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) a chlorophyll metal complex salt derivative.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] In this situation, various studies have been conducted. 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 level. On the other hand, Patent Document 2 discloses a composition for eliminating periodontal disease bacteria present inside oral cells, etc., which contains copper chlorophyllin salt as an active ingredient, and attempts to purify the inside of the cells by killing periodontal disease bacteria that have invaded oral cells. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] US Patent Application Publication No. 2016 / 0151428 [Patent Document 2] Japanese Patent Application Publication No. 2023-34874 Summary of the Invention [Problem to be solved by the invention]

[0005] However, 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 is given to selectively and effectively promoting the growth of Neisseria bacteria 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 Neisseria and / or Russia bacteria in the oral flora, thereby effectively improving the oral flora. [Means for solving the problem]

[0007] Therefore, the inventors conducted extensive research to solve the above problems and discovered an oral composition that contains a nitrate ion supplying compound and a chlorophyll metal complex derivative, which can selectively and effectively promote the growth of Neisseria and Russica bacteria in the oral flora.

[0008] That is, the present invention provides a composition comprising the following components (A) and (B): (A) Nitrate ion donor compound (B) Chlorophyll metal complex derivatives The present invention provides an oral composition containing the above. [Effects of the Invention]

[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" 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 the present invention, "improving" the oral bacterial flora means selectively promoting the growth of Neisseria and / or Russia bacteria (hereinafter collectively referred to as "Neisseria, etc.") 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 and / or Russia bacteria in the oral bacterial flora.

[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, bacteria of the genus Veillonella, Porphyromonas gingivalis (Pg), Fusobacterium nucleatum (Fn), or Tannerella forsythia.

[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 use component (A) to produce nitric oxide in the oral cavity, the chlorophyll metal complex salt derivative of component (B), which will be described later, exerts some kind of synergistic effect. As a result, these components greatly contribute to promoting the growth of Neisseria bacteria and the proportion of Neisseria bacteria in the oral flora can be rapidly increased.

[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 viewpoint of increasing the growth-promoting effect of Neisseria bacteria and the like in 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 even 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, etc. Among these, copper chlorophyllin sodium is preferred from the viewpoint of enhancing the growth-promoting effect on Neisseria bacteria and other bacteria in the oral flora. In the present invention, the chlorophyll metal complex derivative of component (B) is involved in the production of nitric oxide by component (A) and produces a synergistic effect, which unexpectedly not only effectively increases the proportion of Neisseria bacteria in the oral flora, but also rapidly improves the oral flora, and also improves the growth restriction of 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 quickly exhibiting the 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 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 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.

[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 of Neisseria and other bacteria in the oral flora, rapidly exerting an effect of improving the oral flora, and further improving the growth-restricting effect of pathogenic bacteria.

[0022] 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 component (C) is preferably 0.5 or more, more preferably 2 or more, even more preferably 4 or more, even more preferably 8 or more, even 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 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 effect of restricting the growth of pathogenic bacteria. In the oral composition of the present invention, the mass ratio (NO3 / F) of the nitric acid (NO3) equivalent amount of the nitrate ion supply compound to the fluorine atom equivalent amount of component (C) 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 of 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 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 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.

[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 of Neisseria bacteria and the like in oral flora. Specific examples of component (E) include one or more selected from citrate, gluconate, succinate, fumarate, lactate, malate, and tartrate, of which citrate, gluconate, succinate, fumarate, lactate, and malate are preferred, and citrate is more preferred. Examples of salts include metal salts such as sodium, potassium, magnesium, aluminum, calcium, etc. Among these, sodium salts and potassium salts are preferred. More specifically, among these components (E), sodium citrate is preferred from the viewpoint of effectively increasing the growth-promoting effect of Neisseria and other bacteria in the oral flora.

[0030] From the viewpoint of effectively increasing the growth-promoting effect of Neisseria bacteria and the like 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 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.

[0036] 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.

[0037] 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.

[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, such an oral flora improving agent comprises the above-mentioned components (A) and (B): (A) Nitrate ion donor compound (B) Chlorophyll metal complex derivatives It is an agent containing: 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 comprises the above-mentioned components (A) and (B): (A) Nitrate ion donor compound (B) Chlorophyll metal complex derivatives It is an agent containing: Furthermore, the present invention is also highly useful as an agent for accelerating the oral flora improving effect. That is, such an agent for accelerating the oral flora improving effect is an agent that can accelerate the oral flora improving effect, and comprises the above-mentioned components (A) and (B): (A) Nitrate ion donor compound (B) Chlorophyll metal complex derivatives It is an agent containing:

[0040] 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) Chlorophyll metal complex derivatives An oral composition comprising: [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 still more preferably 7% by mass or less. [4] The oral composition of any one of the above [1] to [3], 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 according to any one of the above [1] to [6], further comprising a fluorine-containing compound (C), said component (C) being preferably one or more selected from a fluoride ion supplying compound and a monofluorophosphate ion supplying compound. [8] The oral composition of [7] above, 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., and more preferably sodium fluoride or stannous fluoride. [9] The oral composition of [7] above, wherein the monofluorophosphate ion supply compound is preferably one or more selected from sodium monofluorophosphate, potassium monofluorophosphate, magnesium monofluorophosphate, calcium monofluorophosphate, etc., and more preferably sodium monofluorophosphate.

[10] Any one of the oral compositions [7] to [9] above, wherein the mass ratio (NO3 / F) of the nitric acid (NO3) equivalent amount of the nitrate ion supply compound to the fluorine atom equivalent amount of component (C) 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.

[11] The oral composition of any one of the above [7] to

[10] , 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 mass%, more preferably 0.3 to 1.4 mass%, and even more preferably 0.4 to 1.3 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 mass%, more preferably 0.4 to 2 mass%, and even more preferably 0.6 to 1.5 mass%.

[0042]

[12] The oral composition according to 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, even more preferably 0.2% by mass or less.

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

[12] above, 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, even more preferably 5% by mass or less.

[14] The oral composition according to 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 sulfate ester salt.

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

[14] 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.

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

[15] above, which has a pH at 25°C of preferably 5.0 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, even more preferably 8 or lower.

[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 a growth promoter for oral Neisseria and / or Neisseria spp.

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

[16] above as an agent for accelerating the oral flora improving 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 Neisseria and / or Neisseria russia in the oral cavity by ingesting any one of the oral compositions [1] to

[16] above.

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

[16] above.

[23] The following components (A) and (B): (A) Nitrate ion donor compound (B) Chlorophyll metal complex derivatives An oral flora improving agent containing

[24] The following components (A) and (B): (A) Nitrate ion donor compound (B) Chlorophyll metal complex derivatives A growth promoter for oral Neisseria and / or Neisseria spp. containing

[25] The following components (A) and (B): (A) Nitrate ion donor compound (B) Chlorophyll metal complex derivatives An agent that accelerates the improvement of oral flora. [Example]

[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 (1) to (4) below, the effect of improving the oral flora was evaluated using the growth-promoting effect of Neisseria bacteria in the dental plaque biofilm flora (increase ratio (fold) and increase amount (%)) as indicators.

[0046] (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.

[0047] (2) Preparation of a dental plaque biofilm model using dental plaque suspension culture Oral compositions were prepared using potassium nitrate (Fujifilm Wako Pure Chemical Industries), copper chlorophyllin sodium (Tama Biochemicals), sodium citrate (Fujifilm Wako Pure Chemical Industries), β-glycyrrhetinic acid (Alps Pharmaceutical Industries), sodium fluoride (Stella Chemifa), and 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 (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. 7A 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.

[0048] (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.

[0049] [Table 1]

[0050] [Table 2]

[0051] (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

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

[0053] Evaluation 1: Neisseria growth promotion effect (increase ratio (times)) Based on the quantitative values ​​of bacteria obtained for each oral composition, 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) 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 example and used as the evaluation standard for the following evaluation 1. Specifically, comparative example 1 was selected as a control example for examples 1 to 5 and 13 to 21, and comparative example 2 was selected as a control example for examples 6 to 12 and 22 to 35.

[0054] [Table 3]

[0055] [Table 4]

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

[0057] [Table 5]

[0058] <Test Example 3 [Example 52]> Mouthwashes were prepared according to the formulation shown in Table 6, with the remainder being water, to a total mass of 100%, and their effect 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 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.

[0060] Next, 500 μL of stimulated saliva was collected after storage 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 for extracting genomic DNA from dental plaque biofilms described above. The proportion 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.

[0061] (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 The relative increase rate of each bacterium was determined to be 100% or more and to have a growth promoting effect, and the relative increase rate of each bacterium was determined to be less than 100% and to have a growth inhibiting effect.

[0062] [Table 6]

Claims

1. The following components (A) and (B): (A) Nitrate ion supplying compound (B) Chlorophyll metal complex derivatives An oral composition comprising:

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 0.00001 or more and 0.6 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 20% by mass or less.

5. 3. The oral composition according to claim 1, wherein component (B) is sodium copper chlorophyllin.

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

7. The oral composition according to claim 1 or 2, further comprising glycyrrhetinic acid (D).

8. The oral composition according to claim 1 or 2, further comprising an organic acid salt (E).

9. 3. The oral composition according to claim 1, wherein the content of component (B) is 0.001% by mass or more and 0.8% by mass or less.

10. The following components (A) and (B): (A) Nitrate ion supplying compound (B) Chlorophyll metal complex derivatives An oral flora improving agent containing

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