KR20040101451A - Stabilized ascorbic acid derivatives - Google Patents

Abstract

An ascorbic acid derivative, which is a compound represented by the following general formula (1) or a salt thereof.

(Wherein X and Y each represent a protecting group of H or OH, R ¹ and R ² each represent an alkyl group having 1 to 19 carbon atoms which may be linear or branched, respectively, and the carbon atoms of R ¹ and R ² The total number is an integer from 5 to 22.)

Description

STABILIZED ASCORBIC ACID DERIVATIVES}

Ascorbic acid has activities such as inhibiting lipid peroxide production, promoting collagen production, delaying melanogenesis and improving immune function or performance. For this reason, ascorbic acid is conventionally used in the fields of medicine, agrochemicals, animal or animal medicines, food, animal feed ingredients, cosmetic preparations and the like. However, ascorbic acid lacks stability over time and has poor lipid solubility. Therefore, the amount of ascorbic acid that penetrates the cell membrane and accumulates in the cells is somewhat limited, and when ascorbic acid itself is used, the physiological action of vitamin C is not necessarily achieved to a satisfactory level. In order to improve the stability of ascorbic acid, JP-B (examined Japanese patent publication) 52-1819 (patent document 1), and JP-A (unexamined Japanese patent publication) 02-279690 (patent document 2) In order to improve the lipid solubility described in the derivative in which the hydroxyl group in the oxidizable 2- or 3-position endiol moiety described in the back is converted into a phosphate ester, or in JP-A-59-170085 (Patent Document 3) and the like, Various derivatives thereof, such as derivatives acylated with fatty acids, have been proposed. However, very few derivatives improve both stability and lipid solubility.

As ascorbic acid for improving both stability and lipid solubility, JP-A-61-152613 (Patent Document 4) describes a cosmetic composition containing a 6-O-higher acyl ascorbic acid-2-phosphate ester salt. . However, in the above-mentioned patent publication, a method for producing sulfuric acid esters (not phosphate esters) is described, and their production method for phosphate esters is not described, and the production of ascorbic acid derivatives described in the above publication is not certain. . From this point of view, it was difficult to admit that the 6-O-higher acyl ascorbic acid-2-phosphate ester is disclosed in a practical manner.

JP-A-10-298174 (Patent Document 5) describes a method for producing 6-O-high acyl ascorbic acid-2-phosphate ester and the results of structural measurement of this substance. It has been demonstrated that the 6-O-higher acyl ascorbic acid-2-phosphate ester prepared by this method improves both stability and lipid solubility and is easy to introduce into cells. However, among these substances, ascorbic acid 2-phosphate ester-6-palmitic acid ester sodium salt and their aqueous solution were still insufficient from the standpoint of stability.

Patent Document 1: JP-B-52-1819

Patent Document 2: JP-A-02-279690

Patent Document 3: JP-A-59-170085

Patent Document 4: JP-A-61-152613

Patent Document 5: JP-A-10-298174

The present invention relates to novel ascorbic acid derivatives. More specifically, the present invention relates to an ascorbic acid derivative which is a stable compound and a method for producing the same. The present invention also relates to ascorbic acid, such as vitamin C preparations or agents containing ascorbic acid derivatives, collagen production promoters, whitening agents, external skin or coating agents, medicines, pesticides, animal or animal medicines, food additives and additives for animal feed ingredients. The present invention relates to various forms or embodiments containing acid derivatives and the like.

It is an object of the present invention to provide an ascorbic acid derivative and a method for producing the ascorbic acid derivative which solve the above problems encountered in the prior art.

Another object of the present invention is a 6-O-high acyl ascorbic acid-2-phosphate ester and / or a salt thereof having improved stability and a novel structure, a preparation method thereof, and the 6-O-high acyl ascorbate. It is providing the formulation (cosmetic material etc.) using an acid 2-phosphate ester and / or its salt.

As a result of earnest examination, the present inventors have found that the 6-O-higher acyl ascorbic acid-2-phosphate ester and / or salt thereof in which the newly synthesized 6-position acyl group (fatty acid residue) branched at the α-position is conventionally used. It has been found that there is a significant improvement in stability compared to 6-O-higher acyl ascorbic acid-2-phosphate esters with linear fatty acid residues and / or salts thereof. The present invention has been accomplished based on this finding.

The ascorbic acid derivative according to the present invention represented by the following general formula (1) is characterized in that the higher fatty acid ester at the 6 position is a fatty acid ester branched at α-carbon.

According to the experiments of the present inventors, the conventional 6-O-high-grade linear fatty acid ester was found to decompose or crack during storage, resulting in a decrease in the ascorbic acid-2-phosphate ester residual rate after storage. On the other hand, ascorbic acid-2-phosphate-6-fatty acid ester according to the present invention has improved stability. According to the investigations and experiences of the present inventors, it is assumed that fatty acid esters (as starting material, ascorbic acid-2-phosphate-6-fatty acid ester synthesized from fatty acids branched from α-carbon) have enhanced ester bonds. It was.

More specifically, the present invention relates to the following matters.

[1] An ascorbic acid derivative, which is a compound represented by the following general formula (1) or a salt thereof.

(Wherein X and Y each represent a protecting group of H or OH, R ¹ and R ² each represent an alkyl group having 1 to 19 carbon atoms which may be linear or branched, respectively, and the carbon atoms of R ¹ and R ² The total number is an integer from 5 to 22.)

[2] The ascorbic acid derivative according to [1], which is at least one metal salt selected from the group consisting of alkali metals, alkaline earth metals, aluminum, iron, zinc and bismuth.

[3] The ascorbic acid derivative according to [1], which is a salt with ammonia, monoethanolamine, diethanolamine, triethanolamine, dicyclohexylamine or 2-amino-1-methylpropanol.

[4] The ascorbic acid derivative according to [1], wherein the total number of carbon atoms in R ¹ and R ² of the general formula (1) is an integer of 8 to 18.

[5] The composition of [4], wherein R ¹ and R ² in the general formula (1) are linear alkyl groups, and the total number of carbon atoms in the linear alkyl groups of R ¹ and R ² is 14 or 16. Ascorbic acid derivatives.

[6] The compound of [5], wherein R ¹ in formula (1) is nC ₉ H ₁₉ and R ² is nC ₇ H ₁₅ ; Or ascorbic acid derivative wherein R ¹ is nC ₈ H ₁₇ and R ² is nC ₆ H ₁₃ .

[7] reacting a compound represented by the following general formula (2) and / or a salt thereof with at least one selected from fatty acids, fatty acid salts, fatty acid esters, fatty acid halides and / or fatty acid anhydrides; The manufacturing method of the ascorbic acid derivative as described in any one of [1]-[6].

Where X and Y each represent a protecting group of H or OH.

[8] The method for producing an ascorbic acid derivative according to [7], wherein the reaction is carried out in the presence of a condensing agent and / or a dehydrating agent.

[9] The method for producing an ascorbic acid derivative according to [8], wherein the dehydrating agent is sulfuric acid.

[10] The ascorbic acid derivative according to [7], wherein the reaction is performed in a solvent selected from the group consisting of water, acetone, dioxane, toluene, ethylbenzene, methyl-tert-butyl ether and sulfuric acid. Manufacturing method.

[11] A vitamin C preparation comprising ascorbic acid derivative according to any one of [1] to [6] as an active ingredient.

[12] A collagen production promoter comprising ascorbic acid derivative according to any one of [1] to [6] as an active ingredient.

[13] A whitening agent comprising ascorbic acid derivative according to any one of [1] to [6] as an active ingredient.

[14] An external preparation for skin comprising ascorbic acid derivative according to any one of [1] to [6] as an active ingredient.

[15] The external preparation for skin according to [14], which contains ascorbic acid-2-phosphate ester and / or a salt thereof.

[16] The external preparation for skin according to [14], which contains sodium salt, potassium salt, manganese salt or zinc salt of ascorbic acid-2-phosphate ester.

[17] A cosmetic material comprising the external preparation for skin according to [14].

[18] A composition comprising the ascorbic acid derivative according to any one of [1] to [6] in the form of a medicine, agrochemical or animal medicine.

[19] A composition comprising the ascorbic acid derivative according to any one of [1] to [6] in the form of a food or feed additive.

Hereinafter, the present invention will be described in detail with reference to the drawings as necessary. In the above description, "%" and "parts" refer to mass ratios or parts by mass unless otherwise specified.

(Ascorbic acid derivative)

Ascorbic acid derivatives according to the present invention are compounds represented by the following general formula (1) and / or salts thereof:

(Wherein X and Y each represent a protecting group of H or OH, R ¹ and R ² each represent an alkyl group having 1 to 19 carbon atoms which may be linear or branched, respectively, and the carbon atoms of R ¹ and R ² The total number is an integer from 5 to 22.)

In the present invention, unless otherwise specified, the ascorbic acid or ascorbic acid derivative is preferably L-type.

Ascorbic acid derivatives according to the present invention have excellent stability without being oxidized since the 2-position of the ascorbic acid is esterified with a phosphate ester.

In addition, in the ascorbic acid derivative according to the present invention, since the 6 position is esterified with a higher fatty acid ester, the compound may have a characteristic of having moderate lipid solubility and facilitating introduction into cells. In addition, the 2-position phosphate group in the compound is easily hydrolyzed by phosphatase in vivo, and the higher fatty acid ester in 6-position is a primary alcohol (6-position) to which a lipase or esterase can act. And esters, and the compound can be easily converted to ascorbic acid in vivo.

(Method for producing ascorbic acid derivative-1)

The compounds and / or salts represented by the general formula (1) according to the invention can be prepared, for example, according to the following schemes:

Wherein X and Y each represent a protecting group of H or OH, R ¹ and R ² each represent an alkyl group having 1 to 19 carbon atoms, and the total number of carbon atoms in R ¹ and R ² is 5 to 22, R ³ represents a hydrogen atom, a cation or an alkyl group having 1 to 5 carbon atoms).

More specifically, the ascorbic acid is reacted with at least one of the fatty acids, esters and salts thereof branched at α-carbon represented by the formula (3) and / or its salt represented by the formula (2). Acid-2-phosphate-6-fatty acid ester (1) and / or salts thereof are prepared.

(Dehydrating or condensing agent)

The reaction is preferably carried out in the presence of a dehydrating agent or a condensing agent.

The dehydrating agent or condensing agent used in such a case is not specifically limited. Preferred examples of the condensing agent include N, N'-dicyclohexyl carbodiimide, N, N'-diisopropyl carbodiimide, N-ethyl-N'-3-dimethylaminopropyl Carbodiimide, benztriazol-1-yl-tris (dimethylamino) phosphonium hexafluorophosphide salt, diphenylphosphoryl azide. Among these, it is preferable to use N, N'- diisopropyl carbodiimide. Preferred examples of such dehydrating agents include phosphorus pentoxide, solid phosphoric acid, titanium oxide, alumina and sulfuric acid. Among them, it is preferable to use sulfuric acid (preferably 95% by mass or more concentrated sulfuric acid) and to react the mixed sulfuric acid, ascorbic acid-2-phosphate ester salt and fatty acid or ester or salts thereof.

In the fatty acid ester of the general formula (3), R ³ represents an alkyl ester having 1 to 5 carbon atoms, preferably a lower alkyl ester having 1 to 3 carbon atoms, more preferably methyl ester or ethyl ester .

The reaction time and the reaction temperature depend on whether the fatty acid is a free acid, ester or salt, or on the type and amount of the condensing agent. However, the reaction time is generally 1 to 120 hours, preferably 4 to 10 hours, the reaction temperature is generally 5 to 70 ° C, and preferably 30 to 50 ° C.

The water content delivered from the starting material or catalyst to the reaction solution is preferably at most 10%, preferably at most 2%.

(solvent)

When a solvent is used during the reaction, sulfuric acid itself as a condensing agent may be used as the solvent. It is also possible to select a solvent from other solvents capable of dissolving the starting material. Specific examples of such other solvents include water, acetone, dioxane, toluene, ethylbenzene, methyl-tert-butyl ether, and the like.

(Production method-2 of ascorbic acid derivative)

The compounds and / or salts represented by the general formula (1) according to the present invention may be prepared, for example, according to the following scheme:

(Wherein X and Y each represent a protecting group of H or OH, R ¹ and R ² each represent an alkyl group having 1 to 19 carbon atoms, and the total number of carbon atoms in R ¹ and R ² is 5 to 22, Z represents halide).

More specifically, ascorbic acid-2-phosphate represented by formula (2) and / or its salt is reacted with a fatty acid halide branched at α-carbon represented by formula (4) to ascorbic acid-2- Phosphoric acid-6-fatty acid ester (1) and / or salts thereof are prepared.

(base)

The reaction is preferably carried out in the presence of a base. The base is not particularly limited as long as it can be generally used as a dehydrogen halide in the reaction of an alcohol with an acid halide. Preferred examples thereof include tertiary amines such as pyridine and triethylamine.

(Production method-3 of ascorbic acid derivative)

The compound represented by formula (1) and / or a salt thereof may be prepared, for example, according to the following scheme:

(Wherein X and Y each represent a protecting group of H or OH, R ¹ and R ² each represent an alkyl group having 1 to 19 carbon atoms, and the total number of carbon atoms in R ¹ and R ² is 5 to 22) .

More specifically, the fatty acid anhydride branched from α-carbon represented by the general formula (5) is reacted with ascorbic acid 2-phosphate and / or a salt thereof represented by the general formula (2), and the above formula (1) To prepare ascorbic acid-2-phosphate-6-fatty acid ester and / or salts thereof.

(Molar ratio)

In the production method according to the present invention, the starting material may be used in an equimolar amount in any of the reactions. However, a slight excess of either starting material may be present (e.g., either starting material may be present in a molar ratio of about 1.0-3.0, unless a substantial problem occurs during purification or isolation occurs after a predetermined reaction. More preferably about 1.0-1.5).

(Purification and / or isolation)

The purification or isolation method is not particularly limited. More specifically, the purification or isolation can be carried out using common methods such as solvent extraction, washing, salting out, or column chromatography. For example, the reaction product may be isolated or purified by either non-polar solvents such as hexane, either by washing or by ether extraction. If necessary, the obtained product may be further purified by reverse phase chromatography or the like.

It is preferable that all the groups represented by X and Y in the 3- and 5- positions of ascorbic acid of the formula (2) are H. However, in any of the above reactions, these groups may be substituted with protecting groups that are not substantially affected by the above reactions.

<Specific example of a water-insoluble protecting group>

Acyl group, alkanesulfonyl group, benzenesulfonyl group which may be substituted, dialkyl carbamoyl group, benzyl group, alkyl group, silyl group.

(Salts of ascorbic acid derivatives)

The salt of the compound represented by following General formula (1) can be obtained by the following method.

(Wherein X and Y each represent a protecting group of H or OH, R ¹ and R ² each represent an alkyl group having 1 to 19 carbon atoms which may be linear or branched, and each of carbon atoms in R ¹ and R ² The total number is an integer from 5 to 22.)

The ascorbic acid 2-phosphate-6-high fatty acid ester thus obtained is, for example, a suitable base (eg, sodium hydroxide, potassium hydroxide, magnesium oxide) in a solvent capable of dissolving ester such as water or methanol. , Calcium hydroxide, ammonia, monoethanolamine, diethanolamine, triethanolamine or dicyclohexylamine) can be neutralized to obtain a salt with the base.

The kind of salt of ascorbic acid derivative is not particularly limited as long as the use of the salt of ascorbic acid derivative is not substantially impaired. In view of ease of availability and their blendability into the formulation, the salt preferably contains alkali metal, alkaline earth metal, aluminum, iron, zinc and bismuth. Of these, alkali metals such as sodium and potassium, and alkaline earth metals such as calcium and magnesium are preferable. You may use these individually or in combination of 2 or more types.

(Protection of hydroxyl group)

In the compound represented by the general formula (1), the hydroxyl group in the 3- or 5-position may be protected by a conventionally known group which is easily converted to a hydroxyl group. The present invention may include compounds having such protecting groups (eg, acyl groups, alkanesulfonyl groups, benzenesulfonyl groups which may be substituted, or dialkylcarbamoyl groups, benzyl groups, alkyl groups, silyl groups, and the like). The protecting group can be introduced into the desired compound before and after the 6-position esterification reaction.

In the reaction, R ¹ and R ² of the general formula (1) as well as the method for preparing 6-O-high fatty acid ester of ascorbic acid-2-phosphate according to the present invention are each CH ₃ or C ₂ H ₅ It can also be used for production of a conventionally known 6-O-lower fatty acid ester.

(Produce)

The ascorbic acid derivative according to the present invention exhibits markedly improved vitamin C activity in both stability and lipid solubility compared to conventionally known ascorbic acid derivatives. Therefore, vitamin C may be supplied as an ascorbic acid derivative according to the present invention or as a preparation (vitamin C preparation) containing ascorbic acid derivative according to the present invention. The use of the ascorbic acid derivative according to the present invention is not particularly limited. For example, when the ascorbic acid derivative according to the present invention is mixed with medicine, pesticide, food, feed or cosmetic preparation, vitamin C can be effectively supplied.

(High fatty acid ester)

The ascorbic acid derivative according to the present invention is preferably L type from the viewpoint of vitamin C activity. In addition, the higher fatty acid esters at the 6-position are characterized in that they are fatty acid esters branched at α-carbon atoms. As described above, according to the experiments of the present inventors, it is understood that the ester bonds of the conventional 6-O-high-grade linear fatty acid esters are decomposed or cracked during storage, thereby reducing the residual rate of ascorbic acid-2-phosphate ester after storage. Found. On the other hand, in the ascorbic acid derivative (for example, ascorbic acid 2-phosphate-6-fatty acid ester synthesized from a fatty acid branched from α carbon), the ester bond is strengthened, so that the ascorbic acid derivative according to the present invention is It is assumed that stability is improved in storage experiments.

In view of the lipid solubility, preferred examples of the 6-O-high fatty acid ester may include 2-butylhexanoic acid ester, 2-hexyldecanoic acid ester and 2-heptyl undecyl acid ester.

(Collagen production promoter, external skin preparation)

The ascorbic acid derivative obtained by the production method according to the present invention has a collagen production promoting effect and a whitening effect, and can be used as a collagen production promoter or a whitening agent. In addition, the ascorbic acid derivative can be effectively used as an external preparation for skin, for example, by preparing with other skin solvents.

When the ascorbic acid derivative is used as a skin solvent, the external preparation for skin according to the present invention, in addition to the ascorbic acid derivative obtained by the production method according to the present invention (represented by the general formula (1)), has the following general formula (2) It may contain ascorbic acid-2-phosphate ester and / or salt thereof.

Wherein X and Y each represent a protecting group of H or OH. In embodiments containing ascorbic acid-2-phosphate ester and / or salts thereof represented by the following general formula (2), the advantageous effect of providing an ascorbic acid source to both the epidermis and the dermis may be achieved.

(Ascorbic acid-2-phosphate ester)

Hereinafter, the ascorbic acid 2-phosphate ester and / or salts thereof will be described in more detail.

The ascorbic acid-2-phosphate ester according to the present invention may be any of D-type, L-type, and DL-type, but L-type is preferred. The salt of the ascorbic acid-2-phosphate ester is, for example, a compound in which the phosphate ester is bonded to the 2-position of the ascorbic acid, and the phosphate group of the phosphate ester forms a salt with a base.

Specific examples of the salt of ascorbic acid-2-phosphate ester include alkali metal salts, alkaline earth metal salts, Zn salts, Al salts, Ti salts, and the like. Among these, Na salt, K salt, Mg salt, and Zn salt are preferable, and Na salt and Mg salt are more preferable from an economic viewpoint.

(Collagen production promoting effect)

In the present invention, the collagen production promoting effect is, for example, when the hydroxyproline content in skin tissue is measured by amino acid analysis, and the data thus obtained are used as an indicator of the collagen production promoting effect, It means that the amount of hydroxyproline in is 1.2 to 2 times or more than the amount of hydroxyproline in the control region.

In the present invention, the collagen production promoter, the whitening agent or the external skin preparation can be used while emphasizing its own effect as the main effect. However, other components may be added thereto to alter or control the effect.

In the collagen production accelerator, whitening agent or external skin preparation, the amount of ascorbic acid derivative obtained by the production method according to the present invention mixed with these preparations is appropriately selected in view of the relationship with other components used in the degree or combination of desired effects. Can be. However, 0.01-30 mass% is good with respect to the whole quantity of a crude product, and 0.03-20 mass% is preferable.

In order to take advantage of the collagen production promoting effect and / or whitening effect, other additives (eg, known ingredients effective for skin aging, known ingredients effective for promoting collagen production and suppressing wrinkles, known whitening agents, etc.) may be added. have.

Of fruit such as tea extract, t-AMCHA, L-lysine, L-arginine, caffeine, tannin, verapamil, transsamine acid, transsamine acid derivative, hyaluronic acid, licorice extract, glabridine, quince, raspberry and avocado Hot water extract, white wine yeast extract, various Japanese and Chinese herbal medicines or extracts thereof, fragrance extract, tocopherol acetate, glycyrrhizin acid, glycyrrhizin derivative, arbutin, yeast (or malt), glucose, fructose, mannose, sucrose, trehalose , Phytoglycogen, retinoic acid, retinol, retinol acetate, retinol palmitate and the like can be mixed as an additive.

The biologically active substance mentioned later which can be used as a whitening agent can also be used in combination.

In addition, various base components may be added depending on the form or dosage form of the external preparation for skin.

Such a base component can be added according to various uses or purposes. Specific examples of the base component include liquid fats and oils, solid fats, waxes, ester oils, hydrocarbon oils, silicone resins, silicones, anionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants and BBs. Mild surfactants, lower alcohols, sterols, water soluble polymers, containment agents (e.g., disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, guruconic acid), neutralizing agents, pH adjusters, fungicides or Antifungal agents and flavorings may be listed.

When the ascorbic acid of the present invention is applied to the skin, other ingredients that can be generally used in the skin solvent can be mixed as long as the effects of the present invention are substantially impaired. Specific examples of ingredients used include Japanese Standards of Cosmetic Ingredients (JSCI), 2nd Edition, Annotation (1984), Yakuji Nippo , published by Yakuji Nippo, Ltd. and edited by Nippon Koteisho Kyokai. Ltd., published by Specifications of Ingredient Other Than Those Listed in JSCI (1993), Yakuji Nippo, Ltd., published by Examination Division, Pharmaceutical Affairs Bureau, Ministry of Health and Welfare. Published by Specification of Ingredient Other Than Those Listed in JSCI, Supplement (1993), Yakuji Nippo, Ltd. , administered by Affairs Bureau, Ministry of Health and Welfare, to Examination Division, Pharmaceutical Affairs Bureau, Ministry of Health and Welfare Drugs listed in The Comprehensive Licensing Standards of Cosmetics by Category (1993) and Niksho Chemicals' Kesho-hin Genryo Jiten (Handbook of Cosmetic Ingredients) (1991) .

Specific examples of materials or medicaments that can be added to the preparations according to the invention are listed below. These examples include oils, higher alcohols, fatty acids, infrared absorbers, powders, pigments, surfactants, polyhydric alcohols and sugars, polymers, biologically active ingredients, solvents, antioxidants, flavorings and disinfectants and the like. However, of course, what can be used for this invention is not limited to these.

(1) Specific example of oil

(Ester Type Oil Phase Component)

Triglyceryl 2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, butyl stearate, butyl Myristate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, Diisopropyl adipate, iso-arachyl neopentanoate, capryl-caprylic acid triglyceride, trimethylolpropane tri-2-ethylhexanoate, trimethyloffane triisostearate, pentaerythritol tetra-2-ethyl Hexanoate, cetyl caprylate, decyl laurate, hexyl laurate, decyl me State, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, isostearyl laurate, isotridecyl myristate, isocetyl myristate, isostearyl myristate, isocetyl Palmitate, isostearyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl oleate, octyldodecyl linoleate, isopropyl isostearate, cetostearyl 2-ethylhexanoate , Stearyl 2-ethylhexanoate, hexyl isostearate, ethylene glycol dioctanoate, ethylene glycol dioleate, propylene glycol dicaprate, propylene glycol di (caprylate / caprate), propylene glycol dicaprylate Neopentyl glycol dicaprate, neopentyl glycol dicap Octanoate, glyceryl tricaprylate, glyceryl triundecylate, glyceryl triisopalmitate, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate, octyl isono Nanoate, hexyldecyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglyserine oleate, polyglycerine isostearate, di Propyl carbonate, dialkyl carbonate (C12-18), triisocetyl citrate, triisoaralkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyl Decyl lactate, triethyl citrate, acetyltriethyl citrate, acetyltributyl citrate, trioctyl citrate , Diisostearyl maleate, 2-ethylhexyl hydroxystearate, 2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate, cholesteryl stearate, cholesteryl Isostearate, cholesteryl hydroxystearate, cholesteryl oleate, dihydrocholesteryl oleate, phytosteryl isostearate, phytosteryl oleate, isocetyl 12-stearoyl hydroxystearate Stearyl 12-stearoylhydroxystearate and isostearyl 12-stearoylhydroxystearate.

(Hydrocarbon type oil phase component)

Squalene, liquid paraffin, α-olefin oligomers, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax and petrolatum.

(Animal and vegetable oils, its cured oils, and waxes of natural origin)

Animal oils and cured oils thereof such as boiled oil, cured boiled oil, lard, cured lard, maloil, cured maloil, mink oil, orange rough oil, fish oil, cured fish oil and egg yolk oil; Avocado oil, almond oil, olive oil, cacao oil, apricot seed oil, coconut oil, sesame oil, wheat germ oil, rice germ oil, rice bran oil, safflower oil, shea butter, soybean oil, evening primrose oil, camellia Wood oil, corn oil, rapeseed oil, hardened seed oil, palm seed oil, hardened palm seed oil, palm oil, hardened palm oil, peanut oil, hardened peanut oil, castor oil, hydrogenated castor oil, sunflower oil, grape seed oil, jojoba oil, hardened jojoba Vegetable oils such as oil, macadamia nut oil, meadowfoam seed oil, cotton seed oil, hardened cotton seed oil, and hardened oils thereof; Waxes such as beeswax, high acid wax, lanolin, reduced lanolin, liquid lanolin, carnauba wax and montan wax.

(Silicone type oil phase component)

Dimethylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, methylhydrogenpolysiloxane, polyether modified organopolysiloxane, dimethylsiloxane, methylcetyloxysiloxane copolymer, dimethylsiloxane, methyl Stearoxysiloxane copolymers, alkyl-modified organopolysiloxanes, terminal modified organopolysiloxanes, dimethiconols, silicone gels, acrylic silicones, trimethylsiloxy silicic acid and silicone RTV rubbers.

(Fluorinated oil phase component)

Perfluoropolyethers, fluorine modified organopolysiloxanes, fluorinated pitches, fluorocarbons, fluoroalcohols and fluoroalkylpolyoxyalkylene-comodified organopolysiloxanes.

(2) Specific example of higher alcohol

Lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol, 2-ethylhexanol, hexadecyl alcohol and octyl dodecanol.

(3) Specific example of fatty acid

Caprylic acid, caprylic acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, palmilean acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, arachnic acid, arachidonic acid, behenic acid Lucanic acid and 2-ethylhexanoic acid.

(4) Specific examples of ultraviolet absorbers

Para-aminobenzoic acid, amyl para-aminobenzoate, ethyldihydroxypropyl para-aminobenzoate, glyceryl para-aminobenzoate, ethyl para-aminobenzoate, octyl para-aminobenzoate, octyldimethyl para-amino Benzoate, ethylene glycol salicylate, octyl salicylate, triethanolamine salicylate, phenyl salicylate, butylphenyl salicylate, benzyl salicylate, octyl para-methoxycinnamate, 2-ethylhexyl para- Methoxycinnamate, glyceryl mono-2-ethylhexanoate di-para-methoxycinnamate, isopropyl para-methoxycinnamate, diethanolamine para-methoxyhydrocinnamate, diisopropyl diiso Propyl cinnamic acid ester mixtures, urocanic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone, sulfonic acid and salts thereof, di Hydroxymethoxybenzophenone, sodium dihydroxymethoxybenzophenonedisulfonate, dihydroxybenzophenone, dihydroxydimethoxybenzophenone, hydroxyoctoxybenzophenone, tetrahydroxybenzophenone, butylmethoxydi Benzoylmethane, 2,4,6-trianilino-p- (carbo-2-ethylhexyl-1-oxy) -1,3,5-triazine, 2- (2-hydroxy-5-methylphenyl) Benzotriazole, methyl-O-aminobenzoate, 2-ethylhexyl-2-cyano-3,3-diphenylacrylate, phenylbenzimidazole sulfonic acid, 3- (4-methylbenzylidene) campo, isopropyl Dibenzoylmethane, 2-ethylhexyl 4- (3,4-dimethoxyphenylmethylene) -2,5-dioxy-1-imidazolidinepropionate and polymer derivatives and silane derivatives thereof.

(5) Specific examples of powders and pigments

Pigments such as Food Red 104, Food Red 201, Food Yellow 4, Food Blue 1 and Food Black 401; Lake pigments such as Food Yellow 4 AL lake and Food Yellow 203 BA lake; Polymers such as nylon powder, silk powder, urethane powder, silicone powder, polymethyl methacrylate powder, cellulose powder, starch, silicone elastomer spherical powder and polyethylene powder; Color pigments such as yellow iron oxide, red iron oxide, black iron oxide, chromium oxide, carbon black, ultramarine blue and royal blue; White pigments such as zinc oxide, titanium oxide and cerium oxide; Extender pigments such as talc, mica, sericite, kaolin and barium sulphate plates; Pearl pigments such as mica titanium; Metal salts such as barium sulphate, calcium carbonate, magnesium carbonate, aluminum silicate and magnesium silicate; Inorganic powders such as silica and aluminum; Metal soaps such as aluminum stearate, magnesium stearate, zinc palmitate, zinc myristate, magnesium myristate, zinc laurate and zinc undecyleneate; Bentonite; Smectite; And boron nitride.

The form (eg, spherical, bar, needle, plate, amorphous, scale, fusiform) and particle size of these powders are not particularly limited.

These powders are fluorine compound treatment, silicone treatment, silicone resin treatment, pendant treatment, salt coupling agent treatment, titanium coupling agent treatment, lubricant treatment, N-acylated lysine treatment, polyacrylic acid treatment, metal soap treatment, amino acid treatment, lecithin The surface may be treated in advance by conventionally known surface treatments such as treatment, inorganic compound treatment, plasma treatment and mechanochemical treatment, or may not be treated.

(6) Specific example of surfactant

(Anionic surfactant)

Fatty acid soaps, α-acyl sulfonates, alkyl sulfonates, alkylallyl sulfonates, alkylnaphthalene sulfonates, alkyl sulfates, POE alkyl ether sulfates, alkylamide sulfates, alkyl phosphates, POE alkyl phosphates, alkylamide phosphates, alkyls Roylalkyl taurine salts, N-acylamino acid salts, POEalkyl ether carbonates, alkyl sulfosuccinates, sodium alkylsulfoacetates, acylated hydrogenated collagen peptide salts and perfluoroalkyl phosphate esters.

(Cationic surfactant)

Alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide , Benzalkonium chloride, behenic acid aminopropyldimethyl hydroxypropylammonium chloride, diethylaminoethylamide stearate, dimethylaminoethylamide stearate, dimethylaminopropylamide stearate and lanolin derivatives quaternary ammonium salts.

(Amphoteric Surfactant)

Carboxybetaine type, amidobetaine type, sulfobetaine type, hydroxysulfobetaine type, amidosulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type and amidoamine type.

(Nonionic surfactant)

Propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE sorbitol fatty acid ester, POE glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE hydrogenated castor oil, POE castor Oils, POE PDP copolymers, POE PDP alkylethers, polyether modified silicone lauric acid alkanolamides, alkyl amine oxides and hydrogenated soybean phospholipids.

(Natural surfactant)

Lecithin, saponins and sugar based surfactants.

(7) specific examples of polyhydric alcohols and sugars

Ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerine, 3-methyl-1,3-butanediol, 1,3-butylene glycol, sorbitol, mannitol , Raffinose, erythritol, glucose, sucrose, fruit sugar, xylitol, lactose, maltose, maltitol, trehalose, alkylated trehalose, mixed isomerized sugars, sulfated trehalose and pullulan. Their chemically modified products can also be used.

(8) Specific Examples of Polymer Compounds

Acrylic ester / methacrylic acid ester copolymer (PLUS-SIZE from Go'o Kagaku KK), vinyl acetate / crotonic acid copolymer (resin 28-1310 from NSC), vinyl acetate / crotonic acid / vinyl neodecanoate copolymer Polymer (28-2930 from NSC), methylvinyl ether maleic acid half ester (GANTREZ ES from ISP), T-butyl acrylate / ethyl acrylate / methacrylic acid copolymer (RUBIMER from BASF), vinylpyrrolidone Vinyl acetate / vinyl propionate copolymer (RUBISCOL VAP from BASF), vinyl acetate / crotonic acid copolymer (RUBISET CA from BASF), vinyl acetate / crotonic acid / vinylpyrrolidone copolymer (RUBISET from BASF CAP), vinylpyrrolidone / acrylate copolymer (RUBIFLEX from BASF), acrylate / acrylamide copolymer (ULTRAHOLD from BASF), vinyl acetate / butyl maleate isoboroyl acrylate copolymer (I Anionic polymer compounds such as ADVANTAGE of SP product, carboxy vinyl polymer (CARBOLOL of BF Goodrich), and acrylic acid alkyl methacrylate copolymer (PAMUREN of BF Goodrich); Both acetic acid amphoteric compounds of dialkylaminoethyl methacrylate polymers (YUKAFORMER from Mitsubishi Chemical) and octylacrylamide acrylate / hydroxypropyl acrylate / butylaminoethyl methacrylate copolymers (AMPHOMER from NSC) Sex polymer compounds; Cationic polymers such as vinylpyrrolidone / dimethylaminoethyl methacrylate quaternary compound and methyl vinyl imidazolium chloride / vinylpyrrolidone copolymer (RUBICOTE from BASF); And nonionic polymer compounds such as polyvinylpyrrolidone / vinylacetate copolymer (RUBISCOL from BASF) and vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (COPOLYMER VC713 from ISP).

In addition, cellulose and its derivatives, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharides, xanthene gum, carrageenan, higher methoxyl pectin, lower methoxyl pectin, guar gum, gum arabin, crystalline cellulose Natural polymer compounds, such as arabino galactan, karaya gum, tragacanth gum, alginate, albumin, casein, cardrun, gellan gum and dextran, can also be preferably used.

(9) Specific examples of biologically active ingredients

The biologically active ingredient, when applied to the skin, may include a substance that can give any biological activity to the skin. Specific examples thereof include a whitening ingredient, an anti-inflammatory agent, an anti-aging agent, a sunscreen agent, a diet agent, a skin enhancer, an antioxidant, a hair regrowth agent, a hair growing agent, a moisturizer, a blood circulation promoter, a bactericide, a fungicide, a desiccant , Coolants, warming agents, vitamin compounds, amino acids, wound healing promoters, torpents, analgesics, cell activators and enzyme components.

Preferred examples of the ingredients to be mixed in this way, angelica extract, avocado extract, hydrangea flower extract, alcia extract, arnica extract, aloe extract, apricot extract, apricot nucleus extract, ginkgo extract, fennel extract, turmeric extract , Oolong Tea Extract, Rose Fruit Extract, Echinacea Mouth Extract, Thimble Root Extract, Yellow Bark Extract, Rhubarb Extract, Barley Extract, Hypericum Extract, White Nettle Extract, Watercress Extract, Orange Liquor, Sea Salt, Seaweed Extracts, hydrolyzed elastin, hydrolyzed wheat flour, hydrolyzed silk, chamomile extracts,

Carrot Extract, Euphorbia Extract, Licorice Extract, Sabdariffa Extract, Piracanta Pocheon Anna Fruit Extract, Kiwi Extract, Guina Extract, Cucumber Extract, Guanosine, Gardenia Extract, Camellia Extract, Red Ginseng Root Extract, Walnut Tree Extract, grapefruit extract, clematis extract, chlorella extract, mulberry bark extract, gentian extract, black tea extract, yeast extract, burdock extract, fermented rice bran extract, rice germ extract, comfrey extract, collagen, bilberry extract, spider leaf root extract, Bupleurum falcatum root extract, umbilical cord extract, sage extract, saponaria extract, bamboo grass extract, krategus extract, xanthoxylum fruit extract, shiitake mushroom extract, turmeric root extract, lithospermum root extract, perilla extract , Linden extract, filipendula extract, peony root extract, iris powder Extracts, Birch Extracts, Cactus Extracts, Ivy Extracts, Hawthorn Extracts, Black Elder Extracts, Yarrow Extracts, Peppermint Extracts, Sage Extracts, Mallow Extracts, Celestial Root Extracts, Sugar Extracts, Soybean Extracts, Jujube Extracts, Thyme extract, green tea extract, clove extract, cogon extract, citrus peel extract, angelica root extract, marigold extract, peach seed extract, bitter orange extract, buckwheat extract, tomato extract, natto extract, Ginseng extract, garlic extract, wild rose extract, hibiscus sabdariffa flower extract, ophiopogon tuber extract, parsley extract, honey, witch hazel extract, pellitory extract, isodonis Extract, Matricaria Extract, Loquat Extract, Coltsfoot Extract, Butterbur scape Extract Water, Bokryeong extract, butcher bloom extract, grape extract,

Beeswax, loofah extract, safflower extract, peppermint extract, linden extract, peony extract, hop extract, pine extract, horse chestnut extract, skunk garbage extract, sapindaceae extract, balm mint extract, peach extract, corn Flower extract, eucalyptus extract, saxifrage extract, citrus extract, yulmu extract, mugwort extract, lavender extract, apple extract, lettuce extract, lemon extract, chinese milk vetch extract, rose extract, rosemary extract, Roman chamomile extract and royal jelly extract may be enumerated.

Other examples include biopolymers such as deoxyribonucleic acid, mucopolysaccharide, sodium hyalurorenite, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan and hydrolyzed egg film; Moisture retention components such as amino acids, hydrolyzed peptides, sodium lactate, urea, sodium pyrrolidonecarboxylate, betaine, whey and trimethylglycine; Oil components such as sphingolipid, ceramide, phytosphingosine, cholesterol, cholesterol derivatives and phospholipids; anti-inflammatory agents such as ε-aminocaprophosphoric acid, glycyrrhizinic acid, β-glycirizinic acid, lysozyme chloride, guaiazlene and hydrocortisone;

Vitamins such as vitamin A, vitamin B ₂ , vitamin B ₆ , vitamin D, vitamin E, calcium pantothenate, biotin and nicotinic acid amide; Active ingredients such as allantoin, diisopropylamine dichloroacetate and 4-aminomethylcyclohexanecarboxylic acid; Antioxidants such as tocopherol, carotenoids, flavonoids, tannins, lignin and saponins; cellular activators such as α-hydroxy acid and β-hydroxy acid; blood circulation promoters such as γ-orizanol and vitamin E derivatives; Wound healing agents such as retinol and retinol derivatives; Whitening agents such as albumin, kojic acid, placental extract, sulfur, ellagic acid, linoleic acid, transsamic acid and glutathione; Separatin, Licorice Extract, Capsicum Tincture, Hinokithiol, Iodide Garlic Extract, Pyridoxine Hydrochloride, DL-α-Tocopherol, DL-α-Tocopheryl Acetate, Nicotinic Acid, Nicotinic Acid Derivative, Calcium Pantothenate, D-Pantothenyl Alcohols, acetyl pantothenylethyl ether, biotin, allantoin, isopropylmethylphenol, estradiol, ethynyl estradiol, capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, takanal, camphor , Salicylic acid, vanylylamide nonylate, vanylylamide nonanoate, pyrroctone olamine, glyceryl pentadecanoate, L-menthol, mononitroguaiacol, resorcinol, γ-aminobutyric acid, benzethium Chloride, Mexiletin Hydrochloride, Auxin, Feminine Hormone, Candida Tincture, Cyclosporine, Zinc Pyrithione, Hydrocrotisone, Minoxidil, Polyoxyethylene A hair restorer, such as Le monostearate, peppermint oil and buy Nishiki (SADANISHIKI) extract is listed.

(10) Specific examples of antioxidant

Sodium hydrogensulfite, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, tolyl biguanide, nordihydroguairetinic acid, parahydroxy anisole, butylhydroxy an Antioxidant effects such as sol, dibutylhydroxy toluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoids, flavonoids, tannins, lignin, saponins and apple extracts and clove extracts Plant extracts.

(11) Specific examples of solvents

Purified water, ethanol, lower alcohol, ether, LPG, fluorocarbon, N-methylpyrrolidone, fluoroalcohol, volatile linear silicone and next-generation freon (fluorocarbon, chlorofluorocarbon, CFC, etc.).

(Cosmetic composition)

In the cosmetic composition according to the present invention, an existing emulsifier or the like may be further added at a general concentration.

(Skin external preparation)

Skin external preparation according to the present invention, skin milk, skin cream, foundation cream, massage cream, cleansing cream, shaving cream, cleansing foam, skin lotion, lotion, pack, shampoo, conditioner, hair restorer, wool, hair dye, hair conditioner, toothpaste It may also be used as a cosmetic material such as gargle, permanent wave, ointment, bath and body soap.

(Cosmetic materials)

Skin external preparations according to the present invention and alcohols such as ethanol or propylene glycol; Preservatives such as methyl para-hydroxybenzoate, ethyl para-hydroxybenzoate, butyl para-hydroxybenzoate or propyl para-hydroxybenzoate; And a cosmetic material can be obtained by mixing purified water etc. However, the cosmetic material is not particularly limited to these specific examples.

Cosmetic materials according to the present invention include, for example, makeup cosmetics such as foundation, face powder, eye shadow, eyeliner, eyebrow, ball touch, lipstick and nail color; Basic cosmetics such as milk lotion, cream, lotion, calamine lotion, sun cream, sun tenant, after shave lotion, pre-shave lotion, pack, acne protection cosmetics and essences; Hair care cosmetics such as shampoo, conditioner, conditioner, hair color, hair tonic, hair setting agent, wool agent and permanent wave agent; Body powders, deodorants, hair loss agents, soaps, body shampoos, baths, hand wash soaps and perfumes. This invention can be used as each cosmetic material.

The shape of the cosmetic material according to the present invention is not particularly limited. The cosmetic material is conventionally known as a two-layer structure, water-in-oil emulsion, oil-in-water emulsion, gel, spray, mousse, oil, solid, sheet and powder form It may have a shape.

(Use of Ascorbic Acid Derivatives)

Ascorbic acid derivatives according to the present invention can be used as medicines, pesticides, animal medicines, food additives and feed additives. Since the content of the ascorbic acid derivative depends on the use, it can not be defined indiscriminately. However, the amount of use can be appropriately increased or decreased depending on the purpose and use. The required amount as ascorbic acid can be appropriately adjusted in accordance with the pharmacist method, the pesticide control method, the regulation rules such as animal medicine, and the food hygiene method.

EXAMPLE

The invention is explained in more detail with reference to the following examples. However, the present invention is not limited to these.

Example A-1

L-ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt:

In 500 g of 95% sulfuric acid, 131 mmol (36 g) of 2-hexyldecanoic acid was dissolved at 40 ° C. To the obtained solution, 146 mmol (50 g) of L-ascorbic acid-2-phosphate sodium salt was added and stirred uniformly for 6 hours. The mixture thus obtained was left at room temperature for 24 hours, and then the reaction mixture was poured into 780 g of ice water, and the obtained precipitate was extracted with 590 g of methyl-tert-butyl ether. 590 g of 13% brine was added to the obtained ether solution, followed by 20% aqueous sodium hydroxy solution until the pH was about 8. The methyl-tert-butyl ether layer was separated with a separatory funnel, and 300 g of methanol was added to the methyl-tert-butyl ether layer to precipitate a precipitate. The precipitate was separated by centrifugation, washed with a small amount of methanol and dried under reduced pressure to obtain 21 g of a powdered L-ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt. (Yield 27%).

The structure was confirmed by nuclear magnetic resonance spectra.

¹ H NMR (270 MHz, D ₂ O; ¹ H NMR apparatus, trade name; JNM-EX270 from Nihon Denshi KK (JEOL LTD.)) Δ:

0.89 ppm (t, 6H, J = 6.6 Hz), 1.30-1.63 (b, 24H), 2.45 (hep, 1H, J = 6.6 Hz), 4.20-4.35 (m, 3H), 4.47 (s, 1H)

¹³ C NMR (67.8 MHz, D ₂ O; ¹³ C NMR apparatus, trade name; JNM-EX270 from Nihon Denshi KK) δ:

16.4 ppm (s, 1C), 25.0 (s, 1C), 25.2 (s, 1C), 29.4 (s, 1C), 29.6 (s, 1C), 31.5 (s, 1C), 31.9 (s, 1C), 32.1 (s, 1C), 34.0 (s, 1C), 34.5 (s, 1C), 47.6 (s, 1C), 67.6 (s, 1C), 69.6 (s, 1C), 80.8 (s, 1C), 115.3 (d, 1C, J = 7.3 Hz), 178.2 (s, 1C), 179.4 (s, 1C), 180.4 (s, 1C)

³¹ P NMR (109 MHz, D ₂ O; ³¹ P NMR apparatus, trade name; JNM-EX270 from Nihon Denshi KK, mfd.) Δ: 4.3 ppm

<Example A-2>

L-ascorbic acid-2-phosphate-6- (2'-n-heptyl undecanoate) sodium salt:

Powder-like L was carried out in the same manner as in Example A-1, except that 2-n-heptylundecanoic acid according to the present invention was used instead of 2-hexyldecanoic acid used in Example A-1. 16 g of ascorbic acid-2-phosphate-6- (2'-n-heptyl undecanoate) sodium salt was obtained.

The structure was confirmed by nuclear magnetic resonance spectra.

¹ H NMR (270 MHz, D ₂ O) δ:

0.89 ppm (t, 6H, J = 6.6 Hz), 1.30-1.63 (b, 24H), 2.43 (hep, 1H, J = 6.3 Hz), 4.18-4.36 (m, 3H), 4.57 (s, 1H)

¹³ C NMR (67.8 MHz, D ₂ O) δ:

16.5 ppm (s, 1C), 25.2 (s, 1C), 25.3 (s, 1C), 29.5 (s, 1C), 29.6 (s, 1C), 31.6 (s, 1C), 31.9 (s, 1C), 32.1 (s, 1C), 32.3 (s, 1C), 33.9 (s, 1C), 34.4 (s, 1C), 34.6 (s, 1C), 47.5 (s, 1C), 67.2 (s, 1C), 69.4 (s, 1C), 80.3 (s, 1C), 115.8 (d, 1C, J = 6.1 Hz), 173.8 (s, 1C), 178.3 (d, 1C, J = 3.7 Hz), 179.9 (s, 1C)

³¹ P NMR (109 MHz, D ₂ O) δ: 4.1 ppm

<Experimental Example A-1>

The L-ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt obtained in Example A-1 was dissolved in purified water to a concentration of 2% by mass, and the solution thus obtained was glass with a lid. Pour into bottle and leave at 40 ° C. (under light blocking conditions) for 10 days. The residual rate of the compound after storage was analyzed using high performance liquid chromatography equipped with Shodex (registered trademark of Showa Denko K.K) SB802.5HQ (manufactured by Showa Denko K.K).

(Measurement conditions of high performance liquid chromatography)

Column: Shodex (registered trademark of Showa Denko K.K.) OHpak SB802.5HQ

Temperature: 40 ℃

Eluent: 0.03M Na ₂ SO ₄ + 0.03M

H ₃ PO ₄ / tetrahydrofuran = 1: 2

Flow rate: 0.5ml / min

Injection volume: 20 μL

Detection: UV 270nm

<Experimental Example A-2>

L-ascorbic acid-2-phosphate-6- (obtained from Example A-2 instead of L-ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt obtained in Example A-1 Stability experiment was performed by the same method as Experimental Example A-1 except using 2'-n-heptyl undecanoate).

<Comparative Example A-1>

The method described in Patent Document 5 (JP-A-10-298174) instead of the L-ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt obtained in Example A-1 Stability experiments were carried out in the same manner as in Experimental Example A-1, except for using the prepared L-ascorbic acid-2-phosphate-6-palmitic acid ester sodium salt.

<Comparative Example A-2>

L-ascorbic acid-2-phosphate sodium salt having excellent stability instead of L-ascorbic acid 2-phosphate-6- (2'-hexyldecanoate) sodium salt obtained in Example A-1 (manufactured by Showa Denko KK) Except for using), the stability experiment was carried out in the same manner as in Experimental Example A-1.

The results obtained in the above Examples, Comparative Examples, and Experimental Examples are all shown in Table 1 below.

Ascorbic acid derivatives Survival rate (%) Example A-1 L-ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt 95.3 Example A-2 L-ascorbic acid-2-phosphate-6- (2'-n-heptyl undecanoate) sodium salt 95.5 Comparative Example A-1 L-ascorbic acid-2-phosphate-6-palmitic acid ester sodium salt 88.6 Comparative Example A-2 L-ascorbic acid-2-phosphate sodium salt 96.9

Prescription examples of cosmetic ingredients are shown below. In the present embodiment, "%" means mass%.

[Prescription A-1]

Cream (1):

1.0% condensed hexaglyceryl ricinolate

Particulate Titanium Oxide 5.0%

2-octyldodecyl pivalate 8.0%

Glyceryl Tri (Caprylate-Caprate) 3.0%

Methylphenylpolysiloxane 7.0%

Decamethylcyclopentasiloxane 2.0%

Setanol 2.0%

2-ethylhexyl para-methoxycinnamate 6.0%

4-tert-butyl-4-methoxybenzoylmethane 2.0%

Decaglyceryl Monoisostearate 3.0%

Xanthan Gum 0.3%

L-ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt 4.0%

Purified water to make the total amount 100%

[Prescription A-2]

Cream (2):

1.0% condensed hexaglyceryl ricinolate

2-octyldodecyl pivalate 8.0%

Glyceryl Tri (Caprylate-Caprate) 3.0%

Methylphenylpolysiloxane 7.0%

Decamethylcyclopentasiloxane 2.0%

Setanol 2.0%

Decaglyceryl Monoisostearate 3.0%

Xanthan Gum 0.3%

L-ascorbic acid-2-phosphate-6- (2'-n-heptyl undecanoate) sodium salt 4.0%

Purified water to make the total amount 100%

[Prescription A-3]

Skin lotion:

L-ascorbic acid-2-phosphate-6- (2'-n-heptyl undecanoate) sodium salt 4.0%

Citric Acid 0.016%

Sodium Citrate 2.0%

1,3-butylene glycol 3.0%

Ethanol 3.0%

Purified water to make the total amount 100%

(Manufacturing method)

The components were dissolved in purified water under heating at 50 ° C. and the resulting solution was cooled under stirring. Subsequently, when temperature reached 30 degreeC, the said stirring was stopped and the solution thus obtained was left to stand.

[Prescription A-4]

Milky Lotion:

L-ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt 4.0%

Glycerin 8.0%

Butylene Glycol 2.0%

Hydrogenated Lecithin 0.1%

Sodium Hyaluronate 0.05%

Hydroxyethyl cellulose 0.3%

Xanthan Gum 0.3%

Sodium Citrate 1.0%

Polyethylene Glycol-50 Hydrogenated Castor Oil 0.5%

Methylparaben 0.2%

Purified water to make the total amount 100%

[Manufacturing method]

Under heating to 80%, the above components except for L-ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt were dissolved in purified water and the resulting solution was cooled under stirring. Subsequently, L-ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt is gradually added to the obtained solution at 50 ° C under stirring, and when the temperature reaches 40-35 ° C, the stirring is performed. It stopped and the solution thus obtained was left to stand.

Example B-1

40 μL of solution obtained by dissolving each of the substances (1) to (3) tested in Dulbecco PBS (-) on the surface of a human skin tissue three-dimensional model (trade name: TESTSKIN LSD-d, manufactured by Toyobo Co., Ltd.). The resulting skin tissue model was incubated at 37 ° C. in the presence of 5% CO ₂ for 2 hours. Subsequently, the experimental solution was removed by aspiration, and then the skin tissue model was incubated for 2 hours, 6 hours and 12 hours, respectively, at 37 ° C. in the presence of 5% CO ₂ .

Each part of the skin model collected at each incubation time was washed with Dulbecco PBS (-), perforated using a perforator having a diameter of 6 mmφ and homogenized in HEPES buffer (pH7.2). Got it. By using the homogenate thus obtained, the amount of ascorbic acid contained in the skin model was quantitatively analyzed using high performance liquid chromatography. Protein content in the skin model was analyzed quantitatively using the Lowry method.

1) 2% ascorbic acid-2-phosphate sodium salt

2) 0.5% ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt

3) 0.5% ascorbic acid-2-phosphate-6- (2'-n-heptyl undecanoate) sodium salt

High Performance Liquid Chromatography

<Ascorbic acid>

Column: Shodex (registered trademark of Showa Denko K.K.) Asahipak NH2P-50 4E

Temperature: 40 ℃

Eluent: acetonitrile: 60 mM H ₃ PO ₄ = 80:20

Flow rate: 0.8ml / min

Detection: UV 245nm

As a result, the amount of ascorbic acid (unit: nmol / mg skin protein) at each incubation time is as follows.

2 hours after incubation 6 hours after incubation 12 hours after incubation

1) 30 24 5

2) 6 10 23

3) 5 11 26

As apparent from the above results, the ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt or 0.5% ascorbic acid-2-phosphate-6- (2'-n-heptyl undecanoate When sodium salts were administered to the skin model, it was confirmed that the concentration of ascorbic acid in the tissues was easily and effectively enhanced over a long period of time immediately after administration, thereby providing an effective concentration for accelerating collagen synthesis.

Example B-2

1) to 3) The collagen synthesis promoting effect of the test substance was compared with each other using a guinea pig model having a cut wound. The base material for dissolving each test substance was purified water containing 20% ethanol and 3% propylene glycol.

1) 2% ascorbic acid-2-phosphate sodium salt

2) 1% ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt

3) 1% ascorbic acid-2-phosphate-6- (2'-n-heptyl undecanoate) sodium salt

In this experiment, two vane wounds each having a length of 2 cm were formed on the back using a scalpel so as to be symmetrically positioned with respect to the center of the back of the guinea pig. Thereafter, 0.2 ml of the test substance solution was administered thereto twice a day for 4 days. After the last administration was completed, 2 cm x 2 cm (square) skin pieces were symmetrically removed from the back of the guinea pig so that the cut wound was substantially positioned at the center of the skin piece. Thereafter, the tension required for separation of the vane wound skin was measured. Five guinea pigs were used for one test substance.

After the measurement of the tension, the vane wound portion is included and the skin portion is removed from the skin piece such that it has a width of 5 mm (ie, the skin portion thus obtained has a total width of 10 mm) on both sides of the vane wound portion. Was taken. The obtained skin part was homogenized in 0.5M acetic acid to obtain homoginate. A mixture of diethyl ether-ethanol (volume ratio = 1: 3) per volume of the homogenate solution was added in two volumes, mixed under stirring, and the solvent layer was removed after centrifugation. Pepsin (manufactured by Waco Pure Chemical Industries, Ltd.) was added to the obtained solvent layer and reacted with the solvent layer at 15 ° C. for 16 hours. After separation by centrifugation, the obtained supernatant was lyophilized. The protein content of the skin sample thus obtained was hydrolyzed by hydrochloric acid and subjected to amino acid analysis using an AccQTag Amino acid Analyzer (manufactured by Waters Co.).

The results of the measurement of the separation tension of the vane wound portion to which each test substance was applied and its hydroxypyrroline content are as follows. Here, the hydroxypyrroline is a substance that can be used as an index of collagen.

Separation Tension Hydroxypyrroline Content

(g / cm) (nmol / skin moisture weight)

1) 123 32.1

2) 181 38.5

3) 187 37.6

As apparent from the above results, ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt or ascorbic acid-2-phosphate-6- (2'-n-heptyl undecanoate) sodium, respectively Has been found to have an effect of accelerating collagen synthesis and promote recovery of cut wound skin.

[Prescription B-1]

Skin lotion

Ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt 2.0%

Citric Acid 0.016%

Sodium Citrate 2.0%

1,3-butylene glycol 3.0%

Ethanol 3.0%

Purified water to make the total amount 100%

(Manufacturing method)

Under warming at 50 ° C., the components were dissolved in purified water and the resulting mixture was cooled under stirring. When the temperature of the mixture reached 30 ° C., stirring was stopped and the mixture was left to stand.

[Prescription B-2]

Skin lotion

Ascorbic acid-2-phosphate-6- (2'-n-heptyl undecanoate) sodium salt 2.0%

Citric Acid 0.016%

Sodium Citrate 2.0%

1,3-butylene glycol 3.0%

Ethanol 3.0%

Purified water to make the total amount 100%

(Manufacturing method)

Under warming at 50 ° C., the components were dissolved in purified water and the resulting mixture was cooled under stirring. When the temperature of the said mixture reached 30 degreeC, stirring was stopped and the mixture was left to stand.

[Prescription B-3]

cream:

Ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt 2.0%

Setanol 5.0%

Cyclomethicone 4.0%

Cetyl Octanoate 4.0%

Trioctanoine 2.0%

Palmityl Alcohol 1.0%

Dimethicone 0.3%

Butylene Glycol 7.0%

Hydrogenated Lecithin 1.0%

Myristic Acid Polyglyceryl-10 1.0%

Sodium Citrate 2.0%

Methyl Paraben 0.15%

Propyl Paraben 0.05%

Xanthan Gum 0.1%

Purified water to make the total amount 100%

(Manufacturing method)

Under heating at 80 ° C., the components (except ascorbic acid-2-phosphate-6- (2′-hexyldecanoate) sodium salt) were dissolved in purified water and the resulting mixture was cooled under stirring. At 50 ° C., ascorbic acid-2-phosphate-6- (2′-hexyl decanoate) sodium salt was slowly added to the mixture. When the temperature of the mixture reached 35 to 30 ° C, the agitation was stopped and the mixture was left to stand.

[Prescription B-4]

cream:

Ascorbic Acid-2-Phosphate-6- (2'-n-hetyldecanoate) Sodium Salt 2.0%

Setanol 5.0%

Cyclomethicone 4.0%

Cetyl Octanoate 4.0%

Trioctanoine 2.0%

Palmityl Alcohol 1.0%

Dimethicone 0.3%

Butylene Glycol 7.0%

Hydrogenated Lecithin 1.0%

Myristic Acid Polyglyceryl-10 1.0%

Sodium Citrate 2.0%

Methyl Paraben 0.15%

Propyl Paraben 0.05%

Xanthan Gum 0.1%

Purified water to make the total amount 100%

(Manufacturing method)

The components (except ascorbic acid-2-phosphate-6- (2′-n-heptyl undecanoate) sodium salt) were dissolved in purified water under heating at 80 ° C. and cooled under stirring of the resulting mixture. At 50 ° C., ascorbic acid-2-phosphate-6- (2′-n-heptyl undecanoate) sodium salt was slowly added to the mixture. When the temperature of the mixture reached 35 to 30 ° C, the agitation was stopped and the mixture was left to stand.

[Prescription B-5]

Milky Lotion:

L-ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt 2.0%

Glycerin 8.0%

Butylene Glycol 2.0%

Hydrogenated Lecithin 0.1%

Sodium Hyaluronate 0.05%

Hydroxyethyl cellulose 0.3%

Xanthan Gum 0.3%

Sodium Citrate 1.0%

Polyethylene Glycol-50 Hydrogenated Castor Oil 0.5%

Methylparaben 0.2%

Purified water to make the total amount 100%

(Manufacturing method)

Under heating at 80 ° C., the components except for L-ascorbic acid-2-phosphate-6- (2′-hexyldecanoate) sodium salt were dissolved in purified water and the resulting solution was cooled under stirring. Thereafter, L-ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt was slowly added to the solution obtained at 50 ° C under stirring, and the stirring was stopped when the temperature reached 40-35 ° C. The solution thus obtained was left to stand.

[Prescription B-6]

Milky Lotion:

L-ascorbic acid-2-phosphate-6- (2'-heptyl undecanoate) sodium salt 2.0%

Glycerin 8.0%

Butylene Glycol 2.0%

Hydrogenated Lecithin 0.1%

Sodium Hyaluronate 0.05%

Hydroxyethyl cellulose 0.3%

Xanthan Gum 0.3%

Sodium Citrate 1.0%

Polyethylene Glycol-50 Hydrogenated Castor Oil 0.5%

Methylparaben 0.2%

Purified water to make the total amount 100%

(Manufacturing method)

Under heating at 80 ° C., the components except for L-ascorbic acid-2-phosphate-6- (2′-heptyl undecanoate) sodium salt were dissolved in purified water and the resulting solution was cooled under stirring. Thereafter, L-ascorbic acid-2-phosphate-6- (2'-heptyl undecanoate) sodium salt was slowly added to the solution obtained at 50 ° C under stirring, and the stirring was stopped when the temperature reached 40-35 ° C. The solution thus obtained was left to stand.

Example C-1 (Whitening)

The quantity of the composition in the Example shown below is described with respect to mass% (wt.%).

Lotion (1)

The components 1) to 4) were uniformly dispersed and dissolved in the following final concentrations. The obtained mixture was added to component 5) under stirring to obtain a lotion (1).

1) ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt 2.00

2) ethanol 5.00

3) Propylene Glycol 5.00

4) methyl para-hydroxy benzoate 0.20

5) Purified Water 87.8

Lotion (2)-(4)

The lotions (2) to (4) were prepared in the same manner as the preparation of the lotion 1, except that the following components were each used in the same concentration instead of the component (1) of the lotion (1).

Lotion (2):

Ascorbic acid-2-phosphate-6- (2'-n-heptyl undecanoate) sodium salt

Lotion (3) (Comparative):

Ascorbic acid-2-phosphate sodium salt

Lotion (4) (Voice Control):

Purified water

In each of the lotions, the components were dissolved uniformly, and all of the lotions showed excellent stability over time.

Example C-2

Lotion (5)

The components 1) to 4) were uniformly dispersed and dissolved in each other so as to have the following final concentrations. The obtained mixture was added to component 5) under stirring to obtain a lotion (5).

1) ascorbic acid-2-phosphate-6- (2'-hexyldecanoate) sodium salt 0.10

2) ethanol 5.00

3) Propylene Glycol 5.00

4) methyl para-hydroxy benzoate 0.20

5) Purified water 89.7

Lotion (6)-(8)

The lotions 6 to 8 were prepared in the same manner as in the preparation of the lotion 5, except that the following components were used at the same concentrations instead of the component 1 of the lotion 5, respectively.

Lotion (6):

Ascorbic acid-2-phosphate-6- (2'-n-heptyl undecanoate) sodium salt

Lotion (7) (Comparative):

Ascorbic acid-2-phosphate sodium salt

Lotion (8) (Voice Contrast):

Purified water

In each of the lotions, the components were dissolved uniformly, and the lotions all exhibited good stability over time.

Example C-3

Gel external preparations (1)

The following component 1) was uniformly dispersed in the following component 2) to the following final concentration, and the obtained mixture was added to the component 3) under stirring to obtain the intended gel external preparation (1).

1) ascorbic acid-2-phosphate-6- (2'-hexyl decanoate) sodium salt 10

2) glycerol 20

3) octyl dodecyl myristate 70

Gel external preparations (2) to (4)

Gel external preparations (2) to (4) were produced by the same method as the preparation of the gel external preparation (1), except that each of the following components was used at the same concentration instead of the component (1) of the gel formulation (1). It was.

Gel Form (2):

Ascorbic acid-2-phosphate-6- (2'-n-heptyl undecanoate) sodium salt

Gelling Agent (3) (Comparative Control):

Ascorbic acid-2-phosphate sodium salt

Gelling agent (4) (negative control):

Purified water

In each of the gel external preparations, the components were dissolved uniformly, and all of the gel external preparations showed excellent stability over time.

Example C-4

(Effect of prevention of coloring)

Thirty seven-week-old male Wizer-Maple guinea pigs (MW, SPF) hairs were shaved using an electric hair clipper (0.05 mm blade), and then the skin was shaved using an electric shaver. The back skin was then covered with back skin with an adhesive stretchable bandage (outside covered with aluminum foil) having four open windows each having a size of 1.5 cm x 1.5 cm. For each window, ten lotions (1) to (8) and gel external preparations (1) to (4) prepared in Examples C-1 to C-3 were sequentially applied in amounts of 0.05 ml, respectively. After 4 hours of application of the crude product, the application site was washed with water using cotton wool soaked with water and then dried. Subsequently, each animal was fixed with a captive device, and each part was treated with a UV-irradiation device (Toshiba FL40S / E30 fluorescent lamp equipped with six SE lamps, manufactured by Shinano Seisakusho) at a distance of about 10 cm at 300 mJ / cm ² . It was irradiated with medium wavelength ultraviolet (UVB) radiation. After the irradiation, each of the lotions (1) to (8) and the gel external preparations (1) to (4) was reapplied to each of the above portions in an amount of 0.05 ml.

This operation was repeated after 3 days. After 14 days from the last irradiation, the degree of coloring obtained was measured according to the evaluation criteria by the following ratings. In addition, the light intensity of the skin was measured using a color difference meter (MINOLTA, CR-20) with respect to the four corners and the central part (total 5 parts) of each administration / irradiation site. For each preparation, the effect of anti-coloring was evaluated from the average of the ratings (10 data for each preparation) and the average of the brightness (50 data for each preparation).

Evaluation criteria of coloring

No coloring confirmed: 0

Slight staining confirmed: rating 1

Low degree of pigmentation found: rating 2

Moderate coloring confirmed: rating 3

High degree of pigmentation confirmed: rating 4

Results (average)

Preparation grade magnitude

Lotion (1) 0.8 63.0

Lotion (2) 1.0 61.1

Lotion (3) 2.1 61.8

Lotion (4) 3.0 59.5

Lotion (5) 2.0 61.7

Lotion (6) 2.2 62.1

Lotion (7) 3.0 59.9

Lotion (8) 3.0 60.1

Gel external preparation (1) 0.5 63.5

Gel external preparation (2) 0.8 62.8

Gel external preparations (3) 1.2 62.1

Gel external preparations (4) 3.0 59.9

As described above, it was confirmed that both the lotion and the gel external preparation containing the ascorbic acid derivative according to the present invention exhibited an excellent effect of preventing coloration.

Example C-5

(Effect of removing pigmentation)

Thirty six-week-old male Wizer-Maple guinea pigs (MW, SPF) were trimmed with an electric hair clipper (0.05 mm blade) and shaved on the skin using an electric shaver. The back skin was covered with an adhesive stretchable bandage (Silky-tex, outside coated with aluminum foil) having four open windows each having a size of 1.5 cm x 1.5 cm. Subsequently, each animal was fixed with a captive device, and each part was subjected to an ultraviolet-irradiation device (Toshiba FL40S / E30 fluorescent lamp equipped with six SE lamps, manufactured by Shinano Seisakusho) at a distance of about 750 mJ / cm ² . It was irradiated with medium wavelength ultraviolet (UVB) radiation. From 4 days after irradiation to 28 days after irradiation, the lotions (1) to (8) and gel external preparations prepared in Examples C-1 to C-3 twice a day (morning and evening) for each window ( 1) to (4) were applied sequentially to 10 sites in an amount of 0.05 ml. After 28 days from the last irradiation, the degree of coloring obtained was measured in accordance with the evaluation criteria based on the ratings in the same manner as in Example C-4. For each preparation, the effect of color removal was evaluated from the mean of the ratings (10 data for each formulation).

Results (average)

Preparation grade

Lotion (1) 2.2

Lotion (2) 2.4

Lotion (3) 3.3

Lotion (4) 3.5

Lotion (5) 2.9

Lotion (6) 3.0

Lotion (7) 3.5

Lotion (8) 3.8

Gal type external preparation (1) 2.2

Gel external preparations (2) 2.5

Gel external preparations (3) 2.9

Gel external preparations (4) 3.5

As described above, it was confirmed that both the lotion and the gel external preparation containing the ascorbic acid derivative according to the present invention exhibit an obvious effect of color removal.

<Example D-1>

43 mass% squid mill, 15 mass% lobster (or shrimp) mill, 10 mass% fish mill, 10 mass% natural (unrefined) fish oil (Nippon Suisan KK), 10 mass% Brewer's yeast, 3% by weight active gluten, 2% by weight starch, 2% by weight ascorbic acid-2-phosphate-6- (2'-hexyl decanoate) sodium salt prepared in Example A-1 and 5 kg of the base component containing 5% by mass of the mineral mixture were mixed. Then, the moisture content of the mixture thus obtained was adjusted to 45%. The mixture was extruded using an extruder so that the product temperature was 115 ℃, and then dried in a dryer to a water content of about 10% to obtain particles of the feed component.

<Comparative Example D-1>

Particles of the feed ingredient were prepared in the same manner as in Example D-1, except that ascorbic acid-2-phosphate-6- (2'-hexyl decanoate) sodium salt was not used.

<Comparative Example D-2, Example D-3>

Breeding experiments were conducted using rainbow trout. Twenty rainbow trout (average fish weight: 0.79 kg) were prepared and housed in two compartments of a circulation and filtered water tank to accommodate ten trout in each compartment. For these rainbow trout, breeding experiments were conducted using the feed ingredients prepared in Example D-1. Here, the feed ingredient prepared in Comparative Example D-1 was fed to the control experimental compartment. The water temperature at the time of breeding was 18 ° C., and the feed rate was set at 4% per fish weight. After the completion of the breeding experiment, all 10 fish were taken out and the fish weight was measured. For the rainbow trout in the experimental zone, the average fish weight was 0.85 kg, and the average fish weight in the control zone was 0.82 kg.

From the above results, the effect of ascorbic acid 2-phosphate-6- (2'-hexyl decanoate) sodium salt according to the present invention was confirmed.

<Example E-1>

25 g of beeswax (melting point 60 ° C, manufactured by Noda wax Co., Ltd.) was added to 1 kg of egg yolk lecithin (trade name "PL-30", product of Kewpie Co., Ltd., PC content about 25%) The mixture was stirred under warming at about 70 ° C. until a uniform mixture. The conditions were maintained for 5 minutes and then cooled. Next, 25 g of ascorbic acid-2-phosphate-6- (2'-hexyl decanoate) sodium salt prepared in Example A-1 was added, and the obtained mixture was stirred until it became a homogeneous mixture. Got it. On the other hand, a mixture obtained by sufficiently mixing 2 kg of gelatin, 1 kg of glycerol and 1.5 kg of water was molded into a sheet. Two gelatine sheets thus formed were set in a rotary capsule forming machine and injected in an amount of 300 mg per capsule of the mixture. The inlet of each capsule was sealed under pressure and 3500 capsules were made.

The novel ascorbic acid derivatives prepared by the production method according to the present invention are easy to bind vertically, and therefore can increase the concentration of ascorbic acid in the cells even when administered in small amounts. In addition, the ascorbic acid derivatives have improved storage stability compared to conventional ascorbic acid derivatives. Therefore, the ascorbic acid derivative according to the present invention can be widely used in various preparations such as vitamin C preparations, external skin preparations, medicines, pesticides, animal medicines, food additives, and feed additives containing ascorbic acid derivatives as active ingredients.

In addition, when the ascorbic acid derivative according to the present invention is added to cosmetics such as an anti-wrinkle agent, the ascorbic acid derivative has an excellent effect of promoting collagen synthesis and an excellent effect of inhibiting collagen degradation, resulting in skin shape with age. Can be prevented or improved. Therefore, the ascorbic acid derivative of the present invention can be widely used in medicine, quasi-drugs, cosmetics and the like.

Claims (19)

An ascorbic acid derivative, which is a compound represented by the following general formula (1) or a salt thereof. (Wherein X and Y each represent a protecting group of H or OH, R ¹ and R ² each represent an alkyl group having 1 to 19 carbon atoms which may be linear or branched, respectively, and the carbon atoms of R ¹ and R ² The total number is an integer from 5 to 22.) The ascorbic acid derivative according to claim 1, which is at least one metal salt selected from the group consisting of alkali metals, alkaline earth metals, aluminum, iron, zinc and bismuth. The ascorbic acid derivative according to claim 1, which is a salt with ammonia, monoethanolamine, diethanolamine, triethanolamine, dicyclohexylamine or 2-amino-1-methylpropanol. The ascorbic acid derivative according to claim 1, wherein the total number of carbon atoms in R ¹ and R ² of the general formula (1) is an integer of 8 to 18. The ascorbic acid according to claim 4, wherein R ¹ and R ² in the general formula (1) are linear alkyl groups, and the total number of carbon atoms in the linear alkyl groups of R ¹ and R ² is 14 or 16. derivative. The compound of claim 5, wherein in formula (1), R ¹ is nC ₉ H ₁₉ and R ² is nC ₇ H ₁₅ ; Or ascorbic acid derivative wherein R ¹ is nC ₈ H ₁₇ and R ² is nC ₆ H ₁₃ . Reacting a compound represented by the following general formula (2) and / or a salt thereof with at least one selected from fatty acids, fatty acid salts, fatty acid esters, fatty acid halides and / or fatty acid anhydrides; The manufacturing method of the ascorbic acid derivative in any one of Claims 1-6. Where X and Y each represent a protecting group of H or OH. The process for producing an ascorbic acid derivative according to claim 7, wherein said reaction is carried out in the presence of a condensing agent and / or a dehydrating agent. The method of claim 8, wherein the dehydrating agent is sulfuric acid. 8. The method of claim 7, wherein the reaction is carried out in a solvent selected from the group consisting of water, acetone, dioxane, toluene, ethylbenzene, methyl-tert-butyl ether and sulfuric acid. A vitamin C preparation comprising ascorbic acid derivative according to any one of claims 1 to 6 as an active ingredient. A collagen production promoter comprising the ascorbic acid derivative according to any one of claims 1 to 6 as an active ingredient. A whitening agent comprising ascorbic acid derivative according to any one of claims 1 to 6 as an active ingredient. The external preparation for skin comprising the ascorbic acid derivative according to any one of claims 1 to 6 as an active ingredient. The external preparation for skin according to claim 14, which contains ascorbic acid-2-phosphate ester and / or salts thereof. The external preparation for skin according to claim 14, which contains sodium salt, potassium salt, manganese salt or zinc salt of ascorbic acid-2-phosphate ester. A cosmetic material comprising the external preparation for skin according to claim 14. A composition comprising the ascorbic acid derivative according to any one of claims 1 to 6 in the form of a medicament, pesticide or animal drug. A composition comprising the ascorbic acid derivative according to any one of claims 1 to 6 in the form of a food or feed additive.