KR20200093514A - Oral biofilm formation inhibitor and oral composition - Google Patents

Abstract

Provided is an oral biofilm formation inhibitor having an excellent effect of inhibiting the formation of an oral biofilm and an oral composition containing the same.
(a) an oral biofilm formation inhibitor containing a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less, the (a) component, and (b) an oral biofilm formation inhibitor containing a nonionic fungicide, and the (a) component And (b) composition for oral use containing a component.

Description

Oral biofilm formation inhibitor and oral composition

The present invention relates to an oral biofilm formation inhibitor and an oral composition containing the same.

Oral diseases are caused by pathogens, but these pathogens settle in the oral cavity by forming plaques (plaques) on the tooth surface and exert pathogenicity. Therefore, plaque control is very important for the prevention of oral diseases. As means of plaque control, formation of plaque, suppression, removal, sterilization, etc. are exemplified, and among these, it is said that removal of plaque is important.

However, in the physical removal method such as brushing, which is the basis of plaque removal, there are some places where the brush is difficult to reach, such as interdental or periodontal pockets, so the removal effect may be limited. Therefore, it is expected to establish a technique for suppressing plaque formation.

Recently, plaques are considered to be biofilms made of bacterial aggregates and non-bacterial metabolites from the recognition of simple bacterial contamination, and since these biofilms are firmly constructed, they are difficult to peel off from resistance to disinfectants and the like. It is also known to have physical resistance. From this current situation, a suppression technique that does not form a highly resistant biofilm is desired.

As a technique for suppressing formation on jig, a technique for improving the retention of triclosan, an antibacterial agent (Patent Document 1; Japanese Patent Publication No. Hei 4-139118), has been proposed, but because it is an effect using an antibacterial agent, the effect on biofilm is sufficient. Is difficult to say. In addition, although a technique for inhibiting jig adhesion by a special acrylic acid copolymer has been proposed (Patent Document 2; Japanese Patent Publication No. Hei 3-14512), it is a technique for inhibiting the initial adhesion of the jig and suppresses the formation of a strong barrier after adhesion. It is not an effect to say, so it cannot be said that it is a sufficient effect.

Japanese Patent Publication No. Hei 4-139118 Japanese Patent Publication No. Hei 3-14512 Japanese Patent Publication No. Hei 7-29907 Japanese Patent Publication 2000-247851

The present invention has been made in view of the above circumstances, and aims to provide a novel oral biofilm formation inhibitor and a composition for oral cavity containing the same.

The present inventors conducted extensive studies to achieve the above object, and as a result, a polyacrylate having a weight average molecular weight of a specific value or less has an effect of inhibiting the formation of an oral biofilm, and exhibits an excellent biofilm formation inhibitory effect. It has been found that when a nonionic fungicide is used in combination, the action by the polyacrylic acid salt is enhanced to significantly improve the biofilm formation inhibitory effect. And, according to this, it was found that the combination of the polyacrylic acid salt, preferably the polyacrylic acid salt and the nonionic bactericidal agent, into the composition for oral cavity provides excellent biofilm formation inhibitory effect, and also gives a good feeling of use. Then, it came to achieve the present invention.

Polyacrylic acid or a salt thereof is known as a caking agent for oral compositions, but generally, a cross-linked polyacrylic acid or a salt thereof having a weight average molecular weight of 100,000 or more and usually about 300,000 is used. On the other hand, in the present invention, the effect of the previously unknown effect of inhibiting the formation of biofilms in the oral cavity in (a) a polyacrylate of a specific molecular weight having a weight average molecular weight of 20,000 or less, particularly a linear polyacrylate, It turns out that there is a polyacrylic acid salt having a weight average molecular weight of more than 20,000, or a weight average molecular weight of 20,000 or less, which can not be achieved when polyacrylic acid is not used in the form of a salt. Was obtained.

As shown in the comparative examples in Tables 1 and 3 described below, the effect of inhibiting biofilm formation by sodium polyacrylate having a weight average molecular weight of 300,000 or polyacrylic acid having a weight average molecular weight of 6,000 was all ×, however, it was carried out in Tables 1 to 3 As shown in the example, the effect of inhibiting the formation of the biofilm by the component (a) was excellent in all of ○ or ◎.

In addition, although it is known that the nonionic disinfectant has a biofilm penetration sterilization action, the inhibitory action of biofilm formation has not been confirmed, and actually, as shown in Comparative Example 3 in Table 3 to be described later, the biofilm with isopropylmethylphenol. The effect of suppressing formation was low. However, in the present invention, when (a) component and (b) nonionic fungicide are used in combination, both act synergistically, while suppressing the unpleasant odor caused by component (a) while significantly inhibiting the formation of biofilm (see Table 1 below). See the examples in -3).

In addition, although the details of the mechanism of action for inhibiting biofilm formation in the present invention are not clear, (a) the component acts on the biofilm itself due to the chemical action peculiar to the component, and in particular, the biofilm from the surface. It is presumed that formation of a new biofilm is prevented by inhibiting the formation of a strong barrier when growing.

In Patent Document 3 (Japanese Patent Publication No. Hei 7-29907), as an anti-tartar agent, a polyacrylic acid polymer or polyacrylic acid copolymer having a weight average molecular weight of about 3,500 to 7,500 is blended into an oral composition in an amount of about 2.5% or more. Is proposing. Patent Document 4 (Japanese Patent Laid-Open No. 2000-247851) proposes a coloring inhibitor coating for teeth containing a polyacrylic acid polymer having a molecular weight of 20,000 or more as a specific anionic polymer compound and/or a salt thereof, but this is caused by coating. It is suppression of coloration, and easy removal and prevention of accumulation of stained pellicles is achieved by hydrophilizing the tooth surface after coating. With respect to these, the present invention is (a) inhibiting the formation of oral biofilms by polyacrylic acid salts of a specific molecular weight, and the effect of this is poor in polyacrylic acid, not in salt form, while on the other hand, the amount of component (a) in the oral composition is 2 It is excellent even if it is less than mass%.

Accordingly, the present invention provides the following oral biofilm formation inhibitors and oral compositions.

[1] (a) An oral biofilm formation inhibitor containing a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less.

[2] (a) A polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less, and

(b) Nonionic fungicide

Oral biofilm formation inhibitor containing a.

In [3] [2],

(b) An oral biofilm formation inhibitor, wherein the component is at least one nonionic fungicide selected from isopropylmethylphenol, triclosan and thymol.

In [4] [2] or [3],

(a)/(b) An oral biofilm formation inhibitor having a mass ratio of 0.01 to 200.

[5] Any one of [1] to [4],

An oral biofilm formation inhibitor having a weight average molecular weight of 1,000 to 10,000 of polyacrylic acid.

[6] (a) A polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less, and

(b) Nonionic fungicide

Oral composition comprising a.

In [7] [6],

Oral composition having a weight average molecular weight of 1,000 to 10,000 of polyacrylic acid.

[8] In [6] or [7],

(b) Oral composition wherein the component is at least one nonionic fungicide selected from isopropylmethylphenol, triclosan and thymol.

[9] The method of any one of [6] to [8],

(a) / (b) Oral composition is 0.01 to 200 as a mass ratio.

[10] The method of any one of [6] to [9],

(a) The composition for oral cavity containing 0.01-2 mass% of components, and (b) 0.01-1 mass% of components.

[11] The method of any one of [6] to [10],

Oral composition for oral biofilm suppression.

[12] The method of any one of [6] to [11],

A composition for oral cavity that is a skirt composition.

According to the present invention, it is possible to provide an oral biofilm formation inhibitor having an excellent effect of inhibiting the formation of an oral biofilm and an oral composition containing the same. The composition for oral cavity of the present invention is suitable for prevention or suppression of oral diseases such as periodontal disease because the biofilm formation inhibitory effect is high and the usability can be effectively suppressed.

Hereinafter, the present invention will be described in more detail. The oral biofilm formation inhibitor of the present invention (a) is a polyacrylic acid salt having a weight average molecular weight of 1,000 or more and 20,000 or less, and contains the component (a) as an active ingredient.

The polyacrylic acid salt of the component (a) has a weight average molecular weight (Mw) of 1,000 or more and 20,000 or less. In this case, the weight average molecular weight is 1,000 or more, and more than 20,000 or less, preferably 10,000 or less, and more preferably 8,000 or less in terms of the effect of inhibiting biofilm formation. When the weight average molecular weight is less than 1,000, the effect of inhibiting biofilm formation is poor. When it exceeds 20,000, the effect of inhibiting biofilm formation is lowered, and a sufficient effect cannot be obtained.

The weight average molecular weight was measured by GPC (Gel Permeation Chromatography) using the method and measurement conditions described in Japanese Patent No. 5740859. Specifically, it is shown below (hereinafter the same).

A method for measuring the 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

Pre-column: TSK guardcolumn α

Standard material: Polyethylene glycol

The polyacrylic acid salt of the component (a) is preferably a linear polyacrylic acid salt from the viewpoint of the biofilm formation inhibitory effect.

As the salt, a monovalent salt is preferable, an alkali metal salt or an ammonium salt is more preferable, more preferably an alkali metal salt, and a sodium salt is particularly preferable.

As such a polyacrylic acid salt, commercial products sold from Polysciences Inc. or Toagosei Co., Ltd. can be used.

As a specific commercial item, sodium polyacrylate (Mw: 1,000); Straight-chain, manufactured by Polysciences Inc., sodium polyacrylate (Mw: 6,000); Straight chain, manufactured by Toagosei Co., Ltd., AC-10NP, AC-10NPD, ARON T-50, sodium polyacrylate (Mw: 8000); Straight-chain, manufactured by Polysciences Inc., sodium polyacrylate (Mw: 20,000); Straight chain, Toagosei Co., Ltd., ARON A-20UN, etc. can be used.

In addition, the polyacrylic acid salt of the component (a) has a weight average molecular weight lower than that of the crosslinked polyacrylic acid salt used in the skirting agent, and is different from the known polyacrylate salt.

In the case of using polyacrylic acid salts other than the component (a) instead of the component (a), or when using polyacrylic acid which is not in the form of a salt, the effect of inhibiting biofilm formation is poor, and even when the component (b) is used in combination, the effect is lowered. In addition, the unpleasant odor is not suppressed and the feeling of use may be deteriorated, and the object of the present invention is not achieved.

In the oral biofilm formation inhibitor of the present invention, it is preferable to use (b) a nonionic fungicide in addition to the component (a) as an active ingredient. When the components (a) and (b) are used in combination, the effect of inhibiting biofilm formation is further improved.

It is known that a nonionic fungicide has a biofilm penetration sterilization action, and it is recognized that there is a slight but at least biofilm formation inhibitory action, but the action is not sufficient. On the other hand, when the component (b) is used in combination with the component (a), the biofilm formation inhibitory effect is enhanced and expressed, and unexpected unexpected action effects are obtained. In addition, even if the sterilizing agent uses a cationic disinfectant in combination with the component (a), it is not confirmed that the enhancement of the biofilm formation inhibitory action is confirmed, which is a unique effect of the component (b).

(b) As the nonionic fungicide, isopropyl methylphenol, triclosan, and thymol can be used. These may be used alone or in combination of two. In addition, isopropyl methylphenol is 4-isopropyl-3-methylphenol (Biosol®). Thymol is 2-isopropyl-5-methylphenol. Among them, isopropyl methylphenol (4-isopropyl-3-methylphenol) is preferred in terms of taste when used as an oral composition. They can use commercial products.

In addition, (a)/(b) showing the ratio between the components (a) and (b) is preferably from 0.01 to 200, more preferably from 0.01 to 100, even more preferably from 0.03 to 100, most preferably as a mass ratio. It is 0.03 to 80. When it is within this range, the biofilm formation inhibitory effect is more excellent.

The oral biofilm formation inhibitor of the present invention can be obtained by using the component (a) alone, preferably also the component (b) in combination, and blending the components as an active ingredient. Further, if necessary, other known ingredients for oral use may be included, and in this case, the known ingredients may be blended within a range that does not interfere with the effects of the present invention.

The composition for oral cavity of this invention contains (a) component and (b) component. As an oral composition, specifically, a paste-like, gel-like, or liquid skirting agent (cream toothpaste, gel-like toothpaste, liquid toothpaste, liquid toothpaste, etc.), mouthwash, mouse spray, coating agent, patch, etc. can be suitably mixed. Especially, it is suitable as a skirt composition, especially as a cream skirt composition. In addition, since it has an excellent biofilm suppression effect, it is suitable as an oral composition for oral biofilm suppression.

In this case, when the components (a) and (b) are used in combination as an oral biofilm formation inhibitor in the present invention, the specific ratio can be defined. Further, in the present invention, the blending amounts of the component (a) and the component (b) are preferably in the ranges described below, respectively, in terms of the biofilm formation inhibitory effect and the usability, and the components are preferably used at a concentration satisfying them. .

(a) As for the compounding quantity of a component, 0.01-2% (mass %, same as follows) of the whole composition is preferable, More preferably, it is 0.01-1%, More preferably, it is 0.03-1%, Most preferably, it is 0.08-0.8. %to be. When it is 0.01% or more, a sufficient biofilm formation inhibitory effect is obtained. If it is 2% or less, unpleasant odor derived from component (a) can be sufficiently suppressed.

The blending amount of the component (b) is preferably 0.01 to 1% of the total composition, and more preferably 0.03 to 0.5%. When it is 0.01% or more, a sufficient biofilm formation inhibitory effect is obtained, and unpleasant odor caused by the component (a) can be sufficiently suppressed. If it is 1% or less, it is possible to suppress the imitation by itself, and sufficiently suppress the bitter taste caused by the use of the components (a) and (b).

In the oral composition of the present invention, a known component according to a formulation or the like can also be blended as required. It is preferred that the optional components are added in a range that does not interfere with the effects of the present invention. Specifically, an abrasive, a caking agent, a viscous agent, a surfactant, a sweetener, a preservative, a colorant, a fragrance, an active ingredient, etc. can be blended with the skirting agent, and these components and water can be mixed to prepare.

The abrasives include, for example, silica-based abrasives such as silicic anhydride, crystalline silica, amorphous silica, silica gel, aluminosilicate, calcium triphosphate, calcium tetraphosphate, calcium hydrogen phosphate anhydride, calcium hydrogen phosphate dihydrate, etc. Calcium phosphate abrasive, zeolite, calcium pyrophosphate, calcium carbonate, sodium hydrogen carbonate, aluminum hydroxide, alumina, magnesium carbonate, triphosphate magnesium, zirconium silicate, hydroxyapatide, synthetic resin abrasives are exemplified. These may be used singly or in combination of two or more, but among them, silica-based abrasives such as silicic anhydride as an inorganic abrasive, calcium phosphate-based abrasives, and particularly silicic anhydride are preferred from the viewpoint of usability (the amount of the abrasive blended is usually 5-60%, 10~55% for cream toothpaste).

In addition, in the case of paste compositions such as cream toothpaste, alginic acid derivatives such as sodium alginate and propylene glycol alginate, xanthan gum, tragacanth gum, gellan gum, karaya gum, gum arabic gum, etc. Crosslinked polyacrylates having an average molecular weight of more than 20,000, carrageenan, cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, sodium carboxymethylhydroxyethylcellulose, polyvinyl alcohol, carboxyvinyl polymer, polyvinylpy An organic caking agent such as lollydon, an inorganic caking agent such as silica gel, aluminum silica gel, bigum, or laponite can be blended (the amount of mixing is usually 0.3 to 10%).

In particular, in the paste or liquid skirting agent, one or two or more polyalcohols such as sugar alcohols such as sorbitol, maltitol, lactitol, and erythritol, or propylene glycol can be blended as a viscous agent (the mixing amount is usually 5 to 70). %).

Surfactants may be combined with anionic surfactants, nonionic surfactants and amphoteric surfactants. These can use 1 type(s) or 2 or more types.

Examples of the anionic surfactant include alkyl sulfates having 12 to 14 carbon atoms, particularly 12 alkyl groups, acylamino acid salts and acyl taurine salts. The acyl group of acylamino acid salt and acyl taurine salt has 12 to 14 carbon atoms, particularly 12.

Specifically, as the alkyl sulfate, as the lauryl sulfate, myristyl sulfate, and acylamino acid, acyl glutamate such as lauroyl glutamate and myristoyl glutamate and acyl sarcosine salts such as lauroyl salcosine salt are exemplified, and acyl taurine As the salt, lauroyl methyl taurine salt is exemplified. The salt is preferably an alkali metal salt such as sodium salt or potassium salt. In particular, alkyl sulfates, acyl sarcosine salts and acyl taurine salts are preferred. Among them, anionic surfactants having a hydrocarbon group (lauryl group) having 12 carbon atoms are preferred, and alkyl sulfates (sodium salt) are more preferable because they are superior in terms of taste than other surfactants.

Examples of the nonionic surfactant include polyoxyethylene alkyl ether, polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene cured castor oil, polyoxyethylene ether of glycerin ester, sucrose fatty acid ester, alkylolamide, sorb Non-fatty acid esters, polyoxyethylene sorbitan fatty acid esters, and glycerin fatty acid esters are exemplified. Of these, polyoxyethylene alkyl ether, polyoxyethylene cured castor oil, alkylolamide, and sorbitan fatty acid ester are suitable from the viewpoint of versatility. The polyoxyethylene alkyl ether preferably has 14 to 30 carbon atoms in the alkyl chain and 3 to 30 ethylene oxide average added moles (average added EO). The polyoxyethylene cured castor oil preferably has an average added EO of 10 to 100. The alkylolamide preferably has 12 to 14 carbon atoms in the alkyl chain. The sorbitan fatty acid ester preferably has 12 to 18 carbon atoms in the fatty acid. The polyoxyethylene sorbitan fatty acid ester preferably has 16 to 18 carbon atoms and 10 to 40 average added EO.

Examples of the amphoteric surfactant include acylaminoacetic acid betaine having an acyl group having 12 to 14 carbon atoms and fatty acid amide propyl betaine. Examples of acylaminoacetic acid betaine include lauroyldimethylaminoacetic acid betaine and fatty acid amidepropyl betaine, and palm oil fatty acid amidepropyl betaine.

The blending amount of the surfactant is usually 0.01 to 15%, particularly 0.01 to 10%.

Further, the blending amount of the anionic surfactant is preferably 0.1 to 3%, particularly 0.5 to 2%, and the blending amount of the nonionic surfactant is preferably 0.01 to 10%.

In the present invention, when a nonionic surfactant (e.g., polyoxyethylene cured castor oil) is used in combination with component (a), the odor and taste may be deteriorated depending on the amount added, but the usability may be reduced, but anionic interfaces such as alkyl sulfates When the nonionic surfactant is added together with the active agent, the deterioration of the odor or taste is prevented, and the effect of suppressing the formation of the biofilm is further improved without lowering the feeling of use.

Sweeteners include sodium saccharin, stevioside, dipotassium glycyrrhizinate, perillartin, taumatin, neohesperidyldihydrocarcon and aspartylphenylalanine methyl ester. Preservatives include paraoxybenzoic acid esters and sodium benzoate.

Coloring agents include blue 1, yellow 4, and titanium dioxide.

Flavors include peppermint oil, spearmint oil, anise oil, eucalyptus oil, winter green 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, chamomile 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 perfumes such as absolute rose, orange flower, and processed perfumes of these natural perfumes (whole milk cut, after milk cut, fractional distillation, liquid extraction, essence, powder flavoring, etc.), and menthol, carbon, anneal Tol, methyl salicylate, cinnamic aldehyde, 3-l-menthoxypropane-1,2-diol, linalool, linaryl acetate, limonene, menton, menthyl acetate, N-substituted-paramentan-3-carboxa Mead, pinene, octylaldehyde, citral, pullegon, carbyl acetate, anisealdehyde, ethyl acetate, ethylbutyrate, allylcyclohexanepropionate, methylanthranylate, ethylmethylphenylglycidate, vanillin, undelacactone, A la carte flavors such as hexanal, isoamyl alcohol, hexenol, dimethyl sulfide, cycloten, furfural, trimethylpyrazine, ethyl lactate, ethylthioacetate, and also strawberry flavor, apple flavor, banana flavor, pineapple flavor, grape Known fragrance materials used in oral compositions, such as flavor combinations such as flavor, mango flavor, butter flavor, milk flavor, fruit mix flavor, and tropical fruit flavor, can be used, and are not limited to the flavor of the embodiment.

In addition, the fragrance material is preferably used 0.000001 to 1% of the total composition. It is preferable to use 0.001 to 2.0% in the composition as the fragrance for fragrance using the fragrance material.

The optional active ingredients include, for example, dextranase, mutanase, lysozyme, amylase, protease, lytic enzyme, enzymes such as SOD (superoxide dismutase); Alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate; Fluorides such as sodium fluoride and stannous fluoride; Anti-inflammatory agents such as tranexamic acid, epsilonaminocaproic acid, allantoin, allantoin chlorohydroxyaluminum, dihydrocholesterol, glycyrrhizic acid and glycyrrhetic acid; Perceptual hypersensitivity improving agents such as potassium nitrate and aluminum lactate; Zinc compounds such as glycerophosphate, chlorophyll, sodium chloride, zinc chloride, zinc oxide, and zinc citrate; Copper compounds such as copper gluconate and copper sulfate; Water-soluble inorganic phosphates such as sodium polyphosphate; Vitamins such as vitamin A, vitamin B group, vitamin C, and vitamin E; Herbal medicines such as yellow and white tea are exemplified. These active ingredients can be used alone or in combination of two or more, and can be blended in an effective amount within a range that does not interfere with the effects of the present invention.

The pH (25°C) of the oral composition is usually in the range, preferably pH 5-9, especially 6-8. Further, the pH may be adjusted by adding a known pH adjusting agent, and for example, hydroxide of an alkali metal such as hydrochloric acid or sodium hydroxide can be used.

Example

Hereinafter, the present invention will be specifically described with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. In addition, in the following example,% represents mass% unless otherwise specified.

In addition, the weight average molecular weight (Mw) was measured by GPC (gel permeation chromatography method) in the same method and measurement conditions as above.

[Examples, Comparative Examples]

A formulation for oral cavity containing a polyacrylic acid salt of the type and amount shown in Table 1 and a component (b) was prepared, and the effect of inhibiting biofilm formation was evaluated by the following method. The results are shown in Table 1.

In addition, the skirt composition (cream toothpaste) of the composition shown in Tables 2 and 3 was prepared by a conventional method, and was filled in an aluminum laminate tube container. The biofilm formation inhibitory effect and the usability (smell) were evaluated by the following method. The results are listed in Tables 2 and 3.

(1) Evaluation method of biofilm formation inhibitory effect

The following four types of bacteria were used to produce the model biofilm.

(i) Actinomyces viscosus ATCC43146

(ii) Fusobacterium nucleatum ATCC10953

(iii) Porphyromonas gingivalis ATCC33277

(iv) Veillonella parvula ATCC17745

The bacteria of (i), (ii), and (iii) were TODD HEWITT Broth (manufactured by Becton and Dickinson) containing 5 mg/L of hemin (manufactured by Sigma) and 1 mg/L of vitamin K (manufactured by Wako Pure Chemical Corporation). Cultured by. The bacteria of (iv) were cultured with TODD HEWITT Broth (Becton and Dickinson) culture solution containing 1.26% sodium lactate (Sigma). In addition, the culture was performed anaerobic culture at 37°C overnight (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% hydrogen).

The cultured 4 strains were previously inoculated to be 1×10 ⁷ cfu/mL in a Rotating Disk Reactor (cultivation tank) containing 3,000 mL of Baysal Medium mucin culture (BMM) ^*1 . The hydroxyapatite plate (manufactured by HOYA Co., Ltd., diameter φ7.0 mm×thickness 3.5 mm, abbreviated as HA plate), treated with human unirritated saliva filtered through a 0.45 μm filter in the culture tank, It was installed as a carrier for model biofilm formation. In this state, culture was performed for 24 hours under anaerobic conditions (95 vol% nitrogen, 5 vol% carbon dioxide).

Subsequently, under anaerobic conditions (95 vol% nitrogen, 5 vol% carbon dioxide), the BMM was replaced with a test solution from a different flow path at a flow rate of 5 vol%/hour (3 times dilution of artificial saliva for oral preparations, BMM for control tests) ) Was continuously cultured for 10 days while continuously supplying each at a flow rate of 5 vol%/hour of substitution.

The HA plate after the continuous culture treatment was taken out, transferred to a 24-well multiplate (manufactured by Sumitomo Bakelite Co., Ltd.), and phosphate buffered physiological saline ^*2 (Phosphate Buffered Saline, hereinafter abbreviated as PBS) 7 times with 1 mL After washing, the biofilm formed on the surface of the HA plate was stained by immersion in a 0.1% crystal violet solution for 15 minutes. The crystal violet solution was removed, washed 5 times with 1 mL of PBS, the pigment was extracted with 2 mL of 30% acetic acid aqueous solution, the absorbance at 550 nm was measured, and the intensity of the absorbance was defined as the amount of biofilm formation.

When the control test was performed, the biofilm formation amount was set to 100, and the biofilm formation rate (%) when each test solution was added thereto was calculated, and the biofilm formation inhibitory effect was evaluated.

Evaluation standard

◎◎: less than 30%

◎: 30% or more but less than 50%

○: 50% or more but less than 70%

△: 70% or more and less than 90%

×: 90% or more

^*1 ; Composition of BMM (expressed as mass in 1 liter)

Proteose peptone (Becton and Dickinson): 4 g/L

Tryptone (manufactured by Becton and Dickinson): 2 g/L

Yeast extract (manufactured by Becton and Dickinson): 2 g/L

Mucin (manufactured by Sigma): 5 g/L

Hemin (manufactured by Sigma): 2.5mg/L

Vitamin K (manufactured by Wako Pure Chemical Corporation): 0.5 mg/L

KCl (manufactured by Wako Pure Chemical Corporation): 1 g/L

Cysteine (manufactured by Wako Pure Chemical Corporation): 0.2 g/L

Distilled water: balance

(Massed up so that the total amount was 1 L, and autoclaved at 120°C for 20 minutes)

^*2 ; Composition of PBS (expressed as mass in 1 liter)

NaCl (manufactured by Wako Pure Chemical Corporation): 8.0 g

KCl (manufactured by Wako Pure Chemical Corporation): 0.2 g

_{Na 2 HPO 4 · 12H 2 O} (Wako Pure Chemical Corporation No.): 3.63g

KH ₂ PO ₄ (manufactured by Wako Pure Chemical Corporation): 0.24 g

Distilled water: balance

(Adjusted to pH7.4 with 1N HCl, and scaled to 1L in total)

(2) How to evaluate usability

The 10 subjects monitor evaluated the feeling of use (smell) when they washed the inside of the mouth by brushing for 3 minutes by putting 1 g of the skirt composition on a toothbrush and evaluating it according to the following rating criteria. The average of 10 evaluation points was calculated and judged according to the following evaluation criteria.

Based on rating of usability (smell)

4 points|pieces: There is no unpleasant smell in the oral cavity.

3 points: A slight unpleasant odor in the oral cavity, but at a level without problems

2 points|pieces: an unpleasant smell in a mouth

1 point: Strong feeling of unpleasant odor in the oral cavity

Evaluation criteria of usability (no smell)

◎: Average score of 3.5 or higher

○: Average score of 3.0 to less than 3.5

△: Average score of 2.0 to less than 3.0

×: less than the average score of 2.0 points

Details of the raw materials used are shown below.

(a) Sodium polyacrylate (Mw: 1,000)

Straight, made by Polysciences Inc.

(a) Sodium polyacrylate (Mw: 6,000)

Straight chain, manufactured by Toagosei Co., Ltd., AC-10NP

(a) Sodium polyacrylate (Mw: 8,000)

Straight, made by Polysciences Inc.

(a) Sodium polyacrylate (Mw: 20,000)

Direct trade, manufactured by Toagosei Co., Ltd., ARON A-20UN

Sodium polyacrylate (Mw: 300,000, comparative product)

Cross-linked, made by Polysciences Inc.

Polyacrylic acid (Mw: 6,000, comparative product)

Direct trade, manufactured by Toagosei Co., Ltd., ARON A-10SL

(b) isopropylmethylphenol

4-isopropyl-3-methylphenol ([biosol]), manufactured by OSAKA KASEI CO., LTD.

(b) thymol

2-isopropyl-5-methylphenol, manufactured by OSAKA KASEI CO., LTD.

(b) Triclosan

BASF Co. Ltd.

Claims (12)

(a) An oral biofilm formation inhibitor containing a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less. (a) a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less, and
(b) Nonionic fungicide
Oral biofilm formation inhibitor containing a. According to claim 2,
(b) An oral biofilm formation inhibitor, wherein the component is at least one nonionic fungicide selected from isopropylmethylphenol, triclosan and thymol. The method of claim 2 or 3,
(a)/(b) An oral biofilm formation inhibitor having a mass ratio of 0.01 to 200. The method according to any one of claims 1 to 4,
An oral biofilm formation inhibitor having a weight average molecular weight of 1,000 to 10,000 of polyacrylic acid. (a) a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less, and
(b) Nonionic fungicide
Oral composition comprising a. The method of claim 6,
Oral composition having a weight average molecular weight of 1,000 to 10,000 of polyacrylic acid. The method according to claim 6 or 7,
(b) Oral composition wherein the component is at least one nonionic fungicide selected from isopropylmethylphenol, triclosan and thymol. The method according to any one of claims 6 to 8,
(a) / (b) Oral composition is 0.01 to 200 as a mass ratio. The method according to any one of claims 6 to 9,
(a) The composition for oral cavity containing 0.01-2 mass% of components, and (b) 0.01-1 mass% of components. The method according to any one of claims 6 to 10,
Oral composition for oral biofilm suppression. The method according to any one of claims 6 to 11,
A composition for oral cavity that is a skirt composition.