JP6887895B2 - Topical composition - Google Patents

Description

The present invention relates to an external composition containing monoterpenes, a phosphocholine group-containing polymer, and water, but in which the formation of precipitates is suppressed.

Monoterpenes such as l-menthol have effects such as imparting a refreshing sensation, anti-inflammatory, and promoting blood circulation, and are widely used in oral or external compositions.

In addition, phosphocholine group-containing polymers such as 2-methacryloyloxyethyl phosphorylcholine and butyl methacrylate copolymer have high affinity for living organisms, and further have moisturizing properties, prevent microorganisms from adhering to the oral cavity, prevent gingitis, etc. Has also been reported, and has been used in oral or external compositions (see, for example, Patent Documents 1 to 3).

On the other hand, conventionally, especially in the composition for external use, the pharmaceutical stability of the composition in which monoterpene and the phosphocholine group-containing polymer are used in combination has not been sufficiently studied.

Japanese Unexamined Patent Publication No. 2006-219450 Japanese Unexamined Patent Publication No. 2011-153101 Japanese Unexamined Patent Publication No. 2015-853

The present inventor investigated the formulation stability of an external composition containing a monoterpene and a phosphocholine group-containing polymer in order to put it into practical use. As a result, no precipitation was observed when the monoterpene was contained alone. When monoterpenes coexist with a phosphocholine group-containing polymer, precipitation occurs, and the new problem of reducing the pharmaceutical stability of the external composition is faced. That is, it has been clarified that the external composition containing the monoterpene and the phosphocholine group-containing polymer has a peculiar problem of forming a precipitate.

Therefore, an object of the present invention is to provide a formulation technique for suppressing the formation of a precipitate while containing a monoterpene, a phosphocholine group-containing polymer, and water in an external composition.

As a result of diligent studies to solve the above problems, the present inventor has found that the external composition contains cetylpyridinium chloride and / or benzalkonium chloride together with monoterpene, a phosphocholine group-containing polymer, and water. Therefore, it was found that the formation of precipitates generated in the coexistence of monoterpenes and phosphocholine group-containing polymers can be suppressed. The present invention has been completed by further studies based on such findings.

That is, the present invention provides the inventions of the following aspects.
Item 1. An external composition containing (A) a monoterpene, (B) a phosphocholine group-containing polymer, (C) cetylpyridinium chloride and / or benzalkonium chloride, and (D) water.
Item 2. Item 2. The external composition according to Item 1, wherein the component (A) is l-menthol.
Item 3. Item 2. The external composition according to Item 1 or 2, wherein the component (B) is a 2-methacryloyloxyethyl phosphorylcholine-butyl methacrylate copolymer.
Item 4. A precipitation inhibitor used to suppress the precipitation of the component (A) in an external composition containing (A) monoterpene, (B) a phosphocholine group-containing polymer, and (D) water.
A precipitation inhibitor containing cetylpyridinium chloride and / or benzalkonium chloride as an active ingredient.
Item 5. A method for suppressing the precipitation of the component (A) in an external composition containing (A) monoterpene, (B) a phosphocholine group-containing polymer, and (D) water.
A method for suppressing precipitation, which comprises blending (C) cetylpyridinium chloride and / or benzalkonium chloride with the component (A), the component (B), and the component (D) for external use.

According to the external composition of the present invention, it is possible to suppress the precipitation of monoterpenes generated in the coexistence state of these components even though it contains monoterpenes, phosphocholine group-containing polymers, and water, and excellent formulation stability can be achieved. Since it has, it is possible to maintain a good appearance shape during storage.

1. 1. External Composition The external composition of the present invention includes a monoterpene (hereinafter, may be referred to as a component (A)), a phosphocholine group-containing polymer (hereinafter, may be referred to as a component (B)), and the like. It is characterized by containing cetylpyridinium chloride and / or benzalkonium chloride (hereinafter, may be referred to as component (C)) and water (hereinafter, may be referred to as component (D)). .. Hereinafter, the external composition of the present invention will be described in detail.

(A) Monoterpene The external composition of the present invention contains a monoterpene as a component (A). The monoterpene is a known component having a structure in which two isoprene units are contained in the molecule and having a cooling action and the like.

The type of monoterpene used in the present invention is not particularly limited as long as it is pharmaceutically acceptable, but for example, alcohol-based monoterpenes such as menthol, thymol, geraniol, linalol, borneol, cineole, and terpineol. Aldehyde-based monoterpenes such as citral, citroneral, perylaldehyde, and safranal; ketone-based monoterpenes such as camphor, menthone, carbomentone, and yonon can be mentioned. These monoterpenes may be d-form, l-form, or dl-form when an optical isomer is present.

Further, in the present invention, the monoterpene may be used in the state of an essential oil containing the monoterpene. The essential oil containing monoterpene can be appropriately selected from known ones and used. Examples of the essential oil containing menthol include peppermint oil, peppermint oil, spearmint oil and the like. In addition, the description about the content and ratio of the component (A) in this specification is a value converted into the amount of monoterpene contained in the essential oil when the essential oil containing monoterpene is used as the component (A).

In the external composition of the present invention, one type of monoterpene may be used alone or two or more types of monoterpenes may be used in combination as the component (A).

Among these components (A), alcohol-based monoterpenes are preferable, and l-menthol is more preferable.

In the external composition of the present invention, the content of the component (A) is not particularly limited and may be appropriately set according to the medicinal effect to be imparted. For example, the total amount of the component (A) is 0.01. By weight or more, preferably 0.01 to 6% by weight, more preferably 0.01 to 2% by weight, more preferably 0.03 to 1% by weight, and particularly preferably 0.05 to 0.5% by weight. Be done.

(B) Phosphocholine Group-Containing Polymer The external composition of the present invention contains a phosphocholine group-containing polymer as the component (B).

The phosphocholine group-containing polymer is a polymer obtained by polymerizing a monomer containing a phosphocholine group (hereinafter, may be referred to as “phosphocholine group-containing monomer”), and is a known component having a moisturizing effect and the like. ..

In the phosphocholine group-containing polymer, the type of the phosphocholine group-containing monomer is not particularly limited, and examples thereof include a monomer having a phosphocholine group and a vinyl group. More specific examples of the phosphocholine group-containing monomer include 2-methacryloyloxyethyl phosphorylcholine and 2-methacryloyloxyethyl phosphorylethanolamine. In the phosphocholine group-containing polymer, the phosphocholine group-containing monomer may be contained alone or in combination of two or more. Among these phosphocholine group-containing monomers, 2-methacryloyloxyethyl phosphorylcholine is preferably mentioned from the viewpoint of further improving the effect of suppressing the formation of monoterpene precipitates.

The phosphocholine group-containing polymer used in the present invention may be a copolymer composed of one kind of phosphocholine group-containing monomer, or may be a copolymer composed of two or more kinds of monomers. Good.

When the phosphocholine group-containing polymer is a copolymer, it may be a copolymer composed of two or more kinds of phosphocholine group-containing monomers, and at least one kind of phosphocholine group-containing monomer and at least one kind. It may be a copolymer composed of a monomer other than the phosphocholine group-containing monomer.

The types of monomers other than the phosphocholine group-containing monomer contained in the phosphocholine group-containing polymer are pharmaceutically acceptable and are particularly limited to being radically polymerizable with a phosphocholine group-containing single amount. Examples include, but are not limited to, monomers having a vinyl group. Specific examples of monomers other than the phosphocholine group-containing monomer include methyl (meth) acrylate, ethyl (meth) acrylate, butyl (meth) acrylate, lauryl (meth) acrylate, stearyl (meth) acrylate, and 2-. Alkyl (meth) acrylates such as ethylhexyl (meth) acrylate; benzyl (meth) acrylate, phenoxyethyl (meth) acrylate, cyclohexyl (meth) acrylate, polypropylene glycol mono (meth) acrylate, polytetramethylene glycol mono (meth) acrylate, Examples thereof include polypropylene glycol di (meth) acrylate, polytetramethylene glycol mono (meth) acrylate, polypropylene glycol polyethylene glycol mono (meth) acrylate, sodium methacrylate, 2-hydroxy-3-methacryloyloxypropyltrimethylammonium and the like. In the phosphocholine group-containing polymer, a monomer other than the phosphocholine group-containing monomer may be contained alone or in combination of two or more. Among the monomers other than these phosphocholine group-containing monomers, alkyl (meth) acrylate is preferable from the viewpoint of further improving the effect of suppressing the formation of monoterpene precipitates while effectively exerting a moisturizing effect. 2-Hydroxy-3-methacryloyloxypropyltrimethylammonium, more preferably an alkyl (meth) acrylate having an alkyl group having 1 to 18 carbon atoms, and more preferably an alkyl (meth) acrylate having an alkyl group having 3 to 5 carbon atoms. Particularly preferred is butyl (meth) acrylate. In addition, in this specification, "(meth) acrylate" means methacrylate and / or acrylate.

Specific examples of the phosphocholine group-containing polymer used in the present invention include polymethacryloyloxyethyl phosphorylcholine copolymer, 2-methacryloyloxyethyl phosphorylcholine-butyl methacrylate copolymer (polyquaternium-51), and 2-methacryloyloxy. Ethylenephosphorylcholine / butylmethacrylate / sodium methacrylate copolymer (polyquaternium-65), 2-methacryloyloxyethyl phosphorylcholine / 2-hydroxy-3-methacryloyloxypropyltrimethylammonium copolymer (polyquaternium-64), 2-methacryloyloxy Examples thereof include an ethylphosphorylcholine / stearyl methacrylate copolymer (polyquaternium-61). In the above notation regarding the phosphocholine group-containing polymer, the names in parentheses indicate the cosmetic ingredient display names.

In the external composition of the present invention, one kind of phosphocholine group-containing polymer may be used as the component (B), or two or more kinds of phosphocholine group-containing polymers may be used in combination.

Among these components (B), 2-methacryloyloxyethyl phosphorylcholine and butyl methacrylate are preferable from the viewpoint of further improving the effect of suppressing the formation of monoterpene precipitates while effectively exerting the moisturizing effect. Combined, polymethacryloyloxyethyl phosphorylcholine copolymer, 2-methacryloyloxyethylphosphorylcholine, 2-hydroxy-3-methacryloyloxypropyltrimethylammonium copolymer; more preferably 2-methacryloyloxyethylphosphorylcholine, butyl methacrylate copolymer , 2-Methylloyloxyethyl phosphorylcholine 2-hydroxy-3-methacryloyloxypropyltrimethylammonium copolymer; particularly preferably, 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer.

In the external composition of the present invention, the content of the component (B) is not particularly limited, and examples thereof include 0.05 to 1% by weight of the total amount of the component (B). From the viewpoint of further improving the effect of suppressing the formation of monoterpene precipitates while effectively exerting the moisturizing effect, the total amount of the component (B) is preferably 0.05 to 0.5% by weight, more preferably 0. .05 to 0.3% by weight, more preferably 0.05 to 0.25% by weight.

In the external composition of the present invention, the ratio of the component (B) to the component (A) is determined according to the contents of the component (A) and the component (B). For example, the total amount of the component (A) is 1. The total amount of the component (B) is 0.01 to 100 parts by weight per part by weight. As the ratio of the component (B) to the component (A), from the viewpoint of further improving the effect of suppressing the formation of monoterpene precipitates while effectively exerting the moisturizing effect, the total amount of the component (A) per 1 part by weight. The total amount of the component (B) is preferably 0.025 to 50 parts by weight, more preferably 0.05 to 20, particularly preferably 0.1 to 10 parts by weight by weight.

(C) Cetylpyridinium Chloride and / or Benzalkonium Chloride The external composition of the present invention contains cetylpyridinium chloride and / or benzalkonium chloride as the component (C). By containing cetylpyridinium chloride and / or benzalkonium chloride in this way, it is possible to suppress the formation of monoterpene precipitates that occur when monoterpenes and phosphocholine group-containing polymers coexist and are stored. Become.

Cetylpyridinium chloride and benzalkonium chloride are both quaternary amine compounds and are known agents that exhibit bactericidal action.

In the external composition of the present invention, either cetylpyridinium chloride or benzalkonium chloride may be used alone as the component (C), or these may be used in combination. Among the components (C), cetylpyridinium chloride is preferably mentioned.

In the external composition of the present invention, the content of the component (C) may be appropriately set according to the type of the component (C) used. For example, the total amount of the component (C) is 0.005% by weight. As mentioned above, 0.005 to 2% by weight is preferable.

More specifically, when cetylpyridinium chloride is used as the component (C), the content of cetylpyridinium chloride is usually 0 from the viewpoint of further improving the effect of suppressing the formation of monoterpene precipitates. 0.01% by weight or more, preferably 0.01 to 2% by weight, more preferably 0.01 to 1% by weight, and particularly preferably 0.01 to 0.5% by weight.

When benzalkonium chloride is used as the component (C), the content of benzalkonium chloride is usually 0.005 from the viewpoint of further improving the effect of suppressing the formation of monoterpene precipitates. By weight or more, preferably 0.005 to 2% by weight, more preferably 0.008 to 1% by weight, and particularly preferably 0.01 to 0.5% by weight.

In the external composition of the present invention, the ratio of the component (C) to the component (A) is determined according to the contents of the component (A) and the component (C). For example, the total amount of the component (A) is 1. The total amount of the component (C) is 0.001 part by weight or more per part by weight.

More specifically, when cetylpyridinium chloride is used as the component (C), the ratio of cetylpyridinium chloride to the component (A) is from the viewpoint of further improving the effect of suppressing the formation of monoterpene precipitates. Therefore, cetylpyridinium chloride is 0.002 parts by weight or more, preferably 0.005 to 200 parts by weight, more preferably 0.01 to 34 parts by weight, and particularly preferably 0. 02 to 10 parts by weight can be mentioned.

When benzalkonium chloride is used as the component (C), the ratio of benzalkonium chloride to the component (A) is from the viewpoint of further improving the effect of suppressing the formation of monoterpene precipitates. Benzalkonium chloride is 0.001 part by weight or more, preferably 0.0025 to 200 parts by weight, more preferably 0.008 to 34 parts by weight, and particularly preferably 0.02, per 1 part by weight of the total amount of the component (A). 10 parts by weight can be mentioned.

(D) the composition for external use of the water present invention contains water as a base. The component (A) tends to precipitate when stored in the presence of water in the presence of the component (B). According to the external composition of the present invention, such a component (A) is precipitated. Can be effectively suppressed.

In the external composition of the present invention, the content of the component (D) is appropriately set according to the formulation form and the like, and is, for example, 1 to 95% by weight, preferably 3 to 95% by weight, more preferably. 5 to 95% by weight is mentioned.

Other Ingredients In addition to the above-mentioned ingredients, the external composition of the present invention contains components usually used in the art, depending on the formulation form of the external composition, as long as the effects of the present invention are not impaired. You may. Such ingredients include, for example, preservatives, bactericides, antibacterial agents, anti-inflammatory agents, glucosyl transferase (GTase) inhibitors, antihistamines, local anesthetics, blood circulation promoters, thickeners, wetting agents, excipients, etc. Examples include fragrances, pigments, deodorants, surfactants, solvents, pH adjusters and the like.

Examples of preservatives, bactericides, and antibacterial agents include hinokithiol, benzoic acids, salicylic acids, sorbic acids, parabens, decalinium chloride, chlorhexidine chloride, chlorhexidine gluconate, isopropylmethylphenol, triclosan, lysozyme chloride, chlorhexidine hydrochloride, and iodine. Examples include potassium oxide.

Examples of anti-inflammatory agents include dipotassium glycyrrhizinate, glycyrrhetinic acid, methyl glycyrrhizinate, stearyl glycyrrhizinate, pyridoxin glycyrrhetinate, stearyl glycyrrhetinate, glyceryl glycyrrhetinate, monoglucuronide glycyrrhetinate, allantin, tranexamic acid, epsilon aminocaproic acid, and azulene. Examples include sodium chloride and vitamins.

Examples of GTase inhibitors include extracts of evening primrose plants of the evening primrose family, extracts of evening primrose plants of the family Evening Primrose, dextranase, mutanase, tastain, tannins, ellagic acid, polyphenols, oolong tea extract, green tea extract, and the like. Examples include assembly, evening primrose, evening primrose, primrose, gentiana, senso, dragon bile, and yellow primrose.

Examples of the antihistamine include diphenhydramine, diphenhydramine hydrochloride and the like.

Examples of the local anesthetic include procaine, tetracaine, bupipacaine, mepipacine, chloroprocaine, proparacaine, meprilcaine or salts thereof, orthocaine, oxesazein, oxypolyentoxydecane, scopolia extract, percamin pase, tesitdecitin and the like.

Examples of the blood circulation promoter include nonylate vanillylamide, nicotinic acid benzyl ester, capsaicin, capsicum extract and the like.

Examples of the thickener include polysaccharides such as purulan, purulan derivatives, and starch; hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl methyl cellulose, carboxymethyl cellulose, and carboxymethyl cellulose salts (sodium carboxymethyl cellulose, potassium carboxymethyl cellulose, etc.). , Methyl cellulose, ethyl cellulose, polyacrylic acid, polyacrylic acid salt (sodium polyacrylic acid, octyl ester copolymer of acrylic acid / acrylate, etc.), copolymer of methacrylic acids (methacrylic acid and n-butyl acrylate) Polymers, polymers of methacrylic acid and methyl methacrylic acid, polymers of methacrylic acid and ethyl acrylate, etc.) and other cellulose-based polymer substances; synthesis of carboxyvinyl polymers, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, etc. Polymeric substances; lectin, alginic acid, alginate (sodium alginate, potassium alginate, magnesium alginate, propylene glycol alginate, triethanolamine alginate, triisopropanolamine alginate, ammonium alginate, butylamine alginate, diamylamine alginate, etc.), sodium chondroitin sulfate, Natural polymer substances such as agar, chitosan, and carrageenan; Amino acid polymer substances such as collagen and gelatin; Rubber polymer substances such as Arabic gum, Karaya gum, Tragacanth gum, Xanthan gum, Locust bean gum, Gua gum, Tamarind gum, Gellan gum, etc. And so on.

Examples of the wetting agent include glycerin, sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, xylitol, maltitol, lactol, and erythritol.

Examples of the excipient include lactose, sucrose, mannitol, starch, dextrin, crystalline cellulose, silica (light anhydrous silicic acid, etc.) and the like.

Examples of the fragrance include natural fragrances (fennel oil and the like), synthetic fragrances, and blended fragrances thereof.

Examples of the dye include natural dyes, synthetic dyes, and mixtures thereof.

Examples of the deodorant include zinc chloride, sodium copper chlorophyllin, green coffee bean extract, burdock powder, green tea, roasted rice bran extract and the like.

Examples of the surfactant include sodium polyoxyethylene lauryl ether sulfate, sodium lauryl sulfate, sodium myristyl sulfate, sodium N-lauroyl sarcosinate, sodium N-myristolyl sarcosinate, sodium dodecylbenzene sulfonate, hydrogenated coconut fatty acid monoglyceride. Anionic surfactants such as sodium monosulfate, sodium lauryl sulfoacetate, sodium α-olefin sulfonate, sodium N-palmitoyl glutarumate, sodium N-methyl-N-acyl taurine; polyoxyethylene hydrogenated castor oil, sho Sugar fatty acid ester, maltose fatty acid ester, maltol fatty acid ester, lactol fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan monostearate, polyoxyethylene higher alcohol ether, polyoxyethylene polyoxypropylene copolymer, polyoxyethylene poly Nonionic surfactants such as oxypropylene fatty acid ester and polyglycerin fatty acid ester; coconut oil fatty acid amide propyl betaine, lauryl dimethylamino acetate betaine, lauryl dimethyl amine oxide, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazole Amphoteric surfactants such as lumbetaine, N-lauryl diaminoethyl glycine, N-myristyl diaminoethyl glycine, N-alkyl-1-hydroxyethyl imidazoline betaine sodium; lauryl trimethyl ammonium chloride, stearyl trimethyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride Such as cationic surfactants.

Examples of the solvent include monohydric alcohols such as ethanol, propanol, butanol, pentanol, hexanol and isopropanol.

Examples of the pH adjuster include acetic acid, hydrochloric acid, sulfuric acid, nitrate, citric acid, malic acid, lactic acid, phosphoric acid, benzoic acid, sodium hydroxide, potassium hydroxide, sodium acetate, sodium carbonate, sodium citrate, and citric acid. Examples thereof include sodium hydrogen hydrogen, sodium lactate, calcium lactate, sodium phosphate, sodium hydrogen phosphate, sodium benzoate and the like.

When these components are contained in the external composition of the present invention, the content thereof may be appropriately set within a range usually used in the art.

pH
The pH of the external composition of the present invention may be appropriately set within a range that allows transdermal application, and is, for example, 4 to 8, preferably 5 to 7.5, and more preferably 6 to 7. Can be mentioned. Here, the pH is a value measured under a temperature condition of 25 ° C.

Formulation form The dosage form of the external composition of the present invention is not particularly limited as long as it can be applied transdermally, and examples thereof include liquid or semi-solid (gel-like or paste-like).

When the external composition of the present invention is used as an external composition, the formulation form thereof is not particularly limited, but for example, a gel agent, a cream agent, a lotion agent, an emulsion agent, a liquid agent, a patch, an aerosol agent, or an ointment. Topical skin preparations such as agents and packs; cosmetics such as gels, creams, emulsions, lotions, lotions, packs and ointments; skin cleansing agents such as body shampoos, hair shampoos and rinses. Among these formulation forms, preferably skin external medicines or cosmetics, more preferably skin external medicines such as gels, creams, lotions and emulsions; cosmetics such as gels, creams, emulsions and lotions can be mentioned. ..

The properties of the external composition of the present invention are not particularly limited, but it is desirable that the composition is translucent, particularly transparent (including both colored transparent and colorless transparent). In the external composition having translucency (particularly transparency), the formed precipitates are easily visible and the appearance is easily deteriorated, but in the external composition of the present invention, the formation of precipitates can be suppressed. , Even if the property has translucency (particularly transparency), a good appearance can be maintained.

2. Monoterpene Precipitation Inhibitor and Monoterpene Precipitation Inhibition Method As described above, cetylpyridinium chloride and / or benzalconium chloride is a monoterpene in an external composition containing a monoterpene, a phosphocholine group-containing polymer and water. Precipitation can be suppressed. Therefore, the present invention is a precipitation inhibitor used for suppressing the precipitation of monoterpenes in an external composition containing monoterpenes, phosphocholine group-containing polymers and water, and is cetylpyridinium chloride and / or chloride. Provided is a precipitation inhibitor containing benzalkonium as an active ingredient. The present invention is a method for suppressing precipitation of monoterpenes in an external composition containing a monoterpene, a phosphocholine group-containing polymer and water, wherein the external composition contains a monoterpene, a phosphocholine group-containing polymer, and the like. And water, together with cetylpyridinium chloride and / or benzalconium chloride, provide a precipitation suppression method.

The precipitation inhibitor is used as an additive for cetylpyridinium chloride and / or benzalkonium chloride, and the precipitation inhibitor method utilizes cetylpyridinium chloride and / or benzalkonium chloride to form a monoterpene. This is a method for suppressing the precipitation of monoterpenes in an external composition containing a phosphocholine group-containing polymer and water.

The types and amounts of the components used in the precipitation inhibitor and the precipitation inhibitor method are as shown in the column of "1. External composition".

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto.

Test Example 1
The liquid preparations having the compositions shown in Table 1 were prepared under a temperature condition of 50 ° C., 5 mL of the obtained liquid preparation was filled in a glass screw tube bottle (capacity 6 mL), and allowed to stand at 4 ° C. for 3 days under light-shielding conditions. .. The appearance of each liquid after standing for 3 days was observed, and the degree of precipitation formation was evaluated according to the criteria shown below. The liquid preparation immediately after preparation had a clear appearance with no precipitates observed.
<Criteria for determining the degree of precipitate formation>
⊚: No deposits were observed, and a clear state could be maintained.
◯: Although only a small amount of precipitates were formed, the overall clear state could be maintained.
X: A large amount of precipitates are formed, and the clear state is lost.
XX: Remarkably large amount of precipitates are formed, and the clear state is lost.

The results obtained are shown in Table 1. In the liquid preparation containing l-menthol alone (Reference Example 1), no precipitation was observed after storage. On the other hand, in the liquid preparations containing l-menthol and a copolymer of 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate (Comparative Examples 1 and 2), the formation of precipitates was observed after storage. On the other hand, in the liquid preparation containing cetylpyridinium chloride and / or benzalkonium chloride together with l-menthol and 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer (Examples 1 to 7), a precipitate was formed after storage. Was able to be suppressed, and a clear appearance property could be maintained.

On the other hand, liquid preparations containing benzethonium chloride together with l-menthol and a copolymer of 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate (Comparative Examples 3 and 4) could not suppress the formation of precipitates after storage. That is, from these results, the effect of suppressing precipitation after storage that occurs in the coexistence of l-menthol and 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer is found among quaternary ammonium salts such as cetylpyridinium chloride and /. Alternatively, it became clear that it is a peculiar effect that can be obtained by selecting benzalkonium chloride. When a liquid preparation having the composition shown in Table 1 was prepared by the same method as in Test Example 1 and allowed to stand at 25 ° C. for 3 days under light-shielding conditions for evaluation, the same tendency was observed regarding the degree of precipitation formation. It was seen.

Example of Preparation An external lotion having the composition shown in Table 2, an external gel having the composition shown in Table 3, an external cream having the composition shown in Table 4, and an external emulsion having the composition shown in Table 5 were produced. In Tables 2 to 5, the unit of the content of each component is% by weight. For each of the obtained external composition, the formation of precipitates could be suppressed after storage.

Claims (5)

An external composition containing (A) a monoterpene, (B) a phosphocholine group-containing polymer, (C) cetylpyridinium chloride and / or benzalkonium chloride, and (D) water. The external composition according to claim 1, wherein the component (A) is l-menthol. The external composition according to claim 1 or 2, wherein the component (B) is a 2-methacryloyloxyethyl phosphorylcholine-butyl methacrylate copolymer. A precipitation inhibitor used to suppress the precipitation of the component (A) in an external composition containing (A) monoterpene, (B) a phosphocholine group-containing polymer, and (D) water.
A precipitation inhibitor containing cetylpyridinium chloride and / or benzalkonium chloride as an active ingredient. A method for suppressing the precipitation of the component (A) in an external composition containing (A) monoterpene, (B) a phosphocholine group-containing polymer, and (D) water.
A method for suppressing precipitation, which comprises blending (C) cetylpyridinium chloride and / or benzalkonium chloride with the component (A), the component (B), and the component (D) for external use.