JP2007320858A - Composition containing ascorbic acid 2-phosphate derivative - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition having remarkably improved stability of a specific ascorbic acid 2-phosphate among ascorbic acid derivatives and exhibiting excellent skin whitening effect and wrinkle preventing and ameliorating effect. <P>SOLUTION: The external preparation for skin comprises a composition obtained by producing a composition comprising a specific ascorbic acid 2-phosphate derivative, a nonionic surfactant and water or a composition comprising a specific ascorbic acid 2-phosphate derivative, a nonionic surfactant, an oil component and water and mixing the produced composition with a bivalent or multivalent metal salt or its aqueous solution. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

The present invention contains an ascorbic acid-2-phosphate ester derivative represented by the formula (1), dramatically improves the stability of the compound, and is particularly excellent in a whitening effect and a wrinkle prevention improving effect. Relates to the composition.

Ascorbic acid and various derivatives thereof are known as compounds showing efficacy effects such as a whitening action, an antioxidant action, and a collagen synthesis promoting action, and are incorporated in pharmaceuticals, cosmetics and the like.

In particular, among the ascorbic acid derivatives, a compound in which the hydroxyl group at the 2-position of ascorbic acid is phosphorylated and the hydroxyl group at the 6-position is esterified with a higher fatty acid has a high affinity for living organisms and is useful for living tissues such as skin. The transition is quick and is expected to be applied to pharmaceuticals and cosmetics.

However, this higher fatty acid ester of ascorbic acid-2-phosphate and / or its salt was not satisfactory in stability in the preparation.

In a skin external preparation containing a salt of a higher fatty acid ester of ascorbic acid-2-phosphate, the pH is adjusted to 7 to 9, thereby suppressing degradation of the ester salt in the agent and stability. A skin external preparation with improved solubility is known (see Patent Document 1). Furthermore, it is also known to improve stability by using in combination with higher alcohol and emulsifying (see Patent Document 2).
JP 2003-176217 A JP 2005-187465 A

However, further stabilization has been demanded for ascorbic acid-2-phosphate ester present in the preparation.

That is, the present invention provides a composition excellent in whitening effect and wrinkle prevention improving effect by dramatically improving the stability of ascorbic acid-2-phosphate ester represented by the formula (1) among the ascorbic acid derivatives. This is the issue.

As a result of intensive studies in view of the above circumstances, the present inventors prepared a composition containing an ascorbyl 2-phosphate ester derivative represented by the above formula (1), a nonionic surfactant, and water. In addition, by mixing this with an alkaline earth metal salt or an aqueous solution thereof, it was found that the decomposition of ascorbic acid-2-phosphate ester can be remarkably suppressed and the physiological activity is improved, and the present invention has been completed. It was.

That is, the present invention is as follows.

[1]
By preparing a composition containing an ascorbic acid-2-phosphate ester derivative represented by the formula (1), a nonionic surfactant and water, and mixing this with a divalent or higher metal salt or an aqueous solution thereof The prepared composition.

[2]
A composition containing an ascorbic acid-2-phosphate derivative represented by the formula (1), a nonionic surfactant, an oil component and water is prepared, and this is mixed with a divalent or higher metal salt or an aqueous solution thereof. A composition prepared by:

[3]
The composition according to [1] or [2], wherein R in the formula (1) is a fatty acid residue having 8 to 22 carbon atoms.

[4]
Content of metal salt more than bivalence is 0.5 times mole or more with respect to 1 mol of compounds of Formula (1), The composition in any one of [1]-[3] characterized by the above-mentioned.

[5]
The composition according to any one of [1] to [4], wherein the HLB of the nonionic surfactant is in the range of 9 to 17.

[6]
An average particle diameter is 300 nm or less, The composition in any one of [1]-[5] characterized by the above-mentioned.

[7]
[1] An external preparation for skin comprising the composition according to any one of [6].

[8]
A composition containing an ascorbic acid-2-phosphate ester derivative represented by the formula (1), a nonionic surfactant and a divalent or higher metal salt, or an ascorbic acid-2-phosphorus represented by the formula (1) A composition comprising an acid ester derivative, a nonionic surfactant, an oily component, and a divalent or higher metal salt.

The ascorbic acid-2-phosphate derivative used in the present invention is a compound represented by the above formula (1), and the hydrogen atom of the 6-position hydroxyl group of the ascorbic acid-2-phosphate is an acyl group. Substituted (R in Formula 1 is an acyl group). As a method for replacing the acyl group, a known method can be used. For example, it can be obtained by reacting ascorbic acid-2-phosphate with an acyl acid or an ester of acyl acid in an acidic catalyst. Examples of acyl acids include aliphatic carboxylic acids and aromatic carboxylic acids. Among these, fatty acids having 8 to 22 carbon atoms are preferable. That is, R in Formula (1) is preferably a fatty acid residue having 8 to 22 carbon atoms. Among these, lauric acid, myristic acid, palmitic acid, stearic acid, 2-hexyldecanoic acid, isostearic acid and the like are preferable in terms of versatility.

In the compound represented by the above formula (1), X is hydrogen and / or an alkali metal. Examples of the alkali metal include lithium, sodium, and potassium. The number of moles of alkali metal substituted for the ascorbic acid-2-phosphate derivative is preferably at least 1 mole, and most preferably at least 2 moles from the standpoint of stability itself.

Examples of the ascorbic acid-2-phosphate derivative include ascorbic acid-2-phosphate-6-laurate sodium, ascorbyl-2-phosphate-6-myristate sodium, ascorbyl-2-phosphate -6-sodium palmitate, ascorbyl 2-phosphate-6-sodium stearate, ascorbyl 2-phosphate-6-isostearate, ascorbyl 2-phosphate-6- (2-hexyldecanoic acid ) Sodium, and those whose sodium is potassium.

These compounds may be used individually by 1 type, and 2 or more types may be mixed and used for them. In the composition of the present invention, the ascorbic acid-2-phosphate derivative is preferably contained in the composition in an amount of 0.0001 to 20% by weight, more preferably 0.01 to 10% by weight. It is good to use.

Nonionic surfactants used in the present invention are polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene castor oil, polyoxyethylene hardened Castor oil, polyoxyethylene sorbitol tetrafatty acid ester, glycerin fatty acid ester, sorbitan fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, alkyl glucoside and the like can be mentioned. Among them, POE (25) lauryl ether, POE (20) oleyl ether, monopalmitic acid POE (20) sorbitan, monostearic acid POE (20) sorbitan, tristearic acid POE (20) sorbitan, monoisostearic acid POE (20) Sorbitan, monooleic acid POE (20) sorbitan, POE (40) hydrogenated castor oil, POE (60) hydrogenated castor oil, POE (30) phytosterol, monostearate decaglyceryl, sucrose stearate monoester and the like are preferable.

These nonionic surfactants may be used singly or in combination of two or more, but the nonionic surfactant mixed HLB used in the present invention (two types) When the above nonionic surfactants are used, the mixed HLB is preferably calculated in a range of 9 to 17). HLB indicates a balance between hydrophilicity and lipophilicity, and the Griffin calculation method was used in the present invention.

In the external preparation for skin of the present invention, the nonionic surfactant varies depending on the amount of oily component used and the like, but is 50% by weight or more based on the ascorbic acid-2-phosphate derivative represented by the formula (1) It is preferably used, more preferably 100% by weight or more, and most preferably 200% by weight or more.

The present invention prepares a composition containing an ascorbic acid-2-phosphate derivative represented by the formula (1), a nonionic surfactant and water, and a divalent or higher valent metal salt or an aqueous solution thereof. A method of obtaining a composition prepared by mixing, a composition containing an ascorbyl 2-phosphate ester derivative represented by the formula (1), a nonionic surfactant, an oil component and water; There is a method of obtaining a composition prepared by mixing this with a divalent or higher metal salt or an aqueous solution thereof, but the latter using an oily component is preferred from the viewpoint of the stability of the preparation (emulsified particles).

Examples of the oil component used in the present invention include hydrocarbons, waxes / esters, fats and oils, and silicone oils. These can be used for cosmetics, quasi drugs and pharmaceuticals. For example, hydrocarbons such as squalene, squalane, liquid paraffin, mineral oil, petrolatum, esters such as isopropyl myristate, isopropyl palmitate, isononyl isononanoate, octyl isononanoate, tridecyl isononanoate, isotridecyl isononanoate, tri-2 -Triglycerides such as glyceryl ethylhexanoate and glyceryl triisostearate, silicone oils such as methylpolysiloxane and methylphenylpolysiloxane, natural oil components, jojoba oil, carnauba wax, candelilla wax, olive oil, macadamia nut oil, Meadow home oil. In addition, oil-soluble vitamins such as tocopherol and retinol, derivatives thereof, and oily components such as astaxanthin and carotene can also be used.

These oily components may be used alone or in combination of two or more. The amount of the oil component used is preferably 20% by weight or more, more preferably 100% by weight or more based on the ascorbic acid-2-phosphate derivative represented by the formula (1).

Examples of the divalent or higher metal salt used in the present invention include alkaline earth metals such as calcium, hydrochlorides such as magnesium and zinc, sulfates, carbonates, phosphates, nitrates, and organic acid salts. . Of these, calcium and magnesium salts are preferable, and magnesium chloride, magnesium sulfate, and calcium chloride are more preferable. The divalent or higher valent metal salt can be directly mixed with the composition containing the ascorbic acid-2-phosphate derivative represented by the above formula (1), or can be mixed in an aqueous solution.

These divalent or higher metal salts may be used alone or in combination of two or more. In the composition of this invention, it is preferable to use 0.1 mol or more with respect to 1 mol of compounds of Formula (1), 0.5 mol or more is more preferable, and 1-5 mol is the most preferable.

The composition of this invention prepares the composition containing the ascorbic acid-2-phosphate ester derivative shown by Formula (1), a nonionic surfactant, and water (and oily component), and this is bivalent. It can be prepared by mixing the above metal salt or an aqueous solution thereof. The mixing method includes a method of adding a bivalent or higher metal salt or an aqueous solution thereof to the composition containing an ascorbic acid-2-phosphate ester derivative, or a bivalent or higher metal salt or an aqueous solution thereof. Although the said composition containing a phosphate ester derivative can be added, the former is preferable from the surface of the stability of a composition.

The composition of the present invention preferably has a pH of 7 or more from the viewpoint of the stability of the ascorbic acid-2-phosphate ester represented by the formula (1). Moreover, it is more preferable that the pH is 7.5 or more and 9 or less. Examples of the base used for pH adjustment include inorganic bases such as sodium hydroxide, potassium hydroxide and sodium carbonate, and organic bases such as triethanolamine, aminomethylpropanediol, arginine and lysine.

In the composition of the present invention, the average particle size is preferably 300 nm or less, and most preferably 200 nm or less in terms of the stability of the preparation. A light scattering particle size measuring device manufactured by Otsuka Electronics Co., Ltd. can be used.

The composition or external preparation for skin of the present invention can be used for cosmetics, quasi-drugs, and pharmaceuticals. Examples of the dosage form include lotions, creams, emulsions, gels, aerosols, and essences. , Packs, cleaning agents, bath preparations, foundations, powders, lipsticks, ointments, poultices and the like.

In the composition of the present invention or the external preparation for skin, a composition containing the above ascorbyl 2-phosphate ester and a metal salt having a valence of 2 or more may be used as it is, and the effect of the present invention is not impaired. Oils, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, metal soaps, pH adjusters, preservatives, fragrances, moisturizers, which are components used in general external preparations Components such as powders, ultraviolet absorbers, thickeners, pigments, antioxidants, whitening agents, anti-inflammatory agents, chelating agents and the like can also be blended.

According to the external preparation for skin of the present invention, the stability of the ascorbic acid-2-phosphate derivative in the preparation is high, the preparation is hardly yellowed or browned by decomposition, and is excellent in whitening effect and wrinkle prevention improving effect. ing.

The present invention will be described in more detail with reference to examples and comparative examples below, but the present invention is not limited to the following examples. In addition, content of each component in prescription shall be weight%.

Evaluation of physical properties and stability of the composition of the present invention Average particle size and discoloration of preparations prepared from nonionic surfactants having various structures, oil components, divalent or higher metal salts, and ascorbic acid derivatives Table 1 shows the results of a comparative study on the residual ratio of the slag. Ascorbic acid derivatives used were those in which Na was substituted by 2 to 3 moles. About the molar ratio of Mg with respect to the ascorbic acid derivative in Table 2, it computed as sodium ascorbic acid-2-phosphate-6-palmitate Mw: 560.46 (3Na body).

In addition, about the manufacturing method of a formulation, it performed in the following procedures. First, part A is mixed at room temperature, and part B at 40 ° C. is gradually added. Next, part C is added in an ultrasonic cleaner and held at 40 ° C. for 15 minutes. After cooling to 30 ° C., D and E parts were added to obtain the desired preparation.

The average particle size was measured with a light scattering type particle size measuring device (FPAR-1000) manufactured by Otsuka Electronics Co., Ltd., and was determined by a cumulant method. The measurement temperature was 25 ± 1 ° C. The average particle size was measured 3 hours after preparation of the preparation.

The time-lapse observation was evaluated after 1 month at 50 ° C., and the indicators were the presence or absence of browning (discoloration) caused by decomposition of ascorbic acid and the like, and the residual rate of ascorbic acid-2-phosphate.

Further, the residual rate (%) of ascorbic acid-2-phosphate in the preparation was measured by high performance liquid chromatography under the following measurement conditions and calculated by the following formula.
As an analysis sample, 0.2 g of each preparation was taken, 1 mL of 20 wt% phosphoric acid aqueous solution was added, and 50 volume% ethanol was added to make 50 mL.

Residual rate (%) = 100 × [Ascorbic acid derivative concentration (g / L) in preparation after 1 month at 50 ° C./Ascorbic acid derivative concentration (g / L) in preparation immediately after preparation]
<High-performance liquid chromatography measurement conditions>
Column: Octadecylated silica gel (ODS) 4.6 mmφ × 250 mm
Column temperature: 40 ° C
Eluent: 20 mM dipotassium hydrogen phosphate (pH 7.0 with phosphoric acid) / acetonitrile = 40/60
Flow rate: 1 mL / min Detection: UV 265 nm

The remaining rate was scored according to the following four evaluation items.
◎: Residual rate 90% or more ○: Residual rate 80% or more and less than 90% △: Residual rate 70% or more and less than 80% ×: Residual rate less than 70%

Comparison was made between the preparation of the present invention and a preparation simply added with magnesium ascorbyl-2-phosphate-6-palmitate, and the stability of the preparation (1 month at 40 ° C.) was evaluated.
Storage stability evaluation item A: Almost no change in emulsified particles is observed.
○: A slight increase in the emulsified particle diameter can be confirmed by observation with a microscope.
X: Phase separation is remarkable.

Production method of Comparative Example 4
Preparation of magnesium ascorbyl-2-phosphate-6-palmitate 2.8 g of sodium ascorbyl-2-phosphate-6-palmitate was dissolved in 350 mL of purified water, and magnesium sulfate heptahydrate An aqueous solution in which 1.85 g was dissolved in 150 mL of purified water was slowly added with stirring and then allowed to react for 30 minutes. The resulting precipitate was filtered and dried to obtain 2.5 g of a white powder.
Preparation of preparation In the formulation of Comparative Example 2 in Table 1, the same procedure was performed except that sodium ascorbyl-2-phosphate-6-palmitate was replaced with the above magnesium ascorbate-2-phosphate-6-palmitate. Comparative Example 4 was produced.

The results of these experiments are shown in Table 5. As a result, when ascorbic acid-2-phosphate-6-palmitic acid magnesium was simply added, the white surfactant was in spite of the same surfactant and amount used, and settled after 3 hours. On the other hand, the formulation of the present invention was a milky white solution and was highly uniform. Further, the stability after one month at 40 ° C. was superior to the comparative example.

Whitening effect of the composition of the present invention (melanin production inhibition test)
The melanoma in the logarithmic growth phase was added to 1.0 mm of a suspension of 3 × 10 ⁴ cells / mL in a 60 mm petri dish, and the sample of each example was adjusted so that ascorbic acid-2-phosphate-6-palmitic acid was 20 μM. Eagles'MEM (containing 10% fetal bovine serum) (3.0 mL) was added, and the mixture was cultured at 37 ° C. under 5% CO ₂ conditions. After 5 days of culturing, the cells were detached from the petri dish, and the cells were sonicated, and then 0.5 mL of 4N aqueous sodium hydroxide solution was added, followed by treatment at 60 ° C. for 2 hours. D. 475 nm was measured. In addition, the cell lysate after sonication is subjected to protein quantification by the Lowry method (J. Biol. Chem., 193, 265-275, 1951), and the amount of melanin per amount of protein is compared, thereby suppressing melanin production. It was used as an index of action.

The results of these experiments are shown in Table 6. As a result, the ascorbic acid derivative of the present invention exhibited a melanin production inhibitory action that was particularly superior to an ascorbic acid derivative that did not use a divalent or higher-valent metal salt. In addition, the preparation containing the ascorbic acid derivative obtained by the production method of the present invention shows a remarkable melanin production inhibitory action as compared with the method of simply adding magnesium ascorbyl-2-phosphate-6-palmitate. It was.

Collagen synthesis promoting effect of the composition of the present invention Collagen promoting activity in cultured human skin fibroblasts was measured under the following conditions. After culturing normal human skin fibroblasts in a confluent state for 24 hours in Eagle's MEM medium supplemented with the samples of each example so that ascorbic acid-2-phosphate-6-palmitic acid was 10 μM, total RNA extraction was performed. Based on the total RNA extracted from normal human skin fibroblasts, the expression level of collagen mRNA was measured by RT-PCR. The RT-PCR method includes TaKaRa RNA PCR Kit (AMV) Ver. 2.1 was used. GAPDH was used as an internal standard. Other operations were carried out in accordance with a predetermined method, and the PCR reaction solution was subjected to agarose gel electrophoresis, and the expression of collagen and GAPDH mRNA was confirmed as a band. These bands were photographed with a camera and quantified using a densitometer, and the expression level of collagen mRNA was determined as a ratio to the expression level of GAPDH mRNA as an internal standard. The collagen synthesis acceleration rate was determined from the value of collagen mRNA expression level when the sample was added to the control collagen mRNA expression level.
Collagen synthesis acceleration rate (%) = A / B × 100
A: expression level of collagen mRNA when sample is added B: expression level of collagen mRNA when sample is not added

The results of these experiments are shown in Table 7. As a result, the ascorbic acid derivative of the present invention showed a collagen synthesis promoting effect particularly superior to that of an ascorbic acid derivative that does not use a divalent or higher valent metal salt. Moreover, the preparation containing the ascorbic acid derivative obtained in the present invention showed a remarkable collagen synthesis promoting effect as compared with the method of simply adding magnesium ascorbyl-2-phosphate-6-palmitate.

Next, the formulation example of the external preparation for skin of this invention is shown.

Formulation Example 1 Concentrated Essence Formulation Components Formulation amount (% by weight)
(1) Sodium ascorbyl-2-phosphate-6-palmitate 5.0
(2) POE monostearate (20) sorbitan 10.0
(3) Isotridecyl isononanoate 5.0
(4) Purified water 56.0
(5) Magnesium chloride hexahydrate 1.8
(6) Purified water 15.2
(7) Potassium hydroxide aqueous solution (5% by weight) 7.0
[Production method] The production method was the same as in Example 1.

Formulation Example 2 Lotion Toner Ingredient Ingredient Amount (wt%)
(1) Concentrated Essence of Formulation Example 1 5.0
(2) 1,3 butylene glycol 5.0
(3) Ethanol 5.0
(4) Preservative appropriate amount (5) Perfume appropriate amount (6) Total amount with purified water 100.0
[Production Method] (1) to (6) are mixed. The average particle size was 220 nm.

Formulation Example 3 Cosmetic liquid Blending ingredients Blending amount (% by weight)
(1) Concentrated essence of Formulation Example 1 40.0
(2) Carboxyvinyl polymer 0.5
(3) Potassium hydroxide appropriate amount (4) Glycerin 10.0
(5) 1,3 butylene glycol 8.0
(6) Ethanol 3.0
(7) Preservative appropriate amount (8) Total amount with purified water 100.0
[Production Method] (1) to (8) are mixed.

As a result of a one month use test of 5 men and 5 women, this serum was evaluated as 80% effective or slightly effective.

Formulation Example 4 Latex Blending ingredients Blending amount (% by weight)
(1) Concentrated Essence of Formulation Example 1 2.0
(2) POE monostearate (5) Glyceryl 1.0
(3) Lipophilic glyceryl monostearate 1.0
(4) Squalane 10.0
(5) Neopentyl glycol dicaprate 5.0
(6) Cetyl palmitate 2.0
(7) Behenyl alcohol 0.4
(8) Glycerin 5.0
(9) 1,3-butylene glycol 8.0
(10) Xanthan gum 0.1
(11) Preservative appropriate amount (12) Total amount with purified water 100.0
(13) Carboxyvinyl polymer 0.2
(14) Purified water 20.0
(15) Potassium hydroxide [Production method] (13) is dispersed well in (12), and (14), (15) and then (8) to (11) are added thereto to obtain an aqueous phase. (2)-(7) The oil phase raw material and the water phase part are heated to 75 ° C. and completely dissolved, then the water phase part is mixed and emulsified in the oil phase part, and (1) is added at 40 ° C. And cool to room temperature.

Formulation Example 5 Cream Blending ingredients Blending amount (% by weight)
(1) Concentrated essence of Formulation Example 1 20.0
(2) POE monostearate (5) Glyceryl 2.0
(3) Glyceryl monostearate 2.0
(4) Cetanol 3.0
(5) Squalane 10.0
(6) Liquid paraffin 5.0
(7) Perfume appropriate amount (8) Glycerin 5.0
(9) 1,3-butylene glycol 5.0
(10) Xanthan gum 0.2
(11) Preservative appropriate amount (12) Total amount with purified water 100.0
[Production Method] The raw materials for the oil phase part (2) to (7) and the raw material for the water phase part (8) to (12) are heated to 75 ° C. and completely dissolved, and then the aqueous phase part is converted to the oil phase part. Mix and emulsify, add (1) at 40 ° C. and cool to room temperature.

Formulation Example 6 Foundation Formulation Components Formulation amount (% by weight)
(1) Concentrated Essence of Formulation Example 1 2.0
(2) POE monostearate (20) sorbitan 1.0
(3) POE (20) cetyl ether 2.0
(4) Cetanol 1.0
(5) Liquid lanolin 2.0
(6) Liquid paraffin 3.0
(7) Isopropyl myristate 6.5
(8) Butyl paraoxybenzoate 0.1
(9) Carboxymethylcellulose sodium 0.1
(10) Bentonite 0.5
(11) Propylene glycol 4.0
(12) Triethanolamine 1.1
(13) Methyl paraoxybenzoate 0.2
(14) Titanium dioxide 8.0
(15) Talc 4.0
(16) Bengala 1.0
(17) Yellow iron oxide 2.0
(18) Fragrance 0.1
(19) Total amount with purified water 100.0
[Production Method] Components (2) to (8) are dissolved by heating and kept at 80 ° C. to obtain an oil phase. The component (9) is well swollen with the component (19), and then the components (10) to (13) are added and mixed uniformly. Components (14) to (17) pulverized and mixed with a pulverizer are added thereto, and the mixture is stirred with a homomixer and kept at 75 ° C. to obtain an aqueous phase. The oil phase is added to this aqueous phase with stirring, cooled, component (18) is added at 45 ° C., and cooled to 30 ° C. with stirring to give a product.

The skin external preparation of the present invention makes it possible to dramatically improve the stability of a specific ascorbyl 2-phosphate ester, and is particularly excellent in a whitening effect and a wrinkle prevention / improvement effect. Can be used for cosmetics, quasi drugs, pharmaceuticals, and the like.

Claims (8)

By preparing a composition containing an ascorbic acid-2-phosphate ester derivative represented by the formula (1), a nonionic surfactant and water, and mixing this with a divalent or higher metal salt or an aqueous solution thereof A composition characterized by being prepared. A composition containing an ascorbic acid-2-phosphate derivative represented by the formula (1), a nonionic surfactant, an oil component and water is prepared, and this is mixed with a divalent or higher metal salt or an aqueous solution thereof. A composition prepared by The composition according to claim 1 or 2, wherein R in the formula (1) is a fatty acid residue having 8 to 22 carbon atoms. The composition according to any one of claims 1 to 3, wherein the content of the metal salt having a valence of 2 or more is 0.5 times mol or more with respect to 1 mol of the compound of the formula (1). The composition according to any one of claims 1 to 4, wherein the mixed HLB of the nonionic surfactant is in the range of 9-17. 6. The composition according to any one of claims 1 to 5, wherein an average particle size is 300 nm or less. A skin external preparation containing the composition according to any one of claims 1 to 6. A composition comprising an ascorbic acid-2-phosphate derivative represented by the formula (1), a nonionic surfactant and a metal salt having a valence of 2 or more;
Or the composition containing the ascorbic acid-2-phosphate ester derivative shown by Formula (1), a nonionic surfactant, an oil-based component, and a bivalent or more metal salt.