JP7780243B2 - External composition - Google Patents

Description

The present invention relates to a topical composition that inhibits the deposition of ceramides.

Ceramides are important components of the skin and are thought to protect the inside of the skin from external stimuli. For this reason, ceramides are incorporated into topical compositions intended to protect the skin. However, ceramides are not very compatible with either water or oily ingredients. For this reason, topical compositions containing ceramides present formulation challenges, such as the formation of insoluble matter during long-term storage.

Various formulations have been reported for stably incorporating ceramides. For example, Patent Document 1 describes that an emulsion composition containing ceramides and an alkyloyl lactate ester salt can suppress the precipitation of ceramides over time. Patent Document 2 describes that a ceramide-containing emulsion composition, which is prepared by emulsifying a mixture containing ceramide; an esterification product of glycerin, a fatty acid having 8 to 30 carbon atoms, and an aliphatic saturated dibasic acid; a polyglycerol fatty acid ester; an oil; and a polyhydric alcohol at a pressure of 500 to 2,000 kg/ ^cm2 , can suppress the precipitation of ceramides over time. Patent Document 3 describes that a cosmetic having an O/W emulsion structure that contains an oily component having a dielectric constant of 2.8 to 7.0, sphingolipids (ceramides) that are dispersed or dissolved in the oily component to form an oily phase, an aqueous phase, and closed vesicles of an amphiphilic substance or particles of a polycondensation polymer having hydroxyl groups, and that maintains an emulsified state by the presence of the closed vesicles of an amphiphilic substance or particles of a polycondensation polymer having hydroxyl groups at the interface between the oily phase and the aqueous phase, can suppress precipitation of ceramides after storage at room temperature or low temperature.

Meanwhile, ufenamate is used as a non-steroidal anti-inflammatory agent in pharmaceutical or quasi-drug topical skin preparations. For example, Patent Document 4 describes that topical skin preparations containing a non-steroidal anti-inflammatory agent such as ufenamate and a specific amide derivative not only have excellent long-lasting efficacy, but also moisturize the skin itself, are low in skin irritation, are effective in improving rough skin, and are pleasant to use.

Japanese Patent Application Laid-Open No. 2000-256188 Japanese Patent Application Laid-Open No. 2007-031381 JP 2015-007014 A Japanese Patent Application Publication No. 11-302198

The formulations described in Patent Documents 1 to 3 can suppress ceramide precipitation over time, but this effect is limited to relatively stable systems in which ceramide does not precipitate immediately after preparation but precipitates after storage.

The present invention therefore aims to provide a new formulation technology that can suppress ceramide precipitation even in unstable systems where ceramide precipitation occurs immediately after preparation.

After extensive research, the inventors surprisingly discovered that by combining ufenamate, which had not previously been known to have any inhibitory effect on ceramide precipitation, with ceramides, it is possible to inhibit ceramide precipitation even in unstable systems where ceramide precipitation occurs immediately after preparation. The present invention was completed through further research based on this finding.

That is, the present invention provides the following aspects.
Item 1. A composition for external use containing (A) a ceramide and (B) ufenamate, wherein the content of component (A) is 0.001 to 4% by weight.
Item 2. The topical composition according to Item 1, wherein the component (B) is contained in a ratio of 0.25 to 20,000 parts by weight per 1 part by weight of the component (A).
Item 3. The composition for external use according to Item 1 or 2, which is an emulsion composition.
Item 4. A method for inhibiting ceramide deposition, comprising blending (B) ufenamate together with (A) a topical composition containing 0.001 to 4% by weight of ceramides.

According to the present invention, a new formulation technology that can inhibit ceramide precipitation makes it possible to inhibit ceramide precipitation even in unstable systems where ceramide precipitates immediately after preparation.

1. Topical Composition The topical composition of the present invention is characterized by containing (A) ceramides (hereinafter also referred to as "component (A)") and (B) ufenamate (hereinafter also referred to as "component (B)"). The topical composition of the present invention is described in detail below.

(A) Ceramides The topical composition of the present invention contains ceramides as component (A). Ceramides include ceramides and pseudoceramides. As the ceramides, either ceramides or pseudoceramides may be used alone, or ceramides and pseudoceramides may be used in combination.

Ceramide is a type of sphingolipid, a well-known component that collectively refers to a group of compounds in which a long-chain fatty acid is amide-bonded to the amino group of sphingosine. Ceramides include ceramide 1, ceramide 2, ceramide 3, ceramide 4, ceramide 5, ceramide 6I, ceramide 6II, ceramide 7, ceramide 8, ceramide 9, and ceramide 10, depending on the structure of sphingosine (such as the structure of the N-acyl group) and the structure of the long-chain fatty acid. These ceramides may be used alone or in combination of two or more. Of these ceramides, ceramide 1, ceramide 2, and ceramide 3 are preferred.

The origin of the ceramide used in the present invention is not particularly limited and may be determined appropriately depending on the type of ceramide, etc. For example, it may be extracted from animals or plants, obtained by microbial fermentation, or chemically synthesized.

Pseudoceramides are ceramide analogs similar in structure and properties to ceramide, and specific examples include compounds selected from compounds represented by the following general formula (I) and compounds represented by the following general formula (II).

In formula (I), R ¹¹ represents a hydrocarbon group having 10 to 26 carbon atoms, R ¹² represents a hydrocarbon group having 9 to 25 carbon atoms, X represents -(CH ₂ ) _n -, and n represents an integer of 2 to 6. The hydrocarbon group is preferably an alkyl group or an alkenyl group. A specific example of the pseudoceramide represented by formula (I) is N-(hexadecyloxyhydroxypropyl)-N-hydroxyethylhexadecanamide.

In formula (II), R ²¹ and R ²² may be the same or different and represent an optionally hydroxylated hydrocarbon group having 1 to 40 carbon atoms, R ²³ represents an alkylene group having 1 to 6 carbon atoms or a single bond, and R ²⁴ represents a hydrogen atom, an alkoxy group having 1 to 12 carbon atoms or a 2,3-dihydroxypropyloxy group. However, when R ²³ is a single bond, R ²⁴ is a hydrogen atom. The hydrocarbon group is preferably an alkyl group or an alkenyl group.

These pseudo-ceramides may be used alone or in combination of two or more.

The content of component (A) in the topical composition of the present invention is a total of 0.001 to 4% by weight, from the viewpoint of obtaining the effects of ceramides and suppressing ceramide precipitation. To obtain these effects even more effectively, the content of component (A) in the topical composition of the present invention is preferably a total of 0.01 to 4% by weight, more preferably 0.01 to 3% by weight, and even more preferably 0.01 to 2.5% by weight.

The topical composition of the present invention has an excellent effect of inhibiting ceramide deposition, and can effectively inhibit ceramide deposition even when the ceramide content is relatively high. From this perspective, the content of component (A) in the topical composition of the present invention may be, for example, 0.1 to 4% by weight, 0.1 to 3% by weight, or 1.0 to 2.5% by weight.

(B) Ufenamate The topical composition of the present invention contains ufenamate as component (B). Ufenamate, also known as butyl flufenamate, is a known component that is poorly water-soluble non-steroidal anti-inflammatory drug.

In the topical composition of the present invention, the content of component (B) is not particularly limited, but may be, for example, 1 to 20% by weight, preferably 2 to 10% by weight, and more preferably 3 to 7% by weight.

In the topical composition of the present invention, the ratio of component (B) to component (A) is determined depending on the respective contents of components (A) and (B). However, from the perspective of achieving a more excellent effect in inhibiting ceramide precipitation, the content of component (B) per total part by weight of component (A) is, for example, 0.25 to 20,000 parts by weight, preferably 0.6 to 20,000 parts by weight, and more preferably 0.6 to 1,000 parts by weight.

The topical composition of the present invention has an excellent effect of inhibiting ceramide deposition, and can effectively inhibit ceramide deposition even when the ceramide content is relatively high. From this perspective, the content of component (B) per part by weight of the total amount of component (A) in the topical composition of the present invention may be, for example, 2 to 50 parts by weight or 2 to 5 parts by weight.

The topical composition of the present invention may further contain an oil component. The oil component can be used appropriately depending on the formulation, etc. For example, the oil component can be used as an oil phase when the topical composition of the present invention is an emulsion composition, or as a base when the topical composition of the present invention is an oily gel composition.

The oils used in the present invention are not particularly limited as long as they are pharmaceutically or cosmetically acceptable, but examples include liquid oils, solid oils, and higher alcohols, with liquid oils being preferred. These oils may be used alone or in combination of two or more.

When oil is contained in the topical composition of the present invention, the content is not particularly limited and may be set appropriately depending on the formulation of the topical composition, etc., but may be, for example, 1 to 60% by weight, preferably 3 to 40% by weight, more preferably 5 to 20% by weight, and even more preferably 5 to 10% by weight.

(liquid oil)
Liquid oils are oils that maintain a liquid state at 25° C. The liquid oils used in the present invention may be any oil that is commonly used in cosmetics, topical pharmaceuticals, etc., and examples thereof include fatty acids such as oleic acid and stearic acid; ester oils such as cetyl ethylhexanoate, ethylhexyl palmitate, octyldodecyl myristate, neopentyl glycol diethylhexanoate, glyceryl tri-2-ethylhexanoate, octyldodecyl oleate, isopropyl myristate, glyceryl triisostearate, and glyceryl di-methylmethoxycinnamate-monoethylhexanoate; silicone oils such as dimethylpolysiloxane, methylhydrogenpolysiloxane, methylphenylpolysiloxane, and octamethylcyclotetrasiloxane; and liquid hydrocarbon oils such as liquid paraffin, squalene, and squalane.

Of these liquid oils, from the viewpoint of achieving even more effective ceramide precipitation inhibition, ester oils and liquid hydrocarbon oils are preferred, and isopropyl myristate and liquid paraffin are more preferred.

These liquid oils may be used alone or in combination of two or more.

When liquid oil is contained in the topical composition of the present invention, the content is not particularly limited and may be set appropriately depending on the formulation of the topical composition, etc., but may be, for example, 0.01 to 30% by weight, preferably 0.1 to 20% by weight, and more preferably 1 to 10% by weight.

When an ester oil is contained in the topical composition of the present invention, its content is not particularly limited and may be set appropriately depending on the formulation of the topical composition, etc., but may be, for example, 0.1 to 10% by weight, preferably 1 to 8% by weight, and more preferably 1 to 5% by weight.

When a liquid hydrocarbon oil is contained in the topical composition of the present invention, its content is not particularly limited and may be set appropriately depending on the formulation of the topical composition, etc., but may be, for example, 0.1 to 10% by weight, preferably 1 to 8% by weight, and more preferably 1 to 5% by weight.

(solid oil)
A solid oil is an oil that maintains a solid form at 25° C. The solid oil used in the present invention may be any oil that is typically used in cosmetics, topical pharmaceuticals, etc., and examples include candelilla wax, rice bran wax, beeswax, cotton wax, carnauba wax, lanolin, shellac wax, ozokerite, ceresin, polyethylene wax, microcrystalline wax, petrolatum, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, 12-hydroxystearic acid, undecylenic acid, myristyl myristate, cetyl myristate, stearyl stearate, cetyl stearate, cetyl palmitate, cholesteryl stearate, cholesteryl oleate, dextrin palmitate, inulin stearate, hydrogenated jojoba oil, ceresin wax, solid paraffin wax, polyethylene wax, and silicone wax.

These solid oils may be used alone or in combination of two or more.

When a solid oil is contained in the topical composition of the present invention, the content thereof is not particularly limited and may be set appropriately depending on the formulation of the topical composition, etc., but may be, for example, 0.1 to 15% by weight, preferably 0.5 to 10% by weight, and more preferably 1.5 to 5% by weight.

(higher alcohol)
A higher alcohol is a monohydric alcohol having 6 or more carbon atoms in one molecule. The higher alcohol used in the present invention may have 6 or more carbon atoms in one molecule, preferably 6 to 34, and more preferably 14 to 22.

The higher alcohols used in the present invention may be any alcohol commonly used in cosmetics and topical pharmaceuticals, and examples include myristyl alcohol, cetyl alcohol (cetanol), oleyl alcohol, stearyl alcohol, isostearyl alcohol, behenyl alcohol, and lanolin alcohol.

These higher alcohols may be used alone or in combination of two or more.

When a higher alcohol is contained in the emulsion composition of the present invention, the content is not particularly limited and may be set appropriately depending on the emulsion type, form, and intended use of the emulsion composition, but may be, for example, 0.1 to 15% by weight, preferably 1 to 10% by weight, and more preferably 2 to 5% by weight.

The topical composition of the present invention may further contain a surfactant. The surfactant can be used appropriately depending on the formulation, etc. For example, when the topical composition of the present invention is an emulsion composition, the surfactant is used to emulsify it. The surfactant is not particularly limited as long as it is pharmaceutically or cosmetically acceptable, and examples thereof include nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, etc., and from the viewpoint of obtaining a more excellent effect of inhibiting ceramide precipitation, nonionic surfactants are preferred.

Specific examples of nonionic surfactants include polyoxyethylene hydrogenated castor oil; sorbitan fatty acid esters (e.g., sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, diglycerol sorbitan penta-2-ethylhexylate, diglycerol sorbitan tetra-2-ethylhexylate, etc.); glycerin fatty acid esters (e.g., monoglyceryl cottonseed oil fatty acid, glyceryl monoerucate, glyceryl sesquioleate, glyceryl monostearate (glycerin stearate), glyceryl α,α'-oleate pyroglutamate, glycerin monostearate, glycerin malate, etc.); propylene glycol fatty acid esters (for example, propylene glycol monostearate, etc.); glycerin alkyl ether; steareth-2; polyoxyethylene sorbitan fatty acid esters (for example, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan isostearate, polyoxyethylene sorbitan tetraoleate, etc.); polyoxyethylene sorbitan fatty acid esters (for example, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan pentaoleate, polyoxyethylene sorbitol monostearate, etc.); polyoxyethylene glycerin fatty acid esters (e.g., polyoxyethylene glycerin monostearate, polyoxyethylene glycerin monoisostearate, polyoxyethylene glycerin triisostearate, etc.); polyoxyethylene fatty acid esters (e.g., polyoxyethylene monooleate, polyoxyethylene monostearate (polyoxyl stearate), polyoxyethylene distearate, polyoxyethylene monodioleate, ethylene glycol distearate, etc.); polyoxyethylene alkyl ethers (e.g., polyoxyethylene lauryl ether, polyoxyethylene oleyl ether, polyoxyethylene stearyl ether, polyoxyethylene behenyl ether, polyoxyethylene 2-octyldodecyl ether, polyoxyethylene cholestanol ether, etc.); Pluronic types (e.g., Pluronic, etc.); 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, etc.); steareth-21, etc.

Of these nonionic surfactants, polyoxyethylene sorbitan fatty acid esters are preferred, and polyoxyethylene sorbitan monostearate is more preferred, from the viewpoint of achieving even more effective ceramide precipitation inhibition.

These surfactants may be used alone or in combination of two or more.

When a surfactant is contained in the topical composition of the present invention, the content is not particularly limited and may be set appropriately depending on the formulation of the topical composition, etc., but may be, for example, 0.5 to 10% by weight, preferably 1 to 8% by weight, and more preferably 3 to 6% by weight.

The topical composition of the present invention may contain water. Water can be used appropriately depending on the formulation, etc. For example, water can be used as the aqueous phase when the topical composition of the present invention is an emulsion composition, or as a base when the topical composition of the present invention is an aqueous liquid composition or an aqueous gel composition.

When the topical composition of the present invention contains water, the content of water may be set appropriately depending on the formulation, but may be, for example, 30 to 99% by weight, preferably 40 to 90% by weight, more preferably 50 to 80% by weight, and even more preferably 60 to 70% by weight.

Other Components In addition to the components described above, the topical composition of the present invention may contain other commonly used additives as needed, such as polyhydric alcohols, thickeners, pH adjusters, buffers, solubilizers, chelating agents, preservatives, antioxidants, stabilizers, fragrances, and colorants.

Polyhydric alcohols are not particularly limited as long as they are pharmaceutically or cosmetically acceptable, but examples include dihydric alcohols such as propylene glycol, 1,3-butylene glycol (BG), ethylene glycol, isoprene glycol, diethylene glycol, and dipropylene glycol; trihydric alcohols such as glycerin; and polyethylene glycols such as Macrogol 4000 and Macrogol 6000. Dihydric and trihydric alcohols are preferred, and 1,3-butylene glycol (BG) and glycerin are more preferred.

These polyhydric alcohols may be used alone or in combination of two or more.

When the topical composition of the present invention contains a polyhydric alcohol, its content may be appropriately determined depending on the formulation, but may be, for example, 1 to 20% by weight, preferably 5 to 17% by weight, and more preferably 10 to 14% by weight.

When the topical composition of the present invention contains a dihydric alcohol, its content may be set appropriately depending on the formulation, but may be, for example, 2 to 12% by weight, preferably 4 to 9% by weight.

When the topical composition of the present invention contains a trihydric alcohol, its content may be set appropriately depending on the formulation, but may be, for example, 2 to 9% by weight, preferably 3 to 6% by weight.

The thickener is not particularly limited as long as it is pharmaceutically or cosmetically acceptable, but examples include xanthan gum, guar gum, locust bean gum, carrageenan, dextran, methylcellulose, ethylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium alginate, propylene glycol alginate, polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl methyl ether, carboxyvinyl polymer, acrylic acid alkyl methacrylate copolymer, sodium polyacrylate bentonite, dextrin fatty acid ester, pectin, etc., with carboxyvinyl polymer being preferred.

These thickeners may be used alone or in combination of two or more.

When the topical composition of the present invention contains a thickener, its content may be set appropriately depending on the type of thickener used, but may be, for example, 0.01 to 5% by weight, preferably 0.01 to 2% by weight, and more preferably 0.05 to 0.5% by weight.

pH adjusters include inorganic acids (hydrochloric acid, sulfuric acid, phosphoric acid, polyphosphoric acid, boric acid, etc.), organic acids (lactic acid, acetic acid, citric acid, tartaric acid, malic acid, succinic acid, oxalic acid, gluconic acid, fumaric acid, propionic acid, acetic acid, aspartic acid, epsilon-aminocaproic acid, glutamic acid, aminoethylsulfonic acid), inorganic bases (sodium bicarbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide), and organic bases (monoethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, lysine, etc.), preferably potassium hydroxide.

Furthermore, in addition to the above-mentioned ingredients, the topical composition of the present invention may contain, as necessary, medicinal ingredients that can exert pharmaceutical or cosmetic physiological functions. Examples of such medicinal ingredients include steroids (dexamethasone, dexamethasone hydrochloride, dexamethasone acetate, hydrocortisone hydrochloride, prednisolone valerate, prednisolone acetate, etc.), antihistamines (diphenhydramine, diphenhydramine hydrochloride, chlorpheniramine maleate, etc.), local anesthetics (lidocaine, dibucaine, procaine, tetracaine, bupivacaine, mepivacaine, chloroprocaine, proparacaine, meprylcaine, or salts thereof), alkyl benzoates (e.g., ethyl aminobenzoate, diethylaminoethyl p-butylaminobenzoate hydrochloride), orthocaine, oxethazaine, oxypolyethylenedioxydecane, Scopolia extract, percaminpase, tesitdesitin, etc.), anti-inflammatory agents (alantoin, salicylic acid, benzoic acid esters ... Examples of medicinal ingredients include benzoyl alcohol, benzoyl alcohol, benzophenone, benzoyl alcohol ... Furthermore, when these medicinal ingredients are contained in the topical composition of the present invention, the amount of each ingredient contained therein may be appropriately determined depending on the type of medicinal ingredient used, the desired effect, etc.

Formulation Form and Use The formulation form of the topical composition of the present invention is not particularly limited, and examples thereof include an aqueous liquid composition, an aqueous gel composition, an oily gel composition, an emulsion composition, etc. From the viewpoint of obtaining a more effective inhibitory effect on ceramide precipitation, preferred formulation forms of the topical composition of the present invention include an aqueous gel composition, an oily gel composition, and an emulsion composition, and more preferred are emulsion compositions. When the topical composition of the present invention is an emulsion composition, the emulsion type may be either an oil-in-water type or a water-in-oil type, but is preferably an oil-in-water type.

The topical composition of the present invention is used for the purpose of inhibiting the precipitation of ceramides. The topical composition of the present invention has an excellent effect of inhibiting the precipitation of ceramides, so it can effectively inhibit the precipitation of ceramides even in systems that are inherently unstable for ceramides, such as those in which ceramides precipitate immediately after preparation when the composition does not contain ufenamate, which exhibits the effect of inhibiting the precipitation of ceramides. In light of these effects of the present invention, the topical composition of the present invention is particularly useful when used for the purpose of inhibiting the precipitation of ceramides immediately after preparation.

The topical composition of the present invention can also be used as an external preparation such as a cosmetic, topical quasi-drug, or topical pharmaceutical. The product form of the topical composition of the present invention is not particularly limited, but examples include creams, ointments, emulsions, gels, oils, lotions, liniments, and aerosols. Among these, gels, creams, ointments, emulsions, and lotions are preferred, and gels and creams are more preferred.

Manufacturing Method The topical composition of the present invention can be manufactured according to known formulation methods depending on the formulation form. For example, the topical composition of the present invention can be manufactured by mixing the above-mentioned component (A) and component (B), other components, medicinal ingredients, additives, etc. in desired amounts. When the topical composition of the present invention is an emulsion composition, it can be manufactured according to known emulsion formulation methods depending on the emulsion type. For example, when the topical composition of the present invention is an emulsion composition, the components to be contained can be divided into water-soluble components and oily components, and an aqueous phase containing the water-soluble components and an oily phase containing the oily components are prepared, and these can be emulsified according to known methods.

2. Method for Inhibiting Ceramide Deposition As described above, ufenamate exhibits an excellent effect of inhibiting ceramide deposition in topical compositions containing ceramides. Therefore, the present invention further provides a method for inhibiting ceramide deposition, which comprises blending (B) ufenamate with component (A) in a topical composition containing 0.001 to 4 wt % of ceramides.

In the method of the present invention for inhibiting ceramide precipitation, the type and content of each component used, the type and content of components incorporated into the emulsion composition, and the formulation are the same as those described above in "1. Composition for topical use."

The present invention will be explained in more detail below using examples, but the present invention is not limited to these examples.

Test Examples Emulsion-type topical compositions shown in Tables 1 and 2 were prepared. Specifically, the components (I) shown in Table 1 were heated and mixed to dissolve the solids, and then components (A) and (B) were mixed and dissolved at 80 to 90°C to obtain an oil phase. To this was added an aqueous phase obtained by heating and mixing the components (II) shown in Table 1 at 75 to 85°C to dissolve the solids, and the mixture was emulsified using a homomixer. The mixture was cooled to 35°C and stirred to produce a creamy oil-in-water emulsion composition.

Details of the ceramides used in preparing the topical composition are as follows.
・Natural ceramide: Ceramide 2
Pseudoceramide: C ₃₇ H ₇₅ NO ₄ (N-(hexadecyloxyhydroxypropyl)-N-hydroxyethylhexadecanamide)

Immediately after preparation, 10 g of each topical composition was filled into a glass bottle (screw tube bottle No. 4, capacity 13.5 mL, Maruem Co., Ltd., transparent), and the presence or absence of crystal precipitation was confirmed using a polarizing microscope (100x magnification). Crystal precipitation was determined to be present when crystals with a maximum width of 100 μm or more were observed under a 100x magnification. The results are shown in Table 1.

As is clear from Tables 1 and 2, topical compositions containing ceramides (Comparative Examples 1 to 6) showed ceramide precipitation immediately after preparation, whereas topical compositions containing ufenamate in addition to ceramides (Examples 1 to 6) suppressed ceramide precipitation. Furthermore, this ceramide precipitation suppression effect was not observed in topical compositions containing ceramides in excess of a predetermined amount (Comparative Example 7), demonstrating that this effect is specific to compositions containing a predetermined amount of ceramides. Furthermore, in the topical compositions of Examples 1, 4, and 5, precipitation was completely suppressed, with no crystals visible even at 100x magnification. In the topical compositions of Examples 2, 3, and 6, slight microcrystals were visible at 100x magnification, but the crystals were so small and few that they dispersed stably without precipitation and had no effect on emulsion stability or usability. Furthermore, the topical compositions of Examples 1 to 6 showed no ceramide precipitation even after two weeks of storage at room temperature, demonstrating excellent formulation stability.

Emulsion-type topical compositions having the formulations shown in Formulation Example Table 3 were prepared in the same manner as in the above test examples. All topical compositions with the formulations suppressed the precipitation of ceramides immediately after preparation, and also had excellent formulation stability.

Claims (4)

A topical composition containing (A) ceramides , (B) ufenamate , and (C) liquid hydrocarbon oil and ester oil , wherein the content of component (A) is 0.001 to 4% by weight, and which is an oil-in-water emulsion composition (excluding, however, [I] topical skin preparations containing allantoin and tocopherol acetate, [II] topical skin preparations containing glycyrrhetinic acid or its ester, lidocaine, oil, a surfactant, and water, [III] topical skin preparations containing polyoxyethylene sorbitan monofatty acid ester, an anionic surfactant, a glycerin fatty acid ester, and water, [IV] topical skin preparations containing polyglycerin fatty acid ester, glycerin fatty acid ester, a fatty acid constituting a fatty acid soap that functions as an anionic surfactant upon being neutralized with a base, the base, oil, and water, and [V] those used for UV protection). The topical composition according to claim 1, wherein the (B) component is contained in a ratio of 0.25 to 20,000 parts by weight per 1 part by weight of the (A) component. The topical composition according to claim 1 or 2, wherein the component (C) is liquid paraffin and isopropyl myristate. A method for inhibiting precipitation of ceramides in a topical composition that is an oil-in-water emulsion composition containing 0.001 to 4% by weight of (A) ceramides and (C) a liquid hydrocarbon oil and an ester oil (excluding [I] topical skin preparations containing allantoin and tocopherol acetate, [II] topical skin preparations containing glycyrrhetinic acid or an ester thereof, lidocaine, an oil, a surfactant, and water, [III] topical skin preparations containing a polyoxyethylene sorbitan monofatty acid ester, an anionic surfactant, a glycerin fatty acid ester, and water, [IV] topical skin preparations containing a polyglycerin fatty acid ester, a glycerin fatty acid ester, a fatty acid that constitutes a fatty acid soap that functions as an anionic surfactant upon being neutralized with a base, the base, the oil, and water, and [V] those used for UV protection), comprising blending (B) ufenamate together with component (A) and component (C) .