Hyaluronic acid receptor expression promoter, topical skin preparation containing same, and method for improving retention efficiency of high molecular weight hyaluronic acid

Abstract

To provide a hyaluronic acid receptor expression promoter that is safe for the human body and has a superior effect of promoting the expression of a hyaluronic acid receptor in skin tissue, and a topical skin preparation or a topical skin preparation set, and to provide a method for improving the retention efficiency of polymer hyaluronic acid in skin tissue.SOLUTION: A hyaluronic acid receptor expression promoter contains brown algae extract of Fucus (Fucaceae, Fucales).SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a hyaluronic acid receptor expression promoter and an external skin preparation containing the same. The present invention also relates to a method for improving the retention efficiency of high molecular weight hyaluronic acid in skin tissue. [Background technology]

[0002] Hyaluronic acid, also known as hyaluronan, is a type of linear glycosaminoglycan (mucopolysaccharide). Hyaluronic acid has high water-retaining properties and plays an important role in the body, including in skin, cartilage, and the eyeball.

[0003] In view of the above circumstances, research has been conducted into techniques for improving the penetration efficiency of hyaluronic acid into skin tissues and techniques for promoting the expression of hyaluronic acid receptors in skin tissues. For example, Patent Document 1 describes an external skin preparation containing (A) phospholipid, (B) glycol ether, and (C) hyaluronic acid, a hyaluronic acid derivative, or a salt thereof, which can improve the penetration efficiency of hyaluronic acid, a hyaluronic acid derivative, or a salt thereof into the skin. Patent Document 2 also describes a cosmetic active agent for improving epidermal hydration by improving the binding of hyaluronic acid to the skin cell surface, which contains a component selected from the group consisting of MnCl2, calcium gluconate, and sodium gluconate in combination with calcium chloride. This cosmetic active agent can increase the expression level of CD44, a hyaluronic acid receptor, in skin tissue. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2007-191396 [Patent Document 2] Patent No. 4708571 Summary of the Invention [Problem to be solved by the invention]

[0005] In view of the above circumstances, an objective of the present invention is to provide a novel agent that promotes the expression of hyaluronic acid receptors and a cosmetic method using the novel agent. [Means for solving the problem]

[0006] The present invention, which solves the above-mentioned problems, provides a hyaluronic acid receptor expression promoter, which contains a brown algae extract of the genus Fucus in the family Fucaceae of the order Fucales. In a preferred embodiment of the present invention, the brown algae extract is a Fucus serratus extract. According to the present invention, the expression of hyaluronic acid receptors in skin tissue can be promoted.

[0007] In a preferred embodiment of the present invention, the content of the seaweed extract in the hyaluronic acid receptor expression promoter is 0.0001% by mass or more on a dry mass basis. According to the present invention, the expression of hyaluronic acid receptors in skin tissue can be promoted.

[0008] In a preferred embodiment of the present invention, the hyaluronic acid receptor expression promoter is an agent for improving the retention efficiency in the epidermal layer of high molecular weight hyaluronic acid supplied from outside the skin tissue. According to the present invention, it is possible to improve the retention efficiency in the epidermal layer of high molecular weight hyaluronic acid supplied from outside the skin tissue.

[0009] The present invention, which solves the above-mentioned problems, is an external skin preparation containing the above-mentioned hyaluronic acid receptor expression promoter. According to the present invention, the expression of hyaluronic acid receptors in skin tissue can be promoted.

[0010] In a preferred embodiment of the present invention, the external skin preparation further contains high molecular weight hyaluronic acid. By combining a hyaluronic acid receptor expression enhancer with high molecular weight hyaluronic acid, the retention efficiency of hyaluronic acid in skin tissue can be improved.

[0011] In a preferred embodiment of the present invention, the external skin preparation is a pack. By using it as a pack, the hyaluronic acid receptor expression promoter can be applied to skin tissue for a certain period of time, further promoting the expression of hyaluronic acid receptors.

[0012] In a preferred embodiment of the present invention, the external skin preparation is an agent for promoting the expression of hyaluronic acid receptors.

[0013] The present invention, which solves the above-mentioned problems, provides a skin topical preparation set comprising a first skin topical preparation containing a brown algae extract of the genus Fucus in the family Fucaceae of the order Fucales, and a second skin topical preparation containing high molecular weight hyaluronic acid. In a preferred embodiment of the present invention, the skin external preparation set is an agent for improving the retention efficiency of high molecular weight hyaluronic acid in skin tissue. According to the present invention, it is possible to promote the expression of hyaluronic acid receptors in skin tissues and improve the retention efficiency of high molecular weight hyaluronic acid in skin tissues.

[0014] In a preferred embodiment of the present invention, the first external skin preparation is a pack. According to the present invention, an extract of brown algae belonging to the genus Fucus and the family Fucales of the order Fucales can be reliably applied to skin tissue for a certain period of time, thereby improving the retention efficiency of high molecular weight hyaluronic acid in skin tissue.

[0015] The present invention, which solves the above-mentioned problems, provides a method for improving the retention efficiency of high molecular weight hyaluronic acid in non-therapeutic skin tissue, by simultaneously or sequentially applying to skin tissue a composition containing a brown algae extract of the genus Fucus in the family Fucaceae of the order Fucales and a composition containing high molecular weight hyaluronic acid. In a preferred embodiment of the present invention, the above-mentioned external skin preparation set is used, and after the second external skin preparation is applied, the first external skin preparation is then applied to the same area. According to the present invention, the retention efficiency of high molecular weight hyaluronic acid in skin tissue can be improved. [Effects of the Invention]

[0016] According to the present invention, it is possible to provide a hyaluronic acid receptor expression promoter and a skin topical preparation or skin topical preparation set that are safe for the human body and have a high effect of promoting the expression of hyaluronic acid receptors in skin tissue. Furthermore, the present invention can provide a method for improving the retention efficiency of high molecular weight hyaluronic acid in skin tissue. [Brief explanation of the drawings]

[0017] [Figure 1] 1 is a graph showing the expression level of hyaluronic acid receptor (CD44) in cells cultured in the presence of 0.25% seaweed extract in Test Example 1. [Figure 2] 10 is a graph showing the rebound recovery time of the skin tissue after the test in Test Example 2, when the rebound recovery time of the skin tissue before the test is set to 1. DETAILED DESCRIPTION OF THE INVENTION

[0018] In the present invention, "skin tissue" refers to the epidermis layer, dermis layer, and subcutaneous tissue that constitute the skin.

[0019] <1> Hyaluronic acid receptor expression promoter and topical skin preparation containing the same The hyaluronic acid receptor expression promoter of the present invention contains a brown algae extract of the genus Fucus in the family Fucaceae of the order Fucales. According to the present invention, the expression of hyaluronic acid receptors in skin tissue can be promoted. Hereinafter, "an extract of brown algae of the genus Fucus, family Fucales, family Fucalaceae" will be simply referred to as "an extract of brown algae of the genus Fucus, family Fucales, family Fucalaceae."

[0020] Examples of brown algae of the Fucales family, Fucalaceae, and Fucus genus include Fucus ceranoides, Fucus distichus, and Fucus serratus. In the present invention, it is preferable to use Fucus serratus (hereinafter simply referred to as Fucus serratus) as the brown algae of the Fucales family, Fucalaceae, and Fucus genus.

[0021] Here, the brown algae extract of Fucus order Fucales family Fucales genus refers not only to the extract derived from Fucus order Fucales brown algae, but also to the general term of the fraction of these extracts, the fraction produced, the extract or fraction, and the solvent-removed product of the product, and can also contain extraction solvent within the range that does not inhibit the effect of promoting hyaluronic acid receptor expression.The brown algae extract of Fucales order Fucales family Fucales genus can be extracted from wild-grown or cultivated plants, or can be commercially available. When extracting brown algae extracts from the genus Fucus in the family Fucales of the order Fucales, any of the whole plant, roots, stems, or leaves of the brown algae may be used for the extraction procedure. It is also preferable to crush or shred these materials in advance to improve extraction efficiency. Suitable examples of the extraction solvent include one or more polar solvents selected from water, alcohols such as ethanol, isopropyl alcohol, and butanol, polyhydric alcohols such as 1,3-butanediol, polypropylene glycol, and glycerin, ketones such as acetone and methyl ethyl ketone, and ethers such as diethyl ether and tetrahydrofuran. Specific extraction methods for the above-mentioned extract include, for example, a method in which 1 to 30 parts by mass of solvent is added to 1 mass of the part of the plant body or its dried material used for extraction, followed by immersion for several days at room temperature or for several hours at a temperature near the boiling point, cooling to room temperature, removing insoluble matter and / or solvent as desired, and fractionating and purifying by column chromatography or the like, but the extraction method is not limited to this.

[0022] The content of brown algae extract of the Fucales family, Fucales genus in the hyaluronic acid receptor expression promoter is preferably 0.0001% by mass or more on a dry mass basis, and more preferably 0.0002% by mass or more on a dry mass basis. In addition, the content of brown algae extract of the Fucales order, Fucalaceae family, Fucal genus in the hyaluronic acid receptor expression promoter can be 0.5% by mass or less on a dry mass basis, and can be 0.3% by mass or less on a dry mass basis. When the brown algae of the genus Fucus in the family Fucales of the order Fucales is Fucusellatus, the content in the hyaluronic acid receptor expression promoter is preferably 0.025 to 0.01% by mass on a dry basis, and more preferably 0.004 to 0.006% by mass on a dry basis. According to the present invention, the expression of hyaluronic acid receptors in skin tissue can be promoted.

[0023] In a preferred embodiment of the present invention, the hyaluronic acid receptor expression promoter is an agent for improving the retention efficiency in the epidermal layer of high molecular weight hyaluronic acid supplied from outside the skin tissue. There have been technologies to increase the penetration efficiency of high molecular weight hyaluronic acid, but increasing the penetration efficiency makes it difficult to retain it in skin tissue (especially the epidermal layer). According to the present invention, the expression of hyaluronic acid receptors in skin tissue can be promoted, thereby improving the retention efficiency of high molecular weight hyaluronic acid supplied from outside the skin tissue in the epidermis layer.

[0024] The dosage form of the hyaluronic acid receptor expression promoter of the present invention is not particularly limited, and it can be in the form of an oral agent or an external agent for skin application by appropriately combining it with any component used in the formulation. From the viewpoint of exerting the effect of promoting hyaluronic acid receptor expression in skin tissue, particularly in the epidermal layer, the hyaluronic acid receptor expression promoter of the present invention is preferably in the form of an external preparation for skin.

[0025] When the hyaluronic acid receptor expression promoter of the present invention is made into an oral preparation, it is preferably made into the form of a food composition that contains the brown algae extract of the Fucales family, Fucales genus as an active ingredient.Specifically, it is preferably made into the form of a supplement that has the dosage form of general food, tablet, granule, drinkable agent, etc.

[0026] The content of brown algae extract of the Fucales family, Fucalaceae family in oral preparations is usually 0.1 mg or more, preferably 1 mg or more, and more preferably 10 mg or more per dose, in terms of dry mass of the extract, depending on the dosage form. Also, it is usually 2000 mg or less, preferably 1000 mg or less, more preferably 500 mg or less.

[0027] When used as an external preparation for skin, examples of the form include cosmetics, quasi-drugs, external medicines for skin, etc. Furthermore, there are no particular limitations on the dosage form. When promoting the expression of hyaluronic acid receptor in skin tissue, especially in epidermal layer, it is preferable to use the cosmetic form that can be used continuously.Specifically, it is preferable to use the form of face wash, cleanser, lotion, beauty essence, emulsion, cream, gel, sun care product, etc.It is also preferable to use the form of face pack. When used as a skin external preparation, the content of the brown algae extract of the Fucales family, Fucal family, Fucus genus can be the same as that of the hyaluronic acid receptor expression promoter.The same applies when the brown algae of the Fucales family, Fucal family, Fucus genus, Fucus serratus is used.

[0028] When the above-mentioned hyaluronic acid receptor expression promoter is used as a cosmetic, whitening ingredients, wrinkle-reducing ingredients, anti-inflammatory ingredients, extracts derived from plants and animals, and ingredients that are normally used in cosmetics other than the active ingredient may be blended as optional ingredients, within a range that does not impair the hyaluronic acid receptor expression promoting effect and safety to the human body. These optional components may be commercially available and used, or may be synthesized by known methods and used.

[0029] As for whitening ingredients, ingredients commonly used in cosmetics can be used without any particular restrictions. For example, 4-n-butylresorcinol, ascorbic acid glucoside, 3-O-ethyl ascorbic acid, tranexamic acid, arbutin, 1-triphenylmethylpiperidine, 1-triphenylmethylpyrrolidine, 2-(triphenylmethyloxy)ethanol, 2-(triphenylmethylamino)ethanol, 2-(triphenylmethyloxy)ethylamine, triphenylmethylamine, triphenylmethanol, triphenylmethane and aminodiphenylmethane, N-(o-toluoyl)cis Theic acid, N-(m-toluoyl)cysteic acid, N-(p-toluoyl)cysteic acid, N-(p-methoxybenzoyl)cysteic acid, N-benzoylserine, N-(p-methylbenzoyl)serine, N-(p-ethylbenzoyl)serine, N-(p-methoxybenzoyl)serine, N-(p-fluorobenzoyl)serine, N-(p-trifluoromethylbenzoyl)serine, N-(2-naphthoyl)serine, N-(4-phenylbenzoyl)serine, N-(p-methylbenzoyl)serine Examples of the benzoyl-O-methylserine include N-(p-methylbenzoyl)serine methyl ester, N-(p-methylbenzoyl)serine ethyl ester, N-(2-naphthoyl)serine methyl ester, N-benzoyl-O-methylserine, N-(p-methylbenzoyl)-O-methylserine, N-(p-methylbenzoyl)-O-acetylserine, and N-(2-naphthoyl)-O-methylserine.

[0030] The content of the whitening ingredient in the cosmetic is usually 0.0001 to 30% by mass, preferably 0.001 to 10% by mass, and more preferably 0.01 to 5% by mass (dry mass in the case of an extract).

[0031] As the wrinkle-reducing component, any component commonly used in cosmetics can be used without any particular limitation. Examples of vitamin A or its derivatives include retinol, retinal, retinoic acid, tretinoin, isotretinoin, tocopherol retinoate, retinol palmitate, and retinol acetate, as well as ursolic acid benzyl ester, ursolic acid phosphate, betulinic acid benzyl ester, and benzilic acid phosphate.

[0032] The content of the wrinkle-reducing ingredient in the cosmetic is usually 0.0001 to 30% by mass, preferably 0.001 to 10% by mass, and more preferably 0.01 to 5% by mass (dry mass in the case of an extract).

[0033] Examples of anti-inflammatory ingredients include kurarinone, glabridin, glycyrrhizinic acid, glycyrrhetinic acid, pantothenyl alcohol, etc., and preferred examples include glycyrrhizinic acid and its salts, alkyl glycyrrhetinates and their salts, and glycyrrhetinic acid and its salts. The content of the anti-inflammatory component in the cosmetic is usually 0.01 to 30% by mass, preferably 0.1 to 10% by mass, and more preferably 1 to 5% by mass (dry mass in the case of an extract).

[0034] Examples of extracts derived from plants and animals include akebia extract, asparagus extract, avocado extract, hydrangea extract, almond extract, arnica extract, aronia extract, apricot extract, ginkgo extract, fennel extract, udo extract, Siberian ginseng extract, emmeiso extract, phellodendron bark extract, Panax ginseng extract, white nettle extract, kakyō extract, pueraria root extract, chamomile extract, carrot extract, artemisia capillaris extract, licorice extract, kiwi extract, cucumber extract, and guava extract. , gardenia extract, kumazasa extract, walnut extract, black rice extract, chlorella extract, mulberry extract, kaempfer extract, alpinia zerumbet extract, gentian extract, rice extract, fermented rice extract, fermented rice bran extract, rice germ oil, salvia extract, soapwort extract, bamboo extract, zanthoxylum extract, Japanese pepper extract, shiitake mushroom extract, rehmannia root extract, lithospermum root extract, perilla extract, linden extract, meadowsweet extract, ginger extract, calamus root extract, horsetail extract, stevia extract, fermented stevia, yarrow Watermelon extract, peppermint extract, sage extract, mallow extract, cnidium extract, Swertia bristle extract, Morus alba extract, rhubarb extract, soybean extract, Chinese laurel extract, dandelion extract, clove extract, chili pepper extract, angelica extract, calendula extract, peach kernel extract, Houttuynia cordata extract, tomato extract, natto extract, carrot extract, garlic extract, hibiscus extract, burdock extract, lotus extract, parsley extract, birch extract, witch hazel extract, holly extract, cypress extract Preferred examples of extracts include loquat extract, coltsfoot extract, butterbur extract, poria extract, loofah extract, peppermint extract, linden extract, pine extract, skunk cabbage extract, melissa extract, mozuku extract, peach extract, cornflower extract, lily extract, coix seed extract, mugwort extract, lavender extract, apple extract, rooibos tea extract, lychee extract, lettuce extract, forsythia extract, astragalus extract, rosemary extract, Roman chamomile extract, and burnet extract.

[0035] The content (dry mass) of the optional animal and plant-derived extract in the cosmetic is usually 0.01 to 30 mass %, preferably 0.1 to 10 mass %, more preferably 0.3 to 3 mass %.

[0036] In addition to active ingredients, ingredients commonly used in cosmetics include polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, propylene glycol, dipropylene glycol, diglycerin, isoprene glycol, polyols such as 1,2-pentanediol, 2,4-hexylene glycol, 1,2-hexanediol, and 1,2-octanediol, fatty acid soaps (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, and triethanolamine alkyl sulfate. anionic surfactants such as esters, cationic surfactants such as stearyltrimethylammonium chloride, benzalkonium chloride, laurylamine oxide, imidazoline-based amphoteric surfactants (2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), betaine-based surfactants (alkyl betaine, amido betaine, sulfobetaine, etc.), amphoteric surfactants such as acyl methyl taurine, sorbitan fatty acid esters (sorbitan monostearate, sorbitan sesquioleate, etc.), glycerin fatty acids (monostearate, Glycerin phosphate, etc.), propylene glycol fatty acid esters (propylene glycol monostearate, etc.), hydrogenated castor oil derivatives, glycerin alkyl ether, POE sorbitan fatty acid esters (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.), POE sorbitan fatty acid esters (POE-sorbitan monolaurate, etc.), POE glycerin fatty acid esters (POE-glycerin monoisostearate, etc.), POE fatty acid esters (polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE 2-octyldodecyl ether, etc.), POE alkyl phenyl ethers (POE nonylphenyl ether, etc.), Pluronic (registered trademark) types, POE·POP alkyl ethers (POE·POP 2-decyltetradecyl ether, etc.), Tetronics, POE castor oil·hydrogenated castor oil derivatives (POE castor oil, POE hydrogenated castor oil, etc.), sucrose fatty acid esters, nonionic surfactants such as alkyl glucosides, moisturizing ingredients such as sodium pyrrolidone carboxylate, lactic acid, sodium lactate, which may be surface-treated,Powders such as mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, silicic anhydride (silica), aluminum oxide, and barium sulfate; inorganic pigments such as cobalt oxide, ultramarine, Prussian blue, and zinc oxide, which may be surface-treated; composite pigments such as sintered iron oxide and titanium dioxide, which may be surface-treated; pearling agents such as titanium dioxide, fish phosphate foil, and bismuth oxychloride, which may be surface-treated; and laked pigments such as Red 202, Red 228, Red 226, Yellow 4, Blue 404, Yellow 5, Red 505, Red 230, Red 223, Orange 201, Red 213, Yellow 204, Yellow 203, Blue 1, Green 201, and Purple 20. Examples of suitable organic pigments include organic dyes such as Red No. 1 and Red No. 204; organic powders such as polyethylene powder, polymethyl methacrylate, nylon powder, and organopolysiloxane elastomer; lower alcohols such as ethanol and isopropanol; vitamin A or a derivative thereof; vitamin B6 hydrochloride, vitamin B6 tripalmitate, vitamin B6 dioctanoate, vitamin B2 or a derivative thereof, vitamin B12, and vitamin B15 or a derivative thereof; vitamin E such as α-tocopherol, β-tocopherol, γ-tocopherol, and vitamin E acetate; vitamin D, vitamin H, pantothenic acid, pantethine, and pyrroloquinoline quinone.

[0037] The present invention also relates to an external skin preparation containing the above-mentioned hyaluronic acid receptor expression promoter. External skin preparations can be applied directly to skin tissue by spreading or applying, and can therefore promote the expression of hyaluronic acid receptors in skin tissue, particularly in the epidermal layer. In the present invention, "applying to skin tissue" means that the effect of the agent of the present invention is exerted in skin tissue (i.e., epidermis layer, dermis layer or subcutaneous fat layer).Specifically, for example, the hyaluronic acid receptor expression promoter or an external skin preparation containing the same is included in the form of being applied or stuck to the surface of skin tissue. Furthermore, when the above-mentioned hyaluronic acid receptor expression promoter or a topical skin preparation containing the same is applied or attached to the surface of skin tissue, it may be removed by rinsing with water or wiping after a certain period of time (for example, 1 to 10 minutes) has elapsed after application or attachment, or it may be removed without removing the agent.

[0038] The matters described above when the hyaluronic acid receptor expression promoter is used as an external preparation for skin can be applied to the present invention.

[0039] In the preferred embodiment of the present invention, the hyaluronic acid receptor expression promoter is preferably used as a pack among cosmetics.The form of pack is not particularly limited, and can be used as a face pack (sheet mask) that covers the whole face, or can be used as a pack that is specialized for specific areas such as around the eyes, nose, neck, hands, etc.

[0040] In a preferred embodiment of the present invention, the composition further comprises high molecular weight hyaluronic acid. According to the present invention, the expression of hyaluronic acid receptors is promoted using a brown algae extract of the Fucus genus, family Fucales, order Fucales, and high molecular weight hyaluronic acid is supplied from outside the skin tissue, thereby improving the retention efficiency of high molecular weight hyaluronic acid in the skin tissue, particularly in the epidermal layer.

[0041] In the present invention, the term "polymeric hyaluronic acid" includes polymeric hyaluronic acid and salts thereof. Examples of salts that constitute hyaluronic acid salts include sodium, potassium, calcium, ammonium, magnesium, and basic amino acid salts. Generally available commercial products can be used as the polymeric hyaluronic acid and its salts.

[0042] In a preferred embodiment of the present invention, the molecular weight of the high molecular weight hyaluronic acid is 100 to 2000 kDa, more preferably 200 to 1500 kDa. By setting the molecular weight of the high molecular weight hyaluronic acid within the above range, the water retention capacity of the skin tissue, particularly the epidermal layer, can be increased.

[0043] In a preferred embodiment of the present invention, the polymeric hyaluronic acid forms a polymeric hyaluronic acid-containing composite particle, and in a more preferred embodiment, the polymeric hyaluronic acid-containing composite particle is a composite particle of polymeric hyaluronic acid and a peptide. In a preferred embodiment of the present invention, the composite particles are nanoparticles. When high molecular weight hyaluronic acid and peptide form composite particles, the particle size of high molecular weight hyaluronic acid can be reduced, so that the penetration efficiency into the inside of skin tissue, especially into the epidermal layer, is improved.That is to say, by supplying high molecular weight hyaluronic acid, which has been formed into composite particles with peptide and has improved penetration ability, from the outside of skin tissue to the skin tissue that has been promoted by the effect of brown algae extract of Fucus family, Fucales order, from the outside of skin tissue, the effect (moisture retention) of high molecular weight hyaluronic acid can be efficiently exerted in skin tissue, especially in the epidermal layer.

[0044] In the present invention, the peptide is not particularly limited as long as it is not harmful to the human body, and may be a peptide consisting of the same amino acid residue or a peptide consisting of multiple types of amino acid residues. The peptide may be natural or synthetic, or may be a peptide obtained by decomposing a natural or synthetic protein. Chemically modified peptides may also be used.

[0045] Specific examples of peptides include water-soluble collagen, oligopeptide-24 (EGF-like synthetic peptide, 13 amino acid sequence, molecular weight 1271), acetyl decapeptide-3 (FGF-like synthetic peptide), oligopeptide-34 (TGFβ-like synthetic peptide, 13 amino acid sequence, molecular weight 1468), oligopeptide-20 (IGF-like synthetic peptide, 12 amino acid sequence, molecular weight 1476), polylysine, polyarginine, etc. Among these, water-soluble collagen, oligopeptide-20, and polyarginine are preferably used as peptides, and water-soluble collagen is more preferably used as peptides.

[0046] When the composite particles of high molecular weight hyaluronic acid and peptide are nanoparticles, the particle diameter of the composite particles can be 1000 nm or less. In a preferred embodiment of the present invention, the particle diameter of the composite particles of water-soluble collagen and peptide is 500 nm or less, more preferably, the particle diameter of the composite particles is 400 nm or less, and even more preferably, the particle diameter of the composite particles is 300 nm or less. The particle size of the composite particles can be measured by a light scattering method using a particle size distribution measuring device.

[0047] Composite particles of polymeric hyaluronic acid and peptide can be prepared by mixing polymeric hyaluronic acid and peptide in an aqueous solvent having a pH of 5 or less. In the present invention, "aqueous solvent" refers to water (e.g., purified water, ion-exchanged water, tap water, etc.) or an aqueous solution of a water-soluble component. The water-soluble component can be used without any particular limitation as long as it does not impair the effects of the present invention. Examples include additives such as powders, moisturizers, thickeners, and preservatives that are usually incorporated into cosmetics and quasi-drugs. When incorporating a water-soluble component with a high melting point, the component can be preheated to dissolve uniformly in water, but after the water-soluble component has dissolved, it is preferable to return the aqueous solution to about room temperature before using it to produce composite particles.

[0048] The upper limit of the pH of the aqueous solvent is 5 or less, preferably 4.5 or less, and more preferably 4.2 or less. The lower limit of the pH of the aqueous solvent is not particularly limited, but is preferably 1 or higher, more preferably 2 or higher, and even more preferably 2.5 or higher.

[0049] When water-soluble collagen is used as the peptide to be combined with high molecular weight hyaluronic acid, the pH of the aqueous solvent is preferably 4 or less, more preferably 3.5 or less, and even more preferably 3 or less. When water-soluble collagen is used as the peptide to be combined with high molecular weight hyaluronic acid, the lower limit of the pH is not particularly limited, but is preferably 2 or higher, more preferably 2.5 or higher, and even more preferably 2.7 or higher.

[0050] Furthermore, when oligopeptide-20 is used as the peptide to be combined with high molecular weight hyaluronic acid, the pH of the aqueous solvent is preferably 4.5 or less, more preferably 4 or less, and even more preferably 3.5 or less. When oligopeptide-20 is used as the peptide to be combined with high molecular weight hyaluronic acid, the lower limit of the pH is not particularly limited, but is preferably 2 or higher, more preferably 2.5 or higher, even more preferably 2.7 or higher, and more preferably 2.75 or higher.

[0051] Furthermore, when polylysine is used as the peptide to be combined with high molecular weight hyaluronic acid, the pH of the aqueous solvent is preferably 4.7 or less, more preferably 4.4 or less, and even more preferably 4.2 or less. When polylysine is used as the peptide to be combined with high molecular weight hyaluronic acid, the lower limit of the pH is not particularly limited, but is preferably 2 or more, more preferably 2.5 or more, even more preferably 3 or more, and more preferably 3.5 or more.

[0052] The form in which the anionic polymer and peptide are mixed in an aqueous solvent is not particularly limited, but a preferred embodiment is to prepare an aqueous solution of the anionic polymer and an aqueous solution of the peptide separately in advance and then mix them. By mixing the aqueous polymer solutions prepared separately in this manner, aggregation of the composite particles can be prevented. There are no particular limitations on the pH of the anionic polymer aqueous solution and the peptide aqueous solution that are prepared in advance, as long as the pH of the aqueous solvent after mixing falls within the above range.

[0053] If the pH of the aqueous solvent after mixing is outside the above range, the pH can be adjusted by adding an acidic aqueous solution. The acidic aqueous solution is not particularly limited as long as it can form composite particles, but preferred examples include aqueous solutions of organic acids such as citric acid, phosphoric acid, malic acid, and lactic acid. Alternatively, a polymeric hyaluronic acid solution adjusted to the desired pH may be mixed with an aqueous peptide solution, which simplifies the process of producing composite particles because there is no need to adjust the pH of the aqueous solvent separately.

[0054] When the aqueous solution of high molecular weight hyaluronic acid is prepared in advance, the concentration of high molecular weight hyaluronic acid in the aqueous solution is preferably 1.7 mM or less, more preferably 1 mM or less, and even more preferably 0.9 mM or less. By adjusting the concentration to such a level, unwanted aggregation of particles can be avoided when mixed with an aqueous peptide solution.

[0055] When an aqueous peptide solution is prepared in advance, the concentration of each peptide in the aqueous solution is preferably 5.1 mM or less, more preferably 3 mM or less, and even more preferably 2.7 mM or less. By adjusting the concentration to such a level, unnecessary aggregation of particles can be avoided when mixing with an aqueous high molecular weight hyaluronic acid solution. The molar concentration of a peptide referred to here is a value calculated by multiplying the molecular weight of each of the constituent amino acids by the constituent ratio, which is set to 1 mole.

[0056] The concentration of the high molecular weight hyaluronic acid in the aqueous solution after mixing is preferably 0.9 mM or less, more preferably 0.5 mM or less. The concentration of the peptide in the aqueous solution after mixing is preferably 2.7 mM or less, more preferably 1.5 mM or less.

[0057] As a mixing method, a method known in the art can be appropriately adopted. For example, a method of mixing each solution at once, a method of adding one solution dropwise to another solution, etc. In either case, it is preferable to mix the solutions while stirring them from the viewpoint of avoiding aggregation.

[0058] The above-mentioned external preparation for skin may be in any dosage form such as a liniment or a pack, but is preferably a pack. By using the skin external preparation as a pack, the brown algae extract of the Fucales family, Fucales genus can be applied to the skin tissue for a certain period of time, so that the effect of promoting the expression of hyaluronic acid receptors in the skin tissue, especially in the epidermis layer, can be fully exerted.This can improve the retention efficiency of high molecular weight hyaluronic acid supplied from outside the skin tissue in the epidermis layer. In addition, when high molecular weight hyaluronic acid or its salt, or the composite particles of these with peptide, can be applied to skin tissue for a certain period of time, so that high molecular weight hyaluronic acid can be supplied to the skin tissue in which the expression of hyaluronic acid receptor is promoted.Therefore, the retention efficiency of high molecular weight hyaluronic acid supplied from outside skin tissue in the epidermis layer can be improved.

[0059] <2> Skin topical preparation set The present invention also relates to an external skin preparation set comprising a first external skin preparation containing an extract of brown algae belonging to the genus Fucus and the family Fucales of the order Fucales, and a second external skin preparation containing high molecular weight hyaluronic acid. As mentioned above, the brown algae extract of Fucus family, Fucales order, has the effect of promoting the expression of hyaluronic acid receptor.Therefore, the first skin external preparation that contains above-mentioned brown algae extract promotes the expression of hyaluronic acid receptor in skin tissue, and the second skin external preparation that contains high molecular weight hyaluronic acid supplies high molecular weight hyaluronic acid to skin tissue, so that the retention efficiency of high molecular weight hyaluronic acid that is supplied from outside skin tissue can be improved in skin tissue, especially in epidermis layer.

[0060] The preferred form of the brown algae extract of the family Fucales, order Fucales, and genus Fucus in the first topical skin preparation, the content of the brown algae extract, and the dosage form are as described above. <1> The matters mentioned in the previous paragraph can be applied. The preferred form of the high molecular weight hyaluronic acid in the second skin topical preparation is as described above. <1> The matters mentioned in the previous paragraph can be applied.

[0061] A preferred embodiment of the present invention is a skin external preparation set for improving the retention efficiency of high molecular weight hyaluronic acid in skin tissue.

[0062] In a preferred embodiment of the present invention, the first external skin preparation containing an extract of brown algae belonging to the genus Fucus of the family Fucales of the order Fucales is a pack. According to the present invention, the brown algae extract can be reliably brought into contact with skin tissue (particularly the epidermal layer) for a certain period of time, and therefore the hyaluronic acid receptor expression effect can be fully exerted.

[0063] In a preferred embodiment of the present invention, the second external skin preparation containing high molecular weight hyaluronic acid is a serum or emulsion.

[0064] <3> Method for improving the retention efficiency of high molecular weight hyaluronic acid in skin tissue The present invention also relates to a method for improving the retention efficiency of high molecular weight hyaluronic acid in skin tissue. Here, the method for improving the retention efficiency of high molecular weight hyaluronic acid according to the present invention is a non-therapeutic method, and the non-therapeutic method is preferably a cosmetic method.

[0065] The method for improving the retention efficiency of high molecular weight hyaluronic acid according to the present invention involves simultaneously or successively applying a brown algae extract of the genus Fucus in the family Fucales of the order Fucales and high molecular weight hyaluronic acid to skin tissue. As mentioned above, the brown algae extract of the Fucus family of the Fucales order can promote the expression of hyaluronic acid receptor in skin tissue.Therefore, by applying the brown algae extract and high molecular weight hyaluronic acid to skin tissue, high molecular weight hyaluronic acid can be supplied to the skin tissue in which the expression of hyaluronic acid receptor is promoted.Therefore, according to the present invention, the retention efficiency of high molecular weight hyaluronic acid in skin tissue (especially epidermal layer) can be improved.

[0066] In the present invention, an example of a form in which a brown algae extract of the Fucales family, Fucal family, genus Fucus is applied "simultaneously" to skin tissue is a form in which a composition containing both a brown algae extract of the Fucales family, Fucales family, genus Fucus and high molecular weight hyaluronic acid is applied to skin tissue. In the present invention, the "sequential" application of a brown algae extract of the Fucales family, Fucal family, and high molecular weight hyaluronic acid to skin tissue can be achieved by applying a first composition containing a brown algae extract of the Fucales family, Fucal family, and a second composition containing high molecular weight hyaluronic acid to skin tissue. In this case, the order of application of the first composition and the second composition to skin tissue does not matter.

[0067] In a preferred embodiment of the present invention, the brown algae extract of the genus Fucus, family Fucales, order Fucales, is contained in a skin topical preparation, in a more preferred embodiment, in a cosmetic preparation, and in an even more preferred embodiment, in a pack preparation. According to the present invention, brown algae extract of the genus Fucus in the family Fucales of the order Fucales can be reliably brought into contact with the epidermal layer (including the stratum corneum) of skin tissue for a certain period of time, thereby fully exerting the effect of promoting hyaluronic acid receptor expression. Regarding the composition containing the extract of brown algae of the Fucales family, Fucales, <1> The matters mentioned in the previous paragraph can be applied.

[0068] In a preferred embodiment of the present invention, the high molecular weight hyaluronic acid is contained in an external skin preparation, more preferably in a cosmetic preparation, and even more preferably in a beauty serum or emulsion. Regarding the composition containing high molecular weight hyaluronic acid, <1> The matters mentioned in the previous paragraph can be applied.

[0069] In a preferred embodiment of the present invention, the above-mentioned external skin preparation set is used to improve the retention efficiency of high molecular weight hyaluronic acid. Specifically, a first topical skin preparation containing a brown algae extract of the Fucales family of the Fucales order is applied to skin tissue, and then a second topical skin preparation containing high molecular weight hyaluronic acid is applied to the skin tissue.Preferably, the above topical skin preparation set is used, in which the first topical skin preparation is a pack and the second topical skin preparation is a serum or emulsion. According to the present invention, by applying a second skin topical preparation containing high molecular weight hyaluronic acid to skin tissue in which the expression of hyaluronic acid receptors has been promoted by the brown algae extract, and supplying high molecular weight hyaluronic acid from outside the skin tissue, the retention efficiency of high molecular weight hyaluronic acid in the skin tissue (especially high molecular weight hyaluronic acid supplied from outside the skin tissue) can be improved.

[0070] <4> Composition and cosmetic method comprising polymeric hyaluronic acid-containing composite particles and a hyaluronic acid receptor expression promoter The present invention also relates to a composition and a cosmetic method comprising a polymeric hyaluronic acid-containing composite particle and a hyaluronic acid receptor expression promoter. According to the present invention, it is possible to improve the retention efficiency of high molecular weight hyaluronic acid (particularly high molecular weight hyaluronic acid supplied from outside the skin tissue) in the skin tissue (particularly the epidermal layer).

[0071] Regarding the polymeric hyaluronic acid-containing composite particles, <1> The matters mentioned in the previous paragraph can be applied.

[0072] In the present invention, the hyaluronic acid receptor expression enhancer can be any composition known in the art that has the effect of enhancing hyaluronic acid receptor expression, without any particular limitation.For example, salvia leaf extract, pomegranate flower extract, pomegranate peel extract, etc. can be used. Also, the above <1> The hyaluronic acid receptor expression enhancers described in the above can also be used. the above <1> A preferred embodiment of the hyaluronic acid receptor expression enhancer described in the above is <1> The matters mentioned in the previous paragraph can be applied.

[0073] Furthermore, the cosmetic method of the present invention is a method in which polymeric hyaluronic acid-containing composite particles and a hyaluronic acid receptor expression enhancer are applied to skin tissue. A preferred embodiment of the cosmetic method of the present invention is <3> The items mentioned above can be provided. [Example]

[0074] The present invention will be described in more detail below with reference to examples, but the technical scope of the present invention is not limited to the following examples.

[0075] <Test Example 1> Selection of extracts with hyaluronic acid receptor expression promoting effect In this test example, an extract was selected that has the effect of promoting the expression of hyaluronic acid receptors in skin tissue.

[0076] Test Example 1 was carried out in the following manner. (1) Normal human epidermal cells were placed in a 24-well plate at 3 × 10 4 The cells were seeded in a medium at 100 cells / well. Humedia-KG2 (Kurabo Industries, Ltd.) was used as the medium. (2) The cells were cultured at 37°C and 5% CO2 for 24 hours. (3) The medium was removed, and Humedia-KG2 containing the extracts listed in Table 1 below at concentrations of 0.125%, 0.25%, and 0.5% was added. As a control, a medium containing glycerin was added in the same manner. (4) The cells were cultured at 37°C and 5% CO2 for 24 hours. (5) The medium was removed and washed with PBS. (6) The cytotoxicity of each extract was examined using Cell Counting Kit-8 (Dojindo Laboratories, Inc.). Furthermore, after cell recovery and mRNA extraction using a known method, the gene expression level of the hyaluronic acid receptor CD44 was measured and analyzed by RT-qPCR. Additionally, the gene expression level of GAPDH was measured and analyzed as an internal standard.

[0077] In RT-qPCR, Hs_CD44_1_SG QuantiTect Primer Assay (QIAGEN) was used as a primer to measure the expression level of CD44. Furthermore, Hs_GAPDH_2_SG QuantiTect Primer Assay (QIAGEN) was used as a primer for measuring the expression level of GAPDH.

[0078] The results of Test Example 1 are shown in Table 1 and Figure 1. Table 1 shows the value obtained by dividing the gene expression level of hyaluronic acid receptor (CD44) in cells cultured in the presence of each extract solvent (control) by the gene expression level of GAPDH in the same cells, where the value obtained by dividing the gene expression level of hyaluronic acid receptor (CD44) in cells cultured in the presence of each extract solvent (control) by the gene expression level of GAPDH in the same cells is set to 1. Figure 1 is a graph showing the value obtained by dividing the gene expression level of hyaluronic acid receptor (CD44) in cells cultured in the presence of each extract solvent (control) by the gene expression level of GAPDH in the same cells, where the seaweed extract concentration is 0.25%. In this test example, the concentration of Fucus Serratus extract in the seaweed extract was 2% by mass. In Table 1, "%" means "% by mass."

[0079] [Table 1]

[0080] Although the results are not shown, confirmation of cytotoxicity revealed that none of the plant extracts used in this test example had cytotoxicity at any concentration.

[0081] As shown in Table 1 and Figure 1, the expression level of the hyaluronic acid receptor (CD44) in the cells was significantly increased only when the seaweed extract was added. These results suggest that seaweed extracts, specifically brown algae extracts from the Fucales family of the Fucales order, have the effect of promoting the expression of hyaluronic acid receptors in cells. These results also suggest that the use of seaweed extracts makes it possible to provide a hyaluronic acid receptor expression promoter and a topical skin preparation containing the same that are non-cytotoxic and safe, as described above.

[0082] Furthermore, as shown in Figure 1, the expression level of hyaluronic acid receptors was promoted when the seaweed extract concentration was 0.25%. As mentioned above, the concentration of Fucus Serratus extract in the seaweed extract was 2%, so in the sample of this test example in which the concentration of seaweed extract was 0.25%, the concentration of Fucus Serratus extract was 0.005%. Table 1 and Figure 1 reveal that the concentration of Fucus Serratus extract is preferably 0.025 to 0.01% (0.125 to 0.5% as seaweed extract), and more preferably 0.004 to 0.0.006% (0.2 to 0.3% as seaweed extract).

[0083] <Test Example 2> Verification of the combined effect of brown algae extract from the Fucales family and high molecular weight hyaluronic acid In this test example, the effect of using a brown algae extract of the Fucus genus in the Fucales family of the Fucales order in combination with high molecular weight hyaluronic acid was examined.

[0084] Test Example 2 was carried out as follows: In this test example, a skin topical preparation set was provided, in which a sheet mask (i.e., a pack) containing 0.005% Fucus Serratus extract was used as the first skin topical preparation containing a brown algae extract of the Fucus family of the Fucales order, and a beauty serum containing 0.5 mM of high molecular weight hyaluronic acid was used as the second skin topical preparation containing high molecular weight hyaluronic acid. <Test Method> (1) The above-mentioned skin topical preparation set was provided to 12 subjects in their 40s and 50s, and they were instructed to use the skin topical preparation set according to the prescribed instructions. (2) The following method of use was instructed. That is, on the first day of the test, only the sheet mask was used, and for the following six days, only the serum was used. This one week (Day 1: only the sheet mask, Days 2 to 7: only the serum) was counted as one cycle, and a total of four cycles were used. In other words, the test period was four weeks.

[0085] Before the test began, the rebound time (the time it takes for the face and cheek area to return to its original position after being pressed) was measured using a ballistometer for the face and cheek area before the test, and after the test, the rebound time was measured for the same face and cheek area in the same way. Figure 2 shows the average rebound time of the skin tissue after the test (i.e., after using the topical skin preparation set), assuming that the average rebound time before the test (i.e., before using the topical skin preparation set) was 1. A short rebound recovery time indicates that the skin tissue has a strong rebound elasticity.

[0086] As shown in Figure 2, the average rebound time after use was significantly shorter than that before use. This result suggests that use of the topical skin preparation set of the present invention increases the rebound elasticity of skin tissue.

[0087] As shown in Test Example 1, an extract of brown algae belonging to the Fucales order, Fucalaceae family, and Fucus genus increases the expression level of CD44, a hyaluronic acid receptor, in cells. It is also known that in order to maintain the elasticity of skin tissue, it is necessary to increase or maintain the amount of hyaluronic acid present in skin tissue (particularly the epidermal layer). From the above, it was suggested that if the brown algae extract of the genus Fucus, family Fucales, order Fucales of the present invention, particularly Fucus Serratus extract, can improve the expression level of hyaluronic acid receptors (CD44) in cells, the retention efficiency of hyaluronic acid in skin tissue (particularly hyaluronic acid supplied from outside the skin tissue) can be improved, and as a result, the rebound elasticity of the skin tissue can be improved. That is, the external skin preparation set according to the present invention can be used to improve the retention efficiency of high molecular weight hyaluronic acid.

[0088] Furthermore, this test example revealed that a cosmetic method can be provided that improves the resilience of skin tissue by applying high molecular weight hyaluronic acid-containing composite particles and a hyaluronic acid receptor expression promoter to skin tissue.

[0089] A formulation example of the hyaluronic acid receptor expression promoter according to the present invention is shown below: This formulation example can be produced by a method known in the art. In this formulation example, the seaweed extract contains 2% by mass of Fucus Serratus extract.

[0090] [Table 2] [Industrial Applicability]

[0091] According to the present invention, it is possible to provide a hyaluronic acid receptor expression promoter and a skin topical preparation or skin topical preparation set that are safe for the human body and have a high effect of promoting the expression of hyaluronic acid receptors in skin tissue. Furthermore, the present invention can provide a method for improving the retention efficiency of high molecular weight hyaluronic acid in skin tissue.

Claims

1. A hyaluronic acid receptor expression promoter in skin tissue, comprising a brown algae extract from the genus Fucus in the family Fucales, family Fucalaceae.

2. The hyaluronic acid receptor expression promoter according to claim 1, wherein the brown algae extract is Fucus serratus extract.

3. The hyaluronic acid receptor expression promoter according to claim 1 or 2, wherein the content of the brown algae extract in the hyaluronic acid receptor expression promoter is 0.0001% by mass or more.

4. The hyaluronic acid receptor expression promoter according to any one of claims 1 to 3, which is an agent for improving the retention efficiency of high molecular weight hyaluronic acid supplied from outside the skin tissue in the epidermis layer.

5. A skin external preparation comprising the hyaluronic acid receptor expression promoter according to any one of claims 1 to 4, and containing a brown algae extract of the genus Fucus in the family Fucales, family Fucalaceae, and polymeric hyaluronic acid-containing composite particles as active ingredients.

6. A topical skin preparation as described in claim 5, wherein the polymeric hyaluronic acid-containing composite particles are composite particles of polymeric hyaluronic acid and a peptide.

7. A topical skin preparation described in claim 5 or 6, wherein the polymeric hyaluronic acid-containing composite particles are nanoparticles.

8. The external skin preparation according to any one of claims 5 to 7, which is a pack.

9. The skin external preparation set comprises a first skin external preparation containing a brown algae extract of the genus Fucus in the family Fucales, family Fucaceae, order Fucales, and a second skin external preparation containing high molecular weight hyaluronic acid.

10. The external skin preparation set according to claim 9, for improving the retention efficiency of high molecular weight hyaluronic acid in skin tissue.

11. The external skin preparation set according to claim 9 or 10, wherein the first external skin preparation is a pack.

12. A method for improving the retention efficiency of high molecular weight hyaluronic acid in non-therapeutic skin tissue, comprising using the skin topical preparation set described in claim 11, applying the first skin topical preparation to the area, and then applying the second skin topical preparation to the area.

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