Ascorbic acid derivative or salt thereof, composition containing same, and cosmetic containing same

Abstract

As an ascorbic acid derivative or salt thereof having better moisturizing properties than prior-art ascorbic acid derivatives, provided is an ascorbic acid derivative or salt thereof in which at least one hydrogen of the hydroxyl groups at the 2- or 3-position of ascorbic acid is substituted with CH2OH-CH(OH)-CH2-O-CH2-CH(OH)-CH2- or CH2OH-CH(OH)-CH2-O-CH2-CH(CH2OH)-. Also provided are an ascorbic acid derivative composition that contains the aforementioned ascorbic acid derivative or salt thereof and a prior-art ascorbic acid derivative, and a cosmetic that contains the aforementioned ascorbic acid derivative or the aforementioned ascorbic acid derivative composition.

Description

Ascorbic acid derivatives or salts thereof, compositions containing them, and cosmetics containing them.

[0001] The present invention relates to ascorbic acid derivatives or salts thereof that are suitably used as raw materials for cosmetics, and more particularly to compositions containing the said ascorbic acid derivatives or salts thereof, and cosmetics containing them.

[0002] Ascorbic acid is a safe and useful antioxidant, known for its excellent skin-whitening properties. However, its instability to light, heat, and oxidation has hindered its use in cosmetics. Therefore, various ascorbic acid derivatives or salts thereof have been proposed as having improved long-term stability compared to ascorbic acid. These have been proposed for incorporation into topical skin whitening preparations (Patent Documents 1 and 2) and into cosmetics (Patent Document 3). However, there is a need for ascorbic acid derivatives with even better long-term stability and efficacy.

[0003] Against this backdrop, the present inventors have proposed ascorbic acid derivatives that have superior temporal stability and functionality compared to ascorbic acid (Patent Documents 4 and 5). However, further improvements are desired regarding the efficacy of these ascorbic acid derivatives.

[0004] JP-A-62-221611 JP-A 2005-060239 JP-A-1-228978 Patent No. 4681670 Patent No. 7267657

[0005] The present invention aims to provide ascorbic acid derivatives or salts thereof that have even better moisturizing effects than conventional ascorbic acid derivatives, ascorbic acid derivative compositions containing them, and cosmetics containing them.

[0006] As a result of intensive studies to solve the above problems, the present inventors have found that a novel ascorbic acid derivative represented by the following general formula (I) or a salt thereof has a better moisturizing effect than conventional ascorbic acid derivatives. Furthermore, it has been found that a composition containing the ascorbic acid derivative represented by the following general formula (I) or a salt thereof and the ascorbic acid derivative represented by general formula (II) or a salt thereof also has a better moisturizing effect than a conventional ascorbic acid derivative or a salt thereof alone. The present invention has been completed based on these findings.

[0007] The first aspect of the present invention is an ascorbic acid derivative or a salt thereof, which is represented by the following general formula (I).

[0008]

[0009] In formula (I), R １ and R ２ are H, an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, a benzyl group, R ３ -CH(CH ２ OH)-, R ３ -CH(OH)-CH ２ -, R ３ -O-CH ２ -CH(OH)-CH ２ -, or R ３ -O-CH ２ -CH(CH ２ OH)-, and here R ３ is H, an alkyl group having 1 to 22 carbon atoms, or CH ２ OH-CH(OH)-CH ２ -. However, at least one of R １ and R ２ is CH ２ OH-CH(OH)-CH ２ -O-CH ２ -CH(OH)-CH ２ - or CH ２ OH-CH(OH)-CH ２ -O-CH ２ -CH(CH ２ OH)-.

[0010] The salt of the ascorbic acid derivative is R in formula (I). １ or R ２ This refers to compounds obtained by substituting an ascorbic acid derivative, in which the hydrogen atom is H, with a cation such as a metal ion or an ammonium ion, and salts of these compounds are also included in the present invention.

[0011] Ascorbic acid derivatives represented by general formula (I) or salts thereof have superior moisturizing effects compared to conventional ascorbic acid derivatives or salts thereof.

[0012] An ascorbic acid derivative represented by general formula (I), R １ and / or R ２ is a diglyceryl group, i.e., CH ２ OH-CH(OH)-CH ２ -O-CH ２ -CH(OH)-CH ２ - or CH ２ OH-CH(OH)-CH ２ -O-CH ２ -CH(CH ２ The OH)- group can be obtained by reacting ascorbic acid with 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane, as described below, to regiospecifically etherify only the 2nd and / or 3rd position of the four hydroxyl groups located at the 2nd, 3rd, 5th, and 6th positions of ascorbic acid, followed by acid treatment. １ and R ２ Ascorbic acid derivatives in which both positions are diglyceryl groups can be synthesized by a two-step method, in which a compound in which a diglyceryl group is introduced to one of the positions 2 or 3 by etherification of one of the positions 2 or 3 followed by acid treatment, and then further etherification and subsequent acid treatment to introduce a diglyceryl group to the other position 2 or 3; or they can be synthesized by a one-step method, in which 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane is reacted with ascorbic acid in amounts of 2 equivalents or more, followed by acid treatment.

[0013] In the reaction between ascorbic acid and 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane, depending on the reaction conditions for etherification, there are two cases in which the hydroxyl group at position 2 is mainly etherified, and cases in which the hydroxyl group at position 3 is mainly etherified. When the hydroxyl group at position 2 is mainly etherified, R ２ However, R ３ -O-CH ２ -CH(OH)-CH ２ - and R ３ -O-CH ２ -CH(CH ２ A mixture with the OH)- may also be formed, and when the hydroxyl group at the 3rd position is mainly etherified, R １ However, R ３ -O-CH ２ -CH(OH)-CH ２ - and R ３ -O-CH ２ -CH(CH ２ A mixture with a substance that is OH)- may also be formed.

[0014] Among the ascorbic acid derivatives represented by general formula (I), R in formula (I) １ or R ２ One of them is R ３ -O-CH ２ -CH(OH)-CH ２ - or R ３ -O-CH ２ -CH(CH ２ A compound that is OH)- and has a C1-C22 alkyl group, a C2-C22 alkenyl group, or a benzyl group is obtained by reacting ascorbic acid with 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane and then performing an acid treatment. １ or R ２ One of them is R ３ -O-CH ２ -CH(OH)-CH ２ - or R ３ -O-CH ２ -CH(CH ２A compound having (OH)− can be obtained by reacting it with glycidol, an alkyl glycidyl ether, an alkenyl glycidyl ether, a phenyl glycidyl ether, a sulfate ester, an alkyl halide, a benzyl halide, an alkenyl halide, etc. Alternatively, a compound obtained by reacting glycidol, an alkyl glycidyl ether, an alkenyl glycidyl ether, a phenyl glycidyl ether, a sulfate ester, an alkyl halide, a benzyl halide, an alkenyl halide, etc. with ascorbic acid on one of R １ or R ２ can also be obtained by reacting the resulting compound with 4−[(2,3−epoxypropoxy)methyl]−2,2−dimethyl−1,3−dioxolane and then performing an acid treatment. Among the ascorbic acid derivatives represented by the general formula (I), in the formula (I), both of R １ and R ２ are R ３ −O−CH ２ −CH(OH)−CH ２ − or R ３ −O−CH ２ −CH(CH ２ OH)− can be synthesized by the above two−step method or one−step method.

[0015] The second aspect of the present invention is a preferred embodiment among the first aspect of the present invention, wherein one of R １ and R ２ is CH ２ OH−CH(OH)−CH ２ −O−CH ２ −CH(OH)−CH ２ −, or CH ２ OH−CH(OH)−CH ２ −O−CH ２ −CH(CH ２ OH)−, and the other is H, an alkyl group having 4 to 18 carbon atoms, CH ２ (OH)−CH(OH)−CH ２ [[ID=;47]]−, CH ２ OH−CH(CH ２ OH)−, CH ２ OH−CH(OH)−CH ２ −O−CH ２-CH(OH)-CH ２ -, or CH ２ OH-CH(OH)-CH ２ -O-CH ２ -CH(CH ２ OH)-. It is characterized by being an ascorbic acid derivative or a salt thereof. These compounds are preferable in that they exhibit a particularly high moisturizing effect.

[0016] The third aspect of the present invention includes an ascorbic acid derivative or a salt thereof represented by the general formula (I) and an ascorbic acid derivative or a salt thereof represented by the following general formula (II), and the content of the ascorbic acid derivative or a salt thereof represented by the general formula (I) is 0.1 to 20% by mass of the total amount of the ascorbic acid derivative or a salt thereof represented by the general formula (I) and the ascorbic acid derivative or a salt thereof represented by the following general formula (II). It is an ascorbic acid derivative composition characterized by this. This ascorbic acid derivative composition is preferable in that it exhibits an excellent moisturizing effect compared to conventional ascorbic acid derivatives.

[0017]

[0018] In the formula, R ４ or R ５ One of them is R ６ -O-CH ２ -CH(OH)-CH ２ -, R ６ -O-CH ２ -CH(CH ２ OH)-, R ６ -CH(CH ２ OH)-, or R ６ -CH(OH)-CH ２ -, and the other is H, an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, a benzyl group, R ６ -O-CH ２ -CH(OH)-CH ２ -, R ６ -O-CH ２ -CH(CH ２ OH)-, R ６ -CH(CH ２ OH)-, or R ６ -CH(OH)-CH ２ -, and R６ This is H, an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, or a phenyl group.

[0019] The ascorbic acid derivatives or salts thereof of the present invention, or compositions containing them, can be incorporated into various cosmetics. The fourth aspect of the present invention is a cosmetic characterized by being formulated with the ascorbic acid derivatives or salts thereof of the first to third aspects of the present invention, or ascorbic acid derivative compositions containing them. The fourth aspect of the present invention is a cosmetic with excellent moisturizing properties.

[0020] The ascorbic acid derivative or salt thereof represented by the general formula (I) of the present invention possesses the excellent properties inherent in ascorbic acid, and also exhibits superior moisturizing effects compared to conventional ascorbic acid derivatives. Furthermore, a composition combining the ascorbic acid derivative or salt thereof represented by general formula (I) with a conventional ascorbic acid derivative or salt thereof represented by general formula (II) exhibits superior moisturizing effects compared to conventional ascorbic acid derivatives alone. Therefore, by incorporating the ascorbic acid derivative or salt thereof of the present invention, or an ascorbic acid derivative composition containing them, into a cosmetic, it is possible to provide a cosmetic with excellent moisturizing effects.

[0021] The following are embodiments for carrying out the present invention, but the scope of the present invention is not limited to the embodiments shown below.

[0022] Specific examples of ascorbic acid derivatives represented by general formula (I) include the compounds listed below, but the scope of the present invention is not limited to those listed below.

[0023] In the following examples, the glyceryl group refers to the CH group represented by the following general formulas (III) and (IV). ２ (OH)-CH(OH)-CH ２ -, or CH ２ (OH)-CH(CH ２ The diglyceryl group is represented by the following general formulas (V) and (VI) of CH ２ (OH)-CH(OH)-CH ２ -O-CH ２ -CH(OH)-CH２ -, or CH ２ (OH)-CH(OH)-CH ２ -O-CH ２ -CH(CH ２ The group is represented as OH)-, and alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, ethylhexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, eicosyl, behenyl, etc., and alkenyl groups include vinyl, allyl, butenyl, isobutenyl, clotyl, octenyl, decenyl, dodecenyl, etc.

[0024]

[0025]

[0026]

[0027]

[0028] In the above formulas (III), (IV), (V), and (VI), * indicates the ether bond site with the 2nd or 3rd position of ascorbic acid.

[0029] In the present invention, glyceryl ascorbic acid refers to ascorbic acid in which a glyceryl group is bonded to any of the hydroxyl groups. Diglyceryl ascorbic acid refers to ascorbic acid in which a diglyceryl group (glyceryl-O-glyceryl) is bonded to any of the hydroxyl groups. The ascorbic acid derivative represented by general formula (I) of the present invention is diglyceryl ascorbic acid in which a diglyceryl group is bonded to the 2nd and / or 3rd position, and specifically, the following can be cited: (1) 2-O-diglyceryl ascorbic acid, (2) 3-O-diglyceryl ascorbic acid, and (3) 2-O-diglyceryl-3-O-diglyceryl ascorbic acid.

[0030] (1) Examples of 2-O-diglyceryl ascorbic acid, that is, 2-O-(glyceryl-O-glyceryl) ascorbic acid, include 2-O-(glyceryl-O-glyceryl)-3-O-alkyl ascorbic acid, 2-O-(glyceryl-O-glyceryl)-3-O-alkenyl ascorbic acid, 2-O-(glyceryl-O-glyceryl)-3-O-glyceryl ascorbic acid, and 2-O-(glyceryl-O-glyceryl)-3-O-benzyl ascorbic acid. Examples of 2-O-(glyceryl-O-glyceryl)-3-O-alkylascorbic acid include 2-O-(glyceryl-O-glyceryl)-3-O-ethylascorbic acid, 2-O-(glyceryl-O-glyceryl)-3-O-butylascorbic acid, 2-O-(glyceryl-O-glyceryl)-3-O-hexylascorbic acid, 2-O-(glyceryl-O-glyceryl)-3-O-octylascorbic acid, 2-O-(glyceryl-O-glyceryl)-3-O-tetradecylascorbic acid, and 2-O-(glyceryl-O-glyceryl)-3-O-hexadecylascorbic acid. Examples of 2-O-(glyceryl-O-glyceryl)-3-O-alkenyl ascorbic acid include 2-O-(glyceryl-O-glyceryl)-3-O-allyl ascorbic acid, 2-O-(glyceryl-O-glyceryl)-3-O-octenyl ascorbic acid, and 2-O-(glyceryl-O-glyceryl)-3-O-dodecenyl ascorbic acid.

[0031] (2) Examples of 3-O-diglyceryl ascorbic acid, i.e., 3-O-(glyceryl-O-glyceryl) ascorbic acid, include 2-O-alkyl-3-O-(glyceryl-O-glyceryl) ascorbic acid, 2-O-alkenyl-3-O-(glyceryl-O-glyceryl) ascorbic acid, 2-O-glyceryl-3-O-(glyceryl-O-glyceryl) ascorbic acid, and 2-O-benzyl-3-O-(glyceryl-O-glyceryl) ascorbic acid. Examples of 2-O-alkyl-3-O-(glyceryl-O-glyceryl)ascorbic acid include 2-O-ethyl-3-O-(glyceryl-O-glyceryl)ascorbic acid, 2-O-hexyl-3-O-(glyceryl-O-glyceryl)ascorbic acid, 2-O-octyl-3-O-(glyceryl-O-glyceryl)ascorbic acid, 2-O-tetradecyl-3-O-(glyceryl-O-glyceryl)ascorbic acid, and 2-O-hexadecyl-3-O-(glyceryl-O-glyceryl)ascorbic acid. Examples of 2-O-alkenyl-3-O-(glyceryl-O-glyceryl)ascorbic acid include 2-O-allyl-3-O-(glyceryl-O-glyceryl)ascorbic acid, 2-O-octenyl-3-O-(glyceryl-O-glyceryl)ascorbic acid, and 2-O-dodecenyl-3-O-(glyceryl-O-glyceryl)ascorbic acid.

[0032] (3) 2-O-diglyceryl-3-O-diglyceryl ascorbic acid, that is, 2-O-(glyceryl-O-glyceryl)-3-O-(glyceryl-O-glyceryl) ascorbic acid, is also included in the ascorbic acid derivatives represented by the general formula (I) of the present invention.

[0033] The ascorbic acid derivative or salt thereof represented by the general formula (I) of the present invention can be produced by various methods. For example, 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane can be reacted with ascorbic acid, followed by an acid treatment to introduce a diglyceryl group to the oxygen bonded at the 2nd or 3rd position of ascorbic acid, thereby synthesizing 2-O-(glyceryl-O-glyceryl)ascorbic acid or 3-O-(glyceryl-O-glyceryl)ascorbic acid. Subsequently, the ascorbic acid derivative of the present invention can be obtained by alkylation or alkenylation of the other oxygen bonded at the 2nd or 3rd position using known means. Alternatively, the compound of the present invention may be obtained by first alkylating or alkenylating the oxygen bonded at the 2nd or 3rd position of ascorbic acid, and then reacting it with 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane. Furthermore, by reacting ascorbic acid with 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane and then subjecting it to an acid treatment, a diglyceryl group can be introduced to the oxygen bonded at the 2nd or 3rd position of ascorbic acid. Then, by similarly introducing a diglyceryl group to the other position in the same reaction, an ascorbic acid derivative of the present invention can be obtained in which diglyceryl groups are introduced at both the 2nd and 3rd positions.

[0034] Examples of compounds into which the diglyceryl group of the present invention is introduced include, but are not limited to, the above-mentioned 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane.

[0035] There are no particular restrictions on the amount of 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane used in the present invention, but when a diglyceryl group is introduced at either the 2nd or 3rd position, the amount is preferably 0.8 to 1.5 moles, and more preferably 1.0 to 1.2 moles. When a diglyceryl group is introduced at both the 2nd and 3rd positions, the amount is preferably 2.0 to 3.0 moles, and more preferably 2.2 to 2.5 moles.

[0036] The solvents used in the reaction include water, dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone, tetrahydrofuran, methanol, and ethanol. The reaction temperature is preferably 20°C to 90°C, and more preferably 30°C to 80°C.

[0037] When 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane reacts with the hydroxyl group at position 2 of the ascorbic acid skeleton, the pH of the reaction system is basic, preferably pH 8.0 to 12.0, more preferably pH 9.0 to 11.0. When 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane reacts with the hydroxyl group at position 3 of the ascorbic acid skeleton, the pH of the reaction system is weakly acidic, preferably pH 3.0 to 6.0, more preferably pH 3.5 to 5.5.

[0038] A diglyceryl group can be introduced by reacting ascorbic acid with 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane and then performing an acid treatment. The pH of the acid treatment is preferably 0.5 to 3.0, more preferably 1.0 to 2.0.

[0039] Examples of pH adjusting agents include lactic acid, citric acid, glycolic acid, succinic acid, tartaric acid, malic acid, gluconic acid, sulfuric acid, hydrochloric acid, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium bicarbonate, ammonium bicarbonate, triethylamine, and diazabicycloundecene.

[0040] Solvents used in the acid treatment include water, dimethylformamide, dimethyl sulfoxide, and N-methylpyrrolidone. The reaction temperature is preferably 0°C to 50°C, and more preferably 10°C to 40°C.

[0041] The compounds synthesized by the above method can be purified by means of column chromatography or crystallization using silica gel, or by column chromatography using resins such as ion exchange resins.

[0042] Ascorbic acid derivatives represented by the above general formula (I) or (II), R １ , R ２ , R ４ or R ５ Compounds in which H can form salts by substituting the dissociated hydrogen ion with a cation such as a metal ion or ammonium ion, and these salts are also included in the scope of the present invention. Examples of these salts include inorganic salts and organic salts. Examples of inorganic salts include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, and ammonium salts. Examples of organic salts include diethanolamine salts, triethanolamine salts, and basic amino acid salts. Salt formation is R １ , R ２ , R ４ or R ５ This can be done by a method similar to that used for the formation of known salts, such as neutralizing an aqueous solution of an ascorbic acid derivative in which is H with a basic substance.

[0043] As described above, the diglyceryl ascorbic acid synthesized can be subjected to alkylation, alkenylation, or benzylation using glycidol, alkyl glycidyl ethers of a specific structure, sulfate esters, alkyl halides, benzyl halides, alkenyl halides, etc., to obtain the ascorbic acid derivative of the present invention represented by general formula (I).

[0044] There are no particular restrictions on the amount of alkyl halides, alkenyl halides, benzyl halides, etc. used for alkylation, alkenylation, benzylation, etc., but it is preferably 0.8 to 3.0 moles, and more preferably 1.0 to 2.5 moles, per mole of diglyceryl ascorbic acid.

[0045] Reactions involving alkyl halides, alkenyl halides, and benzyl halides can be carried out using the same solvent, reaction temperature, and pH as those used for introducing diglyceryl groups. By purifying these reactions using methods such as silica gel column chromatography, ion exchange resin column chromatography, activated carbon treatment, extraction, distillation, and crystallization, the ascorbic acid derivatives represented by the general formula (I) of the present invention can be synthesized.

[0046] The present invention also provides an ascorbic acid derivative composition obtained by combining the conventional ascorbic acid derivative represented by the general formula (II) with the ascorbic acid derivative of the present invention represented by the general formula (I) or a salt thereof in a specific ratio. By combining the ascorbic acid derivative synthesized with the general formula (I) or a salt thereof with the conventional ascorbic acid derivative represented by the general formula (II) in a specific ratio, it is possible to achieve a higher moisturizing effect than that of the conventional ascorbic acid derivative alone.

[0047] The proportion of the ascorbic acid derivative represented by general formula (I) in the above ascorbic acid derivative composition is not particularly limited, but is preferably 0.1 to 20% by mass. Within this range, a particularly high moisturizing effect can be obtained when incorporated into a cosmetic composition, while it is difficult to obtain a high moisturizing effect below 0.1% by mass, and conversely, even if the proportion exceeds 20% by mass, a commensurate effect may not be obtained. The proportion of the ascorbic acid derivative represented by general formula (I) in the above composition is more preferably 5 to 20% by mass, and even more preferably 10 to 20% by mass.

[0048] The ascorbic acid derivative represented by the general formula (II) can be produced by the method described in Japanese Patent Publication No. 4681670, but is not limited to these production methods.

[0049] The ascorbic acid derivatives or salts thereof of the present invention, and compositions thereof, can be applied to various cosmetics such as topical skin preparations and hair cosmetics. These cosmetics may contain, as long as stability and other properties are not impaired, any ingredients commonly used in cosmetics, depending on their intended use.

[0050] Ingredients commonly used in cosmetics may be appropriately blended, such as oily components, surfactants and emulsifiers, high-molecular-weight compounds such as thickeners, whitening agents, texture enhancers, pharmaceuticals, UV absorbers, proteins, protein hydrolysates or their derivatives, amino acids or their derivatives, antioxidants, metal ion chelating agents, pH adjusters, preservatives, humectants, pigments, colorants, and fragrances.

[0051] Examples of oily components, polymer compounds such as surfactants, emulsifiers, and thickeners, whitening agents, texture improvers, pharmaceuticals, UV absorbers, proteins, protein hydrolysates or their derivatives, amino acids or their derivatives, antioxidants, metal ion chelating agents, pH adjusters, preservatives, humectants, pigments, colorants, fragrances, etc., are similar to those described in Publication WO 2022 / 080287.

[0052] The ingredients commonly used in the above-mentioned cosmetics can be used individually or in combination of two or more.

[0053] The formulation system of the cosmetic composition of the present invention is arbitrary and can be any of the following: solution system, solubilization system, emulsion system, gel system, powder dispersion system, water-oil bilayer system, etc. Depending on the target product, it can be manufactured by combining an ascorbic acid derivative represented by the general formula (I) or a salt thereof, or a composition further mixed with an ascorbic acid derivative represented by the general formula (II), with the above-mentioned arbitrary components.

[0054] Next, embodiments for carrying out the present invention will be specifically described by reference to examples, but the scope of the present invention is not limited by these examples. Prior to the examples, a synthesis example of the production of the ascorbic acid derivative represented by the general formula (I) of the present invention used in the examples is shown.

[0055] Synthesis Example 1: Synthesis of 2-O-(glyceryl-O-glyceryl)ascorbic acid In a round-bottom flask, 9.5 ml of deionized water, 8.5 g of ascorbic acid, and 2.2 g of sodium hydroxide were added and heated to 55°C. Then, 10.0 g of 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane (1.0 g: 1.1 eq relative to ascorbic acid) was added and the mixture was stirred for 4.5 hours. After neutralization with 1% hydrochloric acid, the mixture was concentrated under reduced pressure. The resulting residue (21.3 g) was subjected to silica gel chromatography and eluted with a chloroform / methanol mixture of 5 / 1 to 1 / 1. The mixture was then concentrated under reduced pressure to obtain 15.0 g of 2-O-(glyceryl-O-isopropylideneglyceryl)ascorbic acid. Then, 44.0 g of 1% hydrochloric acid was added and the mixture was stirred overnight at room temperature. Subsequently, the solution was concentrated under reduced pressure, and the resulting residue (18.3 g) was subjected to silica gel chromatography and eluted with a chloroform / methanol mixture of 2 / 1 to 1 / 1. The solution was then concentrated under reduced pressure to obtain the product (10.2 g).

[0056] The obtained product was subjected to mass spectrometry. 1 H-NMR, １３ 1C-NMR measurement confirmed that the substance is 2-O-(glyceryl-O-glyceryl)ascorbic acid, represented by the following structural formula.

[0057]

[0058] Furthermore, in the synthesis examples shown below, the obtained products were subjected to mass spectrometry. 1 H-NMR, and １３ 13C-NMR measurements were performed, and the results confirmed that each product is an ascorbic acid derivative represented by the structural formula or compound name shown in each synthesis example. Mass spectrometry was performed on the products obtained in the synthesis examples. 1 H-NMR and １３ The 1C-NMR measurement results are shown in Tables 1-3.

[0059] Synthesis Example 2: Synthesis of 3-O-(glyceryl-O-glyceryl)ascorbic acid In a round-bottom flask, 2.2 ml of deionized water, 7.0 g of ascorbic acid, and 0.32 g of sodium hydroxide were added and heated to 60°C. Then, 8.3 g of 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane (1.1 eq relative to ascorbic acid) was added and the mixture was stirred at 70°C for 5 hours. The mixture was then concentrated under reduced pressure. The resulting residue (12.9 g) was subjected to silica gel chromatography and eluted with a chloroform / methanol mixture of 5 / 1 to 1 / 1. The mixture was then concentrated under reduced pressure to obtain 3-O-(glyceryl-O-isopropylideneglyceryl)ascorbic acid (9.4 g). Then, 1% hydrochloric acid (12.0 g) was added and the mixture was stirred overnight at room temperature. Subsequently, the solution was concentrated under reduced pressure, and the resulting residue (10.2 g) was subjected to silica gel chromatography and eluted with a chloroform / methanol mixture of 5 / 1 to 2 / 1. Further concentration under reduced pressure was then performed to obtain 3-O-(glyceryl-O-glyceryl)ascorbic acid (5.5 g), represented by the following structural formula.

[0060]

[0061] Synthesis Example 3 Synthesis of 2-O-(glyceryl-O-glyceryl)-3-O-ethyl ascorbic acid In a round-bottom flask, 1.50 g of 2-O-(glyceryl-O-glyceryl) ascorbic acid obtained in Synthesis Example 1, 9.0 ml of DMF, 1.33 g of triethylamine, and 1.42 g of diethyl sulfate (2.0 eq relative to 2-O-(glyceryl-O-glyceryl) ascorbic acid) were added, and the mixture was stirred at 70°C for 5 hours. Then, the process of adding water and concentrating under reduced pressure was repeated three times, and the resulting residue (2.3 g) was subjected to silica gel chromatography and eluted with a chloroform / methanol mixture of 10 / 1 to 2 / 1. Then, the mixture was concentrated under reduced pressure to obtain 2-O-(glyceryl-O-glyceryl)-3-O-ethyl ascorbic acid (620.5 mg) shown in the structural formula below.

[0062]

[0063] Synthesis Example 4 Synthesis of 2-O-(glyceryl-O-glyceryl)-3-O-butylascorbic acid In a round-bottom flask, 1.50 g of 2-O-(glyceryl-O-glyceryl)ascorbic acid obtained in Synthesis Example 1, 7.5 ml of DMF, 0.33 g of potassium carbonate, and 0.70 g of butyl bromide (1.1 eq relative to 2-O-(glyceryl-O-glyceryl)ascorbic acid) were added, and the mixture was stirred at 80°C for 4 hours. After cooling and standing, only the supernatant was collected to remove precipitated salts or bases. The supernatant was concentrated by adding water under reduced pressure, and this process was repeated three times. The resulting residue (1.86 g) was subjected to silica gel chromatography and eluted with a chloroform / methanol mixture of 10 / 1 to 5 / 1. Subsequently, the solution was concentrated under reduced pressure to obtain 2-O-(glyceryl-O-glyceryl)-3-O-butylascorbic acid (630.2 mg), represented by the structural formula shown below.

[0064]

[0065] Synthesis Example 5 Synthesis of 2-O-(glyceryl-O-glyceryl)-3-O-hexyl ascorbic acid The same method as in Synthesis Example 4 was used, except that hexyl bromide (0.84 g) was used instead of butyl bromide, to obtain 2-O-(glyceryl-O-glyceryl)-3-O-hexyl ascorbic acid (601.2 mg) shown in the following structural formula.

[0066]

[0067] Synthesis Example 6 Synthesis of 2-O-(glyceryl-O-glyceryl)-3-O-octyl ascorbic acid The same method as in Synthesis Example 4 was used, except that octyl bromide (1.0 g) was used instead of butyl bromide, to obtain 2-O-(glyceryl-O-glyceryl)-3-O-octyl ascorbic acid (637.4 mg) shown in the following structural formula.

[0068]

[0069] Synthesis Example 7 Synthesis of 2-O-(glyceryl-O-glyceryl)-3-O-tetradecylascorbic acid 2-O-(glyceryl-O-glyceryl)-3-O-tetradecylascorbic acid (521.2 mg) was obtained by the same method as in Synthesis Example 4, except that tetradecyl bromide (1.41 g) was used instead of butyl bromide.

[0070]

[0071] Synthesis Example 8 Synthesis of 2-O-(glyceryl-O-glyceryl)-3-O-hexadecylascorbic acid 2-O-(glyceryl-O-glyceryl)-3-O-hexadecylascorbic acid (804.3 mg) was obtained in the same manner as in Synthesis Example 4, except that hexadecyl bromide (1.04 g) was used instead of butyl bromide.

[0072]

[0073] Synthesis Example 9 Synthesis of 2-O-(glyceryl-O-glyceryl)-3-O-glyceryl ascorbic acid 3-O-glyceryl ascorbic acid was synthesized according to the method and conditions described as Example 1 in Japanese Patent Publication No. 4681670. Subsequently, 1.8 g of 3-O-glyceryl ascorbic acid, 1.0 ml of deionized water, 0.06 g of sodium bicarbonate, and 1.5 g of 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane (1.5 g: 1.1 eq relative to 3-O-glyceryl ascorbic acid) were added to a round-bottom flask, and the mixture was stirred at 60°C for 5 hours. After that, the mixture was concentrated under reduced pressure. The obtained residue (2.20 g) was subjected to silica gel chromatography and eluted with a chloroform / methanol = 5 / 1 mixture. Concentration under reduced pressure yielded 2-O-(glyceryl-O-isopropylideneglyceryl)-3-O-glyceryl ascorbic acid (530.7 mg). Subsequently, 1% hydrochloric acid (2.0 g) was added and the mixture was stirred overnight at room temperature. After neutralization with a 1% sodium hydroxide aqueous solution, the mixture was concentrated under reduced pressure. The obtained residue (660.3 mg) was subjected to silica gel chromatography and eluted with a chloroform / methanol = 5 / 1 to 2 / 1 mixture. Concentration under reduced pressure yielded 2-O-(glyceryl-O-glyceryl)-3-O-glyceryl ascorbic acid (316.5 mg), represented by the structural formula shown below.

[0074]

[0075] Synthesis Example 10 Synthesis of 2-O-ethyl-3-O-(glyceryl-O-glyceryl)ascorbic acid 1.0 g of 3-O-(glyceryl-O-glyceryl)ascorbic acid obtained in Synthesis Example 2, 5.0 ml of DMF, 0.65 g of potassium carbonate, and 0.93 g of diethyl sulfate (2.0 eq relative to 3-O-(glyceryl-O-glyceryl)ascorbic acid) were added to a round-bottom flask, and the mixture was stirred at 70°C for 3 hours. After cooling and standing, only the supernatant was collected to remove precipitated salts or bases. The supernatant was concentrated by adding water under reduced pressure, and this process was repeated three times. The resulting residue (1.34 g) was subjected to silica gel chromatography and eluted with a chloroform / methanol mixture of 10 / 1 to 2 / 1. Subsequently, the solution was concentrated under reduced pressure to obtain 2-O-ethyl-3-O-(glyceryl-O-glyceryl)ascorbic acid (696.2 mg), represented by the structural formula shown below.

[0076]

[0077] Synthesis Example 11 Synthesis of 2-O-butyl-3-O-(glyceryl-O-glyceryl)ascorbic acid 1.0 g of 3-O-(glyceryl-O-glyceryl)ascorbic acid obtained in Synthesis Example 2, 5.0 ml of DMF, 0.17 g of sodium carbonate, and 0.45 g of butyl bromide (1.1 eq relative to 3-O-(glyceryl-O-glyceryl)ascorbic acid) were added to a round-bottom flask, and the mixture was stirred overnight at 50°C. After neutralization with 1% hydrochloric acid, the supernatant was concentrated by adding water under reduced pressure, and this process was repeated three times. The resulting residue (1.93 g) was subjected to silica gel chromatography and eluted with a chloroform / methanol mixture of 10 / 1 to 5 / 1. Subsequently, the solution was concentrated under reduced pressure to obtain 2-O-butyl-3-O-(glyceryl-O-glyceryl)ascorbic acid (462.6 mg), represented by the structural formula shown below.

[0078]

[0079] Synthesis Example 12 Synthesis of 2-O-hexyl-3-O-(glyceryl-O-glyceryl)ascorbic acid Except for using hexyl bromide (0.55 g) instead of butyl bromide, 2-O-hexyl-3-O-(glyceryl-O-glyceryl)ascorbic acid (423.1 mg) represented by the following structural formula was obtained by the same method as in Synthesis Example 11.

[0080]

[0081] Synthesis Example 13 Synthesis of 2-O-octyl-3-O-(glyceryl-O-glyceryl)ascorbic acid Except for using octyl bromide (0.64 g) instead of butyl bromide, 2-O-octyl-3-O-(glyceryl-O-glyceryl)ascorbic acid (437.6 mg) shown in the following structural formula was obtained by the same method as in Synthesis Example 11.

[0082]

[0083] Synthesis Example 14 Synthesis of 2-O-tetradecyl-3-O-(glyceryl-O-glyceryl)ascorbic acid Except for using tetradecyl bromide (0.92 g) instead of butyl bromide, 2-O-tetradecyl-3-O-(glyceryl-O-glyceryl)ascorbic acid (310.2 mg), shown in the following structural formula, was obtained by the same method as in Synthesis Example 11.

[0084]

[0085] Synthesis Example 15 Synthesis of 2-O-glyceryl-3-O-(glyceryl-O-glyceryl)ascorbic acid 2-O-glyceryl ascorbic acid was synthesized by the method described as Example 3 in Japanese Patent Publication No. 4681670. 2-O-glyceryl ascorbic acid (2.5 g), deionized water (0.8 ml), and sodium hydroxide (0.12 g) were added to a round-bottom flask and heated to 60°C. Then, 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane (2.1 g: 1.1 eq relative to 2-O-glyceryl ascorbic acid) was added and stirred at 72°C for 5 hours. After that, the mixture was concentrated under reduced pressure, and the resulting residue (4.28 g) was subjected to silica gel chromatography and eluted with a chloroform / methanol mixture of 5 / 1 to 1 / 1. Subsequently, the solution was concentrated under reduced pressure to obtain 2-O-glyceryl-3-O-(glyceryl-O-isopropylideneglyceryl)ascorbic acid (1.89 g). Then, 1% hydrochloric acid (5.78 g) was added and the mixture was stirred overnight at room temperature. After neutralization with 1% aqueous sodium hydroxide solution, the solution was concentrated under reduced pressure, and the resulting residue (2.01 g) was subjected to silica gel chromatography and eluted with a chloroform / methanol mixture of 5 / 1 to 2 / 1. Subsequently, the solution was concentrated under reduced pressure to obtain 2-O-glyceryl-3-O-(glyceryl-O-glyceryl)ascorbic acid (1.42 g) represented by the structural formula shown below.

[0086]

[0087] Mass spectrometry was performed on the products obtained in Synthesis Examples 1 to 15 using LC-MS-2020 (Shimadzu Corporation). The measurement results are shown in Table 1.

[0088]

[0089] Products obtained in Synthesis Examples 1-15 1 H-NMR was performed using a JNM-ECS400 (manufactured by JEOL Ltd.). The measurement results are shown in Table 2.

[0090]

[0091] Products obtained in Synthesis Examples 1-15 1３C-NMR was performed using a JNM-ECS400 (manufactured by JEOL Ltd.). The measurement results are shown in Table 3.

[0092]

[0093] Test Example 1 [Moisture Retention Test: Measurement of Moisture Retention Effect by Water Retention Capacity] Each sample listed in Table 4 below was vacuum dried, and approximately 400 mg of each was obtained (this weight is W ０ The sample was divided into weighing bottles (1.7 cm in diameter, 4.0 cm in height excluding the lid). Each sample in the weighing bottle was left to stand in a constant humidity and temperature chamber (LTI-1200, manufactured by Tokyo Rikakikai Co., Ltd.) at a temperature of 25°C and a humidity of 75%. The weight was measured periodically and left to stand until sufficient moisture had been absorbed and the weight no longer changed. After that, it was transferred to an environment of 25°C and 35% humidity (in a sealed container filled with saturated potassium acetate aqueous solution at the bottom), and the weight after 7 days (this weight was used as W) was measured. １ (Assuming this is the case), the amount of water retained per gram of dry sample is W, according to the following formula. ｈ The (mg / g) was calculated. W ｈ = (W １ -W ０ ) / W ０ The water retention amount W calculated in this way ｈ The moisturizing effect was determined based on the following criteria, and the results are shown in Table 4. (Criteria) ◎: 60 mg / g or more ○: 45 mg / g or more and less than 60 mg / g △: 20 mg / g or more and less than 45 mg / g ×: less than 10 mg / g

[0094]

[0095] The results in Table 4 show that the ascorbic acid derivative or salt of the present invention retains a larger amount of water per gram of sample compared to conventional ascorbic acid derivatives having a glyceryl group. In particular, Examples 1 and 2 retained about twice as much water, demonstrating excellent water retention capabilities.

[0096] Test Example 2 [Moisture Retention Test: Measurement of Moisture Retention Effect in an Obstructed Environment] A weighing bottle (7 mm in diameter, 3.2 cm in height excluding the lid) containing 200 mg of deionized water was covered with cellulose filter paper (8 mm in diameter, 0.19 mm thick). The following samples were prepared as 1.5 mmol / g aqueous solutions, and 5 μl of each solution was spread thinly and evenly onto the cellulose filter paper. The weighing bottle was stored in a 60°C constant temperature bath for 5 hours. The weight (mg) was measured, and the amount of water lost (this weight was measured in W) was measured. d (Assuming this is the case) the remaining water content (X%) in the weighing bottle was calculated using the following formula: X = 100 - (W ｄ ( / 200 × 100) In addition, as a control experiment, 5 μl of deionized water was applied and the retention rate was determined to be 70.5%. The difference from the retention rate of the sample (this difference is denoted as d (%)) was calculated using the following formula: d = X - 70.5 From the results calculated in this way, the moisturizing effect was determined based on the following criteria, and the results are shown in Table 5.

[0097] (Criteria for evaluation) ◎: 15.0% or more ○: 10.0% or more and less than 15.0% △: 5.0% or more and less than 10.0% ×: Less than 5.0%

[0098]

[0099] The results in Table 5 clearly show that the ascorbic acid derivative or salt of the present invention has a superior moisturizing effect compared to conventional ascorbic acid derivatives or salts having a glyceryl group.

[0100] Test Example 3 [Moisture Retention Test 2: Measurement of Moisture Retention Effect by Water Retention Capacity 2] For compositions in the proportions shown in Examples 12 to 19 and Comparative Examples 12 and 13 listed in Tables 6 and 7 below, the amount of water retention W per 1 g of dry sample was measured using the method described in Test Example 1. ｈ The (mg / g) was calculated, and the moisturizing effect was determined based on the following criteria. The results are shown in Tables 6 and 7.

[0101] (Criteria for evaluation) ◎: 75 mg or more ○: 55 mg or more but less than 75 mg △: 35 mg or more but less than 55 mg ×: less than 35 mg

[0102]

[0103]

[0104] The results in Tables 6 and 7 clearly show that adding a small amount of ascorbic acid derivative containing diglyceryl groups to a conventional ascorbic acid derivative containing glyceryl groups significantly increases the moisturizing effect of the ascorbic acid derivative containing glyceryl groups.

[0105] Example 20: A lotion is prepared by mixing the ingredients (1) to (6) shown in Table 8 while stirring well. In Tables 8 and beyond, the amounts are expressed in parts by mass.

[0106]

[0107] Example 21 Emulsion The raw materials for the oil phase (1) to (9) and the raw materials for the aqueous phase (10) to (13) of the composition shown in Table 9 are heated to 70°C and dissolved to prepare the oil phase and aqueous phase, respectively. Then, the oil phase is added to the aqueous phase and pre-emulsified, and after uniform emulsification with a homomixer, the emulsion is prepared by cooling to room temperature while stirring well.

[0108]

[0109] Example 22 Cream The raw materials for the oil phase (1) to (5) and the raw materials for the aqueous phase (6) to (10) of the composition shown in Table 10 are heated to 70°C and dissolved to prepare the oil phase and aqueous phase, respectively. Then, the oil phase is added to the aqueous phase and pre-emulsified, and after uniform emulsification with a homomixer, the cream is prepared by cooling to room temperature while stirring well.

[0110]

Claims

1. An ascorbic acid derivative or a salt thereof, characterized by being represented by the following general formula (I). [In formula (I), R ２ , ２ , ２ , ２ , ２ , ２ , ２ and R ２ are H, an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, a benzyl group, R ３ -CH(CH ２ OH)-, R ３ -CH(OH)-CH ２ -, R ３ -O-CH ２ -CH(OH)-CH ２ -, or R ３ -O-CH ２ -CH(CH ２ OH)-, where R ３ is H, an alkyl group having 1 to 22 carbon atoms, or CH ２ OH-CH(OH)-CH ２ -. However, at least one of R １ and R ２ is CH ２ OH-CH(OH)-CH ２ -O-CH ２ -CH(OH)-CH ２ - or CH ２ OH-CH(OH)-CH ２ -O-CH ２ -CH(CH ２ OH)-.] 2. In the above general formula (I), R １ and R ２ One of them is CH ２ OH-CH(OH)-CH ２ -O-CH ２ -CH(OH)-CH ２ -, or CH ２ OH-CH(OH)-CH ２ -O-CH ２ -CH(CH ２ One is OH)-, and the other is H, an alkyl group having 4 to 18 carbon atoms, CH ２ (OH)-CH(OH)-CH ２ - CH ２ OH-CH(CH ２ OH)-, CH ２ OH-CH(OH)-CH ２ -O-CH ２ -CH(OH)-CH ２ -, or CH ２ OH-CH(OH)-CH ２ -O-CH ２ -CH(CH ２ The ascorbic acid derivative or salt thereof according to claim 1, characterized in that it is OH)-.

3. An ascorbic acid derivative composition comprising an ascorbic acid derivative or salt thereof represented by the general formula (I) and an ascorbic acid derivative or salt thereof represented by the following general formula (II), wherein the content of the ascorbic acid derivative or salt thereof represented by the general formula (I) is 0.1 to 20% by mass of the total amount of the ascorbic acid derivative or salt thereof represented by the general formula (I) and the ascorbic acid derivative or salt thereof represented by the following general formula (II). [In formula (II), R ４ or ５ One of them is R ６ -O-CH ２ -CH(OH)-CH ２ -, R ６ -O-CH ２ -CH(CH ２ OH)-, R ６ -CH(CH ２ OH)-, R ６ -CH(OH)-CH ２ - and the other is H, an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, a benzyl group, R ６ -O-CH ２ -CH(OH)-CH ２ -, R ６ -O-CH ２ -CH(CH ２ OH)-, R ６ -CH(CH ２ OH)-, R ６ -CH(OH)-CH ２ - and R ６ This is H, an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, or a phenyl group.

4. A cosmetic composition characterized by comprising an ascorbic acid derivative or salt thereof as described in claim 1 or 2, or an ascorbic acid derivative composition as described in claim 3.

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