Composition for improving intraoral flora

Abstract

To provide a technique that can efficiently improve intraoral flora.SOLUTION: A composition for improving intraoral flora contains cetylpyridinium chloride and benzalkonium chloride and / or benzethonium chloride.SELECTED DRAWING: None

Description

Technical Field

[0001] The present disclosure relates to a composition for improving the oral flora, etc. The contents of all documents described in this specification are incorporated herein by reference.

Background Art

[0002] A wide variety of bacteria (oral bacteria) exist in the oral cavity and constitute the oral microbiota (oral flora). In recent years, it has been pointed out that the oral flora may be greatly involved in various diseases, similar to the gut flora, and research is underway. In particular, it is considered important to improve or maintain the balance of the oral flora by increasing bacteria that have a beneficial effect on humans (commonly referred to as good bacteria) and reducing bacteria that have a harmful effect on humans (commonly referred to as bad bacteria).

[0003] In addition, in recent years, it has been considered that the oral environment greatly affects the overall health condition, and in particular, periodontal disease has been pointed out to have a negative impact not only on the oral cavity but also on the whole body. For example, it has been reported that when periodontal disease progresses, inflammatory substances are diffused by the blood flow or the gut microbiota changes, which may affect systemic diseases.

Prior Art Documents

Non-Patent Documents

[0004]

Non-Patent Document 1

Non-Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0005] The inventors focused on the possibility that the oral flora may be related to periodontal disease and, ultimately, overall health, and particularly considered whether it was possible to improve the oral flora (especially the balance of each bacterium in the oral flora) by efficiently sterilizing bacteria related to the onset and exacerbation of periodontal disease in the oral flora.

[0006] Regarding the relationship between periodontal disease and the oral flora, for example, it is known that plaque (dental plaque) can cause periodontal disease. Plaque (dental plaque) is a biofilm formed by the aggregation of oral bacteria. Generally speaking, plaque is formed as follows. First, a thin film of protein derived from saliva and physiological gingival sulcus exudate called "pellicle" is formed on the surface of the teeth, and facultative anaerobic bacteria such as streptococci (initial adherent bacteria) adhere to the tooth surface through the pellicle. Mediating bacteria such as Fusobacterium that co-aggregate with various oral bacteria adhere to the initial adherent bacteria, and further, anaerobic bacteria such as Porphyromonas gingivalis (Porphyromonas gingivalis) and Treponema denticola (Treponema denticola) and other late adherent bacteria adhere and aggregate, and the plaque matures. In particular, late adherent bacteria are known to cause periodontal disease and are directly or indirectly related to the destruction of periodontal tissues.

Means for Solving the Problems

[0007] The inventors found the possibility that the oral flora can be efficiently improved by using a combination of cetylpyridinium chloride and benzalkonium chloride and / or benzethonium chloride, and further conducted repeated studies.

[0008] This disclosure includes, for example, the subject matter described in the following items. Item 1. Cetylpyridinium chloride and A composition for improving the oral flora containing at least one selected from the group consisting of benzalkonium chloride and benzethonium chloride. Item 2. To reduce Fusobacterium bacteria in the oral cavity and / or to reduce Veillonella bacteria in the oral cavity and / or to increase the proportion of Actinomyces bacteria in the oral flora, a composition containing at least one selected from the group consisting of cetylpyridinium chloride and benzalkonium chloride and benzethonium chloride. Item 3. The composition according to item 1 or 2, containing cetylpyridinium chloride and benzalkonium chloride. Item 4. The composition according to any one of items 1 to 3, containing 1 to 100 parts by mass of benzalkonium chloride with respect to 100 parts by mass of cetylpyridinium chloride. Item 5. The composition according to any one of items 1 to 4, which is an oral composition.

Advantages of the Invention

[0009] A method for efficiently improving the oral flora is provided.

Brief Description of the Drawings

[0010]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Mode for Carrying Out the Invention

[0011] Hereinafter, each embodiment included in the present disclosure will be described in more detail. The present disclosure preferably includes a composition for improving oral flora containing specific components and its use, etc., but is not limited thereto, and the present disclosure includes all that are disclosed in this specification and can be recognized by those skilled in the art.

[0012] The composition for improving oral flora included in the present disclosure contains cetylpyridinium chloride and benzalkonium chloride and / or benzethonium chloride. The composition may be referred to as the composition of the present disclosure. Further, cetylpyridinium chloride may be abbreviated as CPC, benzalkonium chloride may be abbreviated as BKC, respectively. Further, benzethonium chloride may be abbreviated as BTC.

[0013] As described above, the composition of the present disclosure contains CPC and at least one selected from the group consisting of BKC and BTC. Among them, it is preferable that CPC and BKC are contained.

[0014] The content ratios of CPC and BKC are not particularly limited as long as the effects are achieved. For example, with respect to 100 parts by mass of CPC, 1 to 100 parts by mass are preferred. The upper or lower limit of this range may be, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99 parts by mass. For example, this range may be 2 to 90 parts by mass or 5 to 50 parts by mass.

[0015] The content ratios of CPC and BTC are not particularly limited as long as the effects are achieved. For example, with respect to 100 parts by mass of CPC, 1 to 100 parts by mass are preferred. The upper or lower limit of this range may be, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99 parts by mass. For example, this range may be 2 to 90 parts by mass or 5 to 50 parts by mass.

[0016] The CPC content in the composition of the present disclosure may be, for example, about 0.005 to 0.5% by mass. The upper or lower limit of this range may be, for example, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.20, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, 0.29, 0.3, 0.31, 32, 0.33, 0.34, 0.35, 0.36, 0.37, 0.38, 0.39, 0.4, 0.41, 0.42, 0.43, 0.44, 0.45, 0.46, 0.47, 0.48, 0.49% by mass. For example, this range may be about 0.01 to 0.3% by mass.

[0017] The BKC content in the composition of the present disclosure may be, for example, about 0.001 to 0.5% by mass. The upper or lower limit of this range may be, for example, 0.002, 0.005, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.20, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, 0.29, 0.3, 0.31, 32, 0.33, 0.34, 0.35, 0.36, 0.37, 0.38, 0.39, 0.4, 0.41, 0.42, 0.43, 0.44, 0.45, 0.46, 0.47, 0.48, 0.49% by mass. For example, this range may be 0.002 to 0.4% by mass or 0.005 to 0.3% by mass.

[0018] The BTC content in the composition of the present disclosure may be, for example, about 0.001 to 0.5% by mass. The upper or lower limit of this range may be, for example, 0.002, 0.005, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18 , 0.19, 0.20, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, 0.29, 0.3, 0.31, 32, 0.33, 0.34, 0.35, 0.36, 0.37, 0.38, 0.39, 0.4, 0.41, 0.42, 0.43, 0.44, 0.45, 0.46, 0.47, 0.48, 0.49% by mass may be used. For example, the range may be 0.002 to 0.4% by mass or 0.005 to 0.3% by mass.

[0019] The composition of the present disclosure can be particularly preferably used as an oral composition. The oral composition may be referred to as the oral composition of the present disclosure. Further, the oral composition of the present disclosure is for improving the oral flora, and in particular, for reducing the bacteria belonging to the genus Fusobacterium and / or for reducing the bacteria belonging to the genus Veillonella, and / or for increasing the proportion of the bacteria belonging to the genus Actinomyces in the oral flora. It can be preferably used for this purpose. Since the bacteria belonging to the genus Fusobacterium are reduced it can also be preferably used to reduce the proportion of Fusobacterium in the oral flora. Further, since the bacteria belonging to the genus Veillonella are reduced it can also be preferably used to reduce the proportion of the bacteria belonging to the genus Veillonella in the oral flora.

[0020] As described above, since Fusobacterium acts as a mediator bacterium that bridges the early adherent bacteria and the late adherent bacteria in plaque formation, it can be said that a reduction is preferable. Although not particularly limited, among Fusobacterium, it can be preferably used to reduce Fusobacterium nucleatum. Veillonella is in symbiosis with other bacteria ​​ There are reports that the amount of biofilm formed increases through cultivation (Hokkaido Medical University Dental Journal 2011, 30(1), p87), and it may play a central role in biofilm formation. In addition, it has also been reported that Veillonella produces vitamin K, which serves as a nutrient source for the genera Prevotella and Porphyromonas (Virulence. 2011 Sep / Oct; 2(5): 435-444 ), and it may also promote the growth of harmful bacteria. From these facts, it is considered preferable to reduce Veillonella. In addition, Actinomyces is a major constituent bacterium of oral resident bacteria. In terms of ratio, it is more abundant in the mouths of healthy humans without periodontitis and decreases in periodontitis patients, and it is regarded as a measure for observing the health status of the mouth. Therefore, it is considered preferable to increase it.

[0021] The oral composition of the present disclosure can be a solid composition or a liquid composition. The oral composition can be used, for example, as a pharmaceutical or quasi-drug. In addition, the form of the oral composition of the present disclosure is not particularly limited, but it can be made into forms (dosage forms) such as ointments, pastes, pasta agents, gels, liquids, sprays, mouthwashes, liquid dentifrices, dentifrices, gum agents, etc. according to conventional methods. Among them, mouthwashes, liquid dentifrices, dentifrices, ointments, pastes, liquids, and gels are preferable.

[0022] The oral composition of the present disclosure may further contain, alone or in combination of two or more, any components that can be formulated in the oral composition as long as the effects are not impaired.

[0023] For example, as the surfactant, a nonionic surfactant, an anionic surfactant, or an amphoteric surfactant can be blended. Specifically, for example, as the nonionic surfactant, sugar fatty acid esters such as sucrose fatty acid ester, maltose fatty acid ester, lactose fatty acid ester; fatty acid alkanolamides; sorbitan fatty acid esters; fatty acid monoglycerides; polyoxyethylene alkyl ethers with a polyoxyethylene addition coefficient of 8 to 10 and an alkyl group having 13 to 15 carbon atoms; polyoxyethylene alkyl phenyl ethers with a polyoxyethylene addition coefficient of 10 to 18 and an alkyl group having 9 carbon atoms; diethyl sebacate; polyoxyethylene hydrogenated castor oil; fatty acid polyoxyethylene sorbitan, etc. are listed. As the anionic surfactant, sulfate esters such as sodium lauryl sulfate, sodium polyoxyethylene lauryl ether sulfate; sulfosuccinates such as sodium lauryl sulfosuccinate, sodium polyoxyethylene lauryl ether sulfosuccinate; acyl amino acid salts such as sodium cocoyl sarcosinate, sodium lauroyl methyl alaninate; sodium cocoyl methyl taurine, etc. are listed. As the amphoteric ion surfactant, betaine type activators such as lauryldimethylaminoacetic acid betaine, coconut oil fatty acid amide propyldimethylaminoacetic acid betaine; imidazoline type activators such as N-cocoyl-N-carboxymethyl-N-hydroxyethyl ethylenediamine sodium; amino acid type activators such as N-lauryl diaminoethyl glycine, etc. are listed. These surfactants can be blended alone or in combination of two or more. The blending amount is usually 0.1 to 5% by mass based on the total amount of the composition.

[0024] In addition, as flavoring agents, for example, menthol, carboxylic acid, anethole, eugenol, methyl salicylate, limonene, ocimene, n-decyl alcohol, citronellal, α-terpineol, methyl acetate, citronellyl acetate, methyleugenol, cineole, linalool, ethyllinalool, thymol, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, cypress oil, perilla oil, wintergreen oil, clove oil, eucalyptus oil, pimento oil, d-camphor, d-borneol, star anise oil, cinnamon oil, cinnamaldehyde, mint oil, vanillin and other fragrances can be used. These can be combined alone or in combination of two or more in an amount of, for example, 0.001 to 1.5% by mass based on the total amount of the composition. They can be combined.

[0025] In addition, as sweetening agents, for example, sodium saccharin, acesulfame potassium, stevioside, neohesperidin dihydrochalcone, perillartine, thaumatin, aspartylphenylalanyl methyl ester, p-methoxycinnamic aldehyde and the like can be used. These can be blended in an amount of, for example, 0.01 to 1% by mass based on the total amount of the composition. They can be blended.

[0026] Furthermore, as wetting agents, sorbitol, ethylene glycol, propylene glycol, glycerin, 1,3-butylene glycol, polypropylene glycol, xylitol, maltitol, lactitol, polyoxyethylene glycol and the like can be blended alone or in combination of two or more.

[0027] As preservatives, parabens such as methylparaben, ethylparaben, propylparaben, butylparaben, sodium benzoate, phenoxyethanol, alkyldiaminoethyl glycine hydrochloride and the like can be blended.

[0028] As colorants, legal dyes such as Blue No. 1, Yellow No. 4, Red No. 202, Green No. 3, mineral dyes such as ultramarine, reinforced ultramarine, cobalt blue, titanium oxide and the like may be blended.

[0029] As a pH adjuster, citric acid, phosphoric acid, malic acid, pyrophosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, or chemically possible salts thereof, sodium hydroxide, etc. may be blended. These can be blended alone or in combination of two or more so that the pH of the composition is in the range of 4 to 8, preferably 5 to 7. The blending amount of the pH adjuster may be, for example, 0.01 to 2% by weight.

[0030] In the oral composition of the present disclosure, not only CPC, BKC, and BTC, but also, as medicinal components, vitamin Es such as dl-α-tocopherol acetate, tocopherol succinate, or tocopherol nicotinate, amphoteric bactericides such as dodecyldiaminoethyl glycine, nonionic bactericides such as triclosan, isopropylmethylphenol, and hinokitiol, anionic bactericides such as sodium lauroyl sarcosinate, cationic bactericides such as chlorhexidine hydrochloride, enzymes such as dextranase, amylase, protease, mutanase, lysozyme, and lysing enzyme (lytech enzyme), alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate, fluorides such as sodium fluoride and stannous fluoride, tranexamic acid and epsilon aminocaproic acid, aluminum chlorohydrol allantoin, dihydrocholesterol, glycyrrhetinic acid, glycyrrhizic acid, sodium copper chlorophyllin, glycerophosphate, chlorophyll, sodium chloride, caropeptide, allantoin, carbazochrom, hinokitiol, potassium nitrate, paratinit, etc. can be blended alone or in combination of two or more.

[0031] In addition, as a base, alcohols, silicon, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, plastic base, etc. can also be added.

[0032] In addition, the oral composition of the present disclosure can be prepared by a known method or a method that can be easily conceived from a known method. For example, it can be prepared by appropriately mixing CPC, BKC, and other components as necessary.

[0033] The subject to which the oral composition of the present disclosure is applied is not particularly limited, and humans and non-human mammals are preferably mentioned. As non-human mammals, livestock, pets, etc. are preferable, and more specifically, for example, dogs, cats, mice, rats, horses, cows, sheep, monkeys, etc. can be mentioned.

[0034] In addition, the description of the oral composition of the present disclosure described above can also be directly applicable to the composition of the present disclosure that is not used as an oral composition (for example, when used for denture cleaning).

[0035] In this specification, "comprising" includes "consisting essentially of" and "consisting of" (The term "comprising" includes "consisting essentially of” and "consisting of."). In addition, the present disclosure includes all arbitrary combinations of the constituent elements described in this specification.

[0036] In addition, the various characteristics (properties, structures, functions, etc.) described for each of the above-described embodiments of the present disclosure may be combined in any manner when specifying the subject matter included in the present disclosure. That is, the present disclosure includes all subject matters consisting of all possible combinations of the respective characteristics that can be combined as described in this specification.

Examples

[0037] Hereinafter, the embodiments of the present disclosure will be described more specifically with examples, but the embodiments of the present disclosure are not limited to the following examples. Unless otherwise specified below, % indicates mass%.

[0038] The effects of each test substance or its combination on the bacterial flora in human saliva were examined as follows. As the test substances, cetylpyridinium chloride (CPC), benzalkonium chloride (BKC), and benzethonium chloride (BTC), which are bactericides, were used. For BKC, the one with a C14 straight chain was used.

[0039] Saliva was collected from three men and women in their 20s and 30s, 1 ml each, mixed well in a vial containing glass beads, and dispersed using a syringe equipped with a 23G injection needle. This was used as the test bacterial solution.

[0040] 20 μl of the test bacterial solution was mixed with 180 μl of the liquid preparation to prepare the mixed solutions (2) and (3 ) for the test. The liquid preparation is a liquid composition obtained by mixing, in addition to each test substance, water, glycerin, fragrance, preservative, and solubilizer (polyoxyethylene hydrogenated castor oil), etc. Also, a 0.05% aqueous solution of CPC (1) was prepared. The test substances and concentrations in the said mixed solution or aqueous solution are as follows. (1) CPC 0.05% (2) CPC 0.05% and BKC 0.01% (3) CPC 0.05% and BTC 0.01%

[0041] 200 μl of the said mixed solution ((2) or (3)) 30 seconds after mixing, or 200 μl of the 0.05% aqueous solution of CPC (1), was added to 1.8 ml of drug-inactivated PBS to which soy lecithin and Tween 80 were added to final concentrations of 0.07% and 0.5% respectively in phosphate-buffered saline (PBS) (10-fold dilution) to inactivate the bactericidal action of the bactericide. Also, each solution after inactivating the bactericidal action with the said drug-inactivated PBS was serially diluted to 10 2 ~10 5 times dilution (serial mixed solution dilutions).

[0042] 50 μl each of the prepared serial mixed solution dilutions was spread on a sheep blood agar medium for CDC anaerobic bacteria (Nippon Becton Dickinson Co., Ltd.), anaerobically cultured at 37°C for 3 days, and the viable cell count was counted.

[0043] Furthermore, plates with a dilution rate where there was no overlap between colonies and 15 or more colonies were culturable were selected and used for subsequent colony identification. The colonies on the selected plates were each cultured (all colonies were collected from the plates on which colony counting had been completed), and each colony was spread on a Well-Plate, and a matrix (1 μL - CHCA (α-cyano-4-hydroxycinnamic acid)) was applied to crystallize it, and an MS spectrum of the protein derived from the bacteria was obtained by MALDI-TOFMS. The obtained spectral pattern was matched with a database to identify related species. (The analytical instrument used was the MALDI Biotyper manufactured by Bruker.) The concentration of the test substance is shown in Fig. 1 for the result of case (1) above, in Fig. 2 for the result of case (2) above, and in Fig. 3 for the result of case (3) above, respectively. Also, the result when water was used instead of (1) to (3) is shown in Fig. 4.

[0044] In Figs. 1 to 4, the detected bacterial names (names of related species) and the number of their colonies are shown, and the rank and goodness or badness (good bacteria or bad bacteria) of the bacteria are also shown. Furthermore, in the lower right of each figure, the ratio of good bacteria (○) and bad bacteria (×) among all the detected bacteria is shown.

[0045] The criteria for the rank and goodness or badness were based on the three-stage classification of oral bacteria described in the above Non-Patent Document 2 (J Family Med Prim Care. 2019 Nov; 8(11): 3480 - 3486). This classification is shown in Fig. 5. In this figure, the classification of bacteria involved in the formation of plaque related to periodontal disease is shown in a pyramid shape, with the initial adhering bacteria at the base part (blue, purple, green, yellow), the bridging bacteria in the middle part (orange), and the late adhering bacteria (periodontal pathogenic bacteria) at the apex part (red), respectively. The color-coding in Figs. 1 to 4 follows the color-coding of the pyramid in Fig. 5, and bacteria not in the classification of Fig. 5 are marked as "out of scope". Also, bacteria classified as orange or red in Fig. 5 were considered bad, and bacteria classified as other colors or bacteria not shown in Fig. 5 were considered good.

[0046] The oral bacteria shown in Fig. 5 are listed below in a table.

[0047]

Table 1

[0048] As can be seen from the results, (1) when treated with 0.05% CPC, the ratios of beneficial bacteria and harmful bacteria were almost the same as those in water. Also, (3) when treated with 0.05% CPC and 0.01% BTC, the ratio of harmful bacteria, in particular, decreased compared to water and the case of (1). On the other hand, (2) when treated with 0.05% CPC and 0.01% BKC, the ratio of harmful bacteria (especially Fusobacterium) decreased significantly compared to water and the case of (1). Furthermore only in the case of treatment with (2), the ratio of Veillonella ( purple) decreased significantly compared to the cases of treatment with (1) and (3), and the ratio of Actinomyces (blue) increased. These are all bacteria (initial adherent bacteria) ranked as beneficial bacteria (the base part of the pyramid) in the above rank, but there is a report that the amount of biofilm formed by Veillonella increases through co-culture with other bacteria (Hokkaido Medical University Dental Journal 2011, 30(1), p87), and it may play a central role in biofilm formation. Also, it has been reported that Veillonella produces vitamin K, which is a nutrient source for the Prevotella genus (orange) and the Porphyromonas genus (red) (Virulence. 2011 Sep / Oct; 2(5): 435 - 444), and it may also promote the growth of harmful bacteria. From these facts, as for the balance of the oral flora, Veillonell um may play a role in promoting the growth of harmful bacteria. From these facts, as for the balance of the oral flora, Veillonell It is considered that a preferably decreases. Actinomyces is a major constituent bacterium of oral resident bacteria. Proportionally, it is abundant in the mouths of healthy humans without periodontitis and is said to decrease in periodontitis patients, and it is regarded as an indicator for observing the health status of the mouth. Therefore, as the balance of the oral flora, it is considered that an increase is preferable. Considering these facts, it was considered that an especially excellent oral flora improving effect was obtained only when CPC and BKC were used in combination.

[0049] Formulation examples are described below. Note that the values of the blending amounts of the respective components in the formulation examples indicate mass%.

[0050] [Table 2]

[0051] [Table 3]

[0052] [Table 4]

[0053] [Table 5]

[0054] [Table 6]

[0055] [Table 7]

[0056] [Table 8]

Claims

**Claim 1** A composition for improving oral flora, comprising 0.01 to 0.3% by mass of cetylpyridinium chloride and 0.005 to 0.3% by mass of benzethonium chloride, and being a composition for reducing the proportion of Veillonella bacteria in oral flora. **Claim 2** The composition according to claim 1, for improving the balance of each bacterium in oral flora. **Claim 3** The composition according to claim 1 or 2, comprising 1 to 100 parts by mass of benzethonium chloride with respect to 100 parts by mass of cetylpyridinium chloride. **Claim 4** The composition according to any one of claims 1 to 3, which is an oral composition. **Claim 5** The composition according to claim 4, which is an oral composition for human use. ​

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