JP5552725B2 - Oral composition and oral biofilm disinfectant - Google Patents

Description

The present invention is excellent in the effect of sterilizing pathogenic plaque (oral biofilm) by sterilizing and bacteriostatic of plaque adhering to the oral cavity, particularly pathogenic bacteria in the oral biofilm, and suppressing the formation of plaque. The present invention relates to a composition for oral cavity and an oral biofilm disinfectant that are effective for the oral cavity.

  The cause of oral diseases such as dental caries, periodontal disease, and bad breath is thought to be due to various bacteria in dental plaque, and caries is streptococcus such as Streptococcus mutans (S. mutans), periodontal disease is It is a bacterial infection mainly consisting of obligate anaerobic gram-negative bacilli such as P. gingivalis, and oral bacteria such as Fusobacterium nucleatum are involved as the cause of bad breath. Yes. Accordingly, it is said that it is useful to suppress plaque, that is, to sterilize and bacterize pathogenic bacteria in the oral cavity as an effective means for prevention and improvement of oral diseases.

  In recent years, plaque has been regarded as a biofilm (see Non-Patent Document 1), and bacteria in oral biofilms have a bacterial protein expression pattern (see Non-Patent Documents 2 and 3) and drug resistance (non-patent documents). Patent Documents 4 and 5) are greatly different, and it has become clear that a drug effective against planktonic bacteria is not effective against biofilm-forming bacteria.

  To date, many antibacterial agents such as cetylpyridinium chloride, chlorhexidine, benzethonium chloride, benzalkonium chloride, depotassium chloride, and other nonionic antibacterial agents such as isopropylmethylphenol and triclosan have been used as bactericidal means. It is conventionally known that it is blended into a composition for use and is effective in preventing and improving oral diseases. For example, triclosan is known to be added to a dentifrice composition as a dental plaque inhibitor (see Patent Document 1), and a phenolic compound such as thymol is also added to the oral composition to suppress dental plaque. Is known (see Patent Document 2).

  However, these antibacterial agents have been confirmed to be insufficient in biofilm suppression effect due to the drug resistance mechanism of biofilm bacteria, and in order to enhance their bactericidal power, the antibacterial agent retention technology (Patent Document 3) (See Patent Documents 4 and 5), and the use of biofragrance ingredients such as farnesol having antiseptic and antibacterial activity has been proposed. As a result, a remarkable effect could not be expected. From such a current situation, an effective sterilization technique is also desired against bacteria in biofilms.

  Further, as a biofilm suppressing composition, a combination of a hydrophobic amino acid and an ammonium salt (see Patent Document 3), a lactone and / or furan derivative (see Patent Document 5), a nonionic antibacterial agent and a dicarboxylic acid compound ( (See Patent Document 6).

  However, these technologies have problems in terms of cost, supplyability, formulation stability, etc., and have not yet been introduced into the market. Effective sterilization against bacteria in oral biofilms is an alternative. Technology development is desired.

JP 60-239410 A Special table 2001-526202 gazette JP 08-26953 A JP 2002-370953 A JP 2004-155681 A JP 2005-015369 A JP 2006-199661 A JP 2007-091703 A Costerton, J.M. W. Stewart, P.M. S. and Greenberg, E .; P. : Bacterial biofilms: a common cause of persistent indications. Science 284: 1318-1322, 1999. Costerton, J.M. W. Lewandowski, Z .; Caldwell, D .; E. Korber, D .; R. and Lappin-Scott, H .; M.M. : Microbiological biofilms. Annu. Rev. Microbiol. 49: 711-745, 1995. Hudson, M.M. C. Curtiss, R .; III: Regulation of expression of Streptococcus mutans genes important to virus. Infect. Immun. 58: 464-470, 1990. Stewart, P.M. S. : Mechanisms of antibiotic resistance in bacterial biofilms. Int. J. et al. Med. Microbiol. 292: 107-113, 2002. Philip Marsh and Michael V. Martin "Oral Microbiology", Wright Publishing, 2000, p. 58-81 (Dental plaque) Avorn, P.M. N. Monane, M .; et al. : Reduction of bacteria and pyria after ingestion of cradle juice. J. et al. Am. Med. associ. 271: 751-754, 1994. Ervin I Weiss, Roni Lev-Dor, Yoel Kashamn: Inhibition interspecies coagulation of plaques with the encryption on actress of actress. JADA. 129: 1719-1723, 1998.

  The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a composition for oral cavity that exhibits high oral biofilm bactericidal action and is effective in inhibiting plaque formation.

The present inventor has conducted extensive studies for achieving the above object, cranberry or in combination with the extract and a non-ionic antibacterial agents, and, by blending an alcohol, the bactericidal effect on biofilm in the oral cavity That the composition for oral cavity is excellent in reducing and preventing oral diseases such as gingivitis, periodontal disease, dental caries, bad breath and so on. I found it.

In addition, cranberries are plants of the genus Vulgaris genus Cirrus, which grows in cold regions such as North America, and produces fruit. Cranberry fruit can be eaten as it is, but it has been widely used as a raw material for beverages such as dried fruits and juices, cooking sauces, jams, and jelly confectionery. Ingestion of cranberry juice is effective for urinary tract infections. It is known (see Non-Patent Document 6). Furthermore, it has been revealed that cranberries have an effect of inhibiting the adhesion of oral streptococci (see Non-Patent Document 7) and the effect of inhibiting coaggregation of oral bacteria (see Patent Document 7). Furthermore, it is disclosed that the cranberry extract has an inhibitory action against protease and biofilm formation produced by periodontal disease-causing bacteria (see Patent Document 8). However, these techniques are the effects of cranberries alone against planktonic bacteria, and have not been shown any bactericidal effects against biofilms formed by oral bacteria. For these, in the present invention, as is clear from experimental examples described later, by using both the cranberry or its extract and a non-ionic antibacterial agents, and blending alcohol, and cranberry or extracts thereof Due to synergistic action with antibacterial agents, superior bactericidal effects on unexpected oral biofilms compared to using these components alone or in combination with both components in an inappropriate amount Is exhibited and the flavor is also good. Thus, it is difficult to predict from the above prior art that a special effect is exhibited by the configuration of the present invention, and the present inventor has newly found out.

Therefore, the present invention
[1] (A) cranberry or its extract, (B ') isopropyl methyl phenol, and one or two non-ionic antibacterial agent selected from phenoxyethanol, (C) lower monohydric C2-4 alcohols, of one or more selected from a polyhydric alcohol containing an alcohol, the component (a) 0.01-5.0 wt% of the total amount the composition of, (B ') ingredient The composition for oral cavity, wherein the blending amount is 0.001 to 3.0% by mass of the whole composition, and (A) / (B ′) is in the range of 50 to 0.025 by mass ratio. object,
[2] (A) cranberry or its extract, (B ') isopropyl methyl phenol, and one or two non-ionic antibacterial agent selected from phenoxyethanol, (C) lower monohydric C2-4 alcohol, and one or more alcohols selected from polyhydric alcohols, (a) / (B ') is contained in an amount of from 50 to 0.025 in mass ratio, and the amount of the component (a) Provides an oral biofilm disinfectant having a content of 0.01 to 5.0 % by mass and a component (B ′) of 0.001 to 3.0 % by mass.

  The composition for oral cavity of the present invention suppresses the activity of pathogenic plaque by sterilizing and / or bacteriopathogenic bacteria in the oral biofilm which is the cause of oral diseases, and has a good flavor, It is excellent in reducing and preventing oral diseases such as gingivitis, periodontal disease, dental caries and bad breath, and is effective as a sterilizing agent for dental plaque, especially an oral biofilm.

Hereinafter, the present invention will be described in more detail.
The oral composition of the present invention is characterized by containing (A) a cranberry or extract thereof, and (B ') a non-ionic antibacterial agents, and (C) an alcohol.

  (A) As cranberries or extracts thereof, for example, juice obtained by squeezing cranberry fruits by a conventional method or concentrated juices thereof, and additives such as dextrin are added to the juices or concentrated juices Mixed cranberry juice obtained by mixing, spray-drying, freeze-drying, etc. and containing cranberry juice solids, or extracted from plants such as cranberry fruits, pericarps and seeds using a suitable solvent A solvent extract or the like can be used.

  Cranberry juice may be 100% fruit juice, which is obtained by squeezing the fruit as it is, but this fruit juice is concentrated 3-6 times by vacuum concentration, freeze concentration, membrane concentration such as ultrafiltration or reverse osmosis membrane, etc. It is preferable to use the obtained fruit juice for improving the biofilm sterilizing effect of the composition.

  When a solvent is used to obtain a cranberry solvent extract from fruits, skins, seeds, etc., the solvent used is not particularly limited, but a normal polar solvent or nonpolar solvent is used, and the solvent is used alone or in combination of two or more. May be used in combination. As the solvent, for example, water, an organic solvent, a mixed solution of water and an organic solvent, or the like is used. Examples of the organic solvent include lower alcohols having 1 to 4 carbon atoms (specifically, methanol, ethanol, propanol, butanol, etc.), ethers (specifically, diethyl ether, etc.), halogenated hydrocarbons (specifically, Include chloroform, etc., nitriles (specifically acetonitrile), esters (specifically ethyl acetate, etc.), ketones (specifically acetone), hexane, dimethyl sulfoxide, etc. From the above aspect, ethanol, methanol, and ethyl acetate are preferable.

  Commercially available products may be used as the cranberries or extracts thereof. For example, a trade name “50MX Cranberry Powder” (Ocean Ocean Spray Cranberries, Inc.), a trade name “Cran-Max CC-100” (US Cape) Cod Biolab Corporation), trade name “cranberry powder” (Nihon Kikkoman), trade name “cranberry extract” (Nikko Kikkoman), and the like.

The amount of cranberry or an extract thereof is from 0.01 to 5.0% in terms of solid content relative to the total amount of the composition (mass%, hereinafter the same) Ru der. When the blending amount is less than 0.001%, a sufficient biofilm sterilizing power enhancing effect cannot be obtained. If it exceeds 10.0%, although effectiveness is obtained, acidity and bitterness may appear and it may not be preferable in use. Therefore, in order to achieve both effectiveness and use, it does not exceed 10.0%.

As the (B ') a non-ionic antibacterial agents, isopropyl methyl phenol, thymol, phenoxyethanol and the like, can be formulated alone or in combination. Of these, isopropylmethylphenol and phenoxyethanol are particularly preferable. In addition, when using 2 or more types together , especially the combined use of isopropylmethylphenol and phenoxyethanol is desirable.

(B ') The compounding quantity of a nonionic antibacterial agent is 0.001-3.0% of the whole composition, and 0.005-2.0% is especially suitable. When the blending amount is less than 0.001%, a sufficient biofilm inhibitory effect cannot be obtained. When the blending amount exceeds 3.0%, the solubility is poor, and precipitation in the preparation is caused. In order to achieve both the effectiveness of the preparation and the feeling of use, it does not exceed 3.0% .

In the present invention, (A) cranberry or an extract thereof is combined with ( B ′) a nonionic antibacterial agent as an antibacterial agent .

In this case, the mass ratio of the cranberry or its extract (in terms of solid content) and the antibacterial agent is (A) When the cranberry or its extract and (B ′) the nonionic antibacterial agent are used in combination, It is effective that the (A) / (B ′) is 50 to 0.025 from the viewpoint of the biofilm suppressing effect and formulation, and preferably (A) / (B ′) is 25 to 0.033. . When the mass ratio (A) / (B ′) exceeds 50, a satisfactory biofilm suppressing effect cannot be obtained, and when it is less than 0.025, an irritating taste is exhibited in the composition, which is not preferable for use.

In addition, as the antibacterial agent , (B ′) in addition to the nonionic antibacterial agent, another antibacterial agent may be blended as necessary within a range not impeding the effects of the present invention. When formulating if (B ') a non-ionic antibacterial agent for example, a cationic antibacterial agent may be added as an optional component.

  Furthermore, in the present invention, when (B) nonionic antibacterial agent is used in combination with (A) cranberry or an extract thereof, (C) alcohol is used as a solubilizer in order to effectively exert the effect of the antibacterial agent. Blend.

  As alcohol, C2-C4 lower monohydric alcohols such as ethanol, isopropanol, butanol, propanol, glycerin, ethylene glycol, diethylene glycol, hexylene glycol, propylene glycol, polyethylene glycol 200 to 20,000, polypropylene glycol 300 to Examples thereof include polyhydric alcohols such as 4,000, and ethanol, propylene glycol, polyethylene glycol 400, and polyethylene glycol 4000 are particularly preferably used. These alcohols may be used alone or in combination of two or more.

  When the alcohol is blended, the blending amount is preferably 0.1 to 35%, more preferably 0.1 to 25% of the entire composition. If the blending amount is less than 0.1%, the nonionic antibacterial agent cannot be stably blended in the preparation, and a satisfactory biofilm suppression effect may not be obtained. If the blending amount exceeds 35%, effectiveness is obtained. However, it is desirable not to exceed 35% in order to achieve both effectiveness and usage. In addition, content of the said alcohol can be made into the quantity including this, when alcohol is contained in a composition as a cranberry extraction solvent.

  The oral composition of the present invention can be in the form of a solid, solid, liquid, liquid, gel, paste, gum, etc., and toothpastes such as toothpaste, liquid toothpaste, liquid toothpaste, and toothpaste. , Mouthwashes, mouthwashes, lozenges, chewing gums, and the like, and the production method can employ conventional methods according to the dosage form. In this case, other appropriate components can be blended in addition to the components described above depending on the purpose of the composition, dosage form, and the like. For example, in the case of a toothpaste, abrasives, thickeners, binders, surfactants, sweeteners, preservatives, active ingredients, pigments, fragrances, etc. can be blended, and these ingredients are mixed with water. it can.

  Specifically, in the case of dentifrice, dibasic calcium hydrogen phosphate, anhydrous and dihydrate, tertiary calcium phosphate, primary calcium phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, alumina, anhydrous One or more kinds of silicic acid, aluminum silicate, insoluble sodium metaphosphate, tribasic magnesium phosphate, magnesium carbonate, magnesium sulfate, bennite, zirconium silicate, polymethyl metaphosphate, and other synthetic resins can be blended (blending amount usually 5 to 5) 60%, 10-55% for toothpaste).

  In the case of paste-like compositions such as toothpaste, an organic or inorganic binder can be added as a binder, for example, carrageenan, carboxymethylcellulose sodium, methylcellulose, hydroxyethylcellulose, cellulose derivatives such as sodium carboxymethylhydroxyethylcellulose, alginic acid, etc. Alginate derivatives such as sodium and propylene glycol alginate, gums such as xanthan gum, tragacanth gum, gela gum, karaya gum and gum arabic, polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, synthetic organic binders such as polyvinylpyrrolidone, silica gel, One or more inorganic binders such as aluminum silica gel, bee gum, and laponite can be blended (mixing amount is usually 0.3 to 10%).

  As the surfactant, an anionic surfactant, a nonionic surfactant, and an amphoteric surfactant can be blended. Examples of anionic surfactants include sodium alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate, sodium N-acyl sarcosinate such as sodium N-lauroyl sarcosinate, sodium N-myristoyl sarcosinate, sodium dodecylbenzenesulfonate, hydrogen Added coconut fatty acid monoglyceride sodium monosulfate, sodium lauryl sulfoacetate, N-acyl glutamate such as sodium N-palmitoyl glutamate, N-methyl-N-acyl taurine sodium, N-methyl-N-acylalanine sodium, α-olefin sulfone Sodium acid or the like is used. Nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid ester, maltose fatty acid ester and lactose fatty acid ester, sugar alcohol fatty acid esters such as maltitol fatty acid ester and lactitol fatty acid ester, polyoxyethylene sorbitan monolaurate, poly Polyoxyethylene sorbitan fatty acid esters such as oxyethylene sorbitan monostearate, polyoxyethylene fatty acid esters such as polyoxyethylene hydrogenated castor oil, lauienic acid mono- or diethanolamide, sorbitan fatty acid ester, polyoxyethylene higher alcohol ether, polyoxyethylene Polyoxypropylene copolymer, polyoxyethylene polyoxypropylene fatty acid ester, etc. are used (mixing amount is usually 0.1 to 5.0%).

  As the thickener, one or more sugar alcohols such as xylitol, maltitol, lactitol, erythritol and the like can be blended (blending amount is usually 5 to 70%).

  As the sweetener, saccharin sodium, stevioside, dipotassium glycyrrhizinate, perilartin, thaumatin, neohesperidyl dihydrochalcone, aspartylphenylalanine methyl ester, and the like can be blended.

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 processed by these natural fragrances (front reservoir cut, rear reservoir cut, fractional distillation, liquid-liquid extraction, essence, powder fragrance, etc.), and Menthol, carvone, anethole, cineol, salicylic acid , Cinnamic aldehyde, eugenol, 3-l-mentoxypropane-1,2-diol, thymol, linalool, linalyl acetate, limonene, menthone, menthyl acetate, N-substituted-paramentane-3-carboxamide, pinene, octyl Aldehyde, citral, pulegone, carbyl acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allyl cyclohexane propionate, methyl anthranilate, ethyl methyl phenyl glycidate, vanillin, undecalactone, hexanal, isoamyl alcohol, hexenol, Single flavors such as dimethyl sulfide, cycloten, furfural, trimethyl pyrazine, ethyl lactate, ethyl thioacetate, and strawberry flavor, Known fragrance materials used in oral compositions can be used, such as blended fragrances such as pullle flavor, banana flavor, pineapple flavor, grape flavor, mango flavor, butter flavor, milk flavor, fruit mix flavor, and tropical fruit flavor. It is not limited to the fragrance | flavor of an Example.
Moreover, although a compounding quantity is not specifically limited, It is preferable to use said fragrance | flavor raw material 0.000001 to 1% in a composition. Moreover, as a fragrance | flavor for perfume using the said fragrance | flavor raw material, it is preferable to use 0.001-2.0% during a composition.

  As an active ingredient, in addition to the above cranberries or extracts thereof, antibacterial agents, for example, enzymes such as dextranase, mutanase, lysozyme, amylase, protease, lytic enzyme, SOD (superoxide dismutase), sodium monofluorophosphate, Alkali metal monofluorophosphates such as potassium monofluorophosphate, fluorides such as sodium fluoride and stannous fluoride, tranexamic acid, epsilon aminocaproic acid, aluminum chlorohydroxyl allantoin, dihydrocholestanol, glycyrrhizic acids, glycyrrhetinic acid, Bisabolol, glycerophosphate, chlorophyll, sodium chloride, xylitol, zinc chloride, water-soluble inorganic phosphate, vitamin A, vitamin B group, vitamin C, vitamin E, etc. Class and one or more known active ingredients such as derivatives thereof can be effectively amount within a range which does not impair the effects of the present invention.

  The pH of the composition for oral cavity of the present invention is preferably 5.0 to 9.0, particularly 5.5 to 8.5. If the pH is lower than 5.0, the teeth may be decalcified. If the pH is higher than 9.0, mucous membrane irritation may occur, which may be undesirable in use. As the pH adjuster, sodium hydroxide, potassium hydroxide, sodium carbonate and the like are appropriately used, but are not limited thereto.

  The composition for oral cavity of the present invention can be used by putting it in a predetermined container such as an aluminum tube, a laminated tube obtained by laminating both surfaces of an aluminum foil with a plastic, a plastic tube, a bottle-shaped container, an aerosol container or the like.

  EXAMPLES Hereinafter, although an experiment example and an Example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. In the following examples, the blending amount is mass%, and the blending amount of the cranberry extract is shown as a solid content conversion amount with respect to the total amount.

[Experimental example]
Test compositions having the compositions shown in Tables 1 and 2 were prepared by the following method, and the biofilm inhibitory effect was evaluated by the following method. The results are shown in Tables 1 and 2.

Preparation of the test composition:
Cranberry extract (cranberry powder: manufactured by Kikkoman), isopropylmethylphenol (manufactured by Wako Pure Chemical Industries), phenoxyethanol (manufactured by Wako Pure Chemical Industries), triclosan (Ciba Specialty Chemicals Co., Ltd.), cetylpyridinium chloride (Tokyo Chemical Industry Co., Ltd.), propylene glycol (Wako Pure Chemical Industries Co., Ltd.), and adjusted to have a pH of around 6-7 with 1N NaOH, The total amount was adjusted to 100 g with purified water.

Evaluation of bactericidal effect in model plaque:
Actinomyces viscosus ATCC43146, Fusobacterium nucleatumum CCCC10953, Porphyromonas gingivalon 27 (Porphyromonas gingivalm3) Porphyromonas gingivalm7 40 μL of the above bacterial solution was added to 4 mL of Todd Hewit broth culture solution (THBHM ^{* 1} ) containing 5 mg / L hemin and 1 mg / L vitamin K, respectively, and anaerobic culture (80 vol% nitrogen, 10 vol% carbon dioxide) at 37 ° C. overnight. 10 vol% hydrogen). Similarly, 80 μL of Veillonella parvula ATCC17745 bacterial solution was added to 4 mL of Todd Hewitt broth culture solution (THBL ^{* 2} ) containing 1.26% sodium lactate and cultured in the same manner. After the culture, 300 μL was collected from each of the three bacterial strains excluding Bayonella parvula, added to 30 mL of THBHM, and further cultured overnight. Similarly, 300 μL was collected from the bacterial solution of Bayonella parvula, added to 30 mL of THBL, and cultured overnight. After re-culture, each bacterial solution was centrifuged (10000 rpm, 10 min), and the supernatant was discarded.

After adding basal medium mucin culture solution (BMM) ^{* 3} to each sediment (bacteria) and resuspending it, the number of each of the above-mentioned bacteria is put in a culture tank (diameter 140 mm × height 200 mm) containing BMM 1000 mL in advance. Each was inoculated to 1 × 10 ⁷ cells / mL and cultured overnight at 37 ° C. under anaerobic conditions (95 vol% nitrogen, 5 vol% carbon dioxide) while stirring with a stirrer (rotating at about 100 rpm). Thereafter, BMM was supplied at a rate of 100 mL / hour, and the culture solution was discharged at the same rate. The culture medium discharged from the culture tank was continuously supplied to another culture tank (diameter 90 mm × height 190 mm) whose liquid volume was maintained at 300 mL. A rotating disk (rotated at about 80 rpm) in the culture tank is filled with a human unstimulated saliva obtained by filtering a hydroxyapatite plate (made by Pentax) having a diameter of 7 mm and a height of 3.5 mm as an attachment carrier through a 0.45 μm filter. A biofilm was formed by attaching the material treated for 2 hours and culturing on the surface for 21 days.

In order to evaluate the biofilm inhibitory effect of the test composition, the hydroxyapatite plate to which the biofilm was attached was taken out of the culture tank, transferred to a petri dish (diameter 35 mm × height 14 mm), and the test compositions shown in Tables 1 and 2 ( The product of the present invention and comparative product) were immersed in 5 g for 10 minutes, washed with 5 g of physiological saline (manufactured by Otsuka Pharmaceutical Co., Ltd.) three times, and the biofilm was added to a test tube (diameter 13 mm × 100 mm) to which 4 mL of THBHM was added. Moved. Immediately, ultrasonic disruption (200 μA output for 10 seconds) and serial dilution (10-fold dilution in 6 stages) were performed, and each bacterial solution was smeared on a blood agar plate medium ^{* 4} . The plate medium was anaerobically cultured (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% hydrogen) until colonies could be confirmed with the naked eye. After counting the number of colonies in each plate medium, the number of viable bacteria (unit: Log cfu / HA plate, CFU: abbreviation of clone forming unit) was calculated. The evaluation of the test composition was as follows: Comparative Example 1 for the composition of Table 1 and Comparative Example 12 for the composition of Table 2, with a decrease of 10 ² orders or more in the number of viable bacteria. Was evaluated as having a biofilm sterilizing effect.

^{* 1} Composition of THBHM: Expressed by mass in 1 liter.
Todd Hewitt Broth (Becton and Dickinson): 30g / L
Hemin (Sigma Aldrich): 5mg / L
Vitamin K (manufactured by Wako Pure Chemical Industries): 1mg / L
Distilled water: Residue (Measured up to a total volume of 1 L and autoclaved at 121 ° C. for 15 minutes.)

^{* 2} THBL composition: Expressed by mass in 1 liter.
Todd Hewitt Broth (Becton and Dickinson): 30g / L
60% sodium lactate aqueous solution (Sigma Aldrich): 21 g / L
Distilled water: Residue (Measured up to a total volume of 1 L and autoclaved at 121 ° C. for 15 minutes.)

^{* 3} Composition of BMM: Expressed by mass in 1 liter.
Proteose peptone (Becton and Dickinson):
4g / L
Tryptone (Becton and Dickinson): 2g / L
East extract (Becton and Dickinson):
2g / L
Mucin (Sigma Aldrich): 5g / L
Hemin (Sigma Aldrich): 2.5mg / 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 (Measured up to a total volume of 1 L and autoclaved at 121 ° C. for 15 minutes.)

^{* 4} Composition of blood agar plate medium: Expressed by mass in 1 liter.
Todd Hewitt Broth (Becton and Dickinson):
30g / L
Agar (Becton and Dickinson): 15g / L
Hemin (manufactured by Sigma): 5mg / L
Vitamin K (manufactured by Wako Pure Chemical Industries): 1mg / L
Distilled water: Residue (Measured up to a total volume of 1 L and autoclaved at 121 ° C. for 15 minutes.)
Horse defibrinated blood (manufactured by Japan Biotest Laboratories)
(After autoclaving, add it after cooling to 50 ° C.)

Moreover, the following method evaluated the solubility of the mixing | blending component in a test composition at the time of mix | blending a nonionic antibacterial agent as an antibacterial agent. The results are shown in Table 2.
Evaluation of solubility:
According to the preparation method of the test composition, using a 100 mL beaker, the total amount was adjusted to 100 g, stirred for 1 minute at 360 rpm, and allowed to stand for 3 minutes. Was evaluated.
Grade ○: Transparent △; Slight turbidity or precipitation is observed ×: Clearly turbidity or precipitation is observed

Moreover, about the flavor of the test composition shown to Table 1, 2, the flavor was determined by the following rating from 10 judges. The result was calculated | required on the following evaluation criteria from the average value of 10 persons. In Table 1, Comparative Example 6 was used as a reference product, and in Table 2, Comparative Example 18 was used as a control product.
Rating 5 points: Does not feel bitter or irritating compared to the control product 4 points: Slightly bitter or irritating compared to the control product, but no problem in use 3 points: Level equivalent to the control product 2 points : Slight bitterness or pungent taste compared to the control product 1 point: Bitterness or irritating taste felt remarkably compared to the control product Evaluation criteria ◎: The score exceeds 4.5 and less than 5 points ○: Rating 4 or more and 4.5 or less △: Score is 3 or more and less than 4 ×: Score is less than 3

As is apparent from Table 1, when a cranberry extract or a cationic antibacterial agent was added alone (Comparative products 2-6, Comparative products 10, 11 and Comparative product 1 were controls), the cranberry extract and the cationic Even if an antibacterial agent is blended, the blending ratio of these components is inappropriate (comparative products 7 and 8), or even if the blending ratio is appropriate, the blending amount of the cationic antibacterial agent exceeds the scope of the present invention. When compared with the case (Comparative Example 9) and as is clear from Table 2, when the cranberry extract or the nonionic antibacterial agent was blended alone and alcohol was used in combination (Comparative products 13 to 16, 18) 19 and comparative product 12 are controls), and when a nonionic antibacterial agent is blended, when cranberry extract and alcohol are not contained (comparative product 17), a cranberry extract and a nonionic antibacterial agent are blended. Also When the blending ratio of both components is inappropriate (Comparative products 20, 21) or when the blending amount of the nonionic antibacterial agent exceeds the range of the present invention (Comparative Example 22) Compared with the case where it does not contain (Comparative product 23), the combination of a cranberry extract and a nonionic antibacterial agent in a specific ratio and blended with alcohol (the product of the present invention) The oral biofilm sterilization effect was clearly observed.

  Examples are shown below. In addition, the fragrance | flavor used in the following example is as follows.

* Fruit mix flavor FM3000 (mixed fragrance)
Strawberry flavor 40%
Apple flavor 15
Melon Flavor 17
Banana Flavor 10
Peach flavor 5
Orange oil 2.5
Raspberry flavor 2.0
Pineapple flavor 1.5
Grape flavor 1.0
Tropical fruit flavor 1.5
Milk flavor 1.0
Grapefruit oil 0.5
Lemon oil 0.5
Rose oil 0.2
Solvent residue
Total 100.0%

[Example 1] Toothpaste dicalcium phosphate 45.0%
Silica anhydride 2.0
Sorbit 25.0
Propylene glycol (Dow Chemical Co., Ltd.) 2.0
Sodium carboxymethylcellulose 1.0
Sodium alginate 0.5
Sodium lauryl sulfate 1.5
Polyoxyethylene (60) hydrogenated castor oil 0.8
Saccharin sodium 1.0
Sodium benzoate 0.1
Isopropylmethylphenol (Wako Pure Chemical Industries, Ltd.) 0.05
Cranberry extract (cranberry powder: manufactured by Kikkoman Corporation) 1.0
Fragrance A 1.0
Purified water remaining
Total 100.0%
((A) Cranberry extract / (B ′) nonionic antibacterial agent = 20)

[Example 2 ] Toothpaste zirconosilicate 25.0%
Silica anhydride 2.0
Sorbit liquid 40.0
Polyethylene glycol 400 (Lion Corporation) 5.0
Sodium polyacrylate 1.0
Sodium lauryl sulfate 1.0
Saccharin sodium 0.2
Methyl paraoxybenzoate 0.1
Butyl paraoxybenzoate 0.1
Cranberry extract (cranberry powder: manufactured by Kikkoman Corporation) 0.02
Phenoxyethanol (Wako Pure Chemical Industries, Ltd.) 1.5
Fragrance C 1.0
Purified water remaining
Total 100.0%
((A) Cranberry extract / (B ′) nonionic antibacterial agent = 0.67)

[Example 3 ] Liquid dentifrice glycerin (manufactured by Sakamoto Pharmaceutical Co., Ltd.) 25.0%
Sorbit liquid 25.0
Propylene glycol (Dow Chemical Co.) 5.0
Silicic anhydride 0.3
Sodium lauryl sulfate (manufactured by Toho Chemical Industry Co., Ltd.) 1.0
Polyoxyethylene (60) hydrogenated castor oil 1.0
Saccharin sodium 0.2
Sodium benzoate 0.3
Cranberry extract (cranberry extract: manufactured by Kikkoman) 1.0
Isopropylmethylphenol (Wako Pure Chemical Industries, Ltd.) 0.05
Fragrance D 1.0
Tranexamic acid 0.1
Purified water remaining
Total 100.0%
((A) Cranberry extract / (B ′) nonionic antibacterial agent = 20)

[Example 4 ] Mouthwash ethanol (manufactured by New Energy and Industrial Technology Development Organization) 16.0%
Glycerin (made by Lion) 10.0
Polyoxyethylene (60) hydrogenated castor oil 1.0
Saccharin sodium 0.1
Lauroyl sarcosine sodium 0.2
Dye 0.001
Fragrance F 3.0
Lysozyme chloride 0.3
Potassium nitrate 5.0
Ammonium sulfate 0.2
Cranberry extract (cranberry powder: manufactured by Kikkoman) 0.1
Isopropylmethylphenol (Wako Pure Chemical Industries, Ltd.) 0.05
Purified water remaining
Total 100.0%
((A) Cranberry extract / (B ′) nonionic antibacterial agent = 2)

[Example 5 ] Chewing gum xylitol 20.0%
Maltitol 10.0
Glycerin (made by Lion) 8.0
Cranberry extract (cranberry extract: manufactured by Kikkoman Corporation) 0.01
Isopropylmethylphenol (Wako Pure Chemical Industries, Ltd.) 0.05
Fragrance G 2.0
Gum base remaining
Total 100.0%
((A) Cranberry extract / (B ′) nonionic antibacterial agent = 0.2)

[Example 6 ] Mouthwash ethanol (manufactured by New Energy and Industrial Technology Development Organization) 10.0%
Glycerin (made by Lion) 2.0
Polyoxyethylene (60) hydrogenated castor oil 0.2
Saccharin sodium 0.1
Sodium lauryl sulfate (manufactured by Toho Chemical Industry Co., Ltd.) 1.0
Fragrance A 3.0
Cranberry extract (cranberry powder: manufactured by Kikkoman) 0.5
Isopropylmethylphenol (Wako Pure Chemical Industries, Ltd.) 0.05
Phenoxyethanol 1.0
Purified water remaining
Total 100.0%
((A) Cranberry extract / (B ′) nonionic antibacterial agent = 0.476)

Claims (6)

(A) and cranberry or extract thereof, (B ') isopropyl methyl phenol, and one or two non-ionic antibacterial agent selected from phenoxyethanol, (C) a lower monohydric alcohol having 2 to 4 carbon atoms, a multi It contains the one or more alcohols selected from polyhydric alcohols, the (a) ~ 0.01 blending amount of the total composition of the components 5.0 wt%, the amount of component (B ') The composition for oral cavity, which is 0.001 to 3.0% by mass of the whole composition, and (A) / (B ′) is in the range of 50 to 0.025 by mass ratio. (A) cranberry or extracts thereof, cranberry juice, concentrates of fruit juices, according to claim 1 An oral composition according those selected from dry matter and cranberry solvent extract containing solids juice. (C) The composition for oral cavity of Claim 1 or 2 whose compounding quantity of alcohol of a component is 0.1-35 mass%.   The oral cavity according to claim 1, 2 or 3, prepared in a dentifrice, mouthwash, mouthwash, troche or chewing gum in the form of a solid, solid, liquid, liquid, gel, paste or gum. Composition. (A) and cranberry or extract thereof, (B ') isopropyl methyl phenol, and one or two non-ionic antibacterial agent selected from phenoxyethanol, (C) a lower monohydric alcohol having 2 to 4 carbon atoms, a multi and one or more alcohols selected from polyhydric alcohols, the content of (a) / (B ') is contained in an amount of from 50 to 0.025 in mass ratio, and the component (a) 0. 01 to 5.0% by weight, (B ') content of the component oral biofilms disinfectant is 0.001 to 3.0 wt%. The oral biofilm disinfectant according to claim 5, wherein the alcohol content of component (C) is 0.1 to 35% by mass.