JP2010024227A - Liquid composition for oral cavity - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a liquid composition for oral cavities which, while improving an adsorption effect of cetylpyridium chloride having sterilization activity against bacteria in the oral cavity on a teeth surface, retains also solution stability of a formulation. <P>SOLUTION: The transparent liquid composition for oral cavities includes cetylpyridium chloride, a water-insoluble component and a nonionic surfactant together with 0-10 wt.% of ethanol. The formulation ratio of the nonionic surfactant to the water-insoluble component is 0.55-3.6. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a liquid oral composition that promotes the effect of adsorbing cetylpyridinium chloride, which has bactericidal activity on oral bacteria, on the tooth surface and is excellent in solution stability.

  Cationic fungicides such as cetylpyridinium chloride have a high bactericidal activity against oral bacteria, adsorb on the oral mucosa and tooth surface, inhibit the adsorption of oral bacteria on the tooth surface, and suppress the formation of plaque Are known.

  Conventionally, various methods for increasing the activity of cationic fungicides have been disclosed. Patent Document 1 discloses that when cetylpyridinium chloride is combined with a lower alkyl ester of an N-long-chain acyl basic amino acid or a salt thereof, adsorption of cetylpyridinium chloride to teeth is promoted. -It is disclosed that the effect of promoting the adsorption of a cationic fungicide on a tooth by a lower alkyl ester of a long-chain acyl basic amino acid or a salt thereof is highest in a pH range of 5.5 to 6.5.

  Patent Document 3 discloses that when a specific compound is added to a composition for oral cavity in which a cationic bactericide and a nonionic surfactant are used in combination, the deactivation of the bactericide is effectively prevented. Is disclosed. Patent Document 4 discloses that the combination of cetylpyridinium chloride with a specific polyoxyethylene hydrogenated castor oil does not inhibit the adsorption of cetylpyridinium chloride to teeth as compared to other surfactants. Furthermore, in Patent Document 5, polyvinyl alcohol is used to enhance the adsorptivity of cetylpyridinium chloride to teeth. As described above, there are many requests for improving the activity of the cationic bactericidal agent, but there is a problem that some special component has to be added separately for that purpose.

JP-A-4-36231 JP-A-9-286712 JP 60-255717 A JP-A-4-173728 Japanese Patent Laid-Open No. 2003-113059

  An object of the present invention is to provide a liquid composition for oral cavity which improves the effect of adsorbing cetylpyridinium chloride having bactericidal activity on oral bacteria to the tooth surface while maintaining the solution stability on the preparation.

  As a result of intensive studies in view of such circumstances, the present inventors formulated cetylpyridinium chloride, a water-insoluble component, and a nonionic surfactant, and formulated a nonionic surfactant with respect to the water-insoluble component. It has been found that when the ratio is a specific ratio, a liquid oral composition can be obtained in which the adsorption effect of cetylpyridinium chloride on the tooth surface is further increased while maintaining the solution stability on the preparation.

That is, this invention provides the composition for oral cavity of the following items 1-6 especially.
Item 1.
Containing cetylpyridinium chloride, a water-insoluble component, a nonionic surfactant, and further containing 0 to 10% by weight of ethanol, the blending ratio of the nonionic surfactant to the water-insoluble component is 0.55 to 3 A transparent liquid oral composition which is .6.
Item 2.
The liquid oral composition according to claim 1, wherein the water-insoluble component comprises a water-insoluble medicinal component and / or a fragrance.
Item 3.
The composition for liquid oral cavity according to claim 2, comprising 0.1 to 0.5% by weight of a water-insoluble component.
Item 4.
The water-insoluble medicinal component is at least one selected from the group consisting of triclosan, tocopherol acetate, β-glycyrrhetinic acid, p-hydroxybenzoate, isopropylmethylphenol, and tocopherol nicotinate. The composition for liquid oral cavity according to 2.
Item 5.
The composition for liquid oral cavity according to any one of claims 1 to 4, comprising 0.01 to 1% by weight of cetylpyridinium chloride.
Item 6.
The liquid oral composition according to any one of claims 1 to 5, wherein the nonionic surfactant is polyoxyethylene hydrogenated castor oil.

  The liquid oral composition of the present invention further enhances the activity of cetylpyridinium chloride to promote the adsorption effect on the tooth surface, thereby adsorbing oral bacteria that cause dental caries and periodontal disease on the tooth surface. It is possible to effectively suppress the formation of plaque by inhibiting, and further improve the solution stability by maintaining the appearance transparency on the formulation, and as a liquid oral composition is good Performance quality can be ensured.

  The composition for liquid oral cavity according to the present invention contains cetylpyridinium chloride, a water-insoluble component, and a nonionic surfactant, and the mixing ratio of the nonionic surfactant to the water-insoluble component is 0.55. It is -3.6. In the present specification, the blending ratio represents a blending weight ratio unless otherwise specified.

  Cetylpyridinium chloride used in the present invention is a cationic bactericidal agent contained in a quaternary ammonium compound and is widely used in the field of oral compositions. Such cetylpyridinium chloride can be blended in an amount of 0.01 to 1% by weight, preferably 0.01 to 0.5% by weight, more preferably 0.00%, based on the total amount of the liquid oral composition of the present invention. 01 to 0.3% by weight can be blended. When the amount is less than 0.01% by weight, the effect of adsorption of cetylpyridinium chloride on the tooth surface is reduced. On the other hand, when the amount exceeds 1% by weight, problems such as bitterness during use and coloring of teeth occur.

  The water-insoluble components used in the present invention mainly include water-insoluble medicinal components and fragrances, and these can be used alone or both at the same time. In the present invention, it is particularly preferable to use a water-insoluble medicinal component and a fragrance as the water-insoluble component, and it is more preferable that the water-insoluble component consists of a water-insoluble medicinal component and / or a fragrance.

  Although it does not specifically limit as a water-insoluble medicinal ingredient, For example, an oil-soluble medicinal ingredient is mentioned. Specifically, for example, a halogenated diphenyl ether such as triclosan (2 ′, 4,4′-trichloro-2-hydroxy-diphenyl ether) as a bactericidal agent or a phenolic compound such as isopropylmethylphenol; dl-α acetate as a blood circulation promoter -Vitamin E such as tocopherol, tocopherol succinate, tocopherol nicotinate; p-hydroxybenzoic acid such as methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate An ester, glycyrrhetinic acid, etc. are mentioned, It can include in the liquid oral cavity composition of this invention individually or in combination of 2 or more types, respectively. Among these water-insoluble medicinal ingredients, halogenated diphenyl ether is preferable from the viewpoint of further enhancing bactericidal activity against oral bacteria, and among them, triclosan is particularly preferable. The amount of the water-insoluble medicinal ingredient is 0.01 to 1% by weight, preferably 0.01 to 0.5% by weight, more preferably 0.01 to 0.1% by weight, based on the total amount of the composition. . When the blending amount is less than 0.01% by weight, sufficient bactericidal power is not exhibited. When the blending amount is more than 1% by weight, irritation to the oral mucosa is exhibited, which is a practical problem.

  Although it does not restrict | limit especially as a fragrance | flavor, It is preferable to use a mint-type fragrance | flavor. Mint fragrances can be obtained by conventional methods. For example, menthol, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, perilla oil, winter green oil, clove Oil, eucalyptus oil, pimento oil, anethole, eugenol, plum oil, menthone and the like can be used. Of these, menthol, spearmint oil, peppermint oil, and menthone can be preferably used. These perfume materials can be used alone or in combination of two or more. The blending amount of the fragrance is usually 0.01 to 1% by weight, preferably 0.05 to 0.5% by weight, based on the total amount of the composition. If the blending amount is less than 0.01% by weight, the flavor is low and the usability is poor, and if it is more than 1% by weight, the flavor is too strong and the usability is poor and the irritation is further increased.

  When the water-insoluble component comprises a water-insoluble medicinal component and / or a fragrance, the water-insoluble component is preferably blended in an amount of 0.1 to 0.5% by weight based on the total amount of the composition. It is more preferable to add ~ 0.4% by weight.

  The nonionic surfactant used in the present invention is not particularly limited, but sugar fatty acid esters such as sucrose fatty acid esters and maltose fatty acid esters; sugar alcohol fatty acid esters such as maltitol fatty acid esters; sorbitan fatty acids such as sorbitan monolaurate Esters; polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monolaurate and polyoxyethylene sorbitan monostearate; fatty acid alkanolamides such as lauric acid diethanolamide; polyoxyethylene stearyl ether, polyoxyethylene oleyl ether, etc. Polyoxyethylene alkyl ethers; polyethylene glycol fats such as polyethylene glycol monooleate and polyethylene glycol monolaurate Esters; alkyl glucosides such as lauryl glucoside and decyl glucoside; polyglycerin fatty acid esters, polyoxyethylene glycerin fatty acid esters, polyoxyethylene fatty acid esters, alkyl glucosides, polyoxyethylene hydrogenated castor oil, glycerin fatty acid esters, polyoxyethylene propylene blocks A copolymer etc. are mentioned, Each can be mix | blended individually or in mixture of 2 or more types. Among these nonionic surfactants, polyoxyethylene hydrogenated castor oil is preferable, and the average added mole number of ethylene oxide is usually 2 to 150, preferably 40 to 100, more preferably 40 to 80. . A nonionic surfactant can mix | blend 0.001-1 weight%, and it is preferable to set it as 0.01-0.5 weight% among them. In the present invention, since the effectiveness of cetylpyridinium chloride is not further impaired, it is particularly preferably 0.1 to 0.4% by weight.

  In the composition for liquid oral cavity of the present invention, while blending cetylpyridinium chloride, a water-insoluble component and a nonionic surfactant are further blended, and the blending amount of the nonionic surfactant is blended with the water-insoluble component. The blending ratio is 0.55 to 3.6 with respect to the amount. The particularly preferable range of the blending ratio varies depending on the amount of ethanol blended in the liquid oral composition. When the amount of ethanol blended with respect to the total amount of the composition is 0 to 2% by weight, the blending ratio is preferably 0.7 to 3.6, more preferably 0.7 to 2.9, and even more preferably 0.7 to 2.5, more preferably 1.0 to 2.0. When the blending amount of ethanol with respect to the total amount of the composition is greater than 2% by weight and 10% by weight or less, the blending ratio is preferably 0.55 to 1.8, more preferably 0.55 to 1.2, Preferably it is 0.65-1.2.

  Although a limited interpretation is not desired, when the blending ratio of the nonionic surfactant with respect to the blending amount of the water-insoluble component is smaller than the above range, the transparency of the composition becomes poor, and conversely, When it is larger than the above range, the amount of adsorption of cetylpyridinium chloride on the teeth tends to decrease.

  The liquid oral cavity composition of the present invention can be provided in the form of a liquid dentifrice, mouthwash, low viscosity gel, and the like. In addition to the components described above, the liquid oral composition can further contain the following suitable components according to the form of the composition within a range not impairing the effects of the present invention.

  For example, examples of the surfactant include amphoteric surfactants, cationic surfactants, and anionic surfactants in addition to the nonionic surfactants. Examples of zwitterionic surfactants include N-alkyldiaminoethylglycine such as N-lauryldiaminoethylglycine and N-myristyldiethylglycine, N-alkyl-N-carboxymethylammonium betaine, and 2-alkyl-1hydroxyethylimidazoline betaine sodium. Can be mentioned. Examples of the cationic surfactant include alkyl trimethyl ammonium chloride, alkyl trimethyl ammonium bromide, and dialkyl dimethyl ammonium chloride. Examples of the anionic surfactant include sodium lauryl sulfate, sodium myristyl sulfate, sodium N-acyl sarcosine, sodium N-acyl glutamate, sodium N-methyl-N-acyl taurate, sodium N-methyl-N-acylalanine, α -Sodium olefin sulfonate and the like. These surfactants can be blended alone or in combination of two or more. The compounding quantity is 0.01 to 1 weight% normally with respect to the composition whole quantity.

  As a flavoring agent, what is handled as a water-soluble fragrance | flavor other than said fragrance | flavor can be used.

  As the wetting agent, sorbit, glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, polypropylene glycol, polyethylene glycol and the like can be used alone or in combination of two or more. A compounding quantity is 3 to 20 weight% normally with respect to the composition whole quantity.

  Furthermore, sweeteners such as saccharin sodium, acesulfame potassium, stevioside, glycyrrhizin, perilartin, thaumatin, aspartylphenylalanyl methyl ester, ρ-methoxycinnamic aldehyde, sucralose, palatinose, mannitol, xylitol, maltitol, lactitol, 0.001 to 1 weight% can be mix | blended with respect to the composition whole quantity.

  Examples of pH adjusters include citric acid, phosphoric acid, malic acid, gluconic acid, maleic acid, aspartic acid, succinic acid, glucuronic acid, fumaric acid, glutamic acid, adipic acid, and salts thereof, hydrochloric acid, sodium hydroxide , Potassium hydroxide, sodium silicate and the like. These components can be contained in the oral composition of the present invention alone or in combination of two or more. In addition, as long as the composition for oral cavity of this invention is a range which can be used in an oral cavity, the pH will not be restrict | limited, However, Usually, pH is 3.0-10.5, Preferably it is pH 5.5-8.0.

  The liquid oral composition of the present invention may contain a water-soluble medicinal component as the medicinal component in addition to the water-insoluble medicinal component. In addition to cetylpyridinium chloride as a water-soluble medicinal ingredient, for example, cationic fungicides such as chlorhexidine hydrochloride, chlorhexidine gluconate, benzethonium chloride and benzalkonium chloride; amphoteric fungicides such as dodecyldiaminoethylglycine; Enzymes such as nuclease, amylase, protease, mutanase, lysozyme, lytic enzyme (lytechenzyme); glycyrrhizinate such as dipotassium glycyrrhizinate as anti-inflammatory agent; tranexamic acid, epsilon aminocaproic acid as antiplasmin agent; ascorbine as bleeding ameliorating agent Acids, etc .; Allantoins, etc. as tissue repair agents; Others include chlorophyll, sodium chloride, caropeptide, zinc chloride, etc., and these may be used alone or in combination of two or more. It is possible to focus. The compounding quantity is 0.001 to 5 weight% normally with respect to the composition whole quantity.

  Further, the liquid oral composition of the present invention includes alkali metal alginates such as cationized hydroxyethyl cellulose and sodium alginate; propylene glycol alginate, xanthan gum, tragacanth gum, karaya gum, arabiya gum, carrageenan and the like. Gums: One or two or more kinds of binders such as polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, polyvinylpyrrolidone, carboxymethylcellulose, and hydroxyethylcellulose can be blended. The compounding quantity in the case of mix | blending these is about 0.001-1 weight% normally.

  Further, the liquid oral composition of the present invention may contain N-long chain acyl basic amino acid lower alkyl ester or a salt thereof. The basic amino acid moiety is particularly ornithine, lysine, or arginine, and these may be either optically active or racemic. The acyl group is a saturated or unsaturated fatty acid residue having 8 to 22 carbon atoms, and examples thereof include single fatty acid residues such as lauroyl group, myristyl group, palmitoyl group, stearoyl group, and coconut oil. Natural mixed fatty acid residues such as fatty acid residues and beef oil fatty acid residues may also be used. Examples of lower alkyl esters include methyl esters, ethyl esters, and propyl esters. As salts of these N-long chain acyl basic amino acid lower alkyl esters, inorganic acid salts such as hydrochloride and sulfate; glutamate, pyroglutamate, acetate, tartrate, citrate, fatty acid salt, Organic acid salts such as acidic amino acid salts are listed. In particular, glutamate, pyroglutamate, acetate, and citrate are preferable. Specific examples of N-long chain acyl basic amino acid lower alkyl esters or salts thereof include N-cocoyl-L-arginine ethyl ester / pyrrolidone carboxylate (CAE), N-lauryl-L-arginine ethyl ester, Examples include pyrrolidone carboxylate. The amount of N-long-chain acyl basic amino acid lower alkyl ester or a salt thereof is preferably about 0.005 to 1% by weight based on the whole oral liquid preparation. Moreover, about 1/5 or more is preferable by weight ratio with respect to cetyl pyridinium chloride. The upper limit of the weight ratio in this case is not particularly limited, but is usually about 10 times.

<Adsorption test of cetylpyridinium chloride on tooth surface>
As a model of tooth enamel, hydroxyapatite powder (BIO-RAD Lab. Hydroxyapatite Bio-Gel HTP Gel) (hereinafter abbreviated as HA) immersed in human saliva at 37 ° C. for 15 hours was used. By dipping in saliva, salivary mucoproteins and the like were adsorbed on the HA surface, and approximated to the actual tooth enamel state wetted by saliva. Each sample shown in Tables 1 and 2 was added to the saliva-treated HA and shaken at 37 ° C. for 15 minutes. Thereafter, cetylpyridinium chloride finally rinsed with distilled water and adsorbed on HA was quantified using liquid chromatography, and the influence of the mixing ratio of the nonionic surfactant to the water-insoluble component was examined. In addition, the judgment criteria are as follows. Here, the unit of the adsorption amount of cetylpyridinium chloride is μg / HA 50 mg.

5: Adsorption amount of cetylpyridinium chloride is 700 or more 4: Adsorption amount of cetylpyridinium chloride is 600 or more and less than 700 3: Adsorption amount of cetylpyridinium chloride is 500 or more and less than 600 2: Adsorption amount of cetylpyridinium chloride is 400 or more and less than 500 1: Adsorption amount of cetylpyridinium chloride is 300 or more and less than 400 0: Adsorption amount of cetylpyridinium chloride is less than 300

In addition, the adsorption amount of cetylpyridinium chloride is preferably 400 or more, and a larger value is more preferable. Those having an adsorption amount of less than 400 are considered to be unable to exhibit a sufficient sterilizing effect, and are not preferable. That is, in the above judgment criteria, those of 0 and 1 are not preferred, those of 2 or more are preferred, and those having a larger reference value are more preferred.

<Appearance evaluation test>
As described above, after preparing each sample shown in Tables 1 and 2, the transparency as a liquid preparation was examined visually. The judgment criteria were as follows. In addition, the numerical value of each component shown in Table 1 and Table 2 shows weight%.

3: colorless and transparent 2: slightly transparent 1: cloudy

Hereinafter, although the formulation of the Example of the liquid oral cavity composition which concerns on this invention is given, this invention is not limited to the following formulation. Unless otherwise specified, the blending amount is% by weight.
Example A Liquid dentifrice Ingredients Blending amount Cetylpyridinium chloride 0.05
Glycerin 10.0
Saccharin sodium 0.01
Fragrance 0.25
Triclosan 0.05
Ethanol 7.0
Polyoxyethylene (60) hydrogenated castor oil 0.2
pH adjuster Appropriate amount of purified water Remainder Total 100.0

Example B Liquid dentifrice Ingredients Blending amount Cetylpyridinium chloride 0.05
Glycerin 10.0
Saccharin sodium 0.01
Fragrance 0.3
Ethanol 7.0
Polyoxyethylene (60) hydrogenated castor oil 0.3
pH adjuster Appropriate amount of purified water Remainder Total 100.0

Example C Liquid dentifrice Ingredients Blending amount Cetylpyridinium chloride 0.05
Glycerin 10.0
Saccharin sodium 0.01
Fragrance 0.25
Tocopherol acetate 0.05
Ethanol 7.0
Sucrose fatty acid ester 0.3
pH adjuster Appropriate amount of purified water Remainder Total 100.0

Example D Liquid dentifrice Ingredient Compounding amount Cetylpyridinium chloride 0.05
Glycerin 10.0
Saccharin sodium 0.01
Fragrance 0.3
Triclosan 0.01
Ethanol 10.0
Polyoxyethylene (60) hydrogenated castor oil 0.25
N-cocoyl-L-arginine ethyl ester / pyrrolidone carboxylate 0.01
pH adjuster Appropriate amount of purified water Remainder Total 100.0

Example E Liquid dentifrice Ingredients Blending amount Cetylpyridinium chloride 0.05
Glycerin 10.0
Saccharin sodium 0.01
Fragrance 0.05
Isopropyl methylphenol 0.05
Polyoxyethylene (60) hydrogenated castor oil 0.15
pH adjuster Appropriate amount of purified water Remainder Total 100.0

Example F Liquid dentifrice Ingredient Amount cetylpyridinium chloride 0.05
Glycerin 10.0
Saccharin sodium 0.01
Fragrance 0.05
Tocopherol acetate 0.01
Polyoxyethylene (60) hydrogenated castor oil 0.15
pH adjuster Appropriate amount of purified water Remainder Total 100.0

Example G Liquid dentifrice Ingredients Blending amount Cetylpyridinium chloride 0.05
Glycerin 10.0
Saccharin sodium 0.01
Fragrance 0.2
Triclosan 0.01
Polyoxyethylene (80) hydrogenated castor oil 0.15
pH adjuster Appropriate amount of purified water Remainder Total 100.0

Example H Liquid dentifrice Ingredient Amount cetylpyridinium chloride 0.05
Glycerin 10.0
Saccharin sodium 0.01
Fragrance 0.15
Triclosan 0.1
Polyoxyethylene (60) hydrogenated castor oil 0.4
N-cocoyl-L-arginine ethyl ester pyrrolidone carboxylate 0.05
pH adjuster Appropriate amount of purified water Remainder Total 100.0

Example I Mouthwash Component Ingredient Amount cetylpyridinium chloride 0.05
Glycerin 10.0
Saccharin sodium 0.01
Fragrance 0.15
Ethanol 3.0
Tocopherol nicotinate 0.05
Polyoxyethylene (60) hydrogenated castor oil 0.3
pH adjuster Appropriate amount of purified water Remainder Total 100.0

Claims (6)

  Containing cetylpyridinium chloride, a water-insoluble component, a nonionic surfactant, and further containing 0 to 10% by weight of ethanol, the blending ratio of the nonionic surfactant to the water-insoluble component is 0.55 to 3 A transparent liquid oral composition which is .6.   The liquid oral composition according to claim 1, wherein the water-insoluble component comprises a water-insoluble medicinal component and / or a fragrance. The composition for liquid oral cavity according to claim 2, comprising 0.1 to 0.5% by weight of a water-insoluble component. The water-insoluble medicinal component is at least one selected from the group consisting of triclosan, tocopherol acetate, β-glycyrrhetinic acid, p-hydroxybenzoate, isopropylmethylphenol, and tocopherol nicotinate. The composition for liquid oral cavity according to 2.   The composition for liquid oral cavity according to any one of claims 1 to 4, comprising 0.01 to 1% by weight of cetylpyridinium chloride.   The liquid oral composition according to any one of claims 1 to 5, wherein the nonionic surfactant is polyoxyethylene hydrogenated castor oil.