Oral composition

Abstract

To provide an oral composition that selectively and efficiently promotes growth of Neisseria and / or Rothia species, non-pathogenic bacteria present in the oral microbiota, enabling effective improvement of the oral microbiota.SOLUTION: An oral composition comprising the following components (A) and (B): (A) a nitrate ion-supplying compound and (B) glycyrrhetinic acid, the composition containing sodium lauryl sulfate in an amount of 0.1 mass% or less or containing no sodium lauryl sulfate.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an oral composition. [Background technology]

[0002] The oral cavity is home to a wide variety of bacteria, and oral flora, consisting of colonies of these bacteria, exists in various locations, such as the tooth surfaces, gums, gingival margin, palate, buccal mucosa, and tongue surface and dorsum. This oral flora contains not only pathogenic bacteria involved in oral diseases such as dental caries and periodontal disease, but also non-pathogenic bacteria as resident bacteria. Maintaining a balance between these non-pathogenic and pathogenic bacteria is believed to be highly useful in preventing or suppressing the onset and progression of oral diseases.

[0003] Under these circumstances, various studies on oral flora are being conducted. For example, Patent Document 1 discloses an oral flora improving agent containing β-glycyrrhetinic acid, which attempts to increase the proportion of bacteria of the genus Streptococcus and the like and reduce the proportion of pathogenic bacteria. Patent document 2 also reports that by incorporating a nitrogen source such as nitrate into the composition, the Neisseria bacteria present in the oral cavity can produce nitric oxide, thereby controlling the bacterial composition of the oral flora to a favorable level. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Publication No. 2022-163809 [Patent Document 2] US Patent Application Publication No. 2016 / 0151428 Summary of the Invention [Problem to be solved by the invention]

[0005] However, even with the composition described in Patent Document 1, sufficient consideration has not been given to selectively and effectively promoting the growth of Neisseria bacteria in the oral cavity. Moreover, Patent Document 2 only describes a so-called probiotic technology in which microorganisms themselves are administered to the human body, and does not disclose or suggest any technical idea of ​​promoting the growth of specific microorganisms in the oral cavity. Thus, there is still ample room for improvement in order to enhance the selective and efficient growth-promoting effect of Neisseria bacteria in the oral flora.

[0006] Therefore, the present invention relates to an oral composition that can selectively and effectively promote the growth of the genus Neisseria in the oral flora, thereby effectively improving the oral flora. [Means for solving the problem]

[0007] Therefore, the present inventors conducted extensive research to solve the above problems and discovered an oral composition that selectively and effectively promotes the growth of Neisseria bacteria in oral flora and also has the effect of controlling the bacterial count, by containing a nitrate ion supplying compound and glycyrrhetinic acid while limiting the content of a specific surfactant.

[0008] That is, the present invention provides a composition comprising the following components (A) and (B): (A) Nitrate ion donor compound (B) Glycyrrhetinic acid and the content of sodium lauryl sulfate is 0.1% by mass or less, or the oral composition does not contain sodium lauryl sulfate. [Effects of the Invention]

[0009] According to the present invention, the growth of Neisseria bacteria in the oral cavity can be selectively promoted, thereby effectively improving the oral flora, and the oral flora can be rapidly improved by controlling the bacterial load. Furthermore, among the normal oral flora, the growth of not only Neisseria bacteria but also Russus bacteria can be selectively promoted, and the growth of Streptococcus bacteria can be selectively suppressed. DETAILED DESCRIPTION OF THE INVENTION

[0010] The present invention will be described in detail below. In the present invention, the term "oral flora" is also referred to as "oral (oral or oral cavity) flora" or "oral (oral or oral cavity) microbiota," and refers to a community formed by a wide variety of bacteria that inhabit the oral cavity. In addition, in the present invention, "improving" the oral flora means selectively promoting the growth of Neisseria bacteria, or even bacteria of the genus Russia, in the oral cavity, thereby increasing the proportion of Neisseria bacteria and bacteria of the genus Russia (hereinafter collectively referred to as "Neisseria bacteria, etc."), in the oral flora; it also means selectively suppressing the growth of Streptococcus bacteria and pathogenic bacteria, thereby increasing the proportion of Neisseria bacteria, etc. in the oral flora. Furthermore, the "bacterial quantity control effect" means the effect of effectively preventing the total quantity of bacteria in the oral cavity from becoming excessive and controlling it to a moderate quantity in order to ensure a good oral environment.

[0011] Here, the genus Neisseria refers to normal oral bacteria belonging to the genus Neisseria in the family Neisseria, including Neisseria mucosa, Neisseria sicca, Neisseria flava, Neisseria subflava, Neisseria flavescens, and Neisseria elongata. Rothia species are Gram-positive cocci or bacilli belonging to the genus Rothia in the family Micrococcaceae, and are normal inhabitants of the oral cavity. The genus Rothia includes species such as Rothia aeria, Rothia mucilaginosa, and Rothia dentocariosa. In the present invention, the term "pathogenic bacteria" specifically refers to bacteria of the genus Prevotella and Veillonella.

[0012] The oral composition of the present invention contains a nitrate ion-donating compound as component (A), which is a compound capable of releasing nitrate (NO3) ions upon contact with water. Although the detailed mechanism of the oral flora-improving effect of the oral composition of the present invention is unclear, it is thought that when Neisseria bacteria and the like in the oral cavity use component (A) to produce nitric oxide, glycyrrhetinic acid, component (B) described below, exerts some kind of synergistic effect. As a result, these components greatly contribute to promoting the growth of Neisseria bacteria and the like, and not only can they rapidly increase the proportion of Neisseria bacteria and the like in the oral flora, but they also have a bacterial mass-controlling effect and can rapidly demonstrate an improving effect on the oral flora.

[0013] Specific examples of component (A) include one or more compounds selected from alkali metal nitrates and alkaline earth metal nitrates. More specifically, the component (A) may be one or more selected from sodium nitrate, potassium nitrate, and calcium nitrate, with potassium nitrate being preferred.

[0014] From the viewpoints of increasing the growth-promoting effect of Neisseria bacteria and the like in oral flora, of the bacterial count controlling effect, and of rapidly exhibiting the oral flora-improving effect, the content of component (A) in the oral composition of the present invention is preferably 0.5% by mass or more, more preferably 1% by mass or more, even more preferably 3% by mass or more, even more preferably 4% by mass or more, preferably 15% by mass or less, more preferably 12% by mass or less, even more preferably 10% by mass or less, even more preferably 8% by mass or less, and even more preferably 6% by mass or less. The content of component (A) in the oral composition of the present invention is preferably 0.5 to 15% by mass, more preferably 1 to 12% by mass, even more preferably 3 to 10% by mass, even more preferably 4 to 8% by mass, and even more preferably 4 to 6% by mass.

[0015] The oral composition of the present invention contains glycyrrhetinic acid as component (B). Glycyrrhetinic acid is a component known to have anti-inflammatory effects, etc. In the present invention, component (B) is involved in the production of nitric oxide by component (A) above, resulting in some kind of synergistic effect, which unexpectedly not only effectively increases the proportion of Neisseria and other bacteria in the oral flora, but also rapidly improves the oral flora. In addition, it improves the growth-restricting effect on Streptococcus, Prevotella, and Veillonella, and also exerts a bacterial mass control effect.

[0016] Specific examples of component (B) include α-glycyrrhetinic acid, β-glycyrrhetinic acid, etc. Of these, β-glycyrrhetinic acid is preferred.

[0017] The content of component (B) in the oral composition of the present invention is preferably 0.001% by mass or more, more preferably 0.008% by mass or more, even more preferably 0.02% by mass or more, and preferably 0.3% by mass or less, more preferably 0.15% by mass or less, and even more preferably 0.05% by mass or less, from the viewpoints of increasing the growth-promoting effect on Neisseria and other bacteria in oral flora, rapidly exhibiting an improving effect on oral flora, and improving the growth-restricting effect on Streptococcus, Prevotella, and Veillonella while also exerting a bacterial load controlling effect. The content of component (B) in the oral composition of the present invention is preferably 0.001% by mass or more and 0.3% by mass or less, more preferably 0.008 to 0.15% by mass, and even more preferably 0.02 to 0.05% by mass.

[0018] The mass ratio ((B) / (A)) of the content of component (B) to the content of component (A) is preferably 0.0001 or more, more preferably 0.0005 or more, even more preferably 0.0015 or more, even more preferably 0.003 or more, preferably 0.4 or less, more preferably 0.1 or less, even more preferably 0.035 or less, and even more preferably 0.02 or less, from the viewpoint of effectively increasing the growth-promoting effect on Neisseria and other bacteria in the oral flora while rapidly exhibiting an effect of improving the oral flora, and further from the viewpoint of improving the growth-restricting effect on Streptococcus, Prevotella, and Veillonella bacteria while also exerting a bacterial quantity control effect. The mass ratio ((B) / (A)) of the content of component (B) to the content of component (A) is preferably 0.0001 to 0.4, more preferably 0.0005 to 0.1, even more preferably 0.0015 to 0.035, and still more preferably 0.003 to 0.02.

[0019] The oral composition of the present invention limits the content of sodium lauryl sulfate from the viewpoint of effectively increasing the growth-promoting effect on Neisseria and other bacteria in the oral flora while rapidly exhibiting an effect of improving the oral flora, and further from the viewpoint of improving the growth-restricting effect on Streptococcus, Prevotella, and Veillonella bacteria while also exerting a bacterial mass control effect.

[0020] The content of sodium lauryl sulfate in the oral composition of the present invention is 0.1% by mass or less, preferably 0.05% by mass or less, and more preferably 0.01% by mass or less, or alternatively, the oral composition of the present invention does not contain sodium lauryl sulfate, from the viewpoints of effectively increasing the growth-promoting effect of Neisseria and other bacteria in the oral flora, rapidly exhibiting an effect of improving the oral flora, and further improving the growth-restricting effect of Streptococcus, Prevotella, and Veillonella bacteria, while also exerting a bacterial quantity control effect.

[0021] The oral composition of the present invention can further contain a fluorine-containing compound (C) from the viewpoint of effectively increasing the growth-promoting effect on bacteria of the genus Neisseria and the like in the oral flora, rapidly exhibiting an effect of improving the oral flora, and further improving the growth-restricting effect on bacteria of the genus Streptococcus, Prevotella, and Veillonella, as well as exerting a bacterial load control effect. Specific examples of such fluorine-containing compounds include one or more compounds selected from fluoride ion-donating compounds and monofluorophosphate ion-donating compounds.

[0022] The fluoride ion supplying compound is a fluorine-containing compound other than a compound that supplies monofluorophosphate ions. Examples of such a fluoride ion supplying compound include one or more compounds selected from sodium fluoride, stannous fluoride, potassium fluoride, zinc fluoride, betaine fluoride, stannous alanine fluoride, sodium fluorosilicate, and hexylamine fluoride. Among these, sodium fluoride or stannous fluoride is preferred.

[0023] The monofluorophosphate ion supply compound may be one or more selected from sodium monofluorophosphate, potassium monofluorophosphate, magnesium monofluorophosphate, calcium monofluorophosphate, etc. Of these, sodium monofluorophosphate is preferred.

[0024] Among these, the fluorine-containing compound is preferably a monofluorophosphate ion supplying compound from the viewpoint of effectively increasing the growth-promoting effect on bacteria of the genus Neisseria and the like in the oral flora while rapidly exhibiting an effect of improving the oral flora, and further from the viewpoint of improving the growth-restricting effect on bacteria of the genus Streptococcus, Prevotella, and Veillonella while also exerting a bacterial quantity control effect.

[0025] In the oral composition of the present invention, the mass ratio (NO3 / F) of the nitrate (NO3) equivalent amount of the nitrate ion supply compound to the fluorine atom equivalent amount of the fluorine-containing compound is preferably 0.5 or more, more preferably 2 or more, even more preferably 4 or more, even more preferably 8 or more, still more preferably 12 or more, even more preferably 14 or more, preferably 50 or less, more preferably 48 or less, even more preferably 46 or less, even more preferably 44 or less, even more preferably 42 or less, and even more preferably 38 or less, from the viewpoint of effectively increasing the growth-promoting effect of Neisseria and other bacteria in the oral flora, rapidly exhibiting an effect of improving the oral flora, further improving the growth-restricting effect of Streptococcus, Prevotella, and Veillonella, and also exerting a bacterial mass control effect. In the oral composition of the present invention, the mass ratio (NO3 / F) of the nitric acid (NO3) equivalent amount of the nitrate ion supplying compound to the fluorine atom equivalent amount of the fluorine-containing compound is preferably 0.5 to 50, more preferably 2 to 48, even more preferably 4 to 46, still more preferably 8 to 44, even more preferably 12 to 42, and still more preferably 14 to 38.

[0026] The content of the fluorine-containing compound in the oral composition of the present invention is, in terms of fluorine atoms, preferably 850 ppm or more, more preferably 900 ppm or more, even more preferably 950 ppm or more, and preferably 5000 ppm or less, more preferably 2000 ppm or less, and even more preferably 1400 ppm or less. The content of the fluorine-containing compound in the oral composition of the present invention is, in terms of fluorine atoms, preferably 850 to 5000 ppm, more preferably 900 to 2000 ppm, and even more preferably 950 to 1400 ppm.

[0027] Furthermore, when the fluorine-containing compound is a fluoride ion supplying compound, the content of such fluoride ion supplying compound in the oral composition of the present invention is preferably 0.1 to 4 mass%, more preferably 0.15 to 2 mass%, and even more preferably 0.2 to 1.5 mass%, from the viewpoints of effectively increasing the growth-promoting effect on Neisseria and other bacteria in the oral flora, rapidly exhibiting an effect of improving the oral flora, and further improving the growth-restricting effect on Streptococcus, Prevotella, and Veillonella bacteria, as well as exerting a bacterial quantity control effect. Furthermore, when the fluorine-containing compound is a fluoride ion supplying compound, the content of such fluoride ion supplying compound in the oral composition of the present invention is preferably 0.1 to 1.5% by mass, more preferably 0.15 to 0.8% by mass, even more preferably 0.18 to 0.6% by mass, and even more preferably 0.25 to 0.4% by mass, from the viewpoints of effectively increasing the growth-promoting effect on Neisseria and other bacteria in the oral flora, rapidly exhibiting an effect of improving the oral flora, and further improving the growth-restricting effect on Streptococcus, Prevotella, and Veillonella bacteria, while also exerting a bacterial count control effect. Furthermore, when the fluorine-containing compound is a monofluorophosphate ion supplying compound, the content of such a monofluorophosphate ion supplying compound in the oral composition of the present invention is preferably 0.2 to 4 mass%, more preferably 0.4 to 2 mass%, and even more preferably 0.8 to 1.5 mass%, from the viewpoints of effectively increasing the growth-promoting effect on Neisseria and other bacteria in the oral flora, rapidly exhibiting an effect of improving the oral flora, and further improving the growth-restricting effect on Streptococcus, Prevotella, and Veillonella bacteria, while also exerting a bacterial quantity control effect.

[0028] The oral composition of the present invention contains water. In the present invention, water refers to the total amount of water contained in the oral composition, including not only purified water or the like contained in the oral composition but also the water contained in each of the components contained therein. By containing such water, the components contained therein can be well dissolved or dispersed, thereby fully exerting the desired effects.

[0029] Specifically, when the oral composition of the present invention is a liquid oral composition such as a mouthwash or liquid dentifrice, the content of water in the oral composition of the present invention is preferably 50% by mass or more, more preferably 70% by mass or more, even more preferably 80% by mass or more, and preferably 99.7% by mass or less, more preferably 99.5% by mass or less, and even more preferably 99.4% by mass or less. Furthermore, when the oral composition of the present invention is a liquid oral composition such as a mouthwash or liquid dentifrice, the content of water in the oral composition of the present invention is preferably 50 to 99.8% by mass, more preferably 70 to 99.5% by mass, and even more preferably 80% by mass or more and 99.4% by mass or less. Furthermore, when the oral composition of the present invention is a dentifrice composition such as a toothpaste or a tooth powder, the content of water in the oral composition of the present invention is preferably 5% by mass or more, more preferably 10% by mass or more, and preferably 60% by mass or less, more preferably 55% by mass or less. Also, when the oral composition of the present invention is a dentifrice composition such as a toothpaste or a tooth powder, the content of water is preferably 5 to 60% by mass, more preferably 10 to 55% by mass.

[0030] It is preferable that the oral composition of the present invention contains limited amounts of bactericides in order to avoid a decrease in the effect of promoting the growth of Neisseria and other bacteria and to improve the growth-promoting effect of Neisseria and other bacteria in the oral flora.

[0031] In order to effectively enhance the growth-promoting effect of Neisseria and other bacteria in the oral flora, the content of the bactericide in the oral composition of the present invention is preferably less than 0.5% by mass, more preferably 0.1% by mass or less, and even more preferably 0.05% by mass or less, or it is preferable that the oral composition of the present invention does not contain any bactericide.

[0032] Furthermore, among the disinfectants, it is preferable to limit the content of cationic disinfectants. Specific examples of cationic disinfectants include one or more selected from quaternary ammonium compounds and biguanide compounds. Examples of cationic disinfectants belonging to quaternary ammonium compounds include one or more selected from cetylpyridinium chloride, benzethonium chloride, depotassium chloride, benzalkonium chloride, alkyldimethylammonium chloride, alkyltrimethylammonium chloride, and methylbenzethonium chloride. Examples of cationic disinfectants belonging to biguanide compounds include one or more selected from chlorhexidine and its salts, such as chlorhexidine gluconate and chlorhexidine hydrochloride.

[0033] In order to effectively enhance the growth-promoting effect of Neisseria and other bacteria in the oral flora, the content of cationic bactericide in the oral composition of the present invention is preferably less than 0.5% by mass, more preferably 0.1% by mass or less, and even more preferably 0.05% by mass or less. Alternatively, it is preferable that the oral composition of the present invention does not contain any cationic bactericide.

[0034] In addition to the above-mentioned components, the oral composition of the present invention may contain appropriate additives such as solvents such as ethanol; pH adjusters; binders; humectants such as glycerin, propylene glycol, or polyethylene glycol; abrasives; sweeteners; foaming agents and foaming aids; preservatives; colorants; and fragrances, within the scope of not impairing the effects of the present invention.

[0035] The pH of the oral composition of the present invention at 25°C is preferably 5 or higher, more preferably 5.5 or higher, even more preferably 6 or higher, and preferably 9 or lower, more preferably 8.5 or lower, and even more preferably 8 or lower, from the viewpoints of effectively increasing the growth-promoting effect on bacteria of the genus Neisseria and the like in oral flora while rapidly exhibiting an effect of improving oral flora, and further improving the growth-restricting effect on bacteria of the genus Streptococcus, Prevotella, and Veillonella, while also exhibiting a bacterial load control effect. The pH of the oral composition of the present invention at 25°C is preferably 5 to 9, more preferably 5.5 to 8.5, and even more preferably 6 to 8. The pH of the oral composition of the present invention is a value measured at 25°C using a pH electrode.

[0036] The oral composition of the present invention selectively and effectively promotes the growth of Neisseria bacteria and the like, thereby effectively increasing the proportion of Neisseria bacteria and the like in the oral flora, and is therefore extremely useful as an oral composition for promoting the growth of Neisseria bacteria and the like, or as an oral composition for improving the oral flora. Similarly, the oral composition of the present invention is also highly useful as an oral flora-improving agent, a growth promoter for Neisseria and / or Russula bacteria, or an agent for accelerating the oral flora-improving effect. These agents contain the above-mentioned components (A) and (B) as active ingredients, and either contain 0.1% by mass or less of sodium lauryl sulfate or are free of sodium lauryl sulfate. If necessary, they may also contain other ingredients similar to those of the oral composition.

[0037] In relation to the above-mentioned embodiment, the present invention further discloses the following oral compositions. [1] The following components (A) and (B): (A) Nitrate ion donor compound (B) Glycyrrhetinic acid and the content of sodium lauryl sulfate is 0.1% by mass or less, or the oral composition is free of sodium lauryl sulfate. [2] The oral composition of [1] above, wherein component (A) is one or more selected from alkali metal nitrates and alkaline earth metal nitrates, preferably one or more selected from sodium nitrate, potassium nitrate, and calcium nitrate, and more preferably potassium nitrate. [3] The oral composition of [1] or [2] above, wherein the content of component (A) is preferably 0.5% by mass or more, more preferably 1% by mass or more, even more preferably 3% by mass or more, still more preferably 4% by mass or more, preferably 15% by mass or less, more preferably 12% by mass or less, even more preferably 10% by mass or less, still more preferably 8% by mass or less, and even more preferably 6% by mass or less. [4] The oral composition of any one of the above [1] to [3], wherein component (B) is preferably one or more selected from α-glycyrrhetinic acid and β-glycyrrhetinic acid, more preferably β-glycyrrhetinic acid. [5] The oral composition of any one of [1] to [4] above, wherein the content of component (B) is preferably 0.001% by mass or more, more preferably 0.008% by mass or more, even more preferably 0.02% by mass or more, and preferably 0.3% by mass or less, more preferably 0.15% by mass or less, even more preferably 0.05% by mass or less. [6] The oral composition of any one of [1] to [5] above, wherein the mass ratio of the content of component (B) to the content of component (A) ((B) / (A)) is preferably 0.0001 or more, more preferably 0.0005 or more, even more preferably 0.0015 or more, even more preferably 0.003 or more, preferably 0.4 or less, more preferably 0.1 or less, even more preferably 0.035 or less, and still more preferably 0.02 or less.

[0038] [7] The oral composition of any one of [1] to [6] above, wherein the content of sodium lauryl sulfate is 0.1% by mass or less, preferably 0.05% by mass or less, and more preferably 0.01% by mass or less, or the oral composition of the present invention does not contain sodium lauryl sulfate. [8] The oral composition according to any one of the above [1] to [7], further comprising a fluorine-containing compound (C), which is preferably one or more selected from a fluoride ion-supplying compound and a monofluorophosphate ion-supplying compound, more preferably a monofluorophosphate ion-supplying compound. [9] The oral composition of [8] above, wherein the mass ratio (NO3 / F) of the nitric acid (NO3) equivalent amount of the nitrate ion supplying compound to the fluorine atom equivalent amount of the fluorine-containing compound is preferably 0.5 or more, more preferably 2 or more, even more preferably 4 or more, still more preferably 8 or more, still more preferably 12 or more, still more preferably 14 or more, preferably 50 or less, more preferably 48 or less, still more preferably 46 or less, still more preferably 44 or less, still more preferably 42 or less, still more preferably 38 or less.

[10] The oral composition of [8] or [9] above, wherein when the fluorine-containing compound is a fluoride ion-donating compound, the content of the fluoride ion-donating compound is preferably 0.1 to 4 mass%, more preferably 0.15 to 2 mass%, and even more preferably 0.2 to 1.5 mass%, and when the fluorine-containing compound is a monofluorophosphate ion-donating compound, the content of the monofluorophosphate ion-donating compound is preferably 0.2 to 4 mass%, more preferably 0.4 to 2 mass%, and even more preferably 0.8 to 1.5 mass%.

[0039]

[11] When the oral composition of the present invention is a liquid oral composition, the water content is preferably 50% by mass or more, more preferably 70% by mass or more, even more preferably 80% by mass or more, and preferably 99.7% by mass or less, more preferably 99.5% by mass or less, and even more preferably 99.4% by mass or less. When the oral composition of the present invention is a dentifrice composition such as toothpaste or powder toothpaste, the water content is preferably 5% by mass or more, more preferably 10% by mass or more, and preferably 60% by mass or less, and more preferably 55% by mass or less. The oral composition of any one of [1] to

[10] above.

[0040]

[12] The oral composition of any one of [1] to

[11] above, wherein the content of the bactericide is preferably less than 0.5% by mass, more preferably 0.1% by mass or less, and even more preferably 0.05% by mass or less, or the oral composition of the present invention preferably does not contain a bactericide.

[13] The oral composition according to any one of [1] to

[11] above, wherein the content of the cationic bactericide is preferably less than 0.5% by mass, more preferably 0.1% by mass or less, and even more preferably 0.05% by mass or less, or the oral composition of the present invention preferably does not contain a cationic bactericide.

[14] The oral composition of any one of [1] to

[13] above, which has a pH at 25°C of preferably 5 or more, more preferably 5.5 or more, even more preferably 6 or more, and preferably 9 or less, more preferably 8.5 or less, even more preferably 8 or less.

[15] The oral composition according to any one of [1] to

[14] above, which is a growth promoter for bacteria of the genus Neisseria and / or bacteria of the genus Russia.

[16] The oral composition according to any one of the above [1] to

[14] , which is an agent for accelerating the oral flora improving effect.

[17] The oral composition according to any one of the above [1] to

[14] , which is an oral flora improving agent. [Example]

[0041] The present invention will be described in detail below with reference to the following examples. Unless otherwise specified in the tables, the content of each component is expressed in mass %.

[0042] <Test Example 1> The growth-promoting effect of Neisseria bacteria in dental plaque biofilm flora (increase factor (fold) and increase amount (%)) was evaluated according to the methods shown in (1) to (4) below.

[0043] (1) Plaque collection and pretreatment Dental plaque from healthy female teeth was collected using a dental scaler, placed in a 1.5 mL tube, and washed twice with PBS(-) by centrifugation at 7,000 g for 2 minutes at room temperature. The pellet containing plaque bacteria was suspended in 300 μL of CELLBANKER (Nippon Zenyaku Kogyo Co., Ltd.), and the prepared plaque suspension was stored at -80°C until use. A portion of this plaque suspension was used to measure the copy number of the total bacterial rRNA16S gene in the plaque suspension using the DNA extraction method and real-time PCR described below.

[0044] (2) Preparation of a dental plaque biofilm model using dental plaque suspension culture Oral compositions were prepared using potassium nitrate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), β-glycyrrhetinic acid (manufactured by Alps Pharmaceutical Industries, Ltd.), dipotassium glycyrrhetinate (manufactured by Alps Pharmaceutical Industries, Ltd.), sodium fluoride (manufactured by Stella Chemifa Co., Ltd.), sodium monofluorophosphate (manufactured by BK Giulini GmbH), with the remainder being water, as shown in Tables 3 to 5. Each of these was diluted 10 times with Brain Heart Infusion (BHI) medium (BD Japan) to prepare evaluation samples. The evaluation samples were used to measure the total bacterial rRNA16S gene copy number of 10 in dental plaque suspensions. 7 A culture medium containing dental plaque bacteria was prepared by diluting the culture medium to 100 copies / mL. 1 mL of the culture medium was added to a Poly-L-Lysine Coated 24-Well Microplate (AGC Techno Glass) and cultured at 37°C under microaerobic conditions using an Anaeropack Bikouki (Mitsubishi Gas Chemical Company, Inc.) for 48 hours to produce dental plaque biofilms.

[0045] (3) Extraction of genomic DNA from dental plaque biofilm The dental plaque biofilm attached to the bottom of the plate was thoroughly mixed with the culture supernatant by pipetting and then collected in a 1.5 mL tube. The plate was then centrifuged (14,000 rpm, room temperature for 10 minutes). The culture supernatant was removed, and the resulting precipitate was added to 200 μL / well of 20 mg / mL lysozyme (Fujifilm Wako Pure Chemical Industries, Ltd.) solution (containing 20 mM Tris-HCl (pH 8.0), 2 mM EDTA, and 1.2% Triton X-100). The plate was then incubated at 37°C for 60 minutes with shaking (160 rpm). Genomic DNA was extracted using the Dneasy Blood & Tissue kit (QIAGEN), and the proportion of each bacterial species was calculated by real-time PCR using Taqman probes. The primers and Taqman probes used and the reaction conditions for real-time PCR are shown in Tables 1 and 2.

[0046] [Table 1]

[0047] [Table 2]

[0048] (4) Calculation of the abundance ratio of each bacteria The abundance ratio (%) of each bacterium was calculated by first creating a calibration curve using PCR products with known copy numbers as standards, then calculating the copy number of the rRNA16S gene of each bacterium using the following formula. Percentage of each bacterium present (%) = (copy number of each bacterium) / (total bacterial copy number) × 100

[0049] [Examples 1 to 21, Comparative Examples 1 to 5] Oral compositions were prepared according to the formulations shown in Tables 3 to 5, with the remainder being purified water to make up 100% by mass, and the bacteria were quantified according to (1) to (4) above. Next, the growth-promoting activity of Neisseria bacteria was evaluated according to the following method. The results are shown in Tables 3 to 5.

[0050] <Neisseria growth promotion effect (increase ratio (times))> Based on the quantitative bacterial counts obtained for each agent, the growth promoting effect of Neisseria bacteria (increase factor (fold)) was calculated using the following formula. Neisseria growth promotion effect (increase ratio (fold)) = (proportion of Neisseria bacteria present) / (the proportion of Neisseria present in the comparative example selected as the control) For Examples 1 to 21, a comparative example containing only the same amount of component (A) was selected as a control example according to the content of component (A) in each Example and used as the evaluation standard. Specifically, for example, Comparative Example 2 was selected as a control example for Examples 1 to 2 and 10, Comparative Example 3 was selected as a control example for Examples 3 and 4, and Comparative Example 4 was selected as a control example for Examples 5 to 9, 11 to 21 and Comparative Example 5.

[0051] [Table 3]

[0052] [Table 4]

[0053] [Table 5]

[0054] <Test Example 2> [Examples 22 to 27, Comparative Examples 6 to 7] In the method shown in (1) to (3) above in Test Example 1, tests similar to (1) to (3) above were conducted to evaluate the rapidity of the onset of the effect of improving the bacterial flora, except that the incubation time of the culture medium was appropriately changed when preparing the dental plaque biofilm in (2) above. Specifically, in Examples 22 to 24 and Comparative Example 6, the culture time was 12 hours, and in Examples 25 to 27 and Comparative Example 7, the culture time was 24 hours. The results are shown in Table 6, including those of Examples 6, 7, and 17 and Comparative Example 4, in which the culture time was 48 hours. For Examples 22 to 24, Comparative Example 6 was selected as a control, and for Examples 25 to 27, Comparative Example 7 was selected as a control, and the growth-promoting activity against Neisseria bacteria was evaluated.

[0055] [Table 6]

[0056] <Test Example 3> According to the method described below, the above Examples 7, 9, 11, and 16 and Comparative Examples 1, 4, 5, and 8 were evaluated for their effect of controlling the bacterial count in dental plaque biofilms. First, a culture medium containing dental plaque bacteria was prepared using the same procedures as those described in (1) and (2) above in Test Example 1. 0.2 mL of the prepared culture medium was added to a non-coated 96-well microplate (AGC TECHNO GLASS) and cultured at 37°C for 15 hours under microaerobic conditions using an Anaeropack Bikouki (Mitsubishi Gas Chemical Company, Inc.) to produce dental plaque biofilms. After 15 hours of culture, the dental plaque biofilm was uniformly dispersed by pipetting, and 0.1 mL of the culture medium was transferred to another non-coated 96-well microplate. The OD600 value was measured using an absorbance meter (Biotech Co., Ltd.). The relative bacterial load was then calculated using the following formula: Relative bacterial quantity = (OD600 value of bacterial solution cultured under each condition) / (OD600 value of blank without added bacteria)

[0057] <Evaluation of bacterial count control effect> Using the relative bacterial count value obtained by the above formula, the bacterial count control effect was evaluated according to the following criteria. The results are shown in Table 7. A: Relative bacterial count is 1.1 or more and less than 3 B: 3 or more and less than 5 C: Relative bacterial count is 5 or more and less than 6.4 D: Relative bacterial count is 6.4 or higher E: The relative bacterial count is less than 1.1. *Bacteria do not grow at all.

[0058] [Table 7]

[0059] <Test Example 4 [Example 28]> Mouthwashes were prepared with a total amount of 100% by mass according to the formulation shown in Table 8. Then, the bacterial growth activity in saliva was evaluated according to the methods shown in (1) and (2) below. The results are shown in Table 8.

[0060] (1) Calculation of the ratio of each bacteria One subject used the mouthwash three times a day (gargling 20 mL of mouthwash for 30 seconds) for three days, and the bacterial ratio in stimulated saliva was compared before and after use. Furthermore, from three days before using the mouthwash until the end of the test period, the subject was required to use the designated commercially available toothpaste and toothbrush to eliminate the influence of oral hygiene practices other than the use of the mouthwash. The stimulated saliva was collected by chewing commercially available paraffin wax gum for 3 minutes, and the leaked saliva was spat out into a plastic container at regular intervals. After collection, the saliva was promptly stored in a freezer at -20°C.

[0061] Next, 500 μL of stimulated saliva after storage was collected and centrifuged (14,000 rpm at room temperature for 10 minutes). The culture supernatant was removed from the precipitate, and genomic DNA was extracted from the precipitate using the same method as in Test Example 1. The ratio of each bacterium was calculated using real-time PCR with a Taqman probe. As in Test Example 1 above, the primers and Taqman probes shown in Table 1 were used, and the real-time PCR reaction conditions shown in Table 2 were followed.

[0062] (2) Calculation of the relative increase rate of each bacterium The abundance ratio (%) of each bacterium was calculated by first creating a calibration curve using PCR products with known copy numbers as standards, then calculating the copy number of the rRNA16S gene of each bacterium using the following formula. Percentage of each bacterium present (%) = (copy number of each bacterium) / (total bacterial copy number) × 100 The relative growth rate of each bacterium was calculated using the following formula. Relative increase rate of each bacteria (%) = (proportion of each bacteria after 3 days of use) / (proportion of each bacteria before use) x 100

[0063] [Table 8]

Claims

1. The following components (A) and (B): (A) Nitrate ion supplying compound (B) Glycyrrhetinic acid and the content of sodium lauryl sulfate is 0.1% by mass or less, or the oral composition does not contain sodium lauryl sulfate.

2. 2. The oral composition according to claim 1, wherein the mass ratio ((B) / (A)) of the content of component (B) to the content of component (A) is 0.0001 or more and 0.4 or less.

3. 3. The oral composition according to claim 1, wherein component (A) is one or more selected from the group consisting of alkali metal nitrates and alkaline earth metal nitrates.

4. 3. The oral composition according to claim 1, wherein the content of component (A) is 0.5% by mass or more and 15% by mass or less.

5. The oral composition according to claim 1 or 2, further comprising a fluorine-containing compound (C).

6. The oral composition according to claim 1 or 2, which is a growth promoter for bacteria of the genus Neisseria and / or bacteria of the genus Russia.

7. The oral composition according to claim 1 or 2, which is an agent for accelerating the oral flora improving effect.

8. The oral composition according to claim 1 or 2, which is an oral flora improving agent.

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