Ascorbic acid derivative or its salt, composition containing them, and cosmetic containing them

Abstract

Provided are an ascorbic acid derivative or a salt thereof having excellent moisture retention properties as compared with conventional ascorbic acid derivatives, a composition containing the same, and a cosmetic product. 【Means for Solving the Problem】 An ascorbic acid derivative or a salt thereof in which at least one of the hydrogens of the hydroxyl group at the 2-position 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)-, an ascorbic acid derivative composition containing these and a conventional ascorbic acid derivative, and a cosmetic product containing the ascorbic acid derivative or the ascorbic acid derivative composition.

Description

Technical Field

[0001] The present invention relates to an ascorbic acid derivative or a salt thereof, which is suitably used as a raw material for cosmetics and the like, and further relates to a composition containing the ascorbic acid derivative or a salt thereof, and a cosmetic containing them.

Background Art

[0002] Ascorbic acid is a safe and useful antioxidant and is known as a compound having excellent whitening effects and the like. On the other hand, it is unstable against light, heat, and oxidation, and its use in the cosmetic field has been hindered. Therefore, various ascorbic acid derivatives or salts thereof have been proposed as those having improved stability over time compared to ascorbic acid, and their incorporation into topical skin whitening agents (Patent Documents 1 and 2) and cosmetics (Patent Document 3) have been proposed. However, there is a demand for ascorbic acid derivatives that are further excellent in stability over time and efficacy.

[0003] Against such a background, the present inventors have proposed ascorbic acid derivatives having better stability over time and functionality than ascorbic acid (Patent Documents 4 and 5). However, further improvement is desired for the efficacy of these ascorbic acid derivatives.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Summary of the Invention

Problems to be Solved by the Invention

[0005] An object of the present invention is to provide an ascorbic acid derivative or a salt thereof having a moisturizing effect more excellent than conventional ascorbic acid derivatives, an ascorbic acid derivative composition containing them, and a cosmetic containing them.

Means for Solving the Problems

[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 moisturizing effect superior to that of conventional ascorbic acid derivatives. Furthermore, it has been found that a composition containing an ascorbic acid derivative represented by the following general formula (I) or a salt thereof and an ascorbic acid derivative represented by the general formula (II) or a salt thereof also has a moisturizing effect superior to that of a conventional ascorbic acid derivative or a salt thereof alone. The present invention has been completed based on these findings.

[0007] A 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]

Chem.

[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(CH2OH)-, R 3 -CH(OH)-CH2-, R 3 -O-CH2-CH(OH)-CH2-, or R 3 -O-CH2-CH(CH2OH)-, where R 3 is H, an alkyl group having 1 to 22 carbon atoms, or CH2OH-CH(OH)-CH2-. However, R1 and R 2 At least one of them is CH2OH-CH(OH)-CH2-O-CH2-CH(OH)-CH2- or CH2OH-CH(OH)-CH2-O-CH2-CH(CH2OH)-

[0010] The salt of the ascorbic acid derivative means a compound in which the ascorbic acid derivative where R 1 or R 2 is H is substituted with a cation such as a metal ion or an ammonium ion, and this salt is also included in the present invention.

[0011] The ascorbic acid derivative represented by the general formula (I) or a salt thereof has an excellent moisturizing effect as compared with conventional ascorbic acid derivatives or salts thereof.

[0012] The ascorbic acid derivative represented by the general formula (I), wherein R 1 and / or R 2 is a diglyceryl group, that is, CH2OH-CH(OH)-CH2-O-CH2-CH(OH)-CH2- or CH2OH-CH(OH)-CH2-O-CH2-CH(CH2OH)-, as described later, can be obtained by reacting ascorbic acid with 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane, and etherifying only the 2-position and / or 3-position among the four hydroxyl groups at the 2-position, 3-position, 5-position, and 6-position of ascorbic acid in a regioselective manner, and then subjecting it to acid treatment. Incidentally, R 1 and R 2Ascorbic acid derivatives in which both are diglyceryl groups can be synthesized by a two-step method in which, after etherification of one of the 2-position or 3-position as described above and then acid treatment to obtain a compound in which a diglyceryl group is introduced into one of the 2-position or 3-position, further etherification and subsequent acid treatment as described above are performed to introduce a diglyceryl group to the other of the 2-position or 3-position, or by a one-step method in which 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane is reacted with ascorbic acid in an amount of 2 equivalents or more and then acid treatment is performed.

[0013] In the reaction of ascorbic acid with 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane, depending on the difference in the reaction conditions of etherification, there are mainly cases where the hydroxyl group at the 2-position is etherified and cases where the hydroxyl group at the 3-position is mainly etherified. When the hydroxyl group at the 2-position is mainly etherified, R 2 is, R 3 -O-CH2-CH(OH)-CH2- and R 3 -O-CH2-CH(CH2OH)- may form a mixture. When the hydroxyl group at the 3-position is mainly etherified, R 1 is, R 3 -O-CH2-CH(OH)-CH2- and R 3 -O-CH2-CH(CH2OH)- may form a mixture.

[0014] Among the ascorbic acid derivatives represented by the general formula (I), in the formula (I), one of R 1 or R 2 is R 3 -O-CH2-CH(OH)-CH2- or R 3 -O-CH2-CH(CH2OH)-, and the other is an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, or a benzyl group. By reacting ascorbic acid with 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane and then performing acid treatment, one of R 1 or R 2 is R3 -O-CH2-CH(OH)-CH2- or R 3 Compounds represented by -O-CH2-CH(CH2OH)- can be obtained by reacting with glycidol, alkyl glycidyl ethers with specific structures, alkenyl glycidyl ethers, phenyl glycidyl ethers, sulfate esters, alkyl halides, benzyl halides, alkenyl halides, etc. Or, Ascorbic acid is reacted with glycidol, alkyl glycidyl ethers with specific structures, alkenyl glycidyl ethers, phenyl glycidyl ethers, sulfate esters, alkyl halides, benzyl halides, alkenyl halides, etc. in R 1 Or R 2 It can also be obtained by reacting the resulting compound with 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane and then performing acid treatment. Among the ascorbic acid derivatives represented by the general formula (I), in the formula (I), R 1 And R 2 Both of which are R 3 -O-CH2-CH(OH)-CH2- or R 3 -O-CH2-CH(CH2OH)- can be synthesized by the above two-step method or one-step method as described above.

[0015] The second of the present invention is a preferred embodiment among the first of the present invention, wherein R 1 And R 2 One of them is CH2OH-CH(OH)-CH2-O-CH2-CH(OH)-CH2-, or CH2OH-CH(OH)-CH2-O-CH2-CH(CH2OH)-, and the other is H, an alkyl group having 4 to 18 carbon atoms, CH2(OH)-CH(OH)-CH2-, CH2OH-CH(CH2OH)-, CH2OH-CH(OH)-CH2-O-CH2-CH(OH)-CH2-, or CH2OH-CH(OH)-CH2-O-CH2-CH(CH2OH)-. It is an ascorbic acid derivative or a salt thereof, and these compounds are preferable in that a particularly high moisturizing effect is recognized.

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

[0017]

Chemical formula

[0018] In the formula, R 4 or R 5 one of which is R 6 -O-CH2-CH(OH)-CH2-, R 6 -O-CH2-CH(CH2OH)-, R 6 -CH(CH2OH)-, or R 6 -CH(OH)-CH2-, 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-CH2-CH(OH)-CH2-, R 6 -O-CH2-CH(CH2OH)-, R 6 -CH(CH2OH)-, or R 6 -CH(OH)-CH2-, and R 6 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 derivative or its salt of the present invention, or a composition containing them can be formulated into various cosmetics. The fourth aspect of the present invention is a cosmetic characterized in that the ascorbic acid derivative or its salt of the first to third aspects of the present invention, or an ascorbic acid derivative composition containing them is formulated. The fourth cosmetic of the present invention is a cosmetic excellent in moisturizing effect.

Effects of the Invention

[0020] The ascorbic acid derivative represented by the general formula (I) of the present invention or its salt has the excellent effects originally possessed by ascorbic acid and also has a moisturizing effect superior to that of conventional ascorbic acid derivatives. In addition, a composition combining the ascorbic acid derivative represented by the general formula (I) or its salt and the conventional ascorbic acid derivative represented by the general formula (II) or its salt exhibits a moisturizing effect superior to that of the conventional ascorbic acid derivative alone. Therefore, by formulating the ascorbic acid derivative or its salt of the present invention, or an ascorbic acid derivative composition containing them into a cosmetic, it becomes possible to provide a cosmetic having an excellent moisturizing effect.

Modes for Carrying Out the Invention

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

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

[0023] In the following examples, The glyceryl group represents CH2(OH)-CH(OH)-CH2- or CH2(OH)-CH(CH2OH)- represented by the following general formulas (III) and (IV), The diglyceryl group refers to CH2(OH)-CH(OH)-CH2-O-CH2-CH(OH)-CH2- or CH2(OH)-CH(OH)-CH2-O-CH2-CH(CH2OH)- represented by the following general formulas (V) and (VI). The alkyl group refers to a methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, pentyl group, hexyl group, ethylhexyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group, tridecyl group, tetradecyl group, pentadecyl group, hexadecyl group, heptadecyl group, octadecyl group, nonadecyl group, eicosyl group, behenyl group, etc. The alkenyl group refers to a vinyl group, allyl group, butenyl group, isobutenyl group, crotyl group, octenyl group, decenyl group, dodecenyl group, etc.

[0024]

Chemical formula

[0025]

Chemical formula

[0026]

Chemical formula

[0027]

Chemical formula

[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 a compound in which a glyceryl group is bonded to any of the hydroxyl groups of ascorbic acid. Also, diglyceryl ascorbic acid refers to a compound in which a diglyceryl group (glyceryl - O - glyceryl) is bonded to any of the hydroxyl groups of ascorbic acid. The ascorbic acid derivative represented by the general formula (I) of the present invention is diglyceryl ascorbic acid in which a diglyceryl group is bonded to the 2 - position and / or 3 - position. Specifically, the following can be mentioned: (1) 2 - O - diglyceryl ascorbic acid, (2) 3 - O - diglyceryl ascorbic acid, and (3) 2 - O - diglyceryl - 3 - O - diglyceryl ascorbic acid.

[0030] (1) 2 - O - diglyceryl ascorbic acid, that is, 2 - O - (glyceryl - O - glyceryl) ascorbic acid, for example, includes 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 - alkyl ascorbic acid include 2 - O - (glyceryl - O - glyceryl) - 3 - O - ethyl ascorbic acid, 2 - O - (glyceryl - O - glyceryl) - 3 - O - butyl ascorbic acid, 2 - O - (glyceryl - O - glyceryl) - 3 - O - hexyl ascorbic acid, 2 - O - (glyceryl - O - glyceryl) - 3 - O - octyl ascorbic acid, 2 - O - (glyceryl - O - glyceryl) - 3 - O - tetradecyl ascorbic acid, and 2 - O - (glyceryl - O - glyceryl) - 3 - O - hexadecyl ascorbic 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, that is, 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 derivative represented by the general formula (I) of the present invention.

[0033] The ascorbic acid derivative represented by the general formula (I) of the present invention or a salt thereof can be produced by various methods. For example, after reacting ascorbic acid with 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane and then performing acid treatment, a diglyceryl group is introduced into the oxygen atom bonded to the 2-position or 3-position of ascorbic acid to synthesize 2-O-(glyceryl-O-glyceryl)ascorbic acid or 3-O-(glyceryl-O-glyceryl)ascorbic acid. Then, by performing alkylation, alkenylation, etc. on the other oxygen atom bonded to the 2-position or 3-position by known means, the ascorbic acid derivative of the present invention can be obtained. First, alkylation, alkenylation, etc. are performed on the oxygen atom bonded to the 2-position or 3-position of ascorbic acid, and then 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane is reacted to obtain the compound of the present invention. Also, after reacting ascorbic acid with 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane and then performing acid treatment to introduce a diglyceryl group into the oxygen atom bonded to the 2-position or 3-position of ascorbic acid, a diglyceryl group is also introduced into the other side by the same reaction to obtain the ascorbic acid derivative of the present invention in which diglyceryl groups are introduced at both the 2-position and 3-position.

[0034] Examples of the compound for introducing the diglyceryl group of the present invention include, but are not particularly limited to, the above-mentioned 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane.

[0035] The amount of 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane used in the present invention is not particularly limited. However, when introducing a diglyceryl group at one of the 2-position or 3-position, it is preferably 0.8 to 1.5 mol, more preferably 1.0 to 1.2 mol. When introducing diglyceryl groups at both the 2-position and 3-position, it is preferably 2.0 to 3.0 mol, more preferably 2.2 to 2.5 mol.

[0036] Examples of the solvent used in the reaction include water, dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone, tetrahydrofuran, methanol, ethanol, etc. The reaction temperature is preferably carried out at 20°C to 90°C, more preferably at 30°C to 80°C.

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

[0038] After reacting ascorbic acid with 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane, an acid treatment can be performed to introduce a diglyceryl group. The pH when performing the acid treatment is preferably pH 0.5 to 3.0, more preferably pH 1.0 to 2.0.

[0039] Examples of the pH adjuster 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, diazabicycloundecene, etc.

[0040] Examples of the solvent used for the acid treatment include water, dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone, etc. The reaction temperature is preferably from 0°C to 50°C, and more preferably from 10°C to 40°C.

[0041] The compound synthesized by the above method can be purified by means such as column chromatography using silica gel, crystallization, and column chromatography using a resin such as an ion exchange resin.

[0042] An ascorbic acid derivative represented by the general formula (I) or (II) above, wherein R 1 , R 2 , R 4 or R 5 is H can form a salt by substituting the dissociated hydrogen ion with a cation such as a metal ion or an ammonium ion, and the salt is also included in the scope of the present invention. Examples of this salt include inorganic salts and organic salts. Examples of the inorganic salts include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, ammonium salts, etc. Examples of the organic salts include diethanolamine salts, triethanolamine salts, basic amino acid salts, etc. The formation of the salt can be carried out by a method similar to the known salt formation method, such as a method of neutralizing an aqueous solution of an ascorbic acid derivative in which R 1 , R 2 , R 4 or R 5 is H with a basic substance.

[0043] For the diglyceryl ascorbic acid synthesized as described above, alkylation, alkenylation, benzylation, etc. are carried out with glycidol, an alkyl glycidyl ether having a specific structure, a sulfate ester, an alkyl halide, a benzyl halide, an alkenyl halide, etc. to obtain the ascorbic acid derivative of the present invention represented by the general formula (I).

[0044] There is no particular limitation on the amount of use of alkyl halides, alkenyl halides, benzyl halides, etc. used for alkylation, alkenylation, benzylation, etc., but it is preferably 0.8 to 3.0 moles, more preferably 1.0 to 2.5 moles, per 1 mole of diglyceryl ascorbic acid.

[0045] Reactions such as those of alkyl halides, alkenyl halides, benzyl halides, etc. can be carried out in the same solvents, reaction temperatures, and pH as the reaction for introducing a diglyceryl group, and the ascorbic acid derivative represented by the general formula (I) of the present invention can be synthesized by purification by means such as column chromatography using silica gel, column chromatography using resins such as ion exchange resins, activated carbon treatment, extraction, distillation, crystallization, etc.

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

[0047] The blending ratio of the ascorbic acid derivative represented by the general formula (I) in the ascorbic acid derivative composition is not particularly limited, but is preferably 0.1 to 20% by mass. If it is within the above range, a particularly high moisturizing effect can be exhibited when blended in cosmetics. If it is less than 0.1% by mass, it is difficult to obtain a high moisturizing effect. On the other hand, if it is combined in excess of 20% by mass, the corresponding effect may not be obtained. The blending ratio of the ascorbic acid derivative represented by the general formula (I) in the 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 No. 4681670, but is not limited to these production methods.

[0049] The ascorbic acid derivative or a salt thereof of the present invention, and compositions thereof can be applied to various cosmetics such as external skin preparations and hair cosmetics. In such cosmetics, components usually used in cosmetics can be arbitrarily contained according to the intended use, as long as the stability and the like are not impaired.

[0050] Examples of components usually used in cosmetics include oily components, surfactants and emulsifiers, polymer compounds such as thickeners, whitening agents, feel improvers, drugs, ultraviolet absorbers, proteins, protein hydrolysates or derivatives thereof, amino acids or derivatives thereof, antioxidants, sequestering agents, pH adjusters, preservatives, moisturizers, pigments, colorants, fragrances, etc., which can be appropriately blended.

[0051] Examples of the oily components, surfactants and emulsifiers, polymer compounds such as thickeners, whitening agents, feel improvers, drugs, ultraviolet absorbers, proteins, protein hydrolysates or derivatives thereof, amino acids or derivatives thereof, antioxidants, sequestering agents, pH adjusters, preservatives, moisturizers, pigments, colorants, fragrances, etc. include those similar to those described in WO2022 / 080287.

[0052] The components usually used in the above cosmetics can be used alone or in combination of two or more.

[0053] The dosage form of the cosmetics of the present invention is arbitrary, and any of a solution system, solubilized system, emulsion system, gel system, powder dispersion system, water-oil two-layer system, etc. is possible. According to the intended product, 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) and the above-mentioned arbitrarily blended components can be blended and produced.

Examples

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

[0055] Synthesis Example 1: Synthesis of 2-O-(glyceryl-O-glyceryl)ascorbic acid Ion-exchanged water (9.5 ml), ascorbic acid (8.5 g), and sodium hydroxide (2.2 g) were added into an eggplant flask and heated to 55°C. Then, 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane (10.0 g: 1.1 eq relative to ascorbic acid) was added, and stirring was carried out for 4.5 hours. Then, after neutralization with 1% hydrochloric acid, concentration was performed under reduced pressure. The obtained residue (21.3 g) was subjected to silica gel chromatography and eluted with a mixed solution of chloroform / methanol = 5 / 1 to 1 / 1. Then, concentration was performed under reduced pressure to obtain 2-O-(glyceryl-O-isopropylidene glyceryl)ascorbic acid (15.0 g). Then, 1% hydrochloric acid (44.0 g) was added, and stirring was carried out overnight at room temperature. Then, concentration was performed under reduced pressure, and the obtained residue (18.3 g) was subjected to silica gel chromatography and eluted with a mixed solution of chloroform / methanol = 2 / 1 to 1 / 1. Then, concentration was performed under reduced pressure to obtain the product (10.2 g).

[0056] For the obtained product, mass spectrometry, 1 1H-NMR, 13 13C-NMR measurements were carried out, and it was confirmed that it was 2-O-(glyceryl-O-glyceryl)ascorbic acid represented by the following structural formula.

[0057]

Chemical formula

[0058] In addition, in the following synthesis examples as well, for the obtained product, mass spectrometry, 1 1H-NMR, and 1313C-NMR measurement was performed, and from the measurement results, it was confirmed that each product is an ascorbic acid derivative represented by the structural formula or compound name shown in each synthesis example. For the products obtained in the synthesis examples, mass spectrometry, 1 1H-NMR and 13 the measurement results of 13C-NMR are shown in Tables 1 to 3.

[0059] Synthesis Example 2: Synthesis of 3-O-(glyceryl-O-glyceryl)ascorbic acid Ion-exchanged water (2.2 ml), ascorbic acid (7.0 g), and sodium hydroxide (0.32 g) were added into an eggplant flask and heated to 60°C. Then, 4-[(2,3-epoxypropoxy)methyl]-2,2-dimethyl-1,3-dioxolane (8.3 g: 1.1 eq relative to ascorbic acid) was added, and stirring was carried out under the condition of 70°C for 5 hours. Then, concentration was performed under reduced pressure. The obtained residue (12.9 g) was subjected to silica gel chromatography and eluted with a mixed solution of chloroform / methanol = 5 / 1 to 1 / 1. Then, concentration was performed under reduced pressure to obtain 3-O-(glyceryl-O-isopropylidene glyceryl)ascorbic acid (9.4 g). Then, 1% hydrochloric acid (12.0 g) was added, and stirring was carried out overnight at room temperature. Then, concentration was performed under reduced pressure, and the obtained residue (10.2 g) was subjected to silica gel chromatography and eluted with a mixed solution of chloroform / methanol = 5 / 1 to 2 / 1. Then, concentration was performed under reduced pressure to obtain 3-O-(glyceryl-O-glyceryl)ascorbic acid (5.5 g) represented by the following structural formula.

[0060]

Chemical formula

[0061] Synthesis Example 3: Synthesis of 2-O-(glyceryl-O-glyceryl)-3-O-ethylascorbic acid Into a eggplant flask, 2-O-(glyceryl-O-glyceryl)ascorbic acid (1.50 g) obtained in Synthesis Example 1, DMF (9.0 ml), triethylamine (1.33 g), and diethyl sulfate (1.42 g: 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 step of adding water and concentrating under reduced pressure was repeated 3 times, and the obtained residue (2.3 g) was subjected to silica gel chromatography and eluted with a mixed solution of chloroform / methanol = 10 / 1 to 2 / 1. Then, concentration was performed under reduced pressure to obtain 2-O-(glyceryl-O-glyceryl)-3-O-ethylascorbic acid (620.5 mg) represented by the following structural formula.

[0062]

Chemical formula

[0063] Synthesis Example 4 Synthesis of 2-O-(glyceryl-O-glyceryl)-3-O-butylascorbic acid Into a eggplant flask, 2-O-(glyceryl-O-glyceryl)ascorbic acid (1.50 g) obtained in Synthesis Example 1, DMF (7.5 ml), potassium carbonate (0.33 g), and butyl bromide (0.70 g: 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. Then, it was cooled and allowed to stand, and only the supernatant was collected to remove the precipitated salt or base. The step of adding water to the supernatant and concentrating under reduced pressure was repeated 3 times. The obtained residue (1.86 g) was subjected to silica gel chromatography and eluted with a mixed solution of chloroform / methanol = 10 / 1 to 5 / 1. Then, concentration was performed under reduced pressure to obtain 2-O-(glyceryl-O-glyceryl)-3-O-butylascorbic acid (630.2 mg) represented by the following structural formula.

[0064]

Chemical formula

[0065] Synthesis Example 5 Synthesis of 2-O-(Glyceryl-O-glyceryl)-3-O-hexylascorbic acid Using the same method as in Synthesis Example 4 except that hexyl bromide (0.84 g) was used instead of butyl bromide, 2-O-(glyceryl-O-glyceryl)-3-O-hexylascorbic acid (601.2 mg) represented by the following structural formula was obtained.

[0066] [Chemical formula]

[0067] Synthesis Example 6 Synthesis of 2-O-(Glyceryl-O-glyceryl)-3-O-octylascorbic acid Using the same method as in Synthesis Example 4 except that octyl bromide (1.0 g) was used instead of butyl bromide, 2-O-(glyceryl-O-glyceryl)-3-O-octylascorbic acid (637.4 mg) represented by the following structural formula was obtained.

[0068] [Chemical formula]

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

[0070] [Chemical formula]

[0071] Synthesis Example 8 Synthesis of 2-O-(Glyceryl-O-glyceryl)-3-O-hexadecylascorbic acid 2-O-(Glyceryl-O-glyceryl)-3-O-hexadecyl ascorbic acid (804.3 mg) represented by the following structural formula 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]

Chemical formula

[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 No. 4681670. Subsequently, into a eggplant flask, 3-O-glyceryl ascorbic acid (1.8 g), ion-exchanged water (1.0 ml), sodium hydrogen carbonate (0.06 g), 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, and the mixture was stirred at 60 °C for 5 hours. Then, it 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 mixed solution, and then concentrated under reduced pressure to obtain 2-O-(glyceryl-O-isopropylidene glyceryl)-3-O-glyceryl ascorbic acid (530.7 mg). Thereafter, 1% hydrochloric acid (2.0 g) was added, and the mixture was stirred overnight at room temperature. After neutralization with 1% aqueous sodium hydroxide solution, it 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 mixed solution. Then, it was concentrated under reduced pressure to obtain 2-O-(glyceryl-O-glyceryl)-3-O-glyceryl ascorbic acid represented by the following structural formula (316.5 mg).

[0074]

Chemical formula

[0075] Synthesis Example 10 Synthesis of 2-O-Ethyl-3-O-(glyceryl-O-glyceryl)ascorbic Acid Into an eggplant flask, 3-O-(glyceryl-O-glyceryl)ascorbic acid (1.0 g) obtained in Synthesis Example 2, DMF (5.0 ml), potassium carbonate (0.65 g), and diethyl sulfate (0.93 g: 2.0 eq relative to 3-O-(glyceryl-O-glyceryl)ascorbic acid) were added, and the mixture was stirred at 70 °C for 3 hours. Then, it was cooled and allowed to stand, and only the supernatant was collected to remove the precipitated salt or base. The step of adding water to the supernatant and concentrating it under reduced pressure was repeated 3 times. The obtained residue (1.34 g) was subjected to silica gel chromatography and eluted with a mixed solution of chloroform / methanol = 10 / 1 to 2 / 1. Then, it was concentrated under reduced pressure to obtain 2-O-ethyl-3-O-(glyceryl-O-glyceryl)ascorbic acid (696.2 mg) represented by the following structural formula.

[0076]

Chemical formula

[0077] Synthesis Example 11 Synthesis of 2-O-Butyl-3-O-(glyceryl-O-glyceryl)ascorbic Acid Into an eggplant flask, 3-O-(glyceryl-O-glyceryl)ascorbic acid (1.0 g) obtained in Synthesis Example 2, DMF (5.0 ml), sodium carbonate (0.17 g), and butyl bromide (0.45 g: 1.1 eq relative to 3-O-(glyceryl-O-glyceryl)ascorbic acid) were added, and the mixture was stirred overnight at 50 °C. After neutralizing with 1% hydrochloric acid, the step of adding water to the supernatant and concentrating it under reduced pressure was repeated 3 times. The obtained residue (1.93 g) was subjected to silica gel chromatography and eluted with a mixed solution of chloroform / methanol = 10 / 1 to 5 / 1. Then, it was concentrated under reduced pressure to obtain 2-O-butyl-3-O-(glyceryl-O-glyceryl)ascorbic acid (462.6 mg) represented by the following structural formula.

[0078]

Chemical formula

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

[0080]

Chemical formula

[0081] Synthesis Example 13 Synthesis of 2-O-octyl-3-O-(glyceryl-O-glyceryl)ascorbic acid 2-O-octyl-3-O-(glyceryl-O-glyceryl)ascorbic acid (437.6 mg) represented by the following structural formula was obtained in the same manner as in Synthesis Example 11, except that octyl bromide (0.64 g) was used instead of butyl bromide.

[0082]

Chemical formula

[0083] Synthesis Example 14 Synthesis of 2-O-tetradecyl-3-O-(glyceryl-O-glyceryl)ascorbic acid 2-O-tetradecyl-3-O-(glyceryl-O-glyceryl)ascorbic acid (310.2 mg) represented by the following structural formula was obtained in the same manner as in Synthesis Example 11, except that tetradecyl bromide (0.92 g) was used instead of butyl bromide.

[0084]

Chemical formula

[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 No. 4681670. Into a eggplant flask, 2-O-glyceryl ascorbic acid (2.5 g), ion-exchanged water (0.8 ml), and sodium hydroxide (0.12 g) were added 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 stirring was carried out for 5 hours under the condition of 72 °C. Then, concentration was performed under reduced pressure, and the obtained residue (4.28 g) was subjected to silica gel chromatography and eluted with a mixed solution of chloroform / methanol = 5 / 1 to 1 / 1. Then, concentration was performed under reduced pressure to obtain 2-O-glyceryl-3-O-(glyceryl-O-isopropylidene glyceryl) ascorbic acid (1.89 g). Then, 1% hydrochloric acid (5.78 g) was added, and stirring was carried out overnight at room temperature. After neutralization with 1% aqueous sodium hydroxide solution, concentration was performed under reduced pressure, and the obtained residue (2.01 g) was subjected to silica gel chromatography and eluted with a mixed solution of chloroform / methanol = 5 / 1 to 2 / 1. Then, concentration was performed under reduced pressure to obtain 2-O-glyceryl-3-O-(glyceryl-O-glyceryl) ascorbic acid (1.42 g) represented by the following structural formula.

[0086]

Chemical formula

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

[0088]

Table 1

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

[0090]

Table 2

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

[0092]

Table 3

[0093] Test Example 1 [Moisturizing Test: Measurement of Moisturizing Effect by Water Retaining Capacity] Each sample described in Table 4 shown below was vacuum dried, and about 400 mg (this weight is designated as W0) was taken and placed in a weighing bottle (diameter 1.7 cm, height 4.0 cm excluding the lid). Each sample in the weighing bottle was allowed to stand in a thermo-hygrostat (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 the sample was allowed to stand until sufficient moisture absorption occurred and the weight change ceased. Then, the sample was transferred to an environment at a temperature of 25°C and a humidity of 35% (inside a sealed container filled with a saturated aqueous solution of potassium acetate at the bottom), and the moisture retention amount W h (mg / g) per 1 g of the dry sample was calculated from the weight after 7 days (this weight is designated as W1) by the following formula. W h = (W1 - W0) / W0 Based on the moisture retention amount W calculated in this way h the moisturizing effect was determined according to 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]

Table 4

[0095] From the results in Table 4, it was revealed that the ascorbic acid derivative or a salt thereof of the present invention has a larger water retention amount per 1 g of the sample compared with the conventional ascorbic acid derivative having a glyceryl group, and particularly in Examples 1 and 2, the water retention amount is about twice, indicating that it has excellent water retention ability.

[0096] Test Example 2 [Moisturizing test: Measurement of moisturizing effect in a closed environment] A weighing bottle (diameter 7 mm, height 3.2 cm excluding the lid) containing 200 mg of ion-exchanged water was covered with a cellulose filter paper (diameter 8 mm, thickness 0.19 mm). The following samples were prepared into 1.5 mmol / g aqueous solutions, and 5 μl thereof was applied while thinly spreading it evenly on the cellulose filter paper. The weighing bottle was stored in a thermostat at 60°C for 5 hours. The weight (mg) was measured, and the residual rate (X%) of the water in the weighing bottle was determined from the decreased amount of water (let this weight be W d ).) by the following formula. X = 100 - (W d / 200 × 100) Also, as a control experiment, when 5 μl of ion-exchanged water was applied and the residual rate was determined, it was 70.5%. The difference from the residual rate of the sample (let this difference be d (%)) was determined by the following formula. d = X - 70.5 Based on the following criteria, the moisturizing effect was determined from the results calculated in this way, and the results are shown in Table 5.

[0097] (Criteria) ◎: 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] [Table 5]

[0099] From the results in Table 5, it was revealed that the ascorbic acid derivative of the present invention or a salt thereof has an excellent moisturizing effect as compared with a conventional ascorbic acid derivative having a glyceryl group or a salt thereof.

[0100] Test Example 3 [Moisturizing Test 2: Measurement of Moisturizing Effect by Water Retaining Capacity 2] Regarding the compositions in the ratios shown in Example Nos. 12 to 19 and Comparative Examples 12 and 13 described in Tables 6 and 7 below, the amount of water W h (mg / g) retained per 1 g of the dry sample was calculated, and the moisturizing effect was determined based on the following criteria, and the results are shown in Tables 6 and 7.

[0101] (Criteria) ◎: 75 mg or more ○: 55 mg or more and less than 75 mg △: 35 mg or more and less than 55 mg ×: Less than 35 mg

[0102]

Table 6

[0103]

Table 7

[0104] From the results in Tables 6 and 7, it was revealed that by adding an ascorbic acid derivative having a small amount of diglyceryl groups to a conventional ascorbic acid derivative having a glyceryl group, the moisturizing effect of the ascorbic acid derivative having a glyceryl group is significantly increased.

[0105] Example 20 Lotion A lotion is prepared by mixing the raw materials (1) to (6) having the composition shown in Table 8 while stirring well. In the tables after Table 8, the blending amounts are represented by parts by mass.

[0106]

Table 8

[0107] Example 21 Emulsion The raw materials of the oil phase part of (1) to (9) and the raw materials of the water phase part of (10) to (13) in the composition shown in Table 9 are each heated to 70°C and dissolved to prepare the oil phase and the water phase respectively. Then, the oil phase is added to the water phase for preliminary emulsification, uniformly emulsified with a homomixer, and then cooled to room temperature while stirring well to prepare an emulsion.

[0108] [Table 9]

[0109] Example 22 Cream The raw materials of the oil phase part of (1) to (5) and the raw materials of the water phase part of (6) to (10) in the composition shown in Table 10 are each heated to 70°C and dissolved to prepare the oil phase and the water phase respectively. Then, the oil phase is added to the water phase for preliminary emulsification, uniformly emulsified with a homomixer, and then cooled to room temperature while stirring well to prepare a cream.

[0110] [Table 10]

Claims

Ascorbic acid derivative or a salt thereof, characterized by being represented by the following general formula (I) 【Chemical 1】 [In formula (I), R1 and R2 are H, an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, a benzyl group, R3-CH(CH2OH)-, R3-CH(OH)-CH2-, R3-O-CH2-CH(OH)-CH2-, or R3-O-CH2-CH(CH2OH)-, where R3 is H, an alkyl group having 1 to 22 carbon atoms, or CH2OH-CH(OH)-CH2-. However, at least one of R1 and R2 is CH2OH-CH(OH)-CH2-O-CH2-CH(OH)-CH2- or CH2OH-CH(OH)-CH2-O-CH2-CH(CH2OH)-.], and, An ascorbic acid derivative composition comprising an ascorbic acid derivative represented by the following general formula (II) or a salt thereof, wherein 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). [Chemical Formula 2] [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 party 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 is H, an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 22 carbon atoms, or a phenyl group. Cosmetic, characterized by containing the ascorbic acid derivative composition according to claim 1

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