Skin care compositions comprising hydroxycinnamic acid and nicotinamide derivatives

Abstract

A low pH aqueous skin care composition comprises from about 0.1% to about 10% of hydroxycinnamic acid (HCA), from about 0.1% to about 10% of a nicotinamide derivative having a free binding energy with HCA of-10 Kcal / mol or more, and water. The composition may have a pH of less than 5.0. The composition provides for reduced HCA crystal formation.

Description

Technical Field

[0001] This disclosure relates to a low-pH aqueous skincare composition comprising: a) about 0.1% to about 10% hydroxycinnamic acid (HCA); and b) about 0.1% to about 10% a niacinamide derivative having a free binding energy to HCA of -10 kcal / mol or higher; and c) water, wherein the pH of the composition is less than 5.0. The composition provides reduced HCA crystal formation. Background Technology

[0002] Skin is the first line of defense against environmental damage, which can otherwise harm sensitive underlying tissues and organs. Furthermore, skin plays a crucial role in a person's physical appearance. Unsurprisingly, most people desire healthy, youthful-looking skin. Unfortunately, for some, signs of aging, such as thinning skin, wrinkles, and age spots, are unwelcome reminders of fading youth. The demand for healthy, youthful-looking skin has led to the development and marketing of numerous skincare products designed to treat various skin conditions associated with aging and unhealthy skin. These products typically contain one or more active ingredients to address the specific skin condition being treated.

[0003] Antioxidants are commonly used as active ingredients in skincare products, for example, as disclosed in WO 2008 / 73684. Hydroxycinnamic acid (HCA) is a particularly well-known antioxidant, as described in, for example, WO 2018 / 081790. However, the use of hydroxycinnamic acid in skincare compositions can present problems. For example, HCA is relatively insoluble in water, which can lead to the formation of undesirable HCA crystals in the product. Additionally, when HCA is used at a neutral pH (e.g., pH 5.0–8.0), which is common in skincare compositions, HCA can oxidize or degrade, causing undesirable color changes, odors, and / or reduced product efficacy. In some cases, formulating compositions at a lower pH can help stabilize HCA, but this can also reduce HCA solubility.

[0004] It is still necessary to provide a low-pH composition containing HCA, which has reduced HCA crystal formation. Summary of the Invention

[0005] This article discloses a low-pH aqueous skincare composition, which comprises:

[0006] a) Approximately 0.1% to approximately 10% hydroxycinnamic acid (HCA); and

[0007] b) Approximately 0.1% to approximately 10% of nicotinamide derivatives with a free binding energy to HCA of -10 kcal / mol or higher; and

[0008] c) Water, wherein the pH of the composition is less than 5.0.

[0009] By using a nicotinamide derivative that has a specific free binding energy with HCA, the composition provides reduced HCA crystal formation.

[0010] Hydroxycinnamic acids (such as para-coumaric acid, hereinafter also referred to as p-coumaric acid) tend to exhibit undesirable solubility and / or stability properties in conventional skincare products. The insolubility of HCAs is even worse in low-pH compositions. However, it has recently been found that low-pH compositions can improve the efficacy of certain skincare active ingredients such as niacinamide (see US 10,874,600). Surprisingly, however, it has been found that niacinamide and HCAs (especially para-coumaric acid) primarily form co-crystals in low-pH compositions, such as those with a pH less than 5, particularly those with a pH of about 3.5 to less than 5, especially when niacinamide is included in the composition at higher concentrations (such as 1% or higher). It has also been surprisingly found that the free binding energy of niacinamide and HCAs (especially para-coumaric acid) can be lower than that of HCA alone, reflecting the observation that niacinamide and HCAs (especially para-coumaric acid) primarily form co-crystals. In the following text, for simplicity, the eutectic between nicotinamide and HCA (especially p-coumaric acid) will be referred to as HCA crystal.

[0011] The inventors have then surprisingly discovered that HCAs (especially p-coumaric acid) with a free binding energy of -10 kcal / mol or higher and certain niacinamide derivatives form reduced cocrystals or no cocrystals at pH less than 5, even at pH from about 3.5 to less than 5, and even when such niacinamide derivatives are included in the composition at higher concentrations (such as 1% or higher). Furthermore, it has been found that methyl niacinamide and its salts provide improved skincare benefits, particularly comparable to and / or improved upon the efficacy of niacinamide as indicated by the PGE2 anti-inflammatory assay. Detailed Implementation

[0012] References to "implementation" or similar methods in this specification mean that the specific materials, features, structures, and / or characteristics described in conjunction with that implementation are included in at least one implementation, or optionally multiple implementations, but do not imply that all implementations include the described materials, features, structures, and / or characteristics. Furthermore, materials, features, structures, and / or characteristics can be combined in any suitable manner in different implementations, and materials, features, structures, and / or characteristics can be omitted or replaced as described. Therefore, unless otherwise stated or declared as incompatible, although not expressly illustrated in the combination, the implementations and aspects described herein may include elements or components of other implementations and / or aspects, or may be combined with elements or components of other implementations and / or aspects.

[0013] 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 representation of significant figures does not express any limitation on the quantity shown or on the accuracy of the measurement. All numerical values ​​should be understood to be modified by the word “about” unless otherwise specified. Unless otherwise indicated, all measurements are understood to have been performed at approximately 25°C and ambient conditions, where “ambient conditions” means conditions at approximately 1 atmosphere and approximately 50% relative humidity. All numerical ranges are narrower ranges including the endpoints; the upper and lower limits of the described ranges are interchangeable to further form ranges not explicitly described.

[0014] The composition may comprise the essential components described herein as well as optional ingredients, and the compositions of the present invention are substantially composed of or comprise of the essential components described herein as well as optional ingredients. As used herein, "substantially composed of" means that the composition or component may contain additional ingredients, provided that the additional ingredients do not substantially alter the essential and novel features of the composition or method protected by the claims. As used in the specification and appended claims, unless the context clearly indicates otherwise, the singular forms "a," "an," and "the (described)" are intended to also include the plural forms.

[0015] definition

[0016] The word “about” modifies a specific value by referring to a range equal to or less than 20 percent (+ / -20%) of the specified value (e.g., less than 15%, 10%, or even less than 5%).

[0017] As used in the reference composition, “application” means applying or spreading the composition onto the surface of human skin (such as the epidermis).

[0018] The "free combination energy" is defined as the difference in Gibbs free energy between the bound and unbound states of two molecules.

[0019] "Cosmetic agent" means any substance and any component thereof intended to be applied to the body of a mammal or any part thereof to provide a cosmetic effect. Cosmetic agents may contain substances generally recognized as safe (GRAS) by the U.S. Food and Drug Administration, food additives, and materials used in non-cosmetic consumer products (including over-the-counter drugs).

[0020] "Effective amount" means an amount of compound or composition sufficient to significantly induce a positive beneficial effect on keratinized tissue during the treatment period. Positive beneficial effects can be health, appearance, and / or sensory benefits, including individual or combined beneficial effects disclosed herein. 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 during a treatment cycle. In some cases, effective amounts may be demonstrated using in vitro and / or ex vivo methods.

[0021] "Hydroxycinnamic acid" (HCA) refers to a class of aromatic acids or phenylpropanoids with a C6-C3 skeleton, which are hydroxyl derivatives of cinnamic acid. Some non-limiting examples of HCA are caffeic acid, chicoric acid, cinnamic acid, chlorogenic acid, ferulic acid, coumaric acid (para, ortho, and meta), ferulic acid, sinapic acid, and α-cyano-4-hydroxycinnamic acid.

[0022] "Improved appearance" refers to providing measurable, desired changes or beneficial effects in the appearance of the skin, which can be quantified, for example, by reducing redness, inflammation, and / or plaque and scale.

[0023] "Low pH" means a pH less than 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.

[0024] "Neutral pH" refers to a pH range of 5.0 to 8.0.

[0025] "Safe effective dose" refers to an effective dose of an ingredient that is low enough to avoid serious side effects (within reasonable medical judgment).

[0026] "Skincare" refers to conditioning and / or improving the condition of the skin. Some non-limiting examples include improving the appearance and / or feel of the skin by providing a smoother, more even look and / or feel; increasing the thickness of one or more layers of the skin; improving the elasticity or resilience of the skin; improving the firmness of the skin; and 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 peeling or flaking; plumping the skin; improving the skin barrier properties; improving skin tone; reducing the appearance of redness or rashes; and / or improving the brightness, radiance, or translucency of the skin.

[0027] "Skincare active ingredients" refer to compounds or combinations of compounds that, when applied to the skin, provide immediate and / or long-lasting beneficial effects to the skin or the cell types typically present therein. Skincare active ingredients can modulate and / or improve the skin or its related cells (e.g., improve skin elasticity, hydration, skin barrier function, and / or improve cell metabolism).

[0028] "Skincare composition" means a composition that contains skincare active ingredients and regulates and / or improves skin condition.

[0029] As used in this article, “treatment cycle” refers to the length of time and / or frequency of applying a material or composition to the target skin surface.

[0030] Composition

[0031] The skincare compositions described herein are low-pH compositions designed for topical application to human skin to improve skin appearance, health, and / or function. The compositions of this invention can be used for non-therapeutic (i.e., cosmetic) treatment of a variety of skin conditions. For example, low-pH compositions are particularly suitable for improving skin appearance, especially fine lines, wrinkles, hyperpigmentation, uneven skin tone, yellowing, and / or skin stability. Improved skin stability means providing reduced daily fluctuations in skin condition.

[0032] The skincare composition described herein is a low-pH aqueous skincare composition, which comprises:

[0033] a) Approximately 0.1% to approximately 10% hydroxycinnamic acid (HCA); and

[0034] b) Approximately 0.1% to approximately 10% of nicotinamide derivatives with a free binding energy to HCA of -10 kcal / mol or higher; and

[0035] c) Water, wherein the pH of the composition is less than 5.0.

[0036] By using a nicotinamide derivative having a specific free binding energy with HCA, this composition provides reduced HCA crystal formation. Preferably, the compositions described herein are free of HCA crystals. Suitable methods for determining whether a composition is free of HCA crystals and / or characterizing HCA crystals in the composition are described in more detail below.

[0037] In some aspects, the composition may include silicone emulsifiers, polymeric thickeners tolerant to low pH environments, low molecular weight silicone liquids, acidic salt pH buffering systems (e.g., lactic acid / sodium lactate buffering systems), and / or other ingredients commonly found in topical skincare compositions. Without being theoretically limited, it is believed that combinations of these ingredients described herein provide stable and effective skincare compositions with good sensory properties and gentleness on the skin.

[0038] The low-pH skincare compositions described herein can be prepared by mixing these ingredients with a dermatologically acceptable carrier using conventional methods known to those skilled in the art. These compositions are available in a variety of product forms, such as solutions, suspensions, lotions, creams, gels, toners, sticks, sprays, aerosols, ointments, cleansing liquids and solid sticks, pastes, foams, mousses, shaving creams, wipes, strips, patches, motorized patches, hydrogels, film-forming products, facial and skin masks (with and without insoluble sheets), etc. The composition form may conform to the specific dermatologically acceptable carrier selected.

[0039] In some cases, the low-pH skincare compositions described herein may be in the form of a serum. A serum is a topical skincare composition in a relatively concentrated formulation, typically having a lower viscosity than conventional cream or lotion-type skincare compositions. Serums can be offered as low-viscosity liquids that are marketed specifically for particular skin conditions and / or for use as the first step in a skincare regimen. The skincare serum products described herein may have a dynamic 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.

[0040] Hydroxycinnamic acid (HCA)

[0041] The low-pH skincare composition described in this article contains a safe and effective amount of HCA. HCA may be present in the composition in amounts from 0.1% to 10% (e.g., 0.5% to 5% or 1% to 4%). Hydroxycinnamic acid is generally considered an antioxidant phenolic compound that can be found in plants, primarily as a component of the cell wall. See HK Kuzaki et al., Journal of Agricultural and Food Chemistry, Vol. 50, pp. 2161-68, 2002.

[0042] In some respects, coumaric acids are desirable for use in low-pH compositions, especially p-coumaric acid (also known as 4-HCA). p-Coumaric acid has the following structure:

[0043]

[0044] In other respects, mixtures of two or more HCAs, such as a mixture of coumaric acid and ferulic acid, may be desired. In these respects, 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 this purpose is LIPOBRITE, which is available from Vantage Personal Care.

[0045] Nicotinamide derivatives with high free binding energy

[0046] To reduce crystallization, the compositions of the present invention comprise a nicotinamide derivative having a free binding energy with HCA of -10 kcal / mol or higher, preferably -7.5 kcal / mol or higher, more preferably -5 kcal / mol or higher.

[0047] The energy of free combination is measured as follows:

[0048] Free combination energy calculation :

[0049] All calculations were performed using the Gaussian 09 package. The gas-phase structures of each molecular system (individual molecules and complexes) were optimized using density functional theory (DFT) methods involving Becke 3-parameter exchange functionals and Lee-Yang-Parr correlation functionals (B3LYP). Vibrational frequencies were calculated to ensure that the optimized geometry was a local minimum. The energies, electronic and thermodynamic parameters, and charges of the optimized p-coumaric acid (HCA) and different HCA-nicotinamide / derived complex structures were calculated at the theoretical 6-311++G(d, p) level. The free binding energy between HCA and nicotinamide / derived complexes was calculated as the difference between the energy of the complex and the sum of the energies of the individual monomers. The free binding energy was calculated using the following relationship:

[0050] ΔE AB = E AB – (E A + E B )

[0051] Where E AB E A and E B These are the energies of the complex and the individual monomers, respectively. Additionally, basis set overlap error (BSSE) correction is calculated to obtain the accurate free binding energy.

[0052] For example, the table below shows the free binding energies of p-coumaric acid with nicotinamide and some of its derivatives.

[0053]

[0054] *In addition, for salts of methylnicotinamide, such salts exist in the composition and, under conditions for measuring free binding energy, in the form of methylnicotinamide.

[0055] Preferably, the nicotinamide derivatives used herein have a pyridine moiety in the composition, wherein nitrogen is protonated. Preferably, the nicotinamide derivatives used herein are selected from the group consisting of methylnicotinamide, salts of methylnicotinamide, nicotinamide mononucleotide, nicotinamide adenine dinucleotide, and mixtures thereof. More preferably, in view of its beneficial skincare effects, particularly its efficacy comparable to and / or improved with nicotinamide in in vitro PGE2 anti-inflammatory effects, the nicotinamide derivatives are selected from the group consisting of methylnicotinamide, salts of methylnicotinamide, and mixtures thereof. Salts of methylnicotinamide can be any salt, as long as the counterion dissociation in the aqueous phase does not affect the free binding energy, including, for example, methylnicotinamide chloride. As described above, the salts of methylnicotinamide are present in the composition and, under conditions for measuring the free binding energy, in the form of methylnicotinamide.

[0056] The compositions of the present invention comprise 0.1% to 10% (e.g., 0.5% to 5% or 1% to 4%) of a niacinamide derivative for regulating a variety of skin conditions, such as that described in U.S. Patent No. 5,939,082.

[0057] In some cases, it may be desirable for the cyclic nitrogen of the vitamin B3 compound to be "non-complexed" (e.g., chemically unbound and / or unhindered) in the composition and / or before application to the target skin surface. For example, the compositions herein may be free of or substantially free of (i.e., less than 3%, 2%, 1%, or even less than 0.5%) salts or complexes of the vitamin B3 compound. Exemplary methods for minimizing or preventing the formation of undesirable salts and / or complexes include excluding substances that form substantially irreversible complexes or other undesirable complexes with the vitamin B3 compound in the composition, pH adjustment, ionic strength adjustment, use of surfactants, and formulation procedures in which the vitamin B3 compound and substances with which it complexes are in different phases.

[0058] Nicotinamide and its derivatives have low free binding energy with HCA

[0059] In addition to the nicotinamide derivatives that have a high free binding energy with HCA mentioned above, the composition may also contain nicotinamide and its derivatives that have a low free binding energy with HCA.

[0060] If included, the weight ratio between “nicotinamide and its derivatives having a low free binding energy with HCA” and “nicotinamide derivatives having a high free binding energy with HCA” is preferably up to about 7:3, more preferably up to about 6:4, even more preferably up to about 5:5, even more preferably up to about 4:6, and even more preferably up to about 3:7.

[0061] If included, blends of “nicotinamide and its derivatives having a low free binding energy with HCA” and “nicotinamide derivatives having a high free binding energy with HCA” provide preferably a relative saturation solubility of more than 110% for individual HCA, more preferably more than 120%, even more preferably more than 130%, and still more preferably more than 140% for individual HCA.

[0062] Tables I-III below are used to explain saturated solubility and relative saturated solubility:

[0063] Table I

[0064]

[0065] *Equilibrate the pH to the listed target pH using HCl / NaOH solution.

[0066] Table II

[0067]

[0068] Table III

[0069]

[0070] Preferably, the composition is substantially free of nicotinamide and its derivatives that have a low free binding energy with HCA, i.e., it contains 0.1% or less, more preferably 0.05% or less of such substances. Even more preferably, the composition is free of such materials, i.e., it contains 0% of such materials.

[0071] Low pH acid buffer system

[0072] When providing low-pH compositions for topical application to the skin, it is highly preferred to include a buffering system to help maintain the pH of the composition for a period of time after application (e.g., up to 5 minutes or longer). On average, human skin pH is typically in the range of about 5.0 to 6.0. To maintain this pH, human skin has evolved a natural buffering system to resist pH changes. Therefore, when a low-pH composition is applied to the skin, the skin's natural buffering system will attempt to adjust the pH of the composition to match the skin's natural pH. Without the addition of a buffer, a low-pH composition may not provide the desired beneficial skincare effects. Therefore, the compositions described herein may include a low-pH acid buffering system.

[0073] The buffer may be selected based on the acid used to lower the pH of the low-pH compositions described herein. For example, lactic acid and gluconic acid may be used to lower the pH of the composition because they are generally considered gentler on the skin (i.e., lower risk of irritation) compared to other α-hydroxy acids. In this example, sodium lactate or sodium gluconate is then selected to provide an acid / salt pH buffering system. The buffer may be present in the low-pH composition in an amount of 0.25% to 4% (e.g., 0.5% to 3%, 0.75% to 2%, or 1% to 1.75%). Non-limiting examples of suitable low-pH buffering systems for use herein are disclosed in co-pending U.S. Serial No. 16 / 891491. It should be understood, of course, that the compositions of the present invention may optionally contain other pH buffers known for use in skin care compositions.

[0074] Thickener

[0075] The composition preferably contains a polymeric thickener that can withstand low-pH electrolytic environments. That is, the thickener will not lose its ability to thicken or stabilize the composition at low pH in the presence of an acid-salt buffer system. Some conventional neutralized thickeners are known to degrade and / or lose their ability to properly thicken the composition at lower pH and / or in the presence of acid-salt buffers (e.g., sodium lactate). For example, some neutralized thickeners degrade 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 turbidity or opacity to the composition when they are in the form of essential oils, serums, etc. It has also been found that some anionic polymeric thickeners can provide suitable tolerance to low-pH environments, but are not tolerant to buffer systems formed by the combination of acids and salts. Therefore, in some cases, the low-pH compositions described herein may contain no or substantially no neutralized thickeners, fatty alcohol thickeners, and anionic thickeners. The thickener may be present in an amount of 0.0001% to 25% (e.g., 0.001% to 20%, 0.01% to 10%, 0.5% to 7%, or 1% or 5%) based on the weight of the composition.

[0076] Other non-limiting examples of thickeners or water-structuring agents that may be used alone or in combination herein include natural or synthetic gums, polysaccharides, carboxylic acid polymers, polyacrylamide polymers, sulfonated polymers, and copolymers thereof. Additional examples include modified gums, cellulose, and superabsorbent polymers. The term “superabsorbent polymer” should be understood to mean a polymer capable of spontaneously absorbing at least 20 times its own weight in an aqueous fluid, particularly water and especially distilled water, in its dry state. Suitable polysaccharides include alkyl hydroxyalkyl cellulose ethers, such as hydroxypropyl methylcellulose stearoxy ether. This material is sold under the trade names SANGELOSE 60L and 90L by Daido Chemical Corp. Another suitable polysaccharide includes hydrophobically modified starches, such as modified potato starch. This material is sold under the trade name STRUCTURE SOLANACE by Nouryon. Another polymer includes crosslinking polymers whose monomers are at least partially composed of acryloyl dimethyl taurate monomers, such as sodium polyacryloyl dimethyl taurate, for example, sold by Clariant under the trade name ARISTOFLEX SILK.

[0077] It has now been found that certain anionic polymer thickeners can provide suitable tolerance to low pH environments and offer the desired feel and opacity properties to the composition. Therefore, a particularly suitable example of anionic thickener is polyacrylate crosspolymer-6, which is commercially available as SEPIMAX ZEN from Seppic, France.

[0078] Low molecular weight organosilicon liquid

[0079] In some cases, anionic polymer thickeners can impart an undesirable sticky feel when low-pH compositions are applied to target skin areas. It has been found that adding low-molecular-weight silicone liquids can reduce or prevent this sticky feel. The molecular weight of a silicone liquid depends on the length of one or more of its silicone polymer chains, which is also proportional to the viscosity of the silicone liquid. Therefore, low-molecular-weight silicone liquids suitable for use in the low-pH compositions of the present invention 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 method for classifying silicone liquids and is available from material suppliers. A particularly suitable example of a low-molecular-weight silicone liquid is a 5 cSt polydimethylsiloxane liquid. As used herein, the term "polydimethylsiloxane" means a polydimethylsiloxane compound having the following formula:

[0080]

[0081] Dermatologically acceptable carriers

[0082] The low-pH compositions described herein contain a dermatologically acceptable carrier (which may be referred to as a "carrier"). The phrase "dermatologically acceptable carrier" means that the carrier is suitable for topical application to keratinocytes, has good aesthetic properties, is compatible with the active substance in the composition, and does not cause any unreasonable safety or toxicity issues. In one embodiment, the carrier is present in an amount 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.

[0083] The carrier can take many forms. In some cases, the solubility or dispersibility of the components (e.g., extracts, sunscreen active ingredients, additives) determines 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, dermatologically acceptable carriers are in the form of emulsions. Emulsions can 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 water-in-oil-in-oil emulsions). The oil phase can contain silicone oils, non-silicone oils (such as hydrocarbon oils), esters, ethers, and mixtures thereof. The aqueous phase typically contains water and water-soluble ingredients (e.g., water-soluble moisturizers, conditioning agents, antimicrobial agents, humectants, and / or other skin-care active ingredients). However, in some cases, the aqueous phase may contain components that are not water, including but not limited to water-soluble moisturizers, conditioning agents, antimicrobial agents, humectants, and / or other water-soluble skin-care active ingredients. In some cases, the non-aqueous components of the composition include wetting agents, such as glycerin and / or other polyols.

[0084] In some cases, the compositions herein are in the form of an oil-in-water (“O / W”) emulsion that provides a mild and non-greasy sensory experience. Suitable O / W emulsions herein may comprise a continuous aqueous phase of greater than 50% by weight of the composition, with the remainder being a dispersed oil phase. The aqueous phase may comprise 1% to 99% water by weight of the aqueous phase, and any water-soluble and / or water-miscible components. In these cases, the dispersed oil phase will typically be 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 undesirable sensory effects of oily compositions. The oil phase may include 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 suitable for use in the compositions of the present invention are disclosed in U.S. Patent 9,446,265 and U.S. Publication 2015 / 0196464.

[0085] The carrier may contain one or more dermatologically acceptable hydrophilic diluents. As used herein, "diluent" includes materials into which vitamin B3 compounds can be dispersed, dissolved, or otherwise incorporated. Hydrophilic diluents include water, organic hydrophilic diluents such as lower monovalent alcohols (e.g., C1-C4) and low molecular weight diols and polyols, including propylene glycol, polyethylene glycol (e.g., molecular weight 200 g / mol to 600 g / mol), polypropylene glycol (e.g., molecular weight 425 g / mol to 2025 g / mol), glycerol, butylene glycol, 1,2,4-butanetriol, sorbitan esters, 1,2,6-hexanetriol, ethanol, isopropanol, sorbitan esters, butylene glycol, ether propanol, ethoxylated ethers, propoxylated ethers, and combinations thereof.

[0086] emulsifier

[0087] When the low-pH compositions described 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 phase separation). The emulsifier may be present in the composition in an amount of 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 suitable for use herein are disclosed in U.S. Patents 3,755,560, 4,421,769 and McCutcheon’s *Detergents and Emulsifiers*, North American Edition, pp. 317-324 (1986).

[0088] Some other non-limiting examples of emulsifiers that may be suitable for use in this document include: ethers of polyethylene glycol and fatty alcohols, esters of polyethylene glycol and fatty acids, glycosylated ethers of polyethylene glycol and fatty alcohols, esters of glycosylated polyethylene glycol and fatty acids, ethers of C12-30 alcohols and glycerol or polyglycerol, esters of C12-30 fatty acids and glycerol or polyglycerol, ethers of olefin-modified C12-30 alcohols and glycerol or polyglycerol, ethers of C12-30 fatty alcohols and sucrose or glucose, esters of sucrose and C1-230 fatty acids, esters of pentaerythritol and C12-30 fatty acids, esters of sorbitol and / or dehydrated sorbitol and C12-30 fatty acids, ethers of sorbitol and / or dehydrated sorbitol and alkoxylated dehydrated sorbitol, ethers of polyethylene glycol and cholesterol, esters of C12-30 fatty acids and alkoxylated ethers of sorbitol and / or dehydrated sorbitol, and combinations thereof. One particularly useful class of emulsifiers is polyethylene glycol ethers of lauryl alcohol, such as lauryl polyoxyethylene ether-1 to lauryl polyoxyethylene ether-50 (e.g., lauryl polyoxyethylene ether-4). Other examples of emulsifiers include ethers of glycerol, polyglycerol, sucrose, glucose, or sorbitol; esters of glycerol, polyglycerol, sucrose, glucose, or sorbitol; and mixtures thereof. Other particularly useful classes of emulsifiers are alkyl esters of sorbitol and sorbitan anhydride, such as polysorbate 20, polysorbate 21, and polysorbate 40.

[0089] In some respects, the inclusion of linear or branched silicone emulsifiers in low-pH compositions is desirable. Particularly useful silicone emulsifiers include polyether-modified silicones such as KF-6011, KF-6012, KF-6013, 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 available from Shin-Etsu. A particularly suitable emulsifier for use herein is PEG-11 methyl ether polydimethylsiloxane, which is available from Shin-Etsu as KF-6011. Surprisingly, it has been found that the PEG-11 methyl ether polydimethylsiloxane emulsifier further reduces the sticky feel of the anionic polymer thickener, thereby improving the overall feel of the low-pH composition. The emulsifier may be present in amounts of 0.1% to 10% (e.g., 1% to 5%, or 2% to 4%).

[0090] Cosolvent

[0091] In some respects, the compositions herein may contain a short-chain diol (e.g., glycol) as a co-solvent to aid in the dissolution of HCA. However, when choosing a glycol as a co-solvent, it may be important to limit the amount of the glycol to less than 25% (e.g., less than 20%, 17%, 15%, or even less than 10%) to reduce the risk of imparting undesirable sensory properties to the composition (e.g., a viscous or oily feel). Some non-limiting examples of glycols suitable for use herein are propylene glycol, dipropylene glycol, butanediol, pentanediol, hexanediol, ethoxydiethylene glycol, and C2-C6 polyethylene glycols (e.g., PEG-3, PEG-4, PEG-4 methyl ether) and combinations thereof.

[0092] antioxidants

[0093] The low-pH compositions described herein may contain antioxidants to combat HCA oxidation and / or degradation. Antioxidants (when included) may be present in amounts from 0.001% to 3% (e.g., 0.01%-2%, 0.05%-1%, or 0.1%-0.5%). Some non-limiting examples of antioxidants suitable for use herein are sodium sulfite, sodium bisulfite, sodium metabisulfite, and butylated hydroxytoluene.

[0094] Water-soluble growth promoters

[0095] The compositions described herein may contain 0.1% to 10% (e.g., 0.5% to 5% or 1% to 3%) of a water-soluble growth promoter to improve the water solubility of HCA. Preferably, the weight ratio of HCA to the water-soluble growth promoter is about 2:1 to about 1:20, more preferably about 1:1 to about 1:10, and even more preferably about 1:1 to about 1:5. HCA compounds typically exhibit particularly poor solubility in low-pH aqueous compositions, such as the low-pH compositions described herein. For example, p-coumaric acid has a solubility of about 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 theoretically limited, it is believed that the solubility of HCA at lower pH levels is reduced due to its decreased ability to undergo acid dissociation (which forms conjugate bases observed at higher pH levels). At pH 7, p-coumaric acid exists as approximately 99.6% of its conjugate base; while at pH 3, the conjugate base form exists at only approximately 13.4%. Due to its relatively poor solubility, HCA tends to crystallize in aqueous, low-pH skincare compositions, even in the absence of niacinamide (hereinafter referred to as HCA monocrystals). HCA monocrystals can impart an undesirable feel to the composition during use (e.g., a rough or granular feel) and / or reduce the efficacy of HCA and / or other ingredients in the composition. This can lead consumers to the undesirable perception of poor product quality.

[0096] The water-soluble growth promoters used in this article are selected from those of: phenolic acids, derivatives of phenolic acids, phenolic alcohols, derivatives of phenolic alcohols, and mixtures thereof; wherein the water-soluble growth promoter has a pKA less than the pH of the formulation; and wherein the water-soluble growth promoter has a partition coefficient (logP) less than 3.0.

[0097] Water-soluble growth promoters should have a pKA lower than the formulation pH and sufficient aqueous solubility at the formulation pH for complete dissolution. An acidic pKA lower than the composition pH may be particularly important for low-pH compositions, as the solubility of HCA decreases at low pH. For example, sodium salicylate with a pKa of 2.8 may be a suitable water-soluble growth promoter for compositions with a pH of 3.8, since carboxylic acids exist primarily as conjugate bases. Conversely, in this example, cinnamic acid or sodium cinnamate with an acidic pKa of 4.32 is not an effective water-soluble growth promoter. Furthermore, the water-soluble growth promoter should not form crystals between the water-soluble growth promoter and the target HCA. Additionally, water-soluble growth promoters 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 water-soluble growth promoters suitable for use herein are salicylic acid, 2,4-dihydroxybenzoic acid, 2,3-dihydroxybenzoic acid, 3-methoxysalicylic acid, salts of these, or combinations thereof. Other non-limiting examples of water-soluble growth promoters applicable to this document are disclosed in PCT Publication WO 2018 / 081790.

[0098] The water-soluble growth promoters used in this paper have a partition coefficient (logP) of less than 3.0. The partition coefficient was calculated using the ACD consensus algorithm (http: / / perceptahelp.acdlabs.com / help_v2020 / index.php / LogP#Consensus_LogP). Below are some examples of ingredients and partition coefficients:

[0099]

[0100] 1 logP ACD, consensus algorithm

[0101] Other optional ingredients

[0102] The compositions of the present invention may optionally contain one or more additives commonly used in cosmetic compositions (e.g., colorants, skin-care active substances, anti-inflammatory agents, sunscreens, emulsifiers, buffers, rheology modifiers, combinations thereof, etc.), provided that the additive does not adversely alter the beneficial effects on skin health or appearance provided by the compositions of the present invention. When incorporated into a composition, the additive should be suitable for contact with human skin tissue without undue toxicity, incompatibility, instability, allergic response, etc. Some non-limiting examples of additional active substances include vitamins, minerals, peptides and peptide derivatives, glycosamines, sunscreens, oil-controlling agents, particles, flavonoids, hair growth regulators, antioxidants and / or antioxidant precursors, preservatives, protease inhibitors, tyrosinase inhibitors, anti-inflammatory agents, moisturizers, exfoliating agents, skin brighteners, sun-free tanning agents, lubricants, anti-acne active substances, anti-cellulite active substances, chelating agents, anti-wrinkle active substances, anti-atrophy active substances, phytosterols and / or plant hormones, N-acyl amino acid compounds, antimicrobial agents, and antifungal agents. Other non-limiting examples of additional ingredients and / or skincare active substances applicable herein are described in U.S. Patent Publications 2002 / 0022040, 2003 / 0049212, 2004 / 0175347, 2006 / 0275237, 2007 / 0196344, 2008 / 0181956, 2008 / 0206373, 2010 / 00092408, 2008 / 0206373, 2010 / 0239510, and 2010 / 0189669. US Patent Nos. 2010 / 0272667, 2011 / 0262025, 2011 / 0097286, 2012 / 0197016, 2012 / 0128683, 2012 / 0148515, 2012 / 0156146 and 2013 / 0022557, and US Patent Nos. 5,939,082, 5,872,112, 6,492,326, 6,696,049, 6,524,598, 5,972,359 and 6,174,533.

[0103] When optional ingredients are included in the compositions described herein, it may be desirable to select ingredients that do not form complexes or otherwise undesirably interact with other ingredients in the low pH composition, especially pH-sensitive ingredients such as niacinamide, salicylates, and peptides. In some cases, it may be desirable to select skincare actives that act via different biological pathways so that the actives do not interfere with each other, which could reduce the efficacy of both agents. When present, optional ingredients may be included in amounts from 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.

[0104] How to use

[0105] The low-pH compositions described herein are formulated for topical application to the skin. Methods of using the low-pH compositions of the present invention involve identifying a target skin portion of a person who needs or desires treatment (e.g., a skin portion exhibiting uneven skin tone, yellowing, pigmentation, fine lines or wrinkles, or skin instability), and applying an effective amount of the low-pH composition to the target skin portion during treatment. The effective amount of the composition can vary depending on the desired beneficial skin effect 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 skin portion can be on the surface of facial skin (such as the forehead, perioral region, chin, periorbital region, nose, and / or cheeks) or another part of the body (e.g., hands, arms, legs, back, chest). In some cases, a target skin portion can be selected that does not currently exhibit signs of skin aging but is an area of ​​skin that typically exhibits such characteristics with age. In these cases, the low-pH composition can be used to help prevent the occurrence of such undesirable skin characteristics.

[0106] The composition may be applied topically to the target skin area requiring treatment at least once daily, twice daily, or more frequently during treatment, and, if necessary, to the surrounding skin. When applied twice daily, the first and second applications should be spaced at least 1 to 12 hours apart. Typically, the composition may be applied in the morning and / or at bedtime. When used according to the methods described herein, the compositions of the invention can improve the appearance and / or function of the skin, for example, by improving skin texture. Improvement in skin texture can be provided, for example, by reducing pore size, reducing skin roughness, reducing the presence and / or size of wrinkles, combinations thereof, etc.

[0107] The treatment period is ideally a sufficient time for the low-pH composition to improve the appearance and / or function of the target skin area. The treatment period typically lasts at least one week (e.g., about two, four, eight, or even twelve weeks). In some cases, the treatment period may be extended to several months (i.e., three to twelve months). In some cases, the composition is applied at least once daily or even twice daily for most of the week during a treatment period of at least two, four, eight, or twelve weeks (e.g., at least four, five, or six days per week).

[0108] The application of the composition can be achieved through topical application. Regarding the application of the composition, the terms "topical," "local," and "partially" refer to delivering the composition to a target area (e.g., psoriatic patches) while minimizing delivery to skin surfaces that are not intended for treatment. The composition may be applied to and gently massaged into the skin area. The form of the composition or a dermatologically acceptable carrier should be chosen to facilitate topical application. While some embodiments herein envision topical application of the composition to a specific area, it should be understood that the compositions herein can be applied more comprehensively or extensively to one or more skin surfaces. In some embodiments, the compositions herein can be used as part of a multi-step cosmetic regimen, wherein the compositions of the present invention may be applied before and / or after one or more other compositions.

[0109] method

[0110] Saturated solubility determination

[0111] This method provides a way to determine the saturated solubility of HCA compositions using UV-Vis spectroscopy.

[0112] Instruments and materials :

[0113] A UV-VIS-NIR spectrophotometer with a computer data system (such as the UV-3600 Shimadzu UV-VIS-NIR spectrophotometer). A suitable sample cell (such as a quartz cell with a 1 cm optical path). A centrifuge (such as a Srvall ST40R centrifuge) and an injection filter (such as a 0.2 μm syringe filter, H-PTFE, 13 mm). A 70% ethanol acidic solution (69.3% ethanol, 29.7% water, 1% HCl), pH < 3.

[0114] Preparation of saturated solubility samples :

[0115] The saturated solubility was measured by preparing a sample with an excess of HCA (precipitation was observed even after mixing overnight). The pH of the solution was adjusted to the target value using HCl / NaOH solution. The solution was allowed to equilibrate overnight. The solution was aliquoted into centrifuge tubes and centrifuged, discarding any undissolved HCA. The required sample volume was filtered through a 0.2 μm syringe filter. The solution was diluted to the desired dilution factor using 70% ethanol acid solution.

[0116] Measurement :

[0117] Perform measurements according to the UV-Vis spectrophotometer manufacturer's guidelines. Turn on the UV instrument and heat the lamp for 20 minutes to ensure calibration and standard dilution curves are generated. Obtain a calibration curve by plotting the absorbance (y-axis) of a set of calibration standards against known concentrations (ppm, x-axis). For HCA, set the wavelength to 200nm-500nm, scan speed: fast, single scan mode with automatic sampling intervals, and absorption mode. Measure the background using a 2× quartz cell and a 70% ethanol acidic solution. Measure the sample and read the absorbance at 311nm (p-coumaric acid) or 325nm (ferulic acid). Calculate the measured HCA concentration based on the absorbance at 311nm (p-coumaric acid) or 325nm (ferulic acid) against the calibration curve, and adjust to the final concentration based on the dilution factor.

[0118] calculate

[0119] Calculation of HCA concentration measured in aqueous phase

[0120]

[0121] The peak of p-coumaric acid is at 311 nm, and the peak of ferulic acid is at 325 nm.

[0122] HCA crystals

[0123] This method provides a way to determine the solubility of HCA in a composition by observing HCA crystals in situ. The method involves cycling the temperature of the test sample between freezing and thawing to simulate environmental conditions experienced by the skincare composition at an accelerated rate. This type of accelerated aging is commonly used in cosmetic stability testing. HCA crystals can be detected using conventional methods such as visual observation and microscopy.

[0124] Place at least 10g (e.g., 20g-60g) of the bulk sample of the test composition in a suitable container (e.g., a clear plastic or glass jar) where the test sample can be visually observed. Expose the test sample to a freeze / thaw temperature cycle of one month to simulate the environmental conditions that skincare products may experience during transport 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 time of one month.

[0125] After the accelerated aging process is completed (i.e., 1 month of temperature cycling), the transparent test sample is visually inspected in situ in a transparent container to determine whether HCA crystallization / precipitation has occurred. For opaque and translucent samples, the entire test sample is removed from the container and transferred to a suitable transparent substrate (e.g., a plastic film or glass plate) to form a film no thicker than 1 mm. The sample is covered with a second transparent substrate to suppress the loss of volatile components during inspection. The sample is backlit using a light source (e.g., an LED lamp or similar) to aid visual inspection. When observed from a distance of 45 cm by a person with 20 / 20 visual acuity, HCA crystals typically appear in the composition as visible precipitates. Any precipitates identified during visual observation can be further evaluated using a microscope capable of providing cross-polarized light for fluorescence birefringence observation to identify anisotropic crystals. 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 no more than one HCA crystal are considered "HCA crystal-free" and recorded as "pass". Test samples containing more than one HCA crystal were recorded as "failure".

[0126] Although not strictly necessary, Fourier-transform infrared spectroscopy (FTIR) can be used to confirm that HCA crystals contain a suitable hydroxycinnamic acid structure. FTIR spectroscopy is known in the art. See US10,912,857, US2020 / 0000697, and Fourier Transform Infrared Spectroscopy in Colloid and Interface Science, DR. Scheuing, ed., American Chemical Society, 225, 1991.

[0127] combination

[0128] 1. A low-pH aqueous skin care composition, the composition comprising:

[0129] a. Hydroxycinnamic acid (HCA) of about 0.1% to about 10%; and

[0130] b. Approximately 0.1% to approximately 10% of nicotinamide derivatives have a free binding energy with HCA of -10 kcal / mol or higher;

[0131] c. Water;

[0132] The pH of the composition is less than 5.0.

[0133] 2. The composition according to the foregoing characteristics, wherein the free binding energy of the nicotinamide derivative with HCA is -7.5 kcal / mol or higher.

[0134] 3. The composition according to any one of the foregoing features, wherein the free binding energy of the nicotinamide derivative with HCA is -5 kcal / mol or higher.

[0135] 4. The composition according to any one of the foregoing features, wherein the nicotinamide derivative has a pyridine moiety in the composition, wherein nitrogen is protonated.

[0136] 5. The composition according to any one of the foregoing features, wherein the nicotinamide derivative is selected from the group consisting of methylnicotinamide, salts of methylnicotinamide, nicotinamide mononucleotide and nicotinamide adenine dinucleotide and mixtures thereof.

[0137] 6. The composition according to any one of the foregoing features, wherein the nicotinamide derivative is selected from the group consisting of methylnicotinamide chloride, salts of methylnicotinamide, and mixtures thereof.

[0138] 7. The composition according to any one of the foregoing features, wherein the pH is from about 3.5 to less than 5.0.

[0139] 8. The composition according to any one of the foregoing features, wherein the HCA is coumaric acid.

[0140] 9. The composition according to any one of the foregoing features, wherein the composition does not contain HCA crystals.

[0141] Example

[0142] The compositions in Tables 1 and 2 below are prepared using conventional methods for manufacturing skincare compositions. Such methods typically involve mixing the ingredients to a relatively homogeneous state in one or more steps, with or without the use of heating, cooling, applying vacuum, etc. Unless otherwise stated, all... ImplementationThe amounts in the examples do not include trace amounts of substances that may be present in commercial products, such as diluents, preservatives, coloring solutions, sensory modification powders, and elastomers. HCA can be added and dissolved in situ in solid form, dissolved as a premix, or provided as a pre-dispersed raw material. For certain Implementation For example, using 4-HCA in PEG-4 (Lipobrite from Vantage) ® A pre-dispersed 15% solution in ( ). For solutions containing Lipobrite ® of Implementation For clarity, the contents of 4-HCA and PEG-4 are listed separately and indicated by superscript for Lipobrite. ® Raw materials. Total Lipobrite added ® The materials are the sum of the listed 4-HCA and PEG-4 components. All other materials are listed "as is" from the supplier and are not broken down into individual components.

[0143] Table 1

[0144]

[0145] *1 Progeline: Available from Lucas Meyer Cosmetics

[0146] *2 SEPIMAX ZEN, available from Seppic

[0147] *3 DC 1503, available from Dow Corning

[0148] *4 KF-6011, available from Shin-Etsu

[0149] *5 Eldew SL205: Available from Ajinomoto

[0150] *6 LIPOBRITE, available from Vantage (15% 4-HCA, 85% PEG-4)

[0151] Table 2

[0152] *1 Progeline: Available from Lucas Meyer Cosmetics

[0153] *2 SEPIMAX ZEN, available from Seppic

[0154] *3 DC 1503, available from Dow Corning

[0155] *4 KF-6011, available from Shin-Etsu

[0156] *5 Eldew SL205: Available from Ajinomoto

[0157] *6 LIPOBRITE, available from Vantage (15% 4-HCA, 85% PEG-4)

[0158] Examples 1 to 5 are embodiments of the present invention. Compared with comparative examples, the embodiments of the present disclosure provide reduced crystal formation.

[0159] The compositions shown in Table 1 were subjected to two freeze / thaw cycles at -7°C / 25°C for one week each, for a total of one month. As can be seen in Table 1, Example 1, which is an example of the present disclosure containing methylnicotinamide chloride, did not contain HCA crystals (“pass”), while Comparative Example (i) containing nicotinamide showed crystal formation (“fail”).

[0160] The dimensions and values ​​disclosed herein should not be construed as strictly limited to the precise numerical values ​​cited. Rather, unless otherwise specified, each such dimension is intended to represent the stated value and the range surrounding its functional equivalent. For example, a dimension disclosed as “40 mm” is intended to represent “approximately 40 mm”.

[0161] Unless expressly excluded or otherwise limited, every reference cited herein, including any cross-references or related patents or patent applications, and any patent application or patent claiming priority to or benefiting from it, is incorporated herein by reference in its entirety. A reference to any document is not an admission that it is prior art concerning any invention disclosed or claimed herein, nor is it an admission that it, alone or in any combination with any other reference, teaches, suggests, or discloses any such invention. Furthermore, where any meaning or definition of a term in this invention conflicts with any meaning or definition of the same term in a referenced document, the meaning or definition given to that term in this invention shall prevail.

[0162] While specific embodiments of the invention have been illustrated and described, it will be apparent 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. Therefore, it is intended that all such changes and modifications falling within the scope of the invention be covered by the appended claims.

Claims

1. A low-pH aqueous skincare composition, said composition comprising: a. Hydroxycinnamic acid (HCA) of about 0.1% to about 10%; and b. Approximately 0.1% to approximately 10% of nicotinamide derivatives have a free binding energy with HCA of -10 kcal / mol or higher; c. Water; The pH of the composition is less than 5.

0.

2. The composition according to claim 1, wherein the free binding energy of the nicotinamide derivative with HCA is -7.5 kcal / mol or greater.

3. The composition according to claim 2, wherein the free binding energy of the nicotinamide derivative with HCA is -5 kcal / mol or greater.

4. The composition according to claim 1, wherein the nicotinamide derivative has a pyridine moiety in the composition, wherein nitrogen is protonated.

5. The composition according to claim 4, wherein the nicotinamide derivative is selected from methylnicotinamide, salts of methylnicotinamide, nicotinamide mononucleotide and nicotinamide adenine dinucleotide or mixtures thereof.

6. The composition according to claim 5, wherein the nicotinamide derivative is selected from methylnicotinamide chloride, salts of methylnicotinamide, or mixtures thereof.

7. The composition according to claim 1, wherein the pH is from about 3.5 to less than 5.

0.

8. The composition according to claim 1, wherein the HCA is coumaric acid.

9. The composition according to claim 1, wherein the composition does not contain HCA crystals.

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