Composition for oral cavity

Abstract

The present invention relates to a composition for oral cavity, which can selectively and effectively promote the growth of bacteria belonging to the genus Neisseria and / or bacteria belonging to the genus Rothia, which are non-pathogenic bacteria in the oral flora, and thereby can effectively improve the oral flora.　The present invention provides a composition for oral cavity, which comprises the following components (A) and (B): (A) a nitrate ion supply compound and (B) a chlorophyll metal complex salt derivative.

Description

Oral composition

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

[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] In light of this situation, various studies have been conducted, and for example, Patent Document 1 reports that by incorporating a nitrogen source such as nitrate into a composition, Neisseria bacteria present in the oral cavity can produce nitric oxide, thereby controlling the bacterial composition of the oral flora to a favorable one. Meanwhile, Patent Document 2 discloses a composition containing copper chlorophyllin salt as an active ingredient for eliminating periodontal disease bacteria present in oral cells, etc., in an attempt to purify the interior of the cells by killing periodontal disease bacteria that have invaded oral cells.

[0004] (Patent Document 1) U.S. Patent Application Publication No. 2016 / 0151428 (Patent Document 2) JP 2023-34874 A

[0005] The present invention provides an oral composition containing the following components (A) and (B): (A) a nitrate ion donating compound, and (B) a chlorophyll metal complex derivative.

[0006] Patent Document 1 only describes the so-called probiotic technology of administering microorganisms themselves to the human body, and does not disclose or suggest any technical idea of ​​promoting the growth of specific microorganisms in the oral cavity. Furthermore, even the composition described in Patent Document 2 only kills periodontal disease bacteria, and no consideration has been given to selectively and effectively promoting the growth of Neisseria bacteria in the oral cavity. Thus, there is still ample room for improvement in terms of enhancing the selective and efficient growth promotion effect of Neisseria bacteria in oral flora.

[0007] Therefore, the present invention relates to an oral composition that can selectively and effectively promote the growth of Neisseria and / or Russia bacteria in the oral flora, thereby effectively improving the oral flora.

[0008] As a result of intensive research to solve the above problems, the inventors have discovered an oral composition that contains a nitrate ion supplying compound and a chlorophyll metal complex derivative, and that can selectively and effectively promote the growth of Neisseria and Russia bacteria in the oral flora.

[0009] According to the present invention, the growth of Neisseria bacteria in the oral cavity can be selectively promoted and the growth of pathogenic bacteria can be selectively inhibited, thereby effectively improving the oral flora, and the improvement of the oral flora can be rapidly achieved.Furthermore, the present invention has the potential to promote the growth of not only Neisseria bacteria but also Russia bacteria. Detailed Description of the Invention

[0010] The present invention will be described in detail below. In the present invention, the term "oral flora," also referred to as "oral (oral or oral) flora" or "oral (oral or oral) microbiota," refers to a community formed by a wide variety of bacteria that inhabit the oral cavity. Furthermore, in the present invention, "improving" the oral flora means selectively promoting the growth of Neisseria and / or Russia bacteria (hereinafter collectively referred to as "Neisseria, etc.") in the oral flora by activating the metabolism of Neisseria and / or Russia bacteria in the oral cavity. It also means selectively suppressing the growth of pathogenic bacteria, thereby increasing the proportion of Neisseria, etc. in the oral flora.

[0011] Here, the genus Neisseria is a normal oral flora belonging to the genus Neisseria in the family Neisseria. Specific examples of the genus Neisseria include Neisseria mucosa, Neisseria sicca, Neisseria flava, Neisseria subflava, Neisseria flavescens, and Neisseria elongata. Furthermore, the genus Neisseria is a gram-positive cocci or bacillus belonging to the genus Neisseria in the family Micrococcaceae, and is a normal oral flora. Bacteria of the genus Rothia include Rothia aeria, Rothia mucilaginosa, Rothia dentocariosa, etc. In the present invention, the term "pathogenic bacteria" specifically refers to bacteria of the genus Prevotella, bacteria of the genus Veillonella, Porphyromonas gingivalis (P.g.), Fusobacterium nucleatum (F.n.), or Tannerella forsythia.

[0012] The oral composition of the present invention contains a nitrate ion-donating compound as component (A). Component (A) provides nitric acid (NO ) when it comes into contact with water. ３ ) ions. 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 and other bacteria in the oral cavity use component (A) to produce nitric oxide, the chlorophyll metal complex salt derivative of component (B), described below, provides some kind of synergistic effect. As a result, these components greatly contribute to promoting the growth of Neisseria and other bacteria, allowing the proportion of Neisseria and other bacteria in the oral flora to be rapidly increased.

[0013] Component (A) may specifically be one or more selected from alkali metal nitrates and alkaline earth metal nitrates. More specifically, component (A) may specifically be one or more selected from sodium nitrate, potassium nitrate, and calcium nitrate. Of these, potassium nitrate is preferred.

[0014] From the viewpoint of increasing the growth-promoting effect of Neisseria and other bacteria in the oral flora, and from the viewpoint 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 0.8% by mass or more, even more preferably 2% by mass or more, still more preferably 3% by mass or more, preferably 20% by mass or less, more preferably 15% by mass or less, even more preferably 10% by mass or less, and still more preferably 7% by mass or less. The content of component (A) in the oral composition of the present invention is preferably 0.5 to 20% by mass, more preferably 0.8 to 15% by mass, even more preferably 2 to 10% by mass, and still more preferably 3 to 7% by mass.

[0015] The oral composition of the present invention contains a chlorophyll metal complex derivative as component (B). Specific examples of the chlorophyll metal complex derivative include one or more selected from copper chlorophyllin sodium, iron chlorophyllin sodium, and the like. Of these, copper chlorophyllin sodium is preferred from the viewpoint of enhancing the growth-promoting effect on Neisseria and other bacteria in oral flora. In the present invention, the chlorophyll metal complex derivative of component (B) contributes to the production of nitric oxide by component (A), resulting in a synergistic effect that not only effectively increases the proportion of Neisseria and other bacteria in oral flora, but also rapidly improves the oral flora. In addition, it also enhances the growth-restricting effect on pathogenic bacteria.

[0016] From the viewpoints of increasing the growth-promoting effect on Neisseria and other bacteria in oral flora, rapidly exhibiting the oral flora-improving effect, and improving the growth-restricting effect on pathogenic bacteria, the content of component (B) in the oral composition of the present invention is preferably 0.001% by mass or more, more preferably 0.007% by mass or more, even more preferably 0.02% by mass or more, and preferably 0.8% by mass or less, more preferably 0.7% by mass or less, and even more preferably 0.6% by mass or less. The content of component (B) in the oral composition of the present invention is preferably 0.001 to 0.8% by mass, more preferably 0.007 to 0.7% by mass, and even more preferably 0.02 to 0.6% by mass.

[0017] The mass ratio ((B) / (A)) of the content of component (B) to the content of component (A) is preferably 0.00001 or more, more preferably 0.0001 or more, even more preferably 0.0015 or more, even more preferably 0.003 or more, and preferably 0.6 or less, more preferably 0.4 or less, and even more preferably 0.3 or less, from the viewpoint of effectively increasing the growth-promoting effect of Neisseria and other bacteria in oral flora and rapidly exhibiting an effect of improving oral flora. The mass ratio ((B) / (A)) of the content of component (B) to the content of component (A) is preferably 0.00001 to 0.6, more preferably 0.0001 to 0.4, even more preferably 0.0015 to 0.3, and even more preferably 0.003 to 0.3.

[0018] The oral composition of the present invention may further contain a fluorine-containing compound (C) from the viewpoint of effectively increasing the growth-promoting effect on Neisseria and other bacteria in the oral flora, rapidly exerting an improving effect on the oral flora, and further improving the growth-restricting effect on pathogenic bacteria. Specific examples of such component (C) include one or more compounds selected from the group consisting of fluoride ion-donating compounds and monofluorophosphate ion-donating compounds.

[0019] 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 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.

[0020] 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.

[0021] Among these, as component (C), a monofluorophosphate ion supplying compound is preferred from the viewpoint of effectively increasing the growth-promoting effect on Neisseria and other bacteria in the oral flora, rapidly exerting an effect of improving the oral flora, and further improving the growth-restricting effect on pathogenic bacteria.

[0022] In the oral composition of the present invention, the nitrate ion-supplying compound nitrate (NO ３ ) equivalent to the fluorine atom equivalent of component (C) (mass ratio (NO ３ From the viewpoints of increasing the growth-promoting effect of Neisseria and the like in the oral flora, rapidly exhibiting an improving effect on the oral flora, and further improving the growth-restricting effect on pathogenic bacteria, the nitrate (NO / F) 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, and still more preferably 38 or less. ３ ) equivalent to the fluorine atom equivalent of component (C) (mass ratio (NO ３ / F) 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.

[0023] The content of component (C) in the oral composition of the present invention, in terms of fluorine atoms, is 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 component (C) in the oral composition of the present invention, in terms of fluorine atoms, is preferably 850 to 5000 ppm, more preferably 900 to 2000 ppm, and even more preferably 950 to 1400 ppm.

[0024] When component (C) is a fluoride ion-donating compound, the content of the fluoride ion-donating compound in the oral composition of the present invention is preferably 0.1 to 1.5% by mass, more preferably 0.3 to 1.4% by mass, and even more preferably 0.4 to 1.3% by mass, from the viewpoints of effectively increasing the growth-promoting effect of Neisseria and other bacteria in the oral flora, rapidly exerting an improving effect on the oral flora, and further improving the growth-restricting effect on pathogenic bacteria. When component (C) is a monofluorophosphate ion-donating compound, the content of the monofluorophosphate ion-donating compound in the oral composition of the present invention is preferably 0.2 to 4% by mass, more preferably 0.4 to 2% by mass, and even more preferably 0.6 to 1.5% by mass, from the viewpoints of effectively increasing the growth-promoting effect of Neisseria and other bacteria in the oral flora, rapidly exerting an improving effect on the oral flora, and further improving the growth-restricting effect on pathogenic bacteria.

[0025] The oral composition of the present invention may further contain glycyrrhetinic acid (D) from the viewpoint of enhancing the growth-promoting effect on Neisseria bacteria and the like in oral flora. Specific examples include α-glycyrrhetinic acid and β-glycyrrhetinic acid. Of these, β-glycyrrhetinic acid is preferred.

[0026] From the viewpoint of enhancing the growth-promoting effect of Neisseria and other bacteria in oral flora, the content of component (D) in the oral composition of the present invention is preferably 0.001% by mass or more, more preferably 0.003% by mass or more, even more preferably 0.008% by mass or more, and preferably 1% by mass or less, more preferably 0.5% by mass or less, and even more preferably 0.2% by mass or less. The content of component (C) in the oral composition of the present invention is preferably 0.001 to 1% by mass, more preferably 0.003 to 0.5% by mass, and even more preferably 0.008 to 0.2% by mass.

[0027] 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.

[0028] Specifically, when the oral composition of the present invention is a liquid oral composition such as a mouthwash or liquid dentifrice, the water content 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. When the oral composition of the present invention is a liquid oral composition such as a mouthwash or liquid dentifrice, the water content 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. When the oral composition of the present invention is a dentifrice composition such as a toothpaste or powder dentifrice, the water content 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, and more preferably 55% by mass or less. When the oral composition of the present invention is a dentifrice composition such as a toothpaste or a tooth powder, the water content is preferably 5 to 60% by mass, more preferably 10 to 55% by mass.

[0029] The oral composition of the present invention may further contain an organic acid salt (E) from the viewpoint of enhancing the growth-promoting effect on Neisseria and other bacteria in the oral flora. Specific examples of component (E) include one or more selected from citrate, gluconate, succinate, fumarate, lactate, malate, and tartrate. Of these, citrate, gluconate, succinate, fumarate, lactate, and malate are preferred, with citrate being more preferred. Examples of salts include metal salts such as sodium, potassium, magnesium, aluminum, and calcium. Of these, sodium salts and potassium salts are preferred. More specifically, of these components (E), sodium citrate is preferred from the viewpoint of effectively enhancing the growth-promoting effect on Neisseria and other bacteria in the oral flora.

[0030] From the viewpoint of effectively increasing the growth-promoting effect of Neisseria and other bacteria in oral flora, the content of component (E) in the oral composition of the present invention is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, even more preferably 0.8% by mass or more, and preferably 18% by mass or less, more preferably 8% by mass or less, and even more preferably 5% by mass or less. The content of component (E) in the oral composition of the present invention is preferably 0.1 to 18% by mass, more preferably 0.5 to 8% by mass, and even more preferably 0.8 to 5% by mass.

[0031] In the oral composition of the present invention, it is preferable to limit the content of sulfate ester salts from the viewpoint of improving the growth-promoting effect on bacteria of the genus Neisseria in oral flora. Examples of such sulfate ester salts include one or more selected from alkyl sulfates, alkenyl sulfates, polyoxyalkylene alkyl ether sulfates, polyoxyalkylene alkenyl ether sulfates, and polyoxyalkylene alkyl phenyl ether sulfates.

[0032] From the viewpoint of effectively enhancing the growth-promoting effect of Neisseria and other bacteria in the oral flora, the content of sulfate ester salts in the oral composition of the present invention is preferably 0.1 mass% or less, more preferably 0.05 mass% or less, and even more preferably 0.01 mass% or less, or it is preferable that the oral composition of the present invention does not contain sulfate ester salts.

[0033] It is preferable that the oral composition of the present invention contains a limited amount of bactericide in order to avoid a decrease in the effect of promoting the growth of Neisseria bacteria and to improve the growth-promoting effect of Neisseria bacteria and other bacteria in the oral flora.

[0034] In order to effectively enhance the growth-promoting effect of Neisseria 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 a bactericide.

[0035] Furthermore, among 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.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.Further, cationic disinfectants belonging to biguanide compounds include one or more selected from chlorhexidine and its salts, such as chlorhexidine gluconate and chlorhexidine hydrochloride.

[0036] From the viewpoint of effectively enhancing the growth-promoting effect of Neisseria and other bacteria in the oral flora, the content of the 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.

[0037] In addition to the above 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; fragrances, etc., within the scope of not inhibiting the effects of the present invention.

[0038] 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 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 pathogenic bacteria. 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.

[0039] Thus, the present invention is highly useful as an oral flora improving agent. That is, the oral flora improving agent contains the above-mentioned components (A) and (B): (A) a nitrate ion-donating compound, and (B) a chlorophyll metal complex derivative. Similarly, the present invention is also highly useful as a growth promoter for oral Neisseria and / or Russian bacteria. That is, the growth promoter for oral Neisseria and / or Russian bacteria is an agent that can promote the growth of oral Neisseria and / or Russian bacteria, and contains the above-mentioned components (A) and (B): (A) a nitrate ion-donating compound, and (B) a chlorophyll metal complex derivative. Furthermore, the present invention is also highly useful as an agent that accelerates the oral flora improving effect. That is, the oral flora improving agent is an agent that can accelerate the oral flora improving effect, and contains the above-mentioned components (A) and (B): (A) a nitrate ion-donating compound, and (B) a chlorophyll metal complex derivative.

[0040] In relation to the above-described embodiment, the present invention further discloses the following oral compositions. [1] An oral composition containing the following components (A) and (B): (A) a nitrate ion donor compound, and (B) a chlorophyll metal complex derivative. [2] The oral composition of [1] above, wherein component (A) is preferably one or more selected from alkali metal nitrates and alkaline earth metal nitrates, more preferably one or more selected from sodium nitrate, potassium nitrate, and calcium nitrate, and even 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 0.8% by mass or more, even more preferably 2% by mass or more, still more preferably 3% by mass or more, and preferably 20% by mass or less, more preferably 15% by mass or less, even more preferably 10% by mass or less, and even more preferably 7% by mass or less. [4] The oral composition of any one of [1] to [3] above, wherein component (B) is preferably one or two selected from copper chlorophyllin sodium and iron chlorophyllin sodium, more preferably copper chlorophyllin sodium. [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 0.007% by mass or more, even more preferably 0.02% by mass or more, and preferably 0.8% by mass or less, more preferably 0.7% by mass or less, even more preferably 0.6% 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 0.00001 or more, more preferably 0.0001 or more, even more preferably 0.0015 or more, even more preferably 0.003 or more, and preferably 0.6 or less, more preferably 0.4 or less, even more preferably 0.3 or less.

[0041] [7] The oral composition of any one of the above [1] to [6], further comprising a fluorine-containing compound (C), wherein the component (C) is preferably one or more selected from a fluoride ion-supplying compound and a monofluorophosphate ion-supplying compound. [8] The oral composition of the above [7], wherein the fluoride ion-supplying compound is preferably one or more selected from sodium fluoride, stannous fluoride, potassium fluoride, zinc fluoride, betaine fluoride, stannous alanine fluoride, sodium fluorosilicate, hexylamine fluoride, etc., more preferably sodium fluoride or stannous fluoride. [9] The oral composition of the above [7], wherein the monofluorophosphate ion-supplying compound is preferably one or more selected from sodium monofluorophosphate, potassium monofluorophosphate, magnesium monofluorophosphate, calcium monofluorophosphate, etc., more preferably sodium monofluorophosphate.

[10] The oral composition of the above [1], wherein the nitrate ion-supplying compound is nitrate (NO ３ ) equivalent to the fluorine atom equivalent of component (C) (mass ratio (NO ３

[11] The oral composition of any one of [7] to [9] above, wherein the value of (R / F) 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, and preferably 50 or less, more preferably 48 or less, even more preferably 46 or less, still more preferably 44 or less, still more preferably 42 or less, and still more preferably 38 or less.

[12] The oral composition of any one of [7] to

[10] above, wherein, when component (C) is a fluoride ion-donating compound, the content of the fluoride ion-donating compound is preferably 0.1 to 1.5% by mass, more preferably 0.3 to 1.4% by mass, and even more preferably 0.4 to 1.3% by mass, and when component (C) is a monofluorophosphate ion-donating compound, the content of the monofluorophosphate ion-donating compound is preferably 0.2 to 4% by mass, more preferably 0.4 to 2% by mass, and even more preferably 0.6 to 1.5% by mass.

[0042]

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

[11] , further comprising glycyrrhetinic acid (D), wherein the content of such component (D) is preferably 0.001% by mass or more, more preferably 0.003% by mass or more, even more preferably 0.008% by mass or more, and preferably 1% by mass or less, more preferably 0.5% by mass or less, and even more preferably 0.2% by mass or less.

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

[12] , further comprising an organic acid salt (E), wherein the content of such component (E) is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, even more preferably 0.8% by mass or more, and preferably 18% by mass or less, more preferably 8% by mass or less, and even more preferably 5% by mass or less.

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

[13] above, wherein the content of sulfate ester salt is preferably 0.1% by mass or less, more preferably 0.05% by mass or less, and even more preferably 0.01% by mass or less, or the oral composition of the present invention preferably does not contain a sulfate ester salt.

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

[14] above, wherein the content of 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.

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

[15] above, wherein the pH at 25°C is preferably 5.0 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, and even more preferably 8 or less.

[0043]

[17] Use of any one of the oral compositions [1] to

[16] above as an agent for improving oral flora.

[18] Use of any one of the oral compositions [1] to

[16] above as an agent for promoting the growth of oral Neisseria and / or Russian bacteria.

[19] Use of any one of the oral compositions [1] to

[16] above as an agent for accelerating the oral flora improvement effect.

[20] A method for improving oral flora by ingesting any one of the oral compositions [1] to

[16] above.

[21] A method for promoting the growth of oral Neisseria and / or Russian bacteria by ingesting any one of the oral compositions [1] to

[16] above.

[22] A method for accelerating the oral flora improvement effect by ingesting any one of the oral compositions [1] to

[16] above.

[23] An oral flora improver containing the following components (A) and (B): (A) a nitrate ion-supplying compound, and (B) a chlorophyll metal complex derivative.

[24] An oral growth promoter for Neisseria and / or Russia bacteria containing the following components (A) and (B): (A) a nitrate ion-supplying compound, and (B) a chlorophyll metal complex derivative.

[25] An oral flora improver that accelerates the action of improving the oral flora, containing the following components (A) and (B): (A) a nitrate ion-supplying compound, and (B) a chlorophyll metal complex derivative.

[0044] 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 %.

[0045] <Test Example 1> According to the methods shown in (1) to (4) below, the oral flora-improving effect was evaluated using the growth-promoting effect of Neisseria bacteria in dental plaque biofilm flora (increase ratio (fold) and increase amount (%)) as indicators.

[0046] (1) Plaque Collection and Pretreatment Plaque adhering to the tooth surface of a healthy female volunteer 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 (manufactured by 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 rRNA 16S gene in the plaque suspension using the DNA extraction method and real-time PCR method described below.

[0047] (2) Preparation of a dental plaque biofilm model by dental plaque suspension culture Oral compositions were prepared using potassium nitrate (Fujifilm Wako Pure Chemical Industries, Ltd.), copper chlorophyllin sodium (Tama Biochemical Co., Ltd.), sodium citrate (Fujifilm Wako Pure Chemical Industries, Ltd.), β-glycyrrhetinic acid (Alps Pharmaceutical Industries, Ltd.), sodium fluoride (Stella Chemifa Co., Ltd.), sodium monofluorophosphate (BK Giulini GmbH), with the remainder being water, as shown in Tables 3 and 4. Each of these was diluted 10-fold with Brain Heart Infusion (BHI) medium (Japan BD) to prepare evaluation samples. In the evaluation samples, the total bacterial rRNA 16S gene copy number of the dental plaque suspension was 10. ７ One 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 prepare a dental plaque biofilm.

[0048] (3) Extraction of genomic DNA from dental plaque biofilms. 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 at room temperature for 10 minutes), and the culture supernatant was removed. 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) was added to the precipitate at 200 μL / well and incubated at 37 °C for 60 minutes with shaking (160 rpm). Genomic DNA was extracted using a Dneasy Blood & Tissue kit (QIAGEN), and the ratio of each bacterium was calculated by real-time PCR using a Taqman probe. The primers and Taqman probes used and the reaction conditions for real-time PCR are shown in Tables 1 and 2.

[0049]

[0050]

[0051] (4) Calculation of the abundance ratio of each bacterium For the abundance ratio (%) of each bacterium, a calibration curve was first prepared using PCR products with known copy numbers as standards, and then the copy number of the rRNA 16S gene of each bacterium was calculated using the following formula: Abundance ratio (%) of each bacterium = (copy number of each bacterium) / (total bacterial copy number) × 100

[0052] [Examples 1 to 35, Comparative Examples 1 and 2] Oral compositions with the remainder being water were prepared according to the formulations shown in Tables 3 and 4, and the resulting oral compositions were diluted 10-fold with BHI medium to prepare evaluation samples, and the bacteria were quantified according to (1) to (4) above. Evaluation 1 was then carried out according to the following method. The results are shown in Tables 3 and 4.

[0053] Evaluation 1: Neisseria growth-promoting effect (increase (fold))) Based on the quantitative bacterial counts determined for each oral composition, the Neisseria growth-promoting effect (increase (fold)) was calculated using the following formula: Neisseria growth-promoting effect (increase (fold)) = (proportion of Neisseria bacteria present) / (proportion of Neisseria bacteria present in a comparative example selected as a control). Note that, depending on the potassium nitrate content in each example, a comparative example containing only the same amount of potassium nitrate was selected as a control and used as the evaluation standard for Evaluation 1 below. Specifically, Comparative Example 1 was selected as a control for Examples 1 to 5 and 13 to 21, and Comparative Example 2 was selected as a control for Examples 6 to 12 and 22 to 35.

[0054]

[0055]

[0056] Test Example 2 [Examples 36 to 51, Comparative Examples 3 to 5] For Examples 36 to 43 and Comparative Example 3, the culture time was set to 12 hours, and for Examples 44 to 51 and Comparative Example 4, the culture time was set to 24 hours, and the rapidity of the bacterial flora-improving effect was evaluated in the same manner as in Test 1. The results are shown in Table 5, including Examples 7, 8, 22, 23, 25, 27, 29, 31 and Comparative Example 5, for which the culture time was 48 hours. Note that Comparative Example 3 was selected as a comparative example for Examples 36 to 43, and Comparative Example 4 was selected as a comparative example for Examples 44 to 51, and these were used as the evaluation criteria for Evaluation 1 above.

[0057]

[0058] Test Example 3 [Example 52] Mouthwashes were prepared according to the formulation shown in Table 6, with the remainder being water, to make up 100% by mass, and the activity of promoting bacterial growth in saliva was evaluated according to the methods shown in (1) and (2) below. The results are shown in Table 6.

[0059] (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 before and after use was compared. The designated commercially available toothpaste and toothbrush were used from three days before using the mouthwash until the end of the test period 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 three minutes, and leaking saliva was spit out into a plastic container at any time. After collection, the saliva was promptly stored in a freezer at -20°C.

[0060] Next, 500 μL of stimulated saliva was collected after storage and centrifuged (14,000 rpm, room temperature for 10 minutes). The culture supernatant was removed from the precipitate, and genomic DNA was extracted from the precipitate in the same manner as in the extraction of genomic DNA from dental plaque biofilms described above. The ratio of each bacterium was calculated by real-time PCR using Taqman probes. 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.

[0061] (2) Calculation of the relative increase rate of each bacterium The abundance rate (%) of each bacterium was calculated by first preparing a calibration curve using PCR products with known copy numbers as standards, and then calculating the copy number of the rRNA 16S gene of each bacterium using the following formula: Abundance rate (%) of each bacterium = (copy number of each bacterium) / (total bacterial copy number) × 100 The relative increase rate of each bacterium was calculated using the following formula: Relative increase rate (%) of each bacterium = (abundance rate of each bacterium after 3 days of use) / (abundance rate of each bacterium before use) × 100 A bacterium with a relative increase rate of 100% or more was considered to have a growth-promoting effect, and a bacterium with a relative increase rate of less than 100% was considered to have a growth-inhibiting effect.

[0062]

Claims

1. An oral composition containing the following components (A) and (B): (A) a nitrate ion supplying compound; and (B) a chlorophyll metal complex derivative.

2. An oral composition as described in claim 1, wherein the mass ratio ((B) / (A)) of the content of component (B) to the content of component (A) is 0.00001 or more and 0.6 or less.

3. An oral composition according to claim 1 or 2, wherein component (A) is one or more selected from alkali metal nitrates and alkaline earth metal nitrates.

4. An oral composition according to any one of claims 1 to 3, wherein the content of component (A) is 0.5% by mass or more and 20% by mass or less.

5. An oral composition according to any one of claims 1 to 4, wherein component (B) is sodium copper chlorophyllin.

6. An oral composition according to any one of claims 1 to 5, further comprising a fluorine-containing compound (C).

7. An oral composition according to any one of claims 1 to 6, further comprising glycyrrhetinic acid (D).

8. An oral composition according to any one of claims 1 to 7, further comprising an organic acid salt (E).

9. An oral composition according to any one of claims 1 to 8, wherein the content of component (B) is 0.001% by mass or more and 0.8% by mass or less.

10. An oral flora improving agent containing the following ingredients (A) and (B): (A) a nitrate ion supplying compound, and (B) a chlorophyll metal complex derivative.

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