Composition for improving urinary tract function and composition for improving blood flow in bladder

Abstract

To provide a novel composition capable of improving urinary function, in particular a novel composition capable of improving urinary tract function and blood flow in the bladder.SOLUTION: A composition for improving urinary tract function or a composition for improving blood flow in the bladder, comprises at least one selected from the group consisting of the following components (1) and (2): (1) at least one selected from the group consisting of ellagic acid, analogues thereof, salts thereof, and hydrates thereof; and (2) at least one selected from the group consisting of punicalagin, salts thereof, and hydrates thereof.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition for improving urinary tract function and a composition for improving bladder blood flow, and also to a method for improving urinary tract function and a method for improving bladder blood flow. [Background technology]

[0002] Decreased urinary function, such as frequent urination, urgency, urinary incontinence, and residual urine, is a symptom that occurs in both men and women and causes various problems in daily life. Causes of decreased urinary function include, for example, neurogenic bladder, urinary tract infection, and benign prostatic hyperplasia, but some of them are not fully understood.

[0003] Anticholinergic drugs have traditionally been used to improve urinary functions such as frequent urination and urgency, but they can also cause side effects such as increased residual urine volume and urinary retention, so caution is required when using them.

[0004] On the other hand, ellagic acid is a type of polyphenol known to date, and is known to be produced by hydrolyzing punicalagin. Ellagic acid has been known to have antioxidant and anticancer effects. Ellagic acid has also been reported to have a whitening effect and promote the absorption of vitamin C in the body (Patent Documents 1 and 2). However, it is not known that ellagic acid or punicalagin can improve urinary function. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Publication No. 2019-14672 [Patent Document 2] Japanese Patent Application Publication No. 2018-138525 Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present invention is to provide a novel composition and the like capable of improving urinary function, particularly, a novel composition and the like capable of improving urinary tract function and bladder blood flow. [Means for solving the problem]

[0007] The present inventors have conducted extensive research in light of the above-mentioned problems and have found that ellagic acid and punicalagin can improve urinary tract function and bladder blood flow. Based on this finding, further research has led to the completion of the present invention, which is described below. Item 1. A composition for improving urinary tract function, comprising, as an active ingredient, at least one selected from the group consisting of the following ingredients (1) and (2): (1) at least one selected from the group consisting of ellagic acid, its analogs, salts thereof, and hydrates thereof; (2) At least one selected from the group consisting of punicalagin, its salts, and hydrates thereof. Item 2. A composition for improving bladder blood flow, comprising, as an active ingredient, at least one selected from the group consisting of the following ingredients (1) and (2): (1) at least one selected from the group consisting of ellagic acid, its analogs, salts thereof, and hydrates thereof; (2) At least one selected from the group consisting of punicalagin, its salts, and hydrates thereof. Item 3. The composition for improving urinary tract function according to Item 1, wherein the improvement of urinary tract function is at least one selected from the group consisting of improvement of frequent urination, improvement of urine retention volume, and improvement of urination volume. Item 4. A composition for improving urinary tract function according to Item 1 or 3, comprising a processed product of a pomegranate plant containing at least one selected from the group consisting of ingredients (1) and (2). Item 5. The composition for improving urinary tract function according to any one of Items 1, 3 and 4, which is a food composition, a pharmaceutical composition, a quasi-drug composition or a feed composition. Item 6. A composition for improving bladder blood flow according to Item 2, comprising a processed product of a pomegranate plant containing at least one selected from the group consisting of ingredients (1) and (2). Item 7. The composition for improving bladder blood flow according to Item 2 or 6, which is a food composition, a pharmaceutical composition, a quasi-drug composition, or a feed composition. Item 8. A composition used to improve urinary tract function, comprising as an active ingredient at least one selected from the group consisting of the following ingredients (1) and (2): (1) at least one selected from the group consisting of ellagic acid, its analogs, salts thereof, and hydrates thereof; (2) At least one selected from the group consisting of punicalagin, its salts, and hydrates thereof. Item 9. The composition according to Item 8, wherein the improvement of urinary tract function is at least one selected from the group consisting of improvement of frequent urination, improvement of urine retention volume, and improvement of urination volume. Item 10. A composition used to improve bladder blood flow, comprising at least one active ingredient selected from the group consisting of the following ingredients (1) and (2): (1) at least one selected from the group consisting of ellagic acid, its analogs, salts thereof, and hydrates thereof; (2) At least one selected from the group consisting of punicalagin, its salts, and hydrates thereof. Item 11. A composition containing a processed pomegranate plant product containing at least one selected from the group consisting of ingredients (1) and (2) described in Item 8 or 10, which is used to improve urinary tract function or bladder blood flow. Item 12. A method for improving urinary tract function, comprising applying, preferably orally administering to a subject, a composition containing at least one active ingredient selected from the group consisting of the following ingredients (1) and (2): (1) at least one selected from the group consisting of ellagic acid, its analogs, salts thereof, and hydrates thereof; (2) At least one selected from the group consisting of punicalagin, its salts, and hydrates thereof. Item 13. The method according to Item 12, wherein the improvement of urinary tract function is at least one selected from the group consisting of improvement of frequent urination, improvement of urine retention volume, and improvement of urination volume. Item 14. A method for improving bladder blood flow, comprising applying, preferably orally administering to a subject, a composition containing at least one active ingredient selected from the group consisting of the following ingredients (1) and (2): (1) at least one selected from the group consisting of ellagic acid, its analogs, salts thereof, and hydrates thereof; (2) At least one selected from the group consisting of punicalagin, its salts, and hydrates thereof. Item 15. The method according to any one of Items 12 to 14, wherein a composition containing a processed product of a pomegranate plant containing at least one selected from the group consisting of the ingredients (1) and (2) is applied to a subject, preferably orally administered. Item 16. Use of at least one selected from the group consisting of the following components (1) and (2) for producing a composition for improving urinary tract function: (1) at least one selected from the group consisting of ellagic acid, its analogs, salts thereof, and hydrates thereof; (2) At least one selected from the group consisting of punicalagin, its salts, and hydrates thereof. Item 17. Use of at least one selected from the group consisting of the following components (1) and (2) for producing a composition for improving bladder blood flow: (1) at least one selected from the group consisting of ellagic acid, its analogs, salts thereof, and hydrates thereof; (2) At least one selected from the group consisting of punicalagin, its salts, and hydrates thereof. [Effects of the Invention]

[0008] According to the present invention, urinary tract function can be improved. Furthermore, according to the present invention, bladder blood flow can be improved. According to the present invention, urinary tract function, particularly frequency of urination, amount of urine stored, and amount of urine excreted can be improved. DETAILED DESCRIPTION OF THE INVENTION

[0009] Composition for improving urinary tract function The present invention relates to a composition for improving urinary tract function, which contains, as an active ingredient, at least one selected from the group consisting of the following ingredients (1) and (2): (1) at least one selected from the group consisting of ellagic acid, its analogs, salts thereof, and hydrates thereof; (2) At least one selected from the group consisting of punicalagin, its salts, and hydrates thereof.

[0010] Composition for improving bladder blood flow The present invention relates to a composition for improving bladder blood flow, which contains, as an active ingredient, at least one selected from the group consisting of the following ingredients (1) and (2): (1) at least one selected from the group consisting of ellagic acid, its analogs, salts thereof, and hydrates thereof; (2) At least one selected from the group consisting of punicalagin, its salts, and hydrates thereof.

[0011] These compositions are described below. In the present disclosure, the term "contain" also encompasses "contain," "consist essentially of," and "consist only of."

[0012] Ingredients (1) Regarding the component (1), the ellagic acid is a conventionally known substance represented by CAS number 476-66-4 (molecular formula C 14 H6O8, molecular weight 302.19). In the present invention, commercially available ellagic acid may be used. Although not limiting the present invention, ellagic acid is commercially available from, for example, Fujifilm Wako Pure Chemical Industries, Ltd., Tokyo Chemical Industry Co., Ltd., etc.

[0013] Examples of the ellagic acid analogs include, but are not limited to, 3-O-methylellagic acid, flabellagic acid, 3,3'-di-O-methylellagic acid, 3,4,3'-trimethylellagic acid, carboxylellagic acid, ellagic acid 4-xyloside, 3'-O-methylellagic acid 4-xyloside, 3-O-methylellagic acid 3'-rhamnoside, ellagic acid 3-glucoside, ellagic acid 4-acetylxyloside, 3'-O-methylellagic acid 4-O-β-D-glucose, etc. These analogs may be used alone or in combination of two or more.

[0014] Examples of the salts of ellagic acid and the salts of the analogues include salts of alkali metals such as sodium and potassium, salts of alkaline earth metals such as calcium and magnesium, ammonium salts, amine salts, etc. These may be used alone or in combination of two or more.

[0015] Examples of the hydrates of ellagic acid, its analogs, and its salts include conventionally known hydrates of these compounds. These may be used alone or in combination of two or more.

[0016] Although not limiting the present invention, component (1) is preferably at least one selected from the group consisting of ellagic acid, its salts, and hydrates thereof, and more preferably ellagic acid.

[0017] Furthermore, the component (1) used in producing the composition for improving urinary tract function and the composition for improving bladder blood flow may be a purified product (pure product), and is not limited thereto as long as it achieves the effects of the present invention. For example, the component (1) may be a processed plant product (processed plant product) containing the component (1), or a crude product of the component (1).

[0018] Although the present invention is not limited to such processed plant products, examples thereof include preferably processed plant products containing at least one selected from the group consisting of ellagic acid, its salts, and hydrates thereof, and more preferably processed plant products containing ellagic acid.

[0019] Although the crude product is not limited to the present invention, examples thereof include preferably at least one crude product selected from the group consisting of ellagic acid, its salts, and hydrates thereof, and more preferably a crude product of ellagic acid.

[0020] These may be used alone or in combination of two or more.

[0021] As examples of the processed plant products and the roughly purified plant products, examples of processed plant products containing ellagic acid and roughly purified plant products of ellagic acid will be described below. However, the same explanation can be given below for processed plant products and roughly purified plant products containing the component (1) other than ellagic acid.

[0022] Examples of plant processed products containing ellagic acid include, but are not limited to, processed products from plants such as strawberries (plants belonging to the genus Fragaria), cranberries (plants belonging to the genus Vaccinium), raspberries (plants belonging to the genus Rubus), grapes (plants belonging to the genus Vitis), walnuts (plants belonging to the genus Juglans), chestnuts (plants belonging to the genus Castanea), pecans (plants belonging to the genus Carya), geranium (plants belonging to the genus Geranium), wolfberry (plants belonging to the genus Lycium), and pomegranate (plants belonging to the genus Punica). For example, although not limiting the present invention, plants belonging to the genus Punica belong to the family Lythraceae. An example of a plant belonging to this genus is Punica granatum, but is not limited to the present invention.

[0023] As long as the plant contains ellagic acid, the part to be used is not particularly limited, and examples thereof include leaves, stems, fruits, pericarp, flowers, buds, branches, trunks, bark, roots, seeds, and seed coats, and may be appropriately selected depending on the plant. For example, in the case of a plant belonging to the genus Pomegranate, preferred parts to be used include fruits, pericarp, seeds, and seed coats, although this does not limit the present invention. The parts to be used may be used alone or in combination of two or more.

[0024] In the present invention, examples of processed plant products include crushed products, dried products, extracts, etc. of the plants that serve as raw materials.

[0025] Although the pulverized material is not limited to the present invention, examples thereof include the above-mentioned plants pulverized by a pulverizer known in the art, such as a jet mill.

[0026] The dried product is not particularly limited as long as it is obtained by drying the plant, and examples include products dried according to conventionally known drying methods such as sun drying, far-infrared irradiation, and dryers (hot air drying, cold air drying, vacuum freeze drying, etc.). Furthermore, the moisture content of the dried product is not a limitation of the present invention, but is preferably 10% by mass or less, more preferably 8% by mass or less. In the present invention, the dried product may be in any form, such as a dried product of the plant (any part) itself, or a pulverized product of the dried product (dried pulverized product). The dried pulverized product can be obtained by pulverizing the dried product according to the same method as for the pulverized product. Furthermore, in the present invention, the dried product may be obtained by subjecting the plant material to fermentation or enzymatic treatment followed by drying.

[0027] The method for producing the extract (extraction method) and the extraction conditions are not particularly limited, and may be any conventionally known method. For example, the plant may be cut, crushed, or dried as needed, and then squeezed or solvent extracted to obtain an extract. As the solvent extraction method, any method known in the art may be used, and conventionally known extraction methods such as water (including warm water and hot water) extraction, alcohol extraction, and supercritical extraction may be used.

[0028] When solvent extraction is performed, examples of the solvent include water; alcohols (whether anhydrous or hydrous) such as lower alcohols such as methanol, ethanol, and isopropanol, 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, benzene, and chloroform. Preferred solvents are water, lower alcohols, and 1,3-butylene glycol, more preferably water, methanol, ethanol, and 1,3-butylene glycol, and even more preferably water, methanol, and hydrous ethanol. These solvents may be used alone or in combination of two or more.

[0029] In the present invention, the extract obtained through solvent extraction in this manner can be particularly referred to as a “solvent extract.” Furthermore, without limiting the present invention, as described above, for example, when water is used as the solvent, it can be called a water extract, when a lower alcohol is used, it can be called a lower alcohol extract, when ethanol is used, it can be called an ethanol extract, etc.

[0030] The obtained extract may be used as is, or may be dried and used in a solid form such as powder or granules. If necessary, the obtained extract may be purified, concentrated, or subjected to a separation process for a highly active fraction. While not limiting the present invention, examples of the purification process include filtration, adsorption using an ion exchange resin or an activated carbon column, and decolorization. Conventional methods such as an evaporator can be used for concentration. For separation of a highly active fraction, known separation processes such as gel filtration, adsorption, silica gel column chromatography, and HPLC (High Performance Liquid Chromatography) can be used.

[0031] Alternatively, the extract obtained as described above (and further its dried product, purified product, concentrated product, or highly active fraction) may be powdered by a conventional method, such as freeze-drying, or spray-drying with the addition of excipients such as dextrin, corn starch, or gum arabic, as needed, to provide the extract used in the present invention. Alternatively, the extract may be dissolved in water, ethanol, or the like as needed.

[0032] Preferred examples of the extract include extracts obtained by drying, crushing, and / or cutting the raw plant material (any part), extracting using a suitable solvent, and filtering, as well as extracts obtained by further drying the extract thus obtained.

[0033] The present invention is not limited to this, and extraction can be performed by a person skilled in the art depending on the part of the plant to be used. The extract can be obtained by immersing 100 g of the plant material, more preferably 100 g of dried, crushed, and / or cut pieces of the plant, in 1 to 50 L of extraction solvent, extracting at a desired temperature (e.g., 15 to 90°C) for a desired time (e.g., 10 minutes to 24 hours) with stirring as needed, and then filtering. Furthermore, as mentioned above, the obtained extract may be subjected to purification, concentration, various separation processes for highly active fractions, etc., as needed.

[0034] The processed plant products may be commercially available products, or may be commercially available products that have been further subjected to appropriate treatment such as drying.

[0035] In the present invention, the processed plant product containing ellagic acid is preferably a processed plant product of the genus pomegranate containing ellagic acid, and more preferably an extract of a plant of the genus pomegranate containing ellagic acid (including a dried product thereof).

[0036] The processed plant products may be used alone or in combination of two or more.

[0037] An example of a crude product of ellagic acid is an ellagic acid fraction prepared from a plant containing ellagic acid. Examples of plants containing ellagic acid include, but are not limited to, the aforementioned plants, and any of the aforementioned parts used. It is known that ellagitannins such as punicalagin, punicalin, and gallic acid produce ellagic acid by hydrolysis or the like. Therefore, an example of a crude product of ellagic acid is an ellagic acid fraction prepared from a plant containing ellagitannin by decomposition treatment such as hydrolysis. It is also known that ellagic acid can be produced by chemical synthesis using gallic acid. Therefore, an example of a crude product of ellagic acid is an ellagic acid fraction prepared by chemical synthesis from a plant containing gallic acid.

[0038] The ellagic acid fraction is not prepared by a single extraction from an ellagic acid-containing plant (any part) with a single solvent (e.g., water; alcohols such as methanol and ethanol; or aqueous alcohols), followed by filtration and concentration. Rather, it refers to a fraction obtained by, for example, repeating solvent extraction multiple times to obtain a fraction with a high degree of ellagic acid purification (purity) or obtaining a concentrated fraction containing ellagic acid at a high concentration, or by any combination of purification procedures such as molecular weight filtration, size exclusion chromatography, and ion exchange chromatography. More specifically, an example of the ellagic acid fraction is a fraction obtained by removing components other than ellagic acid from an ellagic acid-containing fraction to increase the ellagic acid content to 50% by mass or more. The ellagic acid content of the ellagic acid fraction is preferably 60 to 100% by mass, more preferably 70 to 100% by mass, even more preferably 80 to 100% by mass, and particularly preferably 90 to 100% by mass.

[0039] From this viewpoint, when the processed plant product is a crude product of ellagic acid, the processed plant product may be used as the crude product.

[0040] These may be used alone or in combination of two or more.

[0041] Ingredients (2) Regarding component (2), punicalagin is a conventionally known substance, and commercially available punicalagin may be used in the present invention. While not limiting the present invention, it is commercially available from, for example, Cayman Chemical, Sigma-Aldrich, etc. Examples of salts of punicalagin include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, ammonium salts, and amine salts. Examples of hydrates of punicalagin and its salts include conventionally known hydrates of these. While not limiting the present invention, a preferred example of component (2) is punicalagin. These may be used alone or in combination of two or more.

[0042] Furthermore, the component (2) used in producing the composition for improving urinary tract function and the composition for improving bladder blood flow may be a purified product (pure product), and is not limited thereto as long as it achieves the effects of the present invention. For example, the component (2) may be a processed plant product (processed plant product) containing the component (2) or a crude product of the component (2).

[0043] Although not limiting the present invention, the processed plant product is preferably a processed plant product containing punicalagin. Furthermore, although not limiting the present invention, the roughly purified product is preferably a roughly purified product of punicalagin.

[0044] These may be used alone or in combination of two or more.

[0045] As examples of the plant processed products and the roughly purified products, examples of plant processed products containing punicalagin and roughly purified products of punicalagin will be described below, but the same explanation will also be given below for plant processed products and roughly purified products containing the component (2) other than punicalagin.

[0046] Examples of processed plant products containing punicalagin include, but are not limited to, processed products of plants such as myrobalan (a plant belonging to the genus Terminalia) and pomegranate (a plant belonging to the genus Punica). Although not limiting the present invention, for example, plants belonging to the genus Punica are explained in the same manner as above. As long as the plant contains punicalagin, the part used is not particularly limited, and examples include leaves, stems, fruits, pericarp, flowers, buds, branches, trunks, bark, roots, seeds, and seed coats, and may be selected appropriately for each plant. Although not limiting the present invention, examples of preferred parts used in plants belonging to the genus Punicalagin include fruits, pericarp, seeds, and seed coats. Each of the parts used may be used alone or in combination of two or more. Regarding processed plant products containing punicalagin, the processed plant product is explained in the same manner as above.

[0047] In the present invention, the processed plant product containing punicalagin is preferably a processed plant product of the genus pomegranate containing punicalagin, and more preferably an extract of a plant of the genus pomegranate containing punicalagin (including its dried product, etc.).

[0048] The processed plant products may be used alone or in combination of two or more.

[0049] An example of a crude product of punicalagin is a punicalagin fraction prepared from a plant containing punicalagin. Examples of plants containing punicalagin include, but are not limited to, the aforementioned plants.

[0050] Punicalagin fractions are described in the same way as the ellagic acid fractions, that is, they are not prepared by a single extraction from a plant (any part) containing punicalagin using a single solvent (e.g., water; alcohols such as methanol and ethanol; aqueous alcohols), followed by filtration and concentration, but rather by repeating solvent extraction multiple times to obtain a fraction with a high degree of purification (purity) of punicalagin or by optionally combining purification procedures such as molecular weight filtration, size exclusion chromatography, and ion exchange chromatography in order to obtain a concentrated fraction containing punicalagin at a high concentration, or by squeezing a plant (any part) containing punicalagin and repeatedly concentrating it by column filtration, etc. More specifically, examples of such fractions include those in which components other than punicalagin have been removed from a fraction containing punicalagin, thereby increasing the punicalagin content to 25% by mass or more, preferably 30% by mass or more. In other words, examples of the punicalagin content in such fractions include 25 to 100% by mass or 30 to 100% by mass, and examples of the punicalagin content in such punicalagin fractions include preferably 50 to 100% by mass, more preferably 70 to 100% by mass, even more preferably 80 to 100% by mass, and particularly preferably 90 to 100% by mass.

[0051] From this viewpoint, when the processed plant product is a crude product of punicalagin, the processed plant product may be used as the crude product.

[0052] These may be used alone or in combination of two or more.

[0053] In each of the composition for improving urinary tract function and the composition for improving bladder blood flow, the content of at least one selected from the group consisting of components (1) and (2) is not limited and may be appropriately determined depending on symptoms, application form, etc. Although not limiting the present invention, the total amount (solid content concentration) of at least one selected from the group consisting of components (1) and (2) in each composition may be more than 0% by mass and less than 100% by mass, preferably 1 to 70% by mass, and more preferably 5 to 30% by mass.

[0054] As described above, in each composition, the content of at least one selected from the group consisting of components (1) and (2) is not limited, but the following contents can be exemplified.

[0055] The content of the component (1) in each composition is not limited and may be determined appropriately depending on the symptoms, application form, etc., but the total amount (solid content concentration) in the composition is preferably 3 to 70 mass %, or 15 to 30 mass %, for example.

[0056] The content of the component (2) in each composition is not limited and may be determined appropriately depending on the symptoms, application form, etc., but the total amount (solid content concentration) in the composition is preferably 1 to 25 mass %, or 5 to 10 mass %, for example.

[0057] When producing these compositions, if a processed plant product containing component (1) and / or a processed plant product containing component (2) is used, the content of the processed plant product can be determined appropriately depending on the symptoms, application form, etc., but is not limited thereto. The total amount (converted to dry mass) of the composition is preferably 1 to 95 mass%, or 30 to 80 mass%, for example. Here, the dried processed plant product can be obtained by freeze-drying the processed product. The freeze-drying process is carried out by vacuum concentration using a general evaporator and freeze-drying in a vacuum.

[0058] In each of the compositions, the amount of administration (ingestion) of at least one selected from the group consisting of the components (1) and (2) is not particularly limited as long as the effects of the present invention are achieved, and may be appropriately determined depending on the symptoms, application form, physique, age, degree of expected effect, etc. of the target (subject, target animal).

[0059] Although not limiting the present invention, for example, the daily dosage (intake) for humans is, in total (solid concentration) of at least one selected from the group consisting of the components (1) and (2), preferably 0.5 to 70 mg / kg body weight, more preferably 1 to 5 mg / kg body weight. Each of the compositions may be administered (ingested) once or multiple times per day, and may be administered (ingested) for any period and at any interval.

[0060] Furthermore, when using a processed plant product containing the component (1) and / or a processed plant product containing the component (2) in producing these compositions, the amount of the processed plant product administered (ingested) is not particularly limited as long as the effects of the present invention are achieved, and may be appropriately determined depending on the symptoms, application form, physique, age, expected degree of effect, etc. of the target (subject, target animal). For example, the daily amount of the processed plant product administered (ingested) to humans is, for example, preferably 1.5 to 80 mg / kg body weight, more preferably 2 to 8 mg / kg body weight, in terms of total dry mass.

[0061] The dosage (intake) for humans can generally be calculated by converting it from the human equivalent dose (HED) 6.2, which is based on the body surface area in rats (see "Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers").

[0062] Each composition is preferably administered orally (ingested), regardless of whether it is orally or parenterally. There are no limitations on the form, and it may be appropriately selected depending on the purpose. Examples of the form include liquid forms such as solutions, emulsions, suspensions, syrups, extracts, spirits, and elixirs, powders, granules, fine granules, tablets (including coated tablets such as sugar-coated tablets), pills, capsules (including hard capsules and soft capsules), troches, chewable tablets, gels, creams, pastes, mousses, sheets, and liquid freeze-dried products, as well as various forms such as aerosols, patches, poultices, and transdermal absorption preparations.

[0063] The manner of use of each composition is not limited and may be appropriately determined depending on the purpose. Examples of the manner of use include food compositions (including beverages, health functional foods (including specified health foods, nutrient functional foods, functional food products, supplements, etc.), and foods for patients), pharmaceutical compositions, quasi-drug compositions, feed compositions, and additives to food compositions, pharmaceutical compositions, quasi-drug compositions, feed, etc.

[0064] Each composition may be produced according to conventional procedures known in the art for the various forms, modes of use, etc. described above, and may be produced by mixing, as necessary, with optional ingredients such as pharmaceutically acceptable ingredients, cosmetically acceptable ingredients, edible ingredients, etc. Examples of optional ingredients include solvents (alcohols (whether anhydrous or hydrous), such as water, lower alcohols such as methanol, ethanol, and isopropanol, and polyhydric alcohols such as propylene glycol and 1,3-butylene glycol), excipients, disintegrants, diluents, lubricants, flavorings, colorants, sweeteners, flavoring agents, suspending agents, humectants, emulsifiers, solubilizers, dispersants, buffers, binders, penetration enhancers, stabilizers, bulking agents, preservatives, thickeners, pH adjusters, surfactants, coating agents, absorption enhancers, adsorbents, fillers, antioxidants, anti-inflammatory agents, cooling agents, film-forming agents, gelling agents, amino acids, vitamins, enzymes, and various nutritional ingredients. These may be used alone or in combination of two or more.

[0065] The subject (subject, subject animal) to which each composition is applied is not limited, and examples thereof include humans and non-human mammals. In addition, in the present invention, the subject (subject animal) to which the composition is applied is preferably a woman (female), but is not limited thereto. In addition, although not limiting the present invention, examples of the subject include those who have or are at risk of having urinary disorders such as daytime or nighttime frequent urination, overactive bladder, urgency or urge urinary incontinence, and those who feel a sense of residual urine.

[0066] This composition for improving urinary tract function can improve urinary tract function by using at least one active ingredient selected from the group consisting of the above-mentioned components (1) and (2). In particular, this composition for improving urinary tract function can improve urinary tract functions such as urinary frequency (bladder contraction interval), urine storage volume (bladder capacity), and / or urination volume. Therefore, it can be said that the present invention provides a method for improving urinary tract function, which is characterized by using at least one active ingredient selected from the group consisting of the above-mentioned components (1) and (2). Therefore, the above explanation applies to the explanation of this method.

[0067] Furthermore, this composition for improving bladder blood flow can improve bladder blood flow by using at least one active ingredient selected from the group consisting of the above-mentioned components (1) and (2). Therefore, the present invention can be said to provide a method for improving bladder blood flow, characterized by using at least one active ingredient selected from the group consisting of the above-mentioned components (1) and (2). Therefore, the above explanation applies to the explanation of this method.

[0068] Therefore, the present invention is also useful for preventing or improving urination disorders such as daytime or nighttime frequent urination, overactive bladder, urgency, and urge urinary incontinence. [Example]

[0069] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0070] Test Example 1: Improvement of bladder blood flow Bladder blood flow assessment procedure Rats (female SD rats (Sprague-Dawley rats), 8-9 weeks old at the start of the experiment (weight 190-220 g / rat)) underwent laparotomy under isoflurane anesthesia, and both common iliac veins and both uterine veins were ligated to create a pelvic congestion model. After suturing the abdominal cavity, the pelvic congestion rat models were housed in cages for 16 days. Standard commercially available feed and water were available ad libitum. Next, tadalafil, pomegranate extract 1 (pomegranate extract containing ellagic acid), pomegranate extract 2 (pomegranate extract containing punicalagin), ellagic acid, or punicalagin was mixed with the feed to prepare a powdered mixed feed. After 16 days of housekeeping, the rat models were divided into five groups (n=6) and given the mixed feed ad libitum for 14 consecutive days. Water was also available ad libitum.

[0071] The mixed feeds are as shown in Table 1 below. For example, in Table 1, "tadalafil group" refers to a group that received tadalafil-mixed feed, and "0.01% mixed feed" in the tadalafil group means that the group received mixed feed prepared by mixing tadalafil into the mixed feed to a concentration of 0.01% by mass (solid content). Furthermore, in the mixed feed, pomegranate extracts 1 and 2 refer to the amount of pomegranate extract calculated on a dry mass basis, and ellagic acid and punicalagin refer to the amount of ellagic acid and punicalagin calculated on a solid content basis. In this test example, tadalafil was used as a positive control for increasing blood flow.

[0072] The tadalafil used is under the trade name Tadalafil (manufactured by Combi-Blocks), pomegranate extract 1 is under the trade name Pomegranate Ellagic Acid (manufactured by Sabinsa Japan Corporation (containing 80% ellagic acid by mass, an ethanol extract of Punica granatum peel)), pomegranate extract 2 is under the trade name Pomanox P30 (manufactured by NC Corporation (containing 30% punicalagin, an extract obtained by squeezing and concentrating the whole fruit including the peel of Punica granatum)), ellagic acid is under the trade name Ellagic Acid (containing 98% ellagic acid by mass, manufactured by Fujifilm Wako Pure Chemical Industries), and punicalagin is under the trade name Punicalagin (containing 40% punicalagin by mass, manufactured by Santa Cruz Biotechnology). In the table, the dosages of tadalafil, ellagic acid, and punicalagin indicate the dosages of these commercially available products.

[0073] On the final day of the study (day 14 of mixed feed intake), under light urethane anesthesia and restraint, one hour after the effects of the anesthesia appeared, the lower abdomen of each rat was incised, the surrounding tissue adhered to the bladder was removed, and saline was injected into the bladder. Bladder blood flow at a bladder capacity of 1 mL was measured using a laser blood flow meter (2D laser blood flow meter OMEGAZONE OZ-1, manufactured by Omega Wave Co., Ltd.).

[0074] The reference group (n=6) was a group in which the same test as above was conducted except that the pelvic congestion was not performed and the general feed (standard sample in Table 1) was given instead of the mixed feed. The comparison group (n=6) was also a group in which the same test as above was conducted except that the pelvic congestion was performed and the general feed was given instead of the mixed feed.

[0075] [Table 1]

[0076] result The results are shown in Table 2.

[0077] [Table 2]

[0078] As shown in Table 2, the bladder blood flow rate in the reference group (average of 6 rats, hereinafter the same) was 17.0 mL / min / 100 g, while that in the comparison group was 11.1 mL / min / 100 g, indicating a decrease in bladder blood flow in the comparison group. In contrast, the pomegranate extract 1 group, pomegranate extract 2 group, ellagic acid group, and punicalagin group all recovered bladder blood flow to the same level as the reference group, and these bladder blood flow rates were similar to that of the positive control tadalafil group.

[0079] This indicates that plant processed products such as ellagic acid, punicalagin, and pomegranate extract containing ellagic acid and pomegranate extract containing punicalagin are useful for increasing bladder blood flow.

[0080] Test Case 2: Improvement of urinary tract function Urinary tract function assessment procedures A pelvic congestion rat model was prepared in the same manner as in Test Example 1 and maintained for 16 days. Next, tadalafil, pomegranate extract 1, pomegranate extract 2, ellagic acid, and punicalagin were mixed with water, and the resulting mixture was orally administered to each group (n=6) once daily for 14 consecutive days using a probe. During this period, the rats were allowed to consume general commercially available feed and water ad libitum. The dosages are as shown in Table 3 below. For example, the "5 mg / 2 mL / kg" listed for the tadalafil group in Table 3 means that 2 mL of the mixture was administered per kg of rat model body weight per day, and that 2 mL of the mixture contained 5 mg of tadalafil.

[0081] The tadalafil, pomegranate extract 1, and pomegranate extract 2 used were the same as those used in Test Example 1. Punicalagin used was purified punicalagin (containing 96.7% by mass of punicalagin) from the trade name Pomanox P30 (manufactured by NC Corporation (containing 30% punicalagin, an extract obtained by squeezing and concentrating the whole fruit of Punica granatum, including the peel)). In the table, the dosages of tadalafil and ellagic acid indicate the dosages of these commercially available products, and the dosage of punicalagin indicates the dosage of the purified product.

[0082] On the final day of the study (day 14 of mixed feed intake), rats were restrained under light urethane anesthesia. One hour after the effects of anesthesia appeared, a catheter was inserted into the urethra of each rat. Normal saline was continuously infused into the bladder at a rate of 3 mL / h, and intravesical pressure was continuously measured. Measurements were performed using a Delfusion Syringe Pump TE-331 (Terumo Corporation), a disposable pressure transducer DX-100 (Nihon Kohden Corporation), a linear coder WR3320A-8H (Graphtec Corporation), an analog input / output USB I / O unit 8ch AIO-160802AY-USB (Contec Co., Ltd.) as an amplifier data acquisition device, and LaBDAQ5-CT ver. 1.06 (Matsuyama Advance Co., Ltd.) as data acquisition software.

[0083] The group in which the test was conducted in the same manner as above except that the pelvic congestion was not performed and water was given instead of the mixed solution was designated as the reference group (n=6).Furthermore, the group in which the test was conducted in the same manner as above except that the pelvic congestion was performed and water was given instead of the mixed solution was designated as the comparison group (n=6).

[0084] [Table 3]

[0085] result The results are shown in Tables 4 to 6.

[0086] [Table 4]

[0087] Table 4 shows the results of bladder contraction intervals (mean values ​​in minutes). As shown in Table 4, the bladder contraction interval in the reference group was 18.9 minutes, while the bladder contraction interval in the comparison group was 11.0 minutes, indicating that the comparison group had a shorter bladder contraction interval. This indicates that the comparison group had a higher urination frequency than the reference group. In contrast, the pomegranate extract 1 group, pomegranate extract 2 group, ellagic acid group, and punicalagin group all had bladder contraction intervals similar to those of the reference group, and these bladder contraction intervals were similar to those of the positive control tadalafil group.

[0088] This indicates that plant processed products such as ellagic acid, punicalagin, and pomegranate extract containing ellagic acid and pomegranate extract containing punicalagin are useful for prolonging the bladder contraction interval.

[0089] [Table 5]

[0090] [Table 6]

[0091] Table 5 shows the results of urination volume. Table 6 shows the results of bladder capacity. As shown in Table 5, the urination volume of the reference group was 0.9 mL, while the urination volume of the comparison group was 0.6 mL. As shown in Table 6, the bladder capacity of the reference group was 1.0 mL, while the bladder capacity of the comparison group was 0.6 mL.

[0092] This indicates that both the amount of urine excreted and the bladder capacity were reduced in the comparison group compared to the reference group.

[0093] In the reference group, the urination volume was 0.9 mL and the bladder capacity was 1.0 mL, indicating that most of the urine accumulated in the bladder was voided. Furthermore, these findings indicate that the reference group had a larger bladder capacity than the comparison group, and therefore was able to store a larger amount of urine in its bladder than the comparison group, and that despite being able to store such a large amount of urine, it was able to urinate the large amount of urine that had accumulated.

[0094] The pomegranate extract 1 group, pomegranate extract 2 group, ellagic acid group, and punicalagin group all showed similar urination volumes and bladder capacities to the reference group, which were also similar to the positive control tadalafil group.

[0095] This shows that plant processed foods such as ellagic acid, punicalagin, and pomegranate extract containing ellagic acid and punicalagin enable subjects to store larger amounts of urine in the bladder than the comparison group, and that despite being able to store larger amounts of urine, the stored urine can still be urinated sufficiently.

Claims

[Claim 1] A composition for improving urinary tract function, comprising at least one active ingredient selected from the group consisting of the following ingredients (1) and (2): (1) at least one selected from the group consisting of ellagic acid, its analogs, salts thereof, and hydrates thereof; (2) At least one selected from the group consisting of punicalagin, its salts, and hydrates thereof.

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