Oil-in-water emulsion composition

Abstract

Provided is an oil-in-water emulsion composition which is excellent in emulsifying stability and contains a drug agent that can be dissolved in both an oil phase and a water phase where the coalescence of oil drops tends to be induced.　This oil-in-water emulsion composition includes an aqueous dispersion medium and oil droplets dispersed in this aqueous dispersion medium. The oil droplets include a drug agent, a surfactant, and an oil component; the drug component has a logP value of -0.7 to 4.0; and the surfactant includes specific three types of non-ionic surfactants and an anionic surfactant.

Description

[Technical Field]

[0001] The present disclosure relates to oil-in-water emulsion compositions. [Background technology]

[0002] For example, in the fields of cosmetics, quasi-drugs, and pharmaceuticals, oil-in-water emulsion compositions containing drugs and the like have been developed.

[0003] Patent Document 1 discloses an oil-in-water emulsion cosmetic that contains 0.1 to 5 mass% of hydrogenated polyisobutene having a number-average molecular weight of 2,000 to 3,000, 0.1 to less than 1 mass% of a higher alcohol, 1 to 25 mass% of oily components including oil-soluble drugs and the like, 0.3 to 5 mass% of a surfactant, 0.05 to 5 mass% of a water-soluble thickener, and an aqueous component, in which the blending amount of non-polar oil is 30% or less of the total amount of the oily components.

[0004] Patent Document 2 discloses an oil-in-water cosmetic composition containing at least one oil, at least one polyglyceryl fatty acid ester having 4 to 6 polyglyceryl moieties derived from glycerin, at least one hydrotrope such as a skin whitening agent having a logP value of -0.7 to 6, and water.

[0005] Patent Document 3 discloses an oil-in-water type external skin composition containing a specific polyoxyethylene dialkyl ester and / or polyoxyethylene dialkyl ether, a specific polyoxyethylene alkyl ester and / or polyoxyethylene alkyl ether, a specific polyoxyethylene sterol ether, and an agent such as a phospholipid or lecithin. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] International Publication No. 2013 / 046770 [Patent Document 2] Japanese Patent Application Laid-Open No. 2014-122195 [Patent Document 3] International Publication No. 2017 / 131217 [Non-patent literature]

[0007] [Non-Patent Document 1] Sakamoto, K., Lochhead, R., Maibach, HI, Yamashita, Y., Eds., “Cosmetic Science and Technology: Theoretical Principles and Applications”, Amsterdam, The Netherlands, Elsevier, 2017, pp.489-506 Summary of the Invention [Problem to be solved by the invention]

[0008] In the fields of cosmetics, quasi-drugs, pharmaceuticals, and the like, drugs such as phenylethyl resorcinol and salicylic acid are used. These drugs have a relatively low molecular weight and are soluble in both the oil phase and the aqueous phase. When such drugs are incorporated into the oil phase (oil droplets) of an oil-in-water emulsion composition, the drugs are not continuously retained in the oil phase but are repeatedly transferred between the oil phase and the aqueous phase due to temperature changes. As a result, a phenomenon known as Ostwald ripening, which induces coalescence of oil droplets, as disclosed in Non-Patent Document 1, is likely to occur, making it difficult to obtain a stable emulsion composition.

[0009] Therefore, an object of the present disclosure is to provide an oil-in-water emulsion composition having excellent emulsion stability, which contains an agent that is soluble in both the oil phase and the aqueous phase and that easily induces the coalescence of oil droplets. [Means for solving the problem]

[0010] <Aspect 1> an aqueous dispersion medium, and Oil droplets dispersed in the aqueous dispersion medium An oil-in-water emulsion composition comprising: the oil droplets contain a drug, a surfactant, and an oil; The agent has a LogP value of -0.7 to 4.0, The surfactant includes a nonionic surfactant and an anionic surfactant represented by the following formulas 1 to 3: Oil-in-water emulsion composition: [ka] In formula 1, R 1 is a linear acyl group or a linear alkyl group having 16 to 24 carbon atoms, R 2 is an alkyl group having 2 to 4 carbon atoms, R 3 is a linear acyl group or a linear alkyl group having 16 to 24 carbon atoms, and k is an integer from 4 to 15; [ka] In formula 2, R 4 is a linear aliphatic acid residue or a linear aliphatic alcohol residue having 16 to 24 carbon atoms, R 5 is an alkyl group having 2 to 4 carbon atoms, and k is an integer from 5 to 20; [ka] In formula 3, R 6 is a cholesterol or phytosterol residue, R 7 is an alkyl group having 2 to 4 carbon atoms, and k is an integer of 5 to 30. <Aspect 2> The composition according to aspect 1, wherein the content of the drug in the composition is 0.1 to 5% by mass with respect to the total amount of the composition. <Aspect 3> the content of the nonionic surfactant of formula 1 in the composition is 0.1 to 2 mass% based on the total amount of the composition; the content of the nonionic surfactant of formula 2 in the composition is 0.1 to 2 mass% based on the total amount of the composition; The content of the nonionic surfactant of formula 3 in the composition is 0.3 to 6 mass% based on the total amount of the composition, and the content of the anionic surfactant in the composition is 0.01 to 0.1% by mass relative to the total amount of the composition; 3. The composition of any one of aspects 1 to 2. <Aspect 4> Aspect 4. The composition according to any one of Aspects 1 to 3, wherein the anionic surfactant is at least one selected from an alkanoyl-N-alkyl taurine salt and an alkanoyl glutamate salt. <Aspect 5> The composition according to any one of Aspects 1 to 4, wherein the agent is at least one selected from phenylethyl resorcinol, 4-(1-phenylethyl)-1,3-diol, benzeneoxothiazolidinecarboxylic acid, nicotinamide, xanthine, ellagic acid, ferulic acid, apigenin, salicylic acid, phloretin, resveratrol, and fragrances. <Aspect 6> Aspect 6. The composition according to any one of Aspects 1 to 5, wherein the oil is at least one selected from liquid oils, solid oils, waxes, hydrocarbon oils, higher fatty acids, synthetic ester oils, and silicone oils. <Aspect 7> A first aqueous phase part is prepared containing the nonionic surfactants of formulas 1 to 3, the anionic surfactant, and water; An oil phase part containing the drug and the oil is prepared, The oil phase part is blended with a part or all of the first aqueous phase part to prepare a preliminary emulsion; mixing the pre-emulsion with the remainder of the first aqueous phase part, or mixing the pre-emulsion with a second aqueous phase part containing water; A method for producing the oil-in-water emulsion composition according to any one of aspects 1 to 6. <Aspect 8> A manufacturing method according to aspect 7, wherein the first aqueous phase part contains at least one glycol component selected from dipropylene glycol, 1,3-butylene glycol, propylene glycol, and polyethylene glycol. <Aspect 9> Aspect 9. The production method according to aspect 8, wherein the content of the glycol component is 40 to 80% by mass with respect to the total amount of the first aqueous phase part. [Effects of the Invention]

[0011] According to the present disclosure, it is possible to provide an oil-in-water emulsion composition having excellent emulsion stability, which contains a drug that is soluble in both the oil phase and the aqueous phase and that easily induces the coalescence of oil droplets. DETAILED DESCRIPTION OF THE INVENTION

[0012] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present disclosure is not limited to the following embodiments, and various modifications can be made within the scope of the present invention.

[0013] The oil-in-water emulsion composition of the present disclosure (sometimes simply referred to as the "composition") comprises an aqueous dispersion medium and oil droplets dispersed in the aqueous dispersion medium, the oil droplets comprising a drug, a surfactant, and an oil component, the drug having a LogP value of -0.7 to 4.0, and the surfactant comprising a nonionic surfactant and an anionic surfactant represented by the above formulas 1 to 3. Here, the "LogP value" is a parameter that represents the ease with which a substance distributes between water and octanol, and is a numerical value that is generally used as an index for determining the degree of hydrophilicity or hydrophobicity of a substance. The smaller the LogP value, the more hydrophilic the substance is intended to be, and the larger the LogP value, the more hydrophobic the substance is intended to be.

[0014] Without being limited by any particular theory, the oil-in-water emulsion composition of the present disclosure has excellent emulsion stability despite containing an agent that is soluble in both the oil phase and the water phase and that easily induces the coalescence of oil droplets (this property is sometimes referred to as "hydrotropic"), i.e., an agent that easily induces the coalescence of oil droplets, and yet the composition contains such an agent, which is soluble in both the oil phase and the water phase (this property is sometimes referred to as "hydrotropic"), and therefore easily induces the coalescence of oil droplets. The mechanism of action is believed to be as follows.

[0015] In the case of an oil-in-water emulsion composition, the surfactant is generally oriented in a film-like manner at the interface between the oil phase and the aqueous phase, i.e., around the oil droplets. The surfactant oriented at such an interface is typically not permanently retained at the interface, but moves between the interface and the aqueous phase. As a result, the movement of the surfactant may temporarily form areas around the oil droplets where no surfactant is present.

[0016] It is believed that drugs with hydrotropic properties can pass through areas where the surfactant is not present, thereby inducing the coalescence of oil droplets in oil-in-water emulsion compositions.

[0017] For example, the technology described in Patent Document 3 employs a specific surfactant to form a stronger interfacial film at the interface of oil droplets, thereby improving emulsion stability. Patent Document 3 describes that agents such as phospholipids, lecithin, lysolecithin, and ceramide can be used, but these agents do not have the hydrotropic properties intended in the present disclosure. The technology described in Patent Document 3 can ensure good emulsion stability when agents such as phospholipids and lecithin are used. However, when agents having the hydrotropic properties intended in the present disclosure are used, the technology described in Patent Document 3 cannot inhibit the agent from passing through the interfacial film, and good emulsion stability cannot be obtained.

[0018] The composition of the present disclosure contains an anionic surfactant as a surfactant in addition to the nonionic surfactants of Formulas 1 to 3 above. The nonionic surfactants of Formulas 1 to 3 have relatively similar properties, and therefore can form an interfacial film associated with these nonionic surfactants around oil droplets without causing problems such as crystal precipitation or increased viscosity. In addition, it is believed that an electrolyte layer associated with the anionic surfactant is also formed simultaneously. As a result, the interfacial film formed by the nonionic surfactant can be reinforced by the electrolyte layer associated with the anionic surfactant, reducing or inhibiting the passage of hydrotropic drugs through the interfacial film, thereby achieving good emulsion stability.

[0019] 《Oil-in-water emulsion composition》 The oil-in-water emulsion composition of the present disclosure has excellent emulsion stability. Here, emulsion stability can refer to a state in which no separation occurs, preferably a state in which there is little change in the size of emulsion particles (oil droplets), in an emulsion stability test conducted at 50°C for 30 days and / or under temperature cycle conditions of 0°C to 40°C, as described below. Note that such emulsion stability tests also qualify as accelerated tests, and therefore emulsion compositions that show good results in such tests can exhibit even better emulsion stability performance at room temperature (e.g., 5 to 35°C).

[0020] In some embodiments, in at least one of the emulsion stability tests, the rate of increase of oil droplets can be suppressed to 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, or 5% or less. There is no particular restriction on the lower limit of the rate of increase of oil droplets, but it can be, for example, 0% or more or more. This rate of increase can be calculated from the initial value of the average particle size of the oil droplets (the value immediately after preparation) and the value of the average particle size of the oil droplets after the emulsion stability test using the following formula 4: Increase rate (%) = {(average oil droplet size after emulsion stability test - initial average oil droplet size) × 100} / (initial average oil droplet size) ...Equation 4

[0021] <Aqueous dispersion medium> The oil-in-water emulsion composition of the present disclosure contains an aqueous dispersion medium. The aqueous dispersion medium is typically composed of water, but may optionally contain various water-soluble or water-dispersible components from among the optional components described below.

[0022] The water that can be used in the oil-in-water emulsion composition of the present disclosure is not particularly limited, and can be water used in cosmetics, quasi-drugs, etc. For example, ion-exchanged water, distilled water, ultrapure water, tap water, etc. can be used.

[0023] The amount of water to be added is not particularly limited, but from the viewpoints of emulsion stability, usability, etc., it can be, for example, 30% by mass or more, 40% by mass or more, or 50% by mass or more, and can be 90% by mass or less, 80% by mass or less, 70% by mass or less, 60% by mass or less, or 50% by mass or less, relative to the total amount of the composition.

[0024] <Oil drop> The oil phase or oil droplets as the dispersed phase in an oil-in-water emulsion composition contain the drug, surfactant, and oil.

[0025] The average particle size of such oil droplets is not particularly limited, and can be, for example, 0.3 μm or more, 0.5 μm or more, 0.7 μm or more, or 1 μm or more immediately after production, and can be 50 μm or less, 40 μm or less, 30 μm or less, 20 μm or less, or 10 μm or less. Here, the average particle size of oil droplets can be defined as the average value of the diameters of circles equivalent to the projected area of 10 or more, preferably 100 or more, oil droplets observed with an optical microscope.

[0026] (drug) The oil-in-water emulsion composition of the present disclosure contains a drug having a LogP value of at least -0.7 to 4.0. Drugs with such LogP values are said to have hydrotropic properties that tend to reduce the emulsion stability of typical oil-in-water emulsion compositions. The LogP value range can be -0.7 or more, -0.5 or more, -0.3 or more, -0.1 or more, 0 or more, or 0.5 or more, and can be 4.0 or less, 3.7 or less, or 3.5 or less. The LogP value can be calculated, for example, using calculation software (PALAAS: manufactured by CompDrug Chemistry Ltd.).

[0027] The content of such drugs is not particularly limited, and for example, from the viewpoint of efficacy, emulsion stability, etc., it can be 0.1% by mass or more, 0.3% by mass or more, 0.5% by mass or more, 0.7% by mass or more, or 1% by mass or more relative to the total amount of the composition, and can be 5% by mass or less, 4% by mass or less, 3% by mass or less, 2% by mass or less, or 1% by mass or less.

[0028] Specific examples of drugs having a LogP value of -0.7 to 4.0 include phenylethylresorcinol (LogP: 3.4), 4-(1-phenylethyl)-1,3-diol (LogP: 3.5), benzeneoxothiazolidinecarboxylic acid (LogP: -0.1), nicotinamide (LogP: -0.4), xanthine (LogP: -0.7), ellagic acid (LogP: 1.1), ferulic acid (LogP: 1.5), apigenin (LogP: 1.7), salicylic acid (LogP: 2.3), phloretin (LogP: 2.6), and resveratrol (LogP: 3.1). These drugs can be used alone or in combination.

[0029] The oil-in-water emulsion composition of the present disclosure may also contain a fragrance as such a drug. The oil-in-water emulsion composition of the present disclosure allows the fragrance to be stably incorporated without the addition of alcohol such as ethanol. The fragrance may be used alone or in combination of two or more types.

[0030] Examples of fragrances having a LogP value of -0.7 to 4.0 include anisaldehyde (LogP: 1.8), benzyl acetate (LogP: 2.0), benzyl alcohol (LogP: 1.1), calone (LogP: 1.8), canthoxal (LogP: 2.0), cis-3-hexenol (LogP: 1.4), coumarin (LogP: 1.4), ethyl acetate (LogP: 0.7), ethyl acetoacetate (LogP: 0.3), ethyl butyrate (LogP: 1.8), ethyl maltol (LogP: 0.5), and ethyl vanillin (LogP :1.8), fructone (LogP:0.8), helional (LogP:1.4), heliotropin (LogP:1.1), hydroxycitronellal (LogP:1.5), indian flor crystal (LogP:1.3), linalool oxide (LogP:1.5), maltol (LogP:-0.1), methyl jasmonate (LogP:1.9), phenylethyl alcohol (LogP:1.2), phenoxyethanol (LogP:1.2), phenylpropyl alcohol (LogP:1.7), prenyl acetate (LogP:1.7) , raspberry ketone (LogP:1.1), styrallyl alcohol (LogP:1.4), vanillin (LogP:1.3), vanillin (LogP:1.8), fructone (LogP:0.8), helional (LogP:1.4), heliotropin (LogP:1.1), amber core (LogP:4.0), α-damascone (LogP:3.6), aldehyde C-14 (LogP:3.8), aldehyde C-16 (LogP:2.8), allyl amyl glycolate (LogP:2.5), benzyl benzoate (LogP:3.9), 3-(4-tert-butyl 2-methylpropional) t-Butylphenyl)propanal (LogP: 3.5), cis-3-hexenyl acetate (LogP: 2.3), citral (LogP: 3.1), citronellol (LogP: 3.3), δ-damascone (LogP: 3.6), dihydromyrcenol (LogP: 3.0), dynascone (LogP: 3.6), ethyl 2-methylbutyrate (LogP: 2.1), eucalyptol (LogP: 2.8), eugenol (LogP: 2.4), floralozone (LogP: 3.5), fluropal (LogP: 3.4), fultate (LogP: 3.4), geraniol (LogP:2.8), geranyl acetate (LogP:3.7), hexyl acetate (LogP:2.8), indole (LogP:2.1), isoamyl acetate (LogP:2.2), ionone alpha (LogP:3.7), ionone beta (LogP:3.8), lactone C-10 gamma (LogP:3.3), lilial (LogP:3.9), linalool (LogP:2.5), linalyl acetate (LogP:3.5), mayol (LogP:3.3), l-menthol (LogP:3.2), l-menthone (LogP:2.8), lyral (LogP:2.2), manzanate (LogP:2.6), methyl dihydroxyjasmonate (LogP:2.4), pamplefleur (LogP:3.0), phenoxyethyl Isobutyrate (LogP:2.9), Poarenate (LogP:3.7), Lubafuran (LogP:2.8), Rose oxide (LogP:2.9), Styrallyl acetate (LogP:2.3), Styrallyl propionate (LogP:2.8), Terpineol (LogP:2.6), Terpinyl acetate (LogP:3.6), Tetrahydrolinalool (LogP:3.5), Tetrahydromugol (L Examples of such amines include tricyclodecenyl acetate (LogP: 2.4), tricyclodecenyl propionate (LogP: 2.9), triplal (LogP: 2.4), undecavertol (LogP: 3.7), citronellal (LogP: 3.5), geraniol (LogP: 3.6), camphor (LogP: 2.1), and acetonaphthone (LogP: 2.9).

[0031] (surfactant) The oil-in-water emulsion composition of the present disclosure contains, as surfactants, at least the nonionic surfactants and anionic surfactants represented by the following formulas 1 to 3.

[0032] a. Nonionic surfactant of formula 1 The surfactant used is a nonionic surfactant of the following formula 1. This surfactant is a double-chain nonionic surfactant having two hydrophobic groups. Such surfactants can be used alone or in combination of two or more: [ka]

[0033] In formula 1, R 1 is a linear acyl group or a linear alkyl group having 16 to 24 carbon atoms, and R 2 is an alkyl group having 2 to 4 carbon atoms, and R 3 is a linear acyl group or a linear alkyl group having 16 to 24 carbon atoms, and k is an integer of 4 to 15.

[0034] R 1 and R 3 The number of carbon atoms in R can be independently 16 or more, 17 or more, or 18 or more, and can be 24 or less, 23 or less, or 22 or less. 2 The number of carbon atoms is preferably 2 to 3, and more preferably 2. Furthermore, k can be 4 or more, 5 or more, 6 or more, or 7 or more, and can be 15 or less, 14 or less, or 13 or less.

[0035] Specific examples of the nonionic surfactant of formula 1 include polyoxyethylene (4 mol) distearate, polyoxyethylene (6 mol) distearate, polyoxyethylene (8 mol) distearate, polyoxyethylene (12 mol) distearate, steareth-4 stearate, steareth-6 stearate, steareth-9 stearate, polyoxyethylene (8 mol) dibehenyl ether, etc. Here, the bonding mode between the polyoxyethylene chain and the alkyl group may be an ester bond or an ether bond, or may include both.

[0036] The content of the nonionic surfactant of formula 1 is not particularly limited, and for example, from the viewpoint of emulsion stability, etc., it can be 0.1 mass % or more or 0.2 mass % or more, and can be 2 mass % or less, 1 mass % or less, 0.7 mass % or less, or 0.5 mass % or less, relative to the total amount of the composition.

[0037] b. Nonionic surfactant of formula 2 The surfactant used is a nonionic surfactant of the following formula 2. Such surfactants can be used alone or in combination of two or more: [ka]

[0038] In formula 2, R 4 is a linear aliphatic acid residue or a linear aliphatic alcohol residue having 16 to 24 carbon atoms, and R 5 is an alkyl group having 2 to 4 carbon atoms, and k is an integer of 5 to 20.

[0039] R 4 The number of carbon atoms in R may be 16 or more, 17 or more, or 18 or more, and may be 24 or less, 23 or less, or 22 or less. 5 The number of carbon atoms is preferably 2 to 3, and more preferably 2. Furthermore, k can be 5 or more, 6 or more, or 7 or more, and can be 20 or less, 18 or less, 16 or less, 14 or less, or 12 or less.

[0040] From the viewpoints of emulsion stability, ease of formation of an interfacial film of oil droplets, etc., the nonionic surfactant of formula 2 preferably has an HLB of 7.0 or more, 8.0 or more, or 9.0 or more, and preferably 15.0 or less, 14.0 or less, or 13.0 or less. Here, HLB is a value that generally indicates the affinity of a surfactant for water and oil, and is a parameter known as the hydrophilic-lipophilic balance, which can be easily determined by known calculation methods such as the Griffin method.

[0041] Specific examples of the nonionic surfactant of formula 2 include polyoxyethylene (20 mol) behenyl ether, polyoxyethylene (10 mol) stearyl ether, and polyoxyethylene (7 mol) cetyl ether.

[0042] The content of the nonionic surfactant of formula 2 is not particularly limited, and for example, from the viewpoint of emulsion stability, etc., it can be 0.1 mass % or more or 0.2 mass % or more, and can be 2 mass % or less, 1 mass % or less, 0.7 mass % or less, or 0.5 mass % or less, relative to the total amount of the composition.

[0043] c. Nonionic surfactant of formula 3 The surfactant used is a nonionic surfactant of the following formula 3 (sometimes referred to as a "polyoxyalkylene sterol ether"). Such surfactants can be used alone or in combination of two or more: [ka]

[0044] In formula 3, R 6 is a cholesterol residue or a phytosterol residue, and R 7 is an alkyl group having 2 to 4 carbon atoms, and k is an integer of 5 to 30.

[0045] R 7 The number of carbon atoms is preferably 2 to 3, and more preferably 2. Furthermore, k can be 5 or more, 6 or more, or 7 or more, and can be 30 or less, 25 or less, 20 or less, 18 or less, 16 or less, 14 or less, or 12 or less.

[0046] Specific examples of the nonionic surfactant of formula 3 include polyoxyethylene (10 mol) phytostearyl, polyoxyethylene (30 mol) polyoxypropylene (7 mol) phytostearyl, polyoxyethylene (10 mol) cholesteryl, and polyoxyethylene (20 mol) cholesteryl.

[0047] The content of the nonionic surfactant of formula 3 is not particularly limited, and from the viewpoint of emulsion stability, etc., it can be, for example, 0.3 mass% or more, 0.4 mass% or more, 0.5 mass% or more, 0.6 mass% or more, or 0.7 mass% or more relative to the total amount of the composition, and can be 6 mass% or less, 4 mass% or less, 2 mass% or less, or 1 mass% or less.

[0048] d. Anionic surfactants The anionic surfactant is not particularly limited, and examples thereof include polyoxyethylene alkyl ether sulfates, higher fatty acid salts, alkyl ether sulfates, alkanoyl-N-alkyl taurine salts, and alkanoyl glutamates. The anionic surfactants can be used alone or in combination. Examples of the salts thereof include alkali metal salts such as sodium, potassium, and lithium, and amine salts such as triethanolamine, diethanolamine, and monoethanolamine.

[0049] Among the above-mentioned anionic surfactants, at least one selected from alkanoyl-N-alkyl taurine salts and alkanoyl glutamates is preferred from the viewpoint of the interfacial membrane reinforcement by the nonionic surfactant and the associated emulsion stability. The number of carbon atoms in the alkanoyl group is preferably 12 or more, 13 or more, or 14 or more, and preferably 22 or less, 21 or less, or 20 or less. Of these, a stearoyl group is particularly preferred. Examples of the alkyl group include methyl, ethyl, and propyl, with methyl being preferred.

[0050] The content of the anionic surfactant is not particularly limited, and for example, from the viewpoint of the reinforcement of the interfacial film by the nonionic surfactant and the resulting emulsion stability, it can be 0.01 mass % or more or 0.02 mass % or more, and can be 0.1 mass % or less, 0.08 mass % or less, 0.06 mass % or less, or 0.05 mass % or less, relative to the total amount of the composition.

[0051] e. Surfactant blend ratio The blending ratio of the surfactants is not particularly limited, but from the viewpoint of, for example, emulsion stability, the blending ratio of the nonionic surfactant of formula 1 to the nonionic surfactant of formula 2 to the nonionic surfactant of formula 3 is preferably in the range of 1:1:2 to 1:1:4 by mass, more preferably in the range of 1:1:2.5 to 1:1:3.5, and particularly preferably in the range of 1:1:2.5 to 1:1:3.

[0052] From the viewpoint of, for example, the reinforcement of the interfacial film by the nonionic surfactant and the resulting emulsion stability, the amount of the anionic surfactant is preferably 0.5 parts by mass or more or 1.0 part by mass or more relative to 100 parts by mass of the nonionic surfactants of Formulas 1 to 3, and is preferably 10 parts by mass or less, 8.0 parts by mass or less, 5.0 parts by mass or less, or 3.0 parts by mass or less.

[0053] (oil content) The oil content in the oil-in-water emulsion composition of the present disclosure is not particularly limited, and, for example, from the standpoint of usability and the like, can be 0.05% by mass or more, 0.1% by mass or more, 0.5% by mass or more, 1% by mass or more, 3% by mass or more, 5% by mass or more, 7% by mass or more, 10% by mass or more, 13% by mass or more, or 15% by mass or more, relative to the total amount of the composition, and can be 50% by mass or less, 40% by mass or less, 30% by mass or less, 25% by mass or less, or 20% by mass or less.

[0054] The oil is not particularly limited, and examples thereof include liquid oils, solid oils, waxes, hydrocarbon oils, higher fatty acids, synthetic ester oils, and silicone oils. The oils can be used alone or in combination.

[0055] Examples of liquid oils and fats include avocado oil, camellia oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, wheat germ oil, camellia oil, castor oil, linseed oil, safflower oil, cottonseed oil, perilla oil, soybean oil, peanut oil, tea seed oil, Japanese kaya oil, rice bran oil, Chinese tung oil, Japanese tung oil, jojoba oil, germ oil, and triglycerin.

[0056] Examples of solid fats and oils include cocoa butter, coconut oil, horse fat, hardened coconut oil, palm oil, beef tallow, mutton tallow, hardened beef tallow, palm kernel oil, lard, beef bone fat, Japan wax kernel oil, hardened oil, beef foot fat, Japan wax, and hardened castor oil.

[0057] Examples of waxes include beeswax, candelilla wax, cotton wax, carnauba wax, bayberry wax, ivory wax, spermaceti wax, montan wax, bran wax, lanolin, kapok wax, acetated lanolin, liquid lanolin, sugarcane wax, lanolin fatty acid isopropyl, hexyl laurate, reduced lanolin, jojoba wax, hard lanolin, shellac wax, polyoxyethylene lanolin alcohol ether, polyoxyethylene lanolin alcohol acetate, polyoxyethylene cholesterol ether, lanolin fatty acid polyethylene glycol, polyoxyethylene hydrogenated lanolin alcohol ether, and cetyl palmitate.

[0058] Examples of hydrocarbon oils include liquid paraffin, ozokerite, squalane, pristane, paraffin, ceresin, squalene, petrolatum, and microcrystalline wax.

[0059] Examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, undecylenic acid, tall acid, isostearic acid, linoleic acid, linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).

[0060] Examples of synthetic ester oils include cetyl octanoate, myristyl myristate, glyceryl tri-2-ethylhexanoate, pentaerythritol tetra-2-ethylhexanoate, dioctyl succinate, and tripropylene glycol dineopentanoate.

[0061] Examples of silicone oils include linear polysiloxanes (e.g., dimethylpolysiloxane, methylphenylpolysiloxane, diphenylpolysiloxane); cyclic polysiloxanes (e.g., octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane), silicone resins that form a three-dimensional network structure, silicone rubber, various modified polysiloxanes (e.g., amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, fluorine-modified polysiloxane), and acrylic silicones.

[0062] <Optional ingredients> The emulsion composition of the present disclosure may contain any other components in addition to the components described above, provided that the components do not affect the effects of the present invention. The optional components may be used alone or in combination of two or more, and may be appropriately blended into the oil phase or the aqueous phase.

[0063] Such optional components include, for example, powder components, amphoteric surfactants, nonionic surfactants other than those mentioned above (e.g., lipophilic nonionic surfactants, hydrophilic nonionic surfactants), higher aliphatic alcohols, polyhydric alcohols, water-soluble polymers (e.g., natural water-soluble polymers, semi-synthetic water-soluble polymers, synthetic water-soluble polymers), ultraviolet absorbers, sequestering agents, pH adjusters, vitamins, antioxidants, and antioxidant aids.

[0064] Examples of powder components include inorganic powders (e.g., talc, kaolin, mica, sericite, muscovite, phlogopite, synthetic mica, lepidolite, biotite, vermiculite, bentonite, hectorite, laponite, magnesium carbonate, calcium carbonate, aluminum silicate, barium silicate, calcium silicate, magnesium silicate, strontium silicate, metal tungstate, magnesium, silica, zeolite, barium sulfate, calcined calcium sulfate (calcined gypsum), calcium phosphate, fluorapatite, hydroxyapatite, ceramic powder, , metal soaps (e.g., zinc myristate, calcium palmitate, aluminum stearate), boron nitride); organic powders (e.g., polyamide resin powder (nylon powder), polyethylene powder, polymethyl methacrylate powder, polystyrene powder, styrene-acrylic acid copolymer resin powder, benzoguanamine resin powder, polytetrafluoroethylene powder, cellulose powder); inorganic white pigments (e.g., titanium dioxide, zinc oxide); inorganic red pigments (e.g., iron oxide (red iron), iron titanate); inorganic brown pigments (e.g., γ-iron oxide); inorganic yellow pigments (e.g., , yellow iron oxide, ochre); inorganic black pigments (e.g., black iron oxide, low-order titanium oxide); inorganic purple pigments (e.g., mango violet, cobalt violet); inorganic green pigments (e.g., chromium oxide, chromium hydroxide, cobalt titanate); inorganic blue pigments (e.g., ultramarine, Prussian blue); pearl pigments (e.g., titanium oxide coated mica, titanium oxide coated bismuth oxychloride, titanium oxide coated talc, colored titanium oxide coated mica, bismuth oxychloride, fish scale foil); metal powder pigments (e.g., aluminum powder, copper powder); zirconia organic pigments such as ammonium, barium, or aluminum lakes (e.g., organic pigments such as Red 201, Red 202, Red 204, Red 205, Red 220, Red 226, Red 228, Red 405, Orange 203, Orange 204, Yellow 205, Yellow 401, and Blue 404, Red 3, Red 104, Red 106, Red 227, Red 230, Red 401, Red 505, Orange 205, Yellow 4, Yellow 5, Yellow 202, Yellow 203, Green 3, and Blue 1); natural pigments (e.g., chlorophyll, beta-carotene).

[0065] Examples of amphoteric surfactants include imidazoline-based amphoteric surfactants (e.g., 2-undecyl-N,N,N-(hydroxyethylcarboxymethyl)-2-imidazoline sodium, 2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt); betaine-based surfactants (e.g., 2-heptadecyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryldimethylaminoacetic acid betaine, alkyl betaine, amido betaine, and sulfobetaine).

[0066] Examples of lipophilic nonionic surfactants include sorbitan fatty acid esters (e.g., sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, diglycerol sorbitan penta-2-ethylhexyl, diglycerol sorbitan tetra-2-ethylhexyl); glycerin polyglycerin fatty acids (e.g., glycerin monocottonseed oil fatty acid, glycerin monoerucate, glycerin sesquioleate, glycerin monostearate, glycerin α,α'-oleic acid pyroglutamate, glycerin monostearate malate); propylene glycol fatty acid esters (e.g., propylene glycol monostearate); hydrogenated castor oil derivatives; and glycerin alkyl ethers.

[0067] Examples of hydrophilic nonionic surfactants include polyoxyethylene sorbitan fatty acid esters (e.g., polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan tetraoleate); polyoxyethylene sorbitan fatty acid esters (e.g., polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan pentaoleate, polyoxyethylene sorbit monostearate); polyoxyethylene glycerin fatty acid esters (e.g., polyoxyethylene monooleates such as polyoxyethylene glycerin monostearate, polyoxyethylene glycerin monoisostearate, and polyoxyethylene glycerin triisostearate); polyoxyethylene fatty acid esters (e.g., polyoxyethylene distearate, polyoxyethylene monodiisostearate, and polyoxyethylene monoisostearate); acrylate, ethylene glycol distearate); polyoxyethylene alkyl ethers (e.g., polyoxyethylene lauryl ether, polyoxyethylene oleyl ether, polyoxyethylene stearyl ether, polyoxyethylene behenyl ether, polyoxyethylene 2-octyldodecyl ether, polyoxyethylene cholestanol ether); Pluronic types (e.g., Pluronic); polyoxyethylene-polyoxypropylene alkyl ethers (e.g., polyoxyethylene-polyoxypropylene-cetyl ether, polyoxyethylene-polyoxypropylene-2-decyltetradecyl ether, polyoxyethylene-polyoxypropylene-monobutyl ether, polyoxyethylene-polyoxypropylene-hydrogenated lanolin, polyoxyethylene-polyoxypropylene-glycerin ether); tetrapolyoxyethylene-tetrapolyoxypropylene-ethylenediamine condensates (e.g., Tetronic);Polyoxyethylene castor oil hydrogenated castor oil derivatives (e.g., polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil monoisostearate, polyoxyethylene hydrogenated castor oil triisostearate, polyoxyethylene hydrogenated castor oil monopyroglutamic acid monoisostearate diester, polyoxyethylene hydrogenated castor oil maleate); polyoxyethylene beeswax and lanolin derivatives (e.g., polyoxyethylene sorbitol beeswax); alkanolamides (e.g., coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide); polyoxyethylene propylene glycol fatty acid esters; polyoxyethylene alkylamines; polyoxyethylene fatty acid amides; sucrose fatty acid esters; alkylethoxydimethylamine oxide; trioleyl phosphate.

[0068] As the higher aliphatic alcohol, for example, a higher aliphatic alcohol having 16 or more carbon atoms can be used for the purpose of improving usability, etc. Specific examples include cetyl alcohol, cetostearyl alcohol, stearyl alcohol, behenyl alcohol, and batyl alcohol.

[0069] Examples of polyhydric alcohols include ethylene glycol, propylene glycol, 1,3-butylene glycol, dipropylene glycol, polyethylene glycol, polypropylene glycol, and polybutylene glycol.

[0070] Examples of natural water-soluble polymers include plant-derived polymers (e.g., gum arabic, tragacanth gum, galactan, guar gum, carob gum, karaya gum, locust bean gum, tamarind gum, carrageenan, pectin, agar, quince seed, algae colloid (cassow extract), starch (rice, corn, potato, wheat), glycyrrhizic acid); microbial-derived polymers (e.g., xanthan gum, dextran, succinoglucan, pullulan); and animal-derived polymers (e.g., collagen, casein, albumin, gelatin).

[0071] Examples of semi-synthetic water-soluble polymers include starch-based polymers (e.g., carboxymethyl starch, methylhydroxypropyl starch); cellulose-based polymers (methyl cellulose, ethyl cellulose, methylhydroxypropyl cellulose, hydroxyethyl cellulose, sodium cellulose sulfate, dialkyldimethylammonium cellulose sulfate, hydroxypropyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, crystalline cellulose, cellulose powder, and hydrophobically modified compounds of these polymers (e.g., partially stearoxy-modified compounds), and cationically modified compounds of these polymers); alginic acid-based polymers (e.g., sodium alginate, propylene glycol alginate); and sodium pectinate.

[0072] Examples of synthetic water-soluble polymers include vinyl polymers (e.g., polyvinyl alcohol, polyvinyl methyl ether, polyvinylpyrrolidone, carboxyvinyl polymers); polyoxyethylene polymers (e.g., polyoxyethylene-polyoxypropylene copolymers of polyethylene glycol 20,000, 40,000, and 60,000); poly(dimethyldiallylammonium halide)-type cationic polymers; cationic polymers of copolymers of dimethyldiallylammonium halide and acrylamide; acrylic polymers (e.g., sodium polyacrylate, polyethyl acrylate, polyacrylamide); polyethyleneimine; cationic polymers; and AlMg silicate (Veegum).

[0073] Examples of the ultraviolet absorber include benzoic acid-based ultraviolet absorbers (e.g., para-aminobenzoic acid (hereinafter abbreviated as "PABA"), PABA monoglycerin ester, N,N-dipropoxy PABA ethyl ester, N,N-diethoxy PABA ethyl ester, N,N-dimethyl PABA ethyl ester, N,N-dimethyl PABA butyl ester, N,N-dimethyl PABA ethyl ester); anthranilic acid-based ultraviolet absorbers (e.g., homomenthyl-N-acetylanthranilate); salicylic acid-based ultraviolet absorbers (e.g., amyl salicylate, cinnamate, menthyl salicylate, homomenthyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, p-isopropanol phenyl salicylate; cinnamic acid-based ultraviolet absorbers (e.g., octyl cinnamate, ethyl-4-isopropyl cinnamate, methyl-2,5-diisopropyl cinnamate, ethyl-2,4-diisopropyl cinnamate, methyl-2,4-diisopropyl cinnamate, propyl-p-methoxycinnamate, isopropyl-p-methoxycinnamate, isoamyl-p-meth cyclohexyl-p-methoxycinnamate, octyl-p-methoxycinnamate (2-ethylhexyl-p-methoxycinnamate), 2-ethoxyethyl-p-methoxycinnamate, cyclohexyl-p-methoxycinnamate, ethyl-α-cyano-β-phenylcinnamate, 2-ethylhexyl-α-cyano-β-phenylcinnamate, glyceryl mono-2-ethylhexanoyl-di-para-methoxycinnamate; benzophenone-based ultraviolet absorbers (e.g., 2,4-dihydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, phenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonate, 4-phenylbenzophenone, 2-ethylhexyl-4'-phenyl-benzophenone-2-carboxylate, 2-hydroxy-4-n-octoxybenzophenone, 4-hydroxy-3-carboxybenzophenone);3-(4'-Methylbenzylidene)-d,l-camphor; 3-benzylidene-d,l-camphor; 2-phenyl-5-methylbenzoxazole; 2,2'-hydroxy-5-methylphenylbenzotriazole; 2-(2'-hydroxy-5'-t-octylphenyl)benzotriazole; 2-(2'-hydroxy-5'-methylphenylbenzotriazole; Dianisoylmethane; 4-Methoxy-4'-t-butyldibenzoylmethane; 5-(3,3-dimethicone triazine-based ultraviolet absorbers (e.g., 2-4[(2-hydroxy-3-dodecyloxypropyl)oxy]-2-hydroxyphenyl)-4,6-bis(2,4-dimethylphenyl)-1,3,5-triazine, 2-4[(2-hydroxy-3-tridecyloxypropyl)oxy]-2-hydroxyphenyl)-4,6-bis(2,4-dimethylphenyl)-1,3,5-triazine);

[0074] Examples of sequestering agents include 1-hydroxyethane-1,1-diphosphonic acid, 1-hydroxyethane-1,1-diphosphonic acid tetrasodium salt, disodium edetate, trisodium edetate, tetrasodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, phosphoric acid, citric acid, ascorbic acid, succinic acid, edetic acid, and trisodium ethylenediaminehydroxyethyltriacetate.

[0075] Examples of pH adjusters include buffers such as lactic acid-sodium lactate, citric acid-sodium citrate, and succinic acid-sodium succinate.

[0076] Examples of vitamins include vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin C, vitamin E and derivatives thereof, pantothenic acid and derivatives thereof, and biotin.

[0077] Examples of antioxidants include tocopherols, dibutylhydroxytoluene, butylhydroxyanisole, and gallic acid esters.

[0078] Examples of antioxidant aids include phosphoric acid, citric acid, ascorbic acid, maleic acid, malonic acid, succinic acid, fumaric acid, cephalin, hexametaphosphate, phytic acid, and ethylenediaminetetraacetic acid.

[0079] Other optional ingredients that can be added include, for example, preservatives (e.g., ethylparaben, butylparaben, 1,2-alkanediol, phenoxyethanol, methylchloroisothiozolinone); anti-inflammatory agents (e.g., glycyrrhizinic acid derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, zinc oxide, allantoin); whitening agents (e.g., saxifrage extract, arbutin); various extracts (e.g., Phellodendron bark, Coptis chinensis, Lithospermum root, Peony, Swertia japonica, Birch, sage, Loquat, Carrot, Aloe, Mallow, Iris, Grape, Job's tears, Luffa, Lily, Saffron, Cnidium rhizome, Angelica acutiloba, Garlic, Chili pepper, Citrus fruit, Angelica acutiloba, Seaweed), activators (e.g., Royal jelly, photosensitizers, cholesterol derivatives); blood circulation promoters (e.g., Examples include nonylic acid valenylamide, nicotinic acid benzyl ester, nicotinic acid β-butoxyethyl ester, capsaicin, zingerone, cantharides tincture, ichthammol, tannic acid, α-borneol, tocopherol nicotinate, inositol hexanicotinate, cyclandelate, cinnarizine, tolazoline, acetylcholine, verapamil, cepharanthine, and γ-oryzanol; antiseborrheic agents (e.g., sulfur, thianthol); anti-inflammatory agents (e.g., tranexamic acid, thiotaurine, and hypotaurine); aromatic alcohols (benzyl alcohol and benzyloxyethanol); moisturizers (e.g., dynamite glycerin); thickeners; film-forming agents; skin nutrients; fragrances other than those mentioned above (e.g., limonene (LogP: 4.8), damascone (LogP: 4.3)); and scrubs.

[0080] <<Uses of the oil-in-water emulsion composition>> The oil-in-water emulsion composition of the present disclosure can be suitably used as an agent that is applied to the skin, for example, an external skin agent such as a cosmetic, quasi-drug, or pharmaceutical.

[0081] The emulsion composition of the present disclosure can be in the form of, for example, a milky lotion, a cream, or a liquid.

[0082] When the emulsion composition of the present disclosure is used, for example, in the field of cosmetics, there are no particular limitations on the product form, and examples thereof include facial cosmetics such as lotion, serum, emulsion, and pack; makeup cosmetics such as foundation and eye shadow; sunscreen cosmetics (sunscreen agents); body cosmetics; skin cleansers such as makeup remover and body shampoo; hair cosmetics such as hair liquid, hair tonic, hair conditioner, shampoo, rinse, and hair growth agent; shaving cosmetics such as shaving cream, pre-shave lotion, and after-shave lotion; ointments, etc.

[0083] <<Method for producing oil-in-water emulsion composition>> The emulsion composition of the present disclosure can be prepared by known methods such as a dispersion method or an aggregation method.

[0084] The dispersion method is a method of mechanically breaking down clumps of the dispersed phase into smaller particles. Specifically, it is a method of emulsifying by utilizing the crushing force of an emulsifier, and an example of such a method is a high-pressure emulsification method in which high shear force is applied using a high-pressure homogenizer.

[0085] The aggregation method is a colloid preparation method that utilizes surface chemistry, in which a uniformly dissolved state is converted into a supersaturated state by some means, resulting in the emergence of a dispersed phase. Specific methods include HLB temperature emulsification, phase inversion emulsification, non-aqueous emulsification, D-phase emulsification, and liquid crystal emulsification. Among these, D-phase emulsification is preferred from the viewpoint of emulsion stability.

[0086] As an example, a suitable method for producing the emulsion composition of the present disclosure will be described below.

[0087] A first aqueous phase part is prepared containing the nonionic surfactant and anionic surfactant represented by Formulas 1 to 3 above, and water. Next, an oil phase part is prepared containing a drug having a LogP value of -0.7 to 4.0 and an oil component. The oil phase part is blended with all or a portion of the first aqueous phase part to prepare a preliminary emulsion. If any first aqueous phase part remains, the preliminary emulsion is mixed with the remainder of the first aqueous phase part. If no first aqueous phase part remains, the preliminary emulsion is mixed with a second aqueous phase part containing water, thereby preparing the oil-in-water emulsion composition of the present disclosure.

[0088] For example, an anionic surfactant may be blended into the aqueous phase part, and a nonionic surfactant of Formula 1 to Formula 3 may be blended into the oil phase part; however, blending the nonionic surfactant of Formula 1 to Formula 3 and the anionic surfactant into the aqueous phase parts, particularly the first aqueous phase part, simultaneously can further improve emulsion stability.

[0089] To obtain fine, uniform emulsion particles (oil droplets), it is preferable to incorporate a dihydric alcohol into the first aqueous phase part, such as at least one glycol component selected from dipropylene glycol, 1,3-butylene glycol, propylene glycol, and polyethylene glycol.

[0090] The amount of dihydric alcohol such as a glycol component is not particularly limited, and can be, for example, 40% by mass or more, 45% by mass or more, or 50% by mass or more relative to the total amount of the aqueous phase parts, and can be 80% by mass or less, 75% by mass or less, or 70% by mass or less.

[0091] The aqueous phase part and / or the oil phase part may be heated as desired. The heating temperature is not particularly limited and may be, for example, 40°C or higher, 50°C or higher, or 60°C or higher, and 90°C or lower, 80°C or lower, or 70°C or lower. [Example]

[0092] The present disclosure will be described in more detail below with reference to examples, but the present disclosure is not limited to these. Note that, hereinafter, unless otherwise specified, the blending amounts are expressed in parts by mass.

[0093] Examples 1 to 2 and Comparative Examples 1 to 5 The oil-in-water emulsion compositions obtained by the formulations shown in Table 1 and the production methods shown below were subjected to the following evaluations, and the results are shown in Table 1.

[0094] Evaluation Method (Emulsion stability test: Evaluation based on the average particle size of oil droplets) The average particle size of oil droplets (emulsified particles) in the oil-in-water emulsion composition was measured by direct visual observation using an optical microscope (BX53, manufactured by Olympus Corporation) and calculating the average diameter of the circle equivalent to the projected area of 10 arbitrarily selected oil droplets. The average particle size was measured immediately after preparation of the composition, after storage at 50°C for 30 days, and after storage under temperature cycling conditions of 0 to 40°C (2 cycles of 0 to 40°C per day, with 2-hour residence times at each of 0°C and 40°C).

[0095] The oil droplet growth rate was calculated from the average particle size of the oil droplets immediately after production and the average particle size of the oil droplets after storage at 50°C for 30 days or after storage under temperature cycle conditions of 0 to 40°C for 30 days, using the following formula 5. Note that in Table 1, for example, when the average particle size of the oil droplets is expressed as "2 to 10," the average value of the sum of the lower limit and upper limit, 6 μm (= (2 + 10) / 2), is introduced into formula 5: Growth rate (%) = {(average particle size of oil droplets after 30 days storage at 50°C or after 30 days storage under temperature cycle conditions of 0 to 40°C - average particle size of oil droplets immediately after production) × 100} / (average particle size of oil droplets immediately after production) ... Equation 5

[0096] The emulsion stability was evaluated according to the following criteria using the rate of increase in oil droplets after 30 days of storage under temperature cycle conditions of 0 to 40°C, where A and B are considered to be acceptable, and C and D are considered to be unacceptable.

[0097] A: The rate of increase in oil droplets was 10% or less. B: The increase rate of oil droplets was more than 10% and 50% or less. C: The increase rate of oil droplets was more than 50% and less than 100%. D: The increase rate of oil droplets was more than 100%.

[0098] <Method for producing oil-in-water emulsion composition> Example 1 Oil-in-water emulsion compositions were produced by the following method using the formulation shown in Table 1. Here, the numbers shown below correspond to the numbers indicating the components on the left side of the formulation in Table 1.

[0099] To a portion of the ion-exchanged water No. 15, surfactants No. 1 to No. 3 and No. 5, and materials No. 16 to No. 21 were added, and the mixture was heated to 70°C and mixed uniformly to prepare a first aqueous phase part.

[0100] After uniformly mixing the oil components No. 9 to No. 13, the chemical No. 14 was added and mixed uniformly to prepare the oil phase part.

[0101] The oil-phase part was added to the first aqueous phase part and mixed uniformly to prepare a preliminary emulsion. The remainder of No. 15 ion-exchanged water (the second aqueous phase part) was added to this preliminary emulsion and mixed uniformly to prepare the oil-in-water emulsion composition of Example 1.

[0102] (Example 2 and Comparative Examples 1 to 5) Oil-in-water emulsion compositions of Example 2 and Comparative Examples 1 to 5 were prepared in the same manner as Example 1, except for changing the formulation to that shown in Table 1. Here, the other nonionic surfactants No. 6 and No. 7 in Table 1 were added simultaneously when the aqueous phase part was prepared, and behenyl alcohol No. 8 was added simultaneously when the oil phase part was prepared. [Table 1]

[0103] <result> As is clear from Table 1, in the case of the emulsion composition of Comparative Example 1, which contains the nonionic surfactants of Formulas 1 to 3 but does not contain anionic surfactants, the rate of increase in oil droplets after storage at 50°C for 30 days could be suppressed to about 50%, but after storage for 30 days under temperature cycle conditions of 0 to 40°C, the increase due to coalescence of oil droplets could not be suppressed.

[0104] Furthermore, the emulsion compositions of Comparative Examples 2 and 3, which used other nonionic surfactants and anionic surfactants, were unable to suppress the increase in oil droplets even after storage at 50°C for 30 days.

[0105] Furthermore, even in the emulsion compositions of Comparative Examples 4 and 5, which used a surfactant and a higher aliphatic alcohol that has the ability to reinforce the interfacial film, the increase in oil droplets could not be suppressed after 30 days of storage under temperature cycle conditions of 0 to 40°C.

[0106] On the other hand, in the case of the emulsion compositions of Examples 1 and 2, which contain an anionic surfactant in addition to the nonionic surfactants of Formulas 1 to 3, no increase in oil droplets was observed after 30 days of storage at 50°C or after 30 days of storage under temperature cycle conditions of 0 to 40°C, indicating that good emulsion stability was obtained.

[0107] It was also found that the emulsion compositions of Examples 1 and 2 did not contain higher aliphatic alcohols, and therefore could reduce stickiness compared to the emulsion compositions of Comparative Examples 4 and 5.

[0108] <Formulation example of oil-in-water emulsion composition> Formulation examples of the oil-in-water emulsion composition of the present disclosure are given below, but the present disclosure is not limited to these examples.

[0109] <Formulation example 1: Emulsion> (component) (mass%) (1) Polyoxyethylene (6 moles) distearyl 0.3 (2) Polyoxyethylene (10 mol) phytosterol 0.5 (3) Polyoxyethylene (20 mol) stearyl 0.27 (4) Sodium stearoyl N-methyl taurate 0.05 (5) Microcrystalline wax 0.5 (6) Vaseline 5.0 (7) Diisostearyl malate 2.0 (8) Glyceryl diisostearate 1.0 (9) Pentaerythrityl tetraethylhexanoate 5.0 (10) Squalane 5.0 (11) Dimethylpolysiloxane 6CS 3.0 (12) Amino-modified polymeric silicone / Dimethylpolysiloxane 20CS 10% solution 0.5 (13) Phenylethylresorcinol 0.5 (14) Dynamite Glycerin 7.0 (15) Dipropylene glycol 5.0 (16) 1,3-butylene glycol 7.0 (17) Mabbit 2.0 (18)PEG1000 1.0 (19) Regular alcohol 95% 5.0 (20) Phenoxyethanol 0.5 (21) Carboxyvinyl polymer 0.015 (22) Caustic potash 0.63 (23) EDTA2Na 2H2O 0.03 (24) Ion-exchanged water residue

[0110] <Formulation example 2: Emulsion> (component) (mass%) (1) Polyoxyethylene (8 moles) distearate 0.2 (2) Polyoxyethylene (10 mol) cholesteryl 0.6 (3) Polyoxyethylene (10 mol) monostearate 0.2 (4) Sodium stearoyl glutamate 0.01 (5) Vaseline 5.0 (6) Diisostearyl malate 2.0 (7) Glyceryl diisostearate 1.0 (8) Pentaerythrityl tetraethylhexanoate 5.0 (9) Squalane 5.0 (10) Dimethylpolysiloxane 6CS 3.0 (11) Amino-modified polymeric silicone / Dimethylpolysiloxane 20CS 10% solution 0.5 (12) 4-(1-phenylethyl)-1,3-diol 1.0 (13) Dynamite Glycerin 7.0 (14) Dipropylene glycol 5.0 (15) 1,3-butylene glycol 7.0 (16) Mabbit 2.0 (17)PEG1000 1.0 (18) Regular alcohol 95% 5.0 (19) Phenoxyethanol 0.5 (20) Carboxyvinyl polymer 0.015 (21) Caustic potash 0.63 (22) EDTA2Na 2H2O 0.03 (23) Ion-exchanged water residue

[0111] <Formulation example 3: Emulsion> (component) (mass%) (1) Polyoxyethylene (6 mol) behenyl 0.3 (2) Polyoxyethylene (20 mol) phytosteryl 0.8 (3) Polyoxyethylene (7 mol) cetyl ether 0.3 (4) Sodium stearoyl N-methyl taurate 0.1 (5)Fragrance 0.1 (6) Pentaerythritol tetra 2-ethylhexanoate 2.0 (7) α-olefin oligomer 3.0 (8) Dimethylpolysiloxane 2.0 (9) Refined Vaseline 1.0 (10) Nicotinamide 5.0 (11) Dipropylene glycol 5.0 (12) 1,3-butylene glycol 2.0 (13) Phenoxyethanol 0.5 (14) Glycerin 4.0 (15) Carboxyvinyl polymer 0.03 (16) Potassium hydroxide 0.01 (17) Tranexamic acid 0.1 (18) Citric acid 0.02 (19) Sodium citrate 0.08 (20) Ion-exchanged water residue

[0112] <Formulation example 4: Emulsion> (component) (mass%) (1) Polyoxyethylene (6 mol) behenyl 0.3 (2) Polyoxyethylene (20 mol) phytosteryl 0.8 (3) Polyoxyethylene (7 mol) cetyl ether 0.3 (4) Sodium lauroyl N-methyl taurate 0.05 (5)Fragrance 0.1 (6) Pentaerythritol tetra 2-ethylhexanoate 2.0 (7) α-olefin oligomer 3.0 (8) Dimethylpolysiloxane 2.0 (9) Refined Vaseline 1.0 (10) Phenylethylresorcinol 1.0 (11) Dipropylene glycol 5.0 (12) 1,3-butylene glycol 2.0 (13) Phenoxyethanol 0.5 (14) Glycerin 4.0 (15) Carboxyvinyl polymer 0.03 (16) Potassium hydroxide 0.01 (17) Potassium 4-methoxysalicylate 3.0 (18) Citric acid 0.02 (19) Sodium citrate 0.08 (20) Ion-exchanged water residue

[0113] The above ingredients were emulsified by a conventional method to obtain each emulsion, which had excellent emulsion stability.

[0114] <Formulation example 5: Non-alcoholic fragrance> (component) (mass%) (1) Polyoxyethylene (6 mol) behenyl 0.27 (2) Polyoxyethylene (20 mol) phytosteryl 0.8 (3) Polyoxyethylene (7 mol) cetyl ether 0.27 (4) Sodium lauroyl N-methyl taurate 0.02 (5) Isododecane 15.0 (6) Glyceryl tri-2-ethylhexanoate 15.0 (7) Fragrance (Anisaldehyde (LogP: 1.8)) 3.0 (8) Dipropylene glycol 5.0 (9) 1,3-butylene glycol 5.0 (10) Phenoxyethanol 0.5 (11) Glycerin 7.0 (12) EDTA2Na 2H2O 0.03 (13) Ion-exchanged water residue

[0115] The above ingredients were emulsified by a conventional method to obtain a non-alcoholic fragrance. The obtained non-alcoholic fragrance had excellent emulsion stability.

Claims

1. an aqueous dispersion medium, and Oil droplets dispersed in the aqueous dispersion medium An oil-in-water emulsion composition comprising: the oil droplets contain a drug, a surfactant, and an oil; the drug has a LogP value of −0.7 to 4.0, and the content of the drug in the composition is 0.1% by mass or more relative to the total amount of the composition; The surfactant includes a nonionic surfactant and an anionic surfactant represented by the following formulas 1 to 3: Oil-in-water emulsion composition: 【Chemical Formula 1】 In formula 1, R １ is a linear acyl group or a linear alkyl group having 16 to 24 carbon atoms, R ２ is an alkyl group having 2 to 4 carbon atoms, R ３ is a linear acyl group or a linear alkyl group having 16 to 24 carbon atoms, and k is an integer from 4 to 15; 【Chemistry 2】 In formula 2, R ４ is a linear aliphatic acid residue or a linear aliphatic alcohol residue having 16 to 24 carbon atoms, R ５ is an alkyl group having 2 to 4 carbon atoms, and k is an integer from 5 to 20; 【Chemistry 3】 In formula 3, R ６ is a cholesterol or phytosterol residue, R ７ is an alkyl group having 2 to 4 carbon atoms, and k is an integer from 5 to 30.

2. The composition according to claim 1, wherein the content of the drug in the composition is 0.1 to 5% by mass based on the total amount of the composition.

3. the content of the nonionic surfactant of formula 1 in the composition is 0.1 to 2% by mass based on the total amount of the composition; the content of the nonionic surfactant of formula 2 in the composition is 0.1 to 2% by mass based on the total amount of the composition; The content of the nonionic surfactant of formula 3 in the composition is 0.3 to 6% by mass based on the total amount of the composition, and The content of the anionic surfactant in the composition is 0.01 to 0.1% by mass based on the total amount of the composition. The composition according to claim 1 or 2.

4. The composition according to any one of claims 1 to 3, wherein the anionic surfactant is at least one selected from an alkanoyl-N-alkyl taurine salt and an alkanoyl glutamate salt.

5. The composition according to any one of claims 1 to 4, wherein the agent is at least one selected from phenylethyl resorcinol, 4-(1-phenylethyl)-1,3-diol, benzeneoxothiazolidinecarboxylic acid, nicotinamide, xanthine, ellagic acid, ferulic acid, apigenin, salicylic acid, phloretin, resveratrol, and a fragrance having a Log P value of -0.7 to 4.

0.

6. The composition according to any one of claims 1 to 5, wherein the oil is at least one selected from the group consisting of liquid oils and fats, solid oils and fats, waxes, hydrocarbon oils, higher fatty acids, synthetic ester oils, and silicone oils.

7. preparing a first aqueous phase part containing the nonionic surfactants of formulas 1 to 3, the anionic surfactant, and water; An oil phase part containing the drug and the oil is prepared, The oil phase part is blended with a part or all of the first aqueous phase part to prepare a preliminary emulsion; mixing the pre-emulsion with the remainder of the first aqueous phase part, or mixing the pre-emulsion with a second aqueous phase part containing water; A method for producing the oil-in-water emulsion composition according to any one of claims 1 to 6.

8. The method according to claim 7, wherein the first aqueous phase part contains at least one glycol component selected from dipropylene glycol, 1,3-butylene glycol, propylene glycol, and polyethylene glycol.

9. The production method according to claim 8, wherein the content of the glycol component is 40 to 80% by mass relative to the total amount of the first aqueous phase part.

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