Bioenergy Combinations and Methods for Using The Same

Abstract

A topical personal care composition for improving cellular energy efficiency by protecting skin from mitochondrial fragmentation occurring in the cells of elderly individuals in need of treatment. Use of a topical personal care composition comprising niacinamide and one or more co-skin benefit agents for reducing cellular mitochondrial fragmentation, wherein the co-agent is selected from the group consisting of 1-methylnicotinamide chloride, N-acetylmethionine, mixtures thereof, and derivatives thereof. Use of niacinamide and a co-skin benefit agent selected from 1-methylnicotinamide chloride, N-acetylmethionine, mixtures thereof, and derivatives thereof 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 a combination of niacinamide and one or more synergistic skin benefit agents to prevent mitochondrial fragmentation in skin cells and increase cellular energy or skin bioenergetics of the skin. [Background technology]

[0002] High energy is commonly associated with desirable attributes such as vitality, health, youth, etc. It is less clear whether or how high energy or related attributes can be achieved, particularly whether or how it can be achieved at a cellular level.

[0003] Although there is a great deal of literature regarding the cellular metabolic energy cycle, the techniques for harnessing the functional components of cells to achieve youth and its perception through appearance remain uncertain. While true for all cells of the body, it is particularly unpredictable as to whether or how the cellular metabolic energy cycle or its manipulation can achieve youthful looking skin.

[0004] Within human cells, the three major energy-generating cellular processes are glycolysis (G), the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation (OP). While G occurs in the cytoplasm of the cell, the TCA and OP processes occur 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 the body of mammals such as 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 from MF, maintain basal levels of ROS, ensure optimal cellular bioenergetic status, 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] When consumers wish to reduce the appearance of lines, wrinkles, and age spots on their skin, they find it desirable to provide skin benefits through a method that relies on the application of a topical composition.There is a constant need for active ingredients to be incorporated into topical compositions that can provide benefits to the consumer's skin.There is a constant need for active ingredients to be incorporated into topical compositions that provide skin benefits by protecting the integrity and function of cellular components involved in the energy cycle of skin cells, thereby providing energy to skin cells.

[0010] Thus, the present invention relates to active and synergistic skin benefit agents for maintaining or optimizing the energy cycle of skin cells, compositions comprising said skin benefit agent combinations, and methods for increasing bioenergetics at the cellular level in the skin, which bioenergetic combinations protect the skin from mitochondrial fragmentation, maintain or reduce reactive oxygen species (ROS), ensure optimal skin cell bioenergetic state, and prevent premature skin aging.

[0011] 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.

[0012] N-acetyl amino acids (e.g., acetyl methionine or "AceMet") are disclosed in WO08 / 063441 and WO00 / 40217. However, no topical cosmetic compositions or methods on the skin have been demonstrated to be effective against mitochondrial fragmentation.

[0013] Efforts to produce formulations for treating the skin have been disclosed. US Patent Application No. 2008 / 0112968 describes a composition containing methylnicotinamide ("MeNAM") and B3 in combination with wakame extract. However, no topical skin cosmetic composition or method has been demonstrated to be effective against mitochondrial fragmentation. WO00 / 40559 discloses 1-methylnicotinic acid derivatives (including MeNAM), but not in combination with B3.

[0014] Still other efforts to create formulations for treating the skin have been disclosed. Certain 1-methylniconinic acid derivatives are disclosed in topical compositions in PL222236, but there is no indication of skin or mitochondrial fragmentation.

[0015] None of the above additional information discloses the mechanism of mitochondrial fragmentation.Furthermore, none of the additional information describes a composition comprising skin benefit agent 1-methylnicotinamide chloride (MeNAM) and / or N-acetylmethionine (AceMet) in combination with niacinamide (B3), which is suitable for MF in skin cells when topically applied to the skin in a cosmetically suitable carrier, reduces oxidative stress, and provides a bioenergetic effect. [Means for solving the problem]

[0016] The present invention overcomes the deficiencies of the prior art by providing topical personal care compositions comprising a combination of B3 and one or more synergistic skin benefit agents MeNAM and / or AceMet, and methods for reducing mitochondrial fragmentation, thereby increasing the bioenergetics of skin cells.

[0017] 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).

[0018] 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.

[0019] In a first aspect, the present invention provides a method for producing a composition comprising the steps of: (a) 0.001 to 10%, preferably 0.01 to 6%, and most preferably 0.05 to 3.5% of a niacinamide (B3) compound of formula 3; and (b) 0.001 to 10%, preferably 0.01 to 6%, of a synergistic skin benefit agent selected from the group consisting of 1-methylnicotinamide chloride compounds of general structural formula I, N-acetylmethionine compounds of general structural formula II, and mixtures thereof; (c) any additional skin benefit agents; and (d) A cosmetically acceptable carrier A topical personal care composition comprising:

[0020] The one or more synergistic skin benefit agents are MeNAM and / or AceMet and / or mixtures thereof.

[0021] The MeNAM compound of formula 1 below is preferred in this combination. [ka]

[0022] The composition may include additional optional skin benefit agents.

[0023] Also preferred are AceMet compounds of formula 2: [ka]

[0024] 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 skin personal care composition comprising a combination of B3 and one or more synergistic skin benefit agents MeNAM and / or AceMet in a cosmetically acceptable vehicle; and any combination thereof.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.The composition of the present invention may optionally include an additional skin benefit agent.

[0025] In a third aspect, the present invention is the use of a composition of the present invention comprising one or more synergistic skin benefit agents MeNAM and / or AceMet, and mixtures thereof, and B3, to reduce mitochondrial fragmentation.

[0026] In a fourth aspect, the present invention is the use of one or more synergistic skin benefit agents MeNAM and / or AceMet, and mixtures thereof, and derivatives thereof, and B3 / niacinamide, in the manufacture of a topical personal care composition for preventing mitochondrial fragmentation in skin cells.

[0027] All other aspects of the present invention will become readily apparent from consideration of the following detailed description and examples.

[0028] Throughout this specification and claims, unless the context clearly dictates otherwise, the following terms have the meanings expressly associated with them herein.

[0029] 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.

[0030] As used herein, "skin" is meant to include the skin of the feet, face (including the oral cavity), neck, chest, back, arms, hands, legs, buttocks and scalp (including hair). The compositions of the present invention include creams, lotions, balms, serums, deodorants and antiperspirants, shampoos, conditioners, bars and liquid cleansing products. In a preferred embodiment, the compositions of the present invention are leave-on compositions, such as leave-on creams or lotions.

[0031] Unless specifically stated otherwise, all ranges set forth herein are meant to include all ranges subsumed therein.

[0032] 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.

[0033] The word "comprising" is intended to mean "including" but not necessarily "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."

[0034] 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."

[0035] "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, lipsticks, foundations, mascaras, sunless tanners, and sunscreen lotions.

[0036] "Skin cosmetic composition" refers to any product that is applied to the human body to improve appearance, protect from the sun, reduce the appearance of wrinkles or other signs of photoaging, control odor, lighten skin, even skin tone, or general aesthetics. The composition of the present invention suitable for providing benefits to the skin can be an emulsion or a water- and emulsifier-free composition. Non-limiting examples of topical cosmetic skin compositions include skin lotions, creams, facial masks, gels, sticks, antiperspirants, deodorants, lipsticks, foundations, mascaras, liquid or gel body washes, bar soaps, sunless tanners, and sunscreen lotions.

[0037] 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

[0038] The present invention relates to a topical personal care composition comprising niacinamide (B3) in combination with one or more synergistic skin benefit agents MeNAM and / or AceMet 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 to the skin the personal care composition of the present invention; the use of the composition of the present invention to prevent or reduce mitochondrial fragmentation; and the use of one or more synergistic skin benefit agents MeNAM and / or AceMet, and mixtures and derivatives thereof, with B3 in the manufacture of a topical personal care composition for preventing mitochondrial fragmentation in skin cells.

[0039] 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).

[0040] In a first aspect, the present invention is a topical personal care composition comprising 0.001-10% of a niacinamide (B3) compound of structural formula 3 and 0.001-10%, preferably 0.01-6%, of one or more synergistic skin benefit agents, MeNAM and / or AceMet, in a cosmetically acceptable vehicle. [ka]

[0041] and AceMet of formula 2: [ka]

[0042] Each of the Niacinamide of structural formula 3: [ka]

[0043] It is preferred in combination with

[0044] In a second aspect, the present invention is a method of preventing mitochondrial fragmentation in the skin of an individual in need of treatment by topically applying to the skin a personal care composition comprising a mixture of one or more synergistic skin benefit agents MeNAM and / or AceMet, and any combination thereof, 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.

[0045] In a third aspect, the present invention is the use of a composition of the present invention comprising one or more synergistic skin benefit agents MeNAM and / or AceMet, and mixtures thereof, and B3, to reduce mitochondrial fragmentation.

[0046] In a fourth aspect, the present invention is the use of one or more synergistic skin benefit agents MeNAM and / or AceMet, and mixtures thereof, and derivatives thereof, and B3, in the manufacture of a topical personal care composition for preventing mitochondrial fragmentation in skin cells.

[0047] Methylnicotinamide ("MeNAM") According to the present invention, the compound 1-methylnicotinamide chloride (Structural Formula 1 shown below) is used in combination with niacinamide. [ka]

[0048] Typically, the amount of 1-methylnicotinamide chloride (MeNAM) used in the compositions of the present invention is 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.

[0049] Acetyl methionine ("AceMet") In accordance with the present invention, the N-acetyl methionine ("AceMet") compound shown below is used in combination with niacinamide.

[0050] Acetylmethionine has the following structural formula 2: [ka]

[0051] Acetylmethionine is the N-acetyl derivative of the amino acid methionine.

[0052] N-acetylmethionine is available from a number of sources, including Sigma-Aldrich.

[0053] Typically, the amount of N-acetyl methionine (AceMet) 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.

[0054] Nicotinamide Nicotinamide, also known as nicotinamide or as a form of vitamin B3, has the following structural formula 3: [ka]

[0055] 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%, inclusive of all ranges, based on the total weight of the composition.

[0056] Advantageously and unexpectedly, the combinations of compounds of the present invention synergistically inhibit mitochondrial fragmentation, with the combinations MeNAM+B3, AceMet+B3, and MeNAM+AceMet+B3 being the most preferred due to their apparent ability to reduce mitochondrial fragmentation in skin cells.

[0057] Salt type The compounds of the invention (MeNAM 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 R 5 CO 2 - These include, but are not limited to, R 5 is C 1 -C 22 It is 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. AceMet can form salts with a variety of physiologically suitable counterions, including, but not limited to, sodium, potassium, calcium, magnesium, ammonium, trialkylammonium, tetraalkylammonium, etc.

[0058] Derivatives of MeNAM and AceMet Derivatives of MeNAM are represented by the following general structural formula I: Simple derivatives of MeNAM include, for example, R 1 = methyl, ethyl, propyl, X - = Compounds of formula I, which are counterions that form salts. [ka]

[0059] Derivatives of AceMet are represented by the following general structural formula II: 2 = methyl, ethyl, propyl, hydroxymethyl, 2-hydroxyethyl and R 3 = ethyl, isopropyl, and the counter ions form salts as shown above. [ka]

[0060] 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.

[0061] 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.

[0062] 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.

[0063] 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.

[0064] 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.

[0065] 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.

[0066] The preferred silicone sources are cyclopentasiloxane and dimethiconol solution.

[0067] Among the suitable esters are the following:

[0068] (1) Alkyl 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.

[0069] In many cases, an oil such as caprylic capric triglyceride is preferred as the carrier.

[0070] 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; C condensed with 2 to 20 moles of alkylene oxide 2 -C 10 Alkylphenols;Mono- and di-fatty acid esters of ethylene glycol;Fatty acid monoglycerides;Sorbitan, mono- and di-C 8 -C 20fatty acids; and polyoxyethylene sorbitan, and combinations thereof.Alkyl polyglycosides and saccharide fatty amides (e.g., methyl gluconamide) are also suitable nonionic emulsifiers.

[0071] Preferred anionic emulsifiers include alkyl ether sulfates and sulfonates, alkyl sulfates and sulfonates, alkyl benzene sulfonates, alkyl and dialkyl sulfosuccinates, C 8 -C 20 Acyl isethionates, C 8 -C 20 These include alkyl ether phosphates, alkyl ether carboxylates, and combinations thereof.

[0072] 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.

[0073] 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.

[0074] 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.

[0075] 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.

[0076] The amount of thickening agent, if used, may range from 0.001 to 5%, preferably from 0.1 to 2%, most preferably from 0.2 to 0.5% by weight of the composition, including all ranges subsumed therein.

[0077] 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.

[0078] Cationic ammonium compounds may be used in the compositions of the present invention to enhance skin moisturization. Such compounds include hydroxypropyltrimethylsilyl (C 1 -C3 Salts of hydroxypropyltri(C alkyl)ammonium monosubstituted saccharides 1 -C 3 alkyl)ammonium monosubstituted polyol salts, dihydroxypropyltri(C 1 -C 3 Alkyl) ammonium salt, dihydroxypropyl di(C 1 -C 3 alkyl) mono(hydroxyethyl) ammonium salt, guar hydroxypropyltrimonium salt, 2,3-dihydroxypropyltri(C 1 -C 3 and mixtures thereof. In a most preferred embodiment, and if desired, the cationic ammonium compound employed in the present invention is the quaternary ammonium compound 1,2-dihydroxypropyltrimonium chloride. When used, such compounds will typically comprise 0.01 to 30% by weight, preferably 0.1 to 15% by weight, of the composition.

[0079] 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.

[0080] 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.

[0081] 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.

[0082] 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.

[0083] The compositions of the present invention may optionally and additionally contain vitamins in addition to the active agents, skin benefit agents, and / or derivatives thereof according to the present invention. Exemplary vitamins are retinol (vitamin A), vitamin B 2 , Vitamin B 6 , 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 vitamin, when present in a composition according to the present invention, may range from 0.0 to 10%, preferably 0.001 to 1%, optimally 0.01 to 0.5% by weight of the composition.

[0084] Any skin benefit agent The compositions of the present invention may include additional optional skin benefit agents (SBA) in addition to niacinamide, skin benefit agents and / or derivatives thereof. Relative to niacinamide, the skin benefit agent and / or derivatives thereof preferably constitutes 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 the portion of the skin benefit agent that is not niacinamide or the co-skin benefit agent and / or derivatives thereof.

[0085] Also optionally suitable for use are chelating agents (e.g., EDTA), opacifying agents (e.g., TiO 2 , particle size 50 to 1200 nm, and preferably 50 to 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.

[0086] 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.

[0087] 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.

[0088] 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.

[0089] 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.

[0090] 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 rebound 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 constructed of cellulose or plastic wrappers, or packaging within a cardboard box, or packaging surrounded by a shrink-wrap plastic film. Squeeze tubes can be used for oral care compositions such as toothpaste.

[0091] The following examples are provided to facilitate understanding of the invention and are not intended to limit the scope of the claims. EXAMPLES

[0092] Experimental Method Materials and cell treatment Test compounds (B3, AceMet, and MeNAM) 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 6Cells) 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). On day 1, cells were started to be treated 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), MeNAM (10 mM), AceMet (500 uM), B3 (10 mM) + AceMet (500 μM) or B3 (10 mM) + MeNAM (500 μM). Cell treatment (25 mL medium with or without test compound as above) continued once a day for another 4 days (non-UV test - Example 1) or 2 more days (UV test - Example 2). For UV testing, 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 for all cell wells to assess mitochondrial fragmentation was performed on days 1, 3, 5, and 8.

[0093] 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.

[0094] HEPES buffer (Sigma) was added to cell cultures in primary keratinocyte growth medium 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) titanium 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 non-descanned detectors. NADH fluorescence images were acquired from this 460 nm channel using 755 nm excitation. FAD fluorescence was isolated using a 525 (± 25) nm emission filter (Chroma, ET525 / 50M-2P) for the other non-descanned detector and 860 nm excitation. The two-photon action cross section of NADH decreases by several orders of magnitude between 755 and 860 nm excitation, thereby allowing efficient isolation 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.

[0095] 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)). That is, 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 only the cell mitochondrial pattern that has no distinct cell boundaries and 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. The inventors fit this portion between 0.1 μm-1 and the frequency of 98% of the total PSD region to an equation of the form R(k)~k-β to obtain the exponent β, which represented mitochondrial fragmentation throughout this study.

[0096] statistical analysis To compare the means between treatments for each day, JMP and Tukey HSD were used for statistical analysis. Also, the significance level of the test (α, the probability of a type I error) was set at 0.05. A P-value of <= 0.05 between two measurements was considered statistically significant.

[0097] Example 1. Mitochondrial fragmentation in keratinocytes The aim of this study was to compare the degree of protection offered to the skin by different actives against mitochondrial fragmentation that occurs as a consequence of ageing.

[0098] 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.

[0099] The effect of B3 alone and in combination with low levels of AceMet and MeNAM on mitochondrial fragmentation in keratinocytes after 5 days of exposure is shown in the table below.

[0100] Table 1 [Table 1]

[0101] As can be seen from the data in Table 1 above, high levels of B3 alone (10 mM) reduce mitochondrial fragmentation in keratinocytes, but B3 in combination with much lower levels of either MeNAM or AceMet (20-fold lower) is more effective at reducing mitochondrial fragmentation. Thus, the addition of relatively very low levels of AceMet and / or MeNAM provides superior protection to skin cells. Results are significantly better than B3 alone.

[0102] The significance of this discovery is that AceMet and MeNAM in combination with B3 improve cellular energy efficiency by protecting the skin from mitochondrial fragmentation that occurs as a consequence of aging.

[0103] Example 2. Mitochondrial fragmentation in keratinocytes - UV study The aim of this study was to compare the degree of protection offered by various actives to the skin against mitochondrial fragmentation that occurs as a consequence of aging with or without UV exposure.

[0104] The table below shows the effect of B3 and low levels of AceMet and MeNAM on mitochondrial fragmentation in keratinocytes before and after 3 days of UV exposure.

[0105] Table 2 [Table 2]

[0106] As can be seen from the data in Table 2 above, treatment of non-UV exposed keratinocytes with high levels of B3 (10 mM) or low levels of AceMet (500 μM) does little to reduce mitochondrial fragmentation, whereas treatment with high levels of MeNAM (10 mM) significantly reduces mitochondrial fragmentation. Unexpectedly, however, combining B3 (10 mM) with lower (20-fold) amounts of MeNAM (500 μM) or AceMet (500 μM) effectively and synergistically reduces mitochondrial fragmentation, with both combinations being significantly more effective than treatment with either B3, MeNAM or AceMet alone. UV exposure alone is also effective in increasing control levels of mitochondrial fragmentation. High doses (10 mM) of either B3 or MeNAM alone are effective in reducing this UV-induced effect to control levels, whereas a much lower dose (500 μM) of AceMet alone increases mitochondrial fragmentation above UV exposure levels. Unexpectedly, however, the combination of B3 (10 mM) with 20-fold lower (1 / 20) concentrations of either MeNAM (500 μM) or AceMet (500 μM) provided a significant synergistic benefit by more effectively and synergistically reducing mitochondrial fragmentation than B3, MeNAM, or AceMet treatment alone and above non-UV-exposed control levels.

[0107] The significance of this discovery is that AceMet and MeNAM in combination with B3 improve cellular energy efficiency by protecting the skin from mitochondrial fragmentation that occurs as a result of aging and daily sun exposure.

[0108] Example 3 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.

[0109] Table 3A - Oil-in-water formulations, lotions, and creams [Table 3]

[0110] TIFF0007608422000014.tif78166

[0111] Table 3B - Water-in-oil topical lotions or creams [Table 4]

[0112] TIFF0007608422000016.tif67165

[0113] Table 3C - Vanishing Cream [Table 5] In one aspect, the present invention provides the following. [Item 1] 1. A topical personal care composition for improving cellular energy efficiency, comprising: (a) 0.001 to 10%, preferably 0.01 to 6%, and most preferably 0.05 to 3.5% by weight of a niacinamide compound of the following structural formula 3: [ka] 0.001 to 10% by weight, preferably 0.01 to 6% by weight, of a synergistic skin benefit agent selected from the group consisting of compounds of general structural formula I: [ka] A compound of the following general structural formula II: 1 = methyl, ethyl, propyl, X - = Counterion that forms a salt.

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Claims

1. 1. A topical personal care composition for improving cellular energy efficiency, comprising: (a) 0.001 to 10% by weight of a niacinamide compound of the following structural formula 3: 【Chemistry 1】 and 0.001 to 10% by weight of a synergistic skin benefit agent comprising N-acetyl methionine of formula 2: 【Chemistry 5】 Synergistic skin benefit agents including (b) any additional skin benefit agents; and (c) A cosmetically acceptable carrier 1. A topical personal care composition comprising:

2. The topical personal care composition of claim 1, wherein the content of the niacinamide compound of structural formula 3 is 0.01 to 6% by weight.

3. The topical personal care composition of claim 1, wherein the content of the niacinamide compound of structural formula 3 is 0.05 to 3.5% by weight.

4. The topical personal care composition of claim 1, wherein the synergistic skin benefit agent is present in an amount of 0.01 to 6% by weight.

5. The topical personal care composition of any one of claims 1 to 4, wherein the composition is a skin cosmetic composition.

6. A method of preventing mitochondrial fragmentation in the skin of an individual in need of treatment by topically applying to the skin a composition according to any one of claims 1 to 5.

7. 7. The method of claim 6, which improves cellular energy efficiency by protecting the skin of an aging individual in need of treatment from mitochondrial fragmentation.

8. 1. Use of a topical personal care composition comprising 0.001-10% by weight of niacinamide and 0.001-10% by weight of one or more co-skin benefit agents, wherein said co-skin benefit agent is N-acetyl methionine, to reduce mitochondrial fragmentation.

9. The use of niacinamide and N-acetylmethionine, a synergistic skin benefit agent, in the manufacture of a topical personal care composition for reducing or preventing mitochondrial fragmentation in skin cells.

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