JP2017081901A - Oil-in-water emulsion composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an oil-in-water emulsion composition that has stabilized emulsification while comprising lower alcohol.SOLUTION: The present invention provides an oil-in-water emulsion composition comprising lower alcohol, and further comprising diclofenac or salt thereof, and thickener.SELECTED DRAWING: None

Description

  The present invention relates to an oil-in-water emulsion composition. More specifically, the present invention relates to an oil-in-water emulsified composition containing a lower alcohol and having a stable emulsification.

  Conventionally, skin external preparations applied to affected areas such as lotions, creams, gels and the like containing anti-inflammatory analgesics that treat or relieve symptoms such as stiff shoulders, low back pain, muscle pain, and joint pain are known. For example, Patent Document 1 discloses a liquid agent in which a phenylacetic acid derivative is dissolved in a relatively large amount of ethanol. In this solution, in addition to the anti-inflammatory analgesic effect of the phenylacetic acid derivative, which is an active ingredient, a large amount of ethanol volatilizes to give a cold feeling to the affected area with heat. It has become.

  In order to treat or alleviate symptoms such as stiff shoulders, back pain, muscle pain, and joint pain, it is also effective to promote blood circulation in the affected area. Vitamin E is mentioned as a blood circulation promotion component used for a skin external preparation. Since vitamin E is an oil-soluble component, when it is used as a skin external preparation, it is prepared as an emulsified skin external preparation such as a cream or an ointment containing the oil component (Patent Document 2).

  Here, if a volatile lower alcohol such as ethanol is blended in the emulsified skin external preparation as in Patent Document 2, an excellent skin having both the effect of an oily active ingredient of vitamin E and the cooling effect of the lower alcohol It is thought that an external preparation is obtained.

  However, since lower alcohols such as ethanol have the property of dissolving in both water and oil, there is a problem that emulsification is not stable when the lower alcohol is blended in the emulsion.

JP 2003-286161 A JP 2000-256167 A

  The main object of the present invention is to provide an oil-in-water emulsified composition containing a lower alcohol and having a stable emulsification. Another object of the present invention is to provide an oil-in-water emulsified skin external preparation, which contains a lower alcohol and has a stable emulsification, particularly a skin external preparation having anti-inflammatory analgesic action.

  The present inventors can stabilize the emulsifiability by blending diclofenac or a salt thereof and a thickener for an oil-in-water emulsion composition in which emulsification becomes unstable when blended with a lower alcohol, It has been found that even if a relatively large amount of a lower alcohol is blended, an emulsion stability after long-term storage is ensured and an oil-in-water emulsion composition in which separation is significantly suppressed can be obtained.

  The present invention has been completed based on such findings, and provides the following oil-in-water emulsion composition and an emulsion stabilization method for an oil-in-water emulsion composition.

(1) Oil-in-water emulsion composition (1-1). An oil-in-water emulsion composition comprising a lower alcohol, diclofenac or a salt thereof, and a thickener.
(1-2). Furthermore, the oil-in-water emulsion composition of (1-1) containing a monoterpene.
(1-3). Furthermore, the oil-in-water emulsion composition as described in (1-1) or (1-2) containing a polyhydric alcohol.
(1-4). The oil-in-water emulsion composition according to any one of (1-1) to (1-3), wherein the content of the lower alcohol is 3 to 30% by weight.
(1-5). The oil-in-water emulsion composition according to any one of (1-1) to (1-4), which is a skin external preparation.

(2) Emulsification stabilization method of oil-in-water emulsion composition containing lower alcohol (2-1). A method for stabilizing an oil-in-water emulsion composition containing a lower alcohol, wherein diclofenac or a salt thereof and a thickener are further added to the oil-in-water emulsion composition.
(2-2). Furthermore, the emulsion stabilization method as described in (2-1) containing at least 1 sort (s) selected from the group which consists of a monoterpene and a polyhydric alcohol.
(2-3). The emulsion stabilization method as described in (2-1) or (2-2) whose content of a lower alcohol is 3 to 30 weight%.
(2-4). The emulsion stabilization method according to any one of (2-1) to (2-3), wherein the oil-in-water emulsion composition is a skin external preparation.

  According to the present invention, it is possible to significantly suppress and improve the decrease in emulsification stability due to the incorporation of the lower alcohol in the oil-in-water emulsion composition. As a result, the present invention provides an oil-in-water emulsion composition in which a lower alcohol is contained in a relatively large amount of 3% by weight or more, 5% by weight or more, particularly 10% by weight or more, and the emulsion stability after long-term storage is ensured. can do. Moreover, according to the present invention, an oil-in-water emulsified skin external preparation having a therapeutic effect and a high feeling of use, which has both an anti-inflammatory analgesic effect of diclofenac or a salt thereof and a cooling effect by volatilization of lower alcohol, can be provided.

(1) Oil-in-water emulsion composition Hereinafter, the oil-in-water emulsion composition of the present invention will be described in detail.

  The oil-in-water emulsion composition of the present invention is an oil-in-water emulsion composition containing a lower alcohol, further diclofenac or a salt thereof (hereinafter collectively referred to as “diclofenacs”) and a thickener. It is characterized by containing.

(Lower alcohol)
In the present invention, the “lower alcohol” means a monovalent alcohol having 1 to 4 carbon atoms. Specific examples include methanol, ethanol, propanol, isopropanol, and butanol. Ethanol and isopropanol are preferable, and ethanol is more preferable.

  Although the content (total amount) of the lower alcohol in the oil-in-water emulsion composition of the present invention is not limited, the viewpoint of imparting a cooling effect due to volatilization, the decrease in emulsion stability due to the lower alcohol, the diclofenacs and the increase thereto. From the viewpoint of stabilization of emulsification by blending with a sticking agent, the lower limit may be 3% by weight or more, preferably 5% by weight or more, and more preferably 10% by weight or more. More specifically, about 3 to 30% by weight, preferably about 5 to 25% by weight, and more preferably about 10 to 25% by weight.

  The oil-in-water emulsion composition of the present invention contains water, an oily component, and a surfactant as basic constituent components in order to obtain an oil-in-water emulsion composition.

(water)
Examples of water that can be used in the present invention include, but are not limited to, purified water, distilled water, sterilized water, and ion exchange water. Preferably it is purified water.

  Although the content rate of the water in the oil-in-water emulsion composition of this invention is not restrict | limited, Usually, about 20 to 80 weight%, Preferably about 30 to 70 weight% is mentioned.

(Oil component)
In the present invention, the oil component (oil phase) is a component constituting the oil phase of the emulsion composition of the present invention. For example, oily ingredients that are usually used in pharmaceuticals, quasi drugs, cosmetics, and the like can be widely used. Such oil components are not particularly limited, but are vegetable oils such as olive oil, wheat germ oil, rice bran oil, safflower oil, soybean oil, camellia oil, corn oil, rapeseed oil, sunflower oil, cottonseed oil, peanut oil; lard, fish oil, squalane Animal oils such as beeswax; mineral oils such as liquid paraffin, gelled hydrocarbons and petrolatum; lecithin derivatives such as soybean lecithin; fatty acid esters such as isopropyl myristate, isopropyl palmitate, cetyl palmitate, diethyl sebacate, and ethyl oleate Silicones such as dimethyl silicone and cyclic silicone; fatty acids such as oleic acid and linoleic acid; hormones such as ethinyl estradiol; essential oils such as fennel oil, clove oil, mint oil, eucalyptus oil, lemon oil; And waxes .

  Moreover, higher alcohol is mentioned as another oil-based component. Examples of the higher alcohol include aliphatic alcohols having 6 or more carbon atoms. Specific examples include cetanol, behenyl alcohol, myristyl alcohol, oleyl alcohol, stearyl alcohol, hexadecyl alcohol, lanolin alcohol, and the like.

  An oil component may be used individually by 1 type, and may be used in combination of 2 or more types arbitrarily. The oil component is preferably liquid at room temperature (25 ° C.) from the viewpoint of securing the fluidity of the oil-in-water emulsion composition. Among the oily components, preferred are vegetable oils, animal oils, mineral oils, and fatty acid esters, more preferably animal oils, minerals, because an emulsion composition having excellent thermal stability and fluidity can be prepared. Oils and fatty acid esters. In particular, liquid paraffin is preferably used alone as mineral oil or in combination with other oil components (vegetable oil, animal oil, mineral oil, fatty acid ester). Furthermore, it is preferable to mix | blend the said higher alcohol with these oil-based components (a vegetable oil, animal oil, mineral oil, fatty acid ester).

  Although the content of the oil component in the oil-in-water emulsion composition of the present invention is not limited, for example, about 1 to 60 parts by weight, preferably 5 to 100 parts by weight of water contained in the oil-in-water emulsion composition. About 50 parts by weight can be mentioned.

(Surfactant)
The surfactant is not particularly limited as long as it is usually used in pharmaceuticals, quasi drugs, cosmetics, and the like, but is preferably a nonionic surfactant from the viewpoint of thermal stability and fluidity. As the nonionic surfactant, a polyoxyethylene (hereinafter referred to as POE) addition type surfactant is suitable, for example, POE (10 to 50 mol) phytosterol ether, POE (10 to 50 mol) dihydrocholesterol ether. POE (10-50 mol) 2-octyldodecyl ether, POE (10-50 mol) decyl tetradecyl ether, POE (10-50 mol) oleyl ether, POE (10-50 mol) behenyl ether, POE (10-10 mol) 50 mol) cetyl ether, POE (5 to 30 mol) polyoxypropylene (5 to 30 mol) 2-decyltetradecyl ether, POE (10 to 50 mol) polyoxypropylene (2 to 30 mol) cetyl ether, etc. Oxyethylene alkyl ethers; these phosphoric acids Phosphate (sodium POE cetyl ether phosphate); POE (20-60 mol) sorbitan monooleate, POE (10-60 mol) sorbitan monoisostearate, POE (10-80 mol) glyceryl monoisostearate, POE (10-30 mol) glyceryl monostearate, POE (20-100) hydrogenated castor oil, POE (20-100) POE / polyoxypropylene modified silicone, POE / alkyl modified silicone, polyethylene glycol monolaurate, monopalmitic acid Polyethylene glycol, polyethylene glycol monostearate, polyethylene glycol dilaurate, polyethylene glycol dipalmitate, polyethylene glycol distearate, polyethylene glycol dioleate, di- Shinorein acid polyethylene glycol, and the like. These surfactants may be used individually by 1 type, and may be used in combination of 2 or more types arbitrarily.

  Although the content of the surfactant in the oil-in-water emulsion composition of the present invention is not limited, for example, about 10 to 100 parts by weight, preferably about 100 parts by weight, preferably 100 parts by weight of the oily component contained in the oil-in-water emulsion composition. About 20-70 weight part is mentioned.

(Diclofenac or its salt)
The oil-in-water emulsion composition of the present invention is characterized by further containing diclofenac or a salt thereof in addition to the above-described lower alcohol, water, oil component, and surfactant.
The diclofenac is an anti-inflammatory analgesic compound based on arylacetic acid, specifically phenylacetic acid. Here, the salt of diclofenac is preferably a pharmaceutically acceptable salt. Examples of the pharmaceutically acceptable salt include alkali metal salts such as diclofenac sodium salt and potassium salt; or alkaline earth metal salts such as lithium salt, calcium salt and magnesium salt. An alkali metal salt is preferable, and a sodium salt is more preferable.

  In the oil-in-water emulsion composition of the present invention, the content (total amount) of diclofenac or a salt thereof is not limited, but is, for example, about 0.1 to 5% by weight, preferably about 0.5 to 3% by weight, more preferably About 0.5-1.5 weight% is mentioned.

(Thickener)
The oil-in-water emulsion composition of the present invention is characterized by further containing a thickener in addition to the above-mentioned lower alcohol, water, oily component, surfactant, and diclofenac or a salt thereof. The thickener that can be used in the present invention is not particularly limited, and examples thereof include hypromellose (HPMC), hydroxypropylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, methylcellulose, carboxyvinyl polymer, and xanthan gum. Preferred are carboxyvinyl polymer, xanthan gum and hydroxypropyl cellulose, and more preferred are carboxyvinyl polymer and xanthan gum. These thickeners may be used individually by 1 type, and may be used in combination of 2 or more types arbitrarily.

  Although the content rate (total amount) of the thickener in the oil-in-water emulsion composition of this invention is not restrict | limited, For example, about 0.05 to 5 weight%, Preferably about 0.1 to 3 weight% is mentioned.

  The oil-in-water emulsion composition of the present invention includes at least one of monoterpene and polyhydric alcohol in addition to the above-mentioned lower alcohol, water, oil component, surfactant, diclofenac or salt thereof, and thickener. Can be blended.

(Monoterpene)
Monoterpenes that can be used in the present invention are not particularly limited, but monoterpene hydrocarbons such as limonene, pinene, and camphor; monoterpene alcohols such as citronellol, geraniol, linalool, menthol, terpineol, and borneol; citronellal, And monoterpene aldehydes such as citral and safranal; monoterpene ketones such as menthone, carbomenton and yonon. A monoterpene alcohol is preferable, and menthol is more preferable. These monoterpenes may be any of d-, l- and dl-forms. These may be used individually by 1 type, and may be used in combination of 2 or more types arbitrarily.

  When the monoterpene is blended with the oil-in-water emulsion composition of the present invention, the blending ratio (total amount) of the monoterpene is not limited, but is, for example, about 0.5 to 10% by weight, preferably about 1 to 6% by weight. Can be mentioned.

(Polyhydric alcohol)
The polyhydric alcohol that can be used in the present invention is not particularly limited. For example, ethylene glycol, propylene glycol, 1,3-butylene glycol, diethylene glycol, dipropylene glycol, triethylene glycol, 1,3-butanediol, Examples include isopropylene glycol, 1,2-pentanediol, 2-methyl-2,4-pentanediol, hexylene glycol, glycerin, sorbitol, and xylitol. From the viewpoint of solubility (compatibility) in diclofenac or a salt thereof, propylene glycol, 1,3-butylene glycol, glycerin and sorbitol are preferable. These may be used individually by 1 type and may be used in combination of 2 or more types arbitrarily.

  When the polyhydric alcohol is blended with the oil-in-water emulsion composition of the present invention, the blending ratio (total amount) is not limited, but is, for example, about 1 to 30% by weight, preferably about 2 to 25% by weight.

(Other ingredients)
If it is a range which does not impair the effect of this invention, if it is a range which does not impair the effect of this invention, it can mix | blend 1 type or 2 types or more together in the oil-in-water emulsion composition of this invention. For example, various additives such as stabilizers, preservatives, buffers, pH adjusters, fragrances and the like generally used for the preparation of liquid agents and semisolid agents can be mentioned. Is mentioned.

  Stabilizer: Dibutylhydroxytoluene, sodium edetate, sodium sulfite, dry sodium sulfite and the like.

  Preservatives: butylparaben, methylparapen, propylparapen, ethylparaben, sodium benzoate, benzyl alcohol, etc.

  Buffer: borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, epsilon-aminocaproic acid, aspartic acid, aspartate and the like.

  pH adjusters: inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, polyphosphoric acid, boric acid; lactic acid, acetic acid, citric acid, tartaric acid, malic acid, succinic acid, oxalic acid, gluconic acid, fumaric acid, propionic acid, acetic acid, Organic acids such as aspartic acid, epsilon-aminocaproic acid, glutamic acid, aminoethylsulfonic acid; inorganic bases such as sodium hydrogen carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide; monoethanolamine, Organic salts such as triethanolamine, diisopropanolamine, triisopropanolamine and lysine.

  Moreover, other active ingredients can be mix | blended with the oil-in-water type emulsion composition of this invention in the range which does not impair the effect of this invention. For example, anti-inflammatory analgesics other than diclofenac (indole acetic acid such as indomethacin; phenylacetic acid such as ibufenac, arcfenac, methazidic acid, ampenac and 4-biphenylacetic acid; indenyl acetic acid such as sulindac; pyrrole acetic acid such as tolmethine; And naphthyl acetates such as nabumetone), tocopherols (α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol) or their derivatives (tocopherol acetate, tocopherol succinate, tocopherol nicotinate, and tocopherol linolenate) Tocopherol organic acid ester), steroids (dexamethasone, dexamethasone hydrochloride, dexamethasone acetate, hydrocortisone hydrochloride, prednisolone valerate, prednisolone acetate, etc.), anti Stamine agents (diphenhydramine, diphenhydramine hydrochloride, chlorpheniramine maleate, etc.), local anesthetics (lidocaine, dibucaine, procaine, tetracaine, bupipacaine, mepipacaine, chloroprocaine, propalacaine, meprilucaine or salts thereof, benzoic acid alkyl esters (for example, Ethyl aminobenzoate, diethylaminoethyl parabutylaminohydrochloride), orthocaine, oxesasein, oxypolyentoxydecane, funnel extract, percaminpase, tesitdecitine, etc.), anti-inflammatory agents (glycyrrhetinic acid, dipotassium glycyrrhizinate, monoammonium glycyrrhetinate, Allantoin, salicylic acid, glycol salicylate, methyl salicylate, etc.), bactericides (benzalkonium chloride, decalinium chloride) , Benzethonium chloride, cetylpyridinium chloride, impropylmethylphenol, chlorhexidine hydrochloride, chlorhexidine gluconate, ammonia water, sulfadiazine, lactic acid, phenol, etc.), antipruritics (crotamiton, thianthol, etc.), skin protectants (collodion, castor oil, etc.) ), Blood circulation promoting components (nonylic acid vanillylamide, nicotinic acid benzyl ester, capsaicin, pepper extract, etc.), vitamins (vitamin A, B, C, D, etc.), mucopolysaccharide (chondroitin sulfate sodium, glucosamine, hyaluronic acid, etc.) Etc.

  Although it does not restrict | limit especially as a method to manufacture the oil-in-water type emulsion composition of this invention, For example, it can manufacture as follows. Aqueous phase (aqueous component: water, thickener, optionally mixed with other water-soluble components [for example, lower alcohol, polyhydric alcohol, etc.)] and oil phase (oil component: surfactant, if necessary) After mixing other oil-soluble components [for example, monoterpene etc.] using a mixer such as a homogenizer while heating, an emulsion is prepared, and then a lower alcohol in which diclofenac or a salt thereof is dissolved is added. The oil-in-water emulsion composition of the present invention can be prepared. In addition, although it does not restrict | limit as said heating temperature, Usually, 50-90 degreeC, Preferably 65-85 degreeC can be illustrated.

  Moreover, the oil-in-water type emulsion composition of this invention can also adjust pH by the manufacturing process as needed. The pH is not particularly limited, but can be adjusted to a range of usually pH 4.5-10. Preferably it is pH 5-9.5, More preferably, it is pH 5.5-9.0. The pH adjustment is usually performed using a pH adjuster.

  The oil-in-water emulsion composition of the present invention can be suitably used as a skin external preparation having the form of a liquid to semi-solid oil-in-water emulsion lotion, cream, or emulsion. Specifically, as an anti-inflammatory analgesic external preparation, it can be applied to the affected area of stiff shoulders or muscle fatigue to loosen or heal muscles.

(2) Emulsification stabilization method of oil-in-water emulsion composition containing lower alcohol The present invention improves the emulsion stability of an oil-in-water emulsion composition whose emulsion stability has been lowered by blending a lower alcohol. And provide a way to improve.

  The said method can be implemented by mix | blending diclofenac or its salt, and a thickener further to the oil-in-water emulsion composition containing a lower alcohol.

  The composition of the oil-in-water emulsified composition of interest and the type and blending ratio of the lower alcohol blended therein are as described in (1) above, and can be incorporated herein. Moreover, the kind of diclofenac or its salt mix | blended with this, the kind of thickener, and the mixture ratio with respect to the oil-in-water emulsion composition are also as above-mentioned (1), and can be used here.

  Furthermore, the emulsion stability of the oil-in-water emulsion composition containing a lower alcohol is blended with at least one selected from the group consisting of monoterpenes and polyhydric alcohols in addition to diclofenac or a salt thereof and a thickener. It improves more by doing. In particular, by incorporating both monoterpene and polyhydric alcohol, the emulsion stability of the oil-in-water emulsion composition containing lower alcohol is further improved, and long-term separation is suppressed even when stored under relatively harsh conditions. can do. The types of monoterpene and polyhydric alcohol used here, and the blending ratio thereof with respect to the oil-in-water emulsion composition are also as described in (1) above, and can be incorporated herein.

  Hereinafter, the present invention will be described based on experimental examples and examples. However, the experimental examples and examples are examples of the present invention, and the present invention is not limited to these experimental examples and examples.

Experimental example 1
Liquid to semi-solid oil-in-water emulsified cream formulations (Reference Example 1, Examples 1 to 12, Comparative Examples 1 to 6) having the formulations shown in Table 1 were prepared. Specifically, an oil phase and an aqueous phase (excluding diclofenac sodium and anhydrous ethanol) were prepared according to the formulation described in Table 1, and these were mixed at 80 ° C. to prepare an oil-in-water emulsion. . Thereafter, Examples 1 to 12 and Comparative Example 5 were prepared by gradually adding diclofenac sodium dissolved in absolute ethanol and mixing them completely and uniformly. The obtained liquid to semi-solid emulsion was filled in a screw tube with a cap of about 20 ml (screw tube No. 5 (27 × 55 mm), manufactured by Maruemu Co., Ltd.) in an amount of 18 ml. And in a constant temperature bath at 60 ° C. (dark place) and stored for one week.

  One week later, the temperature was returned to room temperature, the properties of the emulsion were visually confirmed, and storage stability (stored at 50 ° C. for 1 week, stored at 60 ° C. for 1 week) was evaluated based on the following criteria.

[Evaluation criteria]
A: No separation is observed. O: Almost no separation is observed. Δ: Some separation is observed. X: Clearly separation (aqueous phase is 1/4 or more of the whole) is recognized.

  The results are shown in Table 1 together with the prescription.

  Emulsions that did not contain ethanol (reference example) were stable without separation under any storage conditions, but it was confirmed that emulsification became unstable and separation occurred by adding ethanol to this (comparison) Example 3). The emulsification instability due to such ethanol blending is based on the formulation of Comparative Example 3, with the removal of monoterpene and polyhydric alcohol (Comparative Example 1), monoterpene removal (Comparative Example 2), monoterpene removal and ethanol blending amount. It was not improved even by the decrease in the amount (Comparative Example 4) and the removal of monoterpene and the incorporation of diclofenac Na (Comparative Example 5). Further, when the monoterpene and the polyhydric alcohol were removed and a thickener was added instead, although some improvement was observed, it was not sufficient (Comparative Example 6). On the other hand, it was confirmed that mixing the thickener and diclofenac Na did not separate under any storage condition and the emulsification was stabilized (Examples 1 and 2). In addition to blending polyhydric alcohol and / or monoterpene in addition to thickener and diclofenac Na, emulsification is further stabilized and particularly severe by blending both polyhydric alcohol and monoterpene. It was confirmed that separation was suppressed even when stored under conditions (Examples 3 to 12, particularly Examples 5 to 12). From these, the liquid to semi-solid oil-in-water emulsified creams (Examples 1 to 12) containing a lower alcohol such as ethanol are stable in emulsification by blending a thickener and diclofenac or a salt thereof. It was confirmed that it was not separated even after long-term storage. Moreover, when it apply | coated to the shoulder, it has confirmed that all had the cool feeling and the pain relief effect (anti-inflammatory analgesic effect) of a stiff shoulder.

Experimental example 2
Oil-in-water emulsified creams (Examples 13 to 23) having the formulations shown in Table 2 were prepared. Specifically, each of an aqueous phase and an oil phase was prepared and mixed at 80 ° C. to obtain an oil-in-water emulsion, and then a lower alcohol (anhydrous ethanol or isopropanol) in which diclofenac sodium was dissolved was gradually added. In addition, it was mixed completely uniformly. An appropriate amount of potassium hydroxide solution was added to the obtained emulsion to adjust the pH to 7 to 8, and then purified water was added to finally make the total amount 100% by weight. The obtained liquid to semi-solid oil-in-water emulsified cream was filled into a 50 ml polyethylene container and stored in a constant temperature bath (dark place) at 4 ° C.

  The above cream was not separated even after storage for 1 month and the emulsification was stable (evaluation: A). Moreover, when it applied to the shoulder, it has confirmed that it had a cool feeling and the pain relieving effect (anti-inflammatory analgesic effect) of a stiff shoulder.

Claims (7)

  An oil-in-water emulsion composition comprising a lower alcohol, diclofenac or a salt thereof, and a thickener.   The oil-in-water emulsion composition according to claim 1, further comprising a monoterpene.   Furthermore, the oil-in-water emulsion composition of Claim 1 or 2 containing a polyhydric alcohol.   The oil-in-water emulsion composition according to any one of claims 1 to 3, wherein the content of the lower alcohol is 3 to 30% by weight.   It is an oil-in-water type emulsified skin external preparation, The oil-in-water type emulsion composition in any one of Claims 1-4.   A method for stabilizing an oil-in-water emulsion composition containing a lower alcohol, which further comprises diclofenac or a salt thereof and a thickener added to the oil-in-water emulsion composition.   The method according to claim 6, wherein the lower alcohol content of the oil-in-water emulsion composition is 3 to 30% by weight.