Mineral facial sunscreen cream

Abstract

The present invention relates generally to methods and compositions suitable for protecting skin from ultraviolet radiation. Disclosed are sunscreen compositions comprising a plurality of dispersions comprising inorganic particles having different average sizes that absorb, reflect and / or scatter ultraviolet rays. Certain aspects describe sunscreen compositions comprising additives that provide additional cosmetic benefits.

Description

[0001] Cross-reference related applications

[0002] This application claims the priority benefit of U.S. Provisional Patent Application Serial No. 63 / 522,953, filed June 23, 2023, which is incorporated herein by reference in its entirety. Background of the Invention

[0004] A. Field of Invention

[0005] This invention generally relates to sunscreen compositions. More specifically, it relates to sunscreen formulations comprising a variety of inorganic particles that provide adequate sun protection factor (SPF) coverage while also providing a nearly transparent formulation.

[0006] B. Relevant Technical Description

[0007] Certain sunscreen compositions are known in the art. Various molecules, including inorganic particles (e.g., zinc oxide, titanium dioxide) and organic UV filters (e.g., oxybenzone), can be incorporated into sunscreen compositions to protect against UV radiation. Typically, zinc and / or zinc plus titanium dioxide mixtures leave a white-like residue on the skin of the end user. This phenomenon is commonly referred to as "ghosting" because it is observable by the user (e.g., giving the end user a white and / or whitish appearance). End users generally consider this appearance undesirable and evidence that the sunscreen composition has not been properly dispersed and / or properly absorbed. There is a need for improved sunscreen compositions that do not cause ghosting while still containing a sufficient concentration of inorganic particles to provide the desired Sun Protection Factor (SPF) rating. Summary of the Invention

[0008] This invention overcomes the shortcomings of the prior art by providing a stable composition comprising a mixture of inorganic particles that provides sufficient SPF protection while offering a near-transparent formulation. Furthermore, some aspects provided herein are sunscreen compositions comprising additives for additional cosmetic benefits.

[0009] In some instances, the composition comprises inorganic particles with a bimodal distribution of average particle diameter. The inventors have discovered that employing a combination of inorganic particles with different and non-overlapping average particle diameters can provide protection against sunlight, particularly against ultraviolet radiation, while avoiding the undesirable whitening effect of many conventional sunscreen compositions. The inorganic particles provide protection against sunlight, particularly against ultraviolet radiation, by absorbing, reflecting, and scattering light, thereby reducing the total amount of light reaching the skin. In some instances, the sunscreen compositions provided herein comprise a mixture of two or more zinc oxide particle dispersions with different average diameters, enabling the composition to provide a sun protection factor (SPF) rating greater than or equal to about 30.

[0010] In one example, the present invention discloses a sunscreen composition comprising a first zinc oxide particle dispersion comprising zinc oxide particles having an average particle diameter of about 110 nanometers (nm) to about 160 nm, the average particle diameter being determined by intensity-weighted average size measurement using dynamic light scattering; and a second zinc oxide particle dispersion comprising zinc oxide particles having an average particle diameter different from that of the first zinc oxide particle dispersion. In some examples, when applied to a surface, the composition provides a sun protection factor (SPF) rating greater than or equal to 30, preferably wherein the SPF is greater than or equal to about 33. In some examples, the composition further comprises at least a third zinc oxide particle dispersion comprising zinc oxide particles having a third average particle diameter different from the average particle diameters of the first and second zinc oxide particle dispersions. In some instances, the second zinc oxide particle dispersion comprises zinc oxide particles having an average particle diameter of about 195 nm to about 245 nm, the average particle diameter being determined by intensity-weighted average size measurement using dynamic light scattering. In some instances, the third zinc oxide particle dispersion comprises zinc oxide particles having an average particle diameter of about 280 nm to 330 nm, the average particle diameter being determined by intensity-weighted average size measurement using dynamic light scattering. At least one of the zinc oxide particle dispersions may have zinc oxide particles coated with a coating, preferably wherein the coating comprises triethoxyoctylsilane and / or hydrogendimethylsiloxane. In some instances, the zinc oxide particles are dispersed in an oil-in-water emulsion.

[0011] The average diameter of the first zinc oxide particle dispersion can be any one of 120nm, 121nm, 122nm, 123nm, 124nm, 125nm, 126nm, 127nm, 128nm, 129nm, 130nm, 131nm, 132nm, 133nm, 134nm, 135nm, 136nm, 137nm, 138nm, 139nm, 140nm, 141nm, 142nm, 143nm, 144nm, and 145nm, smaller than any of the above values, larger than any of the above values, between any of the above values, or any range thereof. The average diameter of the second zinc oxide particle dispersion can be any one of 210nm, 211nm, 212nm, 213nm, 214nm, 215nm, 216nm, 217nm, 218nm, 219nm, 220nm, 221nm, 222nm, and 223nm, smaller than any of the above values, larger than any of the above values, between any of the above values, or any range thereof. The average diameter of the third zinc oxide particle dispersion can be any one of 295nm, 296nm, 297nm, 298nm, 299nm, 300nm, 301nm, 302nm, 303nm, 304nm, 305nm, 306nm, 307nm, 308nm, 309nm, 310nm, 311nm, 312nm, 313nm, 314nm, and 315nm, smaller than any of the above values, larger than any of the above values, between any of the above values, or any range thereof. In some aspects, the first zinc oxide particle dispersion comprises particles having an average diameter of about 120 nm to about 145 nm, and the second zinc oxide particle dispersion comprises particles having an average diameter of about 210 nm to about 223 nm, the average diameter being determined by intensity-weighted average size measurement using dynamic light scattering. In other aspects, the third zinc oxide particle dispersion comprises zinc oxide particles having an average particle diameter of about 295 nm to 315 nm, the average particle diameter being determined by intensity-weighted average size measurement using dynamic light scattering.

[0012] In one aspect, the first zinc oxide particle dispersion comprises particles having an average diameter of about 137 nm, and the second zinc oxide particle dispersion comprises particles having an average diameter of about 221 nm, the average diameter being determined by intensity-weighted average size measurement using dynamic light scattering. In another aspect, the third zinc oxide particle dispersion comprises particles having an average diameter of about 305 nm, the average diameter being determined by intensity-weighted average size measurement using dynamic light scattering.

[0013] The sunscreen compositions disclosed herein may contain zinc oxide in amounts of any one of 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 11 wt%, 12 wt%, 13 wt%, 14 wt%, 15 wt%, 16 wt%, 17 wt%, 18 wt%, 19 wt%, 20 wt%, 21 wt%, 22 wt%, 23 wt%, 24 wt%, 25 wt%, 26 wt%, 27 wt%, 28 wt%, 29 wt%, 30 wt%, 31 wt%, 32 wt%, 33 wt%, 34 wt%, 35 wt%, 36 wt%, 37 wt%, 38 wt%, 39 wt%, and 40 wt%, less than any of the aforementioned values, greater than any of the aforementioned values, between any of the aforementioned values, or any range thereof. In some examples, the compositions contain less than or equal to 35 wt% zinc oxide, preferably less than or equal to 25 wt% zinc oxide, and more preferably about 22 wt% to 23 wt% zinc oxide. In some aspects, the composition comprises about 10% to about 30% by weight of zinc oxide, preferably about 15% to about 23% by weight. In some examples, the composition has a pH of about 5.5 to about 8.0; an initial viscosity of about 19,000 centipoise (cP) to about 80,000 cP; a viscosity of about 30,000 cP to about 120,000 cP 24 hours after the initial production of the composition; a specific gravity of about 0.9 to about 1.25; and / or a hardness of about 28.00 to about 88.20, which is measured using a hemispherical probe (TA43).

[0014] The composition may also contain one or more of the ingredients described herein. For example, the composition may also contain one or more cosmetic and / or therapeutic agents, preferably said cosmetic and / or therapeutic agents are redness-reducing agents. In some aspects, said redness-reducing agents contain Myrothamnus flabellifolia and / or bisabolol. In some instances, compositions according to this disclosure may comprise any one, any combination thereof, or all of the following: water, isononyl isononanoate, propylene glycol, glyceryl stearate, cetearyl alcohol polyether-25, polydimethylsiloxane, cetearyl alcohol, silica, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, disodium dicofol PEG-15 disulfide, squalane, phenoxyethanol, tocopheryl acetate, caprylyl glycol, polysorbate 60, chlorophenoxyethanol, bisabolol, disodium EDTA, xanthan gum, C12-15 alkyl benzoate, triethoxyoctylsilane, hydrogenated polydimethylsiloxane, and / or polyhydroxystearic acid. The amounts of the components in the composition may vary (e.g., from as low as 0.000001% by weight to as high as 80% by weight or any range thereof). In one example, the composition comprises 30% to 50% by weight of water, 10% to 15% by weight of isononyl isononanoate, 1% to 5% by weight of propylene glycol, 1% to 5% by weight of glyceryl stearate, 1% to 3% by weight of cetearyl alcohol polyether-25, 0.1% to 3% by weight of polydimethylsiloxane, 0.1% to 3% by weight of cetearyl alcohol, 0.1% to 3% by weight of silica, 0.1% to 3% by weight of hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, 0.1% to 1% by weight of disodium dicocoyl ethylenediamine PEG-15 disulfide, 0.1% to 1% by weight of squalane, 0.1% to 1% by weight of phenoxyethanol, and 0. 0.01 wt% to 0.5 wt% of tocopheryl acetate, 0.01 wt% to 0.5 wt% of octyl glycol, 0.01 wt% to 0.5 wt% of polysorbate 60, 0.01 wt% to 0.5 wt% of chlorphenesin, 0.01 wt% to 0.5 wt% of bisabolol, 0.01 wt% to 0.5 wt% of disodium EDTA, 0.01 wt% to 0.5 wt% of xanthan gum, 5 wt% to 15 wt% of C12-15 alkyl benzoate, 0.1 wt% to 3 wt% of triethoxyoctylsilane, 0.01 wt% to 1 wt% of hydrogenated polydimethylsiloxane and / or 0.1 wt% to 3 wt% of polyhydroxystearic acid, wherein all amounts are weight percentages based on the total weight of the composition.

[0015] Methods of using the compositions disclosed herein are also disclosed. In one aspect, the compositions disclosed herein can be used to protect skin from ultraviolet radiation. In some instances, the method includes applying any of the compositions disclosed herein topically to the skin, such as the skin of the face, around the eyes, neck, torso, and / or arms. In some instances, the method of protecting skin from ultraviolet radiation includes applying a composition as disclosed herein to the skin in need, preferably facial skin. In one aspect, the disclosed compositions are used as sunscreen compositions and provide an SPF rating of greater than or equal to 30 when applied to the skin, while providing a clear or nearly clear formulation. In some aspects, when the composition is applied to the skin, the composition is rubbed onto the skin until the composition no longer appears white. In some aspects, when the composition is applied to the skin, the composition is rubbed onto the skin to provide a sun protection factor (SPF) rating of greater than or equal to 30 to the skin. In one aspect, any of the compositions disclosed herein are applied topically and left on the application area, removed from the application area after a period of time, and / or removed immediately after application.

[0016] The compositions disclosed herein may comprise at least, at most, or exactly two, three, four, or five different dispersions of inorganic particles comprising different average particle diameters. In some aspects, the inorganic particles may be, but are not limited to, zinc oxide and / or titanium dioxide. In some aspects, the composition comprises three different dispersions of zinc oxide particles comprising different average particle diameters. In some aspects, the composition comprises two different dispersions of zinc oxide particles comprising different average particle diameters, and a third dispersion comprising titanium dioxide particles. In some aspects, the composition comprises three different dispersions of zinc oxide particles comprising different average particle diameters.

[0017] In certain aspects, the compositions of the present invention are formulated as topical skin compositions. The compositions may have dermatologically acceptable carriers or precipitants for the compounds, compositions, and extracts. The compositions may also contain moisturizing agents or humectants, surfactants, polysiloxane-containing compounds, ultraviolet agents, oils, and / or other ingredients identified herein or known in the art. The compositions may be lotions, creams, body lotions, masks, scrubs, washes, gels, serums, emulsions (e.g., oil-in-water, water-in-oil, polysiloxane-in-water, polysiloxane-in-water, water-in-oil-in-water, oil-in-water-in-oil, polysiloxane-in-water-in-oil, etc.), solutions (e.g., aqueous solutions or hydro-alcoholic solutions), anhydrous bases (e.g., lipsticks or powders), ointments, milks, creams, aerosols, solid forms, eye gels, etc. The compositions may be in powder form (e.g., dried, lyophilized, granular, etc.). The composition can be formulated to be applied at least once, twice, three times, four times, five times, six times, seven times, or more than seven times daily during use. In some aspects of the invention, the composition can be storage-stable or color-stable, or both.It is also envisioned that the viscosity of the composition can be selected to achieve the desired result. For example, depending on the type of composition desired, the viscosity of such composition can be from about 1 cps to more than 1 million cps or any range or integer derived therefrom (e.g., 2 cps, 3 cps, 4 cps, 5 cps, 6 cps, 7 cps, 8 cps, 9 cps, 10 cps, 20 cps, 30 cps, 40 cps, 50 cps, 60 cps, 70 cps, 80 cps, 90 cps, 100 cps, 200 cps, 300 cps, 400 cps, 500 cps, 600 cps, 700 cps, 800 cps, 900 cps, 1000 cps, 2000 cps, 3000 cps, 4000 cps, 5000 cps, 6000 cps, 7000 cps). , 8000cps, 9000cps, 10000cps, 20000cps, 30000cps, 40000cps, 50000cps, 60000cps, 70 000cps, 80000cps, 90000cps, 100000cps, 200000cps, 300000cps, 400000cps, 500000cps The values ​​were 600,000 cps, 700,000 cps, 800,000 cps, 900,000 cps, 1,000,000 cps, 2,000,000 cps, 3,000,000 cps, 4,000,000 cps, 5,000,000 cps, and 10,000,000 cps, etc. (measured using a Brookfield viscometer at 2.5 rpm and 25°C with a TC rotor).

[0018] The compositions of the present invention can also be modified to have a desired oxygen radical scavenging capacity (ORAC) value. In some non-limiting aspects, the compositions of the present invention or their components or extracts identified in this specification can be modified to have an ORAC value of at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, 95, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, 10000, 15000, 20000, 30000, 50000, 100000 or higher than 100000 or any range derived therefrom.

[0019] In a non-limiting aspect, the pH of the composition can be from about 6 to about 9. In some aspects, the pH can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14. The composition may contain triglycerides. Non-limiting examples include short-chain triglycerides, medium-chain triglycerides, and long-chain triglycerides. In some aspects, the triglyceride is a medium-chain triglyceride (e.g., caprylic / capric triglyceride). The composition may also contain a preservative. Non-limiting examples of preservatives include phenoxyethanol, methylparaben, propylparaben, or any mixture thereof. In some embodiments, the composition is free of parabens.

[0020] The compositions of the present invention may have UVA and UVB absorption properties. The compositions may have a sun protection factor (SPF) of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60 or higher, or any integer or range of SPF derived therefrom. The compositions may be sunscreen lotions, sprays, or creams.

[0021] The compositions of the present invention may further comprise any one, any combination, or all of the following additional ingredients: water, conditioning agents, chelating agents, humectants, pH adjusters, inorganic salts, preservatives, thickeners, polysiloxane-containing compounds, essential oils, structuring agents, vitamins, pharmaceutical ingredients, or antioxidants, or any combination or mixture of such ingredients. In some aspects, the compositions may comprise at least two, three, four, five, six, seven, eight, nine, ten, or more than ten, or all, of these additional ingredients identified in the foregoing sentences. Non-limiting examples of these additional ingredients are described throughout this specification and are incorporated herein by reference. The amount of such ingredients may be from 0.0001% to 99.9% by weight or volume of the composition, or any integer or range thereof disclosed in other parts of this specification, which are incorporated herein by reference.

[0022] Kits comprising the compositions of the present invention are also envisioned. In some embodiments, the composition is contained in a container. The container may be a bottle, dispenser, or box. The container may dispense a predetermined amount of the composition. In some aspects, the composition is dispensed as a spray, mist, clump, or liquid. The container may have markings on its surface. The markings may be words, abbreviations, pictures, or symbols.

[0023] In the context of this invention, aspects 1 to 20 are also disclosed. Aspect 1 is a sunscreen composition comprising a first zinc oxide particle dispersion comprising zinc oxide particles having an average particle diameter of about 110 nanometers (nm) to about 160 nm, the average particle diameter being determined by intensity-weighted average size measurement using dynamic light scattering; and a second zinc oxide particle dispersion comprising zinc oxide particles having an average particle diameter different from that of the first zinc oxide particle dispersion. Aspect 2 is a composition of aspect 1, further comprising at least a third zinc oxide particle dispersion comprising zinc oxide particles having a third average particle diameter different from the average particle diameter of the first and second zinc oxide particle dispersions. Aspect 3 is a composition of aspect 1 or 2, wherein the second zinc oxide particle dispersion comprises zinc oxide particles having an average particle diameter of about 195 nm to about 245 nm, the average particle diameter being determined by intensity-weighted average size measurement using dynamic light scattering. Aspect 4 is a composition of aspect 2 or 3, wherein the third zinc oxide particle dispersion comprises zinc oxide particles having an average particle diameter of about 280 nm to 330 nm, the average particle diameter being determined by intensity-weighted average size measurement using dynamic light scattering. Aspect 5 is a composition of any one of aspects 1 to 4, wherein the first zinc oxide particle dispersion comprises particles having an average diameter of about 120 nm to about 145 nm, and the second zinc oxide particle dispersion comprises particles having an average diameter of about 210 nm to about 223 nm, the average diameter being determined by intensity-weighted average size measurement using dynamic light scattering. Aspect 6 is a composition of any one of aspects 2 to 5, wherein the third zinc oxide particle dispersion comprises zinc oxide particles having an average particle diameter of about 295 nm to 315 nm, the average particle diameter being determined by intensity-weighted average size measurement using dynamic light scattering. Aspect 7 is a composition of any one of Aspects 1 to 6, wherein the first zinc oxide particle dispersion comprises particles having an average diameter of about 137 nm, and the second zinc oxide particle dispersion comprises particles having an average diameter of about 221 nm, the average diameter being determined by intensity-weighted average size measurement using dynamic light scattering. Aspect 8 is a composition of any one of Aspects 2 to 7, wherein the third zinc oxide particle dispersion comprises particles having an average diameter of about 305 nm, the average diameter being determined by intensity-weighted average size measurement using dynamic light scattering. Aspect 9 is a composition of any one of Aspects 1 to 8, wherein the zinc oxide particles of the at least one zinc oxide particle dispersion are coated with a coating, preferably wherein the coating comprises triethoxyoctylsilane and / or hydrogenated polydimethylsiloxane.Aspect 10 is a composition of any one of aspects 1 to 9, wherein the zinc oxide particles are dispersed in an oil-in-water emulsion. Aspect 11 is a composition of any one of aspects 1 to 10, wherein when applied to a surface, the composition provides a sun protection factor (SPF) rating of greater than or equal to 30, preferably wherein the SPF is greater than or equal to about 33. Aspect 12 is a composition of any one of aspects 1 to 11, wherein the composition contains less than 35% by weight of zinc oxide, preferably less than 25% by weight of zinc oxide, more preferably about 22% to 23% by weight of zinc oxide. Aspect 13 is a composition of any one of aspects 1 to 12, wherein: a) pH is from about 5.5 to about 8.0; b) initial viscosity is from about 19,000 centipoise (cP) to about 80,000 centipoise (cP); c) viscosity after 24 hours is from about 30,000 cP to about 120,000 cP; d) specific gravity is from about 0.9 to about 1.25; and / or e) hardness is from about 28.00 to about 88.20, measured using a hemispherical probe (TA43). Aspect 14 is a composition of any one of aspects 1 to 13, comprising from about 10% to about 30% by weight of zinc oxide, preferably from about 15% to about 23% by weight. Aspect 15 is a composition of any one of aspects 1 to 14, further comprising one or more cosmetic and / or therapeutic agents, preferably said cosmetic and / or therapeutic agents being redness-reducing agents. Aspect 16 is a composition of aspect 15, wherein the redness-reducing agent comprises myrothamnus flabellifolia and / or bisabolol. Aspect 17 is a composition of any one of aspects 1 to 16, further comprising water, isononyl isononanoate, propylene glycol, glyceryl stearate, cetearyl alcohol polyether-25, polydimethylsiloxane, cetearyl alcohol, silica, hydroxyethyl acrylate / sodium acryloyl dimethyl taurate copolymer, disodium ethylene dicocamide PEG-15 disulfate, squalane, phenoxyethanol, tocopheryl acetate, caprylyl glycol, polysorbate 60, chlorophenoxysilane, bisabolol, disodium EDTA, xanthan gum, C12-15 alkyl benzoate, triethoxyoctylsilane, hydrogenated polydimethylsiloxane, and / or polyhydroxystearic acid.Aspect 18 is a composition of aspect 17, comprising 30% to 50% water, 10% to 15% isononyl isononanoate, 1% to 5% propylene glycol, 1% to 5% glyceryl stearate, 1% to 3% cetearyl alcohol polyether-25, 0.1% to 3% polydimethylsiloxane, 0.1% to 3% cetearyl alcohol, 0.1% to 3% silica, 0.1% to 3% hydroxyethyl acrylate / sodium acryloyl dimethyl taurate copolymer, 0.1% to 1% disodium dicocoyl ethylenediamine PEG-15 disulfide, 0.1% to 1% squalane, and 0.1% to 1% phenoxyethanol. 0.01 wt% to 0.5 wt% of tocopheryl acetate, 0.01 wt% to 0.5 wt% of octyl glycol, 0.01 wt% to 0.5 wt% of polysorbate 60, 0.01 wt% to 0.5 wt% of chlorphenesin, 0.01 wt% to 0.5 wt% of bisabolol, 0.01 wt% to 0.5 wt% of disodium EDTA, 0.01 wt% to 0.5 wt% of xanthan gum, 5 wt% to 15 wt% of C12-15 alkyl benzoate, 0.1 wt% to 3 wt% of triethoxyoctylsilane, 0.01 wt% to 1 wt% of hydrogenated polydimethylsiloxane and / or 0.1 wt% to 3 wt% of polyhydroxystearic acid, wherein all amounts are weight percentages based on the total weight of the composition. Aspect 19 is a method for protecting skin from ultraviolet radiation, comprising applying the composition of any one of aspects 1 to 18 to the skin in need, preferably facial skin. Aspect 20 is a method of aspect 19, wherein applying the composition to the skin comprises rubbing the composition onto the skin until the composition does not appear white and / or rubbing the composition onto the skin to provide the skin with a sun protection factor (SPF) rating of greater than or equal to 30.

[0024] It is also envisioned that the compositions disclosed in this specification can be used as leave-on or rinse-off compositions. For example, a leave-on composition may be a leave-on composition applied topically to the skin and left on the skin for a period of time (e.g., at least 5, 6, 7, 8, 9, 10, 20, or 30 minutes, or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours, or overnight or all day). Alternatively, a rinse-off composition may be a product (e.g., with water) designed to be applied to the skin and then rinsed off or washed away from the skin for a period of time (e.g., less than 5, 4, 3, 2, or 1 minute). Examples of rinse-off compositions include skin cleansers, shampoos, conditioners, or soaps. Examples of leave-in compositions include skin moisturizers, sunscreens, face masks, night creams, or day creams.

[0025] It is contemplated that any embodiment discussed in this specification can be implemented with respect to any method or composition of the present invention, and vice versa. Furthermore, the compositions of the present invention can be used to implement the methods of the present invention.

[0026] In some embodiments, the compositions of the present invention may be pharmaceutically elegant or cosmetically elegant, or may have pleasant tactile properties. "Pharmaceutically elegant," "cosmetically elegant," and / or "pleasant tactile properties" describe compositions having specific tactile properties that feel comfortable on the skin (e.g., compositions that are not too thin or too oily, compositions with a silky texture, non-sticky or viscous compositions, etc.). Pharmaceutically elegant or cosmetically elegant may also refer to the creamy or lubricating properties of the composition, or the moisturizing properties of the composition.

[0027] Products comprising the compositions of the present invention are also envisioned. In a non-limiting aspect, the products may be cosmetic products. These cosmetic products may be those described in other parts of this specification or known to those skilled in the art. Non-limiting examples of products include moisturizers, creams, lotions, skin softeners, serums, gels, washes, body lotions, scrubs, foundations, night creams, lipsticks, facial cleansers, toners, sunscreens, face masks, anti-aging products, deodorants, antiperspirants, perfumes, colognes, etc.

[0028] "Topical application" refers to applying or spreading the composition onto the surface of the lips or stratum corneum. "Topical skin composition" includes compositions suitable for topical application to the skin, lips, and / or stratum corneum. Such compositions are generally dermatologically acceptable because they do not exhibit excessive toxicity, incompatibility, instability, allergic reactions, etc., when applied to the lips, skin, and / or stratum corneum. The topical skin care compositions of the present invention may have a selected viscosity to avoid significant dripping or accumulation after application to the lips, skin, and / or stratum corneum.

[0029] "Keratinous tissue" includes the keratin-containing layer that forms the outermost protective layer of mammals, including but not limited to the lips, skin, hair, and nails.

[0030] The terms "about" or "approximately" are defined as close to what a person skilled in the art would understand. In one non-limiting embodiment, these terms are defined as within ±10%, preferably within ±5%, more preferably within ±1%, and most preferably within ±0.5%.

[0031] The term "substantially" and its variations are defined as, as understood by one of ordinary skill in the art, to a large extent but not necessarily entirely, what is specified, and in a non-limiting embodiment, substantially means within ±10%, ±5%, ±1%, or ±0.5%.

[0032] The terms “inhibit” or “reduce” or any variations thereof include any measurable reduction or complete inhibition to achieve the desired result. The terms “promote” or “increase” or any variations thereof include any measurable increase, such as a measurable increase of a protein or molecule (e.g., matrix proteins such as fibronectin, laminin, collagen, or elastin, or molecules such as hyaluronic acid) to achieve the desired result.

[0033] The term "effective," as used in the specification and / or claims, means sufficient to achieve the desired, anticipated, or anticipated result.

[0034] When used in the claims and / or description in conjunction with the terms "comprising," "including," "having," or "containing," or any variations thereof, the absence of a quantifier or singular designation before an element may mean "one / type," but it is also consistent with the meaning of "one / type or more / types," "at least one / type," and "one / type or more than one / type."

[0035] As used in this specification and claims, the terms "comprising," "having," "including," or "containing" are inclusive or open-ended and do not exclude additional, unlisted elements or method steps.

[0036] The composition and its method of use may "comprise / include", "consistently constitute" or "consistent with" any of the ingredients or steps disclosed in this specification. Regarding the phrase "consistently constitute", the fundamental and novel feature of the compositions and methods of the present invention is the ability to provide a sufficient SPF grade while avoiding whitening by using a combination of inorganic particles with different average particle diameters.

[0037] The phrase "ghosting" or "ghostly" as used in this article refers to an abnormally pale and / or white appearance of the skin due to the presence of a noticeable layer of residue or residue-like deposits. This phenomenon is usually visible to the naked eye.

[0038] The phrase "and / or" means "and," "or," or "or." For illustration, A, B, and / or C include: A alone, B alone, C alone, a combination of A and B, a combination of A and C, a combination of B and C, or a combination of A, B, and C.

[0039] Other objects, features, and advantages of the present invention will become apparent from the following detailed description. However, it should be understood that while the detailed description and examples point to specific embodiments of the invention, they are given by way of illustration only. Furthermore, variations and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. Detailed Implementation

[0040] As described above, several unique aspects of this invention lie in combining multiple inorganic particulate dispersions with different average particle diameters. This allows for the benefit of providing a sufficient SPF grade while maintaining a transparent or near-transparent formulation to avoid a whitish appearance.

[0041] The non-limiting aspects of the invention are described in more detail in the following subsections.

[0042] Some of the compositions disclosed herein are designed for use as sunscreen compositions. In some instances, the compositions rely on a unique combination of any one, any combination, or all of certain compositions comprising one or a combination of predominantly micron-sized zinc oxide particles, nano-sized zinc oxide particles, and micron-sized and / or nano-sized titanium dioxide particles. Non-limiting examples of such compositions are provided in Examples 4, Tables 8, 9, and 10.

[0043] Some of the compositions disclosed herein can be applied to the skin or hair and remain on the skin or hair for a period of time (e.g., at least 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 10 minutes, 20 minutes, 30 minutes, or 60 minutes or more). Afterward, if necessary, the composition can be rinsed off or peeled off the skin. Some of the compositions disclosed herein can be applied to the skin and immediately rinsed off. Some of the compositions disclosed herein can be applied to the skin and at least partially absorbed by the skin.

[0044] These and other non-limiting aspects of the invention are described in the following sections.

[0045] A. Active ingredients

[0046] This invention is based on the determination that various zinc oxide dispersions comprising particles with different average particle diameters can be used to create sunscreen compositions capable of providing an SPF rating greater than 30 while avoiding a white cast appearance. In some instances, the sunscreen compositions described herein comprise at least one zinc oxide dispersion containing zinc oxide particles having an average particle diameter of about 110 nm to about 160 nm. In some instances, the sunscreen compositions comprise at least a second zinc oxide dispersion containing zinc oxide particles having an average particle diameter of about 195 nm to about 245 nm. In some instances, the sunscreen compositions provided herein provide an SPF rating greater than or equal to 30 while avoiding a white cast appearance.

[0047] Zinc oxide is an inorganic particulate that protects users from UV damage by absorbing, reflecting, and / or scattering ultraviolet (UV) rays. In some instances, this ingredient is commercially available, such as from Kobo Products Inc., which offers zinc oxide dispersions containing zinc oxide particles, the average particle diameter of which is determined by intensity-weighted average size measurement using dynamic light scattering, for example, formulations under the trade names TNP65MZS, TNPB80MZCM-G, and TNP70ZSI. As described herein, these ingredients have been identified as suitable for use in combination with other ingredients to provide sunscreen compositions with an adequate SPF rating while avoiding a white cast appearance.

[0048] In some instances, the compositions provided herein comprise at least one dispersion of zinc oxide particles, the dispersion comprising zinc oxide particles having an average particle diameter of about 110 nm to about 160 nm, said average particle diameter being determined by intensity-weighted average size measurement using dynamic light scattering. In some instances, the average diameter of the zinc oxide particles in the dispersion may be 110 nm, 111 nm, 112 nm, 113 nm, 114 nm, 115 nm, 116 nm, 117 nm, 118 nm, 119 nm, 120 nm, 121 nm, 122 nm, 123 nm, 124 nm, 125 nm, 126 nm, 127 nm, 128 nm, 129 nm, 130 nm, 131 nm, 132 nm, 133 nm, 134 nm, 135 nm, 13 The size is any one of the following: 6nm, 137nm, 138nm, 139nm, 140nm, 141nm, 142nm, 143nm, 144nm, 145nm, 146nm, 147nm, 148nm, 149nm, 150nm, 151nm, 152nm, 153nm, 154nm, 155nm, 156nm, 157nm, 158nm, 159nm, and 160nm, smaller than any of the above values, larger than any of the above values, or between any of the above values. In some instances, the size is determined in an organic solvent (e.g., hexane) or a non-organic solvent (e.g., water).

[0049] In some instances, the compositions provided herein comprise at least a second dispersion of zinc oxide particles, the second dispersion comprising secondary zinc oxide particles having an average particle diameter of about 195 nm to about 245 nm, said average particle diameter being determined by intensity-weighted average size measurement using dynamic light scattering. In some embodiments, the average diameter of the secondary zinc oxide particles in the second dispersion may be 195 nm, 196 nm, 197 nm, 198 nm, 199 nm, 200 nm, 201 nm, 202 nm, 203 nm, 204 nm, 205 nm, 206 nm, 207 nm, 208 nm, 209 nm, 210 nm, 211 nm, 212 nm, 213 nm, 214 nm, 215 nm, 216 nm, 217 nm, 218 nm, 219 nm, 220 nm, etc. The values ​​are: m, 221nm, 222nm, 223nm, 224nm, 225nm, 226nm, 227nm, 228nm, 229nm, 230nm, 231nm, 232nm, 233nm, 234nm, 235nm, 236nm, 237nm, 238nm, 239nm, 240nm, 241nm, 242nm, 243nm, 244nm, and 245nm, any one of the above values, less than any of the above values, greater than any of the above values, or between any of the above values.

[0050] In some instances, the compositions provided herein comprise at least a third dispersion of zinc oxide particles, the third dispersion comprising tertiary zinc oxide particles having an average particle diameter of about 280 nm to about 330 nm, said average particle diameter being determined by intensity-weighted average size measurement using dynamic light scattering. In some embodiments, the average diameter of the tertiary zinc oxide particles in the third dispersion may be 280 nm, 281 nm, 282 nm, 283 nm, 284 nm, 285 nm, 286 nm, 287 nm, 288 nm, 289 nm, 290 nm, 291 nm, 292 nm, 293 nm, 294 nm, 295 nm, 296 nm, 297 nm, 298 nm, 299 nm, 300 nm, 301 nm, 302 nm, 303 nm, 304 nm, or 305 nm. The values ​​are: m, 306nm, 307nm, 308nm, 309nm, 310nm, 311nm, 312nm, 313nm, 314nm, 315nm, 316nm, 317nm, 318nm, 319nm, 320nm, 321nm, 322nm, 323nm, 324nm, 325nm, 326nm, 327nm, 328nm, 329nm, and 330nm, any one of the above values, less than any of the above values, greater than any of the above values, or between any of the above values.

[0051] This combination of ingredients can be used in different product forms to treat various skin conditions and / or protect the skin from various conditions, such as sunburn. By way of non-limiting examples, the combination of ingredients can be formulated in emulsions (e.g., oil-in-water, water-in-oil), gels, serums, gel emulsions, gel serums, lotions, masks, scrubs, lotions, creams, or body lotions.

[0052] The extracts described herein can be extracts prepared by extraction methods and combinations thereof known in the art. Non-limiting examples of extraction methods include the use of liquid-liquid extraction, solid-phase extraction, water extraction, ethyl acetate extraction, alcohol extraction, acetone extraction, oil extraction, supercritical carbon dioxide extraction, thermal extraction, pressure extraction, pressure drop extraction, ultrasonic extraction, etc. The extracts can be liquids, solids, dried liquids, resuspended solids, etc.

[0053] B. Dosage of ingredients

[0054] It is envisioned that the compositions of the present invention may contain any amount of the ingredients discussed in this specification. The compositions may also contain any combination of additional ingredients (e.g., pigments or additional cosmetic or pharmaceutical ingredients) described throughout this specification. The concentration of any ingredient in the composition may vary. For example, in a non-limiting embodiment, the composition in its final form may contain, substantially consist of, or consist of, for example, at least about 0.0001%, 0.0002%, 0.0003%, 0.0004%, 0.0005%, 0.0006%, 0.0007%, 0.0008%, 0.0009%, 0.0010%, 0.0011%, 0.0012%, 0.0013%, 0.0014%, 0.0015%, 0.0016%, 0.0017%, 0.0018%, 0.0019%, 0.0020%, 0.0021%, and 0.0022%. 0.0023%, 0.0024%, 0.0025%, 0.0026%, 0.0027%, 0.0028%, 0.0029%, 0.0030%, 0.0031%, 0.0032%, 0.0033%, 0.0034%, 0.0035%, 0.0036%, 0.0037%, 0.0038%, 0.0039%, 0.0040%, 0.0041%, 0.0042%, 0.0043%, 0.0044%, 0.0045%, 0.0046%, 0.0047%, 0.0048%, 0.0049%, 0.0050%, 0 0.0051%, 0.0052%, 0.0053%, 0.0054%, 0.0055%, 0.0056%, 0.0057%, 0.0058%, 0.0059%, 0.0060%, 0.0061%, 0.0062%, 0.0063%, 0.0064%, 0.0065%, 0.0066%, 0.0067%, 0.0068%, 0.0069%, 0.0070%, 0.0071%, 0.0072%, 0.0073%, 0.0074%, 0.0075%, 0.0076%, 0.0077%, 0.0078%, 0 0.0079%, 0.0080%, 0.0081%, 0.0082%, 0.0083%, 0.0084%, 0.0085%, 0.0086%, 0.0087%, 0.0088%, 0.0089%, 0.0090%, 0.0091%, 0.0092%, 0.0093%, 0.0094%, 0.0095%, 0.0096%, 0.0097%, 0.0098%, 0.0099%, 0.0100%, 0.0200%, 0.0250%, 0.0275%, 0.0300%, 0.0325%, 0.0350%, 0.0375%、0.0400%、0.0425%、0.0450%、0.0475%、0.0500%、0.0525%、0.0550%、0.0575%、0.0600%、0.0625%、0.0650%、0.0675%、0.0700%、0.0725%、0.0750%、0.0775%、0.0800%、0.0825%、0.0850%、0.0875%、0.0900%、0.0925%、0.0950%、0.0975%、0.1000%、0.1250%、0.1500%、0.1750%、0.2000%、0.2250%、0.2500%、0.2750%、0.3000%、0.3250%、0.3500%、0.3750%、0.4000%、0.4250%、0.4500%、0.4750%、0.5000%、0.5250%、0.5500%、0.5750%、0.6000%、0.6250%、0.6500%、0.6750%、0.7000%、0.7250%、0.7500%、0.7750%、0.8000%、0.8250%、0.8500%、0.8750%、0.9000%、0.9250%、0.9500%、0.9750%、1.0%、1.1%、1.2%、1.3%、1.4%、1.5%、1.6%、1.7%、1.8%、1.9%、2.0%、2.1%、2.2%、2.3%、2.4%、2.5%、2.6%、2.7%、2.8%、2.9%、3.0%、3.1%、3.2%、3.3%、3.4%、3.5%、3.6%、3.7%、3.8%、3.9%、4.0%、4.1%、4.2%、4.3%、4.4%、4.5%、4.6%、4.7%、4.8%、4.9%、5.0%、5.1%、5.2%、5.3%、5.4%、5.5%、5.6%、5.7%、5.8%、5.9%、6.0%、6.1%、6.2%、6.3%、6.4%、6.5%、6.6%、6.7%、6.8%、6.9%、7.0%、7.1%、7.2%、7.3%、7.4%、7.5%、7.6%、7.7%、7.8%、7.9%、8.0%、8.1%、8.2%、8.3%、8.4%、8.5%、8.6%、8.7%、8.8%、8.9%、9.0%、9.1%、9.2%、9.3%、9.4%、9.5%、9.6%、9.7%、9.8%、9.9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 35%, 40%, 45%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99%, or any range thereof, at least one of the ingredients mentioned throughout this specification and claims. In a non-limiting respect, percentages may be calculated by weight or volume of the total composition. Those skilled in the art will understand that concentrations can vary depending on the addition, substitution, and / or reduction of ingredients in a given composition.

[0055] C. Carrier

[0056] The compositions of the present invention can comprise or be incorporated into all types of carriers and supports. The carriers or supports can be pharmaceutically or dermatologically acceptable. Non-limiting examples of carriers or supports include water, glycerin, alcohol, oils, silicon-containing compounds, silicone compounds, and waxes. Variations and other suitable carriers will be apparent to those skilled in the art and are applicable to the present invention. In some aspects, the concentrations and combinations of compounds, ingredients, and reagents can be selected such that the combinations are chemically compatible and do not form complexes that precipitate from the finished product.

[0057] D. Structure

[0058] The compositions of the present invention can be structured or formulated into a variety of different forms. Non-limiting examples include emulsions (e.g., water-in-oil, water-in-oil, water-in-oil, water-in-polysiloxane, polysiloxane-in-water, oil-in-water-in-oil, polysiloxane-in-water-in-oil emulsions), creams, lotions, solutions (aqueous solutions and hydroalcoholic solutions), anhydrous bases (e.g., lipsticks and powders), gels, masks, scrubs, body lotions, peeling agents, and ointments. Variations and other structures will be apparent to those skilled in the art and are applicable to the present invention.

[0059] E. Additional ingredients

[0060] In addition to the combinations of ingredients disclosed by the inventors, the compositions may also include additional ingredients, such as cosmetic ingredients and pharmaceutical active ingredients. Non-limiting examples of these additional ingredients are described in the following subsections.

[0061] 1. Cosmetic ingredients

[0062] The CTFA International Dictionary and Handbook of Cosmetic Ingredients (2004 and 2008) describes a variety of non-limiting cosmetic ingredients that can be used in the context of this invention. Examples of these ingredient categories include: fragrances (artificial and natural; e.g., gluconic acid, phenoxyethanol, and triethanolamine), dyes and coloring agents (e.g., Blue 1, Blue 1 Lake, Red 40, titanium dioxide, D&C Blue 4, D&C Green 5, D&C Orange 4, D&C Red 17, D&C Red 33, D&C Violet 2, D&C Yellow 10, D&C Yellow 11), flavorings / fragrances (e.g., stevia). Rebaudiana extract and menthol), adsorbents, lubricants, solvents, moisturizers (including, for example, emollients, humectants, film-forming agents, occlusive agents, and agents that affect the skin's natural moisturizing mechanisms), waterproofing agents, ultraviolet absorbers (physical and chemical absorbers, such as para-aminobenzoic acid ("PABA") and corresponding PABA derivatives, titanium dioxide, zinc oxide, etc.), essential oils, vitamins (e.g., vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, and vitamin K), trace metals (e.g., zinc, calcium, and selenium), anti-irritants (e.g., steroidal and nonsteroidal anti-inflammatory drugs), plant extracts (e.g., aloe vera, chamomile, cucumber extract, ginkgo biloba extract), and other plant extracts. Biloba, ginseng and rosemary), antimicrobial agents, antioxidants (e.g., BHT and tocopherol), chelating agents (e.g., disodium EDTA and tetrasodium EDTA), preservatives (e.g., methylparaben and propylparaben), pH adjusters (e.g., sodium hydroxide and citric acid), absorbents (e.g., aluminum octenyl succinate, kaolin, corn starch, oat starch, cyclodextrin, talc and zeolite), skin whitening agents and brightening agents (…). Examples include hydroquinone, nicotinamide lactate, humectants (e.g., sorbitol, urea, methyl gluceth-20, saccharide isomers, and mannitol), exfoliants, waterproofing agents (e.g., magnesium hydroxide / aluminum stearate), and skin conditioning agents (e.g., aloe vera extract, allantoin, bisabolol, ceramides, dimethicone, hyaluronic acid, biosaccharide gum-1, ethylhexylglycerin, pentylene glycol, hydrogenated polydecene, octyl dodecyl oleate, and dipotassium glycyrrhizate). The following subsections provide non-limiting examples of some of these ingredients.

[0063] a. Ultraviolet absorbers and / or reflectors

[0064] Ultraviolet absorbing and / or reflecting agents that can be used in combination with the compositions of the present invention include chemical sunscreens and physical sunscreens. Non-limiting examples of chemical sunscreens that can be used include para-aminobenzoic acid (PABA), PABA esters (glyceryl PABA ester, dimethyl PABA pentyl ester, and dimethyl PABA octyl ester), butyl PABA, ethyl PABA, ethyl dihydroxypropyl PABA, benzophenone (hydroxybenzophenone, sulphone, benzophenone, and benzophenone-1 to benzophenone-12), cinnamic acid esters (octinoxate, isoamyl p-methoxycinnamic acid, octyl methoxycinnamic acid ester, cinoxate, diisopropyl methylcinnamic acid, DEA salt of methoxycinnamic acid, ethyl diisopropyl cinnamic acid, glyceryl caprylate dimethoxycinnamic acid ester, and ethyl methoxycinnamic acid ester). Cinnamon esters, salicylates (homomethylsalicylate, benzyl salicylate, ethylene glycol salicylate, isopropyl benzyl salicylate, etc.), anthranilates, ethyl urocarbamate, homosalate, octyl salicylate, dibenzoylmethane derivatives (e.g., avobenzone), octocrylene, octyl triazine, galloyl gallate trioleate, glyceryl aminobenzoate, lawsone and dihydroxyacetone, ethylhexyl triazine, dioctylbutamidotriazine, benzyllidene propylene glycol polysiloxane. (malonate polysiloxane), terephthalimide dicamphor sulfonic acid, disodium phenyl dibenzimidazole tetrasulfonate, hexyl diethylaminohydroxybenzoylbenzoate, bis(diethylaminohydroxybenzoyl)benzoate, bis(benzoxazolyl)phenylethylhexyliminotriazine, cresoltrazolium trisiloxane, methylene bis-benzotriazolyl tetramethylbutylphenol, bis-ethylhexyloxyphenol methoxyphenyltriazine, 4-methylbenzyl camphor, and isoamyl 4-methoxycinnamate. Non-limiting examples of physical sunscreens include kaolin, talc, petrolatum, and metal oxides (e.g., titanium dioxide and zinc oxide). Certain UV-absorbing and / or reflective agents, including one or more agents disclosed herein, are also contemplated and may be excluded from the compositions of the invention. Specifically, chemical sunscreens, i.e., organic compound sunscreens, are excluded from certain compositions disclosed herein.

[0065] b. Moisturizer

[0066] Non-limiting examples of moisturizers that can be used with the compositions of the present invention include amino acids, chondroitin sulfate, diglycerides, erythritol, fructose, glucose, glycerin, glycerol polymers, ethylene glycol, 1,2,6-hexanetriol, honey, hyaluronic acid, hydrogenated honey, hydrogenated starch hydrolysate, inositol, lactitol, maltitol, maltose, mannitol, natural moisturizing factors, PEG-15 butylene glycol, polyglycerol sorbitol, salts of pyrrolidone carboxylic acid, potassium PCA, propylene glycol, sugar isomers, sodium glucuronide, sodium PCA, sorbitol, sucrose, trehalose, urea, and xylitol.

[0067] Other examples include acetylated lanolin, acetylated lanolin alcohol, alanine, algae extracts, Aloe barbadensis, Aloe barbadensis extract, Aloe barbadensis gel, Althea officinalis extract, Prunus armeniaca kernel oil, arginine, arginine aspartate, Arnica montana extract, aspartic acid, Persea gratissima oil, barrier sphingolipids, butanol, beeswax, behenol, β-sitosterol, Betula alba bark extract, Borago officinalis extract, Ruscus aculeatus extract, butylene glycol, Calendula officinalis extract, calendula oil, Euphorbia cerifera wax, rapeseed oil, caprylic / capric triglycerides, and Elettaria cardamom. Cardamomum oil, Copernicia cerifera wax, Daucus carota sativa oil, Ricinus communis oil, ceramide, ceresin, cetearyl alcohol polyether-5, cetearyl alcohol polyether-12, cetearyl alcohol polyether-20, cetearyl alcohol caprylate, cetearyl alcohol polyether-20, cetearyl alcohol polyether-24, cetearyl acetate, cetearyl caprylate, cetearyl palmitate, Anthemis nobilis oil, cholesterol, cholesterol ester, cholesterol hydroxystearate, citric acid, clary sage (Southern European sage),Salvia sclarea oil, cocoa butter (Theobroma cacao), cocoyl caprylate / caprylate, coconut oil (Cocos nucifera), collagen, collagen amino acids, corn oil (Zea mays), fatty acids, decyl oleate, polydimethylsiloxane copolyol, polydimethylsiloxane alcohol, dioctyl adipate, dioctyl succinate, pentaerythritol hexacaprylate / hexacaprylate, DNA, erythritol, ethoxydiethylene glycol, ethyl linoleate, eucalyptus globulus oil, evening primrose oil (Oenothera biennis), fatty acids, geranium maculatum oil, glucosamine, glucosamine glutamate. glutamate, glutamic acid, glyceryl polyether-26, glycerin, glycerol, glyceryl distearate, glyceryl hydroxystearate, glyceryl laurate, glyceryl linoleate, glyceryl myristate, glyceryl oleate, glyceryl stearate, glyceryl stearate SE, glycine, ethylene glycol stearate, ethylene glycol stearate SE, glycosaminoglycans, grape (Vitis vinifera) seed oil, hazelnut (American hazelnut, Corylus americana) nut oil, hazelnut (European hazelnut, Corylus avellana) nut oil, hexanediol, hyaluronic acid, hybrid safflower (Carthamus tinctorius) Tinctorius oil, hydrogenated castor oil, hydrogenated coconut oil glycerides, hydrogenated coconut oil, hydrogenated lanolin, hydrogenated lecithin, hydrogenated palm oil glycerides, hydrogenated palm kernel oil, hydrogenated soybean oil, hydrogenated tallow glycerides, hydrogenated vegetable oil, hydrolyzed collagen, hydrolyzed elastin, hydrolyzed glycosaminoglycans, hydrolyzed keratin, hydrolyzed soybean protein, hydroxylated lanolin, hydroxyproline, isocetyl stearate, isocetyl stearyloxystearate, isodecanoleate, isopropyl isostearate, isopropyl lanolinate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isostearamide DEA, isostearic acid, isostearyl lactate, isostearyl neopentanoate, jasmine (pure square flower),Jasminum officinale oil, jojoba (Buxus chinensis) oil, kelp, kukui (Aleurites moluccana) nut oil, lactamide MEA, lanolin alcohol polyether-16, lanolin alcohol polyether-10 acetate, lanolin, lanolin acid, lanolin alcohol, lanolin oil, lanolin wax, lavender (Lavandula angustifolia) oil, lecithin, lemon (Citrus medicalimonum) oil, linoleic acid, linolenic acid, macadamia ternifolia nut oil, maltitol, chamomile (Chamomilla) Recutita oil, methyl glucosesquistearate, methylsilanol PCA, mineral oil, mink oil, *Morchella esculenta* oil, myristyl lactate, myristyl myristate, myristyl propionate, neopentyl glycol dicaprylate / dicaprylate, octyl dodecyl alcohol, octyl dodecyl myristate, octyl stearate, octyl hydroxystearate, octyl palmitate, octyl salicylate, octyl stearate, oleic acid, olive oil, orange oil, palm oil, palmitic acid, panthenyl thioethylamine, panthenol, panthenol, paraffin wax, PCA, peach kernel oil, peanut oil, PEG-8 C12-18 ester, PEG-15 cocoamine, PEG-150 distearate, PEG-60 isostearyl glyceride, PEG-5 stearyl glyceride, PEG-30 stearyl glyceride, PEG-7 hydrogenated castor oil, PEG-40 hydrogenated castor oil, PEG-60 hydrogenated castor oil, PEG-20 methylglucose sesquistearate, PEG-40 sorbitan peroleate, PEG-5 soybean sterol, PEG-10 soybean sterol, PEG-2 stearate, PEG-8 stearate, PEG-20 stearate, PEG-32 stearate, PEG-40 stearate, PEG-50 stearate, PEG-100 stearate, PEG-150 stearate, pentadecyl lactone, peppermint (Mentha) Piperrita oil, petrolatum, phospholipids, plankton extract, polyamino acid polysaccharide condensate, polyglycerol-3 diisostearate, polyquaternium-24, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, polysorbate 85, potassium myristate, potassium palmitate, propylene glycol, propylene glycol dicaprylate / dicaprylate, propylene glycol dicaprylate, propylene glycol dinonanoate, propylene glycol laurate, propylene glycol stearate, propylene glycol stearate SE, PVP, pyridoxine dipalmitate, retinol, retinyl palmitate, rice (paddy rice)Oryza sativa oil, RNA, rosemary (Rosmarinus officinalis) oil, rose oil, safflower (Carthamus tinctorius) oil, sage (Salvia officinalis) oil, sandalwood (Santalum album) oil, serine, serum protein, sesame (Sesamum indicum) oil, shea butter (Butyrospermum parkii) fat, silk powder, sodium chondroitin sulfate, sodium hyaluronate, sodium lactate, sodium palmitate, sodium PCA, sodium polyglutamate, soluble collagen, sorbitan laurate, sorbitan oleate, sorbitan palmitate, sorbitan sesquioleate, sorbitan stearate, sorbitol, soybean (Glycine) The composition includes: sphingolipids, squalane, squalene, stearamide MEA-stearate, stearic acid, stearoxydimethylsiloxane, stearoxytrimethylsilane, stearyl alcohol, stearyl glycyrrhetinic acid, stearyl heptanoate, stearyl stearate, sunflower (Helianthus annuus) seed oil, sweet almond (Prunus amygdalus dulcis) oil, synthetic beeswax, tocopherol, tocopheryl acetate, tocopheryl linoleate, triterpenoid, tridecyl pentocarboxylate, tridecyl stearate, triethanolamine, triglyceride, urea, vegetable oils, water, waxes, wheat (Triticum vulgare) germ oil, and ylang-ylang (Cananga odorata) oil. Certain humectants, including one or more agents disclosed herein, are also contemplated and may be excluded from the compositions of the invention.

[0068] c. Antioxidants

[0069] Non-limiting examples of antioxidants that can be used with the compositions of the present invention include acetylcysteine, ascorbic acid peptides, ascorbate dipalmitate, ascorbate methylsilanol pectate, ascorbate palmitate, ascorbate stearate, BHA, BHT, tert-butylhydroquinone, cysteine, cysteine ​​HCl, dipentylhydroquinone, ditert-butylhydroquinone, diceryl thiodipropionate, dioleotocopherol methylsilanol, disodium ascorbate sulfate, distearate thiodipropionate, ditridecyl thiodipropionate, dodecyl gallate, isoascorbic acid, ascorbate ester, ethyl ferulic acid, ferulic acid, gallate, and hydrogen. Quinones, isooctyl mercaptoacetate, kojic acid, magnesium ascorbate, magnesium ascorbate phosphate, methylsilanol ascorbic acid, natural plant antioxidants such as green tea extract or grape seed extract, nordihydroguaiac acid, octyl gallate, phenylmercaptoacetic acid, potassium ascorbate tocopheryl phosphate, potassium sulfite, propyl gallate, quinones, rosmarinic acid, sodium ascorbate, sodium bisulfite, sodium isoascorbate, sodium metabisulfite, sodium sulfite, superoxide dismutase, sodium mercaptoacetate, sorbitol furfural, thiodiglycol, thiodiglycolamide, thiodiglycolic acid The following are listed: tocopherol, thioglycolic acid, thiolactic acid, thiosalicylic acid, tocopherol polyether-5, tocopherol polyether-10, tocopherol polyether-12, tocopherol polyether-18, tocopherol polyether-50, tocopherol, tocophersolan, tocopherol acetate, tocopherol linoleate, tocopherol nicotinate, tocopherol succinate, and tris(nonylphenyl) phosphite. Certain antioxidants, including one or more agents disclosed herein, are also contemplated to be excluded from the compositions of the invention.

[0070] d. Structuring agents

[0071] In other non-limiting aspects, the compositions of the present invention may contain a structuring agent. Structuring agents contribute to providing rheological properties to the composition in some respects, thereby contributing to the stability of the composition. In other respects, structuring agents may also act as emulsifiers or surfactants. Non-limiting examples of structuring agents include stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, stearic acid, palmitic acid, polyethylene glycol ethers of stearyl alcohol having an average of about 1 to about 21 ethylene oxide units, polyethylene glycol ethers of cetyl alcohol having an average of about 1 to about 5 ethylene oxide units, and mixtures thereof. Certain structuring agents, including one or more agents disclosed herein, are also contemplated for exclusion from the compositions of the present invention.

[0072] e. Emulsifiers

[0073] In some aspects of the invention, the composition does not contain an emulsifier. However, in other aspects, the composition may contain one or more emulsifiers. Emulsifiers can reduce interfacial tension between phases and improve the formulation and stability of the emulsion. The emulsifier may be a nonionic, cationic, anionic, or amphoteric emulsifier (see U.S. Patent Nos. 5,011,681, 4,421,769, and 3,755,560). Non-limiting examples include esters of glycerol, esters of propylene glycol, fatty acid esters of polyethylene glycol, fatty acid esters of polypropylene glycol, esters of sorbitol, esters of dehydrated sorbitan anhydride, carboxylic acid copolymers, esters and ethers of glucose, ethoxylated ethers, ethoxylated alcohols, alkyl phosphates, polyoxyethylene fatty ether phosphates, fatty acid amides, acyl lactates, soaps, TEA stearate / salt, oleyl alcohol polyether-3 phosphate DEA salt, polyethylene glycol 20 dehydrated sorbitan monolaurate (polysorbate 20), polyethylene glycol 5 soybean sterol, stearyl alcohol polyether-2, stearyl alcohol polyether-20. Cetearyl alcohol polyether-21, cetearyl alcohol polyether-20, cetearyl alcohol glucoside, cetearyl alcohol, C12-13 alkyl alcohol polyether-3, PPG-2 methyl gluconate distearate, PPG-5-cetearyl alcohol polyether-20, bis-PEG / PPG-20 / 20 polydimethylsiloxane, cetearyl alcohol polyether-10, polysorbate 80, cetyl phosphate, potassium cetyl phosphate, diethanolamine cetyl phosphate, polysorbate 60, glyceryl stearate, PEG-100 stearate, arachidyl alcohol, arachidyl glucoside, and mixtures thereof. Certain emulsifiers, including one or more agents disclosed herein, are also contemplated and may be excluded from the compositions of the invention.

[0074] f. Compounds containing polysiloxanes

[0075] In a non-limiting sense, polysiloxane-containing compounds include any member of the polymer family whose molecular backbone consists of alternating silicon and oxygen atoms and whose side groups are attached to silicon atoms. By varying the length of the -Si-O- chains, the side groups, and the crosslinking, polysiloxanes can be synthesized into a variety of materials. Their consistency can vary from liquid to gel to solid.

[0076] The polysiloxane-containing compounds that can be used in the context of this invention include those described herein or known to those skilled in the art. Non-limiting examples include silicone oils (e.g., volatile and non-volatile oils), gels, and solids. In some aspects, the polysiloxane-containing compounds include silicone oils, such as polyorganosiloxanes. Non-limiting examples of polyorganosiloxanes include polydimethylsiloxane, cyclomethicone, polysiloxane-11, phenyltrimethylsiloxane, trimethylsilyl-terminated trimethylsiloxane, stearoxytrimethylsilane, or mixtures of these substances and other organopolysiloxane materials in any given proportion to achieve desired consistency and application properties according to the intended use (e.g., for specific areas such as skin, hair, or eyes). "Volatile silicone oil" includes silicone oils with low heat of vaporization, typically less than about 50 calories per gram. Non-limiting examples of volatile silicone oils include: cyclomethyl polysiloxanes, such as Dow Corning 344 fluid, Dow Corning 345 fluid, Dow Corning 244 fluid, and Dow Corning 245 fluid, Volatile Silicon 7207 (Union Carbide Corp., Danbury, Conn.); and low-viscosity polydimethylsiloxanes, i.e., polydimethylsiloxanes with a viscosity of about 50 cst or less (e.g., polydimethylsiloxanes such as Dow Corning 200-0.5 cst fluid). Dow Corning fluids are available from Dow Corning Corporation (Midland, Michigan). Cyclomethyl polysiloxanes and polydimethylsiloxanes are described in the third edition of the CTFA Dictionary of Cosmetic Ingredients (incorporated by reference) as mixtures of cyclic dimethyl polysiloxane compounds and fully methylated linear siloxane polymers capped with trimethylsiloxy units, respectively. Other non-limiting volatile silicone oils that may be used in the context of this invention include those available from General Electric Co., Silicone Products Div., Waterford, NY, and Stauffer Chemical Co., Adrian, Michigan, and SWS Silicones Div. Certain polysiloxane-containing compounds, including one or more agents disclosed herein, are also contemplated for exclusion from the compositions of this invention.

[0077] g. Exfoliating agent

[0078] Exfoliants comprise ingredients that remove dead skin cells from the outer surface of the skin. These agents can act mechanically, chemically, and / or otherwise. Non-limiting examples of mechanical exfoliants include abrasives such as pumice, silica, fabrics, paper, shells, beads, solid crystals, solid polymers, etc. Non-limiting examples of chemical exfoliants include acid exfoliants and enzyme exfoliants. Acids that can be used as exfoliants include, but are not limited to, glycolic acid, lactic acid, citric acid, α-hydroxy acids, β-hydroxy acids, etc. Other exfoliants known to those skilled in the art are also contemplated as useful in the context of this invention. Certain exfoliants, including one or more agents disclosed herein, are also contemplated as being excluded from the compositions of this invention.

[0079] h. Essential oils

[0080] Essential oils comprise oils derived from herbs, flowers, trees, and other plants. These oils typically exist as tiny droplets between plant cells and can be extracted using several methods known to those skilled in the art (e.g., steam distillation, enfleurage (using fats), maceration, solvent extraction, or mechanical pressing). When these types of oils are exposed to air, they tend to evaporate (i.e., they are volatile). Therefore, although many essential oils are colorless, they oxidize and darken over time. Essential oils are insoluble in water but soluble in alcohols, ethers, non-volatile oils (vegetable oils), and other organic solvents. Typical physical properties found in essential oils include boiling points ranging from about 160°C to 240°C and densities from about 0.759 to about 1.096.

[0081] Essential oils are typically named after the plant from which they are found. For example, rose oil or peppermint oil comes from the plant of rose or mint, respectively. Non-limiting examples of essential oils that may be used in the context of this invention include sesame oil, macadamia oil, tea tree oil, evening primrose oil, Spanish sage oil, Spanish rosemary oil, coriander oil, thyme oil, allspice oil, rose oil, fennel oil, balsam oil, bergamot oil, rosewood oil, cypress oil, chamomile oil, sage oil, clary sage oil, clove oil, cypress oil, eucalyptus oil, fennel oil, sea fennel oil, frankincense oil, geranium oil, ginger oil, grapefruit oil, jasmine oil, juniper oil, lavender oil, lemon oil, lemongrass oil, lime oil, citrus oil, marjoram oil, myrrh oil, neroli oil, orange oil, patchouli oil, pepper oil, black pepper oil, petitgrain oil, pine oil, and rose of Otto. Otto oil, rosemary oil, sandalwood oil, spearmint oil, spikenard oil, vetiver oil, wintergreen oil, or ylang-ylang oil. Other essential oils known to those skilled in the art are also contemplated as useful in the context of this invention. Certain essential oils, including one or more agents disclosed herein, are also contemplated as being excluded from the compositions of this invention.

[0082] i. Thickener

[0083] Thickeners, including thickeners or gelling agents, include substances that can increase the viscosity of a composition. Thickeners include those that can increase the viscosity of a composition without substantially altering the efficacy of the active ingredients within the composition. Thickeners can also improve the stability of the compositions of the present invention. In some aspects of the invention, thickeners include hydrogenated polyisobutylene, trihydroxystearin, ammonium acryloyldimethyl taurate / VP copolymer, or mixtures thereof.

[0084] Non-limiting examples of additional thickeners that may be used in the context of this invention include carboxylic acid polymers, crosslinked polyacrylate polymers, polyacrylamide polymers, polysaccharides, and gums. Examples of carboxylic acid polymers include crosslinked compounds comprising one or more monomers derived from acrylic acid, substituted acrylic acid, and salts and esters of such acrylic and substituted acrylic acids, wherein the crosslinking agent comprises two or more carbon-carbon double bonds and is derived from a polyol (see U.S. Patent Nos. 5,087,445, 4,509,949, and 2,798,053; CTFA International Cosmetic Ingredient Dictionary, Fourth edition, 1991, pp. 12 and 80). Examples of commercially available carboxylic acid polymers include carbomers, which are homopolymers of acrylic acid crosslinked with allyl ethers of sucrose or pentaerythritol (e.g., CARBOPOL™ 900 series from BF GOODRICH).

[0085] Non-limiting examples of crosslinked polyacrylate polymers include cationic and nonionic polymers. Examples are described in U.S. Patent Nos. 5,100,660, 4,849,484, 4,835,206, 4,628,078, and 4,599,379.

[0086] Non-limiting examples of polyacrylamide polymers (including nonionic polyacrylamide polymers, which include substituted branched or linear polymers) include polyacrylamide, isoparaffins and lauryl ether-7, acrylamide and substituted acrylamide multiblock copolymers with acrylic acid and substituted acrylic acid.

[0087] Non-limiting examples of polysaccharides include cellulose, carboxymethyl hydroxyethyl cellulose, cellulose acetate propionate carboxylate, hydroxyethyl cellulose, hydroxyethyl ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl hydroxyethyl cellulose, microcrystalline cellulose, sodium cellulose sulfate, and mixtures thereof. Another example is alkyl-substituted cellulose, wherein the hydroxyl groups of the cellulose polymer are hydroxyalkylated (preferably hydroxyethylated or hydroxypropylated) to form hydroxyalkylated cellulose, and then further modified with C10-C30 straight-chain or branched alkyl groups via ether bonds. Typically, these polymers are ethers of C10-C30 straight-chain or branched alcohols with hydroxyalkyl cellulose. Other useful polysaccharides include stearin, which comprises a straight chain containing (1 to 3) linked glucose units, with one (1 to 6) linked glucose units for every three units.

[0088] Non-limiting examples of gums that can be used with the present invention include gum arabic, agar, alginic acid, ammonium alginate, amylopectin, calcium alginate, calcium carrageenan, carnitine, carrageenan, dextrin, gelatin, gellan gum, guar gum, guar gum hydroxypropyltrimethylammonium chloride, lithium montmorillonite, hyaluronic acid, hydrated silica, hydroxypropyl chitosan, hydroxypropyl guar gum, black privet gum, kelp, locust bean gum, natto gum, potassium alginate, potassium carrageenan, propylene glycol alginate, sclerotinia gum, sodium carboxymethyl dextran, sodium carrageenan, astragalus gum, xanthan gum, and mixtures thereof.

[0089] It is also envisioned that certain thickeners, including one or more agents disclosed herein, may be excluded from the compositions of the present invention.

[0090] j. Preservatives

[0091] Non-limiting examples of preservatives that may be used in the context of this invention include quaternary ammonium salt preservatives, such as polyquaternary ammonium salt-1 and benzalkonium halide (e.g., benzalkonium chloride ("BAC") and benzalkonium bromide), parabens (e.g., methylparaben and propylparaben), phenoxyethanol, benzyl alcohol, chlorobutanol, phenol, sorbic acid, thimerosal, or combinations thereof. Certain preservatives, including one or more agents disclosed herein, are also contemplated that may be excluded from the compositions of this invention.

[0092] k. Moisturizer

[0093] Useful emollients include the following: (a) silicone oils and their modifications, such as linear and cyclic polydimethylsiloxanes; amino silicone oils, alkyl silicone oils, alkylaryl silicone oils, and aryl silicone oils; (b) fats and oils, including natural fats and oils such as jojoba oil, soybean oil, sunflower oil, rice bran oil, avocado oil, almond oil, olive oil, sesame oil, peach kernel oil, castor oil, coconut oil, and mink oil; cocoa butter; tallow and lard; hardened oils obtained by hydrogenation of the above oils; and synthetic monoglycerides, diglycerides, and triglycerides, such as glyceryl myristate and glyceryl 2-ethylhexanoate; (c) waxes, such as carnauba wax, cetearyl wax, beeswax, lanolin, and their derivatives; (d) hydrophobic plant extracts; (e) hydrocarbons, such as liquid paraffin, petrolatum, microcrystalline wax, ceresin, squalene, pterostilbene, and mineral oils; (f) Higher fatty acids, such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, lanolinic acid, isostearic acid, arachidonic acid, and polyunsaturated fatty acids (PUFAs); (g) higher alcohols, such as lauryl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, behenyl alcohol, cholesterol, and 2-hexyldecyl alcohol; (h) esters, such as cetyl caprylate, myristyl lactate, cetyl lactate, isopropyl myristate, myristyl myristate, isopropyl palmitate, isopropyl adipate, butyl stearate, decyl oleate, cholesterol isostearate, glyceryl monostearate, glyceryl distearate, glyceryl tristearate, alkyl lactate, alkyl citrate, and alkyl tartrate; (i) Essential oils and their extracts, such as spearmint, jasmine, camphor, white cypress, bitter orange peel, ryu, turpentine, cinnamon, bergamot, Satsuma mandarin, calamus, pine, lavender, bay leaf, clove, hiba, eucalyptus, lemon, borage, thyme, peppermint, rose, sage, sesame, ginger, basil, juniper, lemongrass, rosemary, rosewood, avocado, grape, grape seed, myrrh, cucumber, watercress, calendula, elderflower, geranium, linden flower, amaranth, seaweed, ginkgo, ginseng, carrot, guarana, tea tree, jojoba, comfrey, oats, cocoa, orange blossom, vanilla, green tea, and pennyc. (j) oils of royal, aloe, menthol, eugenol, citral, citronellal, borneol, linalool, geraniol, evening primrose, camphor, thymol, spirantol, pinene, limonene, and terpenoids; (j) lipids, such as cholesterol, ceramides, sucrose esters, and pseudoceramides, as described in European Patent Specification No. 556957; (k) vitamins, minerals, and skin nutrients, such as vitamin A, vitamin E, and vitamin K; vitamin alkyl esters, including vitamin C alkyl esters; magnesium, calcium, and milk;(l) sunscreens, such as octyl methoxycinnamate (Parsol MCX) and butyl methoxybenzoylmethane (Parsol 1789); (l) phospholipids; (m) polyols, such as glycerin and propylene glycol; and polyols, such as polyethylene glycol; (n) anti-aging compounds, such as α-hydroxy acids and β-hydroxy acids; and (o) any mixture of the foregoing components, etc. Certain emollients, including one or more agents disclosed herein, are also contemplated and may be excluded from the compositions of the present invention.

[0094] l. Tackifier

[0095] Examples of suitable tackifiers include, but are not limited to, aliphatic hydrocarbon resins, aromatic modified aliphatic hydrocarbon resins, hydrogenated polycyclopentadiene resins, polycyclopentadiene resins, rosin, rosin esters, wood rosin, wood rosin esters, tall oil rosin, tall oil rosin esters, polyterpenes, aromatic modified polyterpenes, terpenoid phenols, aromatic modified hydrogenated polycyclopentadiene resins, hydrogenated aliphatic resins, hydrogenated aliphatic aromatic resins, hydrogenated terpenes and modified terpenes, hydrogenated rosin acids, hydrogenated rosin esters, polyisoprene, partially or fully hydrogenated polyisoprene, polybutene, partially or fully hydrogenated polybutene, etc. As some of the cited examples demonstrate, tackifiers can be fully or partially hydrogenated. Tackifiers can also be nonpolar (nonpolar means that the tackifier is substantially free of monomers having polar groups. Preferably, polar groups are absent, but if present, they are preferably present in an amount of up to about 5% by weight, preferably up to about 2% by weight, more preferably up to about 0.5% by weight). Certain tackifiers, including one or more agents disclosed herein, are also contemplated to be excluded from the compositions of the invention.

[0096] m. Coloring agent

[0097] The compositions of the present invention may also contain at least one cosmetically acceptable colorant, such as a pigment or dye. Examples of suitable pigments include, but are not limited to, inorganic pigments, organic pigments, lakes, pearlescent pigments, iridescent pigments, or optically variable pigments and mixtures thereof. Pigments should be understood as inorganic or organic, white or colored particles. Within the scope of the invention, said pigments may optionally be surface-treated, but are not limited to, treatments with, for example, polysiloxanes, perfluorinated compounds, lecithin, and amino acids. Certain colorants, including one or more agents disclosed herein, are also contemplated to be excluded from the compositions of the present invention.

[0098] n. surfactant

[0099] Surfactants suitable for use as surfactant components in the compositions of the present invention include nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, and zwitterionic surfactants, and can be used in combination with each other. Certain surfactants, including one or more agents disclosed herein, are also contemplated for exclusion from the compositions of the present invention.

[0100] o. pH adjuster

[0101] pH adjusters include inorganic and organic acids and bases, particularly ammonia, citric acid, phosphoric acid, acetic acid, sodium hydroxide, lactic acid, levulinic acid, glycolic acid, tartaric acid, malic acid, pyrrolidone carboxylic acid (PCA), succinic acid, citric acid, glutamic acid, 2-amino-2-methyl-1-propanol (AMP), and triethanolamine (TEA). Certain pH adjusters, including one or more reagents disclosed herein, are also contemplated and may be excluded from the compositions of the present invention.

[0102] p. reducing agent

[0103] Suitable reducing agents include, but are not limited to, salts of thiourea, thiosulfate, sulfite, bisulfite, metabisulfite, borohydride, and hypophosphite (e.g., sodium salts), ascorbic acid and its salts, esters, and derivatives (e.g., ascorbate palmitate and ascorbate polypeptides), and tocopherol and its salts, esters, and derivatives (e.g., tocopherol acetate). Other reducing agents are listed on pages 1655-56 of the INCI manual. Certain reducing agents, including one or more agents disclosed herein, are also contemplated to be excluded from the compositions of the present invention.

[0104] q. Fragrance

[0105] The compositions disclosed herein may optionally contain fragrances. Examples of possible fragrances include natural oils or naturally derived materials, as well as synthetic fragrances such as hydrocarbons, alcohols, aldehydes, ketones, esters, lactones, ethers, nitriles, and polyfunctional compounds. Non-limiting examples of natural oils include: basil (Ocimum basilicum) oil, bay laurel (Pimento acris) oil, lemon balm (Monarda didyma) oil, bergamot (Citrus aurantium bergamia) oil, cardamom (Elettaria cardamomum) oil, cedarwood (Cedrus atlantica) oil, chamomile (Anthemis nobilis) oil, cinnamon (Cinnamomum cassia) oil, lemongrass (Cymbopogonnardus) oil, sage (Salvia sclarea) oil, clove (Eugenia caryophyllus) oil, clove (Eufenia caryophyllus) oil, sedge (Cyperus esculentus) oil, and cypress (Cupressus esculentus) oil. Eucalyptus sempervirens oil, Eucalyptus citriodora oil, Geranium maculatum oil, Zingiber officinale oil, Citrus grandis oil, Hazelnut (Corylus avellana) nut oil, Jasminum officinale oil, Juniper (Juniperus communis) oil, Juniper (Juniperus oxycedrus) tar, Juniper (Juniperus virginiana) oil, Actinidia chinensis water, Lavandula hybrida oil, Lavandula angustifolia oil, Lavandula angustifolia water, Citrus medica oil. Limonum oil, lemongrass (Cymbopogon schoenanthus) oil, lemon (Citrus aurantifolia) oil, linden (heartleaf linden, Tiliacordata) oil, linden (heartleaf linden,Tilia cordata water, Citrus nobilis oil, Myristica fragrans oil, Citrus aurantium dulcis flower oil, Citrus aurantium dulcis oil, Citrus aurantium dulcis water, Pogostemoncablin oil, Menthe piperita oil, Menthe peperita water, Rosmarinus officinalis oil, Rose oil, Rosa damascena extract, Rosa multiflora extract, Aniba rosaeodora extract, Salvia officinalis oil, Santalum Oils of various aromatic compounds include: *Melaleuca alternifolia* (tea tree), *Melaleuca alternifolia* (tea tree), and *Cananga odorata* (ylang-ylang). Some non-limiting examples of synthetic hydrocarbon aromatics include caryophyllene, β-farnesene, limonene, α-pinene, and β-pinene. Some non-limiting examples of synthetic alcohol aromatics include 2-methylenebenzeneylbutanol (santalinol), citronellol, linalool, phenethyl alcohol, and α-terpineol (R=H). Some non-limiting examples of synthetic aldehyde aromatics include 2-methylundecaldehyde, citral, hexylcinnamaldehyde, isocycolcitral, lily of the valley aldehyde, and 10-undecenal. Some non-limiting examples of synthetic ketone fragrances include cashmeran, α-ionone, isocyclemone E, koavone, muscone, and tuna musk. Some non-limiting examples of synthetic ester fragrances include benzyl acetate, 4-tert-butylcyclohexyl acetate (cis and trans), cypress acetate, tricyclodecenyl acetate, isoborneol acetate, and α-terpineol acetate (R=acetyl). Some non-limiting examples of synthetic lactone fragrances include coumarin, jasmine lactone, muskalactone, and peach aldehyde. Some non-limiting examples of synthetic ether fragrances include ambroxan, anther, and galaxolide. Some non-limiting examples of synthetic nitrile fragrances include cinnamonitrile and gernonitrile. Finally,Some non-limiting examples of synthesized multifunctional fragrances include amyl salicylate, isoeugenol, hedione, piperaldehyde, neolizurol, and vanillin. Certain fragrances, including one or more agents disclosed herein, are also contemplated as being excluded from the compositions of the present invention.

[0106] r. foaming agent

[0107] Foaming agents include, for example, sodium lauryl sulfate, sodium lauroyl sarcosinate, sodium alkyl sulfosuccinate, sodium coconut oil fatty acid monoglyceride sulfonate, sodium α-olefin sulfonate, N-acyl amino acid salts such as N-acyl glutamate, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazoline betaine, maltitol fatty acid esters, sucrose fatty acid esters, polyglycerol fatty acid esters, fatty acid diethanolamides, polyoxyethylene sorbitan monostearate, polyoxyethylene hydrogenated castor oil, and polyoxyethylene fatty acid esters. These foaming agents can be used alone or in combination of two or more. Certain foaming agents, including one or more agents disclosed herein, are also contemplated as being excluded from the compositions of the present invention.

[0108] s. tanning agents

[0109] Suitable tanning agents include, but are not limited to, α-hydroxy aldehydes and α-hydroxy ketones, glyceraldehyde and related alcohol aldehydes, various indoles, imidazoles and their derivatives, and various approved pigmenting agents. Other suitable tanning agents include, but are not limited to, methylglyoxal, glyceraldehyde, erythritol, alloxan, 2,3-dihydroxysuccinaldehyde, 2,3-dimethoxysuccinaldehyde, 2-amino-3-hydroxysuccinaldehyde, and 2-benzylamino-3-hydroxysuccinaldehyde. Certain tanning agents, including one or more agents disclosed herein, are also contemplated to be excluded from the compositions of the present invention.

[0110] t. Astringent

[0111] Suitable astringents include, but are not limited to, aluminum citrate, aluminum lactate, birch extract, coffee extract, evening primrose extract, grape extract, henna extract, ivy extract, lemon extract, witch hazel extract, ammonium alum and potassium alum, aluminum triphosphate, aluminum glycinate and aluminum phenol sulfate, aluminum cloxa, aluminum allantoin, aluminum stearate, aluminum sulfate and aluminum citrate, sodium aluminum phosphate, sodium alum, sodium chlorohydroxylactic acid, calcium lactate, calcium chloride, hydrated calcium sulfate, aluminum sodium lactate, zinc acetate, zinc chloride, zinc sulfate, zinc lactate, zinc zeolite, zinc phenolsulfonate, and combinations thereof. "Extract" means whole fruit, legume, and / or plant or selected components of such fruit, legume, and / or plant. Certain astringents, including one or more agents disclosed herein, are also contemplated and may be excluded from the compositions of the present invention.

[0112] u. Preservatives

[0113] Suitable preservatives include, but are not limited to, methyl, ethyl, propyl, or butyl para-hydroxybenzoic acid, phenoxyethanol, o-phenylphenol, dehydroacetic acid or its salts, p-cresol, m-cresol, o-chloro-m-xylenol, peppermint oil, echinacea, safranin, cayenne pepper, tea tree oil, wild bergamot, chaparral, stinging metal, laurel, myrrh, rhatany bark, toothache tree, calendula, chamomile, mupirocin, neomycin sulfate, bacitracin, polymyxin B, levofloxacin, tetracyclines (chlortetracycline hydrochloride, oxytetracycline hydrochloride, and tetracycline hydrochloride), clindamycin phosphate, gentamicin sulfate, benzalkonium chloride, benzyl chloride, hexylresorcinol, methylbenzylethoxymonochloride, phenol, quaternary ammonium compounds, triclocarban, triclosan, and tea tree oil. It is also envisioned that certain preservatives, including one or more agents disclosed herein, may be excluded from the compositions of the present invention.

[0114] v. Deodorants and antiperspirants

[0115] Suitable antiperspirants and deodorants include, but are not limited to, zinc salts such as zinc sulfate and zinc chloride, glycine salts such as aluminum zirconium glycinate, aluminum hydroxychloride, aluminum hydroxyzirconium tetrachloride, zinc carbonate, o-phenylphenol, and quaternary ammonium compounds such as dimethyl benzyl ammonium chloride and hexamethyl ammonium chloride. Certain deodorants and / or antiperspirants, including one or more agents disclosed herein, are also contemplated as being excluded from the compositions of the present invention.

[0116] w. Brightening agent

[0117] Examples of skin brightening agents include, but are not limited to, hydroquinone, kojic acid, licorice and / or its derivatives, ascorbic acid and / or its derivatives, arbutin, bearberry extract, licorice root extract and its derivatives, Chlorella vulgaris extract, perilla extract, coconut fruit extract and / or other depigmenting agents. Certain skin brightening agents, including one or more agents disclosed herein, are also contemplated and may be excluded from the compositions of the present invention.

[0118] x. Biocides

[0119] Examples of biocides include, but are not limited to, triclosan, 3,4,4'-trichlorocarbazide (triclocarban); 3,4,4'-trifluoromethyl-4,4'-dichlorocarbazide (halocarban); 5-chloro-2-methyl-4-isothiazolin-3-one; iodopropynyl butylcarbamate; 8-hydroxyquinoline; 8-hydroxyquinoline citrate; 8-hydroxyquinoline sulfate; 4-chloro-3,5-xylenol (p-chloro-m-xylenol); 2-bromo-2-nitropropane-1,3-diol; diazoalkylurea; butoconazole; nystatin (NYS) Tatin; teconazole; nitrofurantoin; phenamethoxazole; acyclovir; clotrimazole; p-chloro-meta-xylenol; chlorhexidine; miconazole; teconazole; butylparaben; ethylparaben; methylparaben; methylparaben; methylchloroisothiazolinone; methylisothiazolinone; a mixture of 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin and 3-iodo-2-propynylbutylcarbamate; hydroxyquinoline; EDTA; tetrasodium EDTA; parabens; alkylpyridinium compounds; cocophosphatidyl PG-dimethylammonium chloride; chlorhexidine gluconate; chlorhexidine digluconate; chlorhexidine acetate; chlorhexidine ethanesulfonate; chlorhexidine hydrochloride; benzalkonium chloride; benzyl chloride; polyhexamethylene biguanide; and mixtures thereof. It is also envisioned that certain biocides, including one or more agents disclosed herein, may be excluded from the compositions of the present invention.

[0120] 2. Drug components

[0121] Pharmaceutical active agents are also envisioned to be suitable for use in the compositions of the present invention. Non-limiting examples of pharmaceutical active agents include anti-acne agents, agents for treating rosacea, analgesics, anesthetics, procuratorial agents, antihistamines, anti-inflammatory agents (including nonsteroidal anti-inflammatory drugs), antibiotics, antifungal agents, antiviral agents, antimicrobial agents, anticancer active agents, anti-scabies agents, antilice agents, antitumor agents, antiperspirants, antipruritics, antipsoriatic agents, antiseborrheic agents, bioactive proteins and peptides, burn treatment agents, cauterizing agents, bleaching agents, depilatory agents, diaper rash treatment agents, enzymes, hair growth stimulants, hair growth depressants (including DFMOs and their salts and analogues), hemostatic agents, keratolytic agents, oral ulcer treatment agents, cold sore treatment agents, dental and periodontal treatment agents, photosensitizing agents, skin protectants / barrier agents, steroids (including hormones and corticosteroids), sunburn treatment agents, sunscreens, transdermal active agents, nasal active agents, vaginal active agents, wart treatment agents, wound treatment agents, wound healing agents, etc.

[0122] F. Reagent kit

[0123] The use of kits in certain aspects of the invention is also contemplated. For example, the compositions of the invention may be included in a kit. The kit may include a container. The container may include a bottle, metal tube, laminated tube, plastic tube, dispenser, pressurized container, isolating container, packaging, compartment, lipstick container, compression container, cosmetic tray for holding a cosmetic composition, or other types of containers, such as injection or blow-molded plastic containers, wherein the dispersion, composition, or desired bottle, dispenser, or packaging is retained. The kit and / or container may include markings on its surface. Such markings may, for example, be words, phrases, abbreviations, pictures, or symbols.

[0124] The container can dispense a predetermined amount of the composition. In other embodiments, the container (e.g., metal, laminated material, or plastic tube) can be squeezed to dispense the desired amount of composition. The composition can be dispensed in the form of a spray, aerosol, liquid, fluid, or semi-solid. The container can have a spraying, pumping, or squeezing machine. The kit may also include instructions for applying the kit components and any other compositions included in the container. The instructions may include explanations of how to apply, use, and maintain the composition.

[0125] Example

[0126] The following embodiments are provided to illustrate preferred embodiments of the present invention. Those skilled in the art should understand that the techniques disclosed in the following embodiments represent techniques discovered by the inventors that have proven effective in implementing the present invention, and therefore can be considered preferred embodiments in practice. However, based on this disclosure, those skilled in the art should understand that many changes can be made to the specific embodiments disclosed, and similar or related results can still be obtained without departing from the spirit and scope of the present invention.

[0127] Based on this disclosure, all compositions and / or methods disclosed and claimed herein can be manufactured and performed without excessive experimentation. Although the compositions and methods of the invention have been described according to preferred embodiments, it will be apparent to those skilled in the art that variations can be made to the compositions and / or methods, and to the steps or sequence of steps of the methods described herein, without departing from the concept, spirit, and scope of the invention. More specifically, it will be apparent that certain chemically and physiologically relevant reagents can substitute for the reagents described herein while achieving the same or similar results. All such similar substitutions and modifications that are apparent to those skilled in the art are considered to fall within the spirit, scope, and concept of the invention as defined by the appended claims.

[0128] Example 1

[0129] (Materials used)

[0130] The active ingredients in Table 1 were used to obtain the data for the following records.

[0131] Table 1

[0132]

[0133] The zinc oxide may be available as a non-limiting example of combinations of components, such as those in Table 2.

[0134] Table 2

[0135]

[0136] Example 2

[0137] (Clinical Study 1)

[0138] In a clinical study involving 10 subjects, the mineral sunscreen composition described herein was determined to provide an SPF of 30 or higher while avoiding a white cast. Results are summarized in Table 3, and the methods used to determine the properties of the ingredients are provided below.

[0139] Table 3

[0140]

[0141] Example 3

[0142] (Clinical Study 2)

[0143] A clinical study was conducted on 292 subjects using the mineral sunscreen compositions shown in Table 7. Subjects were divided into skin tone groups (e.g., light and dark) and cosmetic use groups (e.g., using cosmetics and not using cosmetics). Subjects used the mineral sunscreen compositions for 7 consecutive days and were asked to provide various qualitative assessments on day 7. The results of these assessments are shown in Tables 4 through 6 below.

[0144] Participants were asked to assess the amount of visible residue after using the mineral sunscreen composition. The data in Table 4 represent the participants' responses. As shown in the responses below, nearly two-thirds (62%) of the women did not experience any visible residue after using the mineral sunscreen composition.

[0145] Table 4

[0146]

[0147] Participants who reported experiencing "small" to "very large" visible residue were asked whether the residue was acceptable. As shown in Table 5, half of the participants who experienced at least a small amount of visible residue considered the residue acceptable. This result did not vary significantly based on skin color or the use of cosmetics.

[0148] Table 5

[0149]

[0150] On day 7 of using the mineral sunscreen, participants were asked whether they agreed that the mineral sunscreen achieved the claims listed in Table 6 below. As shown below, approximately 70% to 80% of participants agreed that the mineral sunscreen composition was easy to rub into the skin, spread evenly on the skin, absorbed quickly into the skin, was non-greasy when rubbed in, had a lightweight texture when rubbed in, felt moisturizing after rubbing in, did not leave hands dirty after use, felt breathable on the skin when rubbed in, and dried quickly.

[0151] Table 6

[0152]

[0153] Subjects were asked on days 1 and 7 of using the mineral sunscreen whether they agreed that the mineral sunscreen fulfilled the claims listed in Table 7 below.

[0154] Table 7

[0155]

[0156] Example 4

[0157] (Example Recipe)

[0158] Formulations having the ingredients from Example 1 were prepared as topical skin compositions. The formulations in Tables 8, 9, and 10 are examples of topical skin compositions prepared as non-whitening mineral sunscreens that provide an SPF rating of 30 or higher.

[0159] Table 8

[0160] Mineral Sunscreen SPF 30 – Water-in-Oil Emulsion #1. *

[0161]

[0162] * The formulation can be prepared by mixing the ingredients in a beaker at 70°C to 75°C until homogeneous. The formulation can then be cooled to room temperature (20°C to 25°C). Furthermore, additional ingredients can be added if desired, for example, to modify the rheological properties of the composition.

[0163] **Excipients can be added, for example, to modify the rheological properties of the composition. Alternatively, the amount of water can be changed.

[0164] Table 9

[0165] Mineral Sunscreen SPF 30 – Water-in-Oil Emulsion #2.

[0166]

[0167] * The formulation can be prepared by mixing the ingredients in a beaker at 70°C to 75°C until homogeneous. The formulation can then be cooled to room temperature (20°C to 25°C). Furthermore, additional ingredients can be added if desired, for example, to modify the rheological properties of the composition.

[0168] **Excipients can be added, for example, to modify the rheological properties of the composition. Alternatively, the amount of water can be changed.

[0169] Table 10

[0170] Mineral Sunscreen SPF 30 – Water-in-Oil Emulsion #1. *

[0171]

[0172] * The formulation can be prepared by mixing the ingredients in a beaker at 70°C to 75°C until homogeneous. The formulation can then be cooled to room temperature (20°C to 25°C). Furthermore, additional ingredients can be added if desired, for example, to modify the rheological properties of the composition.

[0173] **Excipients can be added, for example, to modify the rheological properties of the composition. Alternatively, the amount of water can be changed.

[0174] Example 5

[0175] (Additional testing)

[0176] Determinations that can be used to determine the efficacy of any single ingredient or any combination of ingredients disclosed throughout the specification and claims, or a composition having a combination of said ingredients, can be determined by methods known to those skilled in the art. The following are non-limiting determinations that can be used and / or have already been used in the context of this invention. It should be recognized that other testing procedures can be used, including, for example, objective and subjective procedures.

[0177] B16 Pigmentation Assay: Melanogenesis is the process by which melanocytes produce melanin, a naturally occurring pigment that gives skin, hair, and eyes color. Inhibiting melanin production helps prevent skin darkening and reduce age-related dark spots. This bioassay utilizes B16-F1 melanocytes (ATCC), an immortalized mouse melanoma cell line, to analyze the effect of compounds on melanogenesis. The endpoints of this assay were spectrophotometric measurements of melanogenesis and cell viability. B16-F1 melanocytes were cultured in standard DMEM growth medium containing 10% fetal bovine serum (MEDIATECH) at 37°C in 10% CO2, and then treated for 6 days with the active ingredient, combination of ingredients, or composition containing said combination as disclosed in the instructions. After incubation, melanin secretion was measured by absorbance at 405 nm, and cell viability was quantified.

[0178] Collagen Stimulation Assay: Collagen is any extracellular matrix protein in cells that is essential for skin structure. Increased collagen synthesis helps improve skin firmness and elasticity. This bioassay can be used to detect the effect of any of the active ingredients, combinations of ingredients, or compositions having said combinations disclosed in the product information on the production of procollagen peptides (precursors to collagen) in human epidermal fibroblasts. The endpoint of this assay is a spectrophotometric measurement that reflects the presence of procollagen peptides and cell viability. This assay employs a quantitative sandwich enzyme immunoassay technique, in which procollagen peptide-specific monoclonal antibodies are pre-coated onto microplates. Standards and samples can be pipetted into the wells, and any present procollagen peptides are bound by the immobilized antibody. After washing away any unbound material, an enzyme-linked polyclonal antibody against procollagen peptides can be added to the wells. After washing to remove any unbound antibody-enzyme reagent, substrate solution can be added to the wells. The solution will develop color in proportion to the amount of procollagen peptide bound in the initial step, and can be detected using a microplate reader at 450 nm. The color development can be stopped, and the color intensity can be measured.

[0179] For the preparation of samples and controls, nearly confluent normal adult epidermal fibroblasts (Cascade Biologics) cultured at 37°C in 10% CO2 in standard DMEM growth medium containing 10% fetal bovine serum (MEDIATECH) were treated for 3 days with a combination of each component disclosed in the instructions or a composition having said combinations. After incubation, the cell culture medium was collected, and the amount of precollagen peptide secretion was quantified using a sandwich enzyme-linked immunosorbent assay (ELISA) from TAKARA (#MK101).

[0180] Elastin Stimulation Assay: Elastin is a connective tissue protein that helps the skin regain its shape after stretching or contraction. Elastin is also an important load-bearing protein, used in areas where mechanical energy needs to be stored. Elastin is produced through a reaction catalyzed by lysyl oxidase, by linking numerous soluble proelastin molecules. Elastin secretion and elastin fibers can be monitored in cultured human fibroblasts by staining them with an immunofluorescent antibody targeting elastin.

[0181] Laminin and Fibronectin Stimulation Assay: Laminins and fibronectins are major proteins at the dermal-epidermal junction (DEJ), also known as the basement membrane. The DEJ lies between the dermis and epidermis, forming finger-like projections called reteridges. Epidermal cells obtain nutrients from blood vessels in the dermis. The reteridges increase the surface area of ​​the epidermis exposed to these vessels and the necessary nutrients. The DEJ provides adhesion between two tissue compartments and controls the structural integrity of the skin. Laminins and fibronectins are two structural glycoproteins located in the DEJ. Laminins and fibronectins are considered adhesives that bind cells together; they are secreted by dermal fibroblasts and contribute to promoting intracellular and intercellular adhesion of epidermal cells to the DEJ. The secretion of laminins and fibronectins can be monitored by quantifying laminins and fibronectins in the cell supernatant of cultured human fibroblasts treated for 3 days with a culture medium containing or without 1.0% of one or more test components at a final concentration. Following incubation, the levels of laminin and fibronectin can be measured using an enzyme-linked immunosorbent assay (ELISA) using immunofluorescent antibodies targeting laminin and antibodies targeting fibronectin directly. Measurements of cellular metabolic activity are standardized, as determined by biotransformation with 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazonium (MTS).

[0182] Tumor necrosis factor-α (TNF-α) assay: TNF-α, the proto-ligand of the TNF superfamily, is a pleiotropic cytokine that plays an important role in inflammation. Increased expression of TNF-α is associated with upregulation of pro-inflammatory activity. This bioassay can be used to analyze the effect of any of the active ingredients, combinations of ingredients, or compositions having said combinations disclosed in the product specification on the production of TNF-α by human epidermal keratinocytes. The endpoint of this assay can be a spectrophotometric measurement reflecting TNF-α and cell viability. This assay employs a quantitative sandwich enzyme immunoassay technique, in which a monoclonal antibody specifically targeting TNF-α has been pre-coated onto a microplate. Standards and samples can be pipetted into the wells, and any present TNF-α is bound by the immobilized antibody. After washing away any unbound material, a TNF-α-specific enzyme-linked polyclonal antibody can be added to the wells. After washing to remove any unbound antibody-enzyme reagent, a substrate solution can be added to the wells, and color development is performed proportionally to the amount of TNF-α bound in the initial step, and detection is performed using a microplate reader at 450 nm. It can stop color development and measure color intensity. It was tested at 37°C in 5% CO2 using EPILIFE. TMNearly confluent normal adult keratinocytes cultured in standard growth medium (Cascade Biologics) can be treated for 6 hours with phorbol 12-tetradecanoate 13-acetate (PMA, 10 ng / ml, SIGMA CHEMICAL, #P1585-1MG) and any one of the active ingredients, combinations of ingredients, or compositions having said combinations disclosed in the instructions. PMA has been shown to induce a significant increase in TNF-α secretion, which peaks at 6 hours post-treatment. After incubation, the cell culture medium can be collected, and TNF-α secretion can be quantified using a sandwich enzyme-linked immunosorbent assay (ELISA) from R&D Systems (#DTA00C).

[0183] Antioxidant (AO) assay: An in vitro bioassay used to measure the total antioxidant capacity of any one of the ingredients, combinations of ingredients, or compositions having said combinations disclosed in the product specification. This assay relies on the antioxidants in the sample inhibiting metmyoglobin from releasing ABTS. ® (2,2'-Azido-bis-[3-ethylbenzothiazoline sulfonate]) oxidized to ABTS ® •+ Capacity. The antioxidant system of living organisms includes enzymes such as superoxide dismutase, catalase, and glutathione peroxidase; macromolecules such as albumin, ceruloplasmin, and ferritin; and a range of small molecules including ascorbic acid, α-tocopherol, β-carotene, reduced glutathione, uric acid, and bilirubin. The sum of endogenous and food-derived antioxidants represents the total antioxidant activity in extracellular fluid. The synergistic effect of all the different antioxidants provides stronger protection against reactive oxygen species or nitrogen free radical attacks than any single compound acting alone. Therefore, total antioxidant capacity provides more relevant biological information than information obtained by measuring individual components, as it takes into account the cumulative effect of all antioxidants present in plasma and body fluids. The ability of antioxidants in a sample to prevent ABTS® oxidation is compared to the ability of the water-soluble tocopherol analog Trolox and quantified as molar equivalents of Trolox. The Antioxidant Capacity Kit #709001 from CAYMAN CHEMICAL (Ann Arbor, Michigan, USA) can be used as an in vitro bioassay to measure the total antioxidant capacity of any one of the active ingredients, combinations of ingredients, or compositions having said combinations disclosed in the product information. The protocol can be performed according to the manufacturer's recommendations.

[0184] ORAC assay: The oxygen radical absorption (or absorbance) capacity (ORAC) of any of the active ingredients, combinations of ingredients, or compositions having said combinations disclosed in the product specification can also be determined by measuring the antioxidant activity of these ingredients or compositions. Antioxidant activity indicates the ability to reduce oxidants (oxidants). This assay quantifies the time and extent required to inhibit the action of oxidants such as oxygen radicals, which are known to damage cells (e.g., skin cells). The ORAC value of any of the ingredients, combinations of ingredients, or compositions having said combinations disclosed in the product specification can be determined by methods known to those skilled in the art (see U.S. Publications 2004 / 0109905 and 2005 / 0163880; and commercially available kits, such as the Zen-Bio ORAC Antioxidant Assay Kit (#AOX-2)). The Zen-Bio ORAC Antioxidant Assay Kit measures the loss of luciferin fluorescence over time due to the formation of peroxy radicals from the decomposition of AAPH (2,2'-azobis-2-methylpropylimidazolium dihydrochloride). The water-soluble vitamin E analog Trolox was used as a positive control in a dose-dependent manner to inhibit fluorescein decay.

[0185] Mushroom Tyrosinase Activity Assay: In mammalian cells, tyrosinase catalyzes two steps in the multi-step biosynthesis of melanin from tyrosine (and from the polymerization of dopachrome). Tyrosinase is located in melanocytes and produces melanin (an aromatic quinone compound), which gives skin, hair, and eye color. Purified mushroom tyrosinase (from SIGMA) can be incubated with its substrate L-Dopa (from FISHER) in the presence or absence of any of each active ingredient, combination of ingredients, or composition having said combinations disclosed in the specification. Pigment formation can be assessed by a microplate reader reading at 490 nm. The percentage of inhibition of mushroom tyrosinase activity can be calculated and compared with an untreated control to determine the ability of the test ingredient or combination thereof to inhibit the activity of the purified enzyme. The inhibitory effect of the test extract is compared with the inhibitory effect of kojic acid (SIGMA).

[0186] Matrix metalloproteinase 3 and matrix metalloproteinase 9 (MMP3; MMP9) activity assays: In vitro assays of matrix metalloproteinase (MMP) inhibition. MMPs are extracellular proteases that function in many normal and disease states due to their broad substrate specificity. MMP3 substrates include collagen, fibronectin, and laminin; while MMP9 substrates include collagen VII, fibronectin, and laminin. Using the Colorimetric Drug Discovery kits for MMP3 (AK-400) and MMP-9 (AK-410) from BioMol International, this assay aims to measure the protease activity of MMPs using a thiopeptide as the chromogenic substrate (Ac-PLG-[2-mercapto-4-methyl-valeryl]-LG-OC2H5)5,6. The peptide bonds at the MMP cleavage site are replaced by thioester bonds in the thiopeptide. MMP hydrolyzes this bond to generate a thiol group, which reacts with DTNB [5,5'-dithiobis(2-nitrobenzoic acid), Ellman's reagent] to form 2-nitro-5-thiobenzoic acid, detectable by its absorbance at 412 nm (ε = 13600 M⁻¹cm⁻¹, pH 6.0 and above 7). The active ingredient disclosed in the product specification, any combination of ingredients, or a combination containing said combinations can be determined.

[0187] Matrix metalloproteinase 1 (MMP1) activity assay: An in vitro assay for the inhibition of matrix metalloproteinases (MMPs). MMPs are extracellular proteases that function in many normal and disease states due to their broad substrate specificity. MMP1 substrates include type IV collagen. The ENZ / CHEK gelatinase / collagenase assay kit (#E12055) utilizes a fluorescent gelatin substrate to detect MMP1 protease activity. A bright green fluorescence is observed during proteolytic cleavage, and the enzyme activity can be monitored using a fluorescent microplate reader.

[0188] The ENZ / CHEK Gelatinase / Collagenase Assay Kit (#E12055) from Invitrogen is designed for the in vitro assay of MMP1 enzyme activity. It can measure the active ingredient disclosed in the instructions, any combination of ingredients, or a combination containing said combinations. This assay relies on the ability of purified MMP1 enzyme to degrade fluorescent gelatin substrates. Once the substrate is specifically cleaved by MMP1, bright green fluorescence appears and can be monitored using a fluorescent microplate reader. Test materials are incubated in the presence or absence of purified enzyme and substrate to determine their protease inhibitory activity.

[0189] Cyclooxygenase (COX) Assay: In vitro inhibition assay of cyclooxygenase-1 and cyclooxygenase-2 (COX-1, COX-2). COX is a bifunctional enzyme with both cyclooxygenase and peroxidase activities. Cyclooxygenase activity converts arachidonic acid into hydroperoxides (prostaglandin G2; PGG2), while the peroxidase component reduces these hydroperoxides (prostaglandin H2; PGH2) into their corresponding alcohols, namely precursors to prostaglandins, thromboxanes, and prostacyclin. This COX inhibitor screening assay measures the peroxidase component of cyclooxygenase. Peroxidase activity is determined colorimetrically by monitoring the presence of oxidized N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD). This inhibitor screening assay includes both COX-1 and COX-2 enzymes to screen for isoenzyme-specific inhibitors. Colorimetric COX (Sheep) Inhibitor Screening Assay (#760111, CAYMAN CHEMICAL) can be used to analyze the effect of each active ingredient, any combination of ingredients, or a combination of said ingredients disclosed in the product information on the activity of purified cyclooxygenase (COX-1 or COX-2). Following the manufacturer's instructions, the purified enzyme, heme, and test extract are mixed in a detection buffer and incubated with shaking at room temperature for 15 minutes. After incubation, arachidonic acid and the colorimetric substrate can be added to initiate the reaction. Colorimetric development can be assessed by reading the microplate reader at 590 nm. The percentage of COX-1 or COX-2 activity inhibition can be calculated and compared to an untreated control to determine the ability of the test extract to inhibit the activity of the purified enzyme.

[0190] Lipoxygenase (LO) Assay: An in vitro assay for lipoxygenase (LO) inhibition. LO is a non-heme iron-containing dioxygenase that catalyzes the addition of molecular oxygen to fatty acids. Linoleic acid and arachidonic acid are the main substrates of LO in plants and animals. Arachidonic acid can then be converted to hydroxyeicosatetrienoic acid (HETE) derivatives, which are subsequently converted into leukotrienes, a potent inflammatory mediator. This assay provides an accurate and convenient method for screening lipoxygenase inhibitors by measuring the hydroperoxides produced during incubation of lipoxygenases (5-LO, 12-LO, or 15-LO) with arachidonic acid. The Colorimetric LO Inhibitor Screening Kit (#760700, CAYMAN CHEMICAL) can be used to determine the ability of each active ingredient, any combination of ingredients, or a combination having the combinations disclosed in the instructions to inhibit enzyme activity. Purified 15-lipoxygenase and the test ingredient can be mixed in assay buffer and incubated with shaking at room temperature for 10 minutes. After incubation, arachidonic acid can be added to initiate the reaction, and the mixture can be incubated for another 10 minutes at room temperature. A colorimetric substrate can be added to terminate the catalysis, and the colorimetric progress can be assessed by fluorescence plate readings at 490 nm. The percentage inhibition of lipoxygenase activity can be calculated compared to the untreated control to determine the ability of each active ingredient, any combination of ingredients, or a composition having the combinations disclosed in the specification to inhibit the activity of the purified enzyme.

[0191] Elastase Assay: The ENZCHEK® Elastase Assay (Kit #E-12056) from MOLECULAR PROBES (Eugene, Oregon USA) can be used as an in vitro enzyme inhibition assay to measure the inhibition of elastase activity of each active ingredient, any combination of ingredients, or a combination of said ingredients disclosed in the instructions. The ENZCHEK kit contains soluble bovine cervical ligament elastin, which can be labeled with a dye so that the fluorescence of the conjugate can be quenched. Non-fluorescent substrates can be digested with elastase or other proteases to produce highly fluorescent fragments. The resulting increase in fluorescence can be monitored using a fluorescence microplate reader. The digestion product of the elastin substrate has maximum absorption at approximately 505 nm and maximum fluorescence emission at approximately 515 nm. When screening for elastase inhibitors using the ENZCHEK ELASTASE ASSAY KIT, the peptide N-methoxysuccinyl-Ala-Ala-Pro-Val-chloromethyl ketone can be used as a selective collective inhibitor of elastase.

[0192] Ceramide production: Ceramide in cell or tissue samples can be incubated at room temperature with a 1 / 50 dilution of mouse monoclonal antibody against ceramide (ENZO LIFE SCIENCE, catalog number ALX-804-196, clone MID15B4) for 2 hours and labeled using a biotin / streptavidin amplification system. Ceramide can be observed using a video microscope (pink staining).

[0193] Oil Control Assay: Measurements of reduced sebum secretion and / or reduced sebum production can be performed using standard techniques known to those skilled in the art. In one case, the forehead may be used. Each active ingredient, any combination of ingredients, or composition having said combination disclosed in the specification may be applied once or twice daily to a portion of the forehead for a set number of days (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or more than 14 days), while another portion of the forehead remains untreated. After the set number of days has elapsed, sebum secretion can be measured by applying fine blotting paper to the treated and untreated forehead skin. First, all sebum is removed from the treated and untreated areas with a damp and then dry cloth. Then, blotting paper can be applied to the treated and untreated areas of the forehead, and an elastic band can be placed around the forehead to gently press the blotting paper onto the skin. After 2 hours, the blotting paper can be removed, allowed to dry, and then transmitted through the light. Darker blotting paper is associated with more sebum production (or lighter blotting paper is associated with less sebum production).

[0194] Erythema Assay: The reduction of skin redness can be assessed using a MINOLTA colorimeter. Applying a 0.2% sodium lauryl sulfate solution to the subject's forearm induces skin erythema. The area is protected with an occlusive patch for 24 hours. After 24 hours, the patch is removed, and the irritation-induced redness is assessed using the a* value of the MINOLTA colorimeter. The a* value measures the change in skin color in the red area. Immediately after reading, the area is treated with the active ingredient, any combination of ingredients, or a composition having the combination disclosed in the instructions. Repeat measurements can be performed periodically to determine the formulation's ability to reduce redness and irritation.

[0195] Skin Moisture / Hydration Assay: Skin moisture / hydration can be measured using impedance measurement with the Nova dermal phase meter. The impedance meter measures changes in skin moisture content. The outer layer of skin has unique electrical properties. When skin is dry, its conductivity is poor. As skin moisture content increases, its conductivity increases. Therefore, changes in skin impedance (related to conductivity) can be used to assess changes in skin hydration. The device can be calibrated according to the instrument instructions each test day. Temperature and relative humidity can also be recorded. Subjects can be assessed as follows: prior to measurement, they can be equilibrated in a room with specified humidity (e.g., 30% to 50%) and temperature (e.g., 68°C to 72°C). Three individual impedance readings can be read on each side of the face, recorded, and averaged. A T5 setting can be used for the impedance meter, which averages the impedance applied to the face every five seconds. Changes can be reported using statistical variance and significance. Each active ingredient, any combination of ingredients, or composition having said combinations disclosed in the instructions can be determined according to the method.

[0196] Determination of skin transparency and reduction of freckles and age spots: Skin transparency and reduction of freckles and age spots can be assessed using a Minolta colorimeter. Using the a* value of a 0.0550 colorimeter, changes in skin color can be assessed to identify potential irritation caused by product treatment. The a* value measures changes in skin color in the red area. This is used to determine whether each active ingredient, any combination of ingredients, or a composition having said combination disclosed in the instructions will cause irritation. Measurements can be taken on each side of the face, and the average value is taken as the left and right face value. Skin transparency can also be measured using a Minolta meter. This measurement is a combination of the a*, b, and L values ​​of the Minolta meter, related to skin brightness and closely related to skin smoothness and hydration. Readings are taken from the skin as described above. In a non-limiting aspect, skin transparency can be described as L / C, where C is chromaticity and is defined as (a... 2 +b 2 ) 1 / 2 .

[0197] Skin dryness, fine lines, skin smoothness, and skin color assessment: Skin dryness, fine lines, skin smoothness, and skin color can be assessed using clinical grading techniques. For example, the clinical grading of dry skin can be determined using the five-point Kligman scale: (0) Skin is soft and moist; (1) Skin appears normal with no visible dryness; (2) Skin feels slightly dry with no visible peeling; (3) Skin feels dry, firm, and has a whitish appearance with some scaling; and (4) Skin feels very dry, rough, and has a whitish appearance with scaling. Assessments can be performed independently by two clinicians, and the average value is taken.

[0198] Clinical grading of skin color: Clinical grading of skin color can be performed using a ten-point analog number scale: (10) Smooth, uniform pinkish-brown skin. No dark, red, or scaly patches are visible when examined with a handheld magnifying glass. The microscopic texture of the skin is very uniform when touched; (7) Uniform skin color is observed without magnification. No scaly areas, but slight discoloration due to pigmentation or erythema. No discoloration exceeding 1 cm in diameter; (4) Skin discoloration and uneven texture are easily noticeable. Slight scaling. Some areas of skin feel rough to the touch; and (1) Uneven skin color and texture. Numerous areas of scaling and discoloration, either due to hypopigmentation or erythema or melanosis. Large areas of uneven color exceeding 1 cm in diameter. The assessment is performed independently by two clinicians and the average is taken.

[0199] Clinical grading of skin smoothness: Clinical grading of skin smoothness can be determined using a ten-point analog number scale: (10) smooth, moist and glossy, with no resistance when dragged with a finger; (7) slightly smooth, with slight resistance; (4) rough, with significantly altered friction when rubbed; and (1) rough, flaky, and uneven surface. Assessments were performed independently by two clinicians, and the average value was taken.

[0200] Assays of skin smoothness and wrinkle reduction were performed using the method disclosed by Packman et al. (1978): Skin smoothness and wrinkle reduction can also be visually assessed using the method disclosed by Packman et al. (1978). For example, at each subject visit, the depth, shallowness, and total number of superficial facial lines (SFLs) for each subject can be carefully scored and recorded. Numerical scores are obtained by multiplying a numerical factor by a depth / width / length factor. Scores for the eye and mouth regions (left and right sides) are obtained and summed to obtain the total wrinkle score.

[0201] Skin firmness can be measured using the Hargens Ballistometer: The Hargens Ballistometer is a device that assesses skin elasticity and firmness by dropping a ball onto the skin and recording its first two rebound peaks. The ballistometer uses a small, lightweight probe with a relatively blunt probe (4 square millimeters of contact area). The probe penetrates the skin slightly and produces measurements that depend on the properties of the outer layers of the skin, which include the stratum corneum and epidermis, as well as some of the dermis.

[0202] Skin softness / flexibility determination using the Gas Bearing Electrodynamometer: Skin softness / flexibility can be assessed using the Gas Bearing Electrodynamometer, an instrument for measuring the stress / strain properties of the skin. Skin viscoelasticity is related to skin hydration. Measurements can be obtained at predetermined locations on the cheek area by attaching a probe to the skin surface with double-sided tape. A force of approximately 3.5 gm can be applied parallel to the skin surface, and the skin displacement can be accurately measured. Skin flexibility can then be calculated and expressed as DSR (Dynamic Elasticity Coefficient in gm / mm).

[0203] Appearance determination of lines and wrinkles using replicas: The appearance of lines and wrinkles on the skin can be evaluated using replicas, which are impressions of the skin surface. Materials similar to silicone rubber can be used. Replicas can be analyzed through image analysis. By obtaining silicone replicas from the subject's face and analyzing the replica images using a computer image analysis system, changes in the visibility of lines and wrinkles can be objectively quantified. Replicas can be photographed from the eye and neck areas using a digital camera with low-angle incident light. Image processing programs can be used to analyze the digital images and identify replicas covered by wrinkles or fine lines.

[0204] Skin surface profile determination using a surface photometer / stylus method: The surface profile of the skin can be measured using a surface photometer / stylus method. This involves shining light on the surface of a replica or dragging a stylus across it. The vertical displacement of the stylus is input into a computer via a distance sensor, and after scanning a replica of a fixed length, a cross-sectional analysis of the skin profile can be generated as a two-dimensional curve. This scan can be repeated an arbitrary number of times along a fixed axis to produce a simulated 3-D image of the skin. Ten random portions of the replica can be obtained using the stylus technique and combined to produce an average value. Values ​​of interest include Ra, which is the arithmetic mean of all roughness (height) values, calculated by integrating the profile height relative to the average profile height. Rt is the maximum vertical distance between the highest peak and the lowest valley, and Rz is the average peak amplitude minus the average peak height. These values ​​are calibration values ​​in mm. Before each use, the device should be standardized by scanning a metal standard with known values. The Ra value can be calculated using the following equation: R a =Standardized roughness; l m = Horizontal (scanning) length; y = Absolute value of the profile position relative to the average profile height (x-axis).

[0205] MELANODERM TMAssay: In other non-limiting respects, the efficacy of each active ingredient, any combination of ingredients, or composition having said combination disclosed in the specification can be determined by the use of a dermal analogue, such as MELANODERM. TM To assess. Melanocytes are a type of cell found in skin analogs that stain positively when exposed to L-dihydroxyphenylalanine (L-DOPA), a precursor to melanin. Skin analog MELANODERM TM Various matrices containing each active ingredient, any combination of ingredients, or compositions having the combinations disclosed in the specification, or the matrix alone, can be used as controls. Alternatively, an untreated sample of the skin mimic can be used as a control.

[0206] Filament production: Changes in filaggrin production in keratinocytes can be measured due to each active ingredient, any combination of ingredients, or a composition having said combinations disclosed in the product specification. Filament is a precursor to natural moisturizing factor (NMF) in the skin. Increased NMF increases skin hydration. The yield of filaggrin in treated and untreated keratinocytes can be determined using a bioassay that measures the concentration of filaggrin in keratinocyte lysates. A non-limiting example of a bioassay that can be used to quantify intermediate filament-associated protein production is the PROTEINSIMPLE® SIMON™ Western blot protocol. For each sample, normal human epidermal keratinocytes (NHEK) were grown in calcium-containing EPI-200–MATTEK EPILIFE® growth medium from Life Technologies (M-EP-500-CA). Prior to treatment, the NHEK were incubated overnight at 37°C in growth medium with 5% CO2. NHEK was then incubated for 24 to 36 hours in growth medium containing 1% of the test compound / extract or without the compound / extract (negative control). The NHEK was then washed, collected, and stored on ice or colder until lysed on ice using lysis buffer and sonication. The protein concentration of the sample could be determined and used for sample standardization. The lysate could be stored at -80°C until used for quantification.

[0207] PROTEINSIMPLE® SIMON™ Protein Blot Bioassay employs quantitative protein blot immunoassay technology, using a polyfilamentin-specific antibody to quantitatively detect polyfilamentin in the test sample. Cell samples are lysed, and protein concentrations are standardized. The standardized sample and molecular weight standards are then loaded onto a denaturing protein separation gel for analysis using capillary electrophoresis. The proteins in the gel are immobilized, and immunoprobe detection is performed using a polyfilamentin-specific primary antibody. Immunoplasmic detection of the immobilized proteins can then be performed using an enzyme-linked immunosorbent assay (ELISA) antibody bound to the primary antibody. A chemiluminescent substrate solution can then be added to the immobilized proteins, ensuring that chemiluminescent development is proportional to the amount of intermediate filament-associated proteins bound in the immobilization. Chemiluminescent development is stopped at a specific time, allowing measurement of the chemiluminescent signal intensity and comparison with positive and negative controls.

[0208] Closure protein production: Changes in closure protein production in keratinocytes can be measured due to each active ingredient, any combination of ingredients, or a composition having said combinations disclosed in the product specification. Closure proteins are proteins essential for the formation of tight junctions and the skin's moisture barrier function. A non-limiting example of how to determine closure protein production in treated and untreated keratinocytes is by using a bioassay to determine the concentration of closure proteins in keratinocyte lysates. Bioanalysis can be performed using the PROTEINSIMPLE® SIMON™ protein blotting protocol. For the sample, adult epidermal keratinocytes (HEKa) from Life Technologies (C-005-5C) can be blotted at EPILIFE. TM EPILIFE was grown in the growth medium at 37°C in 5% CO2 for 24 hours. TM The growth medium was supplemented with calcium (M-EP-500-CA) from Life Technologies and keratinocyte growth supplement (HKGS) (S-101-5) from Life Technologies. HEKa samples were then incubated for 24 to 48 hours in growth medium containing the test compound / extract, growth medium without the compound / extract as a negative control, or growth medium containing 1 mM CaCl2 as a positive control. The HEKa samples were then washed, collected, and stored on ice or colder until lysed on ice using lysis buffer and sonication. The protein concentration of the sample can be determined and used for sample standardization. Lysates were stored at -80°C until used for bioassays.

[0209] PROTEINSIMPLE® SIMON™ Protein Blot Bioassay employs quantitative protein blot immunoassay technology, using antibodies specific to closure proteins to quantitatively detect closure proteins in test samples. Cell samples are lysed, and protein concentrations are standardized. The standardized sample and molecular weight standards are then loaded onto a denaturing protein separation gel and analyzed using capillary electrophoresis. The proteins in the gel are then fixed and detected using an immunoprobe with a primary antibody specific to the closure protein. Immunoplasmic detection is performed on the fixed proteins using an enzyme-linked immunosorbent assay (ELISA) antibody bound to the primary antibody. A chemiluminescent substrate solution is then added to the fixed proteins, ensuring that chemiluminescent development is proportional to the amount of closure protein bound in the fixation. Chemiluminescent development can be stopped at specific times, and the intensity of the chemiluminescent signal can be measured and compared with positive and negative controls.

[0210] Keratinocyte monolayer permeability: Changes in keratinocyte monolayer permeability caused by each active ingredient, any combination of ingredients, or a composition having said combinations, as disclosed in the product information can be measured. Keratinocyte monolayer permeability is a measure of skin barrier integrity. As a non-limiting example, the in vitro vascular permeability assay of MILLIPORE (ECM642) can be used to determine the keratinocyte monolayer permeability in treated and untreated keratinocytes. This assay analyzes the adsorption, transport, and permeability of endothelial cells. Briefly, adult epidermal keratinocytes (C-005-5C) from Life Technologies can be seeded onto a porous collagen-coated membrane within collection wells. The keratinocytes are then subjected to EPILIFE... TM The culture medium was incubated at 37°C in 5% CO2 for 24 hours, containing EPILIFE. TMThe growth medium was supplemented with calcium (M-EP-500-CA) from LIFE TECHNOLOGIES and keratinocyte growth supplement (HKGS) (S-101-5) from LIFE TECHNOLOGIES. This culture time allowed cells to form a monolayer and close the membrane pores. The keratinocytes were then cultured for another 48 hours at 37°C in 5% CO2 after replacing the medium with either fresh medium containing the test compound / extract (test sample) or fresh medium without the test compound / extract (untreated control). To determine the permeability of the keratinocyte monolayer after culture with / without the test compound / extract, the medium was replaced with fresh medium containing high molecular weight fluorescein isothiocyanate (FITC)-glucan, and the keratinocytes were cultured for 4 hours at 37°C in 5% CO2. During the 4-hour incubation, FITC could pass through the keratinocyte monolayer and porous membrane at a rate proportional to the monolayer permeability into the collection wells. After 4 hours of incubation, cell viability and FITC content in the collection wells could be measured. For FITC content, the culture medium in the collection wells was used to measure fluorescence at 480 nm (Em) when excited at 520 nm. Permeability percentage and percentage change compared to the untreated control could be determined by the following equations: Permeability percentage = ((average Ex / Em of test sample) / average Ex / Em of untreated control) * 100; Permeability change percentage = Permeability percentage of test sample – Permeability percentage of untreated control.

[0211] Hyaluronic acid production: Changes in hyaluronic acid production in human skin fibroblasts can be measured by each active ingredient disclosed in the product specification, any combination of ingredients, or a composition having said combinations. HA is a polysaccharide associated with the stability of the matrix structure and is involved in providing turgor pressure to tissues and cells.

[0212] As a non-limiting example, the production of HA in treated and untreated adult dermal fibroblasts (HDFa) can be determined using the R&DSystems Hyaluronic Acid DuoSet ELISA Kit (DY3614). In this assay, to produce samples, nearly confluent HDFa cells (C-13-5C) from Cascade Biologics were cultured for 72 hours at 37°C in 10% CO2 in starvation medium (Dulbecco modified Eagle medium containing 0.15% fetal bovine serum and 1% penicillin-streptomycin solution) prior to treatment. The cells were then incubated for 24 hours with fresh starvation medium containing the test compound, positive controls (phorbol 12-tetradecanoate 13-acetate from SIGMA-ALDRICH and platelet-derived growth factor from SIGMA-ALDRICH (P3201)) or no additives. The medium was then collected and frozen at -80°C until used for the ELISA assay.

[0213] In short, the ELISA assay employs a quantitative sandwich enzyme immunoassay technique, whereby HA-specific capture antibodies are pre-coated onto a microplate. Standards and culture medium from treated and untreated cells are pipetted into the wells of the microplate to allow any present HA to bind to the immobilized antibodies. After washing away any unbound material, HA-specific enzyme-linked detection antibodies are added to the wells. After washing to remove any unbound antibody-enzyme reagent, substrate solution is added to the wells to allow color development proportional to the amount of HA bound in the initial step. Color development is terminated at a specific time, and the color intensity at 450 nm is measured using a microplate reader.

[0214] As another non-limiting example, human skin explants can be cultured in a viable explant medium at 37°C in humid air supplemented with 5% CO2. Explant treatment can be performed by topical application of the sample product (n=3) on days D0, D2, D3, D6, D8, and D9. Control explants (n=3) are treated without any changes except for replacement of the viable explant medium. On days D3, D6, and D8, half the volume of viable medium can be replaced. On D9, three explants from each condition can be removed and cut in half. One half of the explant is fixed in buffered formalin, and the other half is frozen at -80°C.

[0215] After fixation in plain Bouin for 48 hours and in formalin for 24 hours, the samples were dried and immersed in paraffin using an automated tissue processor, Leica TP 1020. Sections of 5 micrometers were prepared using a microtome (LEICA RM2125 Minota) and mounted on SUPERFROST™ histological slides. Microscopic observation was performed using an optical microscope with a LEICA ORTHOPLAN or LEICA DM LB microscope. Images were taken using an OLYMPUS DP72 camera and CELL^D software. General morphology could be examined on paraffin sections stained with Masson's trichrome Goldner variant. Hyaluronic acid staining was performed at room temperature with a 1 / 100 dilution of anti-hyaluronic acid biotinylated protein (HABP) (SEIKAGAKU, catalog number 400763-1A) and a magnification system of biotin / streptavidin (VECTOR, VECTASTAIN PK-7200) for 1 hour.

[0216] Inhibition of hyaluronidase activity: Changes in hyaluronidase activity caused by each active ingredient, any combination of ingredients, or a composition having said combinations, as disclosed in the product specification can be measured. Hyaluronidase is an enzyme that degrades hyaluronic acid. HA is a polysaccharide associated with the stability of the matrix structure and is related to providing turgor pressure for tissues and cells. As a non-limiting example, hyaluronidase activity can be determined using an in vitro protocol modified from SIGMA-ALDRICH protocol #EC 3.2.1.35. Briefly, 1-S type hyaluronidase (H3506) from SIGMA-ALDRICH is added to microplate reaction wells containing the test compound or a control. Tannins can be used as a positive control inhibitor, the control enzyme can be without the test compound, and wells containing the test compound or a positive control but without hyaluronidase can be used as a background negative control. The wells are incubated at 37°C for 10 minutes before adding the substrate (HA). The substrate is added, and the reaction is incubated at 37°C for 45 minutes. A portion of each reaction solution was then transferred to a solution of sodium acetate and acetic acid at pH 3.75 and gently mixed to terminate that portion of the reaction (terminus well). After adding a portion of the reaction solution to the terminus well, both the terminus well and the reaction well should contain the same volume of solution. Both the reaction well and the terminus well were incubated at room temperature for 10 minutes. The absorbance of the reaction well and the terminus well at 600 nm was then measured. Inhibition can be calculated using the following formulas: Inhibitor (or control) activity = (Absorbance of inhibitor terminus well at 600 nm - Absorbance of inhibitor reaction well at 600 nm); Initial activity = Absorbance of control enzyme at 600 nm; Inhibition percentage = [(Initial activity / Inhibitor activity) * 100] - 100.

[0217] Peroxisome proliferator-activated receptor γ (PPAR-γ) activity: Changes in PPAR-γ activity caused by each active ingredient, any combination of ingredients, or a composition having said combinations, as disclosed in the specification can be measured. PPAR-γ is a key receptor for sebum production. As a non-limiting example, PPAR-γ activity can be determined using a bioassay that analyzes the ability of a test compound or composition to inhibit ligand binding. Briefly, the fluorescent small molecule pan-PPAR ligand, FLUORMONE™ Pan-PPAR Green, available from Life Technologies (PV4894), can be used to determine whether a test compound or composition can inhibit the binding of a ligand to PPAR-γ. Sample wells include PPAR-γ and the fluorescent ligand, and: the test compound or composition (test); the reference inhibitor rosiglitazone (positive control); or no test compound (negative control). The wells are incubated for a set time to allow the ligand to bind to PPAR-γ. The fluorescence polarization of each sample well can then be measured and compared with the negative control wells to determine the percentage inhibition by the test compound or composition.

[0218] Cytokine array: Human epidermal keratinocytes were cultured to 70%-80% confluence. The culture medium was aspirated from the plates, and 0.025% trypsin / EDTA was added. When the cells became rounded, the culture dish was gently tapped to release the cells. The trypsin / EDTA containing the cells was removed from the culture dish and neutralized. The cells were centrifuged at 180xg for 5 minutes to form a cell pellet. The supernatant was aspirated. The resulting pellet was resuspended in EPILIFE. TM In Cascade Biologics culture medium. Seed cells at approximately 10% to 20% confluence in 6-well plates. Once cell confluence reaches approximately 80%, aspirate the culture medium and add 1.0 ml of EPILIFE. TM Phorbolol 13-tetradecanoate 12-acetate (“PMA”) (a known inflammatory inducer) and test composition diluent were added to two replicate wells (i.e., 1.0% (100 μL of 100X stock solution) and 0.1% (10 μL of 100X stock solution) of the test composition were diluted to a final volume of 1 ml of EPILIFE. TM (In the growth medium). Gently stir the medium to ensure thorough mixing. Additionally, add 1.0 ml of EPILIFE to the control wells. TM With and without additional PMA. After administration, the culture plates were incubated at 37±1℃ and 5.0%±1% CO2 for approximately 5 hours. After 5 hours of incubation, all culture media were collected in conical tubes and frozen at -70℃.

[0219] For analysis, 16-well hybridization chambers were attached to 16-well fast slides, arranged in triplicate with 16 anti-cytokine antibodies and experimental controls (WHATMAN BIOSCIENCES), and the slides were placed in a FASTFrame (4 slides per frame) for processing. The array was blocked for 15 minutes. 70 ml of S&S protein array blocking buffer (WHATMAN SCHLEICHER AND SCHEULL) was used at room temperature. The blocking buffer was removed, and 70 ml of each supernatant sample was added to each array. The array was incubated with gentle stirring at room temperature for 3 hours. The array was washed three times with TBS-T. The array was then treated with 70 ml of an antibody mixture containing one biotinylated antibody corresponding to the capture antibody for each arrangement. The array was incubated with gentle stirring at room temperature for 1 hour. The array was washed three times with TBS-T. The array was then incubated with 70 ml of a solution containing streptavidin-Cy5 conjugates with gentle stirring at room temperature for 1 hour. The array was washed three times with TBS-T, rapidly rinsed in deionized water, and dried.

[0220] The slides can be imaged using the PERKIN-ELMER SCANARRAY 4000 confocal fluorescence imaging system. Array images can be saved and analyzed using the imaging research software ARRAYVISION. In short, spot intensity is determined by subtracting the background signal. Spotting replicates under each sample condition can be averaged and then compared with appropriate controls.

[0221] Endothelial tube formation: Endothelial tube formation involves angiogenesis and microvascular capillary formation. Capillary formation and angiogenesis can contribute to skin redness and rosacea. In the presence or absence of test extracts and compounds, the ability of endothelial cells to form tubes can be determined using a capillary disruption assay, which utilizes pre-formed primary human umbilical vein endothelial cells (HUVECs) in a cell culture system.

[0222] In short, culturing HUVECs in vitro on the extracellular matrix stimulates endothelial cell attachment and tubular morphogenesis, forming capillary-like luminal structures. These in vitro-formed capillaries are similar to human vascular capillaries in many ways. Capillary assays are based on this phenomenon and are used to evaluate potential vascular targets.

[0223] HUVEC cultures were grown in a 5% CO2, 37°C cell culture incubator. The complete growth medium for HUVECs was endothelial cell basal medium (EBM) supplemented with 2% fetal bovine serum (FBS), 12 μg / ml bovine brain extract, 1 μg / ml hydrocortisone, and 1 μg / ml GA-1000 (gentamicin-amphotericidal). HUVEC cultures between passage 3 and passage 8 were used for all assays.

[0224] HUVECs were pre-labeled with the fluorescent agent calcein AM and seeded in 96-well culture plates coated with extracellular matrix containing their complete growth medium. Endothelial capillaries should form approximately four hours after morphogenesis. Then, a 50 µl volume of the designed test reagent was applied as a treatment to the formed capillary culture. An untreated control could be added with a carrier of the test reagent. The FDA-approved anti-angiogenic drug SUTENT was used. ® Its concentration can be used as a performance control for the assay. Approximately six hours after treatment, the morphology of the endothelial tubules in each well is examined under a microscope for imaging, allowing for quantitative analysis of capillary destructive activity under the treatment conditions. Each test condition can be performed in duplicate wells, including controls.

[0225] * * * * * * * * * * * * * *

[0226] Based on this disclosure, all compositions and / or methods disclosed and claimed herein can be manufactured and performed without excessive experimentation. Although the compositions and methods of the invention have been described according to preferred embodiments, it will be apparent to those skilled in the art that changes can be made to the compositions and / or methods described herein, as well as the steps or sequence of steps, without departing from the concept, spirit, and scope of the invention. More specifically, it will be apparent that certain chemically and physiologically relevant reagents can be substituted for the reagents described herein while achieving the same or similar results. All such similar substitutions and modifications that are apparent to those skilled in the art are considered to fall within the spirit, scope, and concept of the invention as defined by the appended claims.

Claims

1. A sunscreen composition comprising a first zinc oxide particle dispersion comprising zinc oxide particles having an average particle diameter of from about 110 nanometers (nm) to about 160 nm, the average particle diameter determined by intensity weighted average size measurement using dynamic light scattering; and a second zinc oxide particle dispersion comprising zinc oxide particles having a different average particle diameter than the first zinc oxide particle dispersion.

2. The sunscreen composition of claim 1, further comprising at least a third zinc oxide particle dispersion comprising zinc oxide particles having a third average particle diameter that is different from the average particle diameters of the first and second zinc oxide particle dispersions.

3. The sunscreen composition of claim 1, wherein the second zinc oxide particle dispersion comprises zinc oxide particles having an average particle diameter of from about 195 nm to about 245 nm, the average particle diameter determined by intensity weighted average size measurement using dynamic light scattering.

4. The sunscreen composition of claim 2, wherein the third zinc oxide particle dispersion comprises zinc oxide particles having an average particle diameter of from about 280 nm to 330 nm, the average particle diameter determined by intensity weighted average size measurement using dynamic light scattering.

5. The sunscreen composition of claim 1, wherein the first zinc oxide particle dispersion comprises particles having an average diameter of from about 120 nm to about 145 nm and the second zinc oxide particle dispersion comprises particles having an average diameter of from about 210 nm to about 223 nm, the average diameter determined by intensity weighted average size measurement using dynamic light scattering.

6. The sunscreen composition of claim 2, wherein the third zinc oxide particle dispersion comprises zinc oxide particles having an average particle diameter of from about 295 nm to 315 nm, the average particle diameter determined by intensity weighted average size measurement using dynamic light scattering.

7. The sunscreen composition of claim 1, wherein the first zinc oxide particle dispersion comprises particles having an average diameter of about 137 nm and the second zinc oxide particle dispersion comprises particles having an average diameter of about 221 nm, the average diameter determined by intensity weighted average size measurement using dynamic light scattering.

8. The sunscreen composition of claim 2, wherein the third zinc oxide particle dispersion comprises particles having an average diameter of about 305 nm, the average diameter determined by intensity weighted average size measurement using dynamic light scattering.

9. The sunscreen composition of claim 1, wherein the zinc oxide particles of at least one zinc oxide particle dispersion are coated with a coating, preferably wherein the coating comprises triethoxycaprylylsilane and / or hydrogenated polydimethylsiloxane.

10. The sunscreen composition of claim 1, wherein the zinc oxide particles are dispersed in an oil-in-water emulsion.

11. The sunscreen composition of claim 1, wherein the composition provides a Sun Protection Factor (SPF) rating greater than or equal to 30 when applied to a surface, preferably wherein the SPF is greater than or equal to about 33.

12. The sunscreen composition of claim 1, wherein the composition comprises less than 35 wt% zinc oxide, preferably less than 25 wt% zinc oxide, more preferably about 22 wt% to about 23 wt% zinc oxide.

13. The sunscreen composition of claim 1, wherein: a) the pH is about 5.5 to about 8.0; b) the initial viscosity is about 19000 to about 80000 centipoise (cP); c) the viscosity after 24 hours is about 30000 to about 120000 cP; d) the specific gravity is about 0.9 to about 1.25; and / or e) the hardness is about 28.00 to about 88.20, as measured using a hemispherical probe (TA 43).

14. The sunscreen composition of claim 1, comprising about 10 wt% to about 30 wt% zinc oxide, preferably about 15 wt% to about 23 wt% zinc oxide.

15. The sunscreen composition of claim 1, further comprising one or more than one cosmetic and / or therapeutic agent, preferably wherein the cosmetic and / or therapeutic agent is a redness-reducing agent.

16. The sunscreen composition of claim 15, wherein the redness-reducing agent comprises myrobalan and / or bisabalol.

17. The sunscreen composition of claim 1, further comprising water, isononyl isononanoate, propylene glycol, glyceryl stearate, cetostearyl peg-pp 25, dimethicone, cetearyl alcohol, silica, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, dicocoyl ethylenediamine peg-15 di sulfate disodium, squalane, phenoxyethanol, tocopheryl acetate, octisalate, polysorbate 60, chlorphenesin, bisabalol, disodium EDTA, xanthan gum, C12-15 alkyl benzoate, triethoxycaprylylsilane, hydrogenated polydimethylsiloxane, and / or polyhydroxystearic acid.

18. The sunscreen composition of claim 17, comprising 30% to 50% by weight of water, 10% to 15% by weight of isononyl isononanoate, 1% to 5% by weight of propylene glycol, 1% to 5% by weight of glyceryl stearate, 1% to 3% by weight of cetostearyl alcohol polyoxyl 25, 0.1% to 3% by weight of dimethicone, 0.1% to 3% by weight of cetostearyl alcohol, 0.1% to 3% by weight of silica, 0.1% to 3% by weight of hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, 0.1% to 1% by weight of dicocoyl ethylenediamine PEG-15 disulfate disodium, 0.1% to 1% by weight of squalane, 0.1% to 1% by weight of phenoxyethanol, 0.01% to 0.5% by weight of tocopheryl acetate, 0.01% to 0.5% by weight of octisalate, 0.01% to 0.5% by weight of polysorbate 60, 0.01% to 0.5% by weight of chlorphenesin, 0.01% to 0.5% by weight of bisabalol, 0.01% to 0.5% by weight of disodium EDTA, 0.01% to 0.5% by weight of xanthan gum, 5% to 15% by weight of C12-15 alkyl benzoate, 0.1% to 3% by weight of triethoxysilane, 0.01% to 1% by weight of hydrogenated polydimethylsiloxane, and / or 0.1% to 3% by weight of polyhydroxystearic acid, wherein all amounts are weight percentages based on the total weight of the composition.

19. A method for protecting skin from ultraviolet radiation comprising applying the sunscreen composition of claim 1 to skin in need thereof, preferably facial skin.

20. The method of claim 19, wherein applying to the skin comprises rubbing the sunscreen composition onto the skin until the composition appears non-white and / or rubbing the composition onto the skin to provide the skin with a sun protection factor (SPF) rating greater than or equal to 30.

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