Topical Compositions and Methods of Use Thereof for Mitochondrial Fragmentation - Patent application

Abstract

A topical personal care composition for improving cellular energy efficiency by protecting skin from mitochondrial fragmentation, which occurs in elderly individuals in need of treatment. Use of a topical personal care composition comprising niacinamide and S-adenosyl-L-methionine. Use of niacinamide and S-adenosyl-L-methionine in the manufacture of a topical personal care composition for reducing or preventing mitochondrial fragmentation in skin cells and increasing skin cell energy.

Description

[Technical field]

[0001] The present invention relates to topical compositions comprising a synergistic combination of niacinamide and S-adenosyl-L-methionine useful against mitochondrial fragmentation in skin cells. [Background technology]

[0002] When consumers wish to reduce the appearance of lines, wrinkles, and age spots on their skin, they find it desirable to provide skin benefits via methods that rely on the application of topical compositions. There is a continuing need for active ingredients for incorporation into topical compositions that can provide benefits to the consumer's skin. There is a continuing need for active ingredients for incorporation into topical compositions that provide skin benefits by protecting the integrity and function of cellular components.

[0003] However, the technology to harness the functional components of cells to achieve youth and its perception through appearance is uncertain. While this is true for all cells in the body, it is particularly unpredictable as to whether or how cellular manipulation can achieve youthful looking skin. A key functional component of cells is the mitochondria.

[0004] In human cells, oxidative phosphorylation occurs within mitochondria, essential cellular components where up to 83% of cellular energy is generated in the form of adenosine triphosphate (ATP). The cellular energy stored in ATP is then used to drive multiple vital biological processes within human cells and, therefore, within mammals, including humans.

[0005] During mitochondrial oxidative phosphorylation, low basal levels of reactive oxygen species (ROS - highly reactive intermediates that can damage cellular components fatty acids, proteins, and DNA, causing cell degeneration and death) are generated. This low level of ROS can be efficiently quenched by constitutive antioxidant enzymes, ROS scavengers, repair enzymes, and removal of damaged components. In contrast, conditions that allow elevated and sustained levels of ROS result in mitochondrial fragmentation ("MF") or dysfunctional mitochondria that cannot meet the energy demands required for normal cellular function, especially under stressful circumstances. Since prolonged solar ultraviolet ("UV") irradiation is one of the major conditions that lead to high levels of ROS, mitochondrial fragmentation is particularly problematic in skin that is not protected from UV radiation that causes photoaging. Mitochondrial fragmentation is also a concern during normal skin aging, when repair cellular mechanisms begin to slow down. Indeed, in vivo studies have revealed that keratinocytes from aged skin have a significantly more fragmented mitochondrial network compared to keratinocytes from young skin (Mellem D, Sattler M, Pagel-Wolff S, Jaspers S, Wenck H, Rubhausen MA, et al.(2017) Fragmentation of the mitochondrial network in skin in vivo.PLoS ONE 12(6):e0174469). [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Mellem D, Sattler M, Pagel-Wolff S, Jaspers S, Wenck H, Rubhausen MA, et al.(2017) Fragmentation of the mitochondrial network in skin in vivo.PLoS ONE 12(6):e0174469 Summary of the Invention [Problem to be solved by the invention]

[0007] Therefore, there is a need for technologies (compounds) that can protect the skin against mitochondrial fragmentation, maintain basal levels of reactive oxygen species, and prevent premature skin aging.

[0008] Without wishing to be bound by theory, the applicant believes that compounds that protect skin cells from mitochondrial fragmentation contribute to increasing the cellular energy required to maintain or improve skin integrity and function. Increasing the amount of such compounds in skin cells is associated with skin benefits (younger skin phenotype).

[0009] Thus, the present invention relates to synergistic skin benefit agents against mitochondrial fragmentation, compositions comprising the skin benefit agent combination, and methods of using the compositions against mitochondrial fragmentation, which protect the skin from mitochondrial fragmentation and maintain or reduce reactive oxygen species, thereby preventing premature skin aging.

[0010] Additional Information Nicotinamide, also known as niacinamide or a form of vitamin B3, is known in the art and is commercially available from sources such as Sigma-Aldrich Chemical Company (St. Louis, Missouri, USA), however, its ability to increase ATP in cells has been questioned and it is believed to reduce ATP levels, decreasing the overall bioenergetic state of the cell. Topical compositions aimed at reducing the signs of aging using B vitamins are disclosed in US2007 / 0110731. NZ526350A discloses an anti-aging composition comprising an amino acid, a B complex vitamin, and preferably further comprising S-adenosyl-L-methionine.

[0011] S-Adenosyl-L-methionine (SAMe) occurs naturally in the body and is used as an oral supplement in humans. SAMe is a key participant in energy metabolism and plays a key role in the transfer of methyl groups to nucleic acids, proteins, lipids and secondary metabolites. SAMe plays an important role in polyamine biosynthesis, cell growth and repair, maintaining proper cell membranes, breakdown of brain chemicals, gene expression and immune system function.

[0012] Topical pharmaceutical compositions containing SAMe are disclosed in US 2006 / 0069059 A1 to Schaller et al. for the treatment of depression.

[0013] Overall, none of the additional information demonstrates that topical cosmetic compositions or methods of applying compositions containing SAMe to the skin are effective in reducing mitochondrial fragmentation. None of the above additional information discloses a mechanism of mitochondrial fragmentation. Furthermore, none of the additional information describes a composition comprising S-adenosyl-L-methionine (SAMe), a skin benefit agent, in combination with niacinamide (B3) to reduce mitochondrial fragmentation and / or reduce oxidative stress in skin cells when topically applied to the skin in a cosmetically suitable carrier. [Means for solving the problem]

[0014] The present invention overcomes the deficiencies of the prior art by providing a topical personal care composition comprising a combination of niacinamide (B3) and S-adenosyl-L-methionine (SAMe), the use of the composition against mitochondrial fragmentation, and a method for reducing mitochondrial fragmentation in skin cells.

[0015] Without wishing to be bound by theory, the applicants believe that the mitochondrial fragmentation level on skin cells can be used as a biomarker for enhancing skin cell energy.Compounds that protect skin cells from mitochondrial fragmentation contribute to the increase in cellular energy required to maintain or improve skin integrity and function.A smaller number of fragmented mitochondria in cells allows for a healthier mitochondrial network that is associated with skin benefits (younger skin phenotype).

[0016] The present invention is based on the discovery of active ingredients for incorporation into topical compositions that can provide skin benefits to consumers by reducing levels of mitochondrial fragmentation in skin cells.

[0017] In a first aspect, the present invention is a topical personal care composition comprising: 0.001-10%, preferably 0.01-6%, and most preferably 0.05-3.5% of a niacinamide (B3) compound; and 0.001-10%, preferably 0.01-6%, of SAMe in a cosmetically acceptable vehicle.

[0018] SAMe is a compound of structural formula 1 below. [ka]

[0019] The composition may include additional optional skin benefit agents.

[0020] In a second aspect, the present invention is a method for preventing mitochondrial fragmentation in the skin of an individual in need of treatment by topically applying to the skin a personal care composition that comprises a combination of B3 and SAMe in a cosmetically acceptable vehicle.Preferably, the method of the present invention protects the skin of an elderly individual in need of treatment from mitochondrial fragmentation.The composition of the present invention can optionally comprise additional skin benefit agents.

[0021] In a third aspect, the present invention is the use of a composition of the present invention comprising SAMe and B3 to reduce mitochondrial fragmentation.

[0022] In a fourth aspect, the present invention is the use of SAMe and B3 / niacinamide in the manufacture of a topical personal care composition for preventing mitochondrial fragmentation in skin cells.

[0023] All other aspects of the present invention will become readily apparent from consideration of the following detailed description and examples.

[0024] Throughout this specification and claims, unless the context clearly dictates otherwise, the following terms have the meanings expressly associated with them:

[0025] As used herein, the phrases "in one embodiment" and "in some embodiments" may refer to the same embodiment(s), but do not necessarily refer to the same embodiment(s). Furthermore, as used herein, the phrases "in another embodiment" and "in some other embodiments" may refer to different embodiments, but do not necessarily refer to different embodiments. Thus, as described below, various embodiments of the invention can be readily combined without departing from the scope or spirit of the invention. In addition, each of the examples provided in conjunction with various embodiments of the invention are intended to be illustrative and not limiting.

[0026] "Skin" as used herein is meant to include the skin on an individual's feet, face (including the oral cavity), neck, chest, back, arms, hands, legs, buttocks and scalp (including hair).

[0027] Unless specifically stated otherwise, all ranges set forth herein are meant to include all ranges subsumed therein.

[0028] Except in the examples, or where otherwise expressly indicated, all numbers in this description describing amounts of ingredients or reaction conditions, physical properties of ingredients and / or use should be understood to be modified by the word "about". All amounts are by weight of the final composition unless otherwise stated. Notwithstanding the fact that claims may be found without multiple dependence or overlap, the disclosure of the invention found herein should be considered to cover all embodiments found in claims that are multiple dependent from one another. In describing any range of concentrations or amounts, any particular upper concentration can be associated with any particular lower concentration or amount.

[0029] The word "comprising" is intended to mean "including" but not necessarily to mean "consisting of" or "consisting of." That is, the listed steps or options need not be exhaustive. The term "comprising" is meant to encompass the terms "consisting essentially of" and "consisting of."

[0030] The compositions of the present invention include creams, lotions, balms, serums, deodorants and antiperspirants, shampoos, conditioners, bars and liquid cleaning products. In a preferred embodiment, the compositions of the present invention are topical leave-on compositions, such as leave-on creams or lotions.

[0031] A "leave-on composition" refers to a composition that is intended to be applied to the skin and not washed or rinsed off for any period of time, particularly several hours, as opposed to a skin cleansing or wash-off or rinse-off composition that is rinsed or washed off immediately or after a few minutes of application. Both leave-on and wash / rinse-off compositions are within the scope of "personal care composition."

[0032] "Personal care composition" refers to a product that is applied to the human body to improve appearance, provide sun protection, cleansing (including oral care), control odor, moisturize, or for general beauty. Non-limiting examples of personal care compositions include skin lotions, creams, gels, lotions, facial masks, sticks, shampoos, conditioners, shower gels, toilet bars, antiperspirants, deodorants, shave creams, depilatories, sunless tanners, and sunscreen lotions.

[0033] "Skin cosmetic composition" refers to any product applied to the human body for improving appearance, sun protection, reducing the appearance of wrinkles or other signs of photoaging, odor control, skin lightening, even skin tone, or general aesthetics. The compositions of the present invention suitable for providing skin benefits can be emulsions or water- and emulsifier-free compositions. Non-limiting examples of topical cosmetic skin compositions include skin lotions, creams, facial masks, gels, sticks, antiperspirants, deodorants, liquid or gel body washes, bar soaps, oral care products, sunless tanners, and sunscreen lotions.

[0034] The use of "against" when referring to mitochondrial fragmentation includes, but is not limited to, providing protection / protection, reducing, maintaining, preventing, particularly in skin exposed to ultraviolet radiation. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0035] The present invention relates to a topical personal care composition comprising niacinamide (B3) in combination with SAMe in a cosmetically acceptable vehicle. Also provided are a method of preventing mitochondrial fragmentation in the skin of an individual in need of treatment by topically applying the personal care composition of the present invention to the skin; the use of the composition of the present invention to prevent or reduce mitochondrial fragmentation; and the use of SAMe and B3 in the manufacture of a topical personal care composition to prevent mitochondrial fragmentation in skin cells.

[0036] The present invention is based on the discovery of active ingredients for incorporation into topical compositions that can benefit consumers' skin by protecting mitochondria and / or reducing mitochondrial fragmentation in skin cells.These compounds are associated with efficient energy use, control of glucose and lipid metabolism, increased cell repair / rejuvenation, and increased antioxidant effects.The personal care benefits of applying the cosmetic composition of the present invention include, but are not limited to, anti-aging and anti-stress (including UV and oxidative stress).

[0037] In a first aspect, the present invention is a topical personal care composition comprising 0.001-10% of a niacinamide (B3) compound and 0.001-10%, preferably 0.01-6%, of SAMe in a cosmetically acceptable vehicle.

[0038] SAMe is a compound of formula 1: [ka] niacinamide of structural formula 2: [ka] It can be combined with.

[0039] In a second aspect, the present invention is a method for preventing mitochondrial fragmentation in the skin of an individual in need of treatment by topically applying to the skin a personal care composition comprising SAMe and B3 in a cosmetically acceptable vehicle.Preferably, the method of the present invention improves cellular energy efficiency by protecting the skin of an elderly individual in need of treatment from mitochondrial fragmentation.

[0040] In a third aspect, the present invention is the use of a composition of the present invention comprising SAMe and B3 for reducing mitochondrial fragmentation.

[0041] In a fourth aspect, the invention is the use of SAMe and B3 in the manufacture of a topical personal care composition for preventing mitochondrial fragmentation in skin cells.

[0042] S-Adenosyl-L-Methionine ("SAMe") According to the present invention, the compound S-adenosyl-L-methionine (Structural Formula 1 shown below) is used in combination with niacinamide. [ka]

[0043] Typically, the amount of S-adenosyl-L-methionine (SAMe) used in the compositions of the present invention will be from 0.001 to 10%, preferably from 0.01 to 6%, and most preferably from 0.05 to 3.5%, based on the total weight of the composition, including all ranges subsumed therein.

[0044] Nicotinamide Nicotinamide, also known as niacinamide or as a form of vitamin B3, has the following structural formula 2: [ka]

[0045] Typically, the amount of nicotinamide used in the compositions of the present invention will be from 0.001 to 10%, preferably from 0.01 to 6%, and most preferably from 0.05 to 3.5%, based on the total weight of the composition, including all ranges subsumed therein.

[0046] Advantageously and unexpectedly, the combination of SAMe+B3 demonstrates the ability to reduce mitochondrial fragmentation in skin cells.

[0047] Salt type The compounds of the present invention (SAMe and nicotinamide) can form salts with a variety of physiologically suitable counter ions, including chloride, bromide, iodide, hydroxide, sulfate, sulfonate, nitrate, phosphate, formate, tartrate, lactate, oxalate, fumarate, maleate, succinate, malonate, citrate, or RCO2. - (R5 is C1-C 22 An alkyl group, which may be linear, branched or cyclic, saturated or unsaturated, and may be substituted with one or more heteroatoms selected from O and S.

[0048] Carrier The compositions of the present invention may have as a cosmetically acceptable carrier a non-polar liquid such as an oil, or such a non-polar liquid may be used as the oil phase when the composition is an emulsion.

[0049] When the compositions of the present invention are emulsions, they will typically contain a cosmetically acceptable carrier component in addition to the non-polar liquid. Water is the most preferred additional carrier. The amount of water can range from 1 to 99% by weight, preferably 5 to 90%, most preferably 35 to 80% by weight, optimally 40 to 75% by weight, based on the total weight of the composition, including all ranges contained therein. Typically, the compositions of the present invention are water and oil emulsions, most preferably oil-in-water. However, water-in-oil emulsions are an option, particularly emulsions generally classified as water-in-oil and high internal phase emulsions. Illustrative examples of high internal phase emulsions suitable as carriers of the present invention are described in commonly owned U.S. Patent Application Publication No. 2008 / 0311058 and U.S. Patent No. 8,425,882, the disclosures of which are incorporated herein by reference.

[0050] Other cosmetically acceptable carriers suitable for use in the present invention, with or without water, can include mineral oil, silicone oil, esters, alcohols, etc. The amount of these materials can range, in total, from 0.1 to 99%, preferably from 0.1 to 45%, most preferably from 1 to 20% by weight of the compositions of the present invention, including all ranges subsumed therein.

[0051] Silicone oils can be divided into volatile and non-volatile forms. The term "volatile" as used herein refers to a material that has a measurable vapor pressure at ambient temperature. Volatile silicone oils are preferably selected from cyclic or linear polydimethylsiloxanes containing 3 to 9, preferably 4 to 5 silicon atoms.

[0052] Linear volatile silicone materials usually have a viscosity of less than 5 centistokes at 25° C., while cyclic materials typically have a viscosity of less than about 10 centistokes.

[0053] Non-volatile silicone oils useful as carrier materials include polyalkyl siloxanes, polyalkylaryl siloxanes, and polyether siloxane copolymers. Essentially non-volatile polyalkyl siloxanes useful herein include, for example, polydimethyl siloxanes (such as dimethicone) having a viscosity of 5 to 100,000 centistokes at 25° C.

[0054] The preferred silicone sources are cyclopentasiloxane and dimethiconol solution.

[0055] Among the suitable esters are the following: (1) Alkenyl or alkyl esters of fatty acids having 10 to 20 carbon atoms, such as isopropyl palmitate, isopropyl isostearate, isononyl isonanoate, oleyl myristate, isopropyl myristate, oleyl stearate, and oleyl oleate; (2) ether esters, such as fatty acid esters of ethoxylated fatty alcohols; (3) Polyhydric alcohol esters such as ethylene glycol mono- and di-fatty acid esters, diethylene glycol mono- and di-fatty acid esters, polyethylene glycol (200-6000) mono- and di-fatty acid esters, propylene glycol mono- and di-fatty acid esters, polypropylene glycol 2000 monooleate, polypropylene glycol 2000 monostearate, ethoxylated propylene glycol monostearate, glyceryl mono- and di-fatty acid esters, polyglycerol polyfatty acid esters, ethoxylated glyceryl monostearate, 1,3-butylene glycol monostearate, 1,3-butylene glycol distearate, polyoxyethylene polyol fatty acid esters, sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters; (4) Wax esters, such as beeswax, spermaceti, myristyl myristate, and stearyl stearate; and (5) Sterol esters, examples of which are soybean sterol and cholesterol fatty acid esters.

[0056] In many cases, an oil such as caprylic capric triglyceride is preferred as the carrier.

[0057] An emulsifier may be present in the compositions of the present invention. The total concentration of the emulsifier may range from about 0.1 to 40%, preferably 1 to 20%, and most preferably 1 to 5% by weight of the composition, including all ranges subsumed therein. The emulsifier may be selected from the group consisting of anionic, nonionic, cationic, and amphoteric actives. Particularly preferred nonionic actives include C6-100 condensed with about 2 to about 100 moles of ethylene oxide or propylene oxide per mole of hydrophobic material. 10 -C 20 Fatty alcohol or acid hydrophobe; C2-C condensed with 2 to 20 moles of alkylene oxide 10 Alkylphenols;Mono- and di-fatty acid esters of ethylene glycol;Fatty acid monoglycerides;Sorbitan, mono- and di-C8-C 20fatty acids; and polyoxyethylene sorbitan, and combinations thereof.Alkyl polyglycosides and saccharide fatty amides (e.g., methyl gluconamide) are also suitable nonionic emulsifiers.

[0058] Preferred anionic emulsifiers include alkyl ether sulfates and sulfonates, alkyl sulfates and sulfonates, alkyl benzene sulfonates, alkyl and dialkyl sulfosuccinates, C8-C 20 Acyl isethionates, C8-C 20 These include alkyl ether phosphates, alkyl ether carboxylates, and combinations thereof.

[0059] Cationic emulsifiers that can be used include, for example, aluminamidopropyltrimonium chloride, distearyldimonium chloride, and mixtures thereof. Useful amphoteric emulsifiers include cocoamidopropyl betaine, C 12 -C 20 These include trialkylbetaines, sodium lauroamphoacetate, and sodium laurodiamphoetate or mixtures thereof.

[0060] Other generally preferred emulsifiers include glyceryl stearate, glycol stearate, stearamide AMP, PEG-100 stearate, cetyl alcohol, and emulsifier / thickener additives such as hydroxyethyl acrylate / sodium acryloyldimethyltaurate copolymer / squalane and mixtures thereof.

[0061] composition Preservatives may desirably be incorporated into the compositions of the present invention to protect against the growth of potentially harmful microorganisms. A conventional preservative suitable for the compositions of the present invention is an alkyl ester of parahydroxybenzoic acid. Other preservatives that have recently come into use include hydantoin derivatives, propionate salts, and various quaternary ammonium compounds. Cosmetic chemists are familiar with appropriate preservatives and routinely select them to satisfy preservative challenge tests and provide product stability. Particularly preferred preservatives are iodopropynyl butylcarbamate, phenoxyethanol, 1,2-octanediol, ethylhexylglycerin, hexylene glycol, methylparaben, propylparaben, imidazolidinyl urea, sodium dehydroacetate, and benzyl alcohol. Preservatives should be selected having regard to the use of the composition and possible incompatibilities between the preservative and other ingredients in the emulsion. Preservatives are preferably used in amounts ranging from 0.01% to 2% by weight of the composition, including all ranges contained therein. A combination of 1,2-octanediol and phenoxyethanol, or iodopropynyl butylcarbamate and phenoxyethanol is preferred, with the phenoxyethanol accounting for 35 to 65% by weight of the total weight of the combination of phenoxyethanol and the preservative.

[0062] Thickening agents may be included in the compositions of the present invention. Particularly useful are polysaccharides. Examples include starches, natural and synthetic gums, and cellulose derivatives. Representative of starches are chemically modified starches such as sodium hydroxypropyl starch phosphate and aluminum starch octenyl succinate. Tapioca starch is often preferred. Suitable gums include xanthan, sclerotium, pectin, karaya gum, arabic gum, agar, guar, carrageenan, alginates, and combinations thereof. Suitable cellulose derivatives include hydroxypropyl cellulose, hydroxypropyl methylcellulose, ethyl cellulose, and sodium carboxymethyl cellulose. Synthetic polymers are yet another class of effective thickening agents. This category includes crosslinked polyacrylates such as the Carbomers, polyacrylamides such as Sepigel 305, and taurate copolymers such as Simulgel EG and Arlstoflex AVC, which are identified in their respective INCI nomenclature as sodium acrylate / sodium acryloyldimethyl taurate and acryloyldimethyl taurate / vinylpyrrolidone copolymers. Another preferred synthetic polymer suitable for thickening is an acrylate-based polymer marketed by Seppic and sold under the name Simulgel INS100.

[0063] The amount of thickener, if used, may range from 0.001 to 5%, preferably from 0.1 to 2%, and most preferably from 0.2 to 0.5% by weight of the composition, including all ranges subsumed therein.

[0064] Fragrances, fixatives and abrasives may also be included in the compositions of the present invention. Each of these materials may range from about 0.05 to about 5% by weight, preferably 0.1 to 3% by weight.

[0065] To enhance skin moisturization, cationic ammonium compounds may be used in the compositions of the present invention to enhance moisturization. Such compounds include salts of hydroxypropyltri(C1-C3 alkyl)ammonium mono-substituted saccharides, salts of hydroxypropyltri(C1-C3 alkyl)ammonium mono-substituted polyols, dihydroxypropyltri(C1-C3 alkyl)ammonium salts, dihydroxypropyldi(C1-C3 alkyl)mono(hydroxyethyl)ammonium salts, guar hydroxypropyltrimonium salts, 2,3-dihydroxypropyltri(C1-C3 alkyl or hydroxyalkyl)ammonium salts or mixtures thereof. In a most preferred embodiment, and if desired, the cationic ammonium compound used in the present invention is 1,2-dihydroxypropyltrimonium chloride, a quaternary ammonium compound. When used, such compounds typically comprise 0.01 to 30% by weight, preferably 0.1 to 15% by weight, of the composition.

[0066] When cationic ammonium compounds are used, the additional additives that are preferred for use therewith are moisturizing agents such as hydroxymethyl urea, hydroxyethyl urea, hydroxypropyl urea; bis(hydroxymethyl)urea; bis(hydroxyethyl)urea; bis(hydroxypropyl)urea; N,N'-dihydroxymethyl urea; N,N'-di-hydroxyethyl urea; N,N'-dihydroxypropyl urea; N,N,N'-trihydroxyethyl urea; tetra(hydroxymethyl)urea; tetra(hydroxyethyl)urea; tetra(hydroxypropyl)urea; N-methyl-N'-hydroxyethyl urea; N-ethyl-N,N'-hydroxyethyl urea; N-hydroxypropyl-N'-hydroxyethyl urea and N,N'-dimethyl-N-hydroxyethyl urea or substituted ureas such as mixtures thereof.When the term hydroxypropyl appears, its meaning is inclusive for any of 3-hydroxy-n-propyl, 2-hydroxy-n-propyl, 3-hydroxy-i-propyl or 2-hydroxy-i-propyl groups. Most preferred is hydroxyethyl urea, the latter being available as a 50% aqueous solution from ICI's National Starch & Chemical Division under the trade name Hydrovance.

[0067] When used in the compositions of the present invention, the amount of substituted urea will range from 0.01 to 20%, preferably 0.5 to 15%, and most preferably 2 to 10%, based on the total weight of the composition, including all ranges subsumed therein.

[0068] Conventional moisturizing agents can be used in the present invention as skin benefit agents and in addition to the bioenergetic combinations of the present invention. These are generally polyhydric alcohol type materials. Representative polyhydric alcohols include glycerol (i.e., glycerine or glycerin), propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol, sorbitol, hydroxypropyl sorbitol, hexylene glycol, 1,3-butylene glycol, isoprene glycol, 1,2,6-hexanetriol, ethoxylated glycerol, propoxylated glycerol, and mixtures thereof. Most preferred are glycerin, propylene glycol, or mixtures thereof. The amount of moisturizing agent used can range from 0.5 to 20% by weight of the composition, preferably 1 to 15% by weight.

[0069] When cationic ammonium compounds and substituted ureas are used, in the most particularly preferred embodiments, at least 1-15% glycerin is used, based on the total weight of the composition, including all ranges subsumed therein.

[0070] The compositions of the present invention may optionally and additionally include vitamins along with the active agents, skin benefit agents, and / or derivatives thereof according to the present invention. Exemplary vitamins are retinol (vitamin A), vitamin B2, vitamin B6, vitamin C, vitamin E, folic acid, and biotin. Derivatives of vitamins may also be used. For example, vitamin C derivatives include ascorbyl tetraisopalmitate, magnesium ascorbyl phosphate, and ascorbyl glycosides. Derivatives of vitamin E include tocopheryl acetate, tocopheryl palmitate, and tocopheryl linoleate. DL-panthenol and derivatives may also be used, with vitamins D and K also being options. The total amount of any vitamins, if present in the compositions according to the present invention, may range from 0.0-10%, preferably 0.001-1%, optimally 0.01-0.5% by weight of the composition.

[0071] Any skin benefit agent The compositions of the present invention may include a skin benefit agent and / or derivatives thereof in addition to niacinamide, an additional optional skin benefit agent (SBA). Relative to niacinamide, the skin benefit agent and / or derivatives thereof preferably constitute at least 25% by weight of the skin benefit agent, preferably at least 40-95% by weight, and most preferably 100% by weight. Optional skin benefit agents or additives may be provided, if desired, to constitute a portion of the skin benefit agent that is not niacinamide or the co-synthetic skin benefit agent and / or derivatives thereof.

[0072] Optionally suitable for use include chelating agents (e.g., EDTA), opacifying agents (e.g., TiO2, particle size 50-1200 nm, and preferably 50-350 nm), C 8-22 Also materials such as fatty acid substituted sugars, lipoic acid, retinoxytrimethylsilane (available from Clariant Corp. under the trade name SilCare IM-75), dehydroepiandrosterone (DHEA) and combinations thereof. Ceramides (such as ceramide I, ceramide 3, ceramide 36 and ceramide 6) and pseudoceramides may also be useful. Amounts of these materials can range from 0.000001 to 10%, preferably 0.0001 to 1% by weight of the compositions of the present invention.

[0073] Sunscreen actives may also be included in the compositions of the present invention. Particularly preferred are materials such as ethylhexyl p-methoxycinnamate available as Parsol MCX, Avobenzene available as Parsol 1789, and benzophenone-3, also known as Oxybenzone. Inorganic sunscreen actives such as ultrafine titanium dioxide, octocrylene zinc oxide, polyethylene and various other polymers may be used.

[0074] Amounts of sunscreen when present may generally range from 0.1 to 30%, preferably from 0.5 to 20%, optimally from 0.75 to 10% by weight.

[0075] Conventional buffers / pH adjusters can be used, including commonly used additives such as sodium hydroxide, potassium hydroxide, hydrochloric acid, citric acid, and citrate / citric acid buffers. In a particularly preferred embodiment, the pH of the compositions of the present invention is 4 to 8, preferably 4.25 to 7.75, and most preferably 6 to 7.5, including all ranges subsumed therein.

[0076] The compositions of the present invention are preferably a leave-on-skin lotion, cream, shampoo, conditioner, shower gel, antiperspirant, deodorant, depilatory, shave cream or toilet bar.

[0077] packaging A wide variety of packaging can be used to store and deliver the compositions of the present invention. Packaging often depends on the type of personal care end use. For example, leave-on skin lotions and creams, shampoos, conditioners, and shower gels generally use plastic containers with an opening at the dispensing end covered with a closure. Representative closures are screw caps, non-aerosol pumps, and flip-top hinged lids. Antiperspirants, deodorants, and depilatories packaging may involve containers with a roll-on ball at the dispensing end. Alternatively, these types of personal care products can be delivered in stick composition formulations in containers with a propellant-repulsion mechanism that moves the stick over a platform toward the dispensing opening. Metal cans pressurized with a propellant and equipped with a spray nozzle serve as packaging for antiperspirants, shaving creams, and other personal care products. Toilet bars can have packaging made of cellulose or plastic wrappers, or packaging that is in a cardboard box, or packaging that is surrounded by a shrink-wrap plastic film.

[0078] The following examples are provided to facilitate understanding of the invention and are not intended to limit the scope of the claims. EXAMPLES

[0079] Experimental Method Materials and cell treatment Test compounds (B3 and SAMe) were purchased from Sigma (St. Louis, MO). Cell culture growth media (Epilife medium with calcium (catalog number MEPI500CA) and Epilife medium supplement HKGS 100X (catalog number S-001-5)) were purchased from Thermofisher (Waltham, MA). Cryopreserved human keratinocyte cells (approximately 1 × 10 6 Cells) were plated at approximately 15% confluence in 12-well glass-bottom plates. The cells were suspended in primary keratinocyte growth medium (Epilife medium with calcium) and incubated at 37°C for 1 day (day 0). Treatment of cells with supplemented primary keratinocyte growth medium (Epilife medium with calcium supplemented with HKGS 100X; 25 mL total) without test compound (control sample) or with test compounds B3 (10 mM), SAMe (500 μM) or B3 (10 mM) + SAMe (500 μM) was started on day 1. Cell treatment (25 mL medium with or without test compound as above) continued once a day for two more days (days 2 and 3). On day 4, the medium was replaced with PBS and the cells were exposed to UV light (4 J / cm 2 Cells were UV-treated by exposing them to 1000 dl of UVA+UVB (UVA+UVB) for 14 min and feeding the cells with medium containing or not the corresponding test compound as defined above. UV treatment was continued once a day for three additional days (days 5, 6, and 7). Image collection and analysis in all wells to assess mitochondrial fragmentation was performed on days 1, 3, 5, and 8.

[0080] Image acquisition For two-photon excited fluorescence (TPEF) imaging, cell cultures were placed in a microscope-compatible microincubator system, which was maintained at 37 °C in a humidified environment throughout the imaging session. HEPES buffer (Sigma) was added to the cell cultures prior to imaging, which maintained the pH of the cell cultures throughout the imaging session. Imaging was performed using a Leica TCS SP8 confocal microscope equipped with a tunable (680-1300 nm) Ti:Sapphire laser (InSight Deep See; Spectra Physics; Mountain View, CA). Images (1024 × 1024 pixels; 386 × 386 μm) were acquired using a water-immersion 25x objective (NA 0.95; 2.4 mm working distance) and collected simultaneously with two nondescanned photomultiplier tube (PMT) detectors using a filter cube containing filters from Chroma (Bellows Falls, VT), including a 700 nm short-pass filter (ET700SP-2P) and a 495 nm dichroic mirror (495DCXR). To isolate NADH fluorescence, a 460 (±20) nm emission filter (Chroma, ET460 / 40M-2P), corresponding to the NADH emission peak, was placed in front of one of the nondescanned detectors. NADH fluorescence images were acquired from this 460 nm channel using 755 nm excitation. FAD fluorescence was separated using a 525 (±25) nm emission filter (Chroma, ET525 / 50M-2P) and 860 nm excitation for other non-descanned detectors. The two-photon action cross section of NADH decreases by several orders of magnitude between 755 nm and 860 nm excitation, thereby allowing efficient separation of FAD at longer wavelengths. Fluorescence lifetime images (512 × 512 pixels; 386 × 386 μm) corresponding to NADH were acquired with the same excitation and emission settings using SymPho software. The PMT gain was adjusted for each image to maximize contrast while preventing saturated pixel intensity values. The PMT gain and laser power were recorded for each image and used to normalize the fluorescence intensity.

[0081] Calculation of mitochondrial fragmentation To evaluate mitochondrial fragmentation, power spectral density (PSD) curves were obtained from each image using an established Fourier transform technique (M. Levitt et al., Diagnostic cellular organization features extracted from autofluorescence images. Opt Lett 32, 3305-3307 (2007); J. Xylas, K. P. Quinn, M. Hunter, I. Georgakoudi, Improved Fourier-based characterization of intracellular fractal features. Opt Express 20, 23442-23455 (2012)). Specifically, the image intensity pattern within the cytoplasmic region of the cell selected by the same binary mask used for redox analysis was copied and randomly placed on the image background to create a new image with no distinct cell boundaries and only a cell mitochondrial pattern that spreads across the entire image (K. P. Quinn et al., Quantitative metabolic imaging using endogenous fluorescence to detect stem cell differentiation. Sci Rep 3, 3432 (2013)). Power spectral density (PSD) curves were created for each image during Fourier transform. Next, the inverse power law behavior of the PSD curve at high spatial frequencies (>0.1 μm-1, corresponding to the size of mitochondria) was confirmed. This portion between 0.1 μm-1 and the frequency of 98% of the total PSD region was fitted to an equation of the form R(k)~k-β, and the exponential power β representing mitochondrial fragmentation was determined throughout this study.

[0082] statistical analysis To compare the means between treatments for each day, JMP and Tukey HSD were used for statistical analysis. The significance level of the test (α, the probability of type I error) was set at 0.05. A P-value of <= 0.05 between two measurements was considered statistically significant.

[0083] Example 1. Mitochondrial fragmentation in keratinocytes - UV study The aim of this study was to compare the degree of protection offered by different actives to the skin against mitochondrial fragmentation that occurs as a consequence of ageing with and without UV exposure.

[0084] The higher the value of mitochondrial fragmentation, the less protection is provided to the skin by a particular active or combination of actives. It should be noted that for a biological system such as mitochondria, which are micro-scale components of skin cells, the absolute value of mitochondrial fragmentation numbers is small and small differences can be important.

[0085] The effects of B3 and low levels of SAMe on mitochondrial fragmentation in keratinocytes before and after 3 days of UV exposure are shown in the table below.

[0086] [Table 1]

[0087] As can be seen from the data in Table 1 above, treatment of non-UV exposed keratinocytes with high levels of B3 (10 mM), low levels of SAMe (500 μM), or a combination of low levels of SAMe (500 μM) + high levels of B3 (10 mM) results in little reduction in mitochondrial fragmentation. Four days of UV exposure alone is effective in increasing the control level of mitochondrial fragmentation. A high dose (10 mM) of B3 alone is effective in reducing this UV-induced effect to control levels, but a much lower dose (500 μM) of SAMe alone increases mitochondrial fragmentation above UV exposure levels. Unexpectedly, however, the combination of B3 (10 mM) with a smaller (20-fold) amount of SAMe (500 μM) provides a significant synergistic benefit by effectively and synergistically reducing mitochondrial fragmentation more effectively than B3 or SAMe treatment alone and above non-UV exposed control levels.

[0088] Example 2 Personal care formulations according to the present invention are set forth in the table below, where all numbers represent the weight percent of the composition.

[0089] [Table 2]

[0090] [Table 3]

[0091] [Table 4]

Claims

1. A topical personal care composition for improving the energy efficiency of skin cells, comprising: (a) 0.001 to 10% by weight of niacinamide: (b) 0.001 to 10% by weight of an S-adenosyl-L-methionine compound of the following structural formula 1: 【Chemistry 1】 (c) any additional skin benefit agents; and (d) A cosmetically acceptable carrier.

20. A method for providing anti-aging and anti-stress benefits to a consumer's skin by protecting mitochondria and / or reducing mitochondrial fragmentation in the skin of an individual in need of treatment by topically applying to the skin said topical personal care composition comprising:

2. The method according to claim 1, wherein the amount of niacinamide is 0.01 to 6 weight percent based on the total weight of the composition.

3. The method according to claim 2, wherein the amount of niacinamide is 0.05 to 3.5 weight percent based on the total weight of the composition.

4. The method according to claim 1, wherein the amount of the S-adenosyl-L-methionine compound is 0.01 to 6% by weight based on the total weight of the composition.

5. The method of any one of claims 1 to 4, which improves cellular energy efficiency by protecting the skin of an aged individual in need of treatment from mitochondrial fragmentation.

6. Use of a topical personal care composition comprising 0.001-10% by weight niacinamide and 0.001-10% by weight S-adenosyl-L-methionine to provide anti-aging and anti-stress benefits to a consumer's skin by protecting mitochondria and / or reducing mitochondrial fragmentation in skin cells.

7. Use of niacinamide and S-adenosine-L-methionine in the manufacture of a topical personal care composition to provide anti-aging and anti-stress benefits to a consumer's skin by protecting mitochondria and / or reducing mitochondrial fragmentation in skin cells.

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