JP2009149535A - Oral composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain an oral composition that exhibits a high germicidal action on an oral biofilm, and is effective for inhibiting bacterial plaque formation. <P>SOLUTION: The oral composition comprises (A) 0.001-5.0 mass% of a pyridinecarboxylic acid or its salt, (B) 0.001-5.0 mass% of a nonionic antimicrobial agent, and (C) a surfactant and/or an alcohol, and the mass ratio of (A)/(B) is 0.5-50. The oral composition has the high germicidal action on the oral biofilm which causes oral diseases, disinfects pathogenic bacteria in an oral biofilm or carries out bacteriostasis of them in order to inhibit the pathogenic bacterial plaque formation, has an excellent flavor and excellent flavor stability, and is effective as an ameliorant or prophylactic of oral diseases caused by oral bacteria of dental caries, gingivitis, periodontitis, foul breath, etc. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention is excellent in the effect of suppressing pathogenic biofilms formed in the oral cavity by sterilizing or bacteriostatic pathogenic bacteria present in oral biofilms such as plaque, and has a good flavor, The present invention relates to a composition for oral cavity effective for caries, periodontal disease, and bad breath suppression.

  Causes of caries, periodontal disease, bad breath, etc. are bacteria living in the oral cavity. Caries are caused by oral streptococci represented by Streptococcus mutans. Periodontal disease is caused by Porphyromonas gingivalis ( It is an infectious disease caused by bacteria mainly composed of obligate anaerobic gram-negative bacilli such as Porphyromonas gingivalis). Moreover, it is said that bad breath is related to gram-negative bacteria such as Fusobacterium nucleum. Therefore, it is considered useful to sterilize or bacteriosize these pathogenic bacteria in the oral cavity as an effective means for prevention and improvement of oral diseases.

  Conventionally, many antibacterial agents, such as cetylpyridinium chloride, chlorhexidine gluconate, benzedonium chloride, benzalkonium chloride, and nonionic compounds such as triclosan, have been used as oral antibacterial means for sterilizing oral bacteria. It is used for the purpose of prevention and improvement of oral diseases. For example, it is known that triclosan is blended in a dentifrice composition as a plaque inhibitor (see Patent Document 1).

  These pathogenic bacteria live in various forms of biofilms such as plaque and tongue coating in the oral cavity, and research on their ecology has been active (see Non-Patent Document 1). In particular, it is clear that bacteria in biofilms are significantly less sensitive to drugs compared to planktonic bacteria that do not form biofilms. Some drugs were effective against planktonic bacteria. It is no longer considered effective against biofilm bacteria (see Non-Patent Document 2).

  Similarly for oral biofilms, antibacterial agents that have been conventionally used in oral compositions are thought to have a high effect on planktonic bacteria and have an inhibitory effect on plaque formation. It is not considered to exert a sufficient effect on the formed bacteria. Therefore, as a method for suppressing bacteria in a biofilm formed in the oral cavity, for example, a technique for increasing the retention of triclosan in the oral cavity (Patent Document 2), a nonionic antibacterial agent, tartaric acid, succinic acid, etc. A technique for enhancing the bactericidal power against biofilms by using a specific dicarboxylic acid in combination (Patent Document 3) has been proposed. Furthermore, a new bactericidal technique more effective against bacteria in oral biofilms has been proposed. Development is desired.

JP 60-239410 A JP 08-26953 A JP 2005-015369 A Japanese translation of PCT publication No. 2002-542338 Special table 2001-510231 gazette JP 2005-145883 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. Stewart, P.M. S. : Mechanisms of antibiotic resistance in bacterial biofilms. Int. J. et al. Med. Microbiol. 292: 107-113, 2002.

  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.

  As a result of intensive studies to achieve the above object, the present inventor has found that pyridinedicarboxylic acid or a salt thereof has a bactericidal activity against bacteria in oral biofilms, and further a nonionic ion specific to pyridinedicarboxylic acid or a salt thereof. By combining the specific antibacterial agent at a specific ratio and blending the surfactant and / or alcohol, these components act synergistically, and the bactericidal effect on the biofilm in the oral cavity is dramatically increased, and the flavor is enhanced. Good and stable in flavor even after long-term storage at high temperature. Therefore, it is excellent for improving or preventing oral diseases such as gingivitis, periodontal disease, dental caries and bad breath, and has good flavor. The inventors have found that a composition can be obtained and have come to make the present invention.

  Note that pyridinedicarboxylic acid or a salt thereof is widely used as a builder or peroxide stabilizer, and is known to be incorporated into oral compositions, and is also known to be incorporated with nonionic antibacterial agents. (See Patent Documents 4, 5, and 6). However, pyridinedicarboxylic acid or a salt thereof has oral biofilm inhibitory activity, and by combining nonionic antibacterial agents with surfactants and / or alcohols, a high oral biochemistry is achieved by the synergistic effect of these components. The present inventor has newly found that a special action and effect that the film bactericidal activity is exhibited and the flavor is good is obtained.

  Therefore, the present invention contains (A) pyridinedicarboxylic acid or a salt thereof, (B) a nonionic antibacterial agent, (C) a surfactant and / or an alcohol, and a blending amount of the component (A). Is 0.001 to 5.0 mass%, the blending amount of component (B) is 0.001 to 5.0 mass%, and (A) / (B) is in the range of 0.5 to 50 by mass ratio. The composition for oral cavity characterized by being is provided.

  The composition for oral cavity of the present invention has a high effect of sterilizing oral biofilm which is a cause of oral disease, sterilizing or bacteriolating pathogenic bacteria in oral biofilm, and suppressing the formation of pathogenic plaque, Moreover, it has a good flavor and good flavor stability, and is effective as an agent for improving or preventing these oral diseases caused by oral bacteria such as caries, gingivitis, periodontitis and bad breath.

Hereinafter, the present invention will be described in more detail.
The composition for oral cavity of the present invention contains (A) pyridinedicarboxylic acid or a salt thereof, (B) a nonionic antibacterial agent, and (C) a surfactant and / or alcohol.

  Examples of (A) pyridinedicarboxylic acid include 2,3-pyridinedicarboxylic acid, 2,4-pyridinedicarboxylic acid, 2,5-pyridinedicarboxylic acid, 2,6-pyridinedicarboxylic acid (also known as dipicolinic acid), 3, Examples include 4-pyridinedicarboxylic acid and 3,5-pyridinedicarboxylic acid. Examples of the salt of pyridinedicarboxylic acid include alkali metal salts such as sodium salt, potassium salt, calcium salt and magnesium salt, and alkaline earth metal salts. As pyridinedicarboxylic acid or a salt thereof, one kind selected from these may be used alone, or two or more kinds may be used in combination, and in particular, 2,6-pyridinedicarboxylic acid, 3,4-pyridinedicarboxylic acid, It is preferable to use one selected from 3,5-pyridinedicarboxylic acid and salts thereof from the viewpoint of the bactericidal effect.

  The blending amount of pyridinedicarboxylic acid or a salt thereof is 0.001 to 5.0% (mass%, the same applies hereinafter) of the entire composition, and preferably 0.01 to 3.0%. When the blending amount is less than 0.001%, a sufficient biofilm suppressing effect cannot be obtained, and when it exceeds 5.0%, an irritating taste such as gummy is expressed, which is not preferable.

  Specific examples of (B) nonionic antibacterial agents include 3-methyl-4-isopropylphenol, triclosan, thymol, carvacrol, farnesol, bisabolol, cineol, and the like, one of these alone or two The above can be combined. Among these, it is preferable from the viewpoint of the bactericidal effect to use a nonionic antibacterial agent selected from 3-methyl-4-isopropylphenol, thymol, farnesol, and bisabolol.

  The compounding quantity of a nonionic antibacterial agent is 0.001-5.0% of the whole composition, Preferably it is 0.001-1.0%. When the blending amount is less than 0.001%, a sufficient biofilm suppressing effect cannot be obtained, and when it exceeds 5.0%, an irritating taste is developed, which is not preferable.

  In the present invention, in order to effectively exhibit the effects of pyridinedicarboxylic acid or a salt thereof and a nonionic antibacterial agent in the preparation, (C) a surfactant and / or alcohol is blended as a solubilizer.

  Here, as the surfactant, one or more selected from anionic surfactants, nonionic surfactants, and zwitterionic surfactants can be used.

  Examples of anionic surfactants include sodium alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate, sodium N-acyl sarcosine such as sodium N-lauroyl sarcosinate, sodium N-myristoyl sarcosinate, sodium dodecylbenzene sulfonate Hydrogenated 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- Sodium olefin sulfonate, sodium dioctyl sulfosuccinate and the like are used. Among these, sodium alkyl sulfates such as sodium lauryl sulfate and sodium N-acyl sarcosinates such as sodium N-lauroyl sarcosinate can be preferably used from the viewpoint of the biofilm bactericidal effect.

  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, and polyoxyethylene sorbitan monolaurate. Polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monostearate, polyoxyethylene fatty acid esters such as polyoxyethylene hydrogenated castor oil, lauric acid mono- or diethanolamide, fatty acid diethanolamides such as myristic acid mono- or diethanolamide, Sorbitan fatty acid ester, fatty acid monoglyceride, polyoxyethylene higher alcohol ether, polyoxyethylene polyoxypropylene Polymers, polyoxyethylene polyoxypropylene fatty acid ester or the like is used. Among these, polyoxyethylene fatty acid esters such as polyoxyethylene hydrogenated castor oil (especially those having an added mole number of ethylene oxide of 20 to 100) can be suitably used from the viewpoint of the biofilm bactericidal effect.

  As the zwitterionic surfactant, N-alkyldiaminoethylglycine such as N-lauryldiaminoethylglycine, N-myristyldiaminoethylglycine, N-alkylN-carboxymethylammonium betaine, 2-alkyl-1-hydroxyethylimidazoline betaine Sodium or the like is used.

  As the surfactant, it is particularly preferable to use an anionic surfactant and a nonionic surfactant in view of solubilization. Particularly, sodium lauryl sulfate, sodium N-lauroyl sarcosinate, and addition of ethylene oxide are preferable. It is preferable to use a combination of polyoxyethylene hydrogenated castor oil having a mole number of 20 to 100.

  When a surfactant is blended, the blending amount is preferably 0.1 to 5%, particularly preferably 0.1 to 2.5% of the entire composition. If the blending amount is less than 0.1%, pyridinedicarboxylic acid or a salt thereof or an antibacterial agent may not be solubilized in the preparation, and the biofilm sterilizing power may not be exhibited. If it exceeds 5%, the effect of pyridinedicarboxylic acid or a salt thereof or an antibacterial agent may be inactivated, or irritation may be given to the oral mucosa.

  Moreover, as alcohol, C2-C4 monohydric alcohol, such as ethanol, isopropanol, butanol, propanol, glycerin, ethylene glycol, diethylene glycol, hexylene glycol, propylene glycol, polyethylene glycol 200-20,000, polypropylene glycol 300 Examples include polyhydric alcohols such as ˜4,000. In particular, ethanol, glycerin, propylene glycol, and polyethylene glycol 400 to 4000 are excellent in the solubilizing ability of nonionic antibacterial agents, and are preferably used from the viewpoint of the biofilm bactericidal effect. 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 45%, particularly preferably 0.1 to 35% of the entire composition. If the blending amount is less than 0.1%, pyridinedicarboxylic acid or a salt thereof and a nonionic antibacterial agent may not be solubilized in the preparation, and biofilm bactericidal power may not be exhibited. If it exceeds 45%, it may irritate the oral mucosa.

  As a solubilizer, a surfactant or an alcohol may be blended, or a surfactant and an alcohol may be used in combination, but blending a surfactant and an alcohol in particular improves the solubility of each blended component. From the point of view, it is more preferable. In particular, an alcohol, an anionic surfactant, and a nonionic surfactant are used in combination, and in particular, an alcohol selected from ethanol, propylene glycol, and polyethylene glycol 400 to 4000 and an added mole number of ethylene oxide of 20 to 100 are used. It is more preferable to add a surfactant selected from oxyethylene hydrogenated castor oil, sodium lauryl sulfate, and sodium N-lauroyl sarcosinate from the viewpoint of effectiveness as a solubilizer.

  The total blending amount of the surfactant and the alcohol is appropriately adjusted according to the type and blending amount of pyridinedicarboxylic acid or a salt thereof and a nonionic antibacterial agent, but is 0.1 to 45% of the total composition, particularly 0. 0.1 to 35% is preferable. If the blending amount is less than 0.1%, pyridinedicarboxylic acid or a salt thereof and a nonionic antibacterial agent may not be solubilized in the preparation, and if it exceeds 45%, irritation to the oral mucosa may occur.

  In the present invention, a combination of (A) pyridinedicarboxylic acid or a salt thereof, (B) a nonionic antibacterial agent, and (C) a surfactant and / or an alcohol component may be combined to achieve high biofilm sterilization. In this case, the mass ratio ((A) / (B)) of pyridinedicarboxylic acid or a salt thereof to the nonionic antibacterial agent is in the range of 0.5 to 50, particularly 0. A range of 5 to 20 is effective from the viewpoint of high biofilm sterilization effect. When the mass ratio is less than 0.5 or exceeds 50, there are problems that a satisfactory biofilm suppressing effect cannot be obtained or the flavor of the composition deteriorates.

  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. It can be made into various dosage forms such as shampoos, mouthwashes, mouthwashes, lozenges, etc., and the production method can adopt a conventional method according to the dosage form. In this case, the composition for oral cavity of the present invention can contain other optional components as appropriate in addition to the above-described components, depending on the purpose and the dosage form of the composition. For example, in the case of toothpaste, abrasives, binders, thickeners, sweeteners, preservatives, active ingredients, pigments, fragrances, and the like can be blended, and these ingredients can be mixed with water.

  Specifically, in the case of dentifrice, as a polishing agent, dibasic calcium hydrogen phosphate, anhydrous and dihydrate, tertiary calcium phosphate, primary calcium phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, alumina, One kind or two or more kinds of anhydrous 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 ( The blending amount is usually 5 to 60%, and 10 to 55% in the case of toothpaste).

  In the case of a paste-like composition such as toothpaste, as a binder, alginate such as carrageenan, sodium carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, sodium carboxymethylhydroxyethylcellulose, etc., sodium alginate, propylene glycol alginate, etc. Derivatives, gums such as xanthan gum, tragacanth gum, gela gum, karaya gum, gum arabic, etc., synthetic binders such as polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, polyvinylpyrrolidone, inorganic viscosity such as silica gel, aluminum silica gel, bee gum, laponite 1 type, or 2 or more types, such as a binder, can be mix | blended (mixing quantity normally 0.3-10%).

  Furthermore, in pasty or liquid oral compositions such as dentifrices, one or more sugar alcohols such as sorbitol, maltitol, lactitol, erythritol can be blended as a thickening agent (blending amount is usually 5). ~ 70%).

  As the sweetener, saccharin sodium, stevioside, dipotassium glycyrrhizinate, perilartin, thaumatin, neohesperidyl dihydrochalcone, aspartylphenylalanine methyl ester, and the like can be blended. Examples of the preservative include paraoxybenzoic acid ester and sodium benzoate.

  In the composition for oral cavity of the present invention, as an active ingredient, enzymes such as dextranase, mutanase, lysozyme, amylase, protease, lytic enzyme, SOD (superoxide dismutase), sodium monofluorophosphate, potassium monofluorophosphate, etc. Alkali metal monofluorophosphate, fluorides such as sodium fluoride and stannous fluoride, tranexamic acid, epsilon aminocaproic acid, aluminum chlorohydroxyl allantoin, dihydrocholestanol, glycyrrhizic acids, glycyrrhetinic acid, glycerophosphate, chlorophyll, 1 of known active ingredients such as sodium chloride, xylitol, zinc chloride, water-soluble inorganic phosphates, vitamins such as vitamin A, vitamin B group, vitamin C, vitamin E and their derivatives Or two or more, can be effectively amount within a range which does not impair the effects of the present invention (amount usually 0.0001 to 5.0%).

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, 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, Known fragrance materials used in oral compositions, such as blended fragrances such as inapple flavor, grape flavor, mango flavor, butter flavor, milk flavor, fruit mix flavor, and tropical fruit flavor, can be used. It is not limited to fragrances.
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 formulation composition. Moreover, as a fragrance | flavor for fragrance | flavor using the said fragrance | flavor raw material, it is preferable to use 0.001-2.0% during a formulation composition.

  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,% is mass% unless otherwise specified.

[Experimental example]
A test composition was prepared by blending each component (all manufactured by Wako Pure Chemical Industries, Ltd.) with the compositions shown in Tables 1 to 4, and the biofilm bactericidal effect was evaluated by the following method. The results are shown in Tables 1-4.

Evaluation of biofilm bactericidal effect in model plaque:
The bacteria used 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 Cultivated with Todd Hewitt broth (manufactured by Becton and Dickinson) medium [THBHM], and Bayonella parvula ATCC17745 is Todd Hewitt broth containing 1.26% sodium lactate (manufactured by Sigma) Becton and Dickinso They were cultured by the Company, Ltd.) culture [THBL]. The culture was anaerobic culture overnight at 37 ° C. (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% hydrogen). After cultivation, the bacterial solution was collected by centrifugation (10000 rpm, 10 min).

Each bacterium collected by centrifugation is resuspended in a basal medium mucin culture solution [BMM] ^* and then inoculated into a culture tank containing 1000 mL of the same medium in advance so that the number of bacteria is 1 × 10 ⁷ cells / mL. And cultured 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 a hydroxyapatite plate. Biofilm removed after incubation with phosphate-buffered saline ^** (Phosphate Buffered Saline, hereinafter referred to as PBS) were washed twice with 5 mL, test compositions are shown in Tables 1 to 4 (present invention product and the comparative Article) It was immersed in 5 g for 10 minutes. The test composition was then washed by washing 3 times with 5 mL PBS. In addition, what was similarly treated with PBS instead of the test composition was used as a control.

In order to evaluate the biofilm bactericidal effect of the test composition, the treated biofilm was transferred to a test tube (diameter 13 mm × 100 mm) to which 4 mL of THBHM was added, and immediately biotreated by sonication (200 μA output for 10 seconds). The film was dispersed. This was serially diluted (6 levels of 10-fold dilution) and smeared on blood agar plates ^*** . The agar plate is anaerobically cultured (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% hydrogen) until colony growth can be confirmed with the naked eye. After counting the number of colonies, the number of viable bacteria (unit: cfu / HA plate, CFU (abbreviation of cloning forming unit) was calculated, and the remaining viable cell count rate and the level of effectiveness with respect to Comparative Example 1 were determined by the following formula. The results are shown in Tables 1-4.
Residual viable count rate = Log (viable count after treatment with test composition / viable count after treatment in Comparative Example 1)

Criteria for determining the effectiveness level ×: The remaining viable cell rate is −1 or more Δ: The remaining viable cell rate is −3 or more and less than −1 ○: The remaining viable cell rate is −5 or more and less than −3 ◎: The remaining viable cell rate Is less than -5

* BMM composition: Expressed by mass in 1 liter.
Proteose peptone (Becton and Dickinson):
4g
Tryptone (Becton and Dickinson): 2g
Yeast extract (Becton and Dickinson): 2g
Mucin (Sigma): 5g
Hemin (manufactured by Sigma): 2.5mg
Vitamin K (Wako Pure Chemical Industries, Ltd.): 0.5mg
KCl (manufactured by Wako Pure Chemical Industries): 1g
Cysteine (Wako Pure Chemical Industries, Ltd.): 0.2g
Distilled water: remaining
(Upgraded so that the total amount is 1L)

** Composition of PBS: expressed in mass in 1 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 a total volume of 1 L)

*** Composition of blood agar plate: expressed in mass per liter.
Todd Hewitt Broth (Becton and Dickinson):
30g
Agar (Becton and Dickinson): 15g
Hemin (manufactured by Sigma): 5mg
Vitamin K (Wako Pure Chemical Industries, Ltd.): 1mg
Rabbit defibrinated blood (Nippon Biotest): 100g
Distilled water: remaining
(Upgraded so that the total amount is 1L)

  Moreover, about the flavor and flavor change of the test composition of Tables 1-4, the flavor was determined by three judges and the score was given according to the following criteria. The change in flavor was determined by comparing a test composition stored at 40 ° C. for 6 months with a control product stored at 4 ° C., and the data was an intermediate value of 3 persons. The results are shown in Tables 1 to 4.

Score:
Judgment Flavor Flavor change ○ No problem Flavor change △ Slightly pungent taste Slightly savory change × Clearly irritating taste Clearly savory change

  As is clear from the results of Tables 1 to 4, pyridinedicarboxylic acid alone has a biofilm bactericidal effect, but it was found that a high biofilm bactericidal effect was exhibited by combining with a specific nonionic antibacterial agent. . Among pyridinedicarboxylic acids, 2,6-pyridinedicarboxylic acid, 3,4-pyridinedicarboxylic acid, and 3,5-pyridinedicarboxylic acid are particularly effective and can be most suitably used for the purpose of expressing bactericidal activity. On the other hand, among the nonionic antibacterial agents used in combination, 3-methyl-4-isopropylphenol, thymol, farnesol, and bisabolol exhibited a strong synergistic effect. In addition, the biofilm bactericidal effect expressed by combining the pyridinedicarboxylic acid or a salt thereof of the present invention with a nonionic antibacterial agent is obtained when sodium tartrate (carboxylic acid) and triclosan are combined or 3-methyl-4- Compared to the combination of isopropylphenol and sodium succinate, it was superior.

  Examples are shown below. In addition, the fragrance | flavor used by the said example and 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 (70% aqueous solution) 25.0
Propylene glycol 2.0
Sodium carboxymethylcellulose 1.0
Sodium alginate 0.5
Sodium lauryl sulfate 1.5
Polyoxyethylene (20) hydrogenated castor oil 0.8
Saccharin sodium 1.0
Sodium benzoate 0.1
2,6-pyridinedicarboxylic acid (manufactured by Wako Pure Chemical Industries, Ltd.) 0.1
3-Methyl-4-isopropylphenol (manufactured by Wako Pure Chemical Industries, Ltd.) 0.1
Fragrance A 1.0
Purified water remaining
Total 100.0%
((A) pyridinedicarboxylic acid / (B) antibacterial agent = 1)

[Example 2] Toothpaste calcium carbonate 40.0%
Propylene glycol 4.0
Glycerin 20.0
Sodium carboxymethylcellulose 1.5
Titanium oxide 0.5
Sodium lauryl sulfate 0.8
Saccharin sodium 0.1
Ethyl paraoxybenzoate 0.1
2,6-pyridinedicarboxylic acid (manufactured by Wako Pure Chemical Industries, Ltd.) 0.1
1,4-cineole (Wako Pure Chemical Industries, Ltd.) 0.001
Bisabolol (Wako Pure Chemical Industries, Ltd.) 0.05
Fragrance B 1.0
Purified water remaining
Total 100.0%
((A) pyridinedicarboxylic acid / (B) antibacterial agent = 1.96)

[Example 3] Toothpaste zirconosilicate 25.0%
Silica anhydride 2.0
Sorbit liquid 40.0
Polyethylene glycol 400 5.0
Sodium polyacrylate 1.0
Sodium lauryl sulfate 1.0
Saccharin sodium 0.2
Methyl paraoxybenzoate 0.1
Butyl paraoxybenzoate 0.1
2,6-pyridinedicarboxylic acid (manufactured by Wako Pure Chemical Industries, Ltd.) 0.2
Triclosan (Wako Pure Chemical Industries, Ltd.) 0.3
Fragrance C 1.0
Purified water remaining
Total 100.0%
((A) pyridinedicarboxylic acid / (B) antibacterial agent = 0.66)

[Example 4] Liquid dentifrice glycerin 25.0%
Sorbit liquid (70% aqueous solution) 25.0
Propylene glycol 5.0
Silicic anhydride 0.3
Sodium lauryl sulfate 1.0
Polyoxyethylene (60) hydrogenated castor oil 1.0
Saccharin sodium 0.2
Sodium benzoate 0.3
2,6-pyridinedicarboxylic acid (manufactured by Wako Pure Chemical Industries, Ltd.) 0.2
Farnesol (Wako Pure Chemical Industries, Ltd.) 0.05
3-Methyl-4-isopropylphenol (manufactured by Wako Pure Chemical Industries, Ltd.) 0.1
Fragrance D 1.0
Tranexamic acid 0.1
Purified water remaining
Total 100.0%
((A) pyridinedicarboxylic acid / (B) antibacterial agent = 1.33)

[Example 5] Mouthwash ethanol 15.0%
Polyoxyethylene (60) hydrogenated castor oil 1.0
Glycerin 15.0
Saccharin sodium 0.01
Sodium benzoate 0.3
Fragrance E 1.0
Dye 0.004
Disodium phosphate 0.05
Potassium nitrate 1.0
Sodium inosinate 1.0
Cetylpyridinium chloride 0.02
2,6-pyridinedicarboxylic acid (Wako Pure Chemical Industries, Ltd.) 0.3
Thymol (Wako Pure Chemical Industries, Ltd.) 0.01
3-Methyl-4-isopropylphenol (Wako Pure Chemical Industries, Ltd.) 0.02
Purified water remaining
Total 100.0%
((A) pyridinedicarboxylic acid / (B) antibacterial agent = 10))

[Example 6] Mouthwash ethanol 16.0%
Glycerin 10.0
Polyoxyethylene (60) hydrogenated castor oil 1.0
Saccharin sodium 0.1
Lauroyl sarcosine sodium 0.2
Dye 0.001
Fragrance F 1.0
Lysozyme chloride 0.3
Potassium nitrate 5.0
Ammonium sulfate 0.2
3,5-pyridinedicarboxylic acid (manufactured by Wako Pure Chemical Industries, Ltd.) 0.3
Carvacrol (Wako Pure Chemical Industries, Ltd.) 0.01
3-methyl-4-isopropylphenol (Wako Pure Chemical Industries, Ltd.) 0.07
Purified water remaining
Total 100.0%
((A) pyridinedicarboxylic acid / (B) antibacterial agent = 3.75))

[Example 7] Mouthwash ethanol 10.0%
Glycerin 2.0
Polyoxyethylene (60) hydrogenated castor oil 0.2
Saccharin sodium 0.1
Phenoxyethanol 0.5
Fragrance G 1.0
2,4-pyridinedicarboxylic acid (manufactured by Wako Pure Chemical Industries, Ltd.) 1.0
3-methyl-4-isopropylphenol (Wako Pure Chemical Industries, Ltd.) 0.05
1,8-Cineol (Wako Pure Chemical Industries, Ltd.) 0.001
Purified water remaining
Total 100.0%
((A) pyridinedicarboxylic acid / (B) antibacterial agent = 19.6))

[Example 8] Mouthwash propylene glycol 4.0%
Glycerin 2.0
Polyoxyethylene (60) hydrogenated castor oil 0.3
Saccharin sodium 0.1
Sodium lauryl sulfate 0.1
Phenoxyethanol 0.2
Fragrance E 1.0
2,6-pyridinedicarboxylic acid (manufactured by Wako Pure Chemical Industries, Ltd.) 0.1
3-methyl-4-isopropylphenol (Wako Pure Chemical Industries, Ltd.) 0.05
Purified water remaining
Total 100.0%
((A) pyridinedicarboxylic acid / (B) antibacterial agent = 2))

Claims (3)

  It contains (A) pyridinedicarboxylic acid or a salt thereof, (B) a nonionic antibacterial agent, (C) a surfactant and / or an alcohol, and the amount of component (A) is 0.001 to 5. 0% by mass, the blending amount of component (B) is 0.001 to 5.0% by mass, and (A) / (B) is in the range of 0.5 to 50 by mass ratio. Oral composition.   The oral composition according to claim 1, wherein the pyridinedicarboxylic acid is one or more selected from 2,6-pyridinedicarboxylic acid, 3,4-pyridinedicarboxylic acid, and 3,5-pyridinedicarboxylic acid.   The oral composition according to claim 1 or 2, wherein the nonionic antibacterial agent is at least one selected from 3-methyl-4-isopropylphenol, thymol, farnesol, and bisabolol.