WO2022202241A1 - Inhibiteur de dommage à l'adn induit par uv - Google Patents

Inhibiteur de dommage à l'adn induit par uv Download PDF

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Publication number
WO2022202241A1
WO2022202241A1 PCT/JP2022/009605 JP2022009605W WO2022202241A1 WO 2022202241 A1 WO2022202241 A1 WO 2022202241A1 JP 2022009605 W JP2022009605 W JP 2022009605W WO 2022202241 A1 WO2022202241 A1 WO 2022202241A1
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WO
WIPO (PCT)
Prior art keywords
inhibitor
oil
tree bark
silk tree
bark extract
Prior art date
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PCT/JP2022/009605
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English (en)
Japanese (ja)
Inventor
知宏 菅原
周平 山本
淳 川井
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東洋紡株式会社
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Publication of WO2022202241A1 publication Critical patent/WO2022202241A1/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 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)
    • 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
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • 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
    • 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
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • 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

  • a technology related to inhibitors of DNA damage caused by ultraviolet rays will be disclosed.
  • Silk trees are deciduous tall trees of the leguminous family that grow naturally in sunny wetlands such as forest edges and wilderness areas in the mountains south of the Tohoku region in Japan. Overseas, they are also distributed and cultivated in China and Southeast Asia. The bark is collected around the time of flowering, washed with water, dried in the sun, and chopped into appropriate lengths. It has been used externally for swelling, bruises, and arthralgia as a cold poultice on the affected area with a decoction, or as a bathing agent. Silk tree bark is known to contain triterpene saponins (many juribrosides), flavonoids (geraldone, isoochanin, luteolin, etc.), tannins, and the like (Non-Patent Document 1).
  • the silk tree extract for example, it is known to be used for skin cells that exhibit an irregular or abnormal clock gene expression rhythm compared to the normal clock gene expression rhythm (patent Reference 1).
  • the main task is to provide inhibitors of DNA damage caused by ultraviolet rays.
  • the present inventors have made intensive studies to solve the above problems, and as a result, as a new application of silk tree bark extract, it is possible to suppress DNA damage [in particular, CPD (cyclobutane-type pyrimidine dimer) production] and cell death caused by ultraviolet rays. and can prevent or treat UV-induced photoaging, inflammation, hyperpigmentation, and/or cancer. Based on such knowledge, further research was repeated, and the present invention was completed.
  • CPD cyclobutane-type pyrimidine dimer
  • the present invention includes the following aspects.
  • Item 1. An inhibitor of DNA damage caused by ultraviolet light, the inhibitor containing a silk tree bark extract.
  • Section 2. An inhibitor of ultraviolet-induced cyclobutane-type pyrimidine dimer production, the inhibitor containing a silk tree bark extract.
  • Item 3. An inhibitor of cell death caused by ultraviolet light, the inhibitor containing a silk tree bark extract.
  • Section 4. A composition for preventing or treating ultraviolet photoaging, inflammation, hyperpigmentation, and/or cancer, the composition comprising a silk tree bark extract.
  • an inhibitor of DNA damage caused by ultraviolet rays an inhibitor of CPD production caused by ultraviolet rays, an inhibitor of cell death caused by ultraviolet rays (hereinafter collectively referred to as "inhibitors”), etc. are provided.
  • FIG. 2 shows that UV-induced cell death was suppressed when GenemclocTM (manufactured by Toyobo Co., Ltd.) was applied to normal human epidermal cells.
  • FIG. 2 shows that UV-induced DNA damage (CPD production) was suppressed when Genemclock (trademark) (manufactured by Toyobo Co., Ltd.) was applied to normal human epidermal cells.
  • Silk tree bark extract The silk tree bark extract is not limited to being extracted only from the bark of a plant of the genus Silk, as long as it contains the bark, even if it is extracted from the whole or a part thereof (e.g., branches and leaves). good.
  • the Albizia genus plant to be subjected to extraction may be cut as it is, or may be pretreated by drying, pulverization, or the like.
  • the silk tree bark extract is preferably obtained by extracting the branches and leaves of the silk tree genus plant raw or after drying and pulverizing as necessary.
  • the extraction solvent is not particularly limited, and examples include water and organic solvents.
  • organic solvents include alcohols such as methanol, ethanol, propanol and butanol; polyhydric alcohols such as propylene glycol and butylene glycol; ketones such as acetone and methyl ethyl ketone; esters such as methyl acetate and ethyl acetate.
  • Chain and cyclic ethers such as tetrahydrofuran and diethyl ether; Polyethers such as polyethylene glycol; Hydrocarbons such as hexane, cyclohexane and petroleum ether; Aromatic hydrocarbons such as benzene and toluene; , waxes, and other oils.
  • An extraction solvent can be used individually by 1 type or in combination of 2 or more types. When two or more extraction solvents are combined, extraction with a mixed solvent in which two or more extraction solvents are mixed may be used, or a combination of extractions with each extraction solvent (for example, a combination of water extraction and organic solvent extraction). There may be.
  • the extraction solvent is preferably water, alcohols, or a mixed solvent thereof, and more preferably water (especially hot water at 70 to 100°C).
  • the extraction conditions vary depending on the solvent used. For example, when extracting with water, 1 to 100 parts by weight of water is used per 1 part by weight of silk tree bark, and the temperature is 4 to 100 ° C. for 10 minutes to 7 days. More preferably, the extraction is carried out using 5 to 20 parts by mass of water per 1 part by mass of silk tree bark at a temperature of 70 to 100° C. for 30 minutes to 2 hours. In the case of hot water extraction, the extraction is typically performed under heating and reflux. In addition, from the viewpoint of further increasing the extraction efficiency, pressurization, stirring, ultrasonic treatment, etc. may be performed during the extraction.
  • the silk tree bark extract may be extracted as it is, or may be subjected to post-treatment such as dilution, concentration, drying, separation, and purification after extraction.
  • Separation methods include, for example, filtration and centrifugation.
  • Purification methods include, for example, fractional extraction, partition between two solvents, fractional adsorption with an adsorbent, elution, chromatography, and the like.
  • the silk tree bark extract may be in any form, for example, it may be in a solid form such as dry powder (including those subjected to processing such as pulverization after drying), extract liquid, dispersion liquid of dry powder Alternatively, it may be in the form of a liquid such as a solution, or in the form of a paste.
  • the silk tree bark extract can be prepared, for example, by the method described in JP-A-2018-58783.
  • the inhibitor is not particularly limited as long as it reduces the level of UV-induced DNA damage, CPD production, and/or cell death.
  • the inhibitor is not particularly limited as long as it contains silk tree bark extract.
  • the content of the silk tree bark extract (content in terms of dry mass) is not particularly limited as long as it is an effective amount to exhibit the inhibitory effect, but for example 0.00001% by mass (or w / v%) or more, preferably 0.00005% by mass (or w/v%) or more, 0.0001% by mass (or w/v%) or more, 0.0005% by mass (or w/v%) or more, and 0.0005% by mass (or w/v%) or more.
  • the content of the silk tree bark extract may be 100% by mass or less, for example, 50% by mass (or w/v%) or less, preferably 30% by mass (or w/v%) or less, 20% by mass. (or w/v%) or less, 10% by mass (or w/v%) or less, or 5% by mass (or w/v%) or less.
  • the inhibitor preferably contains a carrier in addition to the silk tree bark extract.
  • the carrier is not particularly limited as long as it is physiologically or pharmaceutically acceptable. Examples include water; phosphate buffer, phosphate buffered saline, HEPES buffer, Tris-HCl buffer, boric acid Buffers such as buffers, acetate buffers, citrate buffers; capryl alcohol, lauryl alcohol, oleyl alcohol, myristyl alcohol, cetyl alcohol, cholesterol, phytosterol, cetanol, stearyl alcohol, hexyldecanol, octyldodecanol, ethanol, isopropanol, etc.
  • capric acid myristic acid, palmitic acid, stearic acid, behenic acid, lanolin fatty acid, linoleic acid, linolenic acid, lauric acid, oleic acid, isostearic acid, undecylenic acid, isononanoic acid, caproic acid, etc.
  • Hydrocarbons such as liquid paraffin, squalane, microcrystalline wax, ceresin wax, paraffin wax, petrolatum; avocado oil, almond oil, fennel oil, perilla oil, olive oil, orange oil, Orange rough oil, sesame oil, cacao oil, chamomile oil, carrot oil, cucumber oil, macadamia nut oil, kukui nut oil, safflower oil, soybean oil, camellia oil, corn oil, rapeseed oil, persic oil, castor oil, cottonseed oil, peanut oil , turtle oil, mink oil, palm oil, palm kernel oil, coconut oil, grapeseed oil, Japanese wax, jojoba oil, beef tallow, beef tallow fatty acid, pork oil, egg yolk oil, hydrogenated oil; lanolin (liquid lanolin, reduced lanolin, hard lanolin, etc.), waxes such as beeswax, carnauba wax, whale wax, candeli
  • lanolin liquid lanolin, reduced lanolin, hard
  • the inhibitor may further contain additives.
  • Additives are not particularly limited as long as they are physiologically or pharmaceutically acceptable, and can be appropriately selected depending on the form and mode of use. Examples include solvents, dispersants, emulsifiers, pH adjusters, agents, thickeners, preservatives, stabilizers, surfactants, excipients, binders, disintegrants, lubricants, sweeteners, flavors, colorants and the like, but are not limited to these.
  • An additive can be used individually by 1 type or in combination of 2 or more types.
  • the inhibitor may be in the form of, for example, pharmaceuticals, reagents, foods, cosmetics (including quasi-drugs), or compositions for use in these.
  • Pharmaceuticals may be tablets, granules, powders, pills, capsules, liquids, suspensions, elixirs, emulsions, ointments, injections, patches and the like.
  • beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks; Frozen desserts such as ice cream, ice sherbet, and shaved ice; Noodles such as soba, udon, vermicelli, Chinese noodles, instant noodles; Candies, gums, chocolates, jellies, jams, creams, snacks, baked goods, breads, and other confectionery products; Processed marine and livestock foods, such as fish cakes, hams, and sausages; Dairy products, such as powdered milk, processed milk, and fermented milk; Margarine, mayonnaise , shortening, whipped cream, dressings and the like; seasonings such as sauces and sauces; retort pouch foods and the like.
  • Noodles such as soba, udon, vermicelli, Chinese noodles, instant noodles
  • Health foods, functional foods, foods for specified health uses, foods with function claims, dietary supplements, supplements, and the like may also be used.
  • basic cosmetics such as lotions, milky lotions, gels, creams, ointments, lotions, oils, packs; facial cleansers; skin cleansers; Hair cosmetics such as hair tonics, hair dyes, and hair tonics; Make-up cosmetics such as foundations, powders, powders, lipsticks, blushers, eye shadows, eyeliners and mascara; Finishing cosmetics such as nail polishes; It may be a screen or the like.
  • the inhibitor When the inhibitor is in the form of a product such as food, the product itself or its container or packaging, for example, inhibits DNA damage, CPD production, or cell death caused by ultraviolet rays, or photoaging, inflammation, or pigmentation caused by ultraviolet rays. , or an indication that it is used for the prevention, improvement, mitigation, delay of progression, or inhibition of progression of cancer (skin cancer, etc.), or similar usage indications may be attached, and the product instructions may be , may include descriptions corresponding to the above indications.
  • Inhibitors are used for the prevention or treatment of photoaging, inflammation, pigmentation, or cancer (including amelioration, alleviation, progression delay, progression inhibition, etc.) caused by ultraviolet rays, or application to subjects in need of these prevention or treatment. It can be suitably used for
  • the method of applying the inhibitor is not particularly limited as long as it exhibits an inhibitory effect, and may be oral administration or parenteral administration.
  • the method of application is preferably topical administration, preferably direct application, spreading, injection or spraying on the skin.
  • the present invention also includes a composition for preventing or treating photoaging, inflammation, pigmentation, or cancer caused by ultraviolet rays, which contains a silk tree bark extract.
  • the constitution of the composition is the same as the constitution described for the inhibitor.
  • UVB-induced cell death inhibitory effect on test sample epidermal cells Normal human epidermal cells (NHEKs) were seeded in a 96-well plate at a density of 2.0 ⁇ 10 4 cells/well using Humadia KG2 (KG2) medium. did. Twenty-four hours after seeding, the medium was replaced with HuMedica KB2 (KB2) medium containing the specified concentration of the test sample ("Genemclock (trademark)" manufactured by Toyobo Co., Ltd., silk tree bark extract). After culturing for 24 hours, the medium was replaced with Hank's buffer (containing no Ca 2+ and Mg 2+ ), and the cells were irradiated with UVB.
  • HuMedica KB2 HuMedica KB2
  • Hank's buffer containing no Ca 2+ and Mg 2+
  • the UVB non-irradiated group (control group) was covered with aluminum foil to completely block UVB.
  • the Hank's buffer solution was replaced with KB2 medium containing the test sample at the specified concentration (“Genemclock (trademark)” manufactured by Toyobo Co., Ltd., silk tree bark extract), and the cells were treated. was cultured for 24 hours. After that, the medium was changed to KB2 medium containing 0.2 mg/mL 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cultured for 1 hour.
  • MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
  • the medium was removed, 2-propanol was added to extract the produced blue formazan, and the absorbance of the extract was measured at 550 nm.
  • the cell death inhibitory action was indicated by Index (%) with respect to the absorbance of the UVB non-irradiated group at each concentration.
  • Statistical processing performed a significant difference test by Student's t-test.
  • UVB-induced DNA damage cyclobutane-type pyrimidine dimer: CPD production
  • HuMedia KG2 HuMedia KG2
  • KG2 HuMedia KG2
  • KB2 HuMedia KB2
  • NHEKs were detached from the dish by trypsin treatment, and nucleic acid was extracted using DNeasy Blood & Tissue Kit (manufactured by QIAGEN). The amount of CPD in 2.5 ng of the extracted nucleic acid was measured using High Sensitivity CPD ELISA kit Ver.2 (manufactured by Cosmo Bio Co., Ltd.). , “CPD amount Index (%)”. Statistical processing performed a significant difference test by Student's t-test.

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Abstract

Un inhibiteur de dommage à l'ADN induit par UV est fourni. Cet inhibiteur de dommage à l'ADN induit par UV contient un extrait d'écorce d'Albizia julibrissin.
PCT/JP2022/009605 2021-03-25 2022-03-07 Inhibiteur de dommage à l'adn induit par uv WO2022202241A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2021052069A JP2022149769A (ja) 2021-03-25 2021-03-25 紫外線によるｄｎａ損傷の抑制剤
JP2021-052069 2021-03-25

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WO2022202241A1 true WO2022202241A1 (fr) 2022-09-29

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021005941A1 (fr) * 2019-07-05 2021-01-14 東洋紡株式会社 Composition contenant un extrait d'albizia julibrissin

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021005941A1 (fr) * 2019-07-05 2021-01-14 東洋紡株式会社 Composition contenant un extrait d'albizia julibrissin

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
AGAR, N. ; YOUNG, A.R.: "Melanogenesis: a photoprotective response to DNA damage?", MUTATION RESEARCH, ELSEVIER, AMSTERDAM, NL, vol. 571, no. 1-2, 1 April 2005 (2005-04-01), AMSTERDAM, NL , pages 121 - 132, XP027632477, ISSN: 0027-5107 *

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