WO2006028297A1 - Water-soluble fullerene, process for producing the same, antioxidant composition and external composition - Google Patents

Abstract

A water-soluble fullerene characterized by being at least one hydroxylated fullerene comprising a fullerene core and, bonded thereto, over 30 hydroxyls (OH), which water-soluble fullerene exhibits a desirable water solubility, having a high active oxygen scavenging potency and can exhibit reduced shade. Further, there is provided a process for mass production thereof in a simple and easy and also efficient manner at low cost. Still further, there are provided an antioxidant composition and external composition comprising the water-soluble fullerene.

Description

 TECHNICAL FIELD Water-soluble fullerene, production method thereof, antioxidant composition and composition for external use

 The invention of this application relates to a new water-soluble fullerene which is a water-soluble and light-colored carbon cluster, a method for producing the same, and an antioxidant composition and an external composition containing these as active ingredients. Background art

 Fullerenes are known to have a high radical scavenging ability, and in particular, the ability to scavenge active oxygen is also known (Patent Document 1, Non-Patent Document 1-16). On the other hand, this active oxygen scavenging ability is attracting attention from the viewpoint of skin care ingredients and cancer prevention effects as a characteristic of vitamin C, polyphenol, catechin and the like, and is expected to be applied to cosmetics and pharmaceuticals. Therefore, fullerenes are also expected to be applied to cosmetics and pharmaceuticals in terms of their ability to scavenge active oxygen. However, fullerenes are a major obstacle to being insoluble or sparingly soluble in water. ing.

 In addition, it has been studied to increase water solubility by using fullerenes as clathrate compounds, but the dark brown color tone of fullerenes becomes a problem in application to cosmetics and the like.

It is known for compounds such as C _6Q H ₃₆ (pale yellow) that the fullerene nucleus is highly substituted, and polysubstituted fullerenes and their derivatives have already been reported along with their synthesis methods. Although it has been reported (Patent Document 1), the synthesis method has problems such as the production of brown fullerene and difficulty in post-reaction treatment (Non-Patent Document 7-9). In addition, even polyhydroxide fullerene, for example, C _6D (OH) ₁₂ has a problem that its solubility in water is extremely low. Patent Document 1: Japanese Patent Laid-Open No. 9-136964

 Non-patent document 1: Science 1991, 254, 1 183

 Non-Patent Document 2: J. Chei. Soc., Chem. Comiun., 1995 28

Three

 Non-Patent Document 3 Neurobiol. Dis. 1996, 3, 129

 Non-patent literature 4 Bioorg. Med. Chem. Lett., 1996, 6, 539 Non-patent literature 5 Fragrance Journal, 2003, 3 1, 40 Non-patent literature 6 Bio Industry, 2003, 20, 82

 Non-patent literature 7 J. Chem. Soc., Chem. Commun., 1 992, 179 Non-patent literature 8 J. Chem. Soc., Chem. Comiun. 994, 463 Non-patent literature 9 J. Chem. Soc., Chem Commun. 993, 178

4 Disclosure of the invention

 The invention of this application provides a water-soluble fullerene that exhibits good water-solubility, has a high active oxygen scavenging ability, and can exhibit a light color, and is simply and efficiently low. It is an object of the present invention to provide a method that can be synthesized in a large amount with Kos koji, an antioxidant composition of the above water-soluble fullerene, and a composition for external use.

 The invention of this application has the following features to solve the above problems.

 <1> A water-soluble fullerene characterized in that it is at least one kind of fullerene hydroxide having more than 30 hydroxyl groups (OH) bonded to the fullerene nucleus.

<2> The above-mentioned water-soluble fullerene, characterized in that it is at least one kind of hydroxylated fullerene bonded with 50 or less hydroxyl groups (OH). <3> The above-mentioned water-soluble fullerene, characterized in that more than 30 hydroxyl groups (OH) are bonded to the fullerene nucleus and is at least one of the hydrated fullerene hydroxides.

4> C ₆₀ (OH) _η · kH ₂ 0 (where n and k are integers of 30 and n and 4 and k).

<5> Water-soluble fullerene represented by either C ₆₀ (OH) 36 * 9H ₂ 0 and C ₆₀ (OH) ₄₀ · 9H ₂ 0.

 <6> A water-soluble fullerene according to any one of the above, wherein a substituent other than a hydroxyl group (OH) is bonded to the fullerene nucleus.

 <7> The above-mentioned water-soluble fullerene, wherein hydrogen atoms are bonded.

<8> C ₆₀ H _m (OH) _η · kH ₂ 0 (n, m, k are integers of 30, n, 2 <m, 4 4 k)

<9> Water-soluble fullerene represented by C ₆₀ H ₄ (OH) 32-6 H ₂ 0. <10> The water-soluble fullerene according to any one of the above, wherein the fullerene nucleus is a C 60, C 70 or higher order fullerene nucleus or nanotube.

 <11> A method for producing any one of the above water-soluble fullerenes, characterized in that a fullerene having a substituent in the fullerene nucleus or having no substituent is reacted with a hydrogen peroxide solution. Manufacturing method.

 <12> The method for producing a water-soluble fullerene according to the above, characterized by reacting a water-insoluble hydroxylated fullerene having 20 or less hydroxyl groups (OH) bonded to a fullerene nucleus.

 <13> A process for producing water-soluble fullerenes characterized by reacting hydrogenated fullerenes.

<14> Use any one of the above water-soluble fullerenes as an active ingredient. Characteristic antioxidant.

15> C ₆₀ (OH) _η · kH ₂ 0 or CeoH ^ (OH) _n · kH ₂ 0 (where n, m, k are integers of 30 <n, 2 <m, 4 <k An antioxidant containing a water-soluble fullerene represented by

<16> Water-soluble fullerene represented by one of C ₆₀ (OH) 36 * 9 H ₂ 0, C ₆₀ (OH) ₄₀ 9H ₂ 0 and C ₆₀ H ₄ (OH) ₃₂ 6 H ₂ 0 Antioxidant containing as an active ingredient.

 <17> Antioxidant composition characterized by comprising as an active ingredient at least one of the above-mentioned water-soluble fullerenes and the above-mentioned water-soluble fullerenes modified or included by organic compounds and their salts object.

<18> C ₆₀ (OH) _η · kH ₂ 0 or C _{6 ()} H _tt (OH) _n · kH ₂ 0 (where n, m, k are 30 <n, 2 <m, 4 <k An antioxidant composition comprising a water-soluble fullerene represented by

19> C ₆₀ (OH) 36-9H ₂ 0, C ₆₀ (OH) ₄₀ 9H ₂ 0 and C ₆₀

An antioxidant composition comprising a water-soluble fullerene represented by any one of H ₄ (OH) _32-6 H ₂ 0 as an active ingredient.

 <20> An antioxidant composition characterized in that the organic compound to be modified or included is an organic oligomer, an organic polymer, cyclodextrin or an analog thereof, and at least one of crown ether or an analog thereof .

 <21> A composition for external use comprising the above-mentioned water-soluble fullerene and the above-mentioned water-soluble fullerene modified or clathrated with an organic compound and at least one of their salts as an active ingredient .

<22> C ₆₀ (OH) _η · kH ₂ 0 or C _{6 ()} H _B (OH) _D · kH ₂ 0 (where n, m, k are 30 <n, 2 <m, 4 <k The composition for external use which uses the water-soluble fullerene represented by this as an active ingredient.

23> C ₆₀ (OH) 36 * 9 H ₂ 0, C ₆₀ (OH) ₄₀ 9H ₂ 0 and C ₆₀

Water-soluble fullerene represented by any of H ₄ (OH) ₃₂ · 6 H ₂ 0 The composition for external use which uses as an active ingredient.

 <24> A composition for external use, wherein the organic compound to be modified or included is at least one of an organic oligomer, an organic polymer, cyclodextrin or an analog thereof, and crown ether or an analog thereof. Brief Description of Drawings

Figure 1 shows the FT-IR spectrum diagram of water-soluble C _{6 ()} (OH) ₃₆ 9 Η ₂₀

Figure 2 is a FT-IR spectrum diagram of insoluble _{C 6fl (OH) 12 · 5Η} 2 0 of reactants.

Figure 3 is a water-soluble _{C 6fl (OH) 36 - 9} H 2 Ru TGA measurement chart der zero.

Figure 4 is a water-soluble C _6D (OH) ₄₀ - is a FT-IR scan Bae spectrum diagram of 9H ₂ 0.

Fig. 5 is a chart of TGA measurement of water-soluble C _{6 ()} (OH) ₄₀ · 9Η ₂₀ .

 Figure 6 is a UV-visible absorption spectrum of water-soluble fullerene hydroxide.

Fig. 7 is an FT-IR spectrum diagram of water-soluble C ₆₀ H ₄ (OH) ₃₂ · 6 Η ₂₀ .

Figure 8 is an FT-IR spectrum diagram of insoluble C _6D H ₃₆ .

Figure 9 shows water-soluble fullerene C ₆ . FIG. 4 is a diagram showing the hydroxyl radical scavenging ability of H ₄ (OH) 32 * 6H ₂₀ as a comparison with insoluble fullerene hydroxide.

 FIG. 10 is a diagram showing changes in the ESR spectrum.

Fig. 11 shows a comparison with vitamins C as in Fig. 9. BEST MODE FOR CARRYING OUT THE INVENTION

 The water-soluble fullerene of the invention of this application is expressed by a general formula:

_{F (OH) n · mH 2} 0

 (F represents an optionally substituted fullerene nucleus, n is a number exceeding 30, and m is 0 or an integer)

It is a water-soluble fullerene that is at least one of the fullerene hydroxides that can be represented by Here, n has an upper limit on the number of hydroxyl groups (OH) that can be bonded to the fullerene nucleus in terms of structure theory.

 For example, practically suitable for its production and application are those in which n is in the range of 50 or less.

 In particular, in the invention of this application, the water-soluble fullerene, which is noted for its excellent action and effect for application to antioxidants, external preparations, etc., is represented by the following formula:

_{C 60 (OH) η · kH} 2 0

C ₆ . H _m (OH) „· kH ₂ 0

 (Where 30 <n, 2 <m, 4 <k)

Is provided. For example, specifically, C 6 ₀ (OH) 36-9H ₂ 0, C ₆ . (OH) ₄ . · 9Η ₂ 0, C ₆₀ H ₄ (OH) ₃₂ · 6 Η ₂ 0 etc.

The fullerene nuclei may be C 60, C 70 or higher, and various kinds including these mixtures. For example, the fullerene nucleus of the invention of this application includes a structure in which a plurality of fullerenes are bonded via an alkylene chain such as a methylene chain, or a structure in which the alkylene chain is bonded to carbon atoms at different positions in the fullerene skeleton. May be. As a derivative having a substituent of fullerene 60, 1 to 40 modifying groups may be bonded to one fullerene molecule. For example, as a derivative of fullerene 70, a modifying group for one fullerene molecule may be used. 1 to 50 are bonded to each other, and each of these modifying groups is independently a hydroxyl group or If the hydroxyl group is an ester group of 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 group of an aldehyde

The fullerene-modified compound or a salt thereof and at least one selected from them may be used. Furthermore, the fullerene of the invention of this application is

C 60 fullerene, C 70 fullerene or nanotube fullerene may be used, or a mixture of one or more selected from them.

 The fullerene hydroxide of the invention of this application exhibits extremely high water solubility, which has never been known before and could not be foreseen. In the invention of this application, such a fullerene hydroxide is obtained by using a substituted fullerene such as an unsubstituted fullerene, a hydrogenated fullerene, or a lower hydroxylated fullerene as a starting material. It can be easily produced by reacting with.

 In this case, the number of bonded hydroxyl groups (OH) can be controlled by appropriate selection and setting of conditions such as the starting material fullerene type, the concentration of hydrogen peroxide solution, its use ratio, and the reaction temperature.

 The starting material fullerene may be various as described above, and may have a hydrolyzable group such as a halogen, a nitro group, or a sulfate ester group as a precursor of the hydroxylated fullerene. Various materials such as hydrogenated fullerene, oxidized (epoxy) fullerene, methano-bridged fullerene, alkyl-substituted fullerene, and aryl-substituted fullerene may be selected.

The hydrogen peroxide solution with respect to these starting material fullerenes may have a concentration of 30%, for example, a weight ratio of about 10 to 100 times. Under the condition of 100 times, H ₂ 0 _{2 of} about 500 equivalents in terms of the molar ratio of C _6D (OH) ₁₂ is present. The amount used can be determined in consideration of such an equivalent ratio.

As the hydrogen peroxide solution, there is a commercially available product having a concentration of 3% to 50%, but in practice it is preferable to use a solution of 30% or more. The reaction temperature is usually from 40 to the boiling point of hydrogen peroxide solution, but is preferably from room temperature (about 18 ^) to 80.

 With respect to the reaction time, it can be estimated until the starting material fullerene is almost completely dissolved. Of course, it is not limited to this.

 For separation and purification after the reaction, it is also effective to use a combination of a solvent that is soluble in water and a solvent that is not. However, it is desirable to combine the water layer and organic layer so that they do not separate.

 In general, combinations of water-soluble solvents such as alcohol, THF, acetone, and acetonitrile with other solvents are considered. For example, a combination of hexanol, 2-propanol, bubutanol, jetyl ether and the like with hexane, heptane, cyclohexane and the like. These solvents are each suitably about 3 to 20 times the amount of the hydrogen peroxide solution, but preferably 5 to 10 times. When the amount is too small, hydrogen peroxide water remains in the precipitated product, resulting in inconveniences such as excessive reaction and hindering drying. The above reaction usually produces a hydrate of fullerene hydroxide, but it can be made anhydrous by heating and heating in a strength range up to about 150 under reduced pressure.

 In the invention of this application, the above water-soluble fullerene can be applied as an antioxidant, an antioxidant composition, and an external composition.

 In particular, in the invention of this application, water-soluble fullerenes that are notable for their excellent effects in application to antioxidants, external preparations, etc.

_{C 60 (OH) η · kH} 2 0

_{C 6fl H n (OH) η} · kH 2 0

 (Where 30 n, 2 <m, 4 k)

Is provided. For example, C 60 (OH) 36 '9H ₂ 0, C ₆₀ (OH) ₄₀ · 9Η ₂ 0, C ₆₀ H ₄ (OH) ₃₂ · 6 H ₂ 0 etc.

 Water-soluble fullerenes or substituted derivatives can also be used as those modified or included by an organic compound.

 Examples of organic compounds that modify or include water-soluble fullerene hydroxide or fullerene derivatives include organic oligomers, organic polymers, and inclusion compounds or inclusion complexes, cyclodextrins (CDs), crown ethers, or their related compounds One or more of these are exemplified as suitable.

Examples of the organic oligomer or organic polymer include polyalkylene glycols such as carboxylic esters, alcohols, saccharides, polysaccharides, polyhydric alcohols, polyethylene glycol, butylene glycol, polypropylene glycol, polyvinyl alcohol, and the like. Polymers of polyhydric alcohols, nonionic water-soluble polymers, including starch derivatives such as dextran, pullulan, starch, hydroxyethyldyne and hydroxypropyl starch, alginic acid, hyaluronic acid, chitosan, chitin derivatives, Anionic or cationic derivatives of these polymers and their glycerin and fatty acids, oils, propylene carbonate, lauryl alcohol, ethoxylated castor oil, polysorbates, and these Esters or ethers, polymers of these, polyester polymers of these, pyrrolidone polymers such as polyvinylpyrrolidone, esters or ethers of unsaturated alcohol polymers, polyoxy An ethylenepolypropylene block copolymer or the like is preferably bonded to fullerene or a derivative thereof, and may be a mixture of one or more of them. Of these, various types such as polyalkylene glycols such as polyethylene dalycol (PEG), PVP, etc. are preferred. In the case of a polymer such as PEG and PVP, the average molecular weight is generally preferably about 200 to 100, 0.00, with water-soluble fullerene hydroxide or a derivative thereof. As a ratio Therefore, it is considered that the molar ratio is about 10/1 or less.

 For example, in addition to the active ingredients as described above, 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. Furthermore, an oil agent, a surfactant, a pigment, a humectant, an excipient or base, a cell activator, and the like as described below may be blended.

 When the water-soluble fullerene-containing composition for external use according to the invention of this application contains water, the pH varies depending on the pH of the fullerene, the fullerene derivative, the fullerene inclusion compound, or a salt thereof. A range of 3 to 10 is preferable because fullerene and its derivatives can be blended stably.

 Measure the pH of a fullerene, fullerene derivative, fullerene clathrate compound, or a salt of its 20%, 0.5% by weight aqueous solution, and round off the number after the decimal point. When n is 3 to 10, the pH of the stable composition for external use should be adjusted in the range of n ± 2 and in the range of pH 3 to 10. In addition, when n is the rounded number of the pH of a 20%, 0.5% by weight aqueous solution of a fullerene, a fullerene derivative, a fullerene-modified or clathrate compound, or a salt thereof, when n is 3 or less, The pH of a stable fullerene topical preparation should be in the range of 3 to 4. If n has a pH of 10 or more, it should be pH 9 to 10. In any case, the pH of the stable fullerene-containing external composition is preferably in the range of 3 to 10.

 In the case of the invention of this application, as the stabilized external composition having a pH of 3 to 10, the total concentration of the transition metal compound contained or mixed therein is more preferably 0.1% or less. desirable.

 In the invention of this application, the number of hydroxyl groups exceeding 30 as described above

A water-soluble fullerene, characterized by being one or more of the hydroxylated fullerenes to which (OH) is bonded, has an antioxidative activity as an excellent action, that is, an hydroxy radical scavenging action. Oxidizing agent, anti It can be applied to cosmetics and pharmaceuticals as an oxidizing composition and a composition for external use.

 First, the activity of scavenging hydroxyl radicals is explained.

 (1) When hydrogen peroxide and ferrous sulfate are mixed, the so-called Fenton reaction is triggered to generate hydroxyl radicals, which are one type of active oxygen. · It is thought to cause cell death by oxidative damage to lipids. The hydroxyl radical generated by this reaction can be efficiently erased by the water-soluble fullerene and its derivatives of the invention of this application. In fact, the hydroxyl radical scavenging activity is equal to or greater than that of provitamin C, ascorbic acid bis 10-phosphate.

 The hydroxyl radical scavenging activity by the water-soluble fullerene of the invention of this application is not limited to scavenging activity against hydroxyl radicals generated by transition metal ions, but it also scavenges hydroxyl radicals generated widely under various conditions in vivo and in the skin. To do.

 Hydroxyl radical scavenging activity protects against DNA cleavage, DNA damage, cell membrane breakdown, and cell death caused by hydroxyl radicals.

 (2) Explaining the activity of scavenging the superoxide two-ion radical generated by the oxygen reaction, the superoxide two-one radical is generated in the process of stagnation of the skin blood flow and skin injury. It is thought to cause oxidative damage to cells and cause cell death. The superoxide dione radical is generated by mixing hypoxanthine and xanthine oxidase, and the water-soluble fullerenes of the invention of this application can efficiently eliminate this.

The superoxide dione radical scavenging activity of the water-soluble fullerenes of this application is superior to that of provitamin C, ascorbic acid 1 2-0-phosphate ester. The superoxide two-one radical scavenging activity by the water-soluble fullerenes of this application is not limited to the scavenging activity against hydroxyl radicals generated by oxygen reaction, but is a wide variety of superoxide two-ions generated under various conditions in the living body and skin. Eliminate radicals.

 The superoxide two-ion radical scavenging activity protects against DNA cleavage, DNA damage, cell membrane rupture, and cell death caused by superoxide two-one radicals.

 (3) Explaining the activity of inhibiting baroxide Z hydrogen peroxide generated in skin cells by ultraviolet rays. When the skin is irradiated with sunlight, the skin is exposed to peroxide / B Hydrogen oxide is generated, and cell death occurs due to DNA breakage, DNA damage, and cell membrane breakdown.

 If the water-soluble fullerenes of the invention of this application are prescribed in advance before irradiation, the amount of peroxide / hydrogen peroxide generated is remarkably suppressed. Peroxide Z hydrogen peroxide scavenging activity of the water-soluble fullerenes of the invention of this application is equal to or higher than that of provitamin C, ascorbic acid 1-20-phosphate.

 Peroxide / hydrogen peroxide permeates the cell membrane and has a long remaining life, so it is a major cause of cell injury, but the water-soluble fullerenes of the invention of this application are not limited to peroxide Z hydrogen peroxide by ultraviolet rays, Widely eliminates peroxide / hydrogen peroxide generated under various conditions in the body and skin.

 The peroxide Z hydrogen peroxide scavenging activity of the water-soluble fullerenes of this application has the effect of protecting against DNA cleavage, DNA damage, cell membrane breakdown, and cell death caused by peroxide hydrogen peroxide.

(4) The activity of inhibiting peroxide Z hydrogen peroxide generated in skin cells by lipid peroxide is explained. Lipids present in the skin are always susceptible to oxidation, and as a result, cause skin cell death. In particular, ceramide squalene, a stratum corneum lipid, is oxidized and converted to hydroperoxide, causing cell death.

 If the water-soluble fullerenes of the invention of this application are preliminarily prescribed, the generation amount of beroxide / hydrogen peroxide is remarkably suppressed. The water-soluble fullerenes of the invention of this application have a baroxide Z hydrogen peroxide scavenging activity equivalent to or higher than that of ascorbic acid 1 2-0-phosphate ester which is provider C.

 The water-soluble fullerenes of the invention of this application eliminate not only peroxide / hydrogen peroxide by lipid peroxide, but also a wide variety of peroxide Z hydrogen peroxide generated under various conditions in vivo and in the skin.

 The peroxidonohydrogen peroxide scavenging activity of the water-soluble fullerenes of the invention of this application has the effect of protecting against DNA cleavage, DNA damage, cell membrane failure, and cell death caused by peroxide Z hydrogen peroxide. As described above, the invention of this application has an activity of eliminating various active oxygens. Therefore, UV damage, lipid peroxide lipid damage, ischemia reactivation caused by active oxygen or disturbed by the active oxygen is prevented. Concentrated injuries · Melanin production · Shizuku Z dullness / sagging · Cellulite wrinkle protection against various skin beautification effects.

 Therefore, by applying as an external composition, 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 Therapeutic effects of treatment, treatment of red face, hair loss treatment, hair growth promotion, burn treatment, skin sterilization, skin mite killing, skin texture improvement are dramatically enhanced.

 In the invention of this application, the antioxidant power can be efficiently exhibited only after being applied and absorbed on the skin, and a clear improvement and therapeutic effect can be exhibited for various skin disorders.

Therefore, the composition for external use of the invention of this application is skin whitening, improvement of acne, improvement of wrinkles, improvement of rough skin, improvement of oily skin, improvement of dry skin, reduction of pores, Clear treatment effects such as improvement of scars, improvement of redness, treatment of hair loss, promotion of hair growth, improvement of burns, skin sterilization, skin mite killing, and improvement of skin texture can be exhibited.

 In other words, it is effective not only for skin beautifying effects but also for skin protecting effects that prevent all skin and subcutaneous inflammation and promote wound healing. Above all, it is effective for inflammation caused by wounds such as bacterial infections, bacterial molds and virus infections, parasitic infections, burns, burns, abrasions, bruises and bruises.

 The administration of water-soluble fullerenes as an antioxidant, an antioxidant composition, and a composition for external use can generally be dealt with as follows.

 (1) Dose

 The concentration of the water-soluble fullerenes of the invention of this application may be from 0.001% to 30% by weight, but preferably 5% or less from the viewpoint of usability. When administered to the skin, the amount of the composition for external application should be 0.000 1 to 20 m 1 of liquid per square meter of skin area, preferably 0.0 1 to 5. It is not good.

 (2) Dosage form

 Examples of the form of the external composition for skin are not particularly limited. For example, all external preparations such as water solvents, ointments, emulsions, creams, diels, packs, bath preparations, cleaning agents, packs, dispersions, etc. There are no particular restrictions on the dosage form, and it is solid, paste, mousse, jelly, powder, solution, solubilization, emulsification, powder dispersion, and multilayer. It can be. Especially for aqueous solutions, emulsions, ointments, diels, water-soluble preparations, cosmetics, and packs, after these agents are applied externally, a humidifier, vibration introducer, ion introducer, sonic introducer, electromagnetic wave introducer By using this, the penetration of water-soluble fullerenes into the skin can be promoted, and a greater effect can be achieved.

For liquids, spraying, sticking, poultice, datebing, masking Any physically possible method such as a screen can be used.

 (3) Composition components

 The antioxidant composition and the external composition of the invention of this application are basically realized as a combination with various components constituting cosmetics and external medicines conventionally known.

 The following outlines these components in general.

 1. Oil

 The water-soluble fullerenes of the invention of this application contain oils, preferably natural oils, more preferably one or more oils selected from orange oil, beaver oil, olive oil, and pine oil. It is preferably dispersed in oil and administered to a living body, particularly the skin.

As an oil agent, if it is used in normal cosmetics, it is a natural oil, a synthetic oil, or a solid, semi-solid, liquid, etc. Any oil such as hydrogen, waxes, fatty acids, higher alcohols, ester oils, silicone oils, fluorine oils, etc. can be used. For example, hydrocarbons such as squalene, squalene, ceresin, paraffin, paraffin wax, liquid paraffin, pristane, polyisobutylene, microcrystalline wax, ヮ serine; wax such as beeswax, carnauba wax, candelilla wax, whale wax; Animal fats such as beef leg fat, beef bone fat, hard beef fat, hard oil, Yui Toru oil, pork fat, horse fat, mink oil, liver oil, egg yolk oil; lanolin, liquid lanolin, reduced lanolin, lanolin alcohol, hard lanolin Lanolin derivatives such as lanolin acetate, lanolin fatty acid isopropyl, POE lanolin alcohol ether, POE lanolin alcohol acetate, lanolin fatty acid polyethylene glycol, POE hydrogenated lanolin alcohol ether; lauric acid, myristic acid, palmitic Fatty acids such as acid, stearic acid, behenic acid, undecylenic acid, oleic acid, arachidonic acid, docosahexaenoic acid (DHA), isostearic acid, and 12-hydroxystearic acid. The

Oils include lauryl alcohol, myristyl alcohol, palmityl alcohol, stearyl alcohol, behenyl alcohol, hexadecyl alcohol, oleyl alcohol, isostearyl alcohol, hexyldodecanol, octyldodecanol, ceto Higher alcohols such as stearyl alcohol, 2-decyltetradecinol, cholesterol, phytosterol, sitosterol, lanosterol, POE cholesterol ether, monostearyl glycerin ether (batyl alcohol); diisoptyl adipate, 1-2-hexyl adipate Decyl, adipic acid-di-2-heptylundecyl, monoisostearic acid-N-alkyldaricol, isocetyl isostearate, triisostearin Trimethylolpropane, di-2-ethyl hexyl ethylene glycol, 2-ethyl cetyl hexyl, tri-2-ethyl hexyl trimethylol propane, tetra-2-ethyl hexanoate pen erythritol, cetyl octanoate , Octyldodecyl gum ester, oleyl oleate, octyldodecyl oleate, decyl oleate, neopentyl daricolate dicaprate, triethyl citrate, 1-ethylhexyl succinate, amyl acetate, ethyl acetate, butyl acetate Isocetyl stearate, pityle stearate, diisopropyl sepacate, di-2-ethylhexyl sepacate, cetyl lactate, myristyl lactate, isopropyl palmitate, 1-ethylhexyl palmitate, 2-hexyl palmitate , 2-heptylundecyl palmitate, cholesteryl 12-hydroxystearylate, dipentylerythritol fatty acid ester, isopropyl myristate, octyldodecyl myristate, 1-hexyldecyl myristate, myristyl myristate, dimethyloctanoic acid Examples include ester oils such as xyldecyl, ethyl laurate, hexyl laurate, N-lauroyl_L-glutamate 1-2-year-old cutyldodecyl ester, and diisostearyl malate. Etc. As oils, acetoglyceride, triisooctanoic acid glyceride, triisostearic acid glyceride, triisopalmitic acid glyceride, tri-2-ethyl hexanoic acid glyceride, monostearic acid glyceride, ji 2-heptylundecanoic acid glyceride, trimyristic acid Glyceride oil such as glyceride; dimethylpolysiloxane, methylphenylpolysiloxane, methylhydropolysiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentaylsiloxane, dodecamethylcyclohexasiloxane, tetramethyltetraoctide Higher alkoxy-modified silicones such as rogencyclotetrasiloxane and stear-mouthed silicone; higher fatty acid-modified silicone, silicone resin, silicone Beam, silicone-based oil agent such as silicone oil; Pafuruoropori ether, par full O b decalin, fluorine-based oil, such as per full O b octane.

 2. Surfactant

 The preparation / cosmetics of the water-soluble fullerenes of the invention of this application may contain force prillic acid monoglyceride and Z or capric acid monodalide, and may further contain lauric acid monoglyceride. Forced prillic acid monoglyceride, forcepuric acid monoglyceride and lauric acid monoglyceride (hereinafter also simply referred to as glycerides) are all designated as food additives; glycerin fatty acid esters, and their safety has been confirmed. It is an emulsifier for food that can be eaten without any problems.

 In order to disperse the water-soluble fullerenes of the invention of this application in water, an emulsifying agent may be added. For example, as the emulsifier, nonionic surfactants such as polyoxyethylene sorbitan fatty acid esters or polyglycerin fatty acid esters such as polyoxyethylene sorbitan monooleate having an HLB of 10 or more, or sodium lauryl sulfate Anionic surfactants such as can also be used.

Surfactants include anionic, cationic, nonionic and amphoteric Activators are used. Examples of anionic surfactants include fatty acid seggen such as sodium stearate and triethanolamine palmitate, alkyl ether carboxylic acid and its salts, carboxylates such as condensates of amino acids and fatty acids, alkyl sulfonic acids, and algene sulfones. Acid salts, sulfonates of fatty acid esters, sulfonates of fatty acid amides, sulfonates of alkyl sulfonates and their formalin condensates, alkyl sulfate esters, secondary higher alcohol sulfate esters, alkyl and aryl ethers Tellurium sulfate ester, Fatty acid ester sulfate ester salt, Fatty acid alkylolamide sulfate ester salt, Sulfate ester salt such as funnel oil, Alkyl phosphate, Ether phosphate, Alkylaryl ether phosphate, Amido phosphate ,

 N-acyl amino acid type active agents and the like can be mentioned.

Examples of cationic surfactants include alkylamine salts, amine salts such as polyamines and amino alcohol fatty acid derivatives, quaternary ammonium salts of alkyl acids, aromatic quaternary ammonium salts, pyridinium salts, imidazolium salts, and the like. . Nonionic surfactants include sorbyl fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, propylene glycol fatty acid ester, polyethylene dallicol fatty acid ester, sucrose fatty acid ester, polyoxyethylene alkyl ether, poly Xylpropylene alkyl ether, polyoxyethylene alkylphenyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbitol fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene propylene darlicol Fatty acid ester, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene phytos , Polyoxyethylene Fi Tosuterorue one ether, polyoxyethylene cholestanol evening Nord ether, Poriokishechi alkylene cholesteryl ether, polyoxyalkylene-modified organopolysiloxane policy Examples include loxane, polyoxyalkylene / alkyl co-modified organopolysiloxanes, alkanolamides, sugar ethers, and sugar amides. Examples of amphoteric surfactants include betaine, aminocarboxylates, imidazoline derivatives, and the like.

 The metal seggen includes: 12-hydroxyaluminum stearate, zinc stearate, aluminum stearate, calcium stearate, magnesium stearate, zinc myristate, magnesium myristate, zinc cetyl phosphate, calcium cetyl phosphate, sodium cetyl phosphate , Zinc laurate, zinc undecylenate and the like.

 3. Pigment

 Since many of the water-soluble fullerenes of the invention of this application are colored, it is desirable to adjust the color tone so that it does not feel uncomfortable by appropriately incorporating pigments as cosmetics. Colored pigments include inorganic red pigments such as iron oxide, iron hydroxide and iron titanate, inorganic brown pigments such as iron monoxide, inorganic yellow pigments such as yellow iron oxide and ocher, black iron oxide, carbon black, etc. Inorganic black pigments, inorganic purple pigments such as manganese violet and cobalt violet, inorganic green pigments such as chromium hydroxide, chromium oxide, cobalt oxide, copal titanate, inorganic blue pigments such as bitumen and ultramarine blue, tar dyes And pigments obtained by lacquering natural pigments, and composite powders obtained by combining these powders. Examples of pale pigments include titanium oxide-coated mica, titanium oxide-coated my strength, bismuth oxychloride, titanium oxide-coated bismuth oxychloride, titanium oxide-coated talc, fish scale foil, and titanium oxide-coated colored mica. Examples of metal powder pigments include aluminum powder, kappa powder, and stainless steel powder.

The tar dyes are Red No. 3, Red No. 10 4, Red No. 10 6, Red No. 2, 01, Red No. 2, No. 2, Red No. 2, No. 4, Red No. 2, No. 5, Red No. 2 20 , Red 2 2 6, Red 2 2 7, Red 2 2 8, Red 2 3 0, Red 4 0 1, Red 5 0 5, Yellow 4, Yellow 5, Yellow 2 0 2 The yellow 2 0 3 No., yellow 2 0 4, yellow 4 0 1, blue 1, blue 2, blue 2 0 1, blue 4 0 4, green 3, green 2 0 1, green 2 0 4, Green No. 20, No. 5, Orange No. 20, No. 1, Orange No. 20, No. 3, Orange No. 20, No. 4, Orange No. 20, No. 6, Orange No. 20, etc. Examples of natural pigments include carminic acid, laccaic acid, calsamine, bradylin, and crocin. The above-mentioned inorganic powders, organic powders, pigments, tar dyes and other powders can be combined or oiled.

Alternatively, the surface treatment may be performed with silicone, or a fluorine compound.

 4. Moisturizer

 Polyhydric alcohols such as propylene glycol, glycerin, polyglycerin, sorbitan and sorbitol are added to relieve skin moisturization and irritation. Examples of moisturizers include alkaline simple hot spring water, deep water, hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin and keratan sulfate, and their salts, collagen, elastin, keratin, etc. Proteins or their derivatives as well as their salts, soy and egg-derived phospholipids, glycolipids, ceramides, mucins, eight chimi, erythritol, maltose, maltitol, xylitol, xylose, pen erythritol, fructose, dextrin And its derivatives, mannitol, sorbitol, inositol, trehalose, glucose and other sugars, urea, asparagine, aspartic acid, alanine, arginine, isoleucine, ortinin, glutamine, glycine, glutamic acid and Derivatives and salts thereof, cysteine, cystine, citrulline, threonine, serine, tyrosine, tryptophan, theanine, parin, histidine, hydroxylysine, hydroxyproline, pyrrolidone carboxylic acid and its salts, proline, phenylalanine Amino acids such as methionine and lysine, and derivatives or salts thereof.

Furthermore, as a moisturizer, D-panthenol, avocado extract, almond oil, carob bean extract, rice extract, strawberry extract, Wikiyo extract, Usbeniai extract, Oren extract, Olive oil, Odorikosou extract, Cocoa butter, Oat extract, Scratch evening extract, Kumazasa extract, Gardenia extract, Grapefruit extract, Gennoshoco extract, Gentian extract , Burdock extract, Copotan extract, Sesame extract, Sapoten extract, Savonso extract, Ginger extract, Ziou extract, Shea butter, Shimokke extract, Senkiyu extract, Zeniaoi extract, Yuchiji Yakkoso extract Extract, persimmon extract, corn extract, eucommia force soup extract, tormentilla extract, dokudami extract, pakumondou extract, hachi bean extract, hamamelis extract, pine force extract, green potato force extract, seiyohakka Extract, parsley extract, para extract, baboonヮ Lily extract, Cypress extract, Loofah extract, Brune extract, Butcher's bloom extract, Polaj oil, Potan extract, Jojoba oil, Podaige extract, Hop extract, Pine extract, Maronier extract, Macadamia Natsu oil, Malmo extract, Murasaki extract, Meadow home oil, Melissa extract, Jagurmasou extract, Lily extract, Yuz extract, Lime extract, Lavender extract, Gentian extract, Salmon extract And apple extract. One or more of the moisturizers listed above can be appropriately selected and blended.

 5. Excipients / Bases

Gelling agents include amino acid derivatives such as N-laureuil L monoglutamic acid, α, jiji η ptylamine, dextrin palmitate ester, dextrin stearate ester, dextrin 2-ethyl hexanoate palmitate ester, etc. Esters, sucrose fatty acid esters such as sucrose palmitate ester, sucrose stearate ester, benzylidene derivatives of sorbitol such as monobenzylidene sorbitol, dibenzylidene sorbitol, dimethyl pendyl decyl ammonium montmorillonite clay Organically modified clay minerals such as dimethyldioctadecylmonium montmorillonite clay It is.

 Examples of alcohols include lower alcohols such as ethanol and isopropanol, glycerin, diglycerin, ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dibropyrene glycol, 1,3-butylene glycol, and polyethylene glycol. Alcohol etc. are mentioned.

Water-soluble polymers include gum-based polymers such as gum arabic, tragacanth, galactan, gyalob gum, guar gum, cara gum, carrageenan, pectin, agar, algae colloid, trant gum, locust bean gum, galactomannan, xanthan gum, Microbial polymers such as dextran, succinoglucan, and pullulan; animal polymers such as casein, albumin, and gelatin; starch-based polymers such as starch, carboxymethyl starch, and methyl hydroxypropyl starch; methylcellulose, ethylcellulose, and methyl Hydroxypropyl cellulose, Carboxy methylcellulose, Hydroxymethylcellulose, Hydroxypropyl cellulose, Nitrocellulose, Sodium cellulose sulfate, Carboxy Cellulose polymers such as sodium chillel, crystalline cellulose, cellulose powder; alginate polymers such as sodium alginate and propylene glycol alginate; vinyls such as polyvinyl methyl ether, force ropoxyvinyl polymer, and alkyl-modified lpoxybinyl polymer Polymers; Polyoxyethylene polymers; Polyoxyethylene polyoxypropylene copolymer polymers; Acrylic polymers such as sodium polyacrylate, polyethylacrylate, and polyacrylamide; Polyethyleneimine, Inorganic water-soluble polymers such as cationic polymer, bentonite, labonite and hectorite. Also included are film forming agents such as polyvinyl alcohol and polyvinyl pyrrolidone. If the powder is used in normal cosmetics, its shape (sphere, needle, plate, etc.), particle size (smoke, fine particles, pigment grade, etc.), particle structure Regardless of (porous, non-porous, etc.), any of inorganic powder, organic powder, pigment and the like can be used. For example, inorganic powders include magnesium oxide, barium sulfate, calcium sulfate, magnesium sulfate, carbonic acid lucium, magnesium carbonate, talc, synthetic mica, my power, kaolin, sericite, muscovite, synthetic mica, phlogopite, Red Mica, Biotite, Lithia Mica, Gaic Acid, Anhydrous Gaic Acid, Aluminum Kainate, Magnesium Agate, Magnesium Aluminum Magnesium, Sulfur-containing Aluminum Kalate, Calcium Calate, Barium Geate, Strontium Kainate, Tungsten Acid metal salt, Hydroxyapatite, Permikilari moth, Yajirite, Montmorillonite, Ze

Olite, ceramic powder, dicalcium 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, polymethylmethacrylate powder, silk powder , Nylon powder, 1 2 nylon, 6 nylon, styrene / acrylic acid copolymer, divinylbenzene / styrene copolymer, vinyl resin, urea resin, phenol resin, fluorine resin, silicone resin, acrylic resin, melamine resin Epoxy resin, polycarbonate resin, microcrystalline fiber powder, lauroyl lysine and the like.

 6. Cell Activator

In order to promote the drug effect by administering the water-soluble fullerenes of the invention of this application to a living body or skin, it is preferable to simultaneously administer a drug for activating cells to be administered. Cell activators include deoxyliponucleic acid and its salts, adenylate derivatives such as adenosine triphosphate and adenosine monophosphate and their salts, liponucleic acid and its salts, cyclic AM P, cyclic GMP, flavin Adenine nucleotide, guanine, adenine, Nucleic acid-related substances such as cytosine, thymine, xanthine and their derivatives caffeine, theopherin and their salts, calf blood extract, blood protein extract, spleen extract, egg components such as birds, chicken crown extract Shell extract, shellfish extract, royal jelly, silk protein and its degradation product or derivatives thereof, hemoglobin or its degradation product, lactoferrin or its degradation product, mollusc extract such as squid, fish meat extract, etc. Extracts derived from microorganisms selected from animal-derived extracts such as mammals, birds, shellfish, insects, fish, mollusks, crustaceans, yeast extracts, lactic acid bacteria extracts, bifidobacteria extracts, etc. Things.

 Furthermore, cell activators include vitamins such as retinol and its derivatives (retinol palmitate, retinol acetate, etc.), retinal and its derivatives, dehydroretinal, tretinoin, carotene and other carotenoids.

A, thiamines (thiamine hydrochloride, thiamine sulfate), riboflavins (riboflavin, riboflavin acetate, etc.), pyridoxines (pyridoxine hydrochloride, pyridoxine dioctanoate, etc.), flavin adenine nucleotides, cyanocobalamin, folic acid , Nicotinic acid (nicotinic acid amide, benzyl nicotinate, etc.), vitamins B such as choline, apricot extract, yew extract, rapeseed extract, barley extract, orange extract, cucumber extract, Kiwi extract, shiitake extract, sugi extract, senpri extract, evening extract, capsicum extract, garlic extract, carrot extract, cucumber extract, peach extract, lettuce extract, lemon extract, Ganoderma extract, Rosemary extract, Asparaga Contains extract, Ibukitorano extract, Endo bean extract, Age extract, Ogon extract, Ononis extract, seaweed extract, raspberry extract, kujin extract, cuckoo extract, gokahi extract, linoleic acid Plant oil, Saishin extract, Hawthorn extract, Sunpens extract, Shirayuri extract, Peonies extract, Sempukuka extract, Sohakaku extract, Soybean extract, Tea extract, Toki extract, Molasses extract , Beechlen extract, Beech extract, Grape seed extract, Flow de Maniyu extract, Hop extract, Maikai extract, Mokka extract, Saxifrage extract, Oysterin extract and Luo

Chinese fruit extract, and moreover, Akane, Aka grape, Akamegashi ヮ, Akebi, Asa, Asagao, Azuki, Azalea, Amachiya, Amachiyaru, Ita Dori, Fig, Ichiyo, Iran Iran, Ubudada, Ume, Kangyu , Yenju, Endo, Opaco, Okra, Ogulma, Onigurumi, Ominaeshi, Dutch Strawberry, Oyster, Kakidoushi, Kashu, Kashichi, Power Nokosou, Karasuuri, Karin, Guarana, Kikiyo, Chrysanthemum, Gycinegi Silves evening, goldfish, guava, wolfberry, kuzu, camphor tree, chestnut, caquette, gecko, caich, gosho strawberries, pepper, coffee, sesame seeds, colompo, southern power, sun ® c, saffron, service class, pomegranate, et rhizoma sophorae tonkinensis, Sanpenzu, Zion, iris, watermelon, stevia, Sumo

Mo, Seizou evening, Seisen pear, Seisen's sawtooth, Seisou Nezu, Seisen's rust, Sekisho, Seri, Senega, Senna, Daio, Daidai, Tamarindo, Taranoki, Dandelion, Chicory, Chiojoji, Chiyoda Nuruna, Teuchigurumi, Tougan, Aoi Chu, Trolley, Nazuna, Natsumikan, Nanten, Futaki, Nogogiri-Sou, Pineapple, Hibiscus, Papaya, Pasil, Lotus, Hadakamigi, Hyogi, Peanut, Hikikohihi , Himematsutake, beakshi, beetle, fuki danpopo, fushinoki, fujibakama, blueberry, bow fu, physalis, honoki, bokeh, maikai, maou, mango, ma Nentake, sewing machine Masaiko, Misohagi, Mitsuba, mimosa, sweet clover, melon, magnolia, Momorudi force-Dallos base Norii, Jew, bean sprouts, Yakuchi, Yakumo Sou, Gagurumasou, palm, Yashaji', Yadorigi, Yanagitade, catcher Ma Extracts such as burdock, bayberry, uzuliha, mugwort, rye, orchid, longan, apple, litchi, forsythia, plant extracts such as hinokitiol, cephalanthin, Q!-And arlinolenic acid, eicosapenic acid and Their derivatives, estradiol and its derivatives and their salts, organic acids such as glycolic acid, succinic acid, lactic acid, salicylic acid and their derivatives and their salts. One or two or more cell activators listed above can be appropriately selected and blended.

 Examples of vitamins include vitamin Ks such as phenadione, menaquinone, menadione and menadiol, biphenyls such as eriocitrin and hesperidin, piotin, carcinine and ferulic acid. Examples of blood circulation promoters include nonyl acid ヮ renylamide, kabusaicin, gingerone, force antaris tincture, iku evening mall, a-borneol, inositol hexanicotinate, cyclantelate, cinnarizine, trazoline, acetycholine, pelapamil, and aliorisanol. It is done. Examples of skin astringents include tannic acid, examples of antiseborrheic agents include thianthol, and examples of enzymes include lipase and papain.

Amino acids include glycine, alanine, parin, isoleucine, serine, threonine, aspartic acid, glutamic acid, asparagine, glutamine, lysine, hydroxylysine, arginine, cystine, methionine, phenylalanine, tyrosine, proline, hydroxyproline, ortinine And amino acids such as citrulline and theanine and derivatives thereof and salts thereof, or amino acid derivatives such as pyrrolidone carboxylic acid and derivatives thereof. Examples of nucleic acid-related substances include deoxyribonucleic acid and salts thereof, adenosine triphosphate, adenosine diphosphate, adenylate derivatives selected from adenosine phosphate and salts thereof, liponucleic acid and salts thereof, cyclic AM P, and cyclic GMP. Flavin adenine nucleotides, guanine, adenine, cytosine, thymine, xanthine and their derivatives caffeine, deophylline and their salts, Examples of hormones include eszaradiol and ethenyl estradiol.

 7. Ascorbic acid

 In the external composition of the invention of this application, ascorbic acid or a derivative thereof is preferably used.

 Among them, the compound represented by the above formula or a salt thereof and at least one selected from them may be used.

 Ascorbic acid itself can be used, and ascorbic acid can be either L-form, D-form or DL-form, ester with inorganic acid or organic acid, glycoside with sugar, or hydroxyl group of ascorbic acid. Among them, two adjacent hydroxyl groups and ketone-bonded ketals or acetals combined with aldehydes may be used.

 In this case, examples of the inorganic acid include phosphoric acid, diphosphoric acid, triphosphoric acid, and sulfuric acid, and phosphoric acid is preferred. 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. Examples of the sugar include glucose, sucrose, and fructose, and dalcose is particularly preferable. Examples of the ketone include acetone and methyl ethyl ketone, and examples of the aldehyde include acetoaldehyde, propyne aldehyde, and benzaldehyde. Examples of the salt include sodium, potassium, magnesium, and calcium, and a sodium salt and a magnesium salt are particularly preferable.

Specific examples of such ascorbic acid derivatives include ascorbic acid 2-phosphate, ascorbic acid 2-diphosphate, ascorbic acid 2-triphosphate, ascorbic acid 2-polyphosphate, and ascorbic acid 2-phosphate. Diester, Ascorbic acid 2 — Phosphoric acid 6 — Palmitic acid, Ascorbic acid 2 — Phosphoric acid 6 — Myristic acid, Ascorbic acid 2 — Phosphoric acid 6 — Stearic acid, Ascorbic acid 2 _ Phosphoric acid 6—Saleic acid, Ascorbine acid 2—Dalcoside, Ascorbic acid 2 —Dalcoside 6 —Palmitic acid, Ascorbic acid 2 —Dalcoside 6 _Myristic acid, Ascorbic acid 2 —Glucoside 6—Stearic acid, Ascorbic acid 2—Dalcoside 6—Oleic acid, Ascorbic acid 2 _Ascorbic acid esters such as sulfuric acid, derivatives of L-ascorbic acid alkyl ester, L-ascorbic acid phosphoric acid ester, L-ascorbic acid sulfuric acid ester, etc., and alkali salts such as sodium salts and potassium salts thereof Alkaline earth metal salts such as metal salts, calcium salts, and magnesium salts may also be used. More specifically, palmitic acid L-ascorbic acid, dipalmitic acid L-ascorbic acid, isosopartic acid L-ascorbic acid, disopalmitic acid L-ascorbic acid, tetraisopalmitic acid L-ascorbic acid, stearic acid L —Ascorbic acid, distearic acid L-ascorbic acid, isostearic acid L-ascorbic acid, diisostearic acid L-ascorbic acid, myristic acid L-ascorbic acid, dimyristic acid L-ascorbic acid, isomyristic acid L-ascorbic acid, diisomyristin Acids L-ascorbic acid, oleic acid L-ascorbic acid, dioleic acid L-ascorbic acid 2-ethyl hexanoic acid L-ascorbic acid, L-ascorbic acid sodium phosphate ester, L-ascorbic acid phosphate L-ascorbic acid phosphate magnesium, L-ascorbic acid phosphate calcium, L-ascorbic acid phosphate aluminum, L-ascorbic acid sodium sulfate, L-ascorbic acid sulfate potassium, L-ascorbic acid sulfate Ester magnesium, calcium L-ascorbate sulfate, aluminum L-ascorbate sulfate, sodium L-ascorbate, L-potassium ascorbate, magnesium L-ascorbate, calcium calcium luscorbate, aluminum L-ascorbate, etc. And their sodium salts, potassium salts, magnesium salts, calcium salts, zinc salts, ammonium salts, alkyl-substituted ammonium salts, hydro And xyalkyl-substituted ammonium salts.

 Further, the ascorbic acid derivative may be bonded to the polymer chain. In particular, ascorbic acid 2-phosphate and ascorbic acid 2-darcoside, and especially the above-mentioned salts thereof are preferred from the viewpoints of formulation convenience such as water solubility, chemical stability of the derivatives, and effects.

8. Preferred examples of the pH adjusting agent include a storage stabilizer, an organic acid having a chelating effect, or a salt thereof. These include erythorbic acid and its salts, dibutylhydroxytoluene, tocopherol and its derivatives, porphyrin ₇ -ptylhydroxyanisole, sodium bisulfite, anhydrous sodium sulfite, gallic acid and its derivatives, alanine, ethylenediaminediamine It is at least one selected from the group consisting of sodium til triacetate, ethylenediaminetetraacetic acid and its salt, quenoic acid and its salt, darconic acid, tartaric acid, phytic acid, sodium polyphosphate, sodium metaphosphate, It may be added in the range of 0.1 to 50% by weight, preferably in the range of 0.1 to 5% by weight with respect to the total weight of the composition for external use. The salt is not particularly limited, but a metal other than a transition metal is desirable from the viewpoint of safety to the skin, and sodium, potassium, magnesium, and calcium are particularly desirable.

 9. Reactive oxygen scavenger

In order to promote the active oxygen scavenging activity of the water-soluble fullerenes of the invention of this application, it is preferable to co-administer another active oxygen scavenger. As active oxygen scavengers, superoxide dismutase, mannitol, pyryrubin, cholesterol, tributophan, histidine, quercetin, quercitrin, catechin, catechin derivatives, rutin, rutin derivative, taurine, thiotaurine, eggshell membrane extract , Gallic acid, gallic acid derivative, yeast extract, ganoderma extract, yashaji extract, genoshoko extract, potampi extract, melissa extract, parsley extract, dicoppi extract, retinol and its derivatives (Retinol palmitate, Reti acetate Retinal and derivatives thereof, vitamin A such as dehydroretinal; thiamine (thiamine hydrochloride, thiamine sulfate, etc.), riboflavin (riboflavin, riboflavin acetate, etc.), pyridoxine (pyridoxine hydrochloride) , Pyridoxine dioctanoate, etc.), flavin adenine nucleotides, cyanoparamine, folic acid, nicotinic acids (nicotinic acid amide, nicotinic acid benzyl, etc.), vitamins B such as choline; ergocalciferol, cholecalciferol, Vitamin D such as dihydroxystannal; tocopherol and its derivatives (d 1—a (j8, r) monotocopherol, acetic acid d I − -tocopherol, nicotinic acid—d 1 mono α; —tocopherol, linoleic acid _d 1 — Α-Tocopherol, succinic acid d 1 — One Kofueroru etc.), vitamin E such as Yubikinon like; dibutylhydroxytoluene Torr Ren 及 Pi butyl hydroxy § two sole like are exemplified up.

 1 0. Other ingredients

 A preservative such as ethanol can be added for the purpose of preserving the composition for external use containing the water-soluble fullerenes of the invention of this application or a diluted solution thereof. In addition, pH can be adjusted by adding pH regulators such as organic acids such as citrate, fumaric acid, succinic acid and lactic acid, and Na O H and K O H.

In any case, in the composition for external use containing the water-soluble fullerenes of the invention of this application, components that are usually used in preparations such as external preparations, that is, water (purified), as long as the pharmacological effect is not impaired. Water, hot spring water, deep water, etc.), oil agent, surfactant, metal sedge, gelling agent, powder, alcohol, water-soluble high molecule, film forming agent, resin, UV protection agent, inclusion compound, antibacterial agent , Fragrance, Deodorant, Salt, PH adjuster, Coolant, Animal, Microbial extract, Plant extract, Blood circulation promoter, Astringent, Antiseborrheic agent, Reactive oxygen scavenger, Cell activator, Moisturizing One, two or more kinds of agents, keratolytic agents, enzymes, hormones, vitamins, etc. can be added as appropriate. Also, as UV protection agents, 2-methoxyethyl paramethoxy key cinnamate, isopropyl para methoxy key cinnamate, diethanolamine salt of para methoxyhydro gal acid, mono-2-ethyl hexyl diparamethoxy key cinnamate Gay cinnamate UV absorbers such as glyceryl, octyl methoxy cinnamate, and methyl diisopropyl cinnamate—2-hydroxy-4-methoxybenzophenone 2-hydroxy-4-methoxybenzophenone 5-sulfuric acid 2-hydroxy mono 4 — Methoxybenzophenone 5-sodium sulfate, 2,4-dihydroxybenzophenone, 2,2'-dihydroxy 4,4'-dimethoxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 2 , 2 ', 4, 4' —tetrahydroxy benzophenone 2-hydroxy-1-4 _ n— Benzophenone-based UV absorbers such as oxybenzophenone, paraaminobenzoic acid, paraaminobenzoic acid edyl, paraaminobenzoic acid ptyl, paradimethylaminobenzoic acid 2-ethylhexyl, paraaminobenzoic acid glyceryl, paraaminobenzoic acid Benzoic acid-based UV absorbers such as Amyl, 1-ethylhexyl salicylate, triethanolamine salicylate, homomenthyl salicylate, dipropylene glycol salicylate, methyl salicylate, ethylene glycol salicylate, phenyl phenyl salicylate, amyl salicylate, salicylate Salicylic acid-based UV absorbers such as benzyl tyrate, isopropyl benzyl salicylate, and lithium salicylate; 4 1 t 1 petit 4'-methoxydibenzoylmethane, 4-isopropyldibenzoylmethane, 4 -Methoxy dibenzoylmethane, 4-tert-butyl-4 '—dibenzoylmethane-based UV absorbers such as hydroxydibenzoylmethane; Menthyl O-aminobenzoate, 2 —Phenol benzimidazole 5 —Sulfuric acid, 2 —Phenyl-5-methylbenzoxazole, 3_ (4-methylbenzylidene) camphor, 2—ethylhexyl 2 —cyanoxyl 3,3-diphenylyllate, 2—ethyl-2-alkylate, 2 —ethyliloxylate 2,3 ’— Diphenyl chloride, 2— (2′—hydroxy-5-methylphenyl) benzotriazol And anthranilic acid UV absorbers such as menthyl anthranilate; urocanic acid UV absorbers such as uric acid ethyl acid; titanium oxide, zirconium oxide, cerium oxide and the like. These metal oxides may be coated with silica. The blending amount of the UV protection agent may be from 0.01 to 50% by weight, and preferably from 0.01 to 10%. Antibacterial agents include: benzoic acid, sodium benzoate, coalic acid, sorbic acid, potassium sorbate, paraoxybenzoic acid ester, parachlorde cresol, hexaclofenfen, benzalkonium chloride, chlorhexidine chloride, trichlorocarbanilide, photosensitivity Examples thereof include zinc, bis (2-pyridylthio-1-oxide), zinc, phenoxyethanol, thianthol, and isopropylmethylphenol. Examples of the pH adjusting agent include potassium carbonate, sodium hydrogen carbonate, ammonium hydrogen carbonate and the like. Examples of the refreshing agent include L-menthol and camphor. Anti-inflammatory agents include dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, glycyrrhizic acid such as / 3-glycyrrhetinic acid, stearyl glycyrrhetinate, disodium 3-succinyloxyglycyrrhetinate and their derivatives and derivatives thereof. Salts, mefenamic acid, phenyl benzoin, indomethacin, ibuprofen, keproprofen, allantoin, guaiazulene, calcium pantetonate, D-pantothenyl alcohol, pantothenyl ether, acetil pantotene Examples include panthenol such as tilether and derivatives thereof and salts thereof, ε-aminocaproic acid, diclofenac sodium, tranexamic acid and the like. The blending amount is 0.01 to 10% by weight, and more preferably 0.01 to 5% by weight. Antioxidants include superoxide dismutase, mannitol, histidine, triftophan, pyryrubin, quercetin, quercitrin, polyphenol, proanthocyanidin, tocotrienol, strength techin, catechin derivatives, rutin and its derivatives, gallic acid and its Invitation Conductors, etc., ubiquinone, astaxanthin, carotene, and other retinol palmitate, retinol and its derivatives such as retinol acetate, retinal and its derivatives, dehydroretinal, carotene, lycopene, carostinotine such as istaxanthin Carotenoids; thiamine hydrochloride, thiamine sulfate, riboflavin, riboflavin acetate, pyridoxine hydrochloride, pyridoxine dioctanoate and other pyridoxines, flavin adenine nucleotides, cyanocoparamine, folic acid, nicotinamide, benzyl nicotinate, etc. Vitamin B such as nicotinic acid and choline; Vitamin D such as ergocalciferol, cholecalciferol, and dihydroxystannal; dl— a (| 3, r) monotocopherol, acetic acid d I--Tocophero Nicotinic acid d I-a-tocopherol, linoleic acid-d1-α-tocopherol, tocopherol and its derivatives such as succinic acid d1-a-tocopherol, vitamin E such as ubiquinone; dibutyl hydroxytoluene and butyl Examples thereof include hydroxyanisol.

 In addition, when the composition for external use of the invention of this application is applied more practically as an external preparation,

 <1> Nonionic surfactant

 <2> Ascorbic acid or its derivative or salt

 <3> UV protection agent

It is preferable to contain at least one of them. More preferably, 1> nonionic surfactant is in the range of 0.0 1% to 50% by weight of the total composition, and one or more selected from the following: That is. POE sorbitan fatty acid esters such as POE sorbitan monooleate, POE sorbitan monostearate, POE sorbitan monolaurate, POE sorbitan tetraoleate, POE sorbite monolaurate, POE sorbite monolaurate, P OE Sorbit Pen Yoleate, POE Sorbit Monos POE sorbite fatty acid esters such as tearate, POE glycerin monostearate, POE glycerin fatty acid esters such as POE glycerol triisostearate, POE fatty acid esters such as POE monooleate, POE alkyl ethers such as POE lauryl ether, P OE POE alkyl phenyl ethers such as octyl phenyl ether, POE POP alkyl ethers such as POE POP cetyl ether, tetra POE tetra tetra ethylene diamine amine condensates, POE castor oil or hardened castor oil derivative, POE Beeswax lanolin derivative, alkanol amides such as lauric acid monoethanolamide, POE propylene glycol fatty acid ester, POE alkylamine, POE fatty acid amide, sucrose fatty acid ester, POE nonylphenylform aldehyde condensate, alkyl Butoxy dimethylamine O dimethylsulfoxide, trio Reirurin acid is at least one selected from polyglycerol fatty acid ester.

 As for <2> ascorbic acids, the range is from 0.01 to 20% by weight, and further from 0.1 to 10% by weight, based on the total amount of the composition. One or more selected from the represented compounds and salts thereof.

<3> The UV protection agent should be in the range of 0.01% to 50% by weight based on the total amount of the composition, and one or more selected from the following: . That is, 2-methoxyethyl hexyl paramethoxy cinnamate, isopropyl para methoxy cinnamate, paramethoxy hydride diethanolamine salt of dimethoxy quine cinnamate, glyceryl mono-2-ethyl hexanoate, octyl methoxy cinnamate 1-hydroxy-4--methoxybenzophenone 2-hydroxy-4-methylbenzophenone 5-sulfuric acid 2-hydroxy-1-4-methoxybenzophenone 1—Sodium sulfate, 2,4-dihydroxybenzophenone, 2, 2′— Dihydroxy-4,4'-dimethoxybenzophenone, 2,2'-dihydroxyl-4-methoxybenzophenone, 2,2 ', 4,4' —tetrahydroxybenzophenone-2-hydroxy-4-n-o Benzophenone-based ultraviolet absorbers such as oxybenzophenone, paraaminobenzoic acid, ethyl paraaminobenzoate, pityl paraaminobenzoate, 2-dimethylhexyl paradimethylaminobenzoate, glyceryl paraaminobenzoate, amyl paraaminobenzoate, etc. Acid UV absorbers, 1-ethylhexyl salicylate, triethanolamine salicylate, homomentyl salicylate, dipropylene glycol salicylate, methyl salicylate, ethylene glycol salicylate, phenyl salicylate, amyl salicylate, benzyl salicylate, Salicylic acid UV absorbers such as isopropylbenzyl salicylate and potassium salicylate; 4—t-Butyl_4′-methoxydibenzoylmethane, 4 Γsopropyldibenzoylmethane, 4-methoxydibenzoylmethane, 4- t-Pitreux 4 '-Hydroxydibenzoylmethane and other dibenzoylmethane-based UV absorbers, menthyl o-aminobenzoate 2-phenyl benzimidazole 5-sulfuric acid 1 2-phenyl benzoxazole, 3— (4-Methylbenzylidene) camphor 1 2-ethylhexyl 1 2-cyanol 3, 3-diphenyl acrylate 2 — ethyl 1 2 — cyano 3, 3 ^f- diphenyl acrylate 2— (2 '— hydroxy 5 —Methylphenyl) Anthranilic acid-based purples such as benzotriazole and menthyl anthranilate Linear absorption agent, Urokanin acid UV absorbers such as Urokanin acid Echiru, titanium oxide, zirconium oxide, cerium oxide, silica coating of zinc oxide 及 Pico these metal oxides.

In order to obtain a stable composition, in the invention of this application, one or more of the following is added to the composition in an amount of 0.01% by weight to 10% by weight: In the range of <4>, it is preferable to blend them as <4> storage stabilizers, organic acids having a chelating effect, or salts thereof. Erythorbic acid and its salts, dibutylhydroxytoluene, tocopherol and its derivatives, porphyrin, ptylhydroxyanisole, sodium bisulfite, anhydrous sodium sulfite, gallic acid and its derivatives, alanine, ethylenediamine hydroxyethyl triacetate And at least one selected from the group consisting of ethylenediamine tetraacetic acid and its salt, quenoic acid and its salt, darconic acid, tartaric acid, phytic acid, sodium polyphosphate, and sodium metaphosphate. The blending amount thereof may be added in the range of 0.1% to 50% by weight, preferably in the range of 0.1% to 5% by weight with respect to the total weight of the external composition. The salt is not particularly limited, but metals other than transition metals are desirable from the viewpoint of safety to the skin, and sodium, potassium, magnesium, and calcium are particularly desirable.

 In such a stabilizing composition, it is particularly preferable for the aqueous composition to have a pH value in the range of 3 to 10 as described above. For the composition of the stabilizing composition, it is particularly desirable that the total concentration of transition metal compounds be 0.1% by weight or less.

 When the antioxidant power of fullerene is applied to an externally applied composition, fullerene is usually easily oxidized due to the strong antioxidant power of fullerene, and even if formulated in an externally applied composition, it tends to be unstable in the preparation.

 In other words, fullerene's strong antioxidant power causes reductivity in the composition for external use and is rapidly oxidized. As a result, when administered to the skin, the antioxidant power is reduced, weakened or deactivated and may not be fully effective. In addition, even if fullerene is applied as an external preparation, its active ingredients are oxidized and decomposed, and some fullerenes change to free radicals due to the influence of ultraviolet rays etc. on the skin, so the effect as an antioxidant is insufficient. However, improvement as a topical agent and therapeutic effects may not be fully exerted, resulting in a protective or preventive effect.

In response to these concerns, good stability is achieved in the above composition. Will be.

 Furthermore, in the invention of this application, as a composition for a practically suitable external preparation, it contains at least one of the following components, thereby whitening the skin, improving pigmentation, and preventing acne. Treatment, improvement of wrinkles, improvement of rough skin, improvement of oily skin, improvement of dry skin, reduction of pores, treatment of scars, treatment of redheads, treatment of hair loss, promotion of hair growth, treatment of burns, skin sterilization, skin A composition for external application of fullerene is provided which has an enhanced effect of miticide and skin texture improvement.

 That is,

 <5> A whitening component of 0.1 to 20% by weight with respect to the total amount of the composition, cystine and its derivatives, and salts thereof, glabrizine, dalaprene, liquiritin, isoliquiritin, placental extract, Hyde mouth quinone and its derivatives, resorcin and its derivatives, and at least one selected from dartathione.

 <6> Glycyrrhizic acid, glycyrrhetinic acid and their derivatives, and their salts, mefenamic acid, feuine as an anti-inflammatory component in the range of 0.01 to 10% by weight relative to the total composition Dirubenzone, indomethacin, ibuprofen, ketoprofen, allantoin, guaiazulene, panthenol and its derivatives, and their salts, ε-amino-aminoproic acid, diclofenac sodium, and tranexamic acid.

<7> Superoxide dismutase, mannitol, histidine, triftophan, pyrilbin, quercetin, querci 卜 phosphorus, as an antioxidant component in the range of 0.01 to 10% by weight based on the total composition Polyphenol, proanthocyanidins, tocotrienols, force techin, catechin derivatives, rutin and its derivatives, gallic acid and its derivatives, ubiquinone, wastaxanthin, carotene, other carotenoids and their derivatives, and their Salt, vitamins, moss and it These derivatives and their salts, vitamin Ds and their derivatives and their salts, vitamin Es and their derivatives and their salts, at least one selected from dibutyl hydroxytoluene and butylhydroxy diazole is there.

 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. Example

Example 1>

(Synthesis of water-soluble fullerene hydroxide 2 from insoluble hydroxylated fullerene 1) Insoluble hydroxylated fullerene 1 (average estimated structure C _6D (OH) ₁₂ · 5 Η ₂ 0) (J. Org. Chem., 1994, 59, (Synthesis according to the description in 3960) To 0.100 g, 1 OmL of 30% aqueous hydrogen peroxide was added, and the suspension was stirred at 60 at 4 days. After confirming that the solution became completely uniform and yellow and transparent, the reaction was stopped, and 5 OmL of 2-propanol, jetyl ether, and hexane were added in this order to precipitate a solid.

 The resulting precipitate is precipitated using a centrifuge, separated by decantation, further washed twice with 5 OmL of ether, and then vacuum-dried for 18 hours to form a water-soluble hydroxide that is a reaction product. 0.097 g of fullerene 2 was obtained as a light ocher powder.

Figure 1 shows the FT-IR spectrum of the powder thus obtained. Broad absorption near 3400 cm- ¹ based on 0-H stretching of the hydroxyl group and broad absorption near 1620, 1370, 1080 cm- ¹ based on C-C and C-0 stretching. These absorption patterns are very similar to the spectrum of insoluble fullerene hydroxide 1 reported by LY Chiang (Fig. 2) (J. Am. Cei. So, 1992, 114, 10154). ), The relative intensity ratio of each absorption was slightly different, suggesting that it is a hydroxylated fullerene with a different number of hydroxyl groups. Also, A small absorption near 1720 cm- ¹ suggests the presence of a ketone group due to the pinacol rearrangement of the hydroxyl group (LY Chiang et al., J. Am. Chem. Soc, 1993, 115, 5453), but usually carbonyl C = 0 Absorption based on expansion and contraction is large, so the existence ratio is judged to be small.

A thermal analysis of this water-soluble fullerene hydroxide 2 using a thermogravimetric analyzer TGA under a nitrogen atmosphere at a heating rate of 5 ^ CZmin resulted in a weight loss of about 9% from room temperature to around 150. Therefore, it was possible to estimate that approximately 9% of the water was strongly adsorbed by the hydroxyl group (Fig. 3). As a result of elemental analysis, the water-soluble fullerene hydroxide 2 was in good agreement as having a composition of C _6fl (OH) _{36-9H 2} 0 in consideration of the water _content described above. The elemental analysis of the above composition is C: 48.20%, H: 3.64%, the experimental values are C: 48.06%, H: 3.61%, and the water content is 10.8%. Estimated.

 The solubility of this water-soluble fullerene hydroxide 2 in water was 17.5 mg / mL (1.8 wt%), which is higher than the water solubilization with clathrate compounds reported so far. It was found to have Example 2>

 (Synthesis of water-soluble fullerene hydroxide 3 from insoluble fullerene hydroxide 1) According to the same procedure as in Example 1, a hydrogen peroxide suspension of insoluble fullerene hydroxide 1 was stirred at 60 for 4 days. After confirming that it became completely uniform yellow and transparent, the reaction was continued for another 10 days. As a result, the color of the solution gradually faded and became pale yellow and transparent. Further, 0.13 g of water-soluble fullerene hydroxide 3 was obtained as a milky white powder by the same operation.

 An FT-IR measurement of the powder thus obtained confirmed that the spectrum was almost the same as that of hydroxylated fullerene 2 (Fig. 4).

A thermal analysis of this water-soluble fullerene hydroxide 3 using a thermogravimetric analyzer TGA under a nitrogen atmosphere at a heating rate of 5 ^ Zmin resulted in a weight loss of about 10% between room temperature and 150. As a result, it was stronger by the hydroxyl group. It was estimated that about 10% of the moisture adsorbed on the water was present (Fig. 5).

The result of elemental analysis, the water-soluble fullerene 3, considering containing water as described _{above, C 6 () (OH)} 40 - were in good agreement with those having 9H ₂ 0 a composition. The elemental analysis of the above composition is C: 46.1 1%, H: 3.74%, the experimental values are C: 46.26%, H: 3.68%, and the water content is 10.4%. It was estimated.

 The solubility of this water-soluble fullerene hydroxide 3 in water was 58.9 mg / mL (5.9 wt%), which is much higher than the water solubilization with clathrate compounds reported so far. It was found to have solubility.

 (Measurement of the color of aqueous fullerene hydroxide 2, 3)

In order to examine the colors of the water-soluble fullerene hydroxides 2 and 3 in Examples 1 and 2, ultraviolet-visible absorption spectrum measurement of the aqueous solution was performed (FIG. 6). Compared to the measured fullerene C _6D (toluene solution) and water-oxidized fullerene 1 (THF solution), water-soluble fullerene hydroxides 2 and 3 clearly have a short wavelength shift in the visible region above 400 nm. It was found that there was almost no absorption in the visible region.

 <Example 3>

(Synthesis of water-soluble fullerene hydroxide 5 from hydrogenated fullerene 4) Hydrogenated fullerene 4 (average estimated structure C _{6 ()} H ₃₆ ) (J. Chem. Soc., Perkin Trans. 2, 1995, 2359 (Synthesis according to the description) To 0.100 g, 1 OmL of 30% aqueous hydrogen peroxide was added, and the suspension was stirred at 60 for 7 days. After confirming that the solution became almost uniform yellow and transparent, the reaction was stopped, and a very small amount of insoluble matter was removed by centrifugation. Then, 5 OmL of 2-propanol, jetyl ether, and hexane were added. Solids were precipitated by adding in order.

The resulting precipitate is allowed to settle using a centrifuge and then decanted. Separated, further washed twice with 5 OmL of ether, and vacuum dried for 18 hours to obtain 0.096 g of water-soluble fullerene hydroxide 5 as a reaction product as a milky white powder.

An FT-IR measurement of the powder thus obtained confirmed that the spectrum was almost the same as that of hydroxylated fullerene 2 (Fig. 7). Absorption due to C—H stretching near 2 80 0-2900 cnT ¹ seen in the spectrum of hydrogenated fullerene 4 as a starting material (Fig. 8) almost disappeared, and instead the absorption due to hydroxyl groups increased. Therefore, it is inferred that the hydrogen of hydrogenated fullerene is replaced by a hydroxyl group.

As a result of elemental analysis, the water-soluble fullerene hydroxide 5 was in good agreement as having a composition of C _{6 ()} H ₄ (OH) ₃₂ -6H ₂ 0. Elemental analysis of the above composition is C: 52. 34%, H: 3.5 1%, experimental values are C: 5 2.6 1%, H: 3.7 6%, and water content is 7 Estimated at 9%. The solubility of this water-soluble fullerene hydroxide 5 in water was found to be 20.2 mg ZmL (2.0 wt%), which is higher than the water solubilization by clathrate compounds reported so far. I found it.

 <Example 4>

Water-soluble fullerene hydroxide 5 obtained in Example 3 above; C ₆₀ H ₄ (OH) 32 * 6 H ₂ 0, commercially available insoluble fullerene hydroxide (water solubility is less than 0.1% and difficult to detect) In comparison, the hydroxy radical scavenging ability was evaluated. The results are shown in FIG.

 Figure 10 also shows the changes in the ESR spin adduct spectrum of DMP O and ΟΗ in the presence of the above water-soluble fullerene hydroxide.

 Furthermore, the hydroxyl radical scavenging ability of the above water-soluble fullerene hydroxide was evaluated as a comparison with vitamin C. Figure 11 shows the results. AA2 G in the figure indicates the case of L-ascorbic acid 1-2-daroxide.

The evaluation method for hydroxy radical scavenging ability was as follows. Specifically, a sample was placed in a 1.5 ml Eppendorf tube, reacted with H ₂ 0 ₂ for 30 seconds, then measured by ESR, and evaluated for hydroxy radical scavenging activity by the ESR trapping method. In the test, when DM PO was added as a spir trap agent that stabilizes unstable hydroxyl radicals as adducts, the electron spin resonance device (manufactured by JEOL Ltd., JES—FR30 type) An electron spin resonance spectrum exhibiting a characteristic quartet is seen, and the amount of hydroxy radicals is calculated in proportion to the intensity of manganese oxide exhibiting a paramagnetic spectrum added as a comparative internal standard. It was.

 DMS O is a hydroxy radical scavenger and has been found to have hydroxy radical scavenging activity.

 The result of the test was evaluated as a residual amount of droxy radical: Relative Signal Intensity (DMP O—OH / MnO).

 As is apparent from the above results, the water-soluble fullerene hydroxide of the invention of this application has a remarkable OH-erasing ability. This has never been foreseen.

 Example 5>

 Using water-soluble fullerene hydroxide (F 1) synthesized in Example 1, water-soluble fullerene hydroxide (F 2) synthesized in Example 2, and water-soluble fullerene hydroxide (F5) synthesized in Example 3 A composition was prepared.

 Invention lotion 1:

 F 1 0. 1%

 Quenic acid 1. 0%

 L-ascorbic acid 2-phosphate N a 1%

 P OE Solpi Yumon Monolate 0.5%

 Paramethyloxycinnamic acid 2-ethylhexyl 0.1%

 Xanthan gum 0.1%

NaOH (adjust pH to 8) Purified water remaining

Invention lotion 2:

 F 2 0. 1%

 Quenic acid 1. 0%

 Xanthan gum 0.2%

 N aOH (pH adjusted to 8)

 Purified water remaining

Invention lotion 3:

 F 5 0. 1%

 L-ascorbic acid 2-phosphate N a 0.5%

 Xanthan gum 0.1%

 N aOH (pH adjusted to 8)

 Purified water remaining

 Invention sunscreen emulsions:

 (Prescription) (%)

 (1) Stearic acid 2, 0, (2) Cetanol 1.0, (3) Polyoxyethylene sorbitan monooleate (20 EO) 0.5, (4) Sorbitan sesquioleate 0.5, (5 ) P-methoxy cinnamate 2 monoethylhexyl (* 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, (1

0) Peppermint extract (* 2) 0.02, (1 1) F 1: 0.1, (1

2) Licorice extract (* 3) 0. 02, (13) Placenta extract (* 4) 0.

3, (14) Acetic acid d 1— α-Toco

 Ferrol (* 5) 0.2, (15) Remaining amount of purified water, (16) Preservative appropriate amount, (17) Titanium oxide 3.0, (1 8) Perfume appropriate amount (1% citrate and Na ΟΗ The pH was adjusted to soil 1.)

* 1 Made by Maruzen Pharmaceutical * 2 — Made by Maru Falcos * 3 Maruzen Pharmaceutical * 4 Made by Nichirei * 5 Made by Eisai

 * Invention liquid foundation:

 (Prescription) (%)

 (1) Lanolin 7.0, (2) Liquid paraffin 5.0, (3) Stearic acid 2.0, (4) Seyunorol 1.0, (5) Macadamia nut oil (* 1) 5.0, (6) F2: 0.5, (7) Malmo extract (* 2) 0.5, (8) Glycerin 5.0, (9) Triethanolamine 1 · 0, (1 0) Carboxymethylcellulose 0.7, (1 1) Purified water balance, (1 2) My power 1 5. 0, (1 3) Talc 6.0, (14) Titanium oxide 3.0, (15) Color pigment 6. 0, (1 6) Dipalmitic acid L —Ascorbic acid (* 3) 0.1, (1 7) D—Panthenol (* 4) 0 · 0 1, (1 8) 4-t-butyl— 4 '— Methoxybenzoylmethane (* 5) 3.5, (1 9) Dalthathion (* 6) 0. 0 0 5, (2 0) Preservative appropriate amount, (2 1) Perfume appropriate amount (Chenic acid 1% And pH adjusted to 7 ± 1 with NaOH.)

 * 1 Made by Nippon Surfactant Co., Ltd. * 2 Made by Koei Kogyo Co., Ltd. * 3 Made by Nippon Surfactant Co., Ltd. * 4 Made by Nippon Roche Co., Ltd. * 5 Made by Gibodan Co., Ltd. * 6 Improvement of deposition, treatment of acne, improvement of wrinkles, improvement of rough skin, improvement of oily skin, improvement of dry skin, reduction of pores, treatment of scars, treatment of red face, treatment of hair loss, promotion of hair growth, treatment of burns Excellent effects in skin sterilization, skin mite killing, skin texture improvement, etc. were observed.

Industrial applicability

 According to the invention of this application as described above, a water-soluble fullerene having good water solubility and high active oxygen scavenging ability is provided. This thing is

• Because the color can be light (milky white), it is suitable for cosmetic use. • Various fullerene derivatives can be used as starting materials, and water-soluble fullerenes modified with substituents can be synthesized, so that other functions can be added, etc. As a manufacturing method,

 • A simple method for synthesizing water-soluble and light-colored fullerene derivatives;

Etc.

 The invention of this application provides technical means for realizing fullerene and its analogs in various fields of biocompatibility and realizing new antioxidant functions, etc. It can provide means for application as cosmetics or externally applied skin prescription drugs.

Claims

The scope of the claims

1. A water-soluble fullerene characterized by being at least one of the fullerene hydroxides having more than 30 hydroxyl groups (OH) bonded to the fullerene nucleus.

 2. The water-soluble fullerene according to claim 1, wherein the water-soluble fullerene is at least one kind of fullerene hydroxide to which 50 or less hydroxyl groups (OH) are bonded.

 3. A water-soluble fullerene characterized by having more than 30 hydroxyl groups (OH) bonded to the fullerene nucleus and being at least one of the hydrated fullerene hydroxides.

4. The water-soluble fullerene according to claim 3, represented by C ₆₀ (OH) _η · kH ₂ 0 (where n and k are integers of 30 <n and 4 <k).

5. C ₆₀ (OH) 36-9H ₂ 0 and C _6Q (OH) ₄ . · The water-soluble fullerene according to claim 4, which is represented by any of 9H ₂ 0.

 6. The water-soluble fullerene according to any one of claims 1 to 5, wherein a substituent other than a hydroxyl group (OH) is bonded to the fullerene nucleus.

 7. The water-soluble fullerene according to claim 6, wherein hydrogen atoms are bonded.

8. The water-soluble fullerene according to claim 7, which is represented by C ₆₀ H _B (OH) _η · k H ₂ 0 (n, m, k are integers of 30, n, 2 <m, 4 <k).

9. The water-soluble fullerene according to claim 8, represented by C ₆₀ H ₄ (OH) 32 * 6 H ₂ 0.

 10. The water-soluble fullerene according to any one of claims 1 to 9, wherein the fullerene nucleus is C60, C70 or a higher-order fullerene nucleus or a nanotube.

1 1. A method for producing a water-soluble fullerene according to any one of claims 1 to 10. A method for producing a water-soluble fullerene, comprising: reacting a fullerene having a substituent in the fullerene nucleus or not having a substituent with a hydrogen peroxide solution.

 12. The method for producing a water-soluble fullerene according to claim 11, wherein a water-insoluble hydroxylated fullerene that binds a fullerene nucleus to 20 or less hydroxyl groups (OH) is reacted.

 13. The method for producing water-soluble fullerene according to claim 11, wherein hydrogenated fullerene is reacted.

 14. An antioxidant comprising the water-soluble fullerene according to any one of claims 1 to 10 as an active ingredient.

15. C ₆₀ (OH) _η · kH ₂ 0 or C _{6 ()} H _n (OH) _η · kH ₂ 0 (where n, m, k are 30 <n, 2 <m, 4 <k 15. The antioxidant according to claim 14, wherein the active ingredient is a water-soluble fullerene represented by the formula:

16. C ₆₀ (OH) 36-9H ₂ 0, C ₆ . (OH) ₄₀ 9H ₂ 0 and C ₆ . The antioxidant according to claim 15, comprising a water-soluble fullerene represented by any one of H ₄ (OH) _32-6 H ₂ 0 as an active ingredient.

 17. An antioxidant characterized in that the water-soluble fullerene according to any one of claims 1 to 10 and an organic compound that modifies or includes the water-soluble fullerene, and at least one of the organic compounds among these salts, is an active ingredient. Composition.

18. C ₆₀ (OH) _η · kH ₂ 0 or C _{6 ()} H _n (OH) _n · kH ₂ 0 (where n, m, k are 30 <n, 2 <m, 4 <k 18. The antioxidant composition according to claim 17, comprising a water-soluble fullerene represented by the following formula as an active ingredient.

19. Effective water-soluble fullerene represented by one of C ₆₀ (OH) 36 * 9H ₂ 0, C ₆₀ (OH) ₄₀ · 9H ₂ 0 and C ₆₀ H ₄ (OH) _32-6 H ₂ 0 The antioxidant composition of claim 18 as a component.

20. The organic compound to be modified or included is characterized in that it is at least one of organic oligomers, organic polymers, cyclodextrins or their analogs, and crown ethers or their analogs. The antioxidant composition according to any one of claims 17 to 19.

21. The water-soluble fullerene according to any one of claims 1 to 10 and the water-soluble fullerene modified or clathrated with an organic compound, and at least one of these salts as an active ingredient Special topical composition.

22. C ₆₀ (OH) _η · kH ₂ 0 or C ₆ . Water-soluble fullerene represented by H _n (OH) _η · kH ₂ 0 (where n, m, k are integers of 30 <n, 2 <m, 4 <k) is used as the active ingredient. The composition for external use according to claim 21.

23. C ₆₀ (OH) 36-9H ₂ 0, C ₆₀ (OH) ₄ . · 9H ₂ 0 and C ₆ . The composition for external use according to claim 22, comprising a water-soluble fullerene represented by any one of H ₄ (OH) _32-6 H ₂ 0 as an active ingredient.

 24. The organic compound to be modified or included is at least one of an organic oligomer, an organic polymer, a cyclodextrin or an analog thereof, and a crown ether or an analog thereof. The composition for external use in any one of 23.