JP4952940B2 - Liquid oral composition - Google Patents

Description

  The present invention relates to a liquid composition for oral cavity that is excellent in bactericidal power against periodontal disease bacteria in the oral cavity biofilm, has a high texture of teeth, and has a good low-temperature storage stability.

  The causes of the two major oral diseases of caries and periodontal disease are thought to be due to various bacteria in the oral plaque. In particular, caries is streptococcus such as Streptococcus mutans (S. mutans), periodontal The disease is an infection caused by bacteria mainly obligate anaerobic gram-negative bacilli such as Porphyromonas gingivalis, and the cause of bad breath is oral bacteria such as Fusobacterium nucleatum. Is involved. Therefore, it is said that it is useful to control plaque control, that is, to keep the number of pathogenic bacteria in the oral cavity at a low level as an effective means for preventing and improving oral diseases.

  As a means of reducing the number of pathogenic bacteria in the oral cavity, it is an effective means to add a poorly water-soluble bactericidal agent or a cationic bactericidal agent to an oral care product. Among them, nonionic fungicides such as isopropylmethylphenol have a characteristic that the antibacterial spectrum tends to be wider than that of cationic fungicides, and are therefore incorporated in several dentifrices and put on the market.

  However, since these oil-soluble disinfectants are hardly soluble in water as they are, when blended into a liquid preparation such as a mouthwash, various surfactants are blended and solubilized. If the active site is inactivated by the surfactant and cannot fully exert the bactericidal power, and if the amount of the surfactant is reduced to improve the bactericidal power, the liquid becomes clouded over time, and the appearance stability of the composition There has been a problem that is significantly impaired. Therefore, research to improve the bactericidal effect by the combination of antibacterial components (see Patent Document 1) and by using a nonionic antibacterial agent and a specific amphoteric surfactant together, the retention of the antibacterial agent in the oral cavity is increased, Although attempts have been made to effectively suppress dental plaque (see Patent Document 2), there is a demand for a liquid oral composition having a higher bactericidal power and a better feeling of use.

Japanese Patent No. 3606023 JP-A-5-124943 JP 2004-323488 A JP 2005-104913 A JP 2005-187437 A

  The present invention has been made in view of the above circumstances, and provides a liquid oral composition that is superior in periodontal disease biofilm sterilizing power, has a high smoothness of teeth, and maintains low-temperature stability (no wrinkles). The purpose is to do.

  As a result of intensive studies to achieve the above object, the present inventors have identified isopropylmethylphenol, sodium myristoyl glutamate, and polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 60 to 100 When used in combination, a liquid oral composition having excellent bactericidal activity against oral biofilms of periodontal disease bacteria, high tooth smoothness, and good low-temperature storage stability (no wrinkles) can be obtained. I found out.

  In addition, isopropylmethylphenol, sodium N-acylglutamate, and polyoxyethylene hydrogenated castor oil are each known as a compounding ingredient for an oral composition (see Patent Documents 3 to 5). To solve this problem, when isopropylmethylphenol is used in combination with sodium myristoyl glutamate, the bactericidal power derived from isopropylmethylphenol is higher than that of a single compound, and the bactericidal power of periodontal disease-causing bacteria on biofilms is improved. The mouth feels smooth when sipped, and when polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 60 to 100 is added, these components are solubilized satisfactorily and have excellent low-temperature storage stability. (No-origin) is maintained, and the sterilizing power and the smoothness of teeth can be increased. Therefore, excellent oral biofilm sterilization power, smoothness of teeth cannot be achieved by blending the above three components in a specific ratio, which cannot be achieved when any of these components are missing or in an inappropriate ratio. And it discovered that the composition for liquid oral cavity which has low-temperature storage stability could be obtained, and came to make this invention.

Therefore, the present invention
(A) Isopropylmethylphenol 0.01-0.1% by mass
(B) Sodium myristoyl glutamate 0.01-0.3% by mass
(C) Polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 60 to 100 0.5 to 2% by mass
And (A) / (B) has a mass ratio of 0.3-5.

  The composition for liquid oral cavity of the present invention is excellent in biofilm sterilizing power of periodontal disease-causing bacteria, has a high sensation of teeth, has good low-temperature storage stability, and is effective in preventing or suppressing periodontal disease. .

  Hereinafter, the present invention will be described in more detail. The liquid oral composition of the present invention has an average added mole number of (A) isopropylmethylphenol, (B) sodium myristoyl glutamate, and (C) ethylene oxide of 60 to 100. Contains polyoxyethylene hydrogenated castor oil.

  The blending amount of component (A) isopropylmethylphenol is 0.01 to 0.1% (mass%, the same applies hereinafter), preferably 0.02 to 0.08%. If it is less than 0.01%, the biofilm bactericidal effect of periodontal disease-causing bacteria is not sufficiently exerted, and if it exceeds 0.1%, orientation will occur.

  As the component (B), myristoyl glutamate, commercially available products such as Amino Surfact manufactured by Asahi Kasei Co., Ltd. and Amisoft MS-11 manufactured by Ajinomoto Co., Inc. can be used, and the blending amount in the composition is 0.01. -0.3%, preferably 0.05-0.2%. If it is less than 0.01%, a satisfactory biofilm sterilizing effect of periodontal disease-causing bacteria cannot be obtained, and the tooth has a slick feel, and if it exceeds 0.3%, the occurrence of orientation occurs and the storage stability is poor.

  The mass ratio of (A) / (B) is 0.3 to 5 and preferably 0.4 to 1.8 in terms of periodontal disease biofilm bactericidal power and tooth smoothness. When (A) / (B) is less than 0.3, a satisfactory biofilm bactericidal effect of periodontal disease-causing bacteria cannot be obtained, and the tooth has a smooth and inferior feeling. The biofilm bactericidal effect of disease-causing bacteria and the smoothness of teeth cannot be obtained.

As the component (C), polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide as a nonionic surfactant of 60 to 100 is used. When the average added mole number of ethylene oxide is less than 60 moles, the occurrence of orientation during low-temperature storage cannot be sufficiently suppressed, and those exceeding 100 moles are generally not commercially available.
These can use a commercial item, for example, Nikko Chemical series NIKKOL series, Nippon Emulsion Co., Ltd. EMALEX series, etc. can be used.

  The blending amount of the polyoxyethylene hydrogenated castor oil is 0.5 to 2%, preferably 0.5 to 1% of the entire composition. If the blending amount is less than 0.5%, the occurrence of orientation cannot be suppressed, and the biofilm bactericidal effect of periodontal disease bacteria and the smoothness of teeth are not improved satisfactorily. The effect is inferior and satisfactory tooth smoothness cannot be obtained.

  The composition for liquid oral cavity of the present invention can be prepared and applied as a mouthwash, a mouth freshener, a concentrated mouthwash, etc. In addition to the above components, an appropriate optional component is blended according to the dosage form can do. For example, wetting agents, thickeners, preservatives, sweeteners, pH adjusters, fragrances and polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 60 to 100, surfactants other than sodium myristoyl glutamate, isopropylmethyl Active ingredients other than phenol, cleaning aids, colorants and the like can be blended.

  As the wetting agent, polyhydric alcohols such as glycerin, sorbitol, propylene glycol, ethylene glycol, polyethylene glycol, xylitol, maltite and lactit, sugar alcohols and the like can be blended. The blending amount is preferably 3 to 50% of the entire composition.

  As a thickener, sodium carboxymethyl cellulose, xanthan gum, carrageenan, hydroxyethyl cellulose, sodium alginate, polyvinyl alcohol, and the like can be blended. Thickeners are usually blended in liquid dentifrices and mouthwashes in an amount of 0.01 to 5%.

  Examples of preservatives include sodium benzoate, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, cetyl pyridinium chloride, potassium sorbate and the like. Moreover, as a sweetening agent, saccharin sodium, stevioside, etc. can be mix | blended.

  Examples of pH adjusters include phthalic acid, phosphoric acid, citric acid, succinic acid, acetic acid, fumaric acid, malic acid and carbonic acid and their potassium, sodium and ammonium salts, ribonucleic acid and its salts, and sodium hydroxide. Or a combination of phosphoric acid, citric acid and their sodium salts is particularly preferred. In this case, the composition of the present invention preferably adjusts the pH at 25 ° C. to 5.5 to 8.5. As a pH adjuster near this neutrality, sodium dihydrogen phosphate and sodium monohydrogen phosphate or citric acid are used. A combination of acid and sodium citrate can be used.

  Perfumes include peppermint oil, spearmint oil, anise oil, eucalyptus oil, winter green oil, cassia oil, cinnamon oil, clove oil, thyme oil, sage oil, cardamom oil, rosemary oil, marjoram oil, lemon oil, orange oil , Natural essential oils such as fennel oil, nutmeg oil, lavender oil, paracres oil, and l-menthol, l-carvone, anethole, 1,8-cineole, methyl salicylate, eugenol, thymol, linalool, limonene, menthone, menthyl acetate , Citral, camphor, borneol, pinene, spirantol, and other fragrance ingredients contained in the above natural essential oils, ethyl acetate, ethyl butyrate, isoamyl acetate, hexanal, hexenal, methyl anthranilate, ethyl methyl Phenylglycidate, benzaldehyde, vanillin, ethyl vanillin, furaneol, maltol, ethyl maltol, gamma / delta decalactone, gamma / deltown decalactone, N-ethyl-p-menthane-3-carboxamide, menthyl lactate, ethylene glycol- Perfume ingredients such as l-menthyl carbonate, as well as some perfume ingredients and natural essential oils, apple, banana, strawberry, blueberry, melon, peach, pineapple, grape, muscat, wine, cherry, squash, coffee One or two or more kinds of blended flavors such as brandy and yogurt can be used in the range of 0.00001 to 3% in the composition of the present invention without impairing the effects of the present invention.

As the surfactant, in addition to sodium myristoyl glutamate of component (B) and polyoxyethylene hydrogenated castor oil of component (C), other commonly used surfactants such as sodium lauryl sulfate, sodium myristyl sulfate, etc. Water-soluble salts of higher alkyl sulfates having 8 to 18 carbon atoms in the alkyl group, sodium lauryl monoglyceride sulfonate, sodium coconut monoglyceride sulfonate, etc. In addition to anionic surfactants such as water-soluble salts, olefin sulfonic acids, paraffin sulfonic acids, sucrose fatty acid esters, polyglycerin fatty acid esters, alkylglycosides, sorbitan fatty acid esters, polyoxyethylene sol Nonionic surfactants such as tan fatty acid ester and alkyldimethylamine oxide, betaine acetate type amphoteric surfactants such as alkyldimethylaminoacetic acid betaine, fatty acid amidopropyldimethylaminoacetic acid betaine, N-fatty acid acyl-N-carboxymethyl- Examples include imidazoline type amphoteric surfactants such as N-hydroxyethylethylenediamine salts. The blending amount of the other surfactants described above is preferably 0 to 10%, particularly 0.1 to 10%.
As the solvent, purified water is generally used.

  Active ingredients include nonionic fungicides other than isopropylmethylphenol, cationic fungicides such as cetylpyridinium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, benzalkonium chloride, benzethonium chloride, tranexamic acid, epsilon-aminocaproic acid, etc. Anti-inflammatory agents, amylase, protease, mutanase, dextranase, lysozyme, lytic enzyme, enzyme such as lytechenzyme, fluoride such as sodium fluoride, sodium monofluorophosphate, stannous fluoride, aluminum chlorohydroxy allantoin, Allantoin, azulene, lysozyme chloride, ascorbic acid and other vitamin C, sodium chloride, dihydrocholesterol, glycyrrhetin salts, glycyrrhetinic acids, hydrocholesterol, black Phil, Sodium copper chlorophyllin, Thyme, Ogon, Clove, Hamamelis plant extracts, Copper gluconate, Caropeptide, Sodium polyphosphate, Water-soluble inorganic phosphate compound, Polyethylene glycol, Polyvinylpyrrolidone, Anticalculus agent, Anti-plaque agent Potassium nitrate, aluminum lactate, etc. can be added. In addition, the addition amount of these arbitrary components can be made into a normal amount 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, and the like can be added.

  PET (polyethylene terephthalate), glass, polypropylene, and polyethylene can be used as the container for storing the liquid oral cavity composition of the present invention. The container of the above material may contain a colorant or an ultraviolet absorber, or may be a film or the like. It is desirable to shield.

  EXAMPLES Hereinafter, although this invention is demonstrated concretely based on an Example and a comparative example, this invention is not restrict | limited by these Examples. In addition, unless otherwise indicated,% shown below means the mass%.

Examples and comparative examples
Prepare liquid oral compositions of the composition shown in Tables 1 and 2 below, and have the following methods for bactericidal activity on periodontal disease-causing biofilms, smoothness of teeth and low-temperature storage stability (the absence of orientation). evaluated. The results are shown in Tables 1 and 2.

Each component used in the examples and comparative examples is as follows.
Isopropyl methylphenol: Osaka Kasei Co., Ltd. sodium myristoyl glutamate: Ajinomoto Co., Ltd. Amisoft MS-11
Sodium stearoyl glutamate: Amisoft HS-11P manufactured by Ajinomoto Co., Inc.
Polyoxyethylene (60) hydrogenated castor oil (average number of moles of ethylene oxide added: 60): HCO-60 manufactured by Nikko Chemicals Co., Ltd.
Polyoxyethylene 100) hydrogenated castor oil (average number of moles of ethylene oxide added 100): HC-100 manufactured by Nippon Emulsion Co., Ltd.
Polyoxyethylene (40) hydrogenated castor oil (average number of added moles of ethylene oxide 40): HC-40 manufactured by Nippon Emulsion Co., Ltd.
Sodium lauryl sulfate: Toho Chemical Industry Co., Ltd. Citric acid: Fuso Chemical Industry Co., Ltd. Sodium citrate: Fuso Chemical Industry Co., Ltd. Glycerin: Lion Oleochemical Co., Ltd. Xylitol: Rocket Japan Co., Ltd. : Japan Alcohol Sales Co., Ltd.

The pH of the prepared liquid oral composition was measured as follows.
A liquid oral composition sample that had been kept at a constant temperature of 25 ° C. was placed in a plastic container, and the calibrated pH electrode was directly inserted into the liquid oral composition, and the reading value after 2 minutes was taken as the pH of the sample. The following apparatus was used for pH measurement.
pH meter: HM-30S manufactured by Toa Denpa Kogyo Co., Ltd.
pH electrode: GST-5721C manufactured by Toa DK Corporation

Evaluation of bactericidal activity against biofilms of periodontal disease-causing bacteria:
(1) Production method of model periodontitis biofilm Biofilm for treatment for 4 hours with human unstimulated saliva obtained by filtering a hydroxyapatite (HA) plate (manufactured by Asahi Optical Co., Ltd.) having a diameter of 7 mm and a thickness of 3.5 mm with a 0.45 μm filter. Was used as a carrier for producing a model periodontal disease biofilm, and the culture solution was 5 mg of hemin (manufactured by Sigma) and menadione (30 mg) in a solution of 30 g of trypticase soy broth (manufactured by Difco) in 1 L of purified water. (Sigma) 0.5mg added. In order to prepare a model periodontal disease biofilm, Streptococcus gordonii ATC 51656 strain and Actinomyces naeslandi ATCC 51655 strain were used as oral resident bacteria, and Porphyromonas gingivalis ATCC 33277 strain was used as a pathogenic bacterium. These three bacterial species were inoculated into the above-mentioned culture solution so as to be 2 × 10 ⁷ cfu / mL (cfu: colony forming units), respectively, at 37 ° C. under anaerobic conditions (5 Vol% carbon dioxide gas, 95 vol% nitrogen) was continuously cultured for 2 weeks (the replacement rate of the culture solution was 10 vol%), and a model periodontal disease bacteria biofilm mixed with 3 species was formed on the HA surface.

(2) Bactericidal effect on model periodontal disease bacteria biofilm The formed model periodontal disease bacteria biofilm was immersed in 2 mL of the sample having the composition shown in Tables 1 and 3 for 3 minutes and washed 6 times with 1 mL of sterile physiological saline. Thereafter, the model periodontitis biofilm was dispersed by sonication (200 μA, 10 seconds) with 4 mL of sterilized physiological saline, and 10% cotton defibrillated blood-containing trypticase soy agar plate (Difco) and kanamycin sulfate ( 200 mg / L (manufactured by Sigma) containing 50 μL of trypticase soy blood agar plate was cultured and cultured under anaerobic conditions. The grown colonies were counted, and the number of remaining Porphyromonas gingivalis bacteria (cfu) was determined and determined according to the following criteria.

Criteria for bactericidal effect ○: Viable count is less than 10 ⁷ △: Viable count is 10 ⁷ or more and less than 10 ⁸ ×: Viable count is 10 ⁸ or more

To evaluate the smoothness of teeth:
A special panel was used to evaluate the smoothness of the teeth. 10ml of liquid oral composition shown in Tables 1 and 2 was rinsed for 20 seconds, and the smoothness when the teeth were touched with the tongue was evaluated in the following four levels, and the average value of 10 professional panels was calculated. did.

Evaluation criteria for the smoothness of teeth 3 points: Good smoothness was recognized.
2 points: Slightly smooth feeling was recognized.
1 point: Almost no slippery feeling was observed.
0 point: A smooth feeling was not recognized.
Rating ◎: 2.5 to 3 points ○: 2 to less than 2.5 points △: 1 point to less than 2 points ×: less than 1 point

Low temperature storage stability evaluation method:
The composition for liquid oral cavity shown in Tables 1 and 2 is put into an 80 mL transparent PET container manufactured by Yoshino Kogyo Co., Ltd., and stored at 5 ° C. in a constant temperature bath (Yamato Scientific Co., Ltd. Incubator IG420) for 1 month, followed by low-temperature storage stability (Ori Existence) was visually determined according to the following evaluation criteria.

Evaluation Criteria for Low-Temperature Stability A: There is no orientation and it is transparent.
○: Although very small suspended matter is recognized when shaken, it is transparent and has no problem.
Δ: Slight orientation is observed.
X: Considerable orientation is recognized.

  From the results of Tables 1 and 2, if any of the components (A) to (C) is missing or the blending amount or blending ratio of these components is outside the range according to the present invention, the biofilm of periodontal disease-causing bacteria However, the liquid oral composition of the present invention is superior in biofilm sterilizing power, mouthwash, while being inferior to any of the sterilizing power against the tooth, the smoothness of teeth and the low-temperature storage stability. It has been found that the tooth has a smooth feeling and a low temperature storage stability.

Claims (1)

(A) Isopropylmethylphenol 0.01-0.1% by mass
(B) Sodium myristoyl glutamate 0.01-0.3% by mass
(C) Polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 60 to 100 0.5 to 2% by mass
And a mass ratio of (A) / (B) is 0.3 to 5, which is a liquid oral composition.