JP7664626B2 - O/D type emulsion composition and oil-in-water type emulsion composition containing glycyrrhetinic acid - Google Patents

Description

The present invention relates to an O/D type emulsion composition containing glycyrrhetinic acid, and an oil-in-water type emulsion composition containing the same. Furthermore, the present invention also relates to a skin topical preparation containing the O/D type emulsion composition or the oil-in-water type emulsion composition.

β-Glycyrrhetinic acid (hereinafter simply referred to as "glycyrrhetinic acid") is the aglycone of glycyrrhizinic acid obtained from the rhizomes of licorice, etc., and is a compound obtained by hydrolysis of glycyrrhizinic acid. Glycyrrhetinic acid is known to have useful effects such as anti-inflammatory and whitening effects, and is incorporated into many skin cosmetics taking advantage of these effects (for example, Non-Patent Document 1).

Shigeru Sekine et al., New Cosmetics Handbook, Nikko Chemicals Co., Ltd. et al., October 30, 2006, pp. 575-577

Although glycyrrhetinic acid has excellent anti-inflammatory properties, it is poorly soluble in water and can only be used under limited conditions. For example, glycyrrhetinic acid is dissolved in ethanol and added to topical skin preparations, or it is dissolved in an oil and then emulsified. However, in either case, glycyrrhetinic acid precipitates when the composition contains a large amount of water, making it difficult to use it as a topical skin preparation that contains a large amount of water, such as a lotion or emulsion.

The present invention has been made in consideration of the above problems, and aims to provide a water-containing composition in which glycyrrhetinic acid is stably dispersed, and a composition useful for obtaining such a water-containing composition.

As a result of research conducted by the present inventors to solve the above problems, they discovered that by using the D (Detergent) phase emulsification method to prepare an O/D type emulsion composition using a specific oil, surfactant, and polyhydric alcohol, and then adding an aqueous medium to this, an oil-in-water emulsion composition in which glycyrrhetinic acid is stably dispersed can be obtained, leading to the completion of the present invention. Specifically, the present invention is as follows.

[1] An O/D type emulsion composition containing glycyrrhetinic acid,
An oil agent (a) comprising at least one of a higher alcohol and an ester oil;
A nonionic surfactant (b); and a polyhydric alcohol (c);
a ratio (b)/(a) of the content of the nonionic surfactant (b) to the content of the oil agent (a) is 0.26 to 3.5;
a ratio (c)/(b) of the content of the polyhydric alcohol (c) to the content of the nonionic surfactant (b) is 0.75 to 6;
An O/D type emulsion composition, characterized in that the water (d) content is 0 to 15 mass %.
[2] The O/D type emulsion composition according to [1], wherein the higher alcohol or the ester oil contains at least one selected from the group consisting of isostearyl alcohol, 2-octyldodecanol, hexyldecanol, ethylhexyl palmitate, and propylene glycol caprylate.
[3] The O/D type emulsion composition according to [1] or [2], wherein the oil (a) contains at least isostearyl alcohol.
[4] The O/D type emulsion composition according to any one of [1] to [3], wherein the oil agent (a) contains a hydrocarbon.
[5] The O/D type emulsion composition according to any one of [1] to [4], wherein the required HLB of the nonionic surfactant (b) in the O/D type emulsion composition is 11 to 16.
[6] The O/D type emulsion composition according to any one of [1] to [5], wherein the polyhydric alcohol (c) includes 1,3-butylene glycol and glycerin.
[7] The O/D type emulsion composition according to any one of [1] to [6], wherein the content of the oil agent (a) is 5 to 70 mass %.
[8] The O/D type emulsion composition according to any one of [1] to [7], wherein the content of the nonionic surfactant (b) is 10 to 30 mass %.
[9] The O/D type emulsion composition according to any one of [1] to [8], wherein the content of the polyhydric alcohol (c) is 16 to 70 mass %.
[10] A method for producing the O/D type emulsion composition according to any one of [1] to [9], comprising the steps of:
The glycyrrhetinic acid is dissolved in the oil agent (a) to prepare an oil component constituting an oil phase;
The nonionic surfactant (b) and the polyhydric alcohol (c) are mixed to prepare a solution constituting a surfactant phase;
A method for producing an O/D type emulsion composition, comprising adding an oil component constituting the oil phase to a solution constituting the surfactant phase.
[11] An oil-in-water emulsion composition comprising the O/D emulsion composition according to any one of [1] to [9] and an aqueous medium.
[12] The oil-in-water emulsion composition according to [11], wherein the water content is 35 to 99.999 mass %.
[13] The oil-in-water emulsion composition according to [11] or [12], wherein the average particle size of the oil droplets is 10 to 200 nm.
[14] Preparing an O/D type emulsion composition according to any one of [1] to [9],
A method for producing an oil-in-water emulsion composition, comprising adding an aqueous medium to the O/D emulsion composition.
[15] A skin external preparation comprising the O/D type emulsion composition according to any one of [1] to [9] or the oil-in-water type emulsion composition according to any one of [10] to [12].

According to the O/D type emulsion composition of the present invention, by adding an aqueous medium, it is possible to obtain an oil-in-water emulsion composition in which glycyrrhetinic acid is stably dispersed. Furthermore, the oil-in-water emulsion composition of the present invention is one in which glycyrrhetinic acid is stably dispersed.

The following describes an embodiment of the present invention.

[O/D type emulsion composition]
The O/D type emulsion composition according to one embodiment of the present invention contains glycyrrhetinic acid, and contains an oil agent (a) containing at least one of a higher alcohol and an ester oil; a nonionic surfactant (b); and a polyhydric alcohol (c).

(1) Glycyrrhetinic acid Glycyrrhetinic acid is a compound obtained by hydrolysis of glycyrrhizin extracted from licorice etc. Glycyrrhetinic acid has an excellent anti-inflammatory effect and is widely used in skin and scalp preparations. Glycyrrhetinic acid may be obtained from an extract from a natural product or may be synthesized by a known synthesis method.

The content of glycyrrhetinic acid in the O/D composition is not particularly limited, but the lower limit can be, for example, 0.001 mass% or more, 0.01 mass% or more, and by containing glycyrrhetinic acid within such a range, the effect of glycyrrhetinic acid can be effectively exerted in the obtained O/D type emulsion composition or oil-in-water type emulsion composition.
On the other hand, the upper limit can be, for example, 3.5 mass% or less, 3.2 mass% or less, 2.5 mass% or less, etc., and when the content of glycyrrhetinic acid is within this range, the dispersibility of glycyrrhetinic acid can be made even better in an O/D type emulsion composition or an oil-in-water type emulsion composition.

(2) Oil agent (a)
(2-1) Higher Alcohol, Ester Oil The oil agent (a) used in this embodiment contains at least one of a higher alcohol and an ester oil.
Since higher alcohols and ester oils dissolve glycyrrhetinic acid well, glycyrrhetinic acid can be stably dispersed in the resulting emulsion compositions (O/D type emulsion compositions and oil-in-water type emulsion compositions).

In the present specification, the term "higher alcohol" refers to a monohydric alcohol having 6 or more carbon atoms. In the present embodiment, the number of carbon atoms is preferably 12 to 22, and more preferably 16 to 20.
Examples of higher alcohols that can be used in the present embodiment include lauryl alcohol, myristyl alcohol, cetyl alcohol (cetanol), hexyldecanol, stearyl alcohol, isostearyl alcohol, 2-octyldodecanol, oleyl alcohol, behenyl alcohol, etc. Among these, branched alcohols are preferred, and isostearyl alcohol, hexyldecanol, and 2-octyldodecanol are preferred.

Examples of ester oils that can be used in the present embodiment include esters of higher fatty acids and monohydric alcohols, esters of higher fatty acids and polyhydric alcohols, etc. In this specification, the term "higher fatty acid" refers to a monovalent carboxylic acid having 6 or more carbon atoms.
Examples of higher fatty acids include capric acid, sebacic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, vaccenic acid, linoleic acid, and linolenic acid.
Examples of alcohols that form esters with fatty acids include monohydric alcohols such as methanol, ethanol, propanol, butanol, pentanol, and ethylhexanol; and polyhydric alcohols such as ethylene glycol, butylene glycol, propylene glycol, and glycerin.

Among the esters of the above-mentioned higher fatty acids and monohydric or polyhydric alcohols, preferred examples include monoesters or diesters such as isopropyl myristate, isopropyl palmitate, diisopropyl sebacate, ethylhexyl myristate, ethylhexyl palmitate, propylene glycol monocaprate, and propylene glycol dicaprate.

The higher alcohols or ester oils may be used alone or in appropriate combination of two or more.
The higher alcohol or the ester oil preferably has fluidity at room temperature (23° C.), that is, the melting point or softening point is preferably 23° C. or lower.

The higher alcohol or ester oil preferably has a solubility of glycyrrhetinic acid of 1% by mass or more at room temperature (23°C), more preferably 2% by mass or more, and particularly preferably 2.5% by mass or more. By using a higher alcohol or ester oil in which the solubility of glycyrrhetinic acid is in this range, the dispersibility of glycyrrhetinic acid can be made particularly excellent in an O/D type emulsion composition or an oil-in-water type emulsion composition.

From the above viewpoints, it is preferable to use isostearyl alcohol, 2-octyldodecanol, hexyldecanol, ethylhexyl palmitate, and propylene glycol caprylate as the higher alcohol or ester oil, and it is particularly preferable to use isostearyl alcohol.
In particular, isostearyl alcohol is liquid at room temperature, and the solubility of glycyrrhetinic acid is more than 3 mass %, so that the dispersibility of glycyrrhetinic acid is particularly excellent. Furthermore, since the emulsion stability is particularly excellent when combined with the nonionic surfactant (b) described later, isostearyl alcohol is particularly preferably used in this embodiment.
When isostearyl alcohol is used, the ratio of glycyrrhetinic acid to isostearyl alcohol in the O/D type emulsion composition (glycyrrhetinic acid/isostearyl alcohol) may be 0.00001 to 0.05, 0.001 to 0.45, or 0.01 to 0.04. Within such a range, the effect of glycyrrhetinic acid is easily exerted effectively, and the dispersibility of glycyrrhetinic acid becomes even more excellent.
In this embodiment, isostearyl alcohol may be used alone as the higher alcohol and ester oil, or may be used in combination with other higher alcohols or ester oils as described above. The ratio of the isostearyl alcohol content to the total content of the higher alcohol and ester oil is preferably 50% by mass or more, more preferably 80% by mass or more, and particularly preferably 90% by mass or more.

(2-2) Hydrocarbon In this embodiment, the oil agent (a) preferably further contains a hydrocarbon. By containing a hydrocarbon, it is possible to suppress the coalescence of micelles in the obtained oil-in-water emulsion composition and to increase the emulsion stability.

Examples of hydrocarbons include squalane, squalene, liquid paraffin, light isoparaffin, light liquid isoparaffin, hydrogenated polybutene, paraffin, petrolatum, microcrystalline wax, ceresin, etc., and one type may be used alone or two or more types may be used in combination. Among these, squalane is particularly preferred.

The ratio of the content of the hydrocarbon to the content of the oil agent (a) is preferably 0.1 to 25% by mass, more preferably 1 to 20% by mass, and particularly preferably 5 to 15% by mass. Within this range, the emulsion stabilizing effect of the hydrocarbon becomes more pronounced.

(2-3) Content of Oil Agent The content of the oil agent (a) in the O/D type emulsion composition is preferably 5 to 70 mass %, more preferably 10 to 65 mass %, and particularly preferably 20 to 60 mass %.
By setting the content of oil agent (a) to 5% by mass or more, it becomes easy to set the content of glycyrrhetinic acid in the obtained O/D type emulsion composition or oil-in-water type emulsion composition within a suitable range, while by setting the content of oil agent (a) to 70% by mass or less, the emulsion stability of the obtained O/D type emulsion composition or oil-in-water type emulsion composition becomes more excellent.

(3) Nonionic surfactant (b)
In this embodiment, a nonionic surfactant is used to emulsify glycyrrhetinic acid and the oil (a). In this embodiment, the nonionic surfactant is excellent in emulsion stability and has low skin irritation, so it is particularly suitable for use as an external preparation for the skin or scalp.

Nonionic surfactants that may be used in this embodiment include propylene glycol fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, POE (polyoxyethylene) sorbitan fatty acid esters, POE sorbitol fatty acid esters, POE glycerin fatty acid esters, POE alkyl ethers, POE fatty acid esters, POE hydrogenated castor oil, POE castor oil, POE phytosterol, POE-POP (polyoxyethylene-polyoxypropylene) copolymers, POE-POP alkyl ethers, polyether-modified silicone lauric acid alkanolamide, alkylamine oxide, and hydrogenated soybean phospholipids.

In selecting the nonionic surfactant (b), it is useful to consider the required HLB of the surfactant in the O/D emulsion composition. In this embodiment, the required HLB of the surfactant in the O/D emulsion composition is preferably 11 to 16, and particularly preferably 12 to 15. When the required HLB of the surfactant in the O/D emulsion composition is 11 or more, liquid/liquid separation between the oil phase and the water phase due to an increase in the water content can be made even less likely to occur when water is added to the O/D emulsion composition to prepare an oil-in-water composition. On the other hand, when the HLB is 16 or less, the average particle size is easily uniform, making it easier to obtain an oil-in-water composition with good emulsion stability.

Here, the required HLB in an O/D type emulsion composition is the weighted average of the HLBs of the surfactants contained in the O/D type emulsion composition, and is expressed by the following formula, where H _i is the HLB of surfactant i and _Xi is the content of surfactant i.

When only one type of surfactant is used, the HLB of the surfactant is the required HLB of the surfactant in the O/D type emulsion composition.
From the viewpoint of making it easier to adjust the required HLB of the surfactant in the O/D type emulsion composition to within the above range, it is preferable to use each nonionic surfactant (b) used in this embodiment that has an HLB of 11 to 16, and it is particularly preferable to use one that has an HLB of 12 to 15.

From this viewpoint, examples of the nonionic surfactant (b) that can be particularly suitably used in this embodiment include POE hydrogenated castor oil, POE pyroglutamic acid isostearic acid hydrogenated castor oil, and POE·POP decyl tetradecyl ether.
The POE hydrogenated castor oil preferably has 30 to 90 moles of POE added, and particularly preferably has 40 to 80 moles of POE added.
The pyroglutamic acid/isostearic acid/POE hydrogenated castor oil preferably has 20 to 80 moles of POE added, and particularly preferably has 30 to 60 moles of POE added.
The POE·POP decyl tetradecyl ether preferably has 20 to 30 moles of POE and 10 to 15 moles of POP added thereto.

The content of the nonionic surfactant (b) in the O/D type emulsion composition is preferably from 10 to 30% by mass, more preferably from 12.5 to 27% by mass, and particularly preferably from 15 to 25% by mass.
When the content of the nonionic surfactant (b) is 10% by mass or more, the oil can be sufficiently emulsified, and an O/D type emulsion composition and an oil-in-water type composition having good emulsion stability can be easily obtained. On the other hand, when the content of the nonionic surfactant (b) is 30% by mass or less, solidification due to an increase in the water content is unlikely to occur, efficient emulsification is possible, and an oil-in-water type composition having good emulsion stability can be easily obtained.

(4) Polyhydric alcohol (c)
In this embodiment, a polyhydric alcohol (c) is used to form a D (detergent) phase in the O/D emulsion composition. By using the polyhydric alcohol (c), the surfactant solution that becomes the D phase has isotropy, and the oil phase (O phase) becomes easily dispersed in the D phase, so that a stable O/D emulsion composition can be obtained.

The polyhydric alcohol (c) used in the present embodiment is not particularly limited as long as it has two or more hydroxyl groups in the molecule.
Specific examples of the polyhydric alcohol (c) include lower polyhydric alcohols such as ethylene glycol, propylene glycol (1,2-propanediol), 1,3-propanediol, glycerin, 1,2-butylene glycol, 1,3-butylene glycol, 1,2-pentanediol, 1,2-hexanediol, and 1,2,4-butanetriol; polyethers of polyhydric alcohols such as diethylene glycol, dipropylene glycol, and diglycerin; sugars such as glucose, maltose, sucrose, and fructose; and sugar alcohols such as xylitol, sorbitol, inositol, and maltitol. These may be used alone or in combination of two or more.
Among these, it is preferable to use 1,3-butylene glycol, 1,3-propanediol, glycerin, and dipropylene glycol, and it is particularly preferable to use 1,3-butylene glycol and glycerin.

Furthermore, in this embodiment, it is particularly preferable to use 1,3-butylene glycol and glycerin in combination. Here, 1,3-butylene glycol is excellent in preventing gelation caused by the nonionic surfactant (b) and in orienting the surfactant at the interface in an orderly manner while maintaining a moderate hardness. On the other hand, glycerin is excellent in preventing extreme gelation of the D phase when water is added to the O/D type emulsion composition and in efficiently emulsifying the composition. Therefore, by using 1,3-butylene glycol and glycerin in combination, the dispersion stability of glycyrrhetinic acid is improved in the oil-in-water emulsion composition obtained by adding water to the O/D type emulsion composition, and the emulsion stability of the obtained O/D type emulsion composition and oil-in-water emulsion composition is more excellent.
When 1,3-butylene glycol and glycerin are used in combination, the ratio of the glycerin content to the 1,3-butylene glycol content (glycerin/1,3-butylene glycol) is preferably 0.1 to 0.5, and more preferably 0.2 to 0.4.

The content of the polyhydric alcohol (c) in the O/D type emulsion composition is preferably from 16 to 70% by mass, more preferably from 18 to 65% by mass, and particularly preferably from 20 to 60% by mass.
When the content of polyhydric alcohol (c) is 16% by mass or more, the viscosity of the O/D emulsion composition due to the addition of water is reduced, and the O/D emulsion composition and the resulting oil-in-water emulsion composition have excellent emulsion stability. On the other hand, when the content of polyhydric alcohol (c) is 70% by mass or less, the nonionic surfactant is orderly oriented at the interface, making it possible to form an O/D emulsion composition that can efficiently disperse oils, and the O/D emulsion composition and the resulting oil-in-water emulsion composition have excellent emulsion stability.

(5) Water (d)
In this embodiment, in forming the D (detergent) phase in the O/D type emulsion composition, water may be used in addition to the nonionic surfactant (b) and the polyhydric alcohol (c). The use of water (d) is preferable because it improves the orientation of the nonionic surfactant to the interface and further improves the dispersibility of the oil phase (O phase) in the D phase.

In the O/D type emulsion composition, water (d) is an optional component, and the content of water (d) may be 0 mass%. However, in order to improve the interface orientation of the nonionic surfactant (b), a small amount of water (d) may be added. For example, the content of water (d) in the O/D type emulsion composition may be 0.1 mass% or more, may be 0.2 mass% or more, or may be 0.5 mass% or more.
The upper limit of the water (d) content in the O/D emulsion composition is preferably 15% by mass or less, more preferably 10% by mass or less, and particularly preferably 8% by mass or less. When the water (d) content in the O/D emulsion composition is equal to or less than the above upper limit, efficient emulsification is possible under conditions in which extreme gelation of the D phase due to the addition of water does not occur, and the O/D emulsion composition and the resulting oil-in-water emulsion composition have excellent emulsion stability.

(6) Content Ratio In the O/D type emulsion composition according to this embodiment, from the viewpoints of the dispersion stability of glycyrrhetinic acid, the emulsion stability of the O/D type emulsion composition, and the emulsion stability of the oil-in-water emulsion composition described below, it is preferable to specify the content ratio of each component within a predetermined range.

In the O/D type emulsion composition of the present embodiment, the ratio (b)/(a) of the content of the nonionic surfactant (b) to the content of the oil agent (a) is preferably 0.26 to 3.5, more preferably 0.3 to 2.5, and particularly preferably 0.5 to 1.5.
When (b)/(a) is 0.26 or more, a sufficient amount of the nonionic surfactant (b) for dispersing the oil agent (a) is contained, and the O/D type emulsion composition and the resulting oil-in-water emulsion composition have excellent emulsion stability.
On the other hand, when (b)/(a) is 3.5 or less, the oil (a) is contained in a sufficient amount within a range that allows good dispersion in an O/D type emulsion composition and an oil-in-water type emulsion composition, and the dispersion stability of glycyrrhetinic acid is particularly excellent.

In the O/D type emulsion composition of this embodiment, the ratio (c)/(b) of the content of the polyhydric alcohol (c) to the content of the nonionic surfactant (b) is preferably 0.75 to 6, more preferably 1.0 to 5, and particularly preferably 1.25 to 4. When (c)/(b) is in this range, the dispersion stabilization effect of the nonionic surfactant (b) on the oil phase (O phase) can be effectively exerted.

In the O/D type emulsion composition of this embodiment, the ratio (d)/(b) of the content of water (d) to the content of nonionic surfactant (b) may be 0.005 or more and less than 1, may be 0.01 to 0.7, or may be 0.05 to 0.6.

(7) Method for Producing O/D Type Emulsion Composition The O/D type emulsion composition according to this embodiment can be produced according to a known D phase emulsification method.
For example, glycyrrhetinic acid is dissolved in an oil solution (a) containing at least one of the higher alcohol and the ester oil. In this case, the solution may be heated as necessary to increase the solubility of glycyrrhetinic acid. A hydrocarbon is added to the obtained solution as necessary to prepare an oil component constituting an oil phase (O phase). In addition, a nonionic surfactant (b), a polyhydric alcohol (c), and water (d) as necessary are mixed to prepare a solution constituting a surfactant phase (D phase).
Next, the oil constituting the O phase is added to the solution constituting the D phase, thereby obtaining the O/D type emulsion composition of the present embodiment. In this case, for example, while stirring the solution constituting the D phase, the oil constituting the O phase is added little by little and further stirred, thereby easily obtaining an O/D type emulsion composition having good emulsion stability, dispersion stability of glycyrrhetinic acid, and further emulsion stability when preparing an oil-in-water emulsion composition described later. The stirring conditions are not particularly limited, and for example, the O phase is well dispersed in the D phase by stirring using a homodisper or the like under conditions of 500 to 2500 rpm, or further under conditions of 1000 to 2000 rpm.

[Oil-in-water emulsion composition]
The oil-in-water emulsion composition according to this embodiment contains the O/D emulsion composition according to the above-described embodiment and an aqueous medium.
The aqueous medium is a liquid containing water as a solvent, and may contain other components as appropriate.

The method for producing an oil-in-water emulsion composition may be to add an aqueous medium to the O/D emulsion composition according to the above embodiment, and may be performed with appropriate stirring or other operations as necessary. In the O/D emulsion composition, the surfactant phase (D phase) is the continuous phase, but by adding an aqueous medium, the continuous phase is replaced by the aqueous phase, and an oil-in-water (O/W) emulsion composition with excellent emulsion stability can be easily obtained.
The mixing ratio of the O/D type emulsion composition and the aqueous medium is not particularly limited, but can be, for example, O/D type emulsion composition:aqueous medium=0.001:99.999 to 65:35.

In the obtained oil-in-water emulsion composition, the water content is preferably 35 to 99.999% by mass, and more preferably 40 to 90% by mass. An oil-in-water emulsion composition containing water in such a range allows glycyrrhetinic acid and the oil phase to be more stably dispersed, has a sufficiently low viscosity, and exhibits favorable properties as a skin topical agent, etc. Here, the water content in the oil-in-water emulsion composition is the sum of the water derived from the water (d) of the O/D emulsion composition and the water derived from the aqueous medium.

The content of glycyrrhetinic acid in the oil-in-water emulsion composition can be set appropriately depending on the content of water and the content of oil agent (a) derived from the O/D emulsion composition in the oil-in-water emulsion composition. For example, the lower limit can be 0.00001% by mass or more, 0.01% by mass or more, and the upper limit can be 3% by mass or less, 2% by mass or less, 1.5% by mass or less.

The oil-in-water emulsion composition of the present embodiment may not substantially contain ethanol.Since glycyrrhetinic acid is soluble in ethanol, conventional skin external preparations containing glycyrrhetinic acid contain a considerable amount of ethanol.However, since there are consumers who are sensitive to ethanol, it may be preferable to use an oil-in-water emulsion composition that does not substantially contain ethanol in order to appeal to such consumers.
More specifically, the oil-in-water emulsion composition being substantially free of ethanol means that the ethanol content in the oil-in-water emulsion composition can be 0.5% by mass or less, 0.1% by mass or less, 0.03% by mass or less, or even that the composition contains no ethanol at all.

In the oil-in-water emulsion composition of this embodiment, the average particle size (volume average particle size) of the oil droplets is preferably 200 nm or less, more preferably 150 nm or less, and particularly preferably 100 nm or less. An oil-in-water emulsion composition having an average particle size of the oil droplets in this range can be said to have excellent emulsion stability with suppressed creaming of the oil droplets. Oil droplets having the above average particle size can be easily obtained with the oil-in-water emulsion composition of this embodiment. The lower limit of the average particle size is not particularly limited, but can be, for example, 10 nm or more. The average particle size of the oil droplets can be measured using a dynamic light scattering particle size distribution measuring device or the like.

[External skin preparations]
The O/D type emulsion composition or oil-in-water type emulsion composition of the above embodiment contains glycyrrhetinic acid, has excellent emulsion stability, and allows the water content to be increased, making it suitable for inclusion in an external skin preparation.
The type of topical skin preparation is not particularly limited as long as it is used transdermally, and examples thereof include skin cosmetics such as creams, milky lotions, skin toners, lotions, and gels; scalp cosmetics such as hair tonics, hair creams, hair liquids, shampoos, pomades, and rinses; and the like.

The skin topical preparation of this embodiment may contain auxiliary agents or other ingredients used in the manufacture of ordinary skin topical preparations, such as astringents, bactericides/antibacterial agents, whitening agents, UV absorbers, moisturizers, cell activators, anti-inflammatory/antiallergic agents, antioxidants/active oxygen removers, pH adjusters, fragrances, etc., as long as they do not interfere with the physiological activities of glycyrrhetinic acid, such as anti-inflammatory effects. These ingredients can be incorporated into the oil-in-water emulsion composition or skin topical preparation by incorporating them into the oil phase (O phase) or surfactant phase (D phase) of the O/D emulsion composition, and/or the aqueous medium of the oil-in-water emulsion composition, depending on their solubility, etc.

According to the O/D type emulsion composition of the embodiment described above, an oil-in-water emulsion composition in which glycyrrhetinic acid is stably dispersed can be easily obtained by adding an aqueous medium. Furthermore, the oil-in-water emulsion composition of the embodiment described above has glycyrrhetinic acid stably dispersed therein and has excellent emulsion stability, making it suitable as an external preparation for the skin.

The above-described embodiments are described to facilitate understanding of the present invention, and are not described to limit the present invention. Therefore, each element disclosed in the above embodiments is intended to include all design modifications and equivalents that fall within the technical scope of the present invention.

The present invention will be explained in more detail below by showing manufacturing examples, test examples, etc., but the present invention is not limited to the following test examples, etc.

[Preparation of O/D type emulsion composition]
0.2975 parts by mass of glycyrrhetinic acid was added to 8.2 parts by mass of isostearyl alcohol and completely dissolved by heating to 100° C. 0.0142 parts by mass of squalane was added to the obtained solution and mixed to prepare an oil component constituting the oil phase (O phase).
4.0 parts by mass of polyoxyethylene (40) hydrogenated castor oil, 4.8 parts by mass of 1,3-butylene glycol, 1.2 parts by mass of glycerin, and 0.5 parts by mass of purified water were stirred and mixed to obtain a homogeneous solution constituting the surfactant phase (D phase). The obtained solution was stirred at 500 rpm using a Homo Disper (2.5 type, manufactured by Primix Corporation), while 8.475 parts by mass of oil constituting the oil phase (O phase) was gradually added. After the addition, the mixture was further stirred at 500 rpm for 1 minute to obtain an O/D type emulsion composition of sample 1.
The composition of each component in the O/D type emulsion composition is shown in the upper part of Table 1.

The stability of the obtained O/D type emulsion composition was evaluated according to the following criteria. The results are shown in Table 1.
A: A clear liquid with very little viscosity.
◯: The liquid was slightly viscous and slightly cloudy.
Δ: A slightly viscous, cloudy liquid.
×: A slightly viscous, cloudy liquid which separated into phases immediately after preparation.

[Preparation of oil-in-water emulsion composition]
19.0117 parts by mass of the O/D type emulsion composition of sample 1 obtained by the above method was stirred at 1000 rpm using a Homo Disper (2.5 type, manufactured by Primix Corporation), while 80.9883 parts by mass of purified water was added, and the mixture was further stirred at 1000 rpm for 1 minute to obtain an oil-in-water emulsion composition.
The composition of each component in the oil-in-water emulsion composition is shown in the lower part of Table 1.

The obtained oil-in-water emulsion composition was stored at 50° C. for 30 days, and then the stability was evaluated according to the following criteria. The results are shown in Table 1.
A: A clear, pale blue liquid.
○: A pale blue liquid.
Δ: A white liquid in which a very small amount of glycyrrhetinic acid was confirmed to have precipitated.
×: The liquid was white and phase-separated, and precipitation of glycyrrhetinic acid was confirmed.
In addition, as the particle size of the oil-in-water emulsion composition decreases, light with a short wavelength is more likely to be scattered, and the liquid color becomes blue. In other words, a light blue color of the liquid indicates that the particle size of the oil-in-water emulsion composition tends to be small.

The obtained oil-in-water emulsion composition was diluted by adding 200 times the amount of purified water immediately after preparation and after storage at 50°C for 30 days, and the particle size distribution of the oil droplets in the diluted solution was measured using a dynamic light scattering particle size distribution measuring device (Nanotrac WaveII-EX150, manufactured by Microtrack Bell Co., Ltd.), and the median diameter (D50) was taken as the average particle size. The results are shown in Table 1.

[Samples 2 to 40]
An O/D type emulsion composition and an oil-in-water type emulsion composition were prepared in the same manner as Sample 1, except that the blending ratio of each component was changed as shown in Table 1. The blending ratio of each component in each O/D type emulsion composition is shown in the upper part of Tables 1 to 3, and the blending ratio of each component in the corresponding oil-in-water type emulsion composition is shown in the lower part of Tables 1 to 3, respectively.

The details of each component used in the preparation of Samples 1 to 40 are as follows.
・Glycyrrhetinic acid (Maruzen Pharmaceuticals)
(Oil agent)
・Isostearyl alcohol (manufactured by Koyu Alcohol Kogyo Co., Ltd.)
Octyldodecanol (product name: Lisonol 20SP, manufactured by Kokyu Alcohol Kogyo Co., Ltd.)
・Ethylhexyl palmitate (product name: NIKKOL IOP, manufactured by Nikko Chemicals Co., Ltd.)
PG caprylate: Propylene glycol monocaprylate (product name: NIKKOL SEFSOL-218, manufactured by Nikko Chemicals)
・Squalane (product name: Olive Squalane, manufactured by Kokyu Alcohol Kogyo Co., Ltd.)
(Nonionic surfactant)
POE (60) hydrogenated castor oil (product name: NIKKOL HCO-60, manufactured by Nikko Chemicals Co., Ltd.)
Pyroglutamic acid isostearic acid POE (40) hydrogenated castor oil (product name: PYROTER CPI-40, manufactured by Nippon Emulsion Co., Ltd.)
POE (20) POP (13) Decyl tetradecyl ether (product name: Unilube 50MT-2200B, manufactured by NOF Corporation)
(Polyhydric alcohol)
1,3-butylene glycol (manufactured by Daicel Chemical Industries, Ltd.)
・Glycerin (manufactured by Sakamoto Pharmaceutical Co., Ltd.)
・Dipropylene glycol (ADEKA)

The stability of the obtained O/D emulsion composition and oil-in-water emulsion composition and the average particle size of the oil droplets in the oil-in-water emulsion composition were measured in the same manner as in Sample 1. The results are shown in Tables 1 to 3.

As shown in Tables 1 to 3, by preparing an oil-in-water emulsion composition from an O/D emulsion composition satisfying the requirements of the present invention, it was possible to obtain an oil-in-water emulsion composition in which glycyrrhetinic acid was stably dispersed and which also had excellent emulsion stability.
In contrast, in the oil-in-water emulsion compositions (samples 29 to 40) prepared from O/D emulsion compositions not satisfying the requirements of the present invention, precipitation of glycyrrhetinic acid, phase separation, etc. were observed.

Regarding the particle size distribution of the oil droplets, for samples 29 to 35 and 40, the oil-in-water emulsion compositions were semi-solid (viscosity 4,000 mPa s or more) or solid (viscosity 10,000 mPa s or more) and were not diluted by adding 200 times the amount of purified water, so the average particle size could not be measured.
For samples 36, 37, 38, and 39, the particle size distribution of the oil droplets did not follow a log-normal distribution, and the peaks were broad or other peaks were observed that were different from the average particle size peak. In addition, after storing sample 36 at 50°C for 30 days, complete phase separation occurred, making it impossible to measure the particle size.

Claims (12)

An O/D type emulsion composition containing glycyrrhetinic acid,
An oil agent (a) comprising at least one of a higher alcohol and an ester oil;
A nonionic surfactant (b); and a polyhydric alcohol (c);
The oil agent (a) contains, as the higher alcohol or the ester oil, at least one selected from the group consisting of isostearyl alcohol, 2-octyldodecanol, hexyldecanol, ethylhexyl palmitate, and propylene glycol caprylate;
The polyhydric alcohol (c) includes at least one selected from the group consisting of ethylene glycol, propylene glycol, 1,3-propanediol, glycerin, 1,2-butylene glycol, 1,3-butylene glycol, 1,2-pentanediol, 1,2-hexanediol, 1,2,4-butanetriol, diethylene glycol, dipropylene glycol, and diglycerin;
a ratio (b)/(a) of the content of the nonionic surfactant (b) to the content of the oil agent (a) is 0.26 to 3.5;
a ratio (c)/(b) of the content of the polyhydric alcohol (c) to the content of the nonionic surfactant (b) is 0.75 to 6;
The content of the glycyrrhetinic acid is 0.001 to 2.5% by mass,
The content of the oil agent (a) is 5 to 65% by mass,
The content of the polyhydric alcohol (c) is 16 to 70 mass %,
An O/D type emulsion composition, characterized in that the water (d) content is 0 to 15 mass %. The O/D type emulsion composition according to claim 1 , wherein the oil (a) contains at least isostearyl alcohol. The O/D type emulsion composition according to claim 1 or 2 , wherein the oil (a) contains a hydrocarbon. The O/D type emulsion composition according to any one of claims 1 to 3 , wherein the required HLB of the nonionic surfactant (b) in the O/D type emulsion composition is 11 to 16. The O/D type emulsion composition according to any one of claims 1 to 4 , wherein the polyhydric alcohol (c) comprises 1,3-butylene glycol and glycerin. The O/D type emulsion composition according to any one of claims 1 to 5 , wherein the content of the nonionic surfactant (b) is 10 to 30 mass %. A method for producing the O/D type emulsion composition according to any one of claims 1 to 6 , comprising the steps of:
The glycyrrhetinic acid is dissolved in the oil agent (a) to prepare an oil component constituting an oil phase;
The nonionic surfactant (b) and the polyhydric alcohol (c) are mixed to prepare a solution constituting a surfactant phase;
A method for producing an O/D type emulsion composition, comprising adding an oil component constituting the oil phase to a solution constituting the surfactant phase. 7. An oil-in-water emulsion composition comprising the O/D emulsion composition according to claim 1 and an aqueous medium. The oil-in-water emulsion composition according to claim 8 , wherein the water content is 35 to 99.999 mass %. 10. The oil-in-water emulsion composition according to claim 8 , wherein the average particle size of the oil droplets is 10 to 200 nm. The O/D type emulsion composition according to any one of claims 1 to 6 is prepared,
A method for producing an oil-in-water emulsion composition, comprising adding an aqueous medium to the O/D emulsion composition. A skin external preparation comprising the O/D type emulsion composition according to any one of claims 1 to 6 or the oil-in-water type emulsion composition according to any one of claims 8 to 10 .