JP3096528B2 - Oral composition - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an oral composition, and more particularly, to an oral composition having excellent plaque control effect by removing microorganisms in the oral cavity.

[0002]

2. Description of the Related Art It is known that a water-insoluble polymer compound having vinylpyridinium as a repeating unit in a molecule (hereinafter, referred to as a vinylpyridinium-based polymer) exhibits a microorganism adsorption ability.
No. 2 and JP-A-3-174419 disclose a microorganism adsorbent containing such an insoluble polymer compound having a pyridinium group as an active ingredient.

[0003]

DISCLOSURE OF THE INVENTION The present inventors have conducted studies to apply this vinylpyridinium-based polymer to oral compositions. The vinylpyridinium-based polymer is generally expected to react with components such as a foaming agent and a binder used in the oral composition to cause a problem that its antibacterial activity is significantly reduced. It is thought that it is necessary to take a means for stabilizing in order to mix in the composition for use.

The present inventors have conducted intensive studies with the aim of stably blending this vinylpyridinium-based polymer into an oral composition. As a result, surprisingly, the present inventors have found that alkyl sulfates and their salts, soaps The present inventors have found that polyoxyethylene alkyl ether phosphate and its salt or an alkylolamide-type surfactant specifically stabilize the vinylpyridinium-based polymer, and have completed the present invention.

[0005]

Means for Solving the Problems The present invention is selected from vinylpyridinium-based polymers, alkyl sulfates and salts thereof, soaps, polyoxyethylene alkyl ether phosphates and salts thereof, and alkylol amide type surfactants. It is intended to provide an oral composition comprising at least one surfactant.

The oral composition of the present invention exhibits an excellent plaque control effect by removing microorganisms in the oral cavity more efficiently and preventing accumulation of the product and lime.

The vinylpyridinium-based polymer used as an active ingredient in the composition of the present invention may be either the polymer itself, a composite material obtained by coating the surface of a water-insoluble substrate with the polymer, or a support material having the polymer supported on a water-insoluble substrate. The vinylpyridinium-based polymer may have a molecular weight of about 1,000 to 1,000,000, preferably about 5000 to 800,000. The polymer may be a crosslinked polymer or a non-crosslinked polymer.

The repeating units of the vinylpyridinium include, for example, (1) the general formula (I):

Embedded image

Wherein R is a benzyl group, a phenethyl group,
X represents a group selected from the group consisting of an alkyl group having 1 to 12 carbon atoms and a pentafluorophenylmethyl group, and X represents a group selected from the group consisting of a chlorine atom and a bromine atom. Or (2) the general formula (II):

[0010]

Embedded image

[Wherein R ₁ , R ₂ and R ₃ each independently represent a hydrogen atom, a linear or branched saturated or unsaturated aliphatic hydrocarbon group having 1 to 20 carbon atoms, an alkyl group,
A group selected from the group consisting of a hydroxyalkyl group, an alkoxyalkyl group, an aryloxyalkyl group and a trialkoxysilylalkyl group, X and Y are each independently a group selected from the group consisting of a chlorine atom and a bromine atom, Represents an integer of 1 to 20].

The vinylpyridinium-based polymer used in the present invention may be any other vinyl monomer copolymerizable with these vinylpyridine and a polyfunctional vinyl monomer, or any other vinyl monomer copolymerizable with vinylpyridine or a polyfunctional vinyl monomer. Can be copolymerized by a method known per se, such as solution polymerization or suspension polymerization, to introduce an alkyl group, and then, if necessary, by reacting with a tertiary amine. For example, the vinylpyridinium-based crosslinked polymer represented by the general formula (I) can be produced as follows.

First, vinylpyridine and a polyfunctional vinyl monomer are copolymerized in the presence or absence of another vinyl monomer copolymerizable therewith to obtain a polymer compound. The agent is reacted to introduce a substituent on the nitrogen atom. Also, non-crosslinked polymers can be similarly prepared from vinylpyridine and copolymerizable vinyl monomers other than polyfunctional vinyl monomers.

Examples of the alkylating agent include benzyl halides such as benzyl chloride, benzyl brolide and benzyl iodide and substituted aromatic rings thereof, and halogenated compounds such as phenylethyl chloride, phenylethyl bromide and phenylethyl iodide. Phenylethyl and its aromatic ring-substituted product, pentafluorophenylmethyl chloride, pentafluorophenylmethyl bromide, pentafluorophenylmethyl halide such as pentafluorophenylmethyl iodide, alkyl halide having 1 to 12 carbon atoms, carbon number Disulfuric acid esters, p-toluenesulfonic acid esters, trifluoromethanesulfonic acid esters and the like of alcohols 1 to 12 are exemplified.

The copolymerizable vinyl monomer includes:
Monoolefins such as ethylene, propylene, butene,
Styrene, vinyl acetate, acrylic acid, acrylic acid ester, methacrylic acid, methacrylic acid ester, aliphatic vinyl ester, acrylonitrile, and monomers of these derivatives, but not limited thereto, various things alone or in combination Can be used.

The crosslinked vinylpyridinium polymer represented by the general formula (II) can be produced, for example, as follows. First, vinyl pyridine and a polyfunctional vinyl monomer are copolymerized in the presence or absence of another vinyl monomer copolymerizable therewith to form a polymer. Next, a dihalogenated alkyl such as dichloroalkyl, dibromoalkyl or diiodoalkyl having 1 to 20 carbon atoms is reacted to introduce a halogenated alkyl group into the nitrogen atom of the vinylpyridine ring. Further, this is reacted with a tertiary amine to form quaternary ammonium.

Further, the non-crosslinked polymer can be similarly produced from vinylpyridine and a copolymerizable vinyl monomer excluding a polyfunctional vinyl monomer. Examples of the copolymerizable vinyl monomer include ethylene, propylene,
Monoolefins such as butene, styrene, vinyl acetate,
Examples include acrylic acid, acrylic acid esters, methacrylic acid, methacrylic acid esters, aliphatic vinyl esters, acrylonitrile, and monomers of their derivatives, but are not limited thereto, and various types can be used alone or in combination.

Examples of the polyfunctional vinyl monomer include divinylbenzene; ethylene glycol di (meth) acrylate, butanediol di (meth) acrylate, trimethylolpropane tri (meth) acrylate, pentaerythritol di (meth) acrylate, Polyfunctional (meth) acrylates such as pentaerythritol tetra (meth) acrylate and polyethylene glycol di (meth) acrylate; methylene bis (meth) acrylamide, propylene bis (meth) acrylamide, N, N '-(1,2-dihydroxyethylene ) Polyfunctional (meth) acrylamides such as bis (meth) acrylamide and N, N '-(carboxymethylene) bis (meth) acrylamide can be used.

As the tertiary amine, trimethylamine,
Triethylamine, methyldiethylamine, N-dodecyldimethylamine, N-dodecenyldimethylamine, N
Saturated or unsaturated aliphatic tertiary amines such as -octyldimethylamine; N-benzyldimethylamine, N-
Aromatic tertiary amines such as phenethylmethylamine; tri
Oxyalkylamines such as (hydroxylethyl) amine and bis (hydroxylethyl) methylamine; N, N-
Dimethyl-3-trimethoxysilylpropylamine, N
Silylalkylamines such as -methyl-N-ethyl-3-trimethoxysilylpropylamine are used.

The water-insoluble substrate coated with the vinylpyridinium-based polymer is not particularly limited as long as it is water-insoluble. For example, silica gel, natural zeolite, calcium hydrogen phosphate, nylon, PMMA, polyethylene, polystyrene and the like are used. be able to. Further, the water-insoluble substrate carrying the vinylpyridinium-based polymer is also not particularly limited, but may be granular, powdery, massive, fibrous, woven,
Nonwoven fabrics, films, sponges, and the like can be used. For example, cross-linked chloromethylstyrene /
Styrene copolymer polymer beads and the like can be used.

The vinylpyridinium-based polymer can be supported on a water-insoluble substrate in the following manner. For example, the formula:

[0022]

Embedded image XCH ₂ −

Wherein X represents a chlorine atom, bromine atom or iodine atom, or a water-insoluble polymer molding having a halomethyl group (hereinafter referred to as halomethyl polymer molding). Reaction of a vinylpyridine homopolymer or a copolymer of vinylpyridine and another monomer with a halomethyl group of a halomethyl polymer molded product and a pyridine ring portion of a vinylpyridine polymer on a water-insoluble substrate. And an unreacted pyridine moiety is quaternized with an alkylating agent.

The surface of the water-insoluble substrate can be coated with the vinylpyridinium-based crosslinked polymer as follows. First, vinylpyridine and a polyfunctional vinyl monomer are copolymerized on the surface of a water-insoluble substrate in the presence or absence of another vinyl monomer copolymerizable therewith. Next, the surface of the composite coated with the vinylpyridinium-based polymer is quaternized by the same method as described above. In order to coat the water-insoluble substrate surface with a non-crosslinked polymer, it can be similarly produced from vinylpyridine and a copolymerizable vinyl monomer excluding a polyfunctional vinyl monomer. Further, in order to coat the water-insoluble substrate surface with a vinylpyridinium-based polymer, the polymer synthesized in addition to the above is dissolved in an organic solvent such as alcohols, esters, and ethers, and impregnation, spraying, coating, and the like are performed. Can be used.

The oral composition of the present invention contains the vinylpyridinium-based polymer thus obtained in an amount of 0.001 to 50% by weight, preferably 0.1 to 50% by weight, based on the total amount of the composition.
It is blended at a ratio of 20% by weight. If the amount is less than 0.001% by weight, a sufficient effect of removing microorganisms is not exhibited.
On the other hand, if it is more than 50% by weight, the properties of the composition become unstable.

The alkyl sulfate type surfactant is
formula:

Embedded image R ₁ —OSO ₃ M ₁

Wherein R ₁ represents an alkyl group having 8 to 18 carbon atoms, and M ₁ represents a cation or hydrogen derived from an alkali metal, ammonia, or an alkanolamine. ] Is a known anionic surfactant represented by
Sodium lauryl sulfate, sodium myristyl sulfate,
Examples thereof include ammonium lauryl sulfate and the like, for example, those sold under the trade name of “Alscope” by Toho Chemical Industry Co., Ltd. can be used.

The soap type surfactant has the formula:

Embedded image R ₂ —COOM ₂

Wherein R ₂ represents an alkyl group having 8 to 18 carbon atoms, and M ₂ represents a cation derived from an alkali metal, ammonia, or an alkanolamine. ], Such as sodium laurate and sodium oleate.

The polyoxyethylene alkyl ether phosphate ester type surfactant has the formula:

Embedded image Or

[0031]

Embedded image

[Wherein R ₃ , R ₄ and R ₅ represent an alkyl group having 8 to 18 carbon atoms, M ₃ , M ₄ and M ₅ represent an alkali metal;
A cation or hydrogen derived from ammonia, alkanolamine. Also, n and (m + 1) are each 1
~ 20. However, m, l ≧ 1. ] Known anionic surfactants, such as sodium polyoxyethylene lauryl ether phosphate, for example, "Phosphanol" from Toho Chemical Industry Co., Ltd.
You can use the ones sold under the brand name.

The alkylol amide type surfactant is
formula:

Embedded image Or

[0034]

Embedded image

Wherein R ₆ and R ₇ represent an alkyl group having 8 to 18 carbon atoms. Known nonionic surfactants represented by the formula: lauric acid monoethanolamide, lauric acid diethanolamide, coconut oil fatty acid monoethanolamide, coconut oil fatty acid diethanolamide, and the like. You can use the ones sold under the brand name “To Hall” by Co., Ltd.

In the oral composition of the present invention, the alkyl sulfate ester and its salt, the soap, the polyoxyethylene alkyl ether phosphate ester and its salt, and the alkylolamide type surfactant are used for foaming which gives excellent foaming properties. In addition to acting as an agent, it has the effect of dramatically improving the microbial removal effect of vinylpyridinium-based polymers.

In the present invention, the alkyl sulfates and salts thereof, soaps, polyoxyethylene alkyl ether phosphates and salts thereof, and alkylol amide type surfactants may be used alone or in combination of two or more. 0.001 to 20% by weight, preferably 0.5 to 5% by weight, based on the total weight of the product. If the amount is less than 0.001% by weight, a sufficient effect cannot be obtained.
On the other hand, if the content is more than 20% by weight, a problem occurs in property stability such as liquid separation.

The binder is preferably a nonionic or cationic binder which does not reduce the microbial removal effect of the vinylpyridinium-based polymer. Examples of the nonionic binder include hydroxyethylcellulose, methylcellulose and the like. Examples include hydroxymethylcellulose and hydroxypropylmethylcellulose, and examples of the cationic binder include a substance obtained by cationizing hydroxyethylcellulose, and these may be used alone or in combination of two or more. The compounding amount is usually 0.01 to 20% by weight based on the total amount of the composition.
It is.

The oral composition of the present invention can be made into a dosage form such as a toothpaste, a toothpaste, an ointment, a pasta, a liniment and a cream by a method known per se.
Abrasives, thickeners, flavoring agents, sweeteners and other medicinal ingredients can be blended according to desired applications such as dentifrices and gingival massage preparations, as long as the effects of the present invention are not impaired. .

For example, in the case of dentifrices, dibasic calcium phosphate dihydrate and anhydride, calcium monobasic phosphate, tribasic calcium phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, alumina, silicic anhydride, silica gel, Aluminum silicate, insoluble sodium metaphosphate, tribasic magnesium phosphate, magnesium carbonate, calcium sulfate, polymethyl methacrylate, bentonite, zirconium silicate, synthetic resin, etc. can be used alone or in combination of two or more. . The compounding amount is usually 5.0 to 90 with respect to the total amount of the composition.
%, Especially 5 to 60% by weight for toothpaste.

As the thickener, sorbitol, glycerin, ethylene glycol, propylene glycol,
1,3-butylene glycol, polyethylene glycol, polypropylene glycol, xylit, maltitol, lactit and the like can be used alone or in combination of two or more. The compounding amount is usually 5 to 70% by weight based on the total amount of the composition.

Further, as a flavoring agent, menthol, carboxylic acid, anethole, eugenol, methyl salicylate, limonene, ocimene, n-decyl alcohol, citronell, α-terbineol, methyl acetate, citronenyl acetate, methyl eugenol, cineole , Linalool, ethyl linalool, crocodile, thymol, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, perilla oil,
Winter green oil, clove oil, eucalyptus oil or the like, alone or in combination of two or more, is blended at a ratio of about 0.1 to 10% by weight, preferably about 0.5 to 5% by weight, based on the total amount of the composition. Can be. In addition, as a sweetener, saccharin sodium, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perillartin, thaumatin, asparatyl phenylalanyl methyl ester, p-methoxycinnamic aldehyde, etc., based on the total amount of the composition It can be added at a ratio of 0.01 to 1% by weight, preferably 0.05 to 0.5% by weight.

Further, the oral composition of the present invention may contain, as a medicinal component, cationic fungicides such as cetylpyridinium chloride and chlorhexidine salts, nonionic fungicides such as triclosan, and amphoteric fungicides such as dodecyldiaminoethylglycine. Enzymes such as dextranase, amylase, protease, mutanase, lysozyme, lytic enzyme (Litech enzyme), alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate, sodium fluoride, sodium fluoride Fluorides such as monotin, tranexamic acid and epsilon aminocaproic acid, aluminum chlorohydroxyl allantoin, dihydrocholesterol, glycyrrhizin salts, glycyrrhetinic acid, glycerophosphate, chlorophyll, and sodium chloride Um, Karopeputaido, a water-soluble inorganic phosphoric acid compounds may be blended singly or in combination of two or more.

[0044]

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to Experimental Examples, Examples and Comparative Examples, but the present invention is not limited to these. Unless otherwise specified, "%" represents% by weight.

Experimental Example 1 The sterilization and removal effects of the various carriers shown in Tables 1 and 2 by the vinylpyridinium-based polymer were evaluated by the following experiments. The results are shown in Tables 1 and 2.

Evaluation Method of Microbial Removal Effect (1) Preparation of Test Bacterial Solution Streptococcus sob
rinz) OMZ176 was cultured in a brain heart infusion liquid medium under anaerobic conditions at 37 ° C. for 20 hours, and then centrifuged (7000 rpm, 10 minutes) to collect the cells. After washing with water, the bacterial concentration is about 1
0 ⁷ cells / ml so that the (OD ₅₆₀ = 0.02), and the ones suspended in sterile saline and tested bacterial solution.

(2) Evaluation of Microbial Removal Effect (Shake Flask Method) A predetermined amount of a sample was put in a 100 ml Erlenmeyer flask, and 36 ml of sterilized water was added to sufficiently disperse the sample. This Erlenmeyer flask was placed in a thermostat at 37 ° C., and 4 ml of the test bacterial solution of the above (1) was added and shaken at 120 strokes / minute for 3 minutes. Thereafter, the Erlenmeyer flask was taken out of the thermostat, allowed to stand for a while, and 1 ml of the supernatant was taken and diluted with sterile physiological saline. Then, 0.1 ml of the diluted product was spread on a Brain Heart Infusion Agar plate, and cultured under anaerobic conditions at 37 ° C. for 48 hours, and the number of colonies formed was counted.
Thereby, the viable cell count after contact with the sample for 3 minutes can be calculated. The microorganism removal rate (%) of the sample was evaluated by the following formula, and 90% or more was judged to have an excellent microorganism removal effect.

[0048]

(Equation 1)

[0049]

[Table 1]

[0050]

[Table 2]

As is clear from the results in Tables 1 and 2, at a concentration of 1.0%, any one of the crosslinked vinylpyridinium polymers of Samples 1 to 8 and the uncrosslinked vinylpyridinium polymer of Samples 12 to 17 was used. The system-based polymers also show high microbial removal rates.
In addition, samples 9 to 11 and 18 to 20 having a concentration of 0.0005% do not exhibit a sufficient microorganism removing effect.

Examples 1 to 8 and Comparative Examples 1 to 6 The vinylpyridinium polymers shown in Tables 1 and 2 were mixed with other components shown in Table 3 according to a conventional method and stirred. The dentifrice compositions of Comparative Examples 1 to 6 were prepared. 10 g of the obtained composition was weighed and the effect of removing microorganisms was evaluated by the above-mentioned evaluation method. Table 3 shows the results.

[0053]

[Table 3]

As is apparent from Table 3, the dentifrice compositions of Examples 1 to 8 were mixed with sodium lauryl sulfate, sodium laurate, sodium polyoxyethylene lauryl ether phosphate, or coconut oil fatty acid diethanolamide and nonionic or Since a cationic binder is compounded, the vinylpyridinium-based polymer is stably compounded, and the microbial removal rate is extremely high at 90% or more.
In addition, the properties of the composition were stable without solid-liquid separation.

Example 9 In this example, a dentifrice was prepared according to the following formulation according to a conventional method. Ingredients Amount (% by weight) Sample 16 (Table 2) 5.0 Cetylpyridinium chloride 0.1 Sodium monofluorophosphate 0.7 Sodium lauryl sulfate 2.0 Hydroxyethyl cellulose 2.0 Calcium hydrogen phosphate 20.0 Glycerin 20 0.0 Perfume 1.0 Saccharin sodium 0.2 Purified water Remaining 100.0 When the microorganism removal rate of the obtained dentifrice was evaluated by the above-mentioned method, a favorable microorganism removal effect and an excellent feeling in use were obtained.

Example 10 In this example, a gingival massage pasta was prepared according to a conventional method according to the following formulation. Component Blended amount (% by weight) Sample 12 (Table 2) 5.0 Tocopherol nicotinate 0.5 Coconut oil fatty acid diethanolamide 2.0 Hydroxyethylcellulose 3.0 Glycerin 20.0 Flavor 0.6 Dipotassium glycyrrhizinate 0.1 Purification Water residue 100.0 When the microorganism removal rate of the obtained dentifrice was evaluated by the above method, a favorable microorganism removal effect and an excellent feeling in use were obtained.

Example 11 In this example, a toothpaste was prepared according to the following formulation in a conventional manner. Ingredients Amount (% by weight) Sample 15 (Table 2) 2.0 Calcium hydrogen phosphate 50.0 Heavy calcium carbonate 20.0 Polyoxyethylene lauryl 1.0 Ether sodium phosphate Cationized hydroxyethyl cellulose 1.0 Glycerin 20 0.0 Perfume 1.0 Saccharin sodium 0.1 Purified water Remaining 100.0 When the microorganism removal rate of the obtained dentifrice was evaluated by the above-mentioned method, a favorable microorganism removal effect and an excellent feeling in use were obtained.

[0058]

According to the present invention, a novel oral composition having an excellent action of removing microorganisms, which is stably blended with a vinylpyridinium-based polymer, can be obtained.

Continuation of front page (56) References JP-A-6-24950 (JP, A) JP-A-5-139944 (JP, A) JP-A-5-139943 (JP, A) JP-A-5-139942 (JP) JP-A-5-194170 (JP, A) JP-A-5-194168 (JP, A) JP-A-5-194167 (JP, A) JP-A-51-32743 (JP, A) 49-66841 (JP, A) JP-A-60-112711 (JP, A) JP-A-2-223511 (JP, A) JP-A-61-226011 (JP, A) JP-A-60-38321 (JP, A A) JP-A-55-13251 (JP, A) JP-B-48-37824 (JP, B1) JP-T-5-506653 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) ) A61K 7/22

Claims (2)

(57) [Claims] 1. A water-insoluble polymer compound having vinylpyridinium as a repeating unit in a molecule, an alkyl sulfate and a salt thereof, a soap, a polyoxyethylene alkyl ether phosphate and a salt thereof, and an alkylol amide type surfactant. An oral composition characterized by comprising at least one surfactant selected from the group consisting of: 2. The oral composition according to claim 1, further comprising at least one binder selected from nonionic and cationic binders.