JP2004250690A - Anti-oxidant composition and composition for external use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a technical means which permits use of fullerene and its analogue in a variety of applications utilizing their biocompatibilities and realizes their new functions, and in particular to provide their application means as cosmetics or prescribed medicines for external use to the skin. <P>SOLUTION: The anti-oxidant composition comprises as an active component at least one of fullerene, an oxygen-containing derivative of fullerene, and the fullerene or the oxygen-containing derivative of fullerene which is modified with or included in an organic compound. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

  The invention of this application relates to an external composition such as an antioxidant composition and a cosmetic composition, and a skin prescription composition.

  In recent years, carbon nanostructures such as fullerenes have been attracting attention as a way to open up new perspectives on carbon materials. Not only electronic materials and electrode materials, but also medical and medical applications and applications for health promotion etc. Interest is growing.

  For example, a fullerene or a fullerene mixture is blended into a makeup cosmetic for the purpose of improving dispersibility and coloring property (Patent Literature 1), and a sun care cosmetic composition using the ultraviolet absorbing effect of fullerene is used. (Patent Document 2), and a method of optically inactivating a virus using fullerene as a photosensitizer (Patent Document 3).

However, studies on the use of fullerenes and the like have only just started, and the actual mechanism of action and the correlation between the chemical composition and the effects have not been elucidated in practice. It is. Actually, for example, even in the above-mentioned proposals, these points have not been studied, so that many problems still remain for the application of fullerenes and the like.
JP-A-6-192039 JP-A-9-278625 JP-A-9-322767

  Therefore, the invention of this application overcomes the limitations of the conventional technology as described above, and enables fullerenes and their analogs to be applied to various fields of biocompatibility and realizes new functions. The task is to provide technical means. In particular, it is another object of the invention of the present application to provide means for application as cosmetics, topical skin prescription drugs, and the like.

  The invention of this application solves the above-mentioned problems. First, fullerenes, fullerene derivatives, and at least one of the fullerenes or fullerene derivatives modified or included by an organic compound, and salts thereof. Secondly, the present invention provides an antioxidant composition characterized by comprising one kind as an active ingredient, and secondly, an organic compound which modifies or includes a fullerene or a fullerene derivative comprises an organic oligomer, an organic polymer, cyclodextrin and a crown ether. An antioxidant composition characterized by being one or more of those analogous compounds, and thirdly, a long-chain carboxylic acid having 10 or more carbon atoms or an ester or salt thereof. The antioxidant composition, fourthly, the fullerene is C60 fullerene, C70 fullerene or the like. Providing antioxidant composition characterized in that a fullerene mixture containing both.

  Fifth, the invention of this application is characterized by containing at least one of fullerene, a fullerene derivative, the fullerene or the fullerene derivative modified or included by an organic compound, and salts thereof. Sixth, the organic compound that modifies or includes fullerene or a fullerene derivative is at least one of organic oligomers, organic polymers, cyclodextrins, crown ethers, and their analogous compounds. Seventh, an external composition characterized by containing a long-chain carboxylic acid having 10 or more carbon atoms or an ester or salt thereof, and eighthly, fullerene is C60. Fullerene, C70 fullerene or fullerene mixture containing both To provide a topical composition.

  Further, the invention of this application ninthly includes the following: a fullerene, a fullerene derivative, and at least one of the aforementioned fullerene or a fullerene derivative modified or included by an organic compound, and a salt thereof. An external composition comprising at least one of the described components is provided.

<1> Nonionic surfactant <2> Ascorbic acid, a derivative thereof or salts thereof <3> Ultraviolet ray protective agent Tenthly, an organic compound which modifies or includes fullerene or a fullerene derivative is an organic oligomer, an organic polymer , A topical composition comprising at least one of cyclodextrin and crown ethers and their analogous compounds. Eleventh, the fullerene is a fullerene mixture containing C60 fullerene, C70 fullerene or both. A skin prescription drug composition is provided.

  As described above, the invention of the present application overcomes the limitations of the prior art and enables fullerenes and their analogs to be applied to various fields of biocompatible applications and realizes new functions. In particular, it is possible to provide a means for application as a cosmetic or a topical skin prescription drug or the like.

  The invention of this application has the features as described above, and embodiments thereof will be described below.

  In the antioxidant composition of the invention of this application, and an external composition such as a cosmetic composition and a skin composition, the active ingredient or the useful ingredient is a fullerene as described above, fullerene, fullerene oxygen-containing derivative, And at least one of the above-mentioned fullerenes or oxygen-containing fullerene derivatives modified or included with an organic compound, and salts thereof.

  Among these fullerenes, various fullerenes such as C60, C70 or a mixture thereof may be used. For example, the fullerene of the invention of this application may be one in which a plurality of fullerenes are bonded via an alkylene chain such as a methylene chain, or one in which an alkylene chain is bonded to a carbon atom at a different position in the fullerene skeleton. . The derivative of fullerene 60 may have one to forty modification groups attached to one fullerene molecule. For example, the derivative of fullerene 70 may have one to 50 modification groups for one fullerene molecule. This modifying group may be independently a hydroxyl group, an ester group of the hydroxyl group and an inorganic or organic acid or a glycoside group of a sugar, or a ketal group of a hydroxyl group and a ketone or an acetal of an aldehyde. Any group may be used as long as it is a fullerene-modified compound or a salt thereof and at least one selected therefrom. Further, the fullerene of the invention of this application may be a C60 fullerene, a C70 fullerene or a nanotube fullerene, or a mixture of one or more selected from them. Further, fullerene in which carbon black (soot including fullerenes) which is a product of fullerene may be left, may be used as long as the carbon black concentration in the fullerene is 0 to 98% by weight.

  As the oxygenated fullerene derivative, those in which an oxygen atom is directly bonded to a carbon atom of a fullerene skeleton or via a carbon chain such as an alkylene chain are considered. For example, hydroxylated fullerene to which an -OH group having a hydroxylation rate of about 50 / mol fullerene or less is directly bonded is exemplified.

  Examples of the organic compound that modifies or includes the fullerene or the fullerene conductor as described above include organic oligomers, organic polymers and inclusion compounds or cyclodextrins (CD) or crown ethers or analogs thereof capable of forming an inclusion complex. One or more types are exemplified as suitable ones.

  Examples of the organic oligomer or organic polymer include carboxylic acid esters, alcohols, saccharides, polysaccharides, polyhydric alcohols, polyalkylene glycols such as polyethylene glycol, butylene glycol, polypropylene glycol, and polyvinyl alcohol, and polyhydric alcohols. Nonionic water-soluble polymers including starch derivatives such as dextran, pullulan, starch, hydroxyethyl starch and hydroxypropyl starch, alginic acid, hyaluronic acid, chitosan, chitin derivatives, and anionics of these polymers Or cationic derivatives thereof and their high molecular weight glycerin and fatty acids, oils, propylene carbonate, lauryl alcohol, ethoxylated castor oil, polysorbates, and esters or ethers thereof. And polymers thereof, and polyester polymers thereof, pyrrolidone polymers such as polyvinylpyrrolidone, esters or ethers of unsaturated alcohol polymers, and polyoxyethylene polyoxypropylene block copolymers. Is preferably bonded to fullerene or a derivative thereof, and may be a mixture of one or more thereof. Among them, various ones such as polyalkylene glycol such as polyethylene glycol (PEG) and PVP are exemplified as preferable ones. In the case of polymers such as PEG and PVP, the average molecular weight is generally preferably about 2000 to 100,000. The molar ratio to fullerene or a fullerene oxygen-containing derivative is not more than 10/1. The degree is considered.

  For example, in the invention of this application, it is also effective to contain a long-chain carboxylic acid having 10 or more carbon atoms, or an ester or salt thereof, in addition to the active ingredient and the fullerene as a useful ingredient as described above. Furthermore, oil agents, surfactants, pigments, humectants, excipients and bases, cell activators, and the like as described below may be added.

  The pH of the fullerene-containing external composition when it contains water varies depending on the pH of the fullerene, the fullerene derivative, the fullerene clathrate, or the raw material of the salt thereof. And its derivatives can be stably compounded.

  The pH of a 0.5% aqueous solution of a fullerene, a fullerene derivative, a fullerene clathrate, or a salt thereof at 20 ° C. and 0.5% by weight is measured, and the number after the decimal point is rounded to n (n is an integer from 0 to 14). ), When n is 3 to 10, the pH of the stable composition for external use may be adjusted in the range of n ± 2 and in the range of pH 3 to 10. When n is a number obtained by rounding a fullerene, a fullerene derivative, a fullerene-modified or clathrate compound, or a salt thereof at 20 ° C. and a pH of a 0.5% by weight aqueous solution to n, when n is 3 or less, The pH of the stable fullerene external preparation is preferably in the range of 3 to 4, and the pH is preferably 9 to 10 when the pH of n is 10 or more. In any case, the pH of the stable fullerene-containing external composition is preferably in the range of 3 to 10.

As for the invention of this application, its activity corresponding to the examples described later, the composition composition to be considered, and the like will be described in detail as follows.
<A> Activity by fullerenes Activity to scavenge hydroxyl radicals generated by transition metal ions When hydrogen peroxide and ferrous sulfate are mixed, a so-called Fenton reaction is caused to generate hydroxyl radicals, a type of active oxygen. Is thought to cause oxidative damage to DNA, proteins and lipids, causing cell death. The fullerenes of the invention of this application can efficiently eliminate hydroxyl radicals generated by this reaction. In fact, the hydroxyl radical scavenging activity of the fullerenes of the present invention is equal to or greater than that of provitamin C, ascorbic acid-2-0-phosphate.

  The hydroxyl radical scavenging activity of the fullerenes of the invention of this application is not limited to the scavenging activity of hydroxyl radicals generated by transition metal ions, but also scavenges hydroxyl radicals generated under various conditions in a living body or skin.

  The hydroxyl radical scavenging activity has an effect of protecting DNA breakage, DNA damage, cell membrane rupture and cell death caused by hydroxyl radical.

2. Activity to eliminate superoxide anion radical generated by oxygen reaction. It is thought that superoxide anion radical is generated during stagnation of skin blood flow and skin injury, causing oxidative damage to DNA, proteins and lipids and causing cell death. Can be The superoxide anion radical is generated by mixing hypoxanthine and xanthine oxidase, but the fullerenes of the invention of this application can efficiently eliminate this.

  The superoxide anion radical scavenging activity of the fullerenes of this application surpasses provitamin C, ascorbic acid-2-0-phosphate.

  The superoxide anion radical scavenging activity by the fullerenes of this application is not limited to the scavenging activity for hydroxyl radicals generated by oxygen reaction, but also scavenges superoxide anion radicals widely generated in various conditions in a living body or skin.

  The superoxide anion radical scavenging activity has an effect of protecting DNA cleavage, DNA damage, cell membrane rupture and cell death caused by the superoxide anion radical.

3. Activity to suppress peroxide / hydrogen peroxide generated in skin cells by ultraviolet rays When the skin is irradiated with sunlight, ultraviolet rays (B waves) in the light rays generate peroxide / hydrogen oxide inside the cells or cut DNA. Or DNA damage or cell membrane disruption causes cell death.

  If the fullerenes of the invention of this application are prescribed before irradiation, the amount of peroxide / hydrogen peroxide generated is significantly suppressed. The peroxide / hydrogen peroxide scavenging activity of the fullerenes of the invention of this application is equal to or higher than ascorbic acid-2-0-phosphate ester, which is provitamin C.

  Peroxide / hydrogen peroxide penetrates cell membranes and has a long remaining life, which is a major cause of cell injury. However, the fullerenes of the invention of this application are not limited to peroxide / hydrogen peroxide caused by ultraviolet rays, but are widely used in vivo. And peroxide / hydrogen peroxide generated under various conditions in the skin.

  The peroxide / hydrogen peroxide scavenging activity of the fullerenes of this application has an effect of protecting DNA breakage, DNA damage, cell membrane rupture and cell death caused by peroxide / hydrogen peroxide.

4. Lipid peroxide inhibits peroxide / hydrogen peroxide generated in skin cells Lipids present in the skin are always susceptible to oxidation, which causes skin cell death. The lipids ceramide and squalene are oxidized and converted to hydroperoxide, causing cell death.

  If the fullerenes of the invention of this application are prescribed beforehand, the amount of peroxide / hydrogen peroxide generated is significantly suppressed. The peroxide / hydrogen peroxide scavenging activity of the fullerenes of the invention of this application is equal to or higher than ascorbic acid-2-0-phosphate ester, which is provitamin C.

  The fullerenes of the invention of the present application eliminate not only peroxide / hydrogen peroxide due to lipid peroxide but also peroxide / hydrogen peroxide widely generated under various conditions in a living body or skin.

  The peroxide / hydrogen peroxide scavenging activity of the fullerenes of the invention of this application has an effect of protecting DNA breakage, DNA damage, cell membrane rupture and cell death caused by peroxide / hydrogen peroxide.

5. Various skin effects and skin protection effects Fullerene derivatives have the activity to scavenge various active oxygens, so UV damage, lipid peroxide lipid damage, ischemia re-concentration damage caused, promoted or impaired repair by active oxygen・ Forms melanin ・ Wrinkles / dullness / sagging ・ Various skin effects to prevent cellulite formation

  By applying as a composition for external use, skin whitening, improvement of pigmentation, treatment of acne, improvement of wrinkles, improvement of rough skin, improvement of oily skin, improvement of dry skin, reduction of pores, treatment of scar, treatment of red face The treatment effects of hair loss treatment, hair growth promotion, burn treatment, skin disinfection, skin miticide killing and skin texture improvement are dramatically enhanced.

  In the invention of this application, the composition for external use itself does not exhibit antioxidant activity and is kept stable, and exhibits its antioxidant power efficiently only after being applied and absorbed on the skin, and is clearly evident against various skin disorders. Expresses improvement and therapeutic effects.

  For this reason, the composition for external use of the invention of the present application provides skin whitening, acne improvement, wrinkle improvement, skin roughness improvement, oily skin improvement, dry skin improvement, pore reduction, scar reduction, red face improvement. It can exert clear therapeutic effects such as treatment of hair loss, promotion of hair growth, improvement of burns, disinfection of skin, killing of mites and improvement of skin texture.

In other words, it is effective not only in the beautiful skin effect but also in the skin protection effect of protecting all skin inflammations and subcutaneous inflammations and promoting wound healing. Among them, it is effective for inflammation caused by wounds such as bacterial infections, bacterial fungi and viral infections, parasitic infections, burns, sunburns, abrasions, bruises, and bites.
<B> Method of administering fullerenes as external preparation Dosage The concentration of the fullerenes of the invention of this application may be 0.00001% to 30% by weight, but is preferably 5% or less from the viewpoint of usability. When applied to the skin, the amount of the composition for external use is preferably 0.001 to 20 mL, preferably 0.01 to 5.0 mL of liquid per square meter of skin area, externally applied, compressed or sprayed.

2. Dosage form Examples of the form of the composition for external use on the skin are not particularly limited, and include, for example, all external preparations such as aqueous solvents, ointments, emulsions, creams, gels, packs, baths, detergents, cataplasms, and dispersions. There is no particular limitation on the dosage form, solid, paste, mousse, gel, powder, solution, solubilization, emulsification, powder dispersion, multilayer It can be. In particular, for aqueous solutions, emulsions, ointments, gels, aqueous preparations, serums, and packs, after externally using these agents, use a humidifier, a vibration introducer, an ion introducer, a sound introducer, and an electromagnetic wave introducer. Thereby, penetration of fullerenes into the skin can be promoted, and a greater effect can be exhibited.

As a coating method, in the case of a liquid agent, any physically possible method such as spraying, pasting, compress, dipping, and mask can be used.
<C> External preparation containing fullerenes The antioxidant composition and the external composition of the present invention are basically realized as a combination with various components constituting a conventionally known cosmetic or external preparation. Is done.

  First, these components are generally described below.

1. Oil agent The fullerenes of the invention of this application are dispersed in oils, preferably natural oils, more preferably orange oils, beaver oils, olive oils, oils containing one or more oils selected from pine oils. It is preferably administered to a living body, particularly to the skin.

  As the oil, if it is one used in ordinary cosmetics, it may be a natural oil, a synthetic oil, or a solid, semi-solid, liquid, etc. Any of oils such as waxes, waxes, fatty acids, higher alcohols, ester oils, silicone oils, and fluorine-based oils can be used. For example, hydrocarbons such as squalane, squalene, ceresin, paraffin, paraffin wax, liquid paraffin, pristane, polyisobutylene, microcrystalline wax, vaseline; waxes such as beeswax, carnauba wax, candelilla wax, whale wax; tallow, cow Animal oils such as leg fat, beef bone fat, hardened tallow, hardened oil, turtle oil, lard, horse fat, mink oil, liver oil, egg yolk oil; lanolin, liquid lanolin, reduced lanolin, lanolin alcohol, hard lanolin, lanolin acetate, Lanolin derivatives such as lanolin fatty acid isopropyl, POE lanolin alcohol ether, POE lanolin alcohol acetate, lanolin fatty acid polyethylene glycol, and POE hydrogenated lanolin alcohol ether; lauric acid, myristic acid, palmitic acid, stearie Acid, behenic acid, undecylenic acid, oleic acid, arachidonic acid, docosahexaenoic acid (DHA), isostearic acid, fatty acids such as 12-hydroxystearic acid.

  Examples of the oil include lauryl alcohol, myristyl alcohol, palmityl alcohol, stearyl alcohol, behenyl alcohol, hexadecyl alcohol, oleyl alcohol, isostearyl alcohol, hexyldecanol, octyldodecanol, cetostearyl alcohol, and 2-decyltetradecinol. Cholesterol, phytosterol, sitosterol, lanosterol, higher alcohols such as POE cholesterol ether, monostearyl glycerin ether (bacyl alcohol); diisobutyl adipate, 2-hexyldecyl adipate, di-2-heptyl undecyl adipate, mono N-alkyl glycol isostearate, isocetyl isostearate, trimethylol triisostearate Lopane, ethylene glycol di-2-ethylhexanoate, cetyl 2-ethylhexanoate, trimethylolpropane tri-2-ethylhexanoate, pentaerythritol tetra-2-ethylhexanoate, cetyl octanoate, octyldodecyl gum ester, olein Oleyl acid, octyl dodecyl oleate, decyl oleate, neopentyl glycol dicaprate, triethyl citrate, 2-ethylhexyl succinate, amyl acetate, ethyl acetate, butyl acetate, isocetyl stearate, butyl stearate, diisopropyl sebacate, Di-2-ethylhexyl sebacate, cetyl lactate, myristyl lactate, isopropyl palmitate, 2-ethylhexyl palmitate, 2-hexyldecyl palmitate, 2-heptyl palmitate Ndecyl, cholesteryl 12-hydroxystearylate, dipentaerythritol fatty acid ester, isopropyl myristate, octyldodecyl myristate, 2-hexyldecyl myristate, myristyl myristate, hexyldecyl dimethyloctanoate, ethyl laurate, hexyl laurate, And ester oils such as N-lauroyl-L-glutamic acid-2-octyldodecyl ester and diisostearyl malate. And the like, oil agents such as acetoglyceride, triisooctanoic acid glyceride, triisostearic acid glyceride, triisopalmitic acid glyceride, tri-2-ethylhexanoic acid glyceride, monostearic acid glyceride, di-2-heptylundecanoic acid glyceride, trimyristin Glyceride oils such as acid glyceride; dimethylpolysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, tetramethyltetrahydrogencyclotetrasiloxane, steer Higher alkoxy-modified silicone such as roxysilicone; higher fatty acid-modified silicone, silicone resin, silicone rubber, silicone Silicone-based oil agent over emissions oil; perfluoropolyether, perfluorodecalin, fluorine-based oils of perfluoro octane.

2. Surfactant The preparation / cosmetic of the fullerenes of the invention of the present application may contain monoglyceride caprylic acid and / or monoglyceride capric acid, and may further contain monoglyceride laurate. Caprylic acid monoglyceride, capric acid monoglyceride, and lauric acid monoglyceride (hereinafter, also simply referred to as glyceride) are all designated as food additives; glycerin fatty acid esters, and their safety has been confirmed, and there is no problem with eating. It is a food emulsifier.

  An emulsifier may be added to the fullerenes of the invention of this application in order to disperse them in water. For example, as an emulsifier, a nonionic surfactant such as polyoxyethylene sorbitan fatty acid ester or polyglycerin fatty acid ester such as polyoxyethylene sorbitan monooleate having an HLB of 10 or more, or an anionic surfactant such as sodium lauryl sulfate is used. Surfactants can also be used.

  As the surfactant, anionic, cationic, nonionic and amphoteric activators are used. Examples of anionic surfactants include fatty acid soaps such as sodium stearate and triethanolamine palmitate, alkyl ether carboxylic acids and salts thereof, carboxylate salts such as condensates of amino acids and fatty acids, alkyl sulfonic acids, and alkene sulfonates. Sulfonic acid salts of fatty acid esters, sulfonic acid salts of fatty acid amides, sulfonic acid salts of alkyl sulfonates and their formalin condensates, alkyl sulfate salts, secondary higher alcohol sulfate salts, alkyl and allyl ether sulfate salts , Sulfates of fatty acid esters, sulfates of fatty acid alkylolamide, sulfates such as funnel oil, alkyl phosphate, ether phosphate, alkyl allyl ether phosphate, amide phosphate, N-acyl amino acid Activators, etc. It is.

  Examples of the cationic surfactant include alkylamine salts, amine salts such as polyamine and amino alcohol fatty acid derivatives, quaternary ammonium salts of alkyl acids, aromatic quaternary ammonium salts, pyridium salts, and imidazolium salts. Nonionic surfactants include sorbitan fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, propylene glycol fatty acid esters, polyethylene glycol fatty acid esters, sucrose fatty acid esters, polyoxyethylene alkyl ethers, polyoxypropylene alkyl ethers, and polyoxypropylene alkyl ethers. Oxyethylene alkyl phenyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbitol fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene propylene glycol fatty acid ester, polyoxyethylene castor oil, polyoxyethylene Hydrogenated castor oil, polyoxyethylene phytostanol ether, polyoxyethylene Down phytosterol ether, polyoxyethylene cholestanol ether, polyoxyethylene cholesteryl ether, polyoxyalkylene-modified organopolysiloxane, polyoxyalkylene-alkyl co-modified organopolysiloxane, alkanolamide, sugar ethers, and sugar amides. Examples of the amphoteric surfactant include betaine, aminocarboxylate, and imidazoline derivative.

  Examples of the metal soap include aluminum 12-hydroxystearate, zinc stearate, aluminum stearate, calcium stearate, magnesium stearate, zinc myristate, magnesium myristate, zinc cetyl phosphate, calcium cetyl phosphate, sodium zinc cetyl phosphate, and zinc laurate. And zinc undecylenate.

3. Pigment Since many of the fullerenes of the invention of the present application are colored, it is desirable to appropriately mix a pigment as a cosmetic to adjust the color tone without any unnatural feeling. Examples of colored pigments include inorganic red pigments such as iron oxide, iron hydroxide, and iron titanate; inorganic brown pigments such as γ-iron oxide; inorganic yellow pigments such as yellow iron oxide and loess; black iron oxide; and carbon black. Inorganic black pigments, inorganic purple pigments such as manganese violet and cobalt violet, inorganic green pigments such as chromium hydroxide, chromium oxide, cobalt oxide, and cobalt titanate; inorganic blue pigments such as navy blue and ultramarine blue; and tar pigments Pigments, pigments in which natural dyes are raked, and composite powders in which these powders are composited. Examples of the pearl pigment include titanium oxide-coated mica, titanium oxide-coated mica, bismuth oxychloride, titanium oxide-coated bismuth oxychloride, titanium oxide-coated talc, fish scale foil, and titanium oxide-coated colored mica. Examples of the metal powder pigment include aluminum powder, copper powder, and stainless powder.

  Examples of tar dyes include Red No. 3, Red No. 104, Red No. 106, Red No. 201, Red No. 202, Red No. 204, Red No. 205, Red No. 220, Red No. 226, Red No. 227, Red No. 228, Red No. 230, Red No. 401, Red No. 505, Yellow No. 4, Yellow No. 5, Yellow No. 202, Yellow No. 203, Yellow No. 204, Yellow No. 401, Blue No. 1, Blue No. 2, Blue No. 201, Blue No. 404 Green No. 3, Green No. 201, Green No. 204, Green No. 205, Orange No. 201, Orange No. 203, Orange No. 204, Orange No. 206, Orange No. 207 and the like. Examples of natural pigments include carminic acid, laccaic acid, calsamine, bradylin, crocin and the like. The above-mentioned powders such as inorganic powders, organic powders, pigments and tar pigments may be compounded or surface-treated with an oil agent, silicone or a fluorine compound.

4. Moisturizers Polyhydric alcohols such as propylene glycol, glycerin, polyglycerin, sorbitan, sorbitol are added to moisturize and relieve skin irritation. As the humectant, alkaline simple hot spring water, deep water, hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparan sulfate, mucopolysaccharides such as heparin and keratan sulfate or salts thereof, collagen, elastin, proteins such as keratin or those thereof Derivatives and their salts, phospholipids, glycolipids derived from soybeans and eggs, ceramide, mucin, honey, erythritol, maltose, maltitol, xylitol, xylose, pentaerythritol, fructose, dextrin and its derivatives, mannitol, sorbitol, inositol, Trehalose, sugars such as glucose, urea, asparagine, aspartic acid, alanine, arginine, isoleucine, ortinine, glutamine, glycine, glutamic acid and derivatives thereof, and their derivatives , Cysteine, cystine, citrulline, threonine, serine, tyrosine, tryptophan, theanine, valine, histidine, hydroxylysine, hydroxyproline, pyrrolidone carboxylic acid and salts thereof, proline, phenylalanine, methionine, amino acids such as lysine and derivatives thereof or their And the like.

  Further, as a humectant, D-panthenol, avocado extract, almond oil, locust bean extract, rice extract, strawberry extract, fennel extract, avenger oil extract, spinach extract, olive oil, hydrangea extract, cacao butter, Oat extract, Kizuta extract, Kumazasa extract, Gardenia extract, Grapefruit extract, Geno ginger extract, Gentian extract, Burdock extract, Kobotdul extract, Sesame extract, Cactus extract, Sapon extract, Ginger extract , Extract of magnolia, shea butter, extract of Spiraea, extract of mallow, extract of mallow, extract of camellia, extract of corn, extract of maize, maize extract, tormentilla extract, pomegranate extract, pakumondo extract, Hawthorn extract, Hama Squirrel extract, peppermint extract, green peppermint extract, common peppermint extract, parsley extract, rose extract, sunflower extract, hinoki extract, loofah extract, prunes extract, butchers bloom extract, borage oil, button Extract, jojoba oil, bodaille extract, hop extract, pine extract, maronier extract, macadamia nut oil, quince extract, murasaki extract, meadow home oil, melissa extract, cornflower extract, lily extract, yuzu An extract, a lime extract, a lavender extract, a gentian extract, a potato extract, an apple extract and the like can be mentioned. One or more of the above-mentioned humectants can be appropriately selected and blended.

5. Excipients / Bases Examples of the gelling agent include N-lauroyl-L-glutamic acid, amino acid derivatives such as α, γ-di-n-butylamine, dextrin palmitate, dextrin stearate, and dextrin 2-ethylhexanoate. Dextrin fatty acid esters such as palmitic acid esters, sucrose fatty acid esters such as sucrose palmitic acid esters and sucrose stearic acid esters, benzylidene derivatives of sorbitol such as monobenzylidene sorbitol and dibenzylidene sorbitol, dimethylbenzyl dodecylammonium montmorillonite clay, dimethyldiethyl sorbitol Organic modified clay minerals such as octadecyl ammonium montmorillonite clay and the like can be mentioned.

  Examples of alcohols include lower alcohols such as ethanol and isopropanol, and polyhydric alcohols such as glycerin, diglycerin, ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, and polyethylene glycol. Can be

  Examples of the water-soluble polymer include plant-based polymers such as gum arabic, tragacanth, galactan, carob gum, guar gum, karaya gum, carrageenan, pectin, agar, algae colloid, trant gum, locust bean gum, and galactomannan; xanthan gum, dextran, succino Microbial polymers such as glucan and pullulan; animal polymers such as casein, albumin and gelatin; starch polymers such as starch, carboxymethyl starch and methylhydroxypropyl starch; methylcellulose, ethylcellulose, methylhydroxypropylcellulose and carboxymethylcellulose , Hydroxymethylcellulose, hydroxypropylcellulose, nitrocellulose, cellulose sodium sulfate, carboxymethylcellulose sodium , Crystalline cellulose, cellulosic polymer of cellulose powder; alginic acid-based polymers such as sodium alginate and propylene glycol alginate; vinyl-based polymers such as polyvinyl methyl ether, carboxyvinyl polymer, alkyl-modified carboxyvinyl polymer; polyoxyethylene-based Polymers: Polyoxyethylene polyoxypropylene copolymer-based polymers; Acrylic polymers such as sodium polyacrylate, polyethyl acrylate, and polyacrylamide; Inorganic aqueous solutions such as polyethylene imine, cationic polymers, bentonite, laponite, and hectorite And the like. In addition, film-forming agents such as polyvinyl alcohol and polyvinyl pyrrolidone are also included therein.

  As the powder, if it is used in ordinary cosmetics, its shape (spherical, needle-like, plate-like, etc.), particle diameter (fog-like, fine particles, pigment grade, etc.), particle structure (porous, Inorganic powders, organic powders, pigments and the like can be used regardless of whether they are nonporous or not. For example, as inorganic powders, magnesium oxide, barium sulfate, calcium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, talc, synthetic mica, mica, kaolin, sericite, muscovite, synthetic mica, phlogopite, mica, Biotite, Lithium mica, silicic acid, silicic anhydride, aluminum silicate, magnesium silicate, aluminum magnesium silicate, aluminum silicate sulfide, calcium silicate, barium silicate, strontium silicate, metal tungstate, hydroxy Examples include apatite, permiculite, heidilite, montmorillonite, zeolite, ceramic powder, dibasic calcium phosphate, alumina, aluminum hydroxide, boron nitride, boron nitride, and the like.

  Organic powders include polyamide powder, polyester powder, polyethylene powder, polypropylene powder, polystyrene powder, polyurethane, benzoguanamine powder, polymethylbenzoguanamine powder, tetrafluoroethylene powder, polymethyl methacrylate powder, silk powder, nylon powder, nylon 12, and nylon 12, 6 nylon, styrene / acrylic acid copolymer, divinylbenzene / styrene copolymer, vinyl resin, urea resin, phenol resin, fluororesin, silicon resin, acrylic resin, melamine resin, epoxy resin, polycarbonate resin, microcrystalline fiber powder Body, lauroyl lysine and the like.

6. Cell activator In order to administer the fullerenes of the invention of the present application to a living body or skin to promote the drug effect, it is preferable to simultaneously administer an agent for activating cells to be administered. Examples of the cell activator include deoxyribonucleic acid and salts thereof, adenylic acid derivatives such as adenosine triphosphate and adenosine monophosphate and salts thereof, ribonucleic acid and salts thereof, cyclic AMP, cyclic GMP, flavin adenine nucleotide, and guanine. , Adenine, cytosine, thymine, xanthine and their derivatives such as caffeine, nucleic acids related substances such as theopherin and their salts, calf blood extract, serum deproteinized extract, spleen extract, egg components such as birds, Chicken extract, shell extract, shell meat extract, royal jelly, silk protein and its degradation products or their derivatives, hemoglobin or its degradation products, lactoferrin or its degradation products, mollusc extracts such as cuttlefish, fish meat extracts, etc. , Mammals, birds, shellfish, insects, fish, mollusks, crustaceans, etc. Extracts from yeast extract, lactic bacteria extract, extracts derived from microorganisms selected from fermentation metabolites of bifidobacteria extract, and the like.

  Examples of cell activators include retinol and its derivatives (retinol palmitate, retinol acetate, etc.), retinal and its derivatives, vitamin A such as carotenoids such as dehydroretinal, tretinoin, carotene, etc., and thiamines (thiamine hydrochloride, thiamine sulfate, etc.). Salts), riboflavins (riboflavin, riboflavin acetate, etc.), pyridoxines (pyridoxine hydrochloride, pyridoxine dioctanoate, etc.), flavin adenine nucleotides, cyanocobalamin, folic acids, nicotinic acids (nicotinamide, benzyl nicotinate, etc.), choline B, apricot extract, ginkgo extract, Panax ginseng extract, barley extract, orange extract, cucumber extract, kiwi extract, shiitake extract, horsetail extract, assembly extract, tiso Extract, Capsicum extract, Garlic extract, Carrot extract, Bulberry extract, Peach extract, Lettuce extract, Lemon extract, Reishi extract, Rosemary extract, Asparagus extract, Ibukitorano extract , Pea extract, Age extract, Japanese gourd extract, Ononis extract, Seaweed extract, Raspberry extract, Kuddin extract, Kayoke extract, Gokahi extract, Vegetable oil containing linoleic acid, Saishin extract, Hawthorn Extract, sampens extract, white lily extract, peonies extract, peony extract, soybean extract, soybean extract, tea extract, touki extract, molasses extract, syrup extract, beech extract, grape seed extract Stuff, flow de manita extract, hop extract, silkworm extract, mocca extract, saxifrage extract , Yokuinin extract and Arhat fruit extract, furthermore, madder, red grape, red moss, akebi, asa, asagao, adzuki, asenyaku, amacha, amachaworu, knotweed, fig, ginkgo, ylang-ylang, mothweed, ume, uwaurushi, unshumikan Eleuthero, Ebisugusa, Enju, Pea, Psyllium, Okra, Ogura, Onigurumi, Ominaeshi, Dutch strawberry, Oyster, Oyster, Kashu, Cashew, Kanokosou, Rasuri, Karin, Guarana, Kikyo, Kiku, Kissage, Kishigishigishi, Kishigishisima , Guava, wolfberry, kudzu, camphor, chestnut, keikei, pepper, coffee, sesame strawberry, colom, sasanqua, sansho, saffron, safranca Kura, pomegranate, sand con, sampens, zion, shobu, watermelon, stevia, plum, pear pear, pear, pear, apocycium, pear, horseradish, sekisho, seri, senega, senna, rhubarb, daidai, tamarind, tanara Chicory, clove, artemisia, chorei, foliage, asiatica, astragalus, asiatica, cranes, teuchigurumi, tougan, eucalypt, troroaoi, nazuna, nazumikan, nanten, nigaki, stalk, pineapple, hibiscus, papaya, oak, basil , Hikikoshi, Hishiboshi, Pistachio, Hiba, Himematsutake, Juniperus, Loquat, Coltsfoot, Fushinoki, Fujibama, Blueberry, Bowberry, Physalis, Physalis, Ke, Maikai, Ephedra, Mango, Mannentake, Mishimasaico, Misohagi, Mitsuba, Mimosa, Melilot, Melon, Magnolia, Momordica Grosvenori, Moroheiya, Sprouts, Yakuchi, Yakumosou, Gagurumasou, Palm, Yasagitsu, Yamagio, Japanese moss Yuzuuriha, mugwort, rye, orchid, longan, apple, reishi, forsythia, etc., extracts derived from plants such as hinokitiol, cepharanthin, α- and γ-linolenic acid, eicosapentaenoic acid and derivatives thereof, estradiol and the like Derivatives and salts thereof, organic acids such as glycolic acid, succinic acid, lactic acid, and salicylic acid, and derivatives and salts thereof. One or more of the above-mentioned cell activators can be appropriately selected and blended.

  Examples of vitamins include vitamin Ks such as phytonadione, menaquinone, menadione, and menadiol; vitamin Ps such as eriocitrin and hesperidin; biotin, carcinine, and ferulic acid. Examples of the blood circulation promoting agent include nonylate valenylamide, capsaicin, gingerone, cantharistin tincture, itctamol, α-borneol, inositol hexanicotinate, cyclanterate, cinnarizine, trazoline, acetylcholine, perapamil, and γ-oryzanol. Examples of skin astringents include tannic acid and the like, examples of antiseborrheic agents include thiantrol, and examples of enzymes include lipase and papain.

  Amino acids include glycine, alanine, valine, isoleucine, serine, threonine, aspartic acid, glutamic acid, asparagine, glutamine, lysine, hydroxylysine, arginine, cystine, methionine, phenylalanine, tyrosine, proline, hydroxyproline, ortinin, citrulline, Examples thereof include amino acids such as theanine and derivatives thereof, and salts thereof, and amino acid derivatives such as pyrrolidonecarboxylic acid or derivatives thereof. As nucleic acid-related substances, deoxyribonucleic acid and its salts, adenylic acid derivatives selected from adenosine triphosphate, adenosine diphosphate and adenosine monophosphate and their salts, ribonucleic acids and their salts, cyclic AMP, cyclic GMP Flavin adenine nucleotide, guanine, adenine, cytosine, thymine, xanthine and their derivatives, such as caffeine and deophylline, and salts and hormones thereof include estradiol and ethenyl estradiol.

7. Ascorbic acid In the composition for external use of the present invention, ascorbic acid or a derivative thereof is preferably used.

  Above all,

(Wherein, R ¹ , R ² , R ³ and R ⁴ each independently represent a hydroxyl group, an ester group of the hydroxyl group and an inorganic or organic acid or a glycoside group of a sugar, or an adjacent 2 group of the hydroxyl group. A ketal group of a hydroxyl group and a ketone or an acetal group of an aldehyde, provided that R ¹ and R ² are not hydroxyl groups at the same time) or a salt thereof, or a salt thereof. At least one type.

  Ascorbic acid itself can be used. Ascorbic acid may be any of L-form, D-form and DL-form, and esters of inorganic or organic acids, glycosides with sugar, and hydroxyl groups of ascorbic acid It may be a ketal in which two adjacent hydroxyl groups are ketone-bonded or an acetal in which aldehyde is bonded.

  In this case, examples of the inorganic acid include phosphoric acid, diphosphoric acid, triphosphoric acid, sulfuric acid and the like, and phosphoric acid is preferable. Examples of the organic acid include acetic acid, propionic acid, butyric acid, isobutyric acid, stearic acid, myristic acid, and palmitic acid, and higher fatty acids such as palmitic acid are particularly preferable. The sugar includes glucose, sucrose, fructose and the like, and glucose is particularly preferable. Ketones include acetone and methyl ethyl ketone, and aldehydes include acetaldehyde, propynaldehyde, benzaldehyde and the like. When a salt is used, sodium, potassium, magnesium, calcium and the like can be mentioned, and a sodium salt and a magnesium salt are particularly preferable.

  Specific examples of such ascorbic acid derivatives include, for example, ascorbic acid 2-phosphate, ascorbic acid 2-diphosphate, ascorbic acid 2-triphosphate, ascorbic acid 2-polyphosphate, ascorbic acid 2-phosphate diester , Ascorbic acid 2-phosphate 6-palmitic acid, ascorbic acid 2-phosphate 6-myristate, ascorbic acid 2-phosphate 6-stearic acid, ascorbic acid 2-phosphate 6-oleic acid, ascorbic acid 2-glucoside Ascorbic acid such as, ascorbic acid 2-glucoside 6-palmitic acid, ascorbic acid 2-glucoside 6-myristic acid, ascorbic acid 2-glucoside 6-stearic acid, ascorbic acid 2-glucoside 6-oleic acid, and ascorbic acid 2-sulfuric acid Esters, alkyl L-ascorbate , L-ascorbic acid phosphate, L-ascorbic acid sulfate, etc., and their salts, such as alkali metal salts such as sodium salt and potassium salt, and alkaline earth metal salts such as calcium salt and magnesium salt. And so on. More specifically, L-ascorbic acid palmitic acid, L-ascorbic acid dipalmitic acid, L-ascorbic acid isopalmitic acid, L-ascorbic acid diisopalmitic acid, L-ascorbic acid tetraisopalmitic acid, L-stearic acid stearic acid -Ascorbic acid, L-ascorbic acid distearate, L-ascorbic acid isostearate, L-ascorbic acid diisostearate, L-ascorbic acid myristic acid, L-ascorbic acid dimyristate, L-ascorbic acid isomyristate, diisodiacid Myristic acid L-ascorbic acid, oleic acid L-ascorbic acid, dioleic acid L-ascorbic acid 2-ethylhexanoic acid L-ascorbic acid, sodium L-ascorbic acid phosphate, potassium L-ascorbic acid phosphate, L Magnesium ascorbate phosphate, calcium L-ascorbate phosphate, aluminum L-ascorbate phosphate, sodium L-ascorbate sulfate, potassium L-ascorbate sulfate, magnesium L-ascorbate sulfate, L -Calcium ascorbate sulfate, aluminum L-ascorbate sulfate, sodium L-ascorbate, potassium L-ascorbate, magnesium L-ascorbate, calcium L-ascorbate, aluminum L-ascorbate, and the like. Sodium salt, potassium salt, magnesium salt, calcium salt, zinc salt, ammonium salt, alkyl-substituted ammonium salt, hydroxyalkyl-substituted ammonium salt, etc. And the like.

  Further, a form in which these ascorbic acid derivatives are bonded to a polymer chain may be used. From the viewpoints of convenience in formulation such as water solubility, the chemical stability of the derivative, and the effect, ascorbic acid 2-phosphate and ascorbic acid 2-glucoside, and the above salts thereof are particularly preferable.

  8. As the pH adjuster, a storage stabilizer or an organic acid having a chelating effect or a salt thereof is preferably exemplified. These include erythorbic acid and its salts, dibutylhydroxytoluene, tocopherol and its derivatives, porphyrin, butylhydroxyanisole, sodium bisulfite, anhydrous sodium sulfite, gallic acid and its derivatives, alanine, sodium ethylenediaminehydroxyethyltriacetate, and ethylenediaminetetraacetic acid. And salts thereof, citric acid and salts thereof, gluconic acid, tartaric acid, phytic acid, sodium polyphosphate, at least one selected from the group consisting of sodium metaphosphate, the amount of which is based on the total weight of the composition for external use In the range of 0.01% to 50% by weight, preferably in the range of 0.1% to 5% by weight. The salt is not particularly limited, but is preferably a metal other than a transition metal from the viewpoint of safety on the skin, and particularly preferably sodium, potassium, magnesium and calcium.

9. Active oxygen scavenger In order to promote the active oxygen scavenging activity of the fullerenes of the present invention, it is preferable to simultaneously administer another active oxygen scavenger. Active oxygen scavengers include superoxide dismutase, mannitol, bilirubin, cholesterol, tryptophan, histidine, quercetin, quercitrin, catechin, catechin derivatives, rutin, rutin derivatives, taurine, thiotaurine, eggshell membrane extract, gallic acid, gallic acid Derivatives, yeast extract, ganoderma extract, yasajitsu extract, geno ginger extract, buttonpi extract, melissa extract, parsley extract and dicoppi extract, retinol and its derivatives (retinol palmitate, retinol acetate, etc.), retinal And derivatives thereof, vitamin A such as dehydroretinal; thiamines (thiamine hydrochloride, thiamine sulfate, etc.), riboflavins (riboflavin, riboflavin acetate, etc.), pyridoxines (pyridoxine hydrochloride, Vitamin B such as doxin dioctanoate), flavin adenine nucleotide, cyanocopalamine, folate, nicotinic acid (nicotinamide, benzyl nicotinate), choline; ergocalciferol, cholecalciferol, dihydroxysta Vitamin Ds such as nal; tocopherol and derivatives thereof (dl-α (β, γ) -tocopherol, dl-α-tocopherol acetate, nicotinic acid-dl-α-tocopherol, linoleic acid-dl-α-tocopherol, succinic acid) vitamin Es such as dl-α-tocopherol) and ubiquinones; dibutylhydroxytolene and butylhydroxyanisole.

10. Other Compounding Agents A preservative such as ethanol can be added for the purpose of storing the composition for external use containing the fullerenes of the present invention or a diluent thereof. Further, the pH can be adjusted by adding a pH adjuster such as an organic acid such as citric acid, fumaric acid, succinic acid, and lactic acid, or NaOH or KOH.

  In any case, the composition for external use containing the fullerenes of the invention of the present application contains, as far as the pharmacological effect is not impaired, components usually used in the preparation of external preparations, that is, water (purified water, hot spring water) Water, deep water, etc.), oils, surfactants, metal soaps, gelling agents, powders, alcohols, water-soluble polymers, film-forming agents, resins, ultraviolet protection agents, clathrate compounds, antibacterial agents, fragrances, Deodorants, salts, pH regulators, fresheners, animal / microbial extracts, plant extracts, blood circulation promoters, astringents, antiseborrheic agents, active oxygen scavengers, cell activators, humectants, keratolytics One, two or more agents, enzymes, hormones, vitamins, and the like can be appropriately added.

  Also, as an ultraviolet ray protective agent, 2-ethylhexyl paramethoxycinnamate, isopropyl paramethoxycinnamate, diethanolamine salt of paramethoxyhydrocinnamate, glyceryl mono-2-ethylhexanoate diparamethoxycinnamate, methoxycinnamate Cinnamic acid-based ultraviolet absorbers such as octyl and methyl diisopropylcinnamate 2-hydroxy-4-methoxybenzophenone-2-hydroxy-4-methoxybenzophenone-5-sulfate 2-hydroxy-4-methoxybenzophenone-5-sulfate Sodium, 2,4-dihydroxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 2,2 ', 4,4'-tetrahydroxybenzophenone- 2-hydroxy- Benzophenone ultraviolet absorbers such as -n-octoxybenzophenone, benzoic acids such as paraaminobenzoic acid, ethyl paraaminobenzoate, butyl paraaminobenzoate, 2-ethylhexyl paradimethylaminobenzoate, glyceryl paraaminobenzoate and amyl paraaminobenzoate; UV absorbers, 2-ethylhexyl salicylate, triethanolamine salicylate, homomenthyl salicylate, dipropylene glycol salicylate, methyl salicylate, ethylene glycol salicylate, phenyl salicylate, amyl salicylate, benzyl salicylate, isopropyl benzyl salicylate, and salicylic acid salts such as potassium salicylate UV absorbers: 4-tert-butyl-4'-methoxydibenzoylmethane, 4-isopropyldibenzoylmethane, 4-meth Dibenzoylmethane-based ultraviolet absorbers such as xidibenzoylmethane and 4-t-butyl-4'-hydroxydibenzoylmethane; menthyl-O-aminobenzoate, 2-phenyl-benzimidazole-5-sulfate, 2-phenyl -5-methylbenzoxazole, 3- (4-methylbenzylidene) camphor, 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate, 2-ethyl-2-cyano-3,3'-diphenyl acrylate, -(2'-hydroxy-5-methylphenyl) benzotriazole, anthranilic acid-based ultraviolet absorbers such as menthyl anthranilate; urocanic acid-based ultraviolet absorbers such as ethyl urocanate; titanium oxide, zirconium oxide, cerium oxide and the like. Can be These metal oxides may be those coated with silica. The blending amount of the ultraviolet ray protective agent may be 0.001 to 50% by weight, preferably 0.01 to 10%.

  Antibacterial agents include benzoic acid, sodium benzoate, carboxylic acid, sorbic acid, potassium sorbate, paraoxybenzoate, parachloromethcresol, hexachlorophene, benzalkonium chloride, chlorhexidine chloride, trichlorocarbanilide, photosensitizer, Examples include bis (2-pyridylthio-1-oxide) zinc, phenoxyethanol and thiantol, and isopropylmethylphenol. Examples of the pH adjuster include potassium carbonate, sodium hydrogen carbonate, and ammonium hydrogen carbonate. Examples of the cooling agent include L-menthol, camphor and the like.

  As anti-inflammatory agents, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, β-glycyrrhetinic acid, stearyl glycyrrhetinate, glycyrrhizic acid such as disodium 3-succinyloxyglycyrrhetinate, or glycyrrhetinic acid and derivatives thereof and salts thereof, Mefenamic acid, phenylbutazone, indomethacin, ibuprofen, ketoprofen, allantoin, guaiazulene, calcium pantetonate, D-pantothenyl alcohol, pantothenyl ethyl ether, panthenol such as acetyl pantothenyl ethyl ether and derivatives thereof and salts thereof, ε-aminocaproic acid, diclofenac sodium, tranexamic acid and the like. The compounding amount is 0.001 to 10% by weight, more preferably 0.01 to 5% by weight.

Antioxidants include superoxide dismutase, mannitol, histidine, tryptophan, bilirubin, quercetin, quercitrin, polyphenol, proanthocyanidin, tocotrienol, catechin, catechin derivative, rutin and its derivatives, gallic acid and its derivatives, ubiquinone, astaxanthin , Carotene, and other retinols such as retinol palmitate and retinol acetate; retinal and its derivatives; retinal and its derivatives; dehydroretinal, carotene, lycopene, carotenoids such as astaxanthin; thiamine hydrochloride, thiamine sulfate, riboflavin, acetic acid Pyridoxines such as riboflavin, pyridoxine hydrochloride, pyridoxine dioctanoate, flavin adenine nucleotide, cyano Vitamin B such as nicotinic acid such as paraamine, folic acid, nicotinamide and benzyl nicotinate, and choline; Vitamin D such as ergocalciferol, cholecalciferol and dihydroxystannal; dl-α (β, γ) -Tocopherols such as tocopherol, dl-α-tocopherol acetate, dl-α-tocopherol nicotinate, dl-α-tocopherol linoleate, dl-α-tocopherol succinate and derivatives thereof, and vitamin Es such as ubiquinones; Examples thereof include dibutylhydroxytoluene and butylhydroxyanisole.
<D> Stable external preparation containing fullerenes When the external composition of the invention of the present application is more practically applied as an external preparation, the components as described above, namely,
<1> Nonionic surfactant <2> Ascorbic acid or a derivative or salt thereof <3> It is preferable to contain at least one or more of ultraviolet protective agents. And, more preferably, the <1> nonionic surfactant is in a range of 0.01% by weight to 50% by weight of the whole composition, and one or more selected from the following. is there. That is, POE sorbitan fatty acid esters such as POE sorbitan monooleate, POE sorbitan monostearate, POE sorbitan monolaurate, POE sorbitan tetraoleate, POE sorbit monolaurate, POE sorbit monooleate, POE sorbit pentaoleate , Sorbitol fatty acid esters such as POE sorbit monostearate, POE glycerin fatty acid esters such as POE glycerin monostearate, POE glycerin triisostearate, POE fatty acid esters such as POE monooleate, and POE alkyl such as POE lauryl ether Ethers, POE alkyl phenyl ethers such as POE octyl phenyl ether, POE / PO such as POE / POP cetyl ether Alkyl ethers, tetra-POE / tetra-POE ethylenediamine condensates, POE castor oil or hydrogenated castor oil derivatives, POE beeswax lanolin derivatives, alkanolamides such as lauric acid monoethanolamide, POE propylene glycol fatty acid esters, POE alkylamines, It is at least one selected from POE fatty acid amide, sucrose fatty acid ester, POE nonylphenylformaldehyde condensate, alkylethoxydimethylamine oxide, trioleyl phosphoric acid, and polyglycerin fatty acid ester.

  <2> Ascorbic acids are contained in the range of 0.01 to 20% by weight, and more preferably 0.1 to 10% by weight, based on the total amount of the composition, and the compound represented by the formula (1) is used. And one or more selected from salts thereof.

  <3> The ultraviolet ray protective agent is in the range of 0.01% by weight to 50% by weight based on the total amount of the composition, and one or more selected from the following. That is, 2-ethylhexyl paramethoxycinnamate, isopropyl paramethoxycinnamate, diethanolamine salt of paramethoxyhydrocinnamate, glyceryl mono-2-ethylhexanoate, octyl methoxycinnamate, diisopropyl cinnamate Cinnamic acid-based ultraviolet absorbers such as methyl cinnamate-2-hydroxy-4-methoxybenzophenone-2-hydroxy-4-methoxybenzophenone-5-sulfate 2-hydroxy-4-methoxybenzophenone-5-sulfate sodium, 2, 4-dihydroxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 2,2 ', 4,4'-tetrahydroxybenzophenone-2-hydroxy- 4-n-oct Benzophenone UV absorbers such as benzophenone, benzoic acid UV absorbers such as paraaminobenzoic acid, ethyl paraaminobenzoate, butyl paraaminobenzoate, 2-ethylhexyl paradimethylaminobenzoate, glyceryl paraaminobenzoate and amyl paraaminobenzoate Salicylic acid-based ultraviolet absorbers, such as 2-ethylhexyl salicylate, triethanolamine salicylate, homomenthyl salicylate, dipropylene glycol salicylate, methyl salicylate, ethylene glycol salicylate, phenyl salicylate, amyl salicylate, benzyl salicylate, isopropyl benzyl salicylate, and potassium salicylate; 4-tert-butyl-4'-methoxydibenzoylmethane, 4-isopropyldibenzoylmethane, 4-methoxydibenzo Dibenzoylmethane-based ultraviolet absorbers such as methane, 4-tert-butyl-4'-hydroxydibenzoylmethane, and menthyl-O-aminobenzoate-2-phenyl-benzimidazole-5-sulfate-2-phenyl-5- Methylbenzoxazole, 3- (4-methylbenzylidene) camfur-2-ethylhexyl-2-cyano-3,3-diphenylacrylate-2-ethyl-2-cyano-3,3'-diphenylacrylate-2- (2 '-Hydroxy-5-methylphenyl) benzotriazole, anthranilic acid-based ultraviolet absorbers such as menthyl anthranilate, urocanic acid-based ultraviolet absorbers such as ethyl urocanate, titanium oxide, zirconium oxide, cerium oxide, zinc oxide and the like. It is a silica coating of a metal oxide.

  And, in order to obtain a stable composition, in the invention of this application, one or more of the following are added in a range of 0.01% by weight to 10% by weight based on the whole composition. And <4> a storage stabilizer or an organic acid having a chelating effect or a salt thereof. That is, erythorbic acid and its salts, dibutylhydroxytoluene, tocopherol and its derivatives, porphyrin, butylhydroxyanisole, sodium bisulfite, anhydrous sodium sulfite, gallic acid and its derivatives, alanine, sodium ethylenediaminehydroxyethyltriacetate, ethylenediaminetetraacetic acid and It is at least one selected from the group consisting of salts thereof, citric acid and salts thereof, gluconic acid, tartaric acid, phytic acid, sodium polyphosphate and sodium metaphosphate.

  In such a stabilizing composition, it is particularly preferable that the pH value of the aqueous composition is in the range of 3 to 10 as described above.

  When the antioxidant power of fullerene is applied to a composition for external use, fullerene is usually easily oxidized due to the strong antioxidant power of fullerene, and tends to be unstable in a preparation even when mixed with the composition for external use.

  In other words, fullerene exerts a reducing property in the composition for external use due to the strong antioxidant power and is rapidly oxidized. As a result, when administered to the skin, the antioxidant power may decrease, weaken, or deactivate, failing to exert a sufficient effect.

  Even when fullerene is applied as an external preparation, the active ingredient is oxidatively decomposed, and some of the fullerenes are converted to free radicals on the skin under the influence of ultraviolet rays or the like, so the effect as an antioxidant is insufficient. There is a case where the effect as an external preparation cannot be sufficiently exhibited and the effect of treatment cannot be sufficiently exerted, so that the effect may be limited to the protective or preventive effect.

In response to such a concern, the above composition will achieve good stability.
<E> External preparation with enhanced effect Further, in the invention of this application, as a composition for a more suitable external preparation, at least one of the following components is contained, so that skin whitening is achieved. , Improve pigmentation, treat acne, improve wrinkles, improve rough skin, improve oily skin, improve dry skin, reduce pores, treat scars, treat redheads, treat hair loss, promote hair growth, and treat burns And a fullerene external composition having enhanced effects of sterilizing skin, killing mites on skin, and improving skin texture.

That is,
<5> A whitening component of 0.01% by weight to 20% by weight based on the total amount of the composition, which is cysteine and its derivatives, salts thereof, glabridine, glabrin, liquiritin, isoliquiritin, placenta extract, hydroquinone and its derivatives. , Resorcin and derivatives thereof, and glutathione.
<6> Glycyrrhizic acid, glycyrrhetinic acid and their derivatives and their salts, mefenamic acid, phenylbutazone, indomethacin, as anti-inflammatory components in the range of 0.001% by weight to 10% by weight based on the whole composition. It is at least one selected from ibuprofen, ketoprofen, allantoin, guaiazulene, panthenol and derivatives thereof and salts thereof, ε-aminocaproic acid, diclofenac sodium, and tranexamic acid.
<7> Superoxide dismutase, mannitol, histidine, tryptophan, bilirubin, quercetin, quercitrin, polyphenol, proanthocyanidin, tocotrienol as antioxidant in the range of 0.001% by weight to 10% by weight based on the whole composition , Catechin, catechin derivatives, rutin and its derivatives, gallic acid and its derivatives, ubiquinone, astaxanthin, carotene, and other carotenoids and their derivatives and their salts, vitamin B and their derivatives and their salts, vitamins It is at least one selected from D and their derivatives and their salts, vitamin E and their derivatives and their salts, dibutylhydroxytoluene and butylhydroxyanisole.

  Therefore, examples will be shown below, and the invention of this application will be described in more detail. Of course, the invention is not limited by the following examples.

<A> Activity test of active ingredient-Part 1
The following samples (A) to (G) were prepared.

F1: MIX fullerene containing C60 fullerene and C70 fullerene (average molecular weight: 744 / powder)
F2: C60 fullerene (molecular weight 720 / powder)
F3: PEG-modified fullerene (average molecular weight 20,000 / 70 mg / ml (pure aqueous solution), PEG: molecular weight 5200: modification ratio 1-4 mol / mol fullerene, MIX fullerene: 744, MIX fullerene concentration: 2 mg / ml)
F4: PVP inclusion fullerene (average molecular weight 40,000 / 70 mg / ml (pure aqueous solution), PVP: molecular weight 40,000, MIX fullerene: 744, MIX fullerene concentration: 0.3 mg / ml)
F5: CD inclusion fullerene (average molecular weight 1235 / 4.8 mg / ml (pure aqueous solution), gamma-CD (cyclodextone): molecular weight 1297: mixing ratio 4 mol / mol fullerene, MIX fullerene: molecular weight 744, MIX fullerene concentration: 0.3mg / ml)
F6: fullerene hydroxide: average molecular weight 958.7 / powder (water-soluble solid), hydroxylation rate 14 OH group / molecule
F7: MIX fullerene / isostearic acid: average molecular weight 744/5 mg / g (solvent isostearic acid: molecular weight 284)
<1> The above sample was placed in a 1.5 ml Eppendorf tube according to the instructions in Table 1 below, added with H ₂ O ₂ , allowed to react for 30 seconds, and then measured by ESR to determine the fullerenes by ESR trapping method. The hydroxy radical scavenging activity was evaluated. In the test, when DMPO was added as a spin trapping agent to stabilize an unstable hydroxyl radical as an adduct, a characteristic of 1: 2: 2: 1 was obtained with an electron spin resonance apparatus (manufactured by JEOL Ltd., JES-FR30 type). Since an electron spin resonance spectrum exhibiting a typical quartet is observed, the amount of hydroxyl radical was calculated by a ratio of this intensity to the intensity of manganese oxide exhibiting a paramagnetic spectrum added as a comparative internal standard.

  For samples F6 and F7, the maximum amount soluble in 70% Ethanol was diluted to 0.2%. In addition, DMSO is a scavenger for hydroxy radicals, and Ethanol has been found to have a hydroxy radical scavenging activity.

  When the results of the test are evaluated as residual amounts of droxyl radicals: Relative Signal Intensity (DMPO-OH / MnO), the results can be exemplified as shown in Table 2 below.

  For example, as shown in Table 2, remarkable hydroxyl radical scavenging activity was recognized in three types of fullerenes (F3, F6, and F7), and all of the existing provitamin C (A2P: Ascorbic Acid 2) frequently used in commercial cosmetics were observed. -Phosphate Na) was slightly superior or equivalent.

  <2> Further, each sample was placed in a 1.5 ml Eppendorf tube according to the instructions in Table 3 below, added with XOD, allowed to react for 30 seconds, and then measured by ESR to determine the superoxide elimination activity by ESR spin trapping. Was evaluated. The test method is the same as in the case of the hydroxyl radical. When a spin trapping agent DMPO is added, an electron spin resonance apparatus (manufactured by JEOL Ltd., JES-FR30 type) exhibits a slightly fine 1: 1: 1: 1 quartet electron spin resonance. Since the spectrum was observed, this intensity was calculated by calculating the amount of the superoxide anion radical based on the ratio of the intensity to the intensity of manganese oxide exhibiting a paramagnetic spectrum added as a comparative internal standard.

  In addition, about F6 and F7, the maximum amount which can be dissolved with 70% Ethanol was diluted to 0.2% in the same manner as described above.

  When the result of the test is evaluated as a superoxide anion radical residual amount: Relative Signal Intensity (DMPO-OOH / MnO), the following Table 4 can be exemplified.

  For example, as shown in Table 4, two types of fullerenes (F3, F4) have remarkable hydroxyl radical scavenging activity, and both of them greatly surpass existing provitamin C (A2P) frequently used in commercial cosmetics. One of them (F3) also had the hydroxyl radical scavenging activity as described above. The other two types (F5 and F6) also had the same or higher erasing activity than provitamin C.

  <3> With respect to various samples, the antioxidant effect on UVB was evaluated using keratinocytes, which are major human cells. As a test method, CDCFH-DA was loaded inside the cell as a redox indicator, and when this was oxidized by peroxide / hydrogen peroxide generated by ultraviolet irradiation, fluorescence was generated. (Model 2350 manufactured by Millipore / Perceptive).

  When the skin is exposed to sunlight, the UVB waves in the light beam cause peroxide / hydrogen peroxide to be generated inside the cells, DNA breakage, DNA damage and cell membrane breakdown, causing cell death.

Then, when UVB waves were irradiated to human skin epidermal keratinocytes at a dose of 40 mJ / cm ² at which erythema of the skin started to form, it was confirmed that the peroxide / hydrogen peroxide in the cells reached the maximum value 4 minutes after irradiation. Therefore, before irradiation, a sample was added in advance to evaluate the antioxidant effect.

  The result is illustrated in FIG. Three types of fullerenes (F4, F5, and F6) exhibited the same activity of scavenging peroxides and hydrogen peroxide in skin cells as the existing provitamin C (Asc2P-Na), that is, an antioxidant effect.

  <4> For each sample, the scavenging activity against peroxide and hydrogen peroxide in skin cell cells induced by lipid peroxide (altered oil) was evaluated.

  Lipids in the skin are always susceptible to oxidation, which causes skin cell death.In particular, lipids in the stratum corneum such as ceramide and squalene are oxidized and converted to hydroperoxide. Causes cell death.

When t-BuOOH (tert-butylhydroperoxide), which is a kind of hydroperoxide, is added to human skin epidermal keratinocytes at a concentration of 140-250 μM which causes cell death of 40-70%, the intracellular peroxide is added 150 minutes after the addition. It has been confirmed by the inventor that hydrogen peroxide has a maximum value. Therefore, before the addition, a sample was added in advance to evaluate the peroxide / hydrogen peroxide scavenging activity.


As a test method, CDCFH-DA was loaded inside the cell as a redox indicator, and when this was oxidized by peroxide / hydrogen peroxide generated by adding t-BuOOH, fluorescence was generated. Was measured using a fluorescent plate reader (manufactured by Millipore / Perceptive, Model 2350).

  The result is illustrated in FIG.

Addition of t-BuOOH, a peroxide model substance that has cell killing ability to human skin keratinocytes, generates peroxide and hydrogen peroxide in the cells. The scavenging activity surpassed that of vitamin C. This fullerene is a specimen sample which has a protective activity against ultraviolet rays and superoxide anion radicals.
<B> Active ingredient activity test-Part 2
First, PVP (polyvinylpyrrolidone) -modified composite fullerene was prepared by the following method in accordance with known literature.

  Here, the notation of PVP molecular weight 60000 indicates a weight average molecular weight (viscosity measurement method) of 60,000. That is, for example, specifically, first, a stirred solution of mixed fullerene (C60: C70 = 3.5 .: 1 mol / mol) (0.8 mg) dissolved in toluene (1.0 ml) is mixed with a PVP molecular weight of 60000 ( (100 mg) in chloroform at room temperature. After thorough mixing, the solvent was evaporated under reduced pressure. The residue was dissolved in 2.0 ml of Milli-Q water, and the suspension temperature was azeotropically distilled to remove toluene.

  An aqueous product was obtained. This was further filtered and dried under reduced pressure to obtain a solid (powder).

  Similarly, fullerene modified and complexed with a PVP molecular weight of 8,000 having a weight average molecular weight of 8,000 was prepared.

  <1> The PVP. The effect of administering fullerene to human skin oxidized cells (HaCaT) was evaluated by measuring cell viability by the WST-1 method. The WST-1 method uses a WST-1 reagent (tetrazolium salt) that is reduced by mitochondrial dehydrogenase in living cells to produce a water-soluble formazan that develops a color. This is a method of measuring with a reader (450 nm).

  FIG. 3 attached shows an example of the result when an aqueous solution of PVP molecular weight 8000 fullerene was administered 3 hours before the addition of t-BuOOH, and FIG. This is an example of the results in the case of fullerene having a molecular weight of 60000.

  For example, from such verification of the cell viability, the optimal dose for producing a cell death protective effect is PVP. In the case of a molecular weight of 8000 (molecular weight of 8,000), it is 100-250 μM (0.08-0.12 wt / wt%), 4-6 ppm in terms of fullerene concentration, and a PVP molecular weight of 60000 (molecular weight of 60,000). In the case of 2, it was confirmed that the concentration was 10-25 μM (0.06-015 wt / wt%), which was 3-7.5 ppm in terms of fullerene concentration.

  FIG. 5 shows the protective effect of PVP fullerene against cell changes of human skin keratinocytes (HaCaT) by lipid peroxide model agent t-BuOOH. It is a case where the molecular weight is 60000. The protective effect is remarkably confirmed.

  FIG. 6 shows the measurement results for vitamin C (L-ascorbic acid) for comparison. In comparison with such vitamin C, for example, in the case of a fullerene complex having a PVP molecular weight of 60000, It is confirmed that a cell death protection effect about 10 times that of vitamin C is realized.

  <2> FIG. FIG. 4 shows the results of evaluating the cell death inhibitory effect (cell viability) upon irradiation with UV light in the case of using a molecular weight of 60000, in the case of pre-administration, and in the case of total administration.

  Here, the pre-administration refers to a state in which the fullerene complex is administered immediately before the UV irradiation and removed immediately before the irradiation, and the whole administration refers to a state in which the fullerene complex is not removed during the measurement. The measurement is based on the WST-1 method as in the above <1>.

It can be seen that the PVP fullerene complex achieves a remarkable effect at the time of all administrations and at the time of UVB irradiation even in the case of pre-administration.
<C> Composition for external use and its effects 1) Composition of composition The following composition was prepared using the fullerenes in the above <A>.

Invention lotion 1
F1 0.1%
Citric acid 1.0%
L-Ascorbic acid 2-phosphate Na 1%
POE sorbitan monooleate 0.5%
2-ethylhexyl paramethoxycinnamate 0.2%
Xanthan gum 0.1%
NaOH (adjust pH to 8)
Purified water Remaining invention lotion 2
F3 0.1%
Citric acid 1.0%
Xanthan gum 0.2%
NaOH (adjust pH to 8)
Purified water Remaining invention lotion 3
F4 0.1%
L-ascorbic acid 2-phosphate Na 0.5%
Xanthan gum 0.1%
NaOH (adjust pH to 8)
Purified water Remaining invention lotion 4
F5 0.1%
POE sorbitan monooleate 0.6%
Xanthan gum 0.1%
NaOH (adjust pH to 8)
Purified water balance Invention lotion 5
F6 0.1%
2-ethylhexyl paramethoxycinnamate 0.1%
Xanthan gum 0.1%
NaOH (adjust pH to 8)
Purified water Remaining lotion of the invention 1:
(Prescription) (Hereinafter indicated by weight%)
(1) F 1: 0.5, (2) 1,3-butylene glycol 5.5, (3) polyoxyethylene (20EO) sorbitan 1.2 monolaurate 5.0, (4) ethyl Alcohol 8.0, (5) Oolong tea extract (* 1) 1.0, (6) Seaweed extract (* 2) 1.0, (7) Magnesium phosphate L-ascorbate (* 3) 0.5 , (8) Sodium 2-hydroxy-4-methoxybenzophenone-5-sulfate (* 4) 1.0, (9) ε-Aminocaproic acid (* 5) 0.2, (10) Preservative, qs, (11) Appropriate amount of flavor, (12) Remaining amount of purified water (pH adjusted to 7 ± 1 with 1% citric acid and NaOH)
* 1 Maruzen Pharmaceutical * 2 Ichimaru Falcos * 3 Wako Pure Chemical * 4
* 5 Sigma (pH adjusted to 7 ± 1 with 1% citric acid and NaOH)
Invention lotion 2:
(Prescription) (Hereinafter indicated by weight%)
(1) F2: 0.5, (2) 1,3-butylene glycol 6.5, (3) polyoxyethylene (20EO) sorbitan 1.2 monolaurate 3.5, (4) ethyl Alcohol 8.0, (5) Oolong tea extract (* 1) 1.0, (6) Seaweed extract (* 2) 1.0, (7) Magnesium phosphate L-ascorbate (* 3) 0.5 , (8) Sodium 2-hydroxy-4-methoxybenzophenone-5-sulfate (* 4) 1.0, (9) ε-Aminocaproic acid (* 5) 0.2, (10) Preservative, qs, (11) Appropriate amount of flavor, (12) Remaining amount of purified water (pH adjusted to 7 ± 1 with 1% citric acid and NaOH)
* 1 Maruzen Pharmaceutical * 2 Ichimaru Falcos * 3 Wako Pure Chemical * 4
Merck * 5 Sigma invention emulsion:
(Prescription) (%)
(1) polyoxyethylene (10EO) sorbitan 1.0 monostearate 7.0, (2) polyoxyethylene (60EO) sorbit 0.5 tetraoleate 2.0, (3) glyceryl Monostearate 1.0, (4) stearic acid 0.5, (5) behenyl alcohol 0.5, (6) F4: 6.0, (7) jojoba oil (* 1) 1.0, (8) tetra Isopalmitic acid L-ascorbic acid (* 2) 2.0, (9) Barley lubricating oil (* 3) 0.1, (10) Carrot extract (* 4) 0.1, (11) D-pan Tenol (* 5) 0.1, (12) Retinol palmitate (* 6) 0.01, (13) Preservative 0.1, (14) Carboxyvinyl polymer 0.1, (15) Sodium hydroxide 0. 05, (16) ethyl alcohol 5.0, (17) Remaining amount of purified water, (18) Appropriate amount of perfume (pH adjusted to 7 ± 1 with 1% citric acid and NaOH)
* 1 High quality alcohol industry * 2 Nippon Surfactant * 3 Technoble * 4 Maruzen Pharmaceutical * 5 Sigma * 6 Nippon Roche invention cream:
(Prescription) (%)
(1) polyoxyethylene (40EO) monostearate 2.0, (2) glycerin monostearate (self-emulsifying type) 5.0, (3) stearic acid 5.0, (4) behenyl alcohol (* 1) 0.5, (5) squalane 15.0, (6) cetyl isooctanoate 5.0, (7) 1,3-butylene glycol 5.0, (8) F7: 1.0, (9) birch Extract (* 2) 0.1, (10) Saxifraga extract (* 3) 0.2, (11) Sodium L-ascorbic acid 2-phosphate (* 4) 1.0, (12) Paramethoxysilicate 2-ethylhexyl cinnamate (* 5) 5.0, (13) Riboflavin (* 6) 0.05, (14) Cysteine (* 7) 0.1, (15) Remaining purified water, (16) Preservative Proper amount, (17) proper amount of flavor (1% citric acid and NaOH It was adjusted to 7 ± 1.)
* 1 Seiwa Kasei Co., Ltd. * 2 Maruzen Pharmaceutical Co., Ltd. * 3 Ichimaru Falcos Co., Ltd. * 4
Sigma * 5 BASF * 6 Sigma * 7 Cysteine (manufactured by Wako Pure Chemical Industries) was diluted with water to 1.0 mg / ml and used.

Inventive gel ointment:
(Prescription) (%)
(1) stearic acid 18.0, (2) cetanol 4.0, (3) triethanolamine 2.0, (4) F5: 1.0, (5) nettle extract (* 1) 0.05, (6) Hawthorn extract (* 2) 0.05, (7) Bodaiju extract (* 3) 0.05, (8) N, N'-diacetylcystine dimethyl (* 4) 0.01, (9) Tranexamic acid (* 5) 0.2, (10) Remaining amount of purified water (pH adjusted to 7 ± 1 with 1% citric acid and NaOH)
* 1 Maruzen Pharmaceutical * 2 Maruzen Pharmaceutical * 3 Maruzen Pharmaceutical * 4 Sigma * 5 Sigma Inventive sunscreen emulsion:
(Prescription) (%)
(1) stearic acid 2.0, (2) cetanol 1.0, (3) polyoxyethylene sorbitan monooleate (20EO) 0.5, (4) sorbitan sesquioleate 0.5, (5) ) 2-Ethylhexyl paramethoxycinnamate (* 1) 8.0, (6) Cetyl 2-ethylhexanoate 12.0, (7) 1,3-butylene glycol 10.0, (8) Carboxyvinyl polymer 0 2, (9) Triethanolamine 0.5, (10) Peppermint extract (* 2) 0.02, (11) F4: 0.1, (12) Licorice extract (* 3) 0.02 (13) Placental extract (* 4) 0.3, (14) dl-α-tocopherol acetate (* 5) 0.2, (15) Remaining purified water, (16) Appropriate amount of preservative, (17) Oxidation Titanium 3.0, (18) Fragrance (The pH was adjusted to 7 ± 1 with 1% acid and NaOH.)
* 1 manufactured by Maruzen Pharmaceutical Co., Ltd. * 2 manufactured by Ichimaru Falcos Co., Ltd. * 3 manufactured by Maruzen Pharmaceutical Co., Ltd. * 4 manufactured by Nichirei Co., Ltd. * 5 manufactured by Eisai Co., Ltd. 2) Stability test 45 ° C. for 3 months using lotions 1 to 5 above As a result of the stability test, the hydroxy radical scavenging activity was measured by the ESR trapping method after adding hydrogen peroxide to the lotion before and after the stability test, and the remaining activity was shown in%.
(Residual rate of hydroxy radical scavenging activity)
Invention lotion 1 91%
Invention lotion 2 87%
Invention lotion 3 94%
Invention lotion 4 84%
Invention lotion 5 81%
From the above results, it was confirmed that high activity of the fullerene external composition of the present invention was maintained.

3) Effect test Among patients who visited the cosmetic dermatology, skin whitening, improvement of pigmentation, treatment of acne, improvement of wrinkles, improvement of rough skin, improvement of oily skin, improvement of dry skin, reduction of pores, scarring 20 patients, 15- to 75-year-old men and women, who are alleged to treat skin, treat baldness, treat hair loss, promote hair growth, treat burns, sterilize skin, kill mites, and improve skin texture The group was divided into two groups, a group using the preparation of lotion 6 of the invention of the following formula and a placebo group, and applied to the affected area twice in the morning and evening for 59 days to 97 days, and the results were subjected to a questionnaire survey based on the score. Table 2 summarizes the results.
(Evaluation criteria)
[Score] [State]
0: Significant effect is recognized 1: Effect is observed 2: Very slight effect is recognized 3: No effect According to the above evaluation criteria, the number of patients out of 20 patients whose scores are 1 or lower is counted. The judgment was made according to the judgment criteria.
(Judgment criteria)
<Judgment><Contents> Excellent Out of 20, 16 or more patients with a score of 1 or lower Efficient Out of 20, 12 to 14 patients with a score of 1 or lower.
Moderately effective Out of 20, 8 to 10 patients have a score of 1 or less.
Ineffective 20 or less patients have a score of 1 or less.

Invention Lotion 6:
F4 0.1%
Citric acid 1.0%
L-ascorbic acid 2-phosphate Na 0.8%
POE sorbitan monooleate 0.5%
2-ethylhexyl paramethoxycinnamate 0.2%
Xanthan gum 0.1%
Gravlidine Glycyrrhizic acid Nicotinic acid amide NaOH (pH adjusted to 8)
Purified water balance Placebo lotion:
Citric acid 1.0%
L-Ascorbic acid 2-phosphate Na 1%
POE sorbitan monooleate 0.5%
2-ethylhexyl paramethoxycinnamate 0.1%
Xanthan gum 0.1%
Gravlidine Glycyrrhizic acid Nicotinic acid amide NaOH (pH adjusted to 8)
Purified water balance

  As a result, in the fullerene-containing topical composition of the present invention, skin whitening, improvement of pigmentation, treatment of acne, improvement of wrinkles, improvement of rough skin, improvement of oily skin, improvement of dry skin, reduction of pores, scarring Excellent effects were observed in all target diseases such as the treatment of swelling, the treatment of red face, the treatment of hair loss, the promotion of hair growth, the treatment of burns, the disinfection of skin, the killing of mites and the improvement of skin texture.

It is the figure which illustrated the evaluation result of the antioxidant activity with respect to UVB irradiation. It is the figure which illustrated the evaluation result of the antioxidant activity with respect to t-BuOOH. PVP. It is a figure which showed the cell death protective effect with respect to t-BuOOH in case of molecular weight 8000. It is a figure which showed the cell death protection effect with respect to t-BuOOH in case of PVP molecular weight 60000. It is a photograph which showed the above-mentioned effect of PVP molecular weight 60000. It is a figure showing the cell death protection effect to t-BuOOH in the case of vitamin C as a comparison. It is a figure showing the cell death protection effect in the case of pre-administration against UV irradiation and all administrations.

Claims (11)

  An antioxidant composition comprising, as an active ingredient, at least one of fullerene, a fullerene derivative, the fullerene modified or included by an organic compound, the fullerene derivative, and a salt thereof.   2. The antioxidant composition according to claim 1, wherein the organic compound that modifies or includes the fullerene or the fullerene derivative is at least one of an organic oligomer, an organic polymer, cyclodextrin, and a crown ether and their analogous compounds. .   The antioxidant composition according to claim 1 or 2, comprising a long-chain carboxylic acid having 10 or more carbon atoms or an ester or salt thereof.   The antioxidant composition according to any one of claims 1 to 3, wherein the fullerene is a C60 fullerene, a C70 fullerene, or a fullerene mixture containing both of them.   An external article composition comprising at least one of fullerene, a fullerene derivative, the fullerene or the fullerene derivative modified or included by an organic compound, and a salt thereof.   The external composition according to claim 5, wherein the organic compound that modifies or includes the fullerene or the fullerene derivative is at least one of an organic oligomer, an organic polymer, a cyclodextrin, a crown ether, and an analogous compound thereof.   The topical composition according to claim 5 or 6, further comprising a long-chain carboxylic acid having 10 or more carbon atoms or an ester or salt thereof.   The external composition according to any one of claims 5 to 7, wherein the fullerene is a C60 fullerene, a C70 fullerene, or a fullerene mixture containing both of them. It comprises at least one of the fullerene, the fullerene derivative, the fullerene modified or included by an organic compound, or the fullerene derivative, or a salt thereof, and at least one of the components described below. An external composition according to claim 5.
<1> Nonionic surfactant <2> Ascorbic acid or a derivative or salt thereof <3> UV protection agent The external composition according to claim 9, wherein the organic compound that modifies or includes the fullerene or the fullerene derivative is at least one of an organic oligomer, an organic polymer, cyclodextrin, a crown ether, and a compound related thereto. The external composition according to claim 9 or 10, wherein the fullerene is a C60 fullerene, a C70 fullerene or a fullerene mixture containing both of them.

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