JP5729252B2 - Oral composition - Google Patents

Description

  The present invention is superior in periodontal pathogenic bacteria tooth surface adhesion inhibitory effect, tooth surface coating effect, penetrating effect and bactericidal effect of bactericidal components to periodontal pathogenic biofilm, and has a high periodontal disease prevention effect, In particular, the present invention relates to an oral composition having a high formulation clarity when prepared into a liquid.

Conventionally, various medicinal ingredients have been incorporated into oral compositions as preventive and therapeutic agents for gingivitis and periodontitis.
Periodontal disease is considered to be an infectious disease that develops due to colonization of pathogenic bacteria in the oral cavity, and it is important to eliminate infected pathogenic bacteria for the prevention and improvement of periodontal disease. For this reason, various bactericides and antibiotics are used, but pathogenic bacteria that cause periodontal disease form biofilms and are known to be resistant to bactericides and antibiotics. In particular, a cationic bactericidal agent cannot be sterilized fundamentally because it adsorbs to the biofilm surface and does not penetrate inside. Therefore, a technology using isopropylmethylphenol, which is a nonionic fungicide that penetrates and sterilizes the periodontopathic biofilm, as a technology that has a high inhibitory effect on the periodontopathogenic biofilm causing periodontal disease. Has been developed.

  Until now, in the technology for preventing oral diseases by using isopropylmethylphenol, isopropylmethylphenol is a low-concentration nonionic surfactant (POE (polyoxyethylene) hydrogenated castor oil) in order to exert its bactericidal effect. Solubilized and formulated (Patent Documents 1 and 2). However, the prevention and improvement of oral diseases due to the sterilizing effect inside these biofilms of isopropylmethylphenol acts on the periodontopathic biofilm generated in the periodontal pocket due to insufficient oral cleaning. Therefore, the effect of suppressing the production of biofilm formed by floating bacteria adhering to the tooth surface, forming micro-colony, and maturation was low and there was room for improvement. Moreover, in the composition for oral cavity which mix | blended isopropylmethylphenol, it is the further subject to make the said useful effect and the clearness of an external appearance compatible.

  On the other hand, for prevention of periodontal disease, not only sterilization of already formed periodontopathic biofilm, but also suppression of colonization of pathogenic bacteria causing periodontal disease in the oral cavity, and suppression of new biofilm formation It is also important to do. In the process of forming a biofilm, a method for suppressing biofilm formation by suppressing the adhesion of planktonic bacteria on the tooth surface, which is the initial stage, has been considered, and several attempts have been made.

  Oral composition with improved oral retention of triclosan and increased prevention of plaque formation and prevention of gingivitis by using alginic acid and its salts or esters in combination with nonionic fungicide triclosan Is described in Patent Document 3. However, this technology has not enough biofilm sterilization effect and has room for improvement.

  Alginate esters such as propylene glycol alginate are mainly used as a binder for dentifrice compositions, and may be used for the purpose of improving liquid separation and viscosity reduction of toothpaste (Patent Document 4, 5) Used for suppressing adsorption of fat-soluble vitamins in containers containing semi-solid preparations (Patent Document 6) or used for masking tastes derived from essential oils (Patent Document 7). For the purpose of preventing oral diseases, a composition having both stable retention of fluoride colloid and prevention of dental caries is disclosed by using water-soluble hydrofluoric acid salt and water-soluble calcium salt together with substances that promote their colloidalization. (Patent Document 8).

International Publication No. 2006/67967 Pamphlet International Publication No. 2007/148551 Pamphlet JP-A-4-139118 JP-A-11-71250 JP-A-11-71251 JP 2005-343834 A Special table 2009-520802 JP-A-4-221307

  The present invention has been made in view of the above circumstances, and is excellent in periodontal pathogenic biofilm production suppression and osmotic sterilization effects, has a high periodontal disease prevention effect, and has high clarity especially when prepared in a liquid. It aims at providing the composition for oral cavity which has a formulation external appearance.

  As a result of intensive studies to achieve the above object, the present inventors have used a combination of alginate propylene glycol ester (A) and isopropylmethylphenol (B), and a specific nonionic surfactant (C). Inhibiting periodontal pathogenic bacteria's tooth surface adhesion and tooth surface coating effects, and improving the sterilization effect derived from isopropylmethylphenol, thereby preventing periodontal pathogenic biofilm formation It was also found that a preparation having a clear appearance can be obtained, particularly when it is prepared in a liquid, which is excellent in osmotic and bactericidal effects and exhibits a high periodontal disease-preventing effect.

  That is, according to the present invention, by using the components (A), (B) and (C) in combination, the effect of suppressing periodontal adhesion of periodontopathogenic bacteria, the effect of tooth surface coating, the periodontal pathogenicity of the bactericidal component The composition for oral cavity which is excellent in the penetration effect to a biofilm and the periodontopathic biofilm sterilization effect and has high clarity can be obtained.

  Furthermore, by blending ethanol and / or polyhydric alcohol (D) into the composition for oral cavity and making the total content of component (D) 3 to 15% by mass, the above effects are excellent and long-term storage at high temperature is possible. The appearance stability at the time can also be improved.

  Furthermore, by incorporating at least one anionic surfactant (E) selected from alkyl sulfates and acyl sarcosinates into the oral composition, the penetration effect on periodontopathic biofilm and sterilization The effect can be enhanced.

There are two ways to prevent and improve periodontal disease: sterilization of the already formed periodontopathic biofilm and suppression of new biofilm formation by inhibiting colonization of pathogenic bacteria causing periodontal disease in the oral cavity. Coping is effective and important. The composition for oral cavity containing isopropylmethylphenol as a bactericidal agent has a bactericidal effect on periodontopathic biofilms, but has little effect of suppressing biofilm formation, and conventional techniques cannot combine these. There wasn't.
In contrast, the present inventors have suppressed the adhesion of periodontal disease-causing bacteria, particularly Porphyromonas gingivalis, to the tooth surface of propylene glycol alginate, which has not been known so far. It has been found that there is an effect of suppressing film formation. Further, by combining this propylene glycol alginate with isopropylmethylphenol and blending the specific nonionic surfactant, the above-described effects are exhibited, the periodontal pathogenic biofilm formation inhibitory effect and osmotic sterilization I found out that there was an effect.
From the prior art, it is impossible to predict that propylene glycol alginate has an effect of suppressing the adhesion of the periodontal disease causing the tooth surface and enhances the biofilm bactericidal effect.

  In the present invention, the mechanism of action is not clear, but by blending a combination of propylene glycol alginate and isopropylmethylphenol, the preparation is effectively coated (coated) on the tooth surface, and the periodontopathic biofilm Effective periodontal disease bacteria with high anti-drug barrier performance that effectively suppress initial periodontal adhesion of periodontopathic bacteria, which is the initial stage of the generation of the drug, and remain in the interdental and gingival margins where cleaning is inadequate Bactericidal component isopropylmethylphenol has high penetrating effect on biofilm, and effective bactericidal effect on oral bacteria such as periodontal disease bacteria in periodontal disease biofilm is effectively expressed, and the clarity of the preparation is improved. It is presumed that they can be combined.

Accordingly, the present invention provides the following oral composition.
[1]
Polyoxyethylene hydrogenated castor oil containing propylene glycol alginate (A) and isopropylmethylphenol (B) and having an average addition mole number of ethylene oxide of 40 to 100 moles, and an alkyl group having 16 to 18 carbon atoms And at least one nonionic surfactant (C) selected from polyoxyethylene alkyl ethers having an average addition mole number of ethylene oxide of 20 to 40 moles and decaglycerin monofatty acid esters of fatty acids having 12 to 18 carbon atoms A composition for oral cavity, comprising:
[2]
The composition for oral cavity according to [1], wherein the mixing ratio of the component (A) and the component (B) is 0.4 to 20 as a mass ratio of (A) / (B).
[3]
The composition for oral cavity according to [1] or [2], containing 0.05 to 0.5% by mass of component (A) and 0.01 to 0.1% by mass of component (B).
[4]
The composition for oral cavity according to [1], [2] or [3], containing 0.1 to 1% by mass of the component (C).
[5]
Furthermore, the composition for oral cavity in any one of [1]-[4] containing ethanol and / or a polyhydric alcohol (D).
[6]
The composition for oral cavity according to [5], wherein the total content of component (D) is 3 to 15% by mass.
[7]
Furthermore, the composition for oral cavity in any one of [1]-[6] containing the at least 1 sort (s) of anionic surfactant (E) chosen from an alkyl sulfate and an acyl sarcosine salt.
[8]
The composition for oral cavity according to any one of [1] to [7], which is prepared as a liquid preparation.

  The composition for oral cavity of the present invention is superior in the effect of suppressing periodontal pathogenic bacteria adhesion on the tooth surface and the effect of tooth surface coating, and has a high penetration effect and bactericidal effect on the periodontal pathogenic biofilm, and is particularly a liquid preparation. It has a clear appearance when prepared and is effective in preventing and improving oral diseases such as periodontal disease.

Hereinafter, the present invention will be described in more detail.
The composition for oral cavity of the present invention comprises propylene glycol alginate (A), isopropylmethylphenol (B) as a bactericidal component, and an average addition mole number (EO addition) of ethylene oxide as a nonionic surfactant (C). Polyoxyethylene hydrogenated castor oil having an abbreviation of “number of moles.” Of 40 to 100 moles, an E.C. O. At least 1 sort (s) chosen from the polyoxyethylene alkyl ether whose addition mole number is 20-40 mol, and the decaglycerin mono fatty acid ester whose carbon number of a fatty acid is 12-18 is mix | blended, It is characterized by the above-mentioned.

  The propylene glycol alginate of component (A) is blended as an adhesion inhibitor for periodontopathic bacteria. As a propylene glycol alginate ester, it is possible to use an ester obtained by introducing a propylene glycol group into a carboxyl group in order to enhance the acid resistance and salt resistance of natural polysaccharide alginic acid unique to brown algae represented by kombu and wakame. , Duckroid manufactured by Food Chemifa Co., Kimiroid manufactured by Kimika Co., Ltd., and those marketed under trade names such as kelp acid.

  The alginic acid skeleton of propylene glycol alginate consists of D-mannuronic acid [M] linked with β-1,4 and L-guluronic acid [G] bonded with α-1,4. The quantitative ratio (M / G ratio molar ratio) between D-mannuronic acid and L-guluronic acid is preferably more than 1.0 from the viewpoint of appearance stability during high-temperature storage, and the upper limit is 2 or less. When the M / G ratio is 1.0 or less, turbidity may occur during storage at high temperatures, and appearance stability may not be ensured. Products exceeding 2 are not commercially available.

  When synthesizing alginate propylene glycol ester from alginic acid by esterification, the degree of substitution of the carboxyl group, that is, the degree of esterification, varies depending on the reaction conditions. The higher the degree of esterification, the higher the effect of inhibiting bacterial adhesion. From the viewpoints of bacterial adhesion inhibiting effect, biofilm permeability and bactericidal effect, the degree of esterification of the carboxyl group is 70% or more, especially 70 to 95%. preferable. If the degree of esterification is less than 70%, turbidity may occur during high-temperature storage, and appearance stability may not be ensured. Those having a degree of esterification exceeding 95% are not commercially available.

  The viscosity of propylene glycol alginate is determined by the method of measuring with a B-type viscometer, which will be described later. The viscosity at 20 ° C. of a 1% aqueous solution (hereinafter the same applies) is clear immediately after preparation of the formulation and is stable in appearance at high temperature storage. From 10 to 150 mPa · s, particularly 10 to 60 mPa · s is preferable. A 1% aqueous solution having a viscosity of less than 10 mPa · s is not commercially available. If it exceeds 150 mPa · s, the clarity of the preparation may not be sufficiently obtained, and the appearance stability during high-temperature storage may not be ensured satisfactorily.

For example, the following commercially available products can be used.
Propylene glycol alginate brand name Kelp acid 503:
1% aqueous solution viscosity 18 mPa · s (rotor No. 1, 60 rpm), M / G ratio = 1.3, degree of esterification = 80% / trade name, manufactured by Kimika Co., Ltd. Kimiloid BF:
1% aqueous solution viscosity 20 mPa · s (rotor No. 1, 60 rpm), M / G ratio = 1.3, degree of esterification = 80% / trade name, manufactured by Kimika Co., Ltd. Kimiloid LLV:
1% aqueous solution viscosity 24 mPa · s (rotor No. 1, 60 rpm), M / G ratio = 1.3, degree of esterification = 80% / trade name, manufactured by Kimika Co., Ltd. Kimiloid NLS-K:
1% aqueous solution viscosity 55 mPa · s (rotor No. 1, 60 rpm), M / G ratio = 1.3, degree of esterification = 80% / trade name, manufactured by Kimika Co., Ltd. Kimiloid LV:
1% aqueous solution viscosity 90 mPa · s (rotor No. 1, 30 rpm), M / G ratio = 1.3, degree of esterification = 80% / trade name, manufactured by Kimika Co., Ltd. Kimiloid MV:
1% aqueous solution viscosity 148 mPa · s (rotor No. 1, 30 rpm), M / G ratio = 1.3, degree of esterification = 80% / trade name, manufactured by Kimika Co., Ltd. Duck Lloyd LF:
1% aqueous solution viscosity 21 mPa · s (rotor No. 1, 60 rpm), M / G ratio = 0.8, degree of esterification = 75% / trade name, manufactured by Food Chemifa Corporation Duck Lloyd PF:
1% aqueous solution viscosity 51 mPa · s (rotor No. 1, 60 rpm), M / G ratio = 0.8, degree of esterification = 75% / manufactured by Food Chemifa Corporation

The viscosity is a value measured by a BL type viscometer, and specifically, a measured value by the following method.
Viscosity measurement method (Duck Lloyd, Food Chemifa Corporation)
4 g of propylene glycol alginate is collected and placed in a 600 mL beaker, and 396 g of purified water is added little by little while stirring with a stir bar. First, dissolve well with a small amount of water. Thereafter, the mixture is allowed to swell for 1 hour, and after 1 hour, the mixture is stirred for 1 minute at 12,000 rpm with a high-speed stirrer (homomixer). This solution is put into a 300 mL tall beaker and allowed to stand in a 20 ° C. water bath. When the foam rises and the beaker solution is clear, remove the top foam with a spoon. A thermometer is put in a beaker to confirm that the test solution has reached 20 ° C., and the viscosity is measured.
Viscometer: Tokyo Keiki BL type viscometer rotor: No. 1
Rotation speed: 60rpm
Measurement time: 1 minute

Viscosity measurement method (Kimiloid, Kimlicum, Kimika Co., Ltd.)
In a 300 mL tall beaker, 297 g of purified water is taken and 3.0 g of alginic acid propylene glycol ester is added and completely dissolved while stirring with a stirrer or three-one motor. Next, after leaving still in a 20 degreeC thermostat for 1 hour, the viscosity after 1 minute is measured correctly using BL type | mold viscometer.
Viscometer: Tokyo Keiki BL type viscometer measurement conditions ・ When 1% aqueous solution viscosity is 10-80 mPa · s: Rotor No. 1. Rotation speed 60rpm
When the 1% aqueous solution viscosity exceeds 80 mPa · s and is 160 mPa · s or less: Rotor No. 1, rotation speed 30rpm
When the 1% aqueous solution viscosity exceeds 160 mPa · s and is 400 mPa · s or less: Rotor No. 2, rotation speed 60rpm
When the 1% aqueous solution viscosity exceeds 400 mPa · s and is 800 mPa · s or less: Rotor No. 2, rotation speed 30rpm
When the 1% aqueous solution viscosity exceeds 800 mPa · s and is 1600 mPa · s or less: Rotor No. 3, rotation speed 60rpm
Measurement time: 1 minute

  The blending amount of propylene glycol alginate is 0.05-0.5% from the viewpoint of the tooth surface adhesion inhibitory effect of periodontopathic bacteria, the tooth surface coating effect, the clarity of the preparation, and the appearance stability during high temperature storage. (Mass%, the same applies hereinafter), and particularly preferably 0.1 to 0.2%. If it is less than 0.05%, the adhesion inhibitory effect on the tooth surface adhesion of the periodontopathic bacteria and the tooth surface coating effect may not be sufficiently exhibited. If it exceeds 0.5%, the solubility of propylene glycol alginate may be insufficient, and the clarity immediately after preparation of the preparation may be impaired, or high-temperature appearance stability may not be ensured.

  Isopropyl methylphenol (B), which is a bactericidal component, is a nonionic bactericide with a broad antibacterial spectrum, such as those commercialized by Takasago Fragrance Co., Ogawa Fragrance Co., Osaka Kasei Co., Ltd., Sumitomo Pharmaceutical Co., Ltd. Commercial products can be used.

  The blending amount of isopropylmethylphenol is the point of clarification of the formulation, appearance stability at high temperature storage and penetration effect of bactericidal components on periodontopathic biofilm, bactericidal effect on periodontopathic biofilm, 0.01 to 0.1%, particularly 0.02 to 0.07% of the whole composition is preferable. If it is less than 0.01%, the penetrating effect of the bactericidal component on the periodontopathic biofilm and the bactericidal effect may not be sufficiently exhibited. If it exceeds 0.1%, the solubility of isopropylmethylphenol itself may be poor, and the clarity immediately after preparation of the preparation may be impaired, or the appearance stability may be impaired due to white turbidity during storage at high temperatures.

  The mass ratio of component (A) / component (B) is not particularly limited, but is preferably 0.4 to 20, particularly 1 to 10. If the mass ratio of component (A) / component (B) is smaller than 0.4 or exceeds 20, the adhesion inhibitory effect of periodontal disease-causing bacteria and the biofilm bactericidal effect may not be sufficiently exhibited.

  The nonionic surfactant of component (C) is in terms of the clarity of the preparation, the appearance stability after high-temperature storage, the penetration effect on periodontopathic biofilm, and the bactericidal effect on periodontopathic biofilm. E. O. A polyoxyethylene hydrogenated castor oil having an addition mole number of 40 to 100 mole, particularly 60 to 100 mole, an alkyl group having 16 (cetyl) to 18 (stearyl) carbon atoms and E. coli. O. One kind selected from polyoxyethylene alkyl ether having an added mole number of 20 to 40, decaglycerin monofatty acid ester having a fatty acid carbon number of 12 (lauric acid) to 18 (stearic acid), particularly 12 to 14 (myristic acid) Or it is 2 or more types. In addition, you may use together the said polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, and decaglycerin monofatty acid ester as a component (C). Ingredient (C) is particularly important for the clarity of the preparation and the effect of penetrating into periodontal pathogenic biofilms. When ingredient (C) is not included, or in place of ingredient (C), other nonionic substances are used. When a surfactant is used, a clear appearance and biofilm penetration effect cannot be obtained.

E. of polyoxyethylene hydrogenated castor oil O. If the number of added moles is less than 40, the solubilizing power is low and the solubility of the surfactant itself is low, solubilization of propylene glycol alginate and isopropylmethylphenol, clearness immediately after preparation of the preparation, and stability of appearance when stored at high temperature. Inferior to sex. More than 100 are not commercially available.
E. of polyoxyethylene alkyl ethers O. If the number of added moles is less than 20, the solubilizing power is low and the solubility of the surfactant itself is low, solubilization of propylene glycol alginate and isopropylmethylphenol, clarity immediately after preparation of the preparation, and appearance stability during high-temperature storage. Inferior to More than 40 are not commercially available. Moreover, in the said polyoxyethylene alkyl ether, when the carbon number of an alkyl group is less than 16 or more than 18, the appearance stability at the time of high temperature storage is inferior.
Decaglycerin monofatty acid esters with fatty acids having less than 12 or more than 18 carbons have low solubilizing power, solubilization of propylene glycol alginate and isopropylmethylphenol, clarity immediately after preparation and high temperature storage Inferior in appearance stability.

  As such nonionic surfactants, for example, as polyoxyethylene hydrogenated castor oil, NIKKOL HCO system manufactured by Nikko Chemicals, Emarex HC system manufactured by Nippon Emulsion Co., and UNIOX HC system manufactured by Nippon Oil & Fats Co., Ltd. As the polyoxyethylene alkyl ether, NIKKOL BC series, NIKKOL BS series manufactured by Nikko Chemicals, Emarex 100 series, Emarex 600 series manufactured by Nihon Emulsion Co., etc., and as decaglycerin monofatty acid ester, Nikko Chemicals NIKKOL Decagln series manufactured by the company, Ryoto (registered trademark) polyglycerester D series manufactured by Mitsubishi Chemical Foods, Inc., etc. are commercialized, and these commercial products can be used.

  The total compounding amount of the component (C) is the effect of suppressing the adhesion of periodontopathic bacteria, the tooth surface coating effect, the solubilization of propylene glycol alginate and isopropylmethylphenol, the clarity of the preparation, and the appearance stability during high temperature storage. In this respect, it is preferably 0.1 to 1%, more preferably 0.3 to 0.7%. If it is less than 0.1%, it may be difficult to maintain the solubilization of propylene glycol alginate and isopropylmethylphenol, the clarity immediately after preparation of the preparation, and the appearance stability during high-temperature storage. If it exceeds 1%, the inhibitory effect of the periodontal pathogenic bacteria on the tooth surface and the tooth surface coating effect may be impaired, and the penetration effect and the bactericidal effect of the bactericidal component on the periodontal pathogenic biofilm may be impaired. .

  The composition of the present invention may further contain ethanol and / or polyhydric alcohol as component (D). Appropriate blending of the specific components can ensure appearance stability during high temperature storage.

  A commercial item can be used for a component (D). Examples of ethanol include fermented alcohol manufactured by Nippon Alcohol Industry, and synthetic alcohol manufactured by Nippon Synthetic Alcohol.

The polyhydric alcohol is preferably one or more selected from ethylene glycol, propylene glycol, butylene glycol, glycerin, and polyethylene glycol having an average molecular weight of 190 to 630 from the viewpoint of appearance stability during high temperature storage.
Examples of polyhydric alcohol include ethylene glycol manufactured by Mitsubishi Chemical Co., Ltd., propylene glycol manufactured by Adeka PG, Asahi Glass Co., propylene glycol, etc., butylene glycol manufactured by Daicel Chemical Co., Ltd. 1,3-BG, etc., average molecular weight As a polyethylene glycol of 190 to 630, a macrogol series manufactured by Sanyo Chemical Co., Ltd., a macrogol series manufactured by Daiichi Kogyo Seiyaku Co., Ltd., etc. are commercialized, and these can be suitably used.

  In addition, the average molecular weight mentioned above shows the average molecular weight described in the Quasi-drug raw material standard 2006, and polyethylene glycol 200 (average molecular weight 190-210), polyethylene glycol 300 (average molecular weight 280) are polyethylene glycol having an average molecular weight 190-630. -320), polyethylene glycol 400 (average molecular weight 380-420), polyethylene glycol 600 (average molecular weight 570-630). Depending on the product, for example, polyethylene glycol # 200, there may be a # between polyethylene glycol and the numerical value.

  The total content of component (D) is the effect of inhibiting periodontal pathogenic bacteria adhesion on the tooth surface, the effect of tooth surface coating, solubilization of propylene glycol alginate (A) and isopropylmethylphenol (B), after storage at high temperature From the viewpoint of appearance stability, 3 to 15% of the entire composition is preferable. In particular, 3.0 to 12.0% is more preferable in terms of the effect of suppressing the adhesion of the periodontopathic bacteria to the tooth surface and the effect of the tooth surface coating. If the total content is less than 3%, the effect of solubilization by solvation of component (D) is small, the solubilization of components (A) and (B) is inferior, and appearance stability after high-temperature storage may be impaired. . When it exceeds 15%, propylene glycol alginate precipitates during storage at high temperature, and appearance stability may be impaired. In addition, the cleaning effect of the tooth surface by the component (D) is strong and the retention is reduced, and the tooth surface coating effect may be lost, or the adhesion inhibitory effect of periodontopathic bacteria may not be exhibited.

Furthermore, it is more preferable that the component (D) is blended so as to satisfy any of the following (d-1) to (d-5) (the contents are all contained in the composition).
That is, when blending ethanol or polyhydric alcohol, the following is preferable.
(D-1) When only ethanol is blended alone, the ethanol content is 3 to 15%.
(D-2) When only polyhydric alcohol is blended, the content of polyhydric alcohol is 5 to 15%.
Moreover, when using ethanol and a polyhydric alcohol together, the following is preferable.
(D-3) When the ethanol content is less than 1% and a polyhydric alcohol is blended, the total content of the polyhydric alcohol is less than 5 to 15%.
(D-4) When ethanol is contained in an amount of 1% to less than 3% and a polyhydric alcohol is blended, the total content of the polyhydric alcohol is 3 to 14%.
(D-5) When ethanol is contained in an amount of 3% to less than 15% and a polyhydric alcohol is blended, the total content of the polyhydric alcohol is 0.01 to 12%.

  (D-1) When only ethanol is used and blended, if the ethanol content is less than 3%, the solubilization effect due to ethanol solvation is small, and propylene glycol alginate and isopropylmethylphenol are satisfactory. It may not be solubilized, and the clarity immediately after preparation of the preparation and the appearance stability after high temperature storage may be insufficient. When it exceeds 15%, propylene glycol alginate precipitates during storage at high temperature, and appearance stability may be impaired. In addition, the cleaning action of the tooth surface by ethanol strongly affects the retention, and the tooth surface coating effect is not sufficient, and the adhesion suppressing effect of periodontopathic bacteria may not be satisfactorily exhibited.

  When (d-2) only polyhydric alcohol is used or blended, or (d-3) ethanol content is less than 1% and polyhydric alcohol is blended, the total content of polyhydric alcohol is If it is less than 5%, the solubilizing effect by solvation of component (D) is small, propylene glycol alginate and isopropylmethylphenol are not solubilized satisfactorily, clarity immediately after preparation of the preparation, appearance stability after high-temperature storage, The penetrating effect of the bactericidal component on the periodontopathic biofilm and the bactericidal effect may be insufficient. If it exceeds 15%, propylene glycol alginate may precipitate during storage at high temperature by component (D), and appearance stability may be impaired. In addition, the tooth surface cleaning action by the component (D) strongly affects the retention, and the tooth surface coating effect is not sufficient, and the adhesion inhibitory effect of periodontopathic bacteria may not be satisfactorily exhibited.

  (D-4) When ethanol is contained in an amount of 1% or more and less than 3%, if the total content of the polyhydric alcohol is less than 3%, the solubilizing effect due to the solvation of component (D) is small. The solubilization of isopropylmethylphenol is inferior, and the clarity immediately after preparation of the preparation, the appearance stability after high-temperature storage, the penetration effect of the bactericidal component on the periodontopathic biofilm and the bactericidal effect may be impaired. If it exceeds 14%, propylene glycol alginate precipitates during storage at high temperature, and appearance stability may be impaired. In addition, the tooth surface cleaning action by the component (D) strongly affects the retention, and the tooth surface coating effect is not sufficient, and the adhesion inhibitory effect of periodontopathic bacteria may not be satisfactorily exhibited.

  (D-5) When ethanol is contained in an amount of 3% or more and less than 15%, if the total content of polyhydric alcohol is less than 0.01%, the solubilizing effect due to the solvation of component (D) is small, and propylene glycol alginate Esters and isopropylmethylphenol are not solubilized satisfactorily, and clarity immediately after preparation preparation, appearance stability after storage at high temperature, penetration of bactericidal components into periodontal pathogenic biofilms and bactericidal effects may be impaired . When it exceeds 12%, propylene glycol alginate precipitates during storage at high temperature, and appearance stability may be impaired. In addition, the tooth surface cleaning action by the component (D) strongly affects the retention, and the tooth surface coating effect is not sufficient, and the adhesion inhibitory effect of periodontopathic bacteria may not be satisfactorily exhibited.

The composition of the present invention may further contain one or more anionic surfactants selected from alkyl sulfates and acyl sarcosine salts as component (E). By blending component (E), the penetration effect and bactericidal effect on periodontopathic biofilms can be enhanced.
The chain length of the alkyl group or fatty acid of the alkyl sulfate and acyl sarcosinate of component (E) is preferably 8 to 12, particularly 12 from the viewpoint of appearance stability during low-temperature storage. Especially as a component (E), sodium lauryl sulfate and / or lauroyl sarcosine sodium are used suitably.

  The compounding amount of component (E) is preferably 0.05 to 1%, particularly 0.05 to 0.5% of the entire composition. If it is less than 0.05%, the penetration effect and bactericidal effect on periodontopathic biofilms may not be improved, and if it exceeds 1%, mucosal irritation is strong and appearance stability during low-temperature storage may be impaired.

  As the container for the composition of the present invention, PET (polyethylene terephthalate), glass, polypropylene, and polyethylene can be used, but the use of PET and glass is preferred from the viewpoint of suppressing adsorption of nonionic fungicides and fragrances.

Although the composition for oral cavity of this invention can be prepared in various forms, it is suitably prepared especially as a liquid formulation. Specifically, it is prepared and applied as a mouthwash of the type that is used as it is, a freshener in the mouth, a mouthwash that is diluted at the time of use in a concentrated type, and a liquid dentifrice that is used by brushing with a toothbrush. In particular, it is suitable as a mouthwash and a liquid dentifrice.
The composition of the present invention has high clarity of appearance of the preparation, particularly when it is prepared as a liquid. Here, “clear” means that the prepared liquid is not turbid.
In the composition of the present invention, in addition to the above-described components, appropriate known components according to the dosage form and the like can be blended as necessary within a range not impairing the effects of the present invention. As optional components, for example, wetting agents, thickeners, preservatives, sweeteners, fragrances, surfactants, active ingredients, coloring agents, pH adjusting agents and the like can be blended. In addition, it is not necessary to mix | blend an abrasive | polishing agent.

  Examples of the wetting agent include sugar alcohols such as sorbitol, xylite, maltite, lactit, trehalose, and tornale. A compounding quantity is 0-25% of the whole composition normally.

Examples of the thickener include xanthan gum, sodium alginate, polyvinyl alcohol, hydroxyethyl cellulose, carrageenan, carboxymethyl cellulose sodium, polyvinyl pyrrolidone and the like. The amount is usually 0 to 3% of the entire composition.
Examples of the preservative include parabens such as sodium benzoate, methyl paraben, ethyl paraben, propyl paraben, and butyl paraben, cetylpyridinium chloride, alkyldiaminoethylglycine hydrochloride, potassium sorbate, and the like.
Examples of sweetening agents include xylitol, maltitol, saccharin, sodium saccharin, steviosite, sucralose, reduced palatinose, erythritol, aspartame and the like.

  Natural flavors such as peppermint oil, spearmint oil, eucalyptus oil, wintergreen oil, clove oil, thyme oil, sage oil, cardamom oil, rosemary oil, marjoram oil, lemon oil, nutmeg oil, lavender oil, paracres oil, etc. Essential oil, and l-menthol, l-carvone, cinnamic aldehyde, orange oil, anethole, 1,8-cineole, methyl salicylate, eugenol, thymol, linalool, limonene, menthone, menthyl acetate, citral, camphor, borneol, pinene, Perfume ingredients contained in the above natural essential oils such as spiranthol, ethyl acetate, ethyl butyrate, isoamyl acetate, hexanal, hexenal, methyl anthranilate, ethyl methyl phenyl glycidate Benzaldehyde, vanillin, ethyl vanillin, furaneol, maltol, ethyl maltol, gamma / delta decalactone, gamma / deltown decalactone, N-ethyl-p-menthane-3-carboxamide, menthyl lactate, ethylene glycol 1-menthyl carbonate Perfume ingredients such as apple, banana, strawberry, blueberry, melon, peach, pineapple, grape, muscat, wine, cherry, squash, coffee, brandy, yogurt 1 type or 2 types or more of compounding flavors, such as these. These fragrance | flavors are 0.00001 to 3% in a composition, and can be used in the range which does not prevent the effect of this invention.

  Surfactants include those other than component (C) and further component (E), such as lauroylmethyltaurine, acylamino acid salts, sodium dodecylbenzenesulfonate, α-sulfo fatty acid alkyl ester / sodium, alkylphosphate ester salts Anionic surfactants such as alkyldimethylaminoacetic acid betaine, fatty acid amidopropyldimethylaminoacetic acid betaine and other ampholytic surfactants, and imidazolines such as N-fatty acid acyl-N-carboxymethyl-N-hydroxyethylethylenediamine salts Type amphoteric surfactants, amino acid type surfactants such as N-fatty acid acyl-L-alginate salts, polyglycerin fatty acid esters other than component (C), polyoxyethylene alkyl ethers, sugar fatty acid esters, sorbitan fatty acid esters, poly Polyoxypropylene block copolymer-type nonionic surfactants, polyoxyethylene fatty acid esters, and the like fatty acid monoglyceride. The amount is usually 0 to 5%.

  Examples of active ingredients include those other than the above components (A) and (B), for example, cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, chlorhexidine hydrochloride, alkyldiaminoethylglycine hydrochloride and the like, tranexamic acid, epsilon- Anti-inflammatory agents such as aminocaproic acid, allatoin, allantoinchlorohydroxyaluminum, allantoindihydroxyaluminum, dextranase, amylase, protease, mutanase, lysozyme, lytic enzyme, enzyme such as lytechenzyme, sodium fluoride, sodium monofluorophosphate, Fluorides such as stannous fluoride, azulene, lysozyme chloride, vitamin C such as ascorbic acid, dihydrocholesterol, glycyrrhetin salts, glycyrrhetinic acids, hydrocholestero , Chlorophyll, copper chlorophyllin sodium, thyme, hornon, clove, hamamelis, etc. plant extracts, copper gluconate, caropeptide, sodium polyphosphate, water-soluble inorganic phosphate compound, polyvinylpyrrolidone, anticalculus agent, anti-plaque agent, Potassium nitrate, aluminum lactate and the like can be added. In addition, the compounding quantity of these other active ingredients can be made into an effective quantity in the range which does not prevent the effect of this invention.

As a colorant, a highly safe water-soluble pigment such as Blue No. 1, Green No. 3, Yellow No. 4, Red No. 105 can be added.
Examples of pH adjusting agents include phthalic acid, phosphoric acid, citric acid, succinic acid, acetic acid, fumaric acid, malic acid, carbonic acid and their potassium salts, sodium salts or ammonium salts, ribonucleic acid and salts thereof, sodium hydroxide, etc. 1 type or 2 or more types can be used, and what combined phosphoric acid and a citric acid, and those sodium salts is especially preferable. In this case, the composition for oral cavity of the present invention is preferably prepared to have a pH at 25 ° C. of 5.5 to 8.5, and sodium dihydrogen phosphate and sodium monohydrogen phosphate as pH adjusters in the vicinity thereof, Alternatively, a combination of citric acid and sodium citrate can be used.

  In addition, although purified water is mix | blended as a solvent, content of the water in a composition is 60% or more, Especially 80% or more, Especially 90% or more is preferable.

Further, the oral composition of the present invention preferably has a viscosity at 25 ° C. of 0 to 50 mPa · s, particularly 0 to 20 mPa · s, measured by the test method described below.
Viscosity measurement method (oral composition)
Weigh 300 g of oral composition in a 300 mL tall beaker. Next, after standing in a constant temperature water bath at 25 ° C. for 1 hour, the viscosity after 1 minute is measured accurately using a BL type viscometer.
Viscometer: manufactured by Tokyo Keiki Co., Ltd. BL viscometer Measurement conditions: Rotor No. 1. 60 rpm

EXAMPLES Hereinafter, although this invention is demonstrated in detail based on an experiment example, an Example, and a comparative example, this invention is not restrict | limited to these Examples. Unless otherwise indicated,% shown in the following examples means mass%, and part means mass part. The parentheses in polyoxyethylene hydrogenated castor oil and polyoxyethylene alkyl ether indicate the average number of moles of ethylene oxide added.
The viscosity of each propylene glycol alginate is a value measured by the method specified for each manufacturer described above (BL viscometer, 20 ° C., 1% aqueous solution, measurement time 1 minute, rotor and rotation speed are individually As described).

The following raw materials were used for the preparation of the oral composition of each example.
Propylene glycol alginate brand name Kelp acid 503:
1% aqueous solution viscosity 18 mPa · s, M / G ratio = 1.3, degree of esterification = 80% (rotor No. 1, 60 rpm) / trade name, manufactured by Kimika Co., Ltd. Kimiloid BF:
1% aqueous solution viscosity 20 mPa · s, M / G ratio = 1.3, degree of esterification = 80% (rotor No. 1, 60 rpm) / trade name, manufactured by Kimika Co., Ltd. Kimiloid LLV:
1% aqueous solution viscosity 24 mPa · s, M / G ratio = 1.3, degree of esterification = 80% (rotor No. 1, 60 rpm) / trade name, manufactured by Kimika Co., Ltd. Kimiloid NLS-K:
1% aqueous solution viscosity 55 mPa · s, M / G ratio = 1.3, degree of esterification = 80% (rotor No. 1, 60 rpm) / trade name, manufactured by Kimika Co., Ltd. Kimiloid LV:
1% aqueous solution viscosity 90 mPa · s, M / G ratio = 1.3, degree of esterification = 80% (rotor No. 1, 30 rpm) / trade name, manufactured by Kimika Co., Ltd. Kimiloid MV:
1% aqueous solution viscosity 148 mPa · s, M / G ratio = 1.3, degree of esterification = 80% (rotor No. 1, 30 rpm) / Kimika Co., Ltd. Isopropylmethylphenol (Osaka Kasei Co., Ltd.)
Polyoxyethylene (40) hydrogenated castor oil (Nikko Chemicals), polyoxyethylene (60) hydrogenated castor oil (Nikko Chemicals), polyoxyethylene (80) hydrogenated castor oil (Nikko Chemicals), polyoxy Ethylene (100) hydrogenated castor oil (Nihon Emulsion), POE (20) cetyl ether (Nikko Chemicals), POE (20) stearyl ether (Nikko Chemicals), POE (40) cetyl ether (Nikko Chemicals) ), Decaglyceryl monostearate (manufactured by Nikko Chemicals), decaglyceryl monomyristate (manufactured by Nikko Chemicals), decaglyceryl monolaurate (manufactured by Nikko Chemicals)
Ethanol (99.5% manufactured by Nippon Alcohol Industry Co., Ltd.), concentrated glycerin (produced by Sakamoto Yakuhin Kogyo Co., Ltd.), propylene glycol (produced by Asahi Glass Co., Ltd.), ethylene glycol (produced by Mitsubishi Chemical Co., Ltd.), butylene glycol (produced by Daicel Chemical Industries, Ltd.), Polyethylene glycol 200 (Macrogor 200, manufactured by Sanyo Chemical Co., Ltd.), Polyethylene glycol 400 (Macrogor 400, manufactured by Sanyo Chemical Co., Ltd.), Polyethylene glycol 600 (Macrogor 600, manufactured by Sanyo Chemical Co., Ltd.)
Sodium lauryl sulfate (manufactured by Toho Chemical Co., Ltd.), sodium myristyl sulfate (manufactured by Nikko Chemicals), sodium lauroyl sarcosine (manufactured by Kawaken Fine Chemical Co., Ltd.), sodium myristoyl sarcosine (manufactured by Kawaken Fine Chemical Co., Ltd.)

Citric acid monohydrate (manufactured by Fuso Chemical Industries), trisodium citrate dihydrate (manufactured by Fuso Chemical Industries), xylitol (manufactured by Rocket Japan), sorbitol (manufactured by Mitsubishi Corporation Foodtech), saccharin ( Daito Chemical Co., Ltd.), sodium benzoate (Fushimi Pharmaceutical Co., Ltd.), methyl paraben (Ueno Pharmaceutical Co., Ltd.), ethyl paraben (manufactured by API Corporation), epsilon-aminocaproic acid (Daiichi Chemicals Co., Ltd.), tranexam Acid (Daiichi Sankyo Propharma Co., Ltd.), Tocopherol acetate (DSM Nutrition Japan Co., Ltd.), Dipotassium glycyrrhizinate (Maruzen Pharmaceutical Co., Ltd.), Polyvinylpyrrolidone (Trade name: Rubiscol K-90, BASF) ), Sodium pyrophosphate (made by Taihei Chemical Industrial Co., Ltd.), sodium tripolyphosphate (thickened) Sangyo Co., Ltd.)

  In the table, POE represents polyoxyethylene, and PEG represents polyethylene glycol. IPMP is an abbreviation for isopropylmethylphenol, and Na is an abbreviation for sodium. % Means mass% unless otherwise specified, and viscosity means 1% aqueous solution viscosity (20 ° C.) unless otherwise specified.

According to the composition in the table, the liquid oral composition is prepared by dissolving a water-soluble raw material (excluding nonionic surfactant and solvent) in purified water, and then adding an oil-soluble raw material in ethanol and / or polyhydric alcohol. A solution in which the nonionic surfactant was dissolved was added with stirring to achieve uniform dissolution. A three-one motor (BL1200, manufactured by HEIDON) was used for manufacturing.
Each of the obtained compositions was a liquid preparation, and the viscosity at 25 ° C. measured by the following test method was in the range of 0 to 16 mPa · s.
Viscosity measurement method:
Weigh 300 g of oral composition in a 300 mL tall beaker. Next, after standing in a constant temperature water bath at 25 ° C. for 1 hour, the viscosity after 1 minute is measured accurately using a BL type viscometer.
Viscometer: manufactured by Tokyo Keiki Co., Ltd. BL viscometer Measurement conditions: Rotor No. 1. 60 rpm

[Experimental Example 1] Periodontal Pathogenic Bacteria Suppressing Effects of Periodontal Pathogenic Bacteria Periodontopathogenic bacteria were obtained from Porphyromonas gingivalis ATCC33277 purchased from American Type Culture Collection (ATCC), and hemin and menadione were used. Incubate to a steady state under anaerobic conditions (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% hydrogen) at 37 ° C. with the todd Hewit broth culture solution (THBHM ^{* 1} ) containing, and the absorbance at 550 nm becomes 1.0 A solution suspended in PBS (manufactured by Wako Pure Chemical Industries, Ltd.) was used for the test.
The adherent carrier was immersed in human unstimulated saliva filtered with a 0.45 μm filter for 1 hour (37 ° C.) using a hydroxyapatite (HA) plate (manufactured by Asahi Optical Co., Ltd.) having a diameter of 7 mm and a thickness of 3.5 mm. The HA surface was coated with saliva components and subjected to the test.

The saliva-coated HA plate was washed once with PBS (manufactured by Wako Pure Chemical Industries, Ltd.) and then immersed in 2 mL of a test solution having the composition shown in Tables 1 to 5 for 5 minutes. After the treatment, the plate was washed once with PBS, and then the HA plate was immersed in the aforementioned Porphyromonas gingivalis solution for 30 minutes (37 ° C.). Thereafter, the HA plate was washed 3 times with 1 mL of PBS, and then the adhered bacteria were dispersed by ultrasonication (200 μA, 10 seconds) in 4 mL of PBS, and 10-fold serial dilution was performed. This was smeared on a blood agar plate ^{* 2} containing 10% sheep defibrillated blood and cultured for about 2 weeks under anaerobic conditions. The number of Porphyromonas gingivalis adhering to the HA plate was determined from the number of grown colonies, and the number of adhering bacteria was calculated as cfu (colony forming unit) / HA plate.
In addition, as a control, what was treated with 2 mL of PBS instead of 2 mL of the sample was used, and the adhesion suppression rate of the test composition with respect to the number of adherent bacteria of the control was determined by the following formula, and the adhesion suppression effect was determined according to the following criteria.
Adhesion inhibition rate (%) = ((number of adherent bacteria in control−number of adherent bacteria in test composition) / (number of adherent bacteria in control)) × 100

Criteria for Adhesion Inhibitory Effect of Periodontal Disease Causative Bacteria ◎: Adhesion inhibition rate is 80% or more and 100% or less ○: Adhesion inhibition rate is 60% or more and less than 80% Δ: Adhesion inhibition rate is 40% or more and less than 60% ×: Adhesion suppression rate is 0% or more and less than 40%

* 1 Composition of THBHM: expressed by mass in 1 liter.
Todd Hewitt Broth (Becton and Dickinson): 30g / L
Hemin (Sigma Aldrich): 5mg / L
Menadion (Wako Pure Chemical Industries, Ltd.): 1mg / L
Distilled water: Residue (The volume was made up so that the total amount was 1 L, and autoclaved at 121 ° C. for 20 minutes.)

* 2 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 (Sigma Aldrich): 5mg / L
Vitamin K (manufactured by Wako Pure Chemical Industries): 1mg / L
Distilled water: Residue (The volume was adjusted so that the total amount was 1 L, and autoclaved at 121 ° C. for 20 minutes.)
100ml of degummed blood from sheep

[Experimental Example 2] Tooth surface coating effect A hydroxyapatite (HA) plate (manufactured by Asahi Optical Co., Ltd.) having a diameter of 7 mm and a thickness of 3.5 mm was mirror-polished using Ecomet (registered trademark) 3000 manufactured by Buehler. did. Next, human stimulated saliva was centrifuged (10,000 rpm, 10 minutes), the HA plate was immersed in the supernatant for 1 minute, and then immersed and washed in 10 mL of ion-exchanged water. Furthermore, after being immersed in 10 mL of a test solution having the composition shown in Tables 1 to 5 for 30 seconds, the sample was immersed and washed in 10 mL of ion-exchanged water. The washed HA plate was dried in a 60 ° C. constant temperature bath for 30 minutes. As a control, the same treatment was performed using ion-exchanged water instead of the test solution.
After drying, the surface roughness was measured under the following conditions using a Keyence Corporation profile micrometer (VF-7510), and the arithmetic average roughness (Ra _s ) on the test solution-treated HA plate was compared with the control average arithmetic roughness. From the value obtained by subtracting (Ra _c ), the tooth surface coating effect was determined according to the following criteria.
<Measurement conditions>
Laser scan pitch = 0.1 μm
Laser travel depth = 3,000 μm

Criterion of the tooth surface coating effect ◎: Ra _s -Ra _c is 250nm or more ○: Ra _s -Ra _c is 100nm or more 250nm less ×: Ra _s -Ra _c is less than 100nm

[Experimental Example 3] Clarity Test A sample immediately after the preparation of the composition shown in Tables 1 to 5 was filled in 80 mL of a 80 mL PET container, and the clarity was determined visually according to the following criteria.
Clarity Evaluation Criteria Immediately after Preparation of Formulation ◎: No negligible. Even if compared with a PET container filled with purified water, no scratch is observed.
○: Slight scratching is observed in comparison with a PET container filled with purified water, but there is no problem because the level cannot be determined without comparison.
Δ: Slightly observed as compared with a PET container filled with purified water. Slightly observed without comparison.
X: Nigori was clearly recognized without comparison with a PET container filled with purified water, and PET
It is so cloudy that it is difficult to see through the container.

[Experimental Example 4] Bactericidal effect test of periodontopathic biofilm (1) Preparation method of model periodontopathic biofilm Hydroxyapatite (HA) plate (made by Asahi Optical Co., Ltd.) having a diameter of 7 mm and a thickness of 3.5 mm What was processed with the human unstimulated saliva filtered with a 0.45 micrometer filter for 4 hours was used for the support | carrier of model biofilm production, and the culture medium used the basal medium mucin culture liquid (BMM) ^{* 3} . The strains used to make the model biofilms were Actinomyces viscosus ATCC 43146, Veilonella parvula 109, and BCC. Porphyromonas gingivalis) ATCC 33277 was used. These 4 bacterial species were inoculated into a rotating disk reactor (culture tank) containing 3,000 mL of BMM in advance so as to be 1 × 10 ⁷ cfu / mL (cfu: colony forming units), respectively, and 37 ° C. together with the HA carrier treated with saliva. The cells were cultured under anaerobic conditions (5% carbon dioxide gas, 95% nitrogen) for 24 hours. Thereafter, a BMM medium was continuously supplied under the same conditions at a replacement rate of 5 vol% / hour and cultured for 10 days to form a model biofilm of a mixture of four bacterial species on the HA surface.

(2) Bactericidal effect on model biofilm The formed model biofilm was transferred to a 24-well multiplate (manufactured by Sumitomo Bakelite Co., Ltd.), added with 2 mL of a sample having the composition shown in Tables 1 to 5, and immersed for 3 minutes. After washing 6 times with 1 mL of Yakuhin Kogyo Co., Ltd., it was dispersed by sonication (200 μA, 10 seconds) in a test tube (diameter 13 mm × 100 mm) added with 4 mL of the same buffer. This dispersion was diluted 10 times with PBS, 50 μL was smeared on a blood agar plate ^{* 4} containing kanamycin sulfate, and cultured under anaerobic conditions. The number of grown colonies was counted, and the viable count (cfu / Biofilm) of periodontal disease bacteria (Porphyromonas gingivalis) per model biofilm was determined.
The biofilm bactericidal effect of the test preparation was determined by calculating the bactericidal rate of periodontal disease bacteria relative to the control (PBS 2 mL treatment) according to the following formula, and determining the biofilm bactericidal effect according to the following criteria.
Periodontal Bactericidal Rate = Control Periodontal Bacteria Count (cfu / Biofilm) / Test Formulation Periodontal Bacteria Count (cfu / Biofilm)

Biofilm bactericidal effect criteria ☆: Bactericidal rate of periodontal disease bacteria is 1,000 or more ◎: Bactericidal rate of periodontal disease bacteria is 100 or more and less than 1,000 ○: Bactericidal rate of periodontal disease bacteria is 10 or more and less than 100 △: Tooth Bactericidal rate of periodontal bacteria is 1 or more and less than 10 ×: Bactericidal rate of periodontal bacteria is less than 1

* 3 Composition of BMM: Expressed by mass in 1 liter.
Proteose peptone (Becton and Dickinson): 4g / L
Tryptone (Becton and Dickinson): 2g / L
Yeast extract (Becton and Dickinson): 2g / L
Mucin (Sigma): 5g / L
Hemin (manufactured by Sigma): 2.5 mg / L
Vitamin K (manufactured by Wako Pure Chemical Industries, Ltd.): 0.5mg / L
KCl (Wako Pure Chemical Industries, Ltd.): 1g / L
Cysteine (Wako Pure Chemical Industries, Ltd.): 0.2 g / L
Distilled water: Residue (The volume was adjusted so that the total amount became 1 L.)

* 4 Composition of blood agar plate containing kanamycin sulfate: expressed in mass in 1 L.
Trypticase Soy Agar (Becton and Dickinson): 40 g / L
Hemin (manufactured by Sigma): 5mg / L
Vitamin K (manufactured by Wako Pure Chemical Industries): 1mg / L
Kanamycin sulfate (Meiji Pharmaceutical Co., Ltd.): 200mg / L
Distilled water: Residue (The volume was adjusted so that the total amount became 1 L.)

[Experimental Example 5] Penetration effect test of periodontopathic biofilm of bactericidal component (1) Method for producing model periodontopathic biofilm for penetration effect test Passage preservation (freezing) at Oral Care Research Laboratories, Lion Corporation Actinomyces naeslundii ATCC 51655 strain, Fusobacterium nucleatum ATCC 10953 strain, Porphyromonas gingivalis strain 33 Todd Hae containing 5 mg / L hemin (Sigma Aldrich) and 1 mg / L vitamin K (Wako Pure Chemical Industries) autoclaved at 121 ° C. for 15 minutes Witbroth (Becton and Dickinson) culture solution (THBHM ^{* 5} ) was added to 4 mL, and anaerobic culture (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% hydrogen) was performed overnight at 37 ° C.

Todd Hewitt Broth (Becton and Dickinson) containing 1.26% sodium lactate (manufactured by Sigma-Aldrich) obtained by autoclaving 80 μL of the Veilloella parvula ATCC 17745 bacterial solution which had been stored in the same manner at 121 ° C. for 15 minutes. It was added to 4 mL of a culture solution (THBL ^{* 6} ) and cultured in the same manner. After culturing, 300 μL of each of the three bacterial strains excluding Bayonella pervula was collected, added to 30 mL of THBHM, and further cultured overnight. Similarly, 300 μL was collected from the bacterial solution of Bayonella pervula, added to 30 mL of THBL, and cultured overnight.

After re-culture, each bacterial solution was centrifuged (10,000 rpm, 10 min), and the supernatant was discarded. A basal medium mucin culture solution (BMM ^{* 7} ) autoclaved at 121 ° C. for 15 minutes was added to each sediment (bacteria), resuspended, and a culture tank (diameter 140 mm × high height) containing 1,000 mL of BMM in advance. 200 mm) and inoculating each of the above numbers of bacteria to 1 × 10 ⁷ cells / mL and stirring with a stirrer (rotating at about 100 rpm) at 37 ° C. under anaerobic conditions (95 vol% nitrogen, 5 vol%) Incubate overnight with carbon dioxide. Thereafter, BMM was supplied at a rate of 100 mL / h, 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 (diameter 140 mm × height 200 mm) whose liquid volume was kept at 1,000 mL. A membrane filter (Millipore, 13 mm in diameter) was attached to a turntable (rotated at about 30 rpm) in the culture tank, and a biofilm was formed on the upper surface thereof. Cultivation by the above method was carried out for 14 days. After completion of the culturing, the membrane filter was taken out, and the biofilm adhering to other than the test surface (upper membrane) was removed with a sterilized cotton swab (manufactured by Suzuran).

* 5 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 (The volume was adjusted so that the total amount became 1 L.)

* 6 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 (The volume was adjusted so that the total amount became 1 L.)

* 7 BMM composition: Expressed by mass in 1 liter.
Proteose peptone (Becton and Dickinson): 2g / L
Tryptone (Becton and Dickinson): 1g / L
Yeast extract (Becton and Dickinson): 1g / L
Mucin (Sigma Aldrich): 2.5g / L
Hemin (Sigma Aldrich): 1mg / L
Vitamin K (manufactured by Wako Pure Chemical Industries, Ltd.): 0.2mg / L
KCl (manufactured by Wako Pure Chemical Industries): 0.5g / L
Cysteine (manufactured by Wako Pure Chemical Industries): 0.1 g / L
Distilled water: Residue (The volume was adjusted so that the total amount became 1 L.)
(1 liter of the above composition was autoclaved at 121 ° C. for 15 minutes, then cooled to 45 ° C. and added.)

(2) Model biofilm penetration effect (biofilm permeability of bactericidal components)
The membrane filter with the biofilm attached thereto was attached to a diffusion cell containing 8 mL of PBS (artificial saliva), and 0.8 mL of the sample having the composition shown in Tables 1 to 5 was added onto the membrane filter. After incubating for 2 hours, the amount of the bactericidal component (isopropylmethylphenol) in PBS was quantified using HPLC, and the ratio of the amount of bactericidal component permeated to the amount of the bactericidal component treated was determined as the penetration rate and evaluated according to the following criteria.

Test conditions Detector: UV absorption photometer (measurement wavelength: 285 nm)
Column: YMC YMC-Pack ODS-A A-303
(Diameter 4.6mmφ × 250mm, reverse phase column)
Column temperature: 45 ° C
Mobile phase: acetonitrile / water / acetic acid (100) mixture (volume ratio 60: 40: 1)
Flow rate: 1 mL / min

Biofilm penetration effect criteria ☆: Penetration rate is 7% or more ◎: Penetration rate is 5% or more and less than 7% ○: Penetration rate is 1% or more and less than 5% ×: Penetration rate is less than 1%

[Experimental Example 6] Appearance stability test at high temperature storage 80 mL of a sample container having a composition shown in Tables 1 to 5 was filled into a 90 mL PET container and stored in a 50 ° C constant temperature bath for 1 month. Visual judgment was made according to the following criteria. If the evaluation differs between the orientation of the orientation and the negative, the worse evaluation point was taken as the evaluation value of the high temperature appearance stability.

Orientation evaluation criteria A: There is no sediment that settles when the PET container is gently displaced.
○: Almost no sediment settles when the PET container is gently displaced.
Δ: Orientation that settles when the PET container is gently displaced is clearly observed.
X: Orientation is recognized without transposing the PET container.

Nigori evaluation criteria A: There is no negligible. Even if compared with a PET container filled with purified water, no scratch is observed.
○: Slight scratching is observed in comparison with a PET container filled with purified water, but there is no problem because the level cannot be determined without comparison.
△: Slightly recognized as compared with a PET container filled with purified water. Slightly negligible even without comparison. X: Clearly observed without comparison with a PET container filled with purified water. PET
It is so cloudy that it is difficult to see through the container.

表中、香料の各組成は表６〜１２に示す通りである。

In the table, each composition of the fragrance is as shown in Tables 6-12.

Claims (8)

  Polyoxyethylene hydrogenated castor oil containing propylene glycol alginate (A) and isopropylmethylphenol (B) and having an average addition mole number of ethylene oxide of 40 to 100 moles, and an alkyl group having 16 to 18 carbon atoms And at least one nonionic surfactant (C) selected from polyoxyethylene alkyl ethers having an average addition mole number of ethylene oxide of 20 to 40 moles and decaglycerin monofatty acid esters of fatty acids having 12 to 18 carbon atoms A composition for oral cavity, comprising:   The composition for oral cavity according to claim 1, wherein the mixing ratio of the component (A) and the component (B) is 0.4 to 20 as a mass ratio of (A) / (B).   The composition for oral cavity of Claim 1 or 2 which contains 0.05-0.5 mass% of component (A), and 0.01-0.1 mass% of component (B).   The composition for oral cavity of Claim 1, 2, or 3 which contains 0.1-1 mass% of components (C).   Furthermore, the composition for oral cavity of any one of Claims 1 thru | or 4 containing ethanol and / or a polyhydric alcohol (D).   The composition for oral cavity according to claim 5, wherein the total content of the component (D) is 3 to 15% by mass.   The oral composition according to any one of claims 1 to 6, further comprising at least one anionic surfactant (E) selected from alkyl sulfates and acyl sarcosine salts.   The composition for oral cavity according to any one of claims 1 to 7, which is prepared as a liquid preparation.