Sterilization composition

Abstract

To provide a composition that efficiently kills Fusobacterium, which is a medium bacterium causing plaque formation, thereby efficiently inhibiting the plaque formation.SOLUTION: The present invention discloses a composition for killing Fusobacterium that contains an alkyl glucoside having a C8-10 alkyl group, or a composition for inhibiting plaque formation that contains an alkyl glucoside having a C8-10 alkyl group. Preferably, the alkyl glucoside comprises a monosaccharide combined with a C8-10 linear alkyl group and the monosaccharide is glucose.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present disclosure relates to a composition for sterilization, etc., and more particularly to a composition for sterilizing Fusobacterium, etc. The contents of all documents described in this specification are incorporated herein by reference. [Background technology]

[0002] Dental plaque is a biofilm formed by the aggregation of oral microorganisms and is thought to be a potential cause of dental caries and periodontal disease.

[0003] Roughly speaking, plaque formation occurs as follows. First, a thin membrane of proteins derived from saliva and physiological gingival crevicular fluid called a "pellicle" forms on the tooth surface. Facultative anaerobic bacteria (early-adhering bacteria) such as streptococci adhere to the tooth surface through this pellicle. These early-adhering bacteria are then joined by vectors such as Fusobacterium, which coaggregate with various oral bacteria. Later-adhering bacteria, such as anaerobic bacteria Porphyromonas gingivalis and Treponema denticola, then adhere and aggregate through these vectors, resulting in plaque maturation. Late-adhering bacteria, in particular, are known to cause periodontal disease and are directly and indirectly involved in the destruction of periodontal tissues. Therefore, inhibiting plaque formation on tooth surfaces, particularly the adhesion and aggregation of later-adhering bacteria and the maturation of plaque, is considered important for preventing periodontal disease. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] J Dent Res 90(11):1271-1278, 2011 Summary of the Invention [Problem to be solved by the invention]

[0005] The present inventors conducted research focusing on the vector bacteria Fusobacterium, because they believe that if the activity of Fusobacterium, a vector bacteria capable of coaggregating with various bacteria, can be inhibited, it will be possible to inhibit the adhesion and aggregation of late-adherent bacteria to the tooth surface, and ultimately to inhibit the maturation of plaque formation.

[0006] Therefore, we investigated methods for sterilizing Fusobacterium. [Means for solving the problem]

[0007] As we continued to investigate methods for sterilizing Fusobacterium, we discovered that certain alkyl glucosides may be able to efficiently sterilize Fusobacterium, and we continued to make further improvements.

[0008] The present disclosure includes, for example, the subject matter described in the following sections: Section 1. A composition for killing Fusobacterium, which contains an alkylglucoside having an alkyl group having 8 to 10 carbon atoms. Section 2. A composition for inhibiting plaque formation, which contains an alkyl glucoside having an alkyl group having 8 to 10 carbon atoms. Section 3. Item 3. The composition according to Item 1 or 2, wherein the alkyl glucoside having an alkyl group having 8 to 10 carbon atoms is an alkyl glucoside having a structure in which a linear alkyl group having 8 to 10 carbon atoms is bonded to a monosaccharide. Section 4. Item 4. The composition according to Item 3, wherein the monosaccharide is glucose. Section 5. Item 5. The composition according to any one of Items 1 to 4, which is an oral composition. [Effects of the Invention]

[0009] This provides a method for efficiently killing Fusobacterium, a bacterium that mediates plaque formation, which also makes it possible to efficiently suppress plaque formation. [Brief explanation of the drawings]

[0010] [Figure 1] The results of examining the bactericidal activity of alkyl glucosides having alkyl groups with different carbon numbers (C8, C10, and C12) against Fusobacterium are shown.

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 compositions such as a composition for killing Fusobacterium and a composition for suppressing plaque formation, 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] Compositions such as the composition for killing Fusobacterium and the composition for suppressing plaque formation included in the present disclosure contain an alkyl glucoside having an alkyl group with 8 to 10 carbon atoms (C8 to C10). The composition according to the present disclosure containing the alkyl glucoside may be referred to as the composition of the present disclosure, and the alkyl glucoside may be referred to as the alkyl glucoside of the present disclosure.

[0013] The alkyl glucoside of the present disclosure has a structure in which an alkyl group having 8 to 10 carbon atoms is bonded to a monosaccharide (more specifically, a hydrogen atom of the OH group of the monosaccharide is substituted with an alkyl group having 8 to 10 carbon atoms). Examples of the number of alkyl groups having 8 to 10 carbon atoms bonded to the monosaccharide include 1, 2, or 3, and particularly preferably 1. Further, as long as an alkyl group having 8 to 10 carbon atoms is bonded, other alkyl groups may be further bonded, but it is preferable that only an alkyl group having 8 to 10 carbon atoms is bonded.

[0014] The alkyl group having 8 to 10 (8, 9, or 10) carbon atoms may be linear or branched, and is preferably linear.

[0015] In addition, glucose is preferably exemplified as the monosaccharide.

[0016] The site of the monosaccharide to which an alkyl group having 8 to 10 carbon atoms is bonded (that is, the position of the OH group having a hydrogen atom substituted with an alkyl group having 8 to 10 carbon atoms) is preferably an OH group bonded to a "carbon atom on the ring bonded to the oxygen atom present on the ring" when the monosaccharide has a cyclic structure.

[0017] More specifically, examples of the alkyl glucoside of the present disclosure preferably include octyl glucoside (particularly n-octyl glucoside), decyl glucoside (particularly n-decyl glucoside), and the like. Further, as the more preferable alkyl glucoside of the present disclosure, for example, formula (A):

[0018]

Chemical formula

[0019] (In the formula, n represents 7, 8, or 9.) The alkyl glucoside represented by is mentioned.

[0020] The alkyl glucoside of the present disclosure can be used alone or in combination of two or more.

[0021] Examples of the content of the alkyl glucoside of the present disclosure in the composition of the present disclosure include 0.01 to 5% by mass. The upper or lower limit of the range may be, for example, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, or 4.9% by mass. For example, the range may be 0.02 to 4.5% by mass.

[0022] The alkyl glucoside of the present disclosure exhibits an excellent bactericidal effect against Fusobacterium. Therefore, the composition containing the alkyl glucoside of the present disclosure (i.e., the composition of the present disclosure) can exhibit an excellent bactericidal effect against Fusobacterium and, consequently, an excellent plaque formation inhibitory effect. For this reason, the composition of the present disclosure can be particularly preferably used as an oral composition. Further, for example, it can be preferably used as a denture cleaning composition. Further, for example, it can also be used as a food composition. Alternatively, it can also be used as a pharmaceutical composition.

[0023] Here, the Fusobacterium is not particularly limited as long as it is a bacterium of the genus Fusobacterium, which is a mediating bacterium between early adherent bacteria and late adherent bacteria in plaque formation, but Fusobacterium nucleatum is preferably exemplified.

[0024] Hereinafter, when the composition of the present disclosure is an oral composition, it will be described in more detail. The oral composition may be referred to as the oral composition of the present disclosure.

[0025] 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. Further, 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, pastilles, gels, liquids, sprays, mouthwashes, liquid dentifrices, dentifrice pastes, chewing gums, etc. according to conventional methods. Among them, mouthwashes, liquid dentifrices, dentifrice pastes, ointments, pastes, liquids, and gels are preferable.

[0026] The oral composition of the present disclosure may further contain, alone or in combination of two or more, optional components that can be incorporated into an oral composition, as long as the effects are not impaired.

[0027] 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. can be mentioned. 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. can be mentioned. As the amphoteric ion surfactant, betaine type surfactants such as lauryldimethylaminoacetic acid betaine, coconut oil fatty acid amide propyldimethylaminoacetic acid betaine; imidazoline type surfactants such as N-cocoyl-N-carboxymethyl-N-hydroxyethyl ethylenediamine sodium; amino acid type surfactants such as N-lauryl diaminoethyl glycine, etc. can be mentioned. 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.

[0028] Flavoring agents that can be used include, for example, menthol, carboxylic acid, anethole, eugenol, methyl salicylate, limonene, ocimene, n-decyl alcohol, citronellol, α-terpineol, methyl acetate, citronenyl acetate, methyl eugenol, cineole, linalool, ethyl linalool, thymol, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, perilla oil, wintergreen oil, clove oil, eucalyptus oil, pimento oil, d-camphor, d-borneol, fennel oil, cinnamon oil, cinnamon aldehyde, peppermint oil, vanillin, etc. These can be blended alone or in combination of two or more types, in an amount of, for example, 0.001 to 1.5% by mass based on the total amount of the composition.

[0029] In addition, sweeteners that can be used include, for example, saccharin sodium, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, perillartine, thaumatin, aspartyl phenylalanyl methyl ester, p-methoxycinnamic aldehyde, etc. These can be blended in an amount of, for example, 0.01 to 1% by mass based on the total amount of the composition.

[0030] Furthermore, as a wetting agent, sorbitol, ethylene glycol, propylene glycol, glycerin, 1,3-butylene glycol, polypropylene glycol, xylitol, maltitol, lactite, polyoxyethylene glycol, etc. may be blended alone or in combination of two or more kinds.

[0031] As preservatives, parabens such as methylparaben, ethylparaben, propylparaben, and butylparaben, sodium benzoate, phenoxyethanol, alkyldiaminoethylglycine hydrochloride, and the like can be added.

[0032] As coloring agents, legal pigments such as Blue No. 1, Yellow No. 4, Red No. 202, and Green No. 3, mineral pigments such as ultramarine, enhanced ultramarine, and Prussian blue, titanium oxide, and the like may be blended.

[0033] The pH adjuster may be citric acid, phosphoric acid, malic acid, pyrophosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, or chemically acceptable salts thereof, or sodium hydroxide. These may be added 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 amount of pH adjuster added may be, for example, 0.01 to 2% by weight.

[0034] The oral composition of the present disclosure contains not only the alkyl glucoside of the present disclosure, but also other active ingredients, such as vitamin E compounds such as dl-α-tocopherol acetate, tocopherol succinate, or tocopherol nicotinate, amphoteric bactericides such as dodecyldiaminoethylglycine, nonionic bactericides such as triclosan, isopropylmethylphenol, or hinokitiol, anionic bactericides such as sodium lauroyl sarcosinate, cationic bactericides such as chlorhexidine hydrochloride or benzethonium chloride, dextranase, amylase, protease, mutanase, lysozyme, or bacteriolytic enzyme (retic enzyme), ), 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, glycyrrhetinic acid, glycyrrhizinic acid, copper chlorophyllin sodium, glycerophosphate, chlorophyll, sodium chloride, callopeptide, allantoin, carbazochrome, hinokitiol, potassium nitrate, palatinit, and the like can be blended alone or in combination of two or more.

[0035] Furthermore, it is also possible to add alcohols, silicone, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, plastibase, etc. as bases.

[0036] 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 the alkyl glucoside of the present disclosure and other components as necessary.

[0037] The subject to which the composition of the present disclosure (especially 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. In addition, as described above, since the oral composition of the present disclosure contains the alkyl glucoside of the present disclosure and can efficiently sterilize Fusobacterium, which is a mediating bacterium, it can be said that it is particularly suitable for application to the oral cavity of a subject in which plaque has not been formed or is in the process of formation (late adherent bacteria have not adhered).

[0038] In addition, the description regarding 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 it is particularly preferably used for denture cleaning), as long as there is no contradiction in the technical field.

[0039] In addition, 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.

[0040] In addition, the various characteristics (properties, structures, functions, etc.) described for each of the above-described embodiments of the present disclosure can be combined in any way when specifying the subject matter included in the present disclosure. That is, the present disclosure includes all the subject matters composed of all possible combinations of the characteristics described in this specification.

Examples

[0041] Hereinafter, 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.

[0042] Examination of the bactericidal effect of alkyl glucosides on Fusobacterium The following three types of alkyl glucosides were dissolved in water to various concentrations (0.1%, 0.5%, 1.0% or 5.0%) and used as a bactericidal solution. Note that the alkyl glucoside concentration (%) of the bactericidal solution is w / v%, but since the solvent is water and the concentration is relatively low, it is almost numerically the same as mass% (w / w%) and can be approximated. n-octyl glucoside (C8 glucoside) n-decyl glucoside (C10 glucoside) n-dodecyl glucoside (C12 glucoside)

[0043] Note that in the formula (A):

[0044]

Chemical formula

[0045] Among the alkyl glucosides represented by, when n = 7, it is the above C8 glucoside, when n = 9, it is the above C10 glucoside, and when n = 11, it is C12 glucoside.

[0046] In addition, as test bacteria, two subspecies of the following Fusobacterium were used. Bacteria 1: Fusobacterium nucleatum subsp. nucleatum ATCC23726 Bacteria 2: Fusobacterium nucleatum subsp. nucleatum ATCC25586

[0047] The test bacteria were each inoculated into 10 ml of GAM broth medium (Nissui Pharmaceutical Co., Ltd.) and anaerobically cultured at 37°C for 2 days. The culture solution was used as the test bacterial solution.

[0048] 200 μl of the test bacterial solution was mixed with 200 μl of the bactericide solution with different concentrations. 100 μl of the mixed solution was collected 30 seconds after mixing, and 900 μl of the drug-inactivated PBS, to which soybean lecithin and Tween 80 were added to final concentrations of 0.07% and 0.5% respectively, was added (the mixed solution was diluted 10-fold) to inactivate the bactericidal action of the bactericide. Also, the mixed solution was serially diluted with the drug-inactivated PBS, and the mixed solution was diluted 1 ~10 7 times (serial mixed solution diluents).

[0049] 100 μl each of the prepared serial mixed solution diluents was spread on the CDC Anaerobic Bacteria Sheep Blood Agar Medium (Nippon Becton Dickinson Co., Ltd.), anaerobically cultured at 37°C for 3 days, and the viable cell count was counted. The results are shown in Fig. 1. These figures are graphs with Log (viable cell count) CFU / ml on the vertical axis, and the detection limit of this value is 2. (If the value is less than 2, it indicates that sterilization was achieved to less than 100 CFU.) Also, the concentrations of each alkyl glucoside (C8, C10, and C12 glucosides) in Fig. 1 indicate the concentrations of the components prepared as the bactericide solution. As described above, since the bactericide solution and the test bacterial solution were mixed in the same amount for the experiment, the bactericidal effect is achieved at a concentration half of the concentration shown in Fig. 1.

[0050] It was found that C12 glucoside showed no bactericidal effect against Fusobacterium, while C8 and C10 glucosides showed bactericidal effects against Fusobacterium even at relatively low concentrations.

[0051] ​

Claims

**Claim 1**: A composition for killing Fusobacterium, containing an alkyl glucoside having a structure in which a linear alkyl group having 8 to 10 carbon atoms is bonded to glucose. **Claim 2**: A composition for suppressing plaque formation, containing an alkyl glucoside having a structure in which a linear alkyl group having 8 to 10 carbon atoms is bonded to glucose. **Claim 3**: The alkyl glucoside is Formula (A): 【Chemical 1】 (In the formula, n represents 7, 8, or 9.) The alkyl glucoside represented by the formula, The composition according to claim 1 or 2. **Claim 4**: The composition according to any one of claims 1 to 3, containing 0.01 to 5% by mass of the alkyl glucoside. **Claim 5** The composition according to any one of claims 1 to 4, which is an oral composition.

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