Topical composition containing ascorbic acid and / or salt thereof

Abstract

To provide a topical composition that has excellent stability and feel of use.　The present invention provides a topical composition that includes (A) at least 25 mass% but less than 40 mass% of ascorbic acid or a salt thereof, (B) a low-molecular-weight betaine, and (C) 15–40 mass% of water such that, by parts by mass, A:B=1:0.55–2.4 and A:C=1:0.38–1.6. Or the present invention provides a topical composition that includes (A) at least 40 mass% but less than 45 mass% of ascorbic acid or a salt thereof, (B) a low-molecular-weight betaine, and (C) 15–40 mass% of water such that, by parts by mass, A:B=1:0.6–0.8 and A:C=1:0.6–1.0. Or the present invention provides a topical composition that includes (A) 45–50 mass% of ascorbic acid or a salt thereof, (B) a low-molecular-weight betaine, and 15–35 mass% of water such that, by parts by mass, A:B=1:0.55–0.88 and A:C=1:0.3–0.67.

Description

External composition containing ascorbic acid and / or its salt

[0001] The present invention relates to an external composition containing ascorbic acid and / or its salt.

[0002] Ascorbic acid exhibits various effects such as anti-inflammatory effect, acne improvement effect, whitening effect, anti-aging effect, antioxidant effect, cell activation effect by promoting the synthesis of biological components such as collagen, and the effect of suppressing cell damage and DNA damage caused by ultraviolet rays in epidermal keratinocytes. It is widely used as a skin external preparation expecting these effects.

[0003] An aqueous skin external preparation containing ascorbic acid has been proposed (for example, Patent Document 1).

[0004] Patent No. 7295809

[0005] An object of the present invention is to provide a skin external composition containing ascorbic acid having good stability while containing a high concentration of ascorbic acid.

[0006] Provided is a highly stable external composition containing ascorbic acid and / or its salt. In particular, a highly stable external composition can be provided against external stimuli such as vibration applied during filling into a container in the manufacturing process or during product transportation.

[0007] According to the studies of the present inventors, it has been found that a composition containing a high concentration of ascorbic acid and / or its salt faces the problem that the solution solidifies and solid components precipitate due to external stimuli such as vibration.

[0008] As a result of intensive studies to solve this problem, the present inventors have found that even when containing a high concentration of ascorbic acid and / or its salt, by strictly defining the concentration ratio of water and trimethylglycine and the amount ratio of each to ascorbic acid, an excellent external composition having good stability against external stimuli applied not only immediately after preparation but also during filling into a container or during product transportation can be obtained, and the present invention has been completed.

[0009] In other words, a preferred embodiment of the present invention provides the following external skin compositions: [1] An external composition comprising (A) 25% by mass or more and less than 40% by mass of ascorbic acid and / or a salt thereof, (B) low molecular weight betaine, and (C) water in a mass ratio of 15 to 40% by mass, where A:B = 1:0.55 to 2.4 and A:C = 1:0.38 to 1.6. [2] An external composition comprising (A) 40% by mass or more and less than 45% by mass of ascorbic acid and / or a salt thereof, (B) low molecular weight betaine, and (C) water in a mass ratio of 15 to 40% by mass, where A:B = 1:0.6 to 0.8 and A:C = 1:0.6 to 1.0. [3] A topical composition comprising (A) 45% to 50% by mass of ascorbic acid and / or its salt, (B) low molecular weight betaine, and (C) 15 to 35% by mass of water, wherein the mass ratio of A:B = 1:0.55 to 0.88 and A:C = 1:0.3 to 0.67.

[0010] The present invention provides a skin-applied composition that exhibits excellent stability even when subjected to external stimuli such as vibration.

[0011] In this specification, the unit of content "mass%" is synonymous with "g / 100g".

[0012] In this specification, when we refer to "X to Y" (where X and Y are any numbers), unless otherwise specified, we mean "X or greater and Y or less."

[0013] <First Embodiment> [Composition for External Use on the Skin] One embodiment of the present invention relates to a composition for external use on the skin, comprising: (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid in an amount of 25% by mass or more and less than 40% by mass; (B) low molecular weight betaine; and (C) water in an amount of 15 to 40% by mass, wherein the mass ratio of component (A) to component (B) is 1:0.55 to 2.4, and the mass ratio of component (A) to component (C) is 1:0.38 to 1.6.

[0014] Normally, in regions where at least one selected from the group consisting of (A) ascorbic acid and salts of ascorbic acid is present in amounts of 25% or more by mass, 26% or more by mass, or 27% or more by mass, the product is unstable to low temperatures, long-term storage, or stress from filling and transportation, and the problem of instability becomes particularly apparent under these conditions.

[0015] In this specification, "long-term storage" refers to, for example, at least one week, two weeks, one month, six months, one year, or two years.

[0016] However, the topical composition of this embodiment contains at least one selected from the group consisting of (A) ascorbic acid and salts of ascorbic acid in a high concentration range, and is stable against external stimuli applied during manufacturing, such as when filling containers or transporting the product.

[0017] ((A) At least one selected from the group consisting of ascorbic acid and salts of ascorbic acid) In this embodiment, ascorbic acid that is commercially available as an ingredient in topical skin preparations in the pharmaceutical, quasi-drug or cosmetic fields can be used, and these usually refer to the L-isomer.

[0018] Salts of ascorbic acid can also be used. Here, salts of ascorbic acid refer to pharmaceutically acceptable salts. While not limited to these, examples include salts with organic bases (e.g., salts with tertiary amines such as trimethylamine salt, triethylamine salt, monoethanolamine salt, triethanolamine salt, pyridine salt, etc., and basic ammonium salts such as arginine), and salts with inorganic bases (e.g., alkali metal salts such as ammonium salt, sodium salt, potassium salt, alkaline earth metal salts such as calcium salt, magnesium salt, aluminum salt, etc.). Particularly preferred salts of ascorbic acid are sodium salt and potassium salt. Specifically, examples include sodium ascorbate, sodium ascorbate monophosphate, sodium ascorbate diphosphate, sodium ascorbate triphosphate, and sodium ascorbic acid-2-sulfate.

[0019] In this embodiment, ascorbic acid or its salts can be used individually or in combination of two or more types.

[0020] In the topical composition of this embodiment, the total content of component (A) relative to the total amount of the topical composition is appropriately set in balance with other components. The total content of component (A) relative to the total amount of the topical composition is not particularly limited as long as it is 25% by mass or more and less than 40% by mass. For example, it can be 26% by mass or more, 27% by mass or more, 28% by mass or more, 29% by mass or more, 30% by mass or more, 31% by mass or more, 32% by mass or more, 33% by mass or more, 34% by mass or more, or 35% by mass or more. Alternatively, for example, it can be 39% by mass or less, 38% by mass or less, 37% by mass or less, 36% by mass or less, 35% by mass or less, 34% by mass or less, 33% by mass or less, 32% by mass or less, 31% by mass or less, or 30% by mass or less. The total content of component (A) relative to the total amount of the topical composition is 25% by mass or more and less than 40% by mass, preferably 27% by mass to 38% by mass, more preferably 28% by mass to 36% by mass.

[0021] (B) Low molecular weight betaine The low molecular weight betaine used in this embodiment can be a compound that is commonly used as an ingredient in topical skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics. In the present invention, low molecular weight betaine refers to a compound that forms an amphoteric ion within a molecule with a molecular weight of 500 or less. Specifically, examples include quaternary ammonium bases, quaternary phosphonium bases, tertiary sulfonium bases, etc., which exhibit almost no surfactant properties. Preferably, the following chemical formula

[0022] Examples of N,N,N-trialkyl amino acids are those represented by the formula (wherein R1, R2, and R3 each independently represent an alkyl group having 1 to 6 carbon atoms, and n represents 1 to 6).

[0023] R1 to R3 can be any linear or branched alkyl group having 1 to 6 carbon atoms. Examples include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, isopentyl group, neopentyl group, tert-pentyl group, hexyl group, isohexyl group, 3-methylpentyl group, 2,2-dimethylbutyl group, or 2,3-dimethylbutyl group. R1 to R3 may be the same or different.

[0024] Specifically, examples include trimethylglycine, triethylglycine, tripropylglycine, and triisopropylglycine (n=1), trimethyl-β-alanine (n=2), and trimethyl-γ-aminobutyric acid (n=3), with trimethylglycine being preferred.

[0025] Furthermore, these low molecular weight betaines may be substituted, specifically N,N,N-trimethylalanine, N,N,N-triethylalanine, N,N,N-triisopropylalanine, N,N,N-trimethylmethylalanine, carnitine, acetylcarnitine, etc., with carnitine being preferred.

[0026] Furthermore, these can be synthesized, or commercially available products can be used as is.

[0027] These low-molecular-weight betaines can be used individually or in combination of two or more.

[0028] In the topical composition of this embodiment, the total content of low molecular weight betaine relative to the total amount of the topical composition is appropriately set in balance with other components. Preferably, it is 13.75% by mass or more, more preferably 15% by mass or more, even more preferably 20% by mass or more, more preferably 23% by mass or more, and most preferably 25% by mass or more, relative to the total amount of the topical composition. Also, the total content of low molecular weight betaine relative to the total amount of the topical composition is preferably 47% by mass or less, more preferably 43% by mass or less, even more preferably 40% by mass or less, more preferably 38% by mass or less, and most preferably 35% by mass or less. Preferably, the total content of low molecular weight betaine relative to the total amount of the topical composition is 13.75% by mass to 47% by mass, more preferably 15% by mass to 43% by mass, even more preferably 20% by mass to 40% by mass, and most preferably 25% by mass to 38% by mass.

[0029] In the external composition of this embodiment, the ratio of the content of component (B) to component (A) is such that, per 1 part by mass of the total content of component (A), the total content of low molecular weight betaine is 0.55 to 2.4 parts by mass, preferably 0.6 to 2 parts by mass, more preferably 0.65 to 1.5 parts by mass, even more preferably 0.7 to 1.2 parts by mass, even more preferably 0.75 to 1.2 parts by mass, or 0.8 to 1.2 parts by mass.

[0030] ((C) Water) In the topical composition of this embodiment, the water content relative to the total amount of the topical composition is preferably 15% by mass or more, more preferably 17% by mass or more, even more preferably 20% by mass or more, even more preferably 23% by mass or more, and most preferably 25% by mass or more, relative to the topical composition, from the viewpoint of low-temperature stability and / or good preparation. The water content relative to the total amount of the topical composition is preferably 40% by mass or less, more preferably 38% by mass or less, even more preferably 36% by mass or less, and even more preferably 34% by mass or less. The total content of component (C) relative to the total amount of the topical composition is preferably 15% by mass to 40% by mass, more preferably 17% by mass to 38% by mass, even more preferably 20% to 36% by mass, and even more preferably 23% to 36% by mass. It is also preferable to have, for example, 15% to 38% by mass, 17% to 34% by mass, 20% to 34% by mass, and 24% to 33.5% by mass. By adjusting the amount of water within the above range, a well-balanced and superior formulation can be obtained in terms of low-temperature stability, long-term stability, and usability.

[0031] In the external composition of this embodiment, the ratio of the content of component (C) to component (A) is 0.38 to 1.6 parts by mass, preferably 0.5 to 1.5 parts by mass, more preferably 0.7 to 1.3 parts by mass, per 1 part by mass of the total content of component (A), and may also be 0.7 to 1.3 parts by mass, 0.7 to 1.25 parts by mass, 0.8 to 1.2 parts by mass, 0.8 to 1.1 parts by mass, etc.

[0032] In the external composition of this embodiment, the ratio of the content of component (C) to component (B) is not particularly limited, but is preferably 0.1 to 1.9 parts by mass, more preferably 0.3 to 1.7 parts by mass, and even more preferably 0.5 to 1.5 parts by mass, per 1 part by mass of the total content of component (B).

[0033] (D) Polyhydric alcohols having 3 to 6 carbon atoms The topical composition of this embodiment may include components other than the above-mentioned components (A), (B), and (C), insofar as they do not hinder the effects of the present invention, from the viewpoint of improving usability and stability. The topical composition of this embodiment may contain polyhydric alcohols having 3 to 6 carbon atoms. The polyhydric alcohols having 3 to 6 carbon atoms are not particularly limited as long as they are used as components of topical skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics. Commercially available polyhydric alcohols having 3 to 6 carbon atoms can be used as is. In addition, from the viewpoint of reducing skin irritation, improving usability, and improving stability, polyhydric alcohols having 3 to 5 carbon atoms are more preferred, with 1,3-propanediol, propylene glycol, 1,3-butylene glycol and / or 3-methyl-1,3-butanediol being preferred, and 1,3-propanediol, propylene glycol, and / or 3-methyl-1,3-butanediol being particularly preferred.

[0034] The content of component (D) relative to the total amount of the topical composition in this embodiment is appropriately set by balancing it with other components. The content of component (D) relative to the total amount of the topical composition is not particularly limited, but can be 0% by mass or more, 0.1% by mass or more, 0.5% by mass or more, or 0.7% by mass or more. The content of component (D) relative to the total amount of the topical composition can be 30% by mass or less, 28% by mass or less, 25% by mass or less, or 20% by mass or less. The content of component (D) relative to the total amount of the topical composition is preferably 0.1 to 30% by mass, more preferably 0.5 to 28% by mass, even more preferably 0.7% to 25% by mass, and particularly preferably 0.7 to 20% by mass. In the topical composition of this embodiment, the content of one component from among 1,3-propanediol, propylene glycol, 1,3-butylene glycol, or 3-methyl-1,3-butanediol relative to the total amount of the topical composition is preferably 0.1 to 30% by mass, more preferably 0.5 to 28% by mass, even more preferably 0.7% to 25% by mass, and particularly preferably 0.7% to 20% by mass, respectively.

[0035] In the external composition of this embodiment, the ratio of the content of component (D) to component (A) is not particularly limited, but is preferably 0 to 1.2 parts by mass, more preferably 0.01 to 1.1 parts by mass, even more preferably 0.02 to 1 part by mass, and particularly preferably 0.02 to 0.5 parts by mass, per 1 part by mass of the total content of component (A). For example, it is also preferable to have 0 to 0.95 parts by mass, 0.01 to 0.95 parts by mass, 0 to 0.9 parts by mass, 0.01 to 0.9 parts by mass, 0 to 0.8 parts by mass, 0.01 to 0.8 parts by mass, 0.6 to 1.2 parts by mass, 0.65 to 1.2 parts by mass, 0.7 to 1.2 parts by mass, 0.8 to 1.1 parts by mass, etc.

[0036] The topical composition of this embodiment may contain glycerin and / or diglycerin. However, the total content may be 20% by mass or less, 10% by mass or less, or 5% by mass or less. In the topical composition of this embodiment, it is preferable that it does not contain glycerin and / or diglycerin.

[0037] (E) Dimethyl isosorbide The topical composition of this embodiment may include components other than the above-mentioned components (A), (B), and (C), in order to improve the feel and stability of the present invention. The topical composition of this embodiment may also contain dimethyl isosorbide (isosorbide dimethyl ether). In this embodiment, dimethyl isosorbide that is commercially available as an ingredient in topical skin preparations in the pharmaceutical, quasi-drug, or cosmetic fields can be used.

[0038] This compound can be synthesized, or commercially available products can be used as is.

[0039] The content of component (E) relative to the total amount of the topical composition in this embodiment is appropriately set by balancing it with other components. The content of component (E) relative to the total amount of the topical composition is not particularly limited, but is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, and even more preferably 0.7% by mass or more. The content of component (E) relative to the total amount of the topical composition is preferably 30% by mass or less, more preferably 28% by mass or less, even more preferably 25% by mass or less, and even more preferably 20% by mass or less. The content of component (E) relative to the total amount of the topical composition is preferably 0.1 to 30% by mass, more preferably 0.5 to 28% by mass, even more preferably 0.7% to 25% by mass, and particularly preferably 0.7 to 20% by mass.

[0040] In the external composition of this embodiment, the ratio of the content of component (A) to component (E) is not particularly limited, but the content of component (E) is preferably 0 to 1.2 parts by mass, more preferably 0.01 to 1.1 parts by mass, even more preferably 0.02 to 1 part by mass, and most preferably 0.02 to 0.5 parts by mass per 1 part by mass of component (A).

[0041] ((F) Lower Alcohol) The topical composition of this embodiment may contain (F) a lower alcohol in addition to the above-mentioned components (A), (B), and (C), in order to improve the feel of use, stability, and promote transdermal absorption, provided that it does not hinder the effects of the present invention. The lower alcohol is not particularly limited as long as it is used as an ingredient in topical skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics. In this specification, "lower alcohol" refers to a monohydric alcohol having 1 to 6 carbon atoms. Of these, alcohols having 2 to 3 carbon atoms can be used in particular preference. Examples of such alcohols include ethanol, n-propanol, isopropanol, etc. Ethanol is particularly preferred.

[0042] The content of component (F) relative to the total amount of the external composition of this aspect is appropriately set according to the balance with other components. The content of component (F) relative to the total amount of the external composition is not particularly limited, but can be 30% by mass or less, 28% by mass or less, 25% by mass or less, or 20% by mass or less, and preferably 10% by mass or less. Also, it can be 0% by mass or more, 0.1% by mass or more, 0.3% by mass or more, 0.7% by mass or more, or 1.0% by mass or more. The lower alcohol contained in the external composition of this aspect is preferably 0 to 30% by mass, more preferably 0.1 to 28% by mass, still more preferably 0.5 to 25% by mass, and even more preferably 1 to 20% by mass. The content of ethanol contained in the external composition of this aspect can be 30% by mass or less, 28% by mass or less, 25% by mass or less, or 20% by mass or less, and particularly preferably 10% by mass or less. Also, it can be 0% by mass or more, 0.1% by mass or more, 0.3% by mass or more, 0.7% by mass or more, or 1.0% by mass or more. The ethanol contained in the external composition of this aspect is preferably 0 to 30% by mass, 0 to 28% by mass, still more preferably 0.3 to 25% by mass, and even more preferably 1 to 20% by mass.

[0043] (Glycol Ether) From the viewpoints of improving the usability and stability, the external composition of this aspect may contain glycol ether in addition to the above components (A), (B), and (C). However, the content thereof can be 20% by mass or less, 10% by mass or less, or 5% by mass or less. In the external composition of this aspect, it is preferable not to contain glycol ether.

[0044] (pH) From the viewpoints of the stability of component (A), low irritation to the skin and mucosa, and good skin usability, the external composition of this aspect is preferably in the acidic range of pH 1.5 to 6.5, more preferably pH 2 to 6, still more preferably pH 2.5 to 5.5, and particularly preferably pH 3 to 5.

[0045] (pH Adjusting Agent) From the viewpoints of improving the usability, stability, and promoting percutaneous absorption, the external composition of this aspect may contain a pH adjusting agent in addition to the above components (A), (B), and (C) as long as the effects of this aspect are not impaired.

[0046] As the pH adjuster used in this embodiment, compounds that are usually used as components of external skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics can be used. Although not particularly limited, pH adjusters having an amine (for example, aspartic acid or its salt, ε-aminocaproic acid or its salt, glutamic acid or its salt, aminoethylsulfonic acid or its salt, monoethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, arginine, lysine, L-carnitine), organic acid salts (for example, sodium lactate, sodium acetate, sodium citrate, sodium succinate, sodium oxalate, calcium gluconate, sodium pyrrolidonecarboxylate, etc.), inorganic acid salts (for example, sodium pyrosulfite, potassium pyrosulfite, sodium phosphate, potassium nitrate, sodium borate, preferably sodium pyrosulfite), basic amino acids and their salts (arginine, lysine, or histidine and their salts), etc. are exemplified.

[0047] (Optional substance) In the external composition of this embodiment, in addition to the above components (A), (B), and (C), for the purpose of enhancing or supplementing various actions of ascorbic acid and adding other useful actions, whitening components, anti-inflammatory components, antibacterial components, cell-activating components, astringent components, antioxidant components, acne-improving components, anti-aging components, components that promote the synthesis of biological components such as collagen, blood circulation-promoting components, moisturizing components, anti-aging components, etc. can be blended by combining one or more of these various components. Preferably, it is one or more components of a whitening component, an anti-inflammatory component, an antibacterial component, a cell-activating component, an astringent component, an antioxidant component, an anti-aging component, or a moisturizing component. Particularly preferred combinations of these components include combinations with a whitening component, combinations of a whitening component and an antioxidant component, combinations with an antioxidant component, combinations with an anti-aging component, and combinations of a whitening component and an anti-aging component. As each of these components, there is no particular limitation as long as they have been conventionally used as components of external skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics and will be used in the future, and any arbitrary ones can be appropriately selected and used.

[0048] In addition to the above components, the topical composition of this embodiment may further contain surfactants, oils and fats, sugars, or transdermal absorption-promoting components. In particular, the inclusion of surfactants or oils and fats can further improve the stability, effectiveness, or feel of ascorbic acid in an aqueous solvent.

[0049] The topical composition of this embodiment may contain, as needed, various components commonly used as components of topical preparations in the pharmaceutical, quasi-drug, or cosmetic fields, within quantitative and qualitative ranges that do not impair the quality such as appearance stability or viscosity, and do not impair the effects of the present invention. These components may include amino acids, irritation reducers, thickeners, preservatives, UV protection agents, colorants, dispersants, additional pH adjusters, fragrances, etc. These components may be used individually or in combination of two or more as desired.

[0050] The topical composition according to this embodiment can be prepared in various desired forms, such as liquid, emulsion, cream, sheet (substrate-supported), aerosol, spray, paste, mousse, or gel. These can be manufactured by conventional methods in the industry.

[0051] The topical composition of this embodiment is particularly preferably a transparent or translucent composition in which ascorbic acid and / or a salt thereof is dissolved. Here, "dissolved" is defined as follows: That is, for example, by ultraviolet-visible absorbance measurement using a spectrophotometer or photoelectric photometer UV-2450 (manufactured by Shimadzu Corporation), the transmittance at a wavelength of 700 nm is in the range of 80 to 100%, preferably 85 to 100%, and more preferably 90 to 100%. Here, the transmittance of water is set to 100%. The topical composition of the present invention has a transparent or translucent appearance. The method for measuring transmittance is, in more detail, in accordance with the method described in the 18th revised Japanese Pharmacopoeia [B] General Test Methods 2. Physical Test Methods Spectroscopic Measurement Methods 2.24 Method for Ultraviolet-Visible Absorbance Measurement.

[0052] (Viscosity) The topical composition of this embodiment can be prepared as a composition having a suitable viscosity, particularly desirable for application to the skin. The viscosity of the topical composition of this embodiment is not particularly limited, but for example, when measured at 25°C using an E-type viscometer, the viscosity is usually about 30 to 300 mPa·s, preferably about 40 to 250 mPa·s, more preferably about 50 to 200 mPa·s, and even more preferably about 70 to 150 mPa·s. When the viscosity is within this range, the usability of the formulation is improved, such as being easy to handle and less likely to spill. The viscosity (at 25°C) refers to the viscosity measured using a single-cylindrical rotational viscometer (Brookfield type viscometer) in accordance with the viscosity measurement method described in the general test methods of the 18th edition of the Japanese Pharmacopoeia. Specifically, it refers to the value measured using a TV-10M (manufactured by Toki Sangyo Co., Ltd.), and the selection of conditions such as rotor and rotation speed is in accordance with the instruction manual of this instrument, and the viscosity at 25°C is measured. More specifically, the viscosity at 25°C is measured using an M1 rotor under the conditions of a rotation speed of 12 rpm and a measurement time of 60 seconds.

[0053] (Uses) The topical composition of this embodiment is particularly effective as a whitening agent, anti-inflammatory agent, and anti-aging agent, and has effects such as preventing and treating acne and antioxidant effects. Furthermore, when applied to the skin, it may enhance skin transparency, retain moisture, refine skin texture, and reduce roughness. In addition, it may have effects such as minimizing the appearance of pores and providing skin conditioning and moisturizing, and can also be used to prevent and treat blemishes.

[0054] The external compositions of this embodiment can be, for example, basic cosmetics such as serums, lotions, sunscreens, emulsions, creams, oils, and packs; or various external compositions belonging to the fields of cosmetics, topical pharmaceuticals, or quasi-drugs, such as deodorants, athlete's foot treatments, antipruritics, wound healing agents, cleansing agents, cleansing agents, anti-inflammatory and analgesic agents, acne treatments, hemorrhoid treatments, antiseptics, disinfectants, whitening agents, and UV protection agents. Due to its effects on the skin, the present invention is preferably used in products applied to the skin, such as topical skin preparations (formulations for the skin). Furthermore, for example, it can be provided as a single-use product in a single packet or as a product with a short shelf life (for example, a shelf life of 730 days, 365 days, or 180 days from the date of manufacture) as an intensive skin care or special care product.

[0055] (Container) The external composition of this embodiment is not limited and can be contained in a container of a shape and material appropriately selected according to the purpose and use. Examples of specific containers include spray type (non-upright or upright specification), bottle type, tube type, jar type, dropper type, dropper tube type, dispenser type, stick type, blister pack, and sachet type. Of these, from the viewpoint of usability, it is particularly preferable to be contained in a bottle equipped with a dropper, a dropper tube, or a blister pack.

[0056] Examples of materials for these containers include polyethylene terephthalate, polypropylene, polyethylene (HDPE, LDPE, LLDPE, etc.), ABS resin, ethylene vinyl alcohol resin, polystyrene, glass, and metal (aluminum, etc.). While there are no particular limitations on the material of the container body, glass is preferred. These materials can also be used as container materials by applying various coating treatments, combining them (for example by mixing them), or laminating them, taking into consideration their strength, flexibility, weather resistance, or component stability. Examples of coating materials include polyethylene terephthalate, epoxy resin, and polyamide-imide. Among these, polypropylene, polyethylene (HDPE, LDPE, LLDPE, etc.), ethylene vinyl alcohol resin, and metal (aluminum, etc.) are preferred. As a resin coating the inner surface, polyethylene (HDPE, LDPE, LLDPE, etc.), polyamide-imide, or polyethylene terephthalate can be used, and are not particularly limited, but polyethylene (HDPE, LDPE, LLDPE, etc.) is preferred, with LLDPE being particularly preferred.

[0057] [Manufacturing Method] The topical composition according to this embodiment is obtained by weighing component (A), component (B), component (C), and other optional components, and stirring and mixing them at room temperature or while heating. In the manufacturing method of the topical composition according to this embodiment, a method can be adopted in which component (A), component (B), component (C), and other additional components necessary for the topical composition are mixed at once without prior pre-preparation of each component or a combination of several components. The topical composition according to this embodiment may be obtained in cases in which ascorbic acid is prepared in advance in the form of a eutectic mixture and a strong hydrogen bond is formed between the ascorbic acid and the eutectic component.

[0058] [Stabilization Method] The present invention also provides a stable formulation containing a high concentration of ascorbic acid by providing a composition containing (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid in an amount of 25% to less than 40% by mass, (B) low molecular weight betaine, and (C) 15 to 40% by mass of water, wherein the mass ratio of component (A) to component (B) is 1:0.55 to 2.4, and the mass ratio of component (A) to component (C) is 1:0.38 to 1.6. Here, stability refers, without limitation, to reducing or preventing the precipitation or solidification of ascorbic acid due to external stimuli. External stimuli are often unavoidably applied during the filling process of the manufacturing process or vibrations during product transportation.

[0059] In the method of the present invention, the components and their ratios are the same as those used in the aforementioned topical skin composition. Furthermore, the product obtained by this method can be used in known or commonly used dosages and administration methods, divided into one to several times per day, depending on the application.

[0060] <Second Embodiment> [Composition for External Use on the Skin] One embodiment of the present invention relates to a composition for external use on the skin, comprising: (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid in an amount of 40% by mass or more and less than 45% by mass; (B) low molecular weight betaine; and (C) water in an amount of 15% by mass or more, wherein the mass ratio of component (A) to component (B) is 1:0.6 to 0.8, and the mass ratio of component (A) to component (C) is 1:0.6 to 1.0.

[0061] The topical composition of this embodiment contains at least one selected from the group consisting of (A) ascorbic acid and salts of ascorbic acid in a high concentration range, and is stable against external stimuli such as vibrations applied during manufacturing, such as when filling containers or transporting products.

[0062] ((A) At least one selected from the group consisting of ascorbic acid and salts of ascorbic acid) In this embodiment, the type and quality of ascorbic acid or its salts shall be the same as in the first embodiment.

[0063] In the topical composition of this embodiment, the total content of component (A) relative to the total amount of the topical composition is appropriately set in balance with other components. The total content of component (A) relative to the total amount of the topical composition is not particularly limited as long as it is 40% by mass or more and less than 45% by mass, but is 41% by mass or more, 42% by mass or more, 42.5% by mass or more, or 43% by mass or more. The total content of component (A) relative to the total amount of the topical composition is less than 45% by mass, 44.5% by mass or less, 44% by mass or less, 43.5% by mass or less, or 43% by mass or less. The total content of component (A) relative to the total amount of the topical composition is preferably 40% by mass or more and less than 45% by mass, more preferably 40% by mass to 44% by mass, and even more preferably 40% by mass to 43% by mass.

[0064] (B) Low molecular weight betaine The type and quality of the low molecular weight betaine used in this embodiment shall be the same as that of the first embodiment.

[0065] In the topical composition of this embodiment, the total content of low molecular weight betaine relative to the total amount of the topical composition is appropriately set in balance with other components. It is 24% by mass or more, more preferably 24.5% by mass or more, and even more preferably 25% by mass or more, relative to the total amount of the topical composition. Furthermore, the total content of low molecular weight betaine relative to the total amount of the topical composition is preferably 32% by mass or less, more preferably 31.5% by mass or less, even more preferably 31% by mass or less, and even more preferably 30% by mass or less. The total content of low molecular weight betaine relative to the total amount of the topical composition is preferably 24% to 32% by mass, more preferably 24.5% to 32% by mass, even more preferably 25% to 31% by mass, and most preferably 25% to 30% by mass.

[0066] In the external composition of this embodiment, the ratio of the content of component (B) to component (A) is such that the total content of low molecular weight betaine is 0.6 to 0.8 parts by mass, preferably 0.61 to 0.79 parts by mass, and more preferably 0.62 to 0.78 parts by mass, per 1 part by mass of the total content of component (A).

[0067] ((C) Water) In the external composition of this embodiment, the water content relative to the total amount of the external composition is preferably 15% by mass or more, more preferably 18% by mass or more, more preferably 20% by mass or more, even more preferably 22% by mass or more, and most preferably 24% by mass or more, from the viewpoint of low-temperature stability and / or good preparation. The water content relative to the total amount of the external composition is preferably 40% by mass or less, more preferably 38% by mass or less, and more preferably 36% by mass or less. The total content of component (C) relative to the total amount of the external composition is preferably 15% to 40% by mass, more preferably 18% to 38% by mass, even more preferably 20% to 36% by mass, even more preferably 22% to 36% by mass, and particularly preferably 24% to 36% by mass.

[0068] In the external composition of this embodiment, the ratio of the content of component (C) to component (A) is 0.6 to 1 part by mass, preferably 0.61 to 0.9 parts by mass, and more preferably 0.61 to 0.88 parts by mass, per 1 part by mass of the total content of component (A).

[0069] In the external composition of this embodiment, the ratio of the content of component (C) to component (B) is not particularly limited, but is preferably 0.7 to 2 parts by mass, more preferably 0.8 to 1.8 parts by mass, and even more preferably 0.7 to 1.5 parts by mass, per 1 part by mass of the total content of component (B).

[0070] (D) Polyhydric alcohols having 3 to 6 carbon atoms. The topical composition of this embodiment may include components other than the above-mentioned components (A), (B), and (C), in order to improve the feel and stability of the present invention. The topical composition of this embodiment may also contain polyhydric alcohols having 3 to 6 carbon atoms. The type and quality of polyhydric alcohols having 3 to 6 carbon atoms used in this embodiment shall be in accordance with the content of the first embodiment.

[0071] The content of component (D) relative to the total amount of the topical composition in this embodiment is appropriately set by balancing it with other components. The content of component (D) relative to the total amount of the topical composition is not particularly limited, but is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, and even more preferably 0.5% by mass or more. The content of component (D) relative to the total amount of the topical composition is preferably 15% by mass or less, more preferably 12% by mass or less, even more preferably 10% by mass or less, and even more preferably 5% by mass or less. The total content of component (D) relative to the total amount of the topical composition is preferably 0 to 15% by mass, more preferably 0.01 to 12% by mass, even more preferably 0.1 to 10% by mass, and particularly preferably 0.5 to 5% by mass. In the topical composition of this embodiment, the content of one component from among 1,3-propanediol, propylene glycol, 1,3-butylene glycol, or 3-methyl-1,3-butanediol relative to the total amount of the topical composition is preferably 0 to 15% by mass, more preferably 0.01 to 12% by mass, even more preferably 0.1 to 10% by mass, and particularly preferably 0.5 to 5% by mass.

[0072] In the external composition of this embodiment, the ratio of the content of component (D) to component (A) is not particularly limited, but is preferably 0.001 to 0.3 parts by mass per 1 part by mass of the total content of component (A). For example, it can be 0.001 to 0.25 parts by mass, 0.001 to 0.2 parts by mass, 0.001 to 0.15 parts by mass, etc.

[0073] The topical composition of this embodiment may contain glycerin and / or diglycerin. However, the total content may be 20% by mass or less, 10% by mass or less, or 5% by mass or less. In the topical composition of this embodiment, it is preferable that it does not contain glycerin and / or diglycerin.

[0074] (E) Dimethyl isosorbide The topical composition of this embodiment may include components other than the above-mentioned components (A), (B), and (C), in order to improve the feel and stability of the present invention. The topical composition of this embodiment may also contain dimethyl isosorbide (isosorbide dimethyl ether). The quality of the dimethyl isosorbide used in this embodiment shall be in accordance with the content of the first embodiment.

[0075] This compound can be synthesized, or commercially available products can be used as is.

[0076] The content of component (E) relative to the total amount of the topical composition is appropriately set in balance with other components. The content of component (E) relative to the total amount of the topical composition is not particularly limited, but is preferably 0% by mass or more, more preferably 0.01% by mass or more, even more preferably 0.1% by mass or more, and even more preferably 0.5% by mass or more. The content of component (E) relative to the total amount of the topical composition is preferably 15% by mass or less, more preferably 12% by mass or less, even more preferably 10% by mass or less, and even more preferably 5% by mass or less. The content of component (E) relative to the total amount of the topical composition is preferably 0 to 15% by mass, more preferably 0.01 to 12% by mass, even more preferably 0.1 to 10% by mass, and particularly preferably 0.5 to 5% by mass.

[0077] In the external composition of this embodiment, the ratio of the content of component (A) to component (E) is not particularly limited, but is preferably 0.001 to 0.3 parts by mass per 1 part by mass of the total content of component (A). For example, it can be 0.001 to 0.25 parts by mass, 0.001 to 0.2 parts by mass, 0.001 to 0.15 parts by mass, etc.

[0078] ((F) Lower Alcohol) In addition to the above-mentioned components (A), (B), and (C), the topical composition of this embodiment may also contain (F) lower alcohol, insofar as it does not hinder the effects of the present invention, from the viewpoint of improving usability, stability, and promoting transdermal absorption. The type and quality of the lower alcohol used in this embodiment shall be in accordance with the content of the first embodiment. The content of the lower alcohol contained in the topical composition of this embodiment may be 10% by mass or less, 1% by mass or less, 8% by mass or less, 5% by mass or less, or 3% by mass or less. It may also be 0% by mass or more, 0.1% by mass or more, 0.5% by mass or more, 1% by mass or more, or 1.5% by mass or more. The amount of lower alcohol contained in the topical composition of this embodiment is 0 to 10% by mass, more preferably 0 to 8% by mass, even more preferably 0.1 to 6% by mass, and even more preferably 0.5 to 5% by mass. The ethanol content in the topical composition of this embodiment can be 10% by mass or less, 8% by mass or less, 6% by mass or less, or 5% by mass or less, with 5% by mass or less being preferred. It can also be 0% by mass or more, 0.1% by mass or more, 0.5% by mass or more, 1% by mass or more, or 1.5% by mass or more. The ethanol content in the topical composition of this embodiment is 0 to 10% by mass, more preferably 0 to 8% by mass, even more preferably 0.1 to 6% by mass, and even more preferably 0.5 to 5% by mass.

[0079] (Glycol ether) In addition to components (A), (B), and (C) described above, the topical composition of this embodiment may also contain glycol ether from the viewpoint of improving usability and stability. However, the content may be 20% by mass or less, 10% by mass or less, or 5% by mass or less. It is preferable that the topical composition of this embodiment does not contain glycol ether.

[0080] (pH) The topical composition of this embodiment preferably has an acidic pH of 1.5 to 6.5, more preferably 2 to 6, even more preferably 2.5 to 5.5, and particularly preferably 3 to 5, from the viewpoint of the stability of component (A), low irritation to the skin and mucous membranes, and good skin feel.

[0081] (pH adjuster) The topical composition of this embodiment may contain a pH adjuster in addition to the above-mentioned components (A), (B), and (C), in order to improve the feel of use, stability, and promote transdermal absorption, provided that it does not interfere with the effects of this embodiment.

[0082] The type and quality of the pH adjuster used in this embodiment shall be the same as those described in the first embodiment.

[0083] (Optional Substances) In addition to components (A), (B), and (C) above, the topical composition of this embodiment may further contain one or more of the following components in combination for the purpose of enhancing or supplementing the various effects of ascorbic acid, and for the purpose of adding other useful effects: whitening components, anti-inflammatory components, antibacterial components, cell activating components, astringent components, antioxidant components, acne-improving components, anti-aging components, components that promote the synthesis of biocomponents such as collagen, blood circulation promoting components, moisturizing components, anti-aging components, etc. The types, quality, and combinations of these components used in this embodiment shall be in accordance with the contents of the first embodiment.

[0084] In addition to the above components, the topical composition of this embodiment may further contain surfactants, oils and fats, sugars, or transdermal absorption-promoting components. In particular, the inclusion of surfactants or oils and fats can further improve the stability, effectiveness, or feel of ascorbic acid in an aqueous solvent.

[0085] The topical composition of this embodiment may contain, as needed, various components commonly used as components of topical preparations in the pharmaceutical, quasi-drug, or cosmetic fields, within quantitative and qualitative ranges that do not impair the quality such as appearance stability or viscosity, and do not impair the effects of the present invention. These components may include amino acids, irritation reducers, thickeners, preservatives, UV protection agents, colorants, dispersants, additional pH adjusters, fragrances, etc. These components may be used individually or in combination of two or more as desired.

[0086] The topical composition according to this embodiment can be prepared in various desired forms, such as liquid, emulsion, cream, sheet (substrate-supported), aerosol, spray, paste, mousse, or gel. These can be manufactured by conventional methods in the industry.

[0087] The topical composition of this embodiment is particularly preferably a transparent or translucent composition in which ascorbic acid and / or a salt thereof is dissolved. Here, "dissolved" is defined as follows: That is, for example, by ultraviolet-visible absorbance measurement using a spectrophotometer or photoelectric photometer UV-2450 (manufactured by Shimadzu Corporation), the transmittance at a wavelength of 700 nm is in the range of 80 to 100%, preferably 85 to 100%, and more preferably 90 to 100%. Here, the transmittance of water is set to 100%. The topical composition of the present invention has a transparent or translucent appearance. The method for measuring transmittance is, in more detail, in accordance with the method described in the 18th revised Japanese Pharmacopoeia [B] General Test Methods 2. Physical Test Methods Spectroscopic Measurement Methods 2.24 Method for Ultraviolet-Visible Absorbance Measurement.

[0088] (Viscosity) The topical composition of this embodiment can be prepared as a composition having a suitable viscosity, especially when used for application to the skin. The viscosity of the topical composition of this embodiment is not particularly limited, but for example, when measured at 25°C using an E-type viscometer, the viscosity is usually about 30 to 300 mPa·s, preferably about 40 to 250 mPa·s, more preferably about 50 to 200 mPa·s, and even more preferably about 70 to 150 mPa·s. When the viscosity is within this range, the usability of the formulation is improved, such as being easy to handle and less likely to spill. The viscosity (at 25°C) refers to the viscosity measured using a single-cylindrical rotational viscometer (Brookfield type viscometer) in accordance with the viscosity measurement method described in the general test methods of the 18th edition of the Japanese Pharmacopoeia. Specifically, it refers to the value measured using TV-10M (manufactured by Toki Sangyo Co., Ltd.), and the selection of conditions such as rotor and rotation speed is in accordance with the instruction manual of this instrument, and the viscosity at 25°C is measured. More specifically, the viscosity at 25°C is measured using an M1 rotor under the conditions of a rotation speed of 12 rpm and a measurement time of 60 seconds.

[0089] (Uses) The topical composition of this embodiment is particularly effective as a whitening agent, anti-inflammatory agent, and anti-aging agent, and has effects such as preventing and treating acne and antioxidant effects. Furthermore, when applied to the skin, it may enhance skin transparency, retain moisture, refine skin texture, and reduce roughness. In addition, it may have effects such as minimizing the appearance of pores and providing skin conditioning and moisturizing, and can also be used to prevent and treat blemishes.

[0090] The topical compositions of this embodiment can be, for example, basic cosmetics such as serums, lotions, sunscreens, emulsions, creams, oils, and packs; or various topical compositions belonging to the fields of cosmetics, topical pharmaceuticals, or quasi-drugs, such as deodorants, athlete's foot treatments, antipruritics, wound healing agents, cleansing agents, cleansing agents, anti-inflammatory and analgesic agents, acne treatments, hemorrhoid treatments, antiseptics, disinfectants, whitening agents, and ultraviolet protection agents. Due to its effects on the skin, the present invention is preferably used in products applied to the skin, such as topical skin preparations (formulations for the skin). Furthermore, for example, it can be provided as an intensive care or special care product, such as a single-use product or a product with a short shelf life (for example, a shelf life of 730 days, 365 days, or 180 days from the date of manufacture).

[0091] (Container) The external composition of this embodiment is not limited and can be contained in a container of a shape and material appropriately selected according to the purpose and use. The type and material of the container used in this embodiment shall be the same as that of the first embodiment.

[0092] [Manufacturing Method] The topical composition of this embodiment is obtained by weighing components (A), (B), and (C), and other optional components, and stirring and mixing them at room temperature or while heating. Similar to the first embodiment, in the manufacturing method of the topical composition of this embodiment, a method can be adopted in which components (A), (B), (C), and other additional components necessary for the topical composition are mixed at once without prior pre-preparation of each component or a combination of several components. The topical composition of this embodiment may be obtained in cases in which ascorbic acid is prepared in advance in the form of a eutectic mixture and a strong hydrogen bond is formed between the ascorbic acid and the eutectic component.

[0093] [Stabilization Method] The present invention also provides a stable formulation containing a high concentration of ascorbic acid by providing a composition containing (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid in an amount of 40% to less than 45% by mass, (B) low molecular weight betaine, and (C) 15 to 40% by mass of water, wherein the mass ratio of component (A) to component (B) is 1:0.6 to 0.8, and the mass ratio of component (A) to component (C) is 1:0.6 to 1.0. Here, stability refers, without limitation, to reducing or preventing the precipitation or solidification of ascorbic acid due to external stimuli. External stimuli are often unavoidably applied during the filling process in manufacturing or vibrations during product transportation.

[0094] In the method of the present invention, the components and their ratios are the same as those used in the aforementioned topical skin composition. Furthermore, the product obtained by this method can be used in known or commonly used dosages and administration methods, divided into one to several times per day, depending on the application.

[0095] <<Third Embodiment>> [Composition for External Skin Use] One embodiment of the present invention relates to a composition for external skin use comprising: (A) 45% to 50% by mass of ascorbic acid and / or a salt thereof; (B) low molecular weight betaine; and (C) 15 to 35% by mass of water, wherein the parts by mass ratio of A:B = 1:0.55 to 0.88 and A:C = 1:0.3 to 0.67.

[0096] The topical composition of this embodiment contains at least one selected from the group consisting of (A) ascorbic acid and salts of ascorbic acid in a high concentration range, and is stable against external stimuli such as vibrations applied during manufacturing, such as when filling containers or transporting products.

[0097] ((A) At least one selected from the group consisting of ascorbic acid and salts of ascorbic acid) In this embodiment, the type and quality of ascorbic acid or its salts shall be the same as in the first embodiment.

[0098] In the topical composition of this embodiment, the total content of component (A) relative to the total amount of the topical composition is appropriately set in balance with other components. The total content of component (A) relative to the total amount of the topical composition is not particularly limited as long as it is 45% by mass or more and 50% by mass or less, but is 45.5% by mass or more, 46% by mass or more, 46.5% by mass or more, 47% by mass or more, or 47.5% by mass or more. The total content of component (A) relative to the total amount of the topical composition is 50% by mass or less, 49.5% by mass or less, 49% by mass or less, 48.5% by mass or less, or 48% by mass or less. The total content of component (A) relative to the total amount of the topical composition is preferably 45% by mass or more and 50% by mass or less, more preferably 45% by mass to 49% by mass, and even more preferably 45% by mass to 48% by mass.

[0099] (B) Low molecular weight betaine The type and quality of the low molecular weight betaine used in this embodiment shall be the same as that of the first embodiment.

[0100] In the topical composition of this embodiment, the total content of low molecular weight betaine relative to the total amount of the topical composition is appropriately set in balance with other components. Preferably, it is 24% by mass or more, more preferably 24.5% by mass or more, and even more preferably 25% by mass or more, relative to the total amount of the topical composition. Also, the total content of low molecular weight betaine relative to the total amount of the topical composition is preferably 38% by mass or less, more preferably 36% by mass or less, even more preferably 35% by mass or less, and even more preferably 32% by mass or less. Preferably, the total content of low molecular weight betaine relative to the total amount of the topical composition is 24% to 38% by mass, more preferably 24.5% to 36% by mass, even more preferably 25% to 35% by mass, and most preferably 25% to 33% by mass.

[0101] In the external composition of this embodiment, the ratio of the content of component (B) to component (A) is such that the total content of low molecular weight betaine is 0.55 to 0.88 parts by mass, preferably 0.55 to 0.85 parts by mass, more preferably 0.55 to 0.8 parts by mass, and even more preferably 0.6 to 0.8 parts by mass, per 1 part by mass of the total content of component (A).

[0102] ((C) Water) In the external composition of this embodiment, the water content relative to the total amount of the external composition is preferably 15% by mass or more, more preferably 17% by mass or more, particularly preferably 18% by mass or more, and most preferably 20% by mass or more, relative to the external composition, from the viewpoint of low-temperature stability and / or good preparation. The water content relative to the total amount of the external composition is preferably 35% by mass or less, more preferably 32% by mass or less, and even more preferably 30% by mass or less. The total content of component (C) relative to the total amount of the external composition is preferably 15% to 35% by mass, more preferably 17% to 32% by mass, even more preferably 18 to 30% by mass, and particularly preferably 10 to 28% by mass.

[0103] In the external composition of this embodiment, the ratio of the content of component (C) to component (A) is 0.3 to 0.67 parts by mass, preferably 0.3 to 0.65 parts by mass, and more preferably 0.35 to 0.61 parts by mass, per 1 part by mass of the total content of component (A).

[0104] In the external composition of this embodiment, the ratio of the content of component (C) to component (B) is not particularly limited, but is preferably 0.1 to 1.4, more preferably 0.3 to 1.3, even more preferably 0.4 to 1.2, and particularly preferably 0.5 to 1.1, per 1 part by mass of the total content of component (B).

[0105] (D) Polyhydric alcohols having 3 to 6 carbon atoms. The topical composition of this embodiment may include components other than the above-mentioned components (A), (B), and (C), in order to improve the feel and stability of the present invention. The topical composition of this embodiment may also contain polyhydric alcohols having 3 to 6 carbon atoms. The type and quality of polyhydric alcohols having 3 to 6 carbon atoms used in this embodiment shall be in accordance with the content of the first embodiment.

[0106] The content of component (D) relative to the total amount of the topical composition in this embodiment is appropriately set by balancing it with other components. The content of component (D) relative to the total amount of the topical composition is not particularly limited, but is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, and even more preferably 0.5% by mass or more. The content of component (D) relative to the total amount of the topical composition is preferably 10% by mass or less, more preferably 8% by mass or less, and even more preferably 5% by mass or less. The total content of component (D) relative to the total amount of the topical composition is preferably 0 to 10% by mass, more preferably 0.01 to 8% by mass, even more preferably 0.1 to 6% by mass, and particularly preferably 0.5 to 5% by mass. In the topical composition of this embodiment, the content of one component from among 1,3-propanediol, propylene glycol, 1,3-butylene glycol, or 3-methyl-1,3-butanediol relative to the total amount of the topical composition is preferably 0 to 10% by mass, more preferably 0.01 to 8% by mass, even more preferably 0.1 to 6% by mass, and particularly preferably 0.5 to 5% by mass, respectively.

[0107] In the external composition of this embodiment, the ratio of the content of component (D) to component (A) is not particularly limited, but it can preferably be 0 to 0.37 parts by mass, 0.0001 to 0.37 parts by mass, 0.001 to 0.3 parts by mass, 0.001 to 0.25 parts by mass, 0.001 to 0.2 parts by mass, etc., per 1 part by mass of the total content of component (A).

[0108] The topical composition of this embodiment may contain glycerin and / or diglycerin. However, the total content may be 20% by mass or less, 10% by mass or less, or 5% by mass or less. In the topical composition of this embodiment, it is preferable that it does not contain glycerin and / or diglycerin.

[0109] (E) Dimethyl isosorbide The topical composition of this embodiment may include components other than the above-mentioned components (A), (B), and (C), in order to improve the feel and stability of the present invention. The topical composition of this embodiment may also contain dimethyl isosorbide (isosorbide dimethyl ether). The quality of the dimethyl isosorbide used in this embodiment shall be in accordance with the content of the first embodiment.

[0110] This compound can be synthesized, or commercially available products can be used as is.

[0111] The content of component (E) relative to the total amount of the topical composition is appropriately set in balance with other components. The content of component (E) relative to the total amount of the topical composition is not particularly limited, but is preferably 0% by mass or more, more preferably 0.01% by mass or more, even more preferably 0.1% by mass or more, and even more preferably 1% by mass or more. The content of component (E) relative to the total amount of the topical composition is preferably 10% by mass or less, more preferably 8% by mass or less, even more preferably 6% by mass or less, and even more preferably 5% by mass or less. The content of component (E) relative to the total amount of the topical composition is preferably 0 to 10% by mass, more preferably 0.01 to 8% by mass, even more preferably 0.1 to 6% by mass, and particularly preferably 0.5 to 5% by mass.

[0112] In the external composition of this embodiment, the ratio of the content of component (A) to component (E) is not particularly limited, but it can preferably be 0 to 0.37 parts by mass, 0.0001 to 0.37 parts by mass, 0.001 to 0.3 parts by mass, 0.001 to 0.25 parts by mass, 0.001 to 0.2 parts by mass, etc., per 1 part by mass of the total content of component (A).

[0113] ((F) Lower Alcohol) The topical composition of this embodiment may contain (F) lower alcohol in addition to the above-mentioned components (A), (B), and (C), in order to improve usability, stability, and promote transdermal absorption, provided that it does not hinder the effects of the present invention. The type and quality of the lower alcohol used in this embodiment shall be the same as that of the first embodiment.

[0114] The lower alcohol content in the topical composition of this embodiment can be 10% by mass or less, 0% by mass or less, 8% by mass or less, 6% by mass or less, or 5% by mass or less, with 0% by mass or less being preferred. It can also be 0% by mass or more, 0.01% by mass or more, 0.1% by mass or more, or 1% by mass or more. The lower alcohol content in the topical composition of this embodiment is preferably 0 to 10% by mass, more preferably 0.01 to 8% by mass, even more preferably 0.1 to 6% by mass, and particularly preferably 0.5 to 5% by mass. The ethanol content in the topical composition of this embodiment can be 10% by mass or less, 0% by mass or less, 8% by mass or less, 6% by mass or less, or 5% by mass or less, with 0% by mass or less being preferred. It can also be 0% by mass or more, 0.01% by mass or more, 0.1% by mass or more, or 1% by mass or more. The lower alcohols contained in the external composition of this embodiment are preferably 0 to 10% by mass, more preferably 0.01 to 8% by mass, even more preferably 0.1 to 6% by mass, and particularly preferably 0.5 to 5% by mass.

[0115] (Glycol ether) In addition to components (A), (B), and (C) described above, the topical composition of this embodiment may also contain glycol ether from the viewpoint of improving usability and stability. However, the content may be 20% by mass or less, 10% by mass or less, or 5% by mass or less. It is preferable that the topical composition of this embodiment does not contain glycol ether.

[0116] (pH) The topical composition of this embodiment preferably has an acidic pH of 1.5 to 6.5, more preferably 2 to 6, even more preferably 2.5 to 5.5, and particularly preferably 3 to 5, from the viewpoint of the stability of component (A), low irritation to the skin and mucous membranes, and good skin feel.

[0117] (pH adjuster) The topical composition of this embodiment may contain a pH adjuster in addition to the above-mentioned components (A), (B), and (C), in order to improve the feel of use, stability, and promote transdermal absorption, provided that it does not interfere with the effects of this embodiment.

[0118] The type and quality of the pH adjuster used in this embodiment shall be the same as those described in the first embodiment.

[0119] (Optional Substances) In addition to components (A), (B), and (C) above, the topical composition of this embodiment may further contain one or more of the following components in combination for the purpose of enhancing or supplementing the various effects of ascorbic acid, and for the purpose of adding other useful effects: whitening components, anti-inflammatory components, antibacterial components, cell activating components, astringent components, antioxidant components, acne-improving components, anti-aging components, components that promote the synthesis of biocomponents such as collagen, blood circulation promoting components, moisturizing components, anti-aging components, etc. The types, quality, and combinations of these components used in this embodiment shall be in accordance with the contents of the first embodiment.

[0120] In addition to the above components, the topical composition of this embodiment may further contain surfactants, oils and fats, sugars, or transdermal absorption-promoting components. In particular, the inclusion of surfactants or oils and fats can further improve the stability, effectiveness, or feel of ascorbic acid in an aqueous solvent.

[0121] The topical composition of this embodiment may contain, as needed, various components commonly used as components of topical preparations in the pharmaceutical, quasi-drug, or cosmetic fields, within quantitative and qualitative ranges that do not impair the quality such as appearance stability or viscosity, and do not impair the effects of the present invention. These components may include amino acids, irritation reducers, thickeners, preservatives, UV protection agents, colorants, dispersants, additional pH adjusters, fragrances, etc. These components may be used individually or in combination of two or more as desired.

[0122] The topical composition according to this embodiment can be prepared in various desired forms, such as liquid, emulsion, cream, sheet (substrate-supported), aerosol, spray, paste, mousse, or gel. These can be manufactured by conventional methods in the industry.

[0123] The topical composition of this embodiment is particularly preferably a transparent or translucent composition in which ascorbic acid and / or a salt thereof is dissolved. Here, "dissolved" is defined as follows: That is, for example, by ultraviolet-visible absorbance measurement using a spectrophotometer or photoelectric photometer UV-2450 (manufactured by Shimadzu Corporation), the transmittance at a wavelength of 700 nm is in the range of 80 to 100%, preferably 85 to 100%, and more preferably 90 to 100%. Here, the transmittance of water is set to 100%. The topical composition of the present invention has a transparent or translucent appearance. The method for measuring transmittance is, in more detail, in accordance with the method described in the 18th revised Japanese Pharmacopoeia [B] General Test Methods 2. Physical Test Methods Spectroscopic Measurement Methods 2.24 Method for Ultraviolet-Visible Absorbance Measurement.

[0124] (Viscosity) The topical composition of this embodiment can be prepared as a composition having a suitable viscosity, especially when used for application to the skin. The viscosity of the topical composition of this embodiment is not particularly limited, but for example, when measured at 25°C using an E-type viscometer, the viscosity is usually about 40 to 300 mPa·s, preferably about 50 to 250 mPa·s, more preferably about 60 to 200 mPa·s, and even more preferably about 70 to 150 mPa·s. When the viscosity is within this range, the usability of the formulation is improved, such as being easy to handle and less likely to spill. The viscosity (at 25°C) refers to the viscosity measured using a single-cylindrical rotational viscometer (Brookfield type viscometer) in accordance with the viscosity measurement method described in the general test methods of the 18th edition of the Japanese Pharmacopoeia. Specifically, it refers to the value measured using TV-10M (manufactured by Toki Sangyo Co., Ltd.), and the selection of conditions such as rotor and rotation speed is in accordance with the instruction manual of this instrument, and the viscosity at 25°C is measured. More specifically, the viscosity at 25°C is measured using an M1 rotor under the conditions of a rotation speed of 12 rpm and a measurement time of 60 seconds.

[0125] (Uses) The topical composition of this embodiment is particularly effective as a whitening agent, anti-inflammatory agent, and anti-aging agent, and has effects such as preventing and treating acne and antioxidant effects. Furthermore, when applied to the skin, it may enhance skin transparency, retain moisture, refine skin texture, and reduce roughness. In addition, it may have effects such as minimizing the appearance of pores and providing skin conditioning and moisturizing, and can also be used to prevent and treat blemishes.

[0126] The topical compositions of this embodiment can be, for example, basic cosmetics such as serums, lotions, sunscreens, emulsions, creams, oils, and packs; or various topical compositions belonging to the fields of cosmetics, topical pharmaceuticals, or quasi-drugs, such as deodorants, athlete's foot treatments, antipruritics, wound healing agents, cleansing agents, cleansing agents, anti-inflammatory and analgesic agents, acne treatments, hemorrhoid treatments, antiseptics, disinfectants, whitening agents, and ultraviolet protection agents. Due to its effects on the skin, the present invention is preferably used in products applied to the skin, such as topical skin preparations (formulations for the skin). Furthermore, for example, it can be provided as an intensive care or special care product, such as a single-use product or a product with a short shelf life (for example, a shelf life of 730 days, 365 days, or 180 days from the date of manufacture).

[0127] (Container) The external composition of this embodiment is not limited and can be contained in a container of a shape and material appropriately selected according to the purpose and use. The type and material of the container used in this embodiment shall be the same as that of the first embodiment.

[0128] [Manufacturing Method] The topical composition of this embodiment is obtained by weighing components (A), (B), and (C), and other optional components, and stirring and mixing them at room temperature or while heating. Similar to the first embodiment, in the manufacturing method of the topical composition of this embodiment, a method can be adopted in which components (A), (B), (C), and other additional components necessary for the topical composition are mixed at once without prior pre-preparation of each component or a combination of several components. The topical composition of this embodiment may be obtained in cases in which ascorbic acid is prepared in advance in the form of a eutectic mixture and a strong hydrogen bond is formed between the ascorbic acid and the eutectic component.

[0129] [Stabilization Method] The present invention also provides a stable formulation containing a high concentration of ascorbic acid by providing a composition containing (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid in an amount of 45% to 50% by mass, (B) low molecular weight betaine, and (C) 15 to 40% by mass of water, wherein the mass ratio of component (A) to component (B) is 1:0.55 to 0.88, and the mass ratio of component (A) to component (C) is 1:0.3 to 0.67. Here, stability refers, without limitation, to reducing or preventing the precipitation or solidification of ascorbic acid due to external stimuli. External stimuli are often unavoidably applied during the filling process of the manufacturing process or vibrations during product transportation.

[0130] In the method of the present invention, the components and their ratios are the same as those used in the aforementioned topical skin composition. Furthermore, the product obtained by this method can be used in known or commonly used dosages and administration methods, divided into one to several times per day, depending on the application.

[0131] The present invention includes the following embodiments: [1] A topical composition comprising (A) 25% by mass or more and less than 40% by mass of ascorbic acid and / or a salt thereof, (B) low molecular weight betaine, and (C) water in a mass ratio of 15 to 40% by mass, where A:B = 1:0.55 to 2.4 and A:C = 1:0.38 to 1.6. [2] A topical composition comprising (A) 40% by mass or more and less than 45% by mass of ascorbic acid and / or a salt thereof, (B) low molecular weight betaine, and (C) water in a mass ratio of 15 to 40% by mass, where A:B = 1:0.6 to 0.8 and A:C = 1:0.6 to 1.0. [3] A topical composition comprising (A) 45% to 50% by mass of ascorbic acid and / or a salt thereof, (B) low molecular weight betaine, and (C) 15 to 35% by mass of water, wherein the mass ratio of A:B = 1:0.55 to 0.88 and A:C = 1:0.3 to 0.67. [4] The topical composition according to any one of [1] to [3], wherein the (B) component is trimethylglycine. [5] The topical composition according to [1], further comprising (D) a polyhydric alcohol having 3 to 5 carbon atoms, wherein the mass ratio of A:D = 1:0.01 to 1.2. [6] The topical composition according to [2], further comprising (D) a polyhydric alcohol having 3 to 5 carbon atoms, wherein the mass ratio of A:D = 1:0.001 to 0.3. [7] The topical composition according to [3], further comprising (D) a polyhydric alcohol having 3 to 5 carbon atoms, with a mass ratio of A:D = 1:0.001 to 0.37. [8] The topical composition according to [1], further comprising (E) dimethyl isosorbide, with a mass ratio of A:E = 1:0.0001 to 1.2. [9] The topical composition according to [2], further comprising (E) dimethyl isosorbide, with a mass ratio of A:E = 1:0.0001 to 0.3.

[10] The topical composition according to [3], further comprising (E) dimethyl isosorbide, with a mass ratio of A:E = 1:0.0001 to 0.37.

[11] A method for suppressing the precipitation of ascorbic acid in a composition, wherein the composition contains (A) 25% by mass or more and less than 40% by mass of ascorbic acid and / or its salt, (B) low molecular weight betaine, and (C) water in a mass ratio of A:B = 1:0.55 to 2.4 and A:C = 1:0.38 to 1.6.

[12] A method for suppressing the precipitation of ascorbic acid in a composition, wherein the composition contains (A) 40% by mass or more and less than 45% by mass of ascorbic acid and / or its salt, (B) low molecular weight betaine, and (C) water in a mass ratio of A:B = 1:0.6 to 0.8 and A:C = 1:0.6 to 1.0.

[13] A method for suppressing the precipitation of ascorbic acid in a composition by including (A) 45% to 50% by mass of ascorbic acid and / or its salt, (B) low molecular weight betaine, and (C) water in a mass ratio of A:B = 1:0.55 to 0.88 and A:C = 1:0.3 to 0.67.

[14] A method for producing an external composition by mixing (A) 25% to less than 40% by mass of ascorbic acid and / or its salt, (B) low molecular weight betaine, and (C) water in a mass ratio of A:B = 1:0.55 to 2.4 and A:C = 1:0.38 to 1.6, the method of production which does not include a step of pre-preparation of each component.

[15] A method for producing an external composition by mixing (A) ascorbic acid and / or its salt in an amount of 40% or more by mass and less than 45% by mass, (B) low molecular weight betaine, and (C) water in an amount of 15 to 40% by mass, wherein the mass ratio of A:B = 1:0.6 to 0.8 and A:C = 1:0.6 to 1.0, and the method does not include a step for pre-preparation of each component.

[16] A method for producing an external composition by mixing (A) ascorbic acid and / or its salt in an amount of 45% or more by mass and 50% by mass, (B) low molecular weight betaine, and (C) water in an amount of 15 to 35% by mass, wherein the mass ratio of A:B = 1:0.55 to 0.88 and A:C = 1:0.3 to 0.67, and the method does not include a step for pre-preparation of each component.

[0132] Next, the present invention will be specifically described with reference to examples, but the present invention is not limited to the following examples. Note that the units for each component amount in the table are in mass percent.

[0133] Topical compositions with the compositions shown in Tables 1 to 7 were prepared according to conventional methods. These compositions were then subjected to testing according to each test item.

[0134] [Solidification Confirmation Test] Topical compositions for reference, examples, and comparative examples were prepared. Specifically, according to the formulations (mass%) described in the various formulation tables, ascorbic acid, trimethylglycine, water, and propanediol were placed in that order in a 50 ml glass vial beaker and stirred at a temperature of 70°C or higher until all components dissolved. After preparation, the mixture was left to stand at room temperature for one day, and the filling process was repeated 10 times between 50 ml glass vials. Then, 40 ml was placed in a 50 ml glass vial, the lid was sealed, and the vial was stored at -8°C. The time until precipitates were observed was then evaluated.

[0135] Time to Precipitation ◎: Prescriptions requiring 1000 hours or more to precipitate ○: Prescriptions requiring 600 hours or more but less than 1000 hours to precipitate ×: Prescriptions requiring less than 600 hours to precipitate

[0136] The evaluation results are also shown in the table.

[0137] The results in Table 1 show that the compositions of the examples were less prone to precipitation due to external stimuli even when the ascorbic acid concentration was 25% by mass or higher, whereas the compositions of the comparative examples were more prone to precipitation. The composition of Example 2 showed particularly excellent stability, with a precipitation time of 3000 hours or more.

[0138]

[0139] The results in Table 2 confirm that, even in formulations with extremely high ascorbic acid concentrations, the compositions of the examples did not solidify or precipitate due to external stimuli for extended periods. The compositions of Examples 4 and 5 showed particularly excellent stability, with precipitation occurring after more than 3000 hours.

[0140]

[0141]

[0142]

[0143] The results in Tables 3-5 clearly show that precipitation is likely to occur in the comparative examples listed in these tables. In the compositions of Comparative Examples 11, 12, 15, and 19, precipitation occurred due to agitation during the filling process after letting them stand at room temperature for 24 hours after preparation. Comparative Examples 6, 7, 8, 14, and 16 did not completely dissolve even after stirring at 70°C for 2 hours.

[0144]

[0145]

[0146] The results in Tables 6-7 confirm that, even in formulations with extremely high ascorbic acid concentrations, solidification or precipitation due to external stimuli did not occur for extended periods in the compositions of the examples.

Claims

1. An external composition comprising (A) 25% by mass or more and less than 40% by mass of ascorbic acid and / or its salt, (B) low molecular weight betaine, and (C) 15 to 40% by mass of water, wherein the mass ratio of A:B = 1:0.55 to 2.4 and A:C = 1:0.38 to 1.

6.

2. An external composition comprising (A) 40% by mass or more and less than 45% by mass of ascorbic acid and / or its salt, (B) low molecular weight betaine, and (C) 15 to 40% by mass of water, wherein the mass ratio of A:B = 1:0.6 to 0.8 and A:C = 1:0.6 to 1.

0.

3. An external composition comprising (A) 45% to 50% by mass of ascorbic acid and / or its salt, (B) low molecular weight betaine, and (C) 15 to 35% by mass of water, wherein the mass ratio of A:B = 1:0.55 to 0.88 and A:C = 1:0.3 to 0.

67.

4. The topical composition according to any one of claims 1 to 3, wherein the component (B) is trimethylglycine.

5. The external composition according to any one of claims 1 to 3, further comprising (D) a polyhydric alcohol having 3 to 5 carbon atoms.

6. The topical composition according to any one of claims 1 to 3, further comprising (E) dimethyl isosorbide.

7. A method for suppressing the precipitation of ascorbic acid in a composition, wherein the composition contains (A) 25% by mass or more and less than 40% by mass of ascorbic acid and / or its salt, (B) low molecular weight betaine, and (C) 15 to 40% by mass of water, with a mass ratio of A:B = 1:0.55 to 2.4 and A:C = 1:0.38 to 1.

6.

8. A method for suppressing the precipitation of ascorbic acid in a composition, wherein the composition contains (A) 40% by mass or more and less than 45% by mass of ascorbic acid and / or its salt, (B) low molecular weight betaine, and (C) 15 to 40% by mass of water, with a mass ratio of A:B = 1:0.6 to 0.8 and A:C = 1:0.6 to 1.

0.

9. A method for suppressing the precipitation of ascorbic acid in a composition, wherein the composition contains (A) 45% to 50% by mass of ascorbic acid and / or its salt, (B) low molecular weight betaine, and (C) 15 to 35% by mass of water, with a mass ratio of A:B = 1:0.55 to 0.88 and A:C = 1:0.3 to 0.67.

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