JP6832665B2 - Aqueous formulation - Google Patents

Description

The present invention relates to an aqueous preparation containing a quaternary ammonium salt, a phosphocholine group-containing polymer, and glycerin, in which the formation of a quaternary ammonium salt precipitate is suppressed.

Quaternary ammonium salts such as cetylpyridinium chloride and benzalkonium chloride have a bactericidal action and are widely used in pharmaceuticals, oral care products, cosmetics and the like. However, the quaternary ammonium salt has a drawback that when it is formulated into an aqueous preparation containing water and stored in a low temperature range, precipitation occurs and the stability of the preparation is lowered.

Therefore, various formulation techniques for suppressing the precipitation of quaternary ammonium salts have been conventionally studied. For example, in Patent Document 1, cetylpyridinium chloride 0.25 to 2.5 w / v%, specific essential oils 1 to 5 w / v%, nonionic surfactant 0.1 to 1.5 w / v%, many. It is disclosed that a mouthwash containing 1 to 6 w / v% of valent alcohol and 35 to 60 w / v% of ethanol is stable without causing cloudiness even after long-term storage. Further, in Patent Document 2, the total content of the quaternary ammonium salt type bactericide, acetic acid esters and lactones is selected from 0.001% by mass to 0.5% by mass, and polyhydric alcohols and sugar alcohols. It has been reported that a liquid oral composition containing 40% by mass to 80% by mass of one or more kinds is excellent in storage stability without white turbidity or separation after storage.

However, the formulation techniques of Patent Documents 1 and 2 may not be able to cope with the diversification of formulation of aqueous preparations in recent years due to restrictions on formulation. Therefore, it is desired to develop a new formulation technology capable of suppressing the precipitation of cetylpyridinium chloride in aqueous formulations.

Japanese Unexamined Patent Publication No. 7-025753 International Publication No. 2010/18720

The present inventor has diligently studied a formulation technique capable of suppressing the formation of quaternary ammonium salt precipitates at low temperatures while containing a quaternary ammonium salt in an aqueous preparation. It was found that the formation of precipitation of quaternary ammonium salt at low temperature can be suppressed by blending a phosphocholine group-containing polymer together with the quaternary ammonium salt. However, when glycerin is added to the aqueous preparation together with the quaternary ammonium salt and the phosphocholine group-containing polymer, a new problem is faced that the formation of quaternary ammonium salt precipitation at low temperature cannot be suppressed.

Therefore, an object of the present invention is to provide a formulation technique capable of suppressing the formation of precipitates at a low temperature while containing a quaternary ammonium salt, a phosphocholine group-containing polymer, and glycerin in an aqueous preparation. ..

As a result of diligent studies to solve the above problems, the present inventor has found that monoterpenes are blended with a quaternary ammonium salt, a phosphocholine group-containing polymer, and glycerin in an aqueous preparation to produce a second product at a low temperature. It has been found that the formation of quaternary ammonium salt precipitation 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 aqueous formulation containing a quaternary ammonium salt, a phosphocholine group-containing polymer, glycerin, and a monoterpene.
Item 2. Item 2. The aqueous preparation according to Item 1, further containing hydroxyethyl cellulose and / and azulene sulfonic acid and / or a salt thereof.
Item 3. Item 2. The aqueous preparation according to Item 1 or 2, wherein the quaternary ammonium salt is cetylpyridinium chloride and / or benzalkonium chloride.
Item 4. Item 3. The aqueous preparation according to any one of Items 1 to 3, wherein the monoterpene is menthol and / or camphor.
Item 5. Item 2. The aqueous preparation according to any one of Items 1 to 4, wherein the phosphocholine group-containing polymer is a 2-methacryloyloxyethyl phosphocholine / butyl methacrylate copolymer.
Item 6. Item 2. The aqueous preparation according to any one of Items 1 to 5, which is a pharmaceutical product, a cosmetic product, a skin cleanser, or an oral care product.
Item 7. With monoterpenes as the active ingredient,
A precipitation inhibitor used to suppress the precipitation of a quaternary ammonium salt in an aqueous preparation containing a quaternary ammonium salt, a phosphocholine group-containing polymer, and glycerin.
Item 8. A method for suppressing the precipitation of a quaternary ammonium salt in an aqueous preparation containing a quaternary ammonium salt, a phosphocholine group-containing polymer, and glycerin.
A method for suppressing precipitation, in which a monoterpene is blended with a quaternary ammonium salt, a phosphocholine group-containing polymer, and glycerin in an aqueous preparation.

According to the aqueous preparation of the present invention, the precipitation of the quaternary ammonium salt is suppressed even though the quaternary ammonium salt, the phosphocholine group-containing polymer, and glycerin are contained, and the preparation has excellent stability. Therefore, in various preparations such as pharmaceuticals, oral care products, and cosmetics, the quaternary ammonium salt can be stably maintained and a good appearance and shape can be maintained during storage.

1. 1. Aqueous formulation The aqueous formulation of the present invention is characterized by containing a quaternary ammonium salt, a phosphocholine group-containing polymer, glycerin, and a monoterpene. Hereinafter, the aqueous preparation of the present invention will be described in detail.

Quaternary Ammonium Salt The aqueous formulation of the present invention contains a quaternary ammonium salt. The type of quaternary ammonium salt used in the present invention is not particularly limited as long as it is pharmaceutically or cosmetically acceptable, but for example, a quaternary ammonium salt having a bactericidal action is preferably used. Can be used. Specific examples of such quaternary ammonium salts include cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, decalinium chloride, alkyldimethylammonium chloride, alkyltrimethylammonium chloride, methylbenzethonium chloride, and lauroyl coliminoformyl chloride. Examples thereof include methylpyridinium. These quaternary ammonium salts may be used alone or in combination of two or more.

Among these quaternary ammonium salts, cetylpyridinium chloride, benzalkonium chloride, and benzethonium chloride, more preferably cetyl chloride, from the viewpoint of more effectively enjoying the effect of suppressing the formation of precipitates. Examples include pyridinium and benzalkonium chloride.

In the aqueous preparation of the present invention, the content of the quaternary ammonium salt may be appropriately set according to the type of the quaternary ammonium salt to be used, the formulation form of the aqueous preparation, and the like. For example, the quaternary ammonium salt may be set. The total amount of salt is 0.0001 to 5% by weight, preferably 0.001 to 5% by weight, more preferably 0.005 to 3% by weight, more preferably 0.01 to 3% by weight, and particularly preferably 0.1. ~ 1.5% by weight can be mentioned.

More specifically, when cetylpyridinium chloride is used as the quaternary ammonium salt, the content thereof is usually 0.001 to 5% by weight, preferably 0.005 to 5% by weight, more preferably 0.005 to 5% by weight. 0.01 to 3% by weight, more preferably 0.01 to 1% by weight, and particularly preferably 0.1 to 0.5% by weight.

When benzalkonium chloride is used as the quaternary ammonium salt, the content thereof is usually 0.0001 to 5% by weight, preferably 0.001 to 3% by weight, and more preferably 0.005. ~ 3% by weight, more preferably 0.01 to 3% by weight, and particularly preferably 0.1 to 1.5% by weight.

Phosphocholine Group-Containing Polymer The aqueous formulation of the present invention further contains a phosphocholine group-containing polymer. 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 may be contained in combination of two or more. Among these phosphocholine group-containing monomers, 2-methacryloyloxyethyl phosphocholine is preferably mentioned.

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 or cosmetically acceptable and can be radically polymerized with a phosphocholine group-containing single amount. The present invention is not particularly limited, and examples thereof include a monomer 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 may be contained in combination of two or more. Among the monomers other than these phosphocholine group-containing monomers, alkyl (meth) acrylate, 2-hydroxy-3-methacryloyloxypropyltrimethylammonium, and more preferably alkyl having an alkyl group having 1 to 18 carbon atoms is preferable. Examples of the (meth) acrylate, more preferably an alkyl (meth) acrylate having an alkyl group having 3 to 5 carbon atoms, and particularly preferably a 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.

One of these phosphocholine group-containing polymers may be used alone, or two or more thereof may be used in combination.

Among these phosphocholine group-containing polymers, 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer, polymethacryloyloxyethyl phosphorylcholine copolymer, 2-methacryloyloxyethyl phosphorylcholine / 2-hydroxy-3-methacryloyl are preferable. Oxypropyltrimethylammonium copolymer; more preferably 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer, 2-methacryloyloxyethylphosphorylcholine / 2-hydroxy-3-methacryloyloxypropyltrimethylammonium copolymer; particularly preferred Examples include 2-methacryloyloxyethyl phosphorylcholine-butyl methacrylate copolymer.

The content of the phosphocholine group-containing polymer in the aqueous preparation of the present invention is not particularly limited, but for example, the total amount of the phosphocholine group-containing polymer is 0.0005 to 5% by weight, preferably 0.001 to 5% by weight. More preferably 0.005 to 1% by weight, more preferably 0.001 to 0.5% by weight, particularly preferably 0.001 to 0.1% by weight, and most preferably 0.01 to 0.1% by weight. Can be mentioned.

In the aqueous preparation of the present invention, the ratio of the quaternary ammonium salt to the phosphocholine group-containing polymer is determined according to the contents of both of these components. For example, per 1 part by weight of the total amount of the quaternary ammonium salt. The total amount of the phosphocholine group-containing polymer is 0.005 to 2 parts by weight, preferably 0.01 to 1 part by weight, more preferably 0.05 to 1 part by weight, and particularly preferably 0.05 to 0.4 parts by weight. Can be mentioned.

Glycerin The aqueous formulation of the present invention contains glycerin. In the aqueous preparation of the present invention, the content of glycerin may be appropriately set according to the formulation form of the aqueous preparation, for example, 5 to 80% by weight, preferably 5 to 60% by weight, more preferably 10. -60% by weight, more preferably 20-50% by weight, particularly preferably 25-50% by weight.

In the aqueous preparation of the present invention, the ratio of the quaternary ammonium salt to the glycerin is determined according to the contents of both of these components. For example, 3 parts by weight of the quaternary ammonium salt is used. It is about 300 parts by weight, preferably 10 to 250 parts by weight, and more preferably 20 to 200 parts by weight.

Monoterpenes The aqueous formulations of the present invention contain monoterpenes in addition to the components described above. Precipitation of the quaternary ammonium salt at low temperature can be suppressed by containing a phosphocholine group-containing polymer in the absence of glycerin, but cannot be suppressed by containing a phosphocholine group-containing polymer in the presence of glycerin. .. On the other hand, in the aqueous preparation of the present invention, the quaternary ammonium salt, glycerin, and phosphocholine group-containing polymer are contained by containing monoterpene together with the quaternary ammonium salt, phosphocholine group-containing polymer, and glycerin. It is possible to suppress the precipitation of the quaternary ammonium salt generated in the coexistence of the above at a low temperature.

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 or cosmetically acceptable, but for example, menthol, timol, geraniol, linalol, borneol, cineol, terpineol and the like. Alcohol-based monoterpenes; aldehyde-based monoterpenes such as citral, citronellal, perylaldehyde, and safranal; ketone-based monoterpenes such as camphor, menthone, borneton, and yonon. These monoterpenes may be d-form, l-form, or dl-form when an optical isomer is present. These monoterpenes may be used alone or in combination of two or more.

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, sparemint oil and the like. In addition, the description about the content and ratio of monoterpenes in this specification is a value converted into the amount of monoterpenes contained in the essential oil when the essential oil containing monoterpenes is used.

Among these monoterpenes, menthol and camphor are preferable, and l-menthol and dl-camphor are more preferable, from the viewpoint of further improving the effect of suppressing the formation of quaternary ammonium salt precipitates.

The content of monoterpenes in the aqueous preparation of the present invention is not particularly limited, and examples thereof include 0.001 to 10% by weight of the total amount of monoterpenes. From the viewpoint of further improving the effect of suppressing the formation of quaternary ammonium salt precipitates, the content of monoterpene is preferably 0.01 to 5% by weight, more preferably 0.01 to 5% by weight, and more. Preferably, it is 0.01 to 3% by weight.

More specifically, when menthol is used as a monoterpene, its content is usually 0.001 to 10% by weight, preferably 0.01 to 5% by weight, and more preferably 0.05 to 5% by weight. By weight%, more preferably 0.05 to 3% by weight.

When camphor is used as a monoterpene, its content is usually 0.001 to 10% by weight, preferably 0.01 to 1% by weight, and more preferably 0.01 to 0.5% by weight. Can be mentioned.

In the aqueous preparation of the present invention, the ratio of the quaternary ammonium salt to the monoterpene is determined according to the contents of both of these components. For example, monoterpene per 1 part by weight of the total amount of the quaternary ammonium salt. The total amount is 0.001 to 10 parts by weight. From the viewpoint of further improving the effect of suppressing the formation of quaternary ammonium salt precipitates, the total amount of monoterpenes per 1 part by weight of the total amount of the quaternary ammonium salt is preferably 0.01 to 5 parts by weight, and further. Preferably, it is 0.03 to 3 parts by weight.

Hydroxyethyl Cellulose The aqueous formulation of the present invention may further contain hydroxyethyl cellulose. By containing hydroxyethyl cellulose, the effect of suppressing the formation of quaternary ammonium salt precipitates can be further improved.

When hydroxyethyl cellulose is contained in the aqueous preparation of the present invention, the content thereof may be appropriately set according to the formulation form of the aqueous preparation and the like, and examples thereof include 0.001 to 10% by weight. From the viewpoint of further improving the effect of suppressing the formation of quaternary ammonium salt precipitates, the content of hydroxyethyl cellulose is preferably 0.01 to 10% by weight, more preferably 0.01 to 3% by weight, and more. It is preferably 0.05 to 3% by weight, and particularly preferably 0.1 to 3% by weight.

When hydroxyethyl cellulose is contained in the aqueous preparation of the present invention, the ratio of the quaternary ammonium salt to the hydroxyethyl cellulose is determined according to the content of both of these components. For example, the total amount of the quaternary ammonium salt is 1. The amount of hydroxyethyl cellulose is 0.002 to 10 parts by weight per part by weight. From the viewpoint of further improving the effect of suppressing the formation of quaternary ammonium salt precipitates, hydroxyethyl cellulose is preferably 0.02 to 5 parts by weight, more preferably 0.02 to 5 parts by weight, per 1 part by weight of the total amount of the quaternary ammonium salt. 0.1 to 3 parts by weight can be mentioned.

Azulene sulfonic acid and / or a salt thereof The aqueous preparation of the present invention may further contain azulene sulfonic acid and / or a salt thereof. When azulene sulfonic acid and / or a salt thereof is contained, the effect of suppressing the formation of quaternary ammonium salt precipitates can be further improved.

Azulene sulfonic acid is a known anti-inflammatory component also called 1,4-dimethyl-7-isopropylazulene-3-sulfonic acid.

The type of salt of azulene sulfonic acid is not particularly limited as long as it is pharmaceutically or cosmetically acceptable, and for example, alkali metal salts such as sodium salt and potassium salt; calcium salt, magnesium salt and the like. Alkaline earth metal salts; other metal salts such as aluminum salts; ammonium salts; acetates, trifluoroacetates, butyrates, palmitates, stearate, fumarates, maleates, succinates, malon Carbolates such as acid salts, lactates, tartrates and citrates; organic sulfonates such as methanesulfonates, toluenesulfonates and tosylates; methylamine salts, triethylamine salts, triethanolamine salts, Organic amine salts such as morpholin salt, piperazine salt, pyrrolidine salt, tripyridine salt and picolin salt; inorganic acid salts such as hydrochloride, sulfate, nitrate, hydrobromide and phosphate can be mentioned.

In the aqueous preparation of the present invention, one type may be selected from azulene sulfonic acid and a salt thereof and used alone, or two or more types may be used in combination.

Among the azulene sulfonic acid and its salts, a salt of azulene sulfonic acid is preferable, and an alkali metal salt of azulene sulfonic acid is more preferable, from the viewpoint of further improving the effect of suppressing the formation of a precipitate of a quaternary ammonium salt. Preferred is sodium azulene sulfonate.

When the aqueous preparation of the present invention contains azulene sulfonic acid and / or a salt thereof, the content thereof is not particularly limited, but for example, the total amount of azulene sulfonic acid and / or a salt thereof is 0.0001 to 10 weight by weight. %. From the viewpoint of further improving the effect of suppressing the formation of quaternary ammonium salt precipitates, the content of azulene sulfonic acid and / or a salt thereof is preferably 0.001 to 5% by weight, more preferably 0.01. -5% by weight, more preferably 0.01 to 3% by weight, and particularly preferably 0.01 to 1% by weight.

When the aqueous preparation of the present invention contains azulene sulfonic acid and / or a salt thereof, the ratio of the quaternary ammonium salt to the azulene sulfonic acid and / or a salt thereof is determined according to the respective contents of both of these components. However, for example, 0.005 to 0.5 parts by weight of azulene sulfonic acid and / or a salt thereof may be mentioned per 1 part by weight of the total amount of the quaternary ammonium salt. From the viewpoint of further improving the effect of suppressing the formation of quaternary ammonium salt precipitates, the total amount of azulene sulfonic acid and / or its salt is preferably 0.01 per 1 part by weight of the total amount of the quaternary ammonium salt. ~ 0.1 parts by weight can be mentioned.

In water this specification, the term "aqueous formulation" is a formulation comprising water, the aqueous formulation of the present invention include water. In the prior art, quaternary ammonium salts tend to precipitate when stored at low temperatures in the presence of water with quaternary ammonium salts, phosphocholine group-containing polymers, and glycerin, but the aqueous formulations of the present invention. Then, such precipitation of the quaternary ammonium salt can be effectively suppressed.

In the aqueous preparation of the present invention, the water content is appropriately set according to the formulation form and the like, and is, for example, 5 to 90% by weight, preferably 5 to 85% by weight, and more preferably 5 to 70% by weight. %, More preferably 5 to 60% by weight. Can be mentioned.

Lower Alcohol The liquid preparation of the present invention may further contain a lower alcohol, if necessary.

The type of lower alcohol used in the present invention is not particularly limited as long as it is pharmaceutically or cosmetically acceptable, but for example, carbon such as ethanol, propanol, butanol, pentanol, hexanol, and isopropanol. The lower alcohols of the number 2 to 6 can be mentioned. Among these lower alcohols, ethanol is preferable. These lower alcohols may be used alone or in combination of two or more.

When the aqueous preparation of the present invention contains a lower alcohol, the content thereof is not particularly limited, but is, for example, 0.001 to 30% by weight, preferably 0.01 to 10% by weight, more preferably 0.1. -8% by weight, more preferably 0.1 to 5% by weight.

Other Ingredients In addition to the above-mentioned ingredients, the aqueous preparation of the present invention may contain, if necessary, a functional ingredient exhibiting physiologically useful functionality. Such functional ingredients are not particularly limited as long as they can be blended in pharmaceuticals, oral care products, cosmetics, etc., but for example, water-soluble vitamins, oil-soluble vitamins, enzymes, etc. Peptides, amino acids, hormones, various cytokines, various animal and plant extracts, steroids, moisturizers, whitening agents, crude drugs, antihistamines, astringents, cell activators, keratin softeners, local anesthetics, anti-inflammatory agents, antioxidants, Antiseptic agents, antibacterial agents, antipruritic agents, skin protectants, blood circulation promoters, sterols, abrasives, glucosyltransferase (GTase) inhibitors, plaque inhibitors, hypersensitivity inhibitors, tartar preventives other than quaternary ammonium salts , Tartar strengthening / remineralizing agent and the like. When these functional components are contained in the aqueous preparation of the present invention, the content thereof may be appropriately set within a range usually used in the art.

In addition to the above-mentioned components, the aqueous preparation of the present invention may contain other bases and additives in order to prepare a desired preparation form. Such bases and additives are not particularly limited as long as they can be blended in pharmaceuticals, oral care products, cosmetics, etc., but for example, oily components, solvents, surfactants, preservatives, and additions. Examples include thickeners, fragrances, pigments, buffers, pH adjusters and the like. When these bases and additives are contained in the aqueous preparation of the present invention, the content thereof may be appropriately set within a range usually used in the art.

Formulation Form The dosage form of the aqueous preparation of the present invention is not particularly limited, and examples thereof include liquid or semi-solid (gel, ointment, paste, etc.), preferably liquid.

The product classification of the aqueous preparation of the present invention is not particularly limited, and may be, for example, any of pharmaceuticals (external use, mucosal use and internal use), cosmetics, skin cleaning agents, oral care products, etc., but is preferable. Is a topical drug for skin; a mucosal drug applied to the oral cavity, pharynx, nasal cavity, eyes, etc .; cosmetics; skin cleaning agent; oral care products, more preferably topical skin drugs, mucosal drugs, cosmetics, particularly preferably skin. Examples include external medicines and mucosal medicines.

When the aqueous preparation of the present invention is used as a pharmaceutical product, the preparation form thereof is not particularly limited, but for example, gels, creams, lotions, emulsions, liquids, patches, aerosols, ointments, packs, etc. Skin external medicines; gels, creams, lotions, emulsions, liquids, ointments and other mucous membrane-applied drugs; liquids, jelly and other internal medicines. Among these, preferably examples thereof include external skin preparations such as gels, creams, lotions, emulsions and liquids, and mucosal application drugs.

When the aqueous preparation of the present invention is used as a cosmetic, the formulation form thereof is not particularly limited, and examples thereof include gels, creams, emulsions, lotions, lotions, packs, and ointments. Among these, cosmetics such as gels, creams, milky lotions, and lotions are preferable.

When the aqueous preparation of the present invention is used as a skin cleansing agent, the preparation form thereof is not particularly limited, and examples thereof include body shampoo, hair shampoo, and rinse.

When the aqueous preparation of the present invention is used as an oral care product, the formulation form thereof is not particularly limited, but for example, liquid dentifrice, liquid dentifrice, dentifrice, and mouthwash (liquid dentifrice, mouthwash are , Generally referred to as mouth rinse, mouth wash, dental rinse, etc.), oral hygiene agents such as mouth refreshing agents (mouth spray, etc.), oral ointments, etc. Among these, preferably liquid dentifrice, liquid dentifrice, dentifrice, mouthwash, and more preferably liquid dentifrice, dentifrice, mouthwash.

The properties of the aqueous preparation of the present invention are not particularly limited, but it is desirable that the aqueous preparation is translucent, particularly transparent (including both colored transparent and colorless transparent). In the aqueous preparation having translucency (particularly transparency), the formed precipitates are easily visible and the appearance is easily deteriorated, but in the aqueous preparation of the present invention, the formation of quaternary ammonium salt precipitates is easy. Therefore, it is possible to maintain a good appearance even if the property has translucency (particularly transparency).

2. 2. Quaternary Ammonium Salt Precipitation Inhibitor and Quaternary Ammonium Salt Precipitation Suppressing Method As described above, monoterpene is used in aqueous preparations containing a quaternary ammonium salt, a phosphocholine group-containing polymer, and glycerin. Precipitation of quaternary ammonium salts at low temperatures can be suppressed. Therefore, the present invention is a precipitation inhibitor used for suppressing the precipitation of a quaternary ammonium salt in an aqueous preparation containing a quaternary ammonium salt, a phosphocholine group-containing polymer, and glycerin, and is a monoterpene. To provide a precipitation inhibitor containing the above as an active ingredient. The present invention is a method for suppressing precipitation of a quaternary ammonium salt in an aqueous preparation containing a quaternary ammonium salt, a phosphocholine group-containing polymer, and glycerin, and the quaternary ammonium is added to the aqueous preparation. Provided is a method for suppressing precipitation, which comprises blending monoterpen with a salt, a phosphocholine group-containing polymer, and glycerin.

The precipitation inhibitor is used as an additive for monoterpenes, and the precipitation inhibitor is used in an aqueous preparation containing a quaternary ammonium salt, a phosphocholine group-containing polymer, and glycerin using monoterpenes. , A method of suppressing the precipitation of quaternary ammonium salts.

Further, as described above, hydroxyethyl cellulose and / or azulene sulfonic acid and / or a salt thereof contains a quaternary ammonium salt, a phosphocholine group-containing polymer, and a quaternary ammonium salt in an aqueous preparation containing glycerin. The effect of suppressing precipitation at low temperatures can be enhanced. Therefore, the precipitation inhibitor may further contain hydroxyethyl cellulose and / or azulene sulfonic acid and / or a salt thereof, and in the precipitation inhibitor method, hydroxyethyl cellulose and / or a salt thereof are further added to the aqueous preparation. / Or azulene sulfonic acid and / or a salt thereof may be blended.

The types and amounts of the components used in the precipitation inhibitor and the precipitation inhibitor method, the form of the aqueous formulation, and the like are as shown in the column of "1. Aqueous formulation".

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

Test Example 1
Liquids having the compositions shown in Tables 1 and 2 were prepared under temperature conditions of 25 ° C. 5 mL of the obtained liquid was filled in a glass screw tube bottle (capacity 6 mL), and allowed to stand at 4 ° C. for 3 hours under light-shielding conditions. After standing for 3 hours, the appearance of each liquid was observed after several rotations of each liquid, and 10 points were observed in Comparative Example 1 in which no precipitate was observed and a clear state could be maintained. The amount of the precipitate was set as one point, and the interval was divided into 10 stages according to the amount of the precipitate and scored. In this test, it was judged that if the score is 7 points or more, the formulation stability is sufficiently satisfactory for the practical level, and if the score is 5 points or less, the practical level cannot be satisfied. In addition, the liquid preparation immediately after preparation had a clear appearance with no precipitates observed.

The results obtained are shown in Tables 1 and 2. In the liquid preparation containing cetylpyridinium chloride alone (Comparative Example 1), remarkable precipitation was observed when stored in a low temperature environment, resulting in a cloudy state. Further, even a solution containing cetylpyridinium chloride and glycerin known as a solubilizer (Comparative Examples 2 and 4) could not suppress the precipitation of cetylpyridinium chloride at all. On the other hand, a liquid preparation containing cetylpyridinium chloride and a methacryloxyethyl phosphorylcholine / butyl methacrylate copolymer (Reference Example 1) was able to suppress the formation of precipitates, but cetylpyridinium chloride, glycerin, and methacryloyloxyethylphosphorylcholine In the liquid preparations containing the butyl methacrylate copolymer (Comparative Examples 3 and 5), remarkable precipitation was observed. On the other hand, liquid preparations containing cetylpyridinium chloride, glycerin, methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer, and monoterpenes (Examples 1 to 4 and 7 to 14) could suppress the formation of precipitates. It was. In particular, liquid preparations containing at least one of hydroxyethyl cellulose or azulene sulfonate (Examples 2 to 4 and 8 to 10 and 12 to 14) together with these four components completely suppress the formation of precipitates and are clear. It was able to maintain a good appearance. Further, the same tendency as in the case of cetylpyridinium chloride was also observed in the liquid preparations (Examples 5 and 6) in which benzalkonium chloride was used instead of cetylpyridinium chloride.

Preparation Example A liquid preparation (mucosal application drug) having the composition shown in Table 3 was prepared. When the appearance of each of the obtained liquids after storage was evaluated under the same conditions as in Test Example 1, the formation of precipitates could be suppressed.

Claims (8)

Quaternary ammonium salts, phosphocholine group-containing polymer, glycerine, containing motor Noterupen, and hydroxyethyl cellulose, an aqueous formulation. Further, containing A Zurensuruhon acid and / or salts thereof, an aqueous formulation of claim 1. The aqueous preparation according to claim 1 or 2, wherein the quaternary ammonium salt is cetylpyridinium chloride and / or benzalkonium chloride. The aqueous preparation according to any one of claims 1 to 3, wherein the monoterpene is menthol and / or camphor. The aqueous preparation according to any one of claims 1 to 4, wherein the phosphocholine group-containing polymer is a 2-methacryloyloxyethyl phosphocholine / butyl methacrylate copolymer. The aqueous preparation according to any one of claims 1 to 5, which is a pharmaceutical product, a cosmetic product, a skin cleanser, or an oral care product. With monoterpenes and hydroxyethyl cellulose as active ingredients,
A precipitation inhibitor used to suppress the precipitation of a quaternary ammonium salt in an aqueous preparation containing a quaternary ammonium salt, a phosphocholine group-containing polymer, and glycerin. A method for suppressing the precipitation of a quaternary ammonium salt in an aqueous preparation containing a quaternary ammonium salt, a phosphocholine group-containing polymer, and glycerin.
A method for suppressing precipitation, which comprises blending a quaternary ammonium salt, a phosphocholine group-containing polymer, and glycerin with monoterpenes and hydroxyethyl cellulose in an aqueous preparation.