WO2023112717A1 - Ｐａｄ１の産生促進薬剤及び新薬剤評価方法 - Google Patents

Ｐａｄ１の産生促進薬剤及び新薬剤評価方法 Download PDF

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WO2023112717A1
WO2023112717A1 PCT/JP2022/044524 JP2022044524W WO2023112717A1 WO 2023112717 A1 WO2023112717 A1 WO 2023112717A1 JP 2022044524 W JP2022044524 W JP 2022044524W WO 2023112717 A1 WO2023112717 A1 WO 2023112717A1
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Prior art keywords
extract
pad1
production
skin
promoting
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English (en)
French (fr)
Japanese (ja)
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大知 村田
雅史 宮井
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Shiseido Co Ltd
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Shiseido Co Ltd
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    • 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)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232—Angelica
    • 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
    • A61K36/539—Scutellaria (skullcap)
    • 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)
    • A61K36/58—Meliaceae (Chinaberry or Mahogany family), e.g. Azadirachta (neem)
    • 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
    • A61K36/732—Chaenomeles, e.g. flowering quince
    • 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)
    • A61K36/77—Sapindaceae (Soapberry family), e.g. lychee or soapberry
    • 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
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A61K8/86—Polyethers
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/15—Medicinal preparations ; Physical properties thereof, e.g. dissolubility
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing

Definitions

  • the present invention relates to a PAD1 production promoter.
  • Keratin fibers in the granular layer of the epidermis bind to a protein called filaggrin during keratinization and aggregate to create a specific morphology called a "keratin pattern".
  • Keratohyalin granules in granule cells contain a large amount of filaggrin precursor profilaggrin (10 to 12 filaggrin units arranged vertically). Aggregates keratin fibers by phosphorylation. After that, it is deiminated by the action of an enzyme called peptidylarginine deiminase (PAD), released from keratin, and then decomposed into amino acids in the upper stratum corneum.
  • PAD peptidylarginine deiminase
  • NMF natural moisturizing factors
  • PAD acts on the arginine residue of filaggrin to deiminate it and convert it to a citrulline residue. Deimination of filaggrin in this way weakens the affinity between filaggrin and keratin fibers, liberates keratin fibers, and as a result, filaggrin becomes susceptible to the action of proteases, and is finally decomposed into NMF. It is considered to be a thing.
  • Calpain-1 and caspase-14 have been identified as enzymes that degrade filaggrin deiminated by PAD. It has been shown to be decomposed into Japanese Unexamined Patent Application Publication No.
  • 2012-193136 discloses a bleomycin hydrolase production-promoting agent containing, as an active ingredient, one or more selected from the group consisting of rose rose extract, angelica extract, Phellodendron bark extract, dead nettle extract, rosemary extract, benzenesulfonyl GABA and erythritol. agents, natural moisturizing factor production promoters, and dry skin improving agents.
  • the present disclosure provides novel PAD1 production promoting agents.
  • PAD1 an NMF-producing enzyme
  • Scutellaria root extract, soapberry extract, neem leaf extract, horse chestnut extract, Chinese quince extract We have found that polyoxyethylene (14) polyoxypropylene (7) dimethyl ether and Angelica keiskei extract have particularly high effects as agents for promoting PAD1 production, and have completed the following invention:
  • a PAD1 production-promoting agent including [Aspect 2] The PAD1 production-promoting agent according to Aspect 1, for promoting the production of natural moisturizing factor (NMF). [Aspect 3] The PAD1 production-promoting agent according to Aspect 1 or 2, for preventing a decrease in skin moisturizing power caused by an occlusion effect that hinders water evaporation.
  • a cosmetic method comprising the step of applying the PAD1 production-promoting agent according to any one of aspects 1 to 3 or the external preparation for skin according to aspect 4 to the skin of a subject.
  • PAD1 production can be promoted by administration of the PAD1 production-promoting drug according to the present disclosure.
  • a composition containing a PAD1 production promoting agent can be provided.
  • NMF natural moisturizing factor
  • FIG. 1 is a graph showing changes in the expression level of PAD1 in an experimental system that mimics the occlusion effect of cosmetic application in vitro.
  • FIG. 2A is a graph showing the result of comparing the PAD1 production-promoting effect of the Scutellaria root extract with the control to which no test substance was added. It is shown as a relative expression level with the PAD1 gene expression level in the control being set to 1.
  • FIG. 2B is a graph showing the result of comparison of the PAD1 production-promoting effect of the soapberry extract with the control to which no test substance was added. It is shown as a relative expression level with the PAD1 gene expression level of the control being set to 1.
  • FIG. 2A is a graph showing the result of comparing the PAD1 production-promoting effect of the Scutellaria root extract with the control to which no test substance was added. It is shown as a relative expression level with the PAD1 gene expression level in the control being set to 1.
  • FIG. 2B is a graph showing the result of comparison of the PAD
  • FIG. 2C is a graph showing the result of comparing the PAD1 production-promoting effect of the neem leaf extract with the control to which no test substance was added. It is shown as a relative expression level with the PAD1 gene expression level in the control being set to 1.
  • FIG. 2D is a graph showing the results of comparison of the PAD1 production-promoting effect of the horse chestnut extract with the control to which no test substance was added. It is shown as a relative expression level with the PAD1 gene expression level in the control being set to 1.
  • FIG. 2E is a graph showing the result of comparing the PAD1 production-promoting effect of Chinese quince extract with that of a control to which no test substance was added. It is shown as a relative expression level with the PAD1 gene expression level of the control being set to 1.
  • FIG. 2F is a graph showing the results of comparing the effect of polyoxyethylene (14) polyoxypropylene (7) dimethyl ether on promoting PAD1 production with a control to which no test substance was added. It is shown as a relative expression level with the PAD1 gene expression level of the control being set to 1.
  • FIG. 2G is a graph showing the result of comparing the PAD1 production-promoting effect of the Angelica keiskei extract with the control to which no test substance was added. It is shown as a relative expression level with the PAD1 gene expression level of the control being set to 1.
  • the present disclosure contains at least one substance selected from the group consisting of Scutellaria root extract, soapberry extract, neem leaf extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract.
  • a PAD1 production promoter containing as an active ingredient.
  • Scutellaria Root Extract is an extract extracted from Scutellaria root, the root of Scutellaria baicalensis, a member of the Labiatae family. Antioxidant, antiallergic, whitening, moisturizing, and barrier function improvement are known as expected effects of this extract. However, it has not been reported that Scutellaria root extract has a PAD1 production-promoting effect, which is a very surprising discovery.
  • Scutellaria root extract for example, Scutellaria root extract BG available from Maruzen Pharmaceutical Co., Ltd. can be used.
  • Sapindus Mukorossi Peel Extract is an extract obtained by extracting from the pericarp of Sapindus Mukorossi. Sapindactyl has long been used as a natural surfactant (cleansing component) for shampooing and washing hair. However, it has not been reported that the soapberry extract has a PAD1 production-promoting effect, which is a very surprising discovery.
  • a soapberry extract powder available from Maruzen Pharmaceutical Co., Ltd. can be used as the soapberry extract.
  • Neem leaf extract (Melia Azadirachta Leaf Extract) is an extract obtained by extracting neem leaves. This extract is known to have an anti-inflammatory action and an action to suppress the production of melanin as expected actions. However, it has not been reported that neem leaf extract has a PAD1 production-promoting effect, which is a very surprising discovery.
  • neem leaf extract BG available from Ichimaru Farcos Co., Ltd. can be used.
  • Horse Chestnut Extract is an extract extracted from horse chestnut (horse chestnut) seeds. Anti-inflammatory, moisturizing, and whitening properties are known as expected effects of this extract. However, it has not been reported that a horse chestnut extract has a PAD1 production-promoting effect, which is a very surprising discovery.
  • the horse chestnut extract can use the horse chestnut extract which can be purchased from Koei Kogyo Co., Ltd., for example.
  • Chinese quince extract (Chaenomeles Sinensis Extract) is an extract obtained by extracting from the fruit of the rose family Chinese quince. This extract is known to have a moisturizing effect by softening the skin surface and an anti-inflammatory effect by inhibiting lipase. However, it has not been reported that quince extract has a PAD1 production-promoting effect, which is a very surprising discovery.
  • Chinese quince extract can be purchased, for example, from Ichimaru Farcos Co., Ltd.
  • Polyoxyethylene (14) polyoxypropylene (7) dimethyl ether (PEG/PPG-14/7 Dimethyl Ether) is a general term for polyoxyethylene polyoxypropylene random copolymer dimethyl ether.
  • Polyoxyethylene (14) polyoxypropylene (7) dimethyl ether is used as a surfactant, skin conditioning agent.
  • polyoxyethylene (14) polyoxypropylene (7) dimethyl ether has a PAD1 production-promoting effect, which is a very surprising discovery.
  • Polyoxyethylene (14) polyoxypropylene (7) dimethyl ether (polyoxyethylene (14) polyoxypropylene (7) dimethyl ether can be used, for example, Macbiobride E-1060 available from NOF Corporation) can.
  • Angelica Keiskei Extract is an extract extracted from Angelica keiskei leaves. Expected actions of this extract are moisturizing, promotion of hyaluronic acid production, promotion of collagen production, and antioxidant. However, Angelica keiskei extract has not been reported to have a PAD1 production promoting effect, which is a very surprising discovery.
  • Angelica keiskei extract for example, Angelica keiskei extract BG available from Ichimaru Farcos Co., Ltd. can be used.
  • plant extracts such as "Scutellaria root extract” and “Sapindactyl extract” used in the present invention can be extracted from plant raw materials by methods known to those skilled in the art.
  • plant extracts can be obtained using any method known to those skilled in the art, such as, for example, extraction methods using solvents, methods involving grinding or pressing steps.
  • the part of the plant to be extracted is washed with water in advance to remove foreign matter, then it is left as it is or dried, then cut into small pieces or pulverized as necessary, and then brought into contact with the extraction solvent for extraction.
  • Extraction can be carried out by contacting with an extraction solvent according to a conventional method such as immersion, but supercritical extraction or steam distillation may also be used.
  • the plant body When performing extraction, the plant body can be used as it is, but it is better to crush it into granules or powder before subjecting it to extraction, as it is possible to extract active ingredients with high extraction efficiency in a short period of time under mild conditions. It can be carried out.
  • the extraction temperature is not particularly limited, and may be appropriately set according to the particle size of the pulverized material, the type of solvent, and the like. Usually, it is set within the range from room temperature to the boiling point of the solvent.
  • the extraction time is also not particularly limited, and may be appropriately set according to the particle size of the pulverized material, the type of solvent, the extraction temperature, and the like. Furthermore, at the time of extraction, stirring may be performed, the liquid may be allowed to stand without stirring, or ultrasonic waves may be applied.
  • extraction solvents include water; lower alcohols such as methanol, ethanol and propanol; higher alcohols such as oleyl alcohol, stearyl alcohol and octyldodecanol; ethylene glycol, 1,3-propanediol, 1,3-butylene glycol, polyhydric alcohols such as glycerin; esters such as ethyl acetate, butyl acetate, methyl propionate and glyceryl trioctanoate; ketones such as acetone and methyl ethyl ketone; ethers such as ethyl ether, isopropyl and ether; n-hexane and toluene , chloroform and other hydrocarbon solvents, and the like, which can be used alone or in combination of two or more.
  • lower alcohols such as methanol, ethanol and propanol
  • higher alcohols such as oleyl alcohol, stearyl alcohol and octy
  • Preferable solvents are polar solvents such as water, lower alcohols and liquid polyhydric alcohols, more preferably water or lower alcohols such as methanol, ethanol or 1,3-butylene glycol.
  • the lower alcohol may be, for example, a hydrous lower alcohol, in which case the water content is, for example, 0-10 v/v%, 10-40 v/v%, 20-30 v/v%, 30-50 v/v%. , 50 to 80 v/v%, 80 to 99.5 v/v%, and the like.
  • the lower alcohol may be, for example, a C1-C5 lower alcohol.
  • These solvents may be used singly or in combination of two or more. Moreover, you may add an enzyme to a solvent and may perform an extraction process.
  • the mixing ratio is, for example, a mixed solvent of water and ethyl alcohol in the range of 1:1 to 25:1 by volume (same below); a mixed solvent of water and glycerin In the range of 1:1 to 15:1; or in the case of a mixed solvent of water and 1,3-propanediol or 1,3-butylene glycol, the range is preferably in the range of 1:1 to 15:1.
  • the pH is not particularly limited, but it is generally preferred to be in the range of pH 3-9.
  • the extraction solvent is blended with an alkalinity adjuster such as sodium hydroxide, sodium carbonate, potassium hydroxide, or an acidity adjuster such as citric acid, hydrochloric acid, phosphoric acid, sulfuric acid, etc. to achieve the desired pH.
  • an alkalinity adjuster such as sodium hydroxide, sodium carbonate, potassium hydroxide, or an acidity adjuster such as citric acid, hydrochloric acid, phosphoric acid, sulfuric acid, etc.
  • Extraction conditions such as extraction temperature and extraction time vary depending on the type and pH of the solvent used, and are not limited.
  • water or 1,3-butylene glycol, or a mixture of water and 1,3-butylene glycol When used as a solvent, the extraction temperature may be in the range of 0°C to 90°C, and the extraction time may be in the range of 0.5 hours to 7 days.
  • the solvent containing the extract may be used as it is, or may be used after being subjected to conventional purification treatments such as sterilization, washing, filtration, decolorization and deodorization. Moreover, you may use, after concentrating or diluting if necessary. Further, the solvent may be entirely volatilized to form a solid (dried product) before use, or the dried product may be redissolved in an arbitrary solvent before use.
  • the extraction site Prior to the extraction process or in parallel with the extraction process, the extraction site may be subjected to hydrolysis treatment as necessary. As a result, there is a possibility that the extract can be used more effectively by improving the skin irritation, efficacy, storage stability, or the like of the extract.
  • the pressed liquid obtained by pressing the raw material plant also contains the same active ingredients as the extract, so the pressed liquid can be used instead of the extract.
  • PAD1 refers to Peptidylarginine Deiminase 1. This gene encodes an enzyme belonging to the peptidylarginine deiminase family and catalyzes the post-translational deimination of proteins by converting arginine residues to citrulline in the presence of calcium ions. Although proteins belonging to this family have different substrate specificities and tissue-specific expression patterns, the PAD1 enzyme is involved in the later stages of epidermal differentiation and maintains stratum corneum hydration to preserve skin barrier function. Deiminates filaggrin and keratin K1.
  • Natural moisturizing factor is one of the moisturizing ingredients present in the stratum corneum and plays an important role in retaining moisture in the stratum corneum.
  • Amino acids the main components of NMF, are produced by degradation of filaggrin protein derived from keratohyalin granules.
  • Filaggrin is a protein consisting of 317 amino acids.
  • PAD acts on the arginine residue of filaggrin to deiminate it and convert it to a citrulline residue. Deimination of filaggrin in this way weakens the affinity between filaggrin and keratin fibers, liberates keratin fibers, and as a result, filaggrin becomes susceptible to the action of proteases, and is finally decomposed into NMF. It is considered to be a thing.
  • the PAD1 production promoting agent can promote the production of natural moisturizing factor (NMF) by promoting the production of PAD1.
  • the "occlusion effect” refers to the effect of suppressing water evaporation from the inside of the body by applying (obstructing) an oil-based base material with low water permeability such as petroleum jelly to the skin, resulting in an increase in the barrier function.
  • the PAD1 production-promoting agent according to the present disclosure can prevent a decrease in skin moisturizing power caused by the occlusion effect caused by the application of cosmetics by promoting the production of PAD1.
  • promotion of PAD1 production means, for example, when the PAD1 production promoter is applied compared to the state (control) where the PAD1 production promoter is not applied, the expression level of the PAD1 gene is, for example, a significant level of 5%. It can mean that it is enhanced with a statistically significant difference (eg, Student's t-test).
  • the promotion of PAD1 production means that, for example, when the PAD1 production promoter is applied, the expression level of the PAD1 gene is, for example, 10% or more, 20 % or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 100% or more, 200% or more, 300% or more, 400% or more, or 500% It can mean that it is enhanced more than
  • the expression level of the PAD1 gene can be determined by any known technique, for example, the method described in Non-Patent Document 6.
  • the present disclosure effectively uses a substance selected from the group consisting of Scutellaria root extract, soapberry extract, neem leaf extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract.
  • a PAD1 production-promoting drug containing as a component.
  • the PAD1 production-promoting agent according to the present disclosure can promote PAD1 production, and thus the production of natural moisturizing factor (NMF).
  • NMF natural moisturizing factor
  • the present disclosure provides Scutellaria root extract, soapberry extract, neem leaf extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract. It also relates to a natural moisturizing factor (NMF) production-promoting agent containing the substance as an active ingredient.
  • NMF natural moisturizing factor
  • the PAD1 production-promoting agent according to the present disclosure can prevent a decrease in skin moisturizing power caused by the occlusion effect caused by the application of cosmetics by promoting PAD1 production.
  • the present disclosure provides Scutellaria root extract, soapberry extract, neem leaf extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract. It also relates to an agent for preventing a decrease in skin moisturizing power caused by an occlusion effect due to the application of cosmetics, which contains the substance as an active ingredient.
  • PAD1 production enhancement and natural moisturizing factor (NMF) production enhancement may be in a tissue or organ such as skin.
  • the present disclosure provides at least one extract selected from the group consisting of Scutellaria root extract, soapberry extract, neem leaf extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract
  • a composition containing a PAD1 production promoter or a natural moisturizing factor (NMF) production promoter containing the substance as an active ingredient is also provided.
  • a composition according to the present disclosure may be a cosmetic composition or a food composition.
  • the composition according to the present disclosure promotes the production of natural moisturizing factor (NMF) through the promotion of PAD1 production, thereby preventing a decrease in skin moisturizing power caused by the occlusion effect of applying cosmetics.
  • the PAD1 production promoter includes Scutellaria root extract, soapberry extract, and neem as active ingredients.
  • At least one substance selected from the group consisting of leaf extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract for example, 10% by mass or more, 20% by mass 30% by mass or more, 40% by mass or more, 50% by mass or more, 60% by mass or more, 70% by mass or more, 80% by mass or more, 90% by mass or more, 95% by mass or more, or 99% by mass or more
  • the PAD1 production promoter, the natural moisturizing factor (NMF) production promoter, the agent for preventing the decrease in skin moisturizing power caused by the occlusion effect caused by the application of cosmetics, or the composition according to the present disclosure includes Scutellaria root extract, soapberry extract, neem leaf extract, It may contain two or all three substances selected from the group consisting of horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract.
  • the PAD1 production promoter, the natural moisturizing factor (NMF) production promoter, or the agent for preventing the decrease in skin moisturizing power caused by the occlusion effect caused by the application of cosmetics is Scutellaria root extract, soapberry extract, and neem leaf. Extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract.
  • At least one substance selected from the group consisting of Scutellaria root extract, soapberry extract, neem leaf extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract used in the present invention can be obtained by any method, and is not limited by the method of production, source of supply, or the like.
  • the PAD1 production promoter, the natural moisturizing factor (NMF) production promoter, the agent for preventing the decrease in skin moisturizing power caused by the occlusion effect caused by the application of cosmetics, or the composition according to the present disclosure can be administered externally or orally.
  • the form of external administration can be arbitrarily selected, for example, cream, milky lotion, liquid, sheet, spray, gel, and the like.
  • Oral administration forms can be arbitrarily selected, for example, tablets, supplements, beverages, powders, and the like.
  • the present disclosure provides a skin external preparation containing a PAD1 production promoting agent, a skin external preparation containing a natural moisturizing factor (NMF) production promoting agent, and an agent for preventing a decrease in skin moisturizing power caused by the occlusion effect caused by the application of cosmetics.
  • a topical skin preparation comprising:
  • the cosmetic composition according to the present disclosure may be various cosmetics such as milky lotions, creams, serums, lotions, packs, facial cleansers, soaps, body soaps and shampoos, and may be liquid, milky, creamy, solid, It may be in various forms such as sheet, spray, gel, foam and powder.
  • the food composition according to the present disclosure may be powder, beverage, or tablet, and may be in various forms such as powder, liquid, solid, granules, granules, paste, and gel.
  • the PAD1 production promoter, the natural moisturizing factor (NMF) production promoter, the agent for preventing the decrease in skin moisturizing power caused by the occlusion effect caused by the application of cosmetics, or the composition according to the present disclosure includes Scutellaria root extract, soapberry extract, neem leaf extract, At least one substance selected from the group consisting of horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract in an amount such that the effect of promoting PAD1 production is sufficiently exhibited It is preferable to contain.
  • PAD1 production promoter according to the present disclosure, natural moisturizing factor (NMF) production promoter, preventive agent for reducing skin moisturizing power caused by occlusion effect due to application of cosmetics, or Scutellaria root extract, soapberry extract, neem leaf extract, horse chestnut in the composition
  • NMF natural moisturizing factor
  • the amount of at least one substance selected from the group consisting of extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract is determined according to their types, purposes, forms, usage methods, etc. can be determined as appropriate.
  • the dosage of at least one substance selected from the group consisting of Scutellaria root extract, soapberry extract, neem leaf extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract When externally administered, for example, at least selected from the group consisting of Scutellaria root extract, soapberry extract, neem leaf extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract
  • the blending amount of one substance is the PAD1 production promoter according to the present disclosure, the natural moisturizing factor (NMF) production promoter, the agent for preventing the decrease in skin moisturizing power caused by the occlusion effect due to the application of cosmetics, or the total weight of the composition 0.001-50% by weight, 0.01-5% by weight, 0.01-1% by weight, 0.01-0.1% by weight, 0.02-0.05% by weight, etc.
  • At least one substance selected from the group consisting of Scutellaria root extract, soapberry extract, neem leaf extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract is the PAD1 production promoter according to the present disclosure, the natural moisturizing factor (NMF) production promoter, the agent for preventing the decrease in skin moisturizing power caused by the occlusion effect due to the application of cosmetics, or the total weight of the composition 0.001 to 50 % by weight, 0.01-5% by weight, 0.01-1% by weight, 0.01-0.1% by weight, 0.02-0.05% by weight, etc., but not limited thereto.
  • NMF natural moisturizing factor
  • the frequency of administration was once every 4 weeks, once every 2 weeks, once a week, once every 3 days, once every 2 days, once a day, twice a day, and 3 times a day. , 4 times a day, 5 times a day, administration as needed, etc. can be arbitrarily selected, but are not limited to these.
  • the PAD1 production promoter, the natural moisturizing factor (NMF) production promoter, the agent for preventing the decrease in moisturizing power of the skin caused by the occlusion effect due to the application of cosmetics, or the composition according to the present disclosure the additive is arbitrarily selected as necessary. can be used together. Excipients and the like can be included as additives.
  • any excipients that are usually used for the desired dosage form may be used, and examples thereof include wheat starch, rice starch, corn starch, potato starch, dextrin, starches such as cyclodextrin, and crystalline celluloses. , lactose, glucose, sugar, reduced maltose, starch syrup, fructooligosaccharide, emulsified oligosaccharide, and sugar alcohols such as sorbitol, erythritol, xylitol, lactitol, and mannitol. These excipients can be used alone or in combination of two or more.
  • additives include colorants, preservatives, thickeners, binders, disintegrants, dispersants, stabilizers, gelling agents, antioxidants, surfactants, preservatives, pH adjusters, oils, Known substances such as water, alcohols, chelating agents, silicones, ultraviolet absorbers, moisturizing agents, fragrances, various medicinal ingredients, preservatives, neutralizers, etc. can be appropriately selected and used.
  • the present disclosure contains at least one substance selected from the group consisting of Scutellaria root extract, soapberry extract, neem leaf extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract. Also provided are methods for promoting PAD1 production by administering.
  • the present disclosure provides at least one extract selected from the group consisting of Scutellaria root extract, soapberry extract, neem leaf extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract.
  • a method for promoting production of natural moisturizing factor (NMF) through promotion of PAD1 production by administering a substance is also provided.
  • the present disclosure provides at least one selected from the group consisting of Scutellaria root extract, soapberry extract, neem leaf extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract.
  • the method according to the present disclosure is a cosmetic method and may not be a treatment by a doctor or a medical practitioner.
  • the present disclosure is directed to the PAD1 production promoting agent according to the present disclosure, the natural moisturizing factor (NMF) production promoting agent, the agent for preventing the decrease in skin moisturizing power caused by the occlusion effect caused by the application of cosmetics, or the external skin preparation.
  • a cosmetic method is also provided, comprising the step of applying to the skin.
  • the present disclosure provides a PAD1 production promoting agent according to the present disclosure, a natural moisturizing factor (NMF) production promoting agent, a preventive agent for reducing the moisturizing power of the skin caused by an occlusion effect that prevents water evaporation, or A method for promoting the production of PAD1, a method for promoting the production of natural moisturizing factor (NMF), or a method for preventing a decrease in skin moisturizing power caused by an occlusion effect due to the application of cosmetics, comprising the step of administering a composition. also provide.
  • NMF natural moisturizing factor
  • the present disclosure relates to a screening method for a substance that prevents a decrease in skin moisturizing power caused by an occlusion effect that hinders water evaporation, using the expression of PAD1 as an index.
  • Expression of PAD1 can be determined using mRNA or protein expression as an indicator. Measurement of mRNA or protein can be performed by any method known to those skilled in the art.
  • the screening method comprises the steps of 1) preparing a sample containing a test agent, 2) contacting the sample with cells, and 3) evaluating the presence or absence of an increase in the expression level of PAD1 in cells.
  • a drug to be tested can be, for example, any substance such as low-molecular-weight compounds, high-molecular polymers, proteins, peptides, antibodies, enzymes, nucleic acids, sugar chains, lipids, etc., and compositions containing them.
  • drugs to be tested include, for example, vitamin C, vitamin E, ⁇ -carotene, astaxanthin, etc., derivatives thereof, and plant extract compositions.
  • drugs to be tested include cosmetics, base materials, pharmaceuticals, and sunscreens.
  • Example 1 Changes in PAD1 expression level in an experimental system mimicking the occlusion effect of cosmetic application
  • a system was constructed in which a three-dimensional skin model was cultured in a state in which contact with the external environment was blocked only by the occlusion effect of petroleum jelly and paper, covered with a paper coated with .
  • a three-dimensional skin model covered with paper not coated with petroleum jelly was used.
  • epidermal keratinocytes were cultured at 45% relative humidity (RH) for 24 hours, and then PAD1 expression in a three-dimensional skin model was examined by quantitative PCR.
  • RH relative humidity
  • Example 2 Scutellaria root extract, soapberry extract, neem leaf extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract PAD1 gene expression enhancement effect (sample preparation)
  • Commercially available Scutellaria root extract, soapberry extract, neem leaf extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract are filter-sterilized and filtered to obtain a concentration of 1M of Scutellaria root extract, soapberry extract, Neem leaf extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract samples were prepared.
  • the Scutellaria root extract used was Scutellaria root extract BG purchased from Maruzen Pharmaceutical Co., Ltd.
  • the scutellaria root extract used was soap extract powder purchased from Maruzen Pharmaceutical Co., Ltd.
  • the neem leaf extract was purchased from Ichimaru Farcos Co., Ltd.
  • Neem leaf extract BG is used, horse chestnut extract purchased from Koei Kogyo Co., Ltd. is used, quince extract is purchased from Ichimaru Farcos Co., Ltd.
  • Polyoxyethylene (14) Polyoxypropylene (7) dimethyl ether used was Macbio Bride E-1060 purchased from NOF Corporation, and Angelica keiskei extract BG purchased from Ichimaru Falcos Co., Ltd. was used as Angelica keiskei extract.
  • keratinocytes derived from normal adult skin (Kurabo) were inoculated into T75 flasks at 5 ⁇ 10 5 cells/flask, and incubated in a keratinocyte medium (Humedia-KG2, Kurabo) at 37°C and 5% CO The cells were cultured under two atmospheres until reaching semi-confluence and used as seed cells. The keratinocytes were collected by trypsinization, inoculated into a 12-well plate at 5 ⁇ 10 4 cells/well, and placed in a keratinocyte medium (Humedia-KG2, Kurabo Industries) at 37° C., 5% CO 2 . It was cultured under atmosphere until confluency was reached.
  • RNA from cells Scutellaria root extract, soapberry extract, neem leaf extract, horse chestnut extract, Chinese quince extract, polyoxyethylene (14) polyoxypropylene (7) dimethyl ether, and Angelica keiskei extract were added 48 hours later, the medium was removed, and commercially available RNA was extracted. Cell lysis and RNA extraction were performed using an extraction reagent (RNeasy Mini Kit, Qiagen).
  • PAD1 gene expression can be promoted by administration of a PAD1 production promoter contained as an active ingredient.
  • administration of a PAD1 production promoter can promote the production of natural moisturizing factor (NMF) through promoting PAD1 gene expression, and by promoting the production of natural moisturizing factor (NMF) , It can prevent the decrease in skin moisturizing power caused by the occlusion effect that hinders water evaporation.
  • NMF natural moisturizing factor

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Publication number Priority date Publication date Assignee Title
JP2002370997A (ja) * 2001-06-14 2002-12-24 Shiseido Co Ltd 乾燥による皮膚傷害の予防または修復
JP2006076902A (ja) * 2004-09-08 2006-03-23 Ogawa & Co Ltd 保湿性植物抽出物並びに該抽出物を含有する外用剤、化粧料、浴用剤及び洗剤
JP2021113172A (ja) * 2020-01-20 2021-08-05 日本メナード化粧品株式会社 ペプチジルアルギニンデイミナーゼ１発現促進剤

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002370997A (ja) * 2001-06-14 2002-12-24 Shiseido Co Ltd 乾燥による皮膚傷害の予防または修復
JP2006076902A (ja) * 2004-09-08 2006-03-23 Ogawa & Co Ltd 保湿性植物抽出物並びに該抽出物を含有する外用剤、化粧料、浴用剤及び洗剤
JP2021113172A (ja) * 2020-01-20 2021-08-05 日本メナード化粧品株式会社 ペプチジルアルギニンデイミナーゼ１発現促進剤

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