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WO2025142973A1 - Agent pour éliminer des cellules sénescentes et agent pour supprimer une diminution de la fonction motrice - Google Patents

Agent pour éliminer des cellules sénescentes et agent pour supprimer une diminution de la fonction motrice Download PDF

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Publication number
WO2025142973A1
WO2025142973A1 PCT/JP2024/045803 JP2024045803W WO2025142973A1 WO 2025142973 A1 WO2025142973 A1 WO 2025142973A1 JP 2024045803 W JP2024045803 W JP 2024045803W WO 2025142973 A1 WO2025142973 A1 WO 2025142973A1
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WIPO (PCT)
Prior art keywords
mass
senescent cells
senescent
cells
agent
Prior art date
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Pending
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PCT/JP2024/045803
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English (en)
Japanese (ja)
Inventor
太輝 長野
英樹 梶浦
素子 木村
宗 山本
友彦 戸村
里奈子 氏家
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Ezaki Glico Co Ltd
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Ezaki Glico Co Ltd
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Publication of WO2025142973A1 publication Critical patent/WO2025142973A1/fr
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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 OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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)
    • 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
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • 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

Definitions

  • the present invention relates to a senescent cell removal agent. More specifically, the present invention relates to a senescent cell removal agent that is characterized by selectively removing senescent cells relative to normal cells.
  • Healthy life expectancy is a health indicator advocated by the World Health Organization (WHO) and refers to the period during which one can live an independent and healthy life, both physically and mentally.
  • WHO World Health Organization
  • the difference between healthy life expectancy and average life expectancy, which is the "unhealthy period" during which daily life is restricted, is thought to be about nine years for Japanese men and about 12 years for Japanese women.
  • Item 1 An agent for removing senescent cells comprising an effective amount of at least one member selected from the group consisting of uniflora flowers, uniflora bark, and extracts thereof.
  • Item 4. The agent for removing senescent cells according to any one of Items 1 to 3, characterized in that the ratio (A/B) of (A) the 50% lethal concentration (LC50) in normal cells to (B) the 50% lethal concentration in senescent cells is greater than 1.1.
  • the Japanese bush clover is a deciduous tree of the Fabaceae subfamily.
  • the Japanese bush clover is also called the Silk Tree, and its name comes from the fact that it closes its leaflets and hangs down during the night.
  • At least one selected from the group consisting of unicorn flower, unicorn bark, and extracts thereof can be suitably used as an agent for selectively removing senescent cells, which can effectively remove senescent cells and preferably selectively remove senescent cells relative to normal cells.
  • test examples a comparison was made between a control group without any additives and a group to which unicorn flower extract was added, and the effect of at least one selected from the group consisting of unicorn flower, unicorn bark, and their extracts in suppressing the decline in motor function was confirmed.
  • At least one or more types of indications selected from the group consisting of "reducing senescent cells,” “removing senescent cells,” “reducing the proportion of senescent cells,” “promoting the reduction of senescent cells,” and “suppressing decline in motor function” may be used, but are not limited to these.
  • At least one of the following claims may be made, but is not limited to, selected from the group consisting of "maintaining bone density,” “relieving knee discomfort,” “supporting flexibility and mobility of the knee joint,” “improving skin moisture retention,” “maintaining skin elasticity,” “regrowing and promoting hair growth,” “regulating stomach condition,” “improving visual function,” “reducing temporary physical and mental fatigue,” “reducing biological age,” “improving sarcopenia,” “improving frailty,” “improving locomotive syndrome,” “improving lifestyle-related diseases,” and “maintaining balance function.”
  • compositions of the present invention may consist of at least one selected from the group consisting of unicorn flower, unicorn bark, and extracts thereof, or may contain at least one selected from the group consisting of unicorn flower, unicorn bark, and extracts thereof.
  • formulation and composition of the present invention are oral preparations, they may contain other additives, such as excipients, binders, disintegrants, emulsifiers, lubricants, flow enhancers, diluents, preservatives, colorants, flavorings, flavorings, stabilizers, moisturizers, preservatives, antioxidants, or suspending agents.
  • additives such as excipients, binders, disintegrants, emulsifiers, lubricants, flow enhancers, diluents, preservatives, colorants, flavorings, flavorings, stabilizers, moisturizers, preservatives, antioxidants, or suspending agents.
  • additives include, but are not limited to, gelatin, sodium alginate, starch, corn starch, white sugar, lactose, glucose, mannitol, carboxymethylcellulose, dextrin, polyvinylpyrrolidone, crystalline cellulose, soybean lecithin, sucrose, fatty acid esters, talc, magnesium stearate, polyethylene glycol, magnesium silicate, anhydrous silicic acid, or synthetic aluminum silicate.
  • the formulations and compositions of the present invention can be administered to humans, but may also be administered to animals other than humans, including pets such as dogs, cats, horses, ponies, donkeys, cows, pigs, sheep, goats, rabbits, monkeys, hamsters, guinea pigs, mice, rats, ferrets, squirrels, and birds; livestock such as cows, chickens, and pigs; and animals kept on farms and zoos (horses, sheep, goats, monkeys, elephants, lions, cheetahs, etc.).
  • pets such as dogs, cats, horses, ponies, donkeys, cows, pigs, sheep, goats, rabbits, monkeys, hamsters, guinea pigs, mice, rats, ferrets, squirrels, and birds
  • livestock such as cows, chickens, and pigs
  • animals kept on farms and zoos horses, sheep, goats, monkeys, elephants, lion
  • the food and drink items include food and beverages.
  • food and beverages include beverages (soft drinks (coffee, cocoa, juice, mineral drinks, tea drinks (green tea, black tea, oolong tea), almond drinks, sports drinks, energy drinks, nutritional drinks, etc.), milk drinks, lactic acid bacteria drinks, yogurt drinks, carbonated drinks, alcoholic beverages, spreads (custard cream, butter cream, peanut cream, chocolate cream, cheese cream, etc.), pastes (fruit paste, vegetable paste, sesame paste, seaweed paste, etc.), Western sweets (chocolate, donuts, pies, muffins, waffles, gum, gummies, jellies, candies, cookies, crackers, biscuits, snacks, cakes, puddings, etc.), Japanese sweets (candy, rice crackers, karinto, arare, dumplings, ohagi, daifuku, bean mochi, mochi, bean paste, buns, Castella cake, Anmitsu, Yokan, etc.), frozen desserts (ice cream, popsicles
  • These foods or beverages may contain food additives and food ingredients, such as, but not limited to, antioxidants, flavorings, acidulants, colorings, emulsifiers, preservatives, seasonings, sweeteners, spices, pH adjusters, stabilizers, vegetable oils, animal oils, sugars and sugar alcohols, vitamins, organic acids, fruit juice extracts, vegetable extracts, grains, beans, vegetables, meat, and seafood, either alone or in combination of two or more.
  • food additives and food ingredients such as, but not limited to, antioxidants, flavorings, acidulants, colorings, emulsifiers, preservatives, seasonings, sweeteners, spices, pH adjusters, stabilizers, vegetable oils, animal oils, sugars and sugar alcohols, vitamins, organic acids, fruit juice extracts, vegetable extracts, grains, beans, vegetables, meat, and seafood, either alone or in combination of two or more.
  • tablets can be prepared by mixing a powdered active ingredient with a pharma- ceutically acceptable carrier component (such as an excipient) and compressing the mixture, and confectionery tablets such as candies can be prepared by pouring the mixture into a mold. Tablets can also be sugar-coated to make them sugar-coated tablets. Furthermore, tablets can be single-layer tablets or layered tablets such as double-layer tablets.
  • a pharma- ceutically acceptable carrier component such as an excipient
  • Capsules can be prepared by filling a capsule (soft or hard capsule) with a powder (powder, granules, etc.) using conventional methods.
  • Liquid preparations can be prepared by dissolving or dispersing each component in an aqueous medium (purified water, purified water containing ethanol, etc.) which is a carrier component, filtering or sterilizing as necessary, filling the mixture into a specified container, and sterilizing the mixture.
  • aqueous medium purified water, purified water containing ethanol, etc.
  • the preferred dosage form of solid preparations is a capsule or tablet, and soft capsules (soft capsules) are more preferred.
  • Soft capsules have a smooth surface and are easy to swallow, making them popular with users.
  • Common methods for manufacturing soft capsules include the flat plate method, the rotary method, and the seamless method.
  • a sheet-like capsule shell sandwiches the flowing filling contents and forms a capsule shape along the holes in a rotating cylindrical die.
  • the seamless method dropping method
  • the capsule shell composition and contents are simultaneously ejected from multiple concentric nozzles to form a seamless capsule shape.
  • the base material for the soft capsule shell is not particularly limited, but may be starch, pullulan, cellulose, polyvinyl alcohol, gelatin, succinated gelatin, etc., with starch, gelatin, and succinated gelatin being preferred, and gelatin and succinated gelatin being more preferred. These may be used alone or in combination of two or more kinds.
  • the daily oral intake or administration amount of unicorn flower, unicorn skin, or an extract thereof for an adult can be determined appropriately depending on the individual's condition, body weight, sex, age, activity of the material, intake or administration route, intake or administration schedule, formulation form, or other factors.
  • the daily oral intake or administration amount of unicorn flower, unicorn skin, or an extract thereof for an adult is, for example, preferably 0.1 mg or more, more preferably 1 mg or more, even more preferably 10 mg or more, particularly preferably 20 mg or more, and most preferably 30 mg or more. It may also be 100 mg or more, 200 mg or more.
  • the daily oral intake or administration amount of unicorn flower, unicorn skin, or an extract thereof for an adult is, for example, preferably 2000 mg or less, more preferably 1500 mg or less, even more preferably 1000 mg or less, and particularly preferably 500 mg or less.
  • the daily oral intake or administration amount of the flower, bark, or extract thereof for an adult is, for example, preferably 0.1 to 2000 mg, more preferably 1 to 1500 mg, even more preferably 10 to 1000 mg, even more preferably 20 to 500 mg, and even more preferably 30 to 500 mg.
  • the daily oral intake or dosage for adults may be divided into 1-6 capsules, 1-4 capsules, 1-3 capsules, or 1-2 capsules depending on the dosage form.
  • composition of the present invention can be taken or administered once or several times a day, typically 1 to 6 times a day, 1 to 3 times a day, 1 to 2 times a day, or at any desired period and interval, but once a day is preferred.
  • Example 1 Ethanol extract 1 3.0 g of dried powder of the rhododendron was added to 30 mL of 99.5% ethanol and stirred at room temperature for 30 minutes to perform extraction. After that, the residue was removed by a conventional method, and the mixture was dried to obtain 0.1326 g of a dried product.
  • Example 2 Ethanol extract 2
  • 3 g of dried powder of the peanut bark was added with 30 mL of 99.5% ethanol and stirred at room temperature for 30 minutes to carry out extraction. After that, the residue was removed by a conventional method, and the mixture was dried to obtain 0.1551 g of a dried product.
  • Hot water extract 1 27 mL of water was added to 3.0 g of dried powder of the Japanese laurel tree, and the mixture was stirred at 90° C. for 1 hour to carry out extraction. After that, the residue was removed by a conventional method, and the mixture was dried to obtain 0.7323 g of a dried product.
  • Example 4. Hot water extract 2 27 mL of water was added to 3.0 g of dried powder of the peanut bark, and the mixture was stirred at 90° C. for 1 hour to carry out extraction. After that, the residue was removed by a conventional method, and the mixture was dried to obtain 0.1851 g of a dried product.
  • Example 5 Alkaline Extract Add 25 mL of water to 3.0 g of dried powder of the Japanese laurel tree, adjust the pH to 9.0 ( ⁇ 0.1) using 0.5 mol/L sodium hydroxide solution, and add water to make a total of 33 g. Stir at 70°C for 1 hour to extract. After adjusting the pH to 7.0 using 0.5 mol/L hydrochloric acid, remove the residue by the usual method, and then dry it to obtain 0.5802 g of dried material.
  • Senescent cell elimination ability LC50 in normal (non-senescent) cells / LC50 in senescent cells
  • the motor function of Drosophila was evaluated by performing a climbing assay and evaluating negative gravitaxis.
  • the climbing assay was performed under the following conditions. Ten Drosophila per vial were transferred to an empty vial containing no food, and the vial was tapped to drop the Drosophila to the bottom, and the Drosophila climbing the wall of the vial was then videotaped. Ten seconds after the Drosophila were dropped to the bottom, the number of flies in the upper 1/3 range, the central 1/3 range, or the lower 1/3 range of the vial was counted.
  • the total score for each group was calculated by giving 3 points for flies in the upper part of the vial, 2 points for flies in the center, and 1 point for flies in the lower part of the vial, and the average climbing score was calculated by dividing the total score by the number of flies.
  • the results of calculating the average climbing scores at each age are shown in Tables 1 and 2, and Figures 2 and 3, respectively.
  • the average climbing score which indicates the motor ability of Drosophila
  • the result was 1.94 at 36 days of age in the group administered the Hemerocallis extract. Since the score at the same age in the control group was 1.49, it was confirmed that Hemerocallis extract has the ability to suppress the decline in motor function.
  • the average climbing score which indicates the motor ability of Drosophila, was calculated and the value was 2.04 at 36 days of age in the group administered with the extract of the skin of the rhododendron bark. Since the score at the same age in the control group was 1.23, it was confirmed that the extract of the skin of the rhododendron bark has the ability to suppress the decline of motor function.

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Abstract

Le but de la présente invention est de fournir une préparation et une composition qui sont efficaces dans l'élimination de cellules sénescentes et qui peuvent être ingérées même dans le domaine des produits alimentaires et des boissons. L'invention concerne un agent pour éliminer des cellules sénescentes, l'agent contenant une quantité efficace d'au moins un élément choisi dans le groupe constitué par les fleurs d'Albizia julibrissin, l'écorce d'Albizia julibrissin et des extraits de ceux-ci.
PCT/JP2024/045803 2023-12-25 2024-12-25 Agent pour éliminer des cellules sénescentes et agent pour supprimer une diminution de la fonction motrice Pending WO2025142973A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP2023-217850 2023-12-25
JP2023217850 2023-12-25
JP2024182207 2024-10-17
JP2024-182207 2024-10-17

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WO2025142973A1 true WO2025142973A1 (fr) 2025-07-03

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VAUGHN KATHERINE, MCCLAIN COLT, CARRIER DANIELLE JULIE, WALLACE SUNNY, KING JERRY, NAGARAJAN SHANMUGAM, CLAUSEN EDGAR: "Effect of Albizia julibrissin Water Extracts on Low-Density Lipoprotein Oxidization", JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 55, no. 12, 1 June 2007 (2007-06-01), US , pages 4704 - 4709, XP093331064, ISSN: 0021-8561, DOI: 10.1021/jf063458e *

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