Oral composition

Abstract

The present application relates to an oral composition which can selectively and effectively promote the growth of non-pathogenic bacteria, i.e., Neisseria bacteria and / or Rothia bacteria, in the oral flora, effectively achieving improvement in the oral flora. That is, the present application provides an oral composition containing the following components (A) and (B): (A) a nitrate ion-providing compound; (B) a chlorophyll metal complex salt derivative.

Description

Technical Field

[0001] This invention relates to a composition for oral use. Background Technology

[0002] The oral cavity is home to a vast array of bacteria. These bacteria form the oral microbiota, which exists in various locations such as the tooth surfaces, gums, gingival margins, palate, buccal mucosa, and tongue surface and dorsum. This oral microbiota includes not only pathogenic bacteria involved in oral diseases such as dental caries and periodontal disease, but also non-pathogenic bacteria that coexist as endemic flora. It is believed that achieving a balance between non-pathogenic and pathogenic bacteria is highly useful in the onset, prevention, and inhibition of the progression of oral diseases.

[0003] In this situation, various studies have been conducted. For example, Patent Document 1 reports that by incorporating nitrogen sources such as nitrates into the composition, Neisseria in the oral cavity can produce nitric oxide, thereby enabling good control of the bacterial composition of the oral flora.

[0004] On the other hand, Patent Document 2 discloses a composition for eliminating periodontal bacteria present in oral cells, which contains copper chlorophyll salt as an active ingredient and attempts to purify the cells by killing periodontal bacteria that invade oral cells.

[0005] (Patent Document 1) U.S. Patent Application Publication No. 2016 / 0151428

[0006] (Patent Document 2) Japanese Patent Application Publication No. 2023-34874 Summary of the Invention

[0007] The present invention provides an oral composition comprising the following components (A) and (B):

[0008] (A) Nitrate ion supply compounds;

[0009] (B) Chlorophyll metal complex salt derivatives.

[0010] Patent Document 1 only describes so-called probiotic technology that involves administering microorganisms directly to the human body. It neither discloses nor provides any technical insights into the concept of promoting the growth of specific microorganisms in the oral cavity. Furthermore, even the composition described in Patent Document 2 only specifically targets periodontal bacteria; no research has been conducted on its ability to selectively and effectively promote the growth of Neisseria species in the oral cavity.

[0011] Therefore, there is still considerable room for improvement in enhancing the selective and effective growth-promoting effect of Neisseria species in the oral flora.

[0012] Therefore, the present invention relates to an oral composition that can selectively and effectively promote the growth of Neisseria and / or Rochezoides in the oral flora, thereby effectively improving the oral flora.

[0013] The inventors have made efforts to solve the above-mentioned technical problems and have discovered an oral composition that, by containing a nitrate ion supply compound and a chlorophyll metal complex salt derivative, can selectively and effectively promote the growth of Neisseria or Rocheria in the oral flora.

[0014] According to the present invention, it is possible to selectively promote the growth of Neisseria species in the oral cavity and selectively inhibit the growth of pathogenic bacteria, effectively improving the oral flora, and furthermore, it can rapidly exhibit the effect of improving the oral flora. In addition, it is possible not only to promote the growth of Neisseria species, but also to promote the growth of Rochetomyces species. Detailed Implementation

[0015] The present invention will now be described in detail.

[0016] Furthermore, in this invention, "oral flora" is also called "oral flora" or "oral microbiota," meaning a community formed by a variety of bacteria living in the oral cavity.

[0017] Furthermore, in this invention, "improving" the oral microbiota means selectively promoting the growth of Neisseria species or, further, Rochezobium species within the oral cavity by activating their metabolism, thereby increasing the proportion of Neisseria or Rochezobium species (hereinafter, also collectively referred to as "Neisseria species, etc.") in the oral microbiota. It also means increasing the proportion of Neisseria species, etc., in the oral microbiota by selectively inhibiting the growth of pathogenic bacteria.

[0018] Here, *Neisseria* refers to oral flora belonging to the genus *Neisseria* within the family Neisseria. Examples of species within this genus include: *Neisseria mucosa*, *Neisseria sicca*, *Neisseria flava*, *Neisseria subflava*, *Neisseria flavescens*, and *Neisseria elongata*.

[0019] In addition, Rothia species are Gram-positive cocci or bacilli belonging to the genus Rothia in the family Micrococcaceae, and are native to the oral cavity. Rothia species include: *Rothia aeria*, *Rothia mucilaginosa*, and *Rothia dentocariosa*, among others.

[0020] Furthermore, in this invention, "pathogenic bacteria" specifically means: bacteria of the genus Prevotella, bacteria of the genus Veillonella, Porphyromonas gingivalis (Pg) , Fusobacterium nucleatum (Fn) , or Tannerella forsythia.

[0021] The oral composition of the present invention contains a nitrate ion-donating compound as component (A). Component (A) is a compound that releases nitrate (NO3) ions upon contact with water.

[0022] The detailed mechanism by which the oral composition of the present invention improves the oral flora is not fully understood, but it is believed that when Neisseria species and the like utilize component (A) to produce nitric oxide in the oral cavity, the chlorophyll metal complex salt derivative of component (B) may have a synergistic effect. As a result, these components greatly promote the growth of Neisseria species and the like, and can rapidly increase the proportion of Neisseria species and the like in the oral flora.

[0023] As a component (A), specifically, one or more of alkali metal nitrates and alkaline earth metal nitrates may be cited.

[0024] More specifically, component (A) may be selected from one or more of sodium nitrate, potassium nitrate, and calcium nitrate. Potassium nitrate is preferred.

[0025] From the viewpoint of promoting the growth of Neisseria species and the like in the oral flora, and further from the viewpoint of rapidly improving the oral flora, in the oral composition of the present invention, the content of component (A) is preferably 0.5% by mass or more, more preferably 0.8% by mass or more, more preferably 2% by mass or more, more preferably 3% by mass or more, and preferably 20% by mass or less, more preferably 15% by mass or less, more preferably 10% by mass or less, and more preferably 7% by mass or less. Furthermore, in the oral composition of the present invention, the content of component (A) is preferably 0.5 to 20% by mass, more preferably 0.8 to 15% by mass, more preferably 2 to 10% by mass, and more preferably 3 to 7% by mass.

[0026] The oral composition of the present invention contains a chlorophyll metal complex salt derivative as component (B). Specifically, one or more chlorophyll metal complex salt derivatives selected from sodium copper chlorophyll and sodium iron chlorophyll can be cited as examples. From the viewpoint of increasing the growth-promoting effect on Neisseria species and the like in the oral flora, sodium copper chlorophyll is preferred.

[0027] In this invention, the chlorophyll metal complex salt derivative of component (B) not only participates in the production of nitric oxide by component (A), resulting in a synergistic effect, but also unexpectedly and effectively increases the proportion of Neisseria species in the oral flora, and further rapidly exhibits an improving effect on the oral flora. In addition, it can enhance the growth-limiting effect on pathogenic bacteria.

[0028] From the perspectives of promoting the growth of Neisseria species and the like in the oral flora, rapidly improving the oral flora, and enhancing the growth-limiting 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, 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 more preferably 0.6% by mass or less. Furthermore, 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 more preferably 0.02 to 0.6% by mass.

[0029] From the viewpoint of effectively increasing the growth-promoting effect of Neisseria species and the like in the oral flora, and rapidly demonstrating an improvement effect on the oral flora, 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. Furthermore, the mass ratio of the content of component (B) to the content of component (A) ((B) / (A)) is preferably 0.00001 to 0.6, more preferably 0.0001 to 0.4, even more preferably 0.0015 to 0.3, even more preferably 0.003 to 0.3.

[0030] From the viewpoint of effectively increasing the growth-promoting effect of Neisseria species and the like in the oral flora, and rapidly exhibiting an improvement effect on the oral flora, thereby enhancing the growth-limiting effect of pathogenic bacteria, the oral composition of the present invention may further contain a fluoride-containing compound (C). Specifically, this component (C) may be selected from one or more of fluoride ion-supplying compounds and monofluorophosphate ion-supplying compounds.

[0031] The fluoride ion-donating compound is a fluorine-containing compound other than a compound that donates monofluorophosphate ions. Examples of such fluoride ion-donating compounds include one or more selected from sodium fluoride, stannous fluoride, potassium fluoride, zinc fluoride, fluorinated betaine, stannous alanine fluoride, sodium fluorosilicate, and hexylamine fluoride. Among these, sodium fluoride or stannous fluoride is preferred.

[0032] Examples of compounds that can be used as monofluorophosphate ion donors include one or more selected from sodium monofluorophosphate, potassium monofluorophosphate, magnesium monofluorophosphate, and calcium monofluorophosphate. Sodium monofluorophosphate is preferred.

[0033] From the viewpoint that component (C) effectively increases the growth-promoting effect of Neisseria species and the like in the oral flora, and rapidly exhibits an improvement effect on the oral flora, thereby enhancing the growth-limiting effect of pathogenic bacteria, a monofluorophosphate ion supply compound is preferred.

[0034] From the viewpoint of increasing the growth-promoting effect of Neisseria species and the like in the oral flora, and rapidly demonstrating the improvement effect of the oral flora, thereby enhancing the growth-limiting effect of pathogenic bacteria, the mass ratio (NO3 / F) of the nitrate ion supply compound to the fluorine atom conversion of the component (C) in the oral composition of the present invention is preferably 0.5 or more, more preferably 2 or more, more preferably 4 or more, more preferably 8 or more, further preferably 12 or more, more preferably 14 or more, and preferably 50 or less, more preferably 48 or less, more preferably 46 or less, more preferably 44 or less, further preferably 42 or less, and more preferably 38 or less. Furthermore, the mass ratio (NO3 / F) of the nitrate ion supply compound to the fluorine atom conversion of component (C) in the oral composition of the present invention is preferably 0.5 to 50, more preferably 2 to 48, even more preferably 4 to 46, even more preferably 8 to 44, further preferably 12 to 42, and even more preferably 14 to 38.

[0035] In the oral composition of the present invention, the content of component (C), in terms of fluorine atoms, is preferably 850 ppm or more, more preferably 900 ppm or more, and 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. Furthermore, in the oral composition of the present invention, the content of component (C), 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.

[0036] Furthermore, when component (C) is a fluoride ion supply compound, from the viewpoint of effectively increasing the growth-promoting effect of Neisseria spp. and the like in the oral flora, and rapidly exhibiting an improvement effect on the oral flora, thereby enhancing the growth-limiting effect of pathogenic bacteria, the content of the fluoride ion supply 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. Furthermore, when component (C) is a monofluorophosphate ion supply compound, from the viewpoint of effectively increasing the growth-promoting effect of Neisseria spp. and the like in the oral flora, and rapidly exhibiting an improvement effect on the oral flora, thereby enhancing the growth-limiting effect of pathogenic bacteria, the content of the monofluorophosphate ion supply 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.

[0037] From the viewpoint of promoting the growth of Neisseria species and the like in the oral flora, the oral composition of the present invention may further contain glycyrrhetinic acid (D). Specifically, α-glycyrrhetinic acid, β-glycyrrhetinic acid, etc., can be cited as examples. Among them, β-glycyrrhetinic acid is preferred.

[0038] From the viewpoint of promoting the growth of Neisseria species and the like in the oral flora, in the oral composition of the present invention, the content of component (D) is preferably 0.001% by mass or more, more preferably 0.003% by mass or more, and 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. Furthermore, in the oral composition of the present invention, the content of component (C) 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.

[0039] The oral composition of the present invention contains water. In this invention, "water" means all the water contained in the oral composition, including not only purified water incorporated in the composition, but also the water contained in each of the constituent ingredients. By containing this water, the aforementioned components can be well dissolved or dispersed, thus fully exerting the desired effect.

[0040] Specifically, when the oral composition of the present invention is a liquid oral composition such as a mouthwash or a liquid dental floss, 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, and 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 a liquid dental floss, 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.

[0041] Furthermore, when the oral composition of the present invention is a dental cleaning composition such as toothpaste or dental powder, 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, more preferably 55% by mass or less. Additionally, when the oral composition of the present invention is a dental cleaning composition such as toothpaste or dental powder, the water content is preferably 5 to 60% by mass, more preferably 10 to 55% by mass.

[0042] From the viewpoint of enhancing the growth-promoting effect of Neisseria species and the like in the oral flora, the oral composition of the present invention may further contain organic acid salts (E).

[0043] Specifically, as component (E), one or more may be selected from citrate, gluconate, succinate, fumarate, lactate, malate, and tartrate. Among these, citrate, gluconate, succinate, fumarate, lactate, and malate are preferred, and citrate is more preferred.

[0044] In addition, examples of salts include metallic salts such as sodium, potassium, magnesium, aluminum, and calcium. Among these, sodium salts and potassium salts are preferred.

[0045] More specifically, among these components (E), sodium citrate is preferred from the viewpoint of effectively increasing the growth-promoting effect of Neisseria species and the like in the oral flora.

[0046] From the viewpoint of effectively increasing the growth-promoting effect of Neisseria species and the like in the oral flora, in the oral composition of the present invention, the content of component (E) is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, and 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. Furthermore, in the oral composition of the present invention, the content of component (E) 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.

[0047] Furthermore, in the oral composition of the present invention, from the viewpoint of enhancing the growth-promoting effect on Neisseria species and the like in the oral flora, it is preferable to limit the content of sulfate salts. Examples of such sulfate salts include one or more selected from alkyl sulfates, alkenyl sulfates, polyoxyalkylene alkyl ether sulfates, polyoxyalkylene alkenyl ether sulfates, and polyoxyalkylene alkylphenyl ether sulfates.

[0048] From the viewpoint of effectively enhancing the growth-promoting effect of Neisseria species and the like in the oral flora, the content of sulfate salt in the oral composition of the present invention 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 is preferably sulfate-free.

[0049] From the viewpoint of avoiding a decrease in the growth-promoting effect of Neisseria species and enhancing the growth-promoting effect of Neisseria species and the like in the oral flora, the oral composition of the present invention is preferably limited in the content of bactericide.

[0050] From the viewpoint of effectively enhancing the growth-promoting effect of Neisseria spp. in the oral flora, the content of bactericide in the oral composition of the present invention is preferably less than 0.5% by mass, more preferably less than 0.1% by mass, and even more preferably less than 0.05% by mass, or the oral composition of the present invention is preferably free of bactericide.

[0051] Furthermore, the presence of cationic bactericides is preferably limited in the bactericide formulation.

[0052] Specifically, examples of cationic bactericides include one or more selected from quaternary ammonium compounds and biguanide compounds. Examples of cationic bactericides belonging to the quaternary ammonium compound category include one or more selected from cetylpyridinium chloride, benzyl chloride, dequinoline chloride, benzalkonium chloride, alkyl dimethyl ammonium chloride, alkyl trimethyl ammonium chloride, and methyl benzyl chloride. Furthermore, examples of cationic bactericides belonging to the biguanide compound category include one or more selected from chlorhexidine gluconate or chlorhexidine hydrochloride and their salts.

[0053] From the viewpoint of effectively enhancing the growth-promoting effect of Neisseria species and the like 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 less than 0.1% by mass, and even more preferably less than 0.05% by mass, or the oral composition of the present invention is preferably free of cationic bactericide.

[0054] The oral composition of the present invention may, in addition to the above-mentioned components, contain, to a extent that does not impair the effects of the present invention, the following: solvents such as ethanol; pH adjusters; binders; humectants such as glycerin, propylene glycol, or polyethylene glycol; abrasives; sweeteners; foaming agents or foaming aids; preservatives; pigments; fragrances, etc.

[0055] From the viewpoint of effectively increasing the growth-promoting effect of Neisseria species and the like in the oral flora, and rapidly exhibiting an improving effect on the oral flora, thereby enhancing the growth-limiting effect on pathogenic bacteria, the oral composition of the present invention preferably has a pH value of 5 or higher at 25°C, more preferably 5.5 or higher, more preferably 6 or higher, and more preferably 9 or lower, more preferably 8.5 or lower, and more preferably 8 or lower. Furthermore, the oral composition of the present invention preferably has a pH value of 5 to 9 at 25°C, more preferably 5.5 to 8.5, and more preferably 6 to 8.

[0056] Furthermore, the pH value of the oral composition of the present invention is a value measured using a pH electrode at 25°C.

[0057] Thus, the present invention is also highly useful as an oral flora improver. That is, the oral flora improver is an agent containing the above-mentioned components (A) and (B):

[0058] (A) Nitrate ion supply compounds;

[0059] (B) Chlorophyll metal complex salt derivatives.

[0060] Furthermore, the present invention is also highly useful as a growth promoter for Neisseria and / or Rheumatoidae in the oral cavity. That is, the growth promoter for Neisseria and / or Rheumatoidae in the oral cavity is an agent capable of promoting the growth of Neisseria and / or Rheumatoidae in the oral cavity, and is an agent containing the aforementioned components (A) and (B):

[0061] (A) Nitrate ion supply compounds;

[0062] (B) Chlorophyll metal complex salt derivatives.

[0063] Furthermore, this invention is also highly useful as an accelerator for improving oral flora. That is, this accelerator for improving oral flora is an agent capable of accelerating the improvement of oral flora, and it contains the aforementioned components (A) and (B):

[0064] (A) Nitrate ion supply compounds;

[0065] (B) Chlorophyll metal complex salt derivatives.

[0066] Regarding the above embodiments, the present invention further discloses the following oral composition.

[0067] [1] An oral composition comprising the following components (A) and (B):

[0068] (A) Nitrate ion supply compounds;

[0069] (B) Chlorophyll metal complex salt derivatives.

[0070] [2] In the oral composition of [1] above, component (A) is preferably selected from one or more of alkali metal nitrates and alkaline earth metal nitrates, more preferably selected from one or more of sodium nitrate, potassium nitrate and calcium nitrate, and even more preferably potassium nitrate.

[0071] [3] In the oral composition of [1] or [2] above, the content of component (A) is preferably 0.5% by mass or more, more preferably 0.8% by mass or more, more preferably 2% by mass or more, more preferably 3% by mass or more, and preferably 20% by mass or less, more preferably 15% by mass or less, more preferably 10% by mass or less, and more preferably 7% by mass or less.

[0072] [4] The oral composition of any one of [1] to [3] above, wherein component (B) is preferably selected from one or two of sodium copper chlorophyllin and sodium iron chlorophyllin, more preferably sodium copper chlorophyllin.

[0073] [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, 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 more preferably 0.6% by mass or less.

[0074] [6] In any of the above [1] to [5] oral composition, 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, more preferably 0.0015 or more, more preferably 0.003 or more, and preferably 0.6 or less, more preferably 0.4 or less, and more preferably 0.3 or less.

[0075] [7] The oral composition of any one of [1] to [6] above, wherein it further contains a fluorine compound (C), which is preferably selected from one or more of a fluoride ion-supplying compound and a monofluorophosphate ion-supplying compound.

[0076] [8] In the oral composition described above [7], the fluoride ion supply compound is preferably selected from one or more of sodium fluoride, stannous fluoride, potassium fluoride, zinc fluoride, fluorinated betaine, stannous alanine fluoride, sodium fluorosilicate, and fluorinated hexylamine, more preferably sodium fluoride or stannous fluoride.

[0077] [9] In the oral composition described above [7], the monofluorophosphate ion supply compound is preferably selected from one or more of sodium monofluorophosphate, potassium monofluorophosphate, magnesium monofluorophosphate, and calcium monofluorophosphate, and more preferably sodium monofluorophosphate.

[0078]

[10] In any of the above [7] to [9] oral compositions, the mass ratio (NO3 / F) of the nitrate ion supply compound to the fluorine atom of component (C) is preferably 0.5 or more, more preferably 2 or more, more preferably 4 or more, more preferably 8 or more, and more preferably 12 or more, more preferably 14 or more, and preferably 50 or less, more preferably 48 or less, more preferably 46 or less, more preferably 44 or less, and more preferably 42 or less, more preferably 38 or less.

[0079]

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

[10] above, wherein when component (C) is a fluoride ion supply compound, the content of the fluoride ion supply 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; when component (C) is a monofluorophosphate ion supply compound, the content of the monofluorophosphate ion supply 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.

[0080]

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

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

[0081]

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

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

[0082]

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

[13] above, wherein the content of sulfate 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 is preferably free of sulfate salt.

[0083]

[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 less than 0.1% by mass, and even more preferably less than 0.05% by mass, or the oral composition of the present invention is preferably free of bactericide.

[0084]

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

[15] above, wherein the pH value at 25°C is preferably 5.0 or higher, more preferably 5.5 or higher, more preferably 6 or higher, and preferably 9 or lower, more preferably 8.5 or lower, and more preferably 8 or lower.

[0085]

[17] Use of any of the oral compositions described in [1] to

[16] above as an oral flora improver.

[0086]

[18] Use of any of the oral compositions described in [1] to

[16] above as a growth promoter for Neisseria and / or Rochezoides in the oral cavity.

[0087]

[19] Use of any of the oral compositions described in [1] to

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

[0088]

[20] A method for improving oral flora, wherein the oral flora is improved by ingesting an oral composition of any one of [1] to

[16] above.

[0089]

[21] A method for promoting the growth of Neisseria and / or Rochezoides in the oral cavity, wherein the growth of Neisseria and / or Rochezoides in the oral cavity is promoted by ingesting the oral composition of any one of [1] to

[16] above.

[0090]

[22] A method for accelerating the improvement of oral flora, wherein the improvement of oral flora is accelerated by ingesting any one of the oral compositions described in [1] to

[16] .

[0091]

[23] An oral flora improver, comprising the following components (A) and (B):

[0092] (A) Nitrate ion supply compounds;

[0093] (B) Chlorophyll metal complex salt derivatives.

[0094]

[24] A growth promoter for oral Neisseria and / or Rochezoides spp., comprising the following components (A) and (B):

[0095] (A) Nitrate ion supply compounds;

[0096] (B) Chlorophyll metal complex salt derivatives.

[0097]

[25] An accelerator for improving oral flora, comprising the following components (A) and (B):

[0098] (A) Nitrate ion supply compounds;

[0099] (B) Chlorophyll metal complex salt derivatives.

[0100] [Example]

[0101] The present invention will now be specifically described based on embodiments. Furthermore, unless otherwise stated in the table, the content of each component is expressed as a percentage by mass.

[0102] <Experimental Example 1>

[0103] The effect of improving oral flora was evaluated by using the growth-promoting effect of Neisseria spp. in dental tartar biofilm flora (increase rate (times) and increase amount (%)) as indicators, according to the methods shown in (1) to (4) below.

[0104] (1) Tartar collection and pretreatment

[0105] Dental plaque adhering to the tooth surface was collected from healthy women using a dental scaler and placed in a 1.5 mL tube. The tube was cleaned twice with PBS (-) at 7,000 g, 2 minutes, and room temperature. The particles containing the plaque bacteria were then suspended in 300 μL of Cellbanker (manufactured by Zenya Kogyo Co., Ltd., Japan). The prepared plaque suspension was stored at -80°C before use. Furthermore, a portion of this plaque suspension was used to determine the copy number of the rRNA 16S gene of all bacteria in the suspension using the DNA extraction method and real-time PCR described below.

[0106] (2) Creation of a dental biofilm model by culturing dental plaque suspension

[0107] Oral compositions with the remainder being water were prepared using potassium nitrate (manufactured by Fujifilm and Kojun Pharmaceutical Co., Ltd.), sodium copper chlorophyllin (manufactured by TAMA BIOCHEMICAL), sodium citrate (manufactured by Fujifilm and Kojun Pharmaceutical Co., Ltd.), β-glycyrrhetinic acid (manufactured by Alps Pharmaceutical Co., Ltd.), sodium fluoride (manufactured by Stella Chemifa Co., Ltd.), and sodium monofluorophosphate (manufactured by BK Giulini GmbH). These compositions were diluted 10-fold using Brain Heart Infusion (BHI) medium (BD, Japan), and the resulting liquids were used as evaluation samples. The evaluation samples were analyzed using the total copy number of the 16S rRNA gene of all bacteria in the plaque suspension as 10-1. 7 The culture medium containing dental plaque was prepared by diluting the solution in copies / mL. 1 mL of the prepared culture medium was added to each well of a poly-L-lysine-coated 24-well microplate (AGCTECHNO GLASS), and the plate was incubated at 37°C under microaerobic conditions using AnaeroPack microaerobic microplate (manufactured by Mitsubishi Gas Chemical Co., Ltd.) for 48 hours to create a dental plaque biofilm.

[0108] (3) Extraction of genomic DNA from dental plaque biofilm

[0109] The dental tartar biofilm adhering to the bottom of the culture dish was thoroughly mixed with the culture supernatant using a pipette and collected into a 1.5 mL tube. Next, centrifugation was performed (at room temperature, 14000 rpm for 10 minutes). 20 μL / well of the precipitate after removing the culture supernatant was added to the precipitate, followed by the addition of 20 mg / mL lysozyme solution (manufactured by Fujifilm and Koden Pharmaceutical Co., Ltd.) containing 20 mM Tris-HCl (pH 8.0), 2 mM EDTA, and 1.2% Triton X-100. The solution was incubated at 37°C for 60 minutes with shaking (160 rpm). Genomic DNA was extracted using the Dneasy Blood & Tissue kit (QIAGEN), and the bacterial ratios were calculated using real-time PCR with TaqMan probes.

[0110] The primers and Taqman probes used, and the reaction conditions for real-time PCR are shown in Tables 1-2.

[0111] [Table 1]

[0112]

[0113] [Table 2]

[0114]

[0115] (4) Calculation of the presence ratio of each bacteria

[0116] Regarding the presence rate (%) of each bacterium, a calibration curve was first prepared using PCR products with known copy numbers as standards. Then, the copy number of the rRNA16S gene of each bacterium was calculated and obtained using the following formula.

[0117] Presence ratio of each bacterium (%) = (Copy number of each bacterium) / (Total bacterial copy number) × 100

[0118] [Examples 1-35, Comparative Examples 1-2]

[0119] Prepare oral compositions with the remainder being water according to the formulations shown in Tables 3-4. For evaluation samples obtained by diluting the oral compositions 10 times using BHI medium, quantify the bacteria according to (1)-(4) above.

[0120] Next, the evaluation will be conducted according to the following method 1.

[0121] The results are shown in Tables 3 and 4.

[0122] Evaluation 1: Growth-promoting effect on Neisseria spp. (increase rate (times))

[0123] Based on the quantitative values ​​of bacteria obtained from each oral composition, the growth-promoting effect (increase rate (times)) of Neisseria spp. was calculated using the following formula.

[0124] Growth-promoting effect of Neisseria spp. (increase rate (times)) = (presence ratio of Neisseria spp.) / (presence ratio of Neisseria spp. in the comparative examples selected as control examples)

[0125] Furthermore, based on the potassium nitrate content in each example, comparative examples containing only the same amount of potassium nitrate were selected as control examples and used as the evaluation benchmark for Evaluation 1 below. Specifically, Comparative Example 1 was selected as the control example for Examples 1-5 and 13-21, and Comparative Example 2 was selected as the control example for Examples 6-12 and 22-35.

[0126] [Table 3]

[0127]

[0128] [Table 4]

[0129]

[0130] <Experimental Example 2 [Examples 36-51, Comparative Examples 3-5]>

[0131] For Examples 36-43 and Comparative Example 3, the incubation time was set to 12 hours, and for Examples 44-51 and Comparative Example 4, the incubation time was set to 24 hours. The rapidity of the microbial community improvement effect was evaluated in the same manner as in Experiment 1.

[0132] The results for Examples 7, 8, 22, 23, 25, 27, 29, and 31, which had a culture time of 48 hours, and Comparative Example 5 are shown in Table 5.

[0133] Furthermore, 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, which were used as the evaluation benchmark for Evaluation 1 above.

[0134] [Table 5]

[0135]

[0136] <Experimental Example 3 [Example 52]>

[0137] Prepare a mouthwash with the remaining amount being water and the total amount being 100% by mass according to the formula shown in Table 6. Evaluate the effect on promoting bacterial growth in saliva according to the methods shown in (1) to (2) below.

[0138] The results are shown in Table 6.

[0139] (1) Calculation of the ratio of each type of bacteria

[0140] One subject used the mouthwash three times a day for three days (gargling with 20 mL of mouthwash for 30 seconds), and the bacterial ratio in saliva was compared before and after use to assess irritation. Furthermore, from three days prior to using the mouthwash until the end of the study period, the subject used the designated commercially available toothpaste and toothbrush to exclude the influence of oral hygiene practices other than mouthwash use.

[0141] For saliva produced during stimulation, any saliva leaking out while chewing commercially available paraffin gum for 3 minutes should be spat into a plastic container for recycling and then quickly stored in a freezer at -20°C.

[0142] Next, 500 μL of stimulated saliva was collected and centrifuged (at 14,000 rpm for 10 minutes at room temperature) to remove the culture supernatant and obtain a precipitate. Genomic DNA was extracted from this precipitate using the same method as that used for extracting genomic DNA from dental plaque biofilms, and the ratio of each bacteria was calculated using real-time PCR with Taqman probes.

[0143] Furthermore, similar to Experiment 1 above, the primers and Taqman probes shown in Table 1 were used, and the reaction conditions for real-time PCR shown in Table 2 were followed.

[0144] (2) Calculation of the relative increase rate of each bacteria

[0145] Regarding the presence rate (%) of each bacterium, a calibration curve was first prepared using PCR products with known copy numbers as standards. Then, the copy number of the rRNA16S gene of each bacterium was calculated and obtained using the following formula.

[0146] Presence ratio of each bacterium (%) = (Copy number of each bacterium) / (Total bacterial copy number) × 100

[0147] In addition, the relative increase rate of each bacterium was calculated using the following formula.

[0148] The relative increase rate (%) of each bacteria = (the presence rate of each bacteria after 3 days of use) / (the presence rate of each bacteria before use) × 100

[0149] Furthermore, bacteria with a relative increase rate of 100% or more are considered to have a growth-promoting effect, while bacteria with a relative increase rate of less than 100% are considered to have a growth-inhibiting effect.

[0150] [Table 6]

[0151]

Claims

1. An oral composition, wherein, The oral composition contains the following components (A) and (B): (A) Nitrate ion supply compounds; (B) Chlorophyll metal complex salt derivatives.

2. The oral composition of claim 1, wherein, The mass ratio of component (B) to component (A) is between 0.00001 and 0.

6.

3. The oral composition as described in claim 1 or 2, wherein, Component (A) is selected from one or more of alkali metal nitrates and alkaline earth metal nitrates.

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

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

6. The oral composition according to any one of claims 1 to 5, wherein, It then contains fluorine-containing compounds (C).

7. The oral composition according to any one of claims 1 to 6, wherein, It also contains glycyrrhetinic acid (D).

8. The oral composition according to any one of claims 1 to 7, wherein, It further contains organic acid salts (E).

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

10. An oral flora improver, wherein, The oral flora improver contains the following ingredients (A) and (B): (A) Nitrate ion supply compounds; (B) Chlorophyll metal complex salt derivatives.

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