JP5043588B2 - Liquid oral composition - Google Patents

Description

  The present invention relates to a liquid oral composition having excellent bactericidal effects on oral bacteria and good stability.

  Cationic bactericides such as benzethonium chloride and cetylpyridinium chloride have high bactericidal activity against oral bacteria and prevent the formation of biofilms such as plaque and tongue liquor, and are therefore incorporated in many oral compositions.

On the other hand, since cationic fungicides generally have a strong taste such as bitterness, oil-soluble fragrances are used in combination to mask this and enhance the feeling of use. However, when an oil-soluble fragrance is blended, it is necessary to further blend an anionic surfactant or a nonionic surfactant to improve the dispersibility of the oil component, but these surfactants are cationic fungicides. There is a tendency to reduce the bactericidal activity. Therefore, as a method for eliminating the inactivation of the cationic bactericidal agent, there is a technique (Patent Document 1) that uses a water-soluble fragrance obtained by extracting an oil-soluble fragrance with a water-containing ethanol solution and does not incorporate a surfactant. However, this method has problems such as lack of refreshing feeling due to the use of a water-soluble fragrance as a fragrance and a low degree of freedom in flavor type. Patent Document 2 proposes a technique of solubilizing an oil-soluble component with a small amount of a surfactant, that is, blending an oil-soluble component: nonionic surfactant in a ratio of 1000: 1 to 1: 1. However, since the polyoxyethylene addition type nonionic surfactant is used, the bactericidal effect of the cationic bactericide is not always sufficient. Further, Patent Document 3 proposes a technique (Patent Document 3) for exhibiting the effect of a bactericide by blending a polyoxyethylene / polyoxypropylene block polymer as a nonionic surfactant. The activator has a weak solubilizing power, and there is a problem in that the refreshing feeling of the oil-soluble fragrance is impaired by the content of the surfactant necessary for obtaining a stable liquid composition that does not precipitate or separate.
JP-A-7-101842 JP 2001-302478 A JP-A-4-202121

  An object of the present invention is to provide a liquid oral composition that contains a cationic bactericidal agent, has an excellent bactericidal effect due to the bactericidal agent, and has good long-term stability.

  Therefore, the present inventor conducted various studies on the bactericidal effect of the cationic bactericidal agent when the composition was used in an oral composition containing an oil-soluble fragrance to mask the taste and irritation of the cationic bactericidal agent. By solubilizing with polyglycerin fatty acid ester to give a specific emulsion particle size, the adsorptive power to teeth is improved without reducing the bactericidal effect of the cationic bactericide, and there is little bitterness and irritation and is stable It has been found that a liquid oral composition having good properties can be obtained.

That is, the present invention includes the following components (A), (B), (C) and (D)
(A) Oil-soluble fragrance (B) Polyglycerin fatty acid ester (C) Cationic fungicide (D) Containing water, (B) Polyglycerin fatty acid ester and (C) Cationic fungicide concentration 10 to 70% by mass A liquid oral composition having an average emulsion diameter of 20 to 150 nm obtained by mixing (A) an oil-soluble fragrance component with an aqueous solution and then mixing with other components.

  When the liquid oral composition of the present invention is used, a strong bactericidal power is obtained because a large amount of the cationic bactericidal agent is adsorbed on the surface of oral tissues such as teeth and oral mucosa. Formation can be strongly suppressed, and as a result, it is excellent in preventing oral troubles such as caries, periodontal disease, and bad breath, and it can be used continuously because there are few bitterness and other off-flavors. Furthermore, a liquid oral composition having good long-term stability can be obtained.

  The (A) oil-soluble fragrance used in the liquid oral cavity composition of the present invention is preferably a fragrance having a ClogP of −0.5 to 6, particularly in terms of masking off tastes such as the bitter taste of a cationic fungicide. Preferably, the fragrance has a ClogP of 0.2 to 5. Here, the ClogP value is a coefficient (calculated value) indicating the affinity of an organic compound for water and 1-octanol, and the 1-octanol / water partition coefficient P is the two-liquid phase of 1-octanol and water. The distribution equilibrium when a trace amount of a compound is dissolved as a solute in a solvent, which is the ratio of the equilibrium concentration of the compound in each solvent, and is a value expressed in the form of their logarithmic log P with respect to the base 10. Daylight Chemical Information Systems, Inc. It can be calculated by the program “CLOGP” available from (Daylight CIS), and many values are listed in the database of Daylight CIS. In the present invention, if there is a measured value of logP, the ClogP value calculated by the program CLOGP v4.01 is used when there is no measured value.

  Synthetic fragrances such as menthol, carvone, anethole, eugenol, cineol, thymol, methyl salicylate, plegon, menthone, pinene, limonene, menthyl acetate; mint oil such as peppermint oil, spearmint oil, mint oil Citrus oil such as lemon, orange, grapefruit, lime, eucalyptus, sage, rosemary, thyme, laurel, basil, perilla, bay, estragon, parsley, celery, coriander, herb oil, cinnamon, pepper, nutmeg, mace, Natural essential oils such as spice oil such as clove, ginger, cardamom, anise; apple, banana, melon, grape, peach, strawberry, blueberry, raspberry, blackcurrant, lychee, star fruit, passion passion Over tool may be used plum, pineapple, and fruit flavors such as Muscat. Among these oil-soluble fragrances, menthol, carvone, peppermint oil, spearmint oil, peppermint oil, methyl salicylate, cineol, limonene, and pinene are particularly preferable from the viewpoint of imparting a refreshing feeling and refreshingness to the oral cavity. These oil-soluble fragrances are used alone or in combination of two or more. In particular, it is preferable to contain at least menthol.

  Component (A) is 0.05 to 2% by mass, more preferably 0.07 to 1% by mass, particularly 0.1 to 0.1% by mass in the composition for liquid oral cavity of the present invention, from the point of obtaining the masking effect of the cationic fungicide. It is preferable to contain -0.7 mass%.

  (B) As for polyglycerol fatty acid ester, the condensation degree of glycerol is 2-20, and also 5-12 are preferable from the point of the adsorption amount improvement to the tooth | gear etc. of a cationic fungicide. Moreover, as a fatty acid part, C6-C24 saturated or unsaturated fatty acid is mentioned, Preferably it is C10-20, and the fatty acid of lauric acid, myristic acid, palmitic acid, and a stearic acid from a stability point. Is particularly preferred. Component (B) is 0.001 to 2% by mass, more preferably 0.01 to 1% by mass, and particularly preferably 0.1 to 0.1% by mass in the liquid oral composition of the present invention in terms of taste and stability, particularly stability. It is preferable to contain 8 mass%. The blending mass ratio of component (A) oil-soluble fragrance and (B) polyglycerin fatty acid ester is 1: 1.5 to 1:10 in terms of stability and improvement in the amount of cationic fungicide adsorbed on teeth, etc. Is preferred.

  (C) Cationic disinfectant adsorbs on oral tissue surfaces such as tooth surfaces, oral mucosa (including gums), etc., and has a bactericidal action against bacteria that cause caries, periodontal disease, bad breath, etc. And quaternary ammonium compounds, biguanide compounds and the like. Examples of the bactericides belonging to the quaternary ammonium compounds include cetylpyridinium chloride, decalinium chloride, benzethonium chloride, benzalkonium chloride, alkyldimethylammonium chloride, alkyltrimethylammonium chloride, methylbenzethonium chloride, lauroylcoraminoformylmethylpyridinium chloride, and the like. Is mentioned. Further, examples of the bactericides belonging to the biguanide compounds include chlorhexidine and salts thereof, and chlorhexidine gluconate and chlorhexidine hydrochloride are preferable. As the component (C), one or more of the above bactericides can be used in combination, but from the viewpoint of bactericidal action and taste, 0.001 to 0.5% by mass in the liquid oral composition of the present invention. Furthermore, it is preferable to contain 0.005-0.2 mass%, especially 0.01-0.05 mass%.

  The liquid oral cavity composition of the present invention prepares an aqueous solution of a surfactant in which (B) a polyglycerin fatty acid ester and (C) a cationic fungicide are dissolved in water so as to have a concentration of 10 to 70% by mass, There, (A) an oil-soluble fragrance component is solubilized to prepare a uniform dispersion solution. By mixing it with a solution in which the remaining water-soluble components are dissolved in water, a liquid oral composition having an average emulsion diameter of 20 to 150 nm can be obtained. That is, by preparing an oily component dispersion in which an oil-soluble fragrance is uniformly dispersed in a high-concentration surfactant aqueous solution and mixing it with a large amount of an aqueous component, even a small amount of an oily component can be stable. A solubilized state can be formed, and the cationic disinfectant can also be excellent in the ability to adsorb into the oral cavity. It is preferable that the density | concentration of this component (B) and (C) aqueous solution is 15-60 mass% from the point of adjustment of a dispersion liquid. When the concentration of the surfactant component solution in which (B) polyglycerol fatty acid ester and (C) cationic fungicide are dissolved in water is too low as less than 10%, (A) the oil-soluble fragrance component may be separated, In addition, if the concentration of the surfactant component solution in which (B) polyglycerin fatty acid ester and (C) cationic fungicide are dissolved in water is too high, more than 70%, the properties of the solution become too viscous. It is not preferable.

  The method for forming a solubilized state of an oil-soluble fragrance by the high-concentration surfactant aqueous solution of the present invention is particularly effective in a liquid oral composition having a low ethanol content. When the blending amount of ethanol is small, it is difficult to obtain a stable emulsion that hardly causes separation only by mixing a small amount of an oily component with a large amount of an aqueous component. The composition for liquid oral cavity of the present invention preferably has an ethanol content of 1% by mass or less (0 to 1% by mass), particularly preferably 0 to 0.5% from the viewpoint of low irritation, It is substantially free of ethanol.

  The liquid oral composition of the present invention can further contain a polyhydric alcohol. By adding a polyhydric alcohol, it is preferable in terms of facilitating handling of a viscous mixed solution when preparing a high concentration surfactant aqueous solution. Polyhydric alcohols include propylene glycol, glycerin, polyethylene glycol and the like, but those which are liquid at 25 ° C. are preferred, and glycerin is particularly preferred. In this invention, content of a polyhydric alcohol becomes like this. Preferably it is 1-15 mass%, Most preferably, it is 3-10 mass%. When blending the polyhydric alcohol, it is preferable to blend a part of it in the step of preparing a high-concentration surfactant aqueous solution.

  By preparing the liquid oral composition of the present invention by the above method, a liquid composition having a fine emulsion diameter with an average particle diameter of 20 to 150 nm can be obtained. In addition, the average particle diameter of the composition for liquid oral cavity can be measured with a dynamic light scattering type particle size distribution measuring apparatus (HORIBA LB-550 etc.).

  Furthermore, in the composition for liquid oral cavity of the present invention, surfactants other than the component (B), sugar alcohol, binder, buffering agent, preservative (preservative), other medicinal agents, sweetener, water, etc. Can be contained. Of these components, the oil-soluble one is preferably added when adding the oil-soluble fragrance to the high-concentration surfactant solution. Here, the content of water in the liquid oral composition is preferably 50 to 99.9% by mass, more preferably 65 to 98% by mass, and particularly preferably 75 to 95% by mass.

  In the present invention, the content of the anionic surfactant is 0.01% by mass or less (0 to 0.01% by mass) in the liquid oral composition from the viewpoint of stimulation and adsorption of the cationic bactericidal agent to the teeth and the like. Is preferred.

  Examples of the sugar alcohol used in the present invention include erythritol, xylitol, ribitol, arabitol, galactitol, sorbitol, mannitol, maltitol, palatinit, lactitol, maltotriitol, isomaltoteitol, maltotetriitol, isomaltotetriol. Among them, erythritol, xylitol, and paratinite are preferable from the viewpoint of suppressing biofilm formation. The sugar alcohol is contained in the composition for liquid oral cavity of the present invention in an amount of 4 to 50% by mass, further 5 to 35% by mass, particularly 6 to 20% by mass in terms of obtaining a good refreshing sensation and a taste and odor prevention effect. Is preferred. Furthermore, the total content (mass ratio) of erythritol, xylitol, and palatinit in the sugar alcohol is preferably 1/2 or more, and more preferably 2/3 or more.

  As a binder, cellulose derivatives such as sodium carboxymethyl cellulose and hydroxyethyl cellulose, alginic acid derivatives such as sodium alginate and propylene glycol alginate, gums such as carrageenan, xanthan gum, duran gum, tragacanth gum and karaya gum, polyvinyl alcohol, sodium polyacrylate, Examples thereof include synthetic binders such as carboxyvinyl polymer, inorganic binders such as silica gel, bee gum and laponite, and starch degradation products such as dextrin and reduced dextrin. These may be used alone or in combination of two or more.

Examples of preservatives include isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, ethyl paraoxybenzoate, butyl paraoxybenzoate, propyl paraoxybenzoate, methyl paraoxybenzoate, benzoic acid, sodium benzoate, methyl salicylate, potassium sorbate and Examples include sodium dehydroacetate. In particular, when the blending amount of ethanol is small, it is preferable to include a preservative. The content of the preservative is preferably 0.001 to 0.1% by mass.
Examples of the buffer include citric acid and its salt, malic acid and its salt, phosphoric acid and its salt, polyphosphoric acid and its salt, and the like. Examples of the sweetener include saccharin sodium, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perilartine, somatotin, asparatylphenylalanyl methyl ester, sucralose and the like. Other medicinal agents include anti-plasmin agents such as tranexamic acid and epsilon aminocaproic acid, vitamins such as ascorbic acid and tocopherol ester, glycyrrhizin salts, allantoins, plant extracts such as buckwheat, oxon, chamomile, latania and myrrh. Enzymes such as stranase, mutanase, lysozyme chloride, alkali metal monofluorophosphates such as sodium monofluorophosphate, fluorides such as sodium fluoride, stannous fluoride, sodium chloride, potassium nitrate, carbonate, bicarbonate , Salts such as sesquicarbonate, copper chlorophyllin sodium, copper gluconate, zinc chloride, zeolite, water-soluble inorganic phosphate compound, aluminum lactate, etc.

  The liquid oral composition of the present invention can be applied as liquid dentifrice, water dentifrice, mouthwash, mouth spray, mouthwash, and the like.

A liquid oral composition was produced according to the formulation in Table 1.
<Production method>
A surfactant aqueous solution was prepared by mixing 1.5% by mass of purified water of Example 1, polyglycerin fatty acid ester (decaglyceryl myristate) and a cationic fungicide. An oil-soluble fragrance was added to the surfactant aqueous solution and mixed well to prepare a solubilized oil-soluble fragrance liquid. Thereafter, the remaining water and other components were mixed to obtain a liquid oral composition. The perfume composition is shown in Table 2.
Examples 2 and 3 were prepared in the same manner as in Example 1 except that the amount of purified water when preparing the surfactant aqueous solution was 0.5 mass%. Examples 4 and 5 were prepared in the same manner as Example 1 except that glycerin was blended in a high-concentration surfactant aqueous solution. Comparative Example 1 was the same as Example 1 except that the amount of purified water in preparing the surfactant aqueous solution was 20% by mass. In Comparative Example 2, a liquid oral composition was obtained in the same manner as in Example 1 except that sodium lauryl sulfate was used instead of decaglyceryl myristate as a solubilizer. In Comparative Example 3, a liquid oral composition was obtained in the same manner as in Example 1 except that the cationic bactericidal agent was omitted.

[Evaluation]
(1) Appearance immediately after preparation and measurement of emulsion diameter The obtained composition for liquid oral cavity was placed in a transparent glass bottle and visually observed according to the following criteria. The emulsion diameter was measured with a dynamic light scattering type particle size distribution analyzer (HORIBA LB-550 etc.). Transparency of appearance decreases as the average emulsion particle size increases. ○: Uniformly dispersed, transparent or blue-white translucent (emulsion average particle size of 20 to 150 nm)
Δ: Evenly dispersed, but less transparent, cloudy (emulsion average particle size> 150 nm)
×: Oil-soluble component is separated

(2) Storage stability test The obtained composition for liquid oral cavity was put into a transparent glass bottle, left in a thermostatic chamber at -5 ° C for 1 month, and visually observed according to the following criteria.
○: No change compared to immediately after preparation Δ: Slightly cloudy or separated compared to immediately after preparation ×: Clearly cloudy or separated compared to immediately after preparation

(3) Bactericidal power As an index of bactericidal power, the minimum growth inhibitory concentration (MIC) by dilution was measured. The measuring method is as follows.
1. A certain amount of sterilized hydroxyapatite beads (manufactured by BDH) is coated with sterilized saliva, and then washed with phosphate sterilized buffered saline (PBS).
2. The hydroxyapatite beads after washing are reacted with the following solution formulation at room temperature for 30 minutes.
3. After completion of the reaction, the solution formulation is removed, and after washing with PBS, BHI medium (Brain Heart Infusion Medium: manufactured by BD) is added.
4). A 2-fold serial dilution series was prepared for each hydroxyapatite bead. After a certain amount of mutans bacteria (Streptococcus mutans JCM5705) is added, anaerobic culture is performed at 37 ° C. for 24 hours.
5. The presence or absence of bacterial growth is judged by visual turbidity, and the minimum growth inhibitory concentration (MIC) based on the dilution factor is measured.
In addition, 0.01% benzethonium chloride aqueous solution was used as a standard cationic germicide solution, and the antibacterial activity of each solution formulation was evaluated according to the following evaluation criteria.
○: Has a MIC almost equivalent to the standard △: Has a MIC of 1/8 or less of the standard ×: Has a MIC of 1/64 or less of the standard

  The evaluation results are shown in Table 1.

  As is apparent from Table 1, the liquid oral composition obtained by the specific production method of the present invention is excellent in appearance immediately after production (transparency or bluish white translucent), excellent in storage stability, and sterilized. Also excellent in power. In Comparative Example 1 in which the concentration of the surfactant aqueous solution at the time of preparation was low, the fragrance could not be dispersed and oil floating occurred. The emulsion diameter could not be measured. In Comparative Example 2 using an anionic activator, a liquid composition could be prepared but did not show bactericidal activity. In Comparative Example 3 containing no cationic bactericidal agent, a liquid composition could be prepared but did not show bactericidal power.

Claims (6)

The following components (A), (B), (C) and (D)
(A) Oil-soluble perfume 0.05-2% by mass
(B) Polyglycerol fatty acid ester 0.001-2 mass%
(C) Cationic fungicide 0.001 to 0.5 mass%
(D) 50-99.9 mass% of water
The method of manufacturing a liquid oral composition containing, a concentration from 15 to 70 wt% by dissolving (D) a portion of the water (B) polyglycerin fatty acid ester and (C) cationic biocides, And after mixing (A) oil-soluble fragrance | flavor component with surfactant aqueous solution prepared so that content of the anionic surfactant in a liquid oral cavity composition may be 0.01 mass% or less , the remaining (D) mixing the other ingredients comprising water and sugar alcohols, the production method of the liquid oral composition having an average particle size of the emulsion is 20 to 150 nm. The manufacturing method of the liquid oral cavity composition of Claim 1 containing 0-1 mass% of ethanol. The method for producing a liquid oral composition according to claim 1 or 2, wherein the blending mass ratio of (A) oil-soluble fragrance and (B) polyglycerin fatty acid ester is 1: 1.5 to 1:10. The method for producing a liquid oral cavity composition according to any one of claims 1 to 3, wherein the polyglycerol fatty acid ester has a glycerol condensation degree of 5 to 12 and a fatty acid having 10 to 20 carbon atoms. Content of the sugar alcohol in a liquid oral cavity composition is 4-50 mass%, The manufacturing method of the liquid oral cavity composition in any one of Claims 1-4. The method for producing a liquid oral composition according to any one of claims 1 to 5, wherein the liquid oral composition further comprises a polyhydric alcohol, and a part of the polyhydric alcohol is blended to prepare a surfactant aqueous solution.