JP7714366B2 - Disinfectant composition - Google Patents

Description

This disclosure relates to compositions for sterilization, and more specifically to compositions for sterilizing Fusobacterium. The contents of all documents cited in this specification are incorporated herein by reference.

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.

Roughly speaking, plaque forms as follows: First, a thin film 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 vector bacteria 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 vector bacteria, resulting in plaque maturation. Late-adhering bacteria, in particular, are known to cause periodontal disease and are directly and indirectly related to the destruction of periodontal tissues. Therefore, inhibiting plaque formation on tooth surfaces, particularly by inhibiting the adhesion and aggregation of later-adhering bacteria and the maturation of plaque, is considered important for preventing periodontal disease.

J Dent Res 90(11):1271-1278, 2011

The inventors conducted their research, focusing on the vector bacteria Fusobacterium. This is 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.

Therefore, we began investigating methods for sterilizing Fusobacterium.

As we continued to investigate methods for sterilizing Fusobacterium, we discovered that a combination of a specific alkyl glucoside and cetylpyridinium chloride could potentially be used to efficiently sterilize Fusobacterium, and further improvements were made.

The present disclosure includes, for example, the subject matter described in the following sections:
Item 1.
A composition for killing Fusobacterium, which contains an alkylglucoside having an alkyl group having 8 to 10 carbon atoms and cetylpyridinium chloride.
Item 2.
A composition for inhibiting plaque formation, comprising an alkyl glucoside having an alkyl group having 8 to 10 carbon atoms and cetylpyridinium chloride.
Item 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.
Item 4.
Item 4. The composition according to Item 3, wherein the monosaccharide is glucose.
Item 5.
Item 5. The composition according to any one of Items 1 to 4, which is an oral composition.

A method is provided for efficiently killing Fusobacterium, a bacterium that mediates plaque formation. This also makes it possible to efficiently suppress plaque formation.

The figures show the results of investigating the bactericidal activity against Fusobacterium when alkylglucosides having alkyl groups with different carbon numbers (C8, C10, and C12) were used in combination with CPC.

Each embodiment included in the present disclosure is described in further detail below. The present disclosure preferably includes compositions such as compositions for killing Fusobacterium and compositions for inhibiting plaque formation, but is not limited to these, and the present disclosure includes all of the compositions disclosed herein and recognizable to those skilled in the art.

Compositions included in the present disclosure, such as compositions for killing Fusobacterium and compositions for inhibiting plaque formation, contain an alkyl glucoside having an alkyl group having 8 to 10 carbon atoms (C8-10) and cetylpyridinium chloride. Compositions according to the present disclosure that contain this alkyl glucoside and cetylpyridinium chloride are sometimes referred to as the composition of the present disclosure, and this alkyl glucoside is sometimes referred to as the alkyl glucoside of the present disclosure. Cetylpyridinium chloride is also sometimes abbreviated as CPC.

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, the hydrogen atom of the OH group of the monosaccharide is substituted with an alkyl group having 8 to 10 carbon atoms). The number of alkyl groups having 8 to 10 carbon atoms bonded to the monosaccharide may be, for example, 1, 2, or 3, with 1 being particularly preferred. Furthermore, as long as an alkyl group having 8 to 10 carbon atoms is bonded, other alkyl groups may also be bonded, but it is preferable that only alkyl groups having 8 to 10 carbon atoms are bonded.

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

A preferred example of a monosaccharide is glucose.

When the monosaccharide has a cyclic structure, the site of the monosaccharide to which the alkyl group having 8 to 10 carbon atoms is bonded (i.e., the position of the OH group having a hydrogen atom substituted with an alkyl group having 8 to 10 carbon atoms) is preferably the OH group bonded to a carbon atom on the ring bonded to an oxygen atom present on the ring.

More specifically, preferred examples of the alkyl glucoside of the present disclosure include octyl glucoside (particularly n-octyl glucoside) and decyl glucoside (particularly n-decyl glucoside). Furthermore, more preferred examples of the alkyl glucoside of the present disclosure include those represented by formula (A):

(In the formula, n represents 7, 8, or 9.)
Examples include alkyl glucosides represented by the following formula:

The alkyl glucosides of the present disclosure can be used alone or in combination of two or more. Although not particularly limited, it is preferable to use a combination of octyl glucoside and decyl glucoside. When using these in combination, although not particularly limited, it is preferable to combine 0.1 to 2 parts by mass of decyl glucoside with 1 part by mass of octyl glucoside. The upper or lower limit of this range (0.1 to 2 parts by mass) may be, for example, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, or 1.9 parts by mass. For example, the range may be 0.2 to 1 part by mass.

The content of the alkyl glucoside of the present disclosure in the composition of the present disclosure can be, for example, 0.01 to 5% by mass. The upper or lower limit of this range can 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, or 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.

The content of CPC in the composition of the present disclosure may be, for example, 0.005 to 0.3% 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, 0.2, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, or 0.29% by mass. For example, the range may be 0.01 to 0.2% by mass.

Furthermore, the mass ratio of the alkyl glucoside and CPC of the present disclosure is preferably, for example, 1 to 50 parts by mass of CPC per 100 parts by mass of the alkyl glucoside of the present disclosure. 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, or 49 parts by mass. For example, the range may be 2 to 20 parts by mass.

By using the alkyl glucoside and CPC of the present disclosure in combination, an excellent anti-Fusobacterium effect is achieved. Therefore, a composition containing the alkyl glucoside and CPC of the present disclosure (i.e., the composition of the present disclosure) can exhibit an excellent anti-Fusobacterium effect, and ultimately an excellent plaque formation inhibitory effect. For this reason, the composition of the present disclosure can be preferably used, in particular, as an oral composition. It can also be preferably used, for example, as a denture cleanser composition. It can also be used, for example, as a food composition. Or, it can be used as a pharmaceutical composition.

The Fusobacterium referred to here is not particularly limited as long as it is a bacterium of the genus Fusobacterium, which acts as an intermediary between early and late adhering bacteria in plaque formation, but a preferred example is Fusobacterium nucleatum.

The following provides a more detailed explanation of the case where the composition of the present disclosure is an oral composition. Such an oral composition may also be referred to as the oral composition of the present disclosure.

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. Furthermore, the form of the oral composition of the present disclosure is not particularly limited, and can be made into forms (dosage forms) such as ointments, pastes, pastes, gels, liquids, sprays, mouthwashes, liquid dentifrices, toothpastes, and gums in accordance with conventional methods. Among these, mouthwashes, liquid dentifrices, toothpastes, ointments, pastes, liquids, and gels are preferred.

The oral composition of the present disclosure may further contain one or more optional components that can be incorporated into the oral composition, as long as the effects are not impaired.

For example, nonionic surfactants, anionic surfactants, or amphoteric surfactants can be used as 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; sorbitan fatty acid esters; fatty acid monoglycerides; polyoxyethylene alkyl ethers having a polyoxyethylene addition coefficient of 8 to 10 and an alkyl group containing 13 to 15 carbon atoms; polyoxyethylene alkylphenyl ethers having a polyoxyethylene addition coefficient of 10 to 18 and an alkyl group containing 9 carbon atoms; diethyl sebacate; polyoxyethylene hydrogenated castor oil; and fatty acid polyoxyethylene sorbitan. Examples of anionic surfactants include sulfate ester salts such as sodium lauryl sulfate and polyoxyethylene lauryl ether sodium sulfate; sulfosuccinates such as sodium lauryl sulfosuccinate and polyoxyethylene lauryl ether sodium sulfosuccinate; acylamino acid salts such as sodium cocoyl sarcosinate and sodium lauroyl methyl alanine; and sodium cocoyl methyl taurate. Examples of zwitterionic surfactants include acetate betaine surfactants such as lauryl dimethylamino acetate betaine and coconut oil fatty acid amidopropyl dimethylamino acetate betaine; imidazoline surfactants such as N-cocoyl-N-carboxymethyl-N-hydroxyethylethylenediamine sodium; and amino acid surfactants such as N-lauryl diaminoethylglycine. These surfactants can be used alone or in combination of two or more. The amount used is typically 0.1 to 5% by mass of the total composition.

Flavors 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, cinnamonaldehyde, peppermint oil, and vanillin. These may be blended alone or in combination of two or more types, at a concentration of, for example, 0.001 to 1.5% by mass based on the total amount of the composition.

Sweetening agents that can be used include, for example, saccharin sodium, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, perillartine, thaumatin, aspartyl phenylalanyl methyl ester, and p-methoxycinnamic aldehyde. These can be incorporated in amounts of, for example, 0.01 to 1% by mass of the total composition.

In addition, humectants such as sorbitol, ethylene glycol, propylene glycol, glycerin, 1,3-butylene glycol, polypropylene glycol, xylitol, maltitol, lactite, and polyoxyethylene glycol can be blended alone or in combination.

Preservatives that can be added include parabens such as methylparaben, ethylparaben, propylparaben, and butylparaben, sodium benzoate, phenoxyethanol, and alkyldiaminoethylglycine hydrochloride.

Coloring agents may include 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, and titanium oxide.

pH adjusters such as 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 may be added. These may be added alone or in combination of two or more types 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.

The oral composition of the present disclosure may further contain, as active ingredients, 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, and hinokitiol; anionic bactericides such as sodium lauroyl sarcosinate; cationic bactericides such as chlorhexidine hydrochloride and benzethonium chloride; enzymes such as dextranase, amylase, protease, mutanase, lysozyme, and lytic enzymes (retic enzymes); monofluroic acid, benzoyl benzoates, and the like. Alkali metal monofluorophosphates such as sodium orophosphate and potassium monofluorophosphate, fluorides such as sodium fluoride and stannous fluoride, tranexamic acid, epsilon aminocaproic acid, aluminum chlorohydroxyl allantoin, dihydrocholesterol, glycyrrhetinic acid, copper chlorophyllin sodium, glycerophosphate, chlorophyll, sodium chloride, callopeptide, allantoin, carbazochrome, hinokitiol, potassium nitrate, palatinit, etc. can be blended alone or in combination of two or more.

Alcohols, silicone, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, plastibase, etc. can also be added as bases.

The oral composition of the present disclosure can be prepared by known methods or methods that can be easily derived from known methods. For example, it can be prepared by appropriately mixing the alkyl glucoside and CPC of the present disclosure, as well as other ingredients, if necessary.

The subject to which the composition of the present disclosure (particularly the oral composition of the present disclosure) is applied is not particularly limited, and preferred examples include humans and non-human mammals. Non-human mammals include livestock and pets, and more specifically, examples include dogs, cats, mice, rats, horses, cows, sheep, and monkeys. Furthermore, as described above, the oral composition of the present disclosure contains a combination of the alkyl glucoside and CPC of the present disclosure, and is therefore capable of efficiently killing the vector bacteria Fusobacterium. Therefore, the oral composition of the present disclosure is particularly suitable for application to the oral cavity of a subject where plaque has not formed or is in the process of forming (where no late-stage adherent bacteria have adhered).

The above description of the oral composition of the present disclosure can also be applied to compositions of the present disclosure that are not used as oral compositions (e.g., compositions that are particularly preferably used for cleaning dentures), unless there is a contradiction in the technical field.

In this specification, the term "comprising" includes "consisting essentially of" and "consisting of." Furthermore, the present disclosure encompasses all arbitrary combinations of the constituent elements described in this specification.

Furthermore, the various characteristics (properties, structures, functions, etc.) described for each embodiment of the present disclosure above may be combined in any way to identify the subject matter encompassed by the present disclosure. In other words, the present disclosure encompasses all subject matter consisting of any combination of the combinable characteristics described in this specification.

The following examples illustrate embodiments of the present disclosure in more detail, but the embodiments of the present disclosure are not limited to the examples below. Note that although the concentrations (%) of the various compositions prepared in the following studies are expressed in w/v%, because the solvent is water and the concentrations are relatively low, the numerical values are almost identical to mass % (w/w%) and can be approximated accordingly.

The following three types of alkylglucosides were used in the study:
n-Octyl glucoside (C8 glucoside)
n-Decyl glucoside (C10 glucoside)
n-Dodecyl glucoside (C12 glucoside)

Note that formula (A):

Among the alkyl glucosides represented by the formula, when n = 7 it is the above-mentioned C8 glucoside, when n = 9 it is the above-mentioned C10 glucoside, and when n = 11 it is the above-mentioned C12 glucoside.

The above C8 glucoside, C10 glucoside, and C12 glucoside, as well as CPC, were mixed according to the formulations in Table 1 to prepare paste-like compositions A and B. The numerical values for each component in Table 1 indicate mass %. The toothpaste base was prepared by mixing purified water, concentrated glycerin, liquid sorbitol, and calcium carbonate with abrasives, thickeners, flavorings, sweeteners, preservatives, etc.

1 g of each of Compositions A and B in Table 1 was weighed into a 50 ml tube, 3 ml of sterile distilled water was added, and the mixture was vigorously stirred in a shaker for 10 minutes to prepare the test solution (Test Solution A and B).

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

The test bacteria were inoculated into 10 ml of GAM bouillon medium (Nissui Pharmaceutical Co., Ltd.) and incubated at 37°C.
The culture was used as the test bacterial solution.

200 μl of test agent solution A or B (or 200 μl of water) was mixed with 200 μl of test bacteria solution. 30 seconds after mixing, 100 μl of the mixture was collected, and 900 μl of drug-inactivated PBS (phosphate-buffered saline (PBS) with soybean lecithin and Tween 80 added to final concentrations of 0.07% and 0.5%, respectively) was added (10-fold dilution of the mixture) to inactivate the bactericidal action of the bactericide. Furthermore, the mixture was serially diluted with drug-inactivated PBS, and the mixture was diluted 10 ¹ to 10 ⁷ times (serial diluted mixture).

100 μl of each of the prepared serially diluted mixtures was smeared onto CDC anaerobic sheep blood agar medium (Becton Dickinson Japan), and cultured anaerobically at 37°C for 3 days, after which the number of viable bacteria was counted.

The results are shown in Figure 1. Note that Figure 1 is a graph with the vertical axis representing Log (viable cell count) CFU/ml, with a value of 2 being the detection limit. (A value less than 2 indicates that sterilization was achieved down to less than 100 CFU.) It was found that composition A, containing C12 glucoside and CPC, did not exhibit a bactericidal effect against Fusobacterium, while composition B, containing C8 glucoside, C10 glucoside, and CPC, did exhibit a bactericidal effect against Fusobacterium. Note that CPC alone did not exhibit a bactericidal effect against Fusobacterium. Furthermore, when a composition obtained by omitting CPC from composition B was used, almost no bactericidal effect against Fusobacterium was observed.

From the above, it was found that using C12 glucoside in combination with CPC does not have a bactericidal effect against Fusobacterium, but using C8 glucoside and/or C10 glucoside in combination with CPC has a particularly excellent bactericidal effect against Fusobacterium.

Claims (6)

A composition for killing Fusobacterium, which contains an alkylglucoside having a structure in which a linear alkyl group having 8 to 10 carbon atoms is bonded to glucose, and cetylpyridinium chloride. A composition for inhibiting plaque formation, comprising an alkyl glucoside having a structure in which a linear alkyl group having 8 to 10 carbon atoms is bonded to glucose, and cetylpyridinium chloride. The alkyl glucoside is
Formula (A):
(In the formula, n represents 7, 8, or 9.)
is an alkyl glucoside represented by the formula:
The composition according to claim 1 or 2. The composition according to any one of claims 1 to 3, containing 0.01 to 5% by mass of the alkyl glucoside. The composition according to any one of claims 1 to 4, containing 0.005 to 0.3% by mass of the cetylpyridinium chloride. The composition according to any one of claims 1 to 5 , which is an oral composition.