WO2018194111A1 - Oral biofilm removing agent and oral composition - Google Patents

Oral biofilm removing agent and oral composition Download PDF

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Publication number
WO2018194111A1
WO2018194111A1 PCT/JP2018/016062 JP2018016062W WO2018194111A1 WO 2018194111 A1 WO2018194111 A1 WO 2018194111A1 JP 2018016062 W JP2018016062 W JP 2018016062W WO 2018194111 A1 WO2018194111 A1 WO 2018194111A1
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Prior art keywords
oral
composition
biofilm
acid
oil
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PCT/JP2018/016062
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French (fr)
Japanese (ja)
Inventor
勇介 川延
康彦 高橋
山本　幸司
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ライオン株式会社
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Priority to MYPI2019005555A priority Critical patent/MY193926A/en
Priority to JP2019513676A priority patent/JPWO2018194111A1/en
Priority to CN201880023827.0A priority patent/CN110494123A/en
Priority to KR1020197025079A priority patent/KR20190139199A/en
Publication of WO2018194111A1 publication Critical patent/WO2018194111A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
    • A61K8/8147—Homopolymers or copolymers of acids; Metal or ammonium salts thereof, e.g. crotonic acid, (meth)acrylic acid; Compositions of derivatives of such polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/255—Esters, e.g. nitroglycerine, selenocyanates of sulfoxy acids or sulfur analogues thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/765—Polymers containing oxygen
    • A61K31/78—Polymers containing oxygen of acrylic acid or derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/59—Mixtures
    • A61K2800/596—Mixtures of surface active compounds

Definitions

  • the present invention relates to an oral biofilm remover and an oral composition containing the same.
  • Plaque control is very important. Plaque control means include suppression of plaque formation and sterilization. Among them, removal of plaque is important. In order to chemically remove plaque, not only bacterial extracellular metabolites such as glucan and protein, but also bacterial aggregates, and biofilms composed of bacterial aggregates and extracellular metabolites in combination It is very important to effectively remove the structure.
  • Patent Document 1 JP-A-2015-20970.
  • the present invention has been made in view of the above circumstances, and an object thereof is to provide a new oral biofilm remover that provides an excellent biofilm removal effect and an oral composition containing the same.
  • a polyacrylic acid salt having a relatively low molecular weight whose weight average molecular weight is not more than a specific value an anionic surfactant or an amphoteric surfactant
  • an anionic surfactant or an amphoteric surfactant it has been found that when combined with, it has an excellent oral biofilm removing action. That is, in the present invention, (a) a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less and (b) one or more selected from anionic surfactants and amphoteric surfactants are used in combination. It was found that an oral biofilm remover with excellent biofilm removal effect and good usability can be obtained.
  • the biofilm removal effect is excellent even when the amount of the component (a) is relatively small, and a good feeling of use (oral irritation) It has been found that it is also possible to impart no odor and no odor), and the present invention has been made.
  • polyacrylic acid having a weight average molecular weight of 100,000 or more, usually about 300,000 or a salt thereof is generally used.
  • a polyacrylic acid polymer having a low molecular weight molecular weight of about 4,000 to 5,500
  • the blending amount in the oral composition should be about 2.5% or more.
  • Patent Document 2 Japanese Patent Publication No. 7-29907
  • surfactants have a cleaning, penetrating, and dispersing action, and are recognized to have a slight plaque-removing action, but the action on biofilms is not sufficient.
  • a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less is obtained from (b) an anionic surfactant and an amphoteric surfactant among the surfactants.
  • a biofilm is a structure that is composed of a complex of bacterial aggregates and extracellular metabolites and is firmly constructed and exhibits high resistance.
  • the biofilm which is a highly resistant deposit was peeled off from the tooth surface and dispersed in the oral cavity, and the biofilm could be removed at a high rate.
  • the effects of the present invention are specific to the combined system of the components (a) and (b), and as shown in Comparative Examples described later, polyacrylic acid and polyacrylate having an inappropriate weight average molecular weight are used. When used in combination with component (b), the biofilm removal effect was poor.
  • Patent Document 3 Japanese Patent Application Laid-Open No. 10-287537
  • Patent Document 4 Japanese Patent Application Laid-Open No. 2002-284, 2004
  • No. -47160 is a suppression of irritation derived from phenoxyethanol or the like by polyacrylate, and sodium acrylate having a molecular weight of about 50,000 is used in the experimental example.
  • Patent Documents 3 and 4 do not mention biofilm removal. From Patent Documents 3 and 4, the improvement of the biofilm removal effect by using the components (a) and (b) of the present invention in combination cannot be predicted.
  • the present invention provides the following oral biofilm remover and oral composition.
  • A a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less;
  • B An oral biofilm remover comprising at least one selected from an anionic surfactant and an amphoteric surfactant.
  • A a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less;
  • An oral biofilm remover comprising at least one selected from an anionic surfactant and an amphoteric surfactant.
  • [3] The oral biofilm remover according to [2], wherein (a) / (b) is 0.02 to 1 as a mass ratio.
  • the anionic surfactant is selected from alkyl sulfates, acyl amino acid salts and acyl taurine salts having an alkyl group having 12 to 14 carbon atoms
  • the amphoteric surfactant is an acylaminoacetic acid having an acyl group having 12 to 14 carbon atoms.
  • the oral biofilm remover according to any one of [1] to [3], which is selected from betaine and fatty acid amidopropyl betaine.
  • composition for oral cavity according to [5] or [6] wherein the content of component (a) is 0.01 to 2% by mass and the content of component (b) is 0.5 to 3% by mass.
  • an oral biofilm remover that has an excellent biofilm removal effect and has a good feeling of use, and an oral composition containing the same.
  • the oral biofilm remover and oral composition of the present invention are effective for the prevention or suppression of periodontal diseases.
  • the oral biofilm remover of the present invention is selected from (a) a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less, and (b) an anionic surfactant and an amphoteric surfactant. More than seeds are active ingredients.
  • the polyacrylate of component (a) has a weight average molecular weight (Mw) of 1,000 or more and 20,000 or less.
  • Mw weight average molecular weight
  • the weight average molecular weight is 1,000 or more, and is 20,000 or less, preferably 10,000 or less.
  • the weight average molecular weight is less than 1,000, the biofilm removal effect is poor.
  • it exceeds 20,000 the effect of removing the biofilm is lowered and a sufficient effect cannot be obtained.
  • the weight average molecular weight was measured by GPC (gel permeation chromatography) under the method and measurement conditions described in Japanese Patent No. 5740859. Specifically, it is shown below.
  • the weight average molecular weight is a value measured using a gel permeation chromatograph / multi-angle laser light scattering detector (GPC-MALLS), and the conditions are as follows.
  • Mobile phase 0.3M NaClO 4 NaN 3 aqueous solution column: 2
  • the polyacrylate is preferably a linear polyacrylate from the viewpoint of the biofilm removal effect.
  • the salt is preferably a monovalent salt, more preferably an alkali metal salt or an ammonium salt, still more preferably an alkali metal salt, especially a sodium salt.
  • a biofilm removal rate is bad, and oral irritation
  • a commercial item can be used as such a polyacrylate.
  • the component (b) is one or more selected from the anionic surfactant (b1) and the amphoteric surfactant (b2), and even if the component (b1) or (b2) is used, (b1) and Although the component (b2) may be used, it is preferable to include at least an anionic surfactant (b1) particularly from the viewpoint of feeling in use, and only the component (b1) is used or (b1) and (b2) It is preferable to use the components in combination.
  • anionic surfactant (b1) examples include alkyl sulfates, acylamino acid salts, and acyl taurine salts having an alkyl group of preferably 12 to 14, particularly 12 carbon atoms.
  • the acyl groups of the acyl amino acid salt and the acyl taurine salt each preferably have 12 to 14 carbon atoms, more preferably 12.
  • Specific examples of the alkyl sulfate include lauryl sulfate and myristyl sulfate.
  • acyl amino acid salts include acyl glutamates such as lauroyl glutamate and myristoyl glutamate, and acyl sarcosine salts such as lauroyl sarcosine salt.
  • acyl taurine salt examples include lauroylmethyl taurine salt.
  • the salt is preferably an alkali metal salt such as a sodium salt or a potassium salt. These can be used alone or in combination of two or more, and alkyl sulfates, acyl sarcosine salts, and acyl taurine salts are particularly preferable.
  • anionic surfactants having a hydrocarbon group having 12 carbon atoms (lauryl group) are preferable, and alkyl sulfates (sodium salts) are particularly preferable because they are superior in taste to other surfactants. .
  • the amphoteric surfactant (b2) is preferably a betaine type, and examples thereof include acylaminoacetic acid betaines having a C 12-14 acyl group and fatty acid amidopropyl betaines.
  • the acylaminoacetic acid betaine preferably has an acyl group having 12 to 14 carbon atoms, and examples include lauroyldimethylaminoacetic acid betaine.
  • the fatty acid amidopropyl betaine includes coconut oil fatty acid amidopropyl betaine. These may be used singly or in combination of two or more, and acylaminoacetic acid betaine is particularly preferred. Among them, those having a hydrocarbon group having 12 carbon atoms (lauryl group) are preferable, and lauryldimethylaminoacetic acid betaine is more preferable.
  • (A) / (b) indicating the quantitative ratio of the component (a) to the component (b) is preferably 0.005 to 2, more preferably 0.005 to 1, and still more preferably 0.02 as a mass ratio. To 1, particularly preferably 0.03 to 0.5.
  • the biofilm removing effect is more excellent, and the odor and taste are better and the feeling of use is further improved.
  • it is 0.005 or more the biofilm removing effect is further improved, and when it is 2 or less, it is possible to sufficiently maintain a good feeling of smell and taste.
  • the oral biofilm remover of the present invention can be obtained by combining the components (a) and (b) as active ingredients. Moreover, although it can be used as an oral biofilm remover consisting of only the above active ingredient, it may further contain other optional ingredients known for oral use as necessary, in which case the optional ingredients are the effects of the present invention. Can be blended within a range not hindering
  • the oral composition of the present invention contains the components (a) and (b) as active ingredients.
  • the composition for oral cavity is specifically a paste, gel or liquid dentifrice composition (toothpaste, gel dentifrice, liquid dentifrice, liquid dentifrice, etc.), mouthwash, mouse spray, coating agent, patch Can be prepared. Of these, toothpaste is preferred.
  • the components (a) and (b), which are effective components for removing the oral biofilm can be defined by the above-mentioned specific ratio.
  • the blending amounts of the components (a) and (b) are preferably in the ranges described below, and it is preferable to use both components at a concentration satisfying these.
  • the blending amount of component (a) is preferably 0.01 to 2% (mass%, the same applies hereinafter), more preferably 0.01 to 1%, still more preferably 0.05 to 0.5% of the entire composition. It is. If the content is 0.01% or more, a sufficient biofilm removal effect can be obtained. If it is 2% or less, the odor and taste can be maintained satisfactorily and sufficiently. If too much is blended, the odor and taste may deteriorate and the usability may be inferior.
  • the blending amount of component (b) is preferably 0.5 to 3% of the total composition, more preferably 0.5 to 2%, and still more preferably 1.0 to 2.0%.
  • the content is 0.5% or more, a sufficient biofilm removal effect can be obtained. If it is 3% or less, oral irritation can be sufficiently suppressed, and the odor and taste can be maintained satisfactorily. If too much is added, the oral irritation becomes stronger, the odor and taste become worse, and the usability may be inferior.
  • a known component according to the dosage form can be further blended as necessary.
  • the optional component is preferably added as long as the effects of the present invention are not hindered.
  • dentifrice compositions include abrasives, binders, thickeners, nonionic surfactants and cationic surfactants as surfactants, as well as sweeteners, preservatives, active ingredients, and pigments. Perfumes can be blended, and these components and water can be mixed and manufactured.
  • dibasic calcium hydrogen phosphate, anhydrous and dihydrate, tricalcium phosphate, primary calcium phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, alumina, anhydrous silicic acid, aluminum silicate, insoluble Sodium metaphosphate, tribasic magnesium phosphate, magnesium carbonate, magnesium sulfate, bentonite, zirconium silicate, polymethyl metaphosphate, and other synthetic resins can be blended (the blending amount is usually 5 to 60%, 10 for toothpaste). ⁇ 55%).
  • paste-like dentifrice compositions such as toothpaste, alginic acid derivatives such as sodium alginate and propylene glycol alginate as a binder, gums such as xanthan gum, tragacanth gum, gela gum, karaya gum, gum arabic, carrageenan, carboxymethylcellulose
  • gums such as xanthan gum, tragacanth gum, gela gum, karaya gum, gum arabic, carrageenan, carboxymethylcellulose
  • Cellulose derivatives such as sodium, methylcellulose, hydroxyethylcellulose, sodium carboxymethylhydroxyethylcellulose
  • organic binders such as polyvinyl alcohol, carboxyvinyl polymer, and polyvinylpyrrolidone
  • inorganic binders such as silica gel, aluminum silica gel, bee gum, and laponite can be blended. (The amount is usually 0.3 to 10%).
  • sugar alcohols such as sorbitol, maltitol, lactitol, erythritol, and polyhydric alcohols such as propylene glycol can be blended as a thickening agent.
  • sorbitol maltitol
  • lactitol lactitol
  • erythritol polyhydric alcohols
  • propylene glycol can be blended as a thickening agent.
  • two or more kinds can be blended (the blending amount is usually 5 to 70%).
  • Nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid esters; sugar alcohol fatty acid esters such as maltitol fatty acid esters; polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monostearate; polyoxyethylene cured castor Polyoxyethylene fatty acid esters such as oil; fatty acid diethanolamides such as lauric acid mono- or diethanolamide; polyoxyethylene higher alcohol ethers can be blended.
  • polyoxyethylene fatty acid ester particularly polyoxyethylene hydrogenated castor oil having an added mole number of ethylene oxide (EO, the same applies hereinafter) of 20 to 100, particularly 20 to 80, is effective in removing biofilms. More preferred.
  • the cationic surfactant examples include alkylammonium salts such as distearylmethylammonium chloride, alkylbenzylammonium salts such as stearyldimethylbenzylammonium chloride, and the like.
  • the total amount of the nonionic surfactant and the cationic surfactant is preferably 0.01 to 10%.
  • the odor and taste may be deteriorated depending on the amount added, but when the nonionic surfactant is added together with the component (b) Thus, the biofilm removal effect is further improved without deteriorating the feeling of use.
  • a nonionic surfactant particularly polyoxyethylene hydrogenated castor oil
  • Sweetening agents include sodium saccharin, stevioside, dipotassium glycyrrhizinate, perilartin, thaumatin, neohesperidyl dihydrochalcone, and aspartylphenylalanine methyl ester.
  • Examples of the preservative include p-hydroxybenzoate ester and sodium benzoate.
  • active ingredients enzymes such as dextranase, mutanase, lysozyme, amylase, protease, lytic enzyme, SOD (superoxide dismutase); 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, dihydrocholestanol, glycyrrhizic acid, glycyrrhetinic acid, glycerophosphate, chlorophyll, sodium chloride, xylitol, zinc chloride, Examples include water-soluble inorganic phosphates and vitamins such as vitamin A, vitamin B group, vitamin C, and vitamin E. These active ingredients can be used alone or in combination of two or more, and can be blended in an effective amount as long as the effects of the present invention are not
  • Perfumes are peppermint oil, spearmint oil, anise oil, eucalyptus oil, wintergreen oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamom oil, coriander oil, mandarin oil, lime Oil, lavender oil, rosemary oil, laurel oil, camomil oil, caraway oil, marjoram oil, bay oil, lemongrass oil, origanum oil, pine needle oil, neroli oil, rose oil, jasmine oil, iris concrete, absolute peppermint Natural fragrances such as absolute rose and orange flower, and fragrances that have been processed (front reservoir cut, rear reservoir cut, fractional distillation, liquid-liquid extraction, essence, powder fragrance, etc.), and Menthol, Carvone, Anethole, Methyl salicylate, Cinnami Cualdehyde, 3-l-menthoxypropane-1,2-diol, linalool, linalyl acetate,
  • fragrance material can be used, and known fragrance materials used in oral compositions can be used. It is not limited to. Further, the above fragrance material is preferably used in an amount of 0.000001 to 1% of the entire composition. As the flavoring fragrance using the fragrance material, it is preferable to use 0.001 to 2.0% in the preparation composition.
  • the pH (25 ° C.) of the oral composition is preferably 5 to 9, more preferably 6 to 8. If the pH is too low, there is a risk of oral irritation and demineralization of enamel and dentin. If the pH is too high, oral irritation and a decrease in formulation stability may occur.
  • a pH adjuster may be added.
  • inorganic acids, organic acids, and salts thereof can be used.
  • examples include sodium hydrogen, sodium phosphate, and sodium dihydrogen phosphate.
  • the oral composition of the present invention can be used by placing it in a predetermined container such as an aluminum tube, a laminated tube obtained by laminating both surfaces of an aluminum foil with plastic, a plastic tube, a bottle-shaped container, an aerosol container or the like.
  • a predetermined container such as an aluminum tube, a laminated tube obtained by laminating both surfaces of an aluminum foil with plastic, a plastic tube, a bottle-shaped container, an aerosol container or the like.
  • % means “% by mass” unless otherwise specified.
  • the weight average molecular weight is a value measured using a gel permeation chromatograph / multi-angle laser light scattering detector (GPC-MALLS), and the conditions are as follows. Mobile phase: 0.3M NaClO 4 NaN 3 aqueous solution column: 2 TSKgel ⁇ -M Precolumn: TSKguardcolumn ⁇ Standard substance: polyethylene glycol The pH of the composition is a value at 25 ° C.
  • Dentifrice compositions (toothpaste) having the compositions shown in Tables 1 to 3 were prepared by the following method, filled in containers (aluminum laminate tubes), and evaluated by the following methods. The results are shown in the table.
  • ⁇ Preparation method> (1) The component (a), other water-soluble components, and a viscosity modifier were mixed and dissolved at room temperature in purified water (mixture X). (2) A binder was dispersed in propylene glycol at room temperature (mixture Y), and the mixture Y was added and mixed into the stirring mixture X to prepare a mixture Z. (3) In the mixture Z, a fragrance
  • ⁇ Evaluation method of biofilm removal effect (1) Method for producing model biofilm
  • the bacteria used for producing the model biofilm were purchased from American Type Culture Collection (ATCC) and precultured by the following method. Actinomyces viscosus ATCC 43146, Fusobacterium nucleatum ATCC10953, Porphyromonas gingivalis, ATCC 33727 Todd Hewitt broth (manufactured by Becton and Dickinson) medium (THBHM) and Baylonella parvula ATCC 17745 is Todd Hewitt broth containing 1.26% sodium lactate (Sigma) (Becton and Dickins They were cultured by n Co., Ltd.) culture [THBL]. The culture was anaerobic culture overnight at 37 ° C.
  • the culture solution discharged from the culture tank was continuously supplied to another culture tank in which the liquid volume was kept at 300 mL.
  • a hydroxyapatite plate (manufactured by PENTAX) having a diameter of 7 mm was attached to the turntable (rotated at about 80 rpm) in the culture tank as a biofilm adhesion carrier.
  • the culture by the above method was carried out continuously for 10 days, and a biofilm was formed on the hydroxyapatite plate.
  • the biofilm-formed hydroxyapatite plate was washed twice with 5 mL of phosphate buffered saline * 2 (hereinafter referred to as PBS) to obtain a model biofilm.
  • PBS phosphate buffered saline * 2
  • the cells were washed 6 times with 1 mL of PBS (manufactured by Wako Pure Chemical Industries, Ltd.), and remained in the test tube (diameter 13 mm ⁇ 100 mm) to which 2 mL of the same buffer was added by sonication (200 ⁇ A, 10 seconds).
  • the film was forced to disperse.
  • the turbidity (OD) at a wavelength of 550 nm of this dispersion was measured, and the residual amount of the biofilm was measured.
  • the biofilm removal effect of the test composition was determined by calculating the removal rate relative to the control by the following formula, and determining the oral biofilm removal effect from this removal rate according to the following criteria.
  • Biofilm removal rate (%) ⁇ (Turbidity of control-turbidity of treated product of test composition) / turbidity of control ⁇ ⁇ 100 Criteria for Biofilm Removal Effect ⁇ : Biofilm removal rate is 90% or more ⁇ : Biofilm removal rate is 70% or more and less than 90% ⁇ : Biofilm removal rate is 50% or more and less than 70% ⁇ : Biofilm removal rate is Less than 50%
  • Evaluation criteria for oral irritation 4 points I do not feel irritation in the oral cavity 3 points: I feel a little irritation in the oral cavity but no problem 2 points: I feel irritation in the oral cavity 1 point: I feel very irritation in the oral cavity Judgment criteria for oral irritation ⁇ : Average score of 3.0 or more ⁇ : Average score of 2.5 or more and less than 3.0 ⁇ : Average score of 1.5 or more and less than 2.5 ⁇ : Average score of 1.5 Less than the point Evaluation criteria for odor 4 points: Feeling unpleasant odor in the oral cavity 3 points: Feeling an unpleasant odor somewhat in the oral cavity but no problem 2 points: Feeling an unpleasant odor in the oral cavity 1 point: In the oral cavity Unpleasant odor is strongly felt Odor judgment criteria ⁇ : Average score of 3.5 points or more ⁇ : Average score of 3.0 points or more and less than 3.5 points ⁇ : Average score of 2.0 points or more and less than 3.0 points ⁇ : Average point less than 2.0

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  • Cosmetics (AREA)

Abstract

An oral biofilm removing agent comprising (a) a polyacrylic acid salt having a weight average molecular weight of 1,000 to 20,000 inclusive and (b) at least one component selected from an anionic surfactant and an amphoteric surfactant, wherein it is more preferred that the (a)/(b) ratio is 0.005 to 2 by mass. An oral composition containing the components (a) and (b), wherein it is more preferred that the (a)/(b) ratio is 0.005 to 2 by mass. According to the present invention, it becomes possible to provide: an oral biofilm removing agent that exhibits an excellent biofilm removing effect and has a comfortable sensation upon use; and an oral composition containing the oral biofilm removing agent.

Description

口腔バイオフィルム除去剤及び口腔用組成物Oral biofilm remover and oral composition
　本発明は、口腔バイオフィルム除去剤及びこれを含有する口腔用組成物に関する。 The present invention relates to an oral biofilm remover and an oral composition containing the same.
　口腔疾患は病原菌が原因で発症するが、この病原菌は歯面にプラーク（歯垢）を形成して口腔内に定着し、病原性を発現するため、歯周病等の口腔疾患の予防にはプラークコントロールが非常に重要である。プラークコントロールの手段としては、プラークの形成抑制や殺菌などがあるが、中でも重要なのがプラークの除去である。プラークを化学的に除去するには、グルカンやタンパクといった細菌の菌体外代謝物だけではなく、細菌凝集体、更には細菌凝集体と菌体外代謝物とで複合的に構成されたバイオフィルム構造物を効果的に除去することが非常に重要である。 Oral diseases develop due to pathogenic bacteria, but these pathogenic bacteria form plaques on the tooth surface and settle in the oral cavity and develop pathogenicity. Plaque control is very important. Plaque control means include suppression of plaque formation and sterilization. Among them, removal of plaque is important. In order to chemically remove plaque, not only bacterial extracellular metabolites such as glucan and protein, but also bacterial aggregates, and biofilms composed of bacterial aggregates and extracellular metabolites in combination It is very important to effectively remove the structure.
　これまでに、アニオン性界面活性剤のα－オレフィンスルホン酸塩又はアルキルスルホ酢酸塩と酵素との併用によるバイオフィルム除去効果が報告されている（特許文献１；特開２０１５－２０９７０号公報）。 Until now, the biofilm removal effect by the combined use of an anionic surfactant α-olefin sulfonate or alkylsulfoacetate and an enzyme has been reported (Patent Document 1; JP-A-2015-20970).
特開２０１５－２０９７０号公報Japanese Patent Laying-Open No. 2015-20970 特公平７－２９９０７号公報Japanese Examined Patent Publication No. 7-29907 特開平１０－２８７５３７号公報Japanese Patent Laid-Open No. 10-287537 特開２００２－４７１６０号公報JP 2002-47160 A
　本発明は、上記事情に鑑みなされたもので、優れたバイオフィルム除去効果を与える新たな口腔バイオフィルム除去剤及びこれを含有する口腔用組成物を提供することを目的とする。 The present invention has been made in view of the above circumstances, and an object thereof is to provide a new oral biofilm remover that provides an excellent biofilm removal effect and an oral composition containing the same.
　本発明者らは、上記目的を達成するため鋭意検討を行った結果、重量平均分子量が特定値以下である比較的低分子量のポリアクリル酸塩と、アニオン性界面活性剤又は両性界面活性剤とを組み合わせると、優れた口腔バイオフィルム除去作用を奏することを見出した。即ち、本発明では、（ａ）重量平均分子量が１，０００以上２０，０００以下であるポリアクリル酸塩と（ｂ）アニオン性界面活性剤及び両性界面活性剤から選ばれる１種以上とを併用することによって、バイオフィルム除去効果が優れ、使用感も良い口腔バイオフィルム除去剤が得られることを知見した。更に、上記（ａ）及び（ｂ）成分を口腔用組成物に配合すると、（ａ）成分量が比較的少なくても、優れたバイオフィルム除去効果を与え、また、良好な使用感（口腔刺激のなさ、臭いのなさ）を付与することもできることを知見し、本発明をなすに至った。 As a result of intensive studies to achieve the above object, the present inventors have found that a polyacrylic acid salt having a relatively low molecular weight whose weight average molecular weight is not more than a specific value, an anionic surfactant or an amphoteric surfactant, It has been found that when combined with, it has an excellent oral biofilm removing action. That is, in the present invention, (a) a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less and (b) one or more selected from anionic surfactants and amphoteric surfactants are used in combination. It was found that an oral biofilm remover with excellent biofilm removal effect and good usability can be obtained. Furthermore, when the above components (a) and (b) are blended into the oral composition, the biofilm removal effect is excellent even when the amount of the component (a) is relatively small, and a good feeling of use (oral irritation) It has been found that it is also possible to impart no odor and no odor), and the present invention has been made.
　口腔用組成物用の粘結剤としては、一般的に重量平均分子量１０万以上、通常は３０万程度のポリアクリル酸又はその塩が用いられている。また、これに比べて低分子量（分子量約４，０００～５，５００）のポリアクリル酸重合体に抗歯石作用があり、口腔用組成物への配合量は約２．５％以上がよいことが特許文献２（特公平７－２９９０７号公報）に提案され、ポリアクリル酸を用いた具体例が示されている。一方、界面活性剤には洗浄作用や浸透、分散作用があり、わずかではあるが歯垢除去作用があると認識されているがバイオフィルムに対する作用は十分でなく、増量すると界面活性剤種によって口腔刺激や味の低下を招くことがあった。これに対して、本発明では、（ａ）重量平均分子量１，０００以上２０，０００以下のポリアクリル酸塩を、界面活性剤のうちの（ｂ）アニオン性界面活性剤及び両性界面活性剤から選ばれる１種以上と組み合わせることによって、意外にも、両者が特異的に相互作用して（ｂ）成分によるバイオフィルム除去作用が格段に向上し、優れたバイオフィルム除去効果を付与できた。また同時に、（ａ）成分によって（ｂ）成分による口腔刺激や臭い等の悪化が抑えられ、使用感も良好に保持できた。なお、重量平均分子量２０，０００以下のポリアクリル酸塩である（ａ）成分を単に使用したのでは、バイオフィルム除去効果がほとんど認められなかった（後述の比較例参照）。
　上述したようにバイオフィルムは、細菌凝集体や菌体外代謝物で複合的に構成されて強固に構築され、高い抵抗性を示す構造物であるが、本発明によれば、このような強固かつ高抵抗性の付着物であるバイオフィルムが歯表面から剥がれて口腔内に分散し、高率でバイオフィルムを除去することができた。本発明の作用効果は（ａ）及び（ｂ）成分の併用系に特異なものであり、後述の比較例にも示すように、ポリアクリル酸や重量平均分子量が不適切なポリアクリル酸塩を（ｂ）成分と併用した場合にはバイオフィルム除去効果が劣っていた。 As a binder for an oral composition, polyacrylic acid having a weight average molecular weight of 100,000 or more, usually about 300,000 or a salt thereof is generally used. In addition, a polyacrylic acid polymer having a low molecular weight (molecular weight of about 4,000 to 5,500) has an anticalculus action, and the blending amount in the oral composition should be about 2.5% or more. Is proposed in Patent Document 2 (Japanese Patent Publication No. 7-29907), and a specific example using polyacrylic acid is shown. On the other hand, surfactants have a cleaning, penetrating, and dispersing action, and are recognized to have a slight plaque-removing action, but the action on biofilms is not sufficient. It may cause irritation and deterioration of taste. In contrast, in the present invention, (a) a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less is obtained from (b) an anionic surfactant and an amphoteric surfactant among the surfactants. By combining with one or more selected ones, surprisingly, both interacted specifically, the biofilm removal action by the component (b) was significantly improved, and an excellent biofilm removal effect could be imparted. At the same time, the deterioration of oral irritation and odor due to the component (b) was suppressed by the component (a), and the feeling of use could be maintained well. In addition, when the component (a) which is a polyacrylate having a weight average molecular weight of 20,000 or less was simply used, the biofilm removal effect was hardly observed (see the comparative example described later).
As described above, a biofilm is a structure that is composed of a complex of bacterial aggregates and extracellular metabolites and is firmly constructed and exhibits high resistance. In addition, the biofilm which is a highly resistant deposit was peeled off from the tooth surface and dispersed in the oral cavity, and the biofilm could be removed at a high rate. The effects of the present invention are specific to the combined system of the components (a) and (b), and as shown in Comparative Examples described later, polyacrylic acid and polyacrylate having an inappropriate weight average molecular weight are used. When used in combination with component (b), the biofilm removal effect was poor.
　なお、特許文献３（特開平１０－２８７５３７号公報）は、無水グルコースを構成単位とする多糖類から誘導されるポリカルボン酸又はその塩によるハイドロキシアパタイトの結晶生成抑制、特許文献４（特開２００２－４７１６０号公報）は、ポリアクリル酸塩による、フェノキシエタノール等由来の刺激の抑制であって実験例では分子量約５０，０００のポリアクリル酸ナトリウムが用いられている。特許文献３、４には、バイオフィルム除去に関する言及もない。特許文献３、４から、本発明の（ａ）及び（ｂ）成分を併用することによる、バイオフィルム除去効果の向上は予測できない。 Patent Document 3 (Japanese Patent Application Laid-Open No. 10-287537) is a patent document 4 (Japanese Patent Application Laid-Open No. 2002-284, 2004) that suppresses the formation of hydroxyapatite crystals by a polycarboxylic acid derived from a polysaccharide having anhydroglucose as a structural unit or a salt thereof. No. -47160) is a suppression of irritation derived from phenoxyethanol or the like by polyacrylate, and sodium acrylate having a molecular weight of about 50,000 is used in the experimental example. Patent Documents 3 and 4 do not mention biofilm removal. From Patent Documents 3 and 4, the improvement of the biofilm removal effect by using the components (a) and (b) of the present invention in combination cannot be predicted.
　従って、本発明は、下記の口腔バイオフィルム除去剤及び口腔用組成物を提供する。
〔１〕
　（ａ）重量平均分子量が１，０００以上２０，０００以下であるポリアクリル酸塩と、
（ｂ）アニオン性界面活性剤及び両性界面活性剤から選ばれる１種以上と
からなる口腔バイオフィルム除去剤。
〔２〕
　（ａ）／（ｂ）が質量比として０．００５～２である〔１〕に記載の口腔バイオフィルム除去剤。
〔３〕
　（ａ）／（ｂ）が質量比として０．０２～１である〔２〕に記載の口腔バイオフィルム除去剤。
〔４〕
　アニオン性界面活性剤が、炭素数１２～１４のアルキル基を有するアルキル硫酸塩、アシルアミノ酸塩及びアシルタウリン塩から選ばれ、両性界面活性剤が、炭素数１２～１４のアシル基を有するアシルアミノ酢酸ベタイン及び脂肪酸アミドプロピルベタインから選ばれる〔１〕～〔３〕のいずれかに記載の口腔バイオフィルム除去剤。
〔５〕
　（ａ）重量平均分子量が１，０００以上２０，０００以下であるポリアクリル酸塩と、
（ｂ）アニオン性界面活性剤及び両性界面活性剤から選ばれる１種以上と
を含有する口腔用組成物。
〔６〕
　（ａ）／（ｂ）が質量比として０．００５～２である〔５〕に記載の口腔用組成物。
〔７〕
　（ａ）成分の含有量が０．０１～２質量％、（ｂ）成分の含有量が０．５～３質量％である〔５〕又は〔６〕に記載の口腔用組成物。
〔８〕
　２５℃におけるｐＨ５～９である〔５〕～〔７〕のいずれかに記載の口腔用組成物。
〔９〕
　歯磨剤組成物である〔５〕～〔８〕のいずれかに記載の口腔用組成物。 Accordingly, the present invention provides the following oral biofilm remover and oral composition.
[1]
(A) a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less;
(B) An oral biofilm remover comprising at least one selected from an anionic surfactant and an amphoteric surfactant.
[2]
The oral biofilm remover according to [1], wherein (a) / (b) is 0.005 to 2 as a mass ratio.
[3]
The oral biofilm remover according to [2], wherein (a) / (b) is 0.02 to 1 as a mass ratio.
[4]
The anionic surfactant is selected from alkyl sulfates, acyl amino acid salts and acyl taurine salts having an alkyl group having 12 to 14 carbon atoms, and the amphoteric surfactant is an acylaminoacetic acid having an acyl group having 12 to 14 carbon atoms. The oral biofilm remover according to any one of [1] to [3], which is selected from betaine and fatty acid amidopropyl betaine.
[5]
(A) a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less;
(B) The composition for oral cavity containing 1 or more types chosen from anionic surfactant and an amphoteric surfactant.
[6]
The composition for oral cavity according to [5], wherein (a) / (b) is 0.005 to 2 as a mass ratio.
[7]
The composition for oral cavity according to [5] or [6], wherein the content of component (a) is 0.01 to 2% by mass and the content of component (b) is 0.5 to 3% by mass.
[8]
The oral composition according to any one of [5] to [7], which has a pH of 5 to 9 at 25 ° C.
[9]
The oral composition according to any one of [5] to [8], which is a dentifrice composition.
　本発明によれば、優れたバイオフィルム除去効果を与え、使用感も良い口腔バイオフィルム除去剤及びこれを含有する口腔用組成物を提供できる。本発明の口腔バイオフィルム除去剤及び口腔用組成物は、歯周疾患の予防又は抑制用として有効である。 According to the present invention, it is possible to provide an oral biofilm remover that has an excellent biofilm removal effect and has a good feeling of use, and an oral composition containing the same. The oral biofilm remover and oral composition of the present invention are effective for the prevention or suppression of periodontal diseases.
　本発明の口腔バイオフィルム除去剤は、（ａ）重量平均分子量が１，０００以上２０，０００以下であるポリアクリル酸塩と、（ｂ）アニオン性界面活性剤及び両性界面活性剤から選ばれる１種以上とが有効成分である。 The oral biofilm remover of the present invention is selected from (a) a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less, and (b) an anionic surfactant and an amphoteric surfactant. More than seeds are active ingredients.
　（ａ）成分のポリアクリル酸塩は、重量平均分子量（Ｍｗ）が１，０００以上２０，０００以下である。この場合、バイオフィルム除去効果の点から、重量平均分子量は１，０００以上であり、また、２０，０００以下、好ましくは１０，０００以下である。重量平均分子量が１，０００未満であると、バイオフィルム除去効果が劣る。２０，０００を超えると、バイオフィルム除去効果が低下し、十分な効果が得られない。
　なお、重量平均分子量の測定は、ＧＰＣ（ゲルパーミェーションクロマトグラフィー法）により、特許第５７４０８５９号公報に記載された方法及び測定条件で行った。具体的には下記に示す。
重量平均分子量の測定方法；
　重量平均分子量は、ゲル浸透クロマトグラフ／多角度レーザー光散乱検出器（ＧＰＣ－ＭＡＬＬＳ）を用いて測定された値であり、条件は以下の通りである。
　移動相：０．３Ｍ　ＮａＣｌＯ4
　ＮａＮ3水溶液カラム：ＴＳＫｇｅｌα－Ｍ　２本
　プレカラム：ＴＳＫｇｕａｒｄｃｏｌｕｍｎ　α
　標準物質：ポリエチレングリコール The polyacrylate of component (a) has a weight average molecular weight (Mw) of 1,000 or more and 20,000 or less. In this case, from the viewpoint of the biofilm removal effect, the weight average molecular weight is 1,000 or more, and is 20,000 or less, preferably 10,000 or less. When the weight average molecular weight is less than 1,000, the biofilm removal effect is poor. When it exceeds 20,000, the effect of removing the biofilm is lowered and a sufficient effect cannot be obtained.
The weight average molecular weight was measured by GPC (gel permeation chromatography) under the method and measurement conditions described in Japanese Patent No. 5740859. Specifically, it is shown below.
Measuring method of weight average molecular weight;
The weight average molecular weight is a value measured using a gel permeation chromatograph / multi-angle laser light scattering detector (GPC-MALLS), and the conditions are as follows.
Mobile phase: 0.3M NaClO 4
NaN 3 aqueous solution column: 2 TSKgelα-M Precolumn: TSKguardcolumn α
Reference material: Polyethylene glycol
　ポリアクリル酸塩は、バイオフィルム除去効果の点から直鎖状のポリアクリル酸塩が好ましい。
　塩としては、一価塩が好ましく、アルカリ金属塩又はアンモニウム塩がより好ましく、更に好ましくはアルカリ金属塩、中でもナトリウム塩がよい。
　なお、（ａ）成分に代えて、（ａ）成分以外のポリアクリル酸塩あるいはポリアクリル酸を使用した場合は、（ｂ）成分と併用してもバイオフィルム除去率が悪く、また、口腔刺激性が強くなったり、臭いや味が悪くなることがあり、本発明の目的は達成されない。
　このようなポリアクリル酸塩としては、市販品を使用し得る。 The polyacrylate is preferably a linear polyacrylate from the viewpoint of the biofilm removal effect.
The salt is preferably a monovalent salt, more preferably an alkali metal salt or an ammonium salt, still more preferably an alkali metal salt, especially a sodium salt.
In addition, when it replaces with (a) component and polyacrylic acid salt or polyacrylic acid other than (a) component is used, even if it uses together with (b) component, a biofilm removal rate is bad, and oral irritation The object of the present invention is not achieved because the property may become strong and the odor and taste may deteriorate.
A commercial item can be used as such a polyacrylate.
　（ｂ）成分は、アニオン性界面活性剤（ｂ１）及び両性界面活性剤（ｂ２）から選ばれる１種又は２種以上であり、（ｂ１）又は（ｂ２）成分を用いても（ｂ１）及び（ｂ２）成分を用いてもよいが、特に使用感の点から、少なくともアニオン性界面活性剤（ｂ１）を含むことが好ましく、（ｂ１）成分だけを用いるか、又は（ｂ１）及び（ｂ２）成分を併用することが好ましい。 The component (b) is one or more selected from the anionic surfactant (b1) and the amphoteric surfactant (b2), and even if the component (b1) or (b2) is used, (b1) and Although the component (b2) may be used, it is preferable to include at least an anionic surfactant (b1) particularly from the viewpoint of feeling in use, and only the component (b1) is used or (b1) and (b2) It is preferable to use the components in combination.
　アニオン性界面活性剤（ｂ１）としては、炭素数が好ましくは１２～１４、特に１２のアルキル基を有するアルキル硫酸塩、アシルアミノ酸塩、アシルタウリン塩が挙げられる。アシルアミノ酸塩及びアシルタウリン塩のアシル基は、それぞれ炭素数１２～１４が好ましく、より好ましくは１２である。
　具体的にアルキル硫酸塩としては、ラウリル硫酸塩、ミリスチル硫酸塩が挙げられる。アシルアミノ酸塩としては、ラウロイルグルタミン酸塩、ミリストイルグルタミン酸塩等のアシルグルタミン酸塩、ラウロイルサルコシン塩等のアシルサルコシン塩が挙げられる。アシルタウリン塩としては、ラウロイルメチルタウリン塩が挙げられる。塩は、ナトリウム塩、カリウム塩等のアルカリ金属塩が好ましい。これらは、１種を単独で又は２種以上を組み合わせて使用できるが、特にアルキル硫酸塩、アシルサルコシン塩、アシルタウリン塩が好ましい。中でも、炭素数１２の炭化水素基（ラウリル基）を有するアニオン性界面活性剤が好ましく、特にアルキル硫酸塩（ナトリウム塩）が、他の界面活性剤よりも味の点で優れることから、より好ましい。 Examples of the anionic surfactant (b1) include alkyl sulfates, acylamino acid salts, and acyl taurine salts having an alkyl group of preferably 12 to 14, particularly 12 carbon atoms. The acyl groups of the acyl amino acid salt and the acyl taurine salt each preferably have 12 to 14 carbon atoms, more preferably 12.
Specific examples of the alkyl sulfate include lauryl sulfate and myristyl sulfate. Examples of acyl amino acid salts include acyl glutamates such as lauroyl glutamate and myristoyl glutamate, and acyl sarcosine salts such as lauroyl sarcosine salt. Examples of the acyl taurine salt include lauroylmethyl taurine salt. The salt is preferably an alkali metal salt such as a sodium salt or a potassium salt. These can be used alone or in combination of two or more, and alkyl sulfates, acyl sarcosine salts, and acyl taurine salts are particularly preferable. Among these, anionic surfactants having a hydrocarbon group having 12 carbon atoms (lauryl group) are preferable, and alkyl sulfates (sodium salts) are particularly preferable because they are superior in taste to other surfactants. .
　両性界面活性剤（ｂ２）としては、ベタイン型が好ましく、炭素数１２～１４のアシル基を有するアシルアミノ酢酸ベタイン、脂肪酸アミドプロピルベタインが挙げられる。アシルアミノ酢酸ベタインとしては、アシル基の炭素数が１２～１４のものが好ましく、ラウロイルジメチルアミノ酢酸ベタインが挙げられ、脂肪酸アミドプロピルベタインとしては、ヤシ油脂肪酸アミドプロピルベタインが挙げられる。これらは、１種を単独で又は２種以上を組み合わせて使用できるが、特にアシルアミノ酢酸ベタインが好ましい。中でも、炭素数１２の炭化水素基（ラウリル基）を有するものが好ましく、ラウリルジメチルアミノ酢酸ベタインが、より好ましい。 The amphoteric surfactant (b2) is preferably a betaine type, and examples thereof include acylaminoacetic acid betaines having a C 12-14 acyl group and fatty acid amidopropyl betaines. The acylaminoacetic acid betaine preferably has an acyl group having 12 to 14 carbon atoms, and examples include lauroyldimethylaminoacetic acid betaine. The fatty acid amidopropyl betaine includes coconut oil fatty acid amidopropyl betaine. These may be used singly or in combination of two or more, and acylaminoacetic acid betaine is particularly preferred. Among them, those having a hydrocarbon group having 12 carbon atoms (lauryl group) are preferable, and lauryldimethylaminoacetic acid betaine is more preferable.
　（ａ）成分と（ｂ）成分との量比を示す（ａ）／（ｂ）は、質量比として０．００５～２が好ましく、より好ましくは０．００５～１、更に好ましくは０．０２～１、とりわけ好ましくは０．０３～０．５である。上記範囲内であると、バイオフィルム除去効果がより優れ、また、臭い、更には味も良く使用感がより改善する。０．００５以上であると、バイオフィルム除去効果がより向上し、２以下であると、臭いや味の良い使用感を十分に保つことができる。 (A) / (b) indicating the quantitative ratio of the component (a) to the component (b) is preferably 0.005 to 2, more preferably 0.005 to 1, and still more preferably 0.02 as a mass ratio. To 1, particularly preferably 0.03 to 0.5. When it is within the above range, the biofilm removing effect is more excellent, and the odor and taste are better and the feeling of use is further improved. When it is 0.005 or more, the biofilm removing effect is further improved, and when it is 2 or less, it is possible to sufficiently maintain a good feeling of smell and taste.
　本発明の口腔バイオフィルム除去剤は、有効成分として（ａ）及び（ｂ）成分を併用し、前記成分を配合することで得ることができる。また、上記有効成分のみからなる口腔バイオフィルム除去剤として使用できるが、必要に応じて、その他の口腔用として公知の任意成分を更に含んでいてもよく、この場合、任意成分は本発明の効果を妨げない範囲で配合し得る。 The oral biofilm remover of the present invention can be obtained by combining the components (a) and (b) as active ingredients. Moreover, although it can be used as an oral biofilm remover consisting of only the above active ingredient, it may further contain other optional ingredients known for oral use as necessary, in which case the optional ingredients are the effects of the present invention. Can be blended within a range not hindering
　本発明の口腔用組成物は、（ａ）及び（ｂ）成分を有効成分として含有する。口腔用組成物は、具体的にはペースト状、ジェル状又は液状の歯磨剤組成物（練歯磨、ジェル状歯磨、液状歯磨、液体歯磨等）、洗口剤、マウススプレー、塗布剤、貼付剤が挙げられ、これらに調製することができる。中でも練歯磨が好適である。 The oral composition of the present invention contains the components (a) and (b) as active ingredients. The composition for oral cavity is specifically a paste, gel or liquid dentifrice composition (toothpaste, gel dentifrice, liquid dentifrice, liquid dentifrice, etc.), mouthwash, mouse spray, coating agent, patch Can be prepared. Of these, toothpaste is preferred.
　この場合、本発明において、口腔バイオフィルム除去の有効成分である（ａ）及び（ｂ）成分は、上記特定の比率で規定することができるが、特に口腔用組成物に応用する場合は、バイオフィルム除去効果及び使用感の点から、（ａ）及び（ｂ）成分の配合量がそれぞれ後述の範囲が好ましく、これらを満たす濃度で両成分を使用することが好ましい。 In this case, in the present invention, the components (a) and (b), which are effective components for removing the oral biofilm, can be defined by the above-mentioned specific ratio. From the standpoint of film removal effect and usability, the blending amounts of the components (a) and (b) are preferably in the ranges described below, and it is preferable to use both components at a concentration satisfying these.
　（ａ）成分の配合量は、組成物全体の０．０１～２％（質量％、以下同様）が好ましく、より好ましくは０．０１～１％、更に好ましくは０．０５～０．５％である。０．０１％以上であると、十分なバイオフィルム除去効果が得られる。２％以下であると、臭いや味を良好かつ十分に維持できる。多く配合し過ぎると、臭いや味が悪くなり使用感が劣ることがある。 The blending amount of component (a) is preferably 0.01 to 2% (mass%, the same applies hereinafter), more preferably 0.01 to 1%, still more preferably 0.05 to 0.5% of the entire composition. It is. If the content is 0.01% or more, a sufficient biofilm removal effect can be obtained. If it is 2% or less, the odor and taste can be maintained satisfactorily and sufficiently. If too much is blended, the odor and taste may deteriorate and the usability may be inferior.
　（ｂ）成分の配合量は、組成物全体の０．５～３％が好ましく、より好ましくは０．５～２％、更に好ましくは１．０～２．０％である。０．５％以上であると、十分なバイオフィルム除去効果が得られる。３％以下であると、十分に口腔刺激を抑え、臭いや味を良好かつ十分に維持できる。多く配合し過ぎると、口腔刺激が強くなったり、臭いや味が悪くなり使用感が劣ることがある。 The blending amount of component (b) is preferably 0.5 to 3% of the total composition, more preferably 0.5 to 2%, and still more preferably 1.0 to 2.0%. When the content is 0.5% or more, a sufficient biofilm removal effect can be obtained. If it is 3% or less, oral irritation can be sufficiently suppressed, and the odor and taste can be maintained satisfactorily. If too much is added, the oral irritation becomes stronger, the odor and taste become worse, and the usability may be inferior.
　本発明の口腔用組成物には、任意成分として、剤型等に応じた公知成分を必要に応じて、更に配合できる。任意成分は、本発明の効果を妨げない範囲で添加することが好ましい。具体的に歯磨剤組成物には、研磨剤、粘結剤、粘稠剤、界面活性剤としてノニオン性界面活性剤やカチオン性界面活性剤、更には、甘味剤、防腐剤、有効成分、色素、香料を配合でき、これら成分と水とを混合し、製造できる。 In the composition for oral cavity of the present invention, as an optional component, a known component according to the dosage form can be further blended as necessary. The optional component is preferably added as long as the effects of the present invention are not hindered. Specifically, dentifrice compositions include abrasives, binders, thickeners, nonionic surfactants and cationic surfactants as surfactants, as well as sweeteners, preservatives, active ingredients, and pigments. Perfumes can be blended, and these components and water can be mixed and manufactured.
　研磨剤としては、第２リン酸水素カルシウム・無水和物や２水和物、第３リン酸カルシウム、第１リン酸カルシウム、炭酸カルシウム、ピロリン酸カルシウム、水酸化アルミニウム、アルミナ、無水ケイ酸、ケイ酸アルミニウム、不溶性メタリン酸ナトリウム、第３リン酸マグネシウム、炭酸マグネシウム、硫酸マグネシウム、ベントナイト、ケイ酸ジルコニウム、ポリメタリン酸メチル、その他合成樹脂を配合できる（配合量は通常、５～６０％、練歯磨の場合には１０～５５％）。 As abrasives, dibasic calcium hydrogen phosphate, anhydrous and dihydrate, tricalcium phosphate, primary calcium phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, alumina, anhydrous silicic acid, aluminum silicate, insoluble Sodium metaphosphate, tribasic magnesium phosphate, magnesium carbonate, magnesium sulfate, bentonite, zirconium silicate, polymethyl metaphosphate, and other synthetic resins can be blended (the blending amount is usually 5 to 60%, 10 for toothpaste). ~ 55%).
　特に練歯磨等のペースト状の歯磨剤組成物には、粘結剤としてアルギン酸ナトリウム、アルギン酸プロピレングリコールエステル等のアルギン酸誘導体、キサンタンガム、トラガカントガム、ジェラガム、カラヤガム、アラビアガム等のガム類、カラギーナン、カルボキシメチルセルロースナトリウム、メチルセルロース、ヒドロキシエチルセルロース、カルボキシメチルヒドロキシエチルセルロースナトリウム等のセルロース誘導体、ポリビニルアルコール、カルボキシビニルポリマー、ポリビニルピロリドン等の有機粘結剤、シリカゲル、アルミニウムシリカゲル、ビーガム、ラポナイト等の無機粘結剤を配合できる（配合量は通常、０．３～１０％）。 Especially for paste-like dentifrice compositions such as toothpaste, alginic acid derivatives such as sodium alginate and propylene glycol alginate as a binder, gums such as xanthan gum, tragacanth gum, gela gum, karaya gum, gum arabic, carrageenan, carboxymethylcellulose Cellulose derivatives such as sodium, methylcellulose, hydroxyethylcellulose, sodium carboxymethylhydroxyethylcellulose, organic binders such as polyvinyl alcohol, carboxyvinyl polymer, and polyvinylpyrrolidone, and inorganic binders such as silica gel, aluminum silica gel, bee gum, and laponite can be blended. (The amount is usually 0.3 to 10%).
　更に、特にペースト状や液状の歯磨剤組成物には、粘稠剤として、ソルビトール、マルチトール、ラクチトール、エリスリトール等の糖アルコール、プロピレングリコール等の多価アルコールを配合でき、これらのうちの１種又は２種以上を配合し得る（配合量は通常、５～７０％）。 Furthermore, particularly in paste-like or liquid dentifrice compositions, sugar alcohols such as sorbitol, maltitol, lactitol, erythritol, and polyhydric alcohols such as propylene glycol can be blended as a thickening agent. Alternatively, two or more kinds can be blended (the blending amount is usually 5 to 70%).
　ノニオン性界面活性剤としては、ショ糖脂肪酸エステル等の糖脂肪酸エステル；マルチトール脂肪酸エステル等の糖アルコール脂肪酸エステル；ポリオキシエチレンソルビタンモノステアレート等のポリオキシエチレンソルビタン脂肪酸エステル；ポリオキシエチレン硬化ヒマシ油等のポリオキシエチレン脂肪酸エステル；ラウリン酸モノ又はジエタノールアミド等の脂肪酸ジエタノールアミド；ポリオキシエチレン高級アルコールエーテルを配合できる。中でも、ポリオキシエチレン脂肪酸エステル、特に酸化エチレンの付加モル数（Ｅ．Ｏ．、以下同様）が２０～１００、とりわけ２０～８０のポリオキシエチレン硬化ヒマシ油が、バイオフィルム除去効果の点で、より好適である。
　カチオン性界面活性剤としては、塩化ジステアリルメチルアンモニウム等のアルキルアンモニウム塩、塩化ステアリルジメチルベンジルアンモニウム等のアルキルベンジルアンモニウム塩等が挙げられる。
　ノニオン性界面活性剤及びカチオン性界面活性剤の配合量は、合計で０．０１～１０％が好ましい。
　なお、本発明では、界面活性剤として（ｂ）成分と共にノニオン性界面活性剤を配合することが好ましい。（ａ）成分に、ノニオン性界面活性剤、特にポリオキシエチレン硬化ヒマシ油を併用するとその添加量によって臭いや味が悪くなることがあるが、（ｂ）成分と共にノニオン性界面活性剤を添加すると、このように使用感が悪化することなくバイオフィルム除去効果がより向上する。 Nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid esters; sugar alcohol fatty acid esters such as maltitol fatty acid esters; polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monostearate; polyoxyethylene cured castor Polyoxyethylene fatty acid esters such as oil; fatty acid diethanolamides such as lauric acid mono- or diethanolamide; polyoxyethylene higher alcohol ethers can be blended. Among them, polyoxyethylene fatty acid ester, particularly polyoxyethylene hydrogenated castor oil having an added mole number of ethylene oxide (EO, the same applies hereinafter) of 20 to 100, particularly 20 to 80, is effective in removing biofilms. More preferred.
Examples of the cationic surfactant include alkylammonium salts such as distearylmethylammonium chloride, alkylbenzylammonium salts such as stearyldimethylbenzylammonium chloride, and the like.
The total amount of the nonionic surfactant and the cationic surfactant is preferably 0.01 to 10%.
In addition, in this invention, it is preferable to mix | blend nonionic surfactant with (b) component as surfactant. When a nonionic surfactant, particularly polyoxyethylene hydrogenated castor oil, is used in combination with the component (a), the odor and taste may be deteriorated depending on the amount added, but when the nonionic surfactant is added together with the component (b) Thus, the biofilm removal effect is further improved without deteriorating the feeling of use.
　甘味剤としては、サッカリンナトリウム、ステビオサイド、グリチルリチン酸ジカリウム、ペリラルチン、ソーマチン、ネオヘスペリジルジヒドロカルコン、アスパラチルフェニルアラニンメチルエステルが挙げられる。防腐剤としては、パラオキシ安息香酸エステル、安息香酸ナトリウムが挙げられる。 Sweetening agents include sodium saccharin, stevioside, dipotassium glycyrrhizinate, perilartin, thaumatin, neohesperidyl dihydrochalcone, and aspartylphenylalanine methyl ester. Examples of the preservative include p-hydroxybenzoate ester and sodium benzoate.
　有効成分としては、デキストラナーゼ、ムタナーゼ、リゾチーム、アミラーゼ、プロテアーゼ、溶菌酵素、ＳＯＤ（スーパーオキシドディスムターゼ）等の酵素；モノフルオロリン酸ナトリウム、モノフルオロリン酸カリウム等のアルカリ金属モノフルオロフォスフェート；フッ化ナトリウム、フッ化第一錫等のフッ化物；トラネキサム酸、イプシロンアミノカプロン酸、アルミニウムクロルヒドロキシルアラントイン、ジヒドロコレスタノール、グリチルリチン酸、グリチルレチン酸、グリセロフォスフェート、クロロフィル、塩化ナトリウム、キシリトール、塩化亜鉛、水溶性無機リン酸化物や、ビタミンＡ、ビタミンＢ群、ビタミンＣ、ビタミンＥ等のビタミン類が挙げられる。これら有効成分は、１種又は２種以上で使用でき、また、本発明の効果を妨げない範囲で有効量配合することができる。 As active ingredients, enzymes such as dextranase, mutanase, lysozyme, amylase, protease, lytic enzyme, SOD (superoxide dismutase); 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, dihydrocholestanol, glycyrrhizic acid, glycyrrhetinic acid, glycerophosphate, chlorophyll, sodium chloride, xylitol, zinc chloride, Examples include water-soluble inorganic phosphates and vitamins such as vitamin A, vitamin B group, vitamin C, and vitamin E. These active ingredients can be used alone or in combination of two or more, and can be blended in an effective amount as long as the effects of the present invention are not hindered.
　香料は、ペパーミント油、スペアミント油、アニス油、ユーカリ油、ウィンターグリーン油、カシア油、クローブ油、タイム油、セージ油、レモン油、オレンジ油、ハッカ油、カルダモン油、コリアンダー油、マンダリン油、ライム油、ラベンダー油、ローズマリー油、ローレル油、カモミル油、キャラウェイ油、マジョラム油、ベイ油、レモングラス油、オリガナム油、パインニードル油、ネロリ油、ローズ油、ジャスミン油、イリスコンクリート、アブソリュートペパーミント、アブソリュートローズ、オレンジフラワー等の天然香料、及び、これら天然香料の加工処理（前溜部カット、後溜部カット、分留、液液抽出、エッセンス化、粉末香料化等）した香料、及び、メントール、カルボン、アネトール、サリチル酸メチル、シンナミックアルデヒド、３－ｌ－メントキシプロパン－１，２－ジオール、リナロール、リナリールアセテート、リモネン、メントン、メンチルアセテート、Ｎ－置換－パラメンタン－３－カルボキサミド、ピネン、オクチルアルデヒド、シトラール、プレゴン、カルビールアセテート、アニスアルデヒド、エチルアセテート、エチルブチレート、アリルシクロヘキサンプロピオネート、メチルアンスラニレート、エチルメチルフェニルグリシデート、バニリン、ウンデカラクトン、ヘキサナール、イソアミルアルコール、ヘキセノール、ジメチルサルファイド、シクロテン、フルフラール、トリメチルピラジン、エチルラクテート、エチルチオアセテート等の単品香料、更に、ストロベリーフレーバー、アップルフレーバー、バナナフレーバー、パイナップルフレーバー、グレープフレーバー、マンゴーフレーバー、バターフレーバー、ミルクフレーバー、フルーツミックスフレーバー、トロピカルフルーツフレーバー等の調合香料が挙げられ、口腔用組成物に用いられる公知の香料素材を使用でき、実施例の香料に限定されない。
　また、上記の香料素材は、組成物全体の０．０００００１～１％使用するのが好ましい。上記香料素材を使用した賦香用香料としては、製剤組成中に０．００１～２．０％使用するのが好ましい。 Perfumes are peppermint oil, spearmint oil, anise oil, eucalyptus oil, wintergreen oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamom oil, coriander oil, mandarin oil, lime Oil, lavender oil, rosemary oil, laurel oil, camomil oil, caraway oil, marjoram oil, bay oil, lemongrass oil, origanum oil, pine needle oil, neroli oil, rose oil, jasmine oil, iris concrete, absolute peppermint Natural fragrances such as absolute rose and orange flower, and fragrances that have been processed (front reservoir cut, rear reservoir cut, fractional distillation, liquid-liquid extraction, essence, powder fragrance, etc.), and Menthol, Carvone, Anethole, Methyl salicylate, Cinnami Cualdehyde, 3-l-menthoxypropane-1,2-diol, linalool, linalyl acetate, limonene, menthone, menthyl acetate, N-substituted-paramentane-3-carboxamide, pinene, octylaldehyde, citral, pulegone, calgon Beer acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allyl cyclohexane propionate, methyl anthranilate, ethyl methyl phenyl glycidate, vanillin, undecalactone, hexanal, isoamyl alcohol, hexenol, dimethyl sulfide, cycloten, furfural, Single flavors such as trimethylpyrazine, ethyl lactate, ethylthioacetate, strawberry flavor, apple flavor, banana flavor, Formulated fragrances such as pineapple flavor, grape flavor, mango flavor, butter flavor, milk flavor, fruit mix flavor, tropical fruit flavor, etc. can be used, and known fragrance materials used in oral compositions can be used. It is not limited to.
Further, the above fragrance material is preferably used in an amount of 0.000001 to 1% of the entire composition. As the flavoring fragrance using the fragrance material, it is preferable to use 0.001 to 2.0% in the preparation composition.
　口腔用組成物のｐＨ（２５℃）は、好ましくは５～９、より好ましくは６～８である。ｐＨが低すぎると、口腔刺激性や、エナメル質及び象牙質の脱灰のおそれがある。ｐＨが高すぎると、口腔刺激性や、製剤安定性の低下が発生する場合がある。 The pH (25 ° C.) of the oral composition is preferably 5 to 9, more preferably 6 to 8. If the pH is too low, there is a risk of oral irritation and demineralization of enamel and dentin. If the pH is too high, oral irritation and a decrease in formulation stability may occur.
　なお、ｐＨ調整剤を添加してもよい。ｐＨ調整剤としては、無機酸、有機酸やこれらの塩を用いることできる。例えば、酢酸、塩酸、硫酸、硝酸、クエン酸、リン酸、リンゴ酸、グルコン酸、マレイン酸、コハク酸、グルタミン酸、水酸化ナトリウム、水酸化カリウム、酢酸ナトリウム、炭酸ナトリウム、クエン酸ナトリウム、クエン酸水素ナトリウム、リン酸ナトリウム、リン酸二水素ナトリウムが挙げられる。 A pH adjuster may be added. As the pH adjuster, inorganic acids, organic acids, and salts thereof can be used. For example, acetic acid, hydrochloric acid, sulfuric acid, nitric acid, citric acid, phosphoric acid, malic acid, gluconic acid, maleic acid, succinic acid, glutamic acid, sodium hydroxide, potassium hydroxide, sodium acetate, sodium carbonate, sodium citrate, citric acid Examples include sodium hydrogen, sodium phosphate, and sodium dihydrogen phosphate.
　本発明の口腔用組成物は、アルミニウムチューブ、アルミニウム箔の両面をプラスチック等でラミネートしたラミネートチューブ、プラスチックチューブ、あるいは、ボトル状容器、エアゾール容器等の所定の容器に入れて使用することができる。 The oral composition of the present invention can be used by placing it in a predetermined container such as an aluminum tube, a laminated tube obtained by laminating both surfaces of an aluminum foil with plastic, a plastic tube, a bottle-shaped container, an aerosol container or the like.
　以下、実施例及び比較例を示し、本発明を具体的に説明するが、本発明は下記の実施例に制限されるものではない。なお、下記の例において％は特に断らない限りいずれも質量％を示す。
　なお、重量平均分子量は、ゲル浸透クロマトグラフ／多角度レーザー光散乱検出器（ＧＰＣ－ＭＡＬＬＳ）を用いて測定された値であり、条件は以下の通りである。
　移動相：０．３Ｍ　ＮａＣｌＯ4
　ＮａＮ3水溶液カラム：ＴＳＫｇｅｌα－Ｍ　２本
　プレカラム：ＴＳＫｇｕａｒｄｃｏｌｕｍｎ　α
　標準物質：ポリエチレングリコール
　また、組成物のｐＨは、２５℃における値である。 EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. In the following examples, “%” means “% by mass” unless otherwise specified.
The weight average molecular weight is a value measured using a gel permeation chromatograph / multi-angle laser light scattering detector (GPC-MALLS), and the conditions are as follows.
Mobile phase: 0.3M NaClO 4
NaN 3 aqueous solution column: 2 TSKgelα-M Precolumn: TSKguardcolumn α
Standard substance: polyethylene glycol The pH of the composition is a value at 25 ° C.
　［実施例、比較例］
　表１～３に示す組成の歯磨剤組成物（練歯磨）を以下の方法で調製して容器（アルミニウムラミネートチューブ）に充填し、下記方法で評価した。結果を表に併記した。 [Examples and Comparative Examples]
Dentifrice compositions (toothpaste) having the compositions shown in Tables 1 to 3 were prepared by the following method, filled in containers (aluminum laminate tubes), and evaluated by the following methods. The results are shown in the table.
＜調製方法＞
（１）精製水中に（ａ）成分、その他の水溶性成分及び粘度調整剤を常温で混合溶解させた（混合物Ｘ）。
（２）プロピレングリコール中に粘結剤を常温で分散させ（混合物Ｙ）、撹拌中の混合物Ｘ中に、混合物Ｙを添加混合して、混合物Ｚを調製した。
（３）混合物Ｚ中に、香料、（ｂ）成分及び研磨剤を、ニーダーを用いて常温で混合し、減圧（５．３ｋＰａ）による脱泡を行い、歯磨剤組成物を得た。
　なお、比較例の歯磨剤組成物は、上記方法に準じて調製した。 <Preparation method>
(1) The component (a), other water-soluble components, and a viscosity modifier were mixed and dissolved at room temperature in purified water (mixture X).
(2) A binder was dispersed in propylene glycol at room temperature (mixture Y), and the mixture Y was added and mixed into the stirring mixture X to prepare a mixture Z.
(3) In the mixture Z, a fragrance | flavor, (b) component, and abrasive | polishing agent were mixed at normal temperature using the kneader, defoaming by pressure reduction (5.3kPa) was performed, and the dentifrice composition was obtained.
In addition, the dentifrice composition of the comparative example was prepared according to the said method.
＜バイオフィルム除去効果の評価方法＞
（１）モデルバイオフィルムの作製方法
　モデルバイオフィルムを作製するために用いた細菌は、アメリカンタイプカルチャーコレクション（ＡＴＣＣ）より購入し、以下の方法によりプレカルチャーを行った。
　アクチノマイセス　ヴィスコサス（Ａｃｔｉｎｏｍｙｃｅｓ　ｖｉｓｃｏｓｕｓ）ＡＴＣＣ４３１４６、フゾバクテリウム　ヌクレアタム（Ｆｕｓｏｂａｃｔｅｒｉｕｍ　ｎｕｃｌｅａｔｕｍ）ＡＴＣＣ１０９５３、ポルフィロモナス　ジンジバリス（Ｐｏｒｐｈｙｒｏｍｏｎａｓ　ｇｉｎｇｉｖａｌｉｓ）ＡＴＣＣ３３２７７は、５ｍｇ／Ｌ　ヘミン（Ｓｉｇｍａ社製）及び１ｍｇ／Ｌ　ビタミンＫ（和光純薬工業社製）を含むトッドへヴィットブロス（Ｂｅｃｔｏｎ　ａｎｄ　Ｄｉｃｋｉｎｓｏｎ社製）培養液〔ＴＨＢＨＭ〕により培養し、ベイヨネラ　パルビュラ（Ｖｅｉｌｌｏｎｅｌｌａ　ｐａｒｖｕｌａ）ＡＴＣＣ１７７４５は、１．２６％乳酸ナトリウム（Ｓｉｇｍａ社製）を含むトッドへヴィットブロス（Ｂｅｃｔｏｎ　ａｎｄ　Ｄｉｃｋｉｎｓｏｎ社製）培養液〔ＴＨＢＬ〕により培養した。なお、培養は、３７℃で一晩嫌気培養（８０ｖｏｌ％窒素、１０ｖｏｌ％二酸化炭素、１０ｖｏｌ％水素）した。
　培養後、菌液は遠心分離（１０，０００ｒｐｍ、１０分）により集菌した。遠心集菌した各細菌は、ベイサルメディウムムチン培養液〔ＢＭＭ〕*1に再懸濁した後、予め同培地１，０００ｍＬを入れた培養槽に、菌数がそれぞれ１×１０7個／ｍＬになるように接種し、３７℃において嫌気条件下（９５ｖｏｌ％窒素、５ｖｏｌ％二酸化炭素）で一晩培養した。その後、ＢＭＭを１００ｍＬ／時間の速度で供給するとともに、同速度で培養液を排出した。上記培養槽から排出された培養液は、液量が３００ｍＬに保たれる別の培養槽に連続的に供給した。この培養槽内の回転盤（約８０ｒｐｍで回転）には、バイオフィルムの付着担体として直径７ｍｍのハイドロキシアパタイト板（ペンタックス社製）を装着した。
　上記方法による培養は、１０日間連続して行い、ハイドロキシアパタイト板上にバイオフィルムを形成させた。培養後、取り出したバイオフィルム形成ハイドロキシアパタイト板をリン酸緩衝生理食塩水*2（Ｐｈｏｓｐｈａｔｅ　Ｂｕｆｆｅｒｅｄ　Ｓａｌｉｎｅ、以下ＰＢＳとする）５ｍＬで２回洗浄し、モデルバイオフィルムを得た。 <Evaluation method of biofilm removal effect>
(1) Method for producing model biofilm The bacteria used for producing the model biofilm were purchased from American Type Culture Collection (ATCC) and precultured by the following method.
Actinomyces viscosus ATCC 43146, Fusobacterium nucleatum ATCC10953, Porphyromonas gingivalis, ATCC 33727 Todd Hewitt broth (manufactured by Becton and Dickinson) medium (THBHM) and Baylonella parvula ATCC 17745 is Todd Hewitt broth containing 1.26% sodium lactate (Sigma) (Becton and Dickins They were cultured by n Co., Ltd.) culture [THBL]. The culture was anaerobic culture overnight at 37 ° C. (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% hydrogen).
After culturing, the bacterial solution was collected by centrifugation (10,000 rpm, 10 minutes). Each bacterium collected by centrifugation was resuspended in a basal medium mucin culture solution [BMM] * 1 and then the number of bacteria was 1 × 10 7 cells / mL in a culture tank containing 1,000 mL of the same medium in advance. And inoculated overnight at 37 ° C. under anaerobic conditions (95 vol% nitrogen, 5 vol% carbon dioxide). Thereafter, BMM was supplied at a rate of 100 mL / hour, and the culture solution was discharged at the same rate. The culture solution discharged from the culture tank was continuously supplied to another culture tank in which the liquid volume was kept at 300 mL. A hydroxyapatite plate (manufactured by PENTAX) having a diameter of 7 mm was attached to the turntable (rotated at about 80 rpm) in the culture tank as a biofilm adhesion carrier.
The culture by the above method was carried out continuously for 10 days, and a biofilm was formed on the hydroxyapatite plate. After the culture, the biofilm-formed hydroxyapatite plate was washed twice with 5 mL of phosphate buffered saline * 2 (hereinafter referred to as PBS) to obtain a model biofilm.
＊１；ＢＭＭの組成（１リットル中の質量で表す。）
プロテオースペプトン（Ｂｅｃｔｏｎ　ａｎｄ　Ｄｉｃｋｉｎｓｏｎ社
製）：　　　　　　　　　　　　　　　　　　　　　　４ｇ／Ｌ
トリプトン（Ｂｅｃｔｏｎ　ａｎｄ　Ｄｉｃｋｉｎｓｏｎ社製）：
　　　　　　　　　　　　　　　　　　　　　　　　　２ｇ／Ｌ
イーストエキス（Ｂｅｃｔｏｎ　ａｎｄ　Ｄｉｃｋｉｎｓｏｎ社製）：
　　　　　　　　　　　　　　　　　　　　　　　　　２ｇ／Ｌ
ムチン（Ｓｉｇｍａ社製）：　　　　　　　　　　　　５ｇ／Ｌ
ヘミン（Ｓｉｇｍａ社製）：　　　　　　　　　　　　２．５ｍｇ／Ｌ
ビタミンＫ（和光純薬工業社製）：　　　　　　　　　０．５ｍｇ／Ｌ
ＫＣｌ（和光純薬工業社製）：　　　　　　　　　　　１ｇ／Ｌ
システイン（和光純薬工業社製）：　　　　　　　　　０．２ｇ／Ｌ
蒸留水：　　　　　　　　　　　　　　　　　　　　　残
（全量が１Ｌになるようにメスアップし、１２１℃で２０分間オートク
レーブした。） * 1; BMM composition (expressed in mass per liter)
Proteose peptone (Becton and Dickinson): 4g / L
Tryptone (Becton and Dickinson):
2g / L
Yeast extract (Becton and Dickinson):
2g / L
Mucin (Sigma): 5g / L
Hemin (manufactured by Sigma): 2.5 mg / L
Vitamin K (manufactured by Wako Pure Chemical Industries, Ltd.): 0.5mg / L
KCl (Wako Pure Chemical Industries, Ltd.): 1g / L
Cysteine (Wako Pure Chemical Industries, Ltd.): 0.2 g / L
Distilled water: Residue (Med up so that the total amount becomes 1 L, and autoclaved at 121 ° C. for 20 minutes.)
＊２；ＰＢＳの組成（１リットル中の質量で表す。）
ＮａＣｌ（和光純薬工業社製）：　　　　　　　　　　８．０ｇ
ＫＣｌ（和光純薬工業社製）：　　　　　　　　　　　０．２ｇ
Ｎａ2ＨＰＯ4・１２Ｈ2Ｏ（和光純薬工業社製）：　　  ３．６３ｇ
ＫＨ2ＰＯ4（和光純薬工業社製）：　　　　　　　　　 ０．２４ｇ
蒸留水：　　　　　　　　　　　　　　　　　　　　　残
（１Ｎ　ＨＣｌによりｐＨ７．４に調整し、全量が１Ｌになるようにメ
スアップした。） * 2: PBS composition (expressed in mass per liter)
NaCl (manufactured by Wako Pure Chemical Industries, Ltd.): 8.0 g
KCl (Wako Pure Chemical Industries, Ltd.): 0.2g
Na 2 HPO 4 · 12H 2 O (manufactured by Wako Pure Chemical Industries): 3.63 g
KH 2 PO 4 (Wako Pure Chemical Industries, Ltd.): 0.24g
Distilled water: remaining (adjusted to pH 7.4 with 1N HCl and made up to 1 L in total)
（２）モデルバイオフィルムの除去効果の評価方法
　（１）で作製したモデルバイオフィルム形成ハイドロキシアパタイト板は、２４穴マルチプレート（住友ベークライト社製）に移した。これに、試験組成物として上記方法で調製した歯磨剤組成物を、人工唾液（５０ｍＭ　ＫＣｌ、１ｍＭ　ＣａＣｌ2、０．１ｍＭ　ＭｇＣｌ2、１ｍＭ　ＫＨ2ＰＯ4、ｐＨ７．０）で３倍希釈した歯磨剤溶液の遠心上清（１０，０００ｒｐｍ、１０分）を２ｍＬ加え、３分間浸漬した。その後、ＰＢＳ（和光純薬工業社製）１ｍＬで６回洗浄し、上記と同バッファー２ｍＬを添加した試験管（直径１３ｍｍ×１００ｍｍ）内で超音波処理（２００μＡ、１０秒間）により、残ったバイオフィルムを強制的に分散させた。この分散液の波長５５０ｎｍでの濁度（ＯＤ）を測定し、バイオフィルムの残存量を測定した。
　試験組成物のバイオフィルム除去効果は、下式によりコントロールに対する除去率を求め、この除去率から、下記基準に則り口腔バイオフィルム除去効果を判定した。
　なお、上記歯磨剤溶液の代わりにＰＢＳ２ｍｌを用いて同様に処置したものをコントロールとした。
　バイオフィルム除去率（％）＝
　｛（コントロールの濁度－試験組成物処置品の濁度）／コントロールの濁
　度｝×１００
　バイオフィルム除去効果の判定基準
　　◎：バイオフィルム除去率が９０％以上
　　○：バイオフィルム除去率が７０％以上９０％未満
　　△：バイオフィルム除去率が５０％以上７０％未満
　　×：バイオフィルム除去率が５０％未満 (2) Method for Evaluating Model Biofilm Removal Effect The model biofilm-formed hydroxyapatite plate produced in (1) was transferred to a 24-hole multiplate (manufactured by Sumitomo Bakelite). To this, a dentifrice composition prepared by the above method as a test composition was diluted 3 times with artificial saliva (50 mM KCl, 1 mM CaCl 2 , 0.1 mM MgCl 2 , 1 mM KH 2 PO 4 , pH 7.0). 2 mL of the centrifugal supernatant (10,000 rpm, 10 minutes) of the agent solution was added and immersed for 3 minutes. After that, the cells were washed 6 times with 1 mL of PBS (manufactured by Wako Pure Chemical Industries, Ltd.), and remained in the test tube (diameter 13 mm × 100 mm) to which 2 mL of the same buffer was added by sonication (200 μA, 10 seconds). The film was forced to disperse. The turbidity (OD) at a wavelength of 550 nm of this dispersion was measured, and the residual amount of the biofilm was measured.
The biofilm removal effect of the test composition was determined by calculating the removal rate relative to the control by the following formula, and determining the oral biofilm removal effect from this removal rate according to the following criteria.
A control treated in the same manner using 2 ml of PBS instead of the above dentifrice solution was used as a control.
Biofilm removal rate (%) =
{(Turbidity of control-turbidity of treated product of test composition) / turbidity of control} × 100
Criteria for Biofilm Removal Effect ◎: Biofilm removal rate is 90% or more ○: Biofilm removal rate is 70% or more and less than 90% △: Biofilm removal rate is 50% or more and less than 70% ×: Biofilm removal rate is Less than 50%
＜使用感の評価方法＞
　１０名の被験者が、歯磨剤組成物１ｇを歯ブラシにのせ、３分間ブラッシングして口腔内を洗浄した際の使用感として口腔刺激性、臭い（口腔刺激のなさ、臭いのなさ）を下記の評価基準により評価した。１０人の評価点の平均を算出し、下記の判定基準により判定した。 <Evaluation method of feeling of use>
Ten test subjects put 1g of the dentifrice composition on a toothbrush and brushed for 3 minutes to clean the oral cavity. As a result, oral irritation and odor (no oral irritation, no odor) were evaluated as follows. Evaluation was made according to the criteria. The average of 10 evaluation points was calculated and determined according to the following criteria.
　口腔刺激性の評価基準
　　４点：口腔内で刺激を感じない
　　３点：口腔内でやや刺激を感じるが問題ないレベル
　　２点：口腔内で刺激を感じる
　　１点：口腔内で非常に刺激を感じる
　口腔刺激性の判定基準
　　◎：平均点３．０点以上
　　○：平均点２．５点以上３．０点未満
　　△：平均点１．５点以上２．５点未満
　　×：平均点１．５点未満
　臭いの評価基準
　　４点：口腔内で不快な臭いを感じない
　　３点：口腔内で不快な臭いをやや感じるが問題ないレベル
　　２点：口腔内で不快な臭いを感じる
　　１点：口腔内で不快な臭いを強く感じる
　臭いの判定基準
　　◎：平均点３．５点以上
　　○：平均点３．０点以上３．５点未満
　　△：平均点２．０点以上３．０点未満
　　×：平均点２．０点未満 Evaluation criteria for oral irritation 4 points: I do not feel irritation in the oral cavity 3 points: I feel a little irritation in the oral cavity but no problem 2 points: I feel irritation in the oral cavity 1 point: I feel very irritation in the oral cavity Judgment criteria for oral irritation ◎: Average score of 3.0 or more ○: Average score of 2.5 or more and less than 3.0 △: Average score of 1.5 or more and less than 2.5 ×: Average score of 1.5 Less than the point Evaluation criteria for odor 4 points: Feeling unpleasant odor in the oral cavity 3 points: Feeling an unpleasant odor somewhat in the oral cavity but no problem 2 points: Feeling an unpleasant odor in the oral cavity 1 point: In the oral cavity Unpleasant odor is strongly felt Odor judgment criteria ◎: Average score of 3.5 points or more ○: Average score of 3.0 points or more and less than 3.5 points △: Average score of 2.0 points or more and less than 3.0 points ×: Average point less than 2.0
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
　なお、使用したポリアクリル酸ナトリウム、ポリアクリル酸の詳細を下記に示す。
（ａ）ポリアクリル酸ナトリウム（Ｍｗ１，０００）：ポリサイエンス
　　　社製
（ａ）ポリアクリル酸ナトリウム（Ｍｗ６，０００）：東亞合成社製、
　　　ＡＣ－１０ＮＰ
（ａ）ポリアクリル酸ナトリウム（Ｍｗ８，０００）：ポリサイエンス
　　　社製
（ａ）ポリアクリル酸ナトリウム（Ｍｗ２０，０００）：東亞合成社製
　　　、アロンＡ－２０ＵＮ
ポリアクリル酸ナトリウム（Ｍｗ３００，０００、比較品）：ポリサイ
エンス社製
ポリアクリル酸（Ｍｗ６，０００、比較品）：東亞合成社製、アロンＡ
－１０ＳＬ Details of the sodium polyacrylate and polyacrylic acid used are shown below.
(A) Sodium polyacrylate (Mw 1,000): manufactured by Polysciences (a) Sodium polyacrylate (Mw 6,000): manufactured by Toagosei Co., Ltd.
AC-10NP
(A) Sodium polyacrylate (Mw 8,000): manufactured by Polysciences (a) Sodium polyacrylate (Mw 20,000): manufactured by Toagosei Co., Ltd., Aron A-20UN
Sodium polyacrylate (Mw 300,000, comparative product): Polyacrylic acid (Mw 6,000, comparative product) manufactured by Polysciences: Toagosei Co., Ltd., Aron A
-10SL

Claims (9)

  1. 　（ａ）重量平均分子量が１，０００以上２０，０００以下であるポリアクリル酸塩と、
    （ｂ）アニオン性界面活性剤及び両性界面活性剤から選ばれる１種以上と
    からなる口腔バイオフィルム除去剤。     (A) a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less;
    (B) An oral biofilm remover comprising at least one selected from an anionic surfactant and an amphoteric surfactant.
  2. 　（ａ）／（ｂ）が質量比として０．００５～２である請求項１記載の口腔バイオフィルム除去剤。 2. The oral biofilm remover according to claim 1, wherein (a) / (b) is 0.005 to 2 as a mass ratio.
  3. 　（ａ）／（ｂ）が質量比として０．０２～１である請求項２記載の口腔バイオフィルム除去剤。 The oral biofilm remover according to claim 2, wherein (a) / (b) is 0.02 to 1 as a mass ratio.
  4. 　アニオン性界面活性剤が、炭素数１２～１４のアルキル基を有するアルキル硫酸塩、アシルアミノ酸塩及びアシルタウリン塩から選ばれ、両性界面活性剤が、炭素数１２～１４のアシル基を有するアシルアミノ酢酸ベタイン及び脂肪酸アミドプロピルベタインから選ばれる請求項１～３のいずれか１項記載の口腔バイオフィルム除去剤。 The anionic surfactant is selected from alkyl sulfates, acyl amino acid salts and acyl taurine salts having an alkyl group having 12 to 14 carbon atoms, and the amphoteric surfactant is an acylaminoacetic acid having an acyl group having 12 to 14 carbon atoms. The oral biofilm remover according to any one of claims 1 to 3, selected from betaine and fatty acid amidopropyl betaine.
  5. 　（ａ）重量平均分子量が１，０００以上２０，０００以下であるポリアクリル酸塩と、
    （ｂ）アニオン性界面活性剤及び両性界面活性剤から選ばれる１種以上と
    を含有する口腔用組成物。     (A) a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less;
    (B) The composition for oral cavity containing 1 or more types chosen from anionic surfactant and an amphoteric surfactant.
  6. 　（ａ）／（ｂ）が質量比として０．００５～２である請求項５記載の口腔用組成物。 The composition for oral cavity according to claim 5, wherein (a) / (b) is 0.005 to 2 as a mass ratio.
  7. 　（ａ）成分の含有量が０．０１～２質量％、（ｂ）成分の含有量が０．５～３質量％である請求項５又は６記載の口腔用組成物。 The oral composition according to claim 5 or 6, wherein the content of the component (a) is 0.01 to 2% by mass, and the content of the component (b) is 0.5 to 3% by mass.
  8. 　２５℃におけるｐＨ５～９である請求項５～７のいずれか１項記載の口腔用組成物。 The oral composition according to any one of claims 5 to 7, which has a pH of 5 to 9 at 25 ° C.
  9. 　歯磨剤組成物である請求項５～８のいずれか１項記載の口腔用組成物。 The oral composition according to any one of claims 5 to 8, which is a dentifrice composition.
PCT/JP2018/016062 2017-04-21 2018-04-19 Oral biofilm removing agent and oral composition WO2018194111A1 (en)

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CN201880023827.0A CN110494123A (en) 2017-04-21 2018-04-19 Oral biological film remover and composition for oral cavity
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