Biofilm dispersant and oral composition

Abstract

To provide a biofilm dispersant that can disperse a biofilm suitably.SOLUTION: A biofilm dispersant contains (A) cetylpyridinium chloride hydrate and (B) at least one selected from the group consisting of nicotinamide, pyrophosphoric acid, pyrophosphate, xylose, and erythritol.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a biofilm dispersant and an oral composition. [Background technology]

[0002] In general, oral diseases such as periodontal disease, gingivitis, dental caries, and halitosis are caused by oral bacteria. Many bacteria in the oral cavity exist as bacterial aggregates called biofilms. Biofilms are composed of bacteria or their corpses, polysaccharides secreted by bacteria, polymeric substances such as proteins, and the like, and have a film-like structure. Therefore, it has been difficult for bactericides used in general oral compositions to penetrate into biofilms.

[0003] For example, Patent Document 1 discloses a biofilm dispersion solution for dispersing and removing such biofilms. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2016-204262 A Summary of the Invention [Problem to be solved by the invention]

[0005] In order to remove formed biofilms, there is a demand for biofilm dispersants that can suitably disperse formed biofilms. [Means for solving the problem]

[0006] Various aspects for solving the above problems will be described below. The biofilm dispersant of embodiment 1 contains (A) cetylpyridinium chloride hydrate and (B) at least one selected from the group consisting of nicotinamide, pyrophosphate, pyrophosphate salts, xylose, and erythritol.

[0007] The oral composition of embodiment 2 contains the biofilm dispersant according to embodiment 1. Effect of the Invention

[0008] The biofilm dispersant and oral composition of the present invention can suitably disperse biofilms formed in the oral cavity. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] An embodiment embodying a biofilm dispersant and an oral composition will be described. In the following, the biofilm dispersant will be mainly described. The oral composition contains the biofilm dispersant described below. In this specification, the oral composition means a composition intended to be used mainly in the oral cavity. It includes not only oral preparations that are discharged from the oral cavity after use, but also ingestible foods and beverages. The biofilm dispersant of this embodiment is not limited to those intended to be used in the oral cavity.

[0010] The biofilm dispersant contains component (A) and component (B). Component (A) is cetylpyridinium chloride hydrate (hereinafter, sometimes referred to as CPC). Component (B) is at least one selected from the group consisting of nicotinamide, pyrophosphate, pyrophosphate salts, xylose, and erythritol.

[0011] <(A)CPC> CPC is generally used as a cationic disinfectant. CPC is also called cetylpyridinium chloride. There is no particular limitation on the CPC, and any known CPC can be used.

[0012] The content of CPC in the biofilm dispersant is not particularly limited, but is, for example, 0.005% by mass or more and 0.3% by mass or less. Hereinafter, the content of each component in the biofilm dispersant may be expressed by abbreviating "%" to "%" instead of "% by mass". The lower limit of the content of CPC is preferably 0.01%, more preferably 0.05%. The upper limit of the content of CPC is preferably 0.2%, more preferably 0.1%. The upper limit or lower limit of the range may be, for example, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.15, 0.2, or 0.25%.

[0013] <(B) component> Nicotinamide is a water-soluble B vitamin. It is the amide of nicotinic acid.

[0014] Pyrophosphate is a type of polyphosphate. The biofilm dispersant may contain a salt of pyrophosphate as component (B). Examples of pyrophosphate salts include sodium pyrophosphate and potassium pyrophosphate.

[0015] Xylose is a type of monosaccharide. Erythritol is a type of sugar alcohol. The biofilm dispersant may contain only one of the above components as component (B), or may contain an appropriate combination of two or more of them.

[0016] The content of the (B) component in the biofilm dispersant is not particularly limited, but is, for example, 0.05% or more and 9% or less. The lower limit of the content of the (B) component is preferably 0.1%, more preferably 0.5%. The upper limit of the content of the (B) component is preferably 6%, more preferably 3%. The upper or lower limit of the range may be, for example, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, or 8.5%.

[0017] The mass ratio ((B) / (A)) of the content of the (B) component to the content of the (A) component in the biofilm dispersant is not particularly limited. For example, the mass ratio is 0.1 to 500, preferably 0.5 to 100, more preferably 1 to 50, and even more preferably 1 to 10.

[0018] <Other ingredients> The biofilm dispersant and the oral composition may contain other components other than the above-mentioned components depending on the application purpose, form, use, etc. Examples of the other components include surfactants, flavoring agents, sweeteners, humectants, binders, preservatives, colorants, pH adjusters, chelating agents, medicinal ingredients, bases, abrasives, stabilizers, etc. The other components may be any known components that are blended into the biofilm dispersant and the oral composition. The biofilm dispersant and the oral composition may contain only one of the above other components alone, or may contain two or more of them in combination.

[0019] Examples of the surfactant include nonionic surfactants, anionic surfactants, amphoteric surfactants, and cationic surfactants. Specific examples of nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid esters, maltose fatty acid esters, and lactose fatty acid esters; fatty acid alkanolamides; glycerin fatty acid esters; sorbitan fatty acid esters; fatty acid monoglycerides; polyoxyethylene alkyl ethers having a polyoxyethylene addition coefficient of 8 to 10 and an alkyl group having 13 to 15 carbon atoms; polyoxyethylene alkyl phenyl ethers having a polyoxyethylene addition coefficient of 10 to 18 and an alkyl group having 9 carbon atoms; diethyl sebacate; polyoxyethylene hydrogenated castor oil; and polyoxyethylene sorbitan fatty acid.

[0020] Specific examples of anionic surfactants include sulfate salts such as sodium lauryl sulfate and sodium polyoxyethylene lauryl ether sulfate; sulfosuccinates such as sodium lauryl sulfosuccinate and sodium polyoxyethylene lauryl ether sulfosuccinate; acylamino acid salts such as sodium lauroyl methyl alanine; and sodium cocoyl methyl taurate.

[0021] Specific examples of amphoteric surfactants include acetate betaine type surfactants such as lauryl dimethylamino acetate betaine and coconut oil fatty acid amidopropyl dimethylamino acetate betaine; imidazoline type surfactants such as N-cocoyl-N-carboxymethyl-N-hydroxyethylethylenediamine sodium; and amino acid type surfactants such as N-lauryl diaminoethyl glycine.

[0022] Specific examples of the cationic surfactant include distearyl dimethyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride, N-coconut oil fatty acid acyl-L-arginine ethyl-DL-pyrrolidone carboxylate, and the like.

[0023] Specific examples of flavoring agents include menthol, carboxylic acid, anethole, eugenol, methyl salicylate, limonene, ocimene, n-decyl alcohol, citronellol, α-terpineol, methyl acetate, citronenyl acetate, methyl eugenol, cineole, thymol, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, perilla oil, wintergreen oil, clove oil, eucalyptus oil, pimento oil, d-camphor, d-borneol, fennel oil, cinnamon oil, anise oil, cinnamaldehyde, peppermint oil, and vanillin.

[0024] Specific examples of sweeteners include saccharin sodium, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, perillartine, thaumatin, aspartyl phenylalanyl methyl ester, and p-methoxycinnamic aldehyde.

[0025] Specific examples of the wetting agent include sorbitol, ethylene glycol, propylene glycol, glycerin, 1,3-butylene glycol, polypropylene glycol, xylitol, maltitol, lactite, polyoxyethylene glycol, and the like.

[0026] Specific examples of binders include cellulose derivatives such as sodium carboxymethylcellulose, carboxymethylethylcellulose salts, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, ethylcellulose, crystalline cellulose, and crystalline cellulose-carmellose sodium; microbially produced polymers such as xanthan gum; natural polymers or natural rubbers such as tragacanth gum, karaya gum, gum arabic, guar gum, carrageenan, dextrin, agar, pectin, pullulan, gellan gum, locust bean gum, and sodium alginate; synthetic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, polyvinyl methyl ether, and sodium polyacrylate; thickening silica, inorganic binders such as Veegum; and cationic binders such as O-[2-hydroxy-3-(trimethylammonio)propyl]hydroxyethylcellulose chloride.

[0027] Specific examples of preservatives include parabens such as methylparaben, ethylparaben, propylparaben, and butylparaben, sodium benzoate, phenoxyethanol, and alkyldiaminoethylglycine hydrochloride.

[0028] Specific examples of colorants include legal dyes such as Blue No. 1, Yellow No. 4, Red No. 202, and Green No. 3; mineral dyes such as ultramarine, enhanced ultramarine, and Prussian blue; and titanium oxide. Specific examples of pH adjusters include citric acid, phosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, or chemically acceptable salts thereof, sodium hydroxide, and the like.

[0029] Specific examples of the chelating agent include edetic acid, sodium edetate, potassium edetate, and phytic acid. Specific examples of medicinal ingredients include vitamin E such as dl-α-tocopherol acetate, tocopherol succinate, or tocopherol nicotinate, vitamin C such as ascorbic acid, sodium ascorbate, or magnesium ascorbyl phosphate, vitamin B6 such as pyridoxine hydrochloride, amphoteric bactericides such as glycyrrhizinate and its derivatives, glycyrrhetinic acid, and dodecyldiaminoethylglycine, nonionic bactericides such as triclosan, isopropylmethylphenol, and polyoxyethylene lauryl ether, anionic bactericides such as sodium cocoyl sarcosine and sorbic acid, chlorhexidine hydrochloride, chlorhexidine gluconate, and benzoyl chloride. Examples of such antiseptic agents include cationic antiseptics such as zalkonium and benzethonium chloride, enzymes such as dextranase, amylase, protease, mutanase, lysozyme, and lytic enzymes (Retech Enzymes), alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate, fluorides such as sodium fluoride and stannous fluoride, tranexamic acid, epsilon aminocaproic acid, aluminum chlorohydroxyl allantoin, dihydrocholesterol, hinokitiol, copper chlorophyllin sodium, chlorophyll, sodium chloride, callopeptide, allantoin, carbazochrome, potassium nitrate, and palatinit.

[0030] Specific examples of the base include alcohols, silicone, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, plastibase, and the like.

[0031] Specific examples of the alcohols include ethyl alcohol, lauryl alcohol, and myristyl alcohol. Specific examples of the abrasive include calcium carbonate, magnesium carbonate, secondary calcium phosphate, tricalcium phosphate, magnesium phosphate, silica, zeolite, sodium metaphosphate, aluminum hydroxide, magnesium hydroxide, red iron oxide, calcium sulfate, and silicic anhydride.

[0032] Specific examples of the stabilizer include sodium thiosulfate, sodium sulfite, calcium lactate, lanolin, triacetin, castor oil, magnesium sulfate, and the like. <Application form, use, and dosage form> The biofilm dispersant and the oral composition can be used to disperse biofilms formed in the oral cavity. For example, they can be used to disperse biofilms formed on the surface of teeth. Specific uses include, for example, chewing agents, oral dissolving agents, oral disintegrating agents, tongue care agents, mouth fresheners, mouthwashes, gargles, dentifrices, oral odor prevention agents, gum massage agents, oral moisturizing agents, tongue coating removers, oral coating agents, oral germicides, throat germicides, oral throat agents, periodontal disease treatment agents, denture coating agents, denture stabilizers, denture preservatives, denture cleaners, implant care agents, etc. Examples of dentifrices include toothpastes, powder dentifrices, liquid dentifrices, and lubricating dentifrices. The biofilm dispersant can be used to disperse biofilms not only in the oral cavity but also in other places.

[0033] The biofilm dispersant and the oral composition contain a solvent such as water, alcohol, etc. The dosage form of the biofilm dispersant and the oral composition is not particularly limited, and can be applied in the form (dosage form) of, for example, ointment, paste, spray, gel, liquid, suspension, gum, tablet, drop, etc.

[0034] <Action and Effects> When a biofilm is formed, it becomes difficult for a bactericide or the like to penetrate. Therefore, even a bactericide or the like that is effective against individual bacteria makes it difficult to remove the biofilm. In this regard, the biofilm dispersant of the present embodiment, which contains the components (A) and (B), can disperse a biofilm that has already been formed.

[0035] The biofilm dispersant of the present embodiment can disperse biofilms. This makes it possible to remove biofilms formed in the oral cavity, etc. The oral composition containing the biofilm dispersant also exhibits the same action and effect. EXAMPLES

[0036] The biofilm dispersant and the oral composition will be described in more detail with reference to the following examples. Note that the biofilm dispersant and the oral composition are not limited to the configurations described in the examples.

[0037] <Preparation of sample solution> Sample solutions of Comparative Examples 1 to 5 were prepared. The components contained in each sample solution are as shown in Table 1. In the sample solutions of Comparative Examples 1 to 4, the content of each component was 0.5%. In the sample solution of Comparative Example 5, the content of CPC was 0.05%.

[0038] [Table 1] Sample solutions of Examples 1 to 4 were prepared. The components contained in each sample solution are as shown in Table 2. In the sample solutions of Examples 1 to 4, the content of component (A) is 0.05%. In the sample solutions of Examples 1 to 4, the content of component (B) is 0.5%.

[0039] [Table 2] <Evaluation test> [Biofilm formation] 5 mL of saliva was collected from one subject. 5 mL of saliva was mixed with 5 mL of PBS to prepare a 2-fold diluted sterile saliva. 500 μL of sterile saliva was dispensed into the wells of a 24-well plate. A hydroxyapatite disk (HA disk) was placed in each well, and the HA disk was immersed in the sterile saliva. After leaving it at room temperature for 1 hour, an HA disk with a pellicle formed on its surface was obtained.

[0040] 1 mL of McBain medium supplemented with 2% sucrose (Mouta, LFGL, et al. “Cymbopogon citratus essential oil increases the effect of digluconate chlorhexidine on microcosm biofilms.” Pathogens 11.10 (2022): 1067.) was dispensed into another well. The HA disk on which the pellicle had formed was moved to a well into which McBain medium supplemented with 2% sucrose had been dispensed. Biofilms were formed on the surface of the HA disk by culturing for 24 hours under anaerobic conditions at 37°C.

[0041] [Treatment with sample solution] 500 μL of the sample solution of each Example and Comparative Example was dispensed into individual wells. The HA disk after biofilm formation was immersed in each well and shaken at 500 rpm for 5 minutes using a plate mixer. The HA disk was then removed and washed with 1 mL of distilled water. The washed HA disk was used as the treated HA disk. In addition, as a negative control (hereinafter also referred to as NC), 500 μL of water was used instead of the sample solution, and the same treatment as above was performed.

[0042] 〔staining〕 500 μL of 0.1% by mass CV (Crystal Violet) solution was dispensed into a 24-well plate. The treated HA disk was immersed in the CV solution and left to stand at room temperature for 20 minutes. The HA disk was then removed and washed with 1 mL of distilled water. The washed HA disk was air-dried at room temperature for 30 minutes to 1 hour to obtain a stained HA disk.

[0043] [Pigment extraction] The stained HA disk was immersed in 500 μL of 33% acetic acid solution and left to stand at room temperature for 30 minutes to obtain an extract containing the extracted pigment.

[0044] [Absorbance measurement] 100 μL of the extract obtained by pigment extraction was transferred to a 96-well plate. Absorbance was measured at 550 nm using Cytation5. N=2 was used for the measurement, and the average value and standard deviation (SD) were calculated. In addition, the average value of each Example and Comparative Example was calculated relative to NC, with the average value of the control being set at 100%. Each value is shown in Table 1 and Table 2.

[0045] 〔evaluation〕 In the staining process, the biofilm formed on the surface of the HA disk is stained. In the absorbance measurement, the absorbance of the extract obtained by extracting the dye from the stained HA disk is measured. Therefore, the larger the average value and the value against NC calculated from the results of the absorbance measurement, the more the remaining amount of the biofilm formed on the surface of the HA disk is. In other words, the smaller the average value and the value against NC, the more the biofilm is removed from the HA disk. In other words, the smaller the average value and the value against NC, the higher the effect of dispersing the biofilm.

[0046] From the results of Comparative Example 1, the effect of dispersing biofilms could not be confirmed. In contrast, from the results of Comparative Example 1 and Example 1, it can be seen that Example 1, in which the (A) component and the (B) component are used in combination, has a high effect of dispersing biofilms. Furthermore, from the results of Comparative Example 5 and Example 1, it can be seen that Example 1, in which the (A) component and the (B) component are used in combination, has a higher effect of dispersing biofilms than Comparative Example 5, in which the (A) component is used alone. In other words, a synergistic effect can be confirmed by combining the (A) component and the (B) component.

[0047] From the results of Comparative Example 2 and Example 2, it can be seen that Example 2, in which the (A) component and the (B) component are used in combination, has a higher effect of dispersing a biofilm than Comparative Example 2, in which the (B) component is used alone. Furthermore, from the results of Comparative Example 5 and Example 2, it can be seen that Example 2, in which the (A) component and the (B) component are used in combination, has a higher effect of dispersing a biofilm than Comparative Example 5, in which the (A) component is used alone. In other words, a synergistic effect can be confirmed by combining the (A) component and the (B) component.

[0048] Similarly, the results of Comparative Example 3 and Example 3, and the results of Comparative Example 4 and Example 4 show that each Example in which the (A) component and the (B) component are used in combination has a higher effect of dispersing a biofilm. Furthermore, the results of Comparative Example 5 and Example 3, and the results of Comparative Example 5 and Example 4 show that each Example in which the (A) component and the (B) component are used in combination has a higher effect of dispersing a biofilm. In other words, a synergistic effect can be confirmed by combining the (A) component and the (B) component.

[0049] Furthermore, when tests similar to those in the above evaluation tests were conducted in the same manner as in Examples 1 to 4 except that the content of component (A) was changed to 0.3%, it was confirmed that a suitable biofilm dispersion effect was obtained due to the synergistic effect of combining component (A) and component (B).

[0050] Furthermore, when tests similar to those in the above evaluation tests were conducted in the same manner as in Examples 1 to 4 except that the content of component (A) was changed to 0.1%, it was confirmed that a suitable biofilm dispersion effect was obtained due to the synergistic effect of combining component (A) and component (B).

[0051] From the above, it has been confirmed that the effect of suitably dispersing biofilms is exerted by containing (A) cetylpyridinium chloride and (B) at least one selected from the group consisting of nicotinamide, pyrophosphate, pyrophosphate salts, xylose, and erythritol.

[0052] <Prescription Examples> An example of the formulation is shown below. The numerical value of each component shown in the table below indicates the content (mass %).

[0053] Table 3 shows Formulation Examples 1 to 12 used as toothpaste, and Table 4 shows Formulation Examples 13 to 24 used as liquid preparations.

[0054] [Table 3]

[0055] [Table 4]

Claims

1. (A) cetylpyridinium chloride hydrate, (B) at least one selected from the group consisting of nicotinamide, pyrophosphoric acid, pyrophosphate salts, xylose, and erythritol. Biofilm dispersant.

2. The biofilm dispersant according to claim 1 is contained. Oral composition.

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