WO2022075059A1 - サーチュイン１活性化剤 - Google Patents

サーチュイン１活性化剤 Download PDF

Info

Publication number
WO2022075059A1
WO2022075059A1 PCT/JP2021/034628 JP2021034628W WO2022075059A1 WO 2022075059 A1 WO2022075059 A1 WO 2022075059A1 JP 2021034628 W JP2021034628 W JP 2021034628W WO 2022075059 A1 WO2022075059 A1 WO 2022075059A1
Authority
WO
WIPO (PCT)
Prior art keywords
sirtuin
activator
present
skin
cells
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2021/034628
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
辰也 金
優美 白井
喜範 片倉
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shiseido Co Ltd
Original Assignee
Shiseido Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shiseido Co Ltd filed Critical Shiseido Co Ltd
Priority to JP2022555347A priority Critical patent/JPWO2022075059A1/ja
Publication of WO2022075059A1 publication Critical patent/WO2022075059A1/ja
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • 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)
    • A61K36/577—Malvaceae (Mallow family)
    • 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
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • A61K36/074—Ganoderma
    • 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)
    • A61K36/24—Apocynaceae (Dogbane family), e.g. plumeria or periwinkle
    • 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)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • 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)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/282—Artemisia, e.g. wormwood or sagebrush
    • 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)
    • A61K36/34—Campanulaceae (Bellflower family)
    • A61K36/346—Platycodon
    • 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)
    • A61K36/45—Ericaceae or Vacciniaceae (Heath or Blueberry family), e.g. blueberry, cranberry or bilberry
    • 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)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537—Salvia (sage)
    • 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)
    • A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
    • 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
    • A61K36/738—Rosa (rose)
    • 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)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • 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)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A61K36/815—Lycium (desert-thorn)
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A61K36/8969—Polygonatum (Solomon's seal)
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A61K36/8998—Hordeum (barley)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • 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

Definitions

  • the present invention provides a sirtuin 1 activator.
  • Sirtuin gene which is a NAD + -dependent deacetylase
  • Sirtuin genes have been identified from sirtuin 1 to sirtuin 7.
  • Sirtuin 1 is attracting attention.
  • the protein targeted by sirtuin 1 has been identified, and it is considered from the study that it is involved in anti-aging, intracellular metabolism, energy expenditure, inflammation, stress response pathway, etc. (Non-Patent Document 1).
  • Non-Patent Document 1 Non-Patent Document 1
  • Japanese Unexamined Patent Publication No. 2019-218296 Japanese Unexamined Patent Publication No. 2018-48152 Japanese Unexamined Patent Publication No. 2018-199680 Japanese Unexamined Patent Publication No. 2017-66128 Japanese Unexamined Patent Publication No. 2014-166982 Japanese Unexamined Patent Publication No. 2013-241380 Japanese Unexamined Patent Publication No. 2012-211106
  • An object of the present invention is to provide a sirtuin 1 activator.
  • the present inventors consist of cowberry, echinacea, bee pollen, goji, keihi, reishi, narco lily, okura, mugwort, edamame, barley young leaves, yuzu, chia seed, kikyo, gymnema, and rose hips. It was found that one or more herbal medicines selected from the group function as a sirtuin 1 activator. Furthermore, the present inventors have also found that these substances act on skin cells via intestinal cells.
  • sirtuin 1 activator according to (1) or (2), wherein the sirtuin 1 activator activates sirtuin 1 of skin cells by oral administration.
  • a food composition for beautiful skin containing the sirtuin 1 activator according to any one of (1) to (3).
  • a food composition for bee pollen containing a plurality of crude drugs as an ingredient for bee pollen having a function of activating sirtuin 1 by oral administration.
  • Sirtuin 1 can be activated by administration of the sirtuin 1 activator of the present invention. According to the present invention, it is possible to provide a composition or an internal preparation containing a sirtuin 1 activator.
  • FIG. 1 is a schematic diagram of the Transwell method used in Experiment 2.
  • FIG. 2 shows the expression level of sirtuin 1 in HaCat (SIRT1p-EGFP) when each sample was added in Experiment 2 as a relative value with a negative control (DMSO only) as 100.
  • Sirtuin 1 can be activated by administration of the sirtuin 1 activator of the present invention.
  • Activation of the Sirtuin 1 gene is a disease in the skin such as anti-aging of the skin, prolongation of life span, repair of DNA damage caused by ultraviolet rays, anti-inflammatory, suppression of oxidative stress, suppression of wrinkles, whitening, suppression of melanin, melanoma, and xeroderma pigmentosum. It has been suggested that it is useful for the treatment and improvement of melanin (Non-Patent Documents 1 to 5).
  • the sirtuin 1 activator of the present invention is expected to contribute to beautiful skin by activating sirtuin 1 of skin cells via the intestinal tract, especially by oral administration.
  • skin beautification is mediated by activation of sirtuin 1 in skin cells such as skin anti-aging, life extension, repair of DNA damage by ultraviolet rays, anti-inflammatory, oxidative stress suppression, wrinkle suppression, whitening, and melanin suppression.
  • skin beautification is mediated by activation of sirtuin 1 in skin cells such as skin anti-aging, life extension, repair of DNA damage by ultraviolet rays, anti-inflammatory, oxidative stress suppression, wrinkle suppression, whitening, and melanin suppression.
  • Activation of sirtuin 1 means, for example, enhancing the expression of the sirtuin 1 gene, for example, the expression of the sirtuin 1 gene is increased when the sirtuin 1 activator is given, as compared with the state (control) in which nothing is given. It can mean that it is enhanced. For example, it may mean that it is enhanced with a statistically significant difference (for example, Student's t-test) with a significance level of 5%.
  • the activation of the sirtuin 1 gene in the present invention means that the expression of the sirtuin 1 gene is, for example, 5% when the sirtuin 1 activator is given, as compared with the state (control) in which nothing is given.
  • sirtuin is determined by any known technique, for example, a method of transfecting a skin cell with the SIRT1 promoter as described in Non-Patent Document 5 and determining the change in EGFP fluorescence derived from SIRT1p-EGFP. be able to.
  • the sirtuin 1 activator of the present invention activates sirtuin 1 of skin cells, especially via intestinal cells.
  • Activating sirtuin 1 of skin cells via intestinal cells means that the active ingredient of the present invention is administered to intestinal cells and absorbed by the intestinal cells so that the same ingredient as the active ingredient is directly produced in the skin cells. Or the active ingredient is absorbed by the intestinal cells and reaches the skin cells in a decomposed or modified state, or the intestinal cells take up the active ingredient to release another different component, and the different components are the skin cells. It refers to the final activation of sirtuin 1 in skin cells via direct or indirect pathways such as acting on.
  • activation of sirtuin 1 of skin cells by oral administration can be mentioned.
  • Activating sirtuin 1 of skin cells by oral administration means that the active ingredient of the present invention is absorbed through the intestinal tract and taken up from the intestine by orally ingesting the sirtuin 1 activator of the present invention. It means that the substance acts directly or indirectly to finally activate sirtuin 1 in skin cells.
  • Non-Patent Documents 6-8 carnosine taken up from the intestine does not directly act on the brain, but activates CREB in intestinal cells, resulting in enhanced BDNF production. Indirect effects such as BDNF activating nerve cells and improving brain function have been reported. Furthermore, it has been suggested that such cerebral-intestinal correlation activation is mediated by exosomes. In other words, it is unclear what kind of action the component has on the target cells even if a certain component is given to the intestine, so give the test substance to the intestinal cells and then confirm what kind of action it will have on the target cells. There is a need.
  • Such actions via intestinal cells can be measured by various methods including in vivo, in vitro, ex vivo and the like. For example, it can be determined by administering the test substance to the intestinal cell layer and determining the activity of sirtuin 1 in the skin cells via the intestinal cell layer.
  • a test substance is added to one side of a layer of intestinal cells such as Caco-2, and skin cells such as HaCaT that pass through this layer and are present on the other side of the layer.
  • It can be determined by the Transwell method to measure the activity of sirtuin 1 in.
  • the Transwell method is known in the art or can be easily implemented by those skilled in the art. However, the measuring method is not limited to the above method, and any other method may be adopted.
  • in vitro methods such as administering a test substance to an intestinal cell culture medium and adding the supernatant to skin cells, or measuring the activity of sirtuin 1 in the skin after oral ingestion by an animal such as a human. You may adopt the in vivo method such as doing.
  • the present invention is selected from the group consisting of cowberry, echinacea, bee pollen, goji, keihi, reishi, narco lily, okra, mugwort, edamame, barley young leaf, yuzu, chia seed, kikyo, gymnema, and rose hip.
  • a sirtuin 1 activator containing a plurality of crude drugs as an active ingredient is provided.
  • the present invention is selected from the group consisting of cowberry, echinacea, bee pollen, goji, keihi, reishi, narco lily, okra, mugwort, edamame, barley young leaves, yuzu, chia seeds, kikyo, gymnema, and rose hips.
  • compositions containing one or more herbal medicines as active ingredients may be in the form of an oral preparation or an enteral preparation, or may be for beautiful skin.
  • the cowberry (Vaccinium vitis-idaea L.) used in the present invention is a shrub of the genus Vaccinium in the family Ericaceae. It is preferable to use fruits. Fruits include resveratrol, anthocyanins, proanthocyanidins, etc.
  • Echinacea purpurea used in the present invention is a perennial plant belonging to the genus Echinacea purpurea in the family Asteraceae. It is preferable to use the above-ground juice of Echinacea at the time of flowering. Echinacea has been reported to have antibacterial and antiviral effects.
  • the bee pollen used in the present invention is a pollen grain (pollen load) collected by honeybees. There are reports that it contains nutrients such as vitamins and minerals. It may be any pollen such as cistus, oak, rose, echium, and chrysanthemum pollen. The place where bee pollen is collected is not limited to Europe such as Spain and Asia such as China.
  • the wolfberry fruit used in the present invention is a fruit of wolfberry (Lycium chinense Miller or L. barbarum Linne (Solanaceae)), which is a deciduous shrub of the Solanaceae family, and contains zeaxanthin, betaine, polyphenol and the like. Lycium chinense has been reported to have a nourishing tonic effect, a blood flow improving effect, a whitening effect, a DNA damage repairing effect, and the like (Non-Patent Document 2 and Patent Document 7).
  • the cinnamon bark used in the present invention is a crude drug obtained by drying the bark of Cinnamomum cassia of the family Lauraceae. It contains phenylpropanoid, cinnamon aldehyde, cinnamon acid and so on. It is known to have sweating action, antipyretic action, and analgesic action.
  • Reishi (Ganoderma lucidum) used in the present invention is a crude drug obtained by drying mushrooms (fruiting bodies) of the family Ganoderma lucidum. It is said to be effective for nourishing and tonic.
  • Narco lily used in the present invention is a perennial herb belonging to the genus Solomon's seal in the family Liliaceae. It is preferable to use it as a crude drug with dried rhizomes. It is said to be effective for nourishing and tonic.
  • the okra used in the present invention is a plant belonging to the genus Abelmoschus manihot in the Malvaceae family. It is preferable to use fruits. It has been reported that fruits contain mucin and pectin and have an effect of adjusting gastrointestinal tone.
  • the mugwort (Artemisia princeps Pampanini) used in the present invention is a plant of the Asteraceae family, and it is preferable to use the above-ground part of the mugwort.
  • Mugwort contains coumarins and caffeic acid derivatives, and is said to be effective for astringent, hemostatic, and antispasmodic effects.
  • Green soybean (Glycinemax) used in the present invention refers to immature seeds harvested before the seeds of plants belonging to the genus Glycine of the family Fabales are fully ripe. Contains isoflavones, vitamins B1, B2, potassium and iron.
  • the young barley leaves used in the present invention are young leaves before heading of barley (Hordeum vulgare), which is a plant belonging to the genus Hordeum of the Gramineae family. It contains various vitamins, minerals, folic acid, SOD enzyme, etc., has a high nutritional effect, and is used as a material for green juice and the like.
  • Yuzu (Citrus junos) used in the present invention is an evergreen small tree of the genus Citrus. It is preferable to use fruits. Yuzu contains hesperidin and vitamin C, and is known to have an immune effect.
  • the chia seeds used in the present invention are the seeds of chia (Salvia hispanica), which is an annual plant belonging to the genus Sage of the Labiatae family. Chia seeds contain ⁇ -linolenic acid, omega-3 fatty acids, various vitamins and minerals, chlorogenic acid, etc., and are known as superfoods.
  • Platycodon grandiflorum used in the present invention is a perennial plant belonging to the genus Platycodon in the family Bellflower family.
  • the root of Platycodon grandiflorum contains saponin and is said to have antitussive expectorant and intestinal regulating effects. It is preferable to use the root part.
  • Gymnema used in the present invention is a climbing plant of the genus Gymnema of the Apocynaceae family. It contains gymnemic acid and glucuronic acid, and has been reported to have an appetite-suppressing effect and an effect of suppressing a rapid rise in blood glucose level. It is preferable to use the leaf part.
  • Rosehip used in the present invention is a plant belonging to the genus Rosa in the family Rosaceae.
  • Vitamin C contains carotenoids, beta-carotene, lutein, zeaxanthin, lycopene and the like, and is known to have skin-beautifying, antibacterial and antiviral effects. It is preferable to use fruits.
  • the above-mentioned crude drug is a known substance, and can be easily dried, purified, extracted, etc. by a known method, and a commercially available product can be easily obtained. It can be used raw or dried, but it can also be used as an extract, a dried product, a dried powder, a powdered raw material, a juice squeezed liquid, or the like from the viewpoint of usability, formulation, and the like. Depending on the raw material, it is possible to appropriately select whether to use the form of the squirrel, and if necessary, sterilization or the like may be performed.
  • the extraction method of the extract can be performed, for example, by solvent extraction.
  • solvent extraction the whole plant or various parts (leaves, flowers, roots, etc.) of the plant are dried as needed, shredded or crushed as needed, and then an aqueous extractant, water, for example, cold water.
  • Hot water hot water having a boiling point or lower temperature, or a hydrous organic solvent, an organic solvent such as ethanol, methanol, ether, 1,3-butylene glycol, etc., as appropriate depending on the properties of the raw materials and the use of the composition. It is extracted by selecting it at room temperature or by heating it.
  • the extraction method is not limited to solvent extraction, and may be a conventional method known in the art, and the extraction method of the extract and the form of the extract used in the present invention are not limited to the effect of the present invention.
  • the form of the extract may be not only the extract itself but also appropriately diluted or concentrated by a conventional method, and is a powdery or lumpy solid obtained by drying the extract. May be good.
  • a water-containing lower alcohol such as water-containing ethanol
  • the water content in that case is, for example, 0 to 10v / v%, 10 to 40v / v%, 20 to 30v / v%, 30. It may be ⁇ 50v / v%, 50-80v / v%, 80-99.5v / v%, or the like.
  • a method for obtaining a dry powder a method of shredding or crushing the whole plant or various parts (leaves, flowers, roots, etc.) of the plant and then drying, or a method of drying the plant and then shredding or crushing the dry powder is obtained. There is a way to get it. Further, a method of shredding or crushing the plant, subjecting it to fermentation or enzyme treatment, drying it, and further crushing it to a predetermined particle size, if necessary, can be appropriately adopted.
  • the sirtuin 1 activator of the present invention is preferably taken orally or enterally, it does not exclude other routes of administration such as transdermal administration.
  • the sirtuin 1 activator of the present invention is administered by various routes of administration, it is preferable to apply the active ingredient of the present invention in an amount such that the effect of sirtuin 1 activation is sufficiently exerted.
  • the blending amount of the plant body of Enmeisou or the solvent extract thereof can be appropriately determined according to the type, purpose, form, usage method and the like thereof.
  • sirtuin 1 activator of the present invention is used as an oral preparation or an enteral preparation, bilberry, echinacea, bee pollen, goji, keihi, reishi, narco lily, etc. It is preferable to prepare the dry weights of okura, yomogi, edamame, young barley leaves, yuzu, chia seeds, goji, gymnema, and rose hips to be about 0.00001 to 0.5% by weight, more preferably about 0.0001 to 0.05% by weight. , 0.001 to 0.005% by weight is more preferable.
  • the concentration in the intestine may be adjusted to be about 0.1 to 100 ⁇ g / ml, more preferably about 0.5 to 50 ⁇ g / ml, and even more preferably about 1 to 10 ⁇ g / ml.
  • sirtuin 1 activator of the present invention When used as an oral preparation or an enteric preparation, bilberry, echinacea, bee pollen, goji seeds, rosehip, reishi, narco lily, okra, yomogi, and edamame per adult. , Barley young leaves, yuzu, chia seeds, lingonberry, gymnema, and rosehip plants or their solvent extracts are, for example, about 0.005 mg to about 0.5 g (dry weight equivalent) per day, more preferably 0.05. It is preferably prepared to be about mg to about 50 mg, more preferably about 0.5 mg to about 5 mg (in terms of dry weight).
  • the frequency of ingestion is not limited, but it may be taken once, but according to one example, for example, once every two weeks, once a week, once every three days, once every two days, one day. It can be taken once, twice a day, three times a day, four times a day, and the like. In addition, it may be ingested each time, continuously, or intermittently, for example, at intervals of several months.
  • the sirtuin 1 activator of the present invention can be contained in a composition for oral or enteral ingestion, for example, a food composition.
  • a composition for oral or enteral ingestion for example, a food composition.
  • powdery, liquid, solid such as tablets, granules, granules, pastes, gels and the like can be arbitrarily selected.
  • Additives can be arbitrarily selected and used in combination with the sirtuin 1 activator and composition of the present invention, if necessary. Excipients and the like can be included as the additive.
  • the excipient may be any starch as long as it is usually used in the desired dosage form, for example, starches such as wheat starch, rice starch, corn starch, potato starch, dextrin, cyclodextrin, and crystalline celluloses.
  • Lactose Lactose, starch, sugar, reduced malt sugar, water candy, fructo-oligosaccharide, emulsified oligosaccharide and other sugars, and sugar alcohols such as sorbitol, erythritol, xylitol, lactitol and mannitol.
  • sugar alcohols such as sorbitol, erythritol, xylitol, lactitol and mannitol.
  • colorants preservatives, thickeners, binders, disintegrants, dispersants, stabilizers, gelling agents, antioxidants, surfactants, preservatives, pH adjusters, etc. Can be selected and used as appropriate.
  • the present invention is selected from the group consisting of cowberry, echinacea, bee pollen, goji, keihi, reishi, narco lily, okura, mugwort, edamame, barley young leaves, yuzu, chia seeds, kikyo, gymnema, and rose hips.
  • a method of activating sirtuin 1 of the skin by administering multiple herbal medicines, for example, by oral or transenteral route.
  • the present invention is also selected from the group consisting of cowberry, echinacea, bee pollen, goji, keihi, reishi, narco lily, okura, mugwort, edamame, barley young leaves, yuzu, chia seed, kikyo, gymnema, and rose hips. Also provided are methods for skin anti-aging via sirtuin 1 activation of the skin, eg, by administering one or more herbal medicines, eg, by oral or enteric route.
  • the method of the present invention is a method for the purpose of cosmetology and may not be treated by a doctor or a medical professional.
  • the present invention relates to bilberries, echinacea, bee pollen, goji, keihi, reishi, narco lilies, okra, mugwort, edamame, young barley leaves in the manufacture of pharmaceuticals such as oral or enteric agents for anti-aging of the skin. Also provided is the use of one or more herbal medicines selected from the group consisting of Yuzu, Chia Seeds, Lingonberry, Gymnema, and Rosehip.
  • the present invention is for bilberries, echinacea, bee pollen, goji, keihi, reishi for use in methods for anti-aging of the skin by activating sirtuin 1 of the skin, for example by oral or enteral administration.
  • one or more herbal medicines selected from the group consisting of, narco lily, lingonberry, yomogi, edamame, young barley leaves, yuzu, chia seed, lingonberry, gymnema, and rosehip.
  • Experiment 1 Preparation of samples As candidate samples for sirtuin 1 activator, bilberry, echinacea, bee pollen, goji, keihi, reishi, narukoyuri, okra, yomogi, edamame, barley young leaves, yuzu, chia seeds, kikyo, gymnema, And rose hips were prepared as shown in the table below.
  • a total of 152 types of candidate samples were prepared, including naturally derived components such as extracts of animals and plants and synthetic components.
  • the sample was adjusted to 10 mg / ml using DMSO, and appropriately diluted with a culture medium to adjust to 10 ⁇ g / ml as an evaluation sample.
  • DMSO containing 10 ⁇ g / ml resveratrol was used as a positive control, DMSO containing nothing as a negative control and DMSO containing 10 ⁇ g / ml astaxanthin.
  • Experiment 2 Construction of a screening system for components that activate the SIRT1 promoter
  • Experiment 2-1 Culture of human skin epidermis-derived cell line HaCaT cells
  • HaCaT cells were used as model cells for human skin.
  • Cells were cultured in a cell culture dish (Greiner bio-one, Tokyo, Japan) using DMEM medium (Dulbecco's Modified Eagle Medium; Nissui, Tokyo, Japan) supplemented with 10% Fetal bovine serum (FBS; Life Technologies, CA, USA). In Japan), subculture was performed at 37 ° C. in the presence of 5% CO 2 .
  • DMEM medium Dulbecco's Modified Eagle Medium
  • Fetal bovine serum Fetal bovine serum
  • DMEM medium 10.0 g of DMEM powder is dissolved in 1 L of Milli-Q water, streptomycin sulfate 0.1 g titer (Meiji. Tokyo, Japan), penicillin G potassium 100,000 U (Meiji), 1 M HEPES. 2.38 g (DOJINDO, Kumamoto, Japan) and 2.0 g of 10% NaHCO 3 (Wako, Osaka, Japan) were added, and 0.22 ⁇ m filter sterilized (Toyo Roshi Kaisha, Tokyo, Japan) was used.
  • Experiment 2-2 Culture of human colon cancer-derived cell line Caco-2 cells
  • human colon cancer-derived Caco-2 cells were used as a human intestinal epithelial model.
  • Caco-2 cells were cultured in a cell culture dish (Greiner) using Dulbecco's Modified Eagle Medium (DMEM) (Nissui, Tokyo, Japan) containing deactivated 10% Fetal Bovine Serum (FBS) (Life Technologies, CA, USA). Bio-one, Tokyo, Japan) was subcultured under the conditions of 37 ° C and 5% CO 2 .
  • DMEM Dulbecco's Modified Eagle Medium
  • FBS Fetal Bovine Serum
  • DMEM medium 10.0 g of DMEM powder is dissolved in 1 L of Milli-Q water, 100 U / mL penicillin (Meiji), 0.1 mg / mL streptomycin (Meiji), 1M HEPES 2.38 g (DOJINDO, Kumamoto, Japan). ), 10% NaHCO 3 2.0 g (Wako, Osaka, Japan) was added, and 0.22 ⁇ m filter sterilized (Tokyo Roshi Kaisha, Tokyo, Japan) was used.
  • SIRT1p-EGFP plasmid
  • HaCat SIRT1p-EGFP
  • the human SIRT1 promoter 1159 to -1
  • the amplified fragment was cloned into pEGFP-C3 (TaKaRa, Japan) from which the CMV promoter was removed by digestion with restriction enzymes AseI and NheI, and the obtained plasmid was designated as SIRT1p-EGFP.
  • this plasmid was stably transfected into the human skin keratinized cell line HaCaT to obtain HaCat (SIRT1p-EGFP), which was used for evaluation of human SIRT1 promoter activity.
  • HA044263-R 5'-TTCGAGGATCTGTGCCAATCATAA-3' (SEQ ID NO: 2)
  • Experiment 2-4 Setting of Transwell method
  • the Caco-2 cells prepared in Experiment 2-2 were seeded at 2.0 ⁇ 10 5 cells / ml on the membrane of a cup of Transwell (Millicell cell culture insert manufactured by Merck). Then, TEER / transepithelial potential measurement was measured. Medium was exchanged every few days to induce differentiation for 14 days. On the 14th day, TEER / transepithelial potential measurement was measured, and it was confirmed that the value was higher than that on the 1st day.
  • Each sample prepared in Experiment 1 was added to Caco-2 cells so as to reach 10 ⁇ g / ml.
  • HaCaT (SIRT1p-EGFP) was seeded on a black plate at 6.0 ⁇ 10 5 cells / ml. After 24 hours, the HaCaT (SIRT1p-EGFP) medium was removed and 100 ⁇ L of Caco-2 permeate was added. After 48 hours, the Caco-2 permeate added to HaCaT (SIRT1p-EGFP) was removed, washed with PBS, and stained with Hoechst 33342. After that, the fluorescence intensity of HaCaT (SIRT1p-EGFP) was measured with IN Cell Analyzer 2000.

Landscapes

  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Mycology (AREA)
  • Botany (AREA)
  • Epidemiology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Biotechnology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Dermatology (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Medicines Containing Plant Substances (AREA)
PCT/JP2021/034628 2020-10-07 2021-09-21 サーチュイン１活性化剤 Ceased WO2022075059A1 (ja)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2022555347A JPWO2022075059A1 (https=) 2020-10-07 2021-09-21

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2020-170097 2020-10-07
JP2020170097 2020-10-07

Publications (1)

Publication Number Publication Date
WO2022075059A1 true WO2022075059A1 (ja) 2022-04-14

Family

ID=81126484

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2021/034628 Ceased WO2022075059A1 (ja) 2020-10-07 2021-09-21 サーチュイン１活性化剤

Country Status (2)

Country Link
JP (1) JPWO2022075059A1 (https=)
WO (1) WO2022075059A1 (https=)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014068190A2 (en) * 2012-11-01 2014-05-08 Lumene Oy Cosmetic compositions containing fractions of lingonberry extracts
JP2015007016A (ja) * 2013-06-26 2015-01-15 ユーハ味覚糖株式会社 新規レスベラトロール誘導体含有エキスの製造方法
JP2018048152A (ja) * 2011-12-27 2018-03-29 油田 正樹 サーチュイン活性化剤
JP2019218296A (ja) * 2018-06-20 2019-12-26 日本精化株式会社 サーチュイン１遺伝子活性化剤

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3993936B2 (ja) * 1998-05-22 2007-10-17 一丸ファルコス株式会社 メラニン生成抑制剤及び化粧料組成物
JP5452827B2 (ja) * 2000-10-30 2014-03-26 株式会社ファンケル 皮膚賦活用組成物
JP4162898B2 (ja) * 2002-01-31 2008-10-08 株式会社ファンケル ラミニン５産生促進剤およびインテグリンα６β４産生促進剤を含む組成物
KR101018531B1 (ko) * 2010-04-09 2011-03-11 일동제약주식회사 대잎둥굴레 또는 층층갈고리둥굴레 추출물을 유효성분으로 포함하는 비만 또는 대사 증후군 예방 및 치료용 조성물
CN103181561B (zh) * 2011-12-31 2015-05-13 谢鸣 一种具有秋季养生保健作用的保健食品及其制备方法
CN107361365A (zh) * 2017-05-26 2017-11-21 深圳市恒善堂生物科技有限公司 一种延缓衰老的保健品

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2018048152A (ja) * 2011-12-27 2018-03-29 油田 正樹 サーチュイン活性化剤
WO2014068190A2 (en) * 2012-11-01 2014-05-08 Lumene Oy Cosmetic compositions containing fractions of lingonberry extracts
JP2015007016A (ja) * 2013-06-26 2015-01-15 ユーハ味覚糖株式会社 新規レスベラトロール誘導体含有エキスの製造方法
JP2019218296A (ja) * 2018-06-20 2019-12-26 日本精化株式会社 サーチュイン１遺伝子活性化剤

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
KATAKURA, YOSHINORI: "Anti-aging activity of Pomegranate-derived Polyphenol", BIO CLINICA, vol. 4, no. 2, 1 January 2015 (2015-01-01), JP , pages 143 - 146, XP009535573, ISSN: 0919-8237 *
TARO UCHIYAMA, MIHO MIYANAGA, OSAMU UEDA, MASASHI OGO: "Oral Intake of Amla Fruit and Lingonberry Extracts Improves Skins Elasticity", PHARMACOMETRICS, vol. 91, no. 3/4, 1 January 2016 (2016-01-01), JP , pages 85 - 91, XP009535578, ISSN: 0300-8533 *
TARO UCHIYAMA, MIHO MIYANAGA, OSAMU UEDA: "The efficacy on the skin of drink with lingonberry and amla fruit", COSMETIC STAGE, vol. 10, no. 4, 1 January 2016 (2016-01-01), JP , pages 71 - 76, XP009535575, ISSN: 1881-4905 *

Also Published As

Publication number Publication date
JPWO2022075059A1 (https=) 2022-04-14

Similar Documents

Publication Publication Date Title
nikarthil Sudhakaran et al. A review on nutritional composition, antinutritional components and health benefits of green gram (Vigna radiata (L.) Wilczek)
Sinicropi et al. Opuntia ficus indica (L.) Mill. An ancient plant source of nutraceuticals
KR101794006B1 (ko) 식물 추출물을 포함하는 염증 개선용 조성물
KR20160056007A (ko) 황칠나무 추출물을 포함하는 염증성 질환의 치료 및 예방용 조성물
KR101484021B1 (ko) 울금포함 복합물 추출물을 함유한 면역증강용 조성물
KR20090050295A (ko) 해방풍 추출물을 유효성분으로 함유하는 부종 또는 피부염예방 및 치료용 조성물
JP2025157621A (ja) Ｒａｌｄｈ２発現増強剤
Singh et al. Phenolic compounds in sea buckthorn (Hippophae rhamnoides L.) and their health-promoting activities: a review
KR101525877B1 (ko) 피부 주름 개선 및 피부 노화 방지를 위한 조성물
KR101052067B1 (ko) 산채류 추출물을 유효성분으로 함유하는 염증성 질환 예방 또는 치료용 조성물
KR20150007810A (ko) 도라지 추출물을 유효성분으로 포함하는 항산화, 항암, 항당뇨 또는 항균 활성을 가지는 약학적 조성물
KR20100041363A (ko) 꾸지뽕나무 열매 추출물을 함유하는 면역기능 강화용 조성물
KR101069844B1 (ko) 바디나물(자화전호) 추출물 또는 이의 분획물을 유효성분으로 함유하는 부종 또는 피부염의 예방 또는 치료용 조성물
WO2022075059A1 (ja) サーチュイン１活性化剤
KR20150132750A (ko) 동과자 추출물 또는 동과자 발효 추출물을 유효성분으로 포함하는 면역증강용 조성물
KR100921971B1 (ko) 블루밍샐리 추출물을 유효성분으로 함유하는 조성물
KR20150083328A (ko) 두메닥나무 추출물 또는 이의 분획물을 포함하는 염증성 질환의 예방 또는 치료용 조성물
ES3020236T3 (en) Superfood for prolonging the longevity of an individual
KR20110083917A (ko) 천문동 추출물로부터 제조한 분획물을 유효성분으로 함유하는 염증성 질환의 예방 및 치료용 조성물
JP2025157607A (ja) グルタチオン産生促進剤
JP2024022503A (ja) Ｎａｍｐｔ活性化剤
KR101375347B1 (ko) 홍삼약초 음료의 제조방법 및 상기 방법으로 제조된 홍삼 음료
KR101060198B1 (ko) 조뱅이(소계) 추출물 또는 이의 분획물을 유효성분으로 함유하는 부종 또는 다양한 염증의 예방 또는 치료용 항염증 조성물
KR20220136748A (ko) 파파야 추출물을 유효성분으로 포함하는 염증성 장질환 예방 또는 치료용 조성물
JP2023098825A (ja) サーチュイン３活性化剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21877360

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2022555347

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21877360

Country of ref document: EP

Kind code of ref document: A1