Emulsion composition for external use

Abstract

Provided is a composition for skin in which it is possible to reduce the adverse effect of skin dryness caused by benzoyl peroxide and to keep the benzoyl peroxide stable.　An emulsion composition for external use for skin, the emulsion composition containing (A) benzoyl peroxide, (B) 0.3-12.5 wt% of at least one liquid oil having an α value of 0-8°, (C) 0.3-2.5 wt% of at least one solid oil, (D) at least one aqueous solvent, and (E) at least one surfactant.

Description

Emulsion-based topical composition

[0001] The present invention relates to topical pharmaceutical compositions useful for the treatment of acne vulgaris. More specifically, the present invention relates to emulsion-type external compositions for skin containing benzoyl peroxide.

[0002] Acne vulgaris, commonly known as "pimples," is a skin disease that frequently occurs on the face, and self-care is commonly performed by applying topical preparations. Benzoyl peroxide is used to treat acne vulgaris in many countries, and for example, Patent Documents 1 and 2 disclose skin compositions containing benzoyl peroxide as an active ingredient.

[0003] JP 9-87140 A JP 2013-241469 A

[0004] Since dry skin at the application site has been reported as a side effect of skin compositions containing benzoyl peroxide, a pharmaceutical composition with fewer such side effects is desired. One method for preventing dryness at the application site is to add oil to the composition to enhance its moisturizing ability, but it has been observed that adding oil to a composition containing benzoyl peroxide tends to reduce the stability of benzoyl peroxide. Therefore, an object of the present invention is to provide a skin composition containing benzoyl peroxide that minimizes the side effect of dry skin caused by benzoyl peroxide and that can maintain benzoyl peroxide stability in the composition.

[0005] As a result of extensive research into solving the above problems, the present inventors have succeeded in providing a skin composition that is excellent in both moisturizing properties and benzoyl peroxide stability by using an emulsion base containing specific amounts of liquid oil and solid oil, an aqueous solvent, and a surfactant as the base of a composition containing benzoyl peroxide.

[0006] That is, the present invention relates to the following emulsion-type topical compositions: [1] A topical emulsion-type composition for skin containing (A) benzoyl peroxide, (B) 0.3 to 12.5% ​​by weight of at least one liquid oil having an alpha value of 0° to 8°, (C) 0.3 to 2.5% by weight of at least one solid oil, (D) at least one aqueous solvent, and (E) at least one surfactant. [2] The topical emulsion-type composition according to [1], which contains only benzoyl peroxide as an active ingredient. [3] The topical emulsion-type composition according to [1] or [2], wherein the liquid oil (B) is selected from the group consisting of squalane, liquid paraffin, light liquid paraffin, octyldodecyl myristate, decyl oleate, and cetyl 2-ethylhexanoate. [4] The emulsion-type topical composition according to any one of [1] to [3], wherein the solid oil (C) is selected from the group consisting of aliphatic alcohols having 16 or more carbon atoms, stearic acid, paraffin, and white beeswax. [5] The emulsion-type topical composition according to any one of [1] to [4], wherein the content of the liquid oil (B) is 0.5 to 10% by weight, and the content of the solid oil (C) is 0.3 to 1.4% by weight. [6] The emulsion-type topical composition according to any one of [1] to [5], wherein the aqueous solvent (D) consists of (d1) 5 to 30% by weight of a polyhydric alcohol and (d2) 50% by weight or more of water. [7] The emulsion-type topical composition according to [1], comprising: as the liquid oil (B), 0.3 to 12.5% ​​by weight of squalane; as the solid oil (C), 0.3 to 2.5% by weight of a fatty alcohol selected from the group consisting of stearyl alcohol, cetostearyl alcohol, and cetyl alcohol; and as the aqueous solvent (D), (d1) 5 to 30% by weight of a polyhydric alcohol, and (d2) 50% by weight or more of water. [8] The emulsion-type topical composition according to [1], comprising: as the liquid oil (B), 1.5 to 5% by weight of squalane; as the solid oil (C), 0.3 to 0.9% by weight of a fatty alcohol selected from the group consisting of stearyl alcohol, cetostearyl alcohol, and cetyl alcohol; as the aqueous solvent (D), (d1) 10 to 25% by weight of a polyhydric alcohol, and (d2) 65% by weight or more of water; and the total content of components other than components [A] to [E] is 5% by weight or less.[9] The emulsion-type external composition according to [7] or [8], which contains only benzoyl peroxide as an active ingredient.

[0007] The emulsion-type external composition of the present invention has excellent moisturizing properties, so that the skin at the application site is less likely to dry out, and the active ingredient, benzoyl peroxide, is highly stable.

[0008] FIG. 1 is a diagram for explaining the moisture evaporation suppression evaluation test.

[0009] The emulsion-type topical composition of the present invention contains benzoyl peroxide (A) as an active ingredient. Benzoyl peroxide can be prepared by adding hydrogen peroxide to sodium hydroxide solution to obtain a sodium peroxide solution, and then adding benzoyl chloride to the sodium peroxide solution. Benzoyl peroxide is also commercially available. The benzoyl peroxide content is preferably 1 to 5 wt%, more preferably 1.5 to 4 wt%, particularly preferably 2 to 3 wt%, and even more preferably 2.5 wt%.

[0010] In this specification, the terms "wt %" and "content" refer to the weight ratio of each component when the total weight of the emulsion-based external composition is taken as 100%.

[0011] It is preferred that benzoyl peroxide (A) is not coated with a metal oxide layer. Furthermore, it is desirable that the emulsion-based topical composition of the present invention contain only benzoyl peroxide as the active ingredient (the ingredient for treating acne). For example, while a combination containing a naphthoic acid compound such as adapalene and benzoyl peroxide as the active ingredients is known as an acne treatment agent, it is preferred that the emulsion-based topical composition of the present invention does not contain a naphthoic acid compound such as adapalene.

[0012] The emulsion-type topical composition of the present invention contains 0.3 to 12.5 wt. % of a liquid oil (B) having an α value of 0° to 8°. In this specification, "liquid oil" refers to an oily component that is liquid at room temperature (25°C). The α value refers to the α value according to an organic conceptual diagram. The organic conceptual diagram was proposed by Atsushi Fujita, and its details are explained in "Pharmaceutical Bulletin," 1954, Vol. 2, pp. 163-173; "Chemical Region," 1957, Vol. 11, pp. 719-725; and "Fragrance Journal," 1981, Vol. 50, pp. 79-82, among others. That is, all organic compounds are considered to be derived from methane (CH4), and all other compounds are considered to be derivatives of methane. A fixed value is assigned to each of the carbon number, substituents, modified parts, rings, etc., and the organic and inorganic values ​​are calculated by adding up the scores. The slope of this value when plotted on a graph with organic values ​​on the X axis and inorganic values ​​on the Y axis is the α value.

[0013] If a liquid oil with an α value of more than 8° is used, the stability of benzoyl peroxide in the emulsion-type topical composition tends to deteriorate. It is more preferable to use a liquid oil with an α value of 7° or less.

[0014] Preferred examples of the liquid oil (B) include liquid hydrocarbons and low-polarity fatty acid ester oils. Examples of the liquid hydrocarbons include squalane (0°), liquid paraffin (0°), light liquid paraffin (0°), light isoparaffin (0°), liquid isoparaffin (0°), squalene (1°), α-olefin oligomer (0°), and polybutene (0°). Examples of the low-polarity fatty acid ester oils include octyldodecyl myristate (5°), oleyl oleate (5°), decyl oleate (6°), and cetyl 2-ethylhexanoate (7°). The numerical value in parentheses following each substance name indicates the α value. All of the above liquid oils can be used alone or in combination. More preferred liquid oils are liquid hydrocarbon oils with an α value of 0°, such as squalane, liquid paraffin, and light liquid paraffin, with squalane being particularly preferred.

[0015] The content of the liquid oil (B) is preferably 0.5 to 10% by weight, more preferably 1 to 8% by weight, particularly preferably 1.5 to 5% by weight, and even more preferably 2 to 4% by weight. If the amount of the liquid oil is too small, the moisturizing ability decreases, while if the amount of the liquid oil is too large, the stability of benzoyl peroxide decreases.

[0016] The emulsion-type external composition of the present invention contains 0.3 to 2.5% by weight of a solid oil (C). In this specification, the term "solid oil" refers to an oily component that is semi-solid or solid at room temperature (25°C).

[0017] Preferred examples of solid oils (C) include aliphatic alcohols having 16 or more carbon atoms, fatty acids having 18 or more carbon atoms, hydrocarbons, and waxes. Examples of aliphatic alcohols having 16 or more carbon atoms include saturated aliphatic alcohols (especially linear ones) having 16 to 22 carbon atoms (more preferably 16 to 20 carbon atoms, and particularly preferably 16 to 18 carbon atoms) with one hydroxyl group only on the terminal carbon. Particularly preferred examples include stearyl alcohol (18 carbon atoms), cetanol (also known as cetyl alcohol; 16 carbon atoms), and cetostearyl alcohol (a mixture of approximately equal amounts of stearyl alcohol and cetanol). Any of the above solid oils can be used alone or in combination. Examples of fatty acids having 18 or more carbon atoms include stearic acid (18 carbon atoms) and behenic acid (22 carbon atoms). Examples of hydrocarbons include paraffin and microcrystalline wax. Examples of waxes include white beeswax and lanolin.

[0018] The content of the solid oil (C) is more preferably 0.3 to 2% by weight, particularly preferably 0.3 to 1.4% by weight, and even more preferably 0.3 to 0.9% by weight. As the amount of the solid oil (C) increases, the moisturizing properties of the emulsion-type topical composition increase, but on the other hand, the stability of benzoyl peroxide decreases.

[0019] Although it is possible to achieve the desired moisturizing effect by using only a large amount of liquid oil (B) and solid oil (C), in this case, benzoyl peroxide becomes unstable, making it impossible to achieve the desired stability. Therefore, the emulsion-type topical composition of the present invention is characterized by containing a specific amount of liquid oil and a specific amount of solid oil in combination. The total amount of the liquid oil and solid oil is preferably at least 0.6% by weight, more preferably 1.0% by weight or more, particularly preferably 1.5% by weight or more, and even more preferably 2.4% by weight or more. In addition, the total amount of the liquid oil and solid oil is preferably 12% by weight or less, more preferably 10% by weight or less, particularly preferably 8% by weight or less, and even more preferably 6% by weight or less.

[0020] The emulsion-type topical composition of the present invention contains an aqueous solvent (D). Preferred examples of aqueous solvents include water (preferably purified water) and polyhydric alcohols. Examples of polyhydric alcohols include polyhydric alcohols having 3 to 6 carbon atoms. Polyhydric alcohols selected from glycerin, propylene glycol, and 1,3-butylene glycol are more preferred, with glycerin and 1,3-butylene glycol being particularly preferred. Any of the above aqueous solvents can be used alone or in combination.

[0021] The content of the aqueous solvent (D) is preferably 60% by weight or more, more preferably 70% by weight or more, particularly preferably 80% by weight or more, and even more preferably 85% by weight or more. The upper limit of the aqueous solvent (D) is preferably 97% by weight or less, more preferably 95% by weight or less.

[0022] Furthermore, the emulsion-type topical composition preferably contains (d1) a polyhydric alcohol and (d2) water (preferably purified water) as the aqueous solvent (D), more preferably 5-30% by weight of polyhydric alcohol and 50% by weight or more of water, particularly preferably 10-25% by weight of polyhydric alcohol and 65% by weight or more of water, and even more preferably 10-20% by weight of polyhydric alcohol and 70% by weight or more of water. The upper limit of water (d2) is preferably 95% by weight or less, more preferably 90% by weight or less, particularly preferably 85% by weight or less, and even more preferably 80% by weight or less. The weight percentages of (d1) and (d2) above do not refer to the total amount of the aqueous solvent (D), but rather refer to the weight percentages when the total amount of the emulsion-type topical composition is taken as 100% by weight.

[0023] Although a lower monohydric alcohol (a monohydric alcohol having 1 to 3 carbon atoms, such as ethanol or isopropanol) may be used as the aqueous solvent (D), it is preferable that the emulsion-based topical composition of the present invention be substantially free of lower monohydric alcohols because lower monohydric alcohols are irritating to the skin. As used herein, the phrase "substantially free of" a substance means that the substance was not intentionally added during the preparation of the emulsion-based topical composition, and therefore the content of the substance in the emulsion-based topical composition is typically less than 1% by weight, more preferably less than 0.5% by weight, and particularly preferably 0% by weight.

[0024] The emulsion-type topical composition of the present invention contains a surfactant (E). Examples of surfactants (emulsifiers) include nonionic surfactants, cationic surfactants, anionic surfactants, and amphoteric surfactants.

[0025] Examples of nonionic surfactants include polyethylene glycol fatty acid esters such as polyethylene glycol monostearate, ethylene glycol monostearate, polyethylene glycol monolaurate, ethylene glycol monostearate, and polyethylene glycol monooleate; polyoxyethylene alkyl ethers such as polyoxyethylene behenyl ether, polyoxyethylene oleyl ether, polyoxyethylene octyldodecyl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, and polyoxyethylene lauryl ether; polyoxyethylene alkylphenol ethers; polyoxyethylene hydrogenated castor oil; glycerin fatty acid esters such as glyceryl monostearate, lipophilic glyceryl monostearate, self-emulsifying glyceryl monostearate, glyceryl myristate, glyceryl monoisostearate, and lipophilic glyceryl monooleate; Examples of the sorbitan fatty acid esters include polyglyceryl monostearate, polyglyceryl monooleate, polyglyceryl monolaurate, polyglyceryl monomyristate, and decaglyceryl pentastearate; sorbitan fatty acid esters such as sorbitan monopalmitate, sorbitan monostearate, sorbitan monooleate, sorbitan cocoate, sorbitan tristearate, and sorbitan trioleate; polyoxyethylene sorbitan fatty acid esters such as polysorbate 60, polysorbate 65, polysorbate 80, and polysorbate 85; polyoxyethylene polyoxypropylene alkyl ethers such as polyoxyethylene polyoxypropylene cetyl ether (20E.O.) (4P.O.) and polyoxyethylene polyoxypropylene cetyl ether (20E.O.) (8P.O.); and polyoxyethylene beeswax derivatives such as polyoxyethylene sorbit beeswax.

[0026] Examples of cationic surfactants include cetyltrimethylammonium chloride, lauryldimethylbenzylammonium chloride, tetrabutylammonium chloride, and dioctadecyldimethylammonium chloride.

[0027] Examples of anionic surfactants include sodium alkylbenzene sulfonate, sodium dodecyl sulfate, sodium coconut alcohol ethoxy sulfate, sodium α-olefin sulfonate, emulsifying cetostearyl alcohol, and the like.

[0028] Examples of amphoteric surfactants include N-alkyl-N,N-dimethylammonium betaine and imidazoline-type amphoteric surfactants.

[0029] The above surfactants (E) can be used alone or in combination. Preferred surfactants are nonionic surfactants, with polyethylene glycol fatty acid esters being more preferred. As mentioned above, the emulsion-type topical composition of the present invention may contain polyoxyethylene alkyl ether (nonionic surfactant), but preferably does not substantially contain polyoxyethylene arachidyl ether (an ether formed from polyoxyethylene and arachidyl alcohol, an aliphatic alcohol having 20 carbon atoms).

[0030] The content of the surfactant (E) is preferably from 0.05 to 2% by weight, more preferably from 0.1 to 1% by weight, and particularly preferably from 0.2 to 0.5% by weight.

[0031] The emulsion-type topical composition of the present invention may contain one or more components other than the above (A) to (E), but the total amount of these components is preferably 5% by weight or less, more preferably 3% by weight or less, and particularly preferably 2% by weight or less. In particular, the emulsion-type topical composition of the present invention may contain polyurethane polymer-type compounds or derivatives thereof, naphthoic acid derivatives such as adapalene, polyoxyethylene arachyl ether, non-irritating benzoic acid esters (C 12 ~C 15 Preferably, the composition is substantially free of materials selected from the group consisting of solvents (such as alkyl benzoates), and film-forming agents (such as polyvinylpyrrolidone).

[0032] The pH value of the emulsion-type topical composition of the present invention is preferably 3 to 7. A pH below 3 may cause irritation to the skin, while a pH above 7 may result in poor stability of benzoyl peroxide. A more preferred pH value is 4 to 6, and an even more preferred pH value is 4 to 5. Examples of pH adjusters include diisopropanolamine, triisopropanolamine, triethanolamine, potassium hydroxide, sodium hydroxide, sodium citrate, phosphoric acid, tartaric acid, dl-malic acid, and glacial acetic acid. Any of the above pH adjusters may be used alone or in combination.

[0033] The emulsion-based topical composition of the present invention may contain a thickener. Examples of thickeners include carboxyvinyl polymers and carboxymethyl cellulose, with carboxyvinyl polymers being particularly preferred. The content of the thickener is preferably 0.2 to 1.5 wt %, more preferably 0.3 to 1.0 wt %, and particularly preferably 0.4 to 0.8 wt %.

[0034] The emulsion composition for external use of the present invention may contain other additives commonly used in external preparations for skin, such as antioxidants (e.g., ascorbic acid, dibutylhydroxytoluene, α-tocopherol, tocopherol acetate), stabilizers (e.g., edetate sodium hydrate, 1-menthol), preservatives (e.g., parahydroxybenzoates, phenoxyethanol), and colorants (e.g., titanium oxide).

[0035] Examples of dosage forms of the emulsion-based topical composition of the present invention include emulsion-based lotions, water-in-oil (W / O) creams, oil-in-water (O / W) creams, topical aerosols, and pump sprays. Emulsion-based lotions (emulsion-type liquid compositions) are particularly preferred. Emulsion-based lotions are oil-in-water (O / W) liquid compositions obtained by emulsifying an oily component (a component that is immiscible with water) and an aqueous component (a component that is miscible with water and water) with a surfactant. Because emulsion-based lotions contain oil, they have higher moisturizing properties than aqueous gels that do not contain oily components. On the other hand, because they are liquid and have low viscosity, they have a refreshing feel and are less likely to cause stickiness or greasiness on the application site, making them suitable for application to the face, a common site for acne vulgaris.

[0036] A preferred example of the emulsion-type external composition of the present invention comprises: (A) benzoyl peroxide; (B) 0.3 to 12.5% ​​by weight (preferably 0.5 to 10% by weight, more preferably 1 to 8% by weight, particularly preferably 1.5 to 5% by weight, and even more preferably 2 to 4% by weight) of at least one liquid oil selected from the group consisting of squalane, liquid paraffin, light liquid paraffin, octyldodecyl myristate, decyl oleate, and cetyl 2-ethylhexanoate; (C) 0.3 to 2.5% by weight (preferably 0.3 to 2.0% by weight, more preferably 0.3 to 1.4% by weight, particularly preferably 0.3 to 0.9% by weight, and even more preferably 0.4 to 0.9% by weight) of at least one solid oil selected from the group consisting of aliphatic alcohols having 16 or more carbon atoms, stearic acid, paraffin, and white beeswax; (D) An emulsion-type topical composition (particularly, an emulsion-type lotion) containing (d1) 5 to 30% by weight (preferably 10 to 25% by weight, more preferably 10 to 20% by weight) of a polyhydric alcohol, (d2) an aqueous solvent consisting of 50% by weight or more (preferably 65% ​​by weight or more, more preferably 70% by weight or more) of water, and (E) at least one surfactant is particularly preferred. In particular, an emulsion-type topical composition in which the total content of components other than (A) to (E) is 5% by weight or less, 3% by weight or less, or 2% by weight or less is preferred.

[0037] A particularly preferred example of the emulsion-type external composition of the present invention includes: (A) benzoyl peroxide; (B) 0.3 to 12.5% ​​by weight (preferably 0.5 to 10% by weight, more preferably 1 to 8% by weight, particularly preferably 1.5 to 5% by weight, and even more preferably 2 to 4% by weight) of squalane; (C) 0.3 to 2.5% by weight (preferably 0.3 to 2.0% by weight, more preferably 0.3 to 1.4% by weight, particularly preferably 0.3 to 0.9% by weight, and even more preferably 0.4 to 0.9% by weight) of at least one solid oil selected from the group consisting of stearyl alcohol, cetostearyl alcohol, and cetyl alcohol; (D) An emulsion-based topical composition (particularly, an emulsion-based lotion) containing (d1) 5 to 30% by weight (preferably 10 to 25% by weight, more preferably 10 to 20% by weight) of a polyhydric alcohol selected from the group consisting of glycerin, 1,3-butylene glycol, and propylene glycol, and (d2) 50% by weight or more (preferably 65% ​​by weight or more, more preferably 70% by weight or more) of an aqueous solvent consisting of water, and (E) at least one surfactant is particularly preferred. An emulsion-based topical composition in which the total content of components other than (A) to (E) is 5% by weight or less, 3% by weight or less, or 2% by weight or less is particularly preferred.

[0038] The emulsion-based topical composition of the present invention can be used to treat acne. For example, it can be used to treat, but is not limited to, acne vulgaris, acne comedonal or polymorphous acne, acne rosacea, nodular cystic acne, acne congregata, senile acne or secondary acne (e.g., actinic acne), drug-induced acne, or occupational acne. The application amount and frequency can be adjusted appropriately depending on the severity of symptoms, the concentration of benzoyl peroxide in the emulsion-based topical composition, and other factors. For example, when used on the face, after washing the face, an amount sufficient to cover the affected area is applied to the skin affected by acne vulgaris once or twice a day.

[0039] In the preceding paragraphs, preferred compound names of the essential components and optional components used in the composition of the present invention have been described, but the composition of the present invention also includes compositions obtained by arbitrarily combining these and compositions obtained by arbitrarily combining the contents of each component. Furthermore, the numerical ranges for each component, pH, etc. can also be arbitrarily combined, and when multiple numerical ranges are described, the upper and lower limits of each numerical range can also be arbitrarily combined.

[0040] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples. The percentages for each component in the examples represent weight percent. A nonionic surfactant was used as the surfactant.

[0041] Example 1 Preparations (emulsion lotions) having the compositions shown in Tables 1 and 2 were prepared. Thereafter, the moisture evaporation inhibition rate of each preparation was measured by the method described below to evaluate its moisturizing ability. When a sensory test was conducted using human panelists, preparations with a moisture evaporation inhibition rate of 25% or more were evaluated as providing a moist feeling that lasted after application (high moisture retention). Therefore, preparations with a moisture evaporation inhibition rate of 25% or more were evaluated as having "good" moisturizing ability, and preparations with a moisture evaporation inhibition rate of less than 25% were evaluated as having "poor" moisturizing ability.

[0042] <Measurement of moisture evaporation inhibitory ability> A circle with a diameter of 4 cm was opened in the center of the lid of a plastic cup, and a carrier film was attached to this area (see Figure 1). This lid was placed on a cup containing 50 g of water, and 100 μL (approximately 0.1 g) of the formulation was then applied to the carrier film. A carrier film without any formulation was also used for comparison. A hydrophobic polytetrafluoroethylene membrane filter (pore size 10 μm, diameter 47 mm) manufactured by Millipore was used as the carrier film. After storage for 4 hours in an environment of 30°C / 40% RH, the amount of moisture evaporated from the cups of the formulation-applied group through the carrier film was measured as WL. Ｘ (g / h), and the amount of water evaporated from the cup of the group without the preparation through the carrier film was WL ０ (g / h), and the moisture evaporation inhibition rate (%), which is a value indicating the occlusion effect, was calculated using the following formula.

[0043] The values ​​of each component shown in Table 1 are in weight percent, and blank spaces indicate 0%. The "appropriate amount" of purified water means the amount of purified water that makes the total amount of the formulation 100% by weight (the same applies to other tables).

[0044] As shown in Table 1, Formulation 1, which contained 0% solid oil, and Formulation 2, which contained 0.25% solid oil, exhibited low moisture evaporation inhibition rates and did not provide sufficient moisturizing power. In contrast, Formulations 3 to 5, which contained 0.5 to 1.8% solid oil, exhibited good moisturizing power. Formulations 6 and 7 (containing no solid oil), which contained higher amounts of polyhydric alcohol than Formulation 1, exhibited higher moisture evaporation inhibition rates than Formulation 1, but did not reach 25%. On the other hand, Formulation 8, which contained 0.5% solid oil and contained a lower amount of polyhydric alcohol than Formulation 3, exhibited good moisturizing power. These results demonstrate that formulations containing a specified amount of solid oil exhibit high moisture evaporation power, while formulations without solid oil, even if they contained a large amount of glycerin, a commonly known moisturizing agent, were unable to achieve the desired moisture evaporation power. Formulations containing 0.5% or more solid oil and with increased amounts of solid oil and liquid oil (Formulations 8A to 8C) also exhibited moisture evaporation inhibition rates of 30% or more and had high moisturizing power.

[0045] The results of changing the type of solid oil are shown in Table 2.

[0046] As shown in Table 2, all of the formulations prepared using aliphatic alcohols having 16 to 18 carbon atoms, stearic acid, paraffin, and white beeswax as solid oils exhibited good moisture evaporation inhibition rates.

[0047] Example 2 Preparations (emulsion lotions) having the compositions shown in Tables 3 to 5 were prepared and tested for the stability of the active ingredient, benzoyl peroxide. After storage at 50°C for two weeks, preparations in which the amount of benzoic acid, a decomposition product of benzoyl peroxide, was 10% or less were evaluated as having "good" stability, and preparations in which the amount of benzoic acid exceeded 10% were evaluated as having "poor" stability. The stability test method was as follows:

[0048] <Stability test method> An amount of formulation equivalent to approximately 50 mg of benzoyl peroxide was weighed out, and tetrahydrofuran and acetonitrile were added for dispersion extraction. Tetrahydrofuran was further added to the extract, and the mixture was filtered to prepare a sample solution. Separately, approximately 0.1 g of benzoic acid was weighed out, and acetonitrile was added to prepare a standard solution. The sample solution and standard solution were tested by liquid chromatography to measure the amount of benzoic acid contained in the formulation.

[0049] Test conditions Detector: Ultraviolet absorption photometer (measurement wavelength: 235 nm) Column: Stainless steel tube with an inner diameter of 4.6 mm and a length of 15 cm packed with 5 μm octadecylsilylated silica gel for liquid chromatography Mobile phase A: Water / acetic acid (100) mixture (1000:1) Mobile phase B: Acetonitrile / acetic acid (100) mixture (1000:1) The mixing ratio of mobile phase A and mobile phase B is changed to control the concentration gradient from mobile phase A-rich to mobile phase B-rich.

[0050]

[0051] As shown in Table 3, when a liquid oil with an α value of 0° to 7° was used (formulations 15 to 20), the desired stability of the active ingredient was achieved. On the other hand, when a liquid oil with an α value of 9° to 22° was used (formulations 21 to 23), the desired stability could not be achieved.

[0052]

[0053] As shown in Table 4, the desired stability was achieved when the amount of benzoyl peroxide was increased to 5% or 10% (Formulations 24-27), when the pH value was changed (Formulations 28-31), or when the amount of polyhydric alcohol was increased and the amount of surfactant was changed (Formulation 32). As the pH value increased, there was a tendency for stability to decrease (the amount of benzoic acid, a decomposition product of the active ingredient, increased), but the desired stability was achieved up to a pH of about 7.

[0054]

[0055] As shown in Table 5, as the amount of solid oil increased (Formulations 33-36), the stability of benzoyl peroxide tended to decrease, and the desired stability could not be achieved when the solid oil concentration reached 3% (Formulation 36). On the other hand, formulations containing 1% or less solid oil (Formulations 37-40) exhibited the desired stability even when the liquid oil concentration was increased to 6%. Furthermore, formulations with low amounts of solid oil (Formulations 40A and 40B) had benzoic acid levels of less than 5% and exhibited very high stability.

[0056] [Example 3] Various formulations (emulsion lotions) containing different amounts of solid oil and liquid oil were prepared, and moisturizing ability tests and stability tests were conducted. The results are shown in Table 6. The test methods were as described in Examples 1 and 2.

[0057]

[0058] As shown in Table 6, as the amount of liquid oil increased from 0.5% to 10% (Formulations 41 to 45), the moisture evaporation inhibition rate tended to increase (improved moisturizing ability). On the other hand, as the amount of liquid oil increased, stability tended to gradually decrease, but the desired stability was achieved even when the amount of liquid oil was increased up to 10%. In addition, the formulation containing 1.5% solid oil and 5% liquid oil (Formulation 46) and the formulation containing 0.5% solid oil and 2.5% liquid oil (Formulation 47) were also able to achieve both the desired moisturizing ability and stability.

[0059] [Example 4] Formulations (emulsion lotions) containing different types of solid oil were prepared and subjected to stability tests. The results are shown in Table 7. The test method was the same as that described in Example 2.

[0060]

[0061] As shown in Table 7, the desired stability was also achieved when fatty acids (Formulation 48), hydrocarbons (Formulation 49), and waxes (Formulation 50) were used as solid oils.

[0062] [Example 5] Preparations (emulsion lotions) containing different types of liquid oil were prepared and subjected to a moisturizing ability test. The results are shown in Table 8. The test method was the same as described in Example 1.

[0063]

[0064] As shown in Table 8, the desired moisturizing ability could be achieved even when liquid oils with α values ​​of 0°, 5°, or 7° were used.

Claims

1. (A) Benzoyl peroxide, (B) 0.3 to 12.5% by weight of at least one liquid oil having an α value of 0 to 8°, (C) 0.3 to 2.5% by weight of at least one solid oil, (D) at least one aqueous solvent, and (E) at least one surfactant containing only benzoyl peroxide as an active ingredient An emulsion-type topical composition for skin.

2. The emulsion-type topical composition according to claim 1, wherein the liquid oil (B) is selected from the group consisting of squalane, liquid paraffin, light liquid paraffin, octyldodecyl myristate, decyl oleate, cetyl 2-ethylhexanoate, and any combination thereof.

3. The emulsion-type topical composition according to claim 1 or 2, wherein the solid oil (C) is selected from the group consisting of aliphatic alcohols having 16 or more carbon atoms, stearic acid, paraffin, beeswax, and any combination thereof.

4. The content of the liquid oil (B) is 0.5 to 10% by weight, The content of the solid oil (C) is 0.3 to 1.4% by weight, The emulsion-type topical composition according to any one of claims 1 to 3.

5. The emulsion-type topical composition according to any one of claims 1 to 4, wherein the aqueous solvent (D) consists of (d1) 5 to 30% by weight of a polyhydric alcohol and (d2) 50% by weight or more of water.

6. As the liquid oil (B), 0.3 to 12.5% by weight of squalane, As the solid oil (C), 0.3 to 2.5% by weight of at least one aliphatic alcohol selected from the group consisting of stearyl alcohol, cetostearyl alcohol, and cetyl alcohol, As the aqueous solvent (D), (d1) 5 to 30% by weight of a polyhydric alcohol and (d2) 50% by weight or more of water The emulsion-type topical composition according to claim 1.

7. As the liquid oil (B), 1.5 to 5% by weight of squalane, As the solid oil (C), 0.3 to 0.9% by weight of at least one aliphatic alcohol selected from the group consisting of stearyl alcohol, cetostearyl alcohol, and cetyl alcohol, As the aqueous solvent (D), (d1) 10 to 25% by weight of a polyhydric alcohol and (d2) 65% by weight or more of water The emulsion-type topical composition according to claim 1, wherein the total content of components other than components (A) to (E) is 5% by weight or less.

8. The content of the liquid oil (B) is 1.5 to 10% by weight, The emulsion-type external composition according to any one of claims 1 to 7, wherein the content of the surfactant (E) is 0.1 to 1% by weight.

9. The emulsion-type external composition according to any one of claims 1 to 8, wherein the surfactant (E) is one kind of surfactant.