WO2021106856A1 - Composition for improving urinary tract function and composition for improving blood flow in bladder - Google Patents

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

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Publication number
WO2021106856A1
WO2021106856A1 PCT/JP2020/043623 JP2020043623W WO2021106856A1 WO 2021106856 A1 WO2021106856 A1 WO 2021106856A1 JP 2020043623 W JP2020043623 W JP 2020043623W WO 2021106856 A1 WO2021106856 A1 WO 2021106856A1
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WO
WIPO (PCT)
Prior art keywords
composition
group
ellagic acid
punicarazine
improving
Prior art date
Application number
PCT/JP2020/043623
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French (fr)
Japanese (ja)
Inventor
雄気 伊藤
理夏子 石橋
Original Assignee
小林製薬株式会社
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Priority to JP2021561414A priority Critical patent/JPWO2021106856A1/ja
Publication of WO2021106856A1 publication Critical patent/WO2021106856A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/111—Aromatic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A61K31/37—Coumarins, e.g. psoralen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7024—Esters of saccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/10—Drugs for disorders of the urinary system of the bladder
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/06—Peri-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/01—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing oxygen

Definitions

  • the present invention relates to a composition for improving urinary tract function and a composition for improving bladder blood flow, and a method for improving urinary tract function and a method for improving bladder blood flow.
  • Urination of urinary function such as frequent urination, urinary urgency, urinary incontinence, and residual urine is a symptom that occurs in both men and women and causes various problems in daily life.
  • Known causes of decreased urinary function include, for example, neurogenic bladder, urinary tract infection, and benign prostatic hyperplasia, but there are some that have not been fully elucidated.
  • anticholinergic drugs may be used to improve urinary function such as frequent urination and urinary urgency, but as side effects, they may cause increased residual urine volume, urinary retention, etc., and are sufficient for their use. You need to be careful.
  • ellagic acid is a kind of conventionally known polyphenol, and it is known that it can be produced by hydrolyzing punicarazine. So far, it is known that ellagic acid has an antioxidant effect, an anticancer effect, and the like. It has also been reported that ellagic acid assists in whitening action and vitamin C absorption promoting action in a living body (Patent Documents 1 and 2). However, it is not known that ellagic acid and punicarazine can improve micturition function.
  • An object of the present invention is to provide a new composition or the like that can improve the urinary function.
  • an object of the present invention is to provide a new composition or the like that can improve urinary tract function and bladder blood flow.
  • a composition for improving urinary tract function containing at least one selected from the group consisting of the following components (1) and (2) as an active ingredient: (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 punicarazine, salts thereof and hydrates thereof.
  • a composition for improving bladder blood flow which comprises at least one selected from the group consisting of the following components (1) and (2) as an active ingredient: (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 punicarazine, salts thereof and hydrates thereof.
  • Item 3. Item 2. The composition for improving urinary tract function according to Item 1, wherein the improvement in urinary tract function is at least one selected from the group consisting of improvement in pollakiuria, improvement in urine storage volume, and improvement in urination volume.
  • Item 5. Item 2. 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. Item 2. The composition for improving bladder blood flow according to Item 2, which contains a processed pomegranate plant containing at least one selected from the group consisting of the components (1) and (2).
  • a method for improving urinary tract function which comprises applying a composition containing at least one selected from the group consisting of the following components (1) and (2) as an active ingredient, preferably orally.
  • (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 punicarazine, salts thereof and hydrates thereof.
  • Item 13 Item 12.
  • the method according to Item 12, wherein the improvement in urinary tract function is at least one selected from the group consisting of improvement in pollakiuria, improvement in urine storage volume, and improvement in urination volume.
  • a method for improving bladder blood flow which comprises applying a composition containing at least one selected from the group consisting of the following components (1) and (2) as an active ingredient, preferably orally.
  • a composition containing at least one selected from the group consisting of the following components (1) and (2) as an active ingredient preferably orally.
  • (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 punicarazine, salts thereof and hydrates thereof.
  • Item 15 Item 12 to Item 12 to which a composition containing a processed pomegranate plant containing at least one selected from the group consisting of the components (1) and (2) is applied, preferably orally administered. The method described.
  • the urinary tract function can be improved. Further, according to the present invention, bladder blood flow can be improved. According to the present invention, it is possible to improve urinary tract functions such as pollakiuria, urine storage volume, and urination volume.
  • composition for improving urinary tract function which comprises at least one selected from the group consisting of the following components (1) and (2) as an active ingredient.
  • composition for improving bladder blood flow which contains at least one selected from the group consisting of the following components (1) and (2) as an active ingredient.
  • containing also includes “containing”, “substantially composed of”, and “consisting of only”.
  • the ellagic acid is a conventionally known substance represented by CAS No. 476-66-4 (molecular formula C 14 H 6 O 8 , molecular weight 302.19), and the ellagic acid is commercially available in the present invention. Goods 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., and the like.
  • the present invention is not limited, but 3-O-methylellagic acid, flaveragic acid, 3,3'-di-O-methylellagic acid, 3,4,3'-trimethylellagic acid.
  • Examples of the salt of ellagic acid and the salt of the analog include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, ammonium salts and amine salts. These may be used individually by 1 type, and may be used in combination of 2 or more type.
  • hydrates of the ellagic acid, the analog, and the salt are conventionally known hydrates. These may be used individually by 1 type, and may be used in combination of 2 or more type.
  • At least one selected from the group consisting of ellagic acid, salts thereof and hydrates thereof is exemplified, and more preferably ellagic acid is exemplified, although the present invention is not limited. Will be done.
  • composition for improving urinary tract function and the component (1) used in producing the composition for improving bladder blood flow may be a refined product (pure product) and exert the effect of the present invention.
  • the present invention is not limited to this, and may be, for example, a processed plant product (processed plant product) containing the component (1) or a crudely purified product of the component (1).
  • the processed plant product is not limited to the present invention, but is preferably a processed plant product containing at least one selected from the group consisting of ellagic acid, salts thereof and hydrates thereof, more preferably ellagic acid.
  • processed plant products include.
  • the present invention is not limited, but at least one crude product selected from the group consisting of ellagic acid, salts thereof and hydrates thereof, more preferably ellagic acid.
  • a crude product is exemplified.
  • Examples of the processed plant product and the crudely purified product include a processed plant product containing ellagic acid and a crudely purified product of ellagic acid.
  • the crude product will be described in the same manner as below.
  • the processed plant products containing ellagic acid do not limit the present invention, but are strawberry (a plant belonging to the genus Fragaria of the Netherlands), cranberry (a plant belonging to the genus Vaccinium), and raspberry (a plant belonging to the genus Vaccinium).
  • Rubus a plant belonging to the genus Fragaria of the Netherlands
  • cranberry a plant belonging to the genus Vaccinium
  • raspberry a plant belonging to the genus Vaccinium
  • Rubus grapes (Vitis), walnuts (Juglans), chestnuts (Castanea), Pecan (Carya)
  • Gennoshouko plant belonging to the genus Geranium
  • Kuko plant belonging to the genus Lycium
  • pomegranate plant belonging to the genus Punica
  • a plant belonging to the genus Pomegranate will be described.
  • the genus Pomegranate belongs to the Lythraceae family, and although it does not limit the present invention
  • the site of use is not particularly limited, and leaves, stems, fruits, peels, flowers, buds, branches, trunks, bark, roots, seeds, seed coats, etc. are exemplified, and appropriately according to each plant. You can select it.
  • leaves, stems, fruits, peels, flowers, buds, branches, trunks, bark, roots, seeds, seed coats, etc. are exemplified, and appropriately according to each plant. You can select it.
  • fruits, pericarps, seeds, and seed coats are exemplified as preferable sites for use.
  • the site of use one type may be used alone, or two or more types may be used in combination.
  • the processed plant product includes a crushed product, a dried product, an extract, etc. of the plant as the raw material.
  • the crushed product does not limit the present invention, but an example thereof is a crushed product obtained by crushing the plant with a crusher known in the art such as a jet mill.
  • the dried product is not particularly limited as long as the plant is dried, and is dried according to a conventionally known drying method such as sun drying, far infrared irradiation, and a dryer (hot air drying, cold air drying, vacuum freeze drying, etc.). An example is the one that has been made to do so.
  • the amount of water in the dried product is not limited to the present invention, but is preferably 10% by mass or less, more preferably 8% by mass or less.
  • the form of the dried product is not limited, and either the dried product of the plant (arbitrary part) itself, the crushed product of the dried product (dried crushed product), or the like may be used.
  • the dried pulverized product can be obtained by pulverizing the dried product according to the same method as the pulverized product. Further, in the present invention, the dried product may be obtained by fermenting or enzymatically treating a plant as a raw material and then drying it.
  • the method for producing the extract is not particularly limited, and conventionally known methods may be followed.
  • the plant can be cut, crushed, dried or the like as it is, if necessary, and then an extract can be obtained by exploitation or solvent extraction.
  • the solvent extraction method a method known in the art may be adopted, and conventionally known extraction methods such as water (including hot water and hot water) extraction, alcohol extraction, supercritical extraction and the like can be used. ..
  • the solvent is, for example, water; lower alcohols such as methanol, ethanol and isopropanol, and alcohols such as polyhydric alcohols such as propylene glycol and 1,3-butylene glycol (whether anhydrous or water-containing). ); Ketones such as acetone, esters such as diethyl ether, dioxane, acetonitrile and ethyl acetate, xylene, benzene, chloroform and the like.
  • the solvent is preferably water, a lower alcohol, 1,3-butylene glycol or the like, more preferably water, methanol, ethanol or 1,3-butylene glycol, and further preferably water, methanol or hydrous ethanol. These solvents may be used alone or in combination of two or more.
  • the extract obtained through solvent extraction in this way can be particularly referred to as a solvent extract.
  • a solvent extract when water is used as a solvent
  • a lower alcohol extract when lower alcohols are used and an ethanol extract when ethanol is used. It can be called a thing or the like.
  • the obtained extract may be used as it is, or may be dried and used in a solid state such as powder or granules. Further, if necessary, the obtained extract may be subjected to purification, concentration treatment, separation treatment of highly active fractions and the like.
  • the purification treatment include treatments such as filtration, adsorption using an ion exchange resin, an activated carbon column, and decolorization.
  • concentration treatment a conventional method such as an evaporator can be used.
  • separation treatment of the highly active fraction known separation treatments such as gel filtration, adsorption treatment, silica gel column chromatography, and HPLC (High performance liquid chromatography) can be used.
  • a method of pulverizing the extract obtained as described above by freeze-drying treatment, if necessary.
  • the extract may be used in the present invention by adding excipients such as dextrin, cornstarch, and arabic rubber and pulverizing according to a conventionally known method such as a method of pulverizing by spray-drying. Further, the extract may be used by dissolving it in water, ethanol or the like, if necessary.
  • the extract is preferably an extract obtained by drying, crushing and / or cutting a plant (arbitrary part) as a raw material, extracting and filtering using a suitable solvent, and an extract thus obtained.
  • An example is an extract obtained by further drying the product.
  • the present invention is not limited, and a person skilled in the art may appropriately extract the extract according to the site of use of the plant, but the extract is a dried or crushed product of the plant as a raw material per 100 g, more preferably. And / or the cut product is immersed in 1 to 50 liters of the extraction solvent per 100 g, and at an arbitrary temperature (for example, 15 to 90 ° C.), with stirring as necessary, for an arbitrary time (for example, 10 minutes to 24 hours). ) Can be obtained by performing extraction and then filtering. Further, as described above, if necessary, the obtained extract may be subjected to purification, concentration treatment, various separation treatments for highly active fractions, and the like.
  • a commercially available product may be used, or the commercially available product may be further subjected to a treatment such as drying.
  • examples of the processed plant product containing ellagic acid are preferably a processed pomegranate plant containing ellagic acid, and more preferably an extract of a pomegranate plant containing ellagic acid (including a dried product thereof). ..
  • the processed plant product may be used alone or in combination of two or more.
  • an ellagic acid fraction prepared from a plant containing ellagic acid can be exemplified.
  • the plant containing ellagic acid are not limited to the present invention, but the above-mentioned plants are exemplified, and the above-mentioned arbitrary sites of use are exemplified.
  • ellagitannins such as punicarazine, punicalin, and galaxic acid produce ellagic acid by their hydrolysis and the like. Therefore, as a crude product of ellagic acid, an ellagic acid fraction prepared from a plant containing ellagitannin by a decomposition treatment such as hydrolysis can also be exemplified.
  • ellagic acid can be produced by chemical synthesis using gallic acid. Therefore, as a crude product of ellagic acid, an ellagic acid fraction prepared by chemical synthesis from a plant containing gallic acid can also be exemplified.
  • the ellagic acid fraction is extracted once from a plant (arbitrary site) containing ellagic acid using one kind of solvent (for example, water; alcohol such as methanol and ethanol; hydrous alcohol), and then filtered and concentrated.
  • solvent for example, water; alcohol such as methanol and ethanol; hydrous alcohol
  • solvent extraction is repeated a plurality of times in order to obtain a fraction having a high degree of purification (purity) of ellagic acid or to obtain a concentrated fraction containing a high concentration of ellagic acid.
  • purification operations such as molecular weight filtration, size exclusion chromatography, and ion exchange chromatography.
  • a fraction in which components other than ellagic acid are removed from the fraction containing ellagic acid and the content of ellagic acid is increased to 50% by mass or more can be exemplified, and the ellagic acid fraction can be exemplified.
  • the content of ellagic acid in the above is preferably 60 to 100% by mass, more preferably 70 to 100% by mass, still more preferably 80 to 100% by mass, and particularly preferably 90 to 100% by mass.
  • the processed plant product when the processed plant product is such a crude product of ellagic acid, the processed plant product may be used as the crude product.
  • punicarazine is a conventionally known substance, and in the present invention, punicarazine may be a commercially available product. Although not limiting the present invention, it is commercially available, for example, by Cayman Chemical, Sigma-Aldrich, and the like.
  • the salt of punicarazine 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 the punicarazine and salts thereof include conventionally known hydrates.
  • punicarazine is preferably exemplified. These may be used individually by 1 type, and may be used in combination of 2 or more type.
  • composition for improving urinary tract function and the component (2) used in producing the composition for improving bladder blood flow may be a refined product (pure product) and exert the effect of the present invention.
  • the present invention is not limited to this, and may be, for example, a processed plant product (processed plant product) containing the component (2) or a crudely purified product of the component (2).
  • the processed plant product does not limit the present invention, but preferably a processed plant product containing punicarazine. Further, as the crude product, a crude product of punicarazine is preferably exemplified, although the present invention is not limited.
  • Examples of the processed plant product and the crudely refined product include a processed plant product containing punicarazine and a crudely purified product of punicarazine.
  • the processed plant product and the crudely refined product containing the component (2) other than punicarazine will be described below. Will be described in the same manner as below.
  • processed plant products containing punicarazine include, but are not limited to, processed products of plants such as myrobalan (a plant belonging to the genus Tropical almond) and pomegranate (a plant belonging to the genus Pomegranate).
  • myrobalan a plant belonging to the genus Tropical almond
  • pomegranate a plant belonging to the genus Pomegranate
  • plants belonging to the genus Pomegranate will be described in the same manner as described above.
  • the site of use is not particularly limited as long as it is a plant containing punicarazine, and leaves, stems, fruits, peels, flowers, buds, branches, trunks, bark, roots, seeds, seed coats, etc. are exemplified and appropriately selected according to each plant. do it.
  • fruits, pericarps, seeds, and seed coats are exemplified as preferable sites for use.
  • the parts to be used one type may be used alone, or two or more types may be used in combination.
  • the processed plant product containing punicarazine the processed plant product is described in the same manner as described above.
  • the processed plant product containing punicarazine is preferably a processed pomegranate plant containing punicarazine, and more preferably an extract of a pomegranate plant containing punicarazine (including a dried product thereof).
  • the processed plant product may be used alone or in combination of two or more.
  • a punicarazine fraction prepared from a plant containing punicarazine can be exemplified.
  • plants containing punicarazine include, but are not limited to, the above-mentioned plants.
  • the punicarazine fraction is also described in the same manner as the ellagic acid fraction, that is, using one kind of solvent (for example, water; alcohol such as methanol and ethanol; hydrous alcohol) from a plant (arbitrary site) containing punicarazine. It is not prepared by extracting once and then filtering and concentrating, but to obtain a fraction with a high degree of purification (purity) of punicarazine or to obtain a concentrated fraction containing a high concentration of punicarazine. Fraction obtained by repeating solvent extraction multiple times or by arbitrarily combining purification operations such as molecular weight filtration, size exclusion chromatography, ion exchange chromatography, etc., and pressing a plant (arbitrary site) containing punicarazine.
  • solvent for example, water; alcohol such as methanol and ethanol; hydrous alcohol
  • the fraction means a fraction obtained by repeating concentration by column filtration or the like. More specifically, it is possible to exemplify a fraction in which components other than punicarazine are removed from the fraction containing punicarazine and the content of punicarazine is increased to 25% by mass or more, preferably 30% by mass or more. 25 to 100% by mass and 30 to 100% by mass are exemplified as the content of punicarazine in the fraction, and the content of punicarazine in the punicarazine fraction is preferably 50 to 100% by mass, more preferably 70 to 100% by mass. %, More preferably 80 to 100% by mass, and particularly preferably 90 to 100% by mass.
  • the processed plant product when the processed plant product is such a crude product of punicarazine, the processed plant product may be used as the crude product.
  • the content of at least one selected from the group consisting of the components (1) and (2) is a symptomatology, an application form, etc. It is not limited as long as it is appropriately determined according to the above.
  • at least one selected from the group consisting of the above components (1) and (2) has a total amount (solid content concentration) of 0% by mass or more. It may be as much as less than 100% by mass, preferably 1 to 70% by mass, and more preferably 5 to 30% by mass.
  • the content of at least one selected from the group consisting of the components (1) and (2) is not limited, but the following content can also be exemplified.
  • the content of the component (1) in each composition may be appropriately determined depending on the symptom, application form, etc., and is not limited, but the total amount (solid content concentration) of the component (1) in the composition is preferably 3. Examples thereof include ⁇ 70% by mass and 15 to 30% by mass.
  • the content of the component (2) in each composition may be appropriately determined depending on the symptom, application form, etc., and is not limited, but the total amount (solid content concentration) thereof in the composition is preferably 1. To 25% by mass, 5 to 10% by mass can be exemplified.
  • the present invention is not limited, but the processed plant product.
  • the content is not limited as it may be appropriately determined according to the symptom, application form, etc., but the total amount (in terms of dry mass) of the composition is preferably 1 to 95% by mass and 30 to 80% by mass. It can be exemplified.
  • the dried product of the processed plant product is obtained by freeze-drying the processed product.
  • the freeze-drying treatment is carried out by concentration under reduced pressure using a general evaporator and freeze-drying in a vacuum state.
  • the dose (intake) 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 exhibited, and is an application target ( It may be appropriately set according to the symptoms, application form, physique, age, degree of expected effect, etc. of the target person (target animal).
  • the daily dose (intake) to humans at least one selected from the group consisting of the above components (1) and (2) is used in a total amount (solid content concentration).
  • a total amount solid content concentration
  • 0.5 to 70 mg / kg body weight, more preferably 1 to 5 mg / kg body weight is exemplified.
  • Each of the compositions may be administered once (intake) or multiple times (intake) per day, and may be administered (intake) at arbitrary periods and intervals.
  • the present invention is not limited, but the processed plant product.
  • the dose (intake) is not particularly limited as long as the effect of the present invention is exhibited, and depends on the symptom, application form, physique, age, degree of expected effect, etc. of the application target (subject, target animal). It may be set appropriately.
  • the daily administration (intake) amount for humans the total amount (in terms of dry mass) of the processed plant product is preferably 1.5 to 80 mg / kg body weight, more preferably 2 to 8 mg / kg. Weight is illustrated.
  • HED human equivalent dose
  • Each composition is preferably orally administered (ingested) regardless of whether it is oral or parenteral.
  • the form is not limited, and may be appropriately set according to the purpose.
  • the forms include liquid forms such as liquids, emulsions, suspensions, syrups, extracts, alcoholic beverages, and elixirs, powders, granules, fine granules, tablets (including coated tablets such as sugar-coated tablets), and pills. , Capsules (including hard capsules and soft capsules), troches, chewables, gels, creams, pastes, mousses, sheets, liquid forms such as lyophilized products, semi-solid or solid forms, and aerosols, etc. , Various forms such as a patch, a pill, and a percutaneous absorption type preparation are exemplified.
  • each composition is not limited, and may be appropriately set according to the purpose.
  • examples of usage include food compositions (including beverages, health functional foods (including foods for specified health use, nutritionally functional foods, foods with functional claims, supplements, etc.), foods for the sick), pharmaceutical compositions, and pharmaceutical departments. It can be used as a foreign product composition, a feed composition, an additive to a food composition, a pharmaceutical composition, a pharmaceutical foreign product composition, a feed, or the like.
  • Each composition may be produced according to a conventionally known conventional procedure in the above-mentioned various forms, usage modes, etc., and if necessary, a pharmaceutically acceptable ingredient, a cosmetic scientifically acceptable ingredient, and the like are acceptable. It may be produced by mixing with an arbitrary component such as an edible component.
  • a solvent water, lower alcohol such as methanol, ethanol, isopropanol, alcohol such as propylene glycol, polyhydric alcohol such as 1,3-butylene glycol (whether anhydrous or water-containing), etc.
  • the target (target person, target animal) to which each composition is applied is not limited, but humans and mammals other than humans are exemplified. Further, in the present invention, a female (female) is preferably exemplified as a subject (target animal) to which the composition is applied, but the present invention is not limited to this.
  • a female female
  • dysuria such as frequent urination during the day or night, overactive bladder, urinary urgency or urge incontinence, and the rest.
  • An example is a person who feels urine.
  • urinary tract function can be improved by using at least one selected from the group consisting of the components (1) and (2) as an active ingredient.
  • urinary tract function such as pollakiuria (bladder contraction interval), urine storage amount (bladder capacity) and / or urination amount can be improved. From this, it can be said that the present invention provides a method for improving urinary tract function, which comprises using at least one selected from the group consisting of the components (1) and (2). For this reason, the above description is applied to the description of the method.
  • bladder blood flow can be improved by using at least one selected from the group consisting of the above components (1) and (2) as an active ingredient. From this, it can be said that the present invention provides a method for improving bladder blood flow, which comprises using at least one selected from the group consisting of the components (1) and (2). For this reason, the above description is applied to the description of the method.
  • the present invention is also useful for preventing or ameliorating urinary disorders such as frequent urination during the day and night, overactive bladder, urinary urgency, and urge incontinence.
  • Test Example 1 Improvement of bladder blood flow Bladder blood flow evaluation procedure Rats (SD female rats (Sprague-Dawley rats), 8-9 weeks old (weight 190-220 g / animal) at the start of the experiment) were opened under isoflurane anesthesia, bilateral common iliac veins and bilateral. A pelvic congestion model was created by ligating the uterine vein. After suturing the abdominal opening, a rat model of pelvic congestion was bred in a cage for 16 days. At this time, general commercially available feed and water were freely ingested.
  • tadalafil pomegranate extract 1 (pomegranate extract containing ellagic acid), pomegranate extract 2 (pomegranate extract containing punicalazine), ellagic acid, or punicarazine were mixed with the feed to prepare a powdered mixed feed.
  • tadalafil group means a group fed with tadalafil mixed feed
  • 0.01% mixed feed described in the tadalafil group means 0.01% by mass of tadalafil in the mixed feed. It means that the mixed feed obtained by mixing so as to have a solid content concentration) was ingested.
  • pomegranate extract 1 and 2 are the amount of pomegranate extract in terms of dry mass
  • ellagic acid and punicarazine are the amount of ellagic acid and punicarazine in terms of solid content concentration.
  • tadalafil was used as a positive control to increase blood flow.
  • the tadalafil used was trade name Tadalafil (manufactured by Combi-Blocks), and pomegranate extract 1 was trade name pomegranate ellagic acid (manufactured by Sabinsa Japan Corporation (containing 80% by mass of ellagic acid, ethanol extract of Punica granatum peel), pomegranate extract.
  • 2 is the trade name Pomanox P30 (manufactured by NC Corporation (containing 30% Punicarazine, an extract obtained by pressing and concentrating the entire fruit including the peel of Punica granatum)
  • ellagic acid is the trade name ellagic acid (98 mass of ellagic acid).
  • Punicaragin is the trade name Punicalagin (containing 40% by mass of Punicarazine, manufactured by Santa Cruise Biotechnology).
  • the doses of tadalafil, ellagic acid, and punicarazine are The doses of these commercially available products are shown.
  • the bladder blood flow in the reference group (average of 6 rats, the same applies hereinafter) was 17.0 mL / min / 100 g, whereas the bladder blood flow in the comparative group was 11.1 mL / min. It was min / 100 g, and the bladder blood flow was decreased in the comparative group.
  • the bladder blood flow in the pomegranate extract 1 group, the pomegranate extract 2 group, the ellagic acid group, and the punicarazine group the bladder blood flow was restored to the same extent as the reference group, and these bladder blood flow were positively controlled by tadalafil. It was about the same as the group.
  • plant processed products such as ellagic acid and punicarazine, pomegranate extract containing ellagic acid, and pomegranate extract containing punicarazine are useful for increasing bladder blood flow.
  • Punicarazine is a refined version of Punicarazine from the trade name Pomanox P30 (manufactured by NC Corporation (containing 30% Punicarazine, an extract obtained by pressing and concentrating the entire fruit including the peel of Punica granatum) (Punicarazine 96.7 mass).
  • the doses of tadalafil and ellagic acid indicate the doses of these commercially available products, and the dose of punicarazine indicates the dose of the purified product.
  • USB I / O unit 8ch AIO-160802AY-USB manufactured by Contec Co., Ltd.
  • LaBDAQ5-CT ver.1.06 manufactured by Matsuyama Advance Co., Ltd.
  • Table 4 shows the results showing the bladder contraction interval (unit of average value: minutes).
  • the bladder contraction interval of the reference group was 18.9 minutes, whereas the bladder contraction interval of the comparison group was 11.0 minutes, and the bladder contraction interval was short in the comparison group. This indicates that the frequency of urination was higher in the comparison group than in the reference group.
  • the pomegranate extract 1 group, the pomegranate extract 2 group, the ellagic acid group, and the punicarazine group all have the same bladder contraction interval as the reference group, and these bladder contraction intervals are the positive control tadalafil group. It was about the same as.
  • processed plant products such as ellagic acid and punicarazine, pomegranate extract containing ellagic acid, and pomegranate extract containing punicarazine are useful for prolonging the bladder contraction interval.
  • Table 5 shows the results showing the amount of urination.
  • Table 6 shows the results showing the bladder capacity. As shown in Table 5, the micturition volume of the reference group was 0.9 mL, while the micturition volume of the comparative group was 0.6 mL. Further, as shown in Table 6, the bladder volume of the reference group was 1.0 mL, whereas the bladder volume of the comparative group was 0.6 mL.
  • the amount of urine was 0.9 mL and the bladder capacity was 1.0 mL, indicating that most of the urine collected in the bladder was urinated.
  • the reference group has a larger bladder capacity itself than the comparison group, and therefore, a larger amount of urine can be collected in the bladder than the comparison group, and thus a large amount of urine can be collected. Nevertheless, it was found that a large amount of accumulated urine could be sufficiently urinated.
  • the pomegranate extract 1 group, pomegranate extract 2 group, ellagic acid group, and punicarazine group all showed the same level of urination volume and bladder volume as the reference group, and these were similar to the positive control tadalafil group.
  • plant products such as ellagic acid, punicarazine, and pomegranate extract containing ellagic acid and punicarazine can also collect a larger amount of urine in the bladder than the comparative group, and also collect a larger amount of urine. Despite this, it was found that the accumulated urine could be sufficiently urinated.

Abstract

The purpose of the present invention is 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.　This composition for improving urinary tract function or composition for improving blood flow in the bladder contains at least one active ingredient 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.

Description

尿路機能改善用組成物及び膀胱血流改善用組成物Composition for improving urinary tract function and composition for improving bladder blood flow
　本発明は、尿路機能改善用組成物及び膀胱血流改善用組成物、また、尿路機能改善方法及び膀胱血流改善方法に関する。 The present invention relates to a composition for improving urinary tract function and a composition for improving bladder blood flow, and a method for improving urinary tract function and a method for improving bladder blood flow.
　頻尿、尿意切迫感、尿失禁、残尿感といった排尿機能の低下は、男女を問わず生じる症状であり、日常生活に様々な支障をきたす。排尿機能低下の原因としては、例えば、神経因性膀胱、尿路感染症、前立腺肥大症等が知られているが、十分に解明されていないところもある。 Deterioration of urinary function such as frequent urination, urinary urgency, urinary incontinence, and residual urine is a symptom that occurs in both men and women and causes various problems in daily life. Known causes of decreased urinary function include, for example, neurogenic bladder, urinary tract infection, and benign prostatic hyperplasia, but there are some that have not been fully elucidated.
　従来、頻尿や尿意切迫感といった排尿機能を改善するために抗コリン薬が使用されることがあるが、その副作用として残尿量増加、尿閉等を引き起こす恐れもあり、その使用には十分な注意が必要である。 Conventionally, anticholinergic drugs may be used to improve urinary function such as frequent urination and urinary urgency, but as side effects, they may cause increased residual urine volume, urinary retention, etc., and are sufficient for their use. You need to be careful.
　一方、エラグ酸は、従来公知のポリフェノールの一種であり、プニカラジンを加水分解することにより産生できることが知られている。これまでに、エラグ酸は抗酸化作用や抗がん作用等を有することが知られている。また、エラグ酸は、美白作用や生体でのビタミンＣ吸収促進作用を助けることも報告されている（特許文献１及び２）。しかし、エラグ酸やプニカラジンが排尿機能を改善できることは知られていない。 On the other hand, ellagic acid is a kind of conventionally known polyphenol, and it is known that it can be produced by hydrolyzing punicarazine. So far, it is known that ellagic acid has an antioxidant effect, an anticancer effect, and the like. It has also been reported that ellagic acid assists in whitening action and vitamin C absorption promoting action in a living body (Patent Documents 1 and 2). However, it is not known that ellagic acid and punicarazine can improve micturition function.
特開２０１９－１４６７２号公報Japanese Unexamined Patent Publication No. 2019-14672 特開２０１８－１３８５２５号公報JP-A-2018-138525
　本発明は、排尿機能を改善できる新たな組成物等を提供することを目的とする。特に、本発明は、尿路機能や膀胱血流を改善できる新たな組成物等を提供することを目的とする。 An object of the present invention is to provide a new composition or the like that can improve the urinary function. In particular, an object of the present invention is to provide a new composition or the like that can improve urinary tract function and bladder blood flow.
　本発明者らは、前記課題に鑑み鋭意検討を行ったところ、エラグ酸、プニカラジンによれば、尿路機能、膀胱血流を改善できることを見出した。本発明は該知見に基づき更に検討を重ねた結果完成されたものであり、次に掲げるものである。
項１．次の成分（１）及び（２）からなる群より選択される少なくとも１種を有効成分として含有する、尿路機能改善用組成物：
（１）エラグ酸、その類縁体、これらの塩及びこれらの水和物からなる群より選択される少なくとも１種、
（２）プニカラジン、その塩及びこれらの水和物からなる群より選択される少なくとも１種。
項２．次の成分（１）及び（２）からなる群より選択される少なくとも１種を有効成分として含有する、膀胱血流改善用組成物：
（１）エラグ酸、その類縁体、これらの塩及びこれらの水和物からなる群より選択される少なくとも１種、
（２）プニカラジン、その塩及びこれらの水和物からなる群より選択される少なくとも１種。
項３．前記尿路機能改善が、頻尿の改善、貯尿量の改善及び排尿量の改善からなる群より選択される少なくとも１種である、項１に記載の尿路機能改善用組成物。
項４．前記成分（１）及び（２）からなる群より選択される少なくとも１種を含むザクロ属植物加工物を含有する、項１または３に記載の尿路機能改善用組成物。
項５．食品組成物、医薬組成物、医薬部外品組成物または飼料組成物である、項１、３及び４のいずれかに記載の尿路機能改善用組成物。
項６．前記成分（１）及び（２）からなる群より選択される少なくとも１種を含むザクロ属植物加工物を含有する、項２に記載の膀胱血流改善用組成物。
項７．食品組成物、医薬組成物、医薬部外品組成物または飼料組成物である、項２または６に記載の膀胱血流改善用組成物。
項８．尿路機能を改善するために使用される、次の成分（１）及び（２）からなる群より選択される少なくとも１種を有効成分として含有する組成物：
（１）エラグ酸、その類縁体、これらの塩及びこれらの水和物からなる群より選択される少なくとも１種、
（２）プニカラジン、その塩及びこれらの水和物からなる群より選択される少なくとも１種。
項９．前記尿路機能改善が、頻尿の改善、貯尿量の改善及び排尿量の改善からなる群より選択される少なくとも１種である、項８に記載の組成物。
項１０．膀胱血流を改善するために使用される、次の成分（１）及び（２）からなる群より選択される少なくとも１種を有効成分として含有する組成物：
（１）エラグ酸、その類縁体、これらの塩及びこれらの水和物からなる群より選択される少なくとも１種、
（２）プニカラジン、その塩及びこれらの水和物からなる群より選択される少なくとも１種。
項１１．尿路機能を改善するために使用される、または、膀胱血流を改善するために使用される、項８または１０に記載する成分（１）及び（２）からなる群より選択される少なくとも１種を含むザクロ属植物加工物を含有する組成物。
項１２．次の成分（１）及び（２）からなる群より選択される少なくとも１種を有効成分として含有する組成物を対象に適用、好ましくは経口投与することを含む、尿路機能改善方法：
（１）エラグ酸、その類縁体、これらの塩及びこれらの水和物からなる群より選択される少なくとも１種、
（２）プニカラジン、その塩及びこれらの水和物からなる群より選択される少なくとも１種。
項１３．前記尿路機能改善が、頻尿の改善、貯尿量の改善及び排尿量の改善からなる群より選択される少なくとも１種である、項１２に記載の方法。
項１４．次の成分（１）及び（２）からなる群より選択される少なくとも１種を有効成分として含有する組成物を対象に適用、好ましくは経口投与することを含む、膀胱血流改善方法：
（１）エラグ酸、その類縁体、これらの塩及びこれらの水和物からなる群より選択される少なくとも１種、
（２）プニカラジン、その塩及びこれらの水和物からなる群より選択される少なくとも１種。
項１５．前記成分（１）及び（２）からなる群より選択される少なくとも１種を含むザクロ属植物加工物を含有する組成物を対象に適用、好ましくは経口投与する、項１２～１４のいずれかに記載の方法。
項１６．尿路機能改善用組成物を製造するための、次の成分（１）及び（２）からなる群より選択される少なくとも１種の使用：
（１）エラグ酸、その類縁体、これらの塩及びこれらの水和物からなる群より選択される少なくとも１種、
（２）プニカラジン、その塩及びこれらの水和物からなる群より選択される少なくとも１種。
項１７．膀胱血流改善用組成物を製造するための、次の成分（１）及び（２）からなる群より選択される少なくとも１種の使用：
（１）エラグ酸、その類縁体、これらの塩及びこれらの水和物からなる群より選択される少なくとも１種、
（２）プニカラジン、その塩及びこれらの水和物からなる群より選択される少なくとも１種。 The present inventors have conducted diligent studies in view of the above problems, and found that ellagic acid and punicarazine can improve urinary tract function and bladder blood flow. The present invention has been completed as a result of further studies based on the findings, and is as follows.
Item 1. A composition for improving urinary tract function containing at least one selected from the group consisting of the following components (1) and (2) as an active ingredient:
(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 punicarazine, salts thereof and hydrates thereof.
Item 2. A composition for improving bladder blood flow, which comprises at least one selected from the group consisting of the following components (1) and (2) as an active ingredient:
(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 punicarazine, salts thereof and hydrates thereof.
Item 3. Item 2. The composition for improving urinary tract function according to Item 1, wherein the improvement in urinary tract function is at least one selected from the group consisting of improvement in pollakiuria, improvement in urine storage volume, and improvement in urination volume.
Item 4. Item 3. The composition for improving urinary tract function according to Item 1 or 3, which contains a processed pomegranate plant containing at least one selected from the group consisting of the components (1) and (2).
Item 5. Item 2. 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. Item 2. The composition for improving bladder blood flow according to Item 2, which contains a processed pomegranate plant containing at least one selected from the group consisting of the components (1) and (2).
Item 7. Item 2. 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 containing at least one selected from the group consisting of the following components (1) and (2) as an active ingredient, which is used to improve 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 punicarazine, salts thereof and hydrates thereof.
Item 9. Item 8. The composition according to Item 8, wherein the improvement in urinary tract function is at least one selected from the group consisting of improvement in pollakiuria, improvement in urine storage volume, and improvement in urination volume.
Item 10. A composition containing at least one selected from the group consisting of the following components (1) and (2) as an active ingredient, which is used to improve 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 punicarazine, salts thereof and hydrates thereof.
Item 11. At least one selected from the group consisting of the components (1) and (2) according to Item 8 or 10, which is used to improve urinary tract function or is used to improve bladder blood flow. A composition containing a processed pomegranate plant containing seeds.
Item 12. A method for improving urinary tract function, which comprises applying a composition containing at least one selected from the group consisting of the following components (1) and (2) as an active ingredient, preferably orally.
(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 punicarazine, salts thereof and hydrates thereof.
Item 13. Item 12. The method according to Item 12, wherein the improvement in urinary tract function is at least one selected from the group consisting of improvement in pollakiuria, improvement in urine storage volume, and improvement in urination volume.
Item 14. A method for improving bladder blood flow, which comprises applying a composition containing at least one selected from the group consisting of the following components (1) and (2) as an active ingredient, preferably orally.
(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 punicarazine, salts thereof and hydrates thereof.
Item 15. Item 12 to Item 12 to which a composition containing a processed pomegranate plant containing at least one selected from the group consisting of the components (1) and (2) is applied, preferably orally administered. The method described.
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 punicarazine, salts thereof 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 punicarazine, salts thereof and hydrates thereof.
　本発明によれば、尿路機能を改善することができる。また、本発明によれば、膀胱血流を改善することができる。本発明によれば、特に、頻尿、貯尿量、排尿量といった尿路機能を改善することができる。 According to the present invention, the urinary tract function can be improved. Further, according to the present invention, bladder blood flow can be improved. According to the present invention, it is possible to improve urinary tract functions such as pollakiuria, urine storage volume, and urination volume.
尿路機能改善用組成物
　本発明は、次の成分（１）及び（２）からなる群より選択される少なくとも１種を有効成分として含有する、尿路機能改善用組成物に関する。
（１）エラグ酸、その類縁体、これらの塩及びこれらの水和物からなる群より選択される少なくとも１種、
（２）プニカラジン、その塩及びこれらの水和物からなる群より選択される少なくとも１種。 Composition for improving urinary tract function The present invention relates to a composition for improving urinary tract function, which comprises at least one selected from the group consisting of the following components (1) and (2) as an active ingredient.
(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 punicarazine, salts thereof and hydrates thereof.
膀胱血流改善用組成物
　本発明は、次の成分（１）及び（２）からなる群より選択される少なくとも１種を有効成分として含有する、膀胱血流改善用組成物に関する。
（１）エラグ酸、その類縁体、これらの塩及びこれらの水和物からなる群より選択される少なくとも１種、
（２）プニカラジン、その塩及びこれらの水和物からなる群より選択される少なくとも１種。 Composition for improving bladder blood flow The present invention relates to a composition for improving bladder blood flow, which contains at least one selected from the group consisting of the following components (1) and (2) as an active ingredient.
(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 punicarazine, salts thereof and hydrates thereof.
　これらの組成物について、以下に説明する。なお、本開示において「含有する」とは、「含有する」、「実質的にからなる」、「のみからなる」をも包含する。 These compositions will be described below. In the present disclosure, "containing" also includes "containing", "substantially composed of", and "consisting of only".
成分（１）
　前記成分（１）について、前記エラグ酸は、ＣＡＳ番号４７６－６６－４で示される従来公知の物質であり（分子式Ｃ１４Ｈ６Ｏ８、分子量３０２．１９）、本発明においてエラグ酸は市販品を用いてもよい。本発明を制限するものではないが、エラグ酸は、例えば富士フイルム和光純薬株式会社、東京化成工業株式会社等から市販されている。 Ingredient (1)
Regarding the component (1), the ellagic acid is a conventionally known substance represented by CAS No. 476-66-4 (molecular formula C 14 H 6 O 8 , molecular weight 302.19), and the ellagic acid is commercially available in the present invention. Goods 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., and the like.
　前記エラグ酸の類縁体として、本発明を制限するものではないが、３－Ｏ－メチルエラグ酸、フラベラグ酸、３，３’－ジ－Ｏ－メチルエラグ酸、３，４，３’－トリメチルエラグ酸、カルボキシルエラグ酸、エラグ酸４－キシロシド、３’－Ｏ－メチルエラグ酸４－キシロシド、３－Ｏ－メチルエラグ酸３’－ラムノシド、エラグ酸３－グルコシド、エラグ酸４－アセチルキシロシド、３’－Ｏ－メチルエラグ酸４－Ｏ－β－Ｄ－グルコース等が例示される。これらは１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。 As an analog of the ellagic acid, the present invention is not limited, but 3-O-methylellagic acid, flaveragic acid, 3,3'-di-O-methylellagic acid, 3,4,3'-trimethylellagic acid. , Carboxyl ellagic acid, ellagic acid 4-xyloside, 3'-O-methylellagic acid 4-xyloside, 3-O-methylellagic acid 3'-ramnoside, ellagic acid 3-glucoside, ellagic acid 4-acetylxylode, 3'- Examples thereof include O-methylellagic acid 4-O-β-D-glucose. These may be used individually by 1 type, and may be used in combination of 2 or more type.
　前記エラグ酸の塩、前記類縁体の塩として、ナトリウム、カリウム等のアルカリ金属塩、カルシウム、マグネシウム等のアルカリ土類金属塩、アンモニウム塩、アミン塩等が例示される。これらは１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。 Examples of the salt of ellagic acid and the salt of the analog include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, ammonium salts and amine salts. These may be used individually by 1 type, and may be used in combination of 2 or more type.
　前記エラグ酸、前記類縁体、前記塩の水和物として、従来公知のこれらの水和物が例示される。これらは１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。 Examples of hydrates of the ellagic acid, the analog, and the salt are conventionally known hydrates. These may be used individually by 1 type, and may be used in combination of 2 or more type.
　成分（１）として、本発明を制限するものではないが、好ましくはエラグ酸、その塩及びこれらの水和物からなる群より選択される少なくとも１種が例示され、より好ましくはエラグ酸が例示される。 As the component (1), at least one selected from the group consisting of ellagic acid, salts thereof and hydrates thereof is exemplified, and more preferably ellagic acid is exemplified, although the present invention is not limited. Will be done.
　また、前記尿路機能改善用組成物、前記膀胱血流改善用組成物を製造するに際して使用する前記成分（１）は、精製品（純品）であってもよく、本発明の効果を奏する限りこれに限定されず、例えば、前記成分（１）を含む植物の加工物（植物加工物）、前記成分（１）の粗精製物であってもよい。 Further, the composition for improving urinary tract function and the component (1) used in producing the composition for improving bladder blood flow may be a refined product (pure product) and exert the effect of the present invention. The present invention is not limited to this, and may be, for example, a processed plant product (processed plant product) containing the component (1) or a crudely purified product of the component (1).
　該植物加工物として、本発明を制限するものではないが、好ましくはエラグ酸、その塩及びこれらの水和物からなる群より選択される少なくとも１種を含む植物加工物、より好ましくはエラグ酸を含む植物加工物が例示される。 The processed plant product is not limited to the present invention, but is preferably a processed plant product containing at least one selected from the group consisting of ellagic acid, salts thereof and hydrates thereof, more preferably ellagic acid. Examples of processed plant products include.
　該粗精製物として、本発明を制限するものではないが、好ましくはエラグ酸、その塩及びこれらの水和物からなる群より選択される少なくとも１種の粗精製物、より好ましくはエラグ酸の粗精製物が例示される。 As the crude product, the present invention is not limited, but at least one crude product selected from the group consisting of ellagic acid, salts thereof and hydrates thereof, more preferably ellagic acid. A crude product is exemplified.
　これらは１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。 These may be used alone or in combination of two or more.
　該植物加工物、該粗精製物として、以下に、エラグ酸を含む植物加工物、エラグ酸の粗精製物の例について説明するが、エラグ酸以外の前記成分（１）を含む植物加工物、粗精製物についても以下と同様に説明される。 Examples of the processed plant product and the crudely purified product include a processed plant product containing ellagic acid and a crudely purified product of ellagic acid. The crude product will be described in the same manner as below.
　エラグ酸を含む植物加工物としては、本発明を制限するものではないが、イチゴ（オランダイチゴ属 (Fragaria)に属する植物）、クランベリー（スノキ属（Vaccinium）に属する植物）、ラズベリー（キイチゴ属（Rubus）に属する植物）、ブドウ（ブドウ属（Vitis）に属する植物）、クルミ（クルミ属（Juglans）に属する植物）、栗（クリ属（Castanea）に属する植物）、ペカン（ペカン属（Carya）に属する植物）、ゲンノショウコ（フクロソウ属（Geranium）に属する植物）、クコ（クコ属（Lycium）に属する植物）、ザクロ（ザクロ属（Punica）に属する植物）といった植物の加工物が例示される。本発明を制限するものではないが、例えばザクロ属に属する植物について説明すると、ザクロ属はミソハギ科に属し、本発明を制限するものではないが、該属に属する植物としてザクロ（Punica granatum）等が例示される。 The processed plant products containing ellagic acid do not limit the present invention, but are strawberry (a plant belonging to the genus Fragaria of the Netherlands), cranberry (a plant belonging to the genus Vaccinium), and raspberry (a plant belonging to the genus Vaccinium). Rubus), grapes (Vitis), walnuts (Juglans), chestnuts (Castanea), Pecan (Carya) Examples of processed products of plants such as Gennoshouko (plant belonging to the genus Geranium), Kuko (plant belonging to the genus Lycium), and pomegranate (plant belonging to the genus Punica). Although not limiting the present invention, for example, a plant belonging to the genus Pomegranate will be described. The genus Pomegranate belongs to the Lythraceae family, and although it does not limit the present invention, plants belonging to the genus include pomegranate (Punica granatum) and the like. Is illustrated.
　エラグ酸を含む植物であれば使用部位は特に限定されず、葉、茎、果実、果皮、花、芽、枝、幹、樹皮、根、種子、種皮等が例示され、各植物に応じて適宜選択すればよい。本発明を制限するものではないが、例えばザクロ属に属する植物では好ましい使用部位として果実、果皮、種子、種皮が例示される。使用部位は、１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。 As long as it is a plant containing ellagic acid, the site of use is not particularly limited, and leaves, stems, fruits, peels, flowers, buds, branches, trunks, bark, roots, seeds, seed coats, etc. are exemplified, and appropriately according to each plant. You can select it. Although not limiting the present invention, for example, in plants belonging to the genus Pomegranate, fruits, pericarps, seeds, and seed coats are exemplified as preferable sites for use. As the site of use, one type may be used alone, or two or more types may be used in combination.
　本発明において植物加工物とは、前記原料となる植物の粉砕物、乾燥物、抽出物等が挙げられる。 In the present invention, the processed plant product includes a crushed product, a dried product, an extract, etc. of the plant as the raw material.
　粉砕物は、本発明を制限するものではないが、ジェットミル等の本分野で公知の粉砕器により前記植物を粉砕したものが例示される。 The crushed product does not limit the present invention, but an example thereof is a crushed product obtained by crushing the plant with a crusher known in the art such as a jet mill.
　乾燥物は、前記植物を乾燥させたものであれば特に限定されず、天日乾燥、遠赤外線照射、乾燥機（熱風乾燥、冷風乾燥、真空凍結乾燥等）等の従来公知の乾燥方法に従って乾燥させたものが例示される。また、乾燥物中の水分量としては、本発明を制限するものではないが、１０質量％以下が好ましく、８質量％以下がより好ましい。本発明において乾燥物の形態は問わず、前記植物（任意部位）そのものの乾燥物、乾燥物の粉砕物（乾燥粉砕物）等のいずれでもよい。乾燥粉砕物は、前記粉砕物と同様の方法に従って乾燥物を粉砕することにより得ることができる。また、本発明においては乾燥物として、原料となる植物を発酵処理や酵素処理した後に乾燥して得られたものであってもよい。 The dried product is not particularly limited as long as the plant is dried, and is dried according to a conventionally known drying method such as sun drying, far infrared irradiation, and a dryer (hot air drying, cold air drying, vacuum freeze drying, etc.). An example is the one that has been made to do so. The amount of water in the dried product is not limited to the present invention, but is preferably 10% by mass or less, more preferably 8% by mass or less. In the present invention, the form of the dried product is not limited, and either the dried product of the plant (arbitrary part) itself, the crushed product of the dried product (dried crushed product), or the like may be used. The dried pulverized product can be obtained by pulverizing the dried product according to the same method as the pulverized product. Further, in the present invention, the dried product may be obtained by fermenting or enzymatically treating a plant as a raw material and then drying it.
　抽出物の製造方法（抽出方法）及び抽出条件等は特に限定されず、従来公知の方法に従えばよい。例えば、前記植物をそのまま、必要に応じて裁断、粉砕または乾燥等した後に、搾取または溶媒抽出によって抽出物を得ることができる。溶媒抽出の方法としては、本分野において公知の方法を採用すればよく、例えば水（温水、熱水を含む）抽出、アルコール抽出、超臨界抽出等の従来公知の抽出方法を利用することができる。 The method for producing the extract (extraction method), the extraction conditions, and the like are not particularly limited, and conventionally known methods may be followed. For example, the plant can be cut, crushed, dried or the like as it is, if necessary, and then an extract can be obtained by exploitation or solvent extraction. As the solvent extraction method, a method known in the art may be adopted, and conventionally known extraction methods such as water (including hot water and hot water) extraction, alcohol extraction, supercritical extraction and the like can be used. ..
　溶媒抽出を行う場合、溶媒としては例えば水；メタノール、エタノール、イソプロパノール等の低級アルコールや、プロピレングリコール、１，３－ブチレングリコール等の多価アルコール等のアルコール類（無水、含水の別を問わない）；アセトン等のケトン類、ジエチルエーテル、ジオキサン、アセトニトリル、酢酸エチルエステル等のエステル類、キシレン、ベンゼン、クロロホルム等が挙げられる。溶媒として好ましくは水、低級アルコール、１，３－ブチレングリコール等であり、より好ましくは水、メタノール、エタノール、１，３－ブチレングリコールであり、更に好ましくは水、メタノール、含水エタノールである。これらの溶媒は１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。 When solvent extraction is performed, the solvent is, for example, water; lower alcohols such as methanol, ethanol and isopropanol, and alcohols such as polyhydric alcohols such as propylene glycol and 1,3-butylene glycol (whether anhydrous or water-containing). ); Ketones such as acetone, esters such as diethyl ether, dioxane, acetonitrile and ethyl acetate, xylene, benzene, chloroform and the like. The solvent is preferably water, a lower alcohol, 1,3-butylene glycol or the like, more preferably water, methanol, ethanol or 1,3-butylene glycol, and further preferably water, methanol or hydrous ethanol. These solvents may be used alone or in combination of two or more.
　本発明において、このように溶媒抽出を経て得た抽出物を特に溶媒抽出物と称することができる。更に、本発明を制限するものではないが、前述のように例えば溶媒として水を用いた場合は水抽出物、低級アルコール類を用いた場合は低級アルコール抽出物、エタノールを用いた場合はエタノール抽出物等と称することができる。 In the present invention, the extract obtained through solvent extraction in this way can be particularly referred to as a solvent extract. Further, although not limiting the present invention, as described above, for example, a water extract when water is used as a solvent, a lower alcohol extract when lower alcohols are used, and an ethanol extract when ethanol is used. It can be called a thing or the like.
　得られた抽出物は、そのままの状態で使用してもよく、乾燥させて粉末状や顆粒状等の固形の状態で使用してもよい。また、必要に応じて、得られた抽出物に精製、濃縮処理、高活性画分の分離処理等を施してもよい。本発明を制限するものではないが、精製処理としては、濾過、イオン交換樹脂や活性炭カラム等を用いた吸着、脱色といった処理が挙げられる。また、濃縮処理としては、エバポレーター等の常法を利用できる。また、高活性画分の分離処理としては、ゲル濾過、吸着処理、シリカゲルカラムクロマトグラフィー、ＨＰＬＣ（High performance liquid chromatography）等の公知の分離処理を利用できる。 The obtained extract may be used as it is, or may be dried and used in a solid state such as powder or granules. Further, if necessary, the obtained extract may be subjected to purification, concentration treatment, separation treatment of highly active fractions and the like. Although not limiting the present invention, examples of the purification treatment include treatments such as filtration, adsorption using an ion exchange resin, an activated carbon column, and decolorization. Further, as the concentration treatment, a conventional method such as an evaporator can be used. Further, as the separation treatment of the highly active fraction, known separation treatments such as gel filtration, adsorption treatment, silica gel column chromatography, and HPLC (High performance liquid chromatography) can be used.
　また、例えば、前述のようにして得られた抽出物（更にはその乾燥物、精製処理物、濃縮処理物、高活性画分）を、凍結乾燥処理に供して粉末化する方法、必要に応じてデキストリン、コーンスターチ、アラビアゴム等の賦形剤を添加して、スプレードライ処理により粉末化する方法等の従来公知の方法に従って粉末化し、本発明で用いる抽出物としてもよい。また、該抽出物を、必要に応じて水、エタノール等に溶解して用いてもよい。 Further, for example, a method of pulverizing the extract obtained as described above (furthermore, its dried product, purified product, concentrated processed product, highly active fraction) by freeze-drying treatment, if necessary. The extract may be used in the present invention by adding excipients such as dextrin, cornstarch, and arabic rubber and pulverizing according to a conventionally known method such as a method of pulverizing by spray-drying. Further, the extract may be used by dissolving it in water, ethanol or the like, if necessary.
　抽出物として好ましくは、原料となる植物（任意部位）を乾燥、破砕及び／または裁断し、好適な溶媒を使用して抽出、濾過して得られる抽出物、また、このようにして得られる抽出物を更に乾燥させることにより得られる抽出物が例示される。 The extract is preferably an extract obtained by drying, crushing and / or cutting a plant (arbitrary part) as a raw material, extracting and filtering using a suitable solvent, and an extract thus obtained. An example is an extract obtained by further drying the product.
　本発明を制限するものではなく、前記植物の使用部位に応じて当業者が適宜抽出すればよいが、抽出物は、原料となる植物を１００ｇあたり、より好ましくは該植物の乾燥物、破砕物及び／または裁断物を１００ｇあたり、抽出溶媒１～５０リットルに浸漬させて、任意の温度（例えば１５～９０℃）で、必要に応じて攪拌しながら、任意の時間（例えば１０分～２４時間）抽出を行い、次いで濾過することにより得ることができる。また、前述の通り、必要に応じて、得られた抽出物に精製、濃縮処理、高活性画分の各種分離処理等を施してもよい。 The present invention is not limited, and a person skilled in the art may appropriately extract the extract according to the site of use of the plant, but the extract is a dried or crushed product of the plant as a raw material per 100 g, more preferably. And / or the cut product is immersed in 1 to 50 liters of the extraction solvent per 100 g, and at an arbitrary temperature (for example, 15 to 90 ° C.), with stirring as necessary, for an arbitrary time (for example, 10 minutes to 24 hours). ) Can be obtained by performing extraction and then filtering. Further, as described above, if necessary, the obtained extract may be subjected to purification, concentration treatment, various separation treatments for highly active fractions, and the like.
　植物加工物は、市販品を用いてもよく、また、市販品に対して更に乾燥等の処理を適宜行ったものでもよい。 As the processed plant product, a commercially available product may be used, or the commercially available product may be further subjected to a treatment such as drying.
　本発明においてエラグ酸を含む植物加工物として、好ましくはエラグ酸を含むザクロ属植物加工物であり、より好ましくはエラグ酸を含むザクロ属植物抽出物（その乾燥物等を含む）が例示される。 In the present invention, examples of the processed plant product containing ellagic acid are preferably a processed pomegranate plant containing ellagic acid, and more preferably an extract of a pomegranate plant containing ellagic acid (including a dried product thereof). ..
　植物加工物は、１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。 The processed plant product may be used alone or in combination of two or more.
　エラグ酸の粗精製物としては、エラグ酸を含む植物から調製されるエラグ酸画分を例示することができる。エラグ酸を含有する植物としては、本発明を制限するものではないが、前述の植物が例示され、また、前述の任意の使用部位が例示される。また、プニカラジン、プニカリン、ガラグ酸等のエラジタンニンは、その加水分解等によりエラグ酸を生成することが知られている。このため、エラグ酸の粗精製物として、エラジタンニンを含む植物から加水分解等の分解処理によって調製されるエラグ酸画分も例示することができる。また、没食子酸を用いた化学合成によりエラグ酸を生成できることが知られている。このため、エラグ酸の粗精製物として、没食子酸を含む植物から化学合成によって調製されるエラグ酸画分も例示することができる。 As the crude product of ellagic acid, an ellagic acid fraction prepared from a plant containing ellagic acid can be exemplified. Examples of the plant containing ellagic acid are not limited to the present invention, but the above-mentioned plants are exemplified, and the above-mentioned arbitrary sites of use are exemplified. Further, it is known that ellagitannins such as punicarazine, punicalin, and galaxic acid produce ellagic acid by their hydrolysis and the like. Therefore, as a crude product of ellagic acid, an ellagic acid fraction prepared from a plant containing ellagitannin by a decomposition treatment such as hydrolysis can also be exemplified. It is also known that ellagic acid can be produced by chemical synthesis using gallic acid. Therefore, as a crude product of ellagic acid, an ellagic acid fraction prepared by chemical synthesis from a plant containing gallic acid can also be exemplified.
　エラグ酸画分は、エラグ酸を含有する植物（任意部位）から一種類の溶媒（例えば、水；メタノール、エタノール等のアルコール；含水アルコール）を用いて単回抽出し、次いでろ過して濃縮して調製されるものではなく、例えば、エラグ酸の精製度（純度）の高い画分を取得したり、エラグ酸を高濃度で含有する濃縮画分を取得するために、溶媒抽出を複数回繰り返したり、分子量ろ過、サイズ排除クロマトグラフィー、イオン交換クロマトグラフィー等の精製操作を任意に組み合わせることで得られる画分を意味する。より具体的には、エラグ酸を含有する画分からエラグ酸以外の成分を除去し、エラグ酸の含有量を５０質量％以上にまで高めた画分を例示することができ、該エラグ酸画分におけるエラグ酸の含有量として、好ましくは６０～１００質量％、より好ましくは７０～１００質量％、更に好ましくは８０～１００質量％、特に好ましくは９０～１００質量％が例示される。 The ellagic acid fraction is extracted once from a plant (arbitrary site) containing ellagic acid using one kind of solvent (for example, water; alcohol such as methanol and ethanol; hydrous alcohol), and then filtered and concentrated. For example, solvent extraction is repeated a plurality of times in order to obtain a fraction having a high degree of purification (purity) of ellagic acid or to obtain a concentrated fraction containing a high concentration of ellagic acid. It also means a fraction obtained by arbitrarily combining purification operations such as molecular weight filtration, size exclusion chromatography, and ion exchange chromatography. More specifically, a fraction in which components other than ellagic acid are removed from the fraction containing ellagic acid and the content of ellagic acid is increased to 50% by mass or more can be exemplified, and the ellagic acid fraction can be exemplified. The content of ellagic acid in the above is preferably 60 to 100% by mass, more preferably 70 to 100% by mass, still more preferably 80 to 100% by mass, and particularly preferably 90 to 100% by mass.
　この観点から、前記植物加工物がこのようなエラグ酸の粗精製物である場合は、該粗精製物として前記植物加工物を用いてもよい。 From this point of view, when the processed plant product is such a crude product of ellagic acid, the processed plant product may be used as the crude product.
　これらはいずれも１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。 Each of these may be used alone or in combination of two or more.
成分（２）
　前記成分（２）について、プニカラジンは、従来公知の物質であり、本発明においてプニカラジンは市販品を用いてもよい。本発明を制限するものではないが、例えばケイマンケミカル（Cayman Chemical社）、シグマアルドリッチ（Sigma-Aldrich 社）等にて市販されている。前記プニカラジンの塩として、ナトリウム、カリウム等のアルカリ金属塩、カルシウム、マグネシウム等のアルカリ土類金属塩、アンモニウム塩、アミン塩等が例示される。前記プニカラジン、その塩の水和物として、従来公知のこれらの水和物が例示される。成分（２）として、本発明を制限するものではないが、好ましくはプニカラジンが例示される。これらは１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。 Ingredient (2)
Regarding the component (2), punicarazine is a conventionally known substance, and in the present invention, punicarazine may be a commercially available product. Although not limiting the present invention, it is commercially available, for example, by Cayman Chemical, Sigma-Aldrich, and the like. Examples of the salt of punicarazine 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 the punicarazine and salts thereof include conventionally known hydrates. As the component (2), although not limiting the present invention, punicarazine is preferably exemplified. These may be used individually by 1 type, and may be used in combination of 2 or more type.
　また、前記尿路機能改善用組成物、前記膀胱血流改善用組成物を製造するに際して使用する前記成分（２）は、精製品（純品）であってもよく、本発明の効果を奏する限りこれに限定されず、例えば、前記成分（２）を含む植物の加工物（植物加工物）、前記成分（２）の粗精製物であってもよい。 Further, the composition for improving urinary tract function and the component (2) used in producing the composition for improving bladder blood flow may be a refined product (pure product) and exert the effect of the present invention. The present invention is not limited to this, and may be, for example, a processed plant product (processed plant product) containing the component (2) or a crudely purified product of the component (2).
　該植物加工物として、本発明を制限するものではないが、好ましくはプニカラジンを含む植物加工物が例示される。また、該粗精製物として、本発明を制限するものではないが、好ましくはプニカラジンの粗精製物が例示される。 The processed plant product does not limit the present invention, but preferably a processed plant product containing punicarazine. Further, as the crude product, a crude product of punicarazine is preferably exemplified, although the present invention is not limited.
　これらは１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。 These may be used alone or in combination of two or more.
　該植物加工物、該粗精製物として、以下に、プニカラジンを含む植物加工物、プニカラジンの粗精製物の例について説明するが、プニカラジン以外の前記成分（２）を含む植物加工物、粗精製物についても以下と同様に説明される。 Examples of the processed plant product and the crudely refined product include a processed plant product containing punicarazine and a crudely purified product of punicarazine. However, the processed plant product and the crudely refined product containing the component (2) other than punicarazine will be described below. Will be described in the same manner as below.
　プニカラジンを含む植物加工物としては、本発明を制限するものではないが、ミロバラン（モモタマナ属（Terminalia）に属する植物）、ザクロ（ザクロ属（Punica）に属する植物）といった植物の加工物が例示される。本発明を制限するものではないが、例えばザクロ属に属する植物は前述と同様に説明される。プニカラジンを含む植物であれば使用部位は特に限定されず、葉、茎、果実、果皮、花、芽、枝、幹、樹皮、根、種子、種皮等が例示され、各植物に応じて適宜選択すればよい。本発明を制限するものではないが、例えばザクロ属に属する植物では好ましい使用部位として果実、果皮、種子、種皮が例示される。使用部位はいずれも、１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。プニカラジンを含む植物加工物において、植物加工物は、前述と同様に説明される。 Examples of processed plant products containing punicarazine include, but are not limited to, processed products of plants such as myrobalan (a plant belonging to the genus Tropical almond) and pomegranate (a plant belonging to the genus Pomegranate). To. Although not limiting the present invention, for example, plants belonging to the genus Pomegranate will be described in the same manner as described above. The site of use is not particularly limited as long as it is a plant containing punicarazine, and leaves, stems, fruits, peels, flowers, buds, branches, trunks, bark, roots, seeds, seed coats, etc. are exemplified and appropriately selected according to each plant. do it. Although not limiting the present invention, for example, in plants belonging to the genus Pomegranate, fruits, pericarps, seeds, and seed coats are exemplified as preferable sites for use. As for the parts to be used, one type may be used alone, or two or more types may be used in combination. In the processed plant product containing punicarazine, the processed plant product is described in the same manner as described above.
　本発明においてプニカラジンを含む植物加工物として、好ましくはプニカラジンを含むザクロ属植物加工物であり、より好ましくはプニカラジンを含むザクロ属植物抽出物（その乾燥物等を含む）が例示される。 In the present invention, the processed plant product containing punicarazine is preferably a processed pomegranate plant containing punicarazine, and more preferably an extract of a pomegranate plant containing punicarazine (including a dried product thereof).
　植物加工物は、１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。 The processed plant product may be used alone or in combination of two or more.
　プニカラジンの粗精製物としては、プニカラジンを含む植物から調製されるプニカラジン画分を例示することができる。プニカラジンを含有する植物としては、本発明を制限するものではないが、前述の植物が例示される。 As the crude product of punicarazine, a punicarazine fraction prepared from a plant containing punicarazine can be exemplified. Examples of plants containing punicarazine include, but are not limited to, the above-mentioned plants.
　プニカラジン画分についても、前記エラグ酸画分と同様に説明され、すなわち、プニカラジンを含有する植物（任意部位）から一種類の溶媒（例えば、水；メタノール、エタノール等のアルコール；含水アルコール）を用いて単回抽出し、次いでろ過して濃縮して調製されるものではなく、プニカラジンの精製度（純度）の高い画分を取得したり、プニカラジンを高濃度で含有する濃縮画分を取得するために、溶媒抽出を複数回繰り返したり、分子量ろ過、サイズ排除クロマトグラフィー、イオン交換クロマトグラフィー等の精製操作を任意に組み合わせることで得られる画分、また、プニカラジンを含有する植物（任意部位）を圧搾し、カラムろ過等により濃縮を繰り返すことで得られる画分を意味する。より具体的には、プニカラジンを含有する画分からプニカラジン以外の成分を除去し、プニカラジンの含有量を２５質量％以上、好ましくは３０質量％以上にまで高めた画分を例示することができ、すなわち該画分におけるプニカラジンの含有量として２５～１００質量％、３０～１００質量％が例示され、該プニカラジン画分におけるプニカラジンの含有量として、好ましくは５０～１００質量％、より好ましくは７０～１００質量％、更に好ましくは８０～１００質量％、特に好ましくは９０～１００質量％が例示される。 The punicarazine fraction is also described in the same manner as the ellagic acid fraction, that is, using one kind of solvent (for example, water; alcohol such as methanol and ethanol; hydrous alcohol) from a plant (arbitrary site) containing punicarazine. It is not prepared by extracting once and then filtering and concentrating, but to obtain a fraction with a high degree of purification (purity) of punicarazine or to obtain a concentrated fraction containing a high concentration of punicarazine. Fraction obtained by repeating solvent extraction multiple times or by arbitrarily combining purification operations such as molecular weight filtration, size exclusion chromatography, ion exchange chromatography, etc., and pressing a plant (arbitrary site) containing punicarazine. However, it means a fraction obtained by repeating concentration by column filtration or the like. More specifically, it is possible to exemplify a fraction in which components other than punicarazine are removed from the fraction containing punicarazine and the content of punicarazine is increased to 25% by mass or more, preferably 30% by mass or more. 25 to 100% by mass and 30 to 100% by mass are exemplified as the content of punicarazine in the fraction, and the content of punicarazine in the punicarazine fraction is preferably 50 to 100% by mass, more preferably 70 to 100% by mass. %, More preferably 80 to 100% by mass, and particularly preferably 90 to 100% by mass.
　この観点から、前記植物加工物がこのようなプニカラジンの粗精製物である場合は、該粗精製物として前記植物加工物を用いてもよい。 From this point of view, when the processed plant product is such a crude product of punicarazine, the processed plant product may be used as the crude product.
　これらはいずれも１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。 Each of these may be used alone or in combination of two or more.
　前記尿路機能改善用組成物、前記膀胱血流改善用組成物のそれぞれにおいて、前記成分（１）及び（２）からなる群より選択される少なくとも１種の含有量は、症状、適用形態等に応じて適宜決定すればよく制限されない。本発明を制限するものではないが、各組成物中、前記成分（１）及び（２）からなる群より選択される少なくとも１種は、その合計量（固形分濃度）で、０質量％より多く１００質量％未満であればよく、好ましくは１～７０質量％、より好ましくは５～３０質量％が例示される。 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 the components (1) and (2) is a symptomatology, an application form, etc. It is not limited as long as it is appropriately determined according to the above. Although not limiting the present invention, in each composition, at least one selected from the group consisting of the above components (1) and (2) has a total amount (solid content concentration) of 0% by mass or more. It may be as much as less than 100% by mass, preferably 1 to 70% by mass, and more preferably 5 to 30% by mass.
　このように、各組成物において、前記成分（１）及び（２）からなる群より選択される少なくとも１種の含有量は制限されないが、例えば、次の含有量も例示することができる。 As described above, in each composition, the content of at least one selected from the group consisting of the components (1) and (2) is not limited, but the following content can also be exemplified.
　各組成物中の前記成分（１）の含有量は、症状、適用形態等に応じて適宜決定すればよく制限されないが、該組成物中、その合計量（固形分濃度）で、好ましくは３～７０質量％、１５～３０質量％を例示することができる。 The content of the component (1) in each composition may be appropriately determined depending on the symptom, application form, etc., and is not limited, but the total amount (solid content concentration) of the component (1) in the composition is preferably 3. Examples thereof include ~ 70% by mass and 15 to 30% by mass.
　各組成物中の前記成分（２）の含有量は、症状、適用形態等に応じて適宜決定すればよく制限されないが、該組成物中、その合計量（固形分濃度）で、好ましくは１～２５質量％、５～１０質量％を例示することができる。 The content of the component (2) in each composition may be appropriately determined depending on the symptom, application form, etc., and is not limited, but the total amount (solid content concentration) thereof in the composition is preferably 1. To 25% by mass, 5 to 10% by mass can be exemplified.
　なお、これらの組成物を製造するに際して前記成分（１）を含む植物加工物及び／または前記成分（２）を含む植物加工物を使用する場合、この限りにおいて制限されないが、該植物加工物の含有量は、症状、適用形態等に応じて適宜決定すればよく制限されないが、該組成物中、その合計量（乾燥質量換算）で、好ましくは１～９５質量％、３０～８０質量％を例示することができる。ここで、植物加工物の乾燥物は、該加工物を凍結乾燥処理することにより得られる。凍結乾燥処理は、一般的なエバポレーターを用いた減圧濃縮及び真空状態での凍結乾燥により行う。 When a processed plant product containing the component (1) and / or a processed plant product containing the component (2) is used in producing these compositions, the present invention is not limited, but the processed plant product. The content is not limited as it may be appropriately determined according to the symptom, application form, etc., but the total amount (in terms of dry mass) of the composition is preferably 1 to 95% by mass and 30 to 80% by mass. It can be exemplified. Here, the dried product of the processed plant product is obtained by freeze-drying the processed product. The freeze-drying treatment is carried out by concentration under reduced pressure using a general evaporator and freeze-drying in a vacuum state.
　該各組成物において、前記成分（１）及び（２）からなる群より選択される少なくとも１種の投与（摂取）量は、本発明の効果が奏される限り特に限定されず、適用対象（対象者、対象動物）の症状、適用形態、体格、年齢、期待される効果の程度等に応じて適宜設定すればよい。 In each of the compositions, the dose (intake) 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 exhibited, and is an application target ( It may be appropriately set according to the symptoms, application form, physique, age, degree of expected effect, etc. of the target person (target animal).
　本発明を制限するものではないが、例えばヒトに対する１日投与（摂取）量として、前記成分（１）及び（２）からなる群より選択される少なくとも１種を総量（固形分濃度）で、好ましくは０．５～７０ｍｇ／ｋｇ体重、より好ましくは１～５ｍｇ／ｋｇ体重が例示される。該各組成物はいずれも、１日あたり単回投与（摂取）であってもよく複数回投与（摂取）であってもよく、また、任意の期間及び間隔で投与（摂取）され得る。 Although not limiting the present invention, for example, as the daily dose (intake) to humans, at least one selected from the group consisting of the above components (1) and (2) is used in a total amount (solid content concentration). Preferably, 0.5 to 70 mg / kg body weight, more preferably 1 to 5 mg / kg body weight is exemplified. Each of the compositions may be administered once (intake) or multiple times (intake) per day, and may be administered (intake) at arbitrary periods and intervals.
　また、これらの組成物を製造するに際して前記成分（１）を含む植物加工物及び／または前記成分（２）を含む植物加工物を使用する場合、この限りにおいて制限されないが、該植物加工物の投与（摂取）量は、本発明の効果が奏される限り特に限定されず、適用対象（対象者、対象動物）の症状、適用形態、体格、年齢、期待される効果の程度等に応じて適宜設定すればよく、例えばヒトに対する１日投与（摂取）量として、前記植物加工物を総量（乾燥質量換算）で、好ましくは１．５～８０ｍｇ／ｋｇ体重、より好ましくは２～８ｍｇ／ｋｇ体重が例示される。 Further, when a processed plant product containing the component (1) and / or a processed plant product containing the component (2) is used in producing these compositions, the present invention is not limited, but the processed plant product. The dose (intake) is not particularly limited as long as the effect of the present invention is exhibited, and depends on the symptom, application form, physique, age, degree of expected effect, etc. of the application target (subject, target animal). It may be set appropriately. For example, as the daily administration (intake) amount for humans, the total amount (in terms of dry mass) of the processed plant product is preferably 1.5 to 80 mg / kg body weight, more preferably 2 to 8 mg / kg. Weight is illustrated.
　なお、ヒトに対する投与（摂取）量は、一般にラットにおける体表面積に基づくヒト等価用量（ＨＥＤ）６．２（「Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers」参照）から換算して求めることができる。 For the dose to be administered to humans, generally refer to the human equivalent dose (HED) 6.2 (“Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers”) based on the body surface area in rats. ) Can be converted and calculated.
　各組成物は、経口、非経口の別を問わず、好ましくは経口投与（摂取）される。その形態も制限されず、目的に応じて適宜設定すればよい。該形態として、液剤、乳剤、懸濁剤、シロップ剤、エキス剤、酒精剤、エリキシル剤等の液状形態、散剤、顆粒剤、細粒剤、錠剤（糖衣錠等の被覆錠剤を含む）、丸剤、カプセル剤（ハードカプセル、ソフトカプセルを含む）、トローチ、チュアブル、ゲル状、クリーム状、ペースト状、ムース状、シート状、液状形態の凍結乾燥物等の半固形または固形形態、この他、エアゾール剤等、貼付剤、ハップ剤、経皮吸収型製剤等の各種形態が例示される。 Each composition is preferably orally administered (ingested) regardless of whether it is oral or parenteral. The form is not limited, and may be appropriately set according to the purpose. The forms include liquid forms such as liquids, emulsions, suspensions, syrups, extracts, alcoholic beverages, and elixirs, powders, granules, fine granules, tablets (including coated tablets such as sugar-coated tablets), and pills. , Capsules (including hard capsules and soft capsules), troches, chewables, gels, creams, pastes, mousses, sheets, liquid forms such as lyophilized products, semi-solid or solid forms, and aerosols, etc. , Various forms such as a patch, a pill, and a percutaneous absorption type preparation are exemplified.
　各組成物の使用態様も制限されず、目的に応じて適宜設定すればよい。使用態様として、食品組成物（飲料を含む、保健機能食品（特定保健用食品、栄養機能食品、機能性表示食品、サプリメント等を含む）、病者用食品を含む）、医薬組成物、医薬部外品組成物、飼料組成物、また、食品組成物、医薬組成物、医薬部外品組成物、飼料等への添加剤等として使用することができる。 The usage mode of each composition is not limited, and may be appropriately set according to the purpose. Examples of usage include food compositions (including beverages, health functional foods (including foods for specified health use, nutritionally functional foods, foods with functional claims, supplements, etc.), foods for the sick), pharmaceutical compositions, and pharmaceutical departments. It can be used as a foreign product composition, a feed composition, an additive to a food composition, a pharmaceutical composition, a pharmaceutical foreign product composition, a feed, or the like.
　各組成物は、前述の各種形態、使用態様等における従来公知の通常の手順に従い製造すればよく、必要に応じて、薬学的に許容される成分、香粧品科学的に許容される成分、可食性の成分といった任意の成分と混合等して製造すればよい。該任意の成分として、溶剤（水、メタノール、エタノール、イソプロパノール等の低級アルコール、プロピレングリコール、１，３－ブチレングリコール等の多価アルコール等のアルコール類（無水、含水の別を問わない）等）、賦形剤、崩壊剤、希釈剤、滑沢剤、香料、着色料、甘味料、矯味剤、懸濁剤、湿潤剤、乳化剤、可溶化剤、分散剤、緩衝剤、結合剤、浸透促進剤、安定剤、増量剤、防腐剤、増粘剤、ｐＨ調整剤、界面活性剤、コーティング剤、吸収促進剤、吸着剤、充填剤、酸化防止剤、抗炎症剤、清涼剤、皮膜形成剤、ゲル化剤、アミノ酸、ビタミン、酵素、各種栄養成分等が例示される。これらは１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。 Each composition may be produced according to a conventionally known conventional procedure in the above-mentioned various forms, usage modes, etc., and if necessary, a pharmaceutically acceptable ingredient, a cosmetic scientifically acceptable ingredient, and the like are acceptable. It may be produced by mixing with an arbitrary component such as an edible component. As the optional component, a solvent (water, lower alcohol such as methanol, ethanol, isopropanol, alcohol such as propylene glycol, polyhydric alcohol such as 1,3-butylene glycol (whether anhydrous or water-containing), etc.), etc. , Excipients, disintegrants, diluents, lubricants, fragrances, colorants, sweeteners, flavoring agents, suspending agents, wetting agents, emulsifiers, solubilizers, dispersants, buffers, binders, penetration promoting Agents, stabilizers, bulking agents, preservatives, thickeners, pH adjusters, surfactants, coating agents, absorption promoters, adsorbents, fillers, antioxidants, anti-inflammatory agents, refreshing agents, film-forming agents , Gelling agents, amino acids, vitamins, enzymes, various nutritional components and the like are exemplified. These may be used individually by 1 type, and may be used in combination of 2 or more type.
　該各組成物を適用する対象（対象者、対象動物）も制限されないが、ヒト、ヒト以外の哺乳動物が例示される。また、本発明において、組成物を適用する対象者（対象動物）として好ましくは女性（雌）が例示されるがこの限りではない。また、本発明を制限するものではないが、該対象として、昼間や夜間の頻尿、過活動膀胱、尿意切迫感または切迫性尿失禁等の排尿障害を有するか、そのおそれのある者、残尿感を感じる者等が例示される。 The target (target person, target animal) to which each composition is applied is not limited, but humans and mammals other than humans are exemplified. Further, in the present invention, a female (female) is preferably exemplified as a subject (target animal) to which the composition is applied, but the present invention is not limited to this. In addition, although not limiting the present invention, those who have or may have dysuria such as frequent urination during the day or night, overactive bladder, urinary urgency or urge incontinence, and the rest. An example is a person who feels urine.
　該尿路機能改善用組成物によれば、前記成分（１）及び（２）からなる群より選択される少なくとも１種を有効成分として尿路機能を改善することができる。特に、該尿路機能改善用組成物によれば、頻尿（膀胱収縮間隔）、貯尿量（膀胱容量）及び／または排尿量といった尿路機能を改善することができる。このことから、本発明は、前記成分（１）及び（２）からなる群より選択される少なくとも１種を用いることを特徴とする、尿路機能の改善方法を提供するといえる。このことから、該方法に関する説明には、前述の説明が適用される。 According to the composition for improving urinary tract function, urinary tract function can be improved by using at least one selected from the group consisting of the components (1) and (2) as an active ingredient. In particular, according to the composition for improving urinary tract function, urinary tract function such as pollakiuria (bladder contraction interval), urine storage amount (bladder capacity) and / or urination amount can be improved. From this, it can be said that the present invention provides a method for improving urinary tract function, which comprises using at least one selected from the group consisting of the components (1) and (2). For this reason, the above description is applied to the description of the method.
　また、該膀胱血流改善用組成物によれば、前記成分（１）及び（２）からなる群より選択される少なくとも１種を有効成分として膀胱血流を改善することができる。このことから、本発明は、前記成分（１）及び（２）からなる群より選択される少なくとも１種を用いることを特徴とする、膀胱血流の改善方法を提供するといえる。このことから、該方法に関する説明には、前述の説明が適用される。 Further, according to the composition for improving bladder blood flow, bladder blood flow can be improved by using at least one selected from the group consisting of the above components (1) and (2) as an active ingredient. From this, it can be said that the present invention provides a method for improving bladder blood flow, which comprises using at least one selected from the group consisting of the components (1) and (2). For this reason, the above description is applied to the description of the method.
　また、このことから本発明は、昼間や夜間の頻尿、過活動膀胱、尿意切迫感、切迫性尿失禁等の排尿障害の予防または改善にも有用である。 From this, the present invention is also useful for preventing or ameliorating urinary disorders such as frequent urination during the day and night, overactive bladder, urinary urgency, and urge incontinence.
　以下、実施例を示して本発明をより詳細に説明するが、本発明はこれらに限定されない。 Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.
試験例１：膀胱血流改善
膀胱血流の評価手順
　ラット（ＳＤ系メスラット（Sprague-Dawley rats）、実験開始時８～９週齢（体重１９０～２２０ｇ／匹））をイソフルレン麻酔下で開腹し、両側総腸骨静脈及び両側子宮静脈を結紮することで骨盤うっ血モデルを作成した。開腹部を縫合後、骨盤うっ血ラットモデルをケージ内で１６日間飼育した。この際、一般的な市販の飼料及び水は自由摂取とした。次いで、該飼料に、タダラフィル、ザクロエキス１（エラグ酸を含むザクロエキス）、ザクロエキス２（プニカラジンを含むザクロエキス）、エラグ酸、またはプニカラジンを混合して、粉末状の混合飼料を調製した。１６日間飼育後の前記ラットモデルを５群に分け（ｎ＝６）、該混合試料を１４日間連続して自由摂取させた。この際、水も自由摂取とした。 Test Example 1: Improvement of bladder blood flow
Bladder blood flow evaluation procedure Rats (SD female rats (Sprague-Dawley rats), 8-9 weeks old (weight 190-220 g / animal) at the start of the experiment) were opened under isoflurane anesthesia, bilateral common iliac veins and bilateral. A pelvic congestion model was created by ligating the uterine vein. After suturing the abdominal opening, a rat model of pelvic congestion was bred in a cage for 16 days. At this time, general commercially available feed and water were freely ingested. Next, tadalafil, pomegranate extract 1 (pomegranate extract containing ellagic acid), pomegranate extract 2 (pomegranate extract containing punicalazine), ellagic acid, or punicarazine were mixed with the feed to prepare a powdered mixed feed. The rat model after breeding for 16 days was divided into 5 groups (n = 6), and the mixed sample was freely ingested for 14 consecutive days. At this time, water was also taken freely.
　各混合飼料は次の表１に示す通りである。例えば、表１中、「タダラフィル群」はタダラフィル混合飼料を摂取させた群を意味し、タダラフィル群に記載する「０．０１％混餌」は、前記混合飼料中、タダラフィルを０．０１質量％（固形分濃度）となるように混合して得た混合飼料を摂取させたことを意味する。また、混合飼料中、ザクロエキス１及び２は乾燥質量換算でのザクロエキス量、エラグ酸、プニカラジンは固形分濃度でのエラグ酸量、プニカラジン量である。なお、本試験例では、タダラフィルは血流を増加させるポジティブコントロールとして使用した。 Each mixed feed is as shown in Table 1 below. For example, in Table 1, "tadalafil group" means a group fed with tadalafil mixed feed, and "0.01% mixed feed" described in the tadalafil group means 0.01% by mass of tadalafil in the mixed feed. It means that the mixed feed obtained by mixing so as to have a solid content concentration) was ingested. Further, in the mixed feed, pomegranate extract 1 and 2 are the amount of pomegranate extract in terms of dry mass, and ellagic acid and punicarazine are the amount of ellagic acid and punicarazine in terms of solid content concentration. In this test example, tadalafil was used as a positive control to increase blood flow.
　使用したタダラフィルは商品名Tadalafil（Combi-Blocks社製）、ザクロエキス１は商品名ザクロエラグ酸（株式会社サビンサジャパンコーポレーション製（エラグ酸８０質量％含有、Punica granatumの果皮のエタノール抽出物）、ザクロエキス２は商品名ポマノックスＰ３０（株式会社エヌ・シー・コーポレーション製（プニカラジン３０％含有、Punica granatumの果皮を含む果実全体を圧搾、濃縮した抽出物）、エラグ酸は商品名エラグ酸（エラグ酸９８質量％含有、富士フイルム和光純薬株式会社製）、プニカラジンは商品名Punicalagin（プニカラジン４０質量％含有、サンタクルーズバイオテクノロジー社製）である。なお、表中、タダラフィル、エラグ酸、プニカラジンの投与量はこれらの市販品の投与量を示す。 The tadalafil used was trade name Tadalafil (manufactured by Combi-Blocks), and pomegranate extract 1 was trade name pomegranate ellagic acid (manufactured by Sabinsa Japan Corporation (containing 80% by mass of ellagic acid, ethanol extract of Punica granatum peel), pomegranate extract. 2 is the trade name Pomanox P30 (manufactured by NC Corporation (containing 30% Punicarazine, an extract obtained by pressing and concentrating the entire fruit including the peel of Punica granatum), and ellagic acid is the trade name ellagic acid (98 mass of ellagic acid). % Content, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), Punicaragin is the trade name Punicalagin (containing 40% by mass of Punicarazine, manufactured by Santa Cruise Biotechnology). In the table, the doses of tadalafil, ellagic acid, and punicarazine are The doses of these commercially available products are shown.
　試験最終日（混合飼料摂取１４日目）に、ウレタン浅麻酔拘束下で、麻酔の効果が現れた１時間後に各ラットの下腹部を切開し、膀胱に癒着する周囲組織を剥離後、膀胱内に生理食塩水を注入し、膀胱容量１ｍＬ時の膀胱血流をレーザー血流測定器（２次元レーザー血流計OMEGAZONE OZ-1、オメガウェーブ株式会社製）を用いて測定した。 On the final day of the test (14th day of mixed feed intake), under the restraint of superficial urethane anesthesia, an incision was made in the lower abdomen of each rat 1 hour after the effect of anesthesia appeared, and after peeling off the surrounding tissue adhering to the bladder, the inside of the bladder The bladder blood flow at a bladder volume of 1 mL was measured using a laser blood flow meter (two-dimensional laser blood flow meter OMEGAZONE OZ-1, manufactured by Omega Wave Co., Ltd.).
　なお、前記骨盤うっ血を行わず、前記混合飼料に代えて前記一般的な飼料（表１中、通常試料）を与えた以外は前述と同様に試験を行った群を参考群（ｎ＝６）とした。また、前記骨盤うっ血を行い、前記混合飼料に代えて一般的な飼料を与えた以外は前述と同様に試験を行った群を比較群（ｎ＝６）とした。 The reference group (n = 6) was a group in which the same test was performed as described above except that the general feed (normal sample in Table 1) was given instead of the mixed feed without performing the pelvic congestion. And said. In addition, the group in which the test was performed in the same manner as described above except that the pelvic congestion was performed and a general feed was given instead of the mixed feed was designated as a comparison group (n = 6).
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
結果
　結果を表２に示す。 Results The results are shown in Table 2.
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
　表２に示す通り、参考群（６匹のラットの平均、以下同様）の膀胱血流量は１７．０ｍＬ／ｍｉｎ／１００ｇであったのに対して、比較群の膀胱血流量は１１．１ｍＬ／ｍｉｎ／１００ｇであり、比較群において膀胱血流量が低下していた。これに対して、ザクロエキス１群、ザクロエキス２群、エラグ酸群、プニカラジン群ではいずれも、参考群と同程度に膀胱血流量が回復し、これらの膀胱血流量は、ポジティブコントロールであるタダラフィル群と同程度であった。 As shown in Table 2, the bladder blood flow in the reference group (average of 6 rats, the same applies hereinafter) was 17.0 mL / min / 100 g, whereas the bladder blood flow in the comparative group was 11.1 mL / min. It was min / 100 g, and the bladder blood flow was decreased in the comparative group. On the other hand, in the pomegranate extract 1 group, the pomegranate extract 2 group, the ellagic acid group, and the punicarazine group, the bladder blood flow was restored to the same extent as the reference group, and these bladder blood flow were positively controlled by tadalafil. It was about the same as the group.
　このことから、エラグ酸、プニカラジン、また、エラグ酸を含むザクロエキス、プニカラジンを含むザクロエキスといった植物加工物によれば、膀胱血流量の増加に有用であることが分かった。 From this, it was found that plant processed products such as ellagic acid and punicarazine, pomegranate extract containing ellagic acid, and pomegranate extract containing punicarazine are useful for increasing bladder blood flow.
試験例２：尿路機能改善
尿路機能の評価手順
　試験例１と同様にして、骨盤うっ血ラットモデルを作成し１６日間飼育した。次いで、タダラフィル、ザクロエキス１、ザクロエキス２、エラグ酸、プニカラジンを水と混合し、得られた混合液を、１日１回、１４日間連続して、ゾンデを用いて各群（ｎ＝６）に経口投与した。この間、一般的な市販の飼料と水は自由摂取とした。投与量は次の表３に示す通りである。例えば、表３中、タダラフィル群に記載する「５ｍｇ／２ｍＬ／ｋｇ」は、ラットモデルの体重１ｋｇあたり、前記混合液を１日あたり２ｍＬ投与し、前記混合液２ｍＬ中タダラフィル含有量が５ｍｇであることを意味する。 Test Example 2: Improvement of urinary tract function
Procedure for evaluating urinary tract function A rat model of pelvic congestion was prepared and bred for 16 days in the same manner as in Test Example 1. Next, tadalafil, pomegranate extract 1, pomegranate extract 2, ellagic acid, and punicarazine were mixed with water, and the obtained mixed solution was used once a day for 14 consecutive days in each group (n = 6). ) Was orally administered. During this period, general commercial feed and water were freely ingested. The dosage is as shown in Table 3 below. For example, in Table 3, "5 mg / 2 mL / kg" shown in the tadalafil group means that 2 mL of the mixed solution is administered per day per 1 kg of the body weight of the rat model, and the tadalafil content in 2 mL of the mixed solution is 5 mg. Means that.
　使用したタダラフィル、ザクロエキス１、ザクロエキス２は試験例１と同じである。プニカラジンは、商品名ポマノックスＰ３０（株式会社エヌ・シー・コーポレーション製（プニカラジン３０％含有、Punica granatumの果皮を含む果実全体を圧搾、濃縮した抽出物）からプニカラジンを精製したもの（プニカラジン９６．７質量％含有）を使用した。表中、タダラフィル、エラグ酸の投与量はこれらの市販品の投与量を示し、プニカラジンの投与量は該精製物の投与量を示す。 The tadalafil, pomegranate extract 1 and pomegranate extract 2 used are the same as in Test Example 1. Punicarazine is a refined version of Punicarazine from the trade name Pomanox P30 (manufactured by NC Corporation (containing 30% Punicarazine, an extract obtained by pressing and concentrating the entire fruit including the peel of Punica granatum) (Punicarazine 96.7 mass). In the table, the doses of tadalafil and ellagic acid indicate the doses of these commercially available products, and the dose of punicarazine indicates the dose of the purified product.
　試験最終日（混合飼料摂取１４日目）に、ウレタン浅麻酔拘束下で、麻酔の効果が現れた１時間後に各ラットの尿道からカテーテルを挿入し、膀胱内に３ｍＬ／時間の速度で生理食塩水を持続注入しながら、連続膀胱内圧の測定を行った。該測定は、デルフュージョンシリンジポンプ TE-331（テルモ株式会社製）、ディスポ圧トランスデューサ DX-100（日本光電工業株式会社製）、リニアコーダ WR3320A-8H（グラフテック株式会社製）、アンプデータ収集機器としてアナログ入出力USBI/Oユニット8ch AIO-160802AY-USB（株式会社コンテック製）、データ計測ソフトウェアとしてLaBDAQ5-CT ver.1.06（株式会社松山アドバンス製）を用いて行った。 On the final day of the test (14th day of mixed feed intake), a catheter was inserted from the urethra of each rat 1 hour after the effect of anesthesia appeared under the restraint of superficial urethane anesthesia, and physiological salt was inserted into the bladder at a rate of 3 mL / hour. Continuous intravesical pressure was measured while continuously injecting water. The measurement was performed by Delfusion syringe pump TE-331 (manufactured by Terumo Co., Ltd.), disposable pressure transducer DX-100 (manufactured by Nippon Koden Kogyo Co., Ltd.), linear coder WR3320A-8H (manufactured by Graphtech Co., Ltd.), and analog as an amplifier data collection device. Input / output USB I / O unit 8ch AIO-160802AY-USB (manufactured by Contec Co., Ltd.) and LaBDAQ5-CT ver.1.06 (manufactured by Matsuyama Advance Co., Ltd.) were used as data measurement software.
　なお、前記骨盤うっ血を行わず、前記混合液に代えて水を与えた以外は前述と同様に試験を行った群を参考群（ｎ＝６）とした。また、前記骨盤うっ血を行い、前記混合液に代えて水を与えた以外は前述と同様に試験を行った群を比較群（ｎ＝６）とした。 The group in which the test was performed in the same manner as described above except that the pelvic congestion was not performed and water was given instead of the mixed solution was designated as a reference group (n = 6). In addition, the group in which the test was performed in the same manner as described above except that the pelvic congestion was performed and water was given instead of the mixed solution was designated as a comparison group (n = 6).
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
結果
　結果を表４～６に示す。 Results The results are shown in Tables 4-6.
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
　表４は、膀胱収縮間隔（平均値の単位：分）を示す結果である。表４に示す通り、参考群の膀胱収縮間隔は１８．９分であったのに対して、比較群の膀胱収縮間隔は１１．０分であり、比較群において膀胱収縮の間隔が短かった。これは、参考群よりも、比較群において排尿回数が多いことを示す。これに対して、ザクロエキス１群、ザクロエキス２群、エラグ酸群、プニカラジン群はいずれも、参考群と同程度の膀胱収縮間隔であり、これらの膀胱収縮間隔は、ポジティブコントロールであるタダラフィル群と同程度であった。 Table 4 shows the results showing the bladder contraction interval (unit of average value: minutes). As shown in Table 4, the bladder contraction interval of the reference group was 18.9 minutes, whereas the bladder contraction interval of the comparison group was 11.0 minutes, and the bladder contraction interval was short in the comparison group. This indicates that the frequency of urination was higher in the comparison group than in the reference group. On the other hand, the pomegranate extract 1 group, the pomegranate extract 2 group, the ellagic acid group, and the punicarazine group all have the same bladder contraction interval as the reference group, and these bladder contraction intervals are the positive control tadalafil group. It was about the same as.
　このことから、エラグ酸、プニカラジン、また、エラグ酸を含むザクロエキス、プニカラジンを含むザクロエキスといった植物加工物は、膀胱収縮間隔の長期化に有用であることが分かった。 From this, it was found that processed plant products such as ellagic acid and punicarazine, pomegranate extract containing ellagic acid, and pomegranate extract containing punicarazine are useful for prolonging the bladder contraction interval.
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000006
Figure JPOXMLDOC01-appb-T000006
　表５は、排尿量を示す結果である。また、表６は、膀胱容量を示す結果である。表５に示す通り、参考群の排尿量は０．９ｍＬであったのに対して、比較群の排尿量は０．６ｍＬであった。また、表６に示す通り、参考群の膀胱容量は１．０ｍＬであったのに対して、比較群の膀胱容量は０．６ｍＬであった。 Table 5 shows the results showing the amount of urination. Table 6 shows the results showing the bladder capacity. As shown in Table 5, the micturition volume of the reference group was 0.9 mL, while the micturition volume of the comparative group was 0.6 mL. Further, as shown in Table 6, the bladder volume of the reference group was 1.0 mL, whereas the bladder volume of the comparative group was 0.6 mL.
　このことから、比較群では、参考群と比較して、排尿量、膀胱容量が共に低減していることが分かった。 From this, it was found that both the micturition volume and the bladder capacity were reduced in the comparison group compared with the reference group.
　参考群については、排尿量が０．９ｍＬ、膀胱容量が１．０ｍＬであったことから、膀胱内に溜まった尿の殆どが排尿されたことが分かった。また、これらのことから、参考群は比較群よりも膀胱容量自体が大きく、従って、比較群よりも多量の尿を膀胱に溜めることができ、また、このように多量の尿を溜めることができるにもかかわらず、溜まった多量の尿を十分に排尿できることが分かった。 For the reference group, the amount of urine was 0.9 mL and the bladder capacity was 1.0 mL, indicating that most of the urine collected in the bladder was urinated. In addition, from these facts, the reference group has a larger bladder capacity itself than the comparison group, and therefore, a larger amount of urine can be collected in the bladder than the comparison group, and thus a large amount of urine can be collected. Nevertheless, it was found that a large amount of accumulated urine could be sufficiently urinated.
　ザクロエキス１群、ザクロエキス２群、エラグ酸群、プニカラジン群はいずれも、参考群と同程度の排尿量及び膀胱容量を示し、これらはポジティブコントロールであるタダラフィル群と同程度であった。 The pomegranate extract 1 group, pomegranate extract 2 group, ellagic acid group, and punicarazine group all showed the same level of urination volume and bladder volume as the reference group, and these were similar to the positive control tadalafil group.
　このことから、エラグ酸、プニカラジン、また、エラグ酸やプニカラジンを含むザクロエキスといった植物加工物によっても、比較群よりも、多量の尿を膀胱に溜めることができ、また、より多量の尿を溜められるにもかかわらず、溜まった尿を十分に排尿できることが分かった。 From this, plant products such as ellagic acid, punicarazine, and pomegranate extract containing ellagic acid and punicarazine can also collect a larger amount of urine in the bladder than the comparative group, and also collect a larger amount of urine. Despite this, it was found that the accumulated urine could be sufficiently urinated.

Claims (7)

  1. 次の成分（１）及び（２）からなる群より選択される少なくとも１種を有効成分として含有する、尿路機能改善用組成物：
    （１）エラグ酸、その類縁体、これらの塩及びこれらの水和物からなる群より選択される少なくとも１種、
    （２）プニカラジン、その塩及びこれらの水和物からなる群より選択される少なくとも１種。     A composition for improving urinary tract function containing at least one selected from the group consisting of the following components (1) and (2) as an active ingredient:
    (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 punicarazine, salts thereof and hydrates thereof.
  2. 次の成分（１）及び（２）からなる群より選択される少なくとも１種を有効成分として含有する、膀胱血流改善用組成物：
    （１）エラグ酸、その類縁体、これらの塩及びこれらの水和物からなる群より選択される少なくとも１種、
    （２）プニカラジン、その塩及びこれらの水和物からなる群より選択される少なくとも１種。     A composition for improving bladder blood flow, which comprises at least one selected from the group consisting of the following components (1) and (2) as an active ingredient:
    (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 punicarazine, salts thereof and hydrates thereof.
  3. 前記尿路機能改善が、頻尿の改善、貯尿量の改善及び排尿量の改善からなる群より選択される少なくとも１種である、請求項１に記載の尿路機能改善用組成物。 The composition for improving urinary tract function according to claim 1, wherein the improvement in urinary tract function is at least one selected from the group consisting of improvement in pollakiuria, improvement in urine storage volume, and improvement in urination volume.
  4. 前記成分（１）及び（２）からなる群より選択される少なくとも１種を含むザクロ属植物加工物を含有する、請求項１または３に記載の尿路機能改善用組成物。 The composition for improving urinary tract function according to claim 1 or 3, which contains a processed pomegranate plant containing at least one selected from the group consisting of the components (1) and (2).
  5. 食品組成物、医薬組成物、医薬部外品組成物または飼料組成物である、請求項１、３及び４のいずれかに記載の尿路機能改善用組成物。 The composition for improving urinary tract function according to any one of claims 1, 3 and 4, which is a food composition, a pharmaceutical composition, a quasi-drug composition or a feed composition.
  6. 前記成分（１）及び（２）からなる群より選択される少なくとも１種を含むザクロ属植物加工物を含有する、請求項２に記載の膀胱血流改善用組成物。 The composition for improving bladder blood flow according to claim 2, which contains a processed pomegranate plant containing at least one selected from the group consisting of the components (1) and (2).
  7. 食品組成物、医薬組成物、医薬部外品組成物または飼料組成物である、請求項２または６に記載膀胱血流改善用組成物。 The composition for improving bladder blood flow according to claim 2 or 6, which is a food composition, a pharmaceutical composition, a quasi-drug composition or a feed composition.
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