JP7328957B2 - External composition containing ascorbic acid and/or its salt - Google Patents

Description

TECHNICAL FIELD The present invention relates to external compositions containing ascorbic acid and/or salts thereof.

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

Several methods have been investigated for stably solubilizing ascorbic acid in aqueous external preparations for skin (for example, Patent Document 1: WO02/19972, Patent Document 2: WO00/78283, Patent Documents 3: JP-A-2002-348228, Patent Document 4: JP-A-2005-225865).

WO02/19972 WO00/78283 JP-A-2002-348228 JP 2005-225865 A

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

A topical composition containing ascorbic acid and/or a salt thereof is provided.

According to the studies of the present inventors, it was found that when ascorbic acid and/or a salt thereof are blended, coloration may be observed from the time of production, or coloration may be observed after a certain period of time. Furthermore, it was found that there are cases where there is a problem of ascorbic acid precipitation during low-temperature storage and a problem of percutaneous absorption.

The present inventors have made intensive studies to solve the present problem, and found that (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid 10% by mass or less, (B) the number of carbon atoms By containing 30% by mass or more of three diols, (C) 20% by mass or less of water, furthermore, the content of ethoxydiglycol is less than 30% by mass, and the pH is 4.5 or less, or (A) 10 to 25% by mass of at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid; ~90% by mass, (C) water, the content of ethoxydiglycol is less than 30% by mass, (C)/(A) = 0.2-5, and the pH is 2.0-6. The present inventors have found that by setting it to 0, it is possible to suppress the coloring of ascorbic acid and obtain a composition for external use that is excellent in percutaneous absorbability (skin penetration) of ascorbic acid, and have completed the present invention.

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

The present invention can provide a composition for external use with excellent stability.

FIG. 1 is a graph showing the results of a percutaneous absorption test of external compositions of Examples and Comparative Examples.

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

A first aspect of the present invention is a case where at least one selected from the group consisting of ascorbic acid and ascorbic acid salts is 10% by mass or less (hereinafter also referred to as the first invention).
The composition for external use of the first invention is
(A) 10% by mass or less of at least one selected from the group consisting of ascorbic acid and salts 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, contains less than 30% by mass of ethoxydiglycol (diethylene glycol monoethyl ether), and has a pH is 4.5 or less.

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

[(A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid]
In the present invention, ascorbic acid that is commercially available as a component of external preparations for skin in the fields of pharmaceuticals, quasi-drugs, or cosmetics can be used, and usually refers to the L-form.

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

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

In the composition for external use of the first invention, the total content of component (A) relative to the total amount of the composition for external use is appropriately set according to the balance with other components. Although the total content of component (A) is not particularly limited as long as it is 10% by mass or less relative to the total amount of the composition for external use, it is preferably 1% by mass or more, more preferably 2% by mass or more, and even more preferably. is 3% by mass or more. The total content of component (A) is 10% by mass or less, preferably 9% by mass or less, and more preferably 8% by mass or less, relative to the total amount of the composition for external use. The total content of component (A) is preferably 1% by mass to 10% by mass, more preferably 2% by mass to 10% by mass, and still more preferably 3% by mass to the total amount of the composition for external use. 8% by mass.

[(B) Diol with 3 carbon atoms]
The diol having 3 carbon atoms to be used in the present invention is not particularly limited as long as it is used as a component of external preparations for skin in the fields of pharmaceuticals, quasi-drugs or cosmetics. The diol having 3 carbon atoms is preferably, but not limited to, 1,3-propanediol (CAS number: 504-63-2, English name: 1,3-Dihydroxypropane or Trimethylene Glycol) or propylene glycol (CAS number: 57 -55-6, English name: 1,2-Dihydroxypropane, Japanese name: 1,2-propanediol). For example, either one or both of 1,3-propanediol and propylene glycol can be used as component (B). Commercially available products of such diols having 3 carbon atoms can be used as they are. From the viewpoints of alleviating irritation to the skin, improving the feeling of use, and suppressing coloration, it is preferable to combine 1,3-propanediol and propylene glycol.

In the composition for external use of the first invention, the total content of component (B) relative to the total amount of the composition for external use 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 component (B) relative to the total amount of the composition for external use is preferably 90% by mass or less, more preferably 85% by mass or less, and even more preferably 80% by mass or less.

The total content of component (B) is preferably 35 to 90% by mass, more preferably 40 to 85% by mass, still more preferably 45 to 80% by mass, relative to the total amount of the composition for external use of the first invention.

In the composition for external use of the first invention, the content ratio of component (B) to component (A) is not particularly limited, but is preferably 3 to 300 parts per part by mass of the total content of component (A). parts 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. Although the proportion of water is not limited, it is preferably 0.1% by mass or more, more preferably 1% by mass or more, and most preferably more than 1% by mass, relative to the topical composition. More than 1% by mass is not limited, but may be, for example, a value of 1.01% by mass or more or 1.1% by mass or more. The proportion 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 component (C) with respect to the total amount of the composition for external use of the first invention is preferably 1% by mass to 15% by mass, more preferably more than 1% by mass to 10% by mass, still more preferably 2 to 10% by mass. % by mass.

In the composition for external use of the first invention, the ratio of the content of component (C) to component (A) is not particularly limited, but is preferably 0.1 per part by mass of the total content of component (A). ~10 parts by mass, more preferably 0.125 to 8 parts by mass, still more preferably 0.2 to 5 parts by mass.

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

[ethoxydiglycol (diethylene glycol monoethyl ether)]
In the present invention, mainly from the viewpoint of improving stability, ethoxydiglycol is not contained, or less than 30% by mass even if it is contained. Ethoxydiglycol contained in the composition for external use in an amount of less than 30% by mass is not particularly limited as long as it is used as a component of external preparations for skin in the fields of pharmaceuticals, quasi-drugs, or cosmetics.

In the topical composition of the first invention, the content of ethoxydiglycol relative to the total amount of the topical composition is less than 30% by mass, preferably 20% by mass or less, more preferably 10% by mass or less. , more preferably 5% by mass or less, and ethoxydiglycol may not be contained in the composition for external use.
The total content of ethoxydiglycol is from 0 to less than 30% by mass, preferably from 0 to 20% by mass, more preferably from 0 to 10% by mass, and even more preferably from 0 to 5% by mass.

In the composition for external use 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). ~5 parts by mass is more preferred. Also, depending on the case, it can be 0.001 to 10 parts by mass, or 0.01 to 5 parts by mass.

[pH]
The first topical composition of the present invention preferably has a pH of 1.5 to 4.5, more preferably pH 1.5 to 4.5, more preferably pH 1.5 to 4.5, from the viewpoints of the stability of the component (A), low irritation to the skin and mucous membranes, and good skin feel. It is desirable to be in the acidic range of pH 2-4.

The external composition of the first invention contains predetermined amounts of components (A), (B), and (C), defines the content of ethoxydiglycol, and has a pH of 4.5 or less. As a result, a composition for external use with good stability is obtained.

[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 preferred. Glycol ethers other than ethoxydiglycol are not particularly limited as long as they are used as components of external preparations for skin in the fields of pharmaceuticals, quasi-drugs, or cosmetics. Any substance that dissolves 10 g or more in 100 g of water may be used. Those having a degree of polymerization of 2 or less are exemplified. 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. 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 Butyl 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 glycol ethers can be used singly or in combination of two or more.

In the topical composition of the first invention, the total content of glycol ethers including ethoxydiglycol is preferably less than 40% by mass, more preferably 30% by mass or less, relative to the total amount of the topical composition. It is more preferably less than 10% by mass, more preferably 10% by mass or less, and the composition for external use may not contain the glycol ether.

The total content of glycol ethers including ethoxydiglycol is preferably from 0 to less than 40% by mass, more preferably from 0 to less than 30% by mass, and even more preferably from 0 to about 10% by mass.

In the composition for external use 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, more than 1 part by mass of the total content of the component (A). Preferably, it is 0 to 10 parts by mass. Also, depending on the case, it can be 0.001 to 20 parts by mass, or 0.01 to 10 parts by mass.

The external composition of the first invention contains predetermined amounts of components (A), (B), and (C), defines the content of the entire glycol ether, and has a pH of 4.5 or less. Thus, a composition for external use with better stability can be obtained.

[Lower alcohol]
The external composition of the first invention, from the viewpoint of improving the feeling of use, stability and promotion of percutaneous absorption, as long as the effects of the present invention are not hindered, the above components (A), (B), and (C) ) component and, if included, glycol ethers such as ethoxydiglycol, as well as lower alcohols. The lower alcohol used in the present invention is not particularly limited as long as it is used as a component of external preparations for skin in the fields of pharmaceuticals, quasi-drugs or cosmetics. As used herein, the term “lower alcohol” refers to C ₁ -C ₆ alcohols. Of these, C ₁ -C ₃ alcohols are particularly preferred. Examples of such include ethanol, methanol, n-propanol, isopropanol, and the like.

In the composition for external use of the first invention, the content of the lower alcohol relative to the total amount of the composition for external use, when included, is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, and even more preferably is 0.25% by weight or more, even more preferably 1% by weight or more, and most preferably 3% by weight or more. The ethanol content is preferably 45% by mass or less, more preferably 40% by mass or less, even more preferably 35% by mass or less, and even more preferably 20% by mass or less.

The content of the lower alcohol contained in the topical 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. , still more preferably 1 to 20% by weight, most preferably 3 to 20% by weight.

[Butylene Glycol]
The composition for external use of the present invention contains the above components (A), (B) and (C) as long as the effects of the present invention are not hindered from the viewpoint of improving the feeling of use, stability and promotion of percutaneous absorption. and, if included, glycol ethers such as ethoxydiglycol, as well as butylene glycol (1,3-butylene glycol).

In the composition for external use of the first invention, the content of butylene glycol relative to the total amount of the composition for external use, when included, is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, and still more preferably is 0.25% by mass or more. The butylene glycol content is preferably 55% by mass or less, more preferably 50% by mass or less, and even more preferably 45% by mass or less.

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

[pH adjuster]
The external composition of the first invention contains the components (A), (B), and the components (A), (B) and In addition to component (C) and, if included, a glycol ether such as ethoxydiglycol, a pH adjuster may be included.

As the pH adjuster used in the first invention, a compound that is commonly used as a component of external preparations for skin in the fields of pharmaceuticals, quasi-drugs, or cosmetics can be used. Although not particularly limited, amine-containing pH adjusters (e.g., aspartic acid or its salts, ε-aminocaproic acid or its salts, glutamic acid or its salts, aminoethylsulfonic acid or its salts, monoethanolamine, triethanolamine, Diisopropanolamine, triisopropanolamine, arginine, lysine, L-carnitine, low-molecular-weight betaine, preferably low-molecular-weight betaine, more preferably trimethylglycine), organic acid salts (e.g., sodium lactate, sodium acetate, sodium citrate, succinate) sodium pyrosulfite, sodium oxalate, calcium gluconate, sodium pyrrolidonecarboxylate, etc.), inorganic acid salts (e.g., sodium pyrosulfite, potassium pyrosulfite, sodium phosphate, potassium nitrate, sodium borate, preferably sodium pyrosulfite), base and salts thereof (arginine, lysine or histidine and salts thereof), 3-O-ethylascorbic acid or salts thereof, and the like.

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

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

[Other ingredients]
The composition for external use of the present invention contains the above components (A), (B), and (C), and, if contained, less than a certain amount of ethoxydiglycol, as well as various types of ascorbic acid. For the purpose of enhancing or supplementing the action of or to add other useful actions, whitening ingredients, anti-inflammatory ingredients, antibacterial ingredients, cell activating ingredients, astringent ingredients, antioxidant ingredients, acne improving ingredients, anti-aging ingredients , biocomponent synthesis-promoting ingredients such as collagen, blood circulation-promoting ingredients, moisturizing ingredients, anti-aging ingredients, and the like can be blended singly or in combination of two or more. One or more of whitening ingredients, anti-inflammatory ingredients, antibacterial ingredients, cell activating ingredients, astringent ingredients, antioxidant ingredients, anti-aging ingredients and moisturizing ingredients are preferred. Particularly preferred combinations of these ingredients include a combination with a whitening ingredient, a combination of a whitening ingredient and an antioxidant ingredient, each combination with an antioxidant ingredient, a combination with an anti-aging ingredient, and a combination of a whitening ingredient and an anti-aging ingredient. Each combination of These components are not particularly limited as long as they are conventionally used as components of external skin preparations in the field of pharmaceuticals, quasi-drugs, or cosmetics, and can be used in the future, and can be selected as appropriate. can be used.

The composition for external use of the present invention may further contain surfactants, solubilizing components, fats and oils, sugars, or percutaneous absorption promoting components in addition to the components described above. In particular, by adding a surfactant, a solubilizing component, or fats and oils, the stability, effectiveness, and feeling of use of ascorbic acid in an aqueous solvent can be further improved.

Pharmaceuticals, quasi-drugs or cosmetics may be added to the composition for external use of the present invention within quantitative and qualitative ranges that do not impair qualities such as appearance stability and viscosity and that do not impair the effects of the present invention. Various ingredients commonly used as components of external preparations in the field, such as amino acids, irritation reducing agents, thickeners, preservatives, UV protection agents, colorants, dispersants, additional pH adjusters, fragrances, etc. can be compounded. In addition, these components can be mix|blended individually by 1 type or 2 or more types arbitrarily.

The composition for external use of the first invention contains (A) 10% by mass or less of at least one selected from the group consisting of ascorbic acid and ascorbic acid salts, and (B) 30% by mass of a diol having 3 carbon atoms. (C) contains 20% by mass or less of water, contains less than 30% by mass of ethoxydiglycol, and has a pH of 4.5 or less; Furthermore, if necessary, by blending other solvents and bases for commonly used external preparations, etc., paste, mousse, gel, liquid, milky lotion, cream, sheet (supporting a base material) , aerosol form, spray form, and the like. These can be manufactured by the usual methods in the industry.

The composition for external use of the present invention is particularly preferably a transparent or 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 700 nm is 80 to 100%, preferably 85 to 100, as a transmittance at a wavelength of 700 nm using a spectrophotometer or a photoelectric photometer UV-2450 (manufactured by Shimadzu Corporation) by an ultraviolet-visible absorbance measurement method. %, more preferably in the range of 90-100%. Here, the water transmittance is assumed to be 100%. The solubilized composition of the present invention has a transparent to translucent appearance. More specifically, the permeability measurement method is based on the 16th revision of the Japanese Pharmacopoeia [B] general test method. Physical test method Spectroscopic measurement method Follow the method described in 2.24 Ultraviolet-Visible Absorbance Measurement Method.

[viscosity]
The topical composition of the present invention can be prepared as a composition having the appropriate viscosity desired when using the topical composition for application to the skin. The viscosity of the composition for external use of the present invention is not particularly limited. , more preferably about 1 to 100 mPa·s, most preferably about 1 to 50 mPa·s. More specifically, the viscosity measurement method is based on the 16th revision of the Japanese Pharmacopoeia [B] general test method. Physical test methods Other physical test methods 2.53 Viscosity measurement methods 2 . Method 2 Rotational viscometer method Follow the method described in 2.1.3 Cone-plate type rotational viscometer (cone plate type viscometer).

[Use]
The composition for external use of the present invention is particularly effective as a whitening agent, anti-inflammatory agent, and anti-aging agent, and has, for example, acne-preventing and treating actions and antioxidant action. Furthermore, when applied to the skin, the effect of increasing the transparency of the skin, retaining moisture, improving texture, and suppressing roughness may be exhibited. Furthermore, in addition to the effects of making pores inconspicuous and moisturizing the skin, it can also be used to prevent and treat blemishes.

The composition for external use of the present invention includes, for example, basic cosmetics such as serums, lotions, sunscreen creams, milky lotions, creams, lotions, oils and packs; foundations, lipsticks, lip balms, mascara, eyeshadows, eyeliners, Makeup cosmetics such as eyebrows and nail polishes; cleaning agents such as facial cleansers, cleansers, and body cleansers; anti-armpit odor agents, athlete's foot treatments, antipruritic agents, wound healing agents, cleansing agents, cleansers, anti-inflammatory analgesics, acne Various external compositions belonging to the field of cosmetics, external pharmaceuticals or external quasi-drugs, such as therapeutic agents, agents for hemorrhoids, antiseptics, whitening agents, and UV protection agents, can be used. Because of its action and effect on the skin, the present invention is preferably used for products applied to the outer skin such as external preparations for skin (formulations for outer skin).

[Stabilization method]
The present invention also includes (A) at least one stabilization method selected from the group consisting of ascorbic acid and salts of ascorbic acid. In the present invention, according to the method for stabilizing ascorbic acid, (A) 10% by mass or less of at least one selected from the group consisting of ascorbic acid and ascorbic acid salts, 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, while containing ascorbic acid, A stable formulation can be obtained. That is, the present invention comprises (A) at least one selected from the group consisting of ascorbic acid and ascorbic acid salts in an amount of 10% by mass or less, (B) a diol having 3 carbon atoms in an amount of 30% by mass or more, and ( C) from the group consisting of (A) ascorbic acid and ascorbic acid salts, by using 20% by mass or less of water in combination, making the content of ethoxydiglycol less than 30% by mass, and making the pH 4.5 or less; A method for imparting stability to a topical composition containing at least one selected material. The term "stabilization" as used herein means, but is not limited to, ensuring stability even at high temperatures or low temperatures, for example. Specifically, precipitation of ascorbic acid or a salt thereof is suppressed even when the composition for external use is stored at 4°C for at least one week, or even after storage at 50°C or storage at 40°C for a certain period of time. This refers to suppression of appearance changes such as coloring.

In the method of the present invention, (A) at least one selected from the group consisting of ascorbic acid and ascorbic acid salts, (B) a diol having 3 carbon atoms, and (C) water and ethoxydiglycol The amount and ratio thereof are the same as those used in the composition for external use. Furthermore, the product obtained by this method can be used once or several times a day in accordance with the known or commonly used dosage and administration, depending on the intended use.

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

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

[(A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid]
In the present invention, ascorbic acid that is commercially available as a component of external preparations for skin in the fields of pharmaceuticals, quasi-drugs, or cosmetics can be used, and usually refers to the L-form.

Salts of ascorbic acid can also be used. Here, the salt of ascorbic acid is the same as defined in the first aspect of the invention. Examples include, but are not limited to, salts with organic bases (e.g., trimethylamine salts, triethylamine salts, monoethanolamine salts, triethanolamine salts, salts with tertiary amines such as pyridine salts, basic ammonium salts such as arginine, etc.). etc.), salts with inorganic bases (eg, alkali metal salts such as ammonium salts, sodium salts and potassium salts, alkaline earth metal salts such as calcium salts and magnesium salts, and aluminum salts). Particularly preferred salts of ascorbic acid are sodium salts and potassium salts. Specific examples include sodium ascorbate, sodium ascorbate monophosphate, sodium ascorbate diphosphate, sodium ascorbate triphosphate, and sodium ascorbate-2-sulfate.

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

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

[(B) Diol with 3 carbon atoms]
The diol having 3 carbon atoms used in the composition for external use in the second invention is not particularly limited as long as it is used as a component of external preparations for skin in the fields of pharmaceuticals, quasi-drugs or cosmetics. It is the same as defined in the case of the first invention. The diol having 3 carbon atoms is preferably, but not limited to, 1,3-propanediol or propylene glycol. For example, either one or both of 1,3-propanediol and propylene glycol can be used as component (B). Commercially available products of such diols having 3 carbon atoms can be used as they are. From the viewpoints of alleviating irritation to the skin, improving the feeling of use, and suppressing coloration, it is preferable to combine 1,3-propanediol and propylene glycol.

In the composition for external use of the second invention, the total content of component (B) relative to the total amount of the composition for external use 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 component (B) relative to the total amount of the composition for external use is preferably 90% by mass or less, more preferably 85% by mass or less, even more preferably 80% by mass or less, and even more preferably 70% by mass. Mass or less.

The total content of component (B) relative to the total amount of the composition for external use is preferably 10 to 90% by mass, more preferably 15 to 85% by mass, even more preferably 20 to 80% by mass, and even more preferably 25% by mass. ~70% by mass.

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

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

[(C) Water]
The composition for external use 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 40% by weight is even more preferred, and 5% to 30% by weight is particularly preferred.

In the composition for external use of the second invention, the ratio of the content of component (C) to component (A) is not particularly limited, but is preferably 0.1 part per 1 part by mass of the total content of component (A). 2 to 5 parts by mass, more preferably 0.5 to 2 parts by mass, still more preferably 0.6 to 1.8 parts by mass.

[ethoxydiglycol (diethylene glycol monoethyl ether)]
In the second invention, mainly from the viewpoint of improving stability, ethoxydiglycol is not contained, or less than 30% by mass even if it is contained. Ethoxydiglycol contained in the composition for external use in an amount of less than 30% by mass is not particularly limited as long as it is used as a component of external preparations for skin in the fields of pharmaceuticals, quasi-drugs, or cosmetics.

In the topical composition of the second invention, the content of ethoxydiglycol relative to the total amount of the topical composition is less than 30% by mass, preferably 20% by mass or less, more preferably 10% by mass or less. , more preferably 5% by mass or less, and ethoxydiglycol may not be contained in the composition for external use.
The total content of ethoxydiglycol is from 0 to less than 30% by mass, preferably from 0 to 20% by mass, more preferably from 0 to 10% by mass, and even more preferably from 0 to 5% by mass.

In the composition for external use 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). ~5 parts by mass is more preferred. Also, depending on the case, it can be 0.001 to 10 parts by mass, or 0.01 to 5 parts by mass.

[pH]
The composition for external use of the present invention may generally have a pH of 1 to 8, but from the viewpoints of stability of ascorbic acid, low irritation to the skin and mucous membranes, and good skin feel, the pH is preferably 2. ~7, more preferably pH 2-6, still 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 preferred. Glycol ethers other than ethoxydiglycol are not particularly limited as long as they are used as components of external preparations for skin in the fields of pharmaceuticals, quasi-drugs, or cosmetics. Any substance that dissolves 10 g or more in 100 g of water may be used. Those having a degree of polymerization of 2 or less are exemplified. 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. 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 Butyl 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 glycol ethers can be used singly or in combination of two or more.

In the composition for external use of the second invention, the total content of glycol ethers including ethoxydiglycol with respect to the total amount of the composition for external use is preferably less than 40% by mass, more preferably 30% by mass or less, It is more preferably less than 10% by mass, more preferably 10% by mass or less, and the composition for external use may not contain the glycol ether.

The total content of glycol ethers including ethoxydiglycol is preferably from 0 to less than 40% by mass, more preferably from 0 to less than 30% by mass, and even more preferably from 0 to about 10% by mass.

In the composition for external use 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, more than 1 part by mass of the total content of the component (A). Preferably, it is 0 to 10 parts by mass. Also, depending on the case, it can be 0.001 to 20 parts by mass, or 0.01 to 10 parts by mass.

The external composition of the second invention contains predetermined amounts of components (A), (B), and (C), defines the content of the entire glycol ether, and has a pH of 1.5 to 4.0. By adjusting the pH to 5 or less, more preferably 2 to 4.5 or less, it is possible to obtain a more stable composition for external use.

[Lower alcohol]
The external composition of the second invention, from the viewpoint of improving the feeling of use, stability and promotion of percutaneous absorption, as long as the effects of the present invention are not hindered, the above components (A), (B), and (C) ) component and, if included, glycol ethers such as ethoxydiglycol, as well as lower alcohols. The lower alcohol used in the present invention is not particularly limited as long as it is used as a component of external preparations for skin in the fields of pharmaceuticals, quasi-drugs or cosmetics. As used herein, the term “lower alcohol” refers to C ₁ -C ₆ alcohols. Of these, C ₁ -C ₃ alcohols are particularly preferred. Examples of such include ethanol, methanol, n-propanol, isopropanol, and the like.

In the composition for external use of the second invention, the content of the lower alcohol relative to the total amount of the composition for external use, when included, is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, and even more preferably is 0.25% by weight or more, even more preferably 1% by weight or more, and most preferably 3% by weight or more. The ethanol content is preferably 45% by mass or less, more preferably 40% by mass or less, even more preferably 35% by mass or less, and even more preferably 20% by mass or less.

The content of the lower alcohol contained in the topical 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. , still more preferably 1 to 20% by weight, most preferably 3 to 20% by weight.

[Butylene Glycol]
The composition for external use of the present invention contains the above components (A), (B) and (C) as long as the effects of the present invention are not hindered from the viewpoint of improving the feeling of use, stability and promotion of percutaneous absorption. and, if included, glycol ethers such as ethoxydiglycol, as well as butylene glycol (1,3-butylene glycol).

In the composition for external use of the second invention, the content of butylene glycol relative to the total amount of the composition for external use, when included, is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, and still more preferably is 0.25% by mass or more. The butylene glycol content is preferably 40% by mass or less, more preferably 35% by mass or less, and even more 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, and still more preferably 0.25 to 30% by mass. be.

[pH adjuster]
The external composition of the second invention, from the viewpoint of improving the feeling of use, stability and promotion of percutaneous absorption, as long as it does not interfere with the effects of the second invention, contains the above components (A), (B), and In addition to component (C) and, if included, a glycol ether such as ethoxydiglycol, a pH adjuster may be included.

As the pH adjuster used in the second invention, compounds that are commonly used as components of external preparations for skin in the fields of pharmaceuticals, quasi-drugs, and cosmetics can be used. Although not particularly limited, amine-containing pH adjusters (e.g., aspartic acid or its salts, ε-aminocaproic acid or its salts, glutamic acid or its salts, aminoethylsulfonic acid or its salts, monoethanolamine, triethanolamine, Diisopropanolamine, triisopropanolamine, arginine, lysine, L-carnitine, low-molecular-weight betaine, preferably low-molecular-weight betaine, more preferably trimethylglycine), organic acid salts (e.g., sodium lactate, sodium acetate, sodium citrate, succinate) sodium pyrosulfite, sodium oxalate, calcium gluconate, sodium pyrrolidonecarboxylate, etc.), inorganic acid salts (e.g., sodium pyrosulfite, potassium pyrosulfite, sodium phosphate, potassium nitrate, sodium borate, preferably sodium pyrosulfite), base and salts thereof (arginine, lysine or histidine and salts thereof), 3-O-ethylascorbic acid or salts thereof, and the like.

In the composition for external use of the second invention, the total content of the pH adjuster relative to the total amount of the composition for external use 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, relative to the total amount of the composition for external use. 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 composition for external use. is.

In the composition for external use of the second invention, the content ratio of the pH adjuster to the component (A) is not particularly limited, but is 0.00001 to 20 parts by mass per 1 part by mass of the total content of the component (A). 0.0001 to 20 parts by weight is more preferred, 0.0005 to 10 parts by weight is even more preferred, 0.005 to 5 parts by weight is even more preferred, and 0.01 to 1 part by weight is most preferred.

[Other ingredients]
The external composition of the second invention further contains ascorbic acid in addition to the above-described components (A), (B), and (C), and less than a certain amount of ethoxydiglycol when included. For the purpose of enhancing or supplementing the various actions possessed, and in order to add other useful actions, whitening ingredients, anti-inflammatory ingredients, antibacterial ingredients, cell activation ingredients, astringent ingredients, antioxidant ingredients, acne improving ingredients, aging It is possible to blend one or a combination of two or more of various components such as a preventive component, a biocomponent synthesis-promoting component such as collagen, a blood circulation-promoting component, a moisturizing component, and an anti-aging component. One or more of whitening ingredients, anti-inflammatory ingredients, antibacterial ingredients, cell activating ingredients, astringent ingredients, antioxidant ingredients, anti-aging ingredients and moisturizing ingredients are preferred. Particularly preferred combinations of these ingredients include a combination with a whitening ingredient, a combination of a whitening ingredient and an antioxidant ingredient, each combination with an antioxidant ingredient, a combination with an anti-aging ingredient, and a combination of a whitening ingredient and an anti-aging ingredient. Each combination of These components are not particularly limited as long as they are conventionally used as components of external skin preparations in the field of pharmaceuticals, quasi-drugs, or cosmetics, and can be used in the future, and can be selected as appropriate. can be used.

The composition for external use of the present invention may further contain surfactants, solubilizing components, fats and oils, sugars, or percutaneous absorption promoting components in addition to the components described above. In particular, by adding a surfactant, a solubilizing component, or fats and oils, the stability, effectiveness, and feeling of use of ascorbic acid in an aqueous solvent can be further improved.

Pharmaceuticals, quasi-drugs or cosmetics may be added to the composition for external use of the present invention within quantitative and qualitative ranges that do not impair qualities such as appearance stability and viscosity and that do not impair the effects of the present invention. Various ingredients commonly used as components of external preparations in the field, such as amino acids, irritation reducing agents, thickeners, preservatives, UV protection agents, colorants, dispersants, additional pH adjusters, fragrances, etc. can be compounded. In addition, these components can be mix|blended individually by 1 type or 2 or more types arbitrarily.

The external composition of the second invention contains (A) 10 to 25% by mass of at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid;
(B) 30 to 90% by mass of a diol having 3 carbon atoms in the components other than (A) and (C); and (C) water containing less than 30% by mass of ethoxydiglycol, ( C) / (A) = 0.2 to 5, and pH is 2.0 to 6.0, and if necessary, the above optional components are blended and mixed, and if necessary, other solvents and commonly used Various desired forms such as paste, mousse, gel, liquid, milky lotion, cream, sheet (supporting a substrate), aerosol, and spray can be obtained by blending the base of the external preparation used. can be prepared to These can be manufactured by the usual methods in the industry.

The composition for external use of the present invention is particularly preferably a transparent or 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 700 nm is 80 to 100%, preferably 85 to 100, as a transmittance at a wavelength of 700 nm using a spectrophotometer or a photoelectric photometer UV-2450 (manufactured by Shimadzu Corporation) by an ultraviolet-visible absorbance measurement method. %, more preferably in the range of 90-100%. Here, the water transmittance is assumed to be 100%. The solubilized composition of the present invention has a transparent to translucent appearance. More specifically, the permeability measurement method is based on the 16th revision of the Japanese Pharmacopoeia [B] general test method. Physical test method Spectroscopic measurement method Follow the method described in 2.24 Ultraviolet-Visible Absorbance Measurement Method.

[viscosity]
The topical composition of the present invention can be prepared as a composition having the appropriate viscosity desired when using the topical composition for application to the skin. The viscosity of the composition for external use of the present invention is not particularly limited. , more preferably about 1 to 100 mPa·s, most preferably about 1 to 50 mPa·s. More specifically, the viscosity measurement method is based on the 16th revision of the Japanese Pharmacopoeia [B] general test method. Physical test methods Other physical test methods 2.53 Viscosity measurement methods 2 . Method 2 Rotational viscometer method Follow the method described in 2.1.3 Cone-plate type rotational viscometer (cone plate type viscometer).

[Use]
The composition for external use of the present invention is particularly effective as a whitening agent, anti-inflammatory agent, and anti-aging agent, and has, for example, acne-preventing and treating actions and antioxidant action. Furthermore, when applied to the skin, the effect of increasing the transparency of the skin, retaining moisture, improving texture, and suppressing roughness may be exhibited. Furthermore, in addition to the effects of making pores inconspicuous and moisturizing the skin, it can also be used to prevent and treat blemishes.

The composition for external use of the present invention includes, for example, basic cosmetics such as serums, lotions, sunscreen creams, milky lotions, creams, lotions, oils and packs; foundations, lipsticks, lip balms, mascara, eyeshadows, eyeliners, Makeup cosmetics such as eyebrows and nail polishes; cleaning agents such as facial cleansers, cleansers, and body cleansers; anti-armpit odor agents, athlete's foot treatments, antipruritic agents, wound healing agents, cleansing agents, cleansers, anti-inflammatory analgesics, acne Various external compositions belonging to the field of cosmetics, external pharmaceuticals or external quasi-drugs, such as therapeutic agents, agents for hemorrhoids, antiseptics, whitening agents, and UV protection agents, can be used. Because of its action and effect on the skin, the present invention is preferably used for products applied to the outer skin such as external preparations for skin (formulations for outer skin).

[Stabilization method]
The present invention also includes (A) at least one stabilization method selected from the group consisting of ascorbic acid and salts of ascorbic acid. In the present invention, according to the method for stabilizing ascorbic acid, (A) 10 to 25% by mass of at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid; 30 to 90% by mass of diol in the components other than (A) and (C); and (C) water, and the content of ethoxydiglycol is less than 30% by mass, (C)/(A)=0 0.2 to 5, and a pH of 2.0 to 6.0, a stable formulation can be obtained while containing ascorbic acid. That is, the present invention provides (A) 10 to 25% by mass of at least one selected from the group consisting of ascorbic acid and ascorbic acid salts; (B) a diol having 3 carbon atoms, (A) and ( C) 30 to 90% by mass in components other than; (A) a method for imparting stability to an external composition containing at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid, by adjusting the ratio to 2.0 to 6.0. The term "stabilization" as used herein means, but is not limited to, ensuring stability even at high temperatures or low temperatures, for example. Specifically, precipitation of ascorbic acid or a salt thereof is suppressed even when the composition for external use is stored at 4°C for at least one week, or even after storage at 50°C or storage at 40°C for a certain period of time. This refers to suppression of appearance changes such as coloring.

In the method of the present invention, (A) at least one selected from the group consisting of ascorbic acid and ascorbic acid salts, (B) a diol having 3 carbon atoms, and (C) water and ethoxydiglycol The amount and ratio thereof are the same as those used in the composition for external use. Furthermore, the product obtained by this method can be used once or several times a day in accordance with the known or commonly used dosage and administration, depending on the intended use.

EXAMPLES Next, the present invention will be specifically described with reference to examples, but the present invention is not limited to the following examples. In addition, the unit of each component amount in the table is % by mass.

Compositions for external use having compositions shown in Tables 1 to 6 were prepared according to a conventional method. After that, these compositions were tested according to each test item.

[Ascorbic acid coloration inhibition confirmation test]
The presence or absence of suppression of coloring after storage at 40° C. or 50° C. of the compositions for external use according to some examples of the present invention and comparative examples was evaluated visually and with a color difference meter. Specifically, ascorbic acid is added to a mixed solution of various components according to the formulation (mass%) described in various recipe tables, and dissolved by heating and mixing at 60 ° C. for 10 minutes to prepare a composition. did. The prepared composition was filled in a transparent glass bottle and allowed to stand in a thermo-hygrostat at 40° C. or 50° C. for 1 week (represented as 1 W) or 4 weeks (represented as 4 W). After each measurement period, the container was taken out from the constant temperature machine and the temperature was constant at 25° C., and then evaluated. Each test liquid was visually observed and measured with a color difference meter to determine the presence or absence and degree of coloring.

In the measurement using a color difference meter, 1 mL of the test solution was placed in a glass cell (CM-A97, thickness 2 mm), and the b value was measured using a spectrophotometer CM-5 (manufactured by Konica Minolta, Inc.). As the measured value, Δb* when purified water was used as a blank was used. Change in color difference was calculated by the following formula.
(Amount of change in color difference (Δb value)) = (measured value of test liquid after heat retention (b value after accelerated test)) - (measured value of test liquid before heat retention (b value before accelerated test))
The b value is used as an indicator of transparency. Therefore, the smaller the Δb value, the less coloring. Further, when the ratio of Δb between the two was 1.4 or less, the difference in coloration was not felt so much. On the other hand, when it exceeds 1.4, it has been found that the difference in coloration is clearly visible, which may cause inconvenience in quality. Therefore, the presence or absence of coloring was determined by determining whether the ratio was 1.4 or less when the Δb value of the sample showing no change in coloring was set to 1.

[Ascorbic acid precipitation suppression confirmation test]
The presence or absence of precipitation of ascorbic acid was visually evaluated when the compositions for external use according to some examples of the present invention and comparative examples were stored at a low temperature. Specifically, ascorbic acid is added to a mixed solution of various components according to the formulation (mass%) described in various recipe tables, and dissolved by heating and mixing at 60 ° C. for 10 minutes to prepare a composition. did. The prepared composition was filled in a transparent glass bottle, allowed to stand at 4°C in the dark, and stored for 1 week or 4 weeks, and each test solution was visually observed to determine the presence of crystal precipitation.

<Evaluation Criteria>
○: A state in which no precipitates can be visually observed. ×: A state in which precipitates can be visually observed.

[Ascorbic acid percutaneous absorption test]
The percutaneous absorbability of external compositions according to some examples and comparative examples of the present invention was verified. As the permeation of ascorbic acid to the inside of the skin is enhanced by improving the transdermal absorbability, a higher anti-aging effect is expected as a composition. That is, in some cases, it is possible to exert the effect of ascorbic acid deep into the stratum corneum.

The percutaneous absorbability of ascorbic acid in the compositions for external use prepared in Examples and Comparative Examples was confirmed by measurement by stratum corneum stripping.

Specifically, first, the amount of ascorbic acid in the stratum corneum of the components that permeated the skin of healthy human upper arms and forearms was confirmed by tape stripping. Two healthy male volunteers who gave voluntary consent to participate in the study were used as subjects. A piece of cotton impregnated with 750 uL of the composition for external use of Example or Comparative Example was applied to a 1.5 cm×1.5 cm inner part of the upper arm of the subject, and allowed to stand for 5 minutes. After removing the cotton, the sample remaining on the skin surface was removed with new cotton, and left 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 Co., Ltd.), tape stripping was performed 7 times continuously from the applied site to exfoliate corneocytes, and all layers of the obtained tape were used as samples for measurement. The number of tape strips was set by confirming in a preliminary test that the required amount of corneocytes was peeled off for each tape strip and that inflammation and pain did not occur after tape stripping.

The resulting sample for measurement was extracted with 1 mL of an extraction solvent consisting of a mixture of Tritonx-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 extracted solution after removing foreign matter with a 0.45 um syringe filter (manufactured by GL Sciences). Agilent HPLC equipped with a reversed-phase column (CAPCELL PAK C18 SG120, manufactured by Shiseido) (mobile phase: acetonitrile/0.02 M phosphoric acid solution (pH 3.0) (1:9), absorbance detection wavelength: 270 nm) and measuring the amount of L-ascorbic acid contained in the solution. The results were compared as permeation amount (ug/cm ² ), which was obtained by averaging the measured values of the measurement specimens taken from each of the three arms of the two subjects.

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

(Examples 1-1 to 1-6, Comparative Examples 1-1 to 1-3)
External compositions of Examples and Comparative Examples having 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 value with the color difference value of the composition for external use in Example 1-1 as the standard (1). That is, the stability ratio represents the ratio of Δb.

Tables 1 and 2 show the results of the ascorbic acid coloration suppression test for the compositions of Examples and Comparative Examples.

The compositions of Examples had a coloration-inhibiting effect even when stored under high-temperature conditions, and exhibited excellent stability over a long period of time. On the other hand, the composition of the comparative example was found to be colored under the storage conditions of the test.

(Examples 2-1 to 2-2, Comparative Example 2-1)
External compositions of Examples and Comparative Examples having 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 value with the color difference value of the composition for external use in Example 2-1 as the standard (1). That is, the stability ratio represents the ratio when the value of Δb in Example 2-1 is set to 1.

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

That is, it can be seen that the compositions shown in the examples achieve 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)
External compositions of Examples and Comparative Examples having compositions shown in Table 4 were prepared according to a conventional method.

Table 4 shows the results of the ascorbic acid coloration suppression confirmation test and the ascorbic acid deposition suppression confirmation test for the compositions of Examples and Comparative Examples.

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

Table 4 shows the results of the ascorbic acid coloration suppression confirmation test and 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 value with the color difference value of the composition for external use in Example 4-1 as the standard (1). That is, the stability ratio represents the ratio when the value of Δb in Example 4-1 is set to 1.

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

Furthermore, Table 6 shows the results of an ascorbic acid coloration inhibition confirmation test, an ascorbic acid precipitation inhibition confirmation test, and a percutaneous absorbability test of the compositions of other Examples and Comparative Examples. Among the evaluation items, the ratio of Δb describes the ratio of the comparative value with the color difference value of the composition for external use in Example 5-1 as the standard (1). That is, the stability ratio represents the ratio when the value of Δb in Example 5-1 is set to 1.

Compared to the compositions of the comparative examples, the compositions of the examples can suppress the precipitation of ascorbic acid even under low-temperature storage, and furthermore, it is possible to achieve both of the properties of suppressing the coloring of the composition during storage. Understood. Furthermore, it was found that the composition of the present invention is also excellent in percutaneous absorbability.

FIG. 1 shows the percutaneous absorbability results of the compositions of Examples 5-1 and 5-2 and Comparative Examples 5-1 and 5-2.

Next, topical compositions having compositions shown in Tables 7 to 9 were prepared according to a conventional method. After that, these compositions were tested according to each test item.

[Ascorbic acid coloration inhibition confirmation test]
The presence or absence of suppression of coloration after storage at 40° C. or 50° C. of the compositions for external use shown in Tables 7 to 9 was evaluated visually and with a color difference meter. Specifically, confirmation tests were conducted in exactly the same manner as in Examples 1-5 and Comparative Examples 1-5.

[Ascorbic acid precipitation suppression confirmation test]
Presence or absence of ascorbic acid precipitation was visually evaluated when the compositions for external use having the compositions shown in Tables 7 to 9 were stored at a low temperature. Specifically, confirmation tests were conducted in exactly the same manner as in Examples 1-5 and Comparative Examples 1-5.

[Ascorbic acid percutaneous absorption test]
The percutaneous absorbability of external compositions according to some examples and comparative examples of the second invention was verified. As the permeation of ascorbic acid to the inside of the skin is enhanced by improving the transdermal absorbability, a higher anti-aging effect is expected as a composition. That is, in some cases, it is possible to exert the effect of ascorbic acid deep into the stratum corneum.

The percutaneous absorbability of ascorbic acid in the compositions for external use prepared in Examples and Comparative Examples was confirmed by measurement by stratum corneum stripping. Specifically, confirmation tests were conducted in exactly the same manner as in Examples 1-5 and Comparative Examples 1-5.

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

Tables 7 to 9 show the results of each test of the compositions of Examples and Comparative Examples.

The compositions of Examples had a coloration-inhibiting effect even when stored under high-temperature conditions, and exhibited excellent stability over a long period of time. On the other hand, the composition of the comparative example was found to be colored under the storage conditions of the test. In addition, the compositions of Examples were more inhibited from precipitation at low temperatures than the compositions of Comparative Examples.

[Prescription example]
Formulation examples are shown in Tables 10 to 12 below. All formulation examples can be suitably used for lotions, beauty essences, and the like. All the contents in the formulation examples are in % by mass.

Claims (13)

(A) 1% by mass or more and 10% by mass or less of at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid;
(B) 30% by mass or more of a diol having 3 carbon atoms; and (C) 5% by mass or more and 20% by mass or less of water, an ethoxydiglycol content of less than 30% by mass, and an ethanol content. is 20% by mass or less and has a pH of 4.5 or less. The composition for external use according to claim 1, wherein the content of the component (B) is 40% by mass or more. 3. The composition for external use according to claim 1, wherein the content of said ascorbic acid or a salt thereof is 3 to 10% by mass. 4. The composition for external use according to any one of claims 1 to 3, wherein the content of water (C) is 10% by mass or less. (A) 10 to 25% by mass of at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid
(B) 30 to 90% by mass of a diol having 3 carbon atoms in components other than (A) and (C); and (C) water containing 0 to 5 % by mass of ethoxydiglycol, ( C)/(A) = 0.2-5 and a composition for external use with a pH of 2.0-6.0. The composition for external use according to any one of claims 1 to 5, further comprising butylene glycol and/or lower alcohol. The composition for external use according to any one of claims 1 to 6, wherein the component (B) is 1,3-propanediol and/or propylene glycol. The composition for external use according to any one of claims 1 to 7, wherein the component (B) contains at least 1,3-propanediol. The composition for external use according to any one of claims 1 to 4 , wherein the content of ethoxydiglycol is 10% by mass or less. The composition for external use according to any one of claims 1 to 9, wherein the composition for external use is a solubilized composition for external use having a transmittance of 85 to 100% at a wavelength of 700 nm. The composition for external use according to any one of claims 1 to 10, which is for promoting percutaneous absorption of ascorbic acid. (A) 1% by mass or more and 10 % by mass or less of at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid;
( B) 30% by mass or more of a diol having 3 carbon atoms; (A) coloring and/or an external composition containing at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid, by adjusting the pH to 20% by mass or less and the pH to 4.5 or less; A method for preventing precipitation of crystals. (A) 10% to 25% by mass of at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid
(B) 30 to 90% by mass of a diol having 3 carbon atoms in components other than (A) and (C); and (C) water containing 0 to 5 % by mass of ethoxydiglycol, (C)/(A) = 0.2 to 5.0 and pH is 2.0 to 6.0, (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid A method for preventing discoloration and/or precipitation of crystals in an external composition containing seeds.

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