Topical composition containing ascorbic acid and / or salt thereof

Abstract

To provide a topical composition that exhibits superior stability and usability.SOLUTION: A skin topical composition is prepared that contains (A) at least one selected from the group consisting of ascorbic acid and salts thereof in an amount of 18 to 50 mass%, (B) water in an amount of 3 to 15 mass%, and (C) trimethylglycine in an amount of 5 to 47 mass%, wherein (A) / (C) is 5.0 or less and (B)×(C) / (A) is less than 11.0. Optionally, a polyhydric alcohol or a lower alcohol having 3 to 5 carbon atoms may also be contained.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a topical composition containing ascorbic acid and / or a salt thereof. [Background technology]

[0002] Ascorbic acid is known to have various effects, such as anti-inflammatory effects, acne treatment, whitening effects, anti-aging effects, antioxidant effects, cell activation effects 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. For these reasons, it is widely used as an external skin agent.

[0003] Aqueous external skin preparations containing ascorbic acid have been proposed (for example, Patent Document 1). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent No. 7295809 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide an ascorbic acid-containing composition for external use on the skin that contains a high concentration of ascorbic acid and has good stability. [Means for solving the problem]

[0006] The present invention provides a highly stable topical composition containing ascorbic acid and / or a salt thereof, particularly in a temperature-varying environment where the user actually uses the composition.

[0007] According to the investigations of the present inventors, when a composition containing a high concentration of ascorbic acid and / or a salt thereof is prepared, problems such as solidification of the solution and precipitation of solid components occur depending on the conditions.

[0008] As a result of extensive research to solve this problem, the inventors discovered that even when a high concentration of ascorbic acid and / or a salt thereof is contained, by strictly specifying the concentrations of water and trimethylglycine and the ratio of the amounts of each ascorbic acid, an excellent topical composition can be obtained that has good stability not only immediately after preparation but also at low temperatures, and thus completed the present invention.

[0009] That is, in one aspect of the present invention, there is provided the following external skin composition. Section 1. (A) 18 to 50 mass% of at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid, (B) 3 to 15 mass% of water, and (C) 5 to 47 mass% of trimethylglycine, (A) / (C) is 5.0 or less, and A composition for topical application to skin, wherein (B)×(C) / (A) is less than 11.0. [Effects of the Invention]

[0010] The present invention can provide a composition for external use on skin that is highly stable even at low temperatures or in a temperature-changing environment. [Brief explanation of the drawings]

[0011] [Figure 1] 1 is a photograph showing the state of coloration of topical skin compositions of Examples and Comparative Examples when stored at 40°C for one month. DETAILED DESCRIPTION OF THE INVENTION

[0012] In this specification, the unit of content "% by mass" is synonymous with "g / 100g".

[0013] [Skin external composition] One aspect of the present invention is a method for producing a medicament for the treatment of a pulmonary arthritis. (A) 18 to 50 mass% of at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid, (B) 3 to 15 mass% of water, and (C) 5 to 47 mass% of trimethylglycine, The present invention relates to a topical skin composition in which (A) / (C) is 5.0 or less and (B) × (C) / (A) is less than 11.0. Such a topical skin composition has good stability. Here, the values ​​of each component are expressed as mass%.

[0014] The topical composition of this embodiment contains (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid in a high concentration range, and is stable even in a low temperature range.

[0015] ((A) At least one selected from the group consisting of ascorbic acid and salts of ascorbic acid) In this embodiment, ascorbic acid commercially available as a component of pharmaceuticals, quasi-drugs, or external skin preparations in the field of cosmetics can be used, and these generally refer to the L-form.

[0016] Salts of ascorbic acid can also be used. Here, the salt of ascorbic acid refers to a pharmaceutically acceptable salt. Examples include, but are not limited to, salts with organic bases (e.g., salts with tertiary amines such as trimethylamine salt, triethylamine salt, monoethanolamine salt, triethanolamine salt, and pyridine salt, basic ammonium salts such as arginine, etc.), salts with inorganic bases (e.g., alkali metal salts such as ammonium salt, sodium salt, and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, and aluminum salt). Particularly preferred salts of ascorbic acid are sodium salts and potassium salts. Specific examples include sodium ascorbate, sodium ascorbic acid monophosphate, sodium ascorbic acid diphosphate, sodium ascorbic acid triphosphate, and sodium ascorbic acid-2-sulfate.

[0017] In this embodiment, ascorbic acid or a salt thereof can be used alone or in combination of two or more kinds.

[0018] The total content of component (A) relative to the total amount of the topical composition is appropriately determined based on the 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 18% by mass or more, but is preferably 19% by mass or more, more preferably 20% by mass or more, even more preferably 25% by mass or more, and even more preferably 30% 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, preferably 45% by mass or less, and even more preferably 40% by mass or less. The total content of component (A) relative to the total amount of the topical composition is preferably 18% by mass to 50% by mass, more preferably 19% by mass to 45% by mass, and even more preferably 20% by mass to 40% by mass.

[0019] ((B)Water) In the topical composition of this embodiment, the water content is preferably 3% by mass or more, more preferably 4% by mass or more, and most preferably 5% by mass or more, 7% by mass or more, or 9% by mass or more, based on the viewpoints of low-temperature stability and / or good preparation. The water content is 15% by mass or less, preferably 13.5% by mass or less, 13% by mass or less, and more preferably 11% by mass or less, based on the topical composition.

[0020] The total content of component (B) relative to the total amount of the topical composition of this embodiment is preferably 3% to 15% by mass, more preferably 3% to 13.5% by mass, even more preferably 4 to 13% by mass, even more preferably 5 to 11% by mass, particularly preferably 7 to 11% by mass, and most preferably 9 to 11% by mass. Setting the amount of water within this range increases the flexibility of the manufacturing process. That is, by adjusting the amount of water, a stable formulation can be prepared regardless of the order in which the components are added during the preparation of the topical composition, and problems such as precipitation can be alleviated.

[0021] In the topical composition of this embodiment, the ratio of the content of component (B) to component (A) is not particularly limited, but is preferably 0.05 to 0.5 parts by mass, more preferably 0.1 to 0.45 parts by mass, even more preferably 0.15 to 0.40 parts by mass, and even more preferably 0.2 to 0.35 parts by mass per part by mass of the total content of component (A). By setting the ratio of each component within the above range, a stable formulation can be prepared regardless of the order in which the components are added during preparation of the topical composition, and problems such as precipitation can be alleviated.

[0022] ((C) Trimethylglycine) In this embodiment, trimethylglycine, which is commercially available as an ingredient in topical skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics, can be used. From the viewpoints of low-temperature stability and / or good preparation, the content of trimethylglycine is preferably 5% by mass or more, more preferably 7% by mass or more, even more preferably 13% by mass or more, and even more preferably 18% by mass or more, based on the composition for topical application. The content of trimethylglycine is preferably 47% by mass or less, based on the composition for topical application. Preferably, the content is 45% by mass or less, more preferably 40% by mass or less, even more preferably 30% by mass or less, even more preferably 27% by mass or less, and most preferably 24% by mass or less. By setting the amount of trimethylglycine in the above range, combined with the amounts of other ingredients, stable formulations can be prepared regardless of the order in which the ingredients are added during the preparation of the topical composition, and problems such as precipitation can be alleviated.

[0023] The total content of component (C) relative to the total amount of the topical composition of this embodiment is preferably 5% by mass to 47% by mass, more preferably 7% by mass to 45% by mass, even more preferably 13% by mass to 40% by mass, even more preferably 15% by mass to 27% by mass, and most preferably 18% by mass to 24% by mass.

[0024] In the topical composition of this embodiment, the ratio of the content of component (A) to the content of component (C) is 5 parts by mass or less, preferably 0.1 to 5 parts by mass, more preferably 0.4 to 4 parts by mass, even more preferably 0.6 to 3.5 parts by mass, even more preferably 0.7 to 2 parts by mass, and most preferably 0.8 to 1.5 parts by mass, per part by mass of the total content of component (C). Within this ratio range, the effect of preventing precipitation in a temperature-varying environment is more pronounced. By setting the ratio of each component within the above range, a stable formulation can be prepared regardless of the order in which the components are added during the preparation of the topical composition, and problems such as precipitation can be alleviated.

[0025] In this embodiment of the topical composition, from the viewpoint of achieving the effects of the present invention, the value obtained by multiplying the concentration of component (B) by the concentration of component (C) and dividing the result by the concentration of component (A) ((B) × (C) / (A)) is less than 11.0. Preferably, it is 0.3 or more and less than 11, and more preferably 0.6 or more and less than 10. Here, the concentration means % by mass. By setting the ratio of each component within the above range, a stable formulation can be prepared regardless of the order in which the components are added during preparation of the topical composition, and problems such as precipitation can be alleviated.

[0026] ((D) Polyhydric alcohols having 3 to 5 carbon atoms) From the viewpoint of improving the feel during use and the stability, the topical composition of this embodiment may contain components other than the above-mentioned components (A), (B), and (C), as long as the effects of the present invention are not impaired. The topical composition of this embodiment may contain a polyhydric alcohol having 3 to 5 carbon atoms. The polyhydric alcohol having 3 to 5 carbon atoms is not particularly limited as long as it is used as a component of topical skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics. The polyhydric alcohol having 3 to 5 carbon atoms is not particularly limited, but preferred examples include diols having 3 carbon atoms, such as 1,3-propanediol or propylene glycol, as well as dipropylene glycol, 3-methyl-1,3-butanediol (isoprene glycol), 1,3-butanediol, 2,3-butanediol, 1,4-butanediol, 1,2-pentanediol, 1,5-pentanediol, 1,2,3-butanetriol, 1,2,3-pentanetriol, glycerin (1,2,3-propanetriol), erythritol, and xylitol. Commercially available polyhydric alcohols having 3 to 5 carbon atoms can also be used as they are. From the viewpoints of reducing skin irritation, improving usability, and improving stability, 1,3-propanediol, propylene glycol, 1,3-butylene glycol, and / or 3-methyl-1,3-butanediol are preferred, and 1,3-propanediol, propylene glycol, and / or 3-methyl-1,3-butanediol are particularly preferred.

[0027] In the topical composition of this embodiment, the total content of the polyhydric alcohol having 3 to 5 carbon atoms relative to the total amount of the topical composition is preferably 0.1 to 75% by mass, more preferably 1 to 60% by mass, even more preferably 10 to 50% by mass, and particularly preferably 15 to 40% by mass. By setting the amount of the polyhydric alcohol having 3 to 5 carbon atoms within the above range, a stable formulation can be prepared regardless of the order in which the components are added during preparation of the topical composition, and problems such as precipitation can be alleviated.

[0028] In the topical composition of this embodiment, the content of any one of 1,3-propanediol, propylene glycol, 1,3-butylene glycol, or 3-methyl-1,3-butanediol relative to the total weight of the topical composition is preferably 0.1 to 75% by mass, more preferably 1 to 50% by mass, even more preferably 3 to 40% by mass, even more preferably 5 to 30% by mass, particularly preferably 6 to 20% by mass, and most preferably 8 to 15% by mass. From another perspective, the content is preferably 41 to 75% by mass, more preferably 45 to 70% by mass, and particularly preferably 50 to 65% by mass. By setting the amount of 1,3-propanediol, propylene glycol, 1,3-butylene glycol, or 3-methyl-1,3-butanediol within the above ranges, stable formulations can be prepared regardless of the order of addition of the components, and problems such as precipitation can be alleviated.

[0029] In the topical composition of this embodiment, the ratio of the content of component (D) to component (A) is not particularly limited, but is preferably 0.5 to 2.5 parts by mass, more preferably 0.9 to 2 parts by mass, even more preferably 1.2 to 1.8 parts by mass, and particularly preferably 1.4 to 1.6 parts by mass per part by mass of the total content of component (A). By setting the ratio of each component within the above range, a stable formulation can be prepared regardless of the order in which the components are added, and problems such as precipitation can be alleviated.

[0030] (Ethoxydiglycol (diethylene glycol monoethyl ether)) In the present invention, primarily from the viewpoint of improving stability and usability, ethoxydiglycol is not contained or, if contained, is less than 30% by mass. The ethoxydiglycol contained in the topical composition at less than 30% by mass is not particularly limited as long as it is used as a component of topical skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics.

[0031] In the topical composition of this embodiment, 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, and even more preferably 5% by mass or less, and ethoxydiglycol may not be included in the topical composition. The total content of ethoxydiglycol is 0 or more and less than 30% by mass, preferably 0 to 20% by mass, more preferably 0 to 10% by mass, and even more preferably about 0 to 5% by mass.

[0032] In the topical composition of this embodiment, the ratio of the content of the ethoxydiglycol component to the total content of component (A) is preferably 0 to 10 parts by mass, more preferably 0 to 5 parts by mass, per part by mass of the total content of component (A).In some cases, it can also be 0.001 to 10 parts by mass, or 0.01 to 5 parts by mass.

[0033] (pH) From the viewpoints of the stability of component (A), low irritation to the skin and mucous membranes, and a pleasant feel on the skin, it is desirable that the topical composition of this embodiment has an acidic pH range of preferably 1.5 to 6.5, more preferably 2 to 6, even more preferably 3 to 5.5, and particularly preferably 4 to 5.

[0034] ((E) Lower alcohol) From the viewpoint of improving the feeling of use, facilitating stability, and promoting transdermal absorption, the topical composition of this embodiment may contain (E) a lower alcohol in addition to the above-mentioned components (A), (B), and (C), as long as the effects of the present invention are not impaired. The lower alcohol is not particularly limited as long as it is used as a component of topical skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics. In this specification, the term "lower alcohol" refers to a C1-C6 monohydric alcohol. Of these, C1-C3 alcohols are particularly preferred. Examples of such alcohols include, in addition to ethanol, methanol, n-propanol, isopropanol, etc. Of these, ethanol is particularly preferred.

[0035] The content of lower alcohol in the topical composition of this embodiment can be 40% by mass or less, 35% by mass or less, 30% by mass or less, or 25% by mass or less, preferably 30% by mass or less. It can also be 1% by mass or more, 3% by mass or more, 5% by mass or more, 8% by mass or more, or 10% by mass or more. The content of lower alcohol in the topical composition of this embodiment is preferably 0 to 40% by mass, more preferably 1 to 35% by mass, even more preferably 3 to 30% by mass, even more preferably 5 to 25% by mass, and most preferably 8 to 20% by mass.

[0036] The ethanol content of the topical composition of this embodiment can be 40% by mass or less, 35% by mass or less, 30% by mass or less, or 25% by mass or less, preferably 30% by mass or less. It can also be 1% by mass or more, 3% by mass or more, 5% by mass or more, 8% by mass or more, or 10% by mass or more. The ethanol content of the topical composition of this embodiment is preferably 0 to 40% by mass, 1 to 35% by mass, more preferably 3 to 30% by mass, even more preferably 5 to 25% by mass, and most preferably 8 to 20% by mass. Alternatively, the ethanol content can be 5 to 10% by mass or 5 to 15% by mass, particularly from the viewpoint of improving the feel during use.

[0037] (pH adjuster) In order to improve the feel when used, the stability, and the transdermal absorption, the topical composition of this embodiment may contain a pH adjuster in addition to the above-mentioned components (A), (B), and (C), as long as the effect of this embodiment is not impaired.

[0038] The pH adjuster used in this embodiment can be a compound that is commonly used as a component of external skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics.Not particularly limited, examples include pH adjusters having amines (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 pyrrolidone carboxylate, 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).

[0039] (optional substance) In addition to the components (A), (B), and (C), the topical composition of this embodiment may further contain one or more of various ingredients, such as whitening ingredients, anti-inflammatory ingredients, antibacterial ingredients, cell activating ingredients, astringent ingredients, antioxidant ingredients, acne-fighting ingredients, anti-aging ingredients, ingredients promoting biocomponent synthesis such as collagen, blood circulation promoting ingredients, moisturizing ingredients, and anti-aging ingredients, in combination, to enhance or complement the various effects of ascorbic acid or to impart other useful effects. Preferred are one or more of the whitening ingredients, anti-inflammatory ingredients, antibacterial ingredients, cell activating ingredients, astringent ingredients, antioxidant ingredients, anti-aging ingredients, and moisturizing ingredients. Particularly preferred combinations of these ingredients include combinations with whitening ingredients, combinations of whitening ingredients and antioxidant ingredients, combinations with antioxidant ingredients, combinations with anti-aging ingredients, and combinations of whitening ingredients and anti-aging ingredients. These components are not particularly limited as long as they have been used in the past as components of topical skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics, or will be used in the future, and any component can be appropriately selected and used.

[0040] In addition to the above-mentioned components, the topical composition of this embodiment may further contain a surfactant, oils and fats, sugars, or a transdermal absorption-promoting component. In particular, the inclusion of a surfactant or oils and fats can further improve the stability, efficacy, or usability of ascorbic acid in an aqueous solvent.

[0041] The topical composition of this embodiment may contain, as needed, various ingredients commonly used as ingredients in topical preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics, such as amino acids, irritation-reducing agents, thickeners, preservatives, UV protection agents, colorants, dispersants, additional pH adjusters, fragrances, etc., within quantitative and qualitative ranges that do not impair the qualities such as appearance stability and viscosity, or that do not impair the effects of the present invention. These ingredients may be used alone, or two or more may be used in combination.

[0042] The topical composition of this embodiment can be prepared in various desired forms, such as a liquid, emulsion, cream, sheet (supported by a substrate), aerosol, spray, paste, mousse, or gel, and can be produced by a method commonly used in the art.

[0043] 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: For example, when measured by ultraviolet-visible absorbance measurement using a spectrophotometer or a UV-2450 photoelectric photometer (Shimadzu Corporation), the transmittance at a wavelength of 700 nm is 80 to 100%, preferably 85 to 100%, and more preferably 90 to 100%. Here, the transmittance of water is defined as 100%. The topical composition for skin of the present invention has a transparent or translucent appearance. The transmittance measurement method is more specifically in accordance with the method described in the 18th Edition of the Japanese Pharmacopoeia [B], General Test Methods, 2. Physical Test Methods, Spectroscopic Measurement Methods, 2.24, Ultraviolet-Visible Absorbance Measurement Method.

[0044] (viscosity) The topical composition of this embodiment can be prepared as a composition with the appropriate viscosity, particularly when applied to the skin. The viscosity of the topical composition of this embodiment is not particularly limited. For example, when measured at 25°C using an E-type viscometer, the viscosity is typically approximately 50 to 400 mPa·s, preferably approximately 80 to 350 mPa·s, more preferably approximately 100 to 300 mPa·s, and even more preferably approximately 120 to 200 mPa·s. A viscosity within this range improves usability, such as ease of handling and reduced spillage. The viscosity (25°C) refers to the viscosity measured using a single-cylindrical rotational viscometer (Brookfield viscometer) in accordance with the viscosity measurement method described in the General Test Methods of the Japanese Pharmacopoeia, 18th Edition. Specifically, the viscosity is measured using a TV-10M (manufactured by Toki Sangyo Co., Ltd.), with the rotor, rotation speed, and other conditions selected in accordance with the instrument's instruction manual, and the viscosity is measured at 25°C. More specifically, the viscosity is measured at 25° C. using an M1 rotor at a rotation speed of 12 rpm for a measurement time of 60 seconds.

[0045] (Application) The topical composition of this embodiment is particularly effective as a whitening agent, anti-inflammatory agent, and anti-aging agent, and has, for example, acne prevention and treatment and antioxidant effects. Furthermore, when applied to the skin, it may have the effects of increasing skin transparency, maintaining moisture, improving skin texture, and reducing roughness. Furthermore, it may have the effects of making pores less noticeable, conditioning skin, and moisturizing the skin, and can also be used to prevent and treat age spots.

[0046] The topical composition of this embodiment can be, for example, a variety of topical compositions belonging to the fields of cosmetics, topical pharmaceuticals, or topical quasi-drugs, such as basic cosmetics such as serums, lotions, sunscreen creams, emulsions, creams, lotions, oils, and packs; makeup cosmetics such as foundations, lipsticks, lip balms, mascaras, eye shadows, eyeliners, eyebrow pencils, and nail polish; cleansers such as facial cleansers, cleansers, and body washes; and various topical compositions belonging to the fields of cosmetics, topical pharmaceuticals, and topical quasi-drugs, such as anti-armpit odor agents, athlete's foot treatments, antipruritics, wound healing agents, cleansing agents, cleansers, anti-inflammatory and analgesic agents, acne treatments, hemorrhoid treatments, germicides, disinfectants, whitening agents, and UV protection agents. In view of its effects on the skin, the present invention is preferably used in products applied to the skin, such as topical skin preparations (preparations for the skin).

[0047] (container) The topical composition of this embodiment can be stored and used in a container of a shape and material appropriately selected depending on the purpose and application, without any limitations. Specific examples of containers include spray types (non-inverted or inverted), bottle types, tube types, jar types, dropper types, drip tube types, dispenser types, stick types, and sachets. From the viewpoint of ease of use, it is particularly preferable that the composition be stored and provided in a bottle equipped with a dropper or a drip tube.

[0048] 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.). The material for the container body is not particularly limited, but glass is preferred. These materials can be used as container materials by applying various coating treatments, combining (e.g., mixing), or laminating them, taking into consideration strength, flexibility, weather resistance, and 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. Resins that can be used to coat the inner surface include polyethylene (HDPE, LDPE, LLDPE, etc.), polyamide-imide, polyethylene terephthalate, etc., and, although not particularly limited, polyethylene (HDPE, LDPE, LLDPE, etc.) is preferred, with LLDPE being particularly preferred.

[0049] [Manufacturing method] The method for producing the topical composition of this embodiment is not limited, and can include the steps of weighing out each of the components (A), (B), and (C) and stirring and mixing them at room temperature or with heating. The order in which the components are added is also not particularly limited, and a stable formulation can be prepared regardless of the order in which the components are added. When the component (D) and / or the component (E) are added, the topical composition of this embodiment can be obtained by stirring and mixing the components at room temperature or with heating.

[0050] [Stabilization method] The present invention also provides a stable formulation containing a high concentration of ascorbic acid by preparing a composition containing 18 to 50% by weight of (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid, 3 to 15% by weight of water, and 5 to 47% by weight of trimethylglycine, where (A) / (C) = 5.0 or less and (B) × (C) / (A) = less than 11.0. Here, stability refers to, but is not limited to, maintaining the formulation's state even at temperatures higher than room temperature or lower. Furthermore, it also refers to the absence of problems such as precipitation during preparation, regardless of the order in which the ingredients are added. Specifically, when the amount of ascorbic acid is 15% by weight or less, the formulation can be prepared even with a relatively small amount of water. However, when the amount of ascorbic acid is high, for example, 18% or 20% by weight, solidification after formulation can occur in systems with low water content. However, in the stabilization method of the present invention, precipitation of ascorbic acid or a salt thereof and solidification of the formulation are inhibited even when the composition is stored for at least one week to one month under cycling conditions in which temperatures between −0.5° C. and 10° C. are repeated every 12 hours, or a decrease in the amount of ascorbic acid or a salt thereof is inhibited even after storage for a certain period at 40° C. That is, the present invention also relates to a method for imparting low-temperature stability to a composition comprising 18 to 50 mass% of at least one member selected from the group consisting of (A) ascorbic acid and salts of ascorbic acid, by adding 3 to 15 mass% of (B) water and 5 to 47 mass% of (C) trimethylglycine, and adjusting (A) / (C) to 5.0 or less and (B)×(C) / (A) to less than 11.0.

[0051] In the method of the present invention, the components and their ratios are the same as those used in the above-mentioned topical skin composition. Furthermore, the product obtained by this method can be used in a known or commonly used dosage, from once to several times a day, depending on the intended use. [Example]

[0052] EXAMPLES Next, the present invention will be described in detail with reference to examples, but the present invention is not limited to the following examples. In the tables, the unit of the amount of each component is % by mass.

[0053] Compositions for external use having the compositions shown in Tables 1 to 6 were prepared in accordance with conventional methods, and then subjected to tests according to the respective test items.

[0054] [Solidification confirmation test] The topical compositions of the Reference Examples, Examples, and Comparative Examples were prepared, and the condition of the compositions was checked within 4 hours after preparation. Specifically, the various components were mixed according to the formulations (mass%) listed in the various recipes, heated and stirred at 75°C for 10 minutes to dissolve, and then cooled to room temperature (20°C to 30°C) to prepare the compositions. <Evaluation criteria> ○: No solidification of the composition was observed within 4 hours ×: Partial solidification was observed within 4 hours.

[0055] [Ascorbic acid precipitation inhibition confirmation test] The topical compositions of the Examples and Comparative Examples were visually evaluated for the presence or absence of ascorbic acid precipitation when stored at low temperatures. Specifically, ascorbic acid was added to a mixed solution of various ingredients other than ascorbic acid according to the formulation (mass%) of each topical composition, and the composition was prepared by heating and mixing at 75°C for 10 minutes to dissolve the ascorbic acid. The prepared compositions were filled into transparent glass bottles and stored in a dark environment, alternating between -0.5°C and 10°C in 12-hour cycles, for 1 to 4 weeks. Each test solution was then visually observed to determine the presence or absence of crystal precipitation.

[0056] <Evaluation criteria> ○: No precipitates can be visually confirmed ×: Precipitates were visible to the naked eye.

[0057] [Viscosity confirmation test] The viscosity (25°C) was 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 Japanese Pharmacopoeia, 18th Edition. Specifically, the viscosity was measured at 25°C using a TV-10M (manufactured by Toki Sangyo Co., Ltd.) with an M1 rotor at a rotation speed of 12 rpm for a measurement time of 60 seconds.

[0058] [Ascorbic acid coloring inhibition confirmation test] The topical compositions of the Examples and Comparative Examples were evaluated for the presence or absence of inhibition of discoloration after storage at 40°C by visual observation and a color difference meter. Specifically, ascorbic acid was added to a mixed solution of various ingredients other than ascorbic acid according to the formulation (mass%) of each topical composition, and the mixture was heated and mixed at 60°C for 10 minutes to dissolve the ascorbic acid, to prepare the composition. The prepared composition was filled into a transparent glass bottle and left to stand in a thermo-hygrostat at 40°C for one month (represented as 1M). At each measurement period, the container was removed from the thermostat and allowed to stand at a constant temperature of 25°C before evaluation. The presence and degree of discoloration of each test solution was determined by visual observation.

[0059] <Evaluation criteria> ○: Almost colorless and transparent △: Slightly yellow ×: Yellow.

[0060] [Ascorbic acid stability test] (Quantitative method: Redox titration of ascorbic acid using iodine) The amounts of ascorbic acid in the topical compositions of the Examples and Comparative Examples after storage at 40°C and 4°C for one month were compared. Accurately measure approximately 1.0 g (1) of L-ascorbic acid and add approximately 9.0 g (2) of purified water to make the standard solution. Ascorbic acid concentration of the standard solution (w / w)% (3) = (weighed amount of L-ascorbic acid (g)) (1) / (weighed amount of L-ascorbic acid (g) (1) ÷ weighed amount of purified water (g)) (2) × 100 Accurately weigh approximately 0.25 g of the standard solution (4) into a beaker, add 10 g of purified water, and then gradually add the titration solution (containing 3.5 g / L of available iodine) with a pipette while stirring with a stirrer until the colorless solution turns light brown. Measure the amount of titration solution (g) (5) required for titration. Calculate the amount of titration solution required for 1 g of ascorbic acid using the following formula. Amount of titrant solution required for 1 g of ascorbic acid (6 g) = Amount of titrant solution (5 g) ÷ (Amount of standard solution (4 g) × (Ascorbic acid concentration of standard solution (3%)) / 100) Accurately weigh approximately 0.10 g (7) of the test sample into a beaker, add 10 g of purified water, and then gradually add the titration solution (iodine 3.5 g / L) with a pipette while stirring with a stirrer until the colorless solution turns light brown. Measure the amount (g) (8) of titration solution required for titration. Calculate the ascorbic acid concentration in the test sample using the following formula. Ascorbic acid concentration in the test sample (w / w)% = (volume of titration solution (g) (8) ÷ weighed amount of test sample (g) (7)) / (volume of titration solution required for 1 g of ascorbic acid (g) (6)) x 100

[0061] <Evaluation criteria> ◎: The amount of ascorbic acid after storage at 40°C for one month is 96% to 100% of the amount of ascorbic acid after storage at 4°C for one month 〇: The amount of ascorbic acid after one month of storage at 40℃ is 90% to less than 96% of the amount of ascorbic acid after one month of storage at 4℃ ×: The amount of ascorbic acid after storage at 40°C for 1 month is less than 90% of the amount of ascorbic acid after storage at 4°C for 1 month

[0062] The results of each evaluation are also shown in the table. [Table 1]

[0063] The results in Table 1 reveal that solidification did not occur in a composition with an ascorbic acid concentration of 15% by mass, whereas solidification occurred when the ascorbic acid concentration was 20% by mass.

[0064] [Table 2] The results in Table 2 show that solidification of the ingredients in compositions that do not contain trimethylglycine was confirmed on the day of preparation. When the amount of trimethylglycine was small, preparation was possible, but precipitation was observed when subjected to a temperature cycle of -0.5°C and 10°C. Furthermore, depending on the balance of the amounts of ascorbic acid, water, and trimethylglycine, precipitation was observed when subjected to a temperature cycle of -0.5°C and 10°C. On the other hand, it was found that precipitation was not observed when the amounts of ascorbic acid, water, and trimethylglycine were strictly specified.

[0065] [Table 3] The results in Table 3 confirm that water is essential to achieve good composition properties.

[0066] [Table 4] The results in Table 4 confirm that the balance between the amounts of water, trimethylglycine, and ascorbic acid is not only important in preparing the composition, but also affects the separation of the formulation during storage at low temperatures.

[0067] [Table 5] The results in Table 5 demonstrate that strict specification of the component ratios is necessary to maintain a good composition state even at low temperatures. The discoloration of the compositions of each Example and Comparative Example after storage at 40°C is shown in Figure 1. Example 4-1 exhibited the same discoloration as Comparative Example 4-1, despite having an ascorbic acid concentration about twice that of Comparative Example 4-1. Example 4-2 exhibited improved discoloration compared to Comparative Example 4-1.

[0068] [Usability test] Approximately 30 μl of each composition was placed on the inside of the forearm, spread with the index finger, and then the stickiness was evaluated.

[0069] <Evaluation criteria> ◎: Less sticky ○: Slightly sticky, but not noticeable ×: Very sticky [Table 6]

[0070] The results in Table 6 show that the incorporation of ethanol reduces the stickiness of the formulation and improves its usability.

[0071] [Prescription example] Formulation examples are shown in the following Tables 7 and 8. The formulation examples can be suitably used for lotions, beauty serums, etc. The contents in the formulation examples are in mass %.

[0072] [Table 7]

[0073] [Table 8]

Claims

1. (A) 18 to 50% by mass of at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid; (B) 3 to 15% by mass of water, and (C) containing 5 to 47% by mass of trimethylglycine; (A) / (C) is 5.0 or less, and A composition for topical application to the skin, wherein (B) x (C) / (A) is less than 11.

0.

2. The external skin composition according to claim 1, further comprising (D) a polyhydric alcohol having 3 to 5 carbon atoms.

3. The topical skin composition according to claim 1 or 2, further comprising (E) a lower alcohol.

4. The composition for external use on skin according to claim 1 or 2, which is contained in a container equipped with a dropper or a dropper-type tube container.

5. A composition comprising 18 to 50% by mass of at least one selected from the group consisting of (A) ascorbic acid and salts of ascorbic acid, 3 to 15% by mass of (B) water, and 5 to 47% by mass of (C) trimethylglycine, wherein (A) / (C) is 5.0 or less, and (B)× A method for imparting low temperature stability to the composition by making (C) / (A) less than 11.0.

Images