JP2005263794A - Collagen synthesis acceleration composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a collagen synthesis acceleration composition and a collagen synthesis accelerator which are highly safe and superior. <P>SOLUTION: The superior collagen synthesis acceleration composition or collagen synthesis accelerator uses at least one kind selected from the group consisting of ascorbic acid, an ascorbic acid derivative, and their salts in combination with δ-tocopheryl retinolate and enhances the collagen synthesis acceleration action to remarkably increase the amount of collagen synthesized. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to at least one selected from the group consisting of ascorbic acid, ascorbic acid derivatives and salts thereof (hereinafter collectively referred to as “ascorbic acids” in the present specification) and δ-tocopheryl. The present invention relates to a collagen synthesis accelerator comprising retinoate.

  Collagen is a major protein that constitutes the connective tissue of animals, and collagen occupies nearly 30% of the total protein of the human body. Since the main function of collagen is in the formation of a skeletal structure of living tissue, it is widely distributed in skin, cartilage tissue, cornea, heart, liver, etc. as the main component constituting the skeletal structure of animal tissue form. Collagen acts specifically on cell adhesion, cell differentiation and proliferation, and also has a role as a regulator of cell function. Collagen reduction is caused by corneal disorders such as corneal ulcer, rheumatism, It may cause various diseases such as arthritis, osteoarthritis, joint disorders such as osteoarthritis, and inflammatory diseases.

  In the cutaneous dermal extracellular matrix, collagen fibers form a mesh-like bundle to maintain the tissue morphology. Collagen fibers become thick and linear fiber bundles when they mature and proliferate and crosslink formation proceeds, giving moderate tension on young skin. However, in aging skin, as fibroblast activity decreases, collagen fibers in the dermal extracellular matrix are remarkably reduced and abnormal aging crosslinks are formed, making it stiff and rich in its original elasticity. The tension will be lost. As a result, wrinkles and tarmi are formed on the skin. Changes in the fiber bundle structure of hairless mice due to photoaging have been studied in detail (Fragrance Journal, 4, p36-37, 1998), so that wrinkles are formed in hairless mice irradiated with UVB, which is consistent with the formation of wrinkles. It has been shown that the collagen fiber bundle structure collapses and the skin elasticity decreases. It is also known that collagen is excellent in water retention function.

  In order to improve the state caused by the decrease in collagen, various collagen synthesis promoting substances have been found. For example, retinoic acid (R. Marks et al, British Journal of Dermatology, 122, 91, 1990), three amino acids consisting of glycine, proline and alanine (Japanese Patent Laid-Open No. 7-194375), licorice, Sakuhakuhi, aloe, sugiina , Plant extracts such as goldfish, duckweed, mussel or gentian (Japanese Patent Laid-Open No. 2001-206835), TGF-β, ascorbic acids and the like are known. Ascorbic acids have a cell activation effect by promoting the synthesis of biological components such as collagen.

  By the way, among vitamin A acid tocopherol ester (tocopheryl retinoate) which is an ester compound of vitamin A acid and tocopherol, α-tocopheryl retinoate has an anti-aging effect, dermatitis (burn ulcer, skin ulcer, zonal) Herpes zoster, cutaneous pruritus, cutaneous keratosis, cracks, redheads, etc.) are known to have therapeutic effects (Patent Documents 1 and 2), and δ-tocopheryl retinoate has an action to remove active oxygen (Non-Patent Document 1) It has been known. However, these were not fully satisfactory in terms of safety and effectiveness.

JP-A-54-92967 JP 61-207332 A Abstracts of the 96th Fragrance Journal Seminar p20-22, 2003

  An object of the present invention is to provide a highly safe composition for promoting collagen synthesis and a collagen synthesis promoter.

  The present inventor has found that there is a synergistic collagen synthesis promoting action by combining δ-tocopheryl retinoate with at least one selected from the group consisting of ascorbic acid, ascorbic acid derivatives and salts thereof. The present invention has been completed.

That is, this invention is the invention hung up below.
(1) A collagen synthesis promoter containing ascorbic acid, at least one selected from the group consisting of ascorbic acid derivatives and salts thereof, and δ-tocopheryl retinoate as an active ingredient,
(2) A composition for promoting collagen synthesis, comprising at least one selected from the group consisting of ascorbic acid, ascorbic acid derivatives and salts thereof, and δ-tocopheryl retinoate,
(3) The composition for promoting collagen synthesis is an anti-wrinkle composition, an anti-tarmi composition, a composition for preventing or treating joint disorders, and a composition for preventing or treating inflammatory diseases. A composition for promoting collagen synthesis,
(4) The composition for promoting collagen synthesis according to (2), comprising at least one selected from the group consisting of ascorbic acid, ascorbic acid derivatives and salts thereof, and δ-tocopheryl retinoate as a collagen synthesis promoter. Stuff,
(5) Containing 0.0005-2.0 parts by weight of δ-tocopheryl retinoate with respect to 1 part by weight of at least one selected from the group consisting of ascorbic acid, ascorbic acid derivatives and salts thereof A composition for promoting collagen synthesis as described in (2),
(6) A method for increasing the amount of collagen synthesis in cells by using δ-tocopheryl retinoate in combination with at least one selected from the group consisting of ascorbic acid, ascorbic acid derivatives and salts thereof.

  According to the present invention, a collagen synthesis promoter containing at least one selected from the group consisting of ascorbic acid, ascorbic acid derivatives and salts thereof and δ-tocopheryl retinoate as active ingredients can be provided. Further, by using both ascorbic acids and δ-tocopheryl retinoate, the amount of collagen synthesis in the cells can be remarkably increased. Furthermore, a composition for promoting collagen synthesis containing ascorbic acids and δ-tocopheryl retinoate prevents collagen decrease, and an anti-wrinkle composition, an anti-tarmi composition, and a composition for preventing or treating joint disorders. It is useful as a composition for preventing or treating inflammatory diseases.

  The ascorbic acid, ascorbic acid derivative and salts thereof of the present invention are not particularly limited as long as they are used in the field of pharmaceuticals, quasi drugs or cosmetics. Specific examples of the ascorbic acid derivatives include L-ascorbic acid phosphates such as L-ascorbic acid monophosphate, L-ascorbic acid diphosphate and L-ascorbyl triphosphate; ascorbyl palmitate, Examples include fat-soluble ascorbic acid derivatives such as ascorbyl stearate and ascorbyl dipalmitate; sugar derivatives such as ascorbic acid glucoside; L-ascorbic acid-2-sulfate, L-ascorbic acid-2-sulfonate, and the like.

  In the present invention, the above ascorbic acid, ascorbic acid derivatives and salts thereof may be used alone or in any combination of two or more. Among the above ascorbic acid, ascorbic acid derivative and salts thereof of the present invention, L-ascorbic acid, L-ascorbic acid phosphate ester derivative, ascorbyl palmitate, tetracordylhexyldecanoate, ascorbyl glucoside, L -Ascorbic acid-2-sulfate ester, ascorbic acid-2-glucoside and salts thereof, L-ascorbic acid and L-ascorbine are particularly preferable because of their high safety and action effect on the skin and mucous membranes. Acid monophosphates or salts thereof, ascorbyl palmitate, ascorbyl tetra-2-hexyldecanoate, and ascorbic acid-2-glucoside. In the present invention, any of d-form, l-form, and dl-form of ascorbic acids can be used.

  Examples of salts of ascorbic acid and ascorbic acid derivatives used in the present invention include various alkali metal salts such as sodium and potassium, alkaline earth metal salts such as magnesium, calcium and barium, and polyvalent metal salts such as aluminum. Metal salts: Examples include ammonium salts such as ammonium and tricyclohexylammonium, and various alkanolamine salts such as monoethanolamine, diethanolamine, triethanolamine, monoisopropanolamine, diisopropanolamine, and triisopropanolamine.

  The amount of ascorbic acid to be blended in the composition for promoting collagen synthesis of the present invention is not particularly limited, but in order to obtain the effects of the present invention, it is usually 0.00001% by weight or more, preferably 0.8%. 001% by weight or more, more preferably 0.01% by weight or more, further preferably 0.1% by weight or more, particularly preferably 1% by weight or more, and the upper limit of blending is preferably 30% by weight or less from the viewpoint of stability. More preferably, it is 20% by weight or less, particularly preferably 10% by weight or less.

  The δ-tocopheryl retinoate of the present invention is an ester compound of δ-tocopherol and vitamin A acid, and is produced by a known method (Japanese Patent Laid-Open No. 4-244076 etc.) or obtained as a commercial product. Any of d-form, l-form, and dl-form can be used.

  The amount of δ-tocopheryl retinoate to be blended in the composition for promoting collagen synthesis of the present invention is not particularly limited, but is preferably 0.0001% by weight based on the entire composition in order to achieve the effects of the invention. Or more, more preferably 0.0005% by weight or more, further preferably 0.001% by weight or more, particularly preferably 0.005% by weight or more, more preferably 0.05% by weight or more, and still more preferably 0.2% by weight. The upper limit of blending is preferably 10% by weight or less, more preferably 5% by weight or less, and further preferably 2% by weight or less.

  In the present invention, ascorbic acids and δ-tocopheryl retinoate are used in a ratio by weight, and usually δ-tocopheryl retinoate is in the range of 0.0005 to 40 parts by weight with respect to 1 part by weight of ascorbic acid. , Preferably 0.001 to 25 parts by weight, more preferably 0.001 to 20 parts by weight, still more preferably 0.01 to 20 parts by weight, still more preferably 0.05 to 20 parts by weight, particularly preferably 0. It is 1-20 weight part, More preferably, it is the range of 1-20 weight part.

  The composition for promoting collagen synthesis of the present invention has the purpose of enhancing or supplementing various actions of ascorbic acids or δ-tocopheryl retinoate in addition to the aforementioned ascorbic acids and δ-tocopheryl retinoate, or collagen synthesis Whitening ingredients, anti-inflammatory ingredients, antibacterial ingredients, cell activation ingredients, astringent ingredients, antioxidant ingredients, acne-improving ingredients, collagen and other biological ingredient synthesis promoting ingredients, blood circulation to add other useful effects to the promoting composition Various components such as an accelerating component, a moisturizing component and an anti-aging component can be blended in one kind or in combination of two or more kinds. Preferred are one or more of whitening components, anti-inflammatory components, antibacterial components, cell activation components, astringent components, antioxidant components, anti-aging components or moisturizing components. These components are not particularly limited as long as they are conventionally used in the pharmaceutical, quasi-drug or cosmetic field, and will be used in the future, and arbitrary components can be appropriately selected and used.

  Examples of whitening components include placenta; arbutin; kojic acid; ellagic acid; phytic acid; lucinol; chamomile ET; vitamin A or a derivative thereof, vitamin E or a derivative thereof, vitamins such as pantothenic acid or a derivative thereof, and the like. . Of these, preferred are pantothenic acid or its derivatives, ellagic acid, phytic acid, vitamin A or its derivatives, vitamin E or its derivatives. These whitening components may be used alone or in combination of two or more.

Plant components having a whitening effect may be used as a whitening component, such as Iris (iris), almond, aloe, ginkgo, oolong tea, Ages, Ogon, Ouren, Hypericum persica, Adrianthus, seaweed, cuckoo, gardenia, Kujin, chlorella, gobaishi, wheat, rice, rice haiga, oryzanol, rice bran, saishin, salamander, perilla, peony, senkyu, sakuhaku, soybeans, natto, tea, toki, eucalyptus, garlic, hamamelis, safflower, buttonpi, yokuinin, Toki, amethyst, asenyaku, acevi bracken, oyster mushroom, enoki, oyster (Diospyros kaki), cowpea, black bean, gentian, gendin, salsa, sweet bean, shokuma, jujuro, sage, senko, radish, azalea, tsuku Ingredients derived from plants such as shigigi, toshin, nigaki, parsley, holly, hops, malbahagi, clove and licorice can be mentioned. Preferably, Iris (Iris), Aloe, Ginkgo, Oolong tea, Ages, Ogon, Oulen, Hypericum, Olysam, Seaweed, Cuckoo, Gardenia, Kujin, Gobaishi, Wheat, Rice, Rice bran, Saishin, Salamander, Perilla, Peonies, Senkyu , Sakuhakuhi, Tea, Toki, Toki-Senka, Hamelis, Safflower, Buttonpi, Yokuinin, Amethyst, Asenyaku, Enoki, Oyster (Diospyros kaki), Cattle, Black Bean, Gentian, Salsa, Soyagen, Juju, Sage, Zenko, Daikon, Tsuji It is a plant-derived component of Tsukuhashigi, Toshin, Nigaki, Parsley, Holly, Hops, Clove, Licorice and Toki, and more preferably Iris (Iris), Aloe, Ginkgo, Ages, Ogon, Oulen, Otogi Riso, gardenia, cucumber, rice, rice bran, saishin, peonies, senkyu, sakuhakuhi, tea, touki, eucalyptus, hamamelis, safflower, buttonpi, amethyst, asenyaku, enoki, oyster (Diospyros kaki), sage, radish, azalea, azalea It is a plant-derived component of hops, licorice and yokuinin.
When these plant components are used in the composition for promoting collagen synthesis of the present invention, the form of the plant components is not particularly limited, but can be generally used in the form of a plant extract (plant extract), an essential oil, or the like. In addition, the inside of () in the said plant component is the kind of plant, an alias, or a crude drug name.

When using the said whitening component, the ratio mix | blended with the composition for collagen synthesis promotion becomes like this. Preferably it is 0.0003 to 10 weight%, More preferably, it is 0.01 to 5 weight%. Further, the whitening component is 0.001 to 1000 parts by weight, preferably 0.005 to 500 parts by weight, more preferably 0.01 to 100 parts by weight with respect to 100 parts by weight of ascorbic acids contained in the composition for promoting collagen synthesis. It is desirable to mix so that it may become a ratio.
When a plant component having a whitening effect is used as the whitening component, one or two or more kinds can be used in any combination depending on the purpose. When the plant component is used as a whitening component, the blending ratio in the composition for promoting collagen synthesis is usually 0.00001 to 20% by weight, preferably 0.0001 to 15% by weight in terms of an extract such as extract or essential oil. More preferably, it is 0.001 to 10% by weight. Moreover, it is desirable that the plant component is blended so as to have a ratio of 0.0001 to 100 parts by weight, preferably 0.001 to 50 parts by weight with respect to 100 parts by weight of ascorbic acids.

  Anti-inflammatory components include allantoin, calamine, glycyrrhizic acid or derivatives thereof, glycyrrhetinic acid or derivatives thereof, zinc oxide, guaiazulene, tocopherol acetate, pyridoxine hydrochloride, menthol, camphor, turpentine oil, indomethacin, salicylic acid or derivatives thereof. . Preferred are allantoin, glycyrrhizic acid or a derivative thereof, glycyrrhetinic acid or a derivative thereof, guaiazulene, or menthol.

  When using the said anti-inflammatory component, the ratio mix | blended with the composition for collagen synthesis promotion becomes like this. Preferably it is 0.0003 to 10 weight%, More preferably, it is 0.01 to 5 weight%. Further, the anti-inflammatory component is 0.001 to 1000 parts by weight, preferably 0.005 to 500 parts by weight, more preferably 0.01 to 100 parts by weight based on 100 parts by weight of ascorbic acids contained in the composition for promoting collagen synthesis. It is desirable to blend so as to have a proportion by weight.

  Antibacterial components include chlorhexidine, salicylic acid, benzalkonium chloride, acrinol, ethanol, benzethonium chloride, cresol, gluconic acid and derivatives thereof, popidone iodine, potassium iodide, iodine, isopropylmethylphenol, triclocarban, triclosan, photosensitizer 101 Photosensitive element 201, paraben, phenoxyethanol, 1,2-pentanediol, alkyldiaminoglycine hydrochloride and the like. Preferably, benzalkonium chloride, benzethonium chloride, gluconic acid and its derivatives, isopropylmethylphenol, triclocarban, triclosan, photosensitizer 101, photosensitizer 201, paraben, phenoxyethanol, 1,2-pentanediol, alkyldiamino hydrochloride Examples include glycine. More preferred are benzalkonium chloride, gluconic acid and its derivatives, benzethonium chloride, and isopropylmethylphenol.

  When the antibacterial component is used, the proportion of the composition for promoting collagen synthesis is preferably 0.0003 to 10% by weight, more preferably 0.01 to 5% by weight. Further, the antibacterial component is 0.001 to 1000 parts by weight, preferably 0.005 to 500 parts by weight, more preferably 0.01 to 100 parts by weight with respect to 100 parts by weight of ascorbic acids contained in the composition for promoting collagen synthesis. It is desirable to blend so as to have a ratio of parts.

  Cell activation components include amino acids such as γ-aminobutyric acid and ε-aminocaproic acid: retinol, thiamine, riboflavin, pyridoxine hydrochloride, pantothenic acids and other vitamins: glycolic acid, α-hydroxy acids such as lactic acid: tannin, Examples include flavonoids, saponins, allantoin, and photosensitizer 301. Preferred are amino acids such as γ-aminobutyric acid and ε-aminocaproic acid: vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride and pantothenic acids.

  When the cell activation component is used, the proportion to be added to the composition for promoting collagen synthesis is preferably 0.0003 to 10% by weight, more preferably 0.01 to 5% by weight. Further, the cell activation component is 0.001 to 1000 parts by weight, preferably 0.005 to 500 parts by weight, more preferably 0.01 to 100 parts by weight based on 100 parts by weight of ascorbic acids contained in the composition for promoting collagen synthesis. It is desirable to blend so as to have a proportion by weight.

  Examples of the astringent component include metal salts such as alum, chlorohydroxyaluminum, aluminum chloride, allantoin aluminum salt, zinc sulfate, and aluminum potassium sulfate; organic acids such as tannic acid, citric acid, lactic acid, and succinic acid. Alum, chlorohydroxyaluminum, aluminum chloride, allantoin aluminum salt, aluminum potassium sulfate, and tannic acid are preferred.

  When using an astringent component, the proportion to be added to the composition for promoting collagen synthesis is usually 0.0003 to 10% by weight, preferably 0.01 to 5% by weight, more preferably 0.01 to 5% by weight. . The astringent component is 0.001 to 1000 parts by weight, preferably 0.005 to 500 parts by weight, more preferably 0.01 to 100 parts by weight, based on 100 parts by weight of ascorbic acids contained in the composition for promoting collagen synthesis. It is desirable to blend so as to have a ratio of parts.

  Antioxidant components include tocopherol and its derivatives, butylhydroxyanisole, dibutylhydroxytoluene, sodium bisulfite, erythorbic acid and its salts, flavonoids, glutathione, glutathione peroxidase, glutathione-S-transferase, catalase, superoxide dismutase, thioredoxin, Examples include taurine, thiotaurine, and hypotaurine. Tocopherol and its derivatives, thiotaurine, hypotaurine, thioredoxin, and flavonoid are preferable.

  In the case of using an antioxidant component, the proportion to be added to the composition for promoting collagen synthesis is usually 0.0001 to 10% by weight, preferably 0.0001 to 5% by weight, more preferably 0.001 to 5% by weight. . The ratio of 0.001 to 1000 parts by weight, preferably 0.005 to 500 parts by weight, and more preferably 0.01 to 100 parts by weight with respect to 100 parts by weight of ascorbic acids contained in the composition for promoting collagen synthesis. It is desirable to blend so that.

  Antiaging components include retinoids (retinol, retinoic acid, retinal, etc.), pangamic acid, kinetin, ursolic acid, turmeric extract, sphingosine derivatives, silicon, silicic acid, N-methyl-L-serine, mevalonolactone, and the like. Preferred are retinoid (retinol, retinoic acid, retinal, etc.) and kinetin.

  When using the said anti-aging component, the ratio mix | blended with the composition for collagen synthesis promotion becomes like this. Preferably it is 0.0003 to 10 weight%, More preferably, it is 0.01 to 5 weight%. The anti-aging component is 0.001 to 1000 parts by weight, preferably 0.005 to 500 parts by weight, more preferably 0.01 to 100 parts by weight based on 100 parts by weight of ascorbic acids contained in the composition for promoting collagen synthesis. It is desirable to blend so as to have a proportion by weight.

  As moisturizing ingredients, amino acids such as alanine, serine, leucine, isoleucine, threonine, glycine, proline, hydroxyproline, glucosamine, theanine and derivatives thereof; peptides such as collagen, collagen peptide, gelatin; glycerin, 1,3-butylene glycol Polyhydric alcohols such as propylene glycol and polyethylene glycol; Sugar alcohols such as sorbitol; Phospholipids such as lecithin and hydrogenated lecithin; Mucopolysaccharides such as propylene glycol hyaluronate, heparin and chondroitin; Lactic acid, sodium pyrrolidonecarboxylate, urea, etc. NMF-derived components and the like. Preferred are alanine, serine, glycine, proline, hydroxyproline, glucosamine, theanine, collagen, collagen peptide, glycerin, 1,3-butylene glycol, hydrogenated lecithin, propylene glycol hyaluronate, heparin, chondroitin, lactic acid, pyrrolidone carboxylic acid It is acid sodium.

  When using a moisturizing component, the proportion to be added to the composition for promoting collagen synthesis is usually 0.1 to 10% by weight, preferably 0.5 to 5% by weight, more preferably 0.5 to 5% by weight. be able to.

  In the composition for promoting collagen synthesis of the present invention, in addition to the above-described components, components usually used in foods, quasi drugs and pharmaceuticals may be appropriately blended depending on the use or dosage form of the composition. The component that can be blended is not particularly limited, but for example, amino acids, alcohols, polyhydric alcohols, saccharides, gums, polysaccharides and other high molecular compounds, surfactants, solubilizing components, fats and oils, transdermal Absorption-promoting ingredients, antiseptic / antibacterial / bactericidal agents, pH adjusters, chelating agents, antioxidants, enzyme components, binders, disintegrating agents, lubricants, fluidizing agents, cooling agents, minerals, cell activation Agents, nourishing tonics, excipients, thickeners, stabilizers, preservatives, isotonic agents, dispersants, adsorbents, disintegration aids, wetting agents or wetting regulators, dampening agents, coloring agents, wearing Perfume or fragrance, fragrance, reducing agent, solubilizer, solubilizer, foaming agent, thickener or thickener, solvent, base, emulsifier, plasticizer, buffer, brightener, etc. be able to. In particular, by adding a surfactant, a solubilizing component, or fats and oils, the stability, effectiveness, and feeling of use of ascorbic acids in an aqueous solvent can be further improved. Moreover, when the composition of this invention is a composition for external use, it is preferable to mix | blend surfactant, a solubilizing component, fats and oils, or a percutaneous absorption promoting component.

  Examples of the surfactant used herein include POE-branched alkyl ethers such as polyoxyethylene (hereinafter referred to as POE) -octyldodecyl alcohol and POE-2-decyltetradecyl alcohol; POE-oleyl alcohol ether and POE-cetyl alcohol. POE-alkyl ethers such as ethers; sorbitan esters such as sorbitan monooleate, sorbitan monoisostearate and sorbitan monolaurate; POE-sorbitan monooleate, POE-sorbitan monoisostearate, and POE-sorbitan monolaurate POE-sorbitan esters such as glycerol; glycerol fatty acid esters such as glycerol monooleate, glycerol monostearate, and glycerol monomyristate; POE-glycerol monoo POE-cured fatty acid esters such as reate, POE-glycerin monostearate, and POE-glycerin monomyristate; POE-cured such as POE-dihydrocholesterol ester, POE-cured castor oil, and POE-cured castor oil isostearate Castor oil fatty acid ester; POE-alkyl aryl ether such as POE-octylphenyl ether; Glycerin alkyl ether such as monoisostearyl glyceryl ether and monomyristyl glyceryl ether; POE such as POE-monostearyl glyceryl ether and POE-monomyristyl glyceryl ether -Glycerin alkyl ethers; diglyceryl monostearate, decaglyceryl decastearate, decaglyceryl decaisostearate, and diglyceride Various nonionic surfactants such as polyglycerin fatty acid esters such as rildiisostearate: or natural surfactants such as lecithin, hydrogenated lecithin, saponin, surfactin sodium, cholesterol, bile acids, etc. can do. These surfactants may be used alone or in any combination of two or more.

  When using a surfactant, the blending ratio in the composition for promoting collagen synthesis is not particularly limited as long as it has no side effects, does not affect the skin and mucous membranes, and does not interfere with the effects of the present invention. It can be appropriately selected and used within a range such that it is contained in the composition for promoting synthesis at a ratio of 0.01 to 30% by weight. From the viewpoint of stability of active ingredients in the composition for promoting collagen synthesis, skin use feeling, and the like, it is preferably 0.1 to 20% by weight, more preferably 0.5 to 10% by weight. .

  The solubilizing component is not particularly limited as long as it is used in the field of pharmaceuticals, quasi drugs or cosmetics. For example, lower alcohols such as ethanol, polyhydric alcohols such as glycerin and ethylene glycol, hydrogenated soybean phospholipid, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene lanolin alcohol, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, Examples thereof include polyoxyethylene sterol, polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene alkylphenyl ether and the like. Preferably, ethanol, glycerin, ethylene glycol, diethylene glycol, dipropylene glycol, hydrogenated soybean phospholipid, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene lanolin alcohol, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxy Ethylene alkyl ether, more preferably ethanol, glycerin, ethylene glycol, diethylene glycol, dipropylene glycol, and hydrogenated soybean phospholipid. These solubilizing components may be used alone or in any combination of two or more.

  When using these solubilized components, the blending ratio in the composition for promoting collagen synthesis is not particularly limited as long as it has no side effects, does not affect the skin and mucous membranes, and does not interfere with the effects of the present invention. The composition for promoting collagen synthesis can be appropriately selected and used within a range of 0.01 to 70% by weight, but the stability of the active ingredient in the composition for promoting collagen synthesis From the viewpoint of skin feeling, etc., the range is preferably 0.1 to 50% by weight, more preferably 0.1 to 30% by weight.

  The fats and oils are not particularly limited as long as they are used as components of external preparations in the field of pharmaceuticals, quasi drugs and cosmetics. For example, synthetic fats and oils such as medium chain fatty acid triglycerides; soybean oil, rice oil, rapeseed oil, cottonseed oil, sesame oil, safflower oil, castor oil, olive oil, cacao oil, coconut oil, sunflower oil, palm oil, flax oil, perilla oil, shea Vegetable oils such as oil, monkey oil, palm oil, tree wax, jojoba oil, grape seed oil, and avocado oil; animal oils such as mink oil, egg yolk oil, beef tallow, milk fat, and pork fat; beeswax, whale wax, lanolin Waxes such as carnauba wax and candelilla wax; hydrocarbons such as liquid paraffin, squalene, squalane, microcrystalline wax, ceresin wax, paraffin wax, petrolatum; lauric acid, myristic acid, stearic acid, oleic acid, isostearic acid, Natural and synthetic fatty acids such as behenic acid; cetanol, stearyl alcohol, hexylde Nord, octyldecanol, natural and synthetic higher alcohols such as lauryl alcohol; isopropyl myristate, isopropyl palmitate, octyldodecyl myristate, octyldodecyl oleate, esters and ethers such as cholesterol oleate; silicone oil, and the like. These fats and oils may be used alone or in any combination of two or more.

  When these fats and oils are used, the blending ratio in the composition for promoting collagen synthesis is not particularly limited as long as it has no side effects, does not affect the skin and mucous membranes, and does not interfere with the effects of the present invention. Although it can be appropriately selected and used within the range of 0.01 to 70% by weight in the composition for promoting collagen synthesis, the stability of the active ingredient in the composition for promoting collagen synthesis and the skin From the viewpoint of the feeling of use and the like, the range is preferably 0.1 to 60% by weight, more preferably 0.1 to 50% by weight.

  The composition for promoting collagen synthesis of the present invention can take a dosage form usually used for foods, quasi-drugs, and cosmetics depending on the use of the composition, and is usually a solid, semi-solid, or liquid. It is. Specifically, tablets (including orally disintegrating tablets, chewable tablets, effervescent tablets, troches, jelly drops, etc.), pills, granules, fine granules, powders, hard capsules, soft capsules , Dry syrups, liquids (including drinks, suspensions, syrups), gels, liposomes, extracts, tinctures, lemonades, ointments, jellys and the like. In addition, pastes, mousses, gels, liquids, emulsions, creams, sheets (substrate support), aerosols can be added by blending other solvents and commonly used bases as necessary. It can be prepared in various desired forms such as spray.

  These can be produced by conventional methods in the art. For example, in the case of a semi-solid preparation, ascorbic acids, δ-tocopheryl retinoate and the above-mentioned optional components are blended and mixed as required, and other solvents and bases for commonly used external preparations as necessary. Etc. can be prepared in various desired forms such as paste, mousse, gel, liquid, emulsion, cream, sheet (supported substrate), aerosol, and spray.

  The composition for accelerating collagen synthesis of the present invention is usually required to have a liquidity of pH 1-8, but when used as a semi-solid or liquid, the stability of ascorbic acids, low irritation to skin and mucous membranes, and From the viewpoint of good skin usability, it is preferably an acidic region of pH 2-7, more preferably pH 2-6.

  The composition for promoting collagen synthesis of the present invention is not particularly limited as long as the effect of the present invention is achieved. For example, pharmaceuticals, quasi drugs, foods [confectionery, health foods, nutritional supplements (balance nutritional foods, supplements, etc.) ), Nutritional functional foods, and foods for specified health use], cosmetics such as foundation, lipstick, mascara, eye shadow, eyeliner, eyebrow, and nail care cosmetics; emulsions, creams, lotions, oils and packs Basic cosmetics such as: facial cleansers, cleansings, body cleansers, bathing agents, etc.

  The composition for promoting collagen synthesis of the present invention may be used as an internal composition or an external composition, but the present invention is preferably used as an external composition. Since the composition of the present invention significantly increases the amount of collagen synthesis, various disorders associated with collagen decrease (corneal disorders such as corneal ulcers, rheumatoid arthritis, osteoarthritis, osteoarthritic joint disorders, inflammatory disorders, etc. ) Or a composition for preventing or treating cosmetic problems (an anti-wrinkle composition, an anti-tarmi composition, etc.).

  Hereinafter, the present invention will be described in more detail based on examples and test examples, but the present invention is not limited to these examples. In the following formulations,% means weight (W / W)% unless otherwise specified.

Test Example 1 Collagen synthesis amount in skin fibroblasts Normal human skin fibroblasts (NHDF; manufactured by Kurabo Industries) were seeded at 1 × 10 ⁴ cells / well on a 24-well culture plate (1 group was defined as 6). Then, a culture medium for dermal fibroblast proliferation (manufactured by Kurabo Industries) was used as a culture solution, and cultured at 37 ° C. under 5% CO ₂ conditions. After culturing for 96 hours, the culture solution is removed from each well, and then the above-mentioned culture solution containing L-ascorbic acid or / and δ-tocopheryl retinoate at the concentrations shown in Table 1, or L-ascorbic acid or δ-tocopheryl 1 ml of the above culture solution (control) containing no retinoate was added to each well and further cultured for 48 hours.
After completion of the culture, the amount of type I procollagen in the culture supernatant was measured by ELISA (Procollagen type I C-peptide EIA Kit; manufactured by Takara Shuzo). Since type I procollagen is a precursor of type I collagen, the amount of type I procollagen was measured as a biochemical indicator of the amount of collagen synthesis.
Next, the number of cells in each well was measured using MTT reagent (Dotite MTT freeze-dried product; Dojindo Laboratories Co., Ltd.), the amount of type I procollagen was divided by the number of cells, and the number of cells between the wells While excluding variations, the amount of collagen synthesis per cell was used.
The results are shown in Table 1. The collagen synthesis rate (%) in the table is the amount of collagen synthesis per cell in the test culture medium (average value per group 6), and the amount of collagen synthesis per cell in the control culture medium (average value per group 6). Divide ratio (%).

  L-ascorbic acid or δ-tocopheryl retinoate alone promotes collagen synthesis in a concentration-dependent manner in skin fibroblasts. Furthermore, it was confirmed that the combined use of both L-ascorbic acid and δ-tocopheryl retinoate markedly increased the amount of collagen synthesis, and the synergistic enhancement of collagen synthesis was promoted by the cooperation of both. .

Example 1 (sunscreen)
δ-tocopheryl retinoate 0.1 (%)
Ascorbyl tetra-2-hexyldecanoate 0.1
2-Ethylhexyl paramethoxycinnamate 10.0
Decamethylcyclopentasiloxane 20.0
Octyl palmitate 10.0
Polyoxyethylene / methylpolysiloxane copolymer 3.0
Low-temperature baked zinc oxide treated with methylhydrogenpolysiloxane 15.0
Polyalkyl acrylate 5.0
Concentrated glycerin 5.0
Absolute ethanol 5.0
1,3-butylene glycol 3.0
Panthenol 0.1
Fragrance 0.1
Phytic acid 0.05
Remaining amount of purified water 100.0% in total.

Example 2 (sunscreen)
δ-tocopheryl retinoate 0.1 (%)
Ascorbyl tetra-2-hexyldecanoate 1.0
2-Ethylhexyl paramethoxycinnamate 10.0
Benzylidene malonate polysiloxane (PARSOL SLX) 5.0
Diethylaminohydroxybenzoyl hexyl benzoate
(Yubinar APlus) 5.0
2-methoxyhexyl dimethoxybenzylideneoxoimidazolidinepropionate
3.0
2,4,6-Tris [4- (2-ethylhexyloxycarbonyl) anilino] -1,3,5-triazine 3.0
Dioctanoic acid isorubide (Solester 208) 10.0
Lauryl polyglyceryl-3 polydimethylsiloxyethyl dimethicone (KF6105) 3.0
Ferulic acid 3.0
Methyl paraoxybenzoate 0.05
Propyl paraoxybenzoate 0.05
Phenylbenzimidazolesulfonic acid 3.0
Triethanolamine 1.5
Cyanocobalamin 0.05
Purified water balance
Total 100.0%.

Example 3 (sunscreen)
δ-tocopheryl retinoate 0.5 (%)
Ascorbyl tetra-2-hexyldecanoate 1.0
Sodium ascorbate 2.0
L-ascorbyl magnesium phosphate 3.0
Ferulic acid 3.0
Phenylbenzimidazolesulfonic acid 3.0
Triethanolamine 1.5
Hydroxymethoxybenzophenonesulfonic acid 1.0
Lauryl dimethicone polyglycerin-3 crosspolymer / glyceryl tri-2-ethylhexanoate (KSG-830) 5.0
Concentrated glycerin 10.0
Cyanocobalamin 0.05
2-Ethylhexyl paramethoxycinnamate 10.0
4-tert-Butyl-4-methoxydibenzoylmethane 2.0
Glyceryl tri-2-ethylhexanoate 5.0
Methyl paraoxybenzoate 0.05
Propyl paraoxybenzoate 0.05
Decamethylcyclopentasiloxane 15.0
Purified water balance
Total 100.0%.

Example 4 (wrinkle and tarmi prevention cream)
δ-tocopheryl retinoate 0.5 (%)
Ascorbyl tetra-2-hexyldecanoate 1.0
Lauryl dimethicone polyglycerin-3 crosspolymer / glyceryl tri-2-ethylhexanoate (KSG-830) 5.0
Cross-linked methylpolysiloxane / methylpolysiloxane (KSG16) 5.0
Cross-linked alkyl-modified silicon / glyceryl tri-2-ethylhexanoate (KGG-43) 3.0
Decamethylcyclopentasiloxane 15.0
Polymethylsilsesquioxane 3.0
(Dimethicone / vinyl dimethicone / methicone) cross polymer 1.0
Polyalkyl acrylate 5.0
Concentrated glycerin 10.0
Magnesium sulfate 0.1
Sodium edetate 0.05
Cyanocobalamin 0.01
Methyl paraoxybenzoate 0.05
Propyl paraoxybenzoate 0.05
Purified water balance
Total 100.0%.

Example 5 (wrinkle and tarmi prevention cream)
δ-tocopheryl retinoate 0.1 (%)
Ascorbyl tetra-2-hexyldecanoate 1.0
Tetra-2-ethylhexanoic acid pentaerythrit 5.0
White petrolatum 2.0
Polyoxyethylene sorbitan stearate 2.0
Carboxyvinyl polymer 0.1
1,3-butylene glycol 5.0
Cetanol 0.5
Concentrated glycerin 5.0
Cyanocobalamin 0.01
L-Arginine 0.1
Xanthan gum 0.1
Hydroxyethyl cellulose 0.1
Sodium alginate 0.1
Methyl paraoxybenzoate 0.05
Propyl paraoxybenzoate 0.05
Purified water balance
Total 100.0%.

Example 6 (wrinkle and tarmi prevention lotion)
δ-tocopheryl retinoate 0.1 (%)
Sodium ascorbate 2.0
L-ascorbyl magnesium phosphate 3.0
Hyaluronic acid 0.05
1,3-butylene glycol 5.0
Polyoxyethylene hydrogenated castor oil (HCO-80) 1.0
Methyl paraoxybenzoate 0.05
Purified water balance
Total 100.0%.

Example 7 (wrinkle and tarmi prevention stick)
δ-tocopheryl retinoate 0.1 (%)
Ascorbyl tetra-2-hexyldecanoate 1.0
Paraffin wax 10.0
White petrolatum 20.0
Phytosteryl oleate 20.0
Sericin 5.0
Carnavalou 5.0
Sara honey bees 5.0
Jojoba oil 10.0
l-Menthol 0.1
Glyceryl tri-2-ethylhexanoate 23.8
Total 100.0%.

Claims (2)

A collagen synthesis promoter comprising at least one selected from the group consisting of ascorbic acid, ascorbic acid derivatives and salts thereof, and δ-tocopheryl retinoate as active ingredients. A composition for promoting collagen synthesis, comprising at least one selected from the group consisting of ascorbic acid, ascorbic acid derivatives and salts thereof, and δ-tocopheryl retinoate.