Aqueous dispersion composition, production method thereof, food, cosmetics, and pharmaceutical

Abstract

To provide an aqueous dispersion composition containing solid particles that includes at least one kind selected from a group consisting of resveratrol superior in dispersibility with inhibition of precipitation or an analog thereof; a production method thereof; and a food, cosmetics, and a pharmaceutical using the aqueous dispersion composition.SOLUTION: An aqueous dispersion composition contains solid particles including at least one kind selected from a group consisting of resveratrol and an analog thereof, an aqueous medium, and a dispersion auxiliary agent. The dispersion auxiliary agent includes at least one kind selected from phospholipid, saponin, sucrose fatty acid ester, polyglyceryl fatty acid ester, sorbitan fatty acid ester, polyoxyethylene phytosterol, polysaccharide, sugar derivative, polyvinyl pyrrolidone, polyvinyl alcohol, and enzyme treated matter.SELECTED DRAWING: None

Description

Technical Field

[0001] The present disclosure relates to an aqueous dispersion composition containing solid particles containing at least one selected from the group consisting of resveratrol and its analogs, a method for producing the same, foods, cosmetics and pharmaceuticals using the aqueous dispersion composition, and a method for producing a powder preparation using the aqueous dispersion composition.

Background Art

[0002] Stilbene compounds used as functional components in pharmaceuticals, functional foods and health foods such as various supplements, and cosmetics are known to have good antioxidant power. In particular, resveratrol, which is 3,4',5-trihydroxy-trans-stilbene, is widely noted because favorable medical effects such as improvement of skin elasticity, anti-atherosclerosis, anti-allergy, enhancement of blood flow, and extension of lifespan are expected. Also, among the analogs of resveratrol, some have similar medical effects, and pterostilbene, piceatannol, etc. are known. (For example, Patent Documents 1 and 2)

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0004] In order to expand the options for the application uses and forms of resveratrol or its analogs, there is often a demand to prepare resveratrol or its analogs in the form of an aqueous dispersion composition in which resveratrol or its analogs are dispersed in an aqueous medium. However, since resveratrol or its analogs are in the form of poorly water-soluble solid particles, when attempting to prepare an aqueous dispersion composition, the particles precipitate in the aqueous dispersion composition, making it difficult to produce an aqueous dispersion with excellent dispersibility. In addition, pterostilbene may generate needle-like crystals in water, and when crystallization progresses during storage, it will gel or have thixotropy and lose its fluidity, so it has been particularly difficult to prepare an aqueous dispersion with excellent long-term storage stability.

[0005] Also, considering maximizing the pharmaceutical effects of resveratrol or its analogs, it is important to micronize the particles of resveratrol or its analogs, increase the specific surface area, and improve the water solubility. However, generally, when the particle size in an aqueous dispersion decreases, the cohesive force acts with the increase in the specific surface area, and it tends to be difficult to ensure the dispersibility of the particles. Therefore, there has been a desire to develop a technology that can ensure the dispersibility even for micronized resveratrol or its analog particles in the form of an aqueous dispersion.

[0006] An object of the present disclosure is to provide an aqueous dispersion composition containing solid particles containing at least one selected from the group consisting of resveratrol and its analogs with suppressed precipitation and excellent dispersibility, a method for producing the same, foods, cosmetics, and pharmaceuticals using the aqueous dispersion composition.

Means for Solving the Problems

[0007] The aqueous dispersion composition, its production method, foods, cosmetics, and pharmaceuticals according to the present disclosure can have the following configurations [1] to

[14] . [1]An aqueous dispersion composition containing at least solid particles (A), a dispersion aid (B), and an aqueous medium (C), wherein the solid particles (A) contain at least one selected from the group consisting of resveratrol and its analogs, and the dispersion aid (B) contains at least one selected from the group consisting of phospholipids, saponins, sucrose fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, polyoxyethylene phytosterol, polysaccharides, sugar derivatives, polyvinylpyrrolidone, polyvinyl alcohol, and enzyme-treated products. [2]The aqueous dispersion composition according to [1], wherein the solid particles (A) contain at least one selected from the group consisting of resveratrol, pterostilbene, raponchigenin, isolaponicin, piceatannol, and pinosylvin. [3]The aqueous dispersion composition according to [1] or [2], wherein the dispersion aid (B) contains at least one selected from the group consisting of lecithin, saponin, sucrose fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, gum arabic, xanthan gum, γ-cyclodextrin, polyvinylpyrrolidone, polyvinyl alcohol, enzyme-treated stevia, enzyme-treated rutin, enzyme-treated naringin, and enzyme-treated hesperidin. [4]The aqueous dispersion composition according to any one of [1] to [3], further containing an oil and fat (D). [5]The aqueous dispersion composition according to any one of [1] to [4], wherein the average particle diameter of the solid particles (A) is 500 nm or less. [6]The aqueous dispersion composition according to any one of claims 1 [1] to [5], wherein the mass ratio of the content of the solid particles (A) to the dispersion aid (B) is 1:1 to 2.5:1. [7]The aqueous dispersion composition according to any one of [1] to [6], wherein the solid particles (A) are a wet-milled and pulverized product. [8]At least solid particles (A) contain at least one selected from the group consisting of resveratrol and its analogs and a water-soluble organic solvent (E), and the water-soluble organic solvent (E) satisfies the following (i) to (iii). (i) It has a molecular weight of 90 to 350. (ii) It has at least two or more functional groups selected from the group consisting of a hydroxyl group, an ester group, and a carboxyl group. (iii) The viscosity at 60 °C is 2 to 150 mPa·s. The aqueous dispersion composition according to [1] to [7], wherein the content of the water-soluble organic solvent (E) is 0.003 to 0.3 parts by mass in 100 parts by mass of the solid particles (A). [9] The aqueous dispersion composition according to [8], wherein the water-soluble organic solvent (E) contains at least one selected from the group consisting of diacetin, triacetin, lactic acid, tripropionin, tributyrin, triethyl citrate, and acetyltriethyl citrate.

[10] The aqueous dispersion composition according to any one of [1] to [9], which is an ultrasonic dispersion-treated product, a homogenizer dispersion-treated product, or a bead mill dispersion-treated product.

[11] A food containing the aqueous dispersion composition according to any one of [1] to

[10] .

[12] A cosmetic containing the aqueous dispersion composition according to any one of [1] to

[10] .

[13] A pharmaceutical containing the aqueous dispersion composition according to any one of [1] to

[10] .

[14] A method for producing an aqueous dispersion composition according to any one of [1] to

[10] , comprising subjecting solid particles (A), a dispersion aid (B), and an aqueous medium (C) to ultrasonic dispersion, homogenizer dispersion, or bead mill dispersion to obtain an aqueous dispersion composition.

[15] A method for producing a powder preparation by drying the aqueous dispersion composition according to any one of [1] to

[10] .

Advantages of the Invention

[0008] According to the present disclosure, there can be provided an aqueous dispersion composition containing solid particles containing at least one selected from the group consisting of resveratrol and its analogs, which has excellent dispersibility with suppressed precipitation, a method for producing the same, foods, cosmetics, and pharmaceuticals using the aqueous dispersion composition.

Embodiments for Carrying Out the Invention

[0009] Hereinafter, the aqueous dispersion composition, its production method, foods, cosmetics, and pharmaceuticals according to the present disclosure will be described. In this specification, "~" indicating a numerical range means including the numerical values described before and after it as the lower limit value and the upper limit value. In the numerical ranges described stepwise in this specification, the upper limit value or the lower limit value described in one numerical range may be replaced with the upper limit value or the lower limit value of the numerical ranges described in other stepwise descriptions. Further, in the numerical ranges described in this specification, the upper limit value or the lower limit value of the numerical range may be replaced with the value shown in the examples. Furthermore, in this specification, the amount of each component contained in the aqueous dispersion composition means the total amount of the plurality of substances corresponding to each component in the composition, unless otherwise specified when a plurality of substances corresponding to each component are contained in the composition.

[0010] <Aqueous Dispersion Composition> The aqueous dispersion composition according to the present disclosure (hereinafter also referred to as the present composition) includes solid particles (A) containing at least one selected from the group consisting of resveratrol and its analogs, an aqueous medium (C), and a specific dispersion aid (B), and may contain other additives as necessary. The dispersion aid (B) contains at least one selected from the group consisting of phospholipids, saponins, sucrose fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, polyoxyethylene phytosterols, polysaccharides, sugar derivatives, polyvinylpyrrolidone, polyvinyl alcohol, and enzyme-treated products. The present composition with such a configuration has excellent dispersibility of solid particles containing at least one selected from the group consisting of resveratrol and its analogs, can stably maintain a dispersed state without precipitation, and can suppress changes in appearance such as color and taste.

[0011] (Solid particles (A)) The aqueous dispersion composition according to the present disclosure contains solid particles (A) containing at least one selected from the group consisting of resveratrol and its analogs. At least one selected from the group consisting of resveratrol and its analogs refers to those represented by the following Chemical Formula 1. Specific examples include resveratrol, pinosylvin, pinosylvin monomethyl ether, pterostilbene, raponchigenin, isolapachigenin, desoxylapachigenin, resveratrol trimethyl ether, piceatannol, and the like.

[0012] Chemical Formula 1 [Chemical Formula] (In the formula, R 1 ~R 6 are each independently a group selected from -H, -OH, and -OR, and R is an alkyl group having 1 to 6 carbon atoms.)

[0013] The solid particles (A) contain at least one selected from the group consisting of resveratrol and its analogs, and may contain other components derived from raw materials, but may also be composed of only resveratrol or its analogs. Examples of other components derived from raw materials include dietary fiber, protein, lipid, and decomposition products of resveratrol or its analogs. The content ratio of at least one selected from the group consisting of resveratrol and its analogs in the solid particles (A) is preferably 1% by mass to 100% by mass.

[0014] As representative examples of commercially available products of solid particles (A) containing at least one selected from the group consisting of resveratrol and its analogs, examples of resveratrol include "Resbenox" (Sabis Japan Corporation), "VINEATROL20M", "VINETAROL WD", "Resveratrox" (Sunbright Co., Ltd.), "trans-resveratrol" (Technoscience Corporation), "Resveratrol P-5", "Resveratrol WSP0.5", "Resveratrol PC-5", "Resveratrol WSPC0.5" (Oriza Yuka Co., Ltd.), "BHN Resveratrol-ε" (BHN Co., Ltd.), examples of pterostilbene include "Silbinol" (Sabis Japan Corporation), and examples of piceatannol include "Pasenol" (Morinaga & Co., Ltd.).

[0015] In this composition, the average particle diameter of the solid particles (A) in the aqueous dispersion is preferably 500 nm or less. If the average particle diameter of the solid particles is 500 nm or less, precipitation of the solid particles (A) in the composition can be easily suppressed, and in addition, solubility is further improved by miniaturization and a pharmaceutical effect can be expected. Further, from the viewpoint of suppressing precipitation, the average particle diameter of the solid particles (A) is more preferably 300 nm or less, and even more preferably 100 nm or less. The method for measuring the average particle diameter of the solid particles (A) will be described later.

[0016] In addition, in this composition, the content ratio of the solid particles (particularly at least one selected from the group consisting of resveratrol and its analogs) can be appropriately set, but from the viewpoint of the degree of freedom in design during formulation of foods, pharmaceuticals, etc., 2% by mass or more is preferable, 5% by mass or more is more preferable, and 10% by mass or more is even more preferable. On the other hand, from the viewpoint of suppressing aggregation and precipitation of the solid particles (A), the content ratio of the solid particles (particularly at least one selected from the group consisting of resveratrol and its analogs) in this composition is preferably 20% by mass or less, and more preferably 15% by mass or less. The content ratio of at least one selected from the group consisting of resveratrol and its analogs in this composition can be quantitatively analyzed by HPLC by a conventionally known method.

[0017] Here, the solid particles (A) in the present composition are preferably a wet-milled and pulverized product from the viewpoint of dispersibility. Further, although the details will be described later, as the method for dispersing the solid particles (A) in the present composition, it is preferable to use ultrasonic treatment (ultrasonic dispersion), homogenizer treatment (homogenizer dispersion), or bead mill dispersion. Therefore, the present composition is preferably an ultrasonic dispersion-treated product, a homogenizer dispersion-treated product, or a bead mill dispersion-treated product using the above solid particles (A), an aqueous medium (C) described later, a dispersion aid (B), and, if necessary, other additives.

[0018] In addition, the solid particles (A) containing at least one selected from the group consisting of resveratrol and its analogs in the present composition may be either crystalline particles or amorphous particles. The discrimination between crystalline particles and amorphous particles with respect to the solid particles (A) is performed by X-ray diffraction method. Specifically, in the measurement result by X-ray diffraction method of the solid particles (A), if there are peaks, the solid particles (A) are determined to be crystalline particles, and if there are no peaks, the solid particles (A) are determined to be amorphous particles. Generally, compared with crystalline particles, although the water solubility of amorphous particles is improved, there are concerns about storage stability such as a decrease in dispersibility such as precipitation and decomposition being observed in the light resistance test.

[0019] (Aqueous medium (C)) The aqueous medium (C) contains at least water and can also consist of water. The water is not particularly limited and can be appropriately set according to the purpose of use. For example, any of tap water, natural water, purified water, distilled water, mineral water, alkaline ion water, deep water, ion-exchanged water, pure water, ultrapure water such as Milli-Q water, etc. can be used. Note that Milli-Q water is ultrapure water obtained by a Milli-Q water production apparatus, which is an ultrapure water production apparatus of Merck Millipore. Among them, from the viewpoint of having few impurities, purified water, distilled water, ion-exchanged water, pure water, Milli-Q water, etc. are preferably used as the water used in the dispersion composition of the present invention.

[0020] The blending ratio of the aqueous medium (C) in the composition can be set as appropriate. From the perspective of the degree of freedom in design during the formulation of foods, pharmaceuticals, etc., 95% by mass or less is preferable, and 90% by mass or less is more preferable. From the perspective of suppressing aggregation and precipitation of the solid particles (A), the blending ratio of the aqueous medium (C) in the composition is preferably 60% by mass or more, and more preferably 75% by mass or more.

[0021] In addition to water, the aqueous medium (C) can further contain at least one component selected from the group consisting of solvents that can be uniformly mixed with water or dissolved in water, such as water-soluble organic solvents, pH adjusters, and preservatives.

[0022] The water-soluble organic solvent refers to an organic solvent having a solubility in water of 10 (g / 100g-H2O) or more at 25°C. From the perspective of being able to stably maintain the dispersion of the solid particles, an organic solvent having a solubility of 30 (g / 100g-H2O) or more is preferable, and an organic solvent having a solubility of 50 (g / 100g-H2O) or more is more preferable.

[0023] Examples of the water-soluble organic solvent include methanol, ethanol, 1-propanol, 2-propanol, 2-butanol, acetone, tetrahydrofuran, acetonitrile, methyl ethyl ketone, dipropylene glycol monomethyl ether, methyl acetate, methyl acetoacetate, N-methylpyrrolidone, dimethyl sulfoxide, ethylene glycol, 1,3-butanediol, 1,4-butanediol, propylene glycol, diethylene glycol, triethylene glycol, glycerin, etc. When the aqueous medium (C) contains a water-soluble organic solvent, only one kind of water-soluble organic solvent may be used, or two or more kinds may be used in combination.

[0024] The content of the water-soluble organic solvent in the aqueous medium (C) can be appropriately selected according to the purpose. From the perspective of ease of biocompatibility, etc., the content of the water-soluble organic solvent is preferably 40% by mass or less in the aqueous medium, and more preferably 1% to 20% by mass. Also, an embodiment in which the aqueous medium does not contain a water-soluble organic solvent is also preferable.

[0025] (Dispersing aid (B)) This composition contains a specific dispersing aid (B). The dispersing aid (B) contains at least one selected from the group consisting of phospholipids, saponins, sucrose fatty acid esters, polyglycerol fatty acid esters, sorbitan fatty acid esters, polyoxyethylene phytosterol, polysaccharides, sugar derivatives, polyvinylpyrrolidone, polyvinyl alcohol, and enzyme-treated products. Among these, from the viewpoint of suppressing precipitation over a long period, the dispersing aid (B) preferably contains at least one selected from the group consisting of lecithin, saponin, sucrose fatty acid ester, polyglycerol fatty acid ester, sorbitan fatty acid ester, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, gum arabic, xanthan gum, γ-cyclodextrin, polyvinylpyrrolidone, polyvinyl alcohol, enzyme-treated stevia, enzyme-treated rutin, enzyme-treated naringin, and enzyme-treated hesperidin.

[0026] The content of the dispersing aid (B) in this composition (when two or more kinds of dispersants are used in combination, the total amount thereof) can be appropriately selected according to the purpose, but from the viewpoint of ensuring stability, 1% by mass or more is preferable, 2.5% by mass or more is more preferable, and 5% by mass or more is even more preferable. Also, from the viewpoint of the degree of freedom in formulation design during the formulation of foods, pharmaceuticals, etc., the content of the dispersing aid in this composition is preferably 20% by mass or less, and more preferably 10% by mass or less.

[0027] The mass ratio of the solid particles (A) to the dispersion aid (B) is preferably 1:1 to 2.5:1, more preferably 1:1 to 1.5:1, from the viewpoint of suppressing precipitation over a long period. The higher the concentration of the solid particles (A) containing at least one selected from the group consisting of resveratrol and its analogs in the present composition, the greater the degree of freedom in formulation design during formulation. Also, depending on the type of the dispersion aid (B), there may be a concern that it may adversely affect the absorbability of at least one selected from the group consisting of resveratrol and its analogs. Therefore, it is desirable that the blending amount be as small as possible. However, since it is a trade-off with dispersibility, it is necessary to appropriately determine the required amount and decide the blending amount. Each dispersion aid will be described below.

[0028] (Phospholipid) Phospholipids are also called phosphatides and include glycerophospholipids and sphingophospholipids. The phospholipids used in the present composition may be either glycerophospholipids or sphingophospholipids. However, from the viewpoint of further improving the dispersibility of the solid particles (A) containing resveratrol or its analogs, glycerophospholipids are preferred, and among them, lecithin and the like are more preferred.

[0029] Lecithin refers to phosphatidylcholine (hereinafter sometimes abbreviated as PC) itself or a mixture containing at least phosphatidylcholine. A mixture containing at least phosphatidylcholine generally contains, in addition to phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, phosphatidylinositol, N-acyl phosphatidylethanolamine, phosphatidylglycerol, phosphatidic acid, lysophosphatidylcholine, lysophosphatidic acid, sphingomyelin, sphingoethanolamine, and the like.

[0030] As lecithin, lecithin derived from soybeans, egg yolks, and any other animal or plant sources can be used. Also, due to the physiological activity of phospholipids themselves and the need for more advanced emulsifiers, highly purified lecithin obtained by improving purity through purification and distillation, and lecithin subjected to various treatments, such as highly purified lecithin, fractionated lecithin, hydrogenated lecithin, and enzymatically decomposed lecithin, can also be used.

[0031] Soybean lecithin is produced by drying and purifying the oil cake that is by-produced in the soybean oil refining process. Usually, paste-like lecithin with a phospholipid content of 70% by mass or less contains about 30% by mass of crude soybean oil. Since it is inexpensive, paste-like lecithin is almost always used, especially in the food field.

[0032] Highly purified lecithin is lecithin that has been deoiled and powdered using a solvent such as acetone. Examples of commercially available products of highly purified lecithin include Phospholipon 20 (trade name, manufactured by Lipoid), Lecion P (trade name, manufactured by Riken Vitamin), SLP-White (trade name, manufactured by Tsujido Oil), Emalmetic 300 (trade name, manufactured by Lucas Meyer Cosmetics), etc.

[0033] Fractionated lecithin is lecithin in which the content of specific phospholipids has been increased by utilizing the difference in solubility in various solvents or by performing operations such as distillation on highly purified lecithin. Examples of commercially available products of fractionated lecithin include Phospholipon 50 (containing 45% by mass of PC), Phospholipon 85G (containing 80% by mass of PC), Phospholipon 90G (containing 94% by mass of PC) (all of the above are trade names, manufactured by Lipoid), Emalmetic 900 (containing 50% by mass of PC), Emalmetic 930 (containing 95% by mass of PC) (all of the above are trade names, manufactured by Lucas Meyer Cosmetics), SLP-PC70, SLP-PC90 (all of the above are trade names, manufactured by Tsujido Oil), etc.

[0034] Hydrogenated lecithin is lecithin in which the polyenoic fatty acids in the lecithin structure are oxidized and hydrogenated to convert them into saturated fatty acids for improved photo stability. Although hydrogenated lecithin can be preferably used in pharmaceuticals such as cosmetics and topical skin preparations, it is difficult to use in food and beverages. Examples of commercially available hydrogenated lecithin include Emalmetic 320 (trade name, manufactured by Lucas Meyer Cosmetics), SLP White H (trade name, manufactured by Tsujii Oil Co., Ltd.), etc. Examples of commercially available lecithin with a higher PC content and further hydrogenation treatment include Emalmetic 950 (trade name, manufactured by Lucas Meyer Cosmetics), SLP-PC92H (trade name, manufactured by Tsujii Oil Co., Ltd.), Phospholipon 90H (trade name, manufactured by Lipoid GmbH), etc.

[0035] Enzymatically hydrolyzed lecithin is usually lecithin obtained by selectively decomposing the ester bond of the fatty acid at the 2-position bound to glycerol with an enzyme, and is also called lysophosphatidylcholine to distinguish it from ordinary lecithin. Lysophosphatidylcholine has improved water solubility and generally improved emulsifying power compared to the lecithin before modification. The enzymatic hydrolysis treatment for preparing lysophosphatidylcholine is usually carried out on paste-like lecithin as a raw material, and the lecithin after the enzymatic hydrolysis treatment is highly purified to obtain lysophosphatidylcholine, but there is also a method of obtaining lysophosphatidylcholine by performing an enzymatic hydrolysis treatment on fractionated lecithin. Examples of representative commercially available lysophosphatidylcholine include SLP White Lysophosphatidylcholine and SLP-LPC70 (both trade names, manufactured by Tsujii Oil Co., Ltd.).

[0036] In addition, as another enzymatically treated lecithin, there is also lecithin obtained by decomposing the ester bond between phosphoric acid and a base. By performing a treatment to decompose the ester bond between phosphoric acid and a base, the base is removed from the phospholipid and it becomes in the form of phosphatidic acid, showing strong anionic properties. Examples of commercially available enzymatically treated lecithin include PA Nagase and Lysophospholipid Nagase H (both trade names, manufactured by Nagase ChemteX Corporation), etc.

[0037] (Saponin) Saponin is a general term for glycosides composed of sapogenin and sugar. It is contained in various plants including soapwort. It is a white amorphous powder and has amphiphilic properties, so it dissolves when mixed with water and exhibits surfactant action.

[0038] (Sucrose fatty acid ester) Sucrose fatty acid ester is obtained by an ester exchange reaction between sucrose and fatty acid methyl. In this composition, the sucrose fatty acid ester is preferably a compound having 12 to 20 carbon atoms in the fatty acid, more preferably a compound having 12 to 18 carbon atoms, still more preferably a compound having 14 to 16 carbon atoms, and particularly preferably a compound having 14 carbon atoms. By setting the carbon number of the fatty acid to 12 or more and 18 or less, the dispersibility of the solid particles (A) is further improved.

[0039] Specific examples of sucrose fatty acid ester include sucrose dioleate, sucrose distearate, sucrose dipalmitate, sucrose dimyristate, sucrose dilaurate, sucrose monooleate, sucrose monostearate, sucrose monopalmitate, sucrose monomyristate, sucrose monolaurate and the like. Among these, as the sucrose fatty acid ester, sucrose monostearate (ingredient display name in cosmetics: sucrose stearate) is preferred.

[0040] As the sucrose fatty acid ester, commercially available products can be used. Examples of commercially available products of sucrose fatty acid esters include "Ryoto (registered trademark) Sugar Ester" series of Mitsubishi Chemical Corporation's "S-070" [HLB (Hydrophilic-Lipophilic Balance) value (catalog value): 1 or less, monoester form (catalog value): about 0% by mass], "S-170" [HLB value (catalog value): about 1, monoester form (catalog value): about 1% by mass], "S-270" [HLB value (catalog value): about 2, monoester form (catalog value): about 10% by mass], "S-370" [HLB value (catalog value): about 3, monoester form (catalog value): about 20% by mass], "S-370F" [HLB value (catalog value): about 3, monoester form (catalog value): about 20% by mass], "S-570" [HLB value (catalog value): about 5, monoester form (catalog value): about 30% by mass], "S-770" [HLB value (catalog value): about 7, monoester form (catalog value): about 40% by mass], "S-970" [HLB value (catalog value): about 9, monoester form (catalog value): about 50% by mass], "S-1170" [HLB value (catalog value): about 11, monoester form (catalog value): about 55% by mass], "S-1170F" [HLB value (catalog value): about 11, monoester form (catalog value): about 55% by mass], "S-1570" [HLB value (catalog value): about 15, monoester form (catalog value): about 70% by mass], "S-1670" [HLB value (catalog value): about 16, monoester form (catalog value): about 75% by mass] (the above are sucrose stearate esters), etc. Also, examples include "SS" [HLB value (catalog value): about 19, monoester form (catalog value): 97% by mass], "F-160", "F-140", "F-110", "F-90", "F-70", "F-50", "F-20W", "F-10", "FA-10E" of the "DK Ester (registered trademark)" series of Daiichi Kogyo Seiyaku Co., Ltd., and "S-10", "S-50", "S-70", "S-110", "S-160", "S-190" [HLB value (catalog value): about 19, monoester form (catalog value): 97% by mass] of the "CosmeLike (registered trademark)" series, etc. Among these, as commercially available products of sucrose fatty acid esters, at least one selected from the group consisting of "Ryouto (registered trademark) Sugar Ester" series "S-1170", "S-1170F", "S-1570", and "S-1670", "DK Ester (registered trademark)" series "SS", "F-160", "F140", and "F110", and "Cosme-like (registered trademark)" series "S-110", "S-160", and "S-190" is preferable. Further, since the content rate of the monoester form in the sucrose fatty acid ester is high, as commercially available products of the sucrose fatty acid ester, at least one selected from "SS" of the "DK Ester (registered trademark)" series and "S-190" of the "Cosme-like (registered trademark)" series is particularly preferable.

[0041] (Polyglycerol fatty acid ester) The polyglycerol fatty acid ester is produced by esterifying a fatty acid to polyglycerol. The polyglycerol fatty acid ester is not particularly limited, but the polyglycerol structure contained in the polyglycerol fatty acid ester may be linear, branched, or cyclic. Examples of the polyglycerol fatty acid ester that can be used in the present composition include esters of polyglycerol having an average degree of polymerization of 2 or more and fatty acids having 8 to 18 carbon atoms. The average degree of polymerization of the polyglycerol that can be used for the preparation of the polyglycerol fatty acid ester is preferably 2 or more, and more preferably 2 to 10. Examples of the fatty acids having 8 to 18 carbon atoms that can be used for the preparation of the polyglycerol fatty acid ester include caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, and the like.

[0042] The polyglycerol fatty acid ester may be one in which one type of fatty acid is ester-bonded to one molecule of polyglycerol, or may be one in which two or more types of fatty acids are ester-bonded to one molecule of polyglycerol.

[0043] As the polyglycerol fatty acid ester, for example, from the viewpoint that the storage stability of the present composition tends to be more excellent, it preferably contains a fatty acid structure having at least one of a branched chain and an unsaturated carbon bond, and more preferably contains a fatty acid structure having either a branched chain or an unsaturated carbon bond.

[0044] Preferred examples of the polyglycerol fatty acid ester that can be used in the present composition include hexaglycerol monooleate, hexaglycerol monostearate, hexaglycerol monopalmitate, hexaglycerol monomyristate, hexaglycerol monolaurate, decaglycerol monooleate, decaglycerol monostearate, decaglycerol monopalmitate, decaglycerol monomyristate, decaglycerol monolaurate and the like. Among them, more preferred examples include decaglycerol monooleate (H LB = 12), decaglycerol monostearate (HLB = 12), decaglycerol monopalmitate (HLB = 13), decaglycerol monomyristate (HLB = 14), decaglycerol monolaurate (HLB = 16) and the like.

[0045] As the polyglycerol fatty acid ester, commercially available products can be used. Examples of commercially available products of polyglycerol fatty acid esters include, for example, NIKKOL DGMS, NIKKOL DGMO-CV, NIKKOL DGMO-90V, NIKKOL DGDO, NIKKOL DGMIS, NIKKOL DGTIS, NIKKOL Tetraglyn 1-SV, NIKKOL Tetraglyn 1-O, NIKKOL Tetraglyn 3 -S, NIKKOL Tetraglyn 5-S, NIKKOL Tetraglyn 5-O, NIKKOL Hexaglyn 1-L, NIKKOL Hexaglyn 1-M, NIKKOL Hexaglyn 1-SV, NIKKOL Hexaglyn 1-O, NIKKOL Hexaglyn 3-S, NIKKOL Hexaglyn4-B, NIKKOL Hexaglyn 5-S, NIKKOL Hexaglyn 5-O, NIKKOL HexaglynPR-15, NIKKOL Decagly n 1-L, NIKKOL Decaglyn 1-M, NIKKOL Decagly n 1-SV, NIKKOL Decaglyn1-50SV, NIKKOL D ecaglyn 1-ISV, NIKKOL Decaglyn 1-O, NIKKOL Decaglyn 1-OV, NIKKOL Decaglyn1-LN, NIKKOL Decaglyn 2-SV, NIKKOL Decaglyn 2-ISV, NIKKOL Decaglyn 3-SV, NIKKOL Decaglyn3-OV, NIKKOL Decaglyn 5-SV, NIKKOL Decaglyn 5-HS, NIKKOL Decaglyn 5-IS, NIKKOL Decaglyn5-OV, NIKKOL Decaglyn 5-O-R, NIKKOL Decaglyn 7-S, NIKKOL Decaglyn 7-O, NIKKOL Decaglyn10-SV, NIKKOL Decaglyn 10-IS, NIKKOL Decaglyn 10-OV, NIKKOL Decaglyn 10-MAC, NIKKOLDecaglyn PR-20 (all of the above are trade names, Nikko Chemicals Co., Ltd.). Note that "NIKKOL" is a registered trademark of Nikko Chemicals Co., Ltd.

[0046] Furthermore, examples include Ryoto (registered trademark) polyglyester L-7D, L-10D, M-7D, M-10D, P-8D, SWA-10D, SWA-15D, SWA-20D, S-24D, S-28D, O-15D, O-50D, B-70D, B-100D, ER-60D, LOP-120DP, DS13W, DS3, HS11, HS9, TS4, TS2, DL15, DO13 (all of the above are product names, Mitsubishi Chemical Corporation), Sunsoft (registered trademark) Q-17UL, Sunsoft Q-14S, Sunsoft A-141C (all of the above are product names, Taiyo Chemical Co., Ltd.), Poem (registered trademark) DO-100, Poem J-0021 (all of the above are product names, Riken Vitamin Co., Ltd.), and the like.

[0047] (Sorbitan fatty acid ester) Sorbitan fatty acid ester is a compound synthesized by the esterification reaction of sorbitol and fatty acid. It may also be in the form of polyoxyethylene sorbitan fatty acid ester obtained by adding ethylene oxide to sorbitan fatty acid ester.

[0048] Examples of sorbitan fatty acid ester include sorbitan monolaurate (Span20), sorbitan monooleate (Span80), and the like.

[0049] As polyoxyethylene sorbitan fatty acid esters, commercially available Tween surfactants are the most representative. Examples of polyoxyethylene sorbitan fatty acid esters include polyoxyethylene sorbitan monolaurate (Polyoxyethylene Sorbitan Monolaurate: Tween20), polyoxyethylene sorbitan monopalmitate (Polyoxyethylene Sorbitan Monopalmitate: Tween40), polyoxyethylene sorbitan monostearate (Polyoxyethylene Sorbitan Monostearate: Tween60), polyoxyethylene sorbitan monooleate (Polyoxyethylene Sorbitan Monooleate: Tween80), and the like.

[0050] (Polyoxyethylene Phytosterol) Polyoxyethylene phytosterol (POE phytosterol) is a compound represented by the following general formula (I). R-O-(EO) n -H General formula (I) In general formula (I), R represents a phytosteryl group. EO represents an ethylene oxide group, and n represents 5 to 60. From the viewpoint of further improving the dispersibility of solid particles, n is preferably in the range of 10 to 50, and more preferably in the range of 10 to 30. As POE phytosterol, within the range that does not impair the effects of the present disclosure, a POE phytosterol containing a polyoxypropylene group (POP) and a polyoxybutylene group (POB) in addition to the polyoxyethylene group in the hydrophilic partial structure may be used. Examples of the POE phytosterol include POE phytosterol ether, POE / POP phytosterol ether, POE / POP / POB phytosterol ether, and POE / POB phytosterol ether. The POE phytosterol ether is commercially available. Specific examples of the commercial products include BPS-5, BPS-10, BPS-20, and BPS-30 of the NIKKOL series (all of the above are product names, manufactured by Nikko Chemicals).

[0051] (Polysaccharide) As the polysaccharide, acidic polysaccharides, neutral polysaccharides, basic polysaccharides, etc. derived from plants, seaweeds, or microorganisms are preferably applicable. Examples of the acidic polysaccharide include pectin, sodium alginate, potassium alginate, gum arabic, xanthan gum, gellan gum, tragacanth gum, inulin, carrageenan, polygalacturonic acid, agar, polyfuran, funoran, and furselan. Examples of the neutral polysaccharide include tamarind seed gum, guar gum, locust bean gum, starch, pullulan, laminaran, and konjac mannan. Examples of the basic polysaccharide include chitosan. Among these, from the viewpoint of dispersibility, it is preferable to use at least one of gum arabic and xanthan gum.

[0052] (Sugar derivative) Examples of the sugar derivative include cellulose derivatives. Examples of the cellulose derivative include etherified cellulose in which a part of the hydroxy groups of glucose constituting cellulose is etherified. Specific examples of the etherified cellulose include methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, and carboxymethylcellulose salts. Here, examples of the carboxymethylcellulose salt include alkali metal salts of carboxymethylcellulose such as sodium carboxymethylcellulose and alkaline earth metal salts of carboxymethylcellulose such as calcium carboxymethylcellulose. Examples of commercially available representative cellulose derivatives include, as hydroxypropyl cellulose, NISSO HPC-SSL, NISSO HPC-SL, NISSO HPC-L (all of the above are trade names, manufactured by Nippon Soda Co., Ltd.), as methyl cellulose, MCE-15, MCE-25, MCE-15, MCE-100, MCE-400, MCE-4000 (all of the above are trade names, manufactured by Shin-Etsu Chemical Co., Ltd.), as hydroxypropyl methyl cellulose, SFE-400, SFE-4000, SE-03, SE-06, SE-50, NE-400, NE-4000 (all of the above are trade names, manufactured by Shin-Etsu Chemical Co., Ltd.), and as carboxymethyl cellulose, Sunrose F, Sunrose A, Sunrose SLD (all of the above are trade names, manufactured by Nippon Paper Industries Co., Ltd.).

[0053] In addition to cellulose derivatives, cyclodextrin is cited as a sugar derivative. Cyclodextrin is an oligosaccharide in which glucose is linked cyclically by α-1,4 bonds, and is also called a cyclic oligosaccharide because of its structure. Furthermore, those containing 6, 7, and 8 glucose molecules in cyclodextrin are called α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin, respectively. Among these sugar derivatives, from the viewpoint of dispersibility, it is preferable to use at least one selected from methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, and γ-cyclodextrin.

[0054] (Polyvinylpyrrolidone) Polyvinylpyrrolidone (PVP) is a nonionic water-soluble polymer compound obtained by polymerizing N-vinyl-2-pyrrolidone. Polyvinylpyrrolidone is a white powder and absorbs moisture in the air well (up to about 18% by mass). Commercially available products of polyvinylpyrrolidone can be used as appropriate. Polyvinylpyrrolidone can be obtained, for example, by synthesizing N-vinyl-2-pyrrolidone from acetylene, ammonia, and formaldehyde and then polymerizing it in the presence of an oxidizing agent or the like.

[0055] (Polyvinyl alcohol) Polyvinyl alcohol is known as a water-soluble synthetic resin. In this composition, conventionally known polyvinyl alcohol can be used as appropriate. Polyvinyl alcohol can be produced, for example, by saponifying polyvinyl acetate obtained by polymerizing vinyl acetate monomer.

[0056] (Enzyme-treated product) In this composition, an enzyme-treated product can be used as the dispersion aid (B). Representative examples of the enzyme-treated product include enzyme-treated stevia, enzyme-treated rutin, enzyme-treated naringin, and enzyme-treated hesperidin. Conventionally known enzyme-treated products can be used. For example, as the enzyme-treated product, those produced by the methods described in JP-A-10-70994, JP-A-3-7593, JP-A-5-194164, etc. can be used. Commercially available products of enzyme-treated rutin include, for example, "αG rutin H", "αG rutin P", "αG rutin PS" (all are trade names, manufactured by Toyo Seito Co., Ltd.). Commercially available products of enzyme-treated naringin include, for example, "αG naringin H" (trade name, manufactured by Toyo Seito Co., Ltd.). Commercially available products of enzyme-treated hesperidin include, for example, "αG hesperidin H", "αG hesperidin PS", "αG hesperidin PA-T", "αG hesperidin PA-LE" (all are trade names, manufactured by Toyo Seito Co., Ltd.), "Hayashibara hesperidin S" (trade name, manufactured by Hayashibara Co., Ltd.), etc. Commercially available products of enzyme-treated stevia include, for example, "αG sweet P", "αG sweet PX", "αG sweet PA", "αG sweet H" (all are trade names, manufactured by Toyo Seito Co., Ltd.), etc.

[0057] (Oil and fat (D)) In the present invention, it is preferable to contain fats and oils. Fats and oils refer to trivalent esters (triglycerides) in which three molecules of higher fatty acids are bonded to one molecule of glycerin. By containing fats and oils in the aqueous dispersion of the present invention, crystal growth of the solid particles (A) is suppressed, and it becomes possible to prepare an aqueous dispersion having excellent long-term storage stability while ensuring fluidity. Although the details of the mechanism by which fats and oils suppress crystal growth are unclear, it is considered that the molecules of hydrophobic fats and oils adsorb on the surface of hydrophobic solid particles, inhibiting the approach of solid particles to each other and suppressing crystal growth. There are liquid and solid fats and oils, but since the aqueous dispersion is in a liquid state, the fats and oils in the present invention are preferably in a liquid state. Examples of the fatty acids contained in the fats and oils (D) include saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids. Examples of the saturated fatty acids include caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, isostearic acid, hydroxystearic acid, and the like. Examples of the monounsaturated fatty acids include palmitoleic acid, oleic acid, elaidic acid, petroselinic acid, erucic acid, ricinoleic acid, and the like. Examples of the polyunsaturated fatty acids include linoleic acid, γ-linolenic acid, α-linolenic acid, dihomo-γ-linolenic acid, arachidonic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and the like. In the present invention, saturated fatty acid oils are preferable from the viewpoint of crystal growth inhibition, and then monounsaturated fatty acid oils are preferable. As the fat or oil (D), edible fats and oils can be preferably used, and examples thereof include animal and vegetable fats and oils suitable for food use, hydrogenated oils thereof, interesterified oils, fractionated oils, and the like. Examples of edible fats and oils include rapeseed oil, palm oil, soybean oil, rice bran oil, sesame oil, sunflower oil, corn oil, cottonseed oil, olive oil, safflower oil, perilla oil, linseed oil, castor oil, salad oil, camellia oil, avocado oil, evening primrose oil, borage oil, wheat germ oil, southernwood oil, macadamia nut oil, peanut oil, tea seed oil, kaya oil, rice bran wax oil, sinagiri oil, Japanese cedar oil, jojoba oil, germ oil, coconut oil, peanut oil, almond oil, hazelnut oil, walnut oil, grape seed oil, and the like. Among these, palm oil, coconut oil, and cottonseed oil, which have a high content of saturated fatty acids, are preferable. Furthermore, from the perspective of the viscosity of the fat or oil itself, medium-chain fatty acid oil having 8 to 12 carbon atoms (MCT oil (Medium Chain Triglyceride)) is most preferable. Since resveratrols and their analogs may be soluble in the fat or oil, the addition amount of the fat or oil (D) needs to be limited to an amount such that resveratrols and their analogs maintain the form of solid particles and are not completely dissolved in the fat or oil. Although it is necessary to determine the addition amount in view of this point, as a guideline, the ratio of the solid particles (A) to the fat or oil (D) is desirably 0.5 to 3 parts by mass of the fat or oil with respect to 1 part by mass of the solid particles. If it is less than 0.5 part by mass, the crystal growth inhibitory effect is poor, and if it exceeds 3 parts by mass, it becomes difficult for the solid particles to maintain the form of solid particles because they dissolve.

[0058] (Other additives) This composition can contain other additives according to the use purpose and the like as long as the effects of the present disclosure are not impaired. Examples of usable additive species include substances described in the 49th Edition of the Compilation of Standards for the Use of Food Additives (Japan Food Hygiene Association, Incorporated Administrative Agency), Pharmaceutical Additive Standards 2018 (Yakujihosha), and the 7th Edition of the Cosmetic Ingredients Guide (Yakujihosha).

[0059] <Method for producing aqueous dispersion composition> By applying a shearing force to a mixture containing solid particles (A), a dispersion aid (B), and an aqueous medium (C), at least one solid particle (A) selected from the group consisting of resveratrol and its analogs can be mechanically refined, and a dispersion containing the solid particle (A) can be prepared. There is no particular limitation on the shearing force application device used for applying the shearing force, but any of ultrasonic dispersion, homogenizer dispersion, or bead mill dispersion is preferred. Among them, bead mill dispersion is particularly preferred from the viewpoint of particle refinement.

[0060] Ultrasonic dispersion is a method of crushing and dispersing particles by the cavitation force generated by immersing a chip that emits ultrasonic waves in a liquid. Examples of commercially available ultrasonic dispersers include UH-50UH-50F, UH-300, UH-600, UH-600S, UH-600SH (all of the above are product names, MS Tech Co., Ltd.), PSF-600, PSF-1200, RUS-600TCVP (all of the above are product names, Nippon Seiki Co., Ltd.), and the like.

[0061] Homogenizer dispersion can be roughly classified into stir-type homogenizers, high-pressure homogenizers, and the like. A stir-type homogenizer is a device that entangles powder in a liquid by the high-speed rotation of stirring blades and at the same time disperses particles by the cutting action of the blades. Examples of commercially available stir-type homogenizers include ClearMix W Motion CLM-1.7 / 5.5W, Clear SS5-100 (both product names) manufactured by M-Technique Co., Ltd., Adi Homomixer 2M type, HV-M (product name) manufactured by Primix Corporation, and the like. A high-pressure homogenizer refers to a device that pressurizes an object to be crushed to high pressure or ultra-high pressure and crushes and disperses it by the shearing force generated when passing through a slit (gap). Generally, it includes devices called high-pressure homogenizers and ultra-high pressure homogenizers. Examples of high-pressure homogenizer devices include Starburst (product name, Sugino Machine Ltd.), Nanovidar (product name, Yoshida Kikai Kogyo Co., Ltd.), Microfluidizer M-110E / H (product name, Mizuho Industries Co., Ltd.), and the like.

[0062] Bead mill dispersion is a method of mixing various components (such as solid particles and dispersion aids) in a solvent (aqueous medium) and pulverizing, refining, and dispersing coarse particles or aggregates (aggregated particles) by the collision force between beads. At this time, the particle surface is coated with a dispersion aid (resin or surfactant). As a result, the stability of the aqueous dispersion composition is improved and long-term precipitation suppression becomes easy. These dispersion methods can be appropriately carried out under conventionally known conditions. For example, bead mill dispersion can be carried out for 0.1 to 20 hours using (zirconia) beads with a diameter of 0.1 to 0.5 mm.

[0063] As the bead mill, commercially available products can be used. Commercially available products of bead mills that can be used for the preparation of this composition include Starmill Nanogetter, Starmill ZRS, Starmill LMZ, Agitator Mill LMK (all of the above are trade names, Asizawa Fine Tech Co., Ltd.), Spike Mill, Mighty Mill, Mighty Mill Mark II, Key Mill (all of the above are trade names, Inoue Manufacturing Co., Ltd.), Apex Mill, Super Apex Mill, Ultra Apex Mill (all of the above are trade names, Hiroshima Metal & Machinery Co., Ltd.), Sand Grinder (SLG), Lady Mill (RMV-03), Nano Lady Mill (RMV-03), Ultra Viscomill (UVM), Ultra-X Viscomill (UVX), New Viscomill (NVM) (all of the above are trade names, Aimex Co., Ltd.), SC Mill, MSC Mill, Attritor, Fine Mill (all of the above are trade names, Nippon Coke Industry Co., Ltd.), Annular Gap Type Bead Mill (trade name, Eurotech Co., Ltd.), Dyno Mill ECM, DYNO-MILL NPM-NANO Performance Mill (all of the above are trade names, Simar Enterprise Co., Ltd.), MicroMedia X1 (trade name, Bühler Co., Ltd.), etc.

[0064] Incidentally, from the perspective of dispersibility, the solid particles (A) are preferably a wet-milled and pulverized product. By using a wet-milled and pulverized product, it becomes possible to produce a fine solid particle powder containing at least one selected from the group consisting of resveratrol and its analogs. By using the micronized solid particles, it becomes possible to prepare a finer aqueous dispersion. It is desirable to micronize the primary particle size of the solid particles (A) to 5 to 300 nm. The method for measuring the primary particle size of the solid particles (A) will be described later. The wet-milled and pulverized product of the solid particles (A) can be obtained, for example, through the following steps. That is, step (a) of mechanically kneading a workpiece containing at least one selected from the group consisting of resveratrol and its analogs, a water-soluble inorganic salt, and a water-soluble organic solvent, and after step (a), by step (b) of removing the water-soluble inorganic salt and the water-soluble organic solvent, a wet-milled and pulverized product of the solid particles (A) can be obtained.

[0065] (Water-soluble inorganic salt) The above water-soluble inorganic salt has the effect of grinding and micronizing the workpiece. By using a water-soluble one, it can be removed by washing. Examples of the inorganic salts that can be used include sodium chloride, potassium chloride, ammonium chloride, sodium sulfate, magnesium sulfate, potassium sulfate, calcium sulfate, sodium malate, sodium citrate, disodium citrate, sodium dihydrogen citrate, potassium dihydrogen citrate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, and dipotassium hydrogen phosphate. Among these, sodium chloride is preferred. The addition amount of the water-soluble inorganic salt is not particularly limited, but from the perspectives of treatment efficiency and production efficiency, it is preferably 50 to 2000 parts by mass, more preferably 300 to 1000 parts by mass, based on 100 parts by mass of the workpiece. Also, the above water-soluble inorganic salt may be used alone or in combination of multiple types.

[0066] (Water-soluble organic solvent (E)) The water-soluble organic solvent used for the wet grinding and pulverization treatment of the solid particles (A) should function to wet the hardly water-soluble object to be treated and the water-soluble inorganic salt, dissolve (mix) in water, and substantially not dissolve the water-soluble inorganic salt to be used. Furthermore, the water-soluble organic solvent used for the wet grinding and pulverization treatment is preferably a water-soluble organic solvent (E) that satisfies the following (i) to (iii). That is, (i) It has a molecular weight of 90 to 350. (ii) It has at least two or more functional groups selected from the group consisting of a hydroxyl group, an ester group, and a carboxyl group. (iii) The viscosity at 60 °C is 2 to 150 mPa·s. It satisfies all of the above conditions. If the viscosity is high, the viscosity of the kneaded product of the solid particles (A) and the inorganic salt will increase, the movement of the inorganic salt as the grinding agent will be inhibited, and the effect of micronizing the solid particles (A) cannot be sufficiently obtained. The viscosity of the water-soluble organic solvent in the specification of this application is the value measured using a cone and plate type rotational viscometer (viscosity measuring instrument manufactured by Toki Sangyo Co., Ltd.: TVE-20L) in accordance with the provisions of JIS Z 8803.

[0067] Examples of water-soluble organic solvents that can be used in wet grinding and pulverization treatment include glycerin, propylene glycol, polyethylene glycol, dipropylene glycol, diethylene glycol, lactic acid, 2-ethyl-1,3-hexanediol, 2,4-diethyl-1,5-pentanediol, monoacetin, diacetin, triacetin, tripropionin, tributyrin, 2-methylpentane-2,4-diol, 2-butyl-2-ethyl-1,3-propanediol, 1,5-pentanediol, 1,6-hexanediol, 1,2,6-hexanetriol, triethyl citrate, and acetyltriethyl citrate. However, as examples of water-soluble organic solvents (D) that satisfy the above (i) to (iii), lactic acid (21.3 mPa·s), 2-ethyl-1,3-hexanediol (16.6 mPa·s), 2,4-diethyl-1,5-pentanediol (67.2 mPa·s), monoacetin (13.7 mPa·s), diacetin (8.2 mPa·s), triacetin (4.1 mPa·s), tripropionin (2.7 mPa·s), tributyrin (3.3 mPa·s), 2-methylpentane-2,4-diol (5.8 mPa·s), 2-butyl-2-ethyl-1,3-propanediol (43.7 mPa·s), 1,5-pentanediol (20.9 mPa·s), 1,6-hexanediol (25.2 mPa·s), 1,2,6-hexanetriol (137.6 mPa·s), triethyl citrate (35.2 mPa·s), and acetyltriethyl citrate (53.7 mPa·s) can be mentioned.

[0068] The addition amount of the water-soluble organic solvent is not particularly limited, but it is preferably 5 to 1000 parts by mass, more preferably 50 to 500 parts by mass, based on 100 parts by mass of the object to be treated. Further, the above water-soluble organic solvent may be used alone or in combination of a plurality of types. The use of solvents other than the water-soluble organic solvent (E) in the present invention is not excluded as long as it does not deviate from the gist of the present invention. However, from the viewpoint of effectively enhancing the micronization of the solid particles (A), it is preferably substantially the water-soluble organic solvent (E) in the present invention that is used.

[0069] (Step (a)) In the wet grinding and pulverization treatment method of the present invention, the kneading device used for mechanically kneading and grinding the object to be treated can be used without particular limitation as long as it has the ability to knead and disperse the object to be treated, water-soluble inorganic salt, and water-soluble organic solvent by mechanical means. Examples of such kneading devices include kneaders, two-roll mills, three-roll mills, ball mills, attritors, horizontal sand mills, vertical sand mills, fret mills, Hoover mixers, disk blade kneading and dispersing machines, and the like. Using these, the treatment conditions and the like may be appropriately adjusted according to the required degree of refinement and the like. The water-soluble inorganic salt acts as a crushing aid and crushes the object to be treated by utilizing the high hardness of the water-soluble inorganic salt during kneading. By optimizing the kneading conditions (temperature, rotational speed, etc.), it is possible to obtain solid particles (A) containing at least one selected from the group consisting of resveratrol having a narrow and sharp particle size distribution and its analogs.

[0070] (Step (b)) After the kneading and grinding of the solid particles (A) are completed, by removing the water-soluble inorganic salt and water-soluble organic solvent used for kneading and grinding, solid particles (A) containing at least one selected from the group consisting of the target resveratrol and its analogs can be obtained. Specifically, in a solvent, after homogenizing the mixture of the object to be treated, water-soluble inorganic salt, and water-soluble organic solvent using a stirring blade, dissolver, homogenizer, etc., the water-soluble inorganic salt and water-soluble solvent are removed by filtration and washing with water.

[0071] The solvent used to make the mixture uniform is not particularly limited as long as it is a solvent in which water-soluble inorganic salts and water-soluble organic solvents are easily dissolved, the ground object to be treated is hardly dissolved, and it is physiologically acceptable. As the solvent, water is preferred, but solvents other than water can also be used. Examples of solvents other than water include mixtures of organic solvents such as acetic acid, methanol, and ethanol with water. Also, the filtration method is not particularly limited and can usually be carried out by known methods used for filtering organic compound-containing substances. Examples of filtration methods include vacuum filtration, pressure filtration, ultrafiltration membrane method, etc.

[0072] After removing the water-soluble inorganic salts and water-soluble organic solvents, a drying treatment can be performed to remove the solvent used for removing salts and the like from the obtained object to be treated. The drying method is not particularly limited and can usually be carried out by methods used for drying organic compounds. Examples of drying methods include vacuum drying, freeze drying, spray drying, freeze spray drying, etc. The drying temperature, drying time, etc. in the drying are not particularly limited, but in order to maintain the chemical stability of the object to be treated and prevent secondary aggregation of particles, drying is preferably carried out at a low temperature, and freeze drying, spray drying, or freeze spray drying is preferably used.

[0073] Also, in order to prevent dry aggregation during the production of the wet-milled pulverized product, when preparing an aqueous dispersion, the aqueous dispersion may be prepared using the wet-milled product in a water-containing state after removing the water-soluble inorganic salts and water-soluble organic solvents.

[0074] In the wet-milled and pulverized product of the present invention, it is preferable that the water-soluble organic solvent (E) remains in a specific range. The residual amount is preferably in the range of 0.003 to 0.3 parts by mass of the water-soluble organic solvent (E) used in the wet-milling and pulverization treatment per 100 parts by mass of the solid particles (A) contained in the aqueous dispersion composition. This is because when the water-soluble organic solvent (E) remains in a specific range, it has the effect of suppressing the aggregation of the refined solid particles (A). From the perspective of residue, a water-soluble organic solvent having no hydroxyl group and carboxyl group and having a total of 2 or more ester groups is more preferable. This is because the hydroxyl group and carboxyl group promote aggregation by hydrogen bonding. Considering these comprehensively, among the water-soluble organic solvents (E) described above, diacetin, triacetin, tripropionin, tributyrin, triethyl citrate, and acetyltriethyl citrate are desirable.

[0075] <Method for Measuring Average Particle Diameter of Solid Particles (A) in Aqueous Dispersion> As a method for measuring the average particle diameter of the solid particles (A) in the aqueous dispersion, it can be measured by known methods such as the dynamic light scattering method and the laser diffraction scattering method. In this composition, the value measured by the dynamic light scattering method is adopted. Examples of the particle size measuring apparatus using the dynamic light scattering method include Zetasizer Nano (trade name, manufactured by Malvern) and Microtrac UPA (trade name, manufactured by Nikkiso Co., Ltd.). As described above, in this composition, the average particle diameter of the solid particles (A) is desirably 500 nm or less. The average particle diameter of the particles may be the particle diameter (D50) at which the cumulative percentage is 50% in the cumulative particle size distribution based on the number.

[0076] <Powder Formulation of Aqueous Dispersion Composition> The aqueous dispersion composition of the present invention may be dried to form a powder formulation. The powder formulation of the aqueous dispersion composition of the present invention contains a dispersion aid (B) in the powder formulation, and thus has excellent water dispersibility when the powder is mixed with water. As the drying method, known methods may be used, and examples include vacuum drying, freeze drying, spray drying, and freeze spray drying. When drying, from the viewpoints of maintaining the shape of the powder, preventing scattering, and suppressing drying aggregation, it is preferable to add an excipient to the dispersion and then dry it. As the excipient, those known for use in foods, cosmetics, pharmaceuticals, and quasi-drugs can be used. Representative examples include sugars and sugar alcohols, starches and their derivatives, celluloses and their derivatives, resins, inorganic salts, etc. Examples of sugars and sugar alcohols include lactose, mannitol, trehalose, maltitol, erythritol, lactitol, xylitol, glucose, sucrose, fructose, sorbitol, cellobiose, etc. Examples of starches and their derivatives include starch, carboxymethyl starch, dextrin, cyclodextrin, dextran, pullulan, etc. Examples of celluloses and their derivatives include crystalline cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, etc. Examples of resins and inorganic salts include calcium carbonate, calcium sulfate, calcium phosphate, calcium stearate, polyvinyl pyrrolidone, etc.

[0077] <Foods, cosmetics, pharmaceuticals, and quasi-drugs> The aqueous dispersion composition of the present invention and the powder preparation obtained by drying the aqueous dispersion composition can be used as materials for foods, cosmetics, pharmaceuticals, and quasi-drugs and can be incorporated therein.

[0078] Examples of the foods (food and drink products) containing this composition include general foods such as edible oils (salad oil), confectioneries (gum, candy, caramel, chocolate, cookies, snacks, jelly, gummies, tablets, etc.), noodles (buckwheat noodles, udon noodles, ramen, etc.), dairy products (milk, ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, black tea, tea, carbonated beverages, sports drinks, etc.), as well as health foods (tablets, capsules, etc.) and dietary supplements (nutritional drinks, etc.).

[0079] These foods can be formulated with various ingredients according to their types. For example, food materials such as glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic, carrageenan, casein, gelatin, pectin, agar, B vitamins, nicotinamide, calcium pantothenate, amino acids, calcium salts, pigments, flavors, preservatives, etc. can be used.

[0080] Furthermore, these foods contain, for example, antioxidants (reduced ascorbic acid (vitamin C), vitamin E, reduced glutathione, tocotrienols, vitamin A derivatives, lycopene, lutein, astaxanthin, zeaxanthin, fucoxanthin, uric acid, ubiquinone, coenzyme Q10, folic acid, garlic extract, allicin, sesamin, lignans, catechins, isoflavones, chalcones, tannins, flavonoids, coumarin, isocoumarins, blueberry extract), health food ingredients (V. (vitamin) A, V.B1, V.B2, V.B6, V.B12, V.C, V.D, V.E, V.P, choline, niacin, pantothenic acid, calcium folate, EPA, oligosaccharides, dietary fiber, squalene, soy lecithin, taurine, dunaliella, protein, octacosanol, DHA, egg yolk lecithin, linoleic acid, lactoferrin, magnesium, zinc, chromium, selenium, potassium, heme iron, oyster meat extract, chitosan, chitooligosaccharides, collagen, chondroitin, turmeric, licorice, kukoshi, cinnamon, Japanese quince, ginger, ganoderma, clam extract, suppon, licorice, kukoshi, cinnamon, Japanese quince, ginger, ganoderma, plantain, chamomile, camomile, dandelion, hibiscus, honey, boren, royal jelly, lime, lavender, rose hip, rosemary, sage, bifidobacterium, faecalibacterium, lactris, wheat germ oil, sesame oil, perilla oil, soybean oil, medium-chain fatty acids, agaricus, ginkgo leaf extract, turmeric, chondroitin, brown rice germ extract, jujube, onion, DHA, EPA, DPA, sweet tea, cordyceps, garlic, bee larvae, papaya, puar, propolis, magnolia tree, yamabushitake, royal jelly, nipa palm, hyaluronic acid, collagen, GABA, harp seal oil, shark cartilage, glucosamine, lecithin, phosphatidylserine, tienchi ginseng, mulberry leaf, soybean extract, echinacea, ezoukogai, barley extract, olive leaf, olive fruit, gymnema, banaba, salacia, garcinia, chitosan, St. John's wort, jujube, carrot, passion flower, broccoli, placenta, adlay, grape seeds, peanut skins, bilberry, black cohosh, maria thistle, laurel tree, sage, rosemary, rhubarb, black vinegar, bitter melon, maca, safflower, flax, oolong tea, flower thistle, caffeine, capsaicin,Xylooligosaccharide, glucosamine, buckwheat, citrus, dietary fiber, protein, prune, spirulina, young barley leaves, nucleic acid, yeast, shiitake mushroom, umeboshi, amino acid, deep-sea shark extract, noni, oyster meat, loach, champignon, plantain, acerola, pineapple, banana, peach, apricot, melon, strawberry, raspberry, orange, fucoidan, maitake mushroom, cranberry, chondroitin sulfate, zinc, iron, ceramide, silk peptide, glycine, niacin, chestnut tree, L-cysteine, red wine leaves, millet, horsetail, biotin, centella asiatica, haskap, picnogenol, fucus, rhubarb, clove, rosemary, catechin, pu-erh, citric acid, brewer's yeast, melilot, black ginger, ginger, kudzu, nattokinase, beni-koji, tocotrienol, lactoferrin, cinnamon, tartary buckwheat, cocoa, yuzu seed extract, perilla seed extract, lychee seed extract, evening primrose extract, black rice extract, alpha-lipoic acid, raw coffee bean extract, etc. can also be blended.

[0081] The content ratio of the present composition in the food can be appropriately set, but from the viewpoint of disease prevention and health maintenance, it is preferably 1 to 30% by mass, and more preferably 1 to 20% by mass.

[0082] Examples of the form of the cosmetic containing the present composition include emulsion, soap, facial wash, bath agent, cream, emulsion, lotion, cologne, beard shaving cream, beard shaving lotion, cosmetic oil, suntan / sunscreen lotion, powder, foundation, perfume, pack, nail cream, enamel, enamel remover, eyebrow pencil, blush, eye cream, eyeshadow, mascara, eyeliner, lipstick, lip cream, shampoo, conditioner, hair dye, dispersion, cleaning agent, etc.

[0083] In addition to the present composition, the above cosmetic can be blended with oil, higher alcohol, fatty acid, ultraviolet absorber, powder, pigment, surfactant, polyhydric alcohol / sugar, polymer, physiologically active ingredient, solvent, antioxidant, fragrance, preservative, etc. within a range that does not impair the effects of the present disclosure.

[0084] Furthermore, this composition can be added as a raw material for drugs (including pharmaceuticals and quasi-drugs), and for example, dosage forms such as solutions, cataplasms, lotions, ointments, tinctures, creams, and external solutions can be adopted. Examples of raw materials that can be included in the drug in addition to this composition are, for example, excipients (glucose, lactose, sucrose, sodium chloride, starch, calcium carbonate, kaolin, crystalline cellulose, cacao butter, hydrogenated vegetable oil, kaolin, talc, etc.), binders (distilled water, physiological saline, ethanol water, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrants (sodium alginate, agar, sodium hydrogen carbonate, calcium carbonate, sodium lauryl sulfate, monoglyceride stearate, starch, lactose, powdered gum arabic, gelatin, ethanol, etc.), disintegration inhibitors (sucrose, stearin, cacao butter, hydrogenated oil, etc.), absorption promoters (quaternary ammonium bases, sodium lauryl sulfate, etc.), adsorbents (glycerin, starch, lactose, kaolin, bentonite, silicic acid, etc.), lubricants (purified talc, stearates, polyethylene glycol, etc.), and the like.

Examples

[0085] Hereinafter, the present disclosure will be described based on examples, but the present disclosure is not limited thereto. In the examples, "parts" and "%" represent "parts by mass" and "mass %", respectively.

[0086] (Measurement of primary particle diameter) The primary particle diameter of the solid particles (A) containing at least one selected from the group consisting of the obtained resveratrol and its analogs was measured by using a transmission electron microscope ("JEM-1200EX" manufactured by JEOL Ltd.) at a magnification of 100,000 times, and the average value of the primary particle diameters of the solid particles (A) in the observation sample was used. When the particle shape was not spherical, the major axis and the minor axis were measured, and the value obtained by (major axis + minor axis) / 2 was taken as the particle diameter.

[0087] (Measurement of residual water-soluble organic solvent) The residual water-soluble organic solvent in the solid particles (A) containing at least one selected from the group consisting of the obtained resveratrol and its analogs was quantified by gas chromatography, and determined by calculating the residual amount of the water-soluble organic solvent with respect to 100 parts by mass of the solid particles (A). The conditions for gas chromatography are shown below. · Separation instrument: GC2010 manufactured by Shimadzu Corporation · Column: DM-5MS (30m x 0.25mm x 0.25μm Film, Agilent Technologies) · Carrier gas: He · Pressure: 120.0 kPa · Total flow rate: 50.0 ml / min · Column flow rate: 1.77 ml / min · Linear velocity: 49.0 cm / sec · Purge flow rate: 3.0 ml / min · Column temperature: Held at 80°C for 4 minutes, then heated up in 16 minutes and held at 320°C for 5 minutes Injection mode: Split-less Mode Injection volume: 1 μL

[0088] The conditions for the mass spectrometer are shown below. · Measuring instrument: GC2010 manufactured by Shimadzu Corporation · Interface temperature: 250°C · Ion source temperature: 200°C · Measurement mode: Scan Mode · Measurement range: m / z = 30 - 500 · Measurement time: 5 - 20 min · Event time: 0.5 sec

[0089] [Preparation of micronized solid particles R-1] First, as the solid particles (A), micronized solid particles containing resveratrol were prepared. Specifically, the following materials were charged into a 1-gallon stainless steel kneader (manufactured by Inoue Manufacturing Co., Ltd.) and kneaded at 50°C for 8 hours. · The object to be treated containing resveratrol Resverox (trade name, manufactured by Sabinsa Japan Corporation): 100 parts by mass, · Water-soluble inorganic salt Sodium chloride: 1000 parts by mass, · Water-soluble organic solvent Diacetin: 150 parts by mass. Next, this kneaded product was put into 10 liters of water, stirred for 1 hour to form a slurry, and filtration and washing were repeated to remove sodium chloride and diacetin, followed by freeze-drying to obtain 97 parts by mass of micronized solid particles R-1, which is a wet-milled and pulverized product. The primary particle size of the obtained micronized solid particles R-1 was 110 nm, and the amount of the remaining water-soluble organic solvent was 0.013 parts by mass with respect to 100 parts by mass of the micronized solid particles.

[0090] [Preparation of micronized solid particles R-2 to 5] Except that the type of the object to be treated containing resveratrol (trade name, etc.), the type / mass part of the water-soluble organic solvent, the mass part of sodium chloride, and the kneading conditions were changed to those described in Table 1, micronized solid particles R-2 to 5 were prepared in the same manner as the preparation of micronized solid particles R-1.

[0091] [Preparation of micronized solid particles R-6 to 13] Except that the type of the object to be treated containing an analog of resveratrol (trade name, etc.), the type / mass part of the water-soluble organic solvent, the mass part of sodium chloride, and the kneading conditions were changed to those described in Table 1, micronized solid particles R-6 to 13 were prepared in the same manner as the preparation of micronized solid particles R-1.

[0092]

Table 1

[0093] [Evaluation of the dispersibility of the aqueous dispersion composition] Subsequently, an aqueous dispersion composition was prepared using solid particles (A), and for the obtained aqueous dispersion composition, evaluation of dispersibility was carried out by evaluating the appearance and particle size distribution. For the appearance, visual evaluation of the appearance was carried out according to the following evaluation criteria to check if there was precipitation or gelation. For the particle size distribution, using a particle size distribution measuring device ("Microtrac UPA" manufactured by Nikkiso Co., Ltd.), the average particle diameter (D50: 50% median diameter) of solid particles (A) containing at least one selected from the group consisting of resveratrol and its analogs in the aqueous dispersion composition was measured. · Evaluation criteria for appearance 〇: No precipitation visually △: Slight precipitation or thixotropic ×: Precipitation or gelled

[0094] <Evaluation of storage stability of aqueous dispersion composition> The prepared aqueous dispersion composition was stored for 7 days in an environment of temperature: 25 °C · relative humidity: 60% RH. After storage, the average particle diameter (D50: 50% median diameter) was measured to evaluate the storage stability of the average particle diameter in the aqueous dispersion composition. Also, visual confirmation of the appearance was carried out to evaluate the storage stability of the appearance. The evaluation criteria are the same as described above. The evaluation results are shown in Tables 2 and 3.

[0095] [Example 1] The following materials were mixed and ultrasonic irradiation was carried out for 2 hours using an ultrasonic device (manufactured by Yamato Scientific Co., Ltd., trade name: "LUH150") to obtain an aqueous dispersion composition S-1. · Solid particles (A) Sylbinol (trade name, manufactured by Sabinsa Japan Corporation): 5 parts by mass, · Dispersion aid (B) Polyglycerin fatty acid ester (manufactured by Mitsubishi Chemical Corporation, trade name: Ryoto Polygly Ester M-7D): 5 parts by mass, · Aqueous medium (C) Purified water: 90 parts by mass.

[0096] [Example 2] The dispersion method was changed from the above ultrasonic device to a stir-type homogenizer (manufactured by M Technique Co., Ltd., trade name: "Clear Mix CLM-0.8S"), and an aqueous dispersion composition S-2 was obtained in the same manner as in Example 1 except that the homogenization treatment was performed for 2 hours.

[0097] [Example 3] The dispersion method was changed from the above ultrasonic device to a high-pressure homogenizer (manufactured by Sugino Machine Ltd., trade name: "Starburst Mini"), and an aqueous dispersion composition S-3 was obtained in the same manner as in Example 1 except that the high-pressure homogenization treatment at 100 MPa was performed 10 times.

[0098] [Example 4] The dispersion method was changed from the above ultrasonic device to an attritor (manufactured by Eiger Japan Co., Ltd., trade name: "Mini Model M-250 MKII") using zirconia beads with a diameter of 0.5 mm, and after dispersing for 3 hours and filtering with a filter having a pore size of 5.0 μm, an aqueous dispersion composition S-4 was obtained in the same manner as in Example 1.

[0099] [Examples 5 to 41, Comparative Examples 1 to 3] Except that the types (trade names, etc.) and parts by mass of the solid particles (A) and the dispersion aid (B) and the parts by mass of the aqueous medium (C) were changed to those described in Tables 2 and 3, aqueous dispersion compositions S-5 to S-44 were prepared in the same manner as in Example 4. In Examples 27 to 41, two types of dispersion aids were used in combination, and in Comparative Examples 1 to 3, no dispersion aid was used.

[0100]

Table 2

[0101]

Table 3

[0102] [Examples 42 to 50] Except for changing the type (trade name, etc.) and parts by mass of the solid particles (A), the dispersion aid (B), the parts by mass of the aqueous medium (C), and the type (trade name, etc.) and parts by mass of the oil and fat (D) to those described in Table 4, aqueous dispersion compositions S-45 to S-53 were prepared in the same manner as in Example 4.

[0103] The prepared aqueous dispersion compositions were confirmed for long-term storage stability. As an evaluation of long-term storage stability, they were stored for 60 days in an environment of temperature: 40 °C and relative humidity: 60% RH, and the average particle diameter was measured and the appearance was visually confirmed. The evaluation results are shown in Table 4. · Evaluation criteria for appearance 〇: No sedimentation visually △: Slight sedimentation or thixotropic ×: Sedimentation or gelled

[0104]

Table 4

[0105] From Tables 2 and 3, it was found that by using the dispersion aid (B), the dispersibility and storage stability of the solid particles (A) containing at least one selected from the group consisting of resveratrol and its analogs are good. Among the dispersion aids (B), polyglycerol fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, lecithin, hydroxypropyl cellulose, polyvinyl alcohol, polyvinylpyrrolidone, and enzyme-treated products gave particularly good results. Also, it was found that by subjecting the solid particles (A) to wet grinding and pulverization treatment, it is possible to prepare a finer aqueous dispersion.

[0106] Furthermore, from Table 4, it was found that the sample containing oil and fat (D) was suitable for long-term storage stability. By adding oil and fat, the thixotropy of the dispersion was suppressed, and the effect of suppressing the change in the average particle size was observed. Among the oils and fats, aqueous dispersions containing palm oil, coconut oil, cottonseed oil, and medium-chain fatty acid oil, which are rich in saturated fatty acids, gave better results.

[0107] <Preparation of Powder Formulation Using Aqueous Dispersion Composition> [Example 51] 150 parts by mass of aqueous dispersion S-31 was subjected to freeze-drying treatment using a freeze dryer (FDU-1200, manufactured by Tokyo Rikakikai Co., Ltd.) to obtain a powder formulation F-1. When the moisture content of the obtained powder formulation was measured with a Karl Fischer moisture meter, it was 2.2% by mass.

[0108] [Example 52] 45 parts by mass of γ-cyclodextrin (Dexy Pearl γ-100, manufactured by Shiohata Sugar Refining Co., Ltd.) was added to 150 parts by mass of aqueous dispersion S-31 and mixed and stirred for 1 hour. The stirred solution was subjected to freeze-drying treatment using a freeze dryer (FDU-1200, manufactured by Tokyo Rikakikai Co., Ltd.) to obtain a powder formulation F-2. When the moisture content of the obtained powder formulation was measured with a Karl Fischer moisture meter, it was 1.4% by mass.

[0109] [Example 53] 45 parts by mass of hydroxypropyl cellulose (HPC-SSL, manufactured by Nippon Soda Co., Ltd.) was added to 150 parts by mass of aqueous dispersion S-31 and mixed and stirred for 1 hour. The stirred solution was subjected to spray-drying treatment using a spray dryer (GB-210, manufactured by Yamato Scientific Co., Ltd.) to obtain a powder formulation F-3. When the moisture content of the obtained powder formulation was measured with a Karl Fischer moisture meter, it was 1.1% by mass.

[0110] [Example 54] To 150 parts by mass of the aqueous dispersion S-31, 45 parts by mass of trehalose (Treha, manufactured by Hayashibara Co., Ltd.) was added, and the mixture was stirred for 1 hour. The stirred liquid was spray-dried using a spray dryer (GB-210, manufactured by Yamato Scientific Co., Ltd.) to obtain a powder formulation F-4. When the moisture content of the obtained powder formulation was measured with a Karl Fischer moisture meter, it was 1.4% by mass.

[0111] [Example 55] To 150 parts by mass of the aqueous dispersion S-52, 45 parts by mass of trehalose (Treha, manufactured by Hayashibara Co., Ltd.) was added, and the mixture was stirred for 1 hour. The stirred liquid was freeze-dried using a freeze dryer (FDU-1200, manufactured by Tokyo Rika Kikai Co., Ltd.) to obtain a powder formulation F-5. When the moisture content of the obtained powder formulation was measured with a Karl Fischer moisture meter, it was 0.9% by mass. [Example 56] To 150 parts by mass of the aqueous dispersion S-52, 45 parts by mass of lactose (Whey, manufactured by Viatris Pharma Co., Ltd.) was added, and the mixture was stirred for 1 hour. The stirred liquid was freeze-dried using a freeze dryer (FDU-1200, manufactured by Tokyo Rika Kikai Co., Ltd.) to obtain a powder formulation F-6. When the moisture content of the obtained powder formulation was measured with a Karl Fischer moisture meter, it was 1.5% by mass. [Example 57] To 150 parts by mass of the aqueous dispersion S-52, 45 parts by mass of dextrin (Pine Dex #2, manufactured by Matsutani Chemical Co., Ltd.) was added, and the mixture was stirred for 1 hour. The stirred liquid was freeze-dried using a freeze dryer (FDU-1200, manufactured by Tokyo Rika Kikai Co., Ltd.) to obtain a powder formulation F-7. When the moisture content of the obtained powder formulation was measured with a Karl Fischer moisture meter, it was 1.7% by mass.

[0112] [Evaluation of Powder Formulations Using Aqueous Dispersion Compositions] Subsequently, the redispersibility of the powder formulation in water was evaluated. 100 parts by mass of water was added to a beaker, and 0.1 part by mass of the powder formulation or untreated resveratrol or pterostilbene was added, followed by stirring at 500 rpm for 1 hour with a stirring blade to disperse the particles in the powder formulation in water. As the evaluation of the aqueous redispersion, the dispersion state of the particles was visually confirmed, and the particle size distribution was evaluated using a particle size distribution measuring device ("Microtrac UPA" manufactured by Nikkiso Co., Ltd.). The visual evaluation criteria were the same as those described in Tables 2 to 4. The results are shown in Table 5. Sedimentation was observed in the solid particles (A) containing untreated resveratrol or its analogs, whereas no sedimentation was observed in the powder formulation of the present invention, and all had good redispersibility in water. Among them, F-2 to 7 to which excipients were added had few foreign substances even in visual evaluation, and the average particle diameter before drying could be reproduced, resulting in good redispersibility in water.

[0113] [Table 5] [Industrial Applicability]

[0114] This composition can be used in various applications such as foods, cosmetics, pharmaceuticals, and quasi-drugs using an aqueous dispersion composition containing solid particles containing at least one selected from the group consisting of resveratrol and its analogs.

Claims

1. An aqueous dispersion composition comprising at least solid particles (A), a dispersion aid (B), and an aqueous medium (C), The solid particles (A) contain at least one selected from the group consisting of resveratrol and its analogues, The aqueous dispersion composition, wherein the dispersing aid (B) contains at least one selected from the group consisting of phospholipids, saponin, sucrose fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, polyoxyethylene phytosterols, polysaccharides, sugar derivatives, polyvinylpyrrolidone, polyvinyl alcohol, and enzyme-treated products.

2. 2. The aqueous dispersion composition according to claim 1, wherein the solid particles (A) contain at least one selected from the group consisting of resveratrol, pterostilbene, rhapontigenin, isorhapontigenin, piceatannol, and pinostilbene.

3. The aqueous dispersion composition according to claim 1, wherein the dispersion aid (B) contains at least one selected from the group consisting of lecithin, saponin, sucrose fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, gum arabic, xanthan gum, γ-cyclodextrin, polyvinylpyrrolidone, polyvinyl alcohol, enzyme-treated stevia, enzyme-treated rutin, enzyme-treated naringin, and enzyme-treated hesperidin.

4. The aqueous dispersion composition according to claim 1, further comprising an oil (D).

5. 2. The aqueous dispersion composition according to claim 1, wherein the solid particles (A) have an average particle size of 500 nm or less.

6. 2. The aqueous dispersion composition according to claim 1, wherein a mass ratio of the solid particles (A) to the dispersing aid (B) is from 1:1 to 2.5:

1.

7. The aqueous dispersion composition according to claim 1 , wherein the solid particles (A) are products of a wet milling process.

8. At least the solid particles (A) contain at least one selected from the group consisting of resveratrol and its analogues and a water-soluble organic solvent (E); The water-soluble organic solvent (E) satisfies the following (i) to (iii), (i) The molecular weight is 90 to 350. (ii) It has at least two functional groups selected from the group consisting of a hydroxyl group, an ester group, and a carboxyl group. (iii) The viscosity at 60°C is 2 to 150 mPa·s.

2. The aqueous dispersion composition according to claim 1, wherein the content of the water-soluble organic solvent (E) is 0.003 to 0.3 parts by mass based on 100 parts by mass of the solid particles (A).

9. 9. The aqueous dispersion composition according to claim 8, wherein the water-soluble organic solvent (E) comprises at least one selected from the group consisting of diacetin, triacetin, lactic acid, tripropionin, tributyrin, triethyl citrate, and acetyltriethyl citrate.

10. 2. The aqueous dispersion composition according to claim 1, which is a product treated with an ultrasonic wave, a homogenizer, or a bead mill.

11. A food product comprising the aqueous dispersion composition according to any one of claims 1 to 10.

12. A cosmetic preparation comprising the aqueous dispersion composition according to any one of claims 1 to 10.

13. A pharmaceutical comprising the aqueous dispersion composition according to any one of claims 1 to 10.

14. A method for producing the aqueous dispersion composition according to any one of claims 1 to 10, comprising the steps of: A method for producing an aqueous dispersion composition, comprising dispersing solid particles (A), a dispersing aid (B) and an aqueous medium (C) by ultrasonic dispersion, homogenizer dispersion or bead mill dispersion to obtain an aqueous dispersion composition.

15. A method for producing a powder formulation, comprising drying the aqueous dispersion composition according to any one of claims 1 to 10.

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