Aqueous solution containing urolithins and method for producing the same

Abstract

To provide an aqueous solution containing urolithins and a method for producing the same, which enable poorly water-soluble urolithins to be contained at a high concentration and dispersed stably in water.SOLUTION: The above problem can be solved by a urolithin-containing aqueous solution containing 1-17 mass% of urolithins, 3-13 mass% of polyglycerin fatty acid ester (stearic acid), 2-7 mass% of lysolecithin, and 11-16 mass% of glycerin.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an aqueous solution containing urolithins and a method for producing the same. [Background technology]

[0002] Urolithins, represented by urolithin A, are known as metabolites of ellagic acid, which is derived from ellagitannins found in pomegranates, raspberries, blackberries, cloudberries, strawberries, walnuts, etc. Ellagitannins are classified as hydrolyzable tannins, and are known to be hydrolyzed in the body and converted into ellagic acid when ingested. Ellagitannins and ellagic acid are said to have very low intestinal absorption in the body, but when ingested, they are known to be further metabolized by the human colonic microflora and converted into urolithins.

[0003] Among urolithins, urolithin A is known to have various beneficial effects, including antioxidant, anti-inflammatory, and anti-glycation effects, and is one of the important compounds in the body. However, because intestinal flora varies from person to person and changes depending on the environment, some people are unable to produce urolithin A. Therefore, there is a need to add urolithins to the raw materials of cosmetics, foods, beverages, and pharmaceuticals, as well as to processed products made from these ingredients.

[0004] Methods for stably incorporating urolithins into formulations include a method of stabilizing urolithins in an aqueous solution using the action of cyclodextrin, as described in Patent Document 1. However, the total concentration of urolithins in the urolithin-containing aqueous solution described in Patent Document 1 is at most about 4 mM, which is not sufficient from the perspective of applying the formulation to a wide range of product forms. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent No. 6787633 Summary of the Invention [Problem to be solved by the invention]

[0006] Patent Document 1 discloses an aqueous solution containing urolithins stably blended therein; however, there has been a need for an aqueous solution containing urolithins with an increased concentration of poorly water-soluble urolithins so that it can be used in a wider range of product forms. Furthermore, in the process of applying poorly water-soluble urolithins to a wide range of product forms, for example, in the production processes of beverages such as juices and sports drinks, and processed foods containing water, aqueous solutions containing urolithins may be exposed to high-temperature and acidic conditions. Therefore, there has been a need for an aqueous solution containing urolithins that can be stably and easily dispersed in water even under high-temperature and acidic conditions. In view of the above, an object of the present invention is to provide an aqueous solution containing poorly water-soluble urolithins at a high concentration, which can be stably dispersed in water, and a method for producing the same. [Means for solving the problem]

[0007] The present invention relates to the following. [1] A urolithin-containing aqueous solution containing urolithins, a polyglycerol fatty acid ester (stearic acid), lysolecithin, and glycerin. [2] The urolithin-containing aqueous solution according to [1] contains, based on the total mass of the urolithin-containing aqueous solution, 1 to 17% by mass of urolithins, 3 to 13% by mass of polyglycerol fatty acid ester (stearic acid), 2 to 7% by mass of lysolecithin, and 11 to 16% by mass of glycerin. [3] The urolithin-containing aqueous solution according to [2], wherein the urolithin is urolithin A. [4] The urolithin-containing aqueous solution according to [2] or [3], wherein the polyglycerol fatty acid ester (stearic acid) has an HLB value of 11 to 16. [5] The urolithin-containing aqueous solution according to any one of [2] to [4], further comprising at least one selected from the group consisting of sodium chloride, potassium carbonate, and ethanol. [6] The urolithin-containing aqueous solution according to any one of [2] to [5], further comprising deionized water. [7] A food or drink comprising the aqueous solution containing urolithins described in [6]. [8] A method for producing an aqueous solution containing urolithins, comprising the steps of preparing a solution containing urolithins, polyglycerol fatty acid ester (stearic acid), lysolecithin, glycerin, sodium chloride, potassium carbonate, and water; stirring the solution at 80 to 100°C to obtain a mixed solution; cooling the mixed solution and then adding ethanol to the mixed solution to obtain a slurry; and wet-pulverizing the slurry to obtain an aqueous solution containing urolithins. [9] The method for producing an aqueous solution containing urolithins according to [8], wherein in the step of preparing the solution, 1 to 17% by mass of urolithins, 3 to 13% by mass of polyglycerol fatty acid ester (stearic acid), 2 to 7% by mass of lysolecithin, and 11 to 16% by mass of glycerin are mixed together, based on the total mass of the aqueous solution containing urolithins.

[10] The method for producing an aqueous solution containing urolithins according to [9], wherein the urolithins are urolithin A.

[11] The urolithin-containing aqueous solution according to any one of [8] to

[10] , wherein the polyglycerol fatty acid ester (stearic acid) has an HLB of 11 to 15.

[12] The method for producing an aqueous solution containing urolithins according to any one of [8] to

[11] , wherein at least one selected from the group consisting of sodium chloride, potassium carbonate, and ethanol is further added in the step of preparing the solution. [Effects of the Invention]

[0008] The present invention provides an aqueous solution containing poorly water-soluble urolithins at a high concentration and capable of being stably dispersed in water, and a method for producing the same. DETAILED DESCRIPTION OF THE INVENTION

[0009] The present invention will be described below with reference to embodiments, but the present invention is not limited to the following embodiments.

[0010] (Urolithin-containing aqueous solution) The urolithin-containing aqueous solution contains urolithins, polyglycerol fatty acid ester (stearic acid), lysolecithin, and glycerin.

[0011] (urolithins) The urolithin-containing aqueous solution contains urolithins. Urolithins are not particularly limited, but are substances whose structure is represented by the following general formula (1). Furthermore, as shown in Table 1, urolithins include, depending on R1 to R6 in the chemical formula, urolithin A, urolithin B, urolithin C, urolithin D, urolithin E, urolithin M3, urolithin M4, urolithin M5, urolithin M6, urolithin M7, and isourolithin A. Any one of the urolithins may be used alone, or two or more may be used in combination. Among these, urolithin A is preferred.

[0012] The content of urolithins is preferably 1% by mass to 17% by mass, more preferably 1% by mass to 13% by mass, even more preferably 2% by mass to 7% by mass, and most preferably 3% by mass to 7% by mass, based on the total mass of the urolithins-containing aqueous solution.

[0013] [ka]

[0014] [Table 1]

[0015] The method for obtaining urolithins is not particularly limited, and commercially available products may be used, or urolithins may be synthesized by chemical synthesis. Examples of commercially available urolithins include urolithin A, urolithin B, urolithin C, and urolithin D (manufactured by Dalton Pharma). Chemical synthesis can be carried out according to a conventional method, for example, by using 2-bromo-5-methoxybenzoic acid and aluminum chloride as raw materials.

[0016] Alternatively, punicalagin, a type of ellagitannin, may be extracted from plants and hydrolyzed to ellagic acid, or ellagic acid may be extracted and then converted into urolithins using microorganisms. The type of plant is not particularly limited, and examples include pomegranate, raspberry, blackberry, cloudberry, boysenberry, strawberry, walnut, Geranium herb, etc. Among these, pomegranate, boysenberry, and Geranium herb are preferred, with pomegranate being more preferred, because they contain a high amount of ellagitannin and / or ellagic acid. These plants may be used alone or in combination of two or more. The extraction method and conditions from the plants are not particularly limited and may be conventional. For example, known extraction methods such as water extraction, hot water extraction, warm water extraction, alcohol extraction, and supercritical extraction may be used.

[0017] When solvent extraction is performed, examples of the solvent include water; alcohols (whether anhydrous or hydrous) such as lower alcohols such as methanol and ethanol, and polyhydric alcohols such as propylene glycol and 1,3-butylene glycol; ketones such as acetone; esters such as diethyl ether, dioxane, acetonitrile and ethyl acetate; xylene; and preferably water, ethanol, etc. These solvents may be used alone or in combination of two or more.

[0018] The method for hydrolyzing the extracted ellagitannins such as punicalagin into ellagic acid is not particularly limited, but examples include methods of hydrolysis using acids, enzymes, and microorganisms.

[0019] The method for converting ellagic acid into urolithins using a microorganism is not particularly limited, and for example, a known method described in Food Funct., 5, 8, 1779-1784 (2014) can be used.

[0020] The obtained urolithins can be used as is, or may be dried and used in powder form. Furthermore, if necessary, the obtained urolithins may be subjected to purification, concentration, or other treatments. Purification treatments include filtration, adsorption using ion exchange resins or activated carbon columns, and decolorization. Concentration treatments can be performed using conventional methods such as an evaporator.

[0021] Alternatively, the obtained urolithins (or purified or concentrated products) may be powdered according to known methods, such as freeze-drying to obtain a powder, or adding an excipient such as dextrin, corn starch, or gum arabic and then spray-drying to obtain a powder. The resulting product may then be dissolved in pure water, ethanol, or the like, as needed, for use.

[0022] (Polyglycerol fatty acid ester) The polyglycerol fatty acid ester is an ester of polyglycerol having an average degree of polymerization of 2 or more, preferably 2 to 10, and a fatty acid having 8 to 18 carbon atoms (for example, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, or linoleic acid). The number of fatty acids added to polyglycerol is a minimum of 1 and a maximum of 2 plus the degree of polymerization of polyglycerol.

[0023] Preferred examples of polyglycerol fatty acid esters include hexaglycerol monooleate, hexaglycerol monostearate, hexaglycerol monopalmitate, hexaglycerol monomyristate, hexaglycerol monolaurate, decaglycerol monooleate, decaglycerol monostearate, decaglycerol monopalmitate, decaglycerol monomyristate, and decaglycerol monolaurate. Any one of these may be used alone, or two or more may be used in combination. Decaglycerol monostearate is particularly preferred.

[0024] Any polyglycerol fatty acid ester can be used as long as it is suitable for use in food products, but an HLB value of 10 to 16 is preferred, 11 to 16 is more preferred, 11 to 15 is even more preferred, and 12 to 15 is most preferred. Here, HLB indicates the hydrophilic-hydrophobic balance used in the field of surfactants, and for example, the following calculation formula (Kawakami formula) can be used. HLB = 7 + 11.7 log(MW / MO) Here, MW is the molecular weight of the hydrophilic group, and MO is the molecular weight of the hydrophobic group. Alternatively, the HLB value listed in a catalog or the like may be used.

[0025] The content of polyglycerol fatty acid ester is not particularly limited as long as it does not affect the properties of the formulation, but is preferably 3% to 13% by mass, more preferably 3% to 10% by mass, and even more preferably 3% to 8% by mass, based on the total mass of the urolithin-containing aqueous solution. If it is less than 3% by mass, dispersion cannot be maintained and solidification is likely to occur, while if it exceeds 13% by mass, the viscosity increases and the grinding efficiency decreases.

[0026] (lysolecithin) Lysolecithin derived from soybeans or egg yolks can be used, with soybean-derived lysolecithin being preferred. Any of crude lysolecithin, purified lysolecithin, fractionated lysolecithin, enzyme-modified lysolecithin, etc. may also be used.

[0027] The content of lysolecithin is not particularly limited as long as it does not affect the properties of the formulation, but is preferably 2% to 7% by mass, more preferably 2% to 6% by mass, and even more preferably 2% to 5% by mass, based on the total mass of the urolithin-containing aqueous solution. If it is less than 2% by mass, the stability of the acidic diluted solution will be reduced, and if it exceeds 7% by mass, the viscosity will increase and the grinding efficiency will be reduced.

[0028] (glycerin) The glycerin content is preferably 10% to 20% by mass, more preferably 10% to 18% by mass, and even more preferably 11% to 16% by mass, based on the total mass of the urolithin-containing aqueous solution. If the content is less than 10% by mass, the stability of the acidic diluted solution will be reduced, and if it exceeds 20% by mass, the viscosity will increase and the grinding efficiency will be reduced.

[0029] (inorganic salts) The inorganic salts are not particularly limited, but examples thereof include sodium bicarbonate, potassium carbonate, sodium chloride, magnesium chloride, etc., which are used for food and are readily available and economical. Potassium carbonate and sodium chloride are preferred. These salts may be used alone or in combination. The amount of inorganic salts to be added is not particularly limited, but is preferably 0.5% by mass or less based on the total mass of the urolithin-containing aqueous solution. Addition of more than 0.5% by mass may adversely affect the stability, viscosity, etc. of the formulation.

[0030] (water) Various types of water can be used without any particular limitation. For example, tap water or deionized water can be used. From the standpoints of economy and ease of use, tap water is preferred. From the standpoint of stability of the resulting aqueous solution containing urolithins, deionized water is preferred. This is because, compared to when tap water is used, the average particle size of the aqueous solution containing urolithins tends to be smaller and stability tends to be improved.

[0031] (others) For the aqueous dispersion of urolithins, ethanol and known additive materials can be used depending on the intended use and form, as long as they do not impair the effects of the invention. Examples of known additives include known excipients, flavorings, colorings, emulsifiers, stabilizers, thickeners, enzymes, preservatives, antibacterial agents, lubricants, surfactants, disintegrants, disintegration inhibitors, binders, absorption enhancers, adsorbents, humectants, solubilizers, preservatives, flavors, sweeteners, and UV absorbers. These additives can be blended as needed within a range that does not impair the effects described above. There are no particular limitations on the amount of these additives, as long as they are within a commonly used range.

[0032] (Uses of aqueous solutions containing urolithins) Aqueous solutions containing urolithins can be used as cosmetics, quasi-drugs, medical supplies, hygiene products, pharmaceuticals, foods and beverages, supplements, etc. The actions of urolithins are expected to provide antioxidant, anti-inflammatory, anti-glycation, and other effects. After being diluted with water, the urolithin-containing aqueous solution has excellent dispersibility in water and stability even under high-temperature and acidic conditions, and can therefore be used in the aforementioned fields even under high-temperature and acidic conditions.

[0033] (cosmetics) When an aqueous solution containing urolithins is used as a cosmetic ingredient, it can be prepared into a variety of desired forms, including liquids such as aqueous solutions, lotions, sprays, suspensions, and emulsions; solids such as powders, granules, and blocks; semisolids such as creams and pastes; and gels. Such cosmetics are useful as a variety of cosmetics, including face washes, emulsions, creams, gels, essences (serums), packs, masks, and other basic cosmetics, makeup cosmetics such as foundations and lipsticks, oral cosmetics, fragrance cosmetics, hair cosmetics, and body cosmetics.

[0034] These cosmetics can be manufactured according to conventional methods. The amount, method, and timing of incorporation of the urolithin-containing aqueous solution into the cosmetics can be selected as appropriate. Furthermore, the cosmetics can be packaged in appropriate containers such as bottles, bags, cans, spray cans, spray containers, boxes, and packs, as needed.

[0035] When the urolithin-containing aqueous solution is used as a cosmetic ingredient, the amount of the urolithin-containing aqueous solution relative to the total amount of the cosmetic is not particularly limited as long as the above-mentioned effects are achieved; however, the total amount of urolithins is typically 0.0001 to 1% by mass, preferably 0.0005 to 0.1% by mass, and more preferably 0.001 to 0.05% by mass.

[0036] When the urolithin-containing aqueous solution is used as a cosmetic ingredient, commonly used known ingredients can be added as appropriate. For example, anionic surfactants (fatty acid soaps, sulfonate-type anionic surfactants, sulfate ester-type anionic surfactants, phosphate ester-type anionic surfactants, acylmethyl taurate salts, monoalkyl phosphates, acyl glutamates, isethionate ester salts, etc.), cationic surfactants (amine salt-type cationic surfactants, quaternary ammonium-type cationic surfactants (tetraalkylammonium type, pyridinium type), nonionic surfactants (glycerin fatty acid esters, propylene glycol fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene sorbitan tetraoleate, polyoxyethylene alkyl ethers, polyoxyethylene polyoxypropylene glycol, polyoxyethylene polyoxypropylene alkyl ethers, polyethylene glycol fatty acid esters, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyglycerin fatty acid esters, etc.), amphoteric surfactants (imidazoline type, betaine type, amino acid type), natural and synthetic surfactants such as fluorine-based surfactants and silicone-based surfactants, alginic acid Sodium, propylene glycol alginate, gum arabic, xanthan gum, pectin, tragacanth, sodium carboxymethylcellulose, methylcellulose, carboxyvinyl polymer, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, cationized cellulose, cationized dextran, cationized dextrin, chitosan, cationized vinylpyrrolidone polymer, N,N-dimethyl-3,5-methylenepiperidinium chloride polymer, milk protein, soy protein, gelatin, egg protein, sodium caseinate, Water-soluble polymers such as whey protein, ginkgo, centella, angelica, ginseng, chickweed, kaempferia, inchiko, yashatsu, licorice fraction, gokahi, senpukuka, hikai, yuzuha, chamomile, horse chestnut, escin, terminalia, ruscogenin, butcher's broom, kola, guarana, mate, coffee, cacao, plectranthus, danshen, visnaga, silymarin, leucocyanin, St. John's wort, bear's goby, perilla, Scutellaria root, kaempferia, rosemary, sage, thyme, mugwort, artemisia capillaris, atractylodes, yarrow, lithospermum root, fennel,Plant ingredients such as Phellodendron bark, Ginger, Angelica sinensis, Cnidium rhododendron, Tibetan valerian, Angelica acutiloba, Spruce, Peony, Safflower, Iris, Poria cocos, and Mint, succinic acid, fumaric acid, citric acid, pyruvic acid, glucuronic acid, 2-hydroxybutyric acid, lactic acid, malic acid, tartaric acid, tartronic acid, methyl pyruvate, ethyl pyruvate, vitamin A acid, vitamin C derivatives, vitamin D, vitamin E, oligopeptides, and tranexamic acid esters, polyhydric alcohols, amino acids, mucopolysaccharides, proteins, biological extracts, fermentation metabolites, polysaccharides, plant extracts, and phospholipids , anti-glycation agents such as ceramide, oils and fats (natural oils and fats such as soybean oil, rice bran oil, jojoba oil, avocado oil, almond oil, cacao oil, olive oil, sesame oil, persic oil, castor oil, palm oil, mink oil, beef tallow, lard, etc., hardened oils obtained by hydrogenating these natural oils and fats, and synthetic triglycerides and diglycerides such as myristate glyceride and 2-ethylhexanoate glyceride), waxes (carnauba wax, whale wax, beeswax, lanolin, etc.), hydrocarbons (liquid paraffin, petrolatum, paraffin, microcrystalline wax, ceresin, squalane, pristine Tan, etc.), higher fatty acids (lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, lanolinic acid, isostearic acid, etc.), higher alcohols (lauryl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, cholesterol, 2-hexyldecanol, etc.), esters (cetyl octanoate, myristyl lactate, cetyl lactate, isopropyl myristate, myristyl myristate, isopropyl palmitate, isopropyl adipate, butyl stearate, olein Decyl isostearate, cholestyl isostearate, etc.), essential oils (peppermint oil, jasmine oil, columbine oil, cypress oil, spruce oil, lychee oil, turpentine oil, cinnamon oil, bergamot oil, mandarin oil, sage oil, bay oil, clove oil, hiba oil, rose oil, eucalyptus oil, lemon oil, peppermint oil, thyme oil, rose oil, sage oil, menthol, cineole, eugenol, citral, citronellal, borneol, linalool, geraniol, camphor, thymol, spilanthol, pinene, limonene, terpene compounds, etc.),Silicone oils and other oil and fat components (emollient components), sodium carbonate, sodium bicarbonate, sodium sesquicarbonate, borax, sodium sulfate, sodium sulfide, sodium nitrate, sodium thiosulfate, sodium polyphosphate, sodium phosphate, potassium chloride, potassium sulfide, calcium oxide, magnesium oxide, calcium carbonate, magnesium carbonate and other inorganic salts, boric acid, metasilicic acid, silicic anhydride and other inorganic acids, Yellow No. 4, Blue No. 1, Yellow No. 202, chlorophyll, riboflavin, safflower, crocin, anthraquinone, etc. Examples of suitable ingredients include pigments, fragrances, polymers such as acrylic resin, styrene resin, epoxy resin, nylon, polyethylene, polypropylene, polyvinyl chloride, polyethylene terephthalate resin, and polytetrafluoroethane, copolymers of these polymers, fine powders such as silicic acid, calcium silicate, natural aluminum silicate, synthetic aluminum silicate, zeolite, titanium oxide, talc, kaolin, mica, and bentonite, sulfur, hot spring deposits, mineral sand, mica powder, neutral clay, roasted bran, disinfectants, preservatives, and other ingredients required for formulation.

[0037] (food and drink) When the urolithin-containing aqueous solution is used as a food ingredient, it can be used as a general food, as well as a food for specified health uses, a nutritional supplement, a functional food, a food for the sick, a food additive, etc. Examples of food forms that contain the aqueous solution include soft drinks, milk, pudding, jelly, candy, chewing gum, gummy candy, yogurt, chocolate, soup, cookies, snacks, ice cream, popsicles, bread, cake, cream puffs, ham, meat sauce, curry, stew, cheese, butter, dressing, etc.

[0038] Urolithin-containing aqueous solutions can be used with water, proteins, carbohydrates, lipids, vitamins, minerals, organic acids, organic bases, fruit juice, flavors, and the like as their main components. Examples of proteins include animal and vegetable proteins such as whole milk powder, skim milk powder, partially skim milk powder, casein, soy protein, egg protein, and meat protein, as well as hydrolysates thereof and butter. Examples of carbohydrates include sugars, modified starch (dextrin, soluble starch, British starch, oxidized starch, starch ester, starch ether, and the like), and dietary fiber. Examples of lipids include vegetable oils and fats such as lard, safflower oil, corn oil, rapeseed oil, palm oil, fractionated oils thereof, hydrogenated oils, and interesterified oils. Examples of vitamins include vitamin A, carotenes, B vitamins, vitamin C, D vitamins, vitamin E, K vitamins, vitamin P, vitamin Q, niacin, nicotinic acid, pantothenic acid, biotin, inositol, choline, and folic acid. Examples of minerals include calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, selenium, and whey minerals. Examples of organic acids include malic acid, citric acid, lactic acid, and tartaric acid. Two or more of these ingredients may be used in combination, and synthetic products and / or foods containing large amounts of these ingredients may also be used.

[0039] When using the urolithin-containing aqueous solution as a food ingredient, it can be produced according to conventional methods. The amount, method, and timing of incorporation into the food can be selected as appropriate. Furthermore, the solution can be packaged in an appropriate container such as a bottle, bag, can, box, or pack, as needed.

[0040] When an aqueous solution containing urolithins is used as a food ingredient, the amount of the aqueous solution relative to the total amount of the food is not particularly limited as long as the above-mentioned effects are exhibited; however, the total amount of urolithins is typically 0.0001 to 10% by mass, preferably 0.001 to 1% by mass, and more preferably 0.01 to 0.1% by mass.

[0041] (supplement) Supplements are a food category consisting of dietary supplements, and in this specification refer to functional auxiliary substances that can provide antioxidant, anti-inflammatory, anti-glycation, etc. When used as a supplement material, the urolithin-containing aqueous solution can be in the form of a solid, gel, or liquid, such as various processed foods and beverages, powders, tablets, pills, capsules, jellies, or granules.

[0042] When used as a supplement material, the urolithin-containing aqueous solution may contain additives such as excipients such as dextrin, preservatives such as vitamin C, flavorings such as vanillin, pigments such as safflower pigment, monosaccharides, oligosaccharides, and polysaccharides (e.g., glucose, fructose, sucrose, saccharose, and carbohydrates containing these), acidulants, flavorings, oils and fats, emulsifiers, whole milk powder, or agar. Two or more of these ingredients may be used in combination, and the solution may contain synthetic products and / or a high content of these.

[0043] When the urolithin-containing aqueous solution is used as a material for a supplement, it can be produced according to a conventional method. The amount, method, and timing of incorporation into the supplement can be selected as appropriate. Furthermore, the solution can be packaged in an appropriate container such as a bottle, bag, can, box, or pack, as needed.

[0044] When an aqueous solution containing urolithins is used as a material for a supplement, the content of the aqueous solution relative to the total amount of the supplement is not particularly limited as long as the above-mentioned effects are exerted; however, the total amount of urolithins is typically 0.0001 to 10% by mass, preferably 0.0005 to 1% by mass, and more preferably 0.001 to 0.1% by mass.

[0045] (display) Cosmetics, quasi-drugs, medical supplies, hygiene products, pharmaceuticals, foods, supplements, etc. that use aqueous solutions containing urolithins may be sold with a label indicating that they are used for antioxidant, anti-inflammatory, anti-glycation, etc.

[0046] The term "labeling" as used above refers to any act intended to inform consumers of the intended use. Any labeling that evokes or infers the intended use falls under this definition, regardless of the purpose, content, object, or medium of labeling. However, it is preferable to label in a manner that directly identifies the intended use to consumers. Specifically, examples include the act of indicating the intended use on products or product packaging, such as cosmetics, quasi-drugs, medical supplies, sanitary products, pharmaceuticals, food, and supplements; the act of transferring, delivering, displaying for transfer or delivery, or importing products or product packaging that indicate the intended use; the act of displaying or distributing product advertisements, price lists, or transaction documents that indicate the intended use; and the act of indicating the intended use in information containing the above content and providing it via electromagnetic means (such as the Internet).

[0047] On the other hand, it is preferable that the display be one approved by the government or the like (for example, a display approved based on various systems established by the government and made in a manner based on such approval), and it is particularly preferable that the display be on promotional materials at the point of sale such as packaging, containers, catalogs, pamphlets, POP, and other documents.

[0048] Furthermore, for example, in the case of a food that uses an aqueous solution containing urolithins, examples of the labeling include health foods, functional foods, foods for special dietary uses, foods with nutrient function claims, and quasi-drugs, as well as other labeling approved by the Ministry of Health, Labor and Welfare, such as foods for specified health uses and labeling approved under similar systems. Examples of the latter include labeling as foods for specified health uses, labeling as conditional foods for specified health uses, labeling indicating an effect on the structure or function of the body, and labeling for disease risk reduction. In more detail, typical examples include labeling as foods for specified health uses (particularly labeling for health uses) as defined in the Enforcement Regulations of the Health Promotion Act (Ministry of Health, Labor and Welfare Ordinance No. 86 of April 30, 2003) and similar labeling.

[0049] (Method of producing an aqueous solution containing urolithins) The method for producing an aqueous solution containing urolithins includes the steps of: preparing a solution containing urolithins, a polyglycerol fatty acid ester (stearic acid), lysolecithin, glycerin, sodium chloride, potassium carbonate, and water; and stirring the solution at 80 to 100°C to obtain a mixed solution. The method includes a step of cooling the mixed liquid and then adding ethanol to the mixed liquid to obtain a slurry, and a wet-pulverization step of wet-pulverizing the slurry to obtain an aqueous solution containing urolithins.

[0050] The machinery used to produce the urolithin-containing aqueous solution is not particularly limited, and machines such as mixers, agitators, dispersers, homomixers, homogenizers, high-pressure homogenizers, ultra-high-pressure homogenizers, ball mills, colloid mills, planetary mills, wet OB mills, rotary grinders, kneaders, kneaders, spray dryers, vacuum dryers, freeze dryers, and vibrating sieves can be used alone or in combination.

[0051] (Mixing process) In the mixing step, it is preferable to use a homomixer. The stirring temperature of the homomixer is preferably 80°C to 100°C, more preferably 80°C to 95°C, and even more preferably 80°C to 90°C. The rotation speed of the homomixer (manufactured by Primix Corporation, device name "TK Robomix", model number "MARKII2.5 type") is preferably 7000 rpm to 16000 rpm, more preferably 7000 rpm to 12000 rpm, and even more preferably 8000 rpm to 9000 rpm.

[0052] (Wet grinding process) In the step of wet-pulverizing the slurry to obtain a urolithin-containing aqueous solution, a practical wet mill is, for example, a bead mill, which uses beads as a milling medium to mill urolithin-containing particles suspended in water. The milling conditions vary depending on the state of the raw material for the urolithin-containing particles, the material and size of the beads, the bead packing ratio, and the mill operating conditions, and therefore cannot be generally determined. However, optimal conditions can be easily found by examining changes in particle size through experiments. The bead diameter is preferably 1 mm.

[0053] (Measurement of average particle size) The device used to measure the average particle size is not particularly limited, and for example, ELS-Z manufactured by Otsuka Electronics Co., Ltd. or SALD2300 manufactured by Shimadzu Corporation can be used.

[0054] With regard to other matters regarding the method for producing an aqueous solution containing urolithins, the explanation given for the aqueous solution containing urolithins applies.

[0055] (Modification of the method for producing an aqueous solution containing urolithins) In the above-described method for producing an aqueous solution containing urolithins, the components of Solution A and Solution B were prepared separately, and then Solution A and Solution B were mixed. However, the method for producing an aqueous solution containing urolithins is not limited to this, and, for example, all of the components may be mixed at once.

[0056] (Other embodiments) As described above, the present invention has been described by way of embodiments, but the statements that form part of this disclosure should not be understood as limiting the present invention. Various alternative embodiments, examples, and application techniques will become apparent to those skilled in the art from this disclosure. For example, a dry solid composition of an aqueous solution containing urolithins and a method for producing the same will be described as an example.

[0057] (Dry solid composition of aqueous solution containing urolithins and method for producing the same) The aqueous solution containing urolithins can be dried and used as a dry solid composition, as long as the effects of the invention are not impaired. The drying method is not particularly limited, and can be carried out using, for example, a known or commercially available droplet spray dryer such as a freeze dryer, spray dryer, or slurry dryer. In this case, the drying temperature of the droplet spray dryer is usually 250° C. or lower, more preferably 130° C. or lower. If necessary, the dried product can be subjected to treatments such as pulverization and classification, and may also be subjected to a molding process such as granulation.

[0058] (Uses of the dry solid composition of the aqueous solution containing urolithins) The dry solid composition can be used as cosmetics, quasi-drugs, medical supplies, hygiene products, pharmaceuticals, foods, supplements, etc. Due to the actions of urolithins, it is expected to provide antioxidant, anti-inflammatory, anti-glycation, and other effects. The description of the uses and forms of the urolithin-containing aqueous solution also applies to the uses and forms of the dry solid composition, and therefore, further description will be omitted here. As such, the present invention naturally includes various embodiments not described herein. Therefore, the technical scope of the present invention is defined only by the invention-specifying matters according to the scope of the claims that are appropriate from the above description. [Industrial Applicability]

[0059] According to the present invention, it is possible to provide a urolithin-containing aqueous solution containing a stable high concentration of urolithins, and to use the same in cosmetics, quasi-drugs, medical products, sanitary products, pharmaceuticals, foods, beverages, supplements, etc. Urolithins are substances that exhibit antioxidant, anti-inflammatory, anti-glycation, and other effects, and are expected to prevent skin aging and wrinkles, have whitening effects, and prevent symptoms such as metabolic syndrome and diabetes. Furthermore, because the present invention is dispersible in water even under high-temperature and acidic conditions and has excellent stability, urolithins can be effectively added and incorporated into beverages such as juices and sports drinks, and processed foods that contain water. [Example]

[0060] The present invention will be described in more detail below based on formulation examples and comparative examples. However, the scope of the present invention is not limited by these formulation examples and comparative examples. Formulation examples 1 to 13 correspond to working examples, and formulation examples 14 to 28 correspond to comparative examples.

[0061] (raw materials) In the examples, the following raw materials were used: Polyglycerin fatty acid ester (stearic acid) HLB: 12...Product name: "Sunsoft Q-18S", manufactured by Taiyo Kagaku Co., Ltd. Polyglycerin fatty acid ester (stearic acid) HLB: 15...Product name: "NIKKOL Decaglyn 1-50SV", manufactured by Nikko Chemicals Co., Ltd. Polyglycerin fatty acid ester (stearic acid) HLB: 9.5...Product name: "NIKKOL Decaglyn 2-SV", manufactured by Nikko Chemicals Co., Ltd. Polyglycerin fatty acid ester (palmitic acid) HLB: 12.5...Product name: "NIKKOL Decaglyn 1-PVEX", manufactured by Nikko Chemicals Co., Ltd. Lysolecithin: Product name: Elmizer A, manufactured by Kyowa Hakko Kogyo Co., Ltd. Sodium chloride: Product name: "Sodium chloride", manufactured by Nihonkaisui Co., Ltd. Potassium carbonate: Product name: "Potassium carbonate", manufactured by Asahi Glass Co., Ltd. Ethanol: Product name: "Specific Alcohol Traceable 99 Grade 1", manufactured by Japan Alcohol Sales Co., Ltd. Glycerin: Product name: "Food Additive Glycerin", manufactured by Sakamoto Pharmaceutical Co., Ltd.

[0062] (1) Preparation of urolithin A aqueous dispersion (Prescription Example 1) (Preparation of Component A) 11.0% by mass of glycerin, 5.3% by mass of polyglycerol fatty acid ester (stearic acid, HLB: 12), and 3.0% by mass of lysolecithin were placed in a container and heated to 80°C to dissolve. 3.1% by mass of urolithin A was then added and stirred to prepare Component A. (Preparation of Component B) Component B was prepared by placing 70.3% by mass of deionized water, 0.1% by mass of sodium chloride, and 0.2% by mass of potassium carbonate in a separate container and heating to 90°C to dissolve them. (Mixing with a homomixer) Component B was added to the container containing component A, and while maintaining the temperature at 90°C, the mixture was stirred with a homomixer at 8500 rpm for 15 minutes. (Cooling and adding ethanol) The slurry in the vessel was cooled to a temperature of 30°C, and then 7.0% by mass of ethanol was added to the vessel. (Wet grinding using a bead mill) The slurry was wet-milled at room temperature in a bead mill using beads with a diameter of 1 mm.

[0063] (Prescription example 2) The same procedure as in Formulation Example 1 was carried out, except that the amount of polyglycerol fatty acid ester (stearic acid, HLB: 12) in Formulation Example 1 was changed from 5.3% by mass to 3.5% by mass, the amount of lysolecithin was changed from 3.0% by mass to 2.0% by mass, and the amount of deionized water was changed from 70.3% by mass to 73.1% by mass.

[0064] (Prescription Example 3) The same procedure as in Formulation Example 1 was carried out, except that the polyglycerol fatty acid ester (stearic acid, HLB: 12) in Formulation Example 1 was changed from 5.3% by mass to 7.0% by mass, the lysolecithin was changed from 3.0% by mass to 4.0% by mass, and the deionized water was changed from 70.3% by mass to 67.6% by mass.

[0065] (Prescription Example 4) The same procedure as in Formulation Example 1 was carried out, except that the diameter of the beads in the bead mill in Formulation Example 1 was changed from 1 mm to 0.3 mm.

[0066] (Prescription Example 5) The same procedure as in Formulation Example 1 was carried out, except that the stirring temperature using the homomixer in Formulation Example 1 was changed from 90°C to 80°C.

[0067] (Prescription Example 6) The same procedure as in Formulation Example 1 was carried out, except that tap water was used instead of deionized water.

[0068] (Prescription Example 7) The same procedure as in Formulation Example 1 was carried out, except that the polyglycerol fatty acid ester (stearic acid, HLB: 12) in Formulation Example 1 was changed to polyglycerol fatty acid ester (stearic acid, HLB: 15).

[0069] (Prescription Example 8) The same procedure as in Formulation Example 1 was carried out, except that the glycerin content in Formulation Example 1 was changed from 11.0% by mass to 16.0% by mass, and deionized water was changed from 70.3% by mass to 65.3% by mass.

[0070] (Prescription Example 9) The same procedure as in Formulation Example 1 was performed, except that the amount of urolithin A in Formulation Example 1 was changed from 3.1% by mass to 6.2% by mass, and deionized water was changed from 70.3% by mass to 67.2% by mass.

[0071] (Prescription Example 10) The same procedure as in Formulation Example 1 was performed, except that the urolithin A in Formulation Example 1 was changed from 3.1% by mass to 10.0% by mass, the polyglycerol fatty acid ester (stearic acid, HLB: 12) was changed from 5.3% by mass to 13.0% by mass, the lysolecithin was changed from 3.0% by mass to 7.0% by mass, the ethanol was changed from 7.0% by mass to 6.0% by mass, and the deionized water was changed from 70.3% by mass to 52.7% by mass.

[0072] (Prescription Example 11) The same procedure as in Formulation Example 1 was performed, except that the urolithin A in Formulation Example 1 was changed from 3.1% by mass to 12.0% by mass, the polyglycerol fatty acid ester (stearic acid, HLB: 12) was changed from 5.3% by mass to 13.0% by mass, the lysolecithin was changed from 3.0% by mass to 7.0% by mass, the ethanol was changed from 7.0% by mass to 6.0% by mass, and the deionized water was changed from 70.3% by mass to 50.7% by mass.

[0073] (Prescription Example 12) The same procedures as in Formulation Example 1 were performed, except that the urolithin A in Formulation Example 1 was changed from 3.1% by mass to 15.0% by mass, the polyglycerol fatty acid ester (stearic acid, HLB: 12) was changed from 5.3% by mass to 13.0% by mass, the lysolecithin was changed from 3.0% by mass to 7.0% by mass, the ethanol was changed from 7.0% by mass to 6.0% by mass, and the deionized water was changed from 70.3% by mass to 47.7% by mass.

[0074] (Prescription Example 13) The same procedures as in Formulation Example 1 were performed, except that the urolithin A in Formulation Example 1 was changed from 3.1% by mass to 17.0% by mass, the polyglycerol fatty acid ester (stearic acid, HLB: 12) was changed from 5.3% by mass to 13.0% by mass, the lysolecithin was changed from 3.0% by mass to 7.0% by mass, the ethanol was changed from 7.0% by mass to 6.0% by mass, and the deionized water was changed from 70.3% by mass to 45.7% by mass.

[0075] (Prescription Example 14) (Preparation of ingredients) 50.0 mass% of glycerin, 2.0 mass% of lysolecithin, 2.0 mass% of urolithin A, and 46.0 mass% of deionized water were placed in a container, heated to 80°C, stirred, and dissolved. (Mixing with a homomixer) While heating to 80°C, the mixture was stirred with a homomixer at 6000 rpm for 10 minutes. (cooling) The slurry in the vessel was cooled to a temperature of 30°C.

[0076] (Prescription Example 15) (Preparation of ingredients) A container was charged with 11.0% by mass of glycerin, 3.5% by mass of polyglycerol fatty acid ester (stearic acid, HLB: 12), 2.0% by mass of lysolecithin, 3.1% by mass of urolithin A, 73.1% by mass of deionized water, 0.1% by mass of sodium chloride, and 0.2% by mass of potassium carbonate, and the mixture was heated to 80°C and stirred to dissolve. (Mixing with a homomixer) While heating to 80°C, the mixture was stirred with a homomixer at 6000 rpm for 30 minutes. (cooling) The slurry in the vessel was cooled to a temperature of 30°C, and 7.0% by mass of ethanol was added and stirred.

[0077] (Prescription Example 16) The same procedure as in Formulation Example 15 was carried out, except that the stirring temperature in the homomixer was changed from 80° C. to 90° C. and the rotation speed of the homomixer was changed from 6000 rpm to 8500 rpm.

[0078] (Prescription Example 17) The same procedure as in Formulation Example 1 was carried out, except that the amount of polyglycerol fatty acid ester (stearic acid, HLB: 12) in Formulation Example 1 was changed from 5.3% by mass to 14.0% by mass, the amount of lysolecithin was changed from 3.0% by mass to 8.0% by mass, the amount of deionized water was changed from 70.3% by mass to 56.6% by mass, the stirring time using the homomixer was changed from 15 minutes to 30 minutes, and wet grinding using a bead mill was not performed.

[0079] (Prescription Example 18) The same procedure as in Formulation Example 15 was performed, except that the polyglycerol fatty acid ester (stearic acid, HLB: 12) in Formulation Example 15 was changed from 3.5% by mass to 14.0% by mass, the lysolecithin was changed from 2.0% by mass to 8.0% by mass, the deionized water was changed from 73.1% by mass to 56.6% by mass, the stirring temperature of the homomixer was changed from 80°C to 90°C, and the rotation speed of the homomixer was changed from 6000 rpm to 8500 rpm.

[0080] (Prescription Example 19) The same procedure as in Formulation Example 1 was carried out, except that the glycerin in Formulation Example 1 was changed from 11.0% by mass to 33.0% by mass, the polyglycerol fatty acid ester (stearic acid, HLB: 12) was changed from 5.3% by mass to 3.5% by mass, the lysolecithin was changed from 3.0% by mass to 2.0% by mass, and deionized water was changed from 70.3% by mass to 51.1% by mass, the stirring time using a homomixer was changed from 15 minutes to 30 minutes, and wet grinding using a bead mill was not performed.

[0081] (Prescription Example 20) (Adjusting ingredients) 3.1% by mass of urolithin A, 0.1% by mass of sodium chloride, 0.2% by mass of potassium carbonate, and 56.6% by mass of deionized water were added to a container and heated to 80°C with stirring. Next, 11.0% by mass of glycerin, 8.0% by mass of lysolecithin, and 14.0% by mass of polyglycerol fatty acid ester (stearic acid, HLB: 12) were added, and the mixture was heated to 90°C with stirring. (Mixing with a homomixer) While heating to 90°C, the mixture was stirred with a homomixer at 8500 rpm for 30 minutes. (cooling) The slurry in the vessel was cooled to a temperature of 30°C, and 7.0% by mass of ethanol was added and stirred.

[0082] (Prescription Example 21) The same procedure as in Formulation Example 1 was carried out, except that the glycerin in Formulation Example 1 was changed from 11.0% by mass to 33.0% by mass, the polyglycerol fatty acid ester (stearic acid, HLB: 12) was changed from 5.3% by mass to 14.0% by mass, the lysolecithin was changed from 3.0% by mass to 8.0% by mass, and deionized water was changed from 70.3% by mass to 34.6% by mass, and the stirring time using the homomixer was changed from 15 minutes to 20 minutes.

[0083] (Prescription Example 22) The same procedure as in Formulation Example 15 was performed, except that the polyglycerol fatty acid ester (stearic acid, HLB: 12) in Formulation Example 15 was changed from 3.5% by mass to 14.0% by mass, the lysolecithin was changed from 2.0% by mass to 8.0% by mass, deionized water was changed from 73.1% by mass to 56.6% by mass, the stirring temperature in the homomixer was changed from 80°C to 90°C, the rotation speed of the homomixer was changed from 6000 rpm to 8500 rpm, the stirring time in the homomixer was changed from 30 minutes to 20 minutes, and wet grinding was performed using a bead mill with 1 mm diameter beads.

[0084] (Prescription Example 23) The same procedure as in Formulation Example 1 was carried out, except that the glycerin in Formulation Example 1 was changed from 11.0% by mass to 22.0% by mass, the polyglycerol fatty acid ester (stearic acid, HLB: 12) was changed from 5.3% by mass to 3.5% by mass, the lysolecithin was changed from 3.0% by mass to 2.0% by mass, the deionized water was changed from 70.3% by mass to 61.1% by mass, and the ethanol was changed from 7.0% by mass to 8.0% by mass.

[0085] (Prescription Example 24) The same procedure as in Formulation Example 1 was carried out, except that the stirring temperature using the homomixer in Formulation Example 1 was changed from 90°C to 60°C.

[0086] (Prescription Example 25) The same procedure as in Formulation Example 1 was carried out, except that the stirring temperature using the homomixer in Formulation Example 1 was changed from 90°C to 70°C.

[0087] (Prescription Example 26) The same procedure as in Formulation Example 1 was carried out, except that the polyglycerin fatty acid ester (stearic acid, HLB: 12) in Formulation Example 1 was replaced with polyglycerin fatty acid ester (stearic acid, HLB: 9.5).

[0088] (Prescription Example 27) The same procedure as in Formulation Example 1 was performed, except that the urolithin A in Formulation Example 1 was changed from 3.1% by mass to 18.0% by mass, the polyglycerol fatty acid ester (stearic acid, HLB: 12) was changed from 5.3% by mass to 13.0% by mass, the lysolecithin was changed from 3.0% by mass to 7.0% by mass, the ethanol was changed from 7.0% by mass to 6.0% by mass, and the deionized water was changed from 70.3% by mass to 44.7% by mass.

[0089] (Prescription Example 28) 2.0% by mass of polyglycerol fatty acid ester (stearic acid, HLB: 12), 1.5% by mass of polyglycerol fatty acid ester (palmitic acid, HLB: 12.5), and 2.0% by mass of lysolecithin were added to 47.5% by mass of deionized water, heated to 85°C, dissolved, then cooled to 30°C, and 25.0% by mass of glycerol, 0.1% by mass of potassium carbonate, and 0.1% by mass of sodium chloride were added and dissolved. 21.8% by mass of urolithin A was then dispersed in this mixture using a homomixer (stirring temperature of the homomixer: 30°C, rotation speed: 8500 rpm, stirring time: 15 minutes). The mixture was then wet-pulverized using a bead mill with 0.3 mm diameter beads.

[0090] (2) Characterization test of 1% diluted Urolithin A solution (Test Example 1) Stability test of 1% acidic diluted solution of urolithin A after heating at 85°C for 30 minutes The aqueous dispersions of urolithin A in Formulation Examples 1 to 28 were diluted to 1% with deionized water, the pH was adjusted to 3, and heated at 85°C for 30 minutes. After that, the appearance was observed, and samples that showed no solidification were rated "Good," samples that showed slight solidification were rated "Good," and samples that showed solidification were rated "Poor." (Test Example 2) Stability test of aqueous dispersion of urolithin A at 40°C The aqueous dispersions of urolithin A in Formulation Examples 1 to 28 were allowed to stand in a 40°C thermostatic chamber for at least two weeks, and the appearance was observed over time after five days and two weeks. Those that did not solidify were rated "Good," those that solidified slightly but were still usable (the solidified material re-dispersed in water when shaken) were rated "Good," and those that solidified were rated "Poor."

[0091] (3) Characterization test of urolithin A aqueous dispersion (Test Example 3) Stability test of aqueous dispersion of urolithin A and change in average particle size over time The aqueous dispersions of urolithin A in Formulation Example 1 were left to stand in thermostatic chambers at 5°C, 25°C, and 40°C for at least two weeks, and the appearance was observed over time. Samples that showed almost no solidification for at least two weeks were marked with an "O" and samples that showed solidification within two weeks were marked with an "X." Furthermore, the aqueous dispersion of urolithin A in Formulation Example 1 that had been left standing in thermostatic baths at 5°C, 25°C, and 40°C for 7.5 months was diluted to 1% with deionized water, and the average particle size of the urolithin A-containing particles was measured by dynamic light scattering using an ELS-Z manufactured by Otsuka Electronics Co., Ltd.

[0092] The compounding ratios of the ingredients in Formulation Examples 1 to 28, the manufacturing conditions, and the results of Test Examples 1 and 2 are shown in Tables 2 and 3. The values ​​for the ingredient combinations in the tables are expressed as mass percentages relative to the total mass. The results of Test Example 3 are shown in Table 4.

[0093] [Table 2]

[0094] [Table 3]

[0095] [Table 4]

[0096] As can be seen from Table 2, all of Formulation Examples 1 to 13 had excellent stability in the diluted solution after heating in an acidic environment, and also had excellent formulation stability after standing at 40°C for 5 days and 2 weeks (hereinafter also referred to as "formulation stability"). On the other hand, as can be seen from Table 3, Formulation Examples 14 to 28 were poor in at least one of the stability of the diluted solution after heating in an acidic environment and the stability of the formulation after standing at 40°C for 5 days and 2 weeks.

[0097] Comparing Formulation Example 2 with Formulation Example 1, Formulation Example 2 contained 3.5% by mass of polyglycerol fatty acid ester (stearic acid) and 2.0% by mass of lysolecithin, and although the blending amounts of polyglycerol fatty acid ester (stearic acid) and lysolecithin were lower than those of Formulation Example 1, the dilution stability and formulation stability after acidic heating were good. Therefore, it was found that when the polyglycerol fatty acid ester (stearic acid) content was 3% by mass or more and the lysolecithin content was 2% by mass or more, an aqueous dispersion of urolithin A with good dilution stability and formulation stability after acidic heating could be obtained.

[0098] Comparing Formulation Example 3 with Formulation Example 1, Formulation Example 3 contained 7.0% by mass of polyglycerol fatty acid ester (stearic acid) and 4.0% by mass of lysolecithin, and although the blending amounts of polyglycerol fatty acid ester (stearic acid) and lysolecithin were greater than those of Formulation Example 1, the dilution stability and formulation stability after acidic heating were good. Furthermore, Formulation Examples 10 to 13 contained 13.0% by mass of polyglycerol fatty acid ester (stearic acid) and 7.0% by mass of lysolecithin, and yet the dilution stability and formulation stability after acidic heating were good. Furthermore, a comparison of Formulation Example 3 and Formulation Example 22 revealed that when the polyglycerol fatty acid ester (stearic acid) content was increased to 14.0% by mass and the lysolecithin content was increased to 8.0% by mass, as in Formulation Example 22, the dilution stability and formulation stability after acidic heating deteriorated. Therefore, it was found that an aqueous dispersion of urolithin A with good dilution stability and formulation stability after acidic heating could be obtained when the polyglycerol fatty acid ester (stearic acid) content was 13% by mass or less and the lysolecithin content was 7% by mass or less.

[0099] Comparing Formulation Example 13 with Formulation Example 1, Formulation Example 13 contained urolithin A at 17.0% by mass, which is a higher amount than Formulation Example 1, but the stability of the diluted solution after heating in an acidic environment and the stability of the formulation were good. On the other hand, when the amount of urolithin A added was increased to 18.0% by mass as in Formulation Example 27, the stability of the diluted solution after heating in an acidic environment deteriorated. Therefore, it was found that an aqueous dispersion of urolithin A with 17.0% by mass or less of urolithin A can be obtained that exhibits good dilution stability and formulation stability after acidic heating. Furthermore, the inclusion of poorly water-soluble urolithins at 17.0% by mass, based on the total mass, is significantly higher than the urolithin concentrations in aqueous solutions containing urolithins according to prior art. Furthermore, the fact that an aqueous solution containing urolithin with good dilution stability and formulation stability after acidic heating was obtained was a surprising result that even those skilled in the art could not have predicted.

[0100] Comparing Formulation Example 8 with Formulation Example 1, Formulation Example 8 contained 16.0% by mass of glycerin, which is a higher amount of glycerin than Formulation Example 1, but the dilution stability and formulation stability after acidic heating were good. Furthermore, comparing Formulation Example 23 with Formulation Example 2, Formulation Example 23 contained 22.0% by mass of glycerin, which was higher than Formulation Example 2, and had poorer dilution stability after acidic heating. Therefore, it was found that when glycerin is 16% by mass or less, an aqueous dispersion of urolithin A can be obtained that has good dilution stability and formulation stability after acidic heating.

[0101] Comparing Formulation Example 26 with Formulation Example 1, Formulation Example 26 had a polyglycerol fatty acid ester (stearic acid) with an HLB of 9.5, which was lower than the HLB of Formulation Example 1, in which the polyglycerol fatty acid ester (stearic acid) had an HLB of 12, and the dilution stability after acidic heating and the formulation stability after standing for 2 weeks at 40°C were poor. Therefore, it was found that when the HLB of the polyglycerol fatty acid ester (stearic acid) is 11 or higher, an aqueous dispersion of urolithin A with good dilution stability after acidic heating and formulation stability can be obtained.

[0102] Comparing Formulation Example 7 with Formulation Example 1, Formulation Example 7 had a polyglycerol fatty acid ester (stearic acid) with an HLB of 15, which was higher than that of Formulation Example 1, but the dilution stability and formulation stability after acidic heating were good or excellent. Therefore, it was found that when the HLB of the polyglycerol fatty acid ester (stearic acid) is 15 or less, an aqueous dispersion of urolithin A with good dilution stability and formulation stability after acidic heating can be obtained.

[0103] Comparing Formulation Example 6 with Formulation Example 1, Formulation Example 6 uses tap water, but similar to Formulation Example 1, which used deionized water, the dilution stability and formulation stability after acidic heating were good. Therefore, it was found that, similar to the case where deionized water was used, the use of tap water also resulted in a urolithin A aqueous dispersion that exhibited good dilution stability and formulation stability after acidic heating.

[0104] Comparing Formulation Example 5 with Formulation Example 1, Formulation Example 5 had a stirring temperature in the homomixer of 80°C, which was lower than Formulation Example 1, which had a stirring temperature of 90°C. However, like Formulation Example 1, the stability of the diluted solution and the formulation after acidic heating were good. Furthermore, a comparison of Formulation Example 25 and Formulation Example 5 revealed that the stability of the diluted solution after acidic heating deteriorated when the stirring temperature in the homomixer was lowered to 70°C, as in Formulation Example 25. Therefore, it was found that when a solution containing urolithins, polyglycerol fatty acid ester (stearic acid), lysolecithin, glycerin, sodium chloride, potassium carbonate, and water was stirred at 80°C to 100°C, an aqueous dispersion of urolithin A with good dilution stability and formulation stability after acidic heating could be obtained.

[0105] Comparing Formulation Example 16 with Formulation Example 2, Formulation Example 16 did not undergo wet pulverization using a bead mill as in Formulation Example 2, and had poor formulation stability after standing at 40°C for 2 weeks. Therefore, it was found that when the slurry is wet pulverized, an aqueous dispersion of urolithin A can be obtained that has good dilution stability and formulation stability after acidic heating.

[0106] Comparing Formulation Example 4 with Formulation Example 1, Formulation Example 4 used beads with a diameter of 0.3 mm in wet pulverization using a bead mill, and similar to Formulation Example 1, which used beads with a diameter of 1 mm, had good dilution stability and formulation stability after acidic heating. Therefore, it was found that when beads with a diameter of 0.3 mm were used in wet pulverization using a bead mill, an aqueous dispersion of urolithin A with good dilution stability and formulation stability after acidic heating could be obtained, similar to when beads with a diameter of 1 mm were used.

[0107] Formulation Example 28 had poor dilution stability and formulation stability after acidic heating. When prepared by the method of Formulation Example 28, the acidic dilution of Test Example 1 generated a considerable amount of precipitate even before heating, and the precipitate did not redisperse even when shaken. Therefore, it was found that a production method such as that of Formulation Example 28 could not produce an aqueous dispersion of urolithin A that had good dilution stability and formulation stability after acidic heating.

[0108] As shown in Table 4, when the aqueous dispersion of urolithin A in Formulation Example 1 was allowed to stand at 5°C, 25°C, and 40°C, almost no solidification occurred for more than two weeks. Furthermore, after 7.5 months, the average particle size was 293 nm at 5°C, 360 nm at 25°C, and 350 nm at 40°C, remaining stable and almost unchanged from the initial average particle size of 200 to 300 nm. Since the average particle size remained unchanged after 7.5 months, it is believed that the average particle size will remain stable even for periods longer than 7.5 months. Furthermore, similar to Formulation Example 1, it was inferred that Formulation Examples 2 to 13, which are working examples, also have long-term stability.

Claims

1. Urolithins and Polyglycerin fatty acid ester (stearic acid) Lysolecithin and An aqueous solution containing urolithins, comprising: glycerin;

2. The urolithin-containing aqueous solution contains, based on the total mass of the urolithin-containing aqueous solution, 1 to 17% by mass of the urolithins; 3 to 13% by mass of the polyglycerol fatty acid ester (stearic acid), 2 to 7% by mass of the lysolecithin; The urolithin-containing aqueous solution according to claim 1, comprising 11 to 16% by mass of glycerin.

3. The urolithin-containing aqueous solution according to claim 2, wherein the urolithin is urolithin A.

4. The urolithins-containing aqueous solution according to claim 2, wherein the polyglycerol fatty acid ester (stearic acid) has an HLB of 11 to 15.

5. The urolithin-containing aqueous solution according to claim 3 or 4, further comprising at least one selected from the group consisting of sodium chloride, potassium carbonate, and ethanol.

6. The urolithin-containing aqueous solution according to claim 5, further comprising deionized water.

7. A food or drink comprising the urolithin-containing aqueous solution according to claim 6.

8. preparing a solution containing urolithins, polyglycerol fatty acid ester (stearic acid), lysolecithin, glycerin, sodium chloride, potassium carbonate, and water; a step of stirring the solution at 80 to 100°C to obtain a mixed solution; a step of cooling the mixture and then adding ethanol to the mixture to obtain a slurry; and wet-pulverizing the slurry to obtain an aqueous solution containing urolithins.

9. In the step of preparing the solution, based on the total mass of the urolithins-containing aqueous solution, 1 to 17% by mass of the urolithins; 3 to 13% by mass of the polyglycerol fatty acid ester (stearic acid), 2 to 7% by mass of the lysolecithin; The method for producing a urolithin-containing aqueous solution according to claim 8, wherein 11 to 16% by mass of glycerin is mixed with

10. The method for producing an aqueous solution containing urolithins according to claim 9, wherein the urolithin is urolithin A.

11. The urolithin-containing aqueous solution according to claim 8 or 9, wherein the polyglycerol fatty acid ester (stearic acid) has an HLB of 11 to 15.

12. 10. The method for producing an aqueous solution containing urolithins according to claim 8 or 9, wherein the step of preparing the solution further comprises adding at least one selected from the group consisting of sodium chloride, potassium carbonate, and ethanol.

Images