WO2018123908A1 - ホスホジエステラーゼ５活性阻害用組成物 - Google Patents

ホスホジエステラーゼ５活性阻害用組成物 Download PDF

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Publication number
WO2018123908A1
WO2018123908A1 PCT/JP2017/046245 JP2017046245W WO2018123908A1 WO 2018123908 A1 WO2018123908 A1 WO 2018123908A1 JP 2017046245 W JP2017046245 W JP 2017046245W WO 2018123908 A1 WO2018123908 A1 WO 2018123908A1
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Prior art keywords
genus
composition according
composition
extract
plant belonging
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PCT/JP2017/046245
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English (en)
French (fr)
Japanese (ja)
Inventor
慎哉 長谷川
淳二 赤木
賢輔 立木
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小林製薬株式会社
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Priority to CN201780081426.6A priority Critical patent/CN110167571A/zh
Publication of WO2018123908A1 publication Critical patent/WO2018123908A1/ja

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
    • 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
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/61—Myrtaceae (Myrtle family), e.g. teatree or eucalyptus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/74—Rubiaceae (Madder family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • 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
    • 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
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to a composition for inhibiting phosphodiesterase 5 activity.
  • Phosphodiesterase is an enzyme that hydrolyzes cyclic GMP (cGMP) and cyclic AMP (cAMP), and there are multiple families in mammals.
  • phosphodiesterase 5 (PDE5) is mainly involved in cGMP degradation.
  • cGMP acts as an intracellular second messenger, relaxes smooth muscle and increases blood flow. For this reason, by suppressing the activity of PDE5, smooth muscle relaxes and blood flow increases.
  • PDE5 inhibitors are known as drugs that utilize this action, and typical drugs such as sildenafil citrate are known.
  • PDE5 inhibitor inhibits the activity of PDE5, suppresses cGMP degradation, and increases local blood flow to improve symptoms such as reduced penile erection ability, bladder and prostate function, and pulmonary hypertension It is utilized as.
  • Patent Document 1 black ginger can inhibit the activity of PDE.
  • An object of the present invention is to provide a new composition capable of inhibiting the activity of PDE5.
  • the present inventors have conducted extensive studies in view of the above problems, and as a result, the following plants: Rubus, Punica, Filipendula, Myrica, Eugenia. ), Lagerstroemia, Terminalia, Haematoxylon, Fallopia or Uncaria, it has been found that the activity of PDE5 can be inhibited.
  • the present invention has been completed as a result of further studies based on this finding, and is as follows. Item 1.
  • compositions for inhibiting phosphodiesterase 5 activity comprising a processed product of at least one plant selected from the group consisting of (Fallopia) and Uncaria.
  • Item 2. The composition according to Item 1, wherein the plant belonging to the genus Rubus is at least one selected from the group consisting of Himalayan blackberry (Rubus armeniacus Focke), Aedesian strawberry (Rubus fruticosus), and American strawberry (Rubus strigosus). .
  • composition according to Item 1 wherein the plant belonging to the genus Pomegranate is pomegranate (Punica granatum).
  • Item 4. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Pleurotus is Filipendula ulmaria.
  • Item 5. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Corpus is at least one selected from the group consisting of Myrica cerifera and Myrica rubura.
  • the composition according to Item 1, wherein the plant belonging to the genus Eugenia is at least one selected from the group consisting of Eugenia uniflora and clove (Eugenia aromaticum).
  • Item 7. Item 2.
  • composition according to Item 1 wherein the plant belonging to the genus Crape myrtle is banaba (Lagerstroemia speciosa).
  • Item 8. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Momotamana is at least one selected from the group consisting of Terminalia catappa and Terminalia bellirica.
  • Item 9. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Akaminoki is Haematoxylon campechianum.
  • Item 11. Item 2.
  • composition according to Item 1 wherein the plant belonging to the genus Kasakazura is Uncaria guianensis.
  • Item 12. Item 12. The composition according to any one of Items 1 to 11, which is for prevention or amelioration selected from the group consisting of penile erection function, lower urinary tract dysfunction, prostate hypertrophy and pulmonary hypertension.
  • Item 13. Item 13. The composition according to any one of Items 1 to 12, which is a food composition, a pharmaceutical composition, or a feed composition.
  • the activity of PDE5 can be inhibited. Therefore, the composition of the present invention is used for the purpose of preventing or ameliorating diseases caused by decreased blood flow accompanying cGMP degradation such as penile erection function, lower urinary tract dysfunction, prostatic hypertrophy, and pulmonary hypertension. can do.
  • diseases caused by decreased blood flow accompanying cGMP degradation such as penile erection function, lower urinary tract dysfunction, prostatic hypertrophy, and pulmonary hypertension. can do.
  • the present invention relates to the genus Rubus, Punica, Filipendula, Myrica, Eugenia, Lagerstroemia, Terminalia, and Haematoxylon. ), A composition for inhibiting phosphodiesterase 5 activity, comprising a processed product of at least one plant selected from the group consisting of Fallopia and Uncaria.
  • the genus Raspberry As raw materials for the processed plant products contained as an active ingredient in the composition of the present invention, the genus Raspberry, Pomegranate, Prunus spp., Prunus genus, Eugenia, Prunus spp., Prunus spp. Plants belonging to any of the genera can be mentioned.
  • the genus Rubus belongs to the family Rosaceae and is not intended to limit the present invention. Examples of plants belonging to the genus include Himalayan blackberry (Rubus armeniacus Focke), Yabu strawberry (Rubus fruticosus), American strawberry (Rubus strigosus), etc. Is done.
  • the pomegranate belongs to the family Lamiaceae and does not limit the present invention, but examples of plants belonging to the genus include pomegranate (Punica granatum).
  • the genus Spiraea belongs to the family Rosaceae and does not limit the present invention, but examples of plants belonging to the genus include Filipendula ulmaria.
  • the genus genus belongs to the genus Dioscorea and does not limit the present invention, but examples of plants belonging to the genus include white licorice (Myrica cerifera), bayberry (Myrica rubura) and the like.
  • the genus Eugenia belongs to the Myrtaceae family and does not limit the present invention, but examples of plants belonging to the genus include Eugenia uniflora and clove (Eugenia aromaticum).
  • the genus Crapery belongs to the family Lamiaceae and does not limit the present invention
  • examples of plants belonging to the genus include banaba (Lagerstroemia speciosa) and the like.
  • Momotamana belongs to the family Cypridaceae and does not limit the present invention
  • examples of plants belonging to the genus include Momotamana (Terminalia catappa), Seitamirobaran (Terminalia bellirica) and the like.
  • the genus Akaminoki belongs to the leguminous family and does not limit the present invention, but examples of plants belonging to the genus include Akaminoki (Haematoxylon campechianum) and the like.
  • the buckwheat genus belongs to the family Taceae and does not limit the present invention, but examples of plants belonging to the genus include Fallopia japonica.
  • the genus Kakazura belongs to the Rubiaceae family and does not limit the present invention, but examples of plants belonging to the genus include cats claw (Uncaria guianensis).
  • the site of use is not particularly limited as long as these plants are used, but examples include leaves, stems, fruits, flowers, buds, branches, stems, bark, roots, florets, seeds, seed coats, and the like, which are appropriately selected according to each plant. That's fine.
  • leaves in the genus Raspberry fruits, fruits in the genus Pomegranate, leaves in the genus Prunus, stems, bark in the genus Genus, Eugenia In the genus, fruit, floret, crape myrtle leaves, momotamana genus fruit, red crested genus stem, buckwheat genus stem, leaf, and genus Kazura genus root, stem, leaf.
  • one kind may be used alone, or two or more kinds may be used in combination.
  • the plant processed product includes a pulverized product, a dried product, and an extract of the plant as the raw material.
  • the pulverized product is not particularly limited as long as the plant is pulverized by a pulverizer 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 obtained according to a conventionally known drying method such as sun drying, far-infrared irradiation, dryer (hot air drying, cold air drying, vacuum freeze drying, etc.) and the like. be able to.
  • the water content in the dried product is preferably 10% by weight or less, and more preferably 8% by weight or less.
  • the form of the dried product is not limited, and any of a dried product of the plant itself and a pulverized product of the dried product may be used.
  • the dried pulverized product can be obtained by pulverizing the dried product according to the same method as the pulverized product.
  • what was obtained by drying after making the plant used as a raw material a fermentation process or an enzyme process as a dried material can also be used.
  • Extract production method extraction method
  • extraction conditions and the like are not particularly limited, and may be a conventionally known method.
  • the plant can be cut, crushed or dried as necessary, and then extracted by extraction or solvent extraction.
  • solvent extraction a known method in this field may be employed.
  • a conventionally known extraction method such as water (including warm water and hot water) extraction, alcohol extraction, supercritical extraction, or the like can be used. .
  • the solvent is, for example, water; alcohols such as lower alcohols such as methanol, ethanol and isopropanol, and polyhydric alcohols such as propylene glycol and 1,3-butylene glycol (anhydrous, regardless of water content). ); 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, lower alcohol, 1,3-butylene glycol or the like, more preferably water, methanol, ethanol or 1,3-butylene glycol, and still more preferably water, methanol or hydrous ethanol. These solvents may be used alone or in combination of two or more.
  • the extract obtained through the 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 water extract, when a lower alcohol is used, a lower alcohol extract, when ethanol is used, an ethanol extraction is used. It can be called a thing etc.
  • the obtained extract may be used as it is, or may be dried and used in a solid state such as powder or granule.
  • the obtained extract may be subjected to purification, concentration treatment, separation treatment of highly active fraction, and the like as necessary.
  • processing such as filtration, adsorption
  • concentration treatment a conventional method such as an evaporator can be used.
  • known separation treatments such as gel filtration, adsorption treatment, silica gel column chromatography, HPLC (High performance liquid chromatography) and the like can be used.
  • a method of subjecting the extract obtained as described above (and its dried product, purified product, concentrated product, and highly active fraction) to lyophilization and pulverization if necessary.
  • an extract such as dextrin, corn starch, gum arabic and the like may be added and powdered according to a conventionally known method such as a method of powdering by spray drying, and the extract used in the present invention may be used.
  • the extract may be used by dissolving it in water, ethanol or the like, if necessary.
  • the plant extract is preferably an extract obtained by drying, crushing and / or cutting a plant (use site) as a raw material, and extracting and filtering using a suitable solvent.
  • the extract obtained by further drying the obtained extract is illustrated.
  • the present invention is not limited, and a person skilled in the art may appropriately extract according to each plant or use site.
  • the extract is 100 g of a plant as a raw material, more preferably a dried product or a crushed product of the plant.
  • / or the cut material is immersed in 1 to 50 liters of extraction solvent per 100 g and at any temperature (for example, 15 to 90 ° C.) with stirring as necessary for any time (for example, 10 minutes to 24 hours). ) Extraction, followed by filtration.
  • a plant extract (including a dried product thereof) is preferably used as a processed plant product.
  • the processed plant product used in the present invention may be a commercially available product, or may be a product obtained by appropriately subjecting the commercially available product to a treatment such as drying.
  • the plant processed product thus obtained may be used alone or in combination of two or more.
  • the content of the processed plant product in the composition of the present invention is not limited as long as the processed plant product is contained in the composition, and the effect of the present invention is obtained.
  • the processed product of the plant is contained in an amount of more than 0% by weight, preferably more than 0% by weight and less than 100% by weight, more preferably in terms of dry matter. Is exemplified by 0.001 to 99% by weight. When two or more kinds of workpieces are used, the total amount satisfies the value.
  • a dried product is obtained by freeze-drying the processed product. The freeze-drying process is performed by vacuum concentration using a general evaporator and freeze-drying in a vacuum state. A more detailed processing procedure follows an embodiment described later.
  • the administration (intake) amount of the processed plant product is not particularly limited as long as the effect of the present invention is exhibited, and the physique, age, symptom, application of the subject (target animal) What is necessary is just to set suitably according to a form, the intended purpose, the grade of the effect expected, etc.
  • a daily administration (intake) amount the processed product of the plant is a total amount (in terms of dry weight), preferably 0.001 to 8000 mg, based on an adult with a body weight of 60 kg. More preferably, 0.01 to 5000 mg is exemplified.
  • the composition of the present invention may be single dose (intake) or multiple dose (intake) per day.
  • the composition of the present invention may be oral or parenteral.
  • the form of the composition of the present invention is not limited, and may be appropriately set depending on the purpose.
  • liquid forms such as liquids, emulsions, suspensions, syrups, extracts, spirits, elixirs, powders, granules, fine granules, tablets, pills, capsules ( (Including hard capsules and soft capsules), troches, chewables, gels, creams, pastes, mousses, sheets, semi-solid or solid forms such as lyophilizates in liquid form, in addition, aerosols and other patches,
  • Various forms such as a haptic agent and a transdermal absorption preparation are exemplified.
  • the composition of the present invention when it is in a solid form, it may be used by mixing with water or the like, and the composition of the present invention may be in a sustained-release dosage form.
  • the tablet can be a tablet with a conventionally known coating, such as a sugar-coated tablet, a gelatin-encapsulated tablet, an enteric-coated tablet, a film-coated tablet, a double tablet, or a multilayer tablet, if necessary. .
  • the use mode of the composition of the present invention is not limited, and may be appropriately set according to the purpose.
  • Examples of usage of the composition of the present invention include food compositions (including beverages, health functional foods (including foods for specified health use, nutritional functional foods, functional display foods, supplements, etc.), foods for the sick, It can be used as an additive to pharmaceutical compositions, feed compositions, food compositions, pharmaceutical compositions, feeds, and the like.
  • composition of the present invention may be produced according to conventionally known ordinary procedures in the above-mentioned various forms, usage modes, etc., and if necessary, pharmaceutically acceptable ingredients, cosmetically acceptable ingredients. What is necessary is just to mix and manufacture with arbitrary components, such as an edible component.
  • Solvents water, lower alcohols such as methanol, ethanol and isopropanol, alcohols such as polyhydric alcohols such as propylene glycol and 1,3-butylene glycol (anhydrous, regardless of water content), etc.
  • Excipients disintegrants, diluents, lubricants, flavors, colorants, sweeteners, flavoring agents, suspending agents, wetting agents, emulsifiers, solubilizers, dispersants, buffers, binders, penetration enhancers Agent, stabilizer, extender, preservative, thickener, pH adjuster, surfactant, coating agent, absorption enhancer, adsorbent, filler, antioxidant, anti-inflammatory agent, cooling agent, film-forming agent And gelling agents, amino acids, vitamins, enzymes, various nutritional components, and the like. These may be used alone or in combination of two or more.
  • the subject (target animal) of the composition is not limited, but humans and mammals other than humans are exemplified.
  • mammals other than humans include animals in which phosphodiesterase 5 promotes the degradation of cGMP, and animals such as mice, rats, guinea pigs, rabbits, dogs, cats, monkeys, pigs, cows, horses, preferably mice. And animals such as rats, guinea pigs, rabbits, dogs and monkeys.
  • the activity of phosphodiesterase 5 can be inhibited using the processed plant product as an active ingredient.
  • this invention provides the manufacturing method of the composition for PDE5 activity inhibition characterized by using the processed material of the said plant.
  • this invention provides the manufacturing method of the composition for PDE5 activity inhibition containing the process of preparing the processed material of the said plant.
  • this invention provides the PDE5 activity inhibition method characterized by using the processed material of the said plant.
  • the activity of PDE5 can be inhibited. Therefore, according to the present invention, the degradation of cGMP can be suppressed, and the composition of the present invention can be used for the purpose of preventing or ameliorating diseases caused by PDE5 activity and local blood flow reduction.
  • the composition of the present invention is useful for the prevention or improvement of penile erection function, lower urinary tract dysfunction, prostatic hypertrophy, pulmonary hypertension, etc., although the present invention is not limited thereto.
  • smooth muscle is relaxed by the PDE5 inhibitory action, thereby improving the penile erection function by increasing the blood flow to the cavernous corpus cavernosum, and lowering the lower urine by increasing the blood flow to the urinary system
  • Can improve tract obstruction can increase prostate blood flow in the prostate and urethra, can alleviate prostate enlargement, and can increase blood flow to the lung tissue to reduce pulmonary artery pressure it can.
  • composition of the present invention can also be preferably applied to subjects who are concerned about male function, subjects who are concerned about urination function, and the like.
  • composition of the present invention includes PDE5 activity inhibitor, penile erection function (deficiency) treatment, lower urinary tract dysfunction treatment, prostate hypertrophy treatment, pulmonary hypertension treatment (particularly pulmonary arterial pulmonary hypertension), etc. Can also be used as
  • Test example 1 Processed Plants Extracts of each plant were prepared using the plants shown in Table 1 as raw materials. Specifically, for Examples 1, 5, 9 and 10, extracts were prepared according to the following procedure, and commercially available products were used for the other examples.
  • Example 1 Himalayan Blackberry Himalayan Blackberry leaves 50 g were crushed, 1000 ml of water was added, and extraction treatment was performed at 80 ° C. for 1 hour. The obtained extract was filtered through Miracloth (manufactured by Merck Millipore), and the filtrate from which insoluble components had been removed was freeze-dried to obtain a Himalayan blackberry extract (7.9 g of dried extract).
  • Example 2 Yab Strawberry An extract of Yab Strawberry (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing dried yab strawberry leaves, extracting with methanol, filtering the resulting extract, and lyophilizing the filtrate from which insoluble components had been removed. is there.
  • Example 3 American Strawberry American strawberry leaf and fruit extracts (made by Nippon Shinyaku Co., Ltd., dry powder) were used. This extract was obtained by crushing a dried product of American strawberry leaves and fruits, extracting by adding methanol, filtering the resulting extract, and lyophilizing the filtrate from which insoluble components had been removed. It is.
  • Example 4 pericarp extract of pomegranate pomegranate (trade name pomegranate rind extract powder, Koei Kogyo Co., Ltd., powder dry matter) was used.
  • Example 5 40 g of dried stems and leaves of C. communis was crushed, 1000 ml of water was added, and extraction was performed at 80 ° C. for 1 hour. The obtained extract was filtered with Miracloth (manufactured by Merck Millipore), and the filtrate from which insoluble components had been removed was freeze-dried to obtain a licorice extract (9.9 g of dried extract).
  • Example 6 An extract of bark of white bayberry (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing a dried white bark bark, adding methanol for extraction, filtering the resulting extract, and lyophilizing the filtrate from which insoluble components had been removed. .
  • Example 7 An extract of bark of yamamomo yamamomo (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing a dried product of bayberry bark, extracting by adding methanol, filtering the obtained extract, and lyophilizing the filtrate from which insoluble components were removed.
  • Example 8 Tachibana adecta fruit extract (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing the dried fruit of Tachibana adek, adding methanol for extraction, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed. .
  • Example 9 50 g of dried clove clove flower was crushed, 1000 ml of water was added, and extraction treatment was performed at 80 ° C. for 1 hour. The obtained extract was filtered with Miracloth (manufactured by Merck Millipore), and the filtrate from which insoluble components were removed was freeze-dried to obtain a clove extract (10.1 g of dried extract).
  • Example 10 banaba banaba crushed dry matter 60g leaf (mass ratio of water and ethanol 1: 1) 50 wt% ethanol 900ml added to 25 ° C., was carried out extraction at 12 hours. The obtained extract was filtered through Miracloth (Merck Millipore), ethanol was distilled off from the filtrate from which insoluble components had been removed, and then freeze-dried to obtain a banaba extract (8.9 g dry extract). Obtained.
  • Example 11 An extract of the fruit of Momota Mana Momota Mana (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing a dried product of Momotamana fruit, adding methanol to perform extraction, filtering the obtained extract, and freeze-drying the filtrate from which insoluble components were removed.
  • Example 12 Seitakamirobaran Fruit extract of Seitakamirobalan (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing the dried fruit of Seitacamilobaran, adding methanol to extract it, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed. is there.
  • Example 13 haematoxylum campechianum stem extract of haematoxylum campechianum (Nippon Shinyaku Co. custom, powder dry matter) was used. This extract was obtained by crushing a dried stem of Akaminoki trunk, adding methanol for extraction, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed.
  • Example 14 Extracts of stems and leaves of Japanese knotweed weeds (special order made by Nippon Shinyaku Co., Ltd., dry powder) were used. This extract was obtained by crushing dried weedbird stems and leaves, extracting with methanol, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed. is there.
  • Example 15 Cats Claw Cats Claw root, stem and leaf extracts (made by Nippon Shinyaku Co., Ltd., dry powder) were used. This extract was obtained by crushing dried catscrow roots, stems and leaves, adding methanol to extract, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed. It is a thing.
  • Comparative Example An extract of rhizomes of black ginger black ginger (trade name: black ginger extract-P, manufactured by Oriza Oil Co., Ltd., dried powder) was used.
  • Black ginger is a plant that is conventionally known to have an inhibitory action on phosphodiesterase (PDE).
  • PDE5A Assay Kit # 60350 (manufactured by BPS Bioscience), 96-well plate, Pipetman, PerkinElmer EnVision 2102 Multilabel Reader (manufactured by PerkinElmer) was used to measure the inhibitory activity according to the instructions attached to the kit. did.
  • Table 1 shows IC50 values.
  • Test example 2 1. Measurement Procedure Using the extracts of Examples 1, 4, 5 and 10 prepared in the above test examples, the extract of the comparative example, and water as a control, the amount of cyclic guanosine monophosphate (cGMP) in rat tissue was measured. did.
  • cGMP cyclic guanosine monophosphate
  • the extract-containing administration liquid 500 mg / 2 mL / kg body weight
  • the amount of cGMP in the penile tissue was measured according to the method described in cGMP ELISA kit.
  • administration was carried out in the stomach in the same manner, and the amount of cGMP in the penile tissue was measured.
  • the amount of cGMP at the time of administration of black ginger was slightly higher than the amount of cGMP at the time of administration of distilled water.
  • the amount of cGMP at the time of administration of the extracts of Examples 1, 4, 5 and 10 was about twice or more than that at the time of administration of black ginger.

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WO2021106856A1 (ja) * 2019-11-29 2021-06-03 小林製薬株式会社 尿路機能改善用組成物及び膀胱血流改善用組成物
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