JP2008255107A - Fullerene liposolution and its aqueous dispersion as well as antioxidant and cell damage inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new technical means that enables antioxidation activity of fullerenes to be markedly expressed in a dissolved state in fat or even in an aqueous state leading to practical development of the fullerenes. <P>SOLUTION: The fullerenes are a fullerene liposolution dissolved in at least one kind of lipid of squalanes, mineral oils and vitamin Es or an aqueous dispersion of the fullerene liposolution where the fullerene liposolution is dispersed in an aqueous solvent. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a fullerene fat solution having an antioxidant activity, an aqueous dispersion thereof, an antioxidant, and a cytotoxicity-preventing formulation useful as cosmetics, pharmaceuticals and the like.

  Fullerenes have excellent effects as antioxidants that suppress the increase in active oxygen associated with ultraviolet irradiation and lipid peroxide treatment on human skin cells, and can be used as external preparations for cosmetics, medicines, etc. This has already been reported and proposed by the present inventors (see, for example, Non-Patent Document 1 and Patent Document 1).

  And, since it is useful in its application to dissolve fullerenes in aqueous solvents, fullerenes can be modified and complexed with water-soluble polymers, inclusion with cyclodextrins, or fullerene hydroxides That has already been proposed.

  In addition, composite materials in which fullerenes are combined with synthetic lipids to maintain the state of polyvalent anions and radical anions from fullerenes stably in water to develop redox-based redox ability in aqueous solutions are also available. It has been proposed (Patent Document 2).

However, regarding the expression of the antioxidant activity of fullerenes, sufficient studies have not been made on the interaction with the accompanying medium. In particular, little is known about the realization of remarkable effects when fullerenes are dissolved in lipids, and this is one of the major limitations from the practical point of view of fullerenes. It was.
BIO INDUSTRY vol.20, No.5, 2003, pp.82-40 JP 2004-250690 A JP 2000-16974 A

  From the background as described above, the present invention can significantly express the antioxidant activity of fullerenes even in a dissolved state in lipids, and can also be expressed in an aqueous state. It is an issue to provide new technical means that can greatly open the way.

  The present invention provides the following to solve the above problems.

  First: Fullerene fat solution in which fullerenes are dissolved in at least one lipid among squalanes, mineral oils and vitamin Es.

  Second: An aqueous dispersion of fullerene fat solution in which the above fullerene fat solution is dispersed in an aqueous solvent.

  Third: The above aqueous dispersion dispersed together with a nonionic surfactant.

  Fourth: A method for producing an aqueous dispersion of a fullerene fat solution in which the fullerene fat solution is dispersed in an aqueous solvent by at least one of ultrasonic irradiation, vortex mixer, and homogenization treatment.

  5th: Antioxidant which uses fullerene fat solution as an active ingredient.

  6th: Antioxidant which uses the aqueous dispersion of fullerene fat solution as an active ingredient.

  Seventh: A cytotoxic inhibitor formulation containing any of the above antioxidants.

  According to the present invention as described above, the antioxidant activity of fullerenes can be remarkably expressed in a dissolved state in lipids, and even in an aqueous state, and can be used as a composition for external use such as cosmetics or as a pharmaceutical formulation. Practical development as a composition or the like can be expanded.

    Embodiments of the present invention will be described below.

  Various fullerenes and derivatives thereof are considered for the fullerene fat solution of the present invention and the fullerenes that can be used in the aqueous dispersion. For example, fullerene is expressed as Cn (n is an integer of 60 or more), and has a carbon skeleton structure such as C60 fullerene, C70 fullerene, etc., and carbon tube fullerene, etc. One or two or more of various types including known ones are listed as examples.

  Such a carbon skeleton structure includes various substituents such as hydrocarbon groups, oxygen cross-linking groups, oxygen-containing groups such as hydroxyl groups, acyl groups, ether groups, and carboxyl groups, amino groups, and nitrogen-containing groups of cyano groups. Etc. may be included.

  Also included are those in which a plurality of fullerenes are bonded via an alkylene chain such as a methylene chain. Derivatives of fullerene C60 are those in which 1 to 40 modifying groups are bonded to one fullerene molecule, and derivatives of fullerene C70 are bonded to 1 to 50 modifying groups in one fullerene molecule. What is doing is illustrated. The modifying group in this case may be independently a hydroxyl group, an ester group of the hydroxyl group and an inorganic or organic acid, a glycoside group of a sugar, 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.

  As for the fullerene oxygen-containing derivative, a compound in which an oxygen atom is bonded directly to a carbon atom of a fullerene skeleton or via a carbon chain such as an alkylene chain is considered. For example, a fullerene hydroxide having an —OH group directly bonded to a hydroxylation rate of up to about 50 / mole fullerene is exemplified.

  For example, hydroxylated fullerenes in which 30 to 36 hydroxyl groups (OH) are bonded per molecule of fullerene are also exemplified as suitable in the present invention.

  For example, as an organic compound that modifies or includes fullerene or fullerene derivatives as described above, cyclodextrin (CD), crown ether, or a green compound thereof capable of forming an organic oligomer, an organic polymer, and an inclusion compound or an inclusion complex One or more of these are exemplified as preferred.

  Examples of the organic oligomer and organic polymer include polyalkylene glycols such as carboxylic acid esters, alcohols, saccharides, polysaccharides, polyhydric alcohols, polyethylene glycol, polybutylene glycol, polypropylene glycol, polyvinyl alcohol, and the like. Polymers of alcohols, nonionic water-soluble polymers including starch derivatives such as dextran, bullan, starch, hydroxyethyl starch and hydroxypropyl starch, alginic acid, hyaluronic acid, chitosan, chitin derivatives, and Anionic or cationic derivatives and their polymeric glycerin and fatty acids, oils, propionate carbonate, lauryl alcohol, ethoxylated castor oil, polysorbates, and esters or esters thereof. Tells, and polymers thereof, polyester polymers thereof, pyrrolidone polymers such as polyvinyl pyrrolidone, esters or ethers of unsaturated alcohol polymers, and polyoxyethylene polyoxypropylene block copolymers Are preferably bonded to fullerene or a derivative thereof, and may be a mixture of one or more of them. Especially, various things, such as polyalkylene glycols, such as polyethyleneglycol (PEG), polyvinylpyrrolidone (PVP), are illustrated as a preferable thing. In the case of polymers such as PEG and PVP, the average molecular weight is generally preferably about 2000 to 100,000. The ratio with fullerene or fullerene oxygen-containing derivatives is 10/1 or less as a molar ratio. It is considered to be a degree.

  For example, the above fullerenes may be any as long as they can retain fat solubility, and may be either synthesized or available as commercial products.

  In the present invention, one or more of these fullerenes are dissolved in a lipid composed of one or more of squalanes, mineral oil and vitamin E to form a fullerene fat solution. The In this case, the squalane may be one or more of various analogs and derivatives including squalane and squalene. The same applies to vitamins E, which may be one or more of various analogs and derivatives such as tocopherol and tocotrienol. As long as fullerenes can be dissolved in these lipids, the ratio of these lipids and fullerenes used is not particularly limited. The means for dissolution may be an appropriate one such as stirring and heating.

  The fullerene fat solution of the present invention is dispersed in an aqueous solvent such as water or an aqueous solvent, for example, a mixture of alcohol and water, so that its antioxidant activity is utilized as an external preparation such as cosmetics. More effectively deployed as a practical technique.

  Dispersion of fullerene fat solution in an aqueous solvent is embodied, for example, as an O / W emulsion. For the production of this aqueous dispersion, treatment with ultrasonic irradiation, a vortex mixer, a homogenizer, or the like is more effective. .

  A nonionic surfactant is also effectively used for dispersing the fullerene fat solution in the aqueous solvent. For example, it is a nonionic surfactant mainly composed of a polyoxyethylene ether structure. The addition amount of these nonionic surfactants is preferably in the range of 0.01 to 2 wt% of the total amount.

  As a homogenizer, for example, a Potter type homogenizer is considered suitable. This is a combination of a glass tube and a fluororesin rotating rod fitted into the tube lumen, and the particles are atomized by the rotation of both and the piston movement. Since it is difficult to entrain air, it is effective for atomizing the antioxidant.

  The dispersion treatment by these means is preferably performed under a reduced bubble condition, and more preferably dispersed in a degassed aqueous solvent. This makes it easy to retain antioxidant activity.

  The fullerene fat solution of the present invention, and its dispersion in an aqueous solvent, is suitable for use as an antioxidant in external preparations such as cosmetics. Such an antioxidant is used as a cytotoxic inhibitor formulation, for example, It is useful for UV injury, sunburn, skin lipid metabolism abnormalities, photoaging, hypersunlight, photocarcinogenesis, etc., treatment and prevention, or skin care.

In the fullerene fat solution of the present invention, the aqueous dispersion can be applied as an external preparation, and for example, the following is considered.
1. Dosage The concentration of the fullerenes of the invention of this application may be 0.00001% 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 use is preferably 0.001 to 20 ml of liquid per square meter of skin area, preferably 0.01 to 5.0 ml, applied externally, or is sprayed.
2. Administration form Examples of the form of the external composition for skin are not particularly limited. For example, all external preparations such as aqueous solvents, ointments, emulsions, creams, gels, packs, bath preparations, cleaning agents, poultices, dispersions, etc. The dosage form is not particularly limited, and may be a paste, mousse, gel, powder, solution system, solubilization system, or emulsification system. Especially for aqueous solutions, emulsions, ointments, gels, water-soluble agents, cosmetics, and packs, after these agents are applied externally, a humidifier, vibration introducer, ion introducer, sonic introducer, electromagnetic wave introducer By using it, the 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, all physically possible methods such as spraying, sticking, poultice, dipping, and mask can be used.
3. Ingredients The antioxidant composition and the external composition of the present invention are basically realized as a combination with various components constituting cosmetics and external medicines conventionally known.

  For example, heat insulating agents, pigments, base materials such as alcohols and water-soluble polymers, cell activators, ascorbic acid or derivatives thereof, active oxygen scavengers, antibacterial agents and the like.

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

  A C60 preparation having a C60 fullerene ratio of approximately 95% is dissolved in each of mineral oil, vegetable squalane and vitamin E (tocopherol), and then the mixture is defoamed with a Potter-type homogenizer (the pressure is reduced by an aspirator to reduce bubbles). To reduce the water) to form an O / W emulsion.

  Each of these emulsions was added to a human skin keratinocyte: HaCaT Cell culture system and evaluated for cell viability.

  FIG. 1 shows the results for mineral oil and plant squalane. The graph shows a comparison between the case of a fullerene-containing emulsion (Lipo Fullereue) and the case of a mineral oil that does not contain fullerene, squalane alone (Oil) under the condition of addition of 20 μM t-BuOOH. The administration concentration V / V% indicates the ratio to water, and ppm indicates the fullerene content (in 1 mL well).

  In the case of the fullerene fat solution emulsion shown as a black bar display in FIG. 1, it can be seen that the cell viability is greatly improved.

  FIG. 2 shows the case of vitamin E under the condition of adding 70 μM t-BuOOH. In the case of the emulsion of fullerene fat solution displayed by the black bar, it can be seen that the cell survival rate is improved as compared with the case of vitamin E alone.

It is the figure which showed the contribution to a cell viability about the water dispersion of the fat solution which melt | dissolved fullerene in mineral oil and squalane. It is the figure which showed the contribution to a cell viability about the aqueous dispersion of the fat solution which melt | dissolved fullerene in vitamin E ((alpha) -tocopherol).

Claims (7)

  A fullerene fat solution, wherein fullerenes are dissolved in at least one lipid selected from squalanes, mineral oils and vitamin Es.   An aqueous dispersion of a fullerene fat solution, wherein the fullerene fat solution according to claim 1 is dispersed in an aqueous solvent.   The aqueous dispersion of fullerene fat solution according to claim 2, wherein the aqueous dispersion is a fullerene fat solution dispersed together with a nonionic surfactant.   4. The method for producing an aqueous dispersion according to claim 2 or 3, wherein the fullerene fat solution is dispersed in an aqueous solvent by at least one of ultrasonic irradiation, vortex mixer and homogenizer treatment. A method for producing an aqueous dispersion of   An antioxidant comprising the fullerene fat solution according to claim 1 as an active ingredient.   An antioxidant comprising an aqueous dispersion of the fullerene fat solution according to claim 2 as an active ingredient.   A cytotoxic injury-prescription formulation comprising the antioxidant according to claim 5 or 6.