WO2021084665A1 - Promoteur de production de facteur de croissance dérivé de plaquettes (pdgf)-bb, stabilisateur de cellules souches contenant ce cernier, et agent anti-âge de la peau contenant ces derniers - Google Patents

Promoteur de production de facteur de croissance dérivé de plaquettes (pdgf)-bb, stabilisateur de cellules souches contenant ce cernier, et agent anti-âge de la peau contenant ces derniers Download PDF

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WO2021084665A1
WO2021084665A1 PCT/JP2019/042689 JP2019042689W WO2021084665A1 WO 2021084665 A1 WO2021084665 A1 WO 2021084665A1 JP 2019042689 W JP2019042689 W JP 2019042689W WO 2021084665 A1 WO2021084665 A1 WO 2021084665A1
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pdgf
extract
skin
production
stem cell
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PCT/JP2019/042689
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English (en)
Japanese (ja)
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雅明 長谷川
太郎 内山
上田　修
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株式会社 資生堂
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Priority to JP2021553970A priority Critical patent/JP7433337B2/ja
Priority to PCT/JP2019/042689 priority patent/WO2021084665A1/fr
Publication of WO2021084665A1 publication Critical patent/WO2021084665A1/fr
Priority to JP2024016646A priority patent/JP2024036562A/ja

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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)
    • 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)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof

Definitions

  • the present invention relates to a platelet-derived growth factor-BB (PDGF-BB) production enhancer, a stem cell stabilizer containing the PDGF-BB production enhancer, and a skin anti-aging agent containing them.
  • PDGF-BB platelet-derived growth factor-BB
  • mesenchymal stem cells differentiate into various cells belonging to the mesenchymal system (osteocytes, muscle cells, chondrocytes, tendon cells, adipocytes, etc.), their application to regenerative medicine is being studied. For example, by stabilizing mesenchymal stem cells, it is effective for various purposes such as blood vessel stabilization, maintenance of tissue homeostasis, prevention / improvement of various states such as repair / regeneration of damaged tissue, and mesenchymal stem cells in the skin. It has been reported that stabilization of mesenchymal stem cells is effective for skin activation and anti-aging (Patent Documents 1 and 2).
  • Platelet-derived growth factor-BB (PDGF-BB) has been reported as a factor that stabilizes mesenchymal stem cells (Patent Documents 1 and 2). Therefore, if an effective component for enhancing the production of PDGF-BB can be found, it can be used to stabilize mesenchymal stem cells, and thus can be effectively used for applications such as skin activation and anti-aging. ..
  • Patent Documents 1 and 2 Retinoic acid, amla extract, lingonberry extract and the like have been reported as effective components for enhancing the production of PDGF-BB (Patent Documents 1 and 2). It is expected to search for various substances that have a high PDGF-BB production enhancing effect.
  • the present invention has been made in view of the above background, and the subject thereof is to provide an agent effective for enhancing the production of PDGF-BB, and to use the agent for stabilizing mesenchymal stem cells in the skin.
  • the purpose is to provide an agent effective for activation and anti-aging of the skin.
  • the present application includes the following inventions: [1] A platelet-derived growth factor-BB (PDGF-BB) production enhancer containing at least one of wasabi extract, chamomile extract, L-theanine, and hibiscus extract as an active ingredient. [2] A stem cell stabilizer comprising the PDGF-BB production enhancer according to [1]. [3] A skin anti-aging agent comprising the PDGF-BB production enhancer according to [1], which suppresses skin aging by stabilizing stem cells in the skin.
  • PDGF-BB platelet-derived growth factor-BB
  • an agent effective for enhancing the production of PDGF-BB is provided, and by using this agent, an agent effective for stabilizing stem cells and the like is also provided. If stem cells are stabilized in the skin, it is effective in suppressing skin aging.
  • FIG. 1 shows the screening results of Experiment 2 and shows the results of the control (0.5% DSMO) as relative values of 100.0.
  • FIG. 2 shows the results of comparing the PDGF-BB production enhancing ability of various samples with the 15 ⁇ g / mL lingon berry extract and the 2 ⁇ g / mL amla extract in Experiment 3, and the results of the control (15 ⁇ g / mL lingon berry extract). The result is shown as a relative value with 100.0.
  • FIG. 1 shows the screening results of Experiment 2 and shows the results of the control (0.5% DSMO) as relative values of 100.0.
  • FIG. 2 shows the results of comparing the PDGF-BB production enhancing ability of various samples with the 15 ⁇ g / mL lingon berry extract and the 2 ⁇ g / mL amla extract in Experiment 3, and the results of the control (15 ⁇ g / mL lingon berry extract). The result is shown as a relative value
  • the present inventors have found that wasabi extract, chamomile extract, L-theanine, and hibiscus extract exhibit remarkable PDGF-BB production enhancing action and stem cell stabilizing action, and the present invention has made such a discovery. Based on.
  • Wasabi extract has been reported to have bactericidal action, antioxidant action, moisturizing action, lipase inhibitory activity, etc. (Japanese Patent Laid-Open No. 2016-124845). It has been reported that the fermented product obtained by fermenting the chamomile extract has a cell differentiation promoting effect (Japanese Patent Laid-Open No. 2015-157772). In addition, the chamomile extract has a stem cell growth factor (SCF) mRNA expression increase inhibitory effect (Japanese Patent Laid-Open No. 2011-1327) and a basic fibroblast growth factor (bFGF) mRNA expression increase inhibitory effect (Japanese Patent Laid-Open No. 2011-1328).
  • SCF stem cell growth factor
  • bFGF basic fibroblast growth factor
  • SCF stem cell factor
  • Japanese Patent Laid-Open No. 2003-194809 Japanese Patent Laid-Open No. 2003-194809
  • theanine has an effect of improving epidermal stem cell functionality (Japanese Patent Laid-Open No. 2015-178485), an effect of suppressing parakeratosis (Japanese Patent Laid-Open No. 2007-204417), and the like.
  • the hibiscus extract has an inhibitor of hyaluronidase activity, an inhibitory effect on the expression of stem cell growth factor mRNA (Japanese Patent Laid-Open No. 2014-218476), and the like.
  • these substances have the PDGF-BB production promoting action and the stem cell stabilizing action of the present invention.
  • PDGF-BB production enhancing action refers to the action of improving the production of platelet-derived growth factor-BB (PDGF-BB) protein.
  • PDGF-BB platelet-derived growth factor-BB
  • the PDGF-BB production-enhancing effect can be evaluated, for example, by measuring the amount of PDGF-BB to determine the amount of protein.
  • This measurement uses PDGF-BB-specific antibodies and is known in the art, such as immunostaining, Western blotting, immunoassays, such as ELISA, using fluorescent substances, dyes, enzymes, etc. It can be implemented by various methods such as RIA method. It can also be determined indirectly by, for example, extracting total RNA in mesenchymal stem cells and measuring the amount of mRNA encoding PDGF-BB, but the method of measuring the actual amount of protein is more direct. Can be evaluated.
  • the stem cell stabilizing action refers to an action of attracting and localizing a stem cell to a target site and / or an action of retaining the stem cell at the target site to maintain a localized state.
  • the stem cell stabilizing action is distinguished from the action of promoting the proliferation of stem cells and / or the action of maintaining the stem cells in an undifferentiated state, and may not include these actions.
  • the stem cell stabilizing action is not limited, but can be measured by, for example, the method described in Patent Document 1 for measuring migration ability or localization in the skin.
  • Skin activation includes, but is not limited to, promoting metabolism and turnover of animal cells including humans, such as skin tissue, improving function, promoting proliferation, suppressing oxidation, and improving resistance to fatigue and external stimuli. Examples include suppression of deterioration of function and activity.
  • the skin is activated, it is expected to have effects such as prevention and improvement of wrinkles, age spots, skin aging, photoaging and the like.
  • [Wasabi extract] Wasabi (Saltwater cress) is a perennial plant of the Brassicaceae genus Wasabi.
  • this wasabi (Eutrema japonicum (Miq.) Koidz.) Is preferable, but other species such as Eutrema pneumonia and related species (Eutrema yunnanense) may be used. ..
  • wasabi leaf extract is preferable, but since seeds, stems, flowers, roots and the like also contain an active ingredient, any one or more of these extracts can be used.
  • the wasabi extract is commercially available from Kinjirushi Co., Ltd., and such a commercially available product can also be used.
  • Chamomile (scientific name: Matricaria chamomilla) is an annual plant belonging to the genus Mayweed in the family Asteraceae.
  • the chamomile extract used in the present invention the chamomile head flower extract is preferable, but since the chamomile seeds, leaves, stems, flowers, roots and the like also contain active ingredients, any of these Or one or more extracts can also be used.
  • the chamomile extract is commercially available from Maruzen Pharmaceuticals Co., Ltd. and the like, and such a commercially available product can also be used.
  • L-Theanine is a type of amino acid represented by the following structural formula.
  • L-theanine is abundantly contained in tea leaves such as green tea and black tea
  • L-theanine contained in these tea leaves may be used, or may be used in the form of an extract of these tea leaves, but artificially. It may be synthesized, or a commercially available product commercially available from Taiyo Kagaku or the like can be used.
  • Hibiscus is an annual or perennial sub-shrub belonging to the genus Confederate rose in the Malvales family Malvales.
  • an extract of roselle Hibiscus sabdariffa
  • Hibiscus flower extracts are preferred, but since hibiscus fruits, seeds, leaves, stems, flowers, roots, etc. also contain active ingredients, use one or more of these extracts. You can also do it.
  • the hibiscus extract is commercially available from Nikken Foods Co., Ltd., and such a commercially available product can also be used.
  • the extraction method is not particularly limited, but an extraction method using a solvent is preferable.
  • the plant body can be used as it is, but it is better to crush it into granules or powder and use it for extraction in a short time under mild conditions with high extraction efficiency. 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 product, the type of solvent, and the like. Usually, it is set in the range from room temperature to the boiling point of the solvent.
  • the extraction time is not particularly limited, and may be appropriately set according to the particle size of the pulverized product, the type of solvent, the extraction temperature, and the like. Further, at the time of extraction, stirring may be performed, the mixture may be allowed to stand without stirring, or ultrasonic waves may be applied.
  • the type of solvent is not particularly limited, but water, lower alcohols such as hydrous ethanol and ethanol, organic solvents such as hexane, and mixed solvents such as hexane / ethanol are preferable. Extraction may be carried out at room temperature, but may be carried out under heating (for example, using a heated solvent such as hot water or hot water). Alternatively, the extraction process may be carried out by adding an enzyme to the solvent. By adding the enzyme, the cell tissue of the plant can be disrupted, which can further increase the extraction efficiency. As the enzyme, it is preferable to use a cell tissue disrupting enzyme.
  • Examples of such an enzyme include pectinase, cellulase, hemicellulase, ⁇ -amylase, and phytase. One of these enzymes may be used alone, or two or more of these enzymes may be mixed and used.
  • the active ingredient is extracted and dissolved in the solvent.
  • the solvent containing the extract may be used as it is, or may be used after undergoing conventional purification treatments such as sterilization, washing, filtration, decolorization, and deodorization. Further, it may be used after being concentrated or diluted if necessary. Further, the solvent may be completely volatilized to form a solid (dried product) before use, or the dried product may be redissolved in an arbitrary solvent before use.
  • the squeezed liquid obtained by squeezing the raw material plant also contains the same active ingredient as the extract, the squeezed liquid can be used instead of the extract.
  • the PDGF-BB production enhancer of the present invention contains at least one of wasabi extract, chamomile extract, L-theanine, and hibiscus extract as an active ingredient.
  • the stem cell stabilizer of the present invention contains the PDGF-BB production enhancer of the present invention containing the above-mentioned active ingredient.
  • the stem cell stabilizer of the present invention can enhance the production of PDGF-BB, and the enhanced production of PDGF-BB can act on stem cells such as mesenchymal stem cells, resulting in stabilization of the stem cells. ..
  • the skin anti-aging agent of the present invention contains the PDGF-BB production enhancer of the present invention containing the above-mentioned active ingredient.
  • the skin anti-aging agent of the present invention enhances the production of PDGF-BB, and the enhanced production of PDGF-BB acts on stem cells such as mesenchymal stem cells, thereby stabilizing the stem cells and activating the skin. By making it, it suppresses the aging of the skin.
  • the PDGF-BB production enhancer, stem cell stabilizer and skin anti-aging agent of the present invention are any one of the above active ingredients. It may be contained alone, or two or more kinds may be contained in any combination and ratio.
  • the agent of the present invention may also be a composition in which the above-mentioned active ingredient is combined with one or more other ingredients such as excipients, carriers and / or diluents.
  • the composition and form of the composition are arbitrary, and may be appropriately selected according to conditions such as the active ingredient and use.
  • the composition can be produced by a conventional method with a formulation appropriately combined with an excipient, a carrier and / or a diluent and the like and other components according to the dosage form.
  • the agent of the present invention can be blended with various foods and drinks and feeds and ingested by humans and animals. Further, it may be blended in cosmetics or the like and used for humans and animals, or may be administered to humans and animals as a pharmaceutical preparation.
  • the blending amount (dry mass) of the plant or its extract is appropriately determined according to their types, purposes, forms, usage methods, and the like. be able to.
  • the daily intake of the plant or its extract for an adult is about 0.5 mg to 3 g (dry residue).
  • 10 mg to 1.5 g (dry residue) of the extract can be ingested per adult per day so that the prescribed effect of the active ingredient of the present invention can be sufficiently exerted. It is preferable to contain it in.
  • the form of food and drink and feed can be any form, for example, granules, granules, pastes, gels, solids, or liquids. These forms include various known substances that are approved to be contained in foods and drinks, such as binders, disintegrants, thickeners, dispersants, reabsorption promoters, emulsifiers, buffers, and surfactants. Excipients such as activators, solubilizers, preservatives, emulsifiers, tonicity agents, stabilizers and pH adjusters can be appropriately contained.
  • the blending amount (dry mass) of the plant or its extract depends on the type, purpose, form, usage method and the like. , Can be decided as appropriate.
  • the wasabi extract can contain 0.00001% to 50% (dry mass conversion) of chamomile extract, L-theanine, and hibiscus extract, respectively, and 0.0001% to 5% (dry mass conversion). ) Is preferable.
  • ingredients usually used for external skin preparations such as cosmetics, pharmaceuticals, quasi-drugs, etc., such as antioxidants, oils, UV protection agents, within the range that does not impair the effects of the present invention.
  • ingredients usually used for external skin preparations such as cosmetics, pharmaceuticals, quasi-drugs, etc., such as antioxidants, oils, UV protection agents, within the range that does not impair the effects of the present invention.
  • Surfactants, thickeners, alcohols, powder components, coloring materials, aqueous components, water, various skin nutrients and the like can be appropriately blended as needed.
  • metal ion blockers such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid, preservatives such as methylparaben, ethylparaben, and butylparaben, caffeine, tannin, Bellapamil, tranexamic acid and its derivatives, licorice extract, glabridin, hot water extract of carin fruit, various crude drugs, tocopherol acetate, glycyrrhizinic acid and its derivatives or salts thereof, vitamin C, magnesium ascorbic acid phosphate, Whitening agents such as ascorbic acid glucoside, arbutin, and kodiic acid, and sugars such as glucose, fructose, mannose, sucrose, and trehalose can also be appropriately added.
  • preservatives such as methylparaben, ethylparaben, and butylparaben, caffeine, tannin, Bellapamil
  • the external preparation for skin of the present invention can be applied as a cosmetic, a non-medicinal product, etc. applied to the outer skin, particularly preferably as a cosmetic, and the dosage form is not limited as long as it can be applied to the skin.
  • Any dosage form such as solution system, solubilization system, emulsification system, powder dispersion system, water-oil two-layer system, water-oil-powder three-layer system, ointment, lotion, gel, aerosol, etc. is applied.
  • the agent of the present invention when used as cosmetics, it is used in lotions, emulsions, foundations, lipsticks, lip balms, cleansing creams, massage creams, facial masks, hand creams, hand powders, body shampoos, body lotions, body creams, bath cosmetics, etc. It may be used as a form.
  • the preparation is appropriately used orally or parenterally (intravenous administration, intraperitoneal administration, etc.).
  • the dosage form is also arbitrary, for example, oral solid preparations such as tablets, granules, powders and capsules, oral liquid preparations such as oral liquids and syrups, and parenteral liquid preparations such as injections.
  • the form of the above can be appropriately prepared by a known method. If it is an external preparation, it can be used in various forms such as a lotion, a suspension / emulsion, a liquid, an ointment, and a patch.
  • formulations include commonly used binders, disintegrants, thickeners, dispersants, reabsorption promoters, flavoring agents, buffers, surfactants, solubilizers, preservatives, emulsifiers, isotonic agents. , Excipients such as stabilizers and pH adjusters may be used as appropriate.
  • the possible forms of the agent of the present invention are not limited to the above-mentioned dosage forms and forms.
  • Experiment 1 Preparation of sample The following samples were used as the samples to be evaluated for the effect of enhancing the production of PDGF-BB.
  • Experiment 2 Evaluation of PDGF-BB production-enhancing effect Measurement was performed using an ELISA kit (product name: EHCSRP2) manufactured by Thermo Fisher Scientific. The contents and amount of the kit are shown below.
  • reagents Preparation of reagents 1. Before measurement, all reagents and samples were returned to room temperature (18-25 ° C). 2. The sample diluent (10 mL ⁇ 50 mL) and the assay diluent (6 mL ⁇ 30 mL) were diluted 5-fold with deionized or distilled water before measurement. Cell lysate buffer was diluted 2-fold with deionized or distilled water. 3. Sample dilution: A measurement sample was prepared by diluting the reaction solution of HUVEC (human umbilical vein endothelial cells) with the sample to be evaluated at least 5 times with 1 ⁇ sample dilution (PDGF-BB level is sample). The optimum dilution factor for each sample was determined as appropriate). 4.
  • HUVEC human umbilical vein endothelial cells
  • Standard preparation 280 ⁇ L of 1 ⁇ sample diluent was added to a lyophilized standard vial to prepare a standard solution of 50 ng / mL. Gently mixed to completely dissolve the powder.
  • 4 ⁇ L PDGF-BB standard solution was added from a reconstituted standard vial to a tube containing 496 ⁇ L sample diluent. Each tube was pipetted with 400 ⁇ L of 1 ⁇ sample diluent. A dilution series was prepared using the stock solution standard solution as shown below. Each tube was thoroughly mixed before the next transfer. The 1 ⁇ sample diluent was used as the zero standard solution (0 pg / mL).
  • wash buffer contained visible crystals, warm to room temperature and mix gently until dissolved.
  • a concentrated solution of 20 mL of wash buffer was diluted with deionized water or distilled water to obtain 400 mL of 1 ⁇ wash buffer.
  • 100 ⁇ L of 1 ⁇ assay diluent was added to the vial to prepare a biotinylated antibody concentrate. Lightly mixed up and down with a pipette. The biotinylated antibody concentrate was diluted 80-fold with 1 ⁇ assay diluent (180 ⁇ L ⁇ 14400 ⁇ L) and used in step 4 of the assay procedure described below.
  • Streptavidin-HRP reagent was diluted 800-fold with 1 ⁇ assay diluent.
  • 20 ⁇ L of HRP-streptavidin concentrate was added to a tube containing 16 mL of 1 ⁇ assay diluent to prepare an 800-fold diluted HRP-streptavidin solution.
  • Assay procedure 1 Before use, all reagents and samples were returned to room temperature (18-25 ° C). All standards and samples were run in at least two runs. 2. 100 ⁇ L of each standard solution was added (see step 3 of the reagent preparation procedure) and the sample was dispensed into the appropriate wells. Wells were covered and incubated for 2.5 hours at room temperature with gentle shaking. 3. The solution was discarded and washed 4 times with 1 x wash buffer. Each well was flushed with wash buffer (300 ⁇ L) using a multi-channel pipette. After the final wash, all remaining wash buffer was removed by suction or decanting. The plate was turned upside down and a clean paper towel was used to thoroughly remove the water. 4.
  • Sensitivity 1 pg / mL
  • LLD lower limit of sensitivity or detection
  • FIG. 1 and Table 3 The ratio to the amount of protein obtained for the negative control (0.5% DMSO without sample) is shown in FIG. 1 and Table 3 below. From the results of FIGS. 1 and 3, it was found that the wasabi extract, chamomile extract, L-theanine, and hibiscus extract were particularly effective among the 52 types of samples, and these components were found to be particularly effective in PDGF-. It can be seen that it has the effect of enhancing the production of BB. In the figure, samples A to C show three samples out of 47 kinds of substances other than wasabi extract, chamomile extract, L-theanine, and hibiscus extract, but other substances are also sample A to C. Similarly, it did not meet the criteria, such as being lower than the negative control (DMSO) or showing no significant difference.
  • DMSO negative control
  • Experiment 3 Comparison with Amla extract and lingon berry extract
  • wasabi extract, chamomile extract, L-theanin, and hibiscus extract which showed a significant PDGF-BB production-enhancing effect in Experiment 2.
  • the amount of PDGF-BB protein was measured according to the above, and compared with the 15 ⁇ g / mL lingon berry extract and the 2 ⁇ g / mL Amla extract, which are known to have a PDGF-BB production-enhancing effect.
  • the amount of protein obtained for the control (15 ⁇ g / mL lingon berry extract) was 100.0 and the ratio to it was shown in FIG. 2, and the amount of protein obtained for the negative control (0.5% DMSO without sample) was 100.0.
  • the ratio is shown in FIG. From FIGS. 2 and 3, PDGF-BB is significantly higher than that of lingonberry extract and amla extract (Patent Document 2), which were previously known to have a high PDGF-BB production enhancing effect as well as a negative control. It was found that it exerts a production-enhancing ability.
  • wasabi extract, chamomile extract, L-theanine, and hibiscus extract are particularly effective in enhancing PDGF-BB production. These substances are expected to stabilize mesenchymal stem cells by enhancing PDGF-BB production, thereby activating the skin and suppressing aging.

Abstract

L'invention concerne un agent efficace pour favoriser la production de PDGF-BB, et un agent qui, à l'aide de cet agent, est efficace dans l'activation et l'effet anti-âge de la peau par stabilisation de cellules souches mésenchymateuses de la peau. Le promoteur de production de PDGF-BB, qui contient, en tant que composant efficace, l'un des extraits suivants : un extrait de wasabi, un extrait de camomille, de la L-théanine et un extrait d'hibiscus, est efficace dans l'activation de la peau et l'effet anti-âge par stabilisation de cellules souches mésenchymateuses.
PCT/JP2019/042689 2019-10-30 2019-10-30 Promoteur de production de facteur de croissance dérivé de plaquettes (pdgf)-bb, stabilisateur de cellules souches contenant ce cernier, et agent anti-âge de la peau contenant ces derniers WO2021084665A1 (fr)

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JP2021553970A JP7433337B2 (ja) 2019-10-30 2019-10-30 血小板由来成長因子（ｐｄｇｆ）－ｂｂ産生亢進剤、及びそれを含む幹細胞安定化剤、並びにそれらを含む皮膚抗老化剤
PCT/JP2019/042689 WO2021084665A1 (fr) 2019-10-30 2019-10-30 Promoteur de production de facteur de croissance dérivé de plaquettes (pdgf)-bb, stabilisateur de cellules souches contenant ce cernier, et agent anti-âge de la peau contenant ces derniers
JP2024016646A JP2024036562A (ja) 2019-10-30 2024-02-06 血小板由来成長因子（ｐｄｇｆ）－ｂｂ産生亢進剤、及びそれを含む幹細胞安定化剤、並びにそれらを含む皮膚抗老化剤

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