Oral composition for non-human mammals and oral care method for non-human mammals

Abstract

To provide means enabling easy improvement of oral hygiene in non-human mammals.SOLUTION: The present invention provides an oral composition for non-human mammals, the composition comprising: (a) a radical generation catalyst; (b) a radical generation source; (c) a thickener; and (d) water, where a content of the thickener is at least 2.0 mass%. The present invention also provides an oral care method for non-human mammals, the method comprising attaching the oral composition to teeth and / or gingiva of the non-human mammals.SELECTED DRAWING: Figure 9

Description

Technical Field

[0001] The present invention relates to an oral composition for non-human mammals and a method for oral care of non-human mammals.

Background Art

[0002] In the case of non-human mammals, they cannot use a toothbrush on their own volition or perform oral disinfection using an oral disinfectant. Such treatments are difficult to achieve sufficient effects unless carried out by a sufficiently trained third party such as an owner or a veterinarian. Periodontal disease is said to affect approximately 80% of dogs and 70% of cats up to 2 years old, and means for effectively treating or preventing periodontal disease are in demand.

[0003] Periodontal disease causes bad breath, and as the symptoms progress, it causes swelling and bleeding of the gums, dissolves the bone supporting the teeth, and the microorganisms causing periodontal disease affect other organs, sometimes causing life-threatening symptoms. In addition, some periodontal diseases do not originate from plaque, and if they become more severe, specialized treatments (mainly chemical therapies such as antibiotics, tooth extraction, etc.) must be received. For example, depending on the administered drug, there is also a concern that various digestive system diseases may be induced as side effects.

[0004] In non-human mammals such as humans and pets, due to different living environments and habits, the oral environment is also different, and the bacterial flora present in the oral cavity is also different. Also, unlike humans, non-human mammals such as pets will reject those with unappealing tastes. In addition, since non-human mammals such as pets cannot gargle, the composition applied to the oral cavity will be swallowed, so a composition with high safety is required. Therefore, since human oral compositions cannot always be directly applied to non-human mammals, it is necessary to develop an oral composition more suitable for pets (for example, Patent Documents 1, 2, etc.).

[0005] Commercially available toothpaste gels for non-human mammals are designed with brushing (physical removal) using a toothbrush in mind. That is, they are designed to remove dirt from teeth and gums, taking into account physical removal by a toothbrush. However, non-human mammals have problems such as experiencing aversion rather than pain when using a toothbrush for a long time and being unable to perform proper brushing. Thus, it is difficult to say that the conventional oral compositions for pets have sufficiently achieved the effect of improving the oral hygiene environment.

[0006] In recent years, sterilization techniques that utilize radicals and are applicable in the oral cavity have been developed. For example, Patent Document 3 discloses an oral agent containing a radical generator, which is an agent for removing oral deposits. However, an oral composition that exhibits an effect in non-human mammals has not been disclosed.

Prior Art Documents

Patent Documents

[0007]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0008] An object of the present invention is to provide a new means for easily improving oral hygiene in non-human mammals.

Means for Solving the Problems

[0009] As a result of investigations to solve the above problems, the inventors have completed an invention related to an oral composition that easily contributes to the improvement of oral hygiene in non-human mammals and an oral care method using the same. That is, the present invention includes the following.

[0010] [1] A composition for the oral cavity of non-human mammals, comprising: (a) A radical-generating catalyst; (b) A radical source; (c) A thickener; and (d) Water The composition for the oral cavity is characterized in that the thickener is contained in an amount of at least 2.0% by mass. [2] The composition for the oral cavity according to item 1, wherein the thickener contains hydroxypropylmethylcellulose. [3] The composition for the oral cavity according to item 1 or 2, wherein the radical-generating catalyst is an ammonium salt having a Lewis acidity of 0.4 eV or more. [4] The composition for the oral cavity according to any one of items 1 to 3, wherein the radical-generating catalyst contains an ammonium salt represented by the following chemical formula (I).

Chemical formula

Chemical formula

[10] The oral composition according to any one of items 1 to 9, further comprising a coloring agent.

[11] The oral composition according to any one of items 1 to 10, which is applied to the oral cavity of the scaled non-human mammal.

[12] The oral composition according to any one of items 1 to 11, wherein the non-human mammal is a dog or a cat.

[13] The oral composition according to any one of items 1 to 12, which is for reducing the type and / or number and / or frequency of occurrence of bacteria and / or related bacteria that cause periodontal disease in non-human mammals, or for suppressing the increase thereof.

[0011]

[14] A method for oral care of non-human mammals, comprising: adhering the oral composition according to any one of items 1 to 13 to the teeth and / or gums of the non-human mammal. A method comprising this.

[15] The method according to item 14, which is applied to the oral cavity of the scaled non-human mammal.

[16] The method according to item 14 or 15, wherein the non-human mammal is a dog or a cat.

[17] The method according to any one of items 14 to 16, which is an oral care method for reducing or suppressing an increase in the type and / or number and / or frequency of occurrence of bacteria or related bacteria causing periodontal disease in non-human mammals.

Advantages of the Invention

[0012] According to the present invention, it is possible to provide an oral composition that easily contributes to the improvement of oral hygiene in non-human mammals and an oral care method using the same.

Brief Description of the Drawings

[0013]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Mode for Carrying Out the Invention

[0014] Hereinafter, embodiments of the present invention will be described in more detail.

[0015] In one embodiment, the present invention is an oral composition for non-human mammals, comprising: (a) A radical generation catalyst; (b) A radical generation source; (c) A thickener; and (d) Water and providing an oral composition, characterized in that the thickener is contained in an amount of at least 2.0% by mass.

[0016] Also, in one embodiment, the present invention provides a method for oral care of non-human mammals, comprising attaching the above oral composition to the teeth and / or gums of the non-human mammals. By practicing the present invention, microorganisms that cause periodontal disease in non-human mammals can be reduced. This can lead to an improvement in the oral hygiene of non-human mammals, and further contribute to an extension of the healthy lifespan of non-human mammals to which the present invention is applied.

[0017] The non-human mammals to which the present invention is applied are not limited, and examples include mice, rats, rabbits, monkeys, pigs, dogs, cows, horses, cats, etc., preferably dogs or cats, more preferably dogs.

[0018] <(a) Radical generation catalyst> The radical generating catalyst contained in the composition of the present invention (hereinafter, sometimes referred to as "the radical generating catalyst of the present invention") is not particularly limited as long as it catalyzes the generation of radicals from a radical generating source, and known compounds can be used. The radical generating catalyst may be used alone or in combination of two or more kinds.

[0019] In the present invention, it is preferable to use a Lewis acid as the radical generating catalyst, and more preferable to use a Lewis acid having a Lewis acidity of 0.4 eV or more. The upper limit of the Lewis acidity is not particularly limited, but is preferably 20 eV or less. The Lewis acidity can be measured, for example, by the method described in Ohkubo, K.; Fukuzumi, S. Chem. Eur.J., 2000, 6, 453 2, J. AM. CHEM.SOC.2002, 124, 10270-10271, or J. Org.Chem. 2003, 68, 4720-4726, and specifically, it can be measured by the following method.

[0020] (Method of measuring Lewis acidity) In the following reaction scheme (A), cobalt tetraphenylporphyrin (CoTPP), saturated O2, and the object to be measured for Lewis acidity (e.g., a cation of a metal, etc., in the following reaction scheme (A), M n+ The change in the UV-visible absorption spectrum of acetonitrile (MeCN) containing the reaction rate constant (k cat ) can be used to calculate the ΔE value (eV), which is an index of Lewis acidity. cat The higher the value, the stronger the Lewis acidity. The Lewis acidity of an organic compound can also be estimated from the energy level of the lowest unoccupied molecular orbital (LUMO) calculated by quantum chemical calculations. The higher the positive value, the stronger the Lewis acidity.

[0021] [ka]

[0022] Examples of the reaction rate constant of CoTPP and oxygen in the presence of a Lewis acid, which is an index of the Lewis acidity measured (calculated) by the above measurement method, are shown below. In Table 1 below, the numerical value represented by "k cat ,M -2 s -1 " is the reaction between CoTPP and oxygen in the presence of a Lewis acid, and the numerical value represented by "LUMO, eV" is the energy level of LUMO.

[0023] [Table 1]

[0024] The radical generation catalyst contained in the composition of the present invention is preferably ammonium or a salt thereof having properties as a Lewis acid. Such ammonium may be, for example, quaternary ammonium, or tertiary, secondary, primary or zero-grade ammonium.

[0025] Examples of ammonium and its salts include cationic surfactants, and among them, quaternary ammonium type cationic surfactants are preferred.

[0026] Examples of the quaternary ammonium type cationic surfactant include benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, hexadecyltrimethylammonium bromide, decamethonium chloride, edrophonium, didecyldimethylammonium chloride, tetramethylammonium chloride, tetrabutylammonium chloride, benzyltriethylammonium chloride, oxybutynin, carbachol, glycopyrronium, safranin, sinapine, tetraethylammonium bromide, hexadecyltrimethylammonium bromide, suxamethonium, sphingomyelin, denatonium, trigonelline, neostigmine, parathion, pyridostigmine, ferodendrine, pralidoxime methyl iodide, betaine, betanin, bethanechol, betaxanthin, lecithin, and cholines (such as choline chloride including benzoylcholine chloride and lauroylcholine chloride hydrate, phosphocholine, acetylcholine, choline, dipalmitoylphosphatidylcholine, and choline bitartrate). These may be used alone or in combination of two or more.

[0027] However, in the present invention, the quaternary ammonium is not limited to surfactants only.

[0028] In the radical generation catalyst contained in the composition of the present invention, the ammonium may be, for example, ammonium represented by the following chemical formula (I).

[0029]

Chemical formula

[0030] In the chemical formula (I), R 1 , R 2 , R 3 and R 4are the same or different and each is a hydrogen atom or an alkyl group, and may contain an ether bond, a ketone (carbonyl group), an ester bond, or an amide bond, or an aromatic ring, and X− is an anion. The alkyl group is preferably a linear or branched alkyl group having 1 to 40 carbon atoms.

[0031] The ammonium represented by the chemical formula (I) is preferably the ammonium represented by the following chemical formula (II).

[0032]

Chemical formula

[0033] In the chemical formula (II), R 11 is an alkyl group having 5 to 40 carbon atoms and may contain an ether bond, a ketone (carbonyl group), an ester bond, or an amide bond, or an aromatic ring, and R 2 and X - are the same as those in the chemical formula (I).

[0034] In the chemical formula (II), R 2 is preferably a methyl group or a benzyl group. The benzyl group may or may not be substituted with one or more hydrogen atoms of the benzene ring by any substituent. The any substituent includes, for example, an alkyl group, an unsaturated aliphatic hydrocarbon group, an aryl group, a heteroaryl group, a halogen, a hydroxy group (-OH), a mercapto group (-SH), and an alkylthio group (-SR, where R is an alkyl group).

[0035] The ammonium represented by the chemical formula (II) is preferably the ammonium represented by the following chemical formula (III).

[0036]

Chemical formula

[0037] In the chemical formula (III), R 11and X - is the same as the said chemical formula (II).

[0038] Specific examples of the ammonium represented by the said chemical formula (I) include, for example, benzethonium chloride, benzalkonium chloride, hexadecyltrimethylammonium chloride, tetramethylammonium chloride, ammonium chloride, and tetrabutylammonium chloride, and it is preferably at least one selected from the group consisting of these. Among them, benzethonium chloride represented by formula (II) is particularly preferred.

[0039] Incidentally, benzethonium chloride (Bzn + Cl - ) can be represented, for example, by the following chemical formula (IV). In formula (IV), Me is a methyl group, t Bu is a tertiary butyl group. Also, benzalkonium chloride can be represented, for example, as a compound in which R 11 in the said chemical formula (III) is an alkyl group having 8 to 18 carbon atoms and X - is a chloride ion.

Chemical formula

[0040] Incidentally, in the said chemical formulas (I), (II) and (III), X - is an arbitrary anion and is not particularly limited. Also, X - is not limited to a monovalent anion, and may be an anion having an arbitrary valence such as divalent or trivalent. When the charge of the anion is plural such as divalent or trivalent, for example, the number of molecules of ammonium (monovalent) in the said chemical formulas (I), (II) and (III) is the number of molecules of the anion × the valence of the anion (for example, when the anion is divalent, the number of molecules of ammonium (monovalent) is twice the number of molecules of the anion). Examples of X - include, for example, halogen ions (fluoride ion, chloride ion, bromide ion, iodide ion), acetate ion, nitrate ion, sulfate ion, etc.

[0041] In addition, the ammonium contained in the composition of the present invention may contain a plurality of ammonium structures (N + ) in one molecule. Further, the ammonium may, for example, form a dimer or trimer by association of a plurality of molecules due to π-electron interaction.

[0042] In the present invention, when isomers such as tautomers or stereoisomers (e.g., geometric isomers, conformational isomers, and optical isomers) exist in a compound (e.g., the organic ammonium, etc.), any of the isomers can be used in the present invention unless otherwise specified.

[0043] In addition, when a compound (e.g., the organic ammonium, etc.) can form a salt, the salt may be an acid addition salt or a base addition salt. Further, the acid forming the acid addition salt may be an inorganic acid or an organic acid, and the base forming the base addition salt may be an inorganic base or an organic base. The inorganic acid is not particularly limited, and examples include sulfuric acid, phosphoric acid, hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, hypofluorous acid, hypochlorous acid, hypobromous acid, hypoiodous acid, fluorous acid, chlorous acid, bromous acid, iodous acid, fluoric acid, chloric acid, bromic acid, iodic acid, perfluoric acid, perchloric acid, perbromic acid, and periodic acid. The organic acid is also not particularly limited, and examples include p-toluenesulfonic acid, methanesulfonic acid, oxalic acid, p-bromobenzenesulfonic acid, carbonic acid, succinic acid, citric acid, benzoic acid, and acetic acid. The inorganic base is not particularly limited, and examples include ammonium hydroxide, alkali metal hydroxides, alkaline earth metal hydroxides, carbonates, and hydrogen carbonates. More specifically, examples include sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, calcium hydroxide, and calcium carbonate. The organic base is also not particularly limited, and examples include ethanolamine, triethylamine, and tris(hydroxymethyl)aminomethane. The method for producing these salts is also not particularly limited, and for example, the salts can be produced by appropriately adding the above-mentioned acids or bases to the compound by a known method.

[0044] In the present invention, unless otherwise specified, the chain-like substituent (for example, a hydrocarbon group such as an alkyl group or an unsaturated aliphatic hydrocarbon group) may be linear or branched, and the number of carbon atoms thereof is not particularly limited, but is preferably, in the following preferred order, 1 to 40, 1 to 32, 1 to 24, 1 to 18, 1 to 12, 1 to 6, or 1 to 2 (2 or more in the case of an unsaturated hydrocarbon group). In the present invention, the number of ring members (the number of atoms constituting the ring) of the cyclic group (for example, an aryl group, a heteroaryl group, etc.) is not particularly limited, but is preferably, in the following preferred order, 5 to 32, 5 to 24, 6 to 18, 6 to 12, or 6 to 10. When isomers exist in substituents or the like, any isomer may be used unless otherwise specified. For example, when simply referred to as a "naphthyl group", it may be a 1-naphthyl group or a 2-naphthyl group.

[0045] In the composition of the present invention, the content of the radical generation catalyst is preferably 0.01 to 1500 mass ppm. If the concentration of the radical generation catalyst in the composition is too low, the generation of radicals may be suppressed and the bactericidal effect or the like may not be obtained. Also, it is preferable that the content of the radical generation catalyst is 1500 mass ppm or less because safety can be ensured. The content of the radical generation catalyst is more preferably 0.1 to 1000 mass ppm in the composition, further preferably 0.1 to 500 mass ppm, particularly preferably 1 to 200 mass ppm, and most preferably 1 to 100 mass ppm. From the viewpoint of preventing the bactericidal effect or the like from being lost due to micelle formation, it is preferable that the concentration of the radical generation catalyst is below the critical micelle concentration.

[0046] <(b) Radical generation source> Examples of the radical generation source include halogen ions, hypohalite ions, halite ions, halate ions, perhalate ions, etc., and it is preferably included at least one selected from the group consisting of these.

[0047] The radical generating source may contain, for example, an oxo acid or its salt (for example, a halogen oxo acid or its salt). Examples of the oxo acid include boric acid, carbonic acid, orthocarbonic acid, carboxylic acid, silicic acid, nitrous acid, nitric acid, phosphorous acid, phosphoric acid, arsenic, sulfurous acid, sulfuric acid, sulfonic acid, sulfinic acid, chromic acid, dichromic acid, and permanganic acid. Halogen oxo acids include chlorine oxo acids such as hypochlorous acid, chlorous acid, chloric acid, and perchloric acid; bromine oxo acids such as hypobromous acid, bromous acid, bromic acid, and perbromic acid; and iodine oxo acids such as hypoiodous acid, iodous acid, iodic acid, and periodic acid. Examples of these salts include alkali metal salts such as sodium and potassium salts.

[0048] Among them, it is more preferable that the radical generating source is at least one selected from the group consisting of hypohalous acids, hypohalite ions, and hypohalite salts. From the viewpoint that the reactivity with the radical generating catalyst is mild and the reaction is easy to control, it is even more preferable that it is at least one selected from the group consisting of chlorous acid, chlorite ions, and chlorite salts. Specifically, sodium chlorite is preferable.

[0049] In the composition of the present invention, the content of the radical generating source is preferably 0.01 to 1500 ppm by mass. If the concentration of the radical generating source in the composition is too low, the amount of radicals generated may be too small, and there is a risk that a sterilizing effect or the like cannot be obtained. Also, although the higher the concentration of the radical generating source, the more a sterilizing effect or the like can be obtained, from the viewpoint of ensuring safety, it is preferably 1500 ppm by mass or less. The content of the radical generating source is more preferably 1 to 1000 ppm by mass in the composition, even more preferably 10 to 500 ppm by mass, and particularly preferably 50 to 250 ppm by mass.

[0050] In the composition of the present invention, the concentration ratio (radical generating source / radical generating catalyst) in the composition of the radical generating source and the radical generating catalyst is not particularly limited and can be set as appropriate.

[0051] <(c) Thickener> In the composition of the present invention in one embodiment, a thickener is contained in an amount of at least 2.0% by mass. As a result, the viscosity of the composition of the present invention increases, and even when adapting to non-human mammals that cannot apply it by themselves due to their main will like humans, the time until the applied composition is removed by the tongue or saliva can be prolonged, retaining the radical generation source which is the active ingredient in the oral cavity and enabling the slow release of the active ingredient for a desired period. As a result, it is possible to promote the effect of reducing the types and / or numbers of microorganisms that deteriorate the oral hygiene environment, for example, bacteria causing periodontal disease and / or related bacteria, or suppressing their increase. Further, thereby, the composition of the present invention contributes to maintaining a good oral cavity environment of non-human mammals.

[0052] In the composition of the present invention in one embodiment, the thickener may be at least 2.0% by mass, for example, 2.0 to 20% by mass, 2.1 to 10% by mass, 2.1 to 5.0% by mass, or 2.1 to 3.0% by mass. Since non-human mammals to which the present invention is applied frequently lick the objects in the oral cavity or frequently move their heads, if the thickener is less than 2.0% by mass, the radical generation source which is the active ingredient contained in the composition of the present invention cannot be retained in the oral cavity for a period during which the effect is exhibited, which is insufficient. The concentration of the thickener contained in the composition of the present invention is desirably contained in an amount such that it remains in the oral cavity (particularly, the crown part, the root part, or the gingival part, etc.) for at least about 5 minutes when applied to non-human mammals. On the other hand, the upper limit of the concentration of the thickener contained in the composition of the present invention is not particularly limited, but as long as the radical generation source which is the active ingredient of the present invention does not cause a burden to non-human mammals and does not react excessively in the oral cavity (particularly, the root part or the gingival part, etc.) and does not cause inflammation, for example, the upper limit may be 20% by mass, 10% by mass, 5.0% by mass, or 3.0% by mass.

[0053] In the composition of the present invention in one embodiment, as the thickener, for example, hydroxypropylmethylcellulose is included. In other embodiments, as the thickener, sodium polyacrylate, smectite, or xanthan gum may be included. Sodium polyacrylate may be cross-linked or non-cross-linked sodium polyacrylate. Xanthan gum may be cationized xanthan gum in which a part of the hydroxyl groups is cationized.

[0054] The composition of the present invention in one embodiment may further contain tamarind gum. In the composition of the present invention in one embodiment, for example, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxybutylcellulose, and further derivatives thereof, for example, hydrophobized hydroxypropylmethylcellulose (hydroxypropylmethylcellulose stearoxy ether) may be included.

[0055] <(d) Water> The composition of the present invention contains water as a solvent for dissolving or dispersing the radical generation catalyst, radical generation source, and thickener.

[0056] Examples of the water include purified water, ion-exchanged water, distilled water, filtered water, sterilized water, and the like.

[0057] The composition of the present invention may contain, as additives, other components other than the radical generation catalyst, radical generation source, thickener, and water described above, as long as the effects of the present invention are not impaired. Examples of the other components include organic solvents, pH adjusters, and the like.

[0058] Examples of the organic solvent include ketones such as acetone, nitrile solvents such as acetonitrile, alcohol solvents such as ethanol and propylene glycol, and these may be used alone or in combination of two or more.

[0059] Examples of the pH adjuster include potassium dihydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, disodium hydrogen phosphate, sodium hydroxide, tris(hydroxymethyl)aminomethane, tris(hydroxymethyl)aminomethane hydrochloride, ethylenediaminetetraacetic acid, and the like. These may be used alone or in combination of two or more.

[0060] The composition of the present invention can be prepared by sequentially mixing (a) a radical generation catalyst, (b) a radical generation source, (c) a thickener, (d) water, and, if desired, other components and uniformly dissolving them.

[0061] Further, the composition of the present invention preferably has a neutral or alkaline property. When the composition is acidic, the radical generation source and the radical generation catalyst react rapidly to generate radicals, so it is difficult to stably generate radicals for a long time. In the present invention, the aqueous radicals (active species) generated in the composition are maintained in a neutral or alkaline environment. Then, when microorganisms, viruses, etc. that are the targets of the reaction are present, the aqueous radicals present in the composition act and these radicals disappear, but new radicals are generated from the composition. Thereby, radicals can be generated when needed. The pH of the composition is more preferably 7 to 10, and even more preferably 7 to 9.

[0062] The composition of the present invention may further contain a colorant. By including a colorant in the composition of the present invention, the sites in the oral cavity (such as the crown, root, and gingiva) where the composition of the present invention is applied can be easily visualized. Thereby, the area where the composition of the present invention is not applied can be reduced, and the oral hygiene state according to the present invention can be further improved. In addition, it facilitates toothbrushing in households and hospitals of non-human mammals, especially pet animals such as dogs or cats. The colorant used is preferably an edible food coloring (food red), and may be, for example, an edible natural pigment or a synthetic colorant. The color used is not particularly limited. For example, if it is an edible synthetic colorant, examples include Food Red No. 2, Food Red No. 3, Food Red No. 40, Food Red No. 102, Food Red No. 104, Food Red No. 105, or Food Red No. 106 in the red series. Also, in the yellow series, examples include Food Yellow No. 4 and Food Yellow No. 5. In the green series, Food Green No. 3 can be mentioned. In the blue series, examples include Food Blue No. 1 and Food Blue No. 2. Also, if it is an edible natural pigment, for example, in the yellow series (such as safflower yellow pigment, turmeric pigment, gardenia yellow pigment, etc.), red series (grape skin pigment, cochineal pigment, beet red, purple sweet potato pigment, etc.), orange series (annatto pigment, capsicum pigment, etc.), green series (green coloring agent preparation, etc.), or blue series (gardenia blue pigment, etc.). Further, a pigment obtained by mixing any of the above pigments may be used. From the viewpoint of visualization in the oral cavity, using a color opposite to the color of the gingiva can enhance visibility. For example, when a blue or green series pigment is included in the composition, the visibility is higher. The colorant may be mixed with the composition of the present invention immediately before application in the oral cavity. Alternatively, the colorant may be packaged separately from the composition of the present invention, and may be provided, for example, as one component of a kit. The concentration of the added colorant may be such that it can be visually grasped that it adheres to the sites in the oral cavity (such as the crown, root, and gingiva) when the composition of the present invention is applied and coated.

[0063] In one embodiment, the composition of the present invention is preferably applied into the oral cavity of the scaled non-human mammal. Scaling refers to removing plaque or tartar adhering to teeth with a dedicated instrument, such as a scaler or a device that generates ultrasonic waves (e.g., ultrasonic scaler). The method of scaling performed in the non-human mammal to which the present invention is applied may be any known method and is not limited. When the composition of the present invention is applied into the oral cavity of the scaled non-human mammal, it can reduce the type and / or number and / or frequency of appearance of microorganisms that deteriorate the oral hygiene environment, such as bacteria causing periodontal disease and / or related bacteria, or promote the effect of suppressing their increase. Thereby, deterioration of the oral cavity environment of the non-human mammal, particularly the development of periodontal disease, can be prevented or contributed to the treatment. As a result, it can reduce the bad breath of the non-human mammal, prevent the inflammation in the oral cavity from spreading throughout the body through the blood, and contribute to reducing the risks of heart disease, kidney disease, diabetes, etc. In addition, it can prevent the chronic inflammation caused by periodontal disease from burdening the immune system and improve the natural healing ability of the non-human mammal. Further, it is expected to reduce the pain and discomfort caused by periodontal disease, increase the appetite, improve the nutritional status, and contribute to the extension of the lifespan. To evaluate the state of the oral hygiene environment, the type and / or number and / or frequency of appearance of microorganisms present in the oral cavity may be analyzed and evaluated by any method, such as genomics using next-generation sequencers. For example, when the target non-human mammal is a dog, microorganisms that deteriorate the oral hygiene environment of the dog, such as bacteria causing periodontal disease, may be analyzed. Although not intended to be limiting, for example, the number, ratio, and / or frequency of appearance of the genus Porphyromonas (e.g., Porphyromonas gulae, Porphyromonas cangingivalis, Porphyromonas gingivalis, etc.), the genus Treponema (e.g., Treponema denticola), or the genus Tannerella (e.g., Tannerella forsythia) may be examined for evaluation. Alternatively, evaluation may be performed by analyzing other microorganisms that affect the oral hygiene environment.

Example

[0064] Hereinafter, examples of the present invention will be described. However, the present invention is not limited to the following examples.

[0065] [Experimental Example 1] An oral agent was prepared. In the following, unless otherwise specified, water was used as the solvent or dispersion medium. Also, the % concentration hereinafter is mass % unless otherwise specified, and the ppm concentration is also mass ppm concentration unless otherwise specified. Further, in the following experimental examples, MA-T (registered trademark, hereinafter also referred to as "MA-T") represents a composition containing sodium chlorite and benzalkonium chloride in a mass ratio of 5:3. For example, the MA-T gel for use in the following experimental examples was specifically prepared as follows.

[0066] A solution containing 40,000 ppm of sodium chlorite and 24,000 ppm of benzalkonium chloride was prepared, and 0.25 mass % was added so that the concentration (final concentration) in the oral agent was 100 ppm. Also, as a thickener, hydroxypropyl methylcellulose (manufactured by Shin-Etsu Chemical Co., Ltd., Methocel (registered trademark) 90SH-100000) was added so that the concentration (final concentration) in the oral agent was 2.2 mass %, and Na2HPO4 / NaH2PO4 was added so that the concentration (final concentration) in the oral agent was 5 mM. Further, purified water was added to make a total of 1 L. To this, 0.067 mass % of a blue food coloring (manufactured by Kyoryoku Shokuhin Co., Ltd., Food Coloring Blue) was added (hereinafter referred to as MA-T gel).

[0067] As a comparative example, 0.067 mass % of a blue food coloring (manufactured by Kyoryoku Shokuhin Co., Ltd., Food Coloring Blue) was added to a commercially available pet toothpaste gel (manufactured by Lion Pet Co., Ltd., PETKISS (registered trademark) Toothpaste Gel, Scent of Leaves) (hereinafter referred to as comparative gel).

[0068] One gram each of the MA-T gel and the comparative gel was applied to a toothbrush. (1) The MA-T (registered trademark) gel was applied to the entire crown and gingiva of the right upper and lower jaws of subject 1 (toy poodle, female, 2 years and 3 months), or (2) the comparative gel was applied to the entire crown and gingiva of the left upper and lower jaws of subject 1 (separately performed on the same day). One minute, 5 minutes, 15 minutes, and 30 minutes after application, the state of the MA-T gel or the comparative gel remaining in the oral cavity of subject 1 was photographed (Figs. 1-2).

[0069] [Experimental Example 2] One gram each of the MA-T gel of Experimental Example 1 and the comparative gel was applied to a toothbrush. (1) The MA-T gel was applied to the entire crown and gingiva of the left upper and lower jaws of subject 1 (toy poodle, female, 2 years and 3 months), subject 2 (toy poodle, male, 4 years and 0 months), and subject 3 (toy poodle, male, 5 years and 8 months), and (2) the comparative gel was applied to the entire crown and gingiva of the right upper and lower jaws of subjects 1-3 ((1) and (2) were applied separately). One minute, 5 minutes, 15 minutes, and 30 minutes after application, the state of the MA-T gel or the comparative gel remaining in the oral cavities of subjects 1-3 was photographed (Figs. 3-8).

[0070] As is clear from Experimental Examples 1 and 2, it was shown that the oral composition of the present invention has a longer residual time in the oral cavity of the subject than the conventionally used oral gel (comparative gel) (MA-T gel: less than 15 minutes; comparative gel: less than 5 minutes).

[0071] [Experimental Example 3] 50 g (49.554 mL) of the MA-T gel prepared in Experimental Example 1 was diluted by adding 10 g (10 mL), 15 g (15 mL), 20 g (20 mL), 30 g (30 mL), 40 g (40 mL), or 50 g (50 mL) of water, respectively. To this, blue food coloring (manufactured by Kyoritsu Shokuhin Co., Ltd., Food Coloring Blue) was added so as to contain 0.067% by mass. The mass% concentration of the thickener in the diluted MA-T gel is as follows.

[0072]

Table 2

[0073] As shown in Table 2, 1 g each of the diluted and adjusted MA-T gels was applied to a toothbrush and applied to the entire crown and gingival portions of the upper and lower left teeth of Subject 1 (toy poodle, female, 1 year and 6 months), Subject 2 (toy poodle, male, 1 year and 2 months), Subject 3 (toy poodle, male, 7 months old), and Subject 4 (toy poodle, female, 4 months old). One minute, 5 minutes, 15 minutes, and 30 minutes after application, the MA-T gel remaining in the oral cavities of Subjects 1 to 4 was observed. The results are shown in Table 2. In the table, "〇" indicates the case where the colored MA-T gel can be visually confirmed at each time, and "×" in the table indicates the case where the colored MA-T gel could not be visually confirmed at each time.

[0074] As a result, the MA-T gel with a thickener mass % concentration of less than 2% described in Table 2 was removed in less than 5 minutes in the oral cavity of the subject.

[0075] [Experimental Example 4] The MA-T gel of Experimental Example 1 (without edible dye) was applied to the subjects (dogs, number of subjects 27) twice a day in the oral cavity (entire crown and gingival portions), and changes in the types and composition ratios of the oral microflora were observed. In each subject, the surface of the tooth root was rubbed with a cotton swab before using the MA-T gel, on the first day after using the MA-T gel, and on the eighth day after using the MA-T gel, and DNA of oral microorganisms was extracted from the collected specimens as follows. For the bacteria constituting the microflora of the collected samples, analysis of the types and composition ratios was performed using the next-generation sequencers MiSeq and Novaseq6000 (Illumina, CA, USA). The average values were compared.

[0076] (Extraction of DNA of Oral Microorganisms) The sample was suspended in a fixative solution (10% EtOH, 1.07% NH4Cl, 5 mM EDTA, 0.09% NaN3). Next, 200 μL of the suspension and 810 μL of Lysis buffer (containing 224 μg / mL of Proteinase K) were added to a bead tube, and bead disruption (6,000 rpm, disruption for 20 seconds, interval of 30 seconds, disruption for 20 seconds) was performed using a bead homogenizer. Subsequently, the sample was left standing on a heat block at 70 °C for 10 minutes for treatment with Proteinase K, and then left standing on a heat block at 95 °C for 5 minutes to inactivate Proteinase K. For the sample subjected to lysis treatment, DNA was automatically extracted using chemagic 360 (PerkinElmer) according to the protocol for the chemagic kit for stool, and 100 μL of DNA extract was obtained.

[0077] (Metagenomic 16S RNA gene sequence analysis) The meta 16S sequence analysis was performed by modifying the Illumina 16S Metagenomic Sequencing Library Preparation (version 15044223 B). First, a 460 bp region containing the variable regions V3-V4 of the 16S rRNA gene was amplified by PCR using universal primers (Illumina_16S_341F and Illumina_16S_805R PCR). The PCR reaction mixture was prepared by mixing 10 μL of DNA extract, 0.05 μL of each primer (100 μM), 12.5 μL of 2x KAPA HiFi Hot-Start ReadyMix (F. Hoffmann-La Roche, Switzerland), and 2.4 μL of PCR grade water. For PCR, after heat denaturation at 95°C for 3 minutes, cycles of 95°C for 30 seconds, 55°C for 30 seconds, and 72°C for 30 seconds were repeated 30 times, and finally an extension reaction at 72°C for 5 minutes was performed. The amplification products were purified using magnetic beads and eluted with 50 μL of Buffer EB (QIAGEN, Germany). The purified amplification products were subjected to PCR using the Nextera XT Index Kit v2 (illumina, CA, US) to add indexes. The PCR reaction mixture was prepared by mixing 2.5 μL of the amplification product, 2.5 μL of each primer, 12.5 μL of 2x KAPA HiFi Hot-Start ReadyMix, and 5 μL of PCR grade water. For PCR, after heat denaturation at 95°C for 3 minutes, cycles of 95°C for 30 seconds, 55°C for 30 seconds, and 72°C for 30 seconds were repeated 12 times, and finally an extension reaction at 72°C for 5 minutes was performed. The amplification products with added indexes were purified using magnetic beads and eluted with 80 - 105 μL of Buffer EB. The concentration of each amplification product was measured using a NanoPhotometer (Implen, CA, US), adjusted to 1.4 nM, and then mixed in equal amounts to obtain a sequencing library. The DNA concentration of the sequencing library and the size of the amplification products were confirmed by electrophoresis and analyzed using MiSeq and Novaseq6000. For the analysis, the MiSeq Reagent Kit V3 was used to perform 2×300 bp paired-end sequencing.The obtained sequences were analyzed using the analysis software QIIME2, and the microbial composition data was obtained by referring to the information registered in Greengenes2 (https: / / greengenes2.ucsd.edu / ).

[0078] The sequences of the universal primers used above are as follows. Commercially available universal primers can be purchased.

[0079] Illumina_16S_341F: 5’-TCGTCGGCAGCGTCAGATGTGTATAAGAGACAGCCTACGGGNGGCWGCAG- 3’(SEQ ID NO: 1)

[0080] llumina_16S_805R: 5’-GTCTCGTGGGCTCGGAGATGTGTATAAGAGACAGGACTACHVGGGTATCTAATCC- 3’(SEQ ID NO: 2)

[0081] As a result, it was confirmed that the total composition ratio of periodontal disease-causing bacteria (Porphyromonas gulae, Porphyromonas cangingivalis, Treponema denticola, Tannerella forsythia) in the bacterial flora of the collected samples decreased on the 8th day after the use of MA-T (registered trademark) gel (Figure 9).

[0082] [Experimental Example 5] The MA-T gel of Experimental Example 1 (without food coloring) was applied twice a day for 7 days to the entire crown and gingival parts of the subject (dog) on which scaling was performed at an animal hospital. After scaling, a subject (dog) that had elapsed 7 days without applying the MA-T gel was used as a control. Before, after, and 1 week after the scaling procedure, the surface of the subject's gingiva was rubbed with a cotton swab, and the collected specimen was analyzed for the types and composition ratios of the microorganisms that make up the bacterial flora of the tooth sample using the next-generation sequencers MiSeq and Novaseq6000 (Illumina, CA, USA) in the same manner as in [Experimental Example 4]. The average values were compared.

[0083] As a result, in the group that used the MA-T gel after scaling, the total composition ratio of the periodontal disease-causing bacteria (Porphyromonas gulae, Porphyromonas cangingivalis, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia) in the bacterial flora of the collected samples was significantly reduced (Figure 10).

[0084] From this experimental example, it was confirmed that by applying the composition of the present invention to a subject (dog) on which scaling was performed, the composition ratio of periodontal disease-causing bacteria can be reduced, and the oral environment can be maintained in a good state.

Claims

**Claim 1** An oral composition for non-human mammals, comprising: (a) A radical generating catalyst; (b) A radical source; (c) A thickener; and (d) Water The oral composition is characterized in that the thickener is contained in an amount of at least 2.0% by mass. **Claim 2** The oral composition according to claim 1, further comprising a coloring agent. **Claim 3** The oral composition according to claim 1, characterized in that it is applied into the scaled oral cavity of the non-human mammal. **Claim 4** The oral composition according to claim 1, which is an oral composition for reducing the type and / or number and / or frequency of occurrence of bacteria causing periodontal disease in non-human mammals and / or related bacteria, or for suppressing the increase thereof. **Claim 5** An oral care method for non-human mammals, comprising: adhering the oral composition according to claim 1 to the teeth and / or gums of the non-human mammal The method includes the above step. **Claim 6** The method according to claim 5, characterized in that it is applied into the scaled oral cavity of the non-human mammal. **Claim 7** The oral care method according to claim 5, which is an oral care method for reducing the type and / or number and / or frequency of occurrence of bacteria causing periodontal disease in non-human mammals and / or related bacteria, or for suppressing the increase thereof.

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