JP2021155364A - Oral composition - Google Patents

Abstract

To provide an oral composition containing a nonionic bactericide that is applied into the mouth and exhibits a bactericidal effect on the bacteria suspended in saliva in a shorter time.SOLUTION: An oral composition contains (A) thymol in combination with (B) at least one selected from the group consisting of amino nicotinic acid, hydroxy nicotinic acid, chloro nicotinic acid, isonicotinic acid, methyl nicotinate, and nicotinic acid.SELECTED DRAWING: None

Description

The present invention relates to shortening the sterilization time by a nonionic bactericidal agent in an oral composition.

Oral bacteria that cause oral diseases such as caries and periodontal disease exist in a suspended state in saliva, and they adhere to pellicle, which is a film of glycoproteins formed on the tooth surface. Is the first step in biofilm formation. Therefore, sterilizing and removing airborne bacteria in saliva suppresses the formation of biofilms, which in turn leads to the prevention of dental caries and periodontal disease.

In order to kill airborne bacteria in saliva, oral compositions such as dentifrices containing thymol, which is a nonionic fungicide, are widely used. For example, in Patent Document 1, benzyl is used with respect to thymol. Oral compositions comprising glyceryl ether, alcohol, and nonionic surfactant have been described.

Japanese Unexamined Patent Publication No. 2011-126785

However, when an oral composition containing a nonionic bactericidal agent is applied into the oral cavity as described above, there are individual differences in the length of time that the user holds the oral composition in the oral cavity, and the user. Since the bactericidal effect may not be sufficiently exhibited depending on the usage mode of the above, an oral composition that exhibits a bactericidal effect against airborne bacteria in a shorter time has been desired.

As a result of diligent research in view of the above problems, the present inventors surprisingly, as opposed to (A) Timor, (B) aminonicotinic acid, hydroxynicotinic acid, chloronicotinic acid, isonicotinic acid, nicotin. It has been found that the above problems can be solved by combining with at least one selected from the group consisting of methyl acid and nicotinic acid.

The present invention includes, for example, the inventions described below.
Item 1.
An oral composition containing (A) thymol (B) at least one selected from the group consisting of aminonicotinic acid, hydroxynicotinic acid, chloronicotinic acid, isonicotinic acid, methyl nicotinate, and nicotinic acid.
Item 2.
The content of the component (A) is 0.01 to 0.3% by mass,
The oral composition according to claim 1, wherein the content of the component (B) is 0.001 to 50% by mass.

Provided is an oral composition that exhibits a bactericidal effect on airborne bacteria in saliva in a shorter time when an oral composition containing a nonionic bactericidal agent is applied into the oral cavity.

Hereinafter, each embodiment included in the present invention will be described in more detail. The present invention is selected from the group consisting of (B) aminonicotinic acid, hydroxynicotinic acid, chloronicotinic acid, isonicotinic acid, methyl nicotinate, and nicotinic acid with respect to the oral composition, particularly (A) Timor. It preferably includes, but is not limited to, an oral composition containing at least one of the above, and the present invention includes all disclosed in the present specification and recognized by those skilled in the art.

The component (A) used in the present invention is thymol. As the thymol, either one extracted from a plant such as thyme or one chemically synthesized can be used, and a commercially available product can be used. In addition, essential oils containing thymol such as thyme may be used, and these may be used alone or in combination. The method for collecting the essential oil is not particularly limited, and examples thereof include a pressing method, a steam distillation method, a solvent extraction method, a fat adsorption method, a supercritical fluid extraction method, and the like, and a steam distillation method is preferably used. The distillation is not particularly limited as long as it is a distillation that does not apply an excessive heat load, and examples thereof include vacuum steam distillation, vacuum simple distillation, vacuum precision distillation, and vacuum precision distillation is preferably used.

The blending amount of the component (A) is preferably 0.01 to 0.3% by mass with respect to the total amount of the composition. If the blending amount is less than 0.01% by mass, the bactericidal effect against airborne bacteria may not be exhibited. On the other hand, if the blending amount exceeds 0.3%, the solubility is low, so that the clarity of the composition is impaired and precipitation may occur during storage. The blending amount of the component (A) is more preferably 0.02 to 0.2% by mass, further preferably 0.05 to 0.15% by mass, and most preferably 0.1% by mass. The blending amounts of the component (A) are 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, It may be 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.2, 0.25 mass%.

The component (B) used in the present invention is at least one selected from the group consisting of aminonicotinic acid, hydroxynicotinic acid, chloronicotinic acid, isonicotinic acid, methyl nicotinate, and nicotinic acid. These can be used in any form as well as those commercially available as reagents. Further, any of these structural isomers can be preferably used, and these may be appropriately combined and blended, but the preferred isomers are 2-hydroxynicotinic acid, 2-chloronicotinic acid, and 6-, respectively. Chloronicotinic acid, 2-aminonicotinic acid, 5-aminonicotinic acid.

The blending amount of the component (B) is preferably 0.001 to 50% by mass with respect to the total amount of the composition. When the blending amount is 0.001% by mass or more, the bactericidal effect of the component (A) is exhibited in a shorter time. On the other hand, if the blending amount exceeds 50% by mass, it is disadvantageous in terms of formulation or cost. The blending amount of the component (B) is more preferably 0.01 to 25% by mass, further preferably 0.05 to 10% by mass, and most preferably 0.1 to 5% by mass. The blending amount of the component (B) is 0.005, 0.01, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50% by mass may be used. ..

The oral composition of the present invention can be produced by a conventional method. Further, as the form of the oral composition of the present invention, it can be used as a dentifrice, a liquid dentifrice, a mouthwash, a gel, a paste, an ointment, a coating agent, a quasi-drug, and a cosmetic.

In the oral composition of the present invention, known arbitrary components that can be generally blended in the oral composition may be further blended alone or in combination of two or more, as long as the effects of the present invention are not impaired. ..

Such known optional components include, for example, surfactants, fungicides, abrasives, wetting agents, thickeners, sweeteners, preservatives, colorants, pH regulators, stabilizers, flavoring agents, astringents. Examples include agents, fragrances, and other medicinal ingredients.

As the surfactant, for example, an anionic surfactant, a nonionic surfactant, or an amphoteric surfactant can be blended. Specifically, examples of the anionic surfactant include alkyl sulfates, polyoxyethylene alkyl ether sulfates, alkyl sulfosuccinates, polyoxyethylene alkyl ether sulfosuccinates, N-acylamino acid salts, and N-. Examples thereof include acyl taurine salts, alkyl ether carboxylates, alkyl phosphates, polyoxyethylene alkyl ether phosphates, fatty acid monoglyceride sulfates, and alkyl sulfoacetate salts. Examples of nonionic surfactants include fatty acid esters, fatty acid alkanolamides, sorbitan fatty acid esters, fatty acid monoglycerides, polyglycerin fatty acid esters, polyoxyethylene alkylphenyl ethers, alkyl glycosides, diethyl sebacate, and polyoxyethylene hydrogenated castor oil. Examples thereof include fatty acid polyoxyethylene sorbitan. Examples of the amphoteric ion surfactant include betaine alkyldimethylaminoacetate, betaine alkylamide propyldimethylaminoacetate, N-acyl-N-carboxymethyl-N-hydroxyethylethylenediamine, N-alkylaminoethylglycine and the like. These surfactants can be blended alone or in combination of two or more. The blending amount is usually 0.1 to 5% by mass based on the total amount of the composition.

Examples of the disinfectant include cationic disinfectants such as benzalkonium chloride, benzethonium chloride and chlorhexidine hydrochloride, vitamin Es such as dl-α-tocopherol acetate, tocopherol succinate, and tocopherol nicotinate, dodecyldiaminoethylglycine and the like. Examples thereof include an amphoteric disinfectant and a nonionic disinfectant such as triclosan. These disinfectants may be further blended alone or in combination of two or more.

As an abrasive, for example, calcium dibasic phosphate / dihydrate and anhydride, calcium phosphate, calcium phosphate tribasic, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, alumina, silicic anhydride, silica gel, aluminum silicate, insoluble metaphosphoric acid. Examples thereof include sodium, tertiary magnesium phosphate, magnesium carbonate, calcium sulfate, polymethyl methacrylate, bentonite, zirconium silicate, hydroxyapatite, synthetic resin and the like. These abrasives can be blended alone or in combination of two or more.

Examples of the wetting agent include ethylene glycol, propylene glycol, 1,3-butylene glycol, polypropylene glycol, xylit, martit, lactite, palatinit, polyethylene glycol and the like. These wetting agents can be blended alone or in combination of two or more.

Examples of the preservative include parabens such as methylparaben, ethylparaben, propylparaben and butylparaben, sodium benzoate, phenoxyethanol, alkyldiaminoethylglycine hydrochloride and the like. These preservatives can be blended alone or in combination of two or more.

Examples of the pH adjuster include citric acid, phosphoric acid, malic acid, pyrophosphate, lactic acid, tartaric acid, glycerophosphate, acetic acid, nitric acid, chemically possible salts thereof, sodium hydroxide and the like. These pH adjusters can be blended alone or in combination of two or more.

Examples of the stabilizer include sodium edetate, sodium thiosulfate, sodium sulfite, sodium chloride, calcium lactate, lanolin, triacetin, castor oil, magnesium sulfate and the like. These stabilizers can be blended alone or in combination of two or more.

Examples of the flavoring agent include tea extract, tea dry distillate, propolis extract, monosodium glutamate and the like.

Examples of the astringent include baking soda, aluminum lactate and the like.

Other medicinal agents include fluorine compounds such as sodium fluoride, sodium monofluorophosphate, stannous fluoride; enzymes such as dextranase, mutanase, amylase, protease, lytic enzyme (Litec Enzyme); tranexamic acid, ε-Aminocaproic acid, aluminum chlorohydroxyalantin, allantoin, dihydrocholesterol, glycyrrhizinic acids, glycyrrhetinic acid, bisabolol, glycerophosphate, chlorophyll, copper gluconate, sodium chloride, water-soluble inorganic phosphate compounds; pyridoxin acetate, ascorbic acid or salts thereof And other vitamins.

Furthermore, the present invention also includes a method of shortening the sterilization time by the component (A) and thymol in the presence of saliva by using the component (B). Even in this case, the blending amount of the component (A) and the component (B) is preferably in the above range.

The present invention will be described in detail below based on examples, but the present invention is not limited to these examples.

[Evaluation of sterilization time for saliva]
(Saliva collection)
Three subjects, A, B, and C, were allowed to brush their teeth with a surfactant-free dentifrice for 1 minute, and after 1 hour of prohibition of eating and drinking, 10 ml of unstimulated saliva was collected. The collected saliva was used by repeatedly dispersing suction and discharge 5 times using a 23 G injection needle and a 10 ml syringe (both manufactured by Terumo Corporation).

(Sterilization test)
(A) The concentration of any one of thymol 0.1% (w / v) and each component 0.1, 0.25, 0.5% (w / v) of (B) shown in Table 1 is further added. A solution containing the mixture was prepared and 200 μl each was dispensed into row A of a 96-well plate. Nicotinic acid, isonicotinic acid, and methyl nicotinate are ethanol solutions with a final concentration of 15% (v / v), 2-hydroxynicotinic acid, 2-chloronicotinic acid, 6-chloronicotinic acid, 2-aminonicotinic acid, 5-Aminonicotinic acid was prepared to be a DMSO solution with a final concentration of 5% (v / v). 200 μl of TSB / Y / VH medium was dispensed into rows B to H for inactivating the fungicide and culturing oral bacteria. The measurement start point was when 60 μl of the above-mentioned subject saliva was added to row A and mixed by pipetting, and 20 μl of the solution in row A was added to row B after 30 seconds, and in row C after 60 seconds, 90. After a second, they were sorted into the D row, after 120 seconds, they were sorted into the E row, after 180 seconds, they were sorted into the F row, after 240 seconds, they were sorted into the G row, and after 300 seconds, they were sorted into the H row. The density of the 15% (v / v) ethanol solution is 0.98024 g / cm ³ according to JIS B 7548 2009 Annex A, so that the component (A) is 0.1% (w / v). ) Is 0.10201583% by mass, and the component (B) 0.5% (w / v) is 0.510007916% by mass. Further, since the density of the 5% (v / v) DMSO solution calculated from JIS K 9702 and JIS Z 8804 is 0.994 g / cm ³ , the above component (A) component 0.1% (w / v). Is 0.10060362% by mass, 0.25% (w / v) of the component (B) is 0.25150905% by mass, and 0.5% (w / v) is 0.50301810% by mass.

After that, it was allowed to stand for 48 hours using Aneropack Kenki (manufactured by Mitsubishi Gas Chemical Company) for anaerobic culture, and if the medium was visually turbid, bacteria would grow and the bacteria in the solution would be completely sterilized. It was judged that it was not. The determination was made for each solution collected from row A after 30 seconds, 60 seconds, 90 seconds, 120 seconds, 180 seconds, 240 seconds, and 300 seconds as described above, and the medium did not become turbid for the first time, and the bacteria in the solution. The time when the substance was completely sterilized was defined as the sterilization time. Table 1 shows the sterilization time when each component (B) was added as a relative value when the sterilization time for saliva of each subject with thymol of component (A) alone was set to 100%.

The TSB / Y / VH medium is prepared by dissolving 30 g of Tripticase Soy Broth (TSB), 1 g of Yeast Extract, 1 g of Hemin / menadetion solution, 0.7 g of lecithin, and 5 g of Tween 805 in distilled water, and autoclaving the medium. Prepared by sterilization. The Hemin / menadion solution was prepared by dissolving 0.25 g of Hemin in 5 ml of 1N NaOH, adding 20 ml of distilled water, and then dissolving 0.025 g of menadione (VitaminK3) in 25 ml of 99% ethanol. It is a thing.

Table 1 shows the examples of the present invention and the results of the sterilization test. The concentration of each component (A) and (B) is% (w / v).

For example, in Example 1, by adding 2-aminonicotinic acid to thymol, the sterilization time was 50% for subject A saliva, 33% for subject B saliva, and 33% for subject C saliva, as compared with thymol alone. The sterilization time was reduced to 83%. It was confirmed that the combination of the component (A) with any of the components (B) has an effect of reducing the sterilization time on the saliva of at least one subject.

The sterilization time shortening effect of thymol is particularly preferable because it is effective for saliva of all three subjects when 2-aminonicotinic acid and 5-amino are blended as in Examples 1 and 2. Further, these B components are preferably used in combination so as to complement each other's effects, such as 2-hydroxynicotinic acid and isonicotinic acid, 2-chloronicotinic acid and methyl nicotinate.

Tables 2 to 4 below show a formulation example of the oral composition of the present invention. The blending amount (%) of each formulation indicates mass% unless otherwise specified.

Claims (2)

An oral composition containing (A) thymol (B) at least one selected from the group consisting of aminonicotinic acid, hydroxynicotinic acid, chloronicotinic acid, isonicotinic acid, methyl nicotinate, and nicotinic acid. The content of the component (A) is 0.01 to 0.3% by mass,
The oral composition according to claim 1, wherein the content of the component (B) is 0.001 to 50% by mass.