How to improve the appearance of your skin

Abstract

A method for improving the appearance of skin using a low pH skin care composition containing a synergistic combination of hydroxycinnamic acid (HCA) and a vitamin B3 compound is disclosed.

Description

[Technical Field]

[0001] The present invention relates to a method for improving the appearance of skin using a low pH skin care composition containing a synergistic combination of stable hydroxycinnamic acid (HCA) and a vitamin B3 compound. [Background technology]

[0002] Skin is the first line of defense against environmental insults that can damage otherwise sensitive underlying tissues and organs.Furthermore, skin plays an important role in human physical appearance.Not surprisingly, most people desire healthy and youthful skin.Unfortunately, for some people, the obvious signs of aging, such as thinning skin, wrinkles, and age spots, are undesirable reminders of lost youth.The desire for healthy and youthful-looking skin has led to the development of numerous skin care products that are marketed to treat various skin conditions related to aging and unhealthy skin.These skin care products typically contain one or more active ingredients for treating targeted skin conditions.

[0003] Hydroxycinnamic acids (HCAs) are well-known skin care actives developed for their powerful antioxidant properties, as described, for example, in WO 2018 / 081790. However, using hydroxycinnamic acids in skin care compositions can be problematic. For example, HCA is relatively insoluble in water, which can lead to the undesirable formation of HCA crystals in the product. Furthermore, when HCA is used at neutral pHs (e.g., pH 5.0-8.0), which are becoming more common in certain skin care compositions, the HCA can oxidize or decompose, causing undesirable color changes, odors, and / or reduced efficacy in the product. In some cases, formulating compositions at a lower pH can help stabilize HCA, but it also reduces its solubility. Due to its potential use as a multifunctional skin active, there is much interest in overcoming HCA's formulation and stability issues.

[0004] To increase the solubility of HCA, some formulators use additional solvents such as glycols, as described in, for example, U.S. Patent No. 9,072,919. However, this approach can have undesirable tradeoffs on the sensory profile of the composition. In particular, because glycols are generally not drying and are not quickly absorbed by the skin, high levels of glycols can impart an undesirable oily feel to skin care compositions. Other attempts to address the solubility of hydroxycinnamic acids include incorporating the material into the oil phase of the composition (i.e., in the case of emulsions) or encapsulating the material. However, these approaches can also be problematic. For example, adding hydroxycinnamic acids to the oil phase can undesirably affect the sensory profile of the composition due to the introduction of oil and additional emulsifiers into the composition, and encapsulation can reduce the amount of hydroxycinnamic acid in the composition due to encapsulation load limitations. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2018 / 081790 [Patent Document 2] U.S. Patent No. 9,072,919 Summary of the Invention [Problem to be solved by the invention]

[0006] Thus, there remains a need to provide methods that provide improved benefits, particularly improved skin appearance, by using aqueous compositions containing hydroxycinnamic acids. [Means for solving the problem]

[0007] Disclosed herein is a method for improving the appearance of skin, comprising identifying a target area of ​​skin where treatment is desired and applying a low pH aqueous skin care composition to the target area of ​​skin for a treatment period. The composition contains a vitamin B3 compound, hydroxycinnamic acid (HCA), and water, and has a pH of less than 5.0. [Brief explanation of the drawings]

[0008] [Figure 1A] HPLC reference spectra of HCA and 4-VP are shown, respectively. [Figure 1B] HPLC reference spectra of HCA and 4-VP are shown, respectively. [Figure 2] The aqueous solubility of HCA across a range of pH values ​​is shown. HCA solubility was predicted using Chemicalize (CAS#501-98-4, 7400-08-0), November 2021, https: / / chemicalize.com / , developed by ChemAxon. DETAILED DESCRIPTION OF THE INVENTION

[0009] Hydroxycinnamic acid such as coumaric acid is known to be a good antioxidant, and is commonly used in skin care compositions.Surprisingly, it has recently been discovered that the low pH skin care composition that contains HCA and niacinamide can synergistically improve skin appearance, especially the skin that looks pale and skin texture and / or skin stability.Improvement of skin stability means reducing the daily fluctuation of skin condition.

[0010] Additionally, in preferred embodiments, it is desirable to improve the HCA solubility and / or stability in such compositions in order to deliver further improved synergistic skin appearance benefits.

[0011] References herein to "embodiments" or "combinations" 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 in multiple embodiments, but do not mean that all embodiments incorporate the described material, feature, structure, and / or characteristic. Furthermore, 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. Accordingly, the embodiments and aspects described herein can include or be combined with elements or components of other embodiments and / or aspects, even if not explicitly illustrated in combination, unless otherwise stated or unless incompatibility is explicitly stated.

[0012] In all embodiments, unless otherwise specified, all percentages are by weight of the cosmetic composition. Unless otherwise specified, all ratios are by weight. All ranges are inclusive and combinable. The number of significant digits does not represent a limitation on the stated amount or on the precision of the measurements. Unless otherwise specified, all quantities are understood to be modified by the word "about." Unless otherwise specified, all measurements are understood to be made at ambient conditions of approximately 25°C, where "ambient conditions" means conditions of about 1 atmosphere and about 50% relative humidity. All numerical ranges are inclusive of smaller ranges. Delimited upper and lower range limits are interchangeable to create additional ranges not expressly delimited.

[0013] 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 include additional ingredients, but only if the additional ingredients 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 as well, unless the context clearly dictates otherwise.

[0014] definition "About" modifies a particular value by referring to a range equal to plus or minus 20 percent (±20%) or less (e.g., less than 15%, 10%, or even less than 5%) of the stated value.

[0015] "Applying" or "application" as used in reference to a composition means applying or spreading a composition of the present invention onto the surface of human skin, such as the epidermis.

[0016] "Cosmetic agent" means any substance and any components thereof intended to be rubbed, poured, sprinkled, sprayed, introduced, or otherwise applied to the mammalian body or any part thereof to produce a cosmetic effect. Cosmetic agents can include substances generally recognized as safe (GRAS) by the U.S. Food and Drug Administration, food additives, and materials used in non-cosmetic consumer products such as over-the-counter drugs.

[0017] "Effective amount" refers to an amount of a compound or composition sufficient to significantly induce a positive effect on keratinous tissue over the course of a treatment period. The positive effect can be an effect on health, appearance, and / or feel, including the effects disclosed herein, independently or in combination. In a specific example, an effective amount of a vitamin B3 compound is an amount sufficient to improve the health and / or appearance of psoriatic skin over the treatment period. In some examples, an effective amount can be demonstrated using ex vivo and / or in vitro methods.

[0018] "Hydroxycinnamic acids" (HCAs) refer to a class of aromatic acids or phenylpropanoids with a C6-C3 skeleton that are hydroxy derivatives of cinnamic acid. Some non-limiting examples of HCAs are caffeic acid, chicoric acid, cinnamic acid, chlorogenic acid, diferulic acid, coumaric acid (p-, o-, and m-), ferulic acid, sinapic acid, sinapic acid, and α-cyano-4-hydroxycinnamic acid.

[0019] "Improving the appearance of" means providing a measurable desired change or effect in the appearance of skin, which can be quantified, for example, by a reduction in redness, inflammation, and / or scaling of spots.

[0020] "Low pH" means a pH below 5.0 (e.g., 1.5 to 4.9, 2.0 to 4.5, 2.5 to 4.0, or 3.5 to 4.0). Suitable methods for determining the pH of a composition are described in more detail below.

[0021] "Neutral pH" means a pH between 5.0 and 8.0.

[0022] By "safe and effective amount" is meant an effective amount of an ingredient that is low enough (within the scope of sound medical judgment) to avoid serious side effects.

[0023] "Skin care" means controlling and / or improving skin condition. Some non-limiting examples include improving the appearance and / or feel of skin by providing a smoother, more uniform appearance and / or feel, increasing the thickness of one or more layers of skin, improving the elasticity or resilience of skin, improving skin firmness, as well as reducing the oily, shiny, and / or dull appearance of skin, improving skin hydration or moisturization, improving the appearance of fine lines and / or wrinkles, improving skin exfoliation or scaling, plumping skin, improving skin barrier properties, improving skin tone, reducing the appearance of redness or skin blemishes, and / or improving skin brightness, radiance, or clarity.

[0024] "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, skin hydration, skin barrier function, and / or cellular metabolism).

[0025] "Skin care composition" means a composition that contains skin care actives and that regulates and / or improves the condition of the skin.

[0026] As used herein, "treatment period" refers to the length of time and / or frequency that a material or composition is applied to a target skin surface.

[0027] composition The skin care compositions described herein are intended to be topically applied to human skin to improve the appearance, health, and / or function of the skin.The compositions can be used for non-therapeutic (i.e., cosmetic) treatment of various skin conditions.For example, low pH compositions can be particularly suitable for improving skin appearance, especially for skin that appears pale and for improving skin texture and / or skin stability.

[0028] The low pH skin care compositions herein comprise a safe and effective amount of a hydroxycinnamic acid (e.g., p-coumaric acid, also known as 4-HCA or p-HCA), a vitamin B3 compound, and optionally a hydrotrope. The combination of HCA and vitamin B3 compound is specifically tailored to provide synergistic improvements in skin appearance. In some embodiments, the compositions may also include silicone emulsifiers, polymeric thickeners that can tolerate low pH environments, low molecular weight silicone fluids, acid salt pH buffer systems (e.g., lactic acid / sodium lactate buffer systems), and / or other ingredients commonly found in topical skin care compositions. Without being bound by theory, it is believed that the combination of ingredients disclosed herein provides stable and effective skin care compositions that have good feel properties and are gentle on the skin.

[0029] Preferably, the low pH composition used in the method herein is formulated to improve HCA solubility in a low pH environment. In aqueous low pH skin care compositions, HCA tends to precipitate from the composition and form crystals ("HCA crystals"), which can undesirably affect the appearance, feel, and / or efficacy of the composition. Conventional low pH compositions often contain HCA crystals. However, in a preferred embodiment of the present invention, the low pH composition herein does not contain HCA crystals because it contains a hydrotrope specifically selected to aid in the solubilization of HCA and inhibit HCA crystallization. Suitable methods for determining whether a composition does not contain HCA crystals and / or for characterizing HCA crystals in a composition are described in more detail below.

[0030] Preferably, the low pH compositions herein are also formulated to improve HCA stability.HCA is a relatively good antioxidant, but it tends to oxidize and / or decompose over time, which may result in skin care compositions showing undesirable color changes (e.g., yellowing), undesirable odors, and / or reduced efficacy.Formulating at a lower pH can improve HCA stability by reducing the rate at which HCA oxidizes, but in some embodiments, it may be desirable to include an antioxidant in the low pH composition to help further reduce HCA oxidation and / or decomposition.

[0031] The low pH skin care composition herein can be prepared by mixing ingredients with dermatologically acceptable carriers using conventional methods known to those skilled in the art.The composition can be provided in various product forms, such as solution, suspension, lotion, cream, gel, toner, stick, spray, aerosol, ointment, cleansing liquid and solid bar, paste, foam, mousse, shaving cream, wipe, strip, patch, electric patch, hydrogel, film-forming product, facial and skin mask (with or without insoluble sheet).The form of the composition can be according to the specific dermatologically acceptable carrier selected.

[0032] In some cases, the low pH skin care compositions herein may be in the form of an essence. Essences are topical skin care compositions with relatively thick formulations, typically with lower viscosities than conventional cream or lotion-type skin care compositions. Essences may be provided in the form of low-viscosity fluids marketed to specifically target specific skin conditions and / or used as the first step in a skin care regimen. Skin care essence products herein may have a kinematic viscosity of 1 centipoise (cP) to 15,000 cP (e.g., 50 cP to 10,000 cP, or 100 cP to 7,500 cP, 200 cP to 5,000 cP, or 300 cP to 2,500 cP) at 25°C. Methods for determining the viscosity of low pH compositions are described in more detail in the Methods section below.

[0033] Hydroxycinnamic acid The low pH skin care compositions herein contain a safe and effective amount of HCA. HCA may be present in the composition at 0.1% to 10% (e.g., 0.5% to 5% or 1% to 4%). Hydroxycinnamic acids are generally recognized as antioxidant phenolic compounds and can be found in plants, primarily as components of cell walls. See HK Kuzaki et al., J. Agric. Food Chem., 50, 2161-68 (2002). In some embodiments, it may be desirable to select coumaric acid, particularly p-coumaric acid (also known as 4-HCA), for use in low pH compositions. p-Coumaric acid has the following structure:

[0034] [ka]

[0035] In other embodiments, it may be desirable to use a mixture of two or more HCAs, such as a mixture of coumaric acid and ferulic acid. In these embodiments, the coumaric acid and ferulic acid may be present in a weight ratio of 2:1 to 1:2 (e.g., 1:1). A particularly suitable example of an HCA material suitable for use herein is LIPOBRITE, available from Vantage Personal Care.

[0036] Vitamin B3 compounds The composition comprises 0.1% to 10% (e.g., 0.5% to 5% or 1% to 4%) of a vitamin B3 compound. As used herein, a "vitamin B3 compound" refers to a compound having the formula:

[0037] [ka] During the ceremony, The term "vitamin B3 compounds" refers to compounds in which R is CONH2 (i.e., niacinamide), COOH (i.e., nicotinic acid), or CH2OH (i.e., nicotinyl alcohol), their derivatives, and salts of any of the foregoing. Exemplary derivatives of vitamin B3 compounds include non-vasodilatory esters of nicotinic acid (e.g., tocopheryl nicotinate, myristyl nicotinate), nicotinamide riboside, nicotinyl amino acids, nicotinyl alcohol esters of carboxylic acids, nicotinic acid N-oxide, and nicotinamide N-oxide, among others. In some cases, vitamin B3 compounds such as niacinamide may have improved efficacy at relatively low pH, as described, for example, in U.S. Patent Application Publication No. 2020 / 0009123.

[0038] In some cases, it may be desirable for the ring nitrogen of the vitamin B3 compound to be "uncomplexed" (e.g., chemically unbound and / or unhindered) in the composition and / or prior to application to the target skin surface. For example, the compositions herein may be free or substantially free (i.e., less than 3%, 2%, 1%, or even less than 0.5%) of salts or complexes of the vitamin B3 compound. Exemplary methods for minimizing or preventing the formation of undesirable salts and / or complexes include removing substances that form substantially irreversible or other undesirable complexes with the vitamin B3 compound in the composition, adjusting pH, adjusting ionic strength, using surfactants, and implementing a formulation process in which the vitamin B3 compound and substances that complex with it are in different phases.

[0039] Hydrotrope HCA compounds generally exhibit particularly low solubility in low pH aqueous compositions, such as the low pH compositions described herein. For example, p-coumaric acid has a solubility of approximately 345 mg / mL in water at pH 7.0 and 20°C, and a solubility of 4 mg / mL in water at pH 3.0 and 20°C. Without being bound by theory, the decreased solubility of HCA at lower pH is believed to be due to a decreased ability of HCA to undergo acid dissociation to form the conjugate base species observed at higher pH levels. At pH 7, approximately 99.6% of coumaric acid exists in its conjugate base form, while at pH 3, only approximately 13.4% exists in the conjugate base form. As a result of this relatively low solubility, HCA tends to form crystals in aqueous low pH skin care compositions. HCA crystals may impart an undesirable feel to the composition during use (e.g., a rough or grainy feel) and / or reduce the effectiveness of HCA and / or other ingredients in the composition. This may lead to an undesirable consumer perception of poor product quality.

[0040] The compositions herein may contain 0.1% to 10% (e.g., 0.5% to 5% or 1% to 3%) of a hydrotrope to enhance the aqueous solubility of HCA. In some embodiments, the hydrotrope may be a phenolic acid (e.g., salicylic acid) or a salt thereof (e.g., sodium salicylate). If the hydrotrope contains a conjugate base of a phenolic acid, the hydrotrope must have a pKa below the formulation pH and sufficient intrinsic water solubility at the formulation pH to be completely dissolved. Because the solubility of HCA is low at low pH, having an acidic pKa below the pH of the composition may be particularly important for low pH compositions. For example, sodium salicylate, with a pKa of 2.8, would be a suitable hydrotrope for use in a composition with a pH of 3.8, since the bound carboxylic acid will exist primarily in the conjugate base form. In contrast, sodium cinnamate, with an acidic pKa of 4.32, would not be an effective hydrotrope in this example. Furthermore, the hydrotrope should be selected to help improve the sensory appeal of the composition by reducing the need for other solubilizers, such as glycols. Some non-limiting examples of hydrotropes that may be suitable for use herein are salicylic acid, 2,4-dihydroxybenzoic acid, 2,3-dihydroxybenzoic acid, 3-methoxysalicylic acid, salts thereof, or combinations thereof. Other non-limiting examples of hydrotropes that may be suitable for use herein are disclosed in WO 2018 / 081790.

[0041] antioxidants The low pH compositions herein may also include an antioxidant to combat oxidation and / or degradation of HCA. When included, the antioxidant may be present at 0.001% to 3% (e.g., 0.01% to 2%, 0.05% to 1%, or 0.1% to 0.5%). Some non-limiting examples of antioxidants that may be suitable for use herein are sodium sulfite, sodium bisulfite, sodium metabisulfite, and butylated hydroxytoluene.

[0042] Low pH acid buffer system When providing a low pH composition for topical application to the skin, it may be important to include a buffer system to help maintain the pH of the composition for a period of time (e.g., up to 5 minutes or more) after application to the skin. On average, the pH of human skin typically ranges from about 5.0 to 6.0. To maintain this pH, human skin has evolved a natural buffer system that resists pH changes. Thus, when a low pH composition is applied to the skin, the skin's natural buffer system attempts to adjust the pH of the composition to match the skin's natural pH. Low pH compositions may not provide the desired skin care benefits without the addition of a buffering agent. Therefore, the compositions herein may include a low pH acid buffer system.

[0043] The buffering agent may be selected depending on the acid used to lower the pH of the low pH compositions herein. For example, lactic acid and gluconic acid are generally considered gentler on the skin (i.e., less likely to cause irritation) compared to other alpha hydroxy acids, and therefore may be used to lower the pH of the composition. In this example, sodium lactate or sodium gluconate would be selected to provide an acid / salt pH buffer system. The salt buffer may be present in the low pH composition at 0.25% to 4% (e.g., 0.5% to 3%, 0.75% to 2%, or 1% to 1.75%). Non-limiting examples of low pH buffer systems suitable for use herein are disclosed in co-pending U.S. patent application Ser. No. 16 / 891,491. Of course, it should be understood that the present compositions may optionally contain other pH buffers known for use in skin care compositions.

[0044] thickener The composition includes a polymeric thickener that can withstand low pH electrolytic environments. That is, the thickener does not lose its ability to thicken or stabilize compositions at low pH in the presence of an acid-salt buffer system. Some conventional neutralized thickeners are known to deteriorate and / or lose their ability to adequately thicken compositions at lower pH and / or in the presence of acid salt buffers (e.g., sodium lactate). For example, some neutralized thickeners decompose in low pH environments. On the other hand, fatty alcohol thickeners, such as cetyl alcohol and stearyl alcohol, are generally stable at low pH, but tend to impart undesirable haze or opacity to compositions in the form of essences, serums, and the like. Certain anionic polymeric thickeners can provide suitable resistance to low pH environments, but have also been found to be unable to withstand buffer systems due to the combination of acid and salt. Therefore, in some cases, the low pH compositions described herein may be free or substantially free of neutralized thickeners, fatty alcohol thickeners, and anionic thickeners. The thickener may be present at 0.0001% to 25% by weight of the composition (e.g., 0.001% to 20%, 0.01% to 10%, 0.5% to 7%, or 1% or 5%).

[0045] Other non-limiting examples of thickeners or water structurants that can be used herein, alone or in combination, include natural or synthetic rubbers, polysaccharides, carboxylic acid polymers, polyacrylamide polymers, sulfonated polymers, and copolymers thereof. Further examples include modified gums, cellulose, and superabsorbent polymers. The term "superabsorbent polymer" is understood to mean a polymer that, in a dry state, can spontaneously absorb at least 20 times its own weight in aqueous fluids, specifically water, especially distilled water. Suitable polysaccharides include alkylhydroxyalkylcellulose ethers, such as hydroxypropylmethylcellulose stearoxy ether. This material is sold by Daido Chemical Corp. under the trade names SANGELOSE 60L and 90L. Another suitable polysaccharide is hydrophobically modified starch, such as modified potato starch. This material is sold by Nouryon under the trade name STRUCTURE SOLANACE. Other polymers include crosslinked polymers where the monomers are at least partially composed of acryloyldimethyltaurate monomers, such as sodium polyacryloyldimethyltaurate, sold, for example, under the trade name ARISTOFLEX SILK by Clariant.

[0046] It has been found that certain anionic polymer thickeners can provide compositions with suitable resistance to low pH environments, as well as desirable feel and opacity. Thus, a particularly suitable example of an anionic thickener is polyacrylate crosspolymer-6, commercially available as SEPIMAX ZEN from Seppic, France.

[0047] Low molecular weight silicone fluid. In some cases, anionic polymer thickeners can impart an undesirable sticky feeling when the low pH composition is applied to the target area of ​​the skin. It has been found that the addition of a low molecular weight silicone fluid can reduce or prevent this sticky feeling. The molecular weight of the silicone fluid depends on the length of its silicone polymer chain, which is also directly proportional to the viscosity of the silicone fluid. Thus, low molecular weight silicone fluids suitable for use in the present low pH compositions have a kinematic viscosity of 100 cSt or less (e.g., 1 cSt to 90 cSt, 5 cSt to 50 cSt, or even 10 cSt to 30 cSt) at 25°C. Kinematic viscosity is a common way of classifying silicone fluids and can be obtained from material suppliers. A particularly suitable example of a low molecular weight silicone fluid is 5 cSt dimethicone fluid. As used herein, "dimethicone" refers to a silicone fluid having the formula

[0048] [ka] means a compound having the formula:

[0049] Dermatologically acceptable carrier The low pH compositions herein may 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 active agents in the composition, and does not raise any undue safety or toxicity concerns. In one embodiment, the carrier is present in a concentration 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 of the composition.

[0050] The carrier may be in a wide variety of forms. In some cases, the form and characteristics of the carrier may be determined by the solubility or dispersibility of the components (e.g., extracts, sunscreen actives, additional ingredients). 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. Emulsions 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 ingredients (e.g., water-soluble moisturizers, conditioning agents, antibacterial agents, humectants, and / or other skin care actives). However, in some cases, the aqueous phase may include 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-water components of the composition include humectants, such as glycerin and / or other polyol(s).

[0051] In some cases, the compositions herein are in the form of oil-in-water ("O / W") emulsions, which provide a light, non-greasy sensory feel. Suitable O / W emulsions herein may comprise greater than 50% by weight of the composition as a continuous aqueous phase, with the remainder being a dispersed oil phase. The aqueous phase may comprise 1% to 99% water, based on the weight of the aqueous 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 oily 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.

[0052] The carrier may contain one or more dermatologically acceptable hydrophilic diluents. As used herein, "diluent" refers to a material capable of dispersing, dissolving, or otherwise incorporating a vitamin B3 compound. 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.

[0053] emulsifier When the low pH compositions herein are in the form of an emulsion (e.g., an oil-in-water emulsion), it may be desirable to include an emulsifier to stabilize the emulsion (i.e., prevent the emulsion from phase separating). The emulsifier may be present in the composition at 0.01% to 10% (e.g., 0.05% to 5%, or 0.1% to 2%). The emulsifier may be nonionic, anionic, or cationic. In some cases, the emulsifier may be a silicone emulsifier. Some non-limiting examples of emulsifiers that may be suitable for use herein are disclosed in U.S. Pat. Nos. 3,755,560 and 4,421,769, and McCutcheon's Detergents and Emulsifiers, North American Edition, pp. 317-324 (1986).

[0054] Some other non-limiting examples of emulsifiers that may be suitable for use herein include ethers of polyglycols and ethers of fatty alcohols, esters of polyglycols and esters of fatty acids, ethers of polyglycols and ethers of glycosylated fatty alcohols, esters of polyglycols and esters of glycosylated fatty acids, ethers of C12-30 alcohols and ethers of glycerol or polyglycerol, esters of C12-30 fatty acids and esters of glycerol or polyglycerol, ethers of oxyalkylene-modified C12-30 alcohols and ethers of glycerol or polyglycerol, ethers of C1-230 fatty alcohols including sucrose or glucose, ethers of sucrose or ethers of glucose, esters of sucrose and esters of C1230 fatty acids, esters of pentaerythritol and esters of C12-30 fatty acids, esters of sorbitol and / or esters of sorbitan and C12 Examples of emulsifiers include esters of C12-30 fatty acids, ethers of sorbitol and / or ethers of sorbitan and ethers of alkoxylated sorbitan, ethers of polyglycols and ethers of cholesterol, esters of C12-30 fatty acids, and alkoxylated ethers of sorbitol and / or sorbitan, and combinations thereof. A particularly useful class of emulsifiers are polyethylene glycol ethers of lauryl alcohol, such as laureth-1 through laureth-50 (e.g., laureth-4). Further examples of emulsifiers include ethers of glycerol, polyglycerol, sucrose, glucose, or sorbitol; esters of glycerol, polyglycerol, sucrose, glucose, or sorbitol; and mixtures thereof. Another particularly useful class of emulsifiers are alkyl esters of sorbitol and sorbitol anhydrides, such as polysorbate 20, polysorbate 21, and polysorbate 40.

[0055] In some embodiments, it may be desirable to include linear or branched silicone emulsifier in low pH composition.Particularly useful silicone emulsifiers include polyether-modified silicones such as KF-6011, KF-6012, KF-6013, KF-6015, KF-6015, KF-6017, KF-6043, KF-6028 and KF-6038, and polyglycerol-modified linear or branched siloxane emulsifiers such as KF-6100, KF-6104 and KF-6105 (all manufactured by Shin-Etsu Co., Ltd.).The emulsifier particularly suitable for use herein is PEG-11 methyl ether dimethicone, sold by Shin-Etsu Co., Ltd. as KF-6011. Surprisingly, it has been found that PEG-11 methyl ether dimethicone emulsifiers improve the overall feel of low pH compositions by further reducing the sticky feel of anionic polymer thickeners. The emulsifiers may be present in an amount of 0.1% to 10% (e.g., 1% to 5%, or 2% to 4%).

[0056] Co-solvent In some embodiments, the compositions herein may contain a short-chain dihydric alcohol (e.g., glycol) cosolvent to aid in the solubilization of HCA. However, if a glycol is selected as the cosolvent, it may be important to limit the amount of glycol to less than 25% (e.g., less than 20%, less than 17%, less than 15%, or even less than 10%) to reduce the risk of imparting undesirable sensory properties (e.g., sticky or greasy) to the composition. Some non-limiting examples of glycols that may be suitable for use herein are propylene glycol, dipropylene glycol, butylene glycol, pentylene glycol, hexylene glycol, ethoxydiglycol, and C2-C6 polyethene glycols (e.g., PEG-3, PEG-4, PEG-4 methyl ether), and combinations thereof.

[0057] Other optional ingredients The present compositions may optionally contain one or more additional ingredients commonly used in cosmetic compositions (e.g., colorants, skin care actives, anti-inflammatory agents, sunscreens, emulsifiers, buffers, rheology modifiers, combinations thereof, etc.), provided that the additional ingredients do not undesirably alter the skin health or appearance benefits provided by the present compositions. If incorporated into the compositions, the additional ingredients should be suitable for use in contact with human skin tissue without undue toxicity, incompatibility, instability, allergic reaction, etc. Some non-limiting examples of additional actives 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, sunless tanning agents, lubricants, anti-acne actives, anti-cellulite actives, chelating agents, anti-wrinkle actives, anti-atrophy actives, phytosterols and / or plant hormones, N-acyl amino acid compounds, antibacterial agents, and antifungal agents. Other non-limiting examples of additional 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 / 00092408, 2008 / 0206373, 2010 / 0239510, 2010 / 0189669, 2010 / 019634 ... Nos. 010 / 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.

[0058] When including optional ingredients in the compositions herein, it may be desirable to select ingredients that do not complex or otherwise interact undesirably with other ingredients in the composition at low pH, particularly pH-sensitive ingredients such as niacinamide, salicylates, and peptides. In some cases, it may be desirable to select skin care actives that function via different biological pathways so that the actives do not interfere with each other, which could reduce the effectiveness of both agents. When present, optional ingredients may be included in amounts of 0.0001% to 50%, 0.001% to 20%, or even 0.01% to 10% (e.g., 50%, 40%, 30%, 20%, 10%, 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.1%) by weight of the composition.

[0059] How to use The low pH cosmetic compositions herein are formulated for topical application to the skin. Methods for using the low pH compositions of the present invention include identifying a target area of ​​skin on a person in need of treatment or where treatment is desired (e.g., paleness, hyperpigmented spots, enlarged pores, or uneven skin color or texture) and applying an effective amount of the low pH composition to the target area of ​​skin for a treatment period. The effective amount of the composition can vary based on the skin effect desired by the user and / or the size of the treatment area. In some cases, the effective amount can range from 0.1 g to 5 g (e.g., 0.2 g to 4 g, 0.3 g to 2 g, or even 0.5 g to 1 g). The target area of ​​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). In some cases, the target area of ​​skin may be selected to be an area of ​​skin that does not currently show signs of cutaneous aging but will commonly exhibit such characteristics with age. In these cases, low pH compositions can be used to prevent the development of such undesirable skin characteristics.

[0060] The composition can be topically applied to the target area of ​​skin requiring treatment and, if necessary, to surrounding skin at least once daily, twice daily, or more frequently than daily during the treatment period. If applied twice daily, the first and second applications are separated by at least 1 to 12 hours. The composition is typically applied in the morning and / or at night before bedtime. When used in accordance with the methods herein, the composition can improve the appearance and / or function of skin, for example, by improving skin texture. Improvement in skin texture may be achieved, for example, by reducing pore size, reducing roughness, reducing the presence and / or size of wrinkles, or a combination thereof.

[0061] The treatment period is ideally long enough for the low pH composition to improve the appearance and / or function of the target area of ​​skin. The treatment period typically lasts for at least one week (e.g., about two, four, eight, or even twelve weeks). In some cases, the treatment period may extend for multiple months (i.e., three to twelve months). In some cases, the composition is applied at least once a day, or even twice a day, on the majority of days of the week (e.g., at least four, five, or six days a week) during a treatment period of at least two, four, eight, or twelve weeks.

[0062] The step of applying the composition herein can be performed by topical application. With respect to the application of a composition, the terms "topical," "topical," or "topically" mean that the composition is delivered to a target area (e.g., a psoriasis plaque) while minimizing delivery to skin surfaces where treatment is not desired. The composition can be applied to a skin area and gently massaged in. The form of the composition or dermatologically acceptable carrier should be selected to facilitate topical application. While certain embodiments herein contemplate applying the composition to a region topically, it will be understood that the compositions herein can also be applied systemically or broadly to one or more skin surfaces. In certain embodiments, the compositions herein can be used as part of a multi-step cosmetic regimen, in which case the composition can be applied before and / or after one or more other compositions.

[0063] method HPLC This method provides a method for determining the weight percent of HCA and 4-vinylphenol (4-VP), respectively, in raw materials or final products using high performance liquid chromatography ("HPLC"). This method can also be used to identify HCA and / or 4VP by matching their wavelength spectra and retention times to their respective known standards. The following equipment and materials are used in this method:

[0064] device: A gradient HPLC system including a gradient HPLC pump, a liquid autosampler, a UV detector (and a diode array detector (DAD) for spectral analysis), and a suitable computing integrator or computer data system (e.g., a Waters 2695 HPLC system or equivalent from Waters Corporation). · 5um, 250mm x 4.6mm ID HPLC column (e.g., C18 column from Alltech Alltima).

[0065] method: Two mobile phases are used to create a gradient at a consistent flow rate of 1.0 mL / min. Mobile phase A consists of 0.5% acetic acid in purified water. Mobile phase B consists of 0.5% acetic acid in acetonitrile. The gradient is shown in Table 1 below.

[0066] [Table 1]

[0067] Calculation: 1. Calculation of the weight percent of HCA in the test sample

[0068]

number

[0069]

number

[0070] Crystallization of HCA This method provides a method for determining the solubility of HCA in a composition by observing HCA crystals in situ. This method involves cycling the temperature of a test sample between freezing and thawing to simulate the environmental conditions experienced by skin care compositions at an accelerated rate. This type of accelerated deterioration is commonly used in cosmetic stability testing. HCA crystals can be detected using conventional means, such as visual observation and microscopic examination.

[0071] A bulk sample of at least 10 g (e.g., 20 g to 60 g) of the composition to be tested is placed in a suitable container (e.g., a clear plastic or glass jar) that allows for visual observation of the test sample. The test sample is subjected to a one-month freeze / thaw temperature cycle to simulate the environmental conditions that a skin care product may experience during shipping and storage. This is sometimes referred to as accelerated aging. The temperature cycle involves a one-week freeze cycle at -7°C, followed by a one-week thaw cycle at 25°C, and then repeating this freeze / thaw cycle for a total temperature cycle period of one month.

[0072] Upon completion of the accelerated aging process (i.e., one-month temperature cycling), the transparent test samples are visually inspected in situ in their transparent containers to determine whether HCA crystallization / precipitation has occurred. For opaque and translucent samples, the entire test sample is removed from the container, transferred to a suitable transparent substrate (e.g., plastic film or glass plate), and formed into a thin film no thicker than 1 mm. To prevent loss of volatile components during inspection, the sample is covered with a second transparent substrate. To aid in visual inspection, a light source (e.g., an LED lamp) is used to illuminate the sample from behind. HCA crystals generally appear as precipitates in the composition that are visible to the naked eye when viewed from 45 cm away by a person with 20 / 20 vision. To identify anisotropic crystals, any precipitates identified during visual observation may be further evaluated using a microscope capable of providing fluorescence birefringence observation with cross-polarized light. Any anisotropic crystals with a longest dimension greater than 0.1 mm are identified as HCA crystals, and the total number of HCA crystals is recorded. Test samples containing one or less HCA crystal are considered "HCA crystal free" and recorded as a "pass." Test samples containing more than one HCA crystal are recorded as a "fail."

[0073] Although not required, Fourier transform infrared spectroscopy (FTIR) can be used to confirm that HCA crystal or co-crystal contains the appropriate hydroxycinnamic acid structure.FTIR spectroscopy is well known in the art.See U.S. Patent No. 10,912,857, U.S. Patent Application Publication No. 2020 / 0000697, and Fourier Transform Infrared Spectroscopy in Colloid and Interface Science, D.R. Cheuing, Ed., American Chemical Society, 225, 1991.

[0074] color This method can be used to determine the color change of a product, material, or substrate. A spectrophotometer (e.g., Spectrophotometer CM-3600A, Konica Minolta, Japan, or equivalent) is used to measure spectral data under lighting and viewing conditions specified by the CIE (International Commission on Illumination), and the associated tristimulus values ​​X, Y, and Z are calculated based on the CIE observer and CIE illuminant standard. The ASTM standard for obtaining spectral data to evaluate the color of an object is ASTM E1164-12(2017)e1, and the values ​​and procedures for calculating CIE tristimulus values ​​from spectral data are outlined in ASTM E308. * a * b * The CIELAB color scale, also known as the L scale, is calculated from tristimulus values ​​defined in ASTM E308. * indicates the perceived lightness of the sample, while a * and b * is related to the inherent color of human vision, and a * is positive in the red direction and negative in the green direction, and b * is positive in the yellow direction and negative in the blue direction.

[0075] The spectrophotometer is operated with a 2° observer and D65 illuminant to measure tristimulus XYZ values ​​and associated CIELAB colors as defined in 1931 CIE. Aliquots are evaluated using a 10 mm optical path length, reflectance measurements, a 25.4 mm aperture at the specimen surface, and a standard white background with no specular component. Acceptable white backgrounds include the white portion of an opaque card or equivalent (e.g., opaque card type 2A, Leneta Company, Inc., Mahwah, NJ). A dust- and debris-free zero calibration box or black trap (e.g., Konica Minolta zero calibration box CM-A155 or equivalent) is used to calibrate the instrument with a zero standard. CIELAB values ​​are reported by the associated instrument software (e.g., SpectroMagic NX) as defined in ASTM E308. Product yellowness shift is measured using a 10 mm optical path length, reflectance measurements, a 25.4 mm aperture at the specimen surface, and a standard white background. Acceptable white backgrounds include the white portion of an opaque card or equivalent (e.g., opaque card type 2A, Leneta Company, Inc., Mahwah, NJ). A dust- and debris-free zero calibration box or black trap (e.g., Konica Minolta zero calibration box CM-A155 or equivalent) is used to calibrate the instrument with a zero standard. CIELAB values ​​are reported by the associated instrument software (e.g., SpectroMagic NX) as defined in ASTM E308. The yellowness shift of the product is measured using a 10 mm optical path length, reflectance measurements, a 25.4 mm aperture at the specimen surface, and a standard white background.* We use the CIELAB color scale to highlight the change in values. * and reported as positive Δb * indicates an increase in yellowness.

[0076] Rheology This method provides a method for measuring the kinematic viscosity of a composition or material using a BROOKFIELD brand viscometer (such as Model DV2T or equivalent) and a suitable spindle (such as RV4 or equivalent) according to the manufacturer's instructions. It should be understood that one skilled in the art can select an appropriate spindle according to the manufacturer's recommendations. After calibrating the viscometer, immerse the spindle in a sufficient volume of test sample (e.g., enough to dip the spindle up to the dip mark on the spindle shaft). Set the spindle rotation speed to 5 rpm and start the viscometer. Wait until the displayed viscosity reading stabilizes (approximately 10-30 seconds). Once the reading stabilizes, take five readings at 10-second intervals. Calculate the viscosity as the average of the five readings.

[0077] Skin stability measurement method Skin appearance stability was measured using eMR Pro, a self-diagnostic facial imaging system developed by P&G Company (Kobe, Japan) (IP Application Serial No. AA1280) and further described in "Daily fluctuation of facial pore area, roughness, and redness among young Japanese women; Beneficial effects of Galactomyces ferment filtrate containing antioxidant skin care formula" by Miyamoto, Kukizo, et al., Journal of Clinical Medicine 10.11 (2021):2502. This method utilizes a commercially available smartphone camera / LED illumination source (iPhone 7 / 8 / SE) with a plastic attachment placed on the cheek area of ​​the face. The attachment is attached to control the intensity of the LED light illuminating the skin surface. Additionally, a color chip is present for image standardization of each image. A small repositionable mirror and an automatic eye / face live view recognition algorithm are incorporated into the eMR application program. The captured images (1080 x 1920 pixels) are encrypted and then analyzed after the target area is masked, aligned, and color standardized. This device allows panelists to perform the imaging themselves at home, increasing the number of measurements. A plastic face attachment ensures a constant distance between the camera head and the skin surface. As described in the following sections, pores, blemishes, and wrinkles can be detected. * , a * , b * Image analysis methods are performed to measure skin characteristics such as color, etc., and uneven appearance.

[0078] The method used to define uneven appearance utilizes entropy statistics and is described in U.S. Patent No. 11348366(B2). As used herein, the term entropy refers to the Shannon entropy (E) of a discrete random distribution (p(x)), which is defined by the following formula:

[0079]

number

[0080] In a non-limiting example where the digital image is an RGB image, the entropy (entropy value) for each R (red), G (green), and B (blue) channel can be calculated separately. The entropy value of the image can be calculated at each pixel location (i,j) by calculating the entropy value of the pixel values ​​within a two-dimensional region centered at (i,j). The two-dimensional region may be a portion of the color channel image. The entropy value can be calculated using a programming software package such as Python. The color channels can be analyzed separately to isolate distinct tonal and texture inhomogeneities. Once an image is acquired with red, green, and blue color channels, it can be compiled into a L2 file for further descriptive analysis. * a * b * The red color channel is L * a * b * When in a color system, a entropy is the entropy value of the filtered red color channel. When the yellow color channel is L * a * b * When in a color system, the b entropy is the entropy value of the filtered yellow color channel. When the blue color channel corresponds to the texture channel, the c entropy is the entropy value of the blue color channel.

[0081] The measure of variability for characterizing skin stability from the acquired time series data used to characterize skin stability is the mean absolute difference for a given measured endpoint.

[0082]

number

[0083]

number

[0084] Each measurement is carried out at different and consistent time points throughout the day.In the described embodiment, measurement set is the morning before washing face, the morning after washing face, and the night after washing face.Then, by using the mean absolute difference formula for a certain time point (for example, the night after washing face), calculate the daily fluctuation.Can use programming software such as Python to calculate mean absolute difference. [Example]

[0085] Example 1: Formulations. Table 2 below provides examples of low pH skin care compositions corresponding to various aspects of the present invention. The compositions can be prepared using conventional methods for manufacturing skin care compositions. Such methods typically involve mixing the ingredients in one or more steps to a relatively uniform state, with or without the use of heating, cooling, application of vacuum, etc. All exemplified amounts exclude minor materials such as diluents, preservatives, color solutions, feel-adjusting powders, and elastomers that may be present in commercially available products, unless otherwise specified. The HCA may be added as a solid form and solubilized in situ, dissolved in a premix, or supplied as a pre-dispersed ingredient. Certain examples use a 15% solution of 4-HCA pre-dispersed in PEG-4 (Lipobrite® from Vantage). For examples containing Lipobrite®, the component levels of 4-HCA and PEG-4 are listed individually for clarity, with superscripts indicating the Lipobrite® ingredient. The total Lipobrite® material added is the sum of the listed 4-HCA and PEG-4 components. All other materials are listed "as is" from the supplier and have not been broken down into individual components.

[0086] The emulsion is prepared by first mixing the water phase ingredients separately from the oil phase and / or silicone phase ingredients, and then combining the two phases appropriately to obtain the desired continuous layer. In some embodiments, exemplary compositions can be made by blending the water phase ingredients in a suitable mixer (e.g., IKA RW20 or equivalent) until all ingredients are dissolved and homogeneous. If present, the optional polymer thickener can be hydrated by slowly adding the thickener directly to the water phase while stirring and continuing to mix until homogeneous. 4-HCA, hydrotrope, and optional glycol can be added together in a separate premix container and mixed until completely dissolved and homogeneous. In some embodiments, the hydrotrope can be pre-neutralized to form a suitable salt (e.g., sodium salicylate) to facilitate mixing / solubilization. The HCA premix can then be added to the main mixing container and further mixed until homogeneous. The formulation may be milled using a suitable mixer (e.g., an IKA Ultra Turrax T-25 or equivalent) to reduce the emulsion particle size until the target viscosity is reached and a uniform composition is obtained. The temperature may be adjusted as needed to control the speed of the process and / or to obtain a homogeneous final product.

[0087] [Table 2]

[0088] [Table 3] 1 SEPIMAX ZEN, available from Seppic 2 ARISTOFLEX SILK available from Clariant 3 Shin-Etsu KF-6011 4 LIPOBRITE (15% 4-HCA, 85% PEG-4) manufactured by Vantage 5 Dow Corning DC 1503 6 Croda's PROMATRIXYL 7 Ferulic acid from Sigma Aldrich * Adjust pH as needed

[0089] Example 2: Δb * and synergistic reduction of skin texture. This example demonstrates the ability of the low pH composition herein to provide synergistic improvement in the appearance of pale-looking skin in clinical trials. Three independent clinical trials were conducted to investigate the beneficial skin effects provided by the compositions of the present invention. Each clinical trial was a 9-week in vivo study using a randomized, vehicle-controlled, round-robin, split-face design, including a 1-week washout period and an 8-week test period. All reported results are from the 8-week test period. The minimum base size per study was 40 subjects. The treatment regimen began with a 1-week washout period. Subjects were instructed to wash their faces with a standard cleanser (Olay Deep Cleansing Facial Cleanser, The Procter & Gamble Company) every morning and evening, gently towel dry, and apply a standard moisturizer (containing 3% glycerin) to both sides of their faces. At baseline, each subject received two coded test formulations to be applied twice daily to either the left or right side of their face. Each morning and evening, subjects washed their faces with a standard cleanser, gently towel-dried, and applied 0.5 g of the appropriate test formulation to both sides of their faces using gentle, circular pressure with their fingers. Positive and negative (vehicle) controls were used in each test. The positive control was a neutral pH composition containing 5% niacinamide and 1% undecylenoyl phenylalanine (SepiWhite from Seppic), a known skin brightener. Test Section A contained 0.9% coumaric acid (6% Lipobrite from Vantage), Test Section B was a low pH (3.8) composition containing 2% niacinamide, and Section C was a low pH composition of the present invention containing 2% niacinamide and 1% coumaric acid (6.67% Lipobrite). Test results are summarized in Tables 3 and 4.

[0090] Images of the facial treatment site were taken at baseline and at 8 weeks of treatment to assess the change in skin color (b * Decrease in value and L *Changes to facial texture (increase in saturation values) and facial texture were analyzed as described below ("Imaging Method"). Prior to image collection, participants washed their faces with a mild cleanser and then allowed to equilibrate for approximately 20 minutes before imaging. Images of the right and left sides of participants' faces were then collected using a digital camera (e.g., a Canon EOS-6D DSLR or similar) fitted with an appropriate lens for facial imaging (e.g., a 60 mm NIKKOR lens or similar) and attached to a standardized lighting and imaging system with head positioning. Suitable imaging designs are the Canfield VISIA and / or OLE imaging systems, or similar imaging systems capable of standardized and reproducible imaging. The Canfield VISIA and OLE imaging systems (Canfield Scientific, Inc., Parsippany, New Jersey, USA) are designed to capture reproducible facial images under controlled lighting and head positioning configurations in clinical research studies. Both the VISIA and OLE imaging systems incorporate a Canon EOS-6D DSLR, which uses a 21 megapixel CMOS sensor with a maximum resolution of 5472 x 3648. The VISIA and OLE imaging systems store both Exif JPEG and Canon raw image files for each captured image.

[0091] To enhance visualization of the skin features under investigation, images of the subjects were collected under various lighting modalities. Automatic flash selection and variable filter controls selected the correct combination of lighting, lighting angle, and filters optimized for enhanced imaging of facial topographical features (e.g., wrinkles, texture) or facial color features (e.g., blemishes, color tone). A live-feed image of the subject superimposed on the baseline image was used to improve reproducibility between time points. The subject was positioned so that all key landmarks on the face in the live image were precisely aligned with the same landmarks in the baseline image. Each image included a color chart with color chips of known values ​​to aid color management. Images captured with the VISIA and OLE imaging systems using Canfield Capture software were saved directly to a data drive on the imaging system computer.

[0092] In this example, the region of interest (ROI) for color and texture measurements covered the upper and lower cheeks of the subjects, but did not extend to the lower part of the eyes or the central part of the crow's feet. The upper limit of the mask was along the upper cheekbones of the subjects. The specific differences in the ROI were attributed to the differences in facial morphology of the subjects. Yellowness (b * ) and lightness (L * ) were analyzed from cross-polarized images highlighting the base skin color via image analysis, and the average b * Value and L * The change in yellowness (Δb * ) and change in brightness (ΔL * ) was calculated as the change from baseline at the desired time point (in this case, 8 weeks). For inter-study comparisons, results were adjusted to vehicle control to account for any study differences and are reported as change from control (treatment effect minus control effect).

[0093] The results in Tables 3 and 4 show the Δb * Change and ΔL *The changes in Δb for test sections A and B are shown in Table 1, and the associated p-values ​​comparing test sections and vehicle control, respectively. Statistical analysis was performed using a mixed model with subject (fitted as a random effect), baseline, treatment, and cheek left / right (fitted as fixed effects) as covariates at each time point. The significance level was set at 0.10 (two-sided) for test comparisons, such that a p-value of less than 0.10 was statistically significant. The expected values ​​were Δb for test sections A and B. * The synergy coefficient is calculated by dividing the observed value (Test Section C) by the expected value. A synergy coefficient greater than 1 indicates a synergistic effect.

[0094] As can be seen in Table 3, test section A showed a small but significant b * In test section B, b * Surprisingly, the composition of the present invention in Test Section C exhibited a significantly greater reduction in b than expected, as evidenced by a synergy coefficient of 3.03. * The value of b in this specification was reduced. * A preferred decrease in value is -0.200 or greater (eg, -0.300, -0.400, -0.500, or even -1.0 or greater).

[0095] [Table 4]

[0096] Skin whitening (L * Regarding the L value, Test Section A showed no skin lightening effect at 8 weeks, while Test Section B showed a very strong skin lightening effect. Surprisingly, the composition of the present invention in Test Section C showed much more L than expected, as evidenced by the synergy coefficient of 2.35. * The value of L * A suitable increase in value is 0.2 or more (eg, 0.2, 0.4, 0.6, or even 1.0 or more).

[0097] [Table 5]

[0098] The appearance of skin texture was also assessed during the study. The method for determining texture area fraction uses standardized, reproducible image capture and objective image analysis, as outlined above. The degree of skin texture within the ROI was objectively quantified using an image analysis algorithm based on the Optimus software platform. This analysis identified texture patterns on the skin surface that correlate with human texture perception, and the total detected texture area was quantified in pixels. Because ROIs vary in shape and size across subjects, the total texture area was normalized to the total ROI size to calculate the texture area fraction (TAF), i.e., the percentage of the ROI area that is occupied by facial texture, in pixels. A summary of the results is shown in Table 5.

[0099] As can be seen in Table 5, the compositions of the present invention synergistically improved the texture area percentage compared to the values ​​of the comparative test sections. Comparative test section A did not improve the appearance of skin texture, while test section B provided a significant improvement in the appearance of skin texture. Surprisingly, test section C provided a synergistic improvement in the appearance of skin texture. A suitable reduction in texture value herein is -0.200 or more (e.g., -0.300, -0.400, -0.500, or even -1.0 or more).

[0100] [Table 6]

[0101] Example 3: Effect of pH and Niacinamide on HCA Stability This example demonstrates the effect of pH and niacinamide on HCA stability.When HCA decomposes (for example, via decarboxylation), 4-vinylphenol (4-VP) is produced as a by-product, which is generally undesirable in skin care compositions.4-VP can cause an unpleasant odor in the composition, and can also react to cause discoloration (for example, yellowing) of the composition.Therefore, it may be desirable to limit the amount of 4-VP in skin care compositions to less than 1500 ppm (for example, less than 1100, 800 ppm, 700 ppm, 600 ppm, 500 ppm, 400 ppm, or even less than 300 ppm).

[0102] The compositions in Table 6 were tested to determine the effect of pH and niacinamide on the degradation of HCA and the formation of 4-VP. The pH of the test compositions was adjusted as needed using 6N HCl or 4% NaOH solution. The test compositions were incubated at 50°C for 3 weeks, and then HCA degradation was monitored by measuring the color change (Δb * ) was tested according to the color method described above.

[0103] [Table 7]

[0104] As can be seen from Table 6, both pH and niacinamide have an effect on HCA degradation, Δb *, and appears to affect 4-VP formation. These data suggest that increasing pH and / or adding niacinamide increases the decomposition of 4-HCA, increases the formation of 4-VP, and causes yellowing in aqueous skin care compositions. Unexpectedly, the data also show that adding niacinamide actually accelerates the formation of 4-VP at higher pH. This is unexpected, since niacinamide was previously never known to contribute to, let alone accelerate, HCA decomposition. Therefore, lowering the pH of a skin care composition containing HCA and niacinamide appears to unexpectedly slow the rate of 4-VP formation.

[0105] The data in Table 6 also show that both pH and niacinamide have an effect on the yellowness (Δb * Surprisingly, at a pH between 3.8 and 6.0 (e.g., about 4.5), the Δb * The yellowing associated with HCA decomposition (i.e., Δb * This result is surprising because the pH (positive change in pH value) was expected to vary with pH in a predictable linear manner, as seen for compositions 6D-6F.

[0106] Example 4: Effect of radical scavengers on yellowing rate. This example demonstrates a reduction in the rate of yellowing (i.e., a lower Δb * The results demonstrate the ability of antioxidants to assist in reducing HCA degradation, as evidenced by the Δb values. The test compositions shown in Table 7 below were tested at pH 3.8 and pH 6.0, both with and without sodium metabisulfite, an oxygen interference reducer. The test compositions were aged under two different accelerated aging conditions: 50°C for 3 weeks (3W50C) and 40°C for 3 months (3M40C). Without being bound by theory, it is believed that the accelerated aging conditions simulate environmental conditions to which skin care products may be exposed during shipping and storage. After accelerated aging, the test compositions were tested according to the color method described above to measure Δb *The test compositions aged at 40°C for 3 months were further tested according to the HPLC method to determine the level of HCA degradation and 4-VP formation.

[0107] The test results are summarized in Table 7 below. As can be seen from Table 7, the addition of sodium metabisulfate (SMBS) significantly reduced the yellowing rate of 7B and 7D compared to compositions 7A and 7C, respectively. Surprisingly, the data show that the effect of the oxygen interference reducing agent was more enhanced than expected at low pH relative to neutral pH (i.e., 20% for 3W50C and 240% for 3M40C, as can be seen from Table 7). Δb * The reduction in yellowing appears to be due to some other unique mechanism of action rather than further reduction in HCA degradation or 4-VP formation. Thus, it is now possible to provide a combination of ingredients that can synergistically reduce the rate of yellowing in low pH compositions containing HCA.

[0108] [Table 8]

[0109] The synergistic results from the studies in this example are shown in Table 8. The synergy coefficient is calculated by dividing the observed value by the predicted value. A synergy coefficient greater than 1 indicates a synergistic effect.

[0110] [Table 9]

[0111] Example 5: Low pH solubility This example demonstrates the ability of the low pH compositions herein to solubilize HCA at low pH. As shown in Figure 2, HCA solubility begins to decrease dramatically at approximately pH 6.0. However, low pH compositions can maintain HCA solubilized at low pH (e.g., pH 3.8) as a result of high concentrations of glycol cosolvents (ethoxydiglycol and PEG-4). To accelerate HCA instability, the test compositions shown in Table 9 were subjected to two 1-week / 1-week freeze / thaw cycles at -7°C / 25°C, for a total of 1 month of temperature cycling. As seen in Table 9, certain test compositions passed the HCA crystallization test until the glycol cosolvent concentration was reduced to a level where HCA was no longer solubilized.

[0112] [Table 10]

[0113] Example 6: Effect of Glycol Cosolvents and Phenolate Hydrotropes on HCA Solubility This example demonstrates how glycol can improve the solubility of HCA. While it is desirable to formulate HCA-containing compositions at a lower pH to reduce 4-VP formation and yellowing, the solubility of HCA at low pH may not be sufficient to add it at the levels required for effective skin care actives. As in Example 5, the test compositions shown in Table 10 were subjected to two 1-week / 1-week freeze / thaw cycles at -7°C / 25°C, for a total of 1 month of temperature cycling. In this example, phenolic acids were neutralized with an aqueous base (e.g., sodium hydroxide) to form the ionized salt form of the species in situ during batch production. The test results are summarized in Table 10 below.

[0114] As can be seen from Table 10, the inventive combination containing the preferred combination of hydrotrope and glycol cosolvent is free of HCA crystals ("pass"), while the comparative example exhibits crystal formation ("fail"). The combination of ethoxydiglycol and sodium salicylate was able to solubilize 0.5% HCA in a low pH aqueous composition, even when the glycol cosolvent level alone was insufficient. Furthermore, the data show that adding sodium salicylate reduces the amount of glycol required to solubilize HCA, and more importantly, it remains below levels (e.g., <25% combined glycol cosolvents) that could cause undesirable sensory issues. Other well-known hydrotropes, such as caffeine and niacinamide, are unable to solubilize HCA, even at higher levels (5%). Testing additional phenolic acids and phenolic alcohols should reveal that phenolic acids with pKas below the formulation pH (3.8 in this case) are more effective at solubilizing HCA than other conventional hydrotropes or chemicals with similar structural characteristics.

[0115] [Table 11]

[0116] [Table 12] * Sodium hydroxide used as a pH adjuster as needed to achieve the target pH level and neutralize phenolic acids

[0117] Example 7: Solubility effect of mixed HCAs. This example demonstrates the unexpected improvement in solubility of a 50:50 mixture of coumaric acid and ferulic acid, even in the absence of a hydrotrope. The test compositions shown in Table 11 were subjected to two 1 week / 1 week freeze / thaw cycles at -7°C / 25°C, for a total of 1 month of temperature cycling. As can be seen from Table 11, Test Composition 11B did not exhibit significant HCA crystallization, even in the absence of an additional hydrotrope or polar emollient, and the combination of ferulic acid and coumaric acid in Composition 11B appears to provide a synergistic enhancement of HCA solubility.

[0118] [Table 13]

[0119] Example 8: Comparative Example This example demonstrates the inability of conventional compositions to solubilize HCA at low pH. Example 2 of U.S. Patent Application Publication No. 2014 / 0107046, along with several formulation variations (Examples A-K), were prepared as described in the application. The test compositions are shown in Table 12 below. The test compositions were subjected to two 1-week / 1-week freeze / thaw cycles at -7°C / 25°C, followed by a 90-day rest period at 25°C. The compositions were then tested for the presence of HCA crystals as described above. As can be seen from Table 12, all of the comparative compositions exhibited crystallization / precipitation. Even when p-coumaric acid was used instead of ferulic acid, as in comparative compositions C, I, and J, the comparative compositions still exhibited HCA crystallization. Thus, none of the comparative compositions exhibit the desired HCA solubility provided by the low pH compositions herein.

[0120] [Table 14]

[0121] [Table 15]

[0122] Example: Increased skin appearance stability In vivo imaging studies were performed using the eMR Pro device, detailed in the Methods Overview section, to assess visual skin appearance stability by measuring daily appearance variability. The study was conducted using a panel of 66 healthy Japanese women aged 22–35 years. For recruitment, panelists self-reported at least two of the following skin problems on their cheeks (uneven skin tone, dark spots, visible pores, or overall oily skin). Exclusion criteria included illness, pregnancy, skin disease or allergies, current dermatological treatment, history of cosmetic surgery / procedure, experience of redness, tightness, or dryness after cleansing, self-reported dry skin, and a consistent history of more than five large acne lesions (>2 mm per side of the face).

[0123] The study was a split-face, round-robin design across three treatments, detailed in Table 13. Tested formulations included a placebo section (Composition A), low pH niacinamide (Composition B), and low pH niacinamide + HCA (Composition C). Product treatments were randomized by combination and side of face. Consumers used eMR Pro to take photographs of their left and right cheeks three times per day (morning: before washing after removing facial oils with tissue; morning: >5 minutes after washing; evening: >5 minutes after washing).

[0124] [Table 16]

[0125] The study included a 4-week standardization period, during which consumers were given a consistent baseline regimen containing commercially available makeup removal oil, cleansing foam, toner, emulsion, and sunscreen for 4 weeks. After the standardization period, consumers added the essence / serum formulations in Table 13 to their regimen. The test products were then used for an additional 4 weeks to evaluate skin stability by variability measurements.

[0126] Statistical analysis was performed using a mixed model with subject as a random effect and baseline unevenness, treatment, and cheek left / right as fixed effects, with covariates at each time point. The significance level was 0.10 (two-sided) for all test comparisons, with p-values ​​of less than 0.10 considered statistically significant. Adjusted mean and comparison p-values ​​are reported in Tables 14, 15, and 16. Results for comparison differences are identified as either vehicle control, normalization period, or treatment comparison.

[0127] [Table 17]

[0128] [Table 18]

[0129] [Table 19]

[0130] Examples / Combinations 1. A method for improving the appearance of skin, comprising: a) identifying a target area of ​​skin where treatment is desired; b) applying a low pH aqueous skin care composition to the target area of ​​the skin for a treatment period, wherein the composition comprises: i) about 0.1% to about 10% of a vitamin B3 compound; ii) about 0.1% to about 10% hydroxycinnamic acid (HCA); and iii) water, wherein the pH of the composition is less than 5.0. 2. The method according to the preceding features, wherein improving the appearance of the skin is improving pale-looking skin, improving skin texture, and / or improving skin stability. 3. The method of any of the preceding features, wherein improving the appearance of the skin is improving pale-looking skin. 4. The method comprises, during the treatment period, * Decrease in value, L* The method of any of the preceding aspects, wherein the method provides at least one of an increase in skin texture value or a decrease in skin texture value. 5. According to the imaging method, * The decrease in value is at least -0.20 and L * The method of any of the preceding aspects, wherein the increase in value is at least 0.25 and / or the decrease in skin texture value is at least −0.25. 6.b * Decrease in value, L * The method of any of the preceding aspects, wherein the increase in value and / or decrease in skin texture value is synergistic. 7. The method of any of the preceding aspects, wherein the composition does not contain HCA crystals. 8. The method of any of the preceding aspects, wherein the vitamin B3 compound is niacinamide. 9. The method of any of the previous aspects, wherein the composition further comprises a hydrotrope selected from salicylic acid, 2,4 dihydroxybenzoic acid, 2,3 dihydroxybenzoic acid, 3-methoxysalicylic acid, salts thereof, and combinations thereof. 10. The method of any of the previous features, wherein the composition further comprises less than 25% of a glycol co-solvent. 11. The method of any of the preceding features, wherein the co-solvent is selected from the group consisting of propylene glycol, dipropylene glycol, butylene glycol, pentylene glycol, hexylene glycol, ethoxydiglycol, C2-C6 polyethene glycol, and combinations thereof. 12. The method of any of the preceding features, wherein the composition further comprises about 1% to about 20% by weight of an antioxidant. 13. The method of any of the preceding features, wherein the antioxidant is selected from the group consisting of sodium sulfite, sodium bisulfite, sodium metabisulfite, and combinations thereof. 14. The method of any of the preceding aspects, wherein the pH is from about 2.0 to about 4.5. 15. The method of any of the preceding aspects, wherein the HCA is coumaric acid. 16. The method of any of the preceding aspects, wherein the composition exhibits less than 25% HCA degradation according to the HPLC method. 17. The method of any of the preceding features, wherein the composition contains less than 1000 ppm of 4-vinylphenol. 18. A method for improving the appearance of skin, comprising: a) identifying a target area of ​​skin where treatment is desired; b) applying a low pH aqueous skin care composition to the target area of ​​the skin for a treatment period, wherein the composition comprises: i) a vitamin B3 compound; ii) a mixture of coumaric acid and ferulic acid, wherein the ratio of coumaric acid to ferulic acid is from about 2:1 to about 1:2; iii) water, wherein the composition has a pH of about 5.0 or less. 19. The method of claim 18, wherein the weight ratio of coumaric acid to ferulic acid is about 1:1. 20. The method comprises, during the treatment period, * Value, L * 19. The method of claim 18, wherein the method provides a synergistic improvement in at least one of the skin texture value and the skin texture value. 21. The method of claim 18, wherein the composition further comprises a hydrotrope selected from salicylic acid, 2,4 dihydroxybenzoic acid, 2,3 dihydroxybenzoic acid, 3-methoxysalicylic acid, salts thereof, and combinations thereof. 22. The method of claim 18, wherein the composition does not contain HCA crystals.

[0131] Dimensions and values ​​disclosed herein should not be understood as being strictly limited to the exact numerical values ​​recited. Instead, unless otherwise specified, 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."

[0132] 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 any such invention, either alone or in combination with any other reference or references. 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.

[0133] 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 method for improving the appearance of skin, comprising: a) identifying a target area of ​​skin where treatment is desired; b) applying a low pH aqueous skin care composition to the target area of ​​skin for a treatment period, wherein the composition comprises: i) 0.1% to 10% of a vitamin B3 compound; ii) 0.1% to 10% coumaric acid; iii) a glycol co-solvent selected from the group consisting of propylene glycol, dipropylene glycol, butylene glycol, pentylene glycol, hexylene glycol, ethoxydiglycol, C2-C6 polyethene glycol, and combinations thereof; iv) one or more hydrotropes selected from salicylic acid, 2,4 dihydroxybenzoic acid, 2,3 dihydroxybenzoic acid, 3-methoxysalicylic acid, salts thereof, and combinations thereof; v) water, wherein the composition contains less than 25% of the glycol co-solvent; The composition is free of HCA crystals and the pH of the composition is less than 5.

0.

2. 10. The method of claim 1, wherein improving the appearance of the skin comprises improving pale-looking skin, improving skin texture, and / or improving skin stability.

3. The method further comprises, during the treatment period: * Decrease in value, L * The method of claim 1 , wherein the method provides at least one of an increase in skin texture value or a decrease in skin texture value.

4. According to the imaging method, b * said decrease in value is at least −0.20, and L * The method of claim 3, wherein said increase in value is at least 0.25 and / or said decrease in skin texture value is at least -0.

25.

5. b * The decrease in value, L * The method of claim 3 , wherein the increase in value and / or decrease in skin texture value is synergistic.

6. The method of claim 1, wherein the composition further comprises 1% to 20% by weight of an antioxidant.

7. 10. The method of claim 1, wherein the composition exhibits less than 25% HCA degradation according to an HPLC method.

8. 10. The method of claim 1, wherein the composition comprises less than 1000 ppm of 4-vinylphenol.

9. 1. A method for improving the appearance of skin, comprising: a) identifying a target area of ​​skin where treatment is desired; b) applying a low pH aqueous skin care composition to the target area of ​​skin for a treatment period, wherein the composition comprises: i) a vitamin B3 compound; and ii) a mixture of coumaric acid and ferulic acid, wherein the ratio of coumaric acid to ferulic acid is from 2:1 to 1:2; and iii) water, wherein the composition has a pH of 5.0 or less.

10. The method further comprises, during the treatment period: * Value, L * 10. The method of claim 9, wherein the method provides a synergistic improvement in at least one of skin texture value and skin texture value.

11. 10. The method of claim 9, wherein the composition further comprises a hydrotrope selected from salicylic acid, 2,4 dihydroxybenzoic acid, 2,3 dihydroxybenzoic acid, 3-methoxysalicylic acid, salts thereof, and combinations thereof.

12. 10. The method of claim 9, wherein the composition is free of HCA crystals.

Images