Methods and compositions for treating oxidative stress in the skin

Abstract

The cellular energy levels in skin cells affected by oxidative stress can be improved through the use of a skin care composition comprising a sucrose ester and a fatty alcohol present in a specific ratio. When incorporated into the skin care composition in a specific ratio, the fatty alcohol and the sucrose ester can provide a synergistic improvement in cellular ATP levels in skin cells affected by oxidative stress.

Description

[Technical field]

[0001] The present disclosure relates generally to improving cellular energy levels in skin cells exposed to oxidative stress. More specifically, the present disclosure relates to a combination of sucrose esters and fatty alcohols that synergistically improve cellular energy levels in skin cells exposed to oxidative stress. [Background technology]

[0002] A fundamental principle of life is the need and ability of cells to generate energy. In humans, food is ingested and ultimately converted into chemical compounds such as adenosine triphosphate ("ATP"), which are used by the body's cells to carry out biological processes that sustain life. The cellular metabolic pathways that convert the useful components of food (e.g., carbohydrates, fats, and proteins) into usable energy are complex and may be influenced by a variety of factors in ways that are not fully understood. Mammalian skin cells are no exception. Skin cells are known to contain a variety of different cell types that function together in a dynamic and complex relationship to maintain skin health. For example, keratinocytes proliferate and differentiate to provide continuous skin turnover, melanocytes provide melanin synthesis for skin pigmentation, and fibroblasts synthesize the extracellular matrix to provide thickness and elasticity to the skin. It is important that skin cells generate energy as efficiently as possible and function at optimal levels to maintain healthy skin.

[0003] It is now known that various environmental stressors can affect cellular bioenergetics and reduce the energy levels of skin cells, which can physically manifest as visible signs of aging (e.g., fine lines, wrinkles, uneven skin tone, hyperpigmentation spots). One theory for why oxidative stress reduces cellular energy levels is that exposure to reactive oxygen species (ROS) causes damage to cell structures and organelles such as mitochondria. ROS are highly reactive molecules that contain oxygen (e.g., oxygen ions and peroxides). In some cases, ROS are formed within cells as natural by-products of normal metabolism and play a role in cell signaling and homeostasis. However, when cells are exposed to stressors such as heat or UV radiation, ROS levels can increase dramatically, even to the point where the cell's antioxidant defense system is overwhelmed. When this happens, cellular damage can result.

[0004] Environmental stressors such as ultraviolet radiation ("UV") and pollutants (e.g., cigarette smoke, automobile exhaust, ozone) can lead to elevated levels of ROS production. As cellular damage caused by ROS accumulates over time, it results in oxidative stress at the cellular level that can ultimately lead to tissue damage and / or organ dysfunction. This damage typically manifests as noticeable changes in skin structure and morphology (e.g., "photodamage") and reduced ATP production. Summary of the Invention [Problem to be solved by the invention]

[0005] Thus, there is a continuing need for skin care actives that reduce, prevent, and / or reverse the decrease in cellular ATP production caused by oxidative stress. [Means for solving the problem]

[0006] Provided herein are compositions and methods for improving cellular energy levels in skin cells affected by oxidative stress. These methods include identifying a target area of ​​skin where treatment is desired and applying a skin care composition comprising a sucrose ester and a fatty alcohol, wherein the weight ratio of the fatty alcohol to the sucrose ester in the skin care composition is 1:4 to 40:1, and the combination of the sucrose ester and the fatty alcohol shows a synergistic improvement in cellular adenosine triphosphate (ATP) levels by oxidative stress testing. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0007] The undesirable effects of oxidative stress on skin function and appearance are known, and there are many skin care compositions available on the market to treat the visible signs of skin aging.Surprisingly, it has now been discovered that the combination of sucrose ester and fatty alcohol in a specific ratio can provide a synergistic improvement in the ATP level of cells exposed to oxidative stress.

[0008] References herein to an "embodiment" or the like mean that a particular material, feature, structure, and / or characteristic described in connection with that embodiment is included in at least one embodiment, and optionally multiple embodiments, but do not mean that all embodiments incorporate the described material, feature, structure, and / or characteristic. Moreover, materials, features, structures, and / or characteristics may be combined in any suitable manner across different embodiments, and materials, features, structures, and / or characteristics may be excluded or substituted from those described. Thus, the embodiments and aspects described herein can include or be combined with elements or components of other embodiments and / or aspects, even if not expressly illustrated in combination, unless otherwise stated or incompatibility is expressly stated.

[0009] In all embodiments, unless otherwise stated, all percentages of ingredients are based on the weight of the cosmetic composition. All ratios are by weight unless otherwise stated. The number of significant digits does not represent a limitation on the amounts indicated, nor does it represent a limitation on the precision of the measurements. All quantities are understood to be modified by the word "about" unless otherwise stated. Unless otherwise indicated, all measurements are understood to be made at ambient conditions of approximately 25°C, where "ambient conditions" means conditions of approximately 1 atmosphere pressure and approximately 50% relative humidity. All numerical ranges are inclusive and can be combined to form narrower ranges not expressly disclosed. For example, the upper and lower range limits delimited are interchangeable to create further ranges.

[0010] The compositions of the present invention can comprise, consist essentially of, or consist of the essential and optional ingredients described herein. As used herein, "consisting essentially of" means that the composition or component may contain only additional ingredients that do not materially alter the basic and novel characteristics of the claimed composition or method. As used in this specification and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms unless the context clearly dictates otherwise.

[0011] definition "About" modifies a particular value by referring to a range equal to plus or minus twenty percent (±20%) or less of the stated value (e.g., less than 15%, 10%, or even 5%).

[0012] "Agent" refers to materials and components thereof intended to provide a particular benefit or function. For example, emollients are materials (e.g., fatty alcohols) intended to provide an emollient benefit to the skin, and thickeners are generally materials intended to increase the viscosity of the composition.

[0013] "Apply" or "application" as used in connection with a composition means applying or spreading the composition herein onto a body surface such as the skin or hair.

[0014] "Cosmetic composition" means a composition that contains a cosmetic agent and is intended for non-therapeutic (i.e., non-medical) use. Examples of cosmetic compositions include color cosmetics (e.g., foundations, lipsticks, concealers, and mascaras), skin care compositions (e.g., moisturizers and sunscreens), personal care compositions (e.g., leave-on and leave-in body washes and soaps), and hair care compositions (e.g., shampoos and conditioners).

[0015] As used herein, "derivative" refers to the amide, ether, ester, amino, carboxyl, acetyl, and / or alcohol derivatives of a given compound.

[0016] "Effective amount" refers to an amount of the compound or composition sufficient to significantly induce a positive effect on keratinous tissue over the course of a treatment period. The positive effect may be a health, appearance, and / or feel effect, including the effects disclosed herein, either individually or in combination. In certain instances, the effective amount of the sucrose ester and fatty alcohol is an amount sufficient to increase cellular ATP levels that are reduced as a result of oxidative stress.

[0017] "Skin care" refers to regulating and / or improving the condition of the skin (e.g., the health, appearance, or texture / feel of the skin). Some non-limiting examples of improving the condition of the skin include improving the appearance and / or feel of the skin by providing a smoother and more uniform appearance and / or feel, increasing the thickness of one or more layers of the skin and improving the elasticity or resilience of the skin, improving the firmness of the skin, reducing the oily, shiny, and / or dull appearance of the skin, improving the hydration or moisturization of the skin, improving the appearance of fine lines and / or wrinkles, improving skin exfoliation or desquamation, plumping the skin, improving skin barrier properties, improving skin tone, reducing the appearance of redness or skin blemishes, and / or improving the brightness, luster, or clarity of the skin.

[0018] "Skin care active" means a compound or combination of compounds that, when applied to the skin, produces an acute and / or chronic effect on the skin or a type of cell normally found in the skin. Skin care actives can regulate and / or improve the skin or cells associated therewith (e.g., improve skin elasticity, hydration, barrier function, and / or cellular metabolism).

[0019] "Skin care composition" means a composition that contains skin care actives and that regulates and / or improves the condition of the skin.

[0020] "Synergy" and variations thereof mean that the effect provided by the combination of two or more materials (e.g., a sucrose ester and a fatty alcohol) is greater than the additive effect expected for those materials. For example, synergy is demonstrated when the combination of a sucrose ester and a fatty alcohol increases cellular ATP levels by greater than their calculated additive effect.

[0021] As used herein, "treatment period" refers to the length of time and / or frequency that a material or composition is applied to a targeted skin surface.

[0022] composition The cosmetic compositions herein are intended for topical application to human skin and contain a synergistic combination of sucrose esters and fatty alcohols disposed in a dermatologically acceptable carrier. The combination of sucrose esters and fatty alcohols is sufficient to synergistically improve cellular ATP levels that are reduced as a result of oxidative stress. When used over the course of a treatment period (e.g., 2, 4, or 8 weeks), the synergistic combination of sucrose esters and fatty alcohols may improve the appearance of visible signs of skin aging. In some cases, the sucrose esters and fatty alcohols are present in a weight ratio of fatty alcohol to sucrose ester of 1:4 to 40:1 (e.g., 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 10:1, 15:1, 20:1, 25:1, or even 30:1). The compositions herein may optionally include one or more additional skin actives or other ingredients of the type commonly included in topical skin care compositions.

[0023] The skin care composition herein can be made using conventional methods of combining skin care composition components.However, in some cases, it may be difficult to solubilize sucrose esters in the composition using conventional methods.In these cases, it may be desirable to solubilize sucrose esters in glycol premixes and then add them to the composition.An example of this process is described in co-pending U.S. Provisional Application No. 63 / 124,870, filed December 14, 2020 by Tanaka et al., entitled "Method of Manufacturing Cosmetic Compositions Comprising Sucrose Esters and Solvents."

[0024] The skin care compositions herein may be cosmetic compositions, pharmaceutical compositions, or cosmeceutical compositions, and may be provided in a variety of product forms, including, but not limited to, solutions, suspensions, lotions, creams, gels, toners, sticks, sprays, aerosols, ointments, cleansing liquid washes and solid bars, pastes, foams, mousses, shaving creams, wipes, strips, patches, powered patches, hydrogels, film-forming products, facial and skin masks (with and without insoluble sheets); make-up such as foundations, eyeliners, and eyeshadows, and the like. In some cases, the form of the composition may be in accordance with the particular dermatologically acceptable carrier selected. For example, the composition (and carrier) may be provided in the form of an emulsion (e.g., water-in-oil, oil-in-water, or water-in-oil-in-water) or an aqueous dispersion.

[0025] Although it may be desirable to provide a skin care composition as an oil-in-water emulsion, the combination of sucrose esters and fatty alcohols may cause stability problems (phase separation, syneresis, etc.). Surprisingly, it has now been found that by selecting certain types of thickeners and emulsifiers, the emulsion stability problems can be overcome. Some non-limiting examples of suitable thickeners and emulsifiers are described in more detail below. Other examples of stable emulsions containing sucrose esters are disclosed in co-pending U.S. Provisional Application No. 63 / 125,021, filed December 14, 2020 by Ehrman et al. and entitled "Stable Skin Care Emulsion and Methods of Using the Same."

[0026] Sucrose Esters The compositions herein comprise an effective amount of an ester of sucrose with a fatty acid, the fatty acid being selected from those having 12 to 24 carbon atoms (e.g., 12 to 22 carbon atoms, or even 12 to about 18 carbon atoms). Particularly suitable fatty acids are selected from those having saturated alkyl groups. In some cases, the sucrose ester is selected from the group consisting of sucrose laurate, sucrose dilaurate, sucrose trilaurate, derivatives thereof, and combinations thereof. As used herein, "sucrose laurate" refers to a sucrose ester having the formula C 24 H 44 O 12 and CAS# 25339-99-5. "Sucrose dilaurate" means a compound having the formula C 36 H 66 O 13 and CAS# 25915-57-5, and "sucrose trilaurate" means a compound having the formula C 48 H 88 O 14 and a compound having CAS# 94031-23-9. The sucrose ester may be present at 0.0001% to 15% (e.g., 0.0002% to 10%, 0.001% to 15%, 0.025% to 10%, 0.05% to 7%, 0.05% to 5%, or even 0.1% to 3%) by weight of the composition.

[0027] In some cases, the sucrose ester may be a blend of two or more sucrose esters, where the two or more sucrose esters are present in a ratio of 1:10 to 1:1 (e.g., 1:7, 1:5, 1:3, or 1:2) of any one sucrose ester to another. In some cases, the sucrose ester may be a blend of sucrose laurate and sucrose dilaurate, where the sucrose laurate is present at 50% to 80% by weight of the sucrose ester and the sucrose dilaurate is present at 20% to 45% by weight of the sucrose ester. Alternatively, the sucrose ester may be a blend of sucrose laurate, sucrose dilaurate, and sucrose trilaurate, where the sucrose dilaurate is present at 35% or more by weight of the sucrose ester. A particularly suitable example of a sucrose ester for use herein is BC10034 from BASF, which is a blend of sucrose laurate and sucrose dilaurate. The BC10034 sucrose ester material may have a ratio of sucrose laurate to sucrose dilaurate ranging from 3:1 to 3:2.

[0028] Fatty alcohol The compositions herein include a fatty alcohol, which refers to a high molecular weight, linear, primary alcohol having the general structure:

[0029] [ka] In the formula, n=8 to 32.

[0030] Fatty alcohols can be natural or synthetic, saturated or unsaturated, branched or straight chain. Some non-limiting examples of fatty alcohols commonly used in skin care compositions include caprylic, capryl, lauryl, myristyl, cetyl, stearyl, and behenyl alcohol. Fatty alcohols herein may be generically referred to by the number of carbon atoms in the molecule. For example, "C12 alcohol" refers to an alcohol with 12 carbon atoms in its chain (i.e., dodecanol). Some non-limiting examples of fatty alcohols that may be suitable for use herein are ricinoleate and 12-hydroxystearate. A particularly suitable fatty alcohol for use herein is hexyldecanol (CAS number 2425-77-6), which has the following structure:

[0031] [ka]

[0032] The fatty alcohol may be included in the composition at 0.0001% to 15% by weight (e.g., 0.0002% to 10%, 0.001% to 15%, 0.025% to 10%, 0.05% to 7%, 0.05% to 5%, or even 0.1% to 3% by weight) of the composition.

[0033] Dermatologically acceptable carrier The compositions disclosed herein include a dermatologically acceptable carrier (sometimes referred to as a "carrier"). The phrase "dermatologically acceptable carrier" means that the carrier is suitable for topical application to keratinous tissue, has good aesthetic properties, is compatible with the actives in the composition, and does not raise any undue safety or toxicity concerns. In one embodiment, the carrier is present at a level of about 50% to about 99%, about 60% to about 98%, about 70% to about 98%, or alternatively about 80% to about 95% by weight.

[0034] The carrier may be in a wide variety of forms. In some cases, the solubility or dispersibility of the components (e.g., extracts, sunscreen actives, additional ingredients) may determine the form and characteristics of the carrier. Non-limiting examples include simple solutions (e.g., aqueous or anhydrous), dispersions, emulsions, and solid forms (e.g., gels, sticks, flowable solids, or amorphous materials). In some cases, the dermatologically acceptable carrier is in the form of an emulsion. An emulsion may have a continuous aqueous phase (e.g., oil-in-water or water-in-oil-in-water emulsions) or a continuous oil phase (e.g., water-in-oil or oil-in-water-in-oil emulsions). The oil phase of the present invention may include non-silicone oils such as silicone oils, hydrocarbon oils, esters, ethers, and mixtures thereof. The aqueous phase typically includes water and water-soluble components (e.g., water-soluble moisturizers, conditioning agents, antibacterial agents, humectants, and / or other skin care actives). In some cases, however, the aqueous phase may contain components other than water, including, but not limited to, water-soluble moisturizers, conditioning agents, antimicrobial agents, humectants, and / or other water-soluble skin care actives. In some cases, the non-aqueous components of the composition include humectants, such as glycerin and / or other polyols.

[0035] In some cases, the compositions herein are in the form of oil-in-water ("O / W") emulsions that provide a light, non-greasy sensory feel. Suitable O / W emulsions herein may comprise more than 50% by weight of the composition of a continuous water phase, with the remainder being a dispersed oil phase. The water phase may comprise 1% to 99% water, based on the weight of the water phase, along with any water-soluble and / or water-miscible ingredients. In these cases, the dispersed oil phase is typically present at less than 30% by weight of the composition (e.g., 1% to 20%, 2% to 15%, 3% to 12%, 4% to 10%, or even 5% to 8%) to help avoid some of the undesirable sensory effects of oil-based compositions. The oil phase may comprise one or more volatile and / or non-volatile oils (e.g., vegetable oils, silicone oils, and / or hydrocarbon oils). Some non-limiting examples of oils that may be suitable for use in the present compositions are disclosed in U.S. Pat. No. 9,446,265 and U.S. Patent Application Publication No. 2015 / 0196464.

[0036] The carrier may contain one or more dermatologically acceptable hydrophilic diluents. As used herein, "diluents" include materials in which the sucrose esters can be dispersed, dissolved, or otherwise incorporated. Hydrophilic diluents include organic hydrophilic diluents such as water, lower monohydric alcohols (e.g., C1-C4), and low molecular weight glycols and polyols, including propylene glycol, polyethylene glycol (e.g., molecular weight 200-600 g / mol), polypropylene glycol (e.g., molecular weight 425-2025 g / mol), glycerol, butylene glycol, 1,2,4-butanetriol, sorbitol esters, 1,2,6-hexanetriol, ethanol, isopropanol, sorbitol esters, butanediol, ether propanol, ethoxylated ethers, propoxylated ethers, and combinations thereof.

[0037] Other Optional Ingredients The composition suitable for use in the method herein may contain one or more optional components known for use in topical skin care compositions, so long as the optional components do not unacceptably alter the desired effect of the composition.In particular, the additional components should not undesirably affect the ability of the sucrose ester fatty alcohol to synergistically increase cellular ATP levels that are reduced as a result of oxidative stress.In some cases, it may be desirable to select skin care actives that function through different biological pathways so that the actives do not interfere with each other.When the composition is in the form of an emulsion, the additional components should not introduce instability (e.g., syneresis) to the emulsion.For example, it may be desirable to select optional components that do not complex with other components in the composition, especially pH-sensitive components such as vitamin B3 compounds, salicylates, and peptides.

[0038] The additional components should be suitable for use in contact with human skin tissue without undue toxicity, incompatibility, instability, allergic response, etc. If present, the optional components may be included in an amount of about 0.001% to 50% by weight (e.g., 0.01% to 40%, 0.1% to 30%, 0.5% to 20%, or 1% to 10% by weight) of the composition. Some non-limiting examples of additional ingredients include vitamins, minerals, peptides and peptide derivatives, sugar amines, sunscreens, oil control agents, microparticles, flavonoid compounds, hair growth regulators, antioxidants and / or antioxidant precursors, preservatives, protease inhibitors, tyrosinase inhibitors, anti-inflammatory agents, moisturizers, exfoliants, skin lightening agents, sunscreens, sunless tanning agents, lubricants, anti-acne agents, anti-cellulite agents, chelating agents, anti-wrinkle actives, anti-atrophy actives, phytosterols and / or plant hormones, N-acyl amino acid compounds, antibacterial agents, and antifungal agents. Some particularly suitable examples of additional ingredients include one or more skin care actives selected from the group consisting of vitamin B3 compounds (e.g., niacinamide), n-acyl amino acids (e.g., undecylenoyl phenylalanine), vitamin E compounds (e.g., tocopheryl acetate), palmitoylated dipeptides (e.g., palmitoyl-lysine-threonine), palmitoylated pentapeptides (e.g., palmitoyl-lysine-threonine-threonine-lysine-serine), vitamin A compounds (e.g., retinol and retinyl propionate), and combinations thereof.Other non-limiting examples of optional ingredients and / or skin care actives that may be suitable for use herein are described in U.S. Patent Application Publication Nos. 2002 / 0022040, 2003 / 0049212, 2004 / 0175347, 2006 / 0275237, 2007 / 0196344, 2008 / 0181956, 2008 / 0206373, 2010 / 0092408, 2008 / 0206373, 2010 / 0239510, 2010 / 0189669, 2010 / 0189702, 2010 / 0189704, 2010 / 0189706, 2010 / 0189708, 2010 / 0189709 ... Nos. 2010 / 0272667, 2011 / 0262025, 2011 / 0097286, 2012 / 0197016, 2012 / 0128683, 2012 / 0148515, 2012 / 0156146, and 2013 / 0022557, as well as U.S. Patent Nos. 5,939,082, 5,872,112, 6,492,326, 6,696,049, 6,524,598, 5,972,359, and 6,174,533.

[0039] Conditioning Agent The compositions herein may include 0.1% to 50% by weight of a conditioning agent (e.g., 0.5% to 30%, 1% to 20%, or even 2% to 15%). The addition of a conditioning agent can help provide the composition with desirable feel characteristics (e.g., silky smooth feel upon application). Some non-limiting examples of conditioning agents include hydrocarbon oils and waxes, silicones, fatty acid derivatives, cholesterol, cholesterol derivatives, diglycerides, triglycerides, vegetable oils, vegetable oil derivatives, acetoglyceride esters, alkyl esters, alkenyl esters, lanolin, wax esters, beeswax derivatives, sterols and phospholipids, salts, isomers, and derivatives thereof, and combinations thereof. Particularly suitable examples of conditioning agents include volatile or non-volatile silicone fluids such as dimethicone copolyol, dimethylpolysiloxane, diethylpolysiloxane, mixed C1-30 alkylpolysiloxane, phenyldimethicone, dimethiconol, dimethicone, dimethiconol, silicone crosspolymers, and combinations thereof.Dimethicone may be particularly suitable because some consumers associate the feel properties provided by certain dimethicone fluids with good moisturization.Other examples of silicone fluids that may be suitable for use as conditioning agents are described in U.S. Pat. No. 5,011,681.

[0040] The compositions herein may include 0.05% to 5% of a hydrophobically modified aqueous rheology modifier (e.g., thickener) to provide the composition with suitable rheology, stability, and skin feel properties. Some non-limiting examples of thickeners that may be suitable for use herein include crosslinked polyacrylate polymers, such as PEMULEN EZ-4U, PEMULEN TR-1, PEMULEN TR-2, and certain ULTREZ brand acrylates / C10-30 alkyl acrylate crosspolymers, all available from Lubrizol. Other examples include acrylate vinyl isodecanoate crosspolymers, such as STABYLEN 30 sold by 3V, polyacrylate crosspolymer-6, such as SEPIMAX ZEN sold by Seppic®, and sodium polyacryloyldimethyltaurate, such as ARISTOFLEX SILK sold by Clariant. In some cases it may be desirable to exclude polyacrylamide based thickeners, such as SEPIGEL 305 brand polyacrylamide thickeners, as these types of thickeners can destabilize emulsions.

[0041] The rheology modifiers of the compositions herein may include medium to long chain fatty acid derived emulsifiers (e.g., about 12-20 carbon chains, alternatively 16-20 carbon chains). In some examples, the emulsifiers may be non-ionic stearic acid derived emulsifiers such as steareth-2 steareth-21, PEG-100 stearate, glycereth-25 pyrrolidone carboxylic acid isostearate, and combinations thereof. "Stearic acid derived emulsifiers" are emulsifiers in which at least one of the surfactant's lipophilic domains is composed of a saturated 18 carbon chain (similar to stearic acid). These emulsifiers typically contain stearate, steareth, or isostearate in their chemical names, and are often derived from stearic acid in combination with other chemical moieties. Particularly suitable emulsifiers include stearic acid derived emulsifiers having a hydrophilic-lipophilic balance (HLB) of 14 or greater. The emulsifier may be present in the composition at 0.05% to 5% (e.g., 0.1% to 4%, 0.5% to 3%, or even 1% to 2%). In some cases, it may be desirable to exclude certain polyether modified silicone emulsifiers, such as PEG-11 methyl ether dimethicone, PEG-12 dimethicone, PEG / PPG 19 / 19 dimethicone, or other PEGylated dimethicones, which may destabilize oil-in-water emulsions.

[0042] How to use The method of using the compositions herein involves identifying a target area of ​​the skin of a person in need of treatment and applying the composition to the target area of ​​the skin over the course of a treatment period. The compositions herein should contain an effective amount of a sucrose ester in combination with an aliphatic alcohol. The target area of ​​the skin may be on the skin surface of the face, such as the forehead, perioral, chin, periorbital, nose, and / or cheeks, or on another part of the body (e.g., hands, arms, legs, back, chest). The person in need of treatment is one whose skin shows signs of oxidative stress, such as fine lines, wrinkles, hyperpigmentation, uneven skin tone, and / or other visible skin features typically associated with aging. In some cases, the target area of ​​the skin may not show visible signs of skin aging, but if it is an area of ​​the skin that typically develops such problems as a person ages, the user (e.g., a relatively young user) may still want to target such skin area. In this way, the method can be used as a preventative measure to delay the onset of visible signs of skin aging.

[0043] The composition can be applied daily, at least once a day, twice a day, or more frequently, to the target area of ​​skin and, if desired, to the surrounding skin during the treatment period. If applied twice a day, the first and second applications are separated by at least 1-12 hours. The composition is typically applied in the morning and / or at night before going to bed. When used according to the methods herein, the composition can improve the appearance of skin affected by oxidative stress by increasing ATP production in skin cells. Changes in cellular ATP production can be determined according to the methods described in more detail below.

[0044] The treatment period herein is ideally long enough for the combination of sucrose ester and fatty alcohol present in the composition to increase ATP production in skin cells undergoing oxidative stress, thereby improving the appearance of visible signs of skin aging. The ATP production effect provided by the method may be indicated by a synergistic increase in ATP production compared to the use of sucrose ester and fatty alcohol individually. In some cases, the method may provide a synergistic increase in ATP production of at least 5% (e.g., 10%, 15%, 20%, 25% or more) compared to the expected increase in ATP production. The treatment period may last for at least 1 week (e.g., about 2 weeks, 4 weeks, 8 weeks, or even 12 weeks). In some cases, the treatment period will extend for several months (i.e., 3 to 12 months). In some cases, the composition may be applied at least once a day, or even twice a day, for a majority of days a week (e.g., at least 4, 5, or 6 days a week) during a treatment period of at least 2 weeks, 4 weeks, 8 weeks, or 12 weeks.

[0045] The step of applying the composition can be performed by topical application. With respect to the application of the composition, the terms "topical", "topical" or "topically" mean that the composition is delivered to a target area (e.g., wrinkles or lines) while minimizing delivery to skin surfaces where treatment is not desired. The composition can be applied to a skin area and gently massaged. The form of the composition or dermatologically acceptable carrier should be selected to facilitate topical application. Although certain embodiments herein contemplate applying the composition to an area topically, it will be understood that the composition herein can be applied broadly to one or more skin surfaces. In certain embodiments, the composition herein can be used as part of a multi-step cosmetic regimen, in which the composition can be applied before and / or after one or more other compositions.

[0046] method Oxidative stress test This test method provides a suitable method for determining the ability of a test agent to improve cellular ATP production in cells exposed to oxidative stress.

[0047] Keratinocytes (e.g., H-tert-keratinocytes from University of Texas Southwestern) are cultured in T150 flasks in EpiLife Medium (e.g., Thermo Fisher Scientific catalog #MEPICFPRF500) supplemented with human keratinocyte growth supplement (e.g., Thermo Fisher Scientific catalog #S-001-5) and 1% penicillin / streptomycin (e.g., Thermo Fisher Scientific catalog #15140-122). When the keratinocytes reach approximately 70% confluency, they are seeded into 96-well plates (white clear bottom with 20,000 cells / well). The plates are incubated for 24 hours before applying experimental stresses and treatments.

[0048] The 96-well plate is divided into three groups of samples (wells) as follows: (i) no stress and no treatment, (ii) stress but no treatment, and (iii) both stress and treatment. In combination experiments, two treatments can be applied in addition to stress. For unstressed / untreated samples (i.e., group (i) above), the culture medium is simply refreshed. For stressed samples (i.e., groups (ii) and (iii) above), culture medium containing 400 μM hydrogen peroxide (HOOH) is used to replace the medium. For treated samples (i.e., group (iii) above), the treatments are pipetted from the 100x master stock into the wells immediately after adding HOOH. The plate is returned to the CO2 incubator for 90 minutes before measuring ATP.

[0049] ATP is measured by removing the medium from the samples and replacing it with ATP Glo® reagent (available from Promega, Madison, WI) or equivalent according to the manufacturer's instructions. After 10 minutes of exposure at room temperature, the luminescence of each sample can be measured using a Perkin Elmer ENVISION brand plate reader or equivalent. Luminescence counts are directly proportional to the ATP levels in the cells. Luminescence counts are recorded for each sample.

[0050] The replicates for each treatment group are averaged together and significance is calculated using standard p-value calculations (2-sided, equal variance). If two treatments appear to synergistically enhance ATP levels, the results of the combined treatments can be compared to the sum of the individual treatments to determine a synergy coefficient. The synergy coefficient is calculated as the ratio of the observed effect from the combined treatment divided by the sum of the results from each individual treatment. A synergy coefficient of 1.00 indicates that the combined treatment performed as expected, whereas a synergy coefficient >1.00 indicates a synergistic effect that exceeds simple additivity / expectation.

[0051] Test agents used in oxidative stress testing are limited to relatively low concentrations due to cytotoxicity. That is, applying high concentrations of test agents directly to "unprotected" keratinocytes may kill some of all cells, which would obviously skew the test results. Normal human skin has a stratum corneum that acts as a barrier against foreign bodies and contaminants, thereby protecting the underlying living epidermis. The stratum corneum has a "brick and mortar" arrangement in which mature keratinocytes ("bricks") are arranged in a lipid matrix ("mortar") of fatty acids, ceramides, and cholesterol. For a topically applied skin care active to be effective, it must penetrate the stratum corneum to reach the living cells in the living epidermis. However, penetration into the stratum corneum effectively dilutes the skin care active anywhere from 10-fold to 10,000-fold, and only a relatively small amount of the applied active actually reaches the living epidermis. Because the keratinocytes used in oxidative stress testing do not have a stratum corneum to dilute the test agent / skin care active, the test agent must be diluted prior to application to the living cells. Thus, results observed in the oxidative stress test for a particular concentration of a test agent are scalable (e.g., 10-10,000 fold) based on the known dilution effects of human stratum corneum. For example, a test agent that demonstrates synergy in the oxidative stress test at a concentration of 10 ppm (0.001%) is expected to provide substantially the same synergy when included in a skin care composition at 0.01%, 0.1%, and / or 1%.

[0052] Examples and Combinations Example 1: Formulation Table 1 below provides examples of skin care compositions containing a synergistic combination of sucrose esters and vitamin B3 compounds. Exemplary compositions can be made using conventional methods. In some cases, when the composition is in the form of an oil-in-water emulsion, it may be desirable to make it as follows: Prepare a sucrose ester premix by combining sucrose esters, pentylene glycol, and QS water and mixing until the sucrose esters are completely dissolved. Heat may be used, if necessary, to aid in dissolving the sucrose esters. Alternatively, the aqueous phase can be prepared by dispersing the thickener and polymeric emulsifier in water. After the thickener is dispersed and homogenous, any additional emulsifiers (e.g., high HLB emulsifiers) are added to the aqueous phase. The remaining aqueous phase ingredients are added and adjusted to the desired pH (e.g., pH 5-7). In a separate container, combine the oil phase ingredients and mix until homogenous, with heating as necessary (e.g., to melt any solid materials). The oil phase is then emulsified into the water phase by slowly adding the oil phase with mixing, and mixing is continued until the emulsion is completely homogenous. After the emulsion is completely homogenous, any remaining ingredients or powder phase materials are added with mixing until homogenous. The sucrose ester premix phase can be added to the batch before or after the emulsification step, and then mixed until the batch is homogenous.

[0053] [Table 1]

[0054] [Table 2]

[0055] [Table 3]

[0056] [Table 4] + Balance to get closer to neutral pH 5-7 1. ELDEW PS-203 available from Ajinomoto 2. KSG-16 available from Shin-Etsu 3. EMULGADE PL68 / 50 available from BASF 4. XIAMETER PMX-1503 available from Dow Corning 5. KF-6011 available from Shin-Etsu 6. BASF BC10034 7. CARBOPOL ULTREZ 20 available from Lubrizol 8. PEMULEN TR-1 available from Lubrizol 9. PEMULEN EZ-4U available from Lubrizol STABLYEN 30 available from 10.3V 11. SEPIGEL 305 available from Seppic 12. SEPIWHITE available from Seppic 13. SEPIMAX ZEN available from Seppic 14. ARISTOFLEX SILK available from Clariant

[0057] Example 2 - Criticality of sucrose ester to fatty alcohol ratio. This example shows the importance of providing suitable ratio of sucrose ester and fatty alcohol in skin care composition.The fatty alcohol tested in this example is hexyldecanol, and the sucrose ester is a mixture of sucrose laurate and sucrose dilaurate (BC10034 from BASF).The ratios of fatty alcohol to sucrose ester of 1:1, 5:1, 50:1 and 1:5 are tested according to the above oxidative stress test.The results of the test are summarized in the following Tables 2, 3, 4 and 5.The test legs with a synergy value greater than 1 and a p-value less than 0.05 are considered to be synergistic.A synergy value of at least 1.05 is preferred (e.g., at least 1.1, 1.2, 1.3, 1.4, 1.5, or even 1.6 or more).

[0058] [Table 5]

[0059] [Table 6]

[0060] [Table 7]

[0061] [Table 8]

[0062] As can be seen in Tables 2, 3, 4, and 5, only ratios of fatty alcohol to sucrose ester of 1:1 and 5:1 provided statistically significant synergistic improvements in ATP production. These data suggest that only certain ratios of fatty alcohol to sucrose ester (e.g., 50:1 to 1:5) may provide the desired synergistic increase in ATP production in oxidatively stressed cells. Thus, the skin appearance benefits provided by skin care compositions intended to treat signs of skin aging associated with oxidative stress may be significantly enhanced when the compositions include a suitable combination of fatty alcohol and sucrose ester.

[0063] Dimensions and values ​​disclosed herein should not be understood as being strictly limited to the exact numerical values ​​recited. Instead, unless otherwise indicated, each such dimension is intended to mean both the recited value and a functionally equivalent range surrounding that value. For example, a dimension disclosed as "40 mm" is intended to mean "about 40 mm."

[0064] All documents cited herein, including any cross-referenced or related patents or patent applications, and any patent applications or patents to which this application claims priority or benefit, are incorporated herein by reference in their entirety, unless expressly stated to the contrary. The citation of any document shall not be deemed to be prior art to any invention disclosed or claimed herein, or to teach, suggest or disclose such invention, either alone or in combination with any other reference(s). Furthermore, to the extent that any meaning or definition of a term in this document conflicts with any meaning or definition of the same term in a document incorporated by reference, the meaning or definition assigned to that term in this document shall govern.

[0065] While particular embodiments of the present invention have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention.

Claims

1. 1. A skin care composition comprising: (i) 0.0001% to 10% of a sucrose ester; (ii) 0.0001% to 10% of a fatty alcohol; and (iii) a dermatologically acceptable carrier; and wherein the fatty alcohol and sucrose ester are present in a weight ratio of 1:1 to 5:1 based on the weight of the composition, and the combination of sucrose ester and fatty alcohol has a synergy coefficient of at least 1.1 according to an Oxidative Stress Test, the sucrose ester comprising a mixture of sucrose laurate and sucrose dilaurate, and the fatty alcohol is selected from the group consisting of hexyldecanol, ricinoleate, 12-hydroxystearate, and combinations thereof.

2. 10. The skin care composition of claim 1, wherein sucrose laurate is present at 55% to 80% by weight of the sucrose ester and sucrose dilaurate is present at 20% to 45% by weight of the sucrose ester.

3. 3. The skin care composition of claim 1 or 2, wherein the sucrose ester and the fatty alcohol are each present at 0.0001% to 10% by weight of the composition.

4. 4. The skin care composition of any one of claims 1 to 3, wherein the composition further comprises at least one additional ingredient selected from the group consisting of vitamins, minerals, peptides, sugar amines, sunscreens, oil control agents, flavonoid compounds, antioxidants, preservatives, protease inhibitors, tyrosinase inhibitors, anti-inflammatory agents, moisturizers, exfoliants, skin lightening agents, lubricants, anti-acne actives, chelating agents, anti-wrinkle actives, anti-atrophy actives, phytosterols, N-acyl amino acid compounds, antibacterial and antifungal agents, conditioning agents, emulsifiers, rheology modifiers, and combinations thereof.

5. 5. The skin care composition of claim 4, wherein the additional ingredient is a skin care active selected from the group consisting of vitamin B3 compounds, undecylenoyl phenylalanine, vitamin E compounds, palmitoylated dipeptides, palmitoylated pentapeptides, vitamin A compounds, and combinations thereof.

6. 6. The skin care composition of claim 1, wherein the composition further comprises a rheology modifier selected from the group consisting of Acrylates / C10-30 Alkyl Acrylate Crosspolymer, Acrylates Vinyl Isodecanoate Crosspolymer, and combinations thereof.

7. 7. The skin care composition of claim 1, wherein the composition further comprises an emulsifier selected from the group consisting of glycereth-25 pyrrolidone carboxylic acid isostearate, PEG-100 stearate, steareth-2, steareth-21, and combinations thereof.

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