阅读说明：本技术 抗坏血酸和/或含有其盐的外用组合物 (Ascorbic acid and/or external composition containing salt thereof ) 是由 北冈侑 羽贺雅俊 于 2018-12-27 设计创作，主要内容包括：本发明提供一种稳定性且使用感优异的外用组合物。制备一种外用组合物,其含有(A)选自抗坏血酸和抗坏血酸的盐中的至少1种、(B)碳原子数三个的二醇、(C)选自低分子甜菜碱、有机酸盐、无机酸盐、碱性氨基酸、碱性氨基酸的盐、3-O-乙基抗坏血酸、以及3-O-乙基抗坏血酸的盐中的至少1种以及(D)水,并且,乙氧基二甘醇的含量小于30质量％。(The invention provides an external composition which is stable and has excellent use feeling. A composition for external use is prepared which contains (A) at least 1 selected from ascorbic acid and a salt of ascorbic acid, (B) a diol having three carbon atoms, (C) at least 1 selected from low-molecular betaines, organic acid salts, inorganic acid salts, basic amino acids, salts of basic amino acids, 3-O-ethyl ascorbic acid, and salts of 3-O-ethyl ascorbic acid, and (D) water, and in which the content of ethoxydiglycol is less than 30% by mass.)

1. A composition for external use comprises the following components:

(A) at least 1 selected from ascorbic acid and salts of ascorbic acid,

(B) a diol having 3 carbon atoms,

(C) at least 1 selected from the group consisting of low molecular weight betaines, organic acid salts, inorganic acid salts, basic amino acids, salts of basic amino acids, 3-O-ethyl ascorbic acid, and salts of 3-O-ethyl ascorbic acid, and

(D) the amount of water is controlled by the amount of water,

and the content of ethoxydiglycol is less than 30 mass%.

2. The composition for external use according to claim 1, wherein the component (B) accounts for 25% by mass or more of the composition for external use.

3. The composition for external use according to claim 1 or 2, wherein the component (D) is 0.01 to 20 parts by mass relative to 1 part by mass of the total content of the component (A).

4. The composition for external use according to any one of claims 1 to 3, wherein component (C) is at least 1 selected from the group consisting of trimethylglycine, carnitine, arginine, sodium citrate, sodium succinate, sodium pyrrolidone carboxylate, 3-O-ethyl ascorbic acid, and a salt of 3-O-ethyl ascorbic acid.

5. The composition for external use according to any one of claims 1 to 4, wherein (B) is 1, 3-propanediol or propylene glycol.

6. The composition for external use according to any one of claims 1 to 5, wherein the concentration of the ascorbic acid or a salt thereof is 3 to 40% by mass.

7. The composition for external use according to any one of claims 1 to 6, further comprising (E) a lower alcohol.

8. The external composition according to any one of claims 1 to 7, wherein the content of ethoxydiglycol is 10% by mass or less of the external composition.

9. The composition for external use according to any one of claims 1 to 8, which contains substantially no ethoxydiglycol.

10. The composition for external use according to any one of claims 1 to 9, wherein the composition for external use is a solubilizing-type composition for external use having a transmittance at a wavelength of 700nm of 85 to 100%.

11. The composition for external use according to any one of claims 1 to 10, wherein the composition for external use is used for promoting percutaneous absorption of ascorbic acid.

12. A method for imparting stability to a composition for external use containing (A) at least 1 selected from ascorbic acid and a salt of ascorbic acid, characterized by using (A) at least 1 selected from ascorbic acid and a salt of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least 1 selected from low-molecular betaines, organic acid salts, inorganic acid salts, basic amino acids, salts of basic amino acids, 3-O-ethyl ascorbic acid, and salts of 3-O-ethyl ascorbic acid, and (D) water in combination, and by using ethoxy diglycol in an amount of less than 30% by mass, thereby imparting stability to the composition for external use.

Technical Field

The present invention relates to an ascorbic acid and/or a composition for external use containing a salt thereof.

Background

Ascorbic acid is known to exhibit various effects such as an anti-inflammatory effect, an acne improvement effect, a whitening effect, an anti-aging effect, an antioxidant effect, an effect of activating cells by promoting the synthesis of biological components such as collagen, and an effect of inhibiting cell damage and DNA damage caused by ultraviolet rays of epidermal keratinocytes, and is expected to be widely used as an external preparation for skin.

In order to make ascorbic acid easily oxidized in the presence of water such as an aqueous solution, it is necessary to reduce the amount of water in the preparation, but a small amount of water cannot sufficiently solubilize ascorbic acid.

Therefore, several methods for stably solubilizing ascorbic acid in aqueous skin external preparations have been studied (for example, patent document 1: WO02/19972, patent document 2: WO00/78283, patent document 3: Japanese patent laid-open No. 2002-348228, and patent document 4: Japanese patent laid-open No. 2005-225865).

Disclosure of Invention

The present invention aims to provide an external composition containing ascorbic acid having good properties.

Provided is a composition for external use containing ascorbic acid and/or a salt thereof, which can be mixed with various concentrations of ascorbic acid and/or a salt thereof.

According to the studies of the present inventors, it has been found that if ascorbic acid and/or a salt thereof is blended at a high concentration, the ascorbic acid and/or a salt thereof may not dissolve from the start of production or may precipitate even if the ascorbic acid and/or a salt thereof dissolves during production, for example, when the ascorbic acid and/or a salt thereof is stored at a low temperature such as 4 ℃. Further, it was found that, in a formulation in which ethoxydiglycol is blended at a high concentration for improving the feeling of use, yellowing occurs during long-term storage although there is no problem in quality.

The present inventors have conducted extensive studies to solve the problem, and as a result, have found that an external composition having excellent stability and percutaneous absorbability (skin permeability) can be obtained by containing (a) at least 1 selected from ascorbic acid and salts of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least 1 selected from low-molecular betaines, organic acid salts, inorganic acid salts, basic amino acids, salts of basic amino acids, 3-O-ethyl ascorbic acid and salts of 3-O-ethyl ascorbic acid, and (D) water, and by making the content of ethoxydiglycol less than 30% by mass, the precipitation of ascorbic acid can be suppressed, the decomposition of ascorbic acid can be suppressed, and the present invention has been completed.

Namely, the present invention provides the following composition for external use.

Item 1.

A composition for external use comprises the following components:

(A) at least 1 selected from ascorbic acid and salts of ascorbic acid;

(B) a diol having 3 carbon atoms;

(C) at least 1 selected from low molecular betaine, organic acid salt, inorganic acid salt, basic amino acid, salt of basic amino acid, 3-O-ethyl ascorbic acid and salt of 3-O-ethyl ascorbic acid;

(D) the amount of water is controlled by the amount of water,

and the content of ethoxydiglycol (diethylene glycol monoethyl ether) is less than 30% by mass.

Item 2.

The composition for external use according to item 1, wherein component (B) is 25% by mass or more of the composition for external use.

Item 3.

The composition for external use according to item 1 or 2, wherein the component (D) is 0.01 to 20 parts by mass relative to 1 part by mass of the total content of the component (A).

Item 4.

The composition for external use according to any one of items 1 to 3, wherein component (C) is at least 1 selected from the group consisting of trimethylglycine, carnitine, arginine, sodium citrate, sodium succinate, sodium pyrrolidone carboxylate, 3-O-ethyl ascorbic acid, and salts of 3-O-ethyl ascorbic acid.

Item 5.

The composition for external use according to any one of claims 1 to 4, wherein the component (B) is 1, 3-propanediol or propylene glycol.

Item 6.

The composition for external use according to any one of claims 1 to 5, wherein the concentration of the ascorbic acid or a salt thereof is 3 to 40% by mass.

Item 7.

The composition for external use according to any one of claims 1 to 6, further comprising (E) a lower alcohol.

Item 8

The external composition according to any one of claims 1 to 7, wherein ethoxydiglycol accounts for 10% by mass or less of the external composition.

Item 9

The composition for external use according to any one of claims 1 to 8, which contains substantially no ethoxydiglycol.

Item 10

The composition for external use according to any one of claims 1 to 9, wherein the composition for external use is a solubilizing-type composition for external use having a transmittance at a wavelength of 700nm of 85 to 100%.

Item 11.

The external composition according to any one of claims 1 to 10, wherein the external composition is used for promoting percutaneous absorption of ascorbic acid.

Item 12.

A method for imparting stability to a composition for external use containing (A) at least 1 selected from ascorbic acid and a salt of ascorbic acid, wherein the composition for external use is imparted with stability by using (A) at least 1 selected from ascorbic acid and a salt of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least 1 selected from low-molecular betaines, organic acid salts, inorganic acid salts, basic amino acids, salts of 3-O-ethyl ascorbic acid and 3-O-ethyl ascorbic acid, and (D) water in combination, and by making ethoxy diglycol less than 30% by mass.

According to the present invention, a composition for external use having excellent stability can be provided.

Detailed Description

In the present specification, the unit of the content "% by mass" means the same as "g/100 g".

The composition for external use of the present invention contains (A) at least 1 selected from ascorbic acid and a salt of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least 1 selected from a low-molecular betaine, a salt of an organic acid, a salt of an inorganic acid, a basic amino acid, a salt of a basic amino acid, 3-O-ethyl ascorbic acid and a salt of 3-O-ethyl ascorbic acid, and (D) water, and the content of ethoxydiglycol is less than 30% by mass.

The composition for external use of the present invention is stable in a wide concentration range of at least 1 selected from the group consisting of ascorbic acid and salts of ascorbic acid (a), and has high safety.

[ (A) at least 1 selected from ascorbic acid and salts of ascorbic acid ]

As the ascorbic acid used in the present invention, ascorbic acid commercially available as a component of skin external preparations in the fields of pharmaceuticals, quasi drugs, and cosmetics can be used, and these are generally referred to as L bodies.

Salts of ascorbic acid may also be used. Here, the salt of ascorbic acid means a pharmaceutically acceptable salt. Examples of the salt include, but are not limited to, salts with organic bases (for example, salts with tertiary amines such as trimethylamine salt, triethylamine salt, monoethanolamine salt, triethanolamine salt, and pyridine salt, and basic ammonium salts such as arginine), salts with inorganic bases (for example, alkali metal salts such as ammonium salt, sodium salt, and potassium salt, alkaline earth metal salts such as calcium salt, magnesium salt, and aluminum salt), and the like. Particularly preferred salts of ascorbic acid are sodium and potassium salts. Specific examples thereof include sodium ascorbate, sodium ascorbyl monophosphate, sodium ascorbyl diphosphate, sodium ascorbyl triphosphate, sodium ascorbyl-2-sulfate, and the like.

In the present invention, 1 or 2 or more kinds of ascorbic acid or a salt thereof may be used in combination.

The total content of the component (a) in the external composition of the present invention relative to the total amount of the external composition can be appropriately set in accordance with the balance with other components. The total content of the component (a) is not particularly limited, but is preferably 0.1% by mass or more, more preferably 1% by mass or more, further preferably 2% by mass or more, further preferably 3% by mass or more, and most preferably 10% by mass or more, relative to the total amount of the external composition. The total content of the component (a) is preferably 50% by mass or less, more preferably 40% by mass or less, further preferably 35% by mass or less, and further preferably 30% by mass or less, relative to the total amount of the external composition. The total content of the component (a) is preferably 0.1 to 50% by mass, more preferably 1 to 40% by mass, even more preferably 3 to 30% by mass, and most preferably 10 to 30% by mass, based on the total amount of the external composition.

[ (B) a diol having 3 carbon atoms ]

The diol having 3 carbon atoms used in the present invention is not particularly limited as long as it is a component used as an external skin preparation in the fields of pharmaceuticals, quasi drugs, and cosmetics. The diol having 3 carbon atoms is not particularly limited, and is preferably 1, 3-propanediol (CAS number: 504-63-2, English name: 1, 3-dihydroxypropane or trimethylene diglycol) or propylene glycol (CAS number: 57-55-6, English name: 1, 2-dihydroxypropane, alias: 1, 2-propanediol), more preferably 1, 3-propanediol. For example, 1 or more of 1, 3-propanediol and propylene glycol can be used as the component (B). As such a diol having 3 carbon atoms, a commercially available product may be used as it is. In addition, from the viewpoint of alleviating irritation to the skin, improving the feeling of use, and suppressing coloring, it is one of preferable embodiments to combine 1, 3-propanediol and propylene glycol, and it is more preferable to contain at least 1, 3-propanediol as the component (B).

In the external composition of the present invention, the total content of the component (B) relative to the total amount of the external composition is not particularly limited, but is preferably 20% by mass or more, more preferably 25% by mass or more, and still more preferably 30% by mass or more.

The total content of the component (B) with respect to the total amount of the external composition is preferably 90% by mass or less, more preferably 85% by mass or less, and still more preferably 80% by mass or less.

The total content of the component (B) is preferably 20 to 90% by mass, more preferably 25 to 85% by mass, and still more preferably 30 to 80% by mass, based on the total amount of the external composition.

In the composition for external use of the present invention, the ratio of the amount of component (B) to component (a) is not particularly limited, but is preferably 0.1 to 100 parts by mass, and more preferably 0.5 to 25 parts by mass, based on 1 part by mass of the total content of component (a).

[ (C) ingredient ]

(Low molecular weight betaine)

As the low-molecular betaine used in the present invention, a compound generally used as a component of a skin external preparation in the fields of pharmaceuticals, quasi drugs, and cosmetics can be used. In the present invention, the low-molecular betaine means that a zwitterion is formed in a molecule having a molecular weight of 500 or lessSpecific examples of the quaternary ammonium salt include quaternary ammonium hydroxide and quaternary phosphonium saltA base, a tertiary sulfonium base, and the like, which hardly exhibit properties as a surfactant. Among them, preferred are N, N, N-trialkylamino acids represented by the following chemical formula,

(in the formula, R₁、R₂And R₃Each independently represents an alkyl group having 1 to 6 carbon atoms, and n represents 1 to 6. ).

As R₁～R₃The alkyl group may be a linear or branched alkyl group having 1 to 6 carbon atoms. That is, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl, 3-methylpentyl, 2-dimethylbutyl, 2, 3-dimethylbutyl, and the like can be given as examples. In addition, R is₁～R₃May be the same or different.

Specifically, trimethylglycine with n-1, triethylglycine, tripropylglycine, triisopropylglycine, trimethyl- β -alanine with n-2, trimethyl- γ -aminobutyric acid with n-3, and the like are mentioned, and trimethylglycine is preferable.

Further, these low molecular weight betaines may be substituted, and specific examples thereof include N, N-trimethylalanine, N-triethylalanine, N-triisopropylalanine, N-trimethylmethylalanine, carnitine, acetyl-carnitine and the like, with carnitine being preferred.

These may be synthesized, or a commercially available product may be used as it is.

These low-molecular betaines may be used in combination of 1 or 2 or more.

In the composition for external use of the present invention, the total content of the low-molecular betaine with respect to the total amount of the composition for external use may be appropriately set in accordance with the balance with other components. The content is preferably 0.00001% by mass or more, more preferably 0.0001% by mass or more, further preferably 0.001% by mass or more, more preferably 0.01% by mass or more, and most preferably 0.05% by mass or more, based on the total amount of the composition for external use. The total content of the low-molecular weight betaine is preferably 30% by mass or less, more preferably 25% by mass or less, even more preferably 20% by mass or less, even more preferably 15% by mass or less, and most preferably 10% by mass or less, based on the total amount of the external composition. The total content of the low-molecular weight betaine is preferably 0.00001 to 30% by mass, more preferably 0.0001 to 25% by mass, even more preferably 0.001 to 20% by mass, and most preferably 0.01 to 10% by mass, based on the total amount of the external composition.

In the composition for external use of the present invention, the ratio of the amount of low-molecular weight betaine to the component (a) is preferably 0.00005 to 1.0 part by mass, more preferably 0.0001 to 0.8 part by mass, even more preferably 0.0005 to 0.5 part by mass, and most preferably 0.001 to 0.4 part by mass, based on 1 part by mass of the total content of the component (a).

(organic acid salt)

As the organic acid salt used in the present invention, a compound generally used as a component of a skin external preparation in the fields of pharmaceuticals, quasi drugs, and cosmetics can be used.

The organic acid salt contributes to the stability of the external composition of the present invention.

Here, in the present invention, the organic acid forming the organic acid salt means an acid of an organic compound having an organic group and a molecular weight of 1000 or less, preferably 700 or less, more preferably 500 or less, and particularly preferably 300 or less. The organic acid means a carboxylic acid having a carboxyl group or a sulfonic acid having a sulfonic group for the most part thereof. More specifically, examples of the acid include, but are not limited to, lactic acid, acetic acid, citric acid, tartaric acid, malic acid, succinic acid, oxalic acid, gluconic acid, fumaric acid, propionic acid, aspartic acid, pyrrolidone carboxylic acid, -aminocaproic acid, glutamic acid, and aminoethylsulfonic acid.

Here, the salt forming the organic acid salt is a pharmaceutically acceptable salt. Examples of the salt include, but are not limited to, salts with organic bases (for example, salts with tertiary amines such as trimethylamine salt, triethylamine salt, monoethanolamine salt, triethanolamine salt, and pyridine salt, and basic ammonium salts such as arginine), salts with inorganic bases (for example, alkali metal salts such as ammonium salt, sodium salt, and potassium salt, alkaline earth metal salts such as calcium salt, and magnesium salt, and aluminum salt). Particularly preferred organic acid salts are sodium salts and calcium salts.

In the present invention, preferable organic acid salts include sodium lactate, sodium acetate, sodium citrate, sodium succinate, sodium oxalate, calcium gluconate, sodium pyrrolidone carboxylate, and the like.

These may be synthesized or commercially available products may be used as they are.

These organic acid salts may be used in combination of 1 or 2 or more.

In the external composition of the present invention, the total content of the organic acid salt relative to the total amount of the external composition may be appropriately set in accordance with the balance of other components. The content is preferably 0.0001% by mass or more, more preferably 0.001% by mass or more, further preferably 0.005% by mass or more, more preferably 0.01% by mass or more, and most preferably 0.05% by mass or more, based on the total amount of the external composition. The total content of the organic acid salt is preferably 10% by mass or less, more preferably 9% by mass or less, further preferably 8% by mass or less, more preferably 7% by mass or less, and most preferably 6% by mass or less, relative to the total amount of the external composition. The total content of the organic acid salt is preferably 0.0001 to 10% by mass, more preferably 0.001 to 9% by mass, even more preferably 0.005 to 8% by mass, and most preferably 0.05 to 6% by mass, based on the total amount of the external composition.

In the external composition of the present invention, the total content of the organic acid salt is preferably 0.00003 to 0.8 parts by mass, more preferably 0.00005 to 0.7 parts by mass, even more preferably 0.00008 to 0.6 parts by mass, and most preferably 0.0001 to 0.5 parts by mass, based on 1 part by mass of the total content of the component (a), with respect to the ratio of the amount of the organic acid salt to be blended with the component (a).

(inorganic acid salt)

As the inorganic acid salt used in the present invention, a compound generally used as a component of a skin external preparation in the fields of pharmaceuticals, quasi drugs, and cosmetics can be used.

The inorganic acid salt contributes to the stability of the composition for external use of the present invention.

In the present invention, the inorganic acid is more specifically, though not limited, and examples thereof include nitric acid, phosphoric acid, sulfuric acid, sulfurous acid, boric acid, and hydrofluoric acid.

Here, the salt forming the inorganic acid salt is a pharmaceutically acceptable salt. Examples include, but are not limited to, salts with inorganic bases (for example, alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as calcium salts and magnesium salts, and aluminum salts). Particularly preferred inorganic acid salts are sodium salts and potassium salts.

In the present invention, preferred inorganic acid salts include sodium metabisulfite, potassium metabisulfite, sodium phosphate, potassium nitrate, sodium borate and the like, and among them, sodium metabisulfite is preferred.

These may be synthesized or commercially available products may be used as they are.

These inorganic acid salts may be used in combination of 1 or 2 or more.

In the external composition of the present invention, the total content of the pyrosulfite with respect to the total amount of the external composition can be appropriately set in accordance with the balance with other components. The content is preferably 0.00001% by mass or more, more preferably 0.0001% by mass or more, further preferably 0.0005% by mass or more, more preferably 0.001% by mass or more, and most preferably 0.005% by mass or more, based on the total amount of the composition for external use. The total content of the pyrosulfite is preferably 1% by mass or less, more preferably 0.8% by mass or less, further preferably 0.5% by mass or less, more preferably 0.4% by mass or less, and most preferably 0.3% by mass or less, based on the total amount of the external composition. The total content of the pyrosulfite is preferably 0.00001 to 1% by mass, more preferably 0.0001 to 0.8% by mass, even more preferably 0.0005 to 0.5% by mass, and most preferably 0.005 to 0.3% by mass, based on the total amount of the composition for external use.

In the composition for external use of the present invention, the ratio of the amount of the pyrosulfite to be incorporated in the component (a) is preferably to 1 part by mass of the total content of the component (a), and the total content of the pyrosulfite is preferably to one part by mass, more preferably to one part by mass, even more preferably to one part by mass, and most preferably to one part by mass.

(basic amino acid or salt thereof)

As the basic amino acid or a salt thereof used in the present invention, a compound generally used as a component of a skin external preparation in the fields of pharmaceuticals, quasi drugs, and cosmetics can be used.

The basic amino acid or a salt thereof contributes to the stability of the composition for external use of the present invention.

Herein, the basic amino acid means arginine, lysine, or histidine.

Here, the salt of a basic amino acid is a pharmaceutically acceptable salt. Examples of the salt include, but are not limited to, salts with organic bases (for example, salts with tertiary amines such as trimethylamine salt, triethylamine salt, monoethanolamine salt, triethanolamine salt, and pyridine salt, and basic ammonium salts such as arginine), salts with inorganic bases (for example, alkali metal salts such as ammonium salt, sodium salt, and potassium salt, alkaline earth metal salts such as calcium salt, and magnesium salt, and aluminum salt). Particularly preferred salts are sodium and calcium salts.

In the present invention, arginine is a preferred basic amino acid or a salt thereof.

These may be synthesized or commercially available products may be used as they are.

These basic amino acids or salts thereof may be used in combination of 1 or 2 or more.

In the external composition of the present invention, the total content of the basic amino acid or a salt thereof relative to the total amount of the external composition may be appropriately set in accordance with the balance with other components. The content is preferably 0.0001% by mass or more, more preferably 0.001% by mass or more, further preferably 0.005% by mass or more, more preferably 0.01% by mass or more, and most preferably 0.05% by mass or more, based on the total amount of the external composition. The total content of the basic amino acid or a salt thereof is preferably 10% by mass or less, more preferably 9% by mass or less, further preferably 8% by mass or less, more preferably 7% by mass or less, and most preferably 6% by mass or less, based on the total amount of the external composition. The total content of the basic amino acid or a salt thereof is preferably 0.0001 to 10% by mass, more preferably 0.001 to 9% by mass, even more preferably 0.005 to 8% by mass, and most preferably 0.05 to 6% by mass, based on the total amount of the external composition.

In the composition for external use of the present invention, the ratio of the amount of the basic amino acid or a salt thereof to be blended with respect to the component (a) is preferably 0.00003 to 0.8 part by mass, more preferably 0.00005 to 0.7 part by mass, even more preferably 0.00008 to 0.6 part by mass, and most preferably 0.0001 to 0.5 part by mass, based on 1 part by mass of the total content of the component (a).

(3-O-Ethyl ascorbic acid or salt thereof)

As the 3-O-ethyl ascorbic acid or a salt thereof used in the present invention, a compound generally used as a component of a skin external preparation in the fields of pharmaceuticals, quasi drugs, and cosmetics can be used.

3-O-Ethyl ascorbic acid can be synthesized by ethoxylating the hydroxyl group at the 3-position of ascorbic acid (for example, according to a known method described in Japanese patent application laid-open No. Hei 8-134055). The 3-O-ethyl ascorbic acid can be used as it is as a commercially available product. Examples of the commercially available products include, but are not limited to, "VC ethyl" manufactured by Japanese Kokai Co., Ltd and products manufactured by pure chemical Co., Ltd.

3-O-ethyl ascorbic acid contributes to the stability of the composition for external use of the present invention.

These may be synthesized, or a commercially available product may be used as it is.

These 3-O-ethyl ascorbic acids or salts thereof may be used in combination of 1 or 2 or more.

3-O-ethyl ascorbic acid may also be used as a salt. Here, the salt of 3-O-ethyl ascorbic acid means a pharmaceutically acceptable salt. Examples of the salt include, but are not limited to, salts with organic bases (for example, salts with tertiary amines such as trimethylamine salt, triethylamine salt, monoethanolamine salt, triethanolamine salt, and pyridine salt, and basic ammonium salts such as arginine), salts with inorganic bases (for example, alkali metal salts such as ammonium salt, sodium salt, and potassium salt, alkaline earth metal salts such as calcium salt, and magnesium salt, and aluminum salt). Particularly preferred salts of 3-O-ethyl ascorbic acid are sodium salts and potassium salts.

In the external composition of the present invention, the total content of 3-O-ethyl ascorbic acid or a salt thereof relative to the total amount of the external composition can be appropriately set in accordance with the balance with other components. The content is preferably 0.0001% by mass or more, more preferably 0.001% by mass or more, further preferably 0.005% by mass or more, more preferably 0.01% by mass or more, and most preferably 0.02% by mass or more, based on the total amount of the composition for external use. The total content of 3-O-ethyl ascorbic acid or a salt thereof is preferably 10% by mass or less, more preferably 8% by mass or less, still more preferably 6% by mass or less, more preferably 5% by mass or less, and most preferably 3% by mass or less, based on the total amount of the composition for external use. The total content of 3-O-ethyl ascorbic acid or a salt thereof is preferably 0.0001 to 10% by mass, more preferably 0.001 to 5% by mass, even more preferably 0.005 to 3% by mass, and most preferably 0.01 to 3% by mass, based on the total amount of the composition for external use.

In the composition for external use of the present invention, the ratio of the amount of 3-O-ethyl ascorbic acid or a salt thereof blended to component (a) is preferably 0.00001 to 1 part by mass, more preferably 0.00005 to 0.8 part by mass, even more preferably 0.0001 to 0.6 part by mass, and most preferably 0.0002 to 0.5 part by mass, based on 1 part by mass of the total content of component (a).

(C) The ingredients contribute to higher stability and percutaneous absorbability of the external composition of the present invention.

At least 1 kind selected from the group consisting of low molecular weight betaines, organic acid salts, inorganic acid salts, basic amino acids, salts of basic amino acids, 3-O-ethyl ascorbic acid, and salts of 3-O-ethyl ascorbic acid may be used in combination of 1 kind or any 2 or more kinds thereof.

Such a combination is not limited, and examples thereof include trimethylglycine and citrate, trimethylglycine and succinate, trimethylglycine and pyrosulfurous acid or a salt thereof, 3-O-ethyl ascorbic acid or a salt thereof and citrate, 3-O-ethyl ascorbic acid or a salt thereof and succinate, 3-O-ethyl ascorbic acid or a salt thereof and trimethylglycine, 3-O-ethyl ascorbic acid or a salt thereof and carnitine, 3-O-ethyl ascorbic acid or a salt thereof and sodium pyrrolidone carboxylate, 3-O-ethyl ascorbic acid or a salt thereof and pyrosulfurous acid or a salt thereof, and the like.

In the external composition of the present invention, the total content of the component (C) relative to the total amount of the external composition is not particularly limited, but is preferably 0.005 mass% or more, and more preferably 0.01 mass% or more. The total content of the component (C) is preferably 25% by mass or less, and more preferably 15% by mass or less, relative to the total amount of the external composition. The content of the component (C) is preferably 0.005 to 25% by mass, more preferably 0.01 to 15% by mass, based on the total amount of the external composition.

In the composition for external use of the present invention, the ratio of the amount of component (C) to be blended with component (a) is not particularly limited, but is preferably 0.00001 to 3 parts by mass, more preferably 0.0005 to 2 parts by mass, further preferably 0.0001 to 1 part by mass, further preferably 0.005 to 0.9 parts by mass, and most preferably 0.008 to 0.8 parts by mass, based on 1 part by mass of the total content of component (a).

[ (D) Water ]

The composition for external use of the present invention is a liquid composition containing water. The proportion of water is not limited, but is preferably 0.01 to 60% by mass, more preferably 0.01 to 50% by mass, and particularly preferably 0.1 to 40% by mass, relative to the composition for external use.

In the composition for external use of the present invention, the ratio of the amount of component (D) to component (a) is not particularly limited, but is preferably 0.01 to 10 parts by mass, more preferably 0.1 to 5 parts by mass, and most preferably 0.2 to 3 parts by mass, based on 1 part by mass of the total content of component (a).

In one embodiment of the present invention, the precipitation of ascorbic acid or a salt thereof can be suppressed even in such a composition containing a small amount of water. Further, decomposition of ascorbic acid can be suppressed.

[ ethoxydiglycol (diethylene glycol monoethyl ether) ]

In the present invention, ethoxy diglycol is not contained or is contained by less than 30% by mass mainly from the viewpoint of improvement in stability. The content of ethoxydiglycol in the external composition is not particularly limited as long as it is used as an ingredient of an external preparation for skin in the fields of pharmaceuticals, quasi-drugs, and cosmetics.

In the external composition of the present invention, the content of ethoxydiglycol relative to the total amount of the external composition is less than 30% by mass, the content of ethoxydiglycol is preferably 10% by mass or less, the content of ethoxydiglycol is more preferably 5% by mass or less, and the external composition may contain no ethoxydiglycol.

The total content of the ethoxydiglycol is 0 or more and less than 30% by mass, more preferably 0 to 10% by mass, and still more preferably about 0 to 5% by mass.

In the composition for external use of the present invention, the ratio of the amount of the ethoxydiglycol component to be incorporated in the component (a) is preferably 0 to 10 parts by mass, more preferably 0 to 5 parts by mass, based on 1 part by mass of the total content of the component (a). In addition, according to the circumstances, can also be 0.001 to 10 parts by mass, or 0.01 to 5 parts by mass.

The composition for external use of the present invention contains (a), (B), (C), and (D), and the content of ethoxydiglycol is defined, whereby the composition for external use of the present invention has good stability.

[ diethylene glycol Ether ]

In the present invention, it is preferable that the total amount of diethylene glycol ethers other than ethoxydiglycol is less than 40% by mass, or, if any, the total amount of diethylene glycol ethers together with ethoxydiglycol, mainly from the viewpoint of stability improvement. Here, the diethylene glycol ether other than ethoxydiglycol is not particularly limited as long as it is used as a component of a skin external preparation in the fields of pharmaceuticals, quasi-drugs, and cosmetics. It can be dissolved in water in an amount of 10g or more per 100g of water. Examples thereof include those having a polymerization degree of 2 or less. Specifically, diethylene glycol monomethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, diethylene glycol monoisobutyl ether, diethylene glycol dimethyl ether, ethylene glycol monobutyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, triethylene glycol monobutyl ether, tetraethylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, dipropylene glycol monopropyl ether, and the like can be exemplified. In addition, diethylene glycol monomethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, diethylene glycol monoisobutyl ether, diethylene glycol dimethyl ether, ethylene glycol monobutyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, triethylene glycol monobutyl ether, tetraethylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, dipropylene glycol monopropyl ether are typical examples. In particular, diethylene glycol monomethyl ether, diethylene glycol monopropyl ether, ethylene glycol monobutyl ether, triethylene glycol monobutyl ether, tetraethylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, dipropylene glycol monopropyl ether are typical examples.

These diethylene glycol ethers may also be used in combinations of 1 or 2 or more.

In the external composition of the present invention, the total content of the diethylene glycol ethers containing ethoxydiglycol with respect to the total amount of the external composition is preferably less than 40% by mass, more preferably less than 30% by mass, and even more preferably 10% by mass or less, and the external composition may contain no diethylene glycol ether.

The total content of the diethylene glycol ethers containing ethoxydiglycol is preferably 0 or more and less than 40% by mass, more preferably 0 or more and less than 30% by mass, even more preferably about 0 to 10% by mass, and most preferably about 0 to 5% by mass.

In the composition for external use of the present invention, the ratio of the diethylene glycol ether component to the diethylene glycol ether component of the component (a) is preferably 0 to 20 parts by mass, and more preferably 0 to 10 parts by mass, based on 1 part by mass of the total content of the component (a). In addition, according to the circumstances, can also be 0.001 to 20 parts by mass or 0.01 to 10 parts by mass.

The composition for external use of the present invention contains (a), (B), (C), and (D) and the content of the whole diethylene glycol ether is defined, whereby the composition for external use of the present invention can have good stability.

[ (E) lower alcohol ]

The composition for external use of the present invention may contain (E) a lower alcohol in addition to the above-mentioned components (a), (B), (C) and (D) and, if contained, a diethylene glycol ether such as ethoxydiglycol, from the viewpoints of improvement of feeling of use, stability and promotion of percutaneous absorption, as long as the effects of the present invention are not inhibited.

The lower alcohol used in the present invention is not particularly limited as long as it is used as a component of an external skin preparation in the fields of pharmaceuticals, quasi drugs, and cosmetics. In the present specification, the term "lower alcohol" means C₁-C₆The alcohol of (1). Among them, C is particularly preferably used₁-C₃The alcohol of (1). Examples of such solvents include methanol, ethanol, n-propanol, and isopropanol.

In the external composition of the present invention, the total content of the component (E) relative to the total amount of the external composition is preferably 0.1% by mass or more, and more preferably 0.5% by mass or more when contained.

(E) The total content of the components is preferably 25% by mass or less, more preferably 20% by mass or less.

(E) The total content of the components is preferably 0.001 to 25% by mass, more preferably 0.1 to 25% by mass, and still more preferably 0.5 to 20% by mass.

In the composition for external use of the present invention, the ratio of the amount of component (E) to the total content of component (a) is preferably 0.001 to 8 parts by mass, more preferably 0.005 to 5 parts by mass, relative to 1 part by mass of the total content of component (a).

[ polyhydric alcohol ]

The composition for external use of the present invention may contain a polyol in addition to the above-mentioned components (a), (B), (C) and (D) and, if contained, less than a certain amount of ethoxydiglycol, as long as the effect of the present invention is not impaired.

The polyhydric alcohol used in the present invention is not particularly limited as long as it is used as a component of an external skin preparation in the fields of pharmaceuticals, quasi drugs, and cosmetics. The polyhydric alcohol is not limited, but may be added for the purpose of moisture retention or as a solubilizer. Specific examples thereof include glycerin, diglycerin, dipropylene glycol, 1, 3-butanediol, and 3-methyl-1, 3-butanediol. Preferably 1, 3-butanediol or dipropylene glycol.

The total content of the polyhydric alcohol including the component (B) is preferably 10 to 90% by mass, more preferably 20 to 80% by mass, still more preferably 25 to 85% by mass, and particularly preferably about 30 to 70% by mass, when contained.

[ other Components ]

In the composition for external use of the present invention, in addition to the above-mentioned (a), (B), (C) and (D) and, if contained, less than a certain amount of ethoxydiglycol, various components such as a whitening component, an anti-inflammatory component, an antibacterial component, a cell activating component, an astringent component, an antioxidant component, an acne improving component, an anti-aging component, a component for promoting the synthesis of a biological component such as collagen, a blood circulation promoting component, a moisturizing component, an anti-aging component and the like may be combined in 1 or 2 or more for the purpose of enhancing or supplementing various actions of ascorbic acid and for adding other useful actions. Preferably 1 or 2 or more of whitening component, antiinflammatory component, antibacterial component, cell activating component, astringent component, antioxidant component, antiaging component or moisture keeping component. Particularly preferred combinations of these ingredients include a combination with a whitening ingredient, a combination with a whitening ingredient and an antioxidant ingredient, a combination with each antioxidant ingredient, a combination with an anti-aging ingredient, and a combination with each whitening ingredient and anti-aging ingredient. The components are not particularly limited as long as they are conventionally usable as a skin preparation for external use in the fields of pharmaceuticals, quasi drugs, and cosmetics, and any component may be appropriately selected and used.

In the composition for external use of the present invention, in addition to the above-mentioned components, a surfactant, a solubilizing component, oils and fats, a saccharide, or a percutaneous absorption-promoting component may be further blended. In particular, by blending a surfactant, a solubilizing component, or oils and fats, the stability, effectiveness, and feeling of use of ascorbic acid in an aqueous solvent can be further improved.

The composition for external use of the present invention may contain, as necessary, various components generally used as components of external preparations in the fields of pharmaceuticals, quasi-drugs, and cosmetics, for example, amino acids, irritation reducing agents, thickening agents, preservatives, ultraviolet protective agents, coloring agents, dispersing agents, additional pH adjusting agents, perfumes, and the like, without impairing the quality such as appearance stability and viscosity, and within an amount and quality range that does not impair the effect of the present invention. These components may be blended in 1 kind alone or 2 or more kinds arbitrarily.

The composition for external use of the present invention can be prepared in various desired forms such as a cream, a mousse, a gel, a liquid, an emulsion, a cream, a sheet (carrier substrate), an aerosol, and a spray by containing (a) at least 1 selected from ascorbic acid and a salt of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least 1 selected from low molecular weight betaines, organic acid salts, inorganic acid salts, basic amino acids, salts of basic amino acids, 3-O-ethyl ascorbic acid, and salts of 3-O-ethyl ascorbic acid, and (D) water, and mixing the above arbitrary components if necessary with a content of ethoxy diglycol of less than 30% by mass, and further mixing other solvents, bases for external use, and the like if necessary. These can be produced by a method generally used in the art.

The external composition of the present invention is particularly preferably a transparent or even translucent composition in which ascorbic acid and/or a salt thereof is solubilized. Here, "solubilization" is defined as follows. That is, for example, the transmittance at a wavelength of 700nm is in the range of 80 to 100%, preferably 85 to 100%, and more preferably 90 to 100% by an ultraviolet-visible absorbance measurement method using a spectrophotometer or a spectrophotometer UV-2450 (manufactured by Shimadzu corporation). Here, the transmittance of water is set to 100%. The solubilizing compositions of the present invention have a transparent or even translucent appearance. More specifically, the transmittance measurement method was carried out based on the 16 th modified Japanese pharmacopoeia [ B ] general test method 2. physical test method spectroscopic measurement method 2.24 method of measuring ultraviolet-visible absorbance.

[ viscosity ]

The composition for external use of the present invention can be prepared into a composition having an appropriate viscosity required particularly for use as a composition for external use suitable for the skin. The viscosity of the composition for external use of the present invention is not particularly limited, and is, for example, generally about 300mPa · s or less, preferably about 200mPa · s or less, more preferably about 100mPa · s or less, and most preferably about 50mPa · s or less when measured at 25 ℃ using an E-type viscometer. More specifically, the viscosity measurement method was carried out based on the 16 th modified Japanese pharmacopoeia [ B ] general test method 2. physical test method and other physical test methods 2.53 viscosity measurement method 2.2 nd rotational viscometer method 2.1.3 cone-plate rotational viscometer (cone-plate viscometer).

[pH]

The composition for external use of the present invention is generally required to have a liquid property of pH1 to 8, and is preferably in an acidic region of pH2 to 7, more preferably of pH2 to 6, and even more preferably of pH2 to 4.5, from the viewpoints of stability of ascorbic acid, low irritation to skin and mucous membrane, and good feeling of use on skin.

[ use ]

The composition for external use of the present invention is particularly effective as a whitening agent, an anti-inflammatory agent, and an anti-aging agent, and has, for example, acne prevention or treatment and antioxidant effects. Further, when applied to the skin, the skin may have a high transparency, be kept moist, have uniform skin texture, and exhibit an effect of preventing roughness. In addition, the composition may exhibit an effect of making pores inconspicuous and moisturizing the whole skin, and may be used for the prevention and treatment of spots.

The composition for external use of the present invention may be, for example, a base cosmetic material such as a cosmetic liquid, a lotion, a sunscreen cream, an emulsion, a cream, an emulsion, an oil, and a mask; makeup cosmetics such as foundation, lipstick, lip cream, mascara, eye shadow, eyeliner, eyebrow black, and nail makeup cosmetics; cleaning materials such as washing pigments, cleansing creams, body cleaning materials and the like; an anti-bromhidrosis agent, tinea pedis therapeutic agent, antipruritic agent, wound therapeutic agent, cleaning agent, anti-inflammatory analgesic, acne therapeutic agent, hemorrhoid agent, antibacterial disinfectant, whitening agent, ultraviolet protective agent, and various topical compositions belonging to the fields of cosmetics, topical pharmaceuticals or topical quasi drugs. The present invention is preferably used for products for external application to the skin (preparations for external application to the skin) such as skin preparations for external application to the skin.

[ stabilizing method ]

The present invention also includes (a) a stabilization method of at least 1 selected from ascorbic acid and a salt of ascorbic acid. In the present invention, a method for stabilizing ascorbic acid is a method in which (a) at least 1 selected from ascorbic acid and a salt of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least 1 selected from low-molecular betaines, organic acid salts, inorganic acid salts, basic amino acids, salts of basic amino acids, 3-O-ethyl ascorbic acid, and salts of 3-O-ethyl ascorbic acid, and (D) water are used in combination, and the content of ethoxydiglycol is less than 30% by mass, whereby a stable preparation can be formed while containing ascorbic acid or a salt thereof. In particular, ascorbic acid or a salt thereof can be contained at a high concentration (for example, 15% by mass or more, or 20% by mass or more) and a stable preparation can be formed. That is, the present invention relates to a method for imparting stability to an external composition containing (a) at least 1 selected from ascorbic acid and a salt of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least 1 selected from a low-molecular betaine, a salt of an organic acid, an inorganic acid salt, a basic amino acid, a salt of a basic amino acid, 3-O-ethyl ascorbic acid, and a salt of 3-O-ethyl ascorbic acid, and (D) water, and wherein the content of ethoxydiglycol is less than 30% by mass. Here, the term "stabilization" refers to, for example, although not limited to, securing stability at a high temperature or a low temperature. Specifically, the composition for external use is inhibited from precipitation of ascorbic acid or a salt thereof even when stored at 4 ℃ for at least 1 week, or is inhibited from changing in appearance such as coloration even after storage at 50 ℃ or 40 ℃.

In the method of the present invention, a) at least 1 selected from ascorbic acid and a salt of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least 1 selected from a low molecular weight betaine, a salt of an organic acid, a salt of an inorganic acid, a basic amino acid, a salt of a basic amino acid, 3-O-ethyl ascorbic acid, and a salt of 3-O-ethyl ascorbic acid, and (D) water are used in combination, and the content of ethoxydiglycol is made to be less than 30 mass%, and the content and the like are the same as those in the case of using the above-mentioned composition for external use. The substance obtained by the method can be used in a known or customary manner and amount from 1 day to 1 to a plurality of times depending on the intended use and the like.

[ improvement of feeling of use ]

In the present invention, the feeling of use of the composition for external use containing (a) at least 1 selected from ascorbic acid and salts of ascorbic acid can also be improved. In the present invention, ascorbic acid or a salt thereof is contained and the feeling of use is improved by using (a) at least 1 selected from ascorbic acid and a salt of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least 1 selected from low-molecular betaines, organic acid salts, inorganic acid salts, basic amino acids, salts of basic amino acids, 3-O-ethyl ascorbic acid, and salts of 3-O-ethyl ascorbic acid, and (D) water in combination, and by making the content of ethoxydiglycol less than 30% by mass. In particular, ascorbic acid or a salt thereof can be contained at a high concentration (for example, 10% by mass or more, or 20% by mass or more) and a good feeling in use can be achieved.

In the present invention, in order to obtain a good feeling of use, (a) at least 1 selected from ascorbic acid and a salt of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least 1 selected from low molecular weight betaines, organic acid salts, inorganic acid salts, basic amino acids, salts of basic amino acids, 3-O-ethyl ascorbic acid, and salts of 3-O-ethyl ascorbic acid, and (D) water are used in combination, and the content of ethoxydiglycol is made to be less than 30 mass%, and the content and the like are the same as those in the case of using the above-mentioned external composition. Here, the favorable use feeling means at least one or all of a feeling of penetration, a reduction in stickiness, a alleviation of a feeling of irritation, and a smoothness of the skin when applied to the skin.