JP7477291B2 - Oral Composition - Google Patents

Description

The present invention relates to shortening the disinfection time of a disinfectant in an oral composition.

Oral bacteria that cause oral diseases such as dental caries and periodontal disease exist in a suspended state in saliva, and the first step in the formation of a biofilm is for them to attach to a glycoprotein membrane that forms on the tooth surface, called a pellicle. Therefore, sterilizing and removing suspended bacteria in saliva inhibits the formation of biofilms, which in turn leads to the prevention of dental caries, periodontal disease, etc.

Oral compositions such as dentifrices containing nonionic bactericides such as isopropylmethylphenol and thymol are widely used to kill bacteria suspended in saliva. For example, Patent Document 1 describes an oral composition containing isopropylmethylphenol or thymol, benzylglyceryl ether, alcohol, and a nonionic surfactant. Patent Document 2 describes an oral composition containing isopropylmethylphenol, cetylpyridinium chloride, an N-acyltaurine salt, and a nonionic surfactant.

JP 2011-126785 A JP 2016-145162 A

However, when an oral composition containing a nonionic bactericide is applied to the oral cavity as described above, the length of time that the user holds the oral composition in the oral cavity varies from person to person, and depending on the manner in which the user uses the composition, the bactericidal effect may not be fully exerted. Therefore, there has been a demand for an oral composition that exerts a bactericidal effect against airborne bacteria in a shorter time.

The inventors of the present invention have conducted intensive research in light of the above problems, and have surprisingly found that the above problems can be solved by incorporating (A) isopropylmethylphenol or thymol with (B) at least one selected from the group consisting of xylose, ribose, galactose, mannose, fructose, arabinose, glucose, sorbitol, and mannitol.

The present invention includes, for example, the inventions described below.
Item 1.
(A) at least one nonionic bactericide selected from isopropylmethylphenol and thymol;
(B) an oral composition containing at least one selected from the group consisting of xylose, ribose, galactose, mannose, fructose, arabinose, glucose, sorbitol, and mannitol.
Item 2.
The content of the component (A) is 0.01 to 0.3 mass %,
The oral composition according to claim 1, wherein the content of component (B) is 0.001 to 50% by mass.

An oral composition containing a nonionic bactericide is provided that exerts a bactericidal effect against bacteria suspended in saliva in a shorter time when applied to the oral cavity.

Each embodiment included in the present invention will be described in more detail below. The present invention preferably includes compositions for oral use, particularly compositions for oral use that contain (A) isopropylmethylphenol or thymol and (B) at least one selected from the group consisting of xylose, ribose, galactose, mannose, fructose, arabinose, glucose, sorbitol, and mannitol, but is not limited thereto, and the present invention includes all of the compositions disclosed in this specification and recognizable by a person skilled in the art.

The component (A) used in the present invention is at least one nonionic fungicide selected from isopropylmethylphenol and thymol. Isopropylmethylphenol is 3-methyl-4-isopropylphenol, also known as cymen-5-ol by its INCI name, and a commercially available product can be used. Thymol is 2-isopropyl-5-methylphenol, and a commercially available product can be used. These may be used alone or in combination in the composition.

The amount of component (A) is preferably 0.01 to 0.3% by mass based on the total amount of the composition. If the amount is less than 0.01% by mass, the bactericidal effect against airborne bacteria may not be exerted. On the other hand, if the amount is more than 0.3%, the clarity of the composition may be impaired due to the low solubility of isopropyl methylphenol, and there is a risk of precipitation occurring during storage, and thymol may reduce the usability of the composition due to the emergence of a peculiar odor. The amount of component (A) is more preferably 0.02 to 0.2% by mass, even more preferably 0.05 to 0.15% by mass, and most preferably 0.1% by mass. The amount of component (A) may be 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.2, or 0.25% by mass.

The component (B) used in the present invention is at least one monosaccharide or sugar alcohol selected from the group consisting of xylose, ribose, galactose, mannose, fructose, arabinose, glucose, sorbitol, and mannitol. These can be used in any form, including those commercially available as reagents. As for the enantiomers, either the D-form or the L-form can be suitably blended, and these may be blended in appropriate combination, but the preferred enantiomers are D-xylose, D-ribose, D-galactose, D-mannose, D-fructose, L-arabinose, D-glucose, D-sorbitol, and D-mannitol.

The amount of the (B) component is preferably 0.001 to 50% by mass based on the total amount of the composition. If the amount is 0.001% by mass or more, the bactericidal effect of the (A) component is exerted in a shorter time. On the other hand, if the amount exceeds 50% by mass, it is disadvantageous in terms of formulation or cost. The amount of the (B) component is more preferably 0.01 to 25% by mass, even more preferably 0.05 to 10% by mass, and most preferably 0.1 to 5% by mass. The amount of the (B) component may also be 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, or 50% by mass.

The oral composition of the present invention can be produced by a conventional method. The oral composition of the present invention can be used in the form of a toothpaste, liquid toothpaste, mouthwash, gel, paste, ointment, liniment, quasi-drug, or cosmetic.

The oral composition of the present invention may further contain any known optional components that can generally be added to oral compositions, either alone or in combination of two or more, to the extent that the effect of the present invention is not impaired.

Examples of such known optional ingredients include surfactants, bactericides, abrasives, wetting agents, thickeners, sweeteners, preservatives, colorants, pH adjusters, stabilizers, flavoring agents, astringents, fragrances, and other medicinal ingredients.

As the surfactant, for example, an anionic surfactant, a nonionic surfactant, or an amphoteric surfactant can be blended. Specifically, as the anionic surfactant, for example, alkyl sulfate ester salt, polyoxyethylene alkyl ether sulfate ester salt, alkyl sulfosuccinate salt, polyoxyethylene alkyl ether sulfosuccinate salt, N-acyl amino acid salt, N-acyltaurine salt, alkyl ether carboxylate salt, alkyl phosphate salt, polyoxyethylene alkyl ether phosphate salt, fatty acid monoglyceride sulfate salt, alkyl sulfoacetate salt, etc. can be mentioned. As the nonionic surfactant, for example, fatty acid ester, fatty acid alkanolamides, sorbitan fatty acid ester, fatty acid monoglyceride, polyglycerin fatty acid ester, polyoxyethylene alkylphenyl ether, alkyl glycoside, diethyl sebacate, polyoxyethylene hydrogenated castor oil, fatty acid polyoxyethylene sorbitan, etc. can be mentioned. As the amphoteric surfactant, for example, alkyl dimethylamino acetate betaine, alkylamidopropyl dimethylamino acetate betaine, N-acyl-N-carboxymethyl-N-hydroxyethyl ethylenediamine, N-alkylaminoethyl glycine, etc. can be mentioned. These surfactants can be used alone or in combination of two or more. The amount used is usually 0.1 to 5% by mass of the total composition.

Examples of bactericides include cationic bactericides such as benzalkonium chloride, benzethonium chloride, and chlorhexidine hydrochloride; vitamin E compounds such as dl-α-tocopherol acetate, tocopherol succinate, and tocopherol nicotinate; amphoteric bactericides such as dodecyldiaminoethylglycine; and nonionic bactericides such as triclosan. These bactericides may be used alone or in combination of two or more.

Examples of abrasives include dibasic calcium phosphate dihydrate and anhydrate, calcium phosphate, tribasic calcium phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, alumina, anhydrous silicic acid, silica gel, aluminum silicate, insoluble sodium metaphosphate, tribasic magnesium phosphate, magnesium carbonate, calcium sulfate, polymethyl methacrylate, bentonite, zirconium silicate, hydroxyapatite, synthetic resins, etc. These abrasives can be formulated alone or in combination of two or more.

Examples of humectants include ethylene glycol, propylene glycol, 1,3-butylene glycol, polypropylene glycol, xylitol, maltitol, lactitol, palatinit, polyethylene glycol, etc. These humectants can be used alone or in combination of two or more.

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

Examples of pH adjusters include citric acid, phosphoric acid, malic acid, pyrophosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, or chemically possible salts thereof, sodium hydroxide, etc. These pH adjusters can be used alone or in combination of two or more.

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

Flavoring agents include, for example, tea extract, tea distillate, propolis extract, and sodium glutamate.

Examples of astringents include baking soda and aluminum lactate.

Other medicinal agents include fluorine compounds such as sodium fluoride, sodium monofluorophosphate, and stannous fluoride; enzymes such as dextranase, mutanase, amylase, protease, and lytic enzymes (retic enzymes); tranexamic acid, ε-aminocaproic acid, aluminum chlorohydroxyallantoin, allantoin, dihydrocholesterol, glycyrrhizic acids, glycyrrhetinic acid, bisabolol, glycerophosphate, chlorophyll, copper gluconate, sodium chloride, and water-soluble inorganic phosphate compounds; and vitamins such as pyridoxine acetate and ascorbic acid or its salts.

Furthermore, the present invention also includes a method for shortening the bactericidal time of component (A), isopropylmethylphenol or thymol in the presence of saliva by using component (B). In this case as well, it is preferable that the blending amounts of component (A) and component (B) are within the above-mentioned ranges.

The present invention will be described in detail below based on examples, but the present invention is not limited to these examples. Examples 8 and 10 to 18 below should be replaced with Reference Examples 8 and 10 to 18.

[Evaluation of bactericidal time against saliva]
(Saliva collection)
Three subjects, A, B, and C, brushed their teeth with a dentifrice that did not contain a surfactant for one minute, and after one hour of abstinence from eating and drinking, 10 ml of unstimulated saliva was collected. The collected saliva was dispersed by repeatedly drawing and discharging the saliva five times using a 23G injection needle and a 10 ml syringe (both manufactured by Terumo Corporation).

(Bactericidal test)
A 0.1% (w/v) solution of each component (A) alone and a solution further containing 0.5% (w/v) of each component (A) and (B) as shown in Table 1 were prepared so as to obtain an ethanol solution with a final concentration of 15% (v/v), and 200 μl of each solution was dispensed into row A of a 96-well plate. 200 μl of TSB/Y/VH medium was dispensed into rows B to H for inactivation of the bactericide and cultivation of oral bacteria. The measurement was started when 60 μl of the subject's saliva was added to row A and mixed by pipetting, and 20 μl of the solution from row A was dispensed into row B after 30 seconds, row C after 60 seconds, row D after 90 seconds, row E after 120 seconds, row F after 180 seconds, row G after 240 seconds, and row H after 300 seconds. According to JIS B 7548 2009 Appendix A, the density of a 15% (v/v) ethanol solution is 0.98024 g/ ^cm3 , so 0.1% (w/v) of the above component (A) is 0.10201583 mass%, and 0.5% (w/v) of the above component (B) is 0.51007916 mass%.

After that, the solution was left to stand for 48 hours for anaerobic culture using Anaeropack Kenki (manufactured by Mitsubishi Gas Chemical Co., Ltd.), and if the medium was visually turbid, it was determined that bacteria had grown and the bacteria in the solution had not been completely killed. This determination was made for each solution collected from row A after 30, 60, 90, 120, 180, 240, and 300 seconds as described above, and the time when the medium did not become turbid and the bacteria in the solution were completely killed was defined as the sterilization time. Table 1 shows the sterilization time when each (B) component was added as a relative value, assuming that the sterilization time for the saliva of each subject using the (A) component isopropyl methylphenol or thymol alone is 100%.

The above TSB/Y/VH medium was prepared by dissolving 30 g of Tripticase Soy Broth (TSB), 1 g of Yeast Extract, 1 g of Hemin/menadion solution, 0.7 g of lecithin, and 5 g of Tween 80 in distilled water, diluting the mixture to 1 L, and sterilizing the mixture in an autoclave. 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 mixing this with 0.025 g of menadion (Vitamin K3) dissolved in 25 ml of 99% ethanol.

Examples of the present invention and the results of the above sterilization test are shown in Table 1. The concentrations of each of the components (A) and (B) are in % (w/v).

For example, in Example 1, the addition of D-xylose to isopropyl methylphenol reduced the bactericidal time in the saliva of subject A by 25%, in the saliva of subject B by 50%, and in the saliva of subject C by 30% compared to isopropyl methylphenol alone. The effect of reducing the bactericidal time was confirmed in the saliva of at least two subjects in any combination of the (A) component with the (B) component.

As for isopropylmethylphenol, when combined with D-xylose, D-mannose, D-fructose, and D-mannitol as in Examples 1, 4, 5, and 9, it was effective on the saliva of all three subjects, which is particularly preferable. As for thymol, when combined with D-xylose, D-fructose, D-glucose, and D-mannitol as in Examples 10, 14, 16, and 18, it was effective on the saliva of all three subjects, which is particularly preferable.

Tables 2 to 4 below show examples of formulations of the oral composition of the present invention. The blending amount (%) of each formulation is by mass % unless otherwise specified.

Claims (3)

(A) isopropyl methylphenol, a nonionic disinfectant;
(B) an oral composition containing at least one selected from the group consisting of xylose, ribose, galactose, mannose, fructose, arabinose, and glucose. The content of the component (A) is 0.01 to 0.3 mass %,
The oral composition according to claim 1 , wherein the content of component (B) is 0.001 to 50% by mass. (A) isopropyl methylphenol, a nonionic disinfectant;
(B) mannitol,
An oral composition having a content of the (B) component of 0.001% by mass or more and less than 3% by mass.