JPH08133937A - Composition for oral cavity application - Google Patents

Abstract

PURPOSE: To obtain an oral cavity application composition having improved compatibility with a cationic disinfectant and exhibiting excellent plaque controlling effect by using a siliceous substance having a specific organosilicon quaternary ammonium salt immobilized to the siliceous substance. CONSTITUTION: This composition for oral cavity application contains a cationic disinfectant (selected from water-soluble pyridinium compound, water-soluble quaternary ammonium compound and bigua-ide-type disinfectant) in combination with a siliceous substance (especially preferably silica) containing an organosilicon quaternary ammonium salt having a specific cation adsorptivity and immobilized to the siliceous substance. The cation adsorptivity of the siliceous substance is <=4.5mg/g determined by a cation adsorption test and calculated by the formula (ABSt, ABSb and ABSc are each a light absorbance measured by a specific method; Wt is weighed siliceous substance (g)). The amount of the organosilicon quaternary ammonium salt immobilized to the siliceous substance is preferably 0.01-10.0wt.% based on the siliceous substance.

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 which exhibits an excellent plaque control effect by sterilizing and removing microorganisms in the oral cavity.

[0002]

2. Description of the Related Art Oral compositions containing a siliceous substance having an organosilicon quaternary ammonium salt immobilized thereon are known. For example, Japanese Patent Application Laid-Open No. 5-310545 discloses such an organosilicon quaternary compound. It has been disclosed that an oral composition containing a siliceous substance having an ammonium salt fixed thereto exhibits a plaque control effect.

[0003]

However, when a siliceous substance having an organosilicon quaternary ammonium salt immobilized thereon is used in combination with a cationic bactericide, the stability of the cationic bactericide deteriorates, There is a problem that the original effectiveness of the cationic bactericide is not exhibited.

[0004]

In view of these problems, the present inventors have proposed that a siliceous substance having an organosilicon quaternary ammonium salt immobilized thereon and a cationic fungicide are stably mixed. As a purpose, we conducted a thorough study. As a result, they have found that a siliceous substance having a specific organosilicon quaternary ammonium salt immobilized thereon has an extremely good compatibility with a cationic bactericide, and thus completed the present invention.

That is, the present invention relates to a siliceous substance having an organosilicon quaternary ammonium salt immobilized thereon, which is compatible with a cationic bactericide, a water-soluble pyridinium compound as a cationic bactericide, One or more selected from the group consisting of a water-soluble quaternary ammonium compound and a biguanide fungicide, especially from the group consisting of cetylpyridinium chloride, chlorhexidine salts and benzalkonium chloride among those cationic fungicides. The present invention provides an oral composition comprising one or more selected medicinal agents.

The above oral composition of the present invention efficiently removes microorganisms in the oral cavity by a siliceous substance having an organosilicon quaternary ammonium salt immobilized thereon, and particularly cetylpyridinium chloride, chlorhexidine salts and benzalkonium chloride. It exhibits a bactericidal effect with one or more kinds of cationic bactericides selected from the group consisting of, and exhibits an excellent plaque control effect. The present invention will be described in detail below.

In the present invention, an organosilicon quaternary ammonium salt is used after being immobilized on a siliceous substance. Examples of this siliceous substance include glass, silica, diatomaceous earth, powdered quartz, mica, zeolite, aluminum silicate, aluminum calcium aluminum silicate, magnesium silicate and zirconium silicate, with silica and zeolite being particularly preferred.

[0008] Organosilicon quaternary ammonium salt used in the present invention provides compounds of _{^{formula: R 1 3 N + R 2}} SiR 3 n X 3-n · Y - in known compound represented by the usually commercially available as an alcohol solution There is. In the above formula, X represents a hydrolyzable group such as a halogen atom, an alkoxy group or an acyl group, and Y represents chlorine or bromine. R ¹ is a monovalent aliphatic hydrocarbon group having 1 to 22 carbon atoms, particularly two of three R ¹ are methyl groups, and the other one is an alkyl group having 8 to 22 carbon atoms. Is preferred. R ² is a divalent hydrocarbon group, particularly an alkylene group having 2 to 4 carbon atoms or a formula: —CH ₂ CH ₂ CH ₂ NHCH ₂ CH ₂
Those represented by-are preferable. R ₃ is a lower alkyl group such as a methyl group, a phenyl group or a CF ₃ CH ₂ CH ₂ group. n represents 0, 1 or 2, and is preferably 0.

The organosilicon quaternary ammonium salt as described above is particularly preferably one represented by the following formula.

Embedded image (In the formula, R ¹ means an alkyl group having 8 to 22 carbon atoms.) Incidentally, these siliceous substances to which organosilicon quaternary ammonium salt is immobilized may be used alone or in combination of two or more. You may use together. Further, the amount of the siliceous substance having the organosilicon quaternary ammonium salt immobilized thereon is usually 0.01 to 40% by weight, preferably 1.0 to 20% by weight, based on the whole oral composition. .

In the siliceous substance to which the organosilicon quaternary ammonium salt of the present invention is immobilized, the adsorption amount of cation per unit gram calculated by an adsorption test using chlorhexidine is 4.5 mg or less, preferably 3.
It will be 0 mg or less.

The amount of cations adsorbed per gram calculated by the adsorption test using chlorhexidine can be calculated by the following method. That is, distilled water 18.0
1.0 ml of a siliceous substance having an organosilicon quaternary ammonium salt immobilized thereon and 1.0 ml of a 1.0% chlorhexidine gluconate gluconate solution are added to and dispersed in ml. The dispersion is stirred at 25 ° C for 3 hours. Then, this dispersion is centrifuged at 17,000 rpm for 5 minutes, and the obtained supernatant is filtered through a Millipore filter having a pore size of 0.45 μm. The obtained filtrate is diluted 10 times with distilled water to obtain a test solution. 1.0% Chlorhexidine Gluconate Solution 1.0 ml
1.0 ml of distilled water is added instead of, and the solution obtained by the same method is used as a base solution. The control solution is prepared by the following method. That is, 1.0 ml of 1.0% chlorhexidine gluconate solution was added to 19.0 ml of distilled water and dispersed. The dispersion is stirred at 25 ° C for 3 hours. The dispersion is then centrifuged at 17,000 rpm for 5 minutes,
The resulting supernatant is filtered through a Millipore filter with a pore size of 0.45 μm. The obtained filtrate is diluted 10 times with distilled water to obtain a control solution.

Next, the prepared test solution, base solution,
Spectrophotometer for absorption of control solution (Shimadzu MPS-2000)
The amount of cation adsorbed per unit gram is calculated by the following formula.

[Equation 2] Where ABSt is the absorbance of the sample solution, ABSb is the absorbance of the base solution, ABSc is the absorbance of the control solution, Wt
Is the weighed amount in grams of siliceous material with immobilized organosilicon quaternary ammonium salt.

The oral composition of the present invention can be made into a dosage form such as a powder toothpaste, a toothpaste, an ointment, a mouthwash, a pasta agent and a liniment by a method known per se. If desired, an abrasive, a foaming agent, a flavoring agent, a sweetening agent, a binding agent / viscosity agent, and other medicinal ingredients may be added to a gingival massage formulation, etc. within a range that does not impair the effects of the invention. You can

For example, as the abrasive, dicalcium phosphate / dihydrate and anhydride, calcium phosphate, tricalcium phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, alumina, silicic anhydride, silica gel, aluminum silicate, insoluble Sodium metaphosphate, magnesium triphosphate, magnesium carbonate,
Calcium sulfate, polymethylmethacrylate, bentonite, zirconium silicate, synthetic resin and the like can be used. These abrasives may be used alone or in combination of two or more, and the compounding amount thereof is usually 5.0 to 90.
In the case of toothpaste, it is 5 to 60% by weight.

For example, the foaming agent mainly includes a nonionic surfactant and an anionic surfactant. The nonionic surfactant is, for example, a fatty acid ester of sugar or sugar alcohol, wherein the fatty acid residue has 12 to 18 carbon atoms and the average degree of esterification is 1.1 to 2.
5, preferably 1.2 to 1.9 can be used. Examples of the fatty acid ester of sugar or sugar alcohol include sucrose fatty acid ester, maltose fatty acid ester, maltitol fatty acid ester, maltotriitol fatty acid ester, maltotetriitol fatty acid ester, maltopentitol fatty acid ester, maltohexayl ester. Examples thereof include tall fatty acid ester, maltoheptaitol fatty acid ester, sorbitan fatty acid ester, lactose fatty acid ester, lactitol fatty acid ester. Other nonionic surfactants include:
Polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monostearate and other polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, polyoxyethylene fatty acid esters, fatty acid monoglycerides, poly Also included are oxyethylene higher alcohol ethers, polyoxyethylene polyoxypropylene fatty acid esters and the like. In addition, these nonionic surfactants may be used alone or in combination of two or more kinds, but the compounding amount in the range that does not impair the effects of the invention is usually 0.01 to the whole composition. 40
%, Preferably 0.05 to 10% by weight.

As the anionic surfactant, for example, a water-soluble salt of a higher alkyl sulfate ester having an alkyl group having 8 to 18 carbon atoms such as sodium lauryl sulfate and sodium myristyl sulfate, α-olefin sulfonate, and higher fatty acid. Sodium monoglyceride monosulfate, sodium-N-methyl-N-palmityl taurate, sodium-N-lauroyl-β-alanine, lauroyl sarcosinate, sodium-N-long chain acyl basic amino acid and the like can be added. In addition, although these anionic surfactants may be used alone or in combination of two or more kinds, the compounding amount in the range that does not impair the effects of the invention is usually 0.001 to 1 with respect to the entire composition. .
It is 0% by weight, preferably 0.01 to 0.05% by weight.

The oral composition of the present invention further includes menthol, carboxylic acid, anethole, eugenol, methyl salicylate, limonene, ocimene, n-decyl alcohol, citronellol, α-terbineol, methyl acetate, citronellyl acetate, methyl eugenol. , Cineole, linalool, ethyl linalool, vanillin, thymol, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, pimento oil, diatom oil, perilla oil, winter green oil, clove oil, A flavoring agent such as eucalyptus oil may be used alone or in combination of two or more kinds, and the blending amount thereof is 0.1 with respect to the entire composition.
10 to 10% by weight, preferably 0.5 to 5% by weight.

Alternatively, sweeteners such as sodium saccharin, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perillin, thaumatin, aspartyl phenylalanine methyl ester and p-methoxycinnamic aldehyde may be used alone. Two or more kinds may be used in combination, and the blending amount thereof is 0.01 to 1% by weight, preferably 0.05 to 0.5% by weight, based on the entire composition.

In the case of a paste composition such as an ointment, a cellulose derivative such as sodium carboxymethylcellulose, an alkali metal alginate such as sodium alginate, a propylene glycol alginate ester, xanthan gum, tragacanth gum, karaya gum, gum arabic, carrageenan. Such as gums, polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, synthetic binders such as polyvinylpyrrolidone, and binders such as silica gel, aluminum silica gel, bee gum, inorganic binders such as Laponite, etc. are used alone. Alternatively, two or more kinds may be used in combination, and the blending amount thereof is usually 0.3 to 5% by weight based on the whole composition.

Further, in the case of a paste composition or a liquid composition, the viscosity of sorbit, glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, polypropylene glycol, xylit, maltite, lactit, etc. The thickener may be used alone or in combination of two or more, and the compounding amount thereof is usually 10 to 70% by weight based on the whole composition.
Is.

Further, bactericides such as triclosan, dextranase, amylase, protease, mutanase,
Lysozyme, enzymes such as lytic enzymes (Litech Enzyme), sodium monofluorophosphate, alkali metal monofluorophosphates such as potassium monofluorophosphate, sodium fluoride, fluorides such as stannous fluoride, tranexamic acid and epsilon aminocapron The active ingredients such as acid, aluminum chlorhydroxylantoin, dihydrocholesterol, glycyrrhizin salts, glycyrrhetinic acid, glycerophosphate, chlorophyll, sodium chloride, caropeptide, water-soluble inorganic phosphate compound may be used alone or in combination.

[0022]

EXAMPLES Next, the present invention will be described more specifically by showing experimental examples and examples, but the present invention is not limited thereto. Experimental Examples (Examples 1 to 8 and Comparative Examples 1 to 5) Preparation of test dentifrice

[Table 1] Using organosilicon shown in Table 1, a toothpaste was prepared by a conventional method according to the following formulation. Ingredients Content (wt%) Dibasic calcium phosphate / anhydride 10 Glycerin 20 Polyoxyethylene polyoxy propylene glycol ether 30 Perfume 1.0 Saccharin sodium 0.3 Silica acid on which organosilicon quaternary ammonium salt shown in Table 1 is immobilized Substance 10 Cationic fungicides shown in Table 0.1 Purified water adjusted to 100% Bactericidal test (1) Preparation of test bacterial solution Streptococcus sobrinas
inus) OMZ176 was cultured in Brain Heart Infusion liquid medium under anaerobic conditions at 37 ° C. for 20 hours, and then centrifuged (7,000 rpm, 10 minutes) to collect the cells, and the obtained cells were sterilized. The cells were washed with physiological saline and suspended in sterile physiological saline so that the bacterial concentration was about 10 ⁷ cells / ml (OD ₅₆₀ = 0.02), and this was used as a test bacterial solution. (2) Evaluation of bactericidal effect (shake flask method) A test dentifrice diluted 10 times was centrifuged at 17,000 rpm, 1 g of the obtained supernatant was placed in a 100 ml Erlenmeyer flask, and 35 ml of sterilized water was added. And disperse well. This Erlenmeyer flask was placed in a constant temperature bath at 37 ° C., 4 ml of the test bacterial solution of (1) was added, and 120 strokes /
Shake for 3 minutes at minutes. Then, the Erlenmeyer flask is taken out of the constant temperature bath and allowed to stand for a while, then 1 ml of the supernatant is taken and diluted with sterile physiological saline. Then, 0.1 ml of this dilution was spread on a Brain Heart Infusion agar plate and cultured at 37 ° C. for 48 hours under anaerobic conditions, and then the number of formed colonies was counted. Thereby, the bactericidal effect can be evaluated by calculating the viable cell count after contacting the test dentifrice for 3 minutes.

The sterilizing effect (%) of the sample is calculated by the formula:

(Equation 3) Evaluation was made, and those showing a value of 90% or more were judged to have an excellent bactericidal effect.

The results are shown in Table 2.

[Table 2]

As is clear from the results in Table 2, the test dentifrice prepared by using the siliceous substance on which the organosilicon quaternary ammonium salt having a cation adsorption amount of 3.0 mg or less per unit gram is immobilized is , Shows a high bactericidal effect. On the other hand, when the cation adsorption amount per unit gram exceeds 4.5 mg, the bactericidal effect is remarkably reduced.

As a result, when a siliceous substance having an organosilicon quaternary ammonium salt immobilized thereon and a cationic bactericide are blended, the cation adsorption amount per unit gram is 4.5 mg, and further 3.0 mg or less. It has been clarified that an excellent bactericidal effect is exhibited by adding a specific organosilicon quaternary ammonium salt.

Example 9 A toothpaste was produced by a conventional method according to the following formulation. Ingredients Content (% by weight) Dibasic calcium phosphate / anhydride 10 Glycerin 20 Polyoxyethylene polyoxypropylene glycol ether 30 Perfume 1.0 Organosilicon quaternary ammonium salt-immobilized siliceous substance NO.5 (Table 1 ) 10 Saccharin sodium 0.2 Sodium monofluorophosphate 0.8 Chlorhexidine hydrochloride 0.1 Cetylpyridinium chloride 0.05 Purified water was added to 100 and the bactericidal effect of the toothpaste was evaluated by the above method. It showed a high bactericidal effect.

Example 10 A toothpaste was produced according to a conventional method according to the following formulation. Ingredients Content (wt%) Dibasic calcium phosphate / dihydrate 20 Glycerin 30 Sodium carboxymethylcellulose 2.0 Perfume 1.0 Sodium lauryl sulfate 2.0 Organosilicon quaternary ammonium salt-immobilized siliceous substance NO. 3 (Table 1) 20 Saccharin sodium 0.3 Sodium monofluorophosphate 0.8 Cetylpyridinium chloride 0.1 Trichlorohydroxydiphenyl ether 0.1 Purified water was added to adjust to 100 The bactericidal effect of the toothpaste obtained was as described above. As a result of evaluation by the method, a high bactericidal effect was shown.

Example 11 A toothpaste was produced by the usual method according to the following formulation. Ingredients Content (wt%) Silica 20 Sorbit 35 Sodium carboxymethyl cellulose 2.0 Perfume 1.0 Organosilicon quaternary ammonium salt-immobilized siliceous substance NO.5 (Table 1) 5.0 Saccharin sodium 0 .2 Sodium fluoride 0.2 Chlorhexidine hydrochloride 0.1 Polyoxyethylene hydrogenated castor oil 0.5 Sucrose fatty acid ester 0.5 Purified water was added to adjust to 100 The bactericidal effect of the toothpaste obtained above was measured by the above method. As a result of evaluation by, a high bactericidal effect was shown.

Example 12 A dentifrice was prepared by the following method according to a conventional method. Ingredients Content (wt%) Sodium alginate 3.0 Sorbit 30.0 Sodium saccharin 0.1 Perfume 1.0 Chlorhexidine gluconate 0.5 Ethanol 10.0 Silica substance immobilized with organosilicon quaternary ammonium salt NO .7 (Table 1) 3.0 Methyl paraoxybenzoate 0.1 Purified water was added to prepare 100. The bactericidal effect of the resulting water toothpaste was evaluated by the above method, and as a result, a high bactericidal effect was shown.

Example 13 A toothpaste was produced by a conventional method according to the following formulation. Ingredients Content (wt%) Sodium alginate 3.0 Sorbit 30.0 Sodium saccharin 0.1 Perfume 1.0 Chlorhexidine gluconate 0.5 Organosilicon quaternary ammonium salt-immobilized siliceous substance NO.7 (Table) 1) 15.0 Ethanol 10.0 Isopropanol 5.0 Methyl paraoxybenzoate 0.1 Purified water Add to adjust to 100 As a result of evaluating the bactericidal effect of the resulting water toothpaste by the above method, a high bactericidal effect was found. Indicated.

[0032]

INDUSTRIAL APPLICABILITY According to the present invention, a cationic bactericide and a siliceous substance having a specific organosilicon quaternary ammonium salt immobilized thereon are blended to efficiently remove the microorganisms in the oral cavity and to make them cationic. Provided is an oral composition that exhibits the effectiveness of a bactericide and exhibits an excellent plaque control effect.

Claims (8)

[Claims] 1. One or more kinds of cationic fungicides selected from water-soluble pyridinium compounds, water-soluble quaternary ammonium compounds and biguanide fungicides,
An oral composition characterized by being blended with a siliceous substance having an organosilicon quaternary ammonium salt immobilized thereon, which has a cation adsorption amount of 4.5 mg or less per unit gram calculated by the following formula in a cation adsorption test. Thing: [Numerical formula 1] [In the formula, ABSt is 1 g of siliceous substance obtained by fixing organosilicon quaternary ammonium salt in 18 ml of distilled water,
1.0 ml of chlorhexidine gluconate (1.0%) was added, and after dispersion, the mixture was stirred at 25 ° C. for 3 hours, the obtained suspension was centrifuged at 17,000 rpm for 5 minutes, and the obtained supernatant was collected. Absorbance obtained by filtering with a Millipore filter having a pore size of 0.45 μm, diluting the obtained filtrate 10 times with distilled water, and measuring at a measurement wavelength of 259 nm; ABSb
Is the absorbance calculated in the same manner as in ABSt above except that 1.0 ml of distilled water was added instead of 1.0 ml of chlorhexidine gluconate 1.0%; ABSc is an organosilicon quaternary ammonium salt. Absorbance calculated by the same method as ABSt above except that 1.0 ml of distilled water was added instead of 1 g of the siliceous substance immobilized; Wt is the siliceous substance having the organosilicon quaternary ammonium salt immobilized. Means the weight of the substance in grams.] 2. The oral composition according to claim 1, wherein the siliceous substance is silica. 3. The oral composition according to claim 1, wherein the water-soluble pyridinium compound is cetylpyridinium chloride. 4. The oral composition according to claim 1, wherein the water-soluble quaternary ammonium compound is benzethonium chloride or benzalkonium chloride. 5. The oral composition according to claim 1, wherein the biguanide fungicide is a chlorhexidine salt. 6. The oral composition according to claim 1, wherein the amount of cation adsorbed per unit gram calculated in the cation adsorption test is 3.0 mg or less. 7. The amount of the organosilicon quaternary ammonium salt immobilized on the siliceous material is 0.001 to 20.0% by weight based on the weight of the siliceous material.
Or the composition for oral cavity according to 2. 8. The immobilization amount of the organosilicon quaternary ammonium salt on the siliceous substance is 0.01% by weight to 10.0% by weight based on the weight of the siliceous substance. 2. The composition for oral cavity according to 2.