JPWO2019189742A1 - Topical composition containing ascorbic acid and / or a salt thereof - Google Patents

Abstract

Provided is an external composition having excellent stability and usability. 10% by mass or less of at least one selected from the group consisting of (A) ascorbic acid and a salt of ascorbic acid; (B) 30% by mass or more of a diol having 3 carbon atoms; and (C) 20% by mass of water. % Or less, the content of ethoxydiglycol is less than 30% by mass, and the pH is 4.5 or less to prepare an external composition. Alternatively, 10 to 25% by weight of at least one selected from the group consisting of (A) ascorbic acid and a salt of ascorbic acid, and (B) a diol having 3 carbon atoms other than (A) and (C). 30-90% by weight of the ingredients; and (C) water, ethoxydiglycol content less than 30% by weight, (C) / (A) = 0.2-5, and pH 2.0- Prepare an external composition of 6.0.

Description

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

Ascorbic acid has anti-inflammatory effect, acne improving effect, whitening effect, anti-aging effect, antioxidant effect, cell activation effect by promoting synthesis of biological components such as collagen, and suppresses cell damage and DNA damage caused by ultraviolet rays of epidermal keratinocytes. It is known to exert various effects such as the effect of collagen, and it is widely used as an external preparation for skin in anticipation of these effects.

Several methods for stably solubilizing ascorbic acid in an aqueous external preparation for skin have been studied (for example, Patent Document 1: WO02 / 19972, Patent Document 2: WO00 / 78283, Patent Documents). 3: Japanese Patent Application Laid-Open No. 2002-348228, Patent Document 4: Japanese Patent Application Laid-Open No. 2005-225856).

WO02 / 19972 WO00 / 78283 JP-A-2002-348228 Japanese Unexamined Patent Publication No. 2005-225856

An object of the present invention is to provide an ascorbic acid-containing external composition having good properties.

An external composition containing ascorbic acid and / or a salt thereof is provided.

According to the studies by the present inventors, it has been found that when ascorbic acid and / or a salt thereof is blended, some of them may be colored from the time of manufacture, or may be colored after a certain period of time. Furthermore, it was found that there may be a problem of ascorbic acid precipitation during low temperature storage and a problem of transdermal absorbability.

As a result of diligent studies to solve this problem, the present inventors have selected at least one kind from the group consisting of (A) ascorbic acid and a salt of ascorbic acid in an amount of 10% by mass or less and (B) carbon number. By containing 30% by mass or more of three diols and 20% by mass or less of (C) water, and further setting the content of ethoxydiglycol to less than 30% by mass and the pH to 4.5% or less, or At least 1 type 10 to 25% by mass (B) diol having 3 carbon atoms selected from the group consisting of (A) ascorbic acid and a salt of ascorbic acid is 30 in the components excluding (A) and (C). It contains ~ 90% by mass, (C) water, further contains less than 30% by mass of ethoxydiglycol, (C) / (A) = 0.2-5, and has a pH of 2.0-6. By setting the value to 0, it was found that an external composition that suppresses the coloring of ascorbic acid and has excellent transdermal absorbability (skin permeability) of ascorbic acid can be obtained, and has completed the present invention.

That is, the present invention provides the following external composition.
Item 1.
(A) 10% by mass or less of at least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid;
(B) Contains 30% by mass or more of a diol having 3 carbon atoms; and (C) Contains 20% by mass or less of water, the content of ethoxydiglycol is less than 30% by mass, and the pH is 4.5 or less. External composition:
Item 2.
Item 2. The external composition according to Item 1, wherein the content of the component (B) is 40% by mass or more.
Item 3.
Item 2. The external composition according to Item 1 or 2, wherein the content of the ascorbic acid or a salt thereof is 3 to 10% by mass.
Item 4.
(C) The external composition according to any one of Items 1 to 3, wherein the content of water is 10% by mass or less:
Item 5.
(A) 10 to 25% by mass of at least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid.
(B) A diol having 3 carbon atoms is contained in the components other than (A) and (C) in an amount of 30 to 90% by mass; and (C) contains water, and the content of ethoxydiglycol is less than 30% by mass, (C. ) / (A) = 0.2 to 5, and an external composition having a pH of 2.0 to 6.0:
Item 6.
Item 2. The external composition according to any one of Items 1 to 5, further containing butylene glycol and / or a lower alcohol:
Item 7.
Item 2. The external composition according to any one of Items 1 to 6, wherein the component (B) is 1,3-propanediol and / or propylene glycol.
Item 8.
Item 2. The external composition according to any one of Items 1 to 7, wherein the component (B) contains at least 1,3-propanediol.
Item 9.
Item 2. The external composition according to any one of Items 1 to 8, wherein the content of ethoxydiglycol is 10% by mass or less.
Item 10.
Item 2. The external composition according to any one of Items 1 to 9, wherein the external composition is a solubilized external composition having a transmittance of 85 to 100% at a wavelength of 700 nm.
Item 11.
Item 2. The external composition according to any one of Items 1 to 10, wherein the external composition is for promoting transdermal absorption of ascorbic acid:
Item 12.
(A) 10% by mass or less of at least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid;
(B) 30% by mass or more of diol having 3 carbon atoms; and (C) 20% by mass or less of water are used in combination, the content of ethoxydiglycol is less than 30% by mass, and the pH is 4.5 or less. (A) A method for preventing coloring and / or precipitation of crystals of an external composition containing at least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid.
Item 13.
(A) 10 to 25% by mass of at least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid.
(B) A diol having 3 carbon atoms is contained in an amount of 30 to 90% by mass in components other than (A) and (C); and (C) water is contained, and the content of ethoxydiglycol is less than 30% by mass. At least one selected from the group consisting of (A) ascorbic acid and a salt of ascorbic acid according to C) / (A) = 0.2 to 5 and a pH of 2.0 to 6.0. A method for preventing coloring and / or precipitation of crystals of the contained external composition.

INDUSTRIAL APPLICABILITY According to the present invention, an external composition having excellent stability can be provided.

FIG. 1 is a graph showing the results of a transdermal absorbability test of the external composition of Examples and Comparative Examples.

In the present specification, the unit of content "mass%" is synonymous with "g / 100g".

The first aspect of the present invention is a case where at least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid is 10% by mass or less (hereinafter, also referred to as the first invention).
The external composition of the first invention is
(A) 10% by mass or less of at least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid;
(B) contains 30% by mass or more of a diol having 3 carbon atoms; and (C) contains 20% by mass or less of water, the content of ethoxydiglycol (diethylene glycol monoethyl ether) is less than 30% by mass, and the pH is The composition for external use is 4.5 or less.

The external composition of the first invention is stable in a relatively low concentration range of at least one selected from the group consisting of (A) ascorbic acid and a salt of ascorbic acid, and has excellent transdermal absorbability.

[(A) At least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid]
In the present invention, ascorbic acid commercially available as a component of an external preparation for skin can be used in the fields of pharmaceuticals, quasi-drugs or cosmetics, and these usually refer to L-form products.

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

In the present invention, ascorbic acid or a salt thereof can be used alone or in combination of two or more.

In the external composition of the first invention, the total content of the component (A) with respect to the total amount of the external composition is appropriately set depending on the balance with other components. The total content of the component (A) is not particularly limited as long as it is 10% by mass or less with respect to the total amount of the external composition, but is preferably 1% by mass or more, more preferably 2% by mass or more, still more preferably. Is 3% by mass or more. The total content of the component (A) is 10% by mass or less, preferably 9% by mass or less, and more preferably 8% by mass or less, based on the total amount of the external composition. The total content of the component (A) is preferably 1% by mass to 10% by mass, more preferably 2% by mass to 10% by mass, and further preferably 3% by mass to the total amount of the external composition. It is 8% by mass.

[(B) Diol with 3 carbon atoms]
The diol having 3 carbon atoms used in the present invention is not particularly limited as long as it is used as a component of an external preparation for skin in the fields of pharmaceuticals, quasi-drugs or cosmetics. The three-carbon diol is preferably, but not limited to, 1,3-propanediol (CAS number: 504-63-2, English name: 1,3-Dihydroxypropane or TrimethyleneGlycol) or propylene glycol (CAS number: 57). -55-6, English name: 1,2-Dihydroxypropane, Japanese name alias: 1,2-propanediol). For example, any one or both 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 can be used as it is. From the viewpoint of alleviating irritation to the skin, improving usability, and suppressing coloration, it is preferable to combine 1,3-propanediol and propylene glycol.

In the external composition of the first invention, the total content of the component (B) with respect to the total amount of the external composition is 30% by mass or more, preferably 35% by mass or more, more preferably 40% by mass or more. More preferably, it is 45% 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, still more preferably 80% by mass or less.

The total content of the component (B) with respect to the total amount of the external composition of the first invention is preferably 35 to 90% by mass, more preferably 40 to 85% by mass, and further preferably 45 to 80% by mass.

In the external composition of the first invention, the ratio of the content of the component (B) to the component (A) is not particularly limited, but is preferably 3 to 300 with respect to 1 part by mass of the total content of the component (A). It is by mass, more preferably 3 to 30 parts by mass, and even more preferably 5 to 25 parts by mass.

[(C) Water]
The external composition of the first invention is a liquid composition containing water. The proportion of water is not limited, but is preferably 0.1% by mass or more, more preferably 1% by mass or more, and most preferably more than 1% by mass with respect to the external composition. The excess of 1% by mass is not limited, but may be, for example, a value of 1.01% by mass or more, 1.1% by mass or more, or the like. The ratio of water is 20% by mass or less with respect to the composition for external use. It is preferably 15% by mass or less, more preferably 10% by mass or less.

The total content of the component (C) with respect to the total amount of the external composition of the first invention is preferably 1% by mass to 15% by mass, more preferably more than 1% by mass to 10% by mass, and further preferably 2 to 10% by mass. It is mass%.

In the external composition of the first invention, the ratio of the content of the component (C) to the component (A) is not particularly limited, but is preferably 0.1 with respect to 1 part by mass of the total content of the component (A). It is 10 parts by mass, more preferably 0.125 to 8 parts by mass, and further preferably 0.2 to 5 parts by mass.

In the present invention, the precipitation of ascorbic acid or a salt thereof can be suppressed even in a composition containing a small amount of water. Further, the composition can be used for external use, which is also excellent in stability. However, from the viewpoint of suppressing the precipitation of ascorbic acid at low temperatures, it is preferable to add even a small amount.

[Ethoxydiglycol (diethylene glycol monoethyl ether)]
In the present invention, ethoxydiglycol is not contained, or even if it is contained, it is less than 30% by mass, mainly from the viewpoint of improving stability. The ethoxydiglycol contained in the external composition in an amount of less than 30% by mass 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 or cosmetics.

In the external composition of the first invention, the content of ethoxydiglycol with respect to the total amount of the external composition is less than 30% by mass, preferably 20% by mass or less, and more preferably 10% by mass or less. , More preferably 5% by mass or less, and ethoxydiglycol may not be contained in the external composition.
The total content of ethoxydiglycol is 0 or more and less than 30% by mass, preferably 0 to 20% by mass, more preferably 0 to 10% by mass, and further preferably about 0 to 5% by mass.

In the external composition of the first invention, the ratio of the content of the ethoxydiglycol component to the component (A) is preferably 0 to 10 parts by mass with respect to 1 part by mass of the total content of the component (A), which is 0. ~ 5 parts by mass is more preferable. Further, depending on the case, it may be 0.001 to 10 parts by mass, or 0.01 to 5 parts by mass.

[pH]
The first external composition of the present invention preferably has a pH of 1.5 to 4.5, more preferably pH 1.5 to 4.5, from the viewpoints of stability of the component (A), hypoallergenicity to the skin and mucous membranes, and good skin usability. It is desirable that the pH is in the acidic region of 2 to 4.

The external composition of the first invention contains a predetermined amount of the component (A), the component (B), and the component (C), defines the content of ethoxydiglycol, and further sets the pH to 4.5 or less. As a result, the composition for external use has good stability.

[Glycol ether]
In the present invention, mainly from the viewpoint of improving stability, glycol ethers other than ethoxydiglycol are not contained, or even if they are contained, the total amount of glycol ethers together with ethoxydiglycol is less than 40% by mass. Is preferable. Here, the glycol ether other than ethoxydiglycol is not particularly limited as long as it is used as a component of an external preparation for skin in the fields of pharmaceuticals, quasi-drugs or cosmetics. Anything that dissolves 10 g or more in 100 g of water may be used. Examples have a degree of polymerization 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. Examples thereof include glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether. Furthermore, 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 mono Typical examples are butyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether. 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 Typical examples are ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether.

These glycol ethers can also be used alone or in combination of two or more.

In the external composition of the first invention, the total content of glycol ether including ethoxydiglycol is preferably less than 40% by mass, more preferably 30% by mass or less, based on the total amount of the external composition. Further preferably, it is less than 10% by mass, more preferably 10% by mass or less, and the glycol ether may not be contained in the external composition.

The total content of the glycol ether including ethoxydiglycol is preferably 0 or more and less than 40% by mass, more preferably 0 or more and less than 30% by mass, and further preferably about 0 or more and 10% by mass.

In the external composition of the first invention, the ratio of the content of the glycol ether component to the component (A) is preferably 0 to 20 parts by mass with respect to 1 part by mass of the total content of the component (A). Preferably, it is 0 to 10 parts by mass. Further, depending on the case, it may be 0.001 to 20 parts by mass or 0.01 to 10 parts by mass.

The external composition of the first invention contains a predetermined amount of the component (A), the component (B), and the component (C), defines the content of the entire glycol ether, and has a pH of 4.5 or less. Therefore, it is possible to obtain a more stable external composition.

[Lower alcohol]
The external composition of the first invention has the above-mentioned components (A), (B), and (C) from the viewpoint of improving usability, stability, and promoting transdermal absorption, as long as the effects of the present invention are not impaired. ) In addition to the component and, if contained, a glycol ether such as ethoxydiglycol, a lower alcohol may be contained. The lower alcohol used in the present invention is not particularly limited as long as it is used as a component of an external preparation for skin in the fields of pharmaceuticals, quasi-drugs or cosmetics. As used herein, the term "lower alcohol" refers to alcohol C ₁ -C _6. Among them, in _particular, it can be preferably used alcohol C 1 -C _3. Examples of such examples include methanol, n-propanol, isopropanol and the like in addition to ethanol.

In the external composition of the first invention, when it is contained, the content of the lower alcohol with respect to the total amount of the external composition is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, still more preferable. Is 0.25% by mass or more, more preferably 1% by mass or more, and most preferably 3% by mass or more. The content of ethanol is preferably 45% by mass or less, more preferably 40% by mass or less, still more preferably 35% by mass or less, still more preferably 20% by mass or less.

The content of the lower alcohol contained in the external composition of the first invention is preferably 0.01 to 45% by mass, more preferably 0.1 to 40% by mass, still more preferably 0.25 to 35% by mass. , Even more preferably 1 to 20% by mass, and most preferably 3 to 20% by mass.

[Butylene glycol]
From the viewpoint of improving usability, stability and promoting transdermal absorption, the external composition of the present invention contains the above-mentioned components (A), (B) and (C) as long as the effects of the present invention are not impaired. , And, if included, butylene glycol (1,3-butylene glycol) may be included in addition to glycol ethers such as ethoxydiglycol.

In the external composition of the first invention, the content of butylene glycol with respect to the total amount of the external composition, when contained, is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, still more preferably. Is 0.25% by mass or more. The content of butylene glycol is preferably 55% by mass or less, more preferably 50% or less by mass, and further preferably 45% by mass or less.

The content of butylene glycol in the external composition of the first invention is preferably 0.01 to 55% by mass, more preferably 0.1 to 50% by mass, still more preferably 0.25 to 45% by mass. is there.

[pH regulator]
The external composition of the first invention has the above-mentioned components (A), (B), and components (B), as long as the effects of the first invention are not impaired, from the viewpoint of improving usability, stability and promoting transdermal absorption. In addition to the component (C) and, if contained, a glycol ether such as ethoxydiglycol, a pH adjuster may be contained.

As the pH adjuster used in the first invention, a compound usually used as a component of a skin external preparation in the fields of pharmaceuticals, quasi-drugs or cosmetics can be used. Although not particularly limited, a pH adjuster having an amine (for example, aspartic acid or a salt thereof, ε-aminocaproic acid or a salt thereof, glutamic acid or a salt thereof, aminoethylsulfonic acid or a salt thereof, monoethanolamine, triethanolamine, etc. Diisopropanolamine, triisopropanolamine, arginine, lysine, L-carnitine, low molecular weight betaine, preferably low molecular weight betaine, more preferably trimethylglycine), organic acid salts (eg, sodium lactate, sodium acetate, sodium citrate, succinate) Sodium acid, sodium oxalate, calcium gluconate, sodium pyrrolidone carboxylate, etc.), inorganic acid salts (eg, sodium pyrosulfate, potassium pyrosulfate, sodium phosphate, potassium nitrate, sodium borate, preferably sodium pyrosulfate), base Examples thereof include sex amino acids and salts thereof (arginine, lysine, or histidine and salts thereof), 3-O-ethylascorbic acid or salts thereof.

In the external composition of the first invention, the total content of the pH adjuster with respect to the total amount of the external composition is not particularly limited, but is preferably 0.01% by mass or more, more preferably 0.05% by mass or more. Is. The total content of the pH adjuster is preferably 10% by mass or less, more preferably 5.0% by mass or less, based on the total amount of the external composition. The content of the pH adjuster having an amine or amino group with respect to the total amount of the external composition is preferably 0.01% by mass to 10% by mass, more preferably 0.05% by mass to 5.0% by mass. %.

In the external composition of the first invention, the ratio of the content of the pH adjuster to the component (A) is not particularly limited, but 0.00001 to 20% by mass with respect to 1 part by mass of the total content of the component (A). Parts are preferable, 0.0001 to 20 parts by mass is more preferable, 0.0005 to 10 parts by mass is further preferable, 0.005 to 5 parts by mass is more preferable, and 0.01 to 1 part by mass is most preferable.

[Other ingredients]
In addition to the above-mentioned component (A), component (B), and component (C), and if contained, less than a certain amount of ethoxydiglycol, the external composition of the present invention further contains various types of ascorbic acid. Whitening ingredient, anti-inflammatory ingredient, antibacterial ingredient, cell activating ingredient, astringent ingredient, antioxidant ingredient, acne improving ingredient, anti-aging ingredient for the purpose of enhancing or supplementing the action of , Collagen and other biological component synthesis promoting components, blood circulation promoting components, moisturizing components, anti-aging components and other various components can be blended in one or a combination of two or more. It is preferably one or more components such as a whitening component, an anti-inflammatory component, an antibacterial component, a cell activating component, an astringent component, an antioxidant component, an antiaging component or a moisturizing component. Particularly preferable combinations of these components are a combination with a whitening component, a combination of a whitening component and an antioxidant component, each combination with an antioxidant component, a combination with an antiaging component, and a whitening component and an antiaging component. Each combination of can be mentioned. Each of these components is not particularly limited as long as it is conventionally used as a component of an external preparation for skin in the fields of pharmaceuticals, quasi-drugs, or cosmetics, and will be used in the future, and any component may be appropriately selected. Can be used.

In addition to each of the above components, the external composition of the present invention may further contain a surfactant, a solubilizing component, oils and fats, sugars, or a transdermal absorption promoting component. In particular, by blending a surfactant, a solubilizing component or oils and fats, the stability, effectiveness and usability of ascorbic acid in an aqueous solvent can be further improved.

The external composition of the present invention includes pharmaceuticals, quasi-drugs or cosmetics as necessary within a quantitative and qualitative range that does not impair quality such as appearance stability and viscosity, and does not impair the effects of the present invention. Various components commonly used as components of external preparations in the field, such as amino acids, irritation reducers, thickeners, preservatives, UV protective agents, colorants, dispersants, additional pH regulators, fragrances, etc. Can be blended. In addition, these components may be used alone or in combination of two or more.

The external composition of the first invention contains 10% by mass or less of at least one selected from the group consisting of (A) ascorbic acid and a salt of ascorbic acid, and (B) 30% by mass of a diol having 3 carbon atoms. As described above, (C) contains 20% by mass or less of water, the content of ethoxydiglycol is less than 30% by mass, and the pH is 4.5 or less, and if necessary, each of the above optional components is mixed and mixed. In addition, by adding other solvents or the base of commonly used external preparations as necessary, paste-like, mousse-like, gel-like, liquid, emulsion-like, cream-like, sheet-like (supporting base material) It can be prepared in various desired forms such as aerosol-like and spray-like. These can be manufactured by the usual methods in the industry.

The external composition of the present invention is particularly preferably a transparent to translucent composition in which ascorbic acid and / or a salt thereof is solubilized. Here, "solubilization" is defined as follows. That is, for example, by the ultraviolet-visible absorbance measurement method, the transmittance is 80 to 100%, preferably 85 to 100, as the transmittance at a wavelength of 700 nm using a spectrophotometer or a photoelectric photometer UV-2450 (manufactured by Shimadzu Corporation). %, More preferably in the range of 90-100%. Here, the transmittance of water is 100%. The solubilized composition of the present invention has a transparent or translucent appearance. For more details, refer to the 16th revised Japanese Pharmacopoeia [B] general test method. Physical test method Spectroscopic measurement method 2.24 Follow the method described in UV-visible absorbance measurement method.

[viscosity]
The external composition of the present invention can be prepared as a composition having an appropriate viscosity desired especially when using an external composition used for application to the skin. The viscosity of the external composition of the present invention is not particularly limited, but for example, the viscosity when measured at 25 ° C. using an E-type viscometer is usually about 1 to 300 mPa · s, preferably about 1 to 200 mPa · s. , More preferably about 1 to 100 mPa · s, and most preferably about 1 to 50 mPa · s. For more details, the viscosity measurement method is the 16th revised Japanese Pharmacopoeia [B] general test method. Physical test method Other physical test method 2.53 Viscosity measurement method 2. Second method Rotational viscometer method 21.3 Conforms to the method described in the cone-plate type rotational viscometer (cone plate type viscometer).

[Use]
The external composition 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, treatment, and antioxidant effects. Further, when applied to the skin, the transparency of the skin is enhanced, the moisture is maintained, the texture is smoothed, and the effect of suppressing roughness may be exhibited. Furthermore, it may have effects such as making pores inconspicuous and moisturizing the skin, and can also be used for prevention and treatment of age spots.

The external composition of the present invention is, for example, basic cosmetics such as beauty liquids, lotions, sunscreen creams, emulsions, creams, lotions, oils and packs; foundations, lip balms, lip balms, mascara, eye shadows, eye liners, etc. Makeup cosmetics such as eyebrows and nail polish; cleaning agents such as pigments, cleansers, and body cleaning agents; axillary odor inhibitors, water bug remedies, antipruritic agents, wound healing agents, cleaning agents, cleaning agents, anti-inflammatory analgesics, acne It can be various external compositions belonging to the field of cosmetics, external pharmaceuticals or external pharmaceutical products such as therapeutic agents, hemorrhagic agents, bactericidal disinfectants, whitening agents and ultraviolet protective agents. From the viewpoint of the effect on the skin, the present invention is preferably used for products applied to the exodermis such as external preparations for the skin (preparations for the exodermis).

[Stabilization method]
The present invention also includes at least one stabilizing method selected from the group consisting of (A) ascorbic acid and a salt of ascorbic acid. In the present invention, according to the method for stabilizing ascorbic acid, at least one selected from the group consisting of (A) ascorbic acid and a salt of ascorbic acid is 10% by mass or less and (B) a diol having 3 carbon atoms. 30% by mass or more and (C) 20% by mass or less of water, the content of ethoxydiglycol is less than 30% by mass, and the pH is 4.5 or less, thereby containing ascorbic acid. It can be a stable preparation. That is, in the present invention, at least one selected from the group consisting of (A) ascorbic acid and a salt of ascorbic acid is 10% by mass or less, (B) a diol having 3 carbon atoms is 30% by mass or more, and ( C) From the group consisting of (A) ascorbic acid and a salt of ascorbic acid by using 20% by mass or less of water in combination, the content of ethoxydiglycol is less than 30% by mass, and the pH is 4.5 or less. It relates to a method of imparting stability to an external composition containing at least one selected. Here, stabilization is not limited, but means that stability is guaranteed even under high temperature or low temperature, for example. Specifically, the precipitation of ascorbic acid or a salt thereof is suppressed even when the external composition is stored at 4 ° C. for 1 week, or even after storage at 50 ° C. or storage at 40 ° C. for a certain period of time. It means that changes in appearance such as coloring are suppressed.

In the method of the present invention, containing (A) at least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid, (B) a diol having three carbon atoms, and (C) water, and ethoxydiglycol. The amount, the ratio thereof, and the like are the same as those used in the external composition. Further, the product obtained by this method can be divided into one to several times a day depending on the intended use and the like, and can be used in a known or commonly used dosage and administration.

A second aspect of the present invention is the case where at least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid is in an amount of 10 to 25% by mass (hereinafter, also referred to as the second invention).
The external composition of the second invention is
(A) 10 to 25% by mass of at least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid.
(B) A diol having 3 carbon atoms is contained in an amount of 30 to 90% by mass in components other than (A) and (C); and (C) water is contained, and the content of ethoxydiglycol is less than 30% by mass. C) / (A) = 0.2 to 5, and an external composition having a pH of 2.0 to 6.0.

The external composition of the second invention is stable in a relatively high concentration range of at least one selected from the group consisting of (A) ascorbic acid and a salt of ascorbic acid, and is excellent in transdermal absorbability.

[(A) At least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid]
In the present invention, ascorbic acid commercially available as a component of an external preparation for skin can be used in the fields of pharmaceuticals, quasi-drugs or cosmetics, and these usually refer to L-form products.

Ascorbic acid salts can also be used. Here, the salt of ascorbic acid is the same as that defined in the case of the first invention. For example, but not limited to, salts with organic bases (eg, salts with tertiary amines such as trimethylamine salt, triethylamine salt, monoethanolamine salt, triethanolamine salt, pyridine salt, basic ammonium salts such as arginine). , Etc.), salts with inorganic bases (for example, alkali metal salts such as ammonium salt, sodium salt, potassium salt, alkaline earth metal salts such as calcium salt, magnesium salt, aluminum salt, etc.) and the like. Particularly preferable salts of ascorbic acid are sodium salt and potassium salt. Specific examples thereof include sodium ascorbic acid, sodium ascorbic acid monophosphate, sodium ascorbic acid diphosphate, sodium ascorbic acid triphosphate, sodium ascorbic acid-2-sulfate, and the like.

In the present invention, ascorbic acid or a salt thereof can be used alone or in combination of two or more.

In the external composition of the second invention, the total content of the component (A) with respect to the total amount of the external composition is appropriately set depending on the balance with other components. The total content of the component (A) is not particularly limited as long as it is 10 to 25% by mass with respect to the total amount of the external composition.

[(B) Diol with 3 carbon atoms]
The diol having 3 carbon atoms used in the external composition in the second invention 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 or cosmetics. It is the same as that defined in the case of the first invention. The diol having 3 carbon atoms is preferably 1,3-propanediol or propylene glycol, although it is not limited. For example, any one or both 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 can be used as it is. From the viewpoint of alleviating irritation to the skin, improving usability, and suppressing coloration, it is preferable to combine 1,3-propanediol and propylene glycol.

In the external composition of the second invention, the total content of the component (B) with respect to the total amount of the external composition is 10% by mass or more, preferably 15% by mass or more, more preferably 20% by mass or more. More preferably, it is 25% 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, still more preferably 80% by mass or less, still more preferably 70% or less. It is less than the mass.

The total content of the component (B) with respect to the total amount of the external composition is preferably 10 to 90% by mass, more preferably 15 to 85% by mass, still more preferably 20 to 80% by mass, still more preferably 25% by mass. ~ 70% by mass.

In the external composition of the second invention, the ratio of the content of the component (B) to the component (A) is not particularly limited, but is preferably 0.5 with respect to 1 part by mass of the total content of the component (A). It is 10 parts by mass, more preferably 0.75 to 8 parts by mass, and further preferably 1 to 7 parts by mass.

In the external composition of the second invention, the content of the component (B) with respect to the component (A) and the component other than the component (C) described later is preferably 30 to 95% by mass, more preferably 40 to 90% by mass. , Even more preferably 50 to 85% by mass.

[(C) Water]
The external composition of the second invention is a liquid composition containing water. The proportion of water is not limited, but is preferably 0.01% by mass to 60% by mass, more preferably 1% by mass to 50% by mass, and 3% by mass to the external composition. It is even more preferably 40% by mass, and particularly preferably 5% by mass to 30% by mass.

In the external composition of the second invention, the ratio of the content of the component (C) to the component (A) is not particularly limited, but is preferably 0. It is 2 to 5 parts by mass, more preferably 0.5 to 2 parts by mass, and even more preferably 0.6 to 1.8 parts by mass.

[Ethoxydiglycol (diethylene glycol monoethyl ether)]
In the second invention, ethoxydiglycol is not contained, or even if it is contained, it is less than 30% by mass, mainly from the viewpoint of improving stability. The ethoxydiglycol contained in the external composition in an amount of less than 30% by mass 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 or cosmetics.

In the external composition of the second invention, the content of ethoxydiglycol with respect to the total amount of the external composition is less than 30% by mass, preferably 20% by mass or less, and more preferably 10% by mass or less. , More preferably 5% by mass or less, and ethoxydiglycol may not be contained in the external composition.
The total content of ethoxydiglycol is 0 or more and less than 30% by mass, preferably 0 to 20% by mass, more preferably 0 to 10% by mass, and further preferably about 0 to 5% by mass.

In the external composition of the second invention, the ratio of the content of the ethoxydiglycol component to the component (A) is preferably 0 to 10 parts by mass with respect to 1 part by mass of the total content of the component (A), which is 0. ~ 5 parts by mass is more preferable. Further, depending on the case, it may be 0.001 to 10 parts by mass, or 0.01 to 5 parts by mass.

[pH]
The external composition of the present invention usually has a liquid property of pH 1 to 8, but is preferably pH 2 from the viewpoint of stability of ascorbic acid, hypoallergenicity to the skin and mucous membranes, and good skin usability. It is desirable that it is in an acidic region of ~ 7, more preferably pH 2-6, even more preferably pH 2-5, and particularly preferably pH 2-4.5.

[Glycol ether]
In the present invention, mainly from the viewpoint of improving stability, glycol ethers other than ethoxydiglycol are not contained, or even if they are contained, the total amount of glycol ethers together with ethoxydiglycol is less than 40% by mass. Is preferable. Here, the glycol ether other than ethoxydiglycol is not particularly limited as long as it is used as a component of an external preparation for skin in the fields of pharmaceuticals, quasi-drugs or cosmetics. Anything that dissolves 10 g or more in 100 g of water may be used. Examples have a degree of polymerization 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. Examples thereof include glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether. Furthermore, 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 mono Typical examples are butyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether. 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 Typical examples are ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether.

These glycol ethers can also be used alone or in combination of two or more.

In the external composition of the second invention, the total content of glycol ether including ethoxydiglycol is preferably less than 40% by mass, more preferably 30% by mass or less, based on the total amount of the external composition. Further preferably, it is less than 10% by mass, more preferably 10% by mass or less, and the glycol ether may not be contained in the external composition.

The total content of the glycol ether including ethoxydiglycol is preferably 0 or more and less than 40% by mass, more preferably 0 or more and less than 30% by mass, and further preferably about 0 or more and 10% by mass.

In the external composition of the second invention, the ratio of the content of the glycol ether component to the component (A) is preferably 0 to 20 parts by mass with respect to 1 part by mass of the total content of the component (A). Preferably, it is 0 to 10 parts by mass. Further, depending on the case, it may be 0.001 to 20 parts by mass or 0.01 to 10 parts by mass.

The external composition of the second invention contains a predetermined amount of the component (A), the component (B), and the component (C), defines the content of the entire glycol ether, and has a pH of 1.5 to 4. By setting the pH to 5 or less, more preferably 2 to 4.5 or less, a more stable external composition can be obtained.

[Lower alcohol]
The external composition of the second invention has the above-mentioned components (A), (B), and (C) from the viewpoint of improving usability, stability, and promoting transdermal absorption, as long as the effects of the present invention are not impaired. ) In addition to the component and, if contained, a glycol ether such as ethoxydiglycol, a lower alcohol may be contained. The lower alcohol used in the present invention is not particularly limited as long as it is used as a component of an external preparation for skin in the fields of pharmaceuticals, quasi-drugs or cosmetics. As used herein, the term "lower alcohol" refers to alcohol C ₁ -C _6. Among them, in _particular, it can be preferably used alcohol C 1 -C _3. Examples of such examples include methanol, n-propanol, isopropanol and the like in addition to ethanol.

In the external composition of the second invention, when it is contained, the content of the lower alcohol with respect to the total amount of the external composition is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, still more preferable. Is 0.25% by mass or more, more preferably 1% by mass or more, and most preferably 3% by mass or more. The content of ethanol is preferably 45% by mass or less, more preferably 40% by mass or less, still more preferably 35% by mass or less, still more preferably 20% by mass or less.

The content of the lower alcohol contained in the external composition of the second invention is preferably 0.01 to 45% by mass, more preferably 0.1 to 40% by mass, still more preferably 0.25 to 35% by mass. , Even more preferably 1 to 20% by mass, and most preferably 3 to 20% by mass.

[Butylene glycol]
From the viewpoint of improving usability, stability and promoting transdermal absorption, the external composition of the present invention contains the above-mentioned components (A), (B) and (C) as long as the effects of the present invention are not impaired. , And, if included, butylene glycol (1,3-butylene glycol) may be included in addition to glycol ethers such as ethoxydiglycol.

In the external composition of the second invention, the content of butylene glycol with respect to the total amount of the external composition, when contained, is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, still more preferably. Is 0.25% by mass or more. The content of butylene glycol is preferably 40% by mass or less, more preferably 35% by mass or less, and further preferably 30% by mass or less.

The content of butylene glycol in the external composition of the second invention is preferably 0.01 to 40% by mass, more preferably 0.1 to 35% by mass, still more preferably 0.25 to 30% by mass. is there.

[pH regulator]
The external composition of the second invention has the above-mentioned components (A), (B), and components (B), as long as the effects of the second invention are not impaired, from the viewpoint of improving usability, stability and promoting transdermal absorption. In addition to the component (C) and, if contained, a glycol ether such as ethoxydiglycol, a pH adjuster may be contained.

As the pH adjuster used in the second invention, a compound usually used as a component of a skin external preparation in the fields of pharmaceuticals, quasi-drugs or cosmetics can be used. Although not particularly limited, a pH adjuster having an amine (for example, aspartic acid or a salt thereof, ε-aminocaproic acid or a salt thereof, glutamic acid or a salt thereof, aminoethylsulfonic acid or a salt thereof, monoethanolamine, triethanolamine, etc. Diisopropanolamine, triisopropanolamine, arginine, lysine, L-carnitine, low molecular weight betaine, preferably low molecular weight betaine, more preferably trimethylglycine), organic acid salts (eg, sodium lactate, sodium acetate, sodium citrate, succinate) Sodium acid, sodium oxalate, calcium gluconate, sodium pyrrolidone carboxylate, etc.), inorganic acid salts (eg, sodium pyrosulfate, potassium pyrosulfate, sodium phosphate, potassium nitrate, sodium borate, preferably sodium pyrosulfate), base Examples thereof include sex amino acids and salts thereof (arginine, lysine, or histidine and salts thereof), 3-O-ethylascorbic acid or salts thereof.

In the external composition of the second invention, the total content of the pH adjuster with respect to the total amount of the external composition is not particularly limited, but is preferably 0.01% by mass or more, more preferably 0.05% by mass or more. Is. The total content of the pH adjuster is preferably 20% by mass or less, more preferably 10% by mass or less, based on the total amount of the external composition. The content of the pH adjuster having an amine or amino group is preferably 0.01% by mass to 20% by mass, more preferably 0.05% by mass to 10% by mass, based on the total amount of the external composition. Is.

In the external composition of the second invention, the ratio of the content of the pH adjuster to the component (A) is not particularly limited, but 0.00001 to 20% by mass with respect to 1 part by mass of the total content of the component (A). Parts are preferable, 0.0001 to 20 parts by mass is more preferable, 0.0005 to 10 parts by mass is further preferable, 0.005 to 5 parts by mass is more preferable, and 0.01 to 1 part by mass is most preferable.

[Other ingredients]
In addition to the above-mentioned component (A), component (B), and component (C), and if contained, less than a certain amount of ethoxydiglycol, the external composition of the second invention further contains ascorbic acid. For the purpose of enhancing or supplementing various actions, and for adding other useful actions, whitening component, anti-inflammatory component, antibacterial component, cell activating component, astringent component, antioxidant component, acne improving component, aging Various components such as an inhibitory component, a biological component synthesis promoting component such as collagen, a blood circulation promoting component, a moisturizing component, and an antiaging component can be blended in one or a combination of two or more. It is preferably one or more components such as a whitening component, an anti-inflammatory component, an antibacterial component, a cell activating component, an astringent component, an antioxidant component, an antiaging component or a moisturizing component. Particularly preferable combinations of these components are a combination with a whitening component, a combination of a whitening component and an antioxidant component, each combination with an antioxidant component, a combination with an antiaging component, and a whitening component and an antiaging component. Each combination of can be mentioned. Each of these components is not particularly limited as long as it is conventionally used as a component of an external preparation for skin in the fields of pharmaceuticals, quasi-drugs, or cosmetics, and will be used in the future, and any component may be appropriately selected. Can be used.

In addition to each of the above components, the external composition of the present invention may further contain a surfactant, a solubilizing component, oils and fats, sugars, or a transdermal absorption promoting component. In particular, by blending a surfactant, a solubilizing component or oils and fats, the stability, effectiveness and usability of ascorbic acid in an aqueous solvent can be further improved.

The external composition of the present invention includes pharmaceuticals, quasi-drugs or cosmetics as necessary within a quantitative and qualitative range that does not impair quality such as appearance stability and viscosity, and does not impair the effects of the present invention. Various components commonly used as components of external preparations in the field, such as amino acids, irritation reducers, thickeners, preservatives, UV protective agents, colorants, dispersants, additional pH regulators, fragrances, etc. Can be blended. In addition, these components may be used alone or in combination of two or more.

The external composition of the second invention comprises 10 to 25% by mass of at least one selected from the group consisting of (A) ascorbic acid and a salt of ascorbic acid;
(B) A diol having 3 carbon atoms is contained in an amount of 30 to 90% by mass in components other than (A) and (C); and (C) water is contained, and the content of ethoxydiglycol is less than 30% by mass. C) / (A) = 0.2 to 5, and pH is 2.0 to 6.0. If necessary, each of the above optional components is blended and mixed, and if necessary, other solvents or usual use are used. By blending the base of the external preparation to be used, various desired forms such as paste-like, mousse-like, gel-like, liquid, milky liquid, cream-like, sheet-like (base material-supported), aerosol-like, and spray-like forms are added. Can be prepared in. These can be manufactured by the usual methods in the industry.

The external composition of the present invention is particularly preferably a transparent to translucent composition in which ascorbic acid and / or a salt thereof is solubilized. Here, "solubilization" is defined as follows. That is, for example, by the ultraviolet-visible absorbance measurement method, the transmittance is 80 to 100%, preferably 85 to 100, as the transmittance at a wavelength of 700 nm using a spectrophotometer or a photoelectric photometer UV-2450 (manufactured by Shimadzu Corporation). %, More preferably in the range of 90-100%. Here, the transmittance of water is 100%. The solubilized composition of the present invention has a transparent or translucent appearance. For more details, refer to the 16th revised Japanese Pharmacopoeia [B] general test method. Physical test method Spectroscopic measurement method 2.24 Follow the method described in UV-visible absorbance measurement method.

[viscosity]
The external composition of the present invention can be prepared as a composition having an appropriate viscosity desired especially when using an external composition used for application to the skin. The viscosity of the external composition of the present invention is not particularly limited, but for example, the viscosity when measured at 25 ° C. using an E-type viscometer is usually about 1 to 300 mPa · s, preferably about 1 to 200 mPa · s. , More preferably about 1 to 100 mPa · s, and most preferably about 1 to 50 mPa · s. For more details, the viscosity measurement method is the 16th revised Japanese Pharmacopoeia [B] general test method. Physical test method Other physical test method 2.53 Viscosity measurement method 2. Second method Rotational viscometer method 21.3 Conforms to the method described in the cone-plate type rotational viscometer (cone plate type viscometer).

[Use]
The external composition 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, treatment, and antioxidant effects. Further, when applied to the skin, the transparency of the skin is enhanced, the moisture is maintained, the texture is smoothed, and the effect of suppressing roughness may be exhibited. Furthermore, it may have effects such as making pores inconspicuous and moisturizing the skin, and can also be used for prevention and treatment of age spots.

The external composition of the present invention is, for example, basic cosmetics such as beauty liquids, lotions, sunscreen creams, emulsions, creams, lotions, oils and packs; foundations, lip balms, lip balms, mascara, eye shadows, eye liners, etc. Makeup cosmetics such as eyebrows and nail polish; cleaning agents such as pigments, cleansers, and body cleaning agents; axillary odor inhibitors, water bug remedies, antipruritic agents, wound healing agents, cleaning agents, cleaning agents, anti-inflammatory analgesics, acne It can be various external compositions belonging to the field of cosmetics, external pharmaceuticals or external pharmaceutical products such as therapeutic agents, hemorrhagic agents, bactericidal disinfectants, whitening agents and ultraviolet protective agents. From the viewpoint of the effect on the skin, the present invention is preferably used for products applied to the exodermis such as external preparations for the skin (preparations for the exodermis).

[Stabilization method]
The present invention also includes at least one stabilizing method selected from the group consisting of (A) ascorbic acid and a salt of ascorbic acid. In the present invention, according to the method for stabilizing ascorbic acid, at least one selected from the group consisting of (A) ascorbic acid and a salt of ascorbic acid is selected from 10 to 25% by mass; (B) having 3 carbon atoms. The diol contains 30 to 90% by mass of the components other than (A) and (C); and (C) water, and the content of ethoxydiglycol is less than 30% by mass, (C) / (A) = 0. By setting the pH to .2 to 5 and the pH to 2.0 to 6.0, a stable preparation can be obtained while containing ascorbic acid. That is, in the present invention, at least one selected from the group consisting of (A) ascorbic acid and a salt of ascorbic acid is 10 to 25% by mass; (B) a diol having 3 carbon atoms is used in (A) and ( 30 to 90% by mass of components other than C); and (C) water, ethoxydiglycol content of less than 30% by mass, (C) / (A) = 0.2 to 5, and pH The present invention relates to a method for imparting stability to an external composition containing at least one selected from the group consisting of (A) ascorbic acid and a salt of ascorbic acid, which is set to 2.0 to 6.0. Here, stabilization is not limited, but means that stability is guaranteed even under high temperature or low temperature, for example. Specifically, the precipitation of ascorbic acid or a salt thereof is suppressed even when the external composition is stored at 4 ° C. for 1 week, or even after storage at 50 ° C. or storage at 40 ° C. for a certain period of time. It means that changes in appearance such as coloring are suppressed.

In the method of the present invention, containing (A) at least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid, (B) a diol having three carbon atoms, and (C) water, and ethoxydiglycol. The amount, the ratio thereof, and the like are the same as those used in the external composition. Further, the product obtained by this method can be divided into one to several times a day depending on the intended use and the like, and can be used in a known or commonly used dosage and administration.

Next, the present invention will be specifically described with reference to Examples, but the present invention is not limited to the following Examples. The unit of each component amount in the table is mass%.

External compositions having the compositions shown in Tables 1 to 6 were prepared according to a conventional method. These compositions were then subjected to testing according to each test item.

[Ascorbic acid color suppression confirmation test]
The presence or absence of suppression of coloration of the external composition after storage at 40 ° C. or 50 ° C. according to some Examples and Comparative Examples of the present invention was evaluated visually and by a color difference meter. Specifically, ascorbic acid is added to a mixed solution of various components according to the formulation (mass%) described in various prescription tables, and the composition is prepared by heating and mixing at 60 ° C. for 10 minutes to dissolve it. did. The prepared composition was filled in a transparent glass bottle and allowed to stand in each constant temperature and humidity chamber at 40 ° C. or 50 ° C. for 1 week (expressed as 1 W) or 4 weeks (expressed as 4 W). The container was taken out from the thermostat for each measurement period and evaluated after constant temperature at 25 ° C. The presence or absence and degree of coloring of each test solution were determined by visual observation and measurement with a color difference meter.

For the measurement by the color difference meter, 1 mL of the test solution was put into a glass cell (CM-A97, thickness 2 mm), and the color difference was measured by the spectrophotometer CM-5 (manufactured by Konica Minolta Co., Ltd.). As the measured value, Δb * when purified water was used as a blank was used. The change in color difference was calculated by the following formula.
(Amount of change in color difference (Δb value)) = (Measured value of test solution after heat retention (b value after accelerated test))-(Measured value of test solution before heat retention (b value before accelerated test))
The b value is used as an index showing a sense of transparency. Therefore, the smaller the Δb value, the less the coloring. Further, when the ratio of Δb between the two was 1.4 or less, the difference in coloring was not felt so much. On the other hand, when it exceeds 1.4, the difference in coloring is clearly visible, and it is found that inconvenience may occur in quality. Therefore, the presence or absence of coloring was determined based on whether or not the ratio when the value of Δb of the sample in which no change in coloring was observed was 1 was 1.4 or less.

[Ascorbic acid precipitation suppression confirmation test]
The presence or absence of ascorbic acid precipitation when the preparation of the external composition according to some Examples and Comparative Examples of the present invention was stored at a low temperature was visually evaluated. Specifically, ascorbic acid is added to a mixed solution of various components according to the formulation (mass%) described in various prescription tables, and the composition is prepared by heating and mixing at 60 ° C. for 10 minutes to dissolve it. did. The prepared composition was filled in a transparent glass bottle, allowed to stand at 4 ° C. under light-shielding conditions, stored for 1 week or 4 weeks, and each test solution was visually observed to determine the presence or absence of crystal precipitation.

<Evaluation criteria>
◯: A state in which the precipitate cannot be visually confirmed ×: A state in which the precipitate can be visually confirmed.

[Ascorbic acid transdermal absorption test]
The transdermal absorbability of the external composition according to some examples and comparative examples of the present invention was verified. By improving transdermal absorbability, ascorbic acid permeates into the skin, which is expected to have a higher anti-aging effect as a composition. That is, in some cases, the effect of ascorbic acid can be exerted deep into the stratum corneum.

The transdermal absorbability of ascorbic acid for the external compositions prepared in Examples and Comparative Examples was confirmed by measuring by evaluation by stratum corneum stripping.

Specifically, first, the amount of ascorbic acid in the stratum corneum, which is a component that penetrated the skin of the upper arm and forearm of a healthy human, was confirmed by tape stripping. The subjects were two healthy male subjects who consented to participate in the test voluntarily. Cotton impregnated with the external composition 750 uL of the example or comparative example was attached to the inner part of the upper arm of the subject 1.5 cm × 1.5 cm, and allowed to stand for 5 minutes. After removing the cotton, the sample remaining on the skin surface was removed with fresh cotton and allowed to stand for 30 minutes. This time was taken as the permeation time of the sample. Then, using a mending tape (manufactured by Sumitomo 3M Ltd.), tape stripping was performed 7 times continuously from the application site to exfoliate the keratinocytes, and all the layers of the obtained tape were used as specimens for measurement. The number of tape strips was set by a preliminary test after confirming that the required amount of keratinocytes was peeled off for each tape strip and that inflammation and pain did not occur after the tape strip.

The obtained measurement sample was extracted with 1 mL of an extraction solvent of a mixed solution of Triton x-100 (manufactured by MP Biomedicals), mercaptoethanol (manufactured by Wako Pure Chemical Industries, Ltd.) and purified water (1: 1: 1000). ^{The permeation amount (ug / cm 2} ) of ascorbic acid was measured by HPLC from the extraction solution from which foreign substances were removed by a 0.45 um syringe filter (manufactured by GL Science Co., Ltd.). Agelent HPLC (mobile phase: acetonitrile / 0.02M phosphoric acid solution (pH 3.0) (1: 9), absorbance detection wavelength: 270 nm) equipped with a reverse phase column (CAPCELL PAK C18 SG120, manufactured by Shiseido). By measuring the amount of L-ascorbic acid contained in the solution. The results were compared by averaging the measured values of the measurement specimens collected from each of the three arms of the two subjects as the permeation amount (ug / cm ^2).

The detection of ascorbic acid by HPLC was performed using an ultraviolet absorptiometer at a wavelength of 270 nm using a reverse phase column (CAPCELL PAK C18 SG120, manufactured by Shiseido Co., Ltd.), and the content was calculated from the calibration curve. ..

(Examples 1-1 to 1-6, Comparative Examples 1-1 to 1-3)
The external compositions of Examples and Comparative Examples of the compositions shown in Table 1 were prepared according to a conventional method. Among the evaluation items, the ratio of Δb describes the ratio of the comparative values based on the color difference value of the external composition in Example 1-1 (1). That is, the stability ratio represents the ratio of Δb.

The results of the ascorbic acid coloring suppression confirmation test of the compositions of Examples and Comparative Examples are also shown in Tables 1 and 2.

The composition of the example had a color-suppressing effect even when stored at a high temperature, and showed excellent stability over a long period of time. On the other hand, the composition of the comparative example was colored under the storage conditions of the test.

(Examples 2-1 to 2-2, Comparative Example 2-1)
The external compositions of Examples and Comparative Examples of the compositions shown in Table 3 were prepared according to a conventional method. Among the evaluation items, the ratio of Δb describes the ratio of the comparative values based on the color difference value of the external composition in Example 2-1 (1). That is, the stability ratio represents the ratio when the value of Δb in Example 2-1 is 1.

Table 3 shows the results of the ascorbic acid coloring suppression confirmation test and the results of the ascorbic acid precipitation suppression confirmation test of the compositions of Examples and Comparative Examples.

That is, it can be seen that the composition shown in the examples achieves both properties of suppressing the precipitation of ascorbic acid and suppressing the coloring of the composition.

(Examples 3-1 to 3-3, Comparative examples 3-1 to 3-2)
The external compositions of Examples and Comparative Examples of the compositions shown in Table 4 were prepared according to a conventional method.

Table 4 shows the results of the ascorbic acid coloring suppression confirmation test and the results of the ascorbic acid precipitation suppression confirmation test of the compositions of Examples and Comparative Examples.

(Examples 4-1 to 4-3, Comparative Examples 4-1 to 4-2)
The external compositions of Examples and Comparative Examples of the compositions shown in Table 5 were prepared according to a conventional method.

Table 4 shows the results of the ascorbic acid coloring suppression confirmation test and the results of the ascorbic acid precipitation suppression confirmation test of the compositions of Examples and Comparative Examples. Among the evaluation items, the ratio of Δb describes the ratio of the comparative values based on the color difference value of the external composition in Example 4-1 (1). That is, the stability ratio represents the ratio when the value of Δb in Example 4-1 is 1.

It was found that the composition shown in the examples achieved both properties of suppressing the precipitation of ascorbic acid at a low temperature and suppressing the coloring of the composition. For example, when the concentration of ethoxydiglucol was as high as 40% by mass or more, precipitation at a low pH, particularly at a low temperature, was observed. In the formulation with a slightly higher pH, precipitation at low temperature was not observed even at a high concentration of ethoxydiglycol, but it was found that the degree of coloring was clearly high at 30% by mass or more. From this, it is preferable that the ethoxydiglycol is less than 30% by mass even if it is blended.

Furthermore, Table 6 shows the results of the ascorbic acid coloration suppression confirmation test, the ascorbic acid precipitation suppression confirmation test, and the transdermal absorbability test of the compositions of the other Examples and Comparative Examples. Among the evaluation items, the ratio of Δb describes the ratio of the comparative values based on the color difference value of the external composition in Example 5-1 (1). That is, the stability ratio represents the ratio when the value of Δb in Example 5-1 is 1.

Compared with the composition of Comparative Example, the composition of Example can suppress the precipitation of ascorbic acid even under low temperature storage, and further, both properties of suppressing the coloring of the composition by storage are achieved. all right. Furthermore, it was found that the composition of the present invention is also excellent in transdermal absorbability.

The results of transdermal absorbability of the compositions of Examples 5-1 to 5-2 and Comparative Examples 5-1 to 5-2 are shown in FIG.

Next, external compositions having the compositions shown in Tables 7 to 9 were prepared according to a conventional method. These compositions were then subjected to testing according to each test item.

[Ascorbic acid color suppression confirmation test]
The presence or absence of suppression of coloration after storage of the external composition having the composition shown in Tables 7 to 9 at 40 ° C. or 50 ° C. was evaluated visually and by a color difference meter. Specifically, the confirmation test was carried out by exactly the same method as that carried out in Examples 1 to 5 and Comparative Examples 1 to 5.

[Ascorbic acid precipitation suppression confirmation test]
The presence or absence of ascorbic acid precipitation was visually evaluated when the preparations of the external compositions having the compositions shown in Tables 7 to 9 were stored at a low temperature. Specifically, the confirmation test was carried out by exactly the same method as that carried out in Examples 1 to 5 and Comparative Examples 1 to 5.

[Ascorbic acid transdermal absorption test]
The transdermal absorbability of the external composition according to some examples and comparative examples of the second invention was verified. By improving transdermal absorbability, ascorbic acid permeates into the skin, which is expected to have a higher anti-aging effect as a composition. That is, in some cases, the effect of ascorbic acid can be exerted deep into the stratum corneum.

The transdermal absorbability of ascorbic acid for the external compositions prepared in Examples and Comparative Examples was confirmed by measuring by evaluation by stratum corneum stripping. Specifically, the confirmation test was carried out by exactly the same method as that carried out in Examples 1 to 5 and Comparative Examples 1 to 5.

(Examples 6-1 to 8-1, Comparative Examples 6-2 to 8-3)
The external compositions of Examples and Comparative Examples of the compositions shown in Table 7 were prepared according to a conventional method. Among the evaluation items in the table, the ratio of Δb describes the ratio of the comparative values based on the color difference value of the external composition in Example 1 as the reference (1). That is, the stability ratio represents the ratio of Δb. In addition, the ratio described in the column of transdermal absorbability test results of the external composition of Examples and Comparative Examples is the transdermal absorption of Comparative Example 5-1 (Formulation 40) containing 1,3-butylene glycol as a base. It is a value obtained by a ratio with the amount as 1.
Ratio = (Transdermal absorption amount of the composition of either Example or Comparative Example (μg / cm ² ) / (Transdermal absorption amount of the composition of Comparative Example 5-1 (μg / cm ² ))

The results of each test of the compositions of Examples and Comparative Examples are shown in Tables 7 to 9.

The composition of the example had a color-suppressing effect even when stored at a high temperature, and showed excellent stability over a long period of time. On the other hand, the composition of the comparative example was colored under the storage conditions of the test. In addition, the composition of the example had suppressed precipitation at a low temperature as compared with the composition of the comparative example.

[Prescription example]
Examples of prescriptions are shown in Tables 10 to 12 below. All of the prescription examples can be suitably used for lotions, beauty essences, and the like. The content in each of the formulation examples is mass%.

Claims (13)

(A) 10% by mass or less of at least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid;
(B) Contains 30% by mass or more of a diol having 3 carbon atoms; and (C) Contains 20% by mass or less of water, the content of ethoxydiglycol is less than 30% by mass, and the pH is 4.5 or less. External composition. The external composition according to claim 1, wherein the content of the component (B) is 40% by mass or more. The external composition according to claim 1 or 2, wherein the content of the ascorbic acid or a salt thereof is 3 to 10% by mass. (C) The external composition according to any one of claims 1 to 3, wherein the content of water is 10% by mass or less. (A) 10 to 25% by weight of at least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid.
(B) A diol having 3 carbon atoms is contained in the components other than (A) and (C) in an amount of 30 to 90% by mass; and (C) contains water, and the content of ethoxydiglycol is less than 30% by mass, (C. ) / (A) = 0.2 to 5, and an external composition having a pH of 2.0 to 6.0. The external composition according to any one of claims 1 to 5, further comprising butylene glycol and / or a lower alcohol. The external composition according to any one of claims 1 to 6, wherein the component (B) is 1,3-propanediol and / or propylene glycol. The external composition according to any one of claims 1 to 7, wherein the component (B) contains at least 1,3-propanediol. The external composition according to any one of claims 1 to 8, wherein the content of ethoxydiglycol is 10% by mass or less. The external composition according to any one of claims 1 to 9, wherein the external composition is a solubilized external composition having a transmittance of 85 to 100% at a wavelength of 700 nm. The external composition according to any one of claims 1 to 10, wherein the external composition is for promoting transdermal absorption of ascorbic acid. (A) 10% by mass or less of at least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid;
(B) 30% by mass or more of diol having 3 carbon atoms; and (C) 20% by mass or less of water are used in combination, the content of ethoxydiglycol is less than 30% by mass, and the pH is 4.5 or less. (A) A method for preventing coloring and / or precipitation of crystals of an external composition containing at least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid. (A) 10% to 25% by mass of at least one selected from the group consisting of ascorbic acid and a salt of ascorbic acid.
(B) A diol having 3 carbon atoms is contained in an amount of 30 to 90% by mass in components other than (A) and (C); and (C) water is contained, and the content of ethoxydiglycol is less than 30% by mass. At least one selected from the group consisting of (A) ascorbic acid and a salt of ascorbic acid by setting C) / (A) = 0.2 to 5.0 and pH 2.0 to 6.0. A method for preventing coloring and / or precipitation of crystals of an external composition containing.

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