Nutritional compositions and methods of use thereof

Abstract

The present invention relates generally to methods and compositions for treating the skin of a subject. In some embodiments, the methods and compositions disclosed herein include topical or oral administration of a nutraceutical composition and / or topical composition wherein the composition comprises at least two of puerarin, collagen, and hyaluronic acid.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of priority to U.S. Provisional Patent Application Serial No. 63 / 401,019, filed on August 25, 2022, the entire contents of which are incorporated herein by reference. Background Art Technical Field

[0003] The present invention relates generally to the field of nutraceutical compositions and topical compositions. More particularly, it relates to the use of nutraceutical compositions for treating skin.

[0004] Description of Related Technology

[0005] Aging, chronic exposure to adverse environmental factors, malnutrition, fatigue, etc., can alter the visual appearance, physical properties, or physiological function of the skin in ways that are considered visually undesirable. The most significant and obvious changes include the formation of fine lines and wrinkles, loss of elasticity, increased sagging, loss of firmness, loss of color uniformity or loss of tone, a rough surface texture, and mottled pigmentation. Less obvious but measurable changes that occur as the skin ages or is subjected to chronic environmental insults include an overall decrease in cell and tissue viability, a decrease in the rate of cell replication, decreased blood flow to the skin, decreased water content, accumulated errors in structure and function, alterations in the normal regulation of common biochemical pathways, and a decrease in the skin's ability to remodel and repair itself. Many changes in the skin's appearance and function are caused by changes in the skin's outer epidermal layer, while other changes are caused by changes in the dermis further below.

[0006] Glycation is a process caused by excess glucose in the skin's fibers. This excess triggers an internal reaction in which sugar molecules attach to collagen and elastin, proteins that normally help keep the skin firm and supple. This leads to aging and moisture loss.

[0007] Typically, compositions for treating visually undesirable skin conditions are formulated for topical use, which can cause skin irritation and lead to additional side effects. Furthermore, the body cannot absorb collagen in its intact form, which presents challenges for oral formulations for treating skin conditions such as fine lines or wrinkles. Furthermore, once ingested, collagen may be deposited in other areas of the body.

[0008] Previous attempts to improve the visual appearance of skin with known skin active ingredients have shown various drawbacks, such as skin irritation and prolonged recovery period. Currently available orally ingestible formulations may contain a variety of additives or fillers that lead to undesirable side effects.

[0009] This article shows that a combination of puerarin, collagen, and / or hyaluronic acid can inhibit glycation, which can maintain skin firmness and hydration. Summary of the Invention

[0010] The methods and compositions of the present disclosure overcome the deficiencies of the prior art by providing a convenient delivery form of an effective combination of ingredients to improve skin elasticity, improve skin hydration, reduce the effects of photoaging, and inhibit glycation on the skin. In some embodiments, these compositions are formulated as orally ingestible compositions.

[0011] In certain embodiments, disclosed herein are compositions useful for combating a wide range of signs of aging. In certain embodiments, the anti-aging compound may be, but is not limited to, puerarin, collagen, and / or hyaluronic acid. In certain embodiments, the collagen is fish collagen. In certain embodiments, the collagen is a collagen peptide. In certain embodiments, the collagen is a fish collagen peptide. In certain embodiments, disclosed herein are compositions and / or methods useful for reducing deep lines and wrinkles, evening out uneven skin tone, increasing skin radiance, increasing skin elasticity, increasing skin firmness, reducing skin sagging, reducing facial volume loss, increasing skin barrier function, inhibiting skin antioxidant capacity, increasing skin collagen expression, increasing skin elastin expression, and inhibiting skin resistance to glycation.

[0012] In some embodiments, compositions disclosed herein include any one, any combination of puerarin, collagen, hyaluronic acid, vitamin C and / or astaxanthin from kudzu root. In some embodiments, compositions may also include ascorbic acid, lycopene, ceramosides, resveratrol, vitamin E, beta-carotene and / or biotin. The amount of composition may vary (e.g., amount may be a minimum of 0.000001 wt % to a maximum of 80 wt % or any range thereof) in the composition. In some cases, ceramosides are plant-derived ceramosides. In some cases, ceramosides derive from wheat, rice and / or peach.

[0013] In some embodiments, the compositions disclosed herein include any one or any combination of puerarin and / or a pueraria extract containing puerarin, hyaluronic acid and / or ceramosides. In some embodiments, the compositions may also include ascorbic acid, lycopene, vitamin C, astaxanthin, resveratrol, vitamin E, beta-carotene, collagen and / or biotin. In some cases, the compositions do not contain collagen. The amount of the ingredients in the compositions may vary (e.g., from a minimum of 0.000001% by weight to a maximum of 80% by weight or any range thereof).

[0014] In certain embodiments, the composition can be formulated as a composition for oral intake. In certain embodiments, the composition can include any one, any combination, or all of puerarin, collagen, hyaluronic acid, vitamin C, and / or astaxanthin from Pueraria lobata. In some embodiments, the composition may also include ascorbic acid, lycopene, ceramosides, and / or biotin. The composition of the present invention may also include any one, any combination, or all of the following additional ingredients: water, pharmaceutical agents, chelating agents, preservatives, thickeners, compounds containing polysiloxanes, essential oils, structuring agents, vitamins, pharmaceutical ingredients, or antioxidants, or non-naturally occurring compounds, or any combination of these ingredients, or a mixture of these ingredients. In some aspects, the composition may include at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or all of the additional ingredients described above. Non-limiting examples of these additional ingredients are described in this specification sheet in full and are incorporated into this section by reference. Amounts of these ingredients may range from 0.0001% to 99.9% by weight or volume of the composition, or any integer or range therebetween as disclosed elsewhere in this specification, which are incorporated by reference into this paragraph.

[0015] In some aspects of the present invention, the composition may also include one or more than one carrier or diluent. These carriers / diluents may be adjuvants, excipients or carriers, such as preservatives, fillers, disintegrants, wetting agents, emulsifiers, suspending agents, sweeteners, flavorings, aromatics, antibacterials, antifungals, lubricants, vitamins, polymers, silicone-containing compounds, essential oils, structurants and dispersants. Each carrier is acceptable in a sense that is compatible with the other ingredients of the preparation and harmless to the object. In some aspects of the present invention, the carrier may include at least one hydrophilic polymer compound selected from gum, cellulose ether, acrylic resin, carbohydrate carrier, talc, lactose, mannitol, glucose, water, gelatin, protein-derived compound, polyvinyl pyrrolidone, magnesium stearate and any combination thereof. The non-limiting examples of diluent / carrier are described in this specification in full and are incorporated into this section by reference. Amounts of these ingredients may range from 0.0001% to 99.9% by weight or volume of the composition, or any integer or range therebetween as disclosed elsewhere in this specification, which are incorporated by reference into this paragraph.

[0016] Stable compound can be stored at room temperature for 1 month, 6 months, 12 months, 18 months or 24 months.In some aspects of the present invention, composition is formulated as edible composition, dietary supplement, nutrient, food additive, food, complex carbohydrate, flour, sugar, beverage, powder, tablet, gel capsule, pearl, edible tablet or chewing thing (soft candy), gelatin, lotion (lotion), transdermal patch or liquid solution for oral administration.In some respects, product can be nutrient product.Nutrient product can be those described in other parts of this specification sheets or those well known by persons skilled in the art.The limiting examples of product comprises pill, tablet, edible chewing thing, capsule, creme, lotion, gel, gelatin, spray, mist, dissolving film agent, nutrient, dietary supplement, food additive, food, complex carbohydrate, flour, sugar, beverage or liquid etc., or its arbitrary combination. The composition can be formulated for oral administration at least 1 time, at least 2 times, at least 3 times, at least 4 times, at least 5 times, at least 6 times, at least 7 times, or more than 7 times per day, or at least once every 2 days, every 3 days, every 4 days, every 5 days, every 6 days, every 7 days, every 8 days, every 9 days, every 10 days, every 11 days, every 12 days, every 13 days, every 14 days, every 15 days, or every more than 15 days during use. In some aspects of the invention, the composition can be storage stable or color stable, or storage stable and color stable.

[0017] In certain embodiments, any one, any combination or all of puerarin, collagen, hyaluronic acid, vitamin C, resveratrol, vitamin E, beta-carotene, lycopene and / or astaxanthin from Pueraria lobata can be formulated as a composition for topical application. In certain embodiments, the compositions disclosed herein may also include any combination of one or more than one ingredients described herein. For example, in certain embodiments, the compositions may include one or more than one active ingredient, regulator, humectant, pH regulator, structuring agent, flavoring, inorganic salt and / or preservative selected from one or more than one additional ingredients. In certain embodiments, the disclosed compositions are used in any one or more than one method described herein.

[0018] In particular, the composition formulated for topical application can have a dermatologically acceptable carrier or vehicle for compound, composition and extract.Composition can also include moisturizing agent or wetting agent, surfactant, compound containing polysiloxane, UV agent, oil and / or other ingredients described in this specification or other ingredients known in the art.Composition can be lotion, cream, body milk, facial mask, scrub, washing liquid, gel, essence, emulsion (for example, oil-in-water, water-in-oil, water-in-polysiloxane, polysiloxane-in-water, water-in-oil-in-water, oil-in-water-in-oil, polysiloxane-in-water-in-oil etc.), solution (for example, aqueous solution or hydroalcoholic solution), anhydrous matrix (for example, lipstick or powder), ointment, emulsion, unguentum, aerosol, solid form, eye gel etc.Composition can be powder form (for example, dry, freeze-dried, granular etc.). The composition can be formulated for topical skin application at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, or more than 7 times per day during use. In some aspects of the invention, the composition can be storage stable or color stable, or both storage stable and color stable. It is also contemplated that the viscosity of the composition can be selected to achieve the desired result. For example, the viscosity of such a composition can range from about 1 cps to well over 1 million cps, or any range or integer derivable therein (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, 8000 cps, 9000 cps, 10000 cps, 20000 cps, 30000 cps, 40000 cps, 50000 cps, 60000 cps, 70000 cps, 80000 cps, 90000 cps, 100000 cps, 200000 cps, 300000 cps, 400000 cps, 500000 cps, 600000 cps, 700000 cps, 800000 cps, 900 000cps, 8000cps, 9000cps, 10000cps, 20000cps, 30000cps, 40000cps, 50000cps, 6000 0cps, 70000cps, 80000cps, 90000cps, 100000cps, 200000cps, 300000cps, 400000cps, 5 00000cps, 600000cps, 700000cps, 800000cps, 900000cps, 1000000cps, 2000000cps, 3000000cps, 4000000cps, 5000000cps, 100000000cps, etc., measured at 25°C on a Brookfield viscometer using a TC spindle at 2.5 rpm).

[0019] In certain embodiments, the compositions disclosed herein do not comprise any one or more ingredients selected from one or more active ingredients, regulators, moisturizers, pH regulators, structurants, inorganic salts and / or preservatives. In certain embodiments, the compositions disclosed herein do not comprise biotin.

[0020] Also disclosed are methods for using the compositions disclosed herein. In certain embodiments, the disclosed compositions comprise, consist essentially of, or consist of any one, any combination, or all of puerarin, collagen, or hyaluronic acid from Pueraria lobata. In some cases, the method includes taking a nutritional supplement. In some embodiments, the composition can be in the form of an edible pill, gel capsule, liquid, powder, spray, foam, tablet, capsule, soft capsule, soft candy, effervescent tablet, liquid beverage, food bar, or other delivery form that can be orally ingested. In some embodiments, the composition can be atomized. In some cases, the method includes topically applying any one of the compositions disclosed herein to skin areas and / or facial areas and / or eye areas in need. In one aspect, any one of the compositions disclosed herein is topically applied, and the composition is allowed to remain on the application area, removed from the application area after a period of time, and / or directly removed after application.

[0021] In other embodiments, compositions comprising, consisting essentially of, or consisting of puerarin, collagen, hyaluronic acid, vitamin C, and / or astaxanthin from Pueraria lobata are disclosed.

[0022] The compositions of the present invention can also be modified to have a desired oxygen radical absorbance capacity (ORAC) value. In certain non-limiting aspects, the compositions of the present invention, or components thereof, or extracts thereof, described throughout this specification can be modified to have 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, 100, 110, 120, 130, 140, 150, 160, 170, 1 ... , 90, 95, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, 10,000, 15,000, 20,000, 30,000, 50,000, 100,000 or an ORAC value greater than 100,000 or any range derivative thereof.

[0023] In non-limiting aspects, the composition can have a pH of about 3 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 can include 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 can also include a preservative. Non-limiting examples of preservatives include phenoxyethanol, methylparaben, propylparaben or any mixture thereof. In some embodiments, the composition does not contain paraben.

[0024] The composition of the present invention may have UVA absorption properties and UVB absorption properties. The composition 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 any derivative thereof. The composition may be a sunscreen lotion, a sunscreen spray or a sunscreen cream.

[0025] The composition of the present invention may also include any one, any combination or all of the following additional ingredients: water, a conditioning agent, a chelating agent, a moisturizing agent, a pH adjusting agent, an inorganic salt, a preservative, a thickening agent, a compound containing polysiloxane, an essential oil, a structuring agent, a vitamin, a pharmaceutical ingredient or an antioxidant, or any combination of these ingredients or a mixture of these ingredients. In some aspects, the composition may include at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten or all of the additional ingredients described above. Non-limiting examples of these additional ingredients are described in the entire specification and are incorporated into this section by reference. The amount of these ingredients can be 0.0001% to 99.9% by weight or volume of the composition, or any integer or any range therebetween as disclosed in other parts of this specification, which are incorporated into this section by reference.

[0026] Also contemplated are kits comprising the compositions of the present invention. In certain embodiments, the composition is contained in a container. The container can be a bottle, dispenser, or package. The container can dispense a predetermined amount of the composition. In certain aspects, the composition is dispensed in the form of a spray, mist, agglomerate, or liquid. The container can include a marking on its surface. The marking can be a word, abbreviation, picture, or symbol.

[0027] It is also contemplated that the compositions disclosed in this specification can be used as leave-in compositions or rinse-out compositions. For example, a leave-in composition can be a composition that is topically applied to the skin and retained on the skin for a period of time (e.g., at least 5 minutes, 6 minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, 20 minutes, or 30 minutes, or at least 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, or 24 hours, or overnight or all day). Alternatively, a rinse-out composition can be a product that is intended to be applied to the skin and then, over a period of time, for example, less than 5 minutes, 4 minutes, 3 minutes, 2 minutes, or 1 minute, removed from the skin or rinsed off (e.g., with water). Examples of rinse-out compositions can be skin cleansers, shampoos, conditioners, or soaps. Examples of leave-on compositions may be skin, sunscreen, face mask, night cream or day cream.

[0028] Aspects 1 to 20 are also disclosed in the context of the present invention. Aspect 1 is a method for treating the skin of a subject comprising administering a nutraceutical composition, wherein the nutraceutical composition comprises puerarin, collagen, and hyaluronic acid. Aspect 2 is the method of aspect 1, wherein the puerarin is a kudzu root extract and / or a pueraria lobate extract. Aspect 3 is the method of aspect 1 or aspect 2, wherein the collagen is fish collagen. Aspect 4 is the method of aspects 1 to 3, wherein the nutraceutical composition further comprises astaxanthin, ascorbic acid, lycopene, ceramosides, and / or biotin. Aspect 5 is the method of aspect 4, wherein the astaxanthin is an encapsulated powder of Haematococcus pluvialis. Aspect 6 is the method of any one of aspects 1 to 5, wherein the nutraceutical composition further comprises sodium hyaluronate and / or citric acid. Aspect 7 is a method according to any one of aspects 1 to 6, wherein the nutritional composition further comprises a flavoring agent, such as blood orange juice powder, rose powder, mixed berry powder, beetroot, lemon juice powder, and / or grapefruit powder. Aspect 8 is a method according to any one of aspects 1 to 7, wherein the nutritional composition further comprises sea buckthorn (Hippophae rhamnoides), resveratrol, vitamin E, and / or beta-carotene. Aspect 9 is a method according to any one of aspects 1 to 8, wherein the nutritional composition further comprises isomalt and / or stevioside. Aspect 10 is a method according to any one of aspects 1 to 9, wherein the nutritional composition is a powder, capsule, tablet, or soft candy. Aspect 11 is a method according to aspects 1 to 10, wherein the nutritional composition inhibits glycation of the skin, such as by inhibiting the production of carboxymethyllysine and / or pentosidine. Aspect 12 is the method of aspects 1 to 11, wherein the nutraceutical composition comprises: 40% to 70% by weight collagen; 0.1% to 2.0% by weight hyaluronic acid; and 2.0% to 15% by weight puerarin. Aspect 13 is the method of aspects 1 to 12, wherein the composition is a dietary supplement. Aspect 14 is the method of aspects 1 to 13, wherein the composition increases skin elasticity. Aspect 15 is the method of aspects 1 to 14, wherein the composition is an emulsion, solution, serum, lotion, cream, gel, gel emulsion, or gel serum. Aspect 16 is the method of aspect 15, wherein the composition is topically applied to the skin and allowed to remain on the skin. Aspect 17 is a nutraceutical composition comprising: puerarin; collagen; and / or hyaluronic acid. Aspect 18 is the composition of aspect 17, wherein the composition further comprises: astaxanthin; ascorbic acid; ceramosides; lycopene; and / or biotin.Aspect 19 is the composition of aspect 17 or 18, wherein the composition further comprises: sodium hyaluronate; citric acid; sea buckthorn; resveratrol; vitamin E; beta-carotene; isomalt; and / or stevioside. Aspect 20 is the composition of aspects 17 to 19, wherein the composition further comprises a flavoring agent, such as: blood orange juice powder; rose powder; mixed berry powder; beetroot; lemon juice powder; and / or grapefruit powder. Aspect 21 is the method of aspects 1 to 16 or the composition of aspects 17 to 20, wherein the composition has a pH of 1.5 to 8.5.

[0029] Aspects 22 to 43 are also disclosed in the context of the present invention. Aspect 22 is a method of treating the skin of a subject, comprising administering a nutraceutical composition, wherein the nutraceutical composition comprises at least two of puerarin, collagen, and hyaluronic acid. Aspect 23 is a method according to aspect 22, wherein the puerarin is a kudzu root extract and / or a kudzu extract. Aspect 24 is a method according to aspects 22 to 23, wherein the collagen is fish collagen. Aspect 25 is a method according to aspects 22 to 24, wherein the nutraceutical composition further comprises astaxanthin, ascorbic acid, lycopene, ceramosides, and / or biotin. Aspect 26 is a method according to aspect 25, wherein the astaxanthin is encapsulated Haematococcus pluvialis powder. Aspect 27 is a method according to aspects 22 to 26, wherein the nutraceutical composition further comprises sodium hyaluronate and / or citric acid. Aspect 28 is the method according to aspects 22 to 27, wherein the nutritional composition further comprises a flavoring agent, such as blood orange juice powder, rose powder, mixed berry powder, beetroot, lemon juice powder, and / or grapefruit powder. Aspect 29 is the method according to aspects 22 to 28, wherein the nutritional composition further comprises sea buckthorn, resveratrol, vitamin E, and / or beta-carotene. Aspect 30 is the method according to aspects 22 to 29, wherein the nutritional composition further comprises isomalt and / or stevioside. Aspect 31 is the method according to aspects 22 to 30, wherein the nutritional composition inhibits glycation of the skin, such as by inhibiting the production of carboxymethyllysine and / or pentosidine. Aspect 32 is the method according to aspects 22 to 31, wherein the nutritional composition increases skin elasticity. Aspect 33 is the method according to aspects 22 to 32, wherein the nutritional composition comprises puerarin, collagen, and hyaluronic acid. Aspect 34 is the method of aspect 33, wherein the nutraceutical composition comprises: 40% to 70% collagen by weight; 0.1% to 2.0% hyaluronic acid by weight; and 2.0% to 15% puerarin by weight. Aspect 35 is the method of aspects 22 to 33, wherein the nutraceutical composition is a dietary supplement. Aspect 36 is the method of aspect 35, wherein the nutraceutical composition is a powder, capsule, tablet, or gummies. Aspect 37 is the method of aspects 22 to 33, wherein the nutraceutical composition is an emulsion, solution, serum, lotion, cream, gel, gel emulsion, or gel serum. Aspect 38 is the method of aspect 37, wherein the nutraceutical composition is topically applied to the skin and allowed to remain on the skin. Aspect 39 is the method of aspects 22 to 38, wherein the nutraceutical composition has a pH of 1.5 to 8.5. Aspect 40 is a nutraceutical composition comprising: puerarin; collagen; and / or hyaluronic acid.Aspect 41 is the nutritional composition of aspect 40, wherein the composition further comprises: astaxanthin; ascorbic acid; ceramosides; lycopene; and / or biotin. Aspect 42 is the nutritional composition of aspects 40-41, wherein the composition further comprises: sodium hyaluronate; citric acid; sea buckthorn; resveratrol; vitamin E; beta-carotene; isomalt; stevioside; blood orange juice powder; rose powder; mixed berry powder; beetroot; lemon juice powder; and / or grapefruit powder. Aspect 43 is the nutritional composition of aspects 40-42, wherein the composition has a pH of 1.5 to 8.5.

[0030] Also disclosed in the context of the present invention are aspects 44 to 64. Aspect 44 is a method of treating the skin of a subject, comprising administering a nutraceutical composition, wherein the nutraceutical composition comprises puerarin, hyaluronic acid, and / or ceramosides. Aspect 45 is the method of aspect 44, wherein the puerarin is a kudzu root extract and / or a kudzu root extract. Aspect 46 is the method of aspects 44 to 45, wherein the nutraceutical composition further comprises astaxanthin, ascorbic acid, lycopene, collagen, and / or biotin. Aspect 47 is the method of aspect 46, wherein the astaxanthin is an encapsulated powder of Haematococcus pluvialis. Aspect 48 is the method of aspects 44 to 47, wherein the nutraceutical composition further comprises sodium hyaluronate and / or citric acid. Aspect 49 is the method of aspects 44 to 48, wherein the nutraceutical composition further comprises a flavoring agent, such as blood orange juice powder, rose powder, mixed berry powder, beetroot powder, lemon juice powder, and / or grapefruit powder. Aspect 50 is the method of aspects 44 to 49, wherein the nutraceutical composition further comprises sea buckthorn, resveratrol, vitamin E, and / or beta-carotene. Aspect 51 is the method of aspects 44 to 50, wherein the nutraceutical composition further comprises isomalt and / or stevioside. Aspect 52 is the method of aspects 44 to 51, wherein the nutraceutical composition inhibits glycation of the skin, for example, inhibits the production of carboxymethyllysine and / or pentosidine. Aspect 53 is the method of aspects 44 to 52, wherein the nutraceutical composition increases skin elasticity. Aspect 54 is the method of aspects 44 to 53, wherein the nutraceutical composition comprises puerarin, ceramosides, and hyaluronic acid. Aspect 55 is the method of aspect 54, wherein the nutraceutical composition comprises: 0.0001% to 15% by weight of ceramosides; 0.1% to 5.0% by weight of hyaluronic acid; and 2.0% to 25% by weight of puerarin. Aspect 56 is the method of aspects 44 to 55, wherein the nutraceutical composition is a dietary supplement. Aspect 57 is the method of aspect 56, wherein the nutraceutical composition is a powder, capsule, tablet, or gummies. Aspect 58 is the method of aspects 44 to 57, wherein the nutraceutical composition is an emulsion, solution, serum, lotion, cream, gel, gel emulsion, or gel serum. Aspect 59 is the method of aspect 58, wherein the nutraceutical composition is topically applied to the skin and allowed to remain on the skin. Aspect 60 is the method of aspects 44 to 59, wherein the nutraceutical composition has a pH of 1.5 to 8.5. Aspect 61 is a nutraceutical composition comprising: puerarin; ceramosides; and / or hyaluronic acid. Aspect 62 is the nutraceutical composition of aspect 61, wherein the composition further comprises: astaxanthin; ascorbic acid; collagen; lycopene; and / or biotin.Aspect 63 is the nutritional composition of aspects 61 to 63, wherein the composition further comprises: sodium hyaluronate; citric acid; sea buckthorn; resveratrol; vitamin E; beta-carotene; isomalt; stevioside; blood orange juice powder; rose powder; mixed berry powder; beetroot; lemon juice powder; and / or grapefruit powder. Aspect 64 is the nutritional composition of aspects 61 to 63, wherein the composition has a pH of 1.5 to 8.5.

[0031] It is contemplated that any embodiment discussed in this specification can be implemented with respect to any method or composition of the invention, and vice versa. Additionally, the compositions of the invention can be used to implement the methods of the invention.

[0032] 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 that have particular tactile properties that feel pleasant on the skin (e.g., compositions that are not too thin or too greasy, compositions with a silky texture, compositions that are non-sticky or non-tacky, etc.). Pharmaceutically elegant or cosmetically elegant can also be related to the creaminess or lubricity of the composition, or to the moisturizing properties of the composition.

[0033] Products comprising the compositions of the present invention are also contemplated. In non-limiting aspects, the product can be a cosmetic. The cosmetic can be those described elsewhere in this specification or known to those skilled in the art. Non-limiting examples of products include moisturizers, creams, lotions, toners, serums, gels, lotions, body milks, scrubs, foundations, night creams, lipsticks, cleansers, lotions, sunscreens, facial masks, anti-aging products, deodorants, antiperspirants, perfumes, colognes, and the like.

[0034] The term "nutraceutical" is art-recognized and is intended to describe specific compounds found in foods that can prevent disease or improve an undesirable condition. Nutraceuticals can be in the form of dietary supplements, nutritional products, food additives, foods, complex carbohydrates, flours, sugars, beverages, or the like, or any combination thereof.

[0035] "Topical application" means applying or spreading the composition onto the surface of the lips or keratinous tissue. "Topical skin compositions" include compositions suitable for topical application to the skin, lips, and / or keratinous tissue. Such compositions are generally dermatologically acceptable in that they do not present excessive toxicity, incompatibility, instability, allergic reactions, etc., when applied to the lips, skin, and / or keratinous tissue. The topical skin care compositions of the present invention may have a selected viscosity to avoid noticeable dripping or pooling after application to the lips, skin, and / or keratinous tissue.

[0036] "Keratinous tissue" includes the keratin-containing layer that is the outermost protective covering of mammals and includes, but is not limited to, lips, skin, hair, and nails.

[0037] The term "about" or "approximately" is defined as close to what is understood by one of ordinary skill in the art. In one non-limiting embodiment, the term is defined as within 10% deviation, preferably within 5% deviation, more preferably within 1% deviation, and most preferably within 0.5% deviation.

[0038] The term "substantially" and variations thereof are defined to a large extent, but not necessarily completely, as understood by one of ordinary skill in the art, and in one non-limiting embodiment, substantially refers to within 10%, within 5%, within 1%, or within 0.5%.

[0039] The terms "inhibit" or "reduce" or any variants of these terms include any measurable reduction or complete inhibition to achieve a desired result. The terms "promote" or "increase" or any variants of these terms include any measurable increase, such as a measurable increase in a protein or molecule (e.g., a matrix protein such as fibronectin, laminin, collagen, or elastin, or a molecule such as hyaluronic acid) to achieve a desired result.

[0040] The term "effective" as used in the specification and / or claims means sufficient to achieve a desired, intended, or objective result.

[0041] In the claims and / or description, when used in conjunction with the terms "includes," "comprising," "having," or "containing," or any variations of these terms, an indefinite quantifier preceding an element may mean "a / an," but it is also consistent with the meaning of "one or more," "at least one," and "one or more than one."

[0042] As used in this specification and in one or more claims, the words "comprising," "having," "including," or "containing" and variations thereof are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.

[0043] The compositions and methods of use thereof may "comprising," "consisting essentially of," or "consisting of" any ingredient or any step disclosed throughout the specification. With respect to the phrase "consisting essentially of," the fundamental and novel properties of the compositions and methods of the present invention are their ability to improve skin elasticity, improve skin hydration, reduce the effects of photoaging, and inhibit glycation on the skin.

[0044] The phrase "and / or" means "and" or "or." For example, A, B, and / or C includes: 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.

[0045] Other objects, features and advantages of the present invention will become apparent from the detailed description below. However, it should be understood that the detailed description and examples, while indicating specific embodiments of the present invention, are provided for illustration only. Furthermore, it is contemplated that variations and modifications within the spirit and scope of the present invention will become apparent to those skilled in the art from this detailed description.

[0046] Description of Illustrative Embodiments

[0047] As described above, in certain embodiments, the present invention provides solutions to problems associated with current cosmetics. In some embodiments, effective amounts of at least two of Pueraria root extract, collagen, and / or hyaluronic acid are used to influence cellular mechanisms associated with collagen I, MMPs, and other measurements. Compositions comprising effective amounts of Pueraria root extract, collagen, and / or hyaluronic acid can be used to reduce fine lines and wrinkles, even out skin tone, brighten skin tone, increase skin radiance, reduce photodamage, increase elasticity, increase skin barrier function, increase skin firmness, and reduce skin sagging, with enhanced and synergistic benefits compared to certain other nutraceutical compositions comprising only one of these ingredients.

[0048] In some embodiments, disclosed herein are compositions and methods for inhibiting skin glycation, inhibiting photoaging and / or improving the compliance of an object to a cosmetic treatment regimen. In certain embodiments, in the compositions and methods disclosed herein, using the fibroblast-UVA model, the composition has significantly better effects on collagen 1, MMP-1, MMP-3, and HAS2 compared to a single component alone. In certain embodiments, the compositions and / or methods disclosed herein improve the visual appearance of the skin. In certain embodiments, the compositions and / or methods disclosed herein improve the compliance of an object to a treatment regimen recommended by a clinician and / or manufacturer. In certain embodiments, the compositions and / or methods disclosed herein reduce discomfort, erythema, and / or dry skin. In certain aspects, the compositions disclosed herein and methods of use thereof may include, but are not limited to, a combination of ingredients to reduce and / or eliminate the appearance of fine lines and / or wrinkles, renew skin, increase skin luster, soothe skin, soothe tissue, reduce and / or eliminate inflammation, even out skin tone, reduce the appearance of hyperpigmented skin, age spots, liver spots, and / or dark spots, and / or increase skin smoothness. In certain embodiments, the compositions and / or methods described herein reduce unwanted side effects, reduce adverse events, and / or increase a subject's compliance with a treatment regimen.

[0049] As shown in Table 2, the combination of collagen peptides, sodium hyaluronate, Haematococcus pluvialis (containing astaxanthin) and / or Pueraria lobata (Willd.) ohwi extract (containing puerarin) expanded previously unknown effective pathways (e.g., MMP-3) and enhanced the effects of other pathways (e.g., collagen 1, MMP-1, HAS2) compared to the individual ingredients, as shown in in vitro tests.

[0050] In some embodiments, the composition comprising collagen peptides, sodium hyaluronate, Haematococcus pluvialis (comprising astaxanthin) and kudzu extract (comprising puerarin) can be designed as a nutraceutical or dietary supplement. The composition can be in the form of an edible pill, gel capsule, liquid, powder, spray, foam, tablet, capsule, soft capsule, soft candy, effervescent tablet, liquid beverage, food bar or other delivery form that can be orally ingested. In some embodiments, the composition can be aerosolized.

[0051] In some embodiments, the composition comprising collagen peptides, sodium hyaluronate, Haematococcus pluvialis (comprising astaxanthin), and kudzu extract (comprising puerarin) can be designed as an emulsion (e.g., oil-in-water, water-in-oil), a gel, an essence, a gel emulsion, a gel essence, a lotion, a mask, a scrub, a lotion, a cream, a facial cleanser, a sunscreen, a cleanser, a day cream, a night cream, a body lotion, other skin treatment products, or any combination thereof.

[0052] Some 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). Thereafter, if desired, the composition can be rinsed off the skin or peeled off the skin. Some compositions disclosed herein can be applied to the skin and immediately rinsed off the skin. Some compositions disclosed herein can be applied to the skin and at least partially absorbed by the skin.

[0053] In summary, the studies described herein demonstrate that a composition comprising collagen peptides, sodium hyaluronate, Haematococcus pluvialis (containing astaxanthin) and kudzu extract (containing puerarin) enhances skin cell bioactivity and has better skin protective effects on collagen 1, MMP-1, MMP-3 and / or HAS2 than any single ingredient.

[0054] A.Active ingredients

[0055] As described above, compositions comprising any combination of collagen peptides, sodium hyaluronate, Haematococcus pluvialis (comprising astaxanthin), and kudzu extract (comprising puerarin) can be used to reduce the appearance of skin aging, improve hydration, increase elasticity, and inhibit glycation and oxidation of the skin.

[0056] Pueraria root, or kudzu root, extracts (containing puerarin) have been traditionally used in Traditional Chinese Medicine to treat various medical conditions. Kudzu, also known as mountain kudzu (Pueraria montana), Chinese arrowroot, and Japanese arrowroot, is a group of climbing, winding, and sprawling perennial deciduous vines native to East Asia, Southeast Asia, and some Pacific islands.

[0057] Astaxanthin is an antioxidant and is naturally produced in the freshwater microalgae Haematococcus pluvialis and the yeast fungus Xanthophyllomyces dendrorhous (also known as Phaffia).

[0058] Hyaluronic acid (also known as hyaluronic acid) is an anionic, non-sulfated glycosaminoglycan that is widely distributed in connective, epithelial, and neural tissues. Sodium hyaluronate is the sodium salt of hyaluronic acid. Hyaluronic acid is a humectant that provides hydration to the skin by binding water to collagen.

[0059] The premise of the present invention is to determine that any combination of a composition comprising collagen peptides, sodium hyaluronate, Haematococcus pluvialis (containing astaxanthin) and kudzu extract (containing puerarin) can be used to enhance the bioactivity of skin cells and has a better skin protective effect on collagen 1, MMP-1, MMP-3 and HAS2 than a single ingredient.

[0060] The ingredients disclosed herein can be used in combination with various other suitable ingredients and / or can be used in different product forms to treat a variety of skin conditions. In some embodiments, the ingredients are used in combination with various other suitable ingredients in a form that can be orally ingested. In some embodiments, the ingredients are used in combination with various other suitable ingredients in a formulation suitable for topical application.

[0061] The extracts described herein may be extracts prepared by extraction methods known in the art and combinations thereof. Non-limiting examples of extraction methods include liquid-liquid extraction, solid phase extraction, water extraction, ethyl acetate extraction, alcohol extraction, acetone extraction, oil extraction, supercritical carbon dioxide extraction, heating extraction, pressure extraction, pressure drop extraction, ultrasonic extraction, and the like. The extracts may be liquid, solid, dried liquid, resuspended solid, and the like.

[0062] B. Amount of ingredients

[0063] It is contemplated that the compositions of the present invention may include any amount of the ingredients discussed in this specification. The compositions may also include any number of combinations of additional ingredients described throughout this specification (e.g., pigments, or additional cosmetic or pharmaceutical ingredients). The concentration of any ingredient in the composition may vary. In non-limiting embodiments, for example, the composition can comprise, consist essentially of, or consist in its final form 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%, 0.0022%, 0.0030%, 0.0031%, 0.0032%, 0.0033%, 0.0034%, 0.0035%, 0.0036%, 0.0037%, 0.0038%, 0.0039%, 0.0140%, 0.0141%, 0.0142%, 0.0143%, 0.0144%, 0.0145%, 0.0146%, 0.0147%, 0.0148%, 0.0149%, 0.025%, 0.026 23%, 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%, 0.0051 %, 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%, 0.0079%, 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％、0.0550％、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 derived therefrom of at least one ingredient as described in the entire specification and claims. In non-limiting aspects, percentages can be calculated by weight or volume of the total composition. It will be understood by those of ordinary skill in the art that concentrations can vary depending on the addition, substitution, and / or reduction of ingredients in a given composition. In certain embodiments, the compositions described herein do not comprise one or more than one of collagen peptides, sodium hyaluronate, Haematococcus pluvialis (comprising astaxanthin), ceramosides, and kudzu extract (comprising puerarin).

[0064] C. Carrier

[0065] The compositions of the present invention may be contained in or incorporated into all types of vehicles and carriers.In some aspects, the concentrations and combinations of compounds, ingredients, and agents may be selected in such a way that the combination is chemically compatible and does not form complexes that precipitate from the final product.

[0066] 1. Nutritional preparations and oral preparations

[0067] In some aspects, the carrier or vehicle can be a nutraceutical or oral carrier or vehicle. Non-limiting examples of such carriers or vehicles include dietary supplements, nutraceuticals, food additives, foods, complex carbohydrates, flour, sugar, beverages, and any combination thereof. Variants and other suitable carriers will be readily apparent to those skilled in the art and are suitable for use in the present invention.

[0068] Suitable carriers or diluents illustratively include, but are not limited to, lactose including anhydrous lactose and lactose monohydrate, starch including directly compressible starch and hydrolyzed starch (e.g., Celutab), alone or in combination. TM and Emdex TM ) including starch, mannitol, sorbitol, xylitol, dextrose (such as Cerelose TM2000) and dextrose monohydrate, calcium hydrogen phosphate dihydrate, sucrose-based diluents, confectioner's sugar, calcium hydrogen sulfate monohydrate, calcium sulfate dihydrate, granulated calcium lactate trihydrate, dextrates, inositol, hydrolyzed cereal solids, amylose, cellulose including microcrystalline cellulose, α-cellulose from food-grade sources and amorphous cellulose (e.g., Rexcel J), powdered cellulose, hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC), calcium carbonate, glycine, clay, bentonite, block copolymers, polyvinyl pyrrolidone, etc. If present, such carriers or diluents constitute a total of about 5% to about 99.999%, about 10% to about 85%, and 20% to about 80% of the total weight of the composition. The selected one or more carriers, one or more diluents preferably exhibit suitable flowability and, if a tablet is desired, compressibility.

[0069] In some cases, the carriers or vehicles disclosed herein as nutraceutical or oral vehicles or vehicles may also be used as vehicles for topical formulations.

[0070] 2. Topical preparations

[0071] In some aspects, the carrier or vehicle can be a pharmaceutically acceptable or dermatologically acceptable carrier or vehicle. Non-limiting examples of such carriers or vehicles include water, glycerol, alcohol, oil, silicon-containing compounds, polysiloxane compounds, and waxes. Variants and other suitable carriers will be readily apparent to those skilled in the art and are suitable for use in the present invention.

[0072] In some cases, a vehicle or carrier for a topical formulation may also serve as a vehicle or carrier for a nutraceutical or oral administration.

[0073] D.Structure

[0074] The composition of the present invention can be constructed or formulated into various forms. In some respects, the composition can be constructed or formulated into a form that can be taken orally. In some respects, the composition of the present invention comprises one or more active ingredients of the desired amount per dosage unit, and can be in the form of, for example, tablets, caplets, pills, hard or soft capsules, lozenges, pouches, dispensable powders, granules, suspensions, elixirs, dispersions, nutraceuticals, or any other form that is reasonably suitable for this use. In some respects, the composition is selected from following nutraceuticals: milk, yogurt, gelatin, ice cream, sorbet, milk shake, smoothie, beverage powder, dairy beverage and non-dairy plant-based beverage. Non-dairy plant-based beverages include fruit juice, vegetable juice, fruit / vegetable juice, nut-based beverages and energy drinks. Variant and other structures are apparent to the technician and are applicable to the present invention.

[0075] In some aspects, the composition can be constructed or formulated for topical application. Non-limiting examples include emulsions (e.g., water-in-oil, water-in-oil-in-water, oil-in-water, silicone-in-water, water-in-oil-in-water, oil-in-oil-in-water, silicone-in-water emulsions), creams, lotions, solutions (aqueous and hydroalcoholic), anhydrous bases (such as lipsticks and loose powders), gels, facial masks, scrubs, body lotions, peels, and ointments. Variants and other structures will be apparent to those skilled in the art and are applicable to the present invention.

[0076] E. Dosage

[0077] Appropriate dosages can vary depending on a variety of factors known to those skilled in the art.

[0078] In some embodiments, the composition or components thereof are administered at a dose of 1 mg / kg to 5000 mg / kg. In some embodiments, the composition or components thereof are administered at a dose of at least, at most, or about 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12 mg / kg, 13 mg / kg, 14 mg / kg, 15 mg / kg, 16 mg / kg, 17 mg / kg, 18 mg / kg, 19 mg / kg, 20 mg / kg, 21 mg / kg, 22 mg / kg, 23 mg / kg, 24 mg / kg, 25 mg / kg, 26 mg / kg, 27 mg / kg, 28 mg / kg, 29 mg / kg kg, 30mg / kg, 31mg / kg, 32mg / kg, 33mg / kg, 34mg / kg, 35mg / kg, 36mg / kg, 37mg / kg, 38mg / kg, 39mg / kg, 40mg / kg, 41mg / kg, 42mg / kg, 43mg / kg, 44mg / kg, 45mg / kg, 46mg / kg, 47mg / kg, 48mg / kg, 49mg / kg, 50mg / kg, 51mg / kg, 52mg / kg, 53mg / kg, 54mg / kg, 55mg / kg, 56mg / kg, 57mg / kg, 58mg / kg, 59mg / kg, 60mg / kg, 61mg / kg, 62mg / kg, 63mg / kg, 64mg / kg, 65mg / kg, 66mg / kg, 67mg / kg, 68mg / kg, 69mg / kg, 70mg / kg, 71mg / kg, 72mg / kg, 73mg / kg, 74m g / kg, 75mg / kg, 76mg / kg, 77mg / kg, 78mg / kg, 79mg / kg, 80mg / kg, 81mg / kg, 82mg / kg, 83mg / kg, 84mg / kg, 85mg / kg, 86mg / kg, 87mg / kg, 88mg / kg, 89 mg / kg, 90mg / kg, 91mg / kg, 92mg / kg, 93mg / kg, 94mg / kg, 95mg / kg, 96mg / kg, 97mg / kg, 98mg / kg, 99mg / kg, 100mg / kg, 101mg / kg, 102mg / kg, 103mg / kg, 104mg / kg, 105mg / kg, 106mg / kg, 107mg / kg, 108mg / kg, 109mg / kg, 110mg / kg, 111mg / kg, 112mg / kg, 113mg / kg, 114mg / kg, 115mg / kg, 116mg / kg,117mg / kg、118mg / kg、119mg / kg、120mg / kg、121mg / kg、122mg / kg、123mg / kg、124mg / kg、125mg / kg、126mg / kg、127mg / kg、128mg / kg、129mg / kg、130mg / kg、131mg / kg、132mg / kg、133mg / kg、134mg / kg、135mg / kg、136mg / kg、137mg / kg、138mg / kg、139mg / kg、140mg / kg、141mg / kg、142mg / kg、143mg / kg、144mg / kg、145mg / kg、146mg / kg、147mg / kg、148mg / kg、149mg / kg、150mg / kg、151mg / kg、152mg / kg、153mg / kg、154mg / kg、155mg / kg、156mg / kg、157mg / kg、158mg / kg、159mg / kg、160mg / kg、161mg / kg、162mg / kg、163mg / kg、164mg / kg、165mg / kg、166mg / kg、167mg / kg、168mg / kg、169mg / kg、170mg / kg、171mg / kg、172mg / kg、173mg / kg、174mg / kg、175mg / kg、176mg / kg、177mg / kg、178mg / kg、179mg / kg、180mg / kg、181mg / kg、182mg / kg、183mg / kg、184mg / kg、185mg / kg、186mg / kg、187mg / kg、188mg / kg、189mg / kg、190mg / kg、191mg / kg、192mg / kg、193mg / kg、194mg / kg、195mg / kg、196mg / kg、197mg / kg、198mg / kg、199mg / kg、200mg / kg、201mg / kg、202mg / kg、203mg / kg、204mg / kg、205mg / kg、206mg / kg、207mg / kg、208mg / kg、209mg / kg、210mg / kg、211mg / kg、212mg / kg、213mg / kg、214mg / kg、215mg / kg、216mg / kg、217mg / kg、218mg / kg、219mg / kg、220mg / kg、221mg / kg、222mg / kg、223mg / kg、224mg / kg、225mg / kg、226mg / kg、227mg / kg、228mg / kg、229mg / kg、230mg / kg、231mg / kg、232mg / kg、233mg / kg、234mg / kg、235mg / kg、236mg / kg、237mg / kg、238mg / kg、239mg / kg、240mg / kg、241mg / kg、242mg / kg、243mg / kg、244mg / kg、245mg / kg、246mg / kg、247mg / kg、248mg / kg、249mg / kg、250mg / kg、251mg / kg、252mg / kg、253mg / kg、254mg / kg、255mg / kg、256mg / kg、257mg / kg、258mg / kg、259mg / kg、260mg / kg、261mg / kg、262mg / kg、263mg / kg、264mg / kg、265mg / kg、266mg / kg、267mg / kg、268mg / kg、269mg / kg、270mg / kg、271mg / kg、272mg / kg、273mg / kg、274mg / kg、275mg / kg、276mg / kg、277mg / kg、278mg / kg、279mg / kg、280mg / kg、281mg / kg、282mg / kg、283mg / kg、284mg / kg、285mg / kg、286mg / kg、287mg / kg、288mg / kg、289mg / kg、290mg / kg、291mg / kg、292mg / kg、293mg / kg、294mg / kg、295mg / kg、296mg / kg、297mg / kg、298mg / kg、299mg / kg、300mg / kg、301mg / kg、302mg / kg、303mg / kg、304mg / kg、305mg / kg、306mg / kg、307mg / kg、308mg / kg、309mg / kg、310mg / kg、311mg / kg、312mg / kg、313mg / kg、314mg / kg、315mg / kg、316mg / kg、317mg / kg、318mg / kg、319mg / kg、320mg / kg、321mg / kg、322mg / kg、323mg / kg、324mg / kg、325mg / kg、326mg / kg、327mg / kg、328mg / kg、329mg / kg、330mg / kg、331mg / kg、332mg / kg、333mg / kg、334mg / kg、335mg / kg、336mg / kg、337mg / kg、338mg / kg、339mg / kg、340mg / kg、341mg / kg、342mg / kg、343mg / kg、344mg / kg、345mg / kg、346mg / kg、347mg / kg、348mg / kg、349mg / kg、350mg / kg、351mg / kg、352mg / kg、353mg / kg、354mg / kg、355mg / kg、356mg / kg、357mg / kg、358mg / kg、359mg / kg、360mg / kg、361mg / kg、362mg / kg、363mg / kg、364mg / kg、365mg / kg、366mg / kg、367mg / kg、368mg / kg、369mg / kg、370mg / kg、371mg / kg、372mg / kg、373mg / kg、374mg / kg、375mg / kg、376mg / kg、377mg / kg、378mg / kg、379mg / kg、380mg / kg、381mg / kg、382mg / kg、383mg / kg、384mg / kg、385mg / kg、386mg / kg、387mg / kg、388mg / kg、389mg / kg、390mg / kg、391mg / kg、392mg / kg、393mg / kg、394mg / kg、395mg / kg、396mg / kg、397mg / kg、398mg / kg、399mg / kg、400mg / kg、401mg / kg、402mg / kg、403mg / kg、404mg / kg、405mg / kg、406mg / kg、407mg / kg、408mg / kg、409mg / kg、410mg / kg、411mg / kg、412mg / kg、413mg / kg、414mg / kg、415mg / kg、416mg / kg、417mg / kg、418mg / kg、419mg / kg、420mg / kg、421mg / kg、422mg / kg、423mg / kg、424mg / kg、425mg / kg、426mg / kg、427mg / kg、428mg / kg、429mg / kg、430mg / kg、431mg / kg、432mg / kg、433mg / kg、434mg / kg、435mg / kg、436mg / kg、437mg / kg、438mg / kg、439mg / kg、440mg / kg、441mg / kg、442mg / kg、443mg / kg、444mg / kg、445mg / kg、446mg / kg、447mg / kg、448mg / kg、449mg / kg、450mg / kg、451mg / kg、452mg / kg、453mg / kg、454mg / kg、455mg / kg、456mg / kg、457mg / kg、458mg / kg、459mg / kg、460mg / kg、461mg / kg、462mg / kg、463mg / kg、464mg / kg、465mg / kg、466mg / kg、467mg / kg、468mg / kg、469mg / kg、470mg / kg、471mg / kg、472mg / kg、473mg / kg、474mg / kg、475mg / kg、476mg / kg、477mg / kg、478mg / kg、479mg / kg、480mg / kg、481mg / kg、482mg / kg、483mg / kg、484mg / kg、485mg / kg、486mg / kg、487mg / kg、488mg / kg、489mg / kg、490mg / kg、491mg / kg、492mg / kg、493mg / kg、494mg / kg、495mg / kg、496mg / kg、497mg / kg、498mg / kg、499mg / kg、500mg / kg、501mg / kg、502mg / kg、503mg / kg、504mg / kg、505mg / kg、506mg / kg、507mg / kg、508mg / kg、509mg / kg、510mg / kg、511mg / kg、512mg / kg、513mg / kg、514mg / kg、515mg / kg、516mg / kg、517mg / kg、518mg / kg、519mg / kg、520mg / kg、521mg / kg、522mg / kg、523mg / kg、524mg / kg、525mg / kg、526mg / kg、527mg / kg、528mg / kg、529mg / kg、530mg / kg、531mg / kg、532mg / kg、533mg / kg、534mg / kg、535mg / kg、536mg / kg、537mg / kg、538mg / kg、539mg / kg、540mg / kg、541mg / kg、542mg / kg、543mg / kg、544mg / kg、545mg / kg、546mg / kg、547mg / kg、548mg / kg、549mg / kg、550mg / kg、551mg / kg、552mg / kg、553mg / kg、554mg / kg、555mg / kg、556mg / kg、557mg / kg、558mg / kg、559mg / kg、560mg / kg、561mg / kg, 562mg / kg, 563mg / kg, 564mg / kg, 565mg / kg, 566mg / kg, 567mg / kg, 568mg / kg, 569mg / kg, 570mg / kg, 571mg / kg, 572mg / kg, 600mg / kg, 700mg / kg, 800mg / kg, 900mg / k g, 1000mg / kg, 1100mg / kg, 1200mg / kg, 1300mg / kg, 1400mg / kg, 1500mg / kg, 1600mg / kg, 1700mg / kg, 1800mg / kg, 1900mg / kg, 2000mg / kg, 2100mg / kg, 2200mg / kg, 2300mg / kg, The composition, or a component thereof, can be administered at a dose of 2400 mg / kg, 2500 mg / kg, 2600 mg / kg, 2700 mg / kg, 2800 mg / kg, 2900 mg / kg, 3000 mg / kg, 3100 mg / kg, 3200 mg / kg, 3300 mg / kg, 3400 mg / kg, 3500 mg / kg, 3600 mg / kg, 3700 mg / kg, 3800 mg / kg, 3900 mg / kg, 4000 mg / kg, 4100 mg / kg, 4200 mg / kg, 4300 mg / kg, 4400 mg / kg, 4500 mg / kg, 4600 mg / kg, 4700 mg / kg, 4800 mg / kg, 4900 mg / kg, or 5000 mg / kg. As a non-limiting example, collagen can be delivered in oral doses of 1 gram to 50 grams per day.

[0079] The dosage amount according to the number of treatments and dosage depends on the desired treatment effect. An effective dose is understood to be the amount necessary to achieve a specific effect. In addition, such a dosage can be administered multiple times a day and / or over several days, weeks, or months.

[0080] The precise amount of active composition is also subject to the judgment of the practitioner and varies from person to person. Factors affecting dosage include the patient's physical and clinical state, route of administration, desired treatment goal (symptom relief versus cure), and the efficacy, stability, and toxicity of the particular therapeutic substance or other therapy the subject may be receiving.

[0081] In some cases, the Haematococcus pluvialis extract is administered at a dose of 10 mg to 300 mg. In some embodiments, the Haematococcus pluvialis extract is administered at a dose of at least, at most, or about 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mg, 26 mg, 27 mg, 28 mg, 29 mg, 30 mg, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg, 50 mg, 51 mg, 52 mg, 53 mg, 54 mg g, 55mg, 56mg, 57mg, 58mg, 59mg, 60mg, 61mg, 62mg, 63mg, 64mg, 65mg, 66mg, 67mg, 68mg, 69mg, 70mg, 71mg, 72mg, 73mg, 74mg, 75mg, 76mg, 77mg, 78mg , 79mg, 80mg, 81mg, 82mg, 83mg, 84mg, 85mg, 86mg, 87mg, 88mg, 89mg, 90mg, 91mg, 92mg, 93mg, 94mg, 95mg, 96mg, 97mg, 98mg, 99mg, 100mg, 101mg, 102 mg, 103mg, 104mg, 105mg, 106mg, 107mg, 108mg, 109mg, 110mg, 111mg, 112mg, 113mg, 114mg, 115mg, 116mg, 117mg, 118mg, 119mg, 120mg, 121mg, 122 mg, 123mg, 124mg, 125mg, 126mg, 127mg, 128mg, 129mg, 130mg, 131mg, 132mg, 133mg, 134mg, 135mg, 136mg, 137mg, 138mg, 139mg, 140mg, 141mg, 142m g, 143mg, 144mg, 145mg, 146mg, 147mg, 148mg, 149mg, 150mg, 151mg, 152mg, 153mg, 154mg, 155mg, 156mg, 157mg, 158mg, 159mg, 160mg, 161mg, 162mg , 163mg, 164mg, 165mg, 166mg, 167mg, 168mg, 169mg, 170mg, 171mg, 172mg, 173mg, 174mg, 175mg, 176mg, 177mg, 178mg, 179mg, 180mg, 181mg, 182mg,183mg, 184mg, 185mg, 186mg, 187mg, 188mg, 189mg, 190mg, 191mg, 192mg, 193mg, 194mg, 195mg, 196mg, 197mg, 198mg, 199mg, 200mg, 201mg, 202mg, 203mg, 204mg, 205mg, 206mg, 207mg, 208mg, 209mg, 210mg, 211mg, 212mg, 213mg, 214mg, 215mg, 216mg, 217mg, 218mg, 219mg, 220mg, 221mg, 222mg, 223mg, 224mg, 225mg, 226mg, 227mg, 228mg, 229mg, 230mg, 231mg, 232mg, 233mg, 234mg, 235mg, 236mg, 237mg, 238mg, 239mg, 240mg, 241mg, 242mg, 243mg, 244mg, 245mg, 246mg, 247mg, 248mg, 249mg, 250mg, 251mg, 252mg, 253mg, 254mg, 255mg, 256mg, 257mg, 258mg, 259mg, 260mg, 261mg, 262mg, 263mg, 264mg, 265mg, 266mg, 267mg, 268mg, 269mg, 270mg, 271mg, 272mg, The Haematococcus pluvialis extract may be administered at a dosage of 273 mg, 274 mg, 275 mg, 276 mg, 277 mg, 278 mg, 279 mg, 280 mg, 281 mg, 282 mg, 283 mg, 284 mg, 285 mg, 286 mg, 287 mg, 288 mg, 289 mg, 290 mg, 291 mg, 292 mg, 293 mg, 294 mg, 295 mg, 296 mg, 297 mg, 298 mg, 299 mg or 300 mg. The dosage may be administered once or more than once daily and / or weekly.

[0082] In some cases, sodium hyaluronate is administered at a dose of 5 mg to 250 mg. In some embodiments, sodium hyaluronate is administered at a dose of at least, at most, or about 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mg, 26 mg, 27 mg, 28 mg, 29 mg, 30 mg, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg, 50mg, 51mg, 52mg, 53mg, 54mg, 55mg, 56mg, 57mg, 58mg, 59mg, 60mg, 61mg, 62mg, 63mg, 64mg, 65mg, 66mg, 67mg, 68mg, 69mg, 70mg, 71mg, 72mg, 73mg, 7 4mg, 75mg, 76mg, 77mg, 78mg, 79mg, 80mg, 81mg, 82mg, 83mg, 84mg, 85mg, 86mg, 87mg, 88mg, 89mg, 90mg, 91mg, 92mg, 93mg, 94mg, 95mg, 96mg, 97mg, 98m g, 99mg, 100mg, 101mg, 102mg, 103mg, 104mg, 105mg, 106mg, 107mg, 108mg, 109mg, 110mg, 111mg, 112mg, 113mg, 114mg, 115mg, 116mg, 117mg, 118mg, 119mg, 120mg, 121mg, 122mg, 123mg, 124mg, 125mg, 126mg, 127mg, 128mg, 129mg, 130mg, 131mg, 132mg, 133mg, 134mg, 135mg, 136mg, 137mg, 138mg, 13 9mg, 140mg, 141mg, 142mg, 143mg, 144mg, 145mg, 146mg, 147mg, 148mg, 149mg, 150mg, 151mg, 152mg, 153mg, 154mg, 155mg, 156mg, 157mg, 158mg, 159m g, 160mg, 161mg, 162mg, 163mg, 164mg, 165mg, 166mg, 167mg, 168mg, 169mg, 170mg, 171mg, 172mg, 173mg, 174mg, 175mg, 176mg, 177mg, 178mg, 179mg,180mg, 181mg, 182mg, 183mg, 184mg, 185mg, 186mg, 187mg, 188mg, 189mg, 190mg, 191mg, 192mg, 193mg, 194mg, 195mg, 196mg, 197mg, 198mg, 199mg, 200mg, 201mg, 202mg, 203mg, 204mg, 205mg, 206mg, 207mg, 208mg, 209mg, 210mg, 211mg, 212mg, 213mg, 214mg, 215mg, The dosage may be administered once daily and / or weekly or more than once a day.

[0083] In some cases, the collagen is administered at a dosage of 0.5 g to 20 g. In some embodiments, the collagen is administered at a dosage of at least, at most, or about 0.5 g, 0.6 g, 0.7 g, 0.8 g, 0.9 g, 1 g, 2 g, 3 g, 4 g, 5 g, 6 g, 7 g, 8 g, 9 g, 10 g, 11 g, 12 g, 13 g, 14 g, 15 g, 16 g, 17 g, 18 g, 19 g, or 20 g. The dosage can be administered once or more than once daily and / or weekly.

[0084] In some cases, kudzu extract is administered at a dose of 50 mg to 2.5 g. In some embodiments, kudzu extract is administered at a dose of at least, at most, or about 50 mg, 51 mg, 52 mg, 53 mg, 54 mg, 55 mg, 56 mg, 57 mg, 58 mg, 59 mg, 60 mg, 61 mg, 62 mg, 63 mg, 64 mg, 65 mg, 66 mg, 67 mg, 68 mg, 69 mg, 70 mg, 71 mg, 72 mg, 73 mg, 74 mg, 75 mg, 76 mg, 77 mg, 78 mg, 79 mg, 80 mg, 81 mg, 82 mg, 83 mg, 84 mg, 85 mg, 86 mg, 87 mg, 88 mg, 89 mg, 90 mg, 91 mg, 92 mg, 93 mg, 94 mg, 95mg, 96mg, 97mg, 98mg, 99mg, 100mg, 101mg, 102mg, 103mg, 104mg, 105mg, 106mg, 107mg, 108mg, 109mg, 110mg, 111mg, 112mg, 113mg, 114mg, 115mg, 116mg, 117mg, 118mg, 119mg, 120mg, 121mg, 122mg, 123mg, 124mg, 125mg, 126mg, 127mg, 128mg, 129mg, 130mg, 131mg, 132mg, 133mg, 134mg, 135mg, 1 36mg, 137mg, 138mg, 139mg, 140mg, 141mg, 142mg, 143mg, 144mg, 145mg, 146mg, 147mg, 148mg, 149mg, 150mg, 151mg, 152mg, 153mg, 154mg, 155mg, 15 6mg, 157mg, 158mg, 159mg, 160mg, 161mg, 162mg, 163mg, 164mg, 165mg, 166mg, 167mg, 168mg, 169mg, 170mg, 171mg, 172mg, 173mg, 174mg, 175mg, 176 mg, 177mg, 178mg, 179mg, 180mg, 181mg, 182mg, 183mg, 184mg, 185mg, 186mg, 187mg, 188mg, 189mg, 190mg, 191mg, 192mg, 193mg, 194mg, 195mg, 196m g, 197mg, 198mg, 199mg, 200mg, 201mg, 202mg, 203mg, 204mg, 205mg, 206mg, 207mg, 208mg, 209mg, 210mg, 211mg, 212mg, 213mg, 214mg, 215mg, 216mg,<h2 style=";text-align:left;direction:ltr">217mg、218mg、219mg、220mg、221mg、222mg、223mg、224mg、225mg、226mg、227mg、228mg、229mg、230mg、231mg、232mg、233mg、234mg、235mg、236mg、237m g、238mg、239mg、240mg、241mg、242mg、243mg、244mg、245mg、246mg、247mg、 248mg、249mg、250mg、251mg、252mg、253mg、254mg、255mg、256mg、257mg、258 mg、259mg、260mg、261mg、262mg、263mg、264mg、265mg、266mg、267mg、268mg 、269mg、270mg、271mg、272mg、273mg、274mg、275mg、276mg、277mg、278mg、2 79mg、280mg、281mg、282mg、283mg、284mg、285mg、286mg、287mg、288mg、289 mg、290mg、291mg、292mg、293mg、294mg、295mg、296mg、297mg、298mg、299mg、 300mg、301mg、302mg、303mg、304mg、305mg、306mg、307mg、308mg、309mg、31 0mg、311mg、312mg、313mg、314mg、315mg、316mg、317mg、318mg、319mg、320m g、321mg、322mg、323mg、324mg、325mg、326mg、327mg、328mg、329mg、330mg、331mg、332mg、333mg、334mg、335mg、336mg、337mg、338mg、339mg、340mg、341 mg、342mg、343mg、344mg、345mg、346mg、347mg、348mg、349mg、350mg、351mg 、352mg、353mg、354mg、355mg、356mg、357mg、358mg、359mg、360mg、361mg、3 62mg、363mg、364mg、365mg、366mg、367mg、368mg、369mg、370mg、371mg、372mg、373mg、374mg、375mg、376mg、377mg、378mg、379mg、380mg、381mg、382mg、383mg、384mg、385mg、386mg、387mg、388mg、389mg、390mg、391mg、392mg、393mg、394mg、395mg、396mg、397mg、398mg、399mg、400mg、401mg、402mg、403mg、404mg、405mg、406mg、407mg、408mg、409mg、410mg、411mg、412mg、413mg、414mg、415mg、416mg、417mg、418mg、419mg、420mg、421mg、422mg、423mg、424mg、425mg、426mg、427mg、428mg、429mg、430mg、431mg、432mg、433mg、434mg、435mg、436mg、437mg、438mg、439mg、440mg、441mg、442mg、443mg、444mg、445mg、446mg、447mg、448mg、449mg、450mg、451mg、452mg、453mg、454mg、455mg、456mg、457mg、458mg、459mg、460mg、461mg、462mg、463mg、464mg、465mg、466mg、467mg、468mg、469mg、470mg、471mg、472mg、473mg、474mg、475mg、476mg、477mg、478mg、479mg、480mg、481mg、482mg、483mg、484mg、485mg、486mg、487mg、488mg、489mg、490mg、491mg、492mg、493mg、494mg、495mg、496mg、497mg、498mg、499mg、500mg、501mg、502mg、503mg、504mg、505mg、506mg、507mg、508mg、509mg、510mg、511mg、512mg、513mg、514mg、515mg、516mg、517mg、518mg、519mg、520mg、521mg、522mg、523mg、524mg、525mg、526mg、527mg、528mg、529mg、530mg、531mg、532mg、533mg、534mg、535mg、536mg、537mg、538mg、539mg、540mg、541mg、542mg、543mg、544mg、545mg、546mg、547mg、548mg、The kudzu extract may be administered at a dose of 549 mg, 550 mg, 551 mg, 552 mg, 553 mg, 554 mg, 555 mg, 556 mg, 557 mg, 558 mg, 559 mg, 560 mg, 561 mg, 562 mg, 563 mg, 564 mg, 565 mg, 566 mg, 567 mg, 568 mg, 569 mg, 570 mg, 571 mg, 572 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, 1800 mg, 1900 mg, 2000 mg, 2100 mg, 2200 mg, 2300 mg, 2400 mg, or 2500 mg. Doses may be administered once or more daily and / or weekly.

[0085] In some cases, ceramosides are administered at a dose of 0.0001 mg to 300 mg. In some embodiments, ceramosides are administered at a dose of at least, at most, or about 0.0001 mg, 0.0002 mg, 0.0003 mg, 0.0004 mg, 0.0005 mg, 0.0006 mg, 0.0007 mg, 0.0008 mg, 0.0009 mg, 0.001 mg, 0.002 mg, 0.003 mg, 0.004 mg, 0.005 mg, 0.006 mg, 0.007 mg, 0.008 mg, 0.009 mg, 0.01 mg, 0.02 mg, 0.03 mg, 0.04 mg, 0.05 mg, 0.06 mg, 0.07 mg, 0.08 mg, 0.09 mg, 0.1 mg, 0.2mg, 0.3mg, 0.4mg, 0.5mg, 0.6mg, 0.7mg, 0.8mg, 0.9mg, 1mg, 2mg, 3mg, 4mg, 5mg, 6mg, 7mg, 8mg, 9mg, 10mg, 11mg, 12mg, 13mg, 14mg, 15mg, 16mg, 1 7mg, 18mg, 19mg, 20mg, 21mg, 22mg, 23mg, 24mg, 25mg, 26mg, 27mg, 28mg, 29mg, 30mg, 31mg, 32mg, 33mg, 34mg, 35mg, 36mg, 37mg, 38mg, 39mg, 40mg, 4 1mg, 42mg, 43mg, 44mg, 45mg, 46mg, 47mg, 48mg, 49mg, 50mg, 51mg, 52mg, 53mg, 54mg, 55mg, 56mg, 57mg, 58mg, 59mg, 60mg, 61mg, 62mg, 63mg, 64mg, 6 5mg, 66mg, 67mg, 68mg, 69mg, 70mg, 71mg, 72mg, 73mg, 74mg, 75mg, 76mg, 77mg, 78mg, 79mg, 80mg, 81mg, 82mg, 83mg, 84mg, 85mg, 86mg, 87mg, 88mg, 8 9mg, 90mg, 91mg, 92mg, 93mg, 94mg, 95mg, 96mg, 97mg, 98mg, 99mg, 100mg, 101mg, 102mg, 103mg, 104mg, 105mg, 106mg, 107mg, 108mg, 109mg, 110mg, 111mg, 112mg, 113mg, 114mg, 115mg, 116mg, 117mg, 118mg, 119mg, 120mg, 121mg, 122mg, 123mg, 124mg, 125mg, 126mg, 127mg, 128mg, 129mg, 130mg,131mg、132mg、133mg、134mg、135mg、136mg、137mg、138mg、139mg、140mg、141mg、142mg、143mg、144mg、145mg、146mg、147mg、148mg、149mg、150mg、151mg、152mg、153mg、154mg、155mg、156mg、157mg、158mg、159mg、160mg、161mg、162mg、163mg、164mg、165mg、166mg、167mg、168mg、169mg、170mg、171mg、172mg、173mg、174mg、175mg、176mg、177mg、178mg、179mg、180mg、181mg、182mg、183mg、184mg、185mg、186mg、187mg、188mg、189mg、190mg、191mg、192mg、193mg、194mg、195mg、196mg、197mg、198mg、199mg、200mg、201mg、202mg、203mg、204mg、205mg、206mg、207mg、208mg、209mg、210mg、211mg、212mg、213mg、214mg、215mg、216mg、217mg、218mg、219mg、220mg、221mg、222mg、223mg、224mg、225mg、226mg、227mg、228mg、229mg、230mg、231mg、232mg、233mg、234mg、235mg、236mg、237mg、238mg、239mg、240mg、241mg、242mg、243mg、244mg、245mg、246mg、247mg、248mg、249mg、250mg、251mg、252mg、253mg、254mg、255mg、256mg、257mg、258mg、259mg、260mg、261mg、262mg、263mg、264mg、265mg、266mg、267mg、268mg、269mg、270mg、271mg、272mg、273mg、274mg、275mg、276mg、277mg、278mg、279mg、280mg、281mg、282mg、283mg、284mg、285mg、286mg、287mg、288mg、289mg、290mg、291mg、292mg、293mg、294mg、295mg、296mg、The ceramosides are administered in doses of 297 mg, 298 mg, 299 mg, or 300 mg. The doses may be administered once or more daily and / or weekly.

[0086] Those skilled in the art will appreciate that dosage units of μg / kg body weight or mg / kg body weight can be converted and expressed as equivalent concentration units of μg / mL or mM. It will also be understood that uptake is species-dependent and organ / tissue-dependent. Applicable conversion factors and physiological assumptions regarding uptake measurements and concentration measurements are well known and allow those skilled in the art to convert one concentration measurement to another and make reasonable comparisons and conclusions about the dosages, efficacy, and results described herein.

[0087] In some cases, it is desirable to administer the composition multiple times, for example, 2, 3, 4, 5, 6, or more than 6 administrations. The intervals between administrations can be 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, or 12 hours, 1 day, or one week, including all ranges therebetween.

[0088] F. Additional Ingredients

[0089] In addition to the combination of ingredients disclosed by the inventors, the composition 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.

[0090] 1. Nutritional ingredients

[0091] The preparation of the present invention may further comprise various ingredients to help stabilize or help promote the bioavailability of the components of the beneficial compositions of the present invention, or as additional nutrients for individual diets. Suitable additives may include vitamins and biologically acceptable minerals. Non-limiting examples of vitamins include vitamin A, B vitamins, vitamin C, vitamin D, vitamin E, vitamin K, and folic acid. Non-limiting examples of minerals include iron, calcium, magnesium, potassium, copper, chromium, zinc, molybdenum, iodine, boron, selenium, manganese, derivatives thereof, or combinations thereof. These vitamins and minerals can be from any source or combination of sources without restriction. Non-limiting exemplary B vitamins include, but are not limited to, thiamine, niacinamide, pyridoxine, riboflavin, cyanocobalamin, biotin, pantothenic acid, or combinations thereof.

[0092] In some embodiments, composition includes one or more than one flavoring and / or aromatics.In multiple embodiments, one or more than one flavoring includes essential oil (or a combination of essential oil), fruit juice, sugar, food, plant extract, mineral etc. In multiple embodiments, one or more than one flavoring in composition includes sugar, molasses, chocolate, one or more than one nut butter, salt, one or more than one pepper, fruit juice, artificial flavoring, essential oil, plant extract etc. Non-limiting examples include but are not limited to honey, grapefruit juice or grapefruit powder or grapefruit oil, blood orange juice or blood orange powder or blood orange oil, rose powder, mixed berry powder, beetroot, monk fruit extract (such as MonkGold50), stevia, stevioside, isomalt, glycerol, peppermint oil or mint flavoring, lemon juice or lemon powder or lemon oil, orange oil or orange flavoring, vanilla, flavoring, bitterness inhibitor etc. or its combination.

[0093] Various additives can be incorporated into the present composition. Optional additives of the present composition include, but are not limited to, antioxidants, such as, but not limited to, vitamins A, C, and E, copper, zinc, selenium, carotenoids, flavonoids, gallates, polyphenols, and the like. Optional additives can also include preservatives, such as, but not limited to, salt, sodium nitrate, spices, vinegar, alcohol, potassium nitrate, potassium nitrite, sodium benzoate, benzoic acid, calcium propionate, potassium sorbate, sodium sorbate, calcium sorbate, sorbic acid, and the like. Optional additives can also include colorants, such as plant extracts, dried plant materials, minerals, FD&C Blue No. 1, FD&C Blue No. 2, FD&C Green No. 3, FD&C Red No. 3, FD&C Red No. 40, FD&C Yellow No. 5, FD&C Yellow No. 6, and the like. Optional additives can also include structuring agents, such as, but not limited to, surfactants, hardeners, thickeners, curing agents, foaming agents, flow enhancers, emulsifiers, lipids, sugars, water, polymers, waxes, proteins, nanoparticles, and the like. Optional additives may also include pH adjusters, such as acids, bases, buffers, and the like.

[0094] Other optional additives include, but are not limited to, hyaluronic acid, phospholipids, starches, sugars, fats, antioxidants, amino acids, proteins, flavorings, coloring agents, one or more hydrolyzed starches and derivatives thereof, or combinations thereof.

[0095] In some cases, nutraceutical ingredients can also be used in topical compositions.In some cases, cosmetic ingredients and topical ingredients can also be used in nutraceutical compositions.

[0096] 2. Cosmetic ingredients

[0097] The CTFA International Cosmetic Ingredient Dictionary and Handbook (2004 and 2008) describes a variety of non-limiting cosmetic ingredients that can be used in the context of the present invention. Examples of these ingredient categories include: fragrances (artificial and natural; for example, gluconic acid, phenoxyethanol, and triethanolamine), dye ingredients and coloring ingredients (for example, Blue 1, Blue 1 Lake, Red 40, titanium dioxide, D&C Blue No. 4, D&C Green No. 5, D&C Orange No. 4, D&C Red No. 17, D&C Red No. 33, D&C Violet No. 2, D&C Yellow No. 10, and D&C Yellow No. 11), flavoring / fragrance agents (for example, Stevia rebaudiana) extract and menthol), adsorbents, lubricants, solvents, humectants (including, for example, emollients, humectants, film formers, occlusives, and agents that affect the skin's natural moisturizing mechanisms), water repellents, UV 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., A, B, C, D, E, and K), trace metals (e.g., zinc, calcium, and selenium), anti-irritants (e.g., steroidal anti-inflammatory drugs and nonsteroidal anti-inflammatory drugs), plant extracts (e.g., aloe vera, chamomile, cucumber extract, Ginkgo biloba), biloba), ginseng, and rosemary), antimicrobials, 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 starch octenylsuccinate, kaolin, corn starch, oat starch, cyclodextrins, talc, and zeolite), skin bleaching and lightening agents (e.g., hydroquinone and niacinamide lactate), humectants (e.g., sorbitol, urea, methyl glucose-20, saccharide isomerate), isomerate and mannitol), exfoliants, water repellents (e.g., aluminum hydroxide / magnesium stearate), skin conditioning agents (e.g., aloe extract, allantoin, bisabolol, ceramides, dimethicone, hyaluronic acid, biosaccharide gum-1, ethylhexylglycerin, pentylene glycol, hydrogenated polydecene, octyldodecyl oleate, and dipotassium glycyrrhizate). Non-limiting examples of some of these ingredients are provided in the following subsections.

[0098] In some cases, cosmetic ingredients may be used in topical and / or nutraceutical compositions, as may be known in the art.

[0099] a. UV absorbers and / or UV reflectors

[0100] UV absorbers and / or UV reflectors 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 amyl ester and dimethyl PABA octyl ester), butyl PABA, ethyl PABA, ethyl dihydroxypropyl PABA, benzophenones (oxybenzone, sulisobenzone, benzophenone and benzophenone-1 to benzophenone-12), cinnamate esters (octyl methoxycinnamate (octinoxate), isoamyl p-methoxycinnamate, octyl methoxycinnamate, cinoxate, diisopropyl methylcinnamate, DEA methoxycinnamate, ethyl diisopropyl cinnamate, glyceryl caprylate dimethoxycinnamate and ethyl methoxycinnamate), esters of cinnamate esters, salicylates (homosalate (homomethyl salicylate), benzyl salicylate, glycol salicylate, isopropyl benzyl salicylate, etc.), anthranilate, ethyl urocanate, homosalate, octyl salicylate, dibenzoylmethane derivatives (such as avobenzone), octocrylene, octyl triazone, galloylgallic acid trioleate, aminobenzoic acid glyceryl ester, 2-hydroxy-1,4-naphthoquinone (lawsone) and dihydroxyacetone, Ethylhexyl triazone, dioctyl butamido triazone, benzyl malonate polysiloxane, terephthalylidene dicamphor sulfonic acid, disodium phenyl dibenzimidazole tetrasulfonate, diethylamino hydroxybenzoyl hexyl benzoate, bis diethylamino hydroxybenzoyl benzoate, bis benzoxazolyl phenyl ethylhexyl imino triazine, drometrizole trisiloxane, methylene bis-benzotriazolyl tetramethylbutylphenol and bis-ethylhexyloxyphenol methoxyphenyl triazine, 4-methylbenzylidene camphor and isoamyl 4-methoxycinnamate. Non-limiting examples of physical sunscreens include kaolin, talc, petrolatum and metal oxides (such as titanium dioxide and zinc oxide).

[0101] b. Moisturizer

[0102] Non-limiting examples of moisturizers that can be used with the compositions of the present invention include amino acids, chondroitin sulfate, diglycerin, 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 factor, PEG-15 butylene glycol, polyglyceryl sorbitol, salts of pyrrolidone carboxylic acid, potassium PCA, propylene glycol, saccharide isomerates, sodium glucuronate, sodium PCA, sorbitol, sucrose, trehalose, urea, and xylitol.

[0103] Other examples include acetylated lanolin, acetylated lanolin alcohol, alanine, algae extract, aloe barbadensis, aloe vera extract, aloe vera gel, Althea officinalis extract, Prunus armeniaca kernel oil, arginine, arginine aspartate, Arnica montana extract, aspartic acid, avocado oil, barrier sphingolipids, butanol, beeswax, behenyl alcohol, beta-sitosterol, Betula alba bark extract, Borago officinalis extract, Ruscus aculeatus extract, butylene glycol, Calendula officinalis extract, calendula oil, Euphorbia cerifera wax, canola oil, caprylic / capric triglyceride, Elettaria cardamomum fruit extract, glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin, PEG-10 glycerin cardamomum oil, Copernicia cerifera wax, Daucus carota sativa (carrot) oil, Ricinus communis (castor) oil, ceramides, ozokerite, ceteareth-5, ceteareth-12, ceteareth-20, cetearyl octanoate, ceteth-20, ceteth-24, cetyl acetate, cetyl octanoate, cetyl palmitate, Anthemis nobilis (chamomile) oil, cholesterol, cholesterol esters, cholesterol hydroxystearate, citric acid, clary sage (salvia clary)Salvia sclarea oil, Cocoa (Theobroma cacao) butter, Coco-caprylate / caprate, Cocos nucifera oil, Collagen, Collagen amino acids, Zea mays oil, Fatty acids, Decyl oleate, Dimethicone copolyol, Dimethiconol, Dioctyl adipate, Dioctyl succinate, Dipentaerythrityl hexacaprylate / hexacaprate, DNA, Erythritol, Ethoxydiglycol, Ethyl Linoleate, Eucalyptus globulus oil, Oenothera biennis (Evening Primrose) oil biennis oil, fatty acids, Geranium maculatum oil, glucosamine, glucosamine glutamate, glutamic acid, glycereth-26, glycerin, glycerol, glyceryl distearate, glyceryl hydroxystearate, glyceryl laurate, glyceryl linoleate, glyceryl myristate, glyceryl oleate, glyceryl stearate, glyceryl stearate SE, glycine, glycol stearate, glycol stearate SE, glycosaminoglycans, grape (Vitis vinifera) seed oil, hazelnut (Corylus americana) nut oil, hazelnut (Corylus avellana) nut oil, hexylene glycol, hyaluronic acid, hybrid safflower (Carthamus tinctorius) oil, hydrogenated castor oil, hydrogenated coco-glycerides, hydrogenated coconut oil, hydrogenated lanolin, hydrogenated lecithin, hydrogenated palm glycerides, hydrogenated palm kernel oil, hydrogenated soybean oil, hydrogenated tallow glycerides, hydrogenated vegetable oil, hydrolyzed collagen, hydrolyzed elastin, hydrolyzed glycosaminoglycans, hydrolyzed keratin, hydrolyzed soy protein, hydroxylated lanolin, hydroxyproline, isocetyl stearate, isocetyl stearoyl stearate, isodecyl oleate, isopropyl isostearate, isopropyl lanolate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isostearamide DEA, isostearic acid, isostearyl lactate, isostearyl neopentanoate, jasmine (Jasminum officinale) oil, jojoba (Buxus chinensis) oil, kelp, Aleurites aurantifolia (Aleurites moschata) seed oil moluccana) nut oil, lactamide MEA, lanolin ether-16, lanolin ether-10 acetate, lanolin, lanolin acid, lanolin alcohol, lanolin oil, lanolin wax, lavender (Lavandula angustifolia) oil, lecithin, lemon (citron,Citrus medica limonum oil, linoleic acid, linolenic acid, macadamia (Macadamia ternifolia) nut oil, maltitol, chamomile (Chamomillarecutita) oil, methyl glucose sesquistearate, methylsilanol PCA, mineral oil, mink oil, mortierella vulgaris oil, myristyl lactate, myristyl myristate, myristyl propionate, neopentyl glycol dicaprylate / dicaprate, octyldodecanol, octyldodecanol myristate, octyldodecanol stearoyl stearate, octyl hydroxystearate, octyl palmitate, octyl salicylate, octyl stearate, oleic acid, olive (Olea europaea) oil, orange (Citrus aurantiumdulcis) oil, palm (Elaeis guineensis) oil, palmitic acid, panthenol, panthenol, panthenol ethyl ether, paraffin, PCA, peach (Prunus persica) kernel oil, peanut (Arachis hypogaea) oil, PEG-8 C12-18 Esters, PEG-15 Cocoamine, PEG-150 Distearate, PEG-60 Glyceryl Isostearate, PEG-5 Glyceryl Stearate, PEG-30 Glyceryl Stearate, PEG-7 Hydrogenated Castor Oil, PEG-40 Hydrogenated Castor Oil, PEG-60 Hydrogenated Castor Oil, PEG-20 Methyl Glucose Sesquistearate, PEG-40 Sorbitan Full Oleate, 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, Pentadecanoate, Peppermint (Peppermint, Mentha piperita oil, petrolatum, lecithin, plankton extract, polyamino acid polysaccharide condensate, polyglyceryl-3 diisostearate, polyquaternium-24, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, polysorbate 85, potassium myristate, potassium palmitate, propylene glycol, propylene glycol dicaprylate / dicaprate, propylene glycol dicaprylate, propylene glycol dipelargonate, propylene glycol laurate, propylene glycol stearate, propylene glycol stearate SE, PVP, pyridoxine dipalmitate, retinol, retinyl palmitate, rice (Oryza sativa) bran oil, RNA, rosemary (Rosmarinus officinalis) oil, rose oil, safflower oil, sage (Salvia officinalis) oil, sandalwood (Santalum) album) oil, serine, serum protein, sesame (Sesamumindicum) oil, shea butter (shea butter,Butyrospermum parkii), 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 soja) oil, sphingolipids, squalane, squalene, stearamide MEA-stearate, stearic acid, stearoxydimethicone, stearoxytrimethylsilane, stearyl alcohol, stearyl glycyrrhetinate, stearyl heptanoate, stearyl stearate, sunflower (Helianthus annuus) seed oil, sweet almond (Prunus amygdalus dulcis) seed oil amygdalusdulcis) oil, synthetic beeswax, tocopherol, tocopheryl acetate, tocopheryl linoleate, tribehenin, tridecyl neopentanoate, tridecyl stearate, triethanolamine, glyceryl stearate, urea, vegetable oil, water, wax, wheat (Triticum vulgare) germ oil and ylang-ylang (Cananga odorata) oil.

[0104] c. Antioxidants

[0105] Non-limiting examples of antioxidants that can be used with the compositions of the present invention include acetylcysteine, ascorbic acid polypeptide, ascorbyl dipalmitate, ascorbyl methylsilanol pectinate, ascorbyl palmitate, ascorbyl stearate, BHA, BHT, t-butylhydroquinone, cysteine, cysteine ​​HCl, diamylhydroquinone, di-t-butylhydroquinone, dicetylthiodipropionate, dioleyl tocopheryl methylsilanol, disodium ascorbyl sulfate, distearylthiodipropionate, ditridecylthiodipropionate, lauryl gallate, isoascorbic acid, ascorbyl esters, ethyl ferulate, ferulic acid, gallic acid esters, Hydroquinone, 2-ethylhexyl thioglycolate, kojic acid, magnesium ascorbate, magnesium ascorbyl phosphate, methylsilanol ascorbic acid, natural plant antioxidants such as green tea extract or grape seed extract, nordihydroguaiaretic acid, octyl gallate, phenylthioglycolic acid, potassium ascorbyl tocopheryl phosphate, potassium sulfite, propyl gallate, quinone, rosmarinic acid, sodium ascorbate, sodium bisulfite, sodium erythorbate, sodium metabisulfite, sodium sulfite, superoxide dismutase, sodium thioglycolate, sorbitol furfural, thiodiglycol, thiodiglycolamide, thiodiacetic acid acid), thioglycolic acid, thiolactic acid, thiosalicylic acid, tocophereth-5, tocophereth-10, tocophereth-12, tocophereth-18, tocophereth-50, tocopherol, tocophersolan, tocopheryl acetate, tocopheryl linoleate, tocopheryl nicotinate, tocopheryl succinate, and tris(nonylphenyl)phosphite.

[0106] d. Structuring agent

[0107] In other non-limiting aspects, the composition of the present invention can include a structuring agent. In some aspects, the structuring agent helps to provide rheological properties for the composition, thereby helping the stability of the composition. In other aspects, the structuring agent also can play the role of an emulsifier or surfactant. The limiting examples of structuring agent include stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, stearic acid, palmitic acid, the polyethylene glycol ether of the stearyl alcohol with an average of about 1 to about 21 ethylene oxide units, the polyethylene glycol ether of the cetyl alcohol with an average of about 1 to about 5 ethylene oxide units, and mixtures thereof.

[0108] e. Emulsifier

[0109] In certain aspects of the invention, the composition does not include an emulsifier. However, in other aspects, the composition may include one or more than one emulsifier. Emulsifiers can reduce the interfacial tension between the phases and improve the formulation and stability of the emulsion. Emulsifiers can be nonionic, cationic, anionic, and zwitterionic emulsifiers (see U.S. Patents Nos. 5,011,681; 4,421,769; 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 sorbitan anhydride, carboxylic acid copolymers, esters and ethers of glucose, ethoxylated ethers, ethoxylated alcohols, alkyl phosphates, polyoxyethylene fatty ether phosphates, fatty acid amides, acyl lactylates, soaps, TEA stearate, oleth-3 phosphate DEA salt, polyethylene glycol 20 sorbitan monolaurate (polysorbate 20), polyethylene glycol 5 soya sterol, steareth-2, steareth-20, steareth-2 1. Ceteareth-20, cetearyl glucoside, cetearyl alcohol, C12-C13 Pareth-3, PPG-2 methyl glucose ether distearate, PPG-5-eth-20, bis-PEG / PPG-20 / 20 dimethicone, pareth-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.

[0110] f. Polysiloxane-containing compounds

[0111] In non-limiting terms, polysiloxane-containing compounds include any member of a family of polymers whose molecular backbone consists of alternating silicon and oxygen atoms with pendant groups attached to the silicon atoms. By varying the length of the -Si-O- chains, the pendant groups, and the crosslinking, polysiloxanes can be synthesized into a wide variety of materials. Their consistency can vary from liquid to gel to solid.

[0112] The compound containing polysiloxane that can be used in the context of the present invention includes those described in this specification or those known to those of ordinary skill in the art. Non-limiting examples include silicone oils (for example, volatile oils and non-volatile oils), gels and solids. In some aspects, silicon-containing compounds include silicone oils, for example polyorganosiloxanes. The non-limiting examples of polyorganosiloxanes include polydimethylsiloxane, cyclomethicone, polysilicone-11, phenyl trimethylsiloxane, trimethylsilyl-terminated polydimethylsiloxane (trimethylsilylamodimethicone), stearoxytrimethylsilane or these substances with other organopolysiloxane materials with a mixture of any given ratio, thereby obtaining desired consistency and application characteristics according to expected application (for example, for specific areas, such as skin, hair or eyes). " Volatile silicone oil " includes silicone oil with low heat of vaporization, i.e., silicone oil with a heat of vaporization usually lower than about 50 cal / g. Non-limiting examples of volatile silicone oils include: cyclomethicone, 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.); low viscosity polydimethylsiloxane, i.e., polydimethylsiloxane having a viscosity of about 50 cst or less (e.g., polydimethylsiloxane such as Dow Corning 200-0.5 cst fluid). Dow Corning fluids are commercially available from Dow Corning Corporation, Midland, Michigan. Cyclomethicone and polydimethylsiloxane are described in the 3rd edition of the CTFA Cosmetic Ingredient Dictionary (incorporated by reference) as a mixture of a cyclic dimethylpolysiloxane compound and a fully methylated linear siloxane polymer end-capped with trimethylsiloxy units, respectively. Other non-limiting volatile silicone oils that can be used in the context of the present invention include those available from General Electric Co., Silicone Products Div., Waterford, NY, and Stauffer Chemical Co., SWS Silicones Div., Adrian, Michigan.

[0113] g. Exfoliating agent

[0114] Exfoliants include ingredients that remove dead skin cells from the outer surface of the skin. These agents can work mechanically, chemically, and / or in other ways. Non-limiting examples of mechanical exfoliants include abrasives such as pumice, silica, fabrics, paper, shells, beads, solid crystals, solid polymers, and the like. 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, alpha hydroxy acids, beta hydroxy acids, and the like. Other exfoliants known to those skilled in the art are also contemplated to be useful in the context of the present invention.

[0115] h. Essential oils

[0116] Essential oils include oils from herbs, flowers, trees, and other plants. This oil is usually present in the form of tiny droplets between plant cells and can be extracted by several methods known to those skilled in the art (for example, steam distillation, enfleurage (i.e., extraction using fat), maceration, solvent extraction, or mechanical pressing). When these types of oils are exposed to air, they tend to evaporate (i.e., volatile oils). Therefore, although many essential oils are colorless, they will oxidize and darken over time. Essential oils are insoluble in water but soluble in alcohols, ethers, fixed oils (vegetable oils), and other organic solvents. Typical physical properties of essential oils include a boiling point that varies from about 160°C to about 240°C and a density of about 0.759 to about 1.096.

[0117] Essential oils are usually named after the plants in which they are found. For example, rose oil or peppermint oil are respectively from the plants of rose or peppermint. The limiting examples of the essential oils that can be used in the context of the present invention include sesame oil, macadamia nut oil, tea tree oil, evening primrose oil, Spanish sage oil, Spanish rosemary oil, coriander oil, thyme oil, allspice oil, rose oil, fennel oil, balsam (balsam) oil, bergamot oil, rosewood oil, cedar oil, chamomile oil, sage oil, clary sage oil, clove oil, cypress oil, eucalyptus oil, fennel oil, sea fennel oil, frankincense oil, geranium (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, rose otto (rose), thyme oil, sesame oil, tea tree oil, evening primrose oil, Spanish sage oil, Spanish rosemary oil, coriander oil, thyme oil, allspice oil, rose oil, fennel oil, balsam (balsam) oil, bergamot oil, rosewood oil, cedar oil, chamomile oil, sage oil, clary sage oil, clove oil, cypress oil, eucalyptus oil, fennel oil, sea fennel oil, frankincense oil, geranium (geranium) oil, ginger oil, grapefruit oil, jasmine oil, juniper oil, lavender oil, lemon oil, lemongrass oil, lime oil, tangerine oil, marjoram oil, myrrh oil, neroli oil, orange oil, patchouli oil, pepper oil, black pepper oil, petitgra It is contemplated that other essential oils known to those skilled in the art may also be used in the context of the present invention.

[0118] i.Thickener

[0119] Thickeners, including thickeners or gelling agents, include substances that can increase the viscosity of the composition. Thickeners include those that can increase the viscosity of the composition without substantially changing the efficacy of the active ingredients in the composition. Thickeners can also increase the stability of the compositions of the present invention. In certain aspects of the present invention, the thickener includes hydrogenated polyisobutylene, trihydroxystearin, ammonium acryloyldimethyltaurate / VP copolymer, or mixtures thereof.

[0120] Non-limiting examples of additional thickening agents that can be used in the context of the present invention include carboxylic acid polymers, cross-linked polyacrylate polymers, polyacrylamide polymers, polysaccharides, and gums. Examples of carboxylic acid polymers include cross-linked compounds containing one or more monomers derived from acrylic acid, substituted acrylic acids, and salts and esters of these acrylic acids and substituted acrylic acids, wherein the cross-linking agent contains two or more carbon-carbon double bonds and is derived from a polyol (see U.S. Patents 5,087,445; 4,509,949; 2,798,053; CTFA International Cosmetic Ingredient Dictionary, Fourth Edition, 1991, pages 12 and 80). Examples of commercially available carboxylic acid polymers include carbomers, which are homopolymers of acrylic acid cross-linked with allyl ethers of sucrose or pentaerythritol (e.g., CARBOPOL from BF GOODRICH). TM 900 series).

[0121] Non-limiting examples of cross-linked polyacrylate polymers include cationic polymers 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.

[0122] Non-limiting examples of polyacrylamide polymers, including nonionic polyacrylamide polymers, including substituted branched or linear polymers, include polyacrylamide, isoparaffin and laureth-7, multi-block copolymers of acrylamide and substituted acrylamides with acrylic acid and substituted acrylic acid.

[0123] 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 an alkyl-substituted cellulose, in which the hydroxyl groups of the cellulose polymer are hydroxyalkylated (preferably hydroxyethylated or hydroxypropylated) to form a hydroxyalkylated cellulose, which is then further modified by an ether linkage with a C10 to C30 straight or branched alkyl group. Typically, these polymers are ethers of a C10 to C30 straight or branched alcohol and a hydroxyalkyl cellulose. Other useful polysaccharides include scleroglucans, which comprise a linear chain of (1 to 3) linked glucose units, with (1 to 6) linked glucose groups for every three units.

[0124] Non-limiting examples of gums that can be used with the present invention include gum arabic, agar, algin, alginic acid, ammonium alginate, pullulan, calcium alginate, calcium carrageenan, carnitine, carrageenan, dextrin, gelatin, gellan gum, guar gum, guar hydroxypropyltrimonium chloride, hectorite, hyaluronic acid, hydrated silica, hydroxypropyl chitosan, hydroxypropyl guar gum, karaya gum, kelp, locust bean gum, natto gum, potassium alginate, potassium carrageenan, propylene glycol alginate, sclerotium gum, sodium carboxymethyl dextran, sodium carrageenan, tragacanth gum, xanthan gum, and mixtures thereof.

[0125] j. Preservatives

[0126] Non-limiting examples of preservatives that can be used in the context of the present invention include quaternary ammonium preservatives such as polyquaternium-1 and benzalkonium halides (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.

[0127] k. Emollients

[0128] Useful emollients include the following: (a) silicone oils and modifications thereof, such as linear and cyclic polydimethylsiloxanes; aminosilicone oils, alkylsilicone oils, alkylarylsilicone oils, and arylsilicone 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, mink oil; cocoa butter; tallow, lard; hardened oils obtained by hydrogenating the above oils; and synthetic mono-, di-, and triglycerides, such as myristyl glyceride and 2-hydroxypropyl glyceride. (c) waxes such as carnauba wax, spermaceti, beeswax, lanolin and its derivatives; (d) hydrophobic plant extracts; (e) hydrocarbons such as liquid paraffin, petrolatum, microcrystalline wax, ozokerite, squalene, pristane and mineral oil; (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 (PUFA); (g) higher alcohols such as lauryl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, behenyl alcohol, cholesterol, and 2-hydroxy-1,2-dextrose. - alcohol of hexyldecanol; (h) esters, such as cetyl octanoate, 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 lactates, alkyl citrates and alkyl tartrates; (i) essential oils and extracts thereof, such as mentha, jasmine, camphor, white cedar, bitter orange peel, ryu, turpentine, cinnamon, bergamot, mandarin orange, sweet calamus Cattail, pine, lavender, bay, clove, hiba, eucalyptus, lemon, borage (starflower), thyme, mint, 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, pennyroyal (i) oils of citric acid, maltose ...(m) polyols, such as glycerol and propylene glycol; and polyols, such as polyethylene glycol; (n) anti-aging compounds, such as alpha hydroxy acids, beta hydroxy acids; and (o) mixtures of any of the foregoing components, etc.;

[0129] 1. Thickener

[0130] Examples of suitable tackifiers include, but are not limited to, aliphatic hydrocarbon resins, aromatic modified aliphatic hydrocarbon resins, hydrogenated polycyclopentadiene resins, polycyclopentadiene resins, gum rosin, rosin esters, wood rosin, wood rosin esters, tall oil rosin, tall oil rosin esters, polyterpenes, aromatic modified polyterpenes, terpene 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 diene, partially or fully hydrogenated polybutene diene, etc. As demonstrated by some of the cited examples, the tackifiers may be fully or partially hydrogenated. The tackifier may also be non-polar (by non-polar is meant that the tackifier is essentially free of monomers having polar groups. Preferably, polar groups are not present, however, if they are present, they are preferably present in an amount up to about 5 wt%, preferably up to about 2 wt%, more preferably up to about 0.5 wt%.).

[0131] m. Colorant

[0132] The compositions of the present invention may also include 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 are understood to be inorganic or organic, white or colored particles. Within the scope of the present invention, the pigments may optionally be surface treated, but are not limited to, treatments such as polysiloxanes, perfluorinated compounds, lecithins, and amino acids.

[0133] surfactant

[0134] Surfactants suitable for use as the surfactant component in the compositions of the present invention include nonionic surfactants, anionic surfactants, cationic surfactants and amphoteric (zwitterionic) surfactants, and may be used in combination with one another.

[0135] o. pH adjuster

[0136] 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, pyrrolidonecarboxylic acid (PCA), succinic acid, citric acid, glutamic acid, 2-amino-2-methyl-1-propanol (AMP), and triethanolamine (TEA).

[0137] p.Reducing agent

[0138] Suitable reducing agents include, but are not limited to, thiourea, thiosulfates, sulfites, bisulfites, metabisulfites, borohydrides, and salts (e.g., sodium salts) of hypophosphites, ascorbic acid and its salts, esters, and derivatives thereof (e.g., ascorbyl palmitate and ascorbic acid polypeptide), and tocopherol and its salts, esters, and derivatives thereof (e.g., tocopheryl acetate).

[0139] q. Aromatherapy

[0140] The compositions disclosed herein may optionally contain a fragrance. Examples of possible fragrances include natural oils or naturally derived materials, and synthetic fragrances such as hydrocarbons, alcohols, aldehydes, ketones, esters, lactones, ethers, nitriles, and polyfunctional compounds. Non-limiting examples of natural oils include the following: 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, citronella (Cymbopogon nardus) oil, clary sage (Salvia sclarea) oil, clove (Eugenia caryophyllus) oil, clove (Eugenia caryophyllus) leaf oil, sedge (Cyperus sculentus) oil, cypress (Cupressus rubrum) oil sempervirens oil, lemon eucalyptus (Eucalyptus citriodora) oil, spotted geranium (Geranium maculatum) oil, ginger (Zingiber officinale) oil, grapefruit (Citrus grandis) oil, hazelnut (Corylus avellana) nut oil, jasmine (Jasminum officinale) oil, European juniper (Juniperus communis) oil, sharp-leaved juniper (Juniperus oxycedrus) tar, North American juniper (Juniperus virginiana) oil, kiwi fruit (Actinidia chinensis) water, lavender (Lavandula hybrida) oil, lavender (Lavandula angustifolia) oil, lavender (Lavandula angustifolia) water, lemon (Citrus medica limonum) oil, lemongrass (Cymbopogon schoenanthus) oil, lemon (Citrus aurantifolia) oil, lime (Tilia corodia) oil, lime (Tilia cordata) water, citrus (Citrus nobilis) oil,Nutmeg (Myristica fragrans) oil, orange (Citrus aurantium dulcis) flower oil, orange (Citrus aurantium dulcis) oil, orange (Citrus aurantium dulcis) water, patchouli (Pogostemoncablin) oil, mint (Menthe piperita) oil, mint (Menthe peperita) water, rosemary (Rosmarinus officinalis) oil, rose oil, rose (Rosa damascena) extract, rose (Rosa multiflora) extract, rosewood (Aniba rosaeodora) extract, sage (Salvia officinalis) oil, sandalwood (Santalum album) oil, spearmint (Mentheviridis) oil, tea tree (Melaleuca alternifolia) alternifolia) oil and Cananga odorata oil. Some non-limiting examples of synthetic hydrocarbon fragrances include caryophyllene, β-farnesene, limonene, α-pinene and β-pinene. Some non-limiting examples of synthetic alcohol fragrances include 2-borneolyl butanol (sandalol, bacdanol), citronellol, linalool, phenylethyl alcohol and α-terpineol (R=H). Some non-limiting examples of synthetic aldehyde fragrances include 2-methylundecanal, citral, hexylcinnamaldehyde, isocycolcitral, lilyral and 10-undecenal. Some non-limiting examples of synthetic ketone fragrances include cashmeran, α-ionone, ambergris E (isocyclemone E), koavone, musk ketone and tuna musk. Some non-limiting examples of synthetic ester fragrances include benzyl acetate, 4-tert-butylcyclohexyl acetate (cis and trans), cedryl acetate, cyclacet acetate, isoborneol acetate, and alpha-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 synthetic multifunctional fragrances include amyl salicylate, isoeugenol, hedione, piperonal, lyral, and vanillin.

[0141] r. Foaming agent

[0142] Foaming agents include, for example, sodium lauryl sulfate, sodium lauroyl sarcosinate, sodium alkyl sulfosuccinate, sodium coconut oil fatty acid monoglycerol sulfonate, sodium α-olefin sulfonate, N-acylamino acid salts such as N-acyl glutamate, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine, maltitol fatty acid ester, sucrose fatty acid ester, polyglycerol fatty acid ester, fatty acid diethanolamide, polyoxyethylene sorbitan monostearate, polyoxyethylene hydrogenated castor oil, and polyoxyethylene fatty acid ester. These foaming agents can be used alone or in combination of two or more.

[0143] s. tanning agent

[0144] Suitable tanning agents include, but are not limited to, α-hydroxyaldehydes and α-hydroxyketones, glyceraldehyde and related alcohol aldehydes, various indoles, imidazoles and their derivatives, and various approved pigmentation agents. Other suitable tanning agents include, but are not limited to, methylglyoxal, glyceraldehyde, erythrulose, alloxan, 2,3-dihydroxysuccinaldehyde, 2,3-dimethoxysuccinaldehyde, 2-amino-3-hydroxysuccinaldehyde, and 2-benzylamino-3-hydroxysuccinaldehyde.

[0145] t. Astringent

[0146] 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 and potassium alum, aluminum triphosphate, aluminum glycinate and aluminum phenol sulfate, Alcloxa, Aldioxa, aluminum stearate, aluminum sulfate and aluminum citrate, sodium aluminum phosphate, sodium alum, sodium aluminum chlorohydroxylactate, calcium lactate, calcium chloride, hydrated calcium sulfate, sodium aluminum lactate, zinc acetate, zinc chloride, zinc sulfate, zinc lactate, zinc zeolite, zinc phenolsulfonate, and combinations thereof. Extract refers to the entire fruit, legume, and / or plant, or selected components of such fruit, legume, and / or plant.

[0147] u.Disinfectant

[0148] Suitable disinfectants include, but are not limited to, methyl, ethyl, propyl, or butyl esters of paraoxybenzoic acid, phenoxyethanol, o-phenylphenol, dehydroacetic acid or its salts, p-cresol, m-cresol, o-chloro-m-xylenol, peppermint oil, echinacea, bloodroot, cayenne, tea tree oil, wild bergamot, chaparral, stinging nettle, 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, benzethonium chloride, hexylresorcinol, methylbenzethonium chloride, phenol, quaternary ammonium compounds, triclocarbon, triclosan, and tea tree oil.

[0149] v. Deodorants and antiperspirants

[0150] Suitable antiperspirants and deodorants include, but are not limited to, zinc salts such as zinc sulfate and zinc chloride, glycinates such as aluminum zirconium glycinate, aluminum chlorohydrate, aluminum zirconium tetrachlorohydrate, zinc carbonate, o-phenylphenol, and quaternary ammonium compounds such as dimethylbenzylammonium chloride and hexamethonium chloride.

[0151] w. Brightener

[0152] Examples of skin lightening agents include, but are not limited to, hydroquinone, kojic acid, licorice and / or its derivatives, ascorbic acid and / or its derivatives, arbutin, bearberry extract, glycyrrhiza glabra and its derivatives, Chlorella vulgaris extract, perilla extract, coconut fruit extract, and / or other depigmenting agents.

[0153] x. Antimicrobial agents

[0154] Examples of antimicrobial agents include, but are not limited to, triclosan, 3,4,4'-trichlorocarbanilide (triclocarban); 3,4,4'-trifluoromethyl-4,4'-dichlorocarbanilide (cloflucarban); 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; diazolidinyl urea; butoconazole; nystatin; terconazole; nitrofurantoin; phenazopyridine; Acyclovir; clotrimazole; parachlorometaxylenol; chlorhexidine; miconazole; terconazole; butylparaben; ethylparaben; 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-dimonium chloride; chlorhexidine gluconate; chlorhexidine digluconate; chlorhexidine acetate; chlorhexidine isethionate; chlorhexidine hydrochloride; benzalkonium chloride; benzethonium chloride; polyhexamethylene biguanide; and mixtures thereof.

[0155] 2. Drug ingredients

[0156] It is contemplated that pharmaceutically active agents are also suitable for use in the compositions of the present invention. Non-limiting examples of pharmaceutically active agents include anti-acne agents, agents for treating rosacea, analgesics, anesthetics, anorectal agents, antihistamines, anti-inflammatory drugs including nonsteroidal anti-inflammatory drugs, antibiotics, antifungals, antivirals, antibacterials, anticancer actives, scabicides, pediculicides, antitumor drugs, antiperspirants, antipruritics, antipsoriatics, antiseborrheic drugs, biologically active proteins and peptides, burn treatments, cautery agents, depigmenting agents, depilatories, diapers, Rash treatment agents, enzymes, hair growth stimulants, hair growth retardants including DFMO and its salts and analogs, hemostatics, keratolytics, oral ulcer treatment agents, cold sore treatment agents, dental and periodontal treatment agents, photosensitizers, skin protectants / skin 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.

[0157] G. Test kit

[0158] It is contemplated that kits are also used in certain aspects of the present invention. For example, the compositions of the present invention may be included in a kit. The kit may include a container. The container may include a bottle, a metal tube, a laminated tube, a plastic tube, a dispenser, a pressurized container, an isolating container, a package, a compartment, a lipstick container, a compressed container, a cosmetic tray or other type of container that can hold a cosmetic composition, such as a syringe or blow-molded plastic container that holds a dispersion or composition or a desired bottle, dispenser or package. The kit and / or container may include a label on its surface. For example, the label may be a word, a phrase, an abbreviation, a picture or a symbol.

[0159] The container can dispense a predetermined amount of composition. In other embodiments, a container (e.g., metal, laminate, 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 semisolid. The container can have a machine for spraying, pumping, or squeezing. The test kit can also include instructions for use of any other composition included in the application kit components and the container. Instructions can include instructions for how to apply, use, and maintain the composition. Example

[0160] The following examples are included to illustrate preferred embodiments of the present invention. It will be appreciated by those skilled in the art that the techniques disclosed in the following examples represent techniques discovered by the inventors to function well in the practice of the present invention and, therefore, can be considered to constitute preferred modes for its practice. However, in light of this disclosure, it will be appreciated by those skilled in the art that many changes may be made to the disclosed specific embodiments without departing from the spirit and scope of the present invention and still obtaining the same or similar results.

[0161] In accordance with the present disclosure, all compositions and / or methods disclosed and claimed herein can be made and implemented without undue experimentation. Although the compositions and methods of the present invention have been described in terms of preferred embodiments, it will be apparent to those skilled in the art that the steps or sequence of steps of the compositions and / or methods and methods described herein may be changed without departing from the concept, spirit, and scope of the present invention. More specifically, it will be apparent that certain reagents that are chemically and physiologically related can replace the reagents described herein while obtaining the same or similar results. All such similar substitutions and modifications apparent to those skilled in the art are considered to be within the spirit, scope, and concept of the present invention as defined by the appended claims.

[0162] Example 1

[0163] (Materials used)

[0164] The active ingredients in Table 1 were used to obtain the in vitro data and / or clinical data reported below and / or described in the associated figures.

[0165] Table 1

[0166] Element CP: Collagen Peptide HA: Sodium Hyaluronate AX: Haematococcus pluvialis (astaxanthin) PE: Pueraria lobata extract (puerarin)

[0167] Example 2

[0168] (In vitro activity)

[0169] As shown in in vitro testing, it was determined that the combination of collagen peptides, sodium hyaluronate, Haematococcus pluvialis (containing astaxanthin) and kudzu extract (containing puerarin) expanded previously unknown effective pathways (such as MMP-3) and enhanced the effects of other pathways (such as collagen 1, MMP-1, HAS2) compared to the same amount of each single ingredient. As shown in in vitro testing, it was also determined that the combination of Haematococcus pluvialis (containing astaxanthin) and kudzu extract (containing puerarin) expanded and / or enhanced the effective pathways compared to the same amount of each single ingredient.

[0170] The results are summarized in Table 2 The methods used to determine the compositional characteristics are as follows.

[0171] The component samples were analyzed for their ability to improve skin cell bioactivity and skin protection compared to the individual components: collagen 1, MMP-1, MMP-3, and hyaluronan synthase 2 (HAS2) were studied using the fibroblast-UVA model; aquaporin 3 mRNA and protein were studied using the keratinocyte (no inducer)-hydrated model; reactive oxygen species (ROS) were studied using the keratinocyte (UVB)-anti-ROS model; and collagen 1 and HAS2 were studied using the fibroblast-anti-blue light model (results are shown in Table 2).

[0172] Table 2 In vitro test results

[0173]

[0174]

[0175] Example 3

[0176] (Exemplary Formulation)

[0177] Formulations with the ingredients from Example 1 were prepared into nutraceutical compositions. The formulations in Table 3, Table 4, Table 5, and Table 6 are examples of nutraceutical formulations.

[0178] Table 3

[0179]

[0180]

[0181] *Excipients may be added, for example, to modify the rheological properties of the composition.

[0182] Table 4

[0183] Element Dosage per Serving Haematococcus pluvialis encapsulated powder 85mg Sodium hyaluronate 60mg Fish collagen 5g Kudzu extract 600mg Excipients*, flavors, preservatives, fragrances, etc. appropriate amount

[0184] *Excipients may be added, for example, to modify the rheological properties of the composition.

[0185] Table 5

[0186]

[0187]

[0188] *Excipients may be added, for example, to modify the rheological properties of the composition.

[0189] Table 6

[0190] Element Dosage per Serving Haematococcus pluvialis encapsulated powder 86mg Sodium hyaluronate 600mg Sea buckthorn juice powder 200mg Stevioside 40mg Anhydrous citric acid 200mg blood orange juice powder 60mg Lemon juice powder 30mg Lemon lime essence 40mg Grapefruit juice powder 100mg grapefruit flavor 150mg Isomalt 1.4g Fish collagen 5g Kudzu extract 600mg excipient* appropriate amount

[0191] *Excipients may be added, for example, to modify the rheological properties of the composition.

[0192] Example 4

[0193] (Measurement)

[0194] Assays that can be used to determine the efficacy of any one or any combination of ingredients disclosed throughout the specification and claims, or compositions having such combinations of ingredients, can be determined by methods known to those of ordinary skill in the art. The following are non-limiting assays that can be used and / or have been used in the context of the present invention. It will be appreciated that other testing procedures, including, for example, objective and subjective procedures, can be used.

[0195] B16 Pigmentation Assay: Melanogenesis is the process by which melanocytes produce melanin, the naturally occurring pigment that gives skin, hair, and eyes its color. Inhibiting melanogenesis is beneficial in preventing skin darkening and reducing dark spots associated with aging. This bioassay utilizes B16-F1 melanocytes (ATCC), an immortalized mouse melanoma cell line, to analyze the effects of compounds on melanogenesis. The endpoints of this assay are spectrophotometric measurement of melanogenesis and cell viability. B16-F1 melanocytes can be cultured in standard DMEM growth medium with 10% fetal bovine serum (MEDIATECH) at 37°C in 10% CO2 and then treated with the active ingredients, combination of ingredients, or compositions having said combinations disclosed in the instructions for 6 days. After incubation, melanin secretion is measured by absorbance at 405nm and cell viability is quantified.

[0196] Collagen Stimulation Assay: Collagen is any of the extracellular matrix proteins found in cells and is crucial to skin structure. Increased collagen synthesis contributes to improved skin firmness and elasticity. This bioassay can be used to measure the effect of any of the active ingredients, combinations of ingredients, or compositions comprising such combinations disclosed in the specification on the production of procollagen peptides (collagen precursors) by human dermal fibroblasts. The assay endpoint is a spectrophotometric measurement, which reflects the presence of procollagen peptides and cell viability. The assay utilizes a quantitative sandwich enzyme immunoassay technique in which a monoclonal antibody specific for procollagen peptides is pre-coated on a microplate. Standards and samples are pipetted into the wells, and any procollagen peptides present are bound by the immobilized antibody. After washing to remove any unbound material, an enzyme-linked polyclonal antibody specific for the procollagen peptides is added to the wells. After washing to remove any unbound antibody-enzyme reagent, a substrate solution is added to the wells, and color develops proportionally to the amount of procollagen peptide bound in the initial step, with detection at 450 nm using a microplate reader. Color development can be stopped and the color intensity can be measured.

[0197] To generate samples and controls, near-confluent normal adult dermal fibroblasts (Cascade Biologics) cultured in standard DMEM growth medium containing 10% fetal bovine serum (MEDIATECH) at 37°C in 10% CO2 can be treated with each combination of ingredients disclosed in the instructions or compositions having such combinations for 3 days. After incubation, the cell culture medium can be collected and the amount of procollagen peptide secretion can be quantified using a sandwich enzyme-linked immunosorbent assay (ELISA) from TAKARA (#MK101).

[0198] 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 where mechanical energy storage is required. Elastin is produced by linking many soluble tropoelastin molecules in a reaction catalyzed by the enzyme lysyl oxidase. Elastin secretion and elastin fibers can be monitored in cultured human fibroblasts by staining the cells with an immunofluorescent antibody against elastin.

[0199] Laminin and Fibronectin Stimulation Assay: Laminin and fibronectin are the major proteins of the dermal-epidermal junction (DEJ), also known as the basement membrane. The DEJ is located between the dermis and epidermis, forming finger-like projections called epithelial ridges. Epidermal cells obtain nutrients from blood vessels in the dermis. Epithelial ridges increase the surface area of ​​the epidermis exposed to these blood vessels and required nutrients. The DEJ provides adhesion between the two tissue compartments and controls the structural integrity of the skin. Laminin and fibronectin are two structural glycoproteins located at the DEJ. Laminin and fibronectin are believed to be the adhesives that bind cells together. They are secreted by dermal fibroblasts and help promote intracellular and intercellular adhesion of epidermal cells to the DEJ. Laminin and fibronectin secretion can be monitored by quantifying laminin and fibronectin in the cell supernatant of cultured human fibroblasts treated for 3 days with culture medium containing or not containing one or more test components at a final concentration of 1.0%. After incubation, the levels of laminin and fibronectin can be measured in an enzyme-linked immunosorbent assay (ELISA) using immunofluorescent antibodies directed against laminin and antibodies directed against fibronectin. Measurements of cellular metabolic activity are normalized, as determined by the biotransformation of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS).

[0200] Tumor Necrosis Factor Alpha (TNF-α) Assay: TNF-α, the prototypic ligand of the TNF superfamily, is a pleiotropic cytokine that plays a central role in inflammation. Increased expression of TNF-α is associated with upregulation of proinflammatory activity. This bioassay can be used to analyze the effects of any of the active ingredients, combinations of ingredients, or compositions comprising such combinations disclosed in the specification on TNF-α production by human epidermal keratinocytes. The assay endpoints can be spectrophotometric measurements reflecting TNF-α and cell viability. The assay utilizes a quantitative sandwich enzyme immunoassay technique in which a monoclonal antibody specific for TNF-α is pre-coated on a microplate. Standards and samples are pipetted into the wells, and any TNF-α present is bound by the immobilized antibody. After washing to remove any unbound material, an enzyme-linked polyclonal antibody specific for TNF-α is added to the wells. After washing to remove any unbound antibody-enzyme reagent, a substrate solution is added to the wells, and color development occurs proportionally to the amount of TNF-α bound in the initial step. Detection is performed using a microplate reader at 450 nm. The color development can be stopped and the color intensity can be measured. TMNearly confluent normal adult human keratinocytes (Cascade Biologics) cultured in standard growth medium (Cascade Biologics) can be treated with phorbol 12-myristate 13-acetate (PMA, 10 ng / ml, SIGMA CHEMICAL, #P1585-1MG) and any of the active ingredients, combinations of ingredients, or compositions comprising such combinations disclosed in the instructions for 6 hours. PMA has been shown to cause a significant increase in TNF-α secretion, which peaks 6 hours after treatment. Following incubation, cell culture medium can be collected and TNF-α secretion quantified using a sandwich enzyme-linked immunosorbent assay (ELISA) from R&D Systems (#DTA00C).

[0201] Antioxidant (AO) assay: An in vitro bioassay used to measure the total antioxidant capacity of any one ingredient, combination of ingredients, or composition comprising said combination disclosed in the specification. This assay relies on the ability of antioxidants in a sample to inhibit the conversion of metmyoglobin to (2,2'-Azobis-[3-ethylbenzothiazoline sulfonate]) is oxidized to ·+ 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 of the extracellular fluid. The synergistic action of all the different antioxidants provides greater protection against attack by reactive oxygen or nitrogen radicals than any single compound acting alone. Therefore, the total antioxidant capacity can provide more relevant biological information than that obtained by measuring the individual components because it takes into account the cumulative effect of all antioxidants present in plasma and body fluids. The antioxidants in the sample that protect against The oxidative capacity is compared with that of the water-soluble tocopherol analog Trolox and quantified as the molar equivalent 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 such combinations disclosed in the instructions. The protocol can be performed according to the manufacturer's recommendations.

[0202] ORAC Assay: The oxygen radical absorbance (or absorbance) capacity (ORAC) of any of the active ingredients, combinations of ingredients, or compositions comprising such combinations disclosed herein can also be determined by measuring the antioxidant activity of such 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 free radicals, which are known to damage cells (e.g., skin cells). The ORAC value of any of the ingredients, combinations of ingredients, or compositions comprising such combinations disclosed herein can be determined by methods known to those skilled in the art (see U.S. Publication Nos. 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 fluorescein fluorescence over time due to the decomposition of AAPH (2,2'-azobis-2-methylpropylideneimidazole, dihydrochloride) to form peroxyl radicals. Trolox, a water-soluble vitamin E analogue, served as a positive control and inhibited fluorescein decay in a dose-dependent manner.

[0203] Mushroom Tyrosinase Activity Assay: In mammalian cells, tyrosinase catalyzes two steps in the multistep biosynthesis of melanin from tyrosine (and from the polymerization of dopachrome). Tyrosinase is located in melanocytes and produces melanin (an aromatic quinone compound), which imparts color to skin, hair, and eyes. Purified mushroom tyrosinase (from SIGMA) can be incubated with its substrate, L-Dopa (from FISHER), in the presence or absence of any of the active ingredients, combinations of ingredients, or compositions comprising such combinations disclosed in the specification. Pigment formation can be assessed by microplate reader reading at 490 nm. The percent inhibition of mushroom tyrosinase activity can be calculated and compared to an untreated control to determine the ability of the test ingredient or combination to inhibit the activity of the purified enzyme. The inhibitory effect of the test extracts was compared to that of kojic acid (SIGMA).

[0204] Matrix metalloproteinase 3 and matrix metalloproteinase 9 enzymatic activity (MMP3; MMP9) assay: In vitro matrix metalloproteinase (MMP) inhibition assay. MMPs are extracellular proteases that play a role 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 Colorimetric Drug Discovery kits for MMP3 (AK-400) and MMP-9 (AK-410) from BioMol International, this assay is designed to measure the protease activity of MMPs using a thiopeptide as a chromogenic substrate (Ac-PLG-[2-mercapto-4-methyl-pentanoyl]-LG-OC2H5)5,6. The MMP cleavage site peptide bond is replaced by a thioester bond in the thiopeptide. MMP hydrolyzes this bond to produce a sulfhydryl group, which reacts with DTNB [5,5'-dithiobis(2-nitrobenzoic acid), Ellman's reagent] to form 2-nitro-5-thiobenzoic acid, which can be detected by its absorbance at 412 nm (ε = 13600 M-1 cm-1, pH 6.0 and above). The active ingredient disclosed in the specification, any combination of ingredients, or a composition comprising such a combination can be assayed.

[0205] Matrix Metalloproteinase 1 (MMP1) Enzyme Activity Assay: This in vitro matrix metalloproteinase (MMP) inhibition assay is performed. MMPs are extracellular proteases that, due to their broad substrate specificity, play a role in many normal and disease states. MMP1 substrates include type IV collagen. The Molecular Probes ENZ / CHEK Gelatinase / Collagenase Assay Kit (#E12055) utilizes a fluorescent gelatin substrate to detect MMP1 protease activity. Upon proteolytic cleavage, bright green fluorescence is exhibited and can be monitored using a fluorescence microplate reader to measure enzyme activity.

[0206] The ENZ / CHEK Gelatinase / Collagenase Assay Kit (#E12055) from Invitrogen is designed as an in vitro assay for measuring MMP1 enzyme activity. The assay can be performed using any of the active ingredients disclosed in the instructions, any combination of ingredients, or compositions comprising such combinations. The assay relies on the ability of purified MMP1 enzyme to degrade a fluorescent gelatin substrate. Once the substrate is specifically cleaved by MMP1, bright green fluorescence is revealed and can be monitored using a fluorescence microplate reader. Test materials are incubated in the presence or absence of the purified enzyme and substrate to determine their protease inhibitory capacity.

[0207] Cyclooxygenase (COX) Assay: In vitro cyclooxygenase-1 and cyclooxygenase-2 (COX-1, COX-2) inhibition assay. COXs are bifunctional enzymes with both cyclooxygenase and peroxidase activities. The cyclooxygenase activity converts arachidonic acid into hydroperoxide endoperoxides (prostaglandin G2; PGG2), while the peroxidase component reduces the endoperoxides (prostaglandin H2; PGH2) into the corresponding alcohols, precursors of prostaglandins, thromboxanes, and prostacyclins. This COX inhibitor screening assay measures the peroxidase component of the cyclooxygenase enzymes. Peroxidase activity is measured colorimetrically by monitoring the appearance 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 isozyme-specific inhibitors. The colorimetric COX (sheep) inhibitor screening assay (#760111, CAYMAN CHEMICAL) can be used to analyze the effect of each active ingredient disclosed in the instructions, any combination of ingredients, or a composition having the combination on the activity of purified cyclooxygenase (COX-1 or COX-2). According to the manufacturer's instructions, the purified enzyme, heme, and test extract can be mixed in the detection buffer and incubated with shaking at room temperature for 15 minutes. After incubation, arachidonic acid and a colorimetric substrate can be added to initiate the reaction. Color development can be assessed by reading the microplate reader at 590nm. The percentage inhibition of COX-1 or COX-2 activity can be calculated and compared with the untreated control to determine the ability of the test extract to inhibit the activity of the purified enzyme.

[0208] Lipoxygenase (LO) Assay: In vitro lipoxygenase (LO) inhibition assay. 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 primary substrates for LO in plants and animals. Arachidonic acid can then be converted to hydroxyeicosatrienoic acid (HETE) derivatives, which are subsequently converted into potent inflammatory mediators, leukotrienes. This assay provides an accurate and convenient method for screening lipoxygenase inhibitors by measuring the hydroperoxides produced during incubation of lipoxygenase (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 composition having the combinations disclosed in the instructions to inhibit enzyme activity. Purified 15-lipoxygenase and the test ingredients 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 an additional 10 minutes at room temperature. A colorimetric substrate can be added to terminate catalysis, and the progress of color development can be assessed by fluorescence plate reading at 490 nm. The percent inhibition of lipoxygenase activity can be calculated compared to an untreated control to determine the ability of each active ingredient, any combination of ingredients, or a composition comprising the combinations disclosed in the specification to inhibit the activity of the purified enzyme.

[0209] Elastase assay: from MOLECULAR PROBES (Eugene, Oregon USA) The Elastase Assay (Kit #E-12056) can be used as an in vitro enzyme inhibition assay to measure inhibition of elastase activity for each active ingredient disclosed in the specification, any combination of ingredients, or compositions comprising such combinations. The ENZCHEK kit contains soluble bovine cervical ligament elastin, which can be labeled with a dye to quench the fluorescence of the conjugate. The non-fluorescent substrate can be digested by elastase or other proteases to produce highly fluorescent fragments. The resulting increase in fluorescence can be monitored using a fluorescence microplate reader. The digestion products of the elastin substrate have an absorption maximum at approximately 505 nm and a fluorescence emission maximum 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 inhibitor of elastase.

[0210] Ceramide production: Ceramide in cells or tissue samples can be labeled by incubating with a mouse monoclonal anti-ceramide antibody (ENZO LIFE SCIENCE, Cat. No. ALX-804-196, clone MID15B4) diluted 1 / 50 for 2 hours at room temperature and using a biotin / streptavidin amplification system. Ceramide can be visualized by video microscopy (pink staining).

[0211] Oil Control Assay: Assays measuring reduced sebum secretion and / or reduced sebum production can be performed using standard techniques known to those of ordinary skill in the art. In one embodiment, the forehead can be used. Each active ingredient, any combination of ingredients, or a composition comprising such combinations disclosed in the specification can 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), while another portion of the forehead remains untreated. After the set number of days has expired, 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 using a wet and dry cloth. Blotting paper can then 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 against the skin. After 2 hours, the blotting paper can be removed, allowed to dry, and then radiographed. Darker blotting papers are associated with greater sebum production (or lighter blotting papers are associated with decreased sebum production).

[0212] Erythema Assay: An assay that measures the reduction of skin redness can be evaluated using a MINOLTA colorimeter. Erythema is induced by applying a 0.2% sodium lauryl sulfate solution to the subject's forearm. The area is protected with an occlusive patch for 24 hours. After 24 hours, the patch is removed and the redness caused by the irritation is assessed using the a* value on a MINOLTA colorimeter. The a* value measures the change in skin color in the red area. Following the reading, the area is immediately treated with the active ingredient, any combination of ingredients, or a composition having such combinations as disclosed in the instructions. Repeated measurements can be made periodically to determine the formulation's ability to reduce redness and irritation.

[0213] Skin Moisture / Hydration Measurement: Skin moisture / hydration can be measured using impedance measurements with the Nova Dermaphase meter. Impedance meters measure changes in skin water content. The outer layer of the skin has unique electrical properties. When dry, it conducts electricity poorly. As skin water content increases, its conductivity increases. Therefore, changes in skin impedance (which is related to conductivity) can be used to assess changes in skin hydration. The device can be calibrated each testing day according to the instrument's instructions. Temperature and relative humidity can also be recorded. Subjects can be assessed as follows: Prior to measurement, they can equilibrate in a room with a specified humidity (e.g., 30% to 50%) and temperature (e.g., 68°C to 72°C). Three separate impedance readings can be taken on each side of the face, recorded, and averaged. The T5 setting can be used for the impedance meter, which averages the impedance values ​​applied to the face every five seconds. Changes can be reported with statistical variance and significance. Each active ingredient disclosed in the instructions, any combination of ingredients, or compositions comprising such combinations can be measured according to the method.

[0214] Determination of Skin Clarity and Reduction of Freckles and Age Spots: Skin clarity and reduction of freckles and age spots can be assessed using a Minolta colorimeter. Using the a* value of the Minolta colorimeter, changes in skin color can be assessed to determine potential irritation caused by product treatment. The a* value measures the change in skin color in the red area. This is used to determine whether each active ingredient disclosed in the instructions, any combination of ingredients, or a composition having said combination will cause irritation. Measurements can be taken on each side of the face and then averaged as the left and right facial values. Skin clarity can also be measured using a Minolta meter. This measurement is a combination of the a*, b, and L values ​​of the Minolta meter and is related to skin brightness and is closely related to skin smoothness and hydration. The skin is read as described above. In one non-limiting aspect, skin clarity can be described as L / C, where C is chromaticity and is defined as (a 2 +b 2 ) 1 / 2 .

[0215] Skin dryness, surface wrinkles, skin smoothness, and skin color measurement: Skin dryness, surface wrinkles, skin smoothness, and skin color can be assessed using clinical grading techniques. For example, the clinical grading of skin dryness can be determined using the five-point standard Kligman scale: (0) skin is soft and moist; (1) skin appears normal with no visible dryness; (2) skin feels slightly dry with no visible flaking; (3) skin feels dry, tough, and has a whitish appearance with some scaling; and (4) skin feels very dry, rough, and has a whitish appearance with scaling. The assessment can be performed independently by two clinicians and the average is then taken.

[0216] Clinical grading of skin color: Skin color can be clinically graded using a ten-point analog-to-digital scale: (10) Smooth, pinkish-brown uniform skin. No dark, red, or scaly patches when examined with a handheld magnifier. The microtexture of the skin is very uniform when touched; (7) Uniform skin color observed without magnification. No scaly areas, but slight discoloration due to hyperpigmentation or erythema. No discoloration greater than 1 cm in diameter; (4) Discoloration and uneven texture of the skin are easily noticed. Slightly scaly. The skin feels rough to the touch in some areas; and (1) Uneven skin color and texture. Numerous areas of scaling and discoloration, either hypopigmentation or erythema or dark spots. Large areas of uneven color greater than 1 cm in diameter. The evaluations were performed independently by two clinicians and averaged.

[0217] Clinical grading of skin smoothness: The clinical grading of skin smoothness was determined using a ten-point analog-to-digital scale: (10) smooth, with the skin moist and shiny, with no resistance when a finger was dragged across the surface; (7) slightly smooth, with slight resistance; (4) rough, with noticeable changes in friction when rubbed; and (1) rough, flaky, and uneven surface. The evaluations were performed independently by two clinicians and the average was calculated.

[0218] Skin smoothness and wrinkle reduction determination 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 (SFL) of each subject can be carefully scored and recorded. A numerical score is obtained by multiplying the numerical factor by the depth / width / length factor. Scores are obtained for the eye area and mouth area (left and right) and added together to form a total wrinkle score.

[0219] Skin firmness measured with a Hargens Ballistometer: Skin firmness can be measured with a Hargens Ballistometer, a device that assesses skin elasticity and firmness by dropping a small ball onto the skin and recording the first two peaks of its rebound. The ballistometry is a small, lightweight probe that uses a relatively blunt tip (4 square millimeter contact area). The tip penetrates the skin slightly and produces measurements that are dependent on the properties of the skin's outer layers, which include the stratum corneum and epidermis, as well as some dermis.

[0220] Skin softness / pliability determination using a Gas Bearing Electrodynamometer: Skin softness / pliability can be assessed using a Gas Bearing Electrodynamometer, an instrument that measures the stress / strain properties of the skin. The viscoelasticity of the skin is related to skin moisturization. By attaching the probe to the skin surface with double-sided tape, measurements can be obtained at predetermined locations in the cheek area. A force of approximately 3.5 gm can be applied parallel to the skin surface, and the displacement of the skin can be accurately measured. Skin pliability can then be calculated and expressed as DSR (dynamic elastic coefficient in gm / mm).

[0221] Determining the Appearance of Lines and Wrinkles Using a Replica: The appearance of lines and wrinkles on the skin can be evaluated using a replica, which serves as an impression of the skin surface. Materials such as silicone rubber can be used. The replica can be analyzed through image analysis. By obtaining a silicon replica of the subject's face and analyzing the replica image using a computer image analysis system, changes in the visibility of lines and wrinkles can be objectively quantified. The replica can be photographed from the eye and neck areas using a digital camera with low-angle incident light. An image processing program can be used to analyze the digital image and identify the replica that is covered by wrinkles or fine lines.

[0222] Determination of the surface profile of the skin using the profilometer / stylus method: The surface profile of the skin can be measured using the profilometer / stylus method. This involves shining a light or dragging a stylus across the surface of a replica. The vertical displacement of the stylus can be input into a computer via a distance sensor and after scanning a fixed length of the replica, a cross-sectional analysis of the skin profile can be generated as a two-dimensional curve. This scan can be repeated any number of times along a fixed axis to produce a simulated 3-D image of the skin. Ten random sections of the replica can be obtained using the stylus technique and combined to produce an average. Values ​​of interest include Ra, which is the arithmetic mean of all the roughness (height) values, which is 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 value, and Rz is the average peak amplitude minus the average peak height. These values ​​are calibrated values ​​in mm. Before each use, the equipment should be calibrated by scanning a metal standard of known value. The Ra value can be calculated using the following equation: R a = Normalized roughness; l m = traverse (scan) length; y = absolute value of the profile position relative to the mean profile height (x-axis).

[0223] MELANODERM TMAssays: In other non-limiting aspects, the efficacy of each active ingredient, any combination of ingredients, or compositions comprising said combinations disclosed in the specification can be determined by using skin analogs, such as MELANODERM TM Melanocytes are a type of cell in the skin analog that stain positively when exposed to L-dihydroxyphenylalanine (L-DOPA), a precursor of melanin. TM Various matrices containing each active ingredient, any combination of ingredients, or compositions having the combinations disclosed in the specification, or matrices alone can be used as controls for treatment. Alternatively, an untreated sample of skin mimic can be used as a control.

[0224] Filaggrin Production: Changes in filaggrin production in keratinocytes due to each active ingredient disclosed in the specification, any combination of ingredients, or compositions having such combinations can be measured. Filaggrin is a precursor to the natural moisturizing factor (NMF) in the skin. Increased NMF increases the moisture content of the skin. Using a bioassay that measures the concentration of filaggrin in keratinocyte lysates, the production of filaggrin in treated and untreated keratinocytes can be measured. Non-limiting examples of bioassays that can be used to quantify the production of intermediate filament-related proteins are SIMON TM Western Blot Protocol. For each sample, normal human epidermal keratinocytes (NHEK) were cultured in EPI-200-MATTEK® containing calcium from Life Technologies (M-EP-500-CA). Grow in growth medium. Before treatment, NHEKs are incubated overnight at 37°C in growth medium with 5% CO2. NHEKs are then incubated for 24 to 36 hours in growth medium containing 1% test compound / extract or no compound / extract (negative control). NHEKs can then be washed, collected, and stored on ice or in a colder place until lysed on ice using lysis buffer and sonication. The protein concentration of the sample can be determined and used for sample standardization. The lysate can be stored at -80°C until used for quantitative determination.

[0225] SIMON TMThe Western blot bioassay utilizes a quantitative Western blot immunoassay technique to quantitatively detect filaggrin in a test sample using a filaggrin-specific antibody. Cell samples are lysed and the protein concentration is normalized. The normalized sample and molecular weight standards can then be loaded onto a denaturing protein separation gel and analyzed using capillary electrophoresis. The proteins in the gel are immobilized and immunoprobed using a primary antibody specific for filaggrin. The immobilized proteins can then be immunoprobed using an enzyme-linked detection antibody that binds to the primary antibody. A chemiluminescent substrate solution can then be added to the immobilized proteins, resulting in chemiluminescence development proportional to the amount of filament-associated protein bound to the immobilized protein. Chemiluminescence development is stopped at a specific time, and the intensity of the chemiluminescent signal can be measured and compared to positive and negative controls.

[0226] Production of occludin: Changes in occludin production in keratinocytes caused by each active ingredient disclosed in the specification, any combination of ingredients, or compositions having such combinations can be measured. Ocludin is a protein that is crucial for the formation of tight junctions and the moisture barrier function of the skin. A non-limiting example of how to determine occludin production in treated and untreated keratinocytes is by using a bioassay that measures occludin concentration in keratinocyte lysates. SIMON TM Western blotting protocols were used for biological analysis. For samples, human adult epidermal keratinocytes (HEKa) from Life Technologies (C-005-5C) were available at EPILIFE. TM The cells were grown in growth medium at 37°C in 5% CO2 for 24 hours, with EPILIFE TM The growth medium is supplemented with calcium from Life Technologies (M-EP-500-CA) and keratinocyte growth supplement (HKGS) from Life Technologies (S-101-5). The HEKa are then incubated for 24 to 48 hours in growth medium containing the test compound / extract, growth medium without compound / extract as a negative control, or growth medium containing 1 mM CaCl2 as a positive control. The HEKa are then washed, collected, and stored on ice or in a colder place until lysed on ice using lysis buffer and sonication. The protein concentration of the sample can be determined and used for sample standardization. The lysate is stored at -80°C until used in the bioassay.

[0227] SIMON TMThe Western Blot Bioassay utilizes a quantitative Western Blot immunoassay technique to quantitatively detect occludin in a test sample using an antibody specific for occludin. Cell samples are lysed and protein concentrations are normalized. The normalized 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 immobilized and immunoprobed using a primary antibody specific for occludin. The immobilized proteins are immunoprobed using an enzyme-linked detection antibody that is bound to the primary antibody. A chemiluminescent substrate solution is then added to the immobilized proteins, resulting in chemiluminescent development proportional to the amount of bound occludin in the fixative. Chemiluminescent development can be stopped at a specific time, and the intensity of the chemiluminescent signal can be measured and compared to positive and negative controls.

[0228] Keratinocyte monolayer permeability: Changes in keratinocyte monolayer permeability caused by each active ingredient disclosed in the specification, any combination of ingredients, or a composition having said combination 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 measure 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 in a collection well. The keratinocytes are then plated on an EPILIFE TM The cells were cultured in growth medium at 37°C in 5% CO2 for 24 hours, with EPILIFE TMThe growth medium is supplemented with calcium (M-EP-500-CA) from LIFE TECHNOLOGIES and keratinocyte growth supplement (HKGS) (S-101-5) from LIFE TECHNOLOGIES. This incubation time allows the cells to form a monolayer and seal the membrane pores. Fresh medium containing the test compound / extract (test sample) or fresh medium without the test compound / extract (untreated control) is then replaced, and the keratinocytes are cultured for an additional 48 hours at 37°C in 5% CO2. To determine the permeability of the keratinocyte monolayer after incubation with / without the test compound / extract, fresh medium containing high molecular weight fluorescein isothiocyanate (FITC)-dextran is replaced, and the keratinocytes are cultured at 37°C in 5% CO2 for 4 hours. During the 4-hour incubation, FITC can pass through the keratinocyte monolayer and the porous membrane at a rate proportional to the monolayer permeability and enter the collection wells. After incubation for 4 hours, cell viability and FITC content in the collection wells can be measured. For FITC content, the culture medium in the wells was collected and the fluorescence of the culture medium was measured at 480 nm (Em) when excited at 520 nm. The percent permeability and percent change compared to the untreated control were determined by the following equations: Permeability = ((Average Ex / Em of test sample) / Average Ex / Em of untreated control) * 100; Percent change = Permeability of test sample - Permeability of untreated control.

[0229] Hyaluronic Acid Production: Changes in hyaluronic acid production in human dermal fibroblasts induced by each of the active ingredients disclosed in the specification, any combination of ingredients, or compositions comprising such combinations can be measured. HA is a polysaccharide involved in stabilizing matrix structure and providing turgor pressure to tissues and cells.

[0230] As a non-limiting example, the HA production in treated and untreated adult human dermal fibroblasts (HDFa) can be determined using the Hyaluronic Acid DuoSet ELISA Kit (DY3614) from R&D Systems. In this assay, to produce samples, nearly confluent HDFa cells (C-13-5C) from Cascade Biologics were cultured in starvation medium (Dulbecco's modified Eagle's medium containing 0.15% fetal bovine serum and 1% penicillin-streptomycin solution) at 37°C in 10% CO2 for 72 hours before treatment. The cells were then incubated for 24 hours with fresh starvation medium containing the test compound, a positive control (phorbol 12-myristate 13-acetate (P1585) from SIGMA-ALDRICH and platelet-derived growth factor (P3201) from SIGMA-ALDRICH) or no addition. The culture medium was then collected and frozen at -80°C until used for ELISA assay.

[0231] In short, the ELISA assay uses a quantitative sandwich enzyme immunoassay technique, whereby a HA-specific capture antibody can be pre-coated onto a microplate. Standards and culture medium from treated and untreated cells are pipetted into the microplate wells to allow any HA present to be bound by the immobilized antibody. After washing away any unbound material, an enzyme-linked detection antibody specific for HA is added to the wells. After washing to remove any unbound antibody-enzyme reagent, a 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 stopped at a specific time, and the color intensity at 450 nm is measured using a microplate reader.

[0232] As another non-limiting example, human skin explants can be cultured in a survival explant culture medium in a humidified atmosphere at 37°C, supplemented with 5% CO2. The treatment of the explant can be carried out by topical application of the sample product (n=3) at D0, D2, D3, D6, D8 and D9 days. Control explants (n=3) are not subjected to any treatment except replacing the survival explant culture medium. At D3, D6 and D8 days, half the volume of the survival culture medium can be replaced. At D9, three explants under each condition can be taken out and cut in half. Half the explant is fixed in buffered formalin and the other half is frozen at -80°C.

[0233] After fixation for 48 h in plain Bouin and 24 h in formalin, the samples can be dried and immersed in paraffin using the automated tissue processor Leica TP 1020. 5 μm sections can be made using a microtome (Minot model LEICA RM2125) and mounted in SUPERFROST TMOn histological slides. Microscopic observation can be carried out by using the optical microscope of a LEICA ORTHOPLAN or LEICA DM LB microscope. Images can be taken with an OLYMPUS DDP72 camera and CELL ® D software. General morphology can be examined on paraffin sections stained with Masson's tricolor Goldner variant. The staining of hyaluronic acid can be carried out by incubating for 1 hour at room temperature with an anti-hyaluronic acid biotinylated protein (HABP) (SEIKAGAKU, article number 400763-1A) diluted to 1 / 100 and an amplification system biotin / streptavidin (VECTOR, VECTASTAIN PK-7200).

[0234] Inhibition of Hyaluronidase Activity: Changes in hyaluronidase activity caused by each active ingredient disclosed in the specification, any combination of ingredients, or a composition having such a combination can be measured. Hyaluronidase is an enzyme that degrades hyaluronic acid. HA is a polysaccharide associated with the stability of matrix structure and is involved in providing turgor pressure to 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, type 1-S hyaluronidase (H3506) from SIGMA-ALDRICH is added to microplate reaction wells containing test compounds or controls. Tannic acid can be used as a positive control inhibitor, and the control enzyme can be treated without the addition of the test compound. Wells containing the test compound or positive control but without hyaluronidase can be used as background negative controls. Before adding the substrate (HA), the wells are incubated at 37°C for 10 minutes. The substrate is added and the reaction is incubated at 37°C for 45 minutes. A portion of each reaction solution is then transferred to a solution of sodium acetate and acetic acid at a pH of 3.75 and gently mixed to terminate the partial reaction (termination well). After adding a portion of the reaction solution to the termination well, the termination well and the reaction well should both contain the same volume of solution. Both the reaction well and the termination well are incubated at room temperature for 10 minutes. The absorbance at 600 nm of the reaction well and the termination well is then measured. Inhibition can be calculated using the following formula: Inhibitor (or control) activity = (absorbance at 600 nm of the inhibitor termination well - absorbance at 600 nm of the inhibitor reaction well); Initial activity = absorbance of the control enzyme at 600 nm; Percent inhibition = [(initial activity / inhibitor activity) * 100] - 100.

[0235] Peroxisome proliferator-activated receptor gamma (PPAR-γ) activity: Changes in PPAR-γ activity caused by each active ingredient disclosed in the specification, any combination of ingredients, or a composition having such a combination can be measured. PPAR-γ is a key receptor for sebum production. As a non-limiting example, the activity of PPAR-γ 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 TM Pan-PPAR Green, available from Life Technologies (PV4894), can be used to determine whether a test compound or composition is able to inhibit the binding of a ligand to PPAR-γ. Sample wells contain PPAR-γ and a fluorescent ligand along with: a test compound or composition (test); a reference inhibitor, rosiglitazone (positive control); or no test compound (negative control). The wells are incubated for a set period of time to allow the ligand an opportunity to bind to PPAR-γ. The fluorescence polarization of each sample well can then be measured and compared to the negative control well to determine the percent inhibition of the test compound or composition.

[0236] Cytokine Array: Culture human epidermal keratinocytes to 70% to 80% confluence. Aspirate the medium from the plate and add 0.025% trypsin / EDTA. When the cells become rounded, gently tap the dish to release the cells. Remove the trypsin / EDTA containing cells from the dish and neutralize. Centrifuge the cells at 180 x g for 5 minutes to form a cell pellet. Aspirate the supernatant. Resuspend the resulting pellet in EPILIFE. TM The cells were seeded in 6-well plates at a confluence of approximately 10% to 20%. After the cells reached a confluence of approximately 80%, the medium was aspirated and 1.0 ml of EPILIFE was added. TM , along with phorbol 13-myristate 12-acetate ("PMA") (a known inflammatory inducer) and test composition dilutions were added to duplicate wells (i.e., 1.0% (100 μL of 100X stock) and 0.1% (10 μL of 100X stock) test compositions were diluted to a final volume of 1 ml of EPILIFE TM Gently agitate the medium to ensure thorough mixing. In addition, add 1.0 ml of EPILIFE TM After dosing, the plates were incubated at 37 ± 1°C and 5.0% ± 1% CO2 for approximately 5 hours. After the 5-hour incubation, all culture media were collected in conical tubes and frozen at -70°C.

[0237] For analysis, a 16-well hybridization chamber was connected to a 16-well fast slide, which was arrayed 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 at room temperature for 3 hours with gentle stirring. The array was washed 3 times with TBS-T. The array was treated with a 70 ml antibody mixture containing a biotinylated antibody corresponding to each arrayed capture antibody. The array was incubated at room temperature for 1 hour with gentle stirring. The array was washed 3 times with TBS-T. The array was incubated with 70 ml of a solution containing streptavidin-Cy5 conjugate at room temperature for 1 hour with gentle stirring. The array was washed 3 times with TBS-T, quickly rinsed in deionized water, and dried.

[0238] Slides can be imaged on a PERKIN-ELMER SCANARRAY 4000 confocal fluorescence imaging system. Array images can be saved and analyzed using the imaging research ARRAYVISION software. Briefly, spot intensity is determined by subtracting background signal. Spot replicates for each sample condition can be averaged and then compared to appropriate controls.

[0239] Endothelial tube formation: Endothelial tube formation involves angiogenesis and microvascular capillary formation. Capillary formation and angiogenesis may contribute to skin redness and rosacea. The ability of endothelial cells to form tubes can be determined using a capillary disruption assay using preformed primary human umbilical vein endothelial cells (HUVECs) in a cell culture system in the presence or absence of test extracts and compounds.

[0240] Briefly, HUVECs are cultured in vitro on an extracellular matrix, stimulating endothelial cell attachment and tubular morphogenesis, resulting in the formation of capillary-like luminal structures. These in vitro-formed capillaries resemble human vascular capillaries in many respects. The capillary assay builds on this phenomenon and is used to evaluate potential vascular targeting agents.

[0241] HUVEC cultures were grown in a 5% CO2, 37°C cell culture incubator. The complete growth medium for HUVEC was endothelial 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-amphotericin). HUVEC cultures between passages 3 and 8 were used for all assays.

[0242] HUVECs are pre-labeled with the fluorescent agent Calcein AM and plated in 96-well culture plates coated with extracellular matrix containing their complete growth medium. After approximately four hours of morphogenesis, endothelial capillaries should form. The test agent is then applied as a treatment condition to the formed capillary cultures in a volume of 50 μl at a designed dose. Untreated controls can be treated with the test agent vehicle. FDA-approved anti-angiogenic drugs This concentration serves as a performance control for the assay. Approximately 6 hours after treatment, endothelial tubule morphology in each well is examined microscopically, allowing for imaging and quantitative analysis of capillary disruption activity under the treatment conditions. Each test condition can be run in replicate wells, including controls.

[0243] **************

[0244] In accordance with the present disclosure, all compositions and / or methods disclosed and claimed herein can be made and implemented without undue experimentation. Although the compositions and methods of the present invention have been described in terms of preferred embodiments, it will be apparent to those skilled in the art that the steps or sequence of steps of the compositions and / or methods and methods described herein may be changed without departing from the concept, spirit, and scope of the present invention. More specifically, it will be apparent that certain reagents that are chemically and physiologically related can replace the reagents described herein while obtaining the same or similar results. All such similar substitutions and modifications apparent to those skilled in the art are considered to be within the spirit, scope, and concept of the present invention as defined by the appended claims.

Claims

1. A method for treating the skin of an object, which comprises applying a nutritional composition, wherein the nutritional composition comprises at least two of puerarin, collagen, and hyaluronic acid.

2. The method according to claim 1, wherein the composition comprises puerarin, and the puerarin is pueraria extract and / or kudzu extract.

3. The method according to claim 1, wherein the composition comprises collagen, and the collagen is fish collagen.

4. The method according to claim 1, wherein the composition has a pH of 1.5 to 8.

5.

5. The method according to claim 1, wherein the nutritional composition further comprises astaxanthin, ascorbic acid, lycopene, ceramosides, and / or biotin.

6. The method according to claim 6, wherein the composition comprises astaxanthin, and the astaxanthin is Haematococcus pluvialis encapsulated powder.

7. The method according to claim 1, wherein the nutritional composition further comprises sodium hyaluronate and / or citric acid.

8. The method according to claim 1, wherein the nutritional composition further comprises blood orange powder, rose powder, mixed berry powder, beetroot, lemon juice powder, and / or grapefruit powder.

9. The method according to claim 1, wherein the nutritional composition further comprises sea buckthorn, resveratrol, vitamin E, and / or beta-carotene.

10. The method according to claim 1, wherein the nutritional composition further comprises isomaltulose and / or stevioside.

11. The method according to claim 1, wherein the nutritional composition inhibits skin glycation.

12. The method according to claim 1, wherein the nutritional composition increases skin elasticity.

13. The method according to claim 1, wherein the nutritional composition comprises puerarin, collagen, and hyaluronic acid.

14. The method according to claim 13, wherein the nutritional composition comprises: 40% to 70% by weight of collagen; 0.1% to 2.0% by weight of hyaluronic acid; and 2.0% to 15% by weight of puerarin.

15. The method according to claim 1, wherein the nutritional composition comprises puerarin, ceramosides, and hyaluronic acid.

16. The method according to claim 15, wherein the nutritional composition comprises: 0.0001% to 15% by weight of ceramosides; 0.1% to 2.0% by weight of hyaluronic acid; and 2.0% to 15% by weight of puerarin.

17. The method according to claim 1, wherein the nutritional composition is a dietary supplement.

18. The method according to claim 15, wherein the nutritional composition is a powder, capsule, tablet, or gummy.

19. The method according to claim 1, wherein the nutritional composition is an emulsion, solution, essence, lotion, cream, gel, gel emulsion, or gel essence.

20. The method according to claim 17, wherein the nutritional composition is topically applied to the skin and allowed to remain on the skin.

21. A nutritional composition comprising two or more of the following substances: Puerarin; Collagen; and / or Hyaluronic acid.

22. The nutritional composition according to claim 19, wherein the composition further comprises: Astaxanthin; Ascorbic acid; Ceramosides; Lycopene; and / or Biotin.

23. The nutritional composition according to claim 19, wherein the composition further comprises: Sodium hyaluronate; Citric acid; Sea buckthorn; Resveratrol; Vitamin E; β-Carotene; Isomaltulose; Stevioside; Blood orange juice powder; Lemon juice powder; and / or Grapefruit powder.

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