods and compositions for improving the aesthetic appearance of the skin.

Description

Title of the invention: TOPICAL COMPOSITION AND ITS USES

[0001] Domain

[0002] Embodiments disclosed herein include topical compositions that comprise a combination of creatine, palmitoylTripeptide-5 (Lys-Val-Lys), and bifida ferment lysate and uses thereof.

[0003] Background

[0004] The invention relates to the continuing search for new topical compositions that are storage stable, easily applied, and effective in combating a variety of disorders.

[0005] Summary

[0006] The present invention relates to topical compositions comprising creatine, palmitoylTripeptide-5 (Lys-Val-Lys) and bifida ferment lysate, as well as at least one excipient and uses thereof. Brief description of the figures

[0007] The figure is a bar graph representing fibronectin levels in fibroblast cells exposed to UV irradiation and treated with creatine, palmitoylTripeptide-5 (Lys-Val-Lys) and / or bifida ferment lysate. The first bar on the left side represents the levels in untreated unexposed cells, the second bar on the left side represents the levels for untreated UVB-exposed cells, the third bar on the left side represents the levels in cells treated with creatine, the fourth bar on the left side represents the levels in cells treated with palmitoylTripeptide-5, the fifth bar on the left side represents the levels in cells treated with bifida ferment lysate, the sixth bar on the left side represents the levels in cells treated with creatine and palmitoylTripeptide-5,The seventh bar from the left represents the levels in cells treated with creatine and bifida ferment lysate, the eighth bar from the left represents the levels in cells treated with palmitoylTripeptide-5 lysate and bifida ferment lysate, and the ninth bar from the left represents the levels in cells treated with creatine, palmitoylTripeptide-5, and bifida ferment lysate. Detailed description

[0008] Embodiments, also referred to hereinafter as "examples", are described in sufficient detail to enable a person skilled in the art to practice the invention. The embodiments may be combined, other Embodiments may be used, or structural and logical modifications may be made without departing from the scope of the present invention. The following detailed description should therefore not be considered limiting, and the scope of the present invention is defined by the appended claims and their equivalents.

[0009] Further, it should be understood that phraseology or terminology used herein, and not defined elsewhere, are used for descriptive purposes only and are not intended to be limiting.

[0010] All percentages and ratios used are by weight of the total composition and all measurements are made at 25°C, unless otherwise stated.

[0011] All numerical ranges include the narrower ranges; the upper and lower limits of the defined ranges are interchangeable to create other ranges not explicitly defined. The number of significant digits does not imply any limitation on the quantities indicated, nor on the precision of the measurements.

[0012] The term "about," as used herein, means approximately, in the vicinity of, roughly, or in the vicinity of. When the term "about" is used in connection with a numerical range, it modifies that range by extending the limits above and below the stated numerical values. The term "about" is generally used to modify a numerical value above and below the stated value by a variance of 10%. Therefore, about 50% therefore means the range of 45% to 55%. The numerical ranges expressed herein by limits include all numbers and fractions within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.90, 4, and 5). It is also understood that all numbers and fractions thereof are intended to be modified by the term "about."

[0013] The compositions of the present invention may comprise, consist essentially of, or consist of the essential as well as optional ingredients and components described herein. As used herein, the term "consisting essentially of" means that the composition or component may include additional ingredients, but only if the additional ingredients do not materially alter the basic and novel characteristics of the claimed compositions or methods.

[0014] The term "topical application" as used herein means the application or spreading of the compositions of the present invention on the surface of the skin as well as on the hair, nails and other keratinous tissues of mammals, including humans.

[0015] The term "dermatologically acceptable" or "cosmetically acceptable" as used herein means that the compositions or their components so described are suitable for use in contact with human skin without undue toxicity, incompatibility, instability, allergic reaction, and the like.

[0016] By "effective amount" is meant a sufficient amount of a compound or composition to significantly induce a positive benefit, preferably a positive benefit to the appearance or feel of the skin, including independently of the benefits described herein, but sufficiently low to avoid serious side effects, i.e., to provide a reasonable benefit relative to the risk, within the scope of sound judgment of one skilled in the art.

[0017] The term "skin care actives" means substances which, when applied to the skin, provide a benefit or improvement to the skin. It should be understood that skin care actives are useful not only for application to the skin, but also to the hair, nails and other keratinous tissues of mammals.

[0018] The term "site" means the place where the composition is applied. Non-limiting examples of a site include the keratin tissues of mammals, such as humans.

[0019] The terms "purified" and similar terms relate to an enrichment of a molecule or compound relative to other components associated with the molecule or compound. The term "purified" does not necessarily indicate that complete purity of the particular molecule has been achieved in the process.

[0020] The term "substantially pure" describes a compound that has been separated from its accompanying components. Typically, a compound is substantially pure when at least 10%, preferably at least 20%, more preferably at least 50%, more preferably at least 60%, more preferably at least 75%, more preferably at least 90%, and most preferably at least 99% of the total material (by volume, wet or dry weight, or mole percent or mole fraction) in a sample is the compound of interest. Purity may be measured by any suitable method, for example, in the case of polypeptides by column chromatography, gel electrophoresis, or HPLC analysis. A compound is also substantially purified when it is essentially free of associated components or when it is separated from native contaminants that accompany it in its natural state.

[0021] The terms "includes," "comprising," and the like may have the meanings ascribed to them in U.S. patent law and may mean "includes," "including," and the like. As used herein, "including" or "included" or the like means including, without limitation.

[0022] Composition

[0023] The invention relates to topical compositions including, but not limited to, a lotion, serum, oil, essence, mask, night cream, stick, eye cream, colored cosmetic or cream comprising a combination of creatine, palmitoylTripeptide-5 (Lys-Val-Lys) and lysate of Bifida ferment.

[0024] Creatine

[0025] The compositions of the present invention may include creatine. Creatine is an organic compound of the formula (H2N)(HN)CN(CH3)CH2CO2H. In solution, creatine exists in different forms (tautomers). Creatine is found in vertebrates, in which it facilitates the recycling of adenosine triphosphate (ATP), primarily in muscle and brain tissue. The recycling is achieved by reconversion of adenosine diphosphate (ADP) to ATP through the donation of phosphate groups. In some aspects, creatine is present from 0.001% to 10% (w / w), including 0.002% to 9.0%, 0.003% to 8%, 0.004% to 7%, 0.02% to 5.0%, 0.05% to 4.0%, 0.10% to 3.0%, 0.20% to 2.0%, 0.04 to 1.5%, including 0.001%, 0.002%, 0.003%, 0.004%, 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.20%, 0.30%, 0.40%, 0.50%, 0.60%, 0.70%, 0.80%, 0.90%, 1.00%, 1.50%, 2.00%, 2.50%, 3.00% 3.50%, 4.00% 4.50%, 5.00%, 5.50%, 6.00%, 6.50%, 7.00%, 7.50%, 8.00%, 8.50%, 9.00%, 9.50% or 10.00% (w / w). .

[0026] PalmitoylTripeptide-5 (Lys-Val-Lys)

[0027] The compositions of the present invention may comprise palmitoyl-Tripeptide-5 (Lys-Val-Lys). PalmitoylTripeptide-5 (Lys-Val-Lys) is a peptide and is commercially available. In some aspects, palmitoylTripeptide-5 (Lys-Val-Lys) is present from 0.000001% to 2% (w / w), including 0.000002% to 1.5%, 0.000003% to 1.0%, including 0.000001%, 0.000002%, 0.000003%, 0.000004%, 0.000005%, 0.000006%, 0.000007%, 0.000008%, 0.000009%, 0.00001%, 0.00002%, 0.00003%, 0.00004%, 0.00005%, 0.000006%, 0.000007%, 0.00008%, 0.00009%, 0.0001%, 0.0002%, 0.0003%, 0.0004%, 0.0005%, 0.0006%, 0.0007%, 0.0008%, 0.0009%, 0.0010%, 0.0020%, 0.0030%, 0.0040%, 0.0050%, 0.0060%, 0.0070%, 0.0080%, 0.0090%, 0.0100% 0.0150% or 0.0200% (w / w)-

[0028] Bifida ferment lysate

[0029] The compositions of the present invention may include bifida ferment lysate. Bifida ferment lysate is a type of probiotic obtained by the fermentation of Bifida. There are commercially available sources of Bifida ferment lysate. In some aspects, the Bifida ferment lysate is present from 0.0001% to 10% (w / w), including 0.0002% to 9%, 0.0003% to 8%, 0.0004% to 7%, 0.003% to 6.5%, 0.06% to 6.0%, 0.03% to 5.5%, 0.04% to 5.0%, 0.05% to 4.5%, 0.06% to 4.0%, including 0.0001, 0.0002, 0.0003, 0.0004, 0.0005, 0.0006, 0.0007, 0.0008, 0.0009, 0.001%, 0.002%, 0.003%, 0.004%, 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.20%, 0.30%, 0.40%, 0.50%, 0.60%, 0.70%, 0.80%, 0.90%, 1.00%, 1.50%, 2.00%, 2.50%, 3.00%, 3.50%, 4.00%, 4.50%, 5.00%, 5.50%, 6.00% 6.50%, 7.00%, 7.50%, 8.00%, 8.50%, 9.00% 9.50% or 10.00 (w / w).

[0030] Support / Administration System

[0031] The actives may be used alone in combination with a carrier / delivery system. The compositions of the present invention comprise from about 0.000001 to about 99% of an acceptable carrier / delivery system, within which creatine, palmitoylTripeptide-5 (Lys-Val-Lys) and / or bifida ferment lysate and additional materials are incorporated to enable these components to be carried / delivered at an appropriate concentration. The carrier may thus act as a diluent, dispersant, solvent or the like for the particulate material which ensures that it can be applied and distributed uniformly to the selected target at an appropriate concentration.The active ingredients may also be encapsulated in one or more encapsulating agents, such as liposomes or other vehicles including biodegradable polymers / nanocapsules, hydrogels, cyclodextrins, poly(lactic-co-glycolic acid) (PLGA) or PLCA microspheres.

[0032] The carrier may contain one or more dermatologically acceptable solid, semi-solid or liquid fillers, diluents, solvents, and the like. The carrier may be solid, semi-solid or liquid.

[0033] The carrier may be substantially liquid. The carrier may itself be inert or provide specific dermatological benefits. Carrier concentrations may vary depending on the carrier chosen and the intended concentrations of the components.

[0034] Suitable carriers include conventional or otherwise known carriers that are dermatologically acceptable. The carrier must also be physically and chemically compatible with the essential components described herein, and must not unduly impair the stability, efficacy, or other use benefits associated with the compositions of the present invention. The components of the compositions of the present invention must be capable of being mixed such that there are no interactions that would substantially reduce the effectiveness of the composition in ordinary use situations.

[0035] The type of carrier used herein depends on the type of product form desired for the composition. The topical compositions useful in the present invention may be prepared in a wide variety of product forms such as those known in the art. These include, but are not limited to, lotions, creams, gels, sticks, mists, ointments, oils, pastes, mousses, and cosmetics (e.g., solid, semi-solid, or liquid makeup, including foundations, eye makeup, pigmented or non-pigmented lip treatments, e.g., lipstick, and analogs). These product forms may include several types of carriers, including, but not limited to, solutions, aerosols, emulsions, gels, solids, and oils.

[0036] The carriers may contain a dermatologically acceptable diluent. As used herein, "diluent" includes materials in which the material may be dispersed, dissolved, or otherwise incorporated, such as a lipophilic diluent / carrier. The solutions of the invention typically include a dermatologically acceptable diluent. The solutions useful in the present invention may contain from about 0.000001 to about 99% of the diluent.

[0037] Aerosols according to the invention may be formed by adding a propellant to a solution as described above. Examples of propellants include low molecular weight chlorofluorohydrocarbons. Other propellants useful herein are described in Sagarin, Cosmetics Science and Technology, 2nd ed., vol. 2, pages 443-465 (1972). Aerosols are typically applied as a sprayed product.

[0038] The carriers may comprise an emulsion comprising a hydrophilic phase comprising a hydrophilic component, for example, water or another hydrophilic diluent, and a hydrophobic phase comprising a hydrophobic component, for example, a lipid, an oil or an oily material. As well known to those skilled in the art, the hydrophilic phase will be dispersed in the hydrophobic phase, or vice versa, to form hydrophilic or hydrophobic dispersed and continuous phases, respectively, depending on the ingredients of the composition. In emulsion technology, the term "dispersed phase" is well known to those skilled in the art and means that the phase exists as small particles or droplets that are suspended in and surrounded by a continuous phase. The dispersed phase is also referred to as the internal or discontinuous phase.The emulsion may be or comprise (e.g., in a triple emulsion or other multi-phase emulsion) an oil-in-water emulsion or a water-in-oil emulsion such as a water-in-silicone emulsion. Oil-in-water emulsions typically comprise from about 1% to about 50% of the dispersed hydrophobic phase and from about 1% to about 98% of the continuous hydrophilic phase; water-in-oil emulsions typically comprise from about 1% to about 98% of the dispersed hydrophilic phase and from about 1% to about 50% of the continuous hydrophobic phase. The emulsion may also comprise a gel network, as described in "Application of Emulsion Stability Theories to Mobile and Semisolid Oil-in-Water Emulsions," Cosmetics and Toiletries, vol. 101, November 1986, pages 73-92.

[0039] The topical compositions of the invention, including, but not limited to, a lotion, a serum, an oil, an elixir, a mask, a night cream, a stick, a eye cream, a colored cosmetic (such as a foundation or concealer), or a cream, may include a dermatologically acceptable emollient. Such compositions may contain from about 2% to about 50% of the emollient. Emollients tend to lubricate the skin, increase the softness and suppleness of the skin, prevent or relieve dryness of the skin, and / or protect the skin. Emollients are typically water-immiscible, oily, or waxy materials. A wide variety of suitable emollients are known and may be used herein. Sagarin, Cosmetics, Science and Technology, 2nd ed., vol. 1, pp. 32-43 (1972), contains numerous examples of materials suitable as an emollient.

[0040] Lotions and creams according to the present invention generally comprise a solution carrier system and one or more emollients. Lotions typically comprise from about 1% to about 20%, such as from about 5% to about 10% emollient; from about 50% to about 90%, including from about 60% to about 80% water. A cream typically comprises from about 5% to about 50%, including from about 10% to about 20% emollient; and from about 45% to about 85%, including from about 50% to about 75% water.

[0041] The ointments of the present invention may comprise a simple carrier base based on animal or vegetable oils or semi-solid (oleaginous) hydrocarbons; ointment absorption bases, which absorb water to form emulsions; or water-soluble carriers, for example, a water-soluble solution carrier. The ointments may further comprise a thickening agent, as described in Sagarin, Cosmetics, Science and Technology, 2nd ed., vol. 1, pages 72-73 (1972), and / or an emollient. For example, an ointment may comprise from about 2% to about 10% of an emollient; and from about 0.1% to about 2% of a thickening agent.

[0042] The compositions of the invention, useful for cleaning ("cleaners"), are formulated with a suitable carrier, for example as described above, and preferably contain one or more dermatologically acceptable surfactants in an amount that is safe and effective for cleaning. Such compositions contain, for example, from about 1% to about 90%, preferably from about 5% to about 10%, of a dermatologically acceptable surfactant. The surfactant may be selected from anionic, cationic, nonionic, zwitterionic, amphoteric and ampholytic surfactants, as well as mixtures of these surfactants. Such surfactants are well known to those skilled in the art of detergents. Non-limiting examples of possible surfactants include isoceteth-20, sodium methyl cocoyl taurate, sodium methyl oleoyl taurate, sodium lauryl sulfate, and betaines, as described herein. See U.S. PatentNo. 4,800,197, to Kowcz et al., issued January 24, 1989, for examples of surfactants that may be . used herein. Examples of a wide variety of additional surfactants useful herein are described in McCutcheon's Detergents and Emulsifiers, North American Edition (1986), published by Allured Publishing Corporation. The cleaning compositions may optionally contain, at their art-established levels, other materials conventionally used in cleaning compositions.

[0043] The physical form of the cleansing compositions may be, for example, formulated as bars, liquids, shampoos, bath gels, conditioners, hair tonics, pastes, or foams. Bars are most preferred because they are the most commonly used form of cleansing agent for washing the skin. Preferred rinse-off cleansing compositions, such as shampoos, include a delivery system suitable for depositing sufficient levels of actives onto the skin and scalp. A delivery system may involve the use of insoluble complexes. For a more complete disclosure of such delivery systems, see U.S. Patent No. 4,835,148, Barford et al., issued May 30, 1989.

[0044] The composition may also be in the form of a cosmetic composition that can be applied to the keratin tissue of mammals, including human skin. The cosmetic compositions may be in various forms. Non-limiting examples of forms include, for example, solutions, suspensions, lotions, oils, creams, gels, toners, sticks, pencils, ointments, pastes, emulsions, powders, foams, shaving foams, wipes, strips, patches, transducer patches, wound dressings and adhesives, hydrogels, film-forming products, face and skin masks, cosmetics (e.g., foundations, eyeliners, eye shadows), and the like.

[0045] Preferably, the cosmetic composition may comprise from 1% to 95% by weight of water. The cosmetic composition may comprise from 1% to 95% by weight of one or more oils. The oils may be used to solubilize, disperse, or support materials that are not suitable for water or water-soluble solvents. Suitable oils include silicones (such as dimethicone), hydrocarbons, esters, amides, ethers, and mixtures thereof. When the cosmetic composition is in the form of an emulsion, the oils are the carriers typically associated with the oily phase. The cosmetic composition may be in the form of a water-in-oil emulsion, an oil-in-water emulsion, or a water-in-silicone emulsion such that the cosmetic composition may include water, a silicone, oil, and combinations thereof. The cosmetic compositions may include an emulsifier.An emulsifier is particularly suitable when the cosmetic composition is in the form of an emulsion or if immiscible materials are combined. The cosmetic composition may . comprise from 0.05%, 0.1%, 0.2%, 0.3%, 0.5%, or 1% to 20%, 10%, 5%, 3%, 2%, or 1% of emulsifier. Emulsifiers may be nonionic, anionic, zwitterionic, or cationic. Structuring agents may be used to increase viscosity, thicken, solidify, or impart a solid or crystalline structure to the cosmetic composition. Structuring agents are typically grouped based on solubility, dispersibility, and phase compatibility. Examples of aqueous or water-based structuring agents include, but are not limited to, polymeric agents, natural or synthetic gums, polysaccharides, and the like. The cosmetic compositions may comprise 0.0001%, 0.001%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 5% to 25%, 20%, 10%, 7%, 5%, 4%, or 2% by weight of the cosmetic composition, of one or more structuring agents.The cosmetic compositions may optionally contain one or more UV actives. As used herein, “UV active” includes both sunscreen agents and physical sunscreens. Suitable UV actives may be organic or inorganic. Examples of some suitable UV actives are listed in the functional category of “Sunscreen Agents” in the Personal Care Product Council’s International Cosmetic Ingredient Dictionary and Handbook, Thirteenth Edition, 2010. The cosmetic compositions may be generally prepared by conventional methods such as those known in the art of making cosmetic compositions. Such methods typically involve mixing ingredients in one or more steps to a relatively uniform state, with or without heating, cooling, application of vacuum, and the like.Typically, emulsions are prepared by first mixing the aqueous phase materials separately from the fatty phase materials and then combining the two phases appropriately to yield the desired continuous phase. Cosmetic compositions are preferably prepared to optimize stability (physical stability, chemical stability, photostability, etc.) and / or delivery of the active ingredients. The cosmetic composition may be presented in a package sized to store a sufficient amount of the cosmetic composition for a treatment period. The size, shape, and design of the package may vary widely.

[0046] Optionally, the present topical composition may include one or more of the compositions of the invention and may optionally include other active and inactive ingredients, including, but not limited to, excipients, fillers, emulsifying agents, antioxidants, surfactants, film-forming agents, chelating agents, gelling agents, thickeners, emollients, humectants, moisturizers, vitamins, minerals, viscosity and / or rheology modifiers, sunscreens, keratolytic agents, depigmenting agents, retinoids, hormonal compounds, alpha-hydroxy acids, alpha- ketoacids, anti-mycobacterial agents, antifungal agents, antimicrobials, antivirals, analgesics, lipid compounds, antiallergenic agents, H1 or H2 antihistamines, anti-inflammatory agents, anti-irritants, antineoplastics, immunostimulating agents, immunosuppressive agents, anti-acne agents, anesthetics, antiseptics, insect repelling agents, skin cooling compounds, skin protectants, skin penetration enhancers, exfoliants, lubricants, perfumes, colorants, marking agents, depigmenting agents, hypopigmenting agents, preservatives, stabilizers, pharmaceutical agents, light-stabilizing agents, and mixtures thereof. In addition to the above, the personal care products of the invention may contain any other compounds for the treatment of skin disorders.

[0047] The cosmetic compositions disclosed herein may be applied to one or more skin surfaces and / or one or more keratin tissue surfaces of mammals, such as humans, as part of a daily routine or plan by a user. Additionally, or alternatively, the present cosmetic compositions may be used "on demand." In some examples, an effective amount of the cosmetic composition may be applied to the target portion of keratin tissue or skin. In some examples, the cosmetic composition may be provided in a package containing written instructions detailing the application plan.

[0048] Their uses

[0049] The compositions of the present invention are useful for topical application, such as a cosmetic product and for improving the aesthetic appearance of the skin, increased amounts of fibronectin in the skin and / or improving wound healing, including visible and / or tactile discontinuities in the skin. Such discontinuities may be induced or caused by internal and / or external factors and include signs of skin aging or skin wounds. The instant compositions and methods increase fibronectin in skin cells. Fibronectin is an adhesive molecule that plays a role in wound healing, including extracellular matrix (ECM) formation as well as re-epithelialization. Fibronectin plays many different roles in the wound healing process due to the presence of functional domains and binding sites in its structure.Fibronectin interacts with different cell types, cytokines and the ECM.

[0050] The term "improving the aesthetic appearance of the skin" includes the prophylactic and / or therapeutic improvement of a condition of a skin disorder, including visible and / or tactile discontinuities of the skin. As used herein, the term prophylactic use means delaying, minimizing and / or preventing discontinuities visible and / or tactile skin. As used herein, the term therapeutic improvement of a skin condition means improving, for example, diminishing, minimizing and / or erasing, skin discontinuities (improving the appearance and / or feel of the skin).

[0051] The compositions of the present invention are useful for preventing or treating or ameliorating signs of skin aging, more particularly visible and / or tactile discontinuities in skin texture associated with aging. Improving the signs of skin aging and / or improving the aesthetic appearance of the skin includes prophylactic and / or therapeutic improvement of one or more of these signs (similarly, improvement of a given sign of skin aging, e.g., fine lines, wrinkles, or pores, includes prophylactic and / or therapeutic improvement of that sign). As used herein, prophylactic use includes delaying, minimizing, and / or preventing the signs of skin aging.As used herein, therapeutic improvement of such signs includes improving, for example, decreasing, minimizing and / or erasing the signs of skin aging.

[0052] “Signs of skin aging” include, but are not limited to, all visibly and tactilely perceptible manifestations as well as any other macro- or micro-effects due to skin aging. Such signs may be induced or caused by intrinsic factors or extrinsic factors, for example, chronological aging and / or environmental damage. These signs may result from processes that include, but are not limited to, the development of textural discontinuities such as wrinkles, including both superficial fine wrinkles (fine lines) and significant deep wrinkles, skin lines, crevices, bumps, large enlargements (e.g., associated with ancillary structures such as sweat gland ducts, sebaceous glands, or hair follicles), roughness, scaling, and / or other forms of skin irregularity or roughness,loss of skin elasticity (loss and / or inactivation of functional skin elastin), sagging (including bags in the eye area and cheeks), loss of skin firmness, loss of skin tightness, loss of skin density, loss of skin tightening capacity after deformation, discoloration (including dark circles), mottling, yellowing, hyperpigmented skin areas such as age spots and freckles, keratoses, abnormal differentiation, hyperkeratinization, elastosis, collagen breakdown, and other histological changes in the stratum corneum, dermis, epidermis, cutaneous vasculature (e.g., telangiectasia or spider veins), and underlying tissues, including those close to the skin.

[0053] It is understood that the present invention should not be limited to the improvement of the “signs of skin aging” referred to above, which result from mechanisms associated with skin aging, but is intended to include an improvement in such signs regardless of the mechanism of origin. As used herein, “improvement of a skin condition” shall include the improvement of such signs regardless of the mechanism of origin.

[0054] The present invention is particularly useful for improving visible and / or tactile discontinuities in the texture of the skin of a mammal, such as a human, including texture discontinuities associated with skin aging. As used herein, therapeutically improving such discontinuities includes improving, for example, decreasing, minimizing, and / or erasing visible and / or tactile discontinuities in the texture of the skin of mammals, humans, to improve the appearance and / or feel of the skin, for example, a smoother, more uniform appearance and / or feel. Such visible and / or tactile discontinuities in skin texture include crevices, bumps, pores, fine lines, wrinkles, scaling, exfoliation, and / or other forms of textural irregularity or roughness associated with skin aging.For example, the length, depth and / or other dimensions of fine lines and / or wrinkles are reduced, the apparent diameter of pores is reduced.

[0055] The present invention is also useful for prophylactic uses which include preventing, inhibiting and delaying visible and / or tactile discontinuities in the texture of the skin of mammals, such as humans, including texture discontinuities associated with skin aging. As used herein, the prophylactic use includes delaying, minimizing and / or preventing visible and / or tactile discontinuities in the texture of the skin of mammals, in order to improve the appearance and / or feel of the skin, e.g., a smoother, more uniform appearance and / or feel.

[0056] The compositions described herein may be used to treat and / or prevent a variety of skin conditions and / or disorders. Skin conditions / disorders may include aging, signs of aging, acne, dermatitis, rosacea, psoriasis, and / or wounds. Signs of aging may include wrinkles, fine lines, creased skin, skin laxity associated with loss or destruction of collagen, loss or reduction of skin integrity, lack of skin elasticity, lack of skin tone, thinning skin, loose skin, skin suffering from breakdown of collagen fibers, sagging skin, and / or skin suffering from internal breakdown. Conditions / disorders may include inflammation, vein breaks, redness, spots, puffy eyes or dark circles, or skin pigmentation disorders.The compositions presented here are also useful for improving wound healing, for promoting the appearance. youthful appearance of the skin, to promote evenness of skin tone by reducing skin redness, or inflammation or UV-induced skin redness, spots or inflammation, to promote skin regeneration to produce greater evenness, to promote / increase fibronectin levels in skin cells, firmer, more toned, more elastic skin, to promote cell longevity, to promote skin clarity, to promote skin texture and evenness of tone and / or to reduce the appearance of skin pigmentation and / or skin darkening, to treat or prevent ulcerated areas or areas of skin stress or damage caused by UV exposure or irritant exposure, to improve skin scaling, improve skin hydration, improve skin radiance and clarity,or to treat or reduce acne or other skin imperfections.

[0057] The compositions disclosed herein may be applied to one or more topical surfaces and / or one or more keratin tissue surfaces of mammals, such as humans, as part of a user's daily routine or plan. Additionally, or alternatively, the compositions of the invention may be used "on demand" and used within the meaning of the given consumer product. The composition may be applied to any article, such as a textile, or to any absorbent article.

[0058] Examples of compositions of the present invention include:

[0059] Composition formulated in the form of a cream comprising: Ingredient Quantity (w / w of final product) Hydrogenated polyisobutene & ethylene / propylene / styrene copolymer & butylene / ethylene / styrene copolymer & pentaerythritol tetra-di-T-butyl hydroxyhydrocinnamate, dicaprylyl carbonate & tocopherol, dimethicone ethyl perfluorobutyl ether & ethyl perfluoroisobutyl ether, tocopheryl acetate Creatine 0.001 - 10.00% Adipocyte stem cell growth factor stimulation, hydro assay (Swertia chirata extract) Alfalfa & coconut oil & squalene Cationic liposome: Lecithin & water Retinyl polysorbate 20 Behentrimonium chloride Potassium phosphate Isopropyl alcohol Tocopheryl alcohol Ascorbyl palmitate PalmitoylTripeptide 5 0.000001- 2.00% Acetyl Dipeptide 1 Cetyl Ester Water, Methylpropanediol, Hyaluronic Acid, Silanetriol and Citric Acid Water; Pentylene Glycol, Lecithin; Alcohol; Glycerin; Xanthan Gum; Caprylyl Glycol; Propanediol; Sodium Hydroxide; Bacillus Ferment; Plankton Extract; Hydrolyzed Vegetable Protein; Micrococcus Lysate; Tetrasodium Glutamate Diacetate Bifida Ferment Lysate, Sodium Benzoate, Acetic Acid, Lactic Acid 0.0001 - 10.00% Phytocell Tech Malus Domestica (Apple) Fruit Cell Culture Extract, Isomalt & Aqua / Water Dimethylmethoxy Chromanol Alpha-Glucan Oligosaccharide Adenosine Niacinamide Glycerin 0.00 - 5%

[0061] Composition formulated in the form of an essence comprising: Ingredient Quantity Creatine 0.001 - 10.00% Sodium Hyaluronate Hydrolyzed Hyaluronic Acid Water, Methylpropanediol, Hyaluronic Acid, Si-lanetriol and Citric Acid Dimethylmethoxy Chromanol Niacinamide Bifida Ferment Lysate, Sodium Benzoate, Acetic Acid, Lactic Acid 0.0001 - 10.00% Alpha-Glucan Oligosaccharide Adenosine Witch Hazel Distillate, Alcohol, Water

[0063] Composition formulated in the form of an eye cream comprising: Active Ingredient Hydrogenated Polyisobutene & Ethylene / Propylene / Styrene Copolymer & Butylene / Ethylene / Styrene Copolymer & Pentaerythrithyl Tetra-Di-T-Butyl Hydroxyhydrocinnamatedicaprylyl Carbonate & Tocopherol, Dimethicone Ethyl Perfluorobutyl Ether & Ethyl Perfluoroisobutyl Ether, Tocopheryl Acetate Creatine 0.001 - 10.00% Adipocyte Stem Cell Growth Factor Stimulation (Swertia Chirata Extract) Alfalfa & Coconut Oil & Squalene Cationic Liposome: Water Lecithin Retinyl Polysorbate 20 Behentrimonium Chloride Potassium Phosphate Isopropyl Alcohol Tocopheryl Alcohol Ascorbyl Palmitate PalmitoylTripeptide-5 0.000001- 2.00% Acetyl dipeptide 1 cetyl ester Water, methylpropanediol, hyaluronic acid, silanetriol and citric acid Bifida ferment lysate 0.0001 - 10.00% Phytocell tech malus domestica (apple) or Dimethylmethoxy chromanol Niacinamide Prebiotic; oligosaccharide Alpha-glucan Caffeine Horse Chestnut: Phytami Horse Chestnut (Aesculus Hypocastanum Seed Extract) Ginkgo Biloba Leaf Extract Adenosine

[0065] In one embodiment, the formulations disclosed herein may be used alone or impregnated into fibrous cellulosic pads for application to the skin. One embodiment consists essentially of creatine, palmitoylTripeptide-5 (Lys-Val-Lys), and bifida ferment lysate (in one embodiment, such a composition is impregnated into fibrous cellulosic pads for application).

[0066] The following examples are intended to further illustrate certain embodiments of the invention and are not intended to limit the scope of the invention in any way. Examples

[0067] Normal human primary fibroblasts were seeded into culture well plates at 200,000 cells / cm2 with DMEM (Dulbecco's Modified Eagle's Medium) culture medium, 24 hours later, culture medium was removed, cells were rinsed with PBS (Phosphate Buffered Saline), and fresh PBS was applied to the cells. The cells were then exposed to UV irradiation (300-400 nm) for a time to cause UV-induced physical and / or chemical change, without exposure to active ingredients. Immediately after irradiation, the PBS was removed and the active ingredients creatine, palmitoyl-Tripeptide-5 (Lys-Val-Lys) and bifida ferment lysate diluted in culture medium were applied for 72 hours. Cells were incubated at +37°C with 5% CO2.

[0068] Quantification of fibronectin release was performed using human magnetic Luminex assays (ref: LXSAHM-03) according to the protocol described by the supplier. Results were expressed in pg / ml.

[0069] As can be seen in Figure 1, surprisingly, a combination of palmitoylTripeptide-5 (Lys-Val-Lys) and bifida ferment lysate or a composition of creatine, palmitoylTripeptide-5 (Lys-Val-Lys) and bifida ferment lysate significantly increases fibronectin levels.

[0070] In particular, UV irradiation results in a decreasing production of fibronectin from 650K pg / ml to 475 pg / ml in fibroblast cells. Creatine alone does not does not appear to exert a positive impact on irradiated cells with respect to fibronectin production, while tripeptide-5 produces increased fibronectin production in irradiated cells at 550K pg / ml, representing a 36.9% increase compared to no treatment or creatine-alone treatment. Tripeptide-5 does this by specific upregulation of fibronectin production. Bifida lysate treatment demonstrates decreased fibronectin production in irradiated cells compared to control cells and cells treated with creatine alone.

[0071] Creatine plus tripeptide-5 shows similar results to tripeptide-5 alone, suggesting that the combination of creatine with tripeptide-5 does not increase tripeptide-5-induced fibronectin production.

[0072] Creatine plus Bifida lysate shows a slight improvement over Bifida lysate alone, but still lower than the control. Palmitoyl tripeptide-5 plus Bifida lysate is equivalent to palmitoyl tripeptide-5 alone, suggesting no synergistic effect between palmitoyl tripeptide-5 and Bifida lysate.

[0073] However, creatine plus Bifida lysate plus tripeptide-5 showed an 82% increase in fibronectin compared to the control, a 46% increase compared to tripeptide-5 alone, and a 35% increase compared to tripeptide plus Bifida lysate. Neither creatine alone nor Bifida lysate alone was shown to have a measurable positive effect; creatine did not increase the effect of tripeptide-5; and Bifida lysate only increased the performance of tripeptide-5 by 11%.

[0074] While not tied to any particular theory, creatine improves energy in cells, and cells require energy for their synthesis. Bifida ferment lysate helps improve cellular repair (it enhances the natural nucleotide excision repair process), which also requires the energy that creatine can provide. The peptide helps the synthesis of fibronectin, with the energy from creatine. These agents work together to enhance energy and create a favorable environment for cellular repair and provide the strongest reinforcement of fibronectin.

[0075] Fibronectin is a homodimer, with two subunits of MW 250K, linked by a disulfide bridge. Fibronectin binds to receptor proteins called integrins that cover the cell membrane, and also binds to extracellular matrix components such as collagen, fibrin, and heparin. Fibronectin is a constituent of the extracellular matrix and mediates cell attachment to cells and the extracellular matrix. Fibronectin plays a role in maintaining skin integrity. Fibronectin, which also plays a role in skin repair, is increased during the wound healing process, plays a role in cell adhesion, growth, migration, and differentiation, and is required for processes such as wound healing and embryonic development. The expression, degradation, and organization of altered fibronectin have been associated with a number of pathologies, including aging, cancer, arthritis, and fibrosis. UV radiation increases the degradation of fibronectin in the skin. In addition, fibronectin has been found at reduced levels in the papillary dermis of aging skin. See Ray D. et al. J Biol Chem. 2006, 281:23060-5; Labat-Robert J. et al. J Photochem Photobiol B. 2000 57(2-3):113-8; Pieraggi MT et al. Ann Pathol. 1984, 4(3): 185-94; ENS RA et al. J Invest Dermatol. 1982, 79(5):264-9; and Clark RAJ Invest Dermatol. 1983, 81(6):475-9.Particularly, with age comes the downregulation of the TGF-beta receptor (Tbeta RII) associated with the reduced expression of Smad3-regulated extracellular matrix components such as type I collagen and fibronectin. During aging, the dermal ECM undergoes fragmentation impairing fibroblast attachment. Furthermore, in aged skin comes the reduced size of fibroblasts accompanied by reduced collagen and fibronectin production.

[0076] Thus, increasing fibronectin levels in skin cells will improve the appearance of aging skin, with respect to fine lines, wrinkles, texture, sagging, laxity, and firmness of the skin.

[0077] The composition and methods of the invention provided herein inhibit and treat conditions requiring increased amounts of fibronectin, including aging skin and wounds.

[0078] In a first aspect, the invention relates to a method for improving the aesthetic appearance of the skin of a human being in need thereof, comprising the topical application to the skin of the human being at least once daily for a period of at least four weeks of a composition comprising an effective amount of creatine, palmitoylTripeptide-5 (Lys-Val-Lys) and bifida ferment lysate in a cosmetically acceptable vehicle for improving the aesthetic appearance of said skin of the human being, wherein said skin is in need of increased fibronectin production.

[0079] The improved aesthetic appearance is due to the improvement, treatment and / or prevention of fine lines and wrinkles.

[0080] In another aspect, the invention relates to a method of treating skin characterized by an insufficient amount of fibronectin, comprising topically applying to the skin in need thereof a composition comprising an effective amount of creatine, palmitoylTripeptide-5 (Lys-Val-Lys) and bifida ferment lysate in a cosmetically acceptable vehicle for a time sufficient to increase fibronectin in the skin.

[0081] In yet another aspect, the invention relates to a method for reducing wrinkles. and / or fine lines of a subject in need thereof, comprising topically applying a composition comprising a cosmetically effective amount of creatine, palmi-toylTripeptide-5 (Lys-Val-Lys) and bifida ferment lysate in a cosmetically acceptable vehicle to wrinkles and / or fine lines on said skin of the subject for a time sufficient to reduce said wrinkles and / or fine lines.

[0082] In certain aspects of the invention, the concentration of creatine is 0.001% to 10% (w / w), the concentration of palmitoylTripeptide-5 (Lys-Val-Lys) is 0.000001 to 2% (w / w) and the concentration of Bifida ferment lysate is 0.0001 to 10%.

[0083] The embodiments are described in sufficient detail to enable a person skilled in the art to practice the invention. Other embodiments may be used and modifications in the formulation and method of use may be made without departing from the scope of the invention. The detailed description is not to be construed as limiting, and the scope of the invention is defined only by the appended claims, and the full scope of equivalences to which these claims give rise.

[0084] It will be apparent to those skilled in the art that modifications could be made to the embodiments described above without departing from the broad inventive concept thereof. It is understood that the present invention is therefore not limited to the particular embodiments disclosed, but is intended to cover modifications within the spirit and scope of the present invention as defined by the present description.

Claims

Claims

1. A composition for use in improving the appearance of the skin of a human suffering from impaired wound healing resulting from reduced production of fibronectin within the skin cells of the human, said composition comprising an effective amount of creatine, palmitoylTripeptide-5 (Lys-Val-Lys) and bifida ferment lysate, the composition being in a form suitable for topical application to the skin to increase the synthesis of fibronectin and thereby provide an anti-aging treatment and / or improved wound healing compared to an untreated control to achieve an improved appearance of human skin.

2. A composition for use according to claim 1, wherein the anti-aging is the improvement, treatment and / or prevention of fine lines and wrinkles.

3. A composition for use according to claim 1, wherein wound healing is improved.

4. A composition for use in improving the appearance of skin of a human in need thereof, said composition comprising an effective amount of creatine, palmitoylTripeptide-5 (Lys-Val-Lys) and bifida ferment lysate in a cosmetically acceptable vehicle for improving the appearance of said skin of the human, the composition being in a form suitable for topical application to the skin of the human, wherein said skin is in need of increased fibronectin production.

5. A composition for use according to claim 4, wherein the improved aesthetic appearance is due to the improvement, treatment and / or prevention of fine lines and wrinkles.

6. A composition for use in treating skin characterized by an insufficient amount of fibronectin, said composition comprising an effective amount of creatine, palmitoylTripeptide-5 (Lys-Val-Lys) and bifida ferment lysate in a cosmetically acceptable vehicle, said composition being in a form suitable for application to skin in need thereof to increase fibronectin in the skin.

7. A composition for use in reducing wrinkles and / or fine lines in a subject in need thereof, said composition comprising a cosmetically effective amount of creatine, palmitoylTripeptide-5

8.

9.

10. (Lys-Val-Lys) and bifida ferment lysate in a cosmetically acceptable vehicle, said composition being in a form suitable for application to a wrinkle and / or fine line on said skin of the subject to reduce said wrinkles and / or fine lines. A composition for use according to any one of claims 1 to 7, wherein the concentration of creatine is 0.001% to 10% (w / w), the concentration of palmitoylTripeptide-5 (Lys-Val-Lys) is 0.000001 to 2% (w / w) and the concentration of Bifida ferment lysate is 0.0001 to 10%. A composition for use according to any one of claims 1-8, wherein the composition is formulated as a lotion, cream, serum, essence, mask, night cream, stick, eye cream or colored cosmetic (such as foundation or concealer). Composition formulated in the form of a cream comprising: Ingredient Quantity (w / w of final product) Hydrogenated polyisobutene & ethylene / propylene / styrene copolymer & butylene / ethylene / styrene copolymer & pentaerythrithyl tetra-di-T-butyl hydroxyhydrocinnamate, di-caprylyl carbonate & tocopherol, dimethicone ethyl perfluorobutyl ether & ethyl perfluoroisobutyl ether, tocopheryl acetate Creatine 0.001 - 10.00% Adipocyte stem cell growth factor stimulation, hydro assay (Swertia chirata extract) Alfalfa & Coconut Oil & Squalene Cationic Liposome: Water Lecithin Retinyl Polysorbate 20 Behentrimonium Chloride Potassium Phosphate Isopropyl Alcohol Tocopheryl Alcohol Ascorbyl Palmitate PalmitoylTripeptide 5 0.000001- 2.00% Acetyl Dipeptide 1 Cetyl Ester Water, Methylpropanediol, Hyaluronic Acid, Si-lanetriol & Citric Acid Water; Pentylene Glycol, Lecithin; Alcohol; Glycerin; Xanthan Gum; Caprylyl Glycol; Propanediol; Sodium Hydroxide; Bacillus Ferment; Plankton Extract; Hydrolyzed Vegetable Protein; Micrococcus Lysate; Tetrasodium glutamate diacetate Bifida ferment lysate, sodium benzoate, acetic acid, lactic acid 0.0001 - 10.00% Phytocell tech malus domestica (apple), culture extract malus domestica fruit cell, isomalt and aqua / water Dimethylmethoxy chromanol Alpha-glucan oligosaccharide Adenosine Niacinamide Glycerin 0.00 - 5%

11. A composition formulated in the form of an essence comprising: Ingredient Quantity Creatine 0.001 - 10.00% Sodium Hyaluronate Hydrolyzed Hyaluronic Acid Water, Methylpro-panediol, Hyaluronic Acid, Silanetriol and Citric Acid PalmitoylTripeptide-5 0.000001- 2.00% Dimethylmethoxy chromanol Niacinamide Bifida Ferment Lysate, Sodium Benzoate, Acetic Acid, Lactic Acid 0.0001- 10.00% Alpha-Glucan Oligosaccharide Adenosine Witch Hazel Distillate, alcohol, water

12. A composition formulated in the form of an eye cream comprising: Active Ingredient Hydrogenated Polyisobutene & Ethylene / Propylene / Styrene Copolymer & Butylene / Ethylene / Styrene Copolymer & Pentaerythrityl Tetra-Di-T-Butyl Hydroxyhydrocinnamatedic Aprylyl Carbonate & Tocopherol, Dimethicone Ethyl Perfluorobutyl Ether & Ethyl Perfluoroisobutyl Ether, Tocopheryl Acetate Creatine 0.001 - 10.00% Adipocyte Stem Cell Growth Factor Stimulation (Swertia Chirata Extract) Alfalfa & Coconut Oil & Squalene Cationic Liposome: Lecithin & Water Retinyl Polysorbate 20 Behentrimonium Chloride Potassium Phosphate Isopropyl Alcohol Tocopherol Alcohol Ascorbyl Palmitate PalmitoylTripeptide-5 0.000001- 2.00% Acetyl dipeptide 1 cetyl ester Water, methylpropanediol, hyaluronic acid, si-lanetriol and citric acid Bifida ferment lysate 0.0001 - 10.00% Phytocell tech malus domestica (apple) or Dimethylmethoxy chromanol Niacinamide Prebiotic; alpha-glucan oligosaccharide Caffeine Horse Chestnut: Phytami Horse Chestnut (Aesculus Hypo-castanum Seed Extract) Ginkgo biloba Leaf Extract Adenosine

Images