Ascorbic acid derivative or salt thereof, and cosmetic thereof

Abstract

To provide a novel ascorbic acid derivative or a salt thereof, and a cosmetic composition containing the same, exhibiting the superior functions originally possessed by ascorbic acid including antioxidant action, collagen production enhancement, and skin moisturization, while maintaining stability over prolonged storage with minimal discoloration, odor change, or loss of activity.SOLUTION: There are provided an ascorbic acid derivative or a salt thereof, in which at least one hydrogen atom of a hydroxyl group in glucopyranosyl ascorbic acid or a phosphate-type ascorbic acid derivative is substituted with HO-C(CH3)2-CH2- or HO-CH2-C(CH3)2-, and a cosmetic composition containing the ascorbic acid derivative.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an ascorbic acid derivative or a salt thereof that is suitable for use as a raw material for cosmetics, and further to a cosmetic containing the ascorbic acid derivative or a salt thereof. [Background technology]

[0002] Ascorbic acid is a safe and useful antioxidant and is known as a compound with excellent whitening properties, but its instability to light, heat, and oxidation has prevented its use in the cosmetics field. Therefore, various ascorbic acid derivatives or salts thereof have been proposed as derivatives with improved stability over time compared to ascorbic acid, and their incorporation into topical skin whitening preparations (Patent Document 1, Patent Document 2) and into cosmetics (Patent Document 3) have been proposed.

[0003] However, many of the above-mentioned ascorbic acid derivatives and their salts have problems such as discoloration and odor generation over time, and their stability over time is still insufficient. In addition, their activity in the body only lasts for a short period of time, and improvements in these areas are desired.

[0004] The present inventors have proposed an ascorbic acid derivative that solves these problems (Patent Document 4), but further improvements are desired. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Publication No. 62-221611 [Patent Document 2] Japanese Patent Application Laid-Open No. 2005-060239 [Patent Document 3] Japanese Patent Application Publication No. 1-228978 [Patent Document 4] Patent No. 4681670 Summary of the Invention [Problem to be solved by the invention]

[0006] The present invention addresses the problem of providing an ascorbic acid derivative or a salt thereof that has the excellent effects inherent to ascorbic acid, such as whitening and moisturizing effects, and that is highly stable with little discoloration, odor change, or activity decrease over time, and further has excellent physiologically active effects, as well as providing a cosmetic preparation containing the same. [Means for solving the problem]

[0007] The present inventors have conducted extensive research in light of the above-mentioned circumstances and have found that novel ascorbic acid derivatives or salts thereof represented by the following formula (I) or (II) are excellent in antioxidant, whitening, moisturizing, etc., and are stable and suffer little discoloration, odor, or activity loss over time. The present invention was completed based on these findings.

[0008] The present invention provides an ascorbic acid derivative or a salt thereof characterized by being represented by the following general formula (I) or (II) (claim 1).

[0009] [ka]

[0010] [In the formula, R 1 is H, HO-C(CH3)2-CH2- or HO-CH2-C(CH3)2-, R 2 and R 3 is H, an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, a benzyl group, R 4 -O-CH2-CH(OH)-CH2-, R 4 -O-CH2-CH(CH2OH)-, HO-C(CH3)2-CH2-, HO-CH2-C(CH3)2-, R 4 -CH(CHOH)-, R 4 -CH(OH)-CH2-, R 4is H, an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, or a phenyl group.

[0011] [ka]

[0012] [In the formula, R 5 is H, HO-C(CH3)2-CH2- or HO-CH2-C(CH3)2-, R 6 , R 7 and R 8 is H, an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, a benzyl group, R 9 -O-CH2-CH(OH)-CH2-, R 9 -O-CH2-CH(CH2OH)-, HO-C(CH3)2-CH2-, HO-CH2-C(CH3)2-, R 7 -CH(CHOH)-, R 7 -CH(OH)-CH2-, R 9 is H, an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, or a phenyl group.

[0013] The salt of the ascorbic acid derivative means a compound in which the H of the hydroxyl group in the formula (I) or (II) is substituted with a cation such as a metal ion or an ammonium ion, and this salt is also included in the present invention.

[0014] The ascorbic acid derivatives or salts thereof represented by general formula (I) or (II) have superior stability over time compared to conventional ascorbic acid derivatives, maintain a high residual rate even when stored for several weeks in a high-temperature environment above room temperature, and are also suppressed from generating odors or causing coloration.

[0015] The ascorbic acid derivative represented by general formula (I) or its salt can be produced by reacting isobutylene oxide or halogenated tert-butyl alcohol with the hydroxyl groups at the 3- and / or 6-positions of the ascorbic acid skeleton of glucopyranosyl ascorbic acid, or the hydroxyl group at the 6'-position of the glucose skeleton. When glucopyranosyl ascorbic acid is reacted with isobutylene oxide or the like, the epoxy ring is opened to generate a primary or secondary hydroxyl group. Therefore, the reaction product is R 1 , R 2 , R 3 However, a mixture of HO-C(CH3)2-CH2- and HO-CH2-C(CH3)2- may occur.

[0016] The ascorbic acid derivative represented by general formula (II) or its salt can be produced by reacting isobutylene oxide or halogenated tert-butyl alcohol with the hydroxyl groups at the 3- and / or 6-positions of the ascorbic acid skeleton of the phosphate-type ascorbic acid derivative, or with the hydroxyl group at the phosphate moiety. When the phosphate-type ascorbic acid derivative is reacted with isobutylene oxide or the like, the epoxy ring opens to generate a primary hydroxyl group or a secondary hydroxyl group. Therefore, the reaction product is R 5 , R 6 , R 7 , R 8 However, a mixture of HO-C(CH3)2-CH2- and HO-CH2-C(CH3)2- may occur.

[0017] Among the ascorbic acid derivatives represented by general formula (I), R 1 is HO-C(CH3)2-CH2- or HO-CH2-C(CH3)2-, and R 2 and R 3 Those in which is H have superior antioxidant effects compared to conventional ascorbic acid derivatives such as glyceryl ascorbate.

[0018] In addition, among the ascorbic acid derivatives represented by the general formula (II), R 6is HO-C(CH3)2-CH2- or HO-CH2-C(CH3)2-, and R 5 , R 7 , R 8 is H, or R 5 , R 6 is HO-C(CH3)2-CH2- or HO-CH2-C(CH3)2-, and R 7 , R 8 Those in which is H have superior antioxidant effects compared to conventional ascorbic acid derivatives such as glyceryl ascorbate.

[0019] Among the ascorbic acid derivatives represented by general formula (I), R 1 is HO-C(CH3)2-CH2- or HO-CH2-C(CH3)2-, and R 2 or R 3 is an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, a benzyl group, R 4 -O-CH2-CH(OH)-CH2-, R 4 -O-CH2-CH(CH2OH)-, R 4 -CH(CHOH)-, R 4 -CH(OH)-CH2- and ascorbic acid derivatives represented by general formula (II), 5 , R 6 , R 7 is HO-C(CH3)2-CH2- or HO-CH2-C(CH3)2-, and R 8 is an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, a benzyl group, R 9 -O-CH2-CH(OH)-CH2-, R 9 -O-CH2-CH(CH2OH)-, R 9 -CH(CHOH)-, R 9 -CH(OH)-CH2- is obtained by reacting glucopyranosyl ascorbic acid or a phosphoric acid type ascorbic acid derivative with isobutylene oxide or halogenated tert-butyl alcohol. 1 , R 5 , R 6 and R 7is HO-C(CH3)2-CH2- or HO-CH2-C(CH3)2-, can be obtained by reacting a compound having the formula: HO-C(CH3)2-CH2- or HO-CH2-C(CH3)2- with glycidol, an alkyl glycidyl ether of a specific structure, an alkenyl glycidyl ether, a phenyl glycidyl ether, a sulfate ester, an alkyl halide, a benzyl halide, an alkenyl halide, an alkylene oxide of a specific structure, an alkenyl oxide, or styrene oxide.

[0020] In addition, glucopyranosyl ascorbic acid and phosphoric acid derivatives of ascorbic acid are used in combination with glycidol, alkyl glycidyl ethers with specific structures, alkenyl glycidyl ethers, phenyl glycidyl ethers, sulfates, alkyl halides, benzyl halides, alkenyl halides, alkylene oxides with specific structures, alkenyl oxides, and styrene oxides. 2 , R 3 or R 8 The compound can also be obtained by reacting the compound obtained by reacting the above with isobutylene oxide or a halogenated tert-butyl alcohol.

[0021] The ascorbic acid derivative or salt thereof of the present invention can be blended into cosmetics (claim 2), and the effects of the present invention are particularly exhibited when blended in an amount of 1 to 20% by weight in cosmetics (claim 3). [Effects of the Invention]

[0022] The ascorbic acid derivative or salt thereof represented by general formula (I) or (II) of the present invention is stable even when stored for a long period of time, exhibits little discoloration, odor, or loss of activity over time, and has high physiological activity, such as antioxidant effect, melanin production inhibitory effect, and collagen production promotion effect. Therefore, by incorporating this compound into cosmetics such as topical skin preparations and hair cosmetics, it is possible to obtain cosmetics that have excellent whitening and moisturizing effects, are stable even when stored for a long period of time, and have high physiological activity. The cosmetics of the present invention are cosmetics (such as whitening cosmetics and moisturizing cosmetics) that are stable even when stored for a long period of time and have high physiological activity. DETAILED DESCRIPTION OF THE INVENTION

[0023] Hereinafter, HO-C(CH)-CH- or HO-CH-C(CH)- will be referred to as a "hydroxyisobutyl group." Hydroxyisobutyl ascorbic acid refers to an ascorbic acid skeleton in which a hydroxyisobutyl group is bonded to one or more oxygen atoms of each hydroxyl group.

[0024] Specific examples of the ascorbic acid derivatives represented by general formula (I) or (II) include the compounds shown below, but the scope of the present invention is not limited to these.

[0025] In the following examples, Glyceryl refers to HOCH2-CH(OH)-CH2- or HOCH2-CH(CH2OH)-; The alkylglyceryl group refers to RO-CH-CH(OH)-CH- or RO-CH-CH(CHOH)- (R represents an alkyl group). The alkyl group refers to a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a pentyl group, a hexyl group, an ethylhexyl group, a heptyl group, an octyl group, a nonyl group, a decyl group, an undecyl group, a dodecyl group, a tridecyl group, a tetradecyl group, a pentadecyl group, a hexadecyl group, a heptadecyl group, an octadecyl group, a nonadecyl group, an eicosyl group, a behenyl group, or the like. The alkenyl group refers to a vinyl group, an allyl group, a butenyl group, an isobutenyl group, a crotyl group, an octenyl group, a decenyl group, a dodecenyl group, and the like.

[0026] (1) 2-glucopyranosyl-3-O-(2-hydroxyisobutyl) ascorbic acid, 2-Glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-alkyl ascorbic acids, such as 2-glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-ethyl ascorbic acid, 2-glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-butyl ascorbic acid, 2-glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-hexyl ascorbic acid, 2-glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-octyl ascorbic acid, 2- Glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-decyl ascorbic acid, 2-glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-ethylhexyl ascorbic acid, 2-glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-dodecyl ascorbic acid, 2-glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-tetradecyl ascorbic acid, 2-glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-hexadecylascorbic acid; 2-Glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-alkenyl ascorbic acid, for example, 2-glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-allylacorbic acid, 2-glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-octenyl ascorbic acid, 2-glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-dodecenyl ascorbic acid; 2-Glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-glyceryl ascorbate; 2-Glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-alkylglyceryl ascorbic acid, for example, 2-glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-butylglyceryl ascorbic acid, 2-glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-ethylhexylglyceryl ascorbic acid, 2-glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-dodecylglyceryl ascorbic acid; 2-Glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-alkenylglyceryl ascorbate, for example, 2-glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-dodecenylglyceryl ascorbate; 2-Glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-phenylglyceryl ascorbate; 2-Glucopyranosyl-3-O-(2-hydroxyisobutyl)-6-O-benzyl ascorbic acid.

[0027] (2) 2-phospho-3-O-(2-hydroxyisobutyl)ascorbic acid, 2-(phospho-2-hydroxyisobutyl)ascorbic acid, 2-(phospho-di-2-hydroxyisobutyl)ascorbic acid, 2-(phospho-2-hydroxyisobutyl)-3-O-(2-hydroxyisobutyl)ascorbic acid; 2-(phospho-2-hydroxyisobutyl)-6-O-alkyl ascorbic acids, such as 2-(phospho-2-hydroxyisobutyl)-6-O-ethyl ascorbic acid, 2-(phospho-2-hydroxyisobutyl)-6-O-butyl ascorbic acid, 2-(phospho-2-hydroxyisobutyl)-6-O-hexyl ascorbic acid, 2-(phospho-2-hydroxyisobutyl)-6-O-octyl ascorbic acid, 2-(phospho-2-hydroxyisobutyl)-6-O-decyl ascorbic acid, 2-(phospho-2-hydroxyisobutyl)-6-O-ethylhexyl ascorbic acid, 2-(phospho-2-hydroxyisobutyl)-6-O-dodecyl ascorbic acid, 2-(phospho-2-hydroxyisobutyl)-6-O-tetradecyl ascorbic acid, 2-(phospho-2-hydroxyisobutyl)-6-O-hexadecylascorbic acid; 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-alkyl ascorbic acids, such as 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-ethyl ascorbic acid, 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-butyl ascorbic acid, 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-hexyl ascorbic acid, 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-octyl ascorbic acid, 2- Phospho-3-O-(2-hydroxyisobutyl)-6-O-decyl ascorbic acid, 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-ethylhexyl ascorbic acid, 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-dodecyl ascorbic acid, 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-tetradecyl ascorbic acid, 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-hexadecyl ascorbic acid; 2-(phospho-2-hydroxyisobutyl)-6-O-alkenyl ascorbic acids, such as 2-(phospho-2-hydroxyisobutyl)-6-O-allylacorbic acid, 2-(phospho-2-hydroxyisobutyl)-6-O-octenyl ascorbic acid, 2-(phospho-2-hydroxyisobutyl)-6-O-dodecenyl ascorbic acid; 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-alkenyl ascorbic acids, such as 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-allylacorbic acid, 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-octenyl ascorbic acid, 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-dodecenyl ascorbic acid; 2-Phospho-3-O-(2-hydroxyisobutyl)-6-O-glyceryl ascorbate; 2-(Phospho-2-hydroxyisobutyl)-6-O-glyceryl ascorbate; 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-alkylglyceryl ascorbic acids, such as 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-butylglyceryl ascorbic acid, 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-ethylhexylglyceryl ascorbic acid, 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-dodecylglyceryl ascorbic acid; 2-(phospho-2-hydroxyisobutyl)-6-O-alkylglyceryl ascorbic acids, such as 2-(phospho-2-hydroxyisobutyl)-6-O-butylglyceryl ascorbic acid, 2-(phospho-2-hydroxyisobutyl)-6-O-ethylhexylglyceryl ascorbic acid, 2-(phospho-2-hydroxyisobutyl)-6-O-dodecylglyceryl ascorbic acid; 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-alkenylglyceryl ascorbate, for example, 2-phospho-3-O-(2-hydroxyisobutyl)-6-O-dodecenylglyceryl ascorbate; 2-Phospho-3-O-(2-hydroxyisobutyl)-6-O-phenylascorbic acid; 2-Phospho-3-O-(2-hydroxyisobutyl)-6-O-benzyl ascorbic acid;

[0028] The ascorbic acid derivatives or salts thereof of the present invention can be produced by various methods. For example, glucopyranosyl ascorbic acid or a phosphate-type ascorbic acid derivative is reacted with isobutylene oxide or a halogenated tert-butyl alcohol to introduce a hydroxyisobutyl group into the hydroxyl group of the ascorbic acid skeleton or the phosphate moiety, thereby synthesizing glucopyranosylhydroxyisobutylascorbic acid or phosphohydroxyisobutylascorbic acid. The ascorbic acid derivatives of the present invention can then be obtained by alkylation, alkenylation, or the like using known methods. Alternatively, the ascorbic acid derivatives or salts thereof of the present invention can be obtained by alkylating or alkenylating glucopyranosyl ascorbic acid or a phosphate-type ascorbic acid derivative, followed by reaction with isobutylene oxide or a halogenated tert-butyl alcohol.

[0029] Examples of the compound for introducing a hydroxyisobutyl group of the present invention include, but are not limited to, isobutylene oxide and halogenated tert-butyl alcohol. Examples of halogenated tert-butyl alcohol include fluorinated tert-butyl alcohol, chlorinated tert-butyl alcohol, and bromized tert-butyl alcohol.

[0030] The amount of isobutylene oxide or halogenated tert-butyl alcohol used in the present invention is not particularly limited, but when one hydroxyisobutyl group is bonded, it is preferably 0.8 to 1.5 mol, more preferably 1.0 to 1.2 mol, per mol of ascorbic acid. When two or more hydroxyisobutyl groups are bonded, it is preferably 5 mol to 15 mol, more preferably 8 to 12 mol, per mol of ascorbic acid.

[0031] The reaction of the present invention can be carried out in various solvents, including, but not limited to, water, lower alcohols such as methanol, ethanol, and isopropanol, dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), tetrahydrofuran (THF), N-methylpyrrolidone, and mixtures thereof.

[0032] The reaction temperature is not particularly limited, but is preferably in the range of 30 to 100°C, more preferably in the range of 50 to 90°C, and particularly preferably in the range of 60 to 90°C.

[0033] The pH of the reaction solvent is not particularly limited, but when producing an ascorbic acid derivative or a salt thereof of the present invention in which a hydroxyisobutyl group has been introduced at the 3-position hydroxyl group of glucopyranosyl ascorbic acid, the reaction is preferably carried out under acidic conditions, with a pH of 2 to 4 being particularly preferred. When producing an ascorbic acid derivative or a salt thereof of the present invention in which a hydroxyisobutyl group has been introduced at the phosphate moiety or the 3-position hydroxyl group of a phosphate-type ascorbic acid derivative, the reaction is preferably carried out under alkaline conditions, with a pH of 8 to 11 being particularly preferred.

[0034] Examples of pH adjusters used during the reaction include hydrochloric acid, lactic acid, citric acid, glycolic acid, succinic acid, tartaric acid, malic acid, gluconic acid, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium hydrogencarbonate, ammonium hydrogencarbonate, and triethylamine.

[0035] The ascorbic acid derivative or a salt thereof of the present invention produced as described above can be purified by means of column chromatography using silica gel, column chromatography using a resin such as an ion exchange resin, activated carbon treatment, extraction, distillation, crystallization, or the like.

[0036] The ascorbic acid derivatives represented by the general formula (I) or (II) can form salts in which the hydrogen ion resulting from dissociation of H is replaced with a cation such as a metal ion or an ammonium ion, and such salts are also included within the scope of the present invention. Examples of such salts include inorganic 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 can be carried out by methods similar to known salt formation methods, such as neutralizing an aqueous solution of the ascorbic acid derivative of the present invention with a basic substance.

[0037] The scope of the present invention also includes ascorbic acid derivatives obtained by alkylating, alkenylating, benzylating, or the like the ascorbic acid derivative having a hydroxyisobutyl group introduced therein, synthesized as described above, with glycidol, alkyl glycidyl ethers of a specific structure, alkenyl glycidyl ethers, phenyl glycidyl ethers, sulfates, alkyl halides, benzyl halides, alkenyl halides, alkylene oxides of a specific structure, alkenyl oxides, styrene oxide, or the like.

[0038] The amount of glycidol, alkyl glycidyl ether, alkylene oxide, alkenyl oxide, styrene oxide, etc. used in alkylation, alkenylation, benzylation, phenylation, etc. is not particularly limited, but when derivatizing one hydroxy group on the ascorbic acid derivative, the amount is preferably 0.8 to 1.5 mol, more preferably 1.0 to 1.2 mol, per mol of hydroxyisobutylascorbic acid. When derivatizing two or more hydroxy groups on the ascorbic acid derivative, the amount is preferably 5 to 15 mol, more preferably 8 to 12 mol, per mol of hydroxyisobutylascorbic acid.

[0039] The reaction with glycidol or alkyl glycidyl ether can be carried out in the same solvent, reaction temperature, and pH range as in the reaction for introducing a hydroxyisobutyl group, and the ascorbic acid derivative of the present invention can be synthesized by purifying the product by means of column chromatography using silica gel, column chromatography using a resin such as an ion exchange resin, activated carbon treatment, extraction, distillation, crystallization, etc. Note that even when first reacting with glycidol or alkyl glycidyl ether, etc., and then introducing a hydroxyisobutyl group into another oxygen, each reaction can be carried out under the same conditions as above.

[0040] The ascorbic acid derivative or salt thereof of the present invention can be suitably used as a component of various cosmetics such as external preparations for skin and hair cosmetics, and can also be used as a food additive, animal feed, etc.

[0041] When the ascorbic acid derivative or salt thereof of the present invention is blended into various cosmetics, the blending amount is preferably 1% to 20% by weight, and particularly preferably 3% to 10% by weight. If the blending amount is less than 1% by weight, the effects of the ascorbic acid derivative or salt thereof of the present invention, such as antioxidant effect, are often not fully exhibited. On the other hand, if the blending amount exceeds 20% by weight, the effects commensurate with the blending amount are often not expected, and there is also a risk of damaging the formulation system.

[0042] In addition to these essential ingredients, the cosmetic of the present invention may contain, as appropriate, commonly used ingredients such as oily raw materials, surfactants, moisturizers, polymeric compounds, antioxidants, whitening agents, pharmaceuticals, ultraviolet absorbers, sequestering agents, proteins, protein hydrolysates or derivatives thereof, amino acids or derivatives thereof, pH adjusters, preservatives, etc. The ascorbic acid derivative or salt thereof of the present invention also exhibits an effect as a moisturizer, and other moisturizers may also be incorporated into the cosmetic of the present invention as appropriate.

[0043] Examples of oily raw materials, surfactants, other moisturizers, polymeric compounds, antioxidants, other whitening agents, drugs, ultraviolet absorbers, sequestering agents, proteins, protein hydrolysates or derivatives thereof, amino acids or derivatives thereof, pH adjusters, preservatives, and the like can include those similar to those described in WO2022 / 080287.

[0044] The cosmetic composition of the present invention may be formulated in any system, including a solution system, a solubilized system, an emulsion system, a gel system, a powder dispersion system, and a water-oil two-layer system, and can be produced by blending the ascorbic acid derivative represented by the above general formula (I) or (II) or a salt thereof with the above-mentioned optional ingredients according to the desired product. [Example]

[0045] Next, specific embodiments for carrying out the present invention will be described in detail with reference to Examples, but the scope of the present invention is not limited to these Examples. Prior to the Examples, production examples of the ascorbic acid derivatives of the present invention used in the Examples and Comparative Examples will be shown as Synthesis Examples.

[0046] Synthesis Example 1: Synthesis of 2-O-glucopyranosyl-3-O-(2-hydroxyisobutyl)ascorbic acid DMF (28 mL), 2-O-glucopyranosyl ascorbic acid (6.77 g), triethylamine (0.40 g), and isobutylene oxide (1.73 g: 1.2 eq) were added to a recovery flask and stirred at 85°C for 4 hours. After the reaction was completed, ion-exchanged water was added and the mixture was concentrated under reduced pressure. The resulting residue (3.74 g) was subjected to silica gel chromatography, eluting with a mixture of chloroform / methanol / ion-exchanged water (10 / 1 / 0 to 7 / 3 / 0.5) and concentrating under reduced pressure to obtain 2-O-glucopyranosyl-3-O-(2-hydroxyisobutyl)ascorbic acid (0.11 g).

[0047] The resulting product was analyzed by mass spectrometry. 1 H-NMR, 13C-NMR measurement was carried out, and the results confirmed that the product was 2-O-glucopyranosyl-3-O-(2-hydroxyisobutyl)ascorbic acid represented by the following structural formula.

[0048] [ka]

[0049] In the synthesis examples shown below, the products obtained were analyzed by mass spectrometry, 1 H-NMR, and 13 C-NMR measurements were carried out, and the results confirmed that each product was an ascorbic acid derivative represented by the structural formula or compound name shown in each synthesis example. 1 H-NMR and 13 The results of C-NMR measurements are shown in Tables 1 to 3.

[0050] Synthesis Example 2: Synthesis of 2-(phospho-2-hydroxyisobutyl)ascorbic acid DMF (3 mL), water (15 mL), trisodium 2-phosphoascorbate (3.22 g), 17% HCl aqueous solution (6.43 g), sodium bicarbonate (2.52 g), and isobutylene oxide (0.87 g: 1.2 eq) were added to a recovery flask and stirred at 55°C for 15 hours. After the reaction was completed, the mixture was concentrated under reduced pressure, and methanol was added. The mixture was then filtered and concentrated under reduced pressure. The resulting residue (1.01 g) was subjected to silica gel chromatography, eluted with a mixture of chloroform and methanol (8 / 2 to 0 / 10), and concentrated under reduced pressure to obtain 2-(phospho-2-hydroxyisobutyl)ascorbic acid (0.12 g) represented by the following structural formula:

[0051] [ka]

[0052] Synthesis Example 3: Synthesis of 2-(phospho-2-hydroxyisobutyl)-6-palmitoyl ascorbic acid DMSO (5 mL), triethylamine (1.19 g), trisodium 2-phospho-6-palmitoyl ascorbate (3.31 g), and isobutylene oxide (0.50 g: 1.2 eq) were added to a recovery flask and stirred at 60°C for 15 hours. After the reaction was completed, ion-exchanged water and ethyl acetate were added and the mixture was separated. The ethyl acetate layer was collected and concentrated under reduced pressure. The resulting residue (1.16 g) was subjected to silica gel chromatography, eluting with a mixture of chloroform / ethyl acetate / methanol (10 / 10 / 1 to 1 / 1 / 1), and concentrated under reduced pressure to obtain 2-(phospho-2-hydroxyisobutyl)-6-palmitoyl ascorbic acid (0.07 g), which has the following structural formula:

[0053] [ka]

[0054] Synthesis Example 4 Synthesis of 2-(phospho-2-hydroxyisobutyl)-3-O-(2-hydroxyisobutyl)ascorbic acid DMF (5 mL), water (5 mL), trisodium 2-phosphoascorbate (5.00 g), 60% concentrated sulfuric acid (2.16 g), and isobutylene oxide (11.0 g: 11.0 eq) were added to a recovery flask and stirred at 55°C for 15 hours. After the reaction was completed, the mixture was concentrated under reduced pressure, and methanol was added. The mixture was then filtered and concentrated under reduced pressure. The resulting residue (8.27 g) was subjected to silica gel chromatography and eluted with a mixture of chloroform / methanol / 0.1% formic acid aqueous solution (9 / 1 / 0 to 7 / 3 / 0.5). The mixture was concentrated under reduced pressure to obtain 2-(phospho-2-hydroxyisobutyl)-3-O-(2-hydroxyisobutyl) (0.01 g), which has the following structural formula:

[0055] [ka]

[0056] Mass spectrometry of the products obtained in Synthesis Examples 1 to 4 was carried out using an LCMS-2020 (Shimadzu Corporation). The measurement results are shown in Table 1.

[0057] [Table 1] *Ionization was performed by electrospray ionization (ESI).

[0058] The products obtained in Synthesis Examples 1 to 4 1 H-NMR was performed using a JNM-ECS400 (manufactured by JEOL Ltd.) The measurement results are shown in Table 2.

[0059] [Table 2]

[0060] The products obtained in Synthesis Examples 1 to 4 13 C-NMR was performed using a JNM-ECS400 (manufactured by JEOL Ltd.) The measurement results are shown in Table 3.

[0061] [Table 3]

[0062] Test Example 1 [Stability test] A 1% aqueous solution of each test sample was adjusted to pH 6 with a dilute potassium hydroxide solution, placed in a 50 mL screw tube, sealed, and stored at 50°C for 4 weeks. HPLC measurement (using a Shimadzu liquid chromatograph) was performed and the residual rate was calculated from the peak area. The residual rate, odor, and coloration were evaluated according to the following methods and criteria, and the results are shown in Table 4.

[0063] Survival rate: ◎: 90% or more ○: 80% or more, less than 90% △: 60% or more, less than 80% ×: 20% or more, less than 60% ××: Less than 20%

[0064] Odor: Evaluation was made by 10 panelists according to the following criteria. 3: Virtually odorless. 2: There is a slight strange odor. 1: A strong odor is detected. Based on the evaluation results, the following classification was made: ◎: Total score of 10 people is 25 or more ○: Total score of 10 people is 20-24 △: Total score of 10 people is 16-19 ×: The total score of 10 people is 15 or less

[0065] Coloring: Evaluation was made by 10 panelists according to the following criteria. 3: Almost no change compared to immediately after preparation. 2: Color changes compared to immediately after preparation. 1: Strongly colored compared to immediately after preparation. Based on the evaluation results, the following classification was made: ○: Total score of 10 people is 25 or more △: Total score of 10 people is 16-24 ×: The total score of 10 people is 15 or less

[0066] [Table 4]

[0067] The ascorbic acid derivatives of the present invention have superior stability over time when stored at 50°C to 2-O-glucopyranosyl ascorbic acid, trisodium 2-phospho-ascorbate, and trisodium 2-phospho-6-palmitoyl ascorbate, and are almost free of odor generation, coloration, etc. In other words, the results shown in Table 4 indicate that the ascorbic acid derivatives of the present invention have improved stability over time, which was a problem with conventional ascorbic acid derivatives, and are therefore more suitable as ingredients for use in cosmetics.

[0068] Test Example 2 [Antioxidant test] Normal human epidermal keratinocytes were collected at 2.0 × 104 Cells were seeded into a 96-well plate using KG2 medium to a cell density of 1000 cells / well. After 24 hours of preincubation, samples adjusted to the desired concentration in KG2 medium were added to each well. After 24 hours of culture, the medium was removed, the cells were washed with HBSS(-), and the ROS-reactive fluorescent probe DCFHDA was allowed to incorporate for 30 minutes. The cells were washed again with HBSS(-), treated with 0.2 mM H2O2, and cultured for 2 hours. Fluorescence intensity was measured, and the amount of ROS produced per unit protein was calculated by dividing the fluorescence intensity by the amount of protein quantified by the BCA method. These results are shown in Table 5.

[0069] The antioxidant effect when the sample was measured at a concentration of 10 mM or less is shown below. Note that the measurement was performed with N=4. <20% :± 20-40% :+ 40-70% :++ 70-100%:+++

[0070] [Table 5]

[0071] The results in Table 5 show that the ascorbic acid derivatives of the present invention have superior antioxidant effects to known ascorbic acid derivatives or salts thereof, i.e., 2-O-glucopyranosyl ascorbic acid, 2-phospho-ascorbic acid trisodium, and 2-phospho-6-palmitoyl ascorbic acid trisodium.

[0072] Test Example 3 [Melanin production inhibitory effect] As a test for whitening effect, the effect on theophylline-induced melanin production in B16 melanoma 4A5 cells was evaluated for the ascorbic acid derivatives of the present invention according to the following procedure. For comparison, a similar evaluation was also performed on a known ascorbic acid derivative. The results are shown in Table 6.

[0073] (1) B16 mouse melanoma 4A5 cells were cultured at 8.0 × 103 The cells were seeded onto a 48-well plate at a cell density of 100 cells / well. (2) After culturing for 24 hours in Dulbecco's modified Eagle's medium (SIGMA, hereafter abbreviated as D-MEM) containing 10% fetal bovine serum, the medium was replaced with D-MEM containing 10% fetal bovine serum containing theophylline (final concentration 1 mM) and a specified concentration of the sample. (3) After culturing for 3 days in the presence of the sample, the medium was removed using an aspirator, distilled water was added, and the cells were disrupted by ultrasonic waves. (4) The protein content was then quantified using a BCA protein assay kit (Pierce), and the amount of melanin produced was measured by the alkaline solubilization method. Sodium hydroxide was added to the cell lysate to a final concentration of 1 mol / L, and the solution was heated and dissolved (60°C, 30 minutes), after which the absorbance at 405 nm was measured using a microplate reader. The amount of melanin was calculated from a calibration curve prepared using synthetic melanin (SIGMA) as a standard. The amount of melanin per unit protein was calculated by dividing the amount of melanin by the amount of protein. (5) The melanin production inhibition rate was calculated using the following formula. Melanin production inhibition rate (%) = [1-(AB) / (CB)] x 100 [In the formula, A represents the amount of melanin per unit protein (g / g) when the sample was added, B represents the amount of melanin per unit protein (g / g) in the normal group, and C represents the amount of melanin per unit protein (g / g) in the control group.]

[0074] The melanin production inhibition rate when the sample was measured at a concentration of 10 mM or less is shown below. Note that the measurement was performed with N=4. <20% :± 20-40% :+ 40-70% :++ 70-100%:+++

[0075] [Table 6]

[0076] The results in Table 6 show that the ascorbic acid derivatives of the present invention have whitening effects equal to or greater than those of known ascorbic acid derivatives, i.e., 2-glucopyranosyl ascorbic acid, 2-phospho-trisodium ascorbate, and 2-phospho-6-palmitoyl trisodium ascorbate.

[0077] Test Example 4 [Collagen production promoting effect] Normal human dermal fibroblasts were cultured at 2.5 × 10 4 The cells were adjusted to a cell density of 100 cells / well with D-MEM containing 5% (v / v) fetal bovine serum and then pre-incubated in a 96-well plate for 24 hours. After removing the medium, samples adjusted to the desired concentration with D-MEM containing 5% (v / v) fetal bovine serum were added to each well and cultured for 48 hours. After incubation, the amount of free collagen in the supernatant was quantified by ELISA. Measurements were performed in triplicate.

[0078] The amount of collagen produced when the sample was measured at a concentration of 10 mM or less was compared with that of the control group, and the results (% values ​​when the control group was taken as 100%) are shown in Table 7 based on the following criteria. <100% :± 100-150%:+ 150%<:++

[0079] [Table 7]

[0080] The results in Table 7 clearly show that the ascorbic acid derivatives of the present invention have the same collagen production-promoting effect as known ascorbic acid derivatives or their salts, i.e., trisodium 2-phospho-ascorbate and trisodium 2-phospho-6-palmitoyl ascorbate.

[0081] Example 16: Lotion A lotion can be prepared by thoroughly mixing the raw materials (1) to (6) in the composition shown in Table 8. In the tables following Table 8, the blending amounts are in parts by mass.

[0082] [Table 8] *The amount required to make the total blended amount 100 parts by mass. The same applies to the following tables.

[0083] Example 17 Cream The oil phase ingredients (1) to (5) and the aqueous phase ingredients (6) to (10) shown in Table 9 were each heated to 70°C and dissolved to prepare an oil phase and an aqueous phase, respectively. The oil phase was then added to the aqueous phase and pre-emulsified, and the mixture was homogeneously emulsified using a homomixer. The mixture was then cooled to room temperature while stirring thoroughly to prepare a cream.

[0084] [Table 9]

[0085] Example 18 Emulsion The oil phase ingredients (1) to (9) and the aqueous phase ingredients (10) to (13) in the compositions shown in Table 10 were each heated to 70°C and dissolved to prepare an oil phase and an aqueous phase, respectively. The oil phase was then added to the aqueous phase and pre-emulsified, and the mixture was homogeneously emulsified using a homomixer. The mixture was then cooled to room temperature while stirring well to prepare an emulsion.

[0086] [Table 10]

[0087] Example 19 Emulsion The oil phase ingredients (5) to (10) and the aqueous phase ingredients (1) to (4) and (11) to (12) in the compositions shown in Table 11 were heated to 70°C and dissolved to prepare the oil phase and aqueous phase, respectively. The oil phase was then added to the aqueous phase and pre-emulsified, and the mixture was homogeneously emulsified using a homomixer. After that, the mixture was cooled to room temperature while stirring well, thereby preparing an emulsion with excellent antioxidant effects.

[0088] [Table 11]

Claims

1. 1. An ascorbic acid derivative or a salt thereof, characterized by being represented by the following general formula (I) or (II): 【Chemical 1】 [In the formula, R １ is H, HO-C(CH ３ ) ２ -CH ２ - or HO-CH ２ -C(CH ３ ) ２ - and R ２ and R ３ represents H, an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, a benzyl group, R ４ -O-CH ２ -CH(OH)-CH ２ -, R ４ -O-CH ２ -CH(CH ２ OH)-, HO-C(CH ３ ) ２ -CH ２ -, HO-CH ２ -C(CH ３ ) ２ -, R ４ -CH(CH ２ OH)-, R ４ -CH(OH)-CH ２ - either R ４ is H, an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, or a phenyl group. ・ 【Chemistry 2】 [In the formula, R ５ is H, HO-C(CH ３ ) ２ -CH ２ - or HO-CH ２ -C(CH ３ ) ２ - and R ６ , R ７ and R ８ represents H, an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, a benzyl group, R ９ -O-CH ２ -CH(OH)-CH ２ -, R ９ -O-CH ２ -CH(CH ２ OH)-, HO-C(CH ３ ) ２ -CH ２ -, HO-CH ２ -C(CH ３ ) ２ -, R ７ -CH(CH ２ OH)-, R ７ -CH(OH)-CH ２ - either R ９ is H, an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, or a phenyl group.

2. A cosmetic preparation comprising the ascorbic acid derivative or salt thereof according to claim 1.

3. A cosmetic preparation containing 1 to 20% by weight of the ascorbic acid derivative or salt thereof according to claim 2.

Images