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    • 专利摘要:
    COMPOSITION AND METHOD FOR PREPARING IT. The present invention relates to compositions comprising: (a) at least two phenolic compounds (one flavonoid and one non-flavonoid); (b) at least one hydrotrope; (c) at least one emulsifier; (d) a lipid-soluble antioxidant; and (e) water. The at least one hydrotrope must be present in an amount that is effective to solubilize said at least two phenolic compounds in the water phase of the composition. The at least one emulsifier must be present in an amount sufficient to create a water-in-oil or oil-in-water emulsion, which is effective in solubilizing the lipid-soluble antioxidant. The compositions are useful for cosmetic and other purposes.
    公开号:BR112015032975B1
    申请号:R112015032975-6
    申请日:2014-06-30
    公开日:2020-12-08
    发明作者:Nannan Chen；Patricia Brieva；Donna McCANN；Anthony Potin
    申请人:L'oreal；
    IPC主号:
    专利说明:

    DESCRIPTIVE REPORT BACKGROUND OF THE INVENTION
    [0001] The present invention relates to compositions comprising: (a) at least two phenolic compounds (one flavonoid and one non-flavonoid); (b) at least one hydrotrope; (c) at least one emulsifier; (d) a lipid-soluble antioxidant; and (e) water. The at least one hydrotrope must be present in an amount that is effective to solubilize said at least two phenolic compounds in the water phase of the composition. The at least one emulsifier must be present in an amount sufficient to create a water-in-oil or oil-in-water emulsion, which is effective in solubilizing the lipid-soluble antioxidant. The compositions are useful for cosmetic purposes.
    [0002] The formation of free radicals is an essentially widely accepted mechanism leading to skin aging. Free radicals are highly reactive molecules with unpaired electrons, which can directly damage various cell membranes, lipids, proteins, RNA and DNA. The damaging effects of these oxygen-reactive species are induced internally during normal metabolism and, externally, through various oxidative stresses. UV exposure and environmental pollution can accelerate skin aging by producing free radicals in the skin. Antioxidants protect cells from oxidative stress damage by scavenging free radicals and inhibiting subsequent oxidation reactions. As the skin ages, the endogenous capacity to protect against oxidative stress drops and makes it necessary to provide extra help to neutralize the oxidative stress produced both internally and externally. The topical application of antioxidants is widely used in skin care products to prevent skin aging.
    [0003] Phenolic compounds (ie phenols and polyphenols), the most abundant antioxidants in the diet, are well known as very effective antioxidants. They have been widely studied in the prevention of degenerative diseases, particularly cardiovascular diseases and cancers. Many phenolic compounds have been formulated in nutritional supplements and consumer products. However, the solubility of most phenolic compounds is very limited, especially in water, which decreases their applications and biological potential in cosmetics. Thus, there is a need for methods of increasing the solubility in water of phenolic compounds.
    [0004] Applications and biological potential of many phenolic compounds in cosmetics are limited due to their poor solubility. Various distribution systems, such as gel carriers (US order publication 20020086042), or nanocrystals (US order publication 2010/0047297), or chemical modification of polyphenols (US order publications 20090233876, 20080095866, e20080176956) have been used to obtain better solubility of phenolic compounds. However, these approaches have disadvantages. Some are linked to specific distribution systems. Modification of phenolic compounds increases costs, the improvement in solubility is still limited, and modifications can reduce the activity of phenolic compounds.
    [0005] Other solutions to the problem of poor solubility include the use of solubilizers, such as strong organic solvents (US Patent 5,532,012) and glycoside diterpene (application publication US 2011/0033525). Even so, these solutions are not safe and are not necessarily compatible with cosmetic formulations. Furthermore, most of the time, when water is added to such compositions, the solubility of phenolic compounds decreases dramatically.
    [0006] Thus, there remains a need for methods to improve the water solubility of phenolic compounds, including polyphenols, for cosmetic and other uses. In addition, in order to provide more complete protection against oxidative stress to the skin, a lipid-soluble antioxidant is desirable to protect against lipid peroxidation, which helps maintain the integrity of cell membranes. Vitamin E (sometimes referred to commercially as "tocopherol") is an essential fat-soluble vitamin that includes eight naturally occurring compounds in two classes designated as tocopherols and tocotrienols. It is a powerful antioxidant. a-tocopherol is the most abundant biologically active form of Vitamin E. The antioxidant properties of Vitamin E work mainly at the cell membrane level, because its lipid solubility allows it to be incorporated into the lipid layer of the cell membrane. However, to incorporate a lipid or fat-soluble antioxidant similar to Vitamin E into a stable water-based or aqueous composition or formulation, it is necessary to create an emulsion. The emulsions described hereinafter are suitable for creating stable compositions or formulations that incorporate both water-soluble phenolic compounds, as well as at least one hydrotrope and the lipid or fat-soluble antioxidant (for example, Vitamin E) for cosmetic use.
    [0007] The terms "fat-soluble", "lipid-soluble", and "oil-soluble" are used synonymously throughout this application, as are the terms "fat", "lipid" and "oil". BRIEF SUMMARY OF THE INVENTION
    [0008] The present invention relates to compositions comprising: (a) at least two phenolic compounds (one flavonoid and one non-flavonoid); (b) at least one hydrotrope; (c) at least one emulsifier; (d) a lipid-soluble antioxidant; and (e) water. The at least one hydrotrope must be present in an amount that is effective to solubilize said at least two phenolic compounds in the water phase of the composition. The at least one emulsifier must be present in an amount sufficient to create a water-in-oil or oil-in-water emulsion, which is effective in solubilizing the lipid-soluble antioxidant. The compositions are useful for cosmetic purposes. The at least one hydrotrope can be a cosmetically acceptable hydrotrope, such as nicotinamide (niacinamide), caffeine, sodium PCA, sodium salicylate, urea, or hydroxyethyl urea. In one aspect of the present invention, the at least one hydrotrope is at least one substance selected from nicotinamide (niacinamide), caffeine, sodium PCA, and sodium salicylate. The at least two phenolic compounds include at least baicalin and resveratrol, but may also include another type of phenol or polyphenol, as long as that additional phenol or polyphenol has no detrimental effect on the composition.
    [0009] Another aspect of the invention provides a method for preparing a composition comprising the inclusion in said composition of: (i) water; (ii) at least two phenolic compounds (one flavonoid and one non-flavonoid); (iii) a lipid-soluble antioxidant; (iv) at least one hydrotrope in an amount that is effective to solubilize said at least two phenolic compounds in the water phase of the composition and (v) at least one emulsifier in an amount sufficient to create a water-in-oil or oil-in-water emulsion , which is effective in solubilizing the lipid-soluble antioxidant.
    [0010] A further aspect of the invention provides a method comprising the application of a composition to the skin (e.g., human skin), the composition comprising (i) water; (ii) at least two phenolic compounds (one flavonoid and one non-flavonoid); (iii) a lipid-soluble antioxidant; (iv) at least one hydrotrope in an amount that is effective to solubilize said at least two phenolic compounds in the water phase of the composition and (v) at least one emulsifier in an amount sufficient to create a water-in-oil or oil-in-water emulsion , which is effective in solubilizing the lipid-soluble antioxidant.
    These and other aspects of the invention are set out in the appended Claims, and described in more detail in the detailed description of the invention. Brief Description of Drawings
    [0012] FIG. 1 shows a graph of baicalin solubility as a function of nicotinamide concentration.
    [0013] FIG. 2 shows a graph of solubility of baicalin as a function of caffeine concentration. DETAILED DESCRIPTION OF THE INVENTION
    [0014] The present invention relates to compositions comprising: (a) at least two phenolic compounds (one flavonoid and one non-flavonoid); (b) at least one hydrotrope; (c) at least one emulsifier; (d) a lipid-soluble antioxidant; and (e) water. The at least one hydrotrope must be present in an amount that is effective to solubilize said at least two phenolic compounds in the water phase of the composition. The at least one emulsifier must be present in an amount sufficient to create a water-in-oil or oil-in-water emulsion that is effective in solubilizing the lipid-soluble antioxidant (i.e., in the oil or lipid phase of the emulsion). The compositions are useful for cosmetic and other purposes. The hydrotrope, like a commercially acceptable hydrotrope, improves the water solubility of phenolic compounds. Hydrotropes can be used to formulate phenolic compounds, especially polyphenols, in all cosmetic formulations that contain water, for topical or injection applications and food applications, such as beverages.
    [0015] Most phenolic compounds, including polyphenols, have very limited solubility (<0.1%) in water, depending on their various structures. Applicants have found that hydrotropes can dramatically increase the water solubility of these poorly water-soluble phenolic compounds by orders of magnitude. Thus, water-containing compositions containing effective amounts of a hydrotrope may contain phenolic compounds in percentage amounts greater than water-containing compositions, in which a hydrotrope is not present. The Applicants also found that combinations of hydrotropes, such as the combination of caffeine and nicotinamide (niacinamide), are more effective than any of the hydrotropes alone for increasing the water solubility of phenolic compounds.
    [0016] Hydrotropes (or hydrotropic agents) are a diverse class of water-soluble compounds, which are characterized by an amphiphilic molecular structure and the ability to dramatically increase the solubility of poorly water-soluble organic molecules.
    [0017] Most hydrotropes have an aromatic structure with an ionic segment, while some of them are of linear alkyl chain, as listed in the table below. Although hydrotropes visibly resemble surfactants and have the ability to reduce surface tension, their small hydrophobic units and relatively shorter alkyl chain distinguish them as a separate class of amphiphiles. Consequently, its hydrophobicity is not sufficient to create well-organized self-associated structures, such as micelles, even with a high concentration.
    [0018] Common hydrotropic molecules include: sodium PCA (DL-2-pyrrolidone-5-sodium carboxylate), sodium 1,3-benzenedisulfonate, sodium benzoate, sodium 4-pyridinecarboxylate, sodium salicylate, benzene sulfonate sodium, caffeine, sodium p-toluene sulfonate, sodium butyl monoglycolsufate, 4-aminobenzoic acid HCl, cumene sulfonate sodium, N, N-diethylnicotinamide, N-picolylnicotinamide, N-allylnicotinamide, 2-methacrylyloxyethyl phosphorylololine, resin , pyrogallol, N-picolylacetamide 3.5, procaine HCl, proline HCl, nicotinamide (niacinamide), pyridine, 3-picolylamine, sodium ibuprofen, sodium xylenesulfonate, ethyl carbamate, pyridoxal hydrochloride, sodium benzoate, 2-pyrrolidone, 2-pyrrolidone, N, N-dimethylacetamide, N-methylacetamide, and isoniazid. Hydrotropes can be found in Lee J. et al., "Hydrotropic Solubilization of Paclitaxel: Analysis of Chemical Structures for Hydrotropic Property", Pharmaceutical Research, Vol. 20, No. 7, 2003; and Lee S. et al., “Hydrotropic Polymers: Synthesis and Characterization of Polymers Containing Picolylnicotinamide Moieties”, Macromolecules, 36, 22482255,2003.
    [0019] Cosmetically acceptable hydrotropes refers to hydrotropes that can be used in cosmetic compositions. While hydrotropes represent a wide class of molecules used in various fields, cosmetic applications will be limited, due to safety and tolerance restrictions. Hydrotropes suitable for use in cosmetics include, but are not limited to, hydrotropes listed below:


    [0020] The solubility of a hydrotrope for use in cosmetic compositions can be determined using tests known in the art for determining skin effects and toxicity to humans.
    [0021] At least one hydrotrope refers to one or a combination of two or more hydrotropes. One or a combination of two or more hydrotropes can be used to improve the solubility of phenolic compounds in water.
    [0022] The at least hydrotrope is present in the composition in amounts effective to increase the solubility of the phenolic compound in water. The amount of hydrotrope (s) will vary depending on the hydrotrope (s) and the type and amount of phenolic compound. The amount of hydrotrope (s) present in the compositions can vary from about 0.1% to about 15%; about 0.1% to about 10%; or about 1% to about 5%, based on the total weight of the composition. In one aspect of the invention, the at least one hydrotrope is a combination of niacinamide and caffeine, wherein the combination is present in an amount of about 0.2-15%; about 1-10%; about 3-9% or about 4-8% by weight, based on the total weight of the composition. Niacinamide can be present in the combination in amounts of about 1-10%; about 3-8% or 5-7% by weight, based on the total weight of the composition. Caffeine can be present in the combination in amounts of about 0.5-7%; about 1-5% or 2-4% by weight, based on the total weight of the composition.
    [0023] Increasing the water solubility of phenolic compounds refers to increasing the solubility of phenolic compounds in water, in comparison with the solubility of phenolic compounds in water in the absence of the hydotrope or hydrotropes.
    [0024] An advantage of using hydrotropes is that, once a stable solution is obtained, further dilution does not influence the stability of the solution. This is very different from organic solvents, which are commonly used to increase the water solubility of phenolic compounds, such as polyphenols. Typically, an aqueous dilution of organic solvents with pre-dissolved phenolic compound (s), such as polyphenol, results in crystallization or precipitation.
    [0025] Phenolic compounds are a structural class of natural, synthetic and semi-synthetic organic compounds, which have one or more phenolic constituents. Phenolic compounds containing multiple phenol groups are known as polyphenols. Polyphenols are normally available in plants and are very useful for protecting plants and animals from the usual health disorders and also the impacts of aging. Polyphenols function as potent free radical scavengers by donating their alcoholic hydrogen or one of their delocalized electrons. The two classes of polyphenols are flavonoids and non-flavonoids.
    [0026] Flavonoids are a specific group of polyphenols, and are the most abundant group of polyphenol compounds, making up about two thirds of the total phenols in the food consumed. Flavonoids are further categorized, according to their chemical structure, into pantons, flavones (eg baicalin), flavanones, flavanols, flavonols, dihydroflavonoids, isoflavonoids, neoflavonoids, catechins, anthocyanidins and tannins. More than 4,000 flavonoids have been identified, many of which occur in fruits, vegetables and drinks (tea, coffee, beer, wine and fruit drinks). Flavonoids have been reported to have antiviral, antiallergic, antiplatelet, anti-inflammatory, anti-tumor and antioxidant activities. Flavonoids protect lipids and vital cellular components from oxidative stress damage by efficiently scavenging free radicals.
    [0027] Non-flavonoid polyphenols include lignans, auronas, stylbenoids, curcuminoids and other phenylpropanoids. Many of them are also well-known antioxidants, such as resveratrol, curcumin and pinoresinol.
    [0028] Other phenolic compounds, in addition to polyphenols, including alkylphenols, betacyanins, capsacinoids, hydroxybenzoketones, methoxyphenols, naphthoquinones and phenolic terpenes. Some popular examples are ferulic acid, hydroxytyrosol, cinnamic acid, caffeic acid, and p-coumaric acid.
    [0029] The at least two phenolic compounds are solubilized in the water phase of the compositions, and the amount of phenolic compounds that are solubilized will depend on the specific phenolic compounds and the type and quantity of the hydrotrope (s) present in the compositions . The amount of phenolic compounds present in the compositions can vary from about 0.01% to about 10%; about 0.1% to about 10%; or about 0.1% to about 5%, based on the total weight of the composition.
    [0030] The lipid-soluble antioxidant present in the composition can be any lipid-soluble antioxidant that helps to protect the skin, especially against lipid peroxidation. The lipid-soluble antioxidant may be present in the composition in amounts of 0.0001% to 6% by weight. When the lipid-soluble antioxidant is Vitamin E (or tocopherol), it is solubilized in the lipid (ie oil) phase of the emulsion, usually in amounts of 0.0001% to 3% by weight or 0.01% to 2 % by weight of the composition.
    [0031] In general, emulsifiers useful for the composition of the present invention are those with an HLB (hydrophilic-lipophilic balance) not greater than 7. Although any cosmetically acceptable emulsifier with an HLB not greater than 7 can be used in the compositions, results Excellent results can be obtained using silicone-based emulsifiers (sometimes referred to in this document as “silicone emulsifiers”). Examples of some useful silicone emulsifiers are: (1) dimethicone and PEG / PPG-18/18 dimethicone (for example, Shin-Etsu's X-22-6711D); (2) dimethicone and dimethicone crospolymer (for example, Dow Corning 9041 Silicone Elastomer Blend); (3) dimethicone and dimethicone / PEG-10/15 crospolymer (KSG-210 from Shin-Etsu); and (4) dimethicone and dimethicone / polyglycerin-3 crospolymer (KSG 710 from Shin-Etsu).
    [0032] The compositions may also comprise at least one additive conventionally used in the field of cosmetics, which does not affect the properties of the compositions according to the invention, such as thickeners, fragrances, pearlescent agents, preservatives, sunscreens, anionic or nonionic polymers or cationic or amphoteric, proteins, protein hydrolysates, fatty acids, such as 18-methyl methylanoic acid, vitamins, panthenol, silicones, vegetable oils, animals, minerals or synthetics, gelling agents, antioxidants, solvents, fragrances, excipients, screening agents ), odor absorbers and coloring materials. These additives can be present in the composition according to the invention in proportions that are not limited, but that fall in the range of 0 to 50% by weight, in relation to the total weight of the composition.
    [0033] When additional solvents are used, the additional solvents may be mixtures of solvents, such as alcohols, glycols or mixtures thereof. Mixtures of one or more alcohols and one or more glycols may be useful, just as they are mixtures of one or more glycols or one or more alcohols. Such mixtures can contain virtually any combination of relative amounts of each individual alcohol or glycol. For example, when a mixture of two glycols is used, the relative amounts of each glycol in the mixture can be 30-70%, 40-60%, 45-55% or even approximately equal amounts (i.e., a 50 / 50) of each glycol.
    [0034] The composition comprises about 20 to 80% by weight of water, in relation to the total weight of the composition. The amount of water in the composition can also vary from about 20 to 60%; or about 30 to 50%, based on the total weight of the composition.
    [0035] The pH of the water phase of the compositions is not limited, but it is generally between 2 and 8, or between 3 and 6. The pH can be adjusted to the desired value by adding a base (organic or inorganic) to the composition, for example, ammonia or a primary, secondary or tertiary (poly) amine, such as monoethanolamine, diethanolamine, triethanolamine, isopropanolamine or 1,3-propanediamine, or, alternatively, by the addition of an inorganic or organic acid, advantageously a carboxylic acid, such as, for example, citric acid.
    [0036] Generally, any composition of the invention can be applied topically to the skin (over any cutaneous region of the body).
    [0037] For topical application to the skin (for example, human skin, the composition may take the form in particular of aqueous or oily solutions or dispersions of lotion or serum type, emulsions with a liquid or semi-liquid milk-like consistency, obtained by dispersion of an oily phase in an aqueous phase (O / W) or vice versa (W / O), or of suspensions or emulsions with a soft consistency of the type cream or aqueous or anhydrous gel These compositions are prepared according to the usual methods.
    [0038] The amounts of the various constituents of the compositions according to the invention are those conventionally used in the fields under consideration.
    [0039] In the field of cosmetics, these compositions constitute, in particular, creams for cleaning, protection, treatment or care for the face, hands, feet, the main anatomical folds or the body (for example, creams day creams, night creams, makeup removal creams, foundation creams or sun creams), liquid bases, makeup removal milks, protective or care body milks, sun milks, lotions, gels or skin care foams, such such as cleansing lotions, sunscreen lotions, tanning lotions, bath compositions, deodorant compositions comprising a bactericidal agent, aftershave gels or lotions, hair removal creams, insect bite or bite fighting compositions, compositions for relief of pain or compositions for the treatment of certain skin diseases, such as eczema, rosacea, psoriasis, lichen and severe itching.
    [0040] Another aspect of the invention provides a method for preparing the compositions comprising including in said composition: (i) at least two phenolic compounds (one flavonoid and one non-flavonoid); (ii) a lipid-soluble antioxidant; (iii) at least one hydrotrope in an amount that is effective to solubilize said at least two phenolic compounds in the water phase of the composition; and (iv) at least one emulsifier in an amount sufficient to create a water-in-oil or oil-in-water emulsion, which is effective in solubilizing the lipid-soluble antioxidant. The general method for preparing the compositions of the present invention involves preparing separately a solution based on water and a solution based on oil or lipid and then joining the two solutions under mixing to form an emulsion (water in oil or oil in water) . Other ingredients, especially those ingredients that may be sensitive to certain process conditions used to form the emulsion or those ingredients for which it is beneficial to solubilize the ingredient in another medium before adding it to water or oil, can be added to the emulsion with mixing after the emulsion is formed. For example, in one aspect of the present invention, an aqueous hydrotropic solution is prepared by completely dissolving one or more hydrotropic agents in water. In a separate oil-based or lipid-based solution, one or more of the phenolic compounds are dissolved in an emulsifier (for example, silicone emulsifier), along with any other appropriate oil or lipid-soluble substances. The aqueous hydrotropic solution and the oil or lipid-based solution are then added together and mixed to form an emulsion. Once the emulsion is prepared, other substances or solutions of substances in other solvents (for example, alcohols and / or glycols) can be added to the emulsion and mixed to form a final emulsion. At each stage of the process, mixing can be conducted by any appropriate method known in the art (for example, using a stir bar or any other mixing device).
    [0041] In one aspect of the present invention, solubilization of at least one of the phenolic compounds in water occurs within minutes and mixing is continued until the maximum concentration of the phenolic compound (s) in the water is reached , which is defined as the solubility of the phenolic compound (s) under the present conditions. A clean stable solution with a concentration that does not exceed solubility is usually achieved after more than an hour of mixing. No heat is required following this procedure to dissolve the phenolic compound (s) in the water. Everything is prepared at room temperature to maintain the stability of the phenolic compound (s). This is extremely useful for protecting the activity of certain phenolic compounds and also makes the process much easier. Once the phenolic compound (s) are completely solubilized in water, the aqueous solution can be mixed with the oil-based or lipid-based solution to form the emulsion. In the aspect of the present invention, where the at least two phenolic compounds in the composition are baicalin (for example, scutellaria baicalensis extract / scutellaria baicalensis root extract; Baicalin 95MM) and resveratrol, hydrotropes that can be used include caffeine, nicotinamide (niacinamide ), Sodium PCA and sodium salicylate. However, in this aspect of the invention, it may be useful to first dissolve resveratrol in a solvent (for example, one or more glycols or a mixture of one or more glycols and denatured alcohol) before contacting resveratrol with water. For example, resveratrol can first be dissolved in a solvent system, such as a mixture of two or more glycols (for example, propylene glycol and dipropylene glycol) and denatured alcohol, and then that solution can be added to the emulsion, thus allowing , that the dissolved resveratrol becomes associated with the water phase of the emulsion.
    [0042] In general, emulsifiers useful for the composition of the present invention are cosmetically acceptable emulsifiers with an HLB (hydrophilic-lipophilic balance) not greater than 7. In the aspect of the present invention, where the lipid-soluble antioxidant is Vitamin E (or tocopherol), a useful silicone emulsifier is PEG / PPG-18/18 dimethicone (for example, Shin-Etsu X-22-6711D) in combination with dimethicone. Other useful silicone emulsifiers are: dimethicone and dimethicone crospolymer (for example, Dow Corning 9041 Silicone Elastomer Blend); dimethicone and dimethicone / PEG-10/15 crospolymer (Shin-Etsu KSG-210); and dimethicone and dimethicone / polyglycerin-3 crospolymer (KSG 710 from Shin-Etsu).
    [0043] In one aspect of the present invention, the composition comprises: (a) baicalin and resveratrol as phenolic compounds; (b) niacinamide and caffeine as hydrotropes; (c) dimethicone and PEG / PPG-18/18 dimethicone as the silicone emulsifier; (d) Vitamin E (or tocopherol) as a lipid-soluble antioxidant; and (e) water. In another aspect of the present invention, the composition comprises: (a) 0.001 - 10% by weight of baicalin and 0.0001-2% by weight of resveratrol; (b) 15% by weight of niacinamide and 0.5-5% by weight of caffeine; (c) 0.1-30% by weight of dimethicone (0.65 to 1000 cst) and 0.1-30% by weight of dimethicone crospolymer as a silicone emulsifier; (d) 0.0013% by weight of Vitamin E (or tocopherol) as a lipid-soluble antioxidant; and (e) 30 to 60% by weight of water.
    [0044] In other aspects of the present invention, the composition comprises: (a) 0.01-5% by weight or 0.1-1% by weight or 0.1-0.8% by weight of baicalin and 0, 01-2% by weight or 0.1-2% by weight or 0.1-1.5% by weight of resveratrol; (b) 1-5% by weight of niacinamide and 0.5-5% by weight of caffeine; (c) 1-30% by weight or 1-18% by weight or 14-17% by weight of dimethicone (0.65 to 1000 cst) and 3-20% by weight or 3-10% by weight or 6- 8% by weight of dimethicone crospolymer as the silicone emulsifier; (d) 0.01-3% by weight or 0.1-3% by weight or 0.1-2% by weight of Vitamin E (or tocopherol) as a lipid-soluble antioxidant; and (e) 30 to 60% by weight or 40-60% by weight of water.
    [0045] In one aspect of the present invention, when the composition contains a silicone emulsifier which is a combination of dimethicone (0.65 to 1000 cst) and dimethicone crospolymer, the combination is normally used in an amount of about 4 to about 50% by weight of the composition or from about 4 to about 30% by weight of the composition. EXAMPLES: EXAMPLE 1 Increased Solubility of Baicalin in Water using Hydrotrope
    [0046] Baicalin, a component of the Chinese medicinal herb Huang-chin, is a flavone, a type of flavonoid. It is a potent antioxidant, which shows potent effects against diseases of oxidative stress, inflammation, allergy, cancer, bacterial infections, etc. However, its solubility in water is extremely low (<0.01% at its natural pH ~ 4.5), especially at low pH, as shown below, and degradation occurs at pH> 5.

    [0047] Although certain organic solvents may increase the solubility of baicalin, such as PEG-4, which can dissolve baicalin 3%, a dilution of these solutions in water is no longer stable. Crystallization or precipitation occurs after mixing the glycol phase and water phase.
    [0048] The solubility of baicalin in water can be increased by increasing the concentration of hydrotropes. In contrast to what happens in organic solvents, such aqueous solutions are still stable if diluted with water.
    [0049] Baicalin water solubility was increased with a nicotinamide concentration function, as shown in Figure 1.
    [0050] Caffeine 2% (w / w) in water improved solubility in baicalin water from <0.01% to 0.11%; and further improvement was observed as more caffeine was dissolved in water with Vit. C 10%, shown in Figure 2. EXAMPLE 2 Increased Solubility of Caffeine in Water Using Nicotinamide (niacinamide)
    [0051] The water solubility of caffeine is approximately 2%, which has limited its function as a hydrotropic agent. By mixing with nicotinamide (niacinamide), the solubility of caffeine can be increased to 5% or more. And the combination of caffeine and nicotinamide is more efficient than any hydrotrope alone for increasing the water solubility of phenolic compounds. The combination of 5% nicotinamide and 5% caffeine in water solubilized approximately 1% baicalin in water, which dramatically increased the solubility in baicalin water by more than 100 times.
    [0052] The combination of hydrotropes, 5% nicotinamide and 5% caffeine has been found to be very effective in increasing the water solubility of numerous polyphenols, including flavonoid and non-flavonoid polyphenols, and other phenolic compounds.
    [0053] The results of water solubility for several phenolic compounds with this combination of hydrotropes are listed in the table below.
    EXAMPLE 3 Compatibility of the Polyphenol / Hydrotrope Complex in Different Systems
    [0054] Preparation A: Serum

    [0055] Preparation A was prepared as follows. The components of the glycol phase (Phase A) were mixed at room temperature. At the same time, the components of the aqueous phase (Phase B) were mixed at room temperature until a clean solution was obtained. The glycol phase was then added to the aqueous phase, with constant stirring, for another hour, and the desired serum was obtained.
    [0056] Preparation B: O / A emulsion (cream)

    [0057] Preparation B was prepared as follows. Phase A1 components were mixed at room temperature until a clean solution was obtained. In separate receptacles, Phase A2 was pre-suspended and then added to Phase A1 with constant stirring and heated to 65 ° C. at the same time, the Phase B components were mixed and completely dissolved at 65 ° C. Then, Phase B was added to Phase A and emulsified for 10-15 minutes. Heating was stopped and mixing was continued when Phase C was added and mixed for another 10 minutes, Phase D was added after the temperature was below 40 ° C, and mixed for 10-15 minutes (side sweep) or until the powders were fully dispersed, and the desired emulsion was obtained.
    [0058] Preparation C: A / Si emulsion (gel)

    [0059] Preparation C was prepared as follows. Phase A components were mixed at room temperature. Phase B1 and Phase B2 were pre-mixed in separate receptacles at room temperature until clean solutions were obtained. Phase B3 was mixed while heating to 75-80 ° C until it was clean. Phase B2 and Phase B3 were added to Phase B1 while mixing. Then, Phase B was slowly added to Phase A, while mixing (as the viscosity increased, the mixing speed was appropriately increased). When the addition was completed, mixing was continued for an additional 10 minutes before adding the pre-mixed Phase C. Phase D was added slowly, mixing until they were unusually dispersed, and the desired emulsion was obtained. EXAMPLE 4 Composition according to the present invention
    [0060] Preparation D: A / Si emulsion (gel)

    [0061] Preparation D was prepared as follows. In a main receptacle, phase A was mixed with a homogenizer. In a separate vessel, phase B was mixed until all solids were completely dissolved. The pH of phase B was then adjusted to 4.5 ± 0.1 with NaOH. In another side receptacle, phase C was mixed until Resveratrol was completely dissolved. Phase B was then slowly added to phase A, to create an emulsion, which was mixed until uniform. Phase C was then gradually added to the main receptacle while mixing. Phase D was then gradually added to the main receptacle while mixing. The mixing was continued after the addition of phase D, until the mixture was uniform and a stable emulsion was present.
    [0062] The three primary antioxidant ingredients in preparation D (ie baicalin, resveratrol and tocopherol) were subjected together as an in-antioxidant test mixture to determine the mixture's antioxidant activity. The tests, known as ORAC and HORAC, are described below. ORAC
    [0063] The Oxygen Radical Absorption Capacity (ORAC) assay is one of the most commonly used methods to assess the ability of antioxidants against ROS (oxygen reactive species), specific to peroxyl, which is one of the most important free radicals present in the human skin environment.
    [0064] The ORAC assay measures the oxidative degradation of the fluorescent probe (fluorescence) after being mixed with free radical generators, such as azo-initiator compounds (2,2'-Azobis dihydrochloride (2-amidinopropane), AAPH). Azoinitiators are considered to produce the peroxyl radical by heating, which damages the fluorescent molecule, resulting in loss of fluorescence. Antioxidants are considered to protect the fluorescence molecule from oxidative degeneration. When quantifying the drop in fluorescence using a fluorometer, the degree of protection is determined by comparing it with a standard control antioxidant Trolox. The result is expressed in gmol equivalent of Trolox per gram of sample (ie, gmolTE / g). Equipment that can automatically measure and calculate capacity is commercially available, as is the Thermo Scientific VarioSkan Flash microplate reader.
    [0065] To test the samples using ORAC, the compounds were dissolved in water-based NaH2PO4 buffer. HORAC
    [0066] The HORAC assay is another common method for examining antioxidant activity. It is specific for hydroxyl radicals.
    [0067] Varioskan Flash is used to quantify the capacity of an antioxidant to prevent free radicals. The hydroxyl radical, generated from hydrogen peroxide and Cobalt (II) fluoride, will abruptly cool a fluorescent probe through a hydrogen atom transfer reaction. In the presence of an antioxidant, however, the molecule will chelate Co (II), preventing the generation of the hydroxyl radical and initially blocking or preventing sudden cooling of the probe, causing a delay in the fluorescence drop profile. The areas under the fluorescence drop curve for samples with and without the presence of an antioxidant molecule are compared to that of a standard reference material and the ability to prevent hydroxyl radical is determined.
    [0068] When quantifying the fluorescence drop using a fluorometer, the degree of protection is determined by comparison with a standard control antioxidant Gallic acid (standard reference material). The result is expressed in gmol equivalent of Gallic Acid per gram of sample (ie, gmolGAE / g). Equipment that can automatically measure and calculate capacity is commercially available, as is the Thermo Scientific VarioSkan Flash microplate reader.
    [0069] To test the samples using HORAC, the compounds were dissolved in water-based NaH2PO4 buffer.
    [0070] The test results are shown in the table below.

    [0071] The expected value shown in the table above is the antioxidant activity calculated based on the known activity of each individual antioxidant in the preparation (that is, the sum of the activities of 0.5% baicalin; resveratrol 1% and Vitamin E 1% (or tocopherol)). The known activity of each of the antioxidants is shown in the table below. In both the ORAC and HORAC tests, the measured activity was much higher than the expected activity, showing that the combination of these three antioxidants in the preparation provided synergistic antioxidant activity.
    [0072] Individual values

    [0073] The composition of Example 4 (i.e. Preparation D) was subjected to stability tests, as described below. The first test was a stability test at room temperature. In this test, the samples were kept for two months at room temperature in sealed receptacles (glass bottles with screw cap; 80% filled). The second test was an accelerated stability test, conducted at 45 ° C. In the second test, the samples were kept at 45 ° C for two months in sealed receptacles (glass bottles with a screw cap; 80% full). These conditions are used to simulate the maintenance of the samples at room temperature for three years.
    [0074] The samples of the stability tests were analyzed to determine the levels of the three active ingredients (baicalin, resveratrol and Vitamin E) before and after the tests. The results, which are provided below in the table, showed that the composition of Example 4 was very stable (i.e., there was very little degradation of the active ingredients during the stability tests). A stable composition containing about 1% by weight of resveratrol, about 0.5% by weight of baicalin and about 1% by weight of Vitamin E is very desirable as a cosmetic composition for application to human skin.
    权利要求:
    Claims (11)
    [0001]
    1. Cosmetic Composition, characterized by the fact that it comprises: (a) at least two phenolic compounds which are baicalin and resveratrol; (b) at least two hydrotropes that are nicotinamide and caffeine; (c) at least one emulsifier; (d) a lipid-soluble antioxidant that is Vitamin E; and (e) water.
    [0002]
    2. Cosmetic composition, according to Claim 1, characterized by the fact that it is for application to the skin.
    [0003]
    Cosmetic Composition according to Claim 1 or 2, characterized by the fact that said at least two hydrotropes are present in said composition in an amount of 0.1% to 15%, based on the total weight of the composition.
    [0004]
    4. Cosmetic composition according to any one of the preceding claims, characterized by the fact that said at least two phenolic compounds are present in said composition in an amount of between 0.01% to 10%, based on the total weight of the composition.
    [0005]
    5. Cosmetic composition, according to any one of the previous Claims, characterized by the fact that it is for application on human skin.
    [0006]
    6. Cosmetic Composition according to any one of the preceding Claims, characterized in that said water is present in said composition in an amount of 40 to 60% by weight of the composition.
    [0007]
    7. Cosmetic composition according to any one of the preceding claims, characterized in that said at least one emulsifier comprises a silicone emulsifier.
    [0008]
    8. Cosmetic composition according to any one of the preceding claims, characterized by the fact that at least one emulsifier is dimethicone and PEG / PPG-18/18 dimethicone; dimethicone and dimethicone cross polymer; dimethicone and dimethicone / PEG-10/15 cross polymer; or dimethicone and dimethicone / polyglycerin-3 cross polymer.
    [0009]
    9. Cosmetic Composition according to Claim 1, characterized by the fact that: (i) said at least two phenolic compounds are baicalin in an amount of 0.001 to 10% by weight of the composition and resveratrol in an amount of 0.0001 to 2 % by weight of the composition; (ii) said at least one hydrotrope is caffeine in an amount of 0.05 to 5% by weight of the composition and nicotinamide in an amount of 1 to 5% by weight of the composition; (iii) said at least one emulsifier comprises a silicone emulsifier in an amount of 4 to 50% by weight of the composition; (iv) said lipid-soluble antioxidant is Vitamin E in an amount of 0.0001 to 3% by weight of the composition; and (v) said water is present in an amount of 30 to 60% by weight of the composition.
    [0010]
    10. Cosmetic composition according to Claim 9, characterized by the fact that the silicone emulsifier is dimethicone (from 0.65 to 1000 cst) and a dimethicone cross polymer.
    [0011]
    11. Method for Treating or Caring for the Face, characterized by the fact that it comprises applying a cosmetic composition to the face, as claimed in any one of Claims 1 to 10.
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    同族专利:
    公开号 | 公开日
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    EP3019148A4|2016-06-15|
    WO2015002872A1|2015-01-08|
    US20150005247A1|2015-01-01|
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    法律状态:
    2018-02-27| B06F| Objections, documents and/or translations needed after an examination request according art. 34 industrial property law|
    2019-07-30| B06U| Preliminary requirement: requests with searches performed by other patent offices: suspension of the patent application procedure|
    2020-05-26| B07A| Technical examination (opinion): publication of technical examination (opinion)|
    2020-09-15| B09A| Decision: intention to grant|
    2020-12-08| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 30/06/2014, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    US13/932,272|US9669242B2|2013-07-01|2013-07-01|Compositions containing at least two phenolic compounds, a lipid-soluble antioxidant and at least one hydrotrope for cosmetic use|
    US13/932,272|2013-07-01|
    PCT/US2014/044850|WO2015002872A1|2013-07-01|2014-06-30|Compositions containing two phenolic compounds for cosmetic use|
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