JP6439425B2 - Liquid oral composition - Google Patents

Description

  The present invention relates to a liquid oral composition suitable for suppression of plaque formation because the adsorption of the tooth surface of the cationic disinfectant is promoted to increase the amount of adsorption on the tooth surface.

  In liquid oral compositions such as liquid dentifrices and mouthwashes, cationic bactericides such as cetylpyridinium chloride and benzethonium chloride are blended as bactericides to suppress plaque and prevent periodontal disease and caries. The cationic bactericidal agent is adsorbed on the tooth surface and the oral mucosa by electrostatic interaction, and stays in the oral cavity to maintain the bactericidal effect and give a plaque formation suppressing effect. Therefore, if the adsorption amount of the cationic bactericidal agent on the tooth surface is increased, the retention in the oral cavity is increased and further effect improvement can be expected.

  On the other hand, in liquid oral compositions, organic acids such as citric acid and malic acid and salts thereof are used as pH adjusters, chelating agents, etc., but organic acids or salts thereof have astringency, bitterness, salty taste. Therefore, there is a problem that adversely affects the flavor of the preparation.

  As a technique related to a cationic fungicide using an organic acid or a salt thereof, Patent Document 1 (JP 2013-256466 A) discloses ascorbic acid phosphate or a salt thereof, a cationic fungicide, two or more carboxyls. Liquid oral compositions containing a group-containing organic acid or a salt thereof and orthophosphoric acid have been proposed. In Patent Document 2 (Japanese Patent Application Laid-Open No. 11-255629), when a specific nonionic surfactant is added to an oral composition containing a cationic bactericide and a chelating agent is blended, the penetrability of the bactericide into plaque is increased. It has been proposed that it promotes and has a superior bactericidal effect, and the taste is improved by the addition of a fragrance component such as anethole. Patent Document 3 (Japanese Patent Application Laid-Open No. 2014-125484) discloses that an oral composition having a pH of 6 or less containing a pH adjuster such as benzaldehyde, cetylpyridinium chloride, organic acid, etc. It proposes excellent storage stability with time and good flavor. However, these Patent Documents 1 to 3 are unclear because there is no mention of the adsorption amount of the cationic fungicide on the tooth surface.

JP 2013-256466 A JP-A-11-255629 JP 2014-125484 A

  Therefore, in the liquid oral composition, it has been desired to develop a technique for increasing the adsorption amount of the cationic bactericidal agent on the tooth surface and further improving the effect.

  The present invention has been made in view of the above circumstances, and provides a liquid oral composition suitable for suppressing plaque formation by increasing the amount of adsorption to the tooth surface by promoting the adsorption of the tooth surface of the cationic bactericidal agent. The purpose is to do.

  As a result of diligent studies to achieve the above object, the present inventors have added (B) citric acid and / or a salt thereof to a liquid oral composition containing (A) cetylpyridinium chloride as a cationic bactericidal agent. 0.20% by mass or more and (C) one or more selected from tartaric acid, malic acid and salts thereof and 0.10% by mass or more, and (B) component and (C) component By making the total blending amount less than 1.50% by mass, (A) the adsorption of the tooth surface of cetylpyridinium chloride is promoted and the amount of adsorption to the tooth surface is increased, and the astringency and taste are suppressed and flavor. As a result, it was found that a liquid preparation that can be suitably used for suppressing plaque formation can be obtained, and the present invention has been made.

  That is, the present inventors think that the liquid oral composition can suppress the plaque formation on the tooth surface more than ever if the adsorption amount of the cationic bactericidal agent on the tooth surface is increased. As a result of further investigation based on the hypothesis, when (B) component and (C) component of organic acid or its salt are combined in an appropriate amount, surprisingly, (A) Tooth surface of cetylpyridinium chloride As shown in the examples described later, an increase in the amount of tooth surface adsorption that can adsorb 1.5 μg or more of cetylpyridinium chloride per 1 mg of hydroxyapatite is obtained. When the organic acids other than the components (B) and (C) or salts thereof were combined, specific and remarkable effects that could not be achieved could be imparted. In addition, the astringent taste, bitterness and saltiness derived from the organic acid or its salt can be suppressed, the flavor can be maintained well, and a preparation suitable for use with a good feeling of use can be obtained. And in the present invention, the increase in the amount of cetylpyridinium chloride adsorbed on the tooth surface improves the retention in the oral cavity and effectively prevents plaque from forming on the tooth surface (oral cavity). Biofilms) formation suppressing effect can be expected, and it is possible to provide a liquid preparation suitable for preventing or suppressing periodontal disease by suppressing plaque formation.

  Patent Document 1 is an invention proposed by the present applicant for the purpose of giving a clear appearance by suppressing coloring and tingling in a liquid preparation, and examines the amount of adsorption of a cationic fungicide on the tooth surface. I have not mentioned it. Although the liquid oral composition of Example 22 of Patent Document 1 contains citric acid and its salt and malate together with cetylpyridinium chloride, citric acid monohydrate and trisodium citrate dihydrate And the amount of disodium malate is small, and the amount of cationic fungicide adsorbed on the tooth surface is inferior to that of the present invention.

Therefore, the present invention
(A) a liquid oral composition containing cetylpyridinium chloride,
(B) 0.20% by mass or more of citric acid and / or a salt thereof,
(C) 0.4-0.8 mass % of 1 type (s) or 2 or more types chosen from tartaric acid, malic acid, and its salt
(B) / (which shows the ratio of the compounding quantity of (B) component and (C) component and 0.84-1.24 mass% and the total compounding quantity of (B) component and (C) component. A liquid oral composition is provided wherein C) is 0.7 to 2.0 as a molar ratio, and pH at 25 ° C is 6.0 to 7.0 .

  According to the present invention, the adsorption of cetylpyridinium chloride on the tooth surface is promoted to increase the amount of adsorption on the tooth surface, and the astringency and off-flavor are suppressed and the flavor is good. An oral composition can be provided.

  The present invention will be described in detail below. The composition for liquid oral cavity of the present invention contains one or more selected from (A) cetylpyridinium chloride, (B) citric acid and / or a salt thereof, (C) tartaric acid, malic acid and a salt thereof. .

As the cetylpyridinium chloride as the component (A), commercially available cetylpyridinium chloride (manufactured by Wako Pure Chemical Industries, Ltd.) can be used.
The blending amount of cetylpyridinium chloride is preferably 0.01 to 0.1% (mass%, the same applies hereinafter) of the entire composition, and more preferably 0.02 to 0.08%. As the amount is increased, the bactericidal effect increases, and when the amount is 0.01% or more, a sufficient bactericidal effect can be provided. When it is 0.1% or less, the bitterness of cetylpyridinium chloride can be suppressed and the feeling of use can be maintained better.

  (B) The citric acid of a component and / or its salt act as a tooth surface adsorption | suction promoter of (A) component by combining with (C) component.

As the salt of citric acid, an alkali metal salt of citric acid can be used, and citric acid and its salt may be anhydrous or hydrated. Specific examples of citric acid and salts thereof include citric acid, citric acid monohydrate, sodium citrate, trisodium citrate monohydrate, trisodium citrate dihydrate, and the like.
In the present invention, the component (B) is more preferably citric acid and citrate, more preferably citric acid and sodium citrate.

The blending amount of the component (B) is 0.20% or more of the whole composition in terms of pure content and is preferably less than 1.40%, more preferably 0.20 to 1.35%, still more preferably 0.00. 3 to 0.8%. If the blending amount is less than 0.20%, the adsorption amount of the tooth surface of cetylpyridinium chloride does not increase, and the object of the present invention cannot be achieved. Further, if it is less than 1.40%, particularly 1.35% or less, it is preferable because the flavor can be maintained better. When the blending amount of the component (B) is too large, the total amount of the organic acid and its salt including the component (C) is excessively increased, sourness derived from the organic acid, bitterness derived from the organic acid salt, astringency and salty In some cases, the flavor may decrease, and it is preferable not to add too much to maintain the flavor well.
In addition, when combining a citric acid and a citrate, each compounding quantity and a compounding ratio can be suitably adjusted according to formulation pH within the range of the compounding quantity of (B) component.

Component (C) is a tooth surface adsorption promoter for cetylpyridinium chloride, and is one or more organic acids selected from tartaric acid, malic acid and salts thereof and / or salts thereof. These may be anhydrides or hydrates, and examples of the salt include alkali metal salts such as sodium salt, but are not limited thereto.
Examples of the component (C) include sodium tartrate dihydrate, sodium malate hemihydrate, etc., and commercially available products such as those manufactured by Komatsuya Co., Ltd. and Fuso Chemical Industry Co., Ltd. are used. it can.

  (C) The compounding quantity of a component is 0.10% or more of the whole composition in conversion of a pure part, Preferably it is 0.10-1.25%, More preferably, it is 0.2-0.8%. When the content is less than 0.10%, the amount of cetylpyridinium chloride adsorbed on the tooth surface does not increase, and the object of the present invention cannot be achieved. Moreover, it is suitable from 1.25% or less from being able to maintain a flavor better. Furthermore, if the blending amount of the component (C) is too large, the component (B) is also blended, so the total amount of the organic acid and its salt is too large, sourness derived from the organic acid and bitterness derived from the organic acid salt. In some cases, astringency or salty taste may occur and the flavor may decrease, and it is preferable not to add too much to maintain a good flavor.

  In this invention, the total compounding quantity of (B) component and (C) component is less than 1.50% of the whole composition, Preferably it is 0.30-1.45%, More preferably, 0.30-1. 0%. If the blending amount is 1.50% or more, the flavor deteriorates, and the amount of cetylpyridinium chloride adsorbed on the tooth surface cannot be increased while maintaining a good flavor. Moreover, when 0.30% or more is mix | blended, the adsorption amount to the tooth surface of a cetyl pyridinium chloride can be increased more, and a flavor can be improved as it is 1.45% or less.

  Moreover, (B) / (C) which shows the mixture ratio of (B) component and (C) component can be 0.2-17 as a molar ratio in conversion of a pure part, Preferably 0.7 ~ 2.0. When the ratio of the blending amount of the component (B) and the component (C) is adjusted within the above range, the cetylpyridinium chloride tooth surface adsorption promoting effect is more excellent, and the amount of adsorption on the tooth surface is increased. The flavor is also improved.

  The liquid oral composition of the present invention preferably has a pH at 25 ° C. of 6.0 or more, more preferably 6.0 to 7.0. When the pH of the composition is 6.0 or more, the tooth surface adsorption promoting effect of cetylpyridinium chloride is more excellent, and the amount of adsorption on the tooth surface is further improved.

  The liquid oral cavity composition of the present invention is prepared as a mouthwash, a liquid dentifrice, and the like, and in addition to the above-mentioned components, other known components can be blended as necessary in a range not impeding the effects of the present invention. Specifically, a wetting agent, a surfactant, a solvent, and a sweetener, a coloring agent, a fragrance, an active ingredient, and the like are blended as necessary.

  Examples of the wetting agent include sugar alcohols such as xylitol and erythritol, and polyhydric alcohols such as propylene glycol and glycerin. The amount of wetting agent is usually 2 to 20% of the total composition.

  As the surfactant, known nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants can be blended, but nonionic surfactants are preferred.

Nonionic surfactants include, for example, sugar alcohol fatty acid esters such as sucrose fatty acid ester, maltose fatty acid ester, maltitol fatty acid ester, lactol fatty acid ester, polyoxyethylene fatty acid ester such as polyoxyethylene hydrogenated castor oil, and alkylol amide. And polyoxyethylene sorbitan fatty acid ester, polyglycerin fatty acid ester, hexaglyceryl monocetylate, fatty acid diethanolamide, sorbitan fatty acid ester, polyoxyethylene higher alcohol ether and the like. Among these, polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 40 to 100 mol is preferable.
Examples of the anionic surfactant include alkyl sulfates such as sodium lauryl sulfate and N-acyl sarcosine salts such as sodium N-lauroyl sarcosine.
Examples of the cationic surfactant include alkyl ammonium and alkyl benzyl ammonium salts, and examples of the amphoteric surfactant include betaine acetate type and imidazoline type.
The blending amount of these surfactants is preferably 0.05 to 8% of the entire composition.

As the colorant, a highly safe water-soluble dye such as Blue No. 1, Green No. 3, Yellow No. 4, Red No. 105, or the like can be added.
Examples of the sweetening agent include xylitol, maltitol, saccharin, saccharin sodium and the like.

  As a fragrance, natural essential oils such as peppermint oil, spearmint oil, eucalyptus oil, winter green oil, clove oil, thyme oil, sage oil, cardamom oil, rosemary oil, marjoram oil, lemon oil, lavender oil, paracres oil, And l-menthol, l-carvone, orange oil, anethole, 1,8-cineole, methyl salicylate, eugenol, thymol, linalool, limonene, menthone, eugenol, menthyl acetate, citral, camphor, borneol, pinene, spirantol, etc. Perfume ingredients contained in natural essential oils, ethyl acetate, ethyl butyrate, isoamyl acetate, hexanal, hexenal, methyl anthranilate, ethyl methyl phenyl glycidate, benzaldehyde Perfume ingredients such as, furaneol, maltol, ethyl maltol, gamma / delta decalactone, gamma / deltown decalactone, N-ethyl-p-menthane-3-carboxamide, menthyl lactate, ethylene glycol 1-menthyl carbonate, One of the flavors of apple, banana, strawberry, blueberry, melon, peach, pineapple, grape, muscat, wine, cherry, squash, coffee, brandy, yogurt, etc. Or 2 or more types can be added in the range which does not inhibit the effect of this invention. The addition amount of the fragrance is usually 0.00001 to 3% in the composition.

  As an active ingredient, in addition to cetylpyridinium chloride, bactericides such as isopropylmethylphenol, enzymes such as dextranase and mutanase, fluorides such as sodium fluoride and sodium monofluorophosphate, vitamins C, thyme, Plant extracts such as hornon, clove, and hamamelis, water-soluble copper compounds such as copper gluconate, and the like can be blended. In addition, the addition amount of these active ingredients can be made into effective amount in the range which does not prevent the effect of this invention.

  As the solvent, water is usually used, and the water content is preferably 60% or more of the entire composition. If necessary, lower monohydric alcohol such as ethanol may be added to 30% or less, particularly about 20% or less, but may be 0%.

EXAMPLES Hereinafter, although an Example , a reference example, and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. In the following examples, “%” means “% by mass” unless otherwise specified. The compounding amount in the table is a pure conversion value, and the pH is a value at 25 ° C.

[Examples, Reference Examples, Comparative Examples]
Liquid oral compositions having the compositions shown in Tables 1 and 2 were prepared by a conventional method, and the obtained liquid oral composition was used as a sample and evaluated by the following method. The results are shown in Tables 1 and 2.

(1) Evaluation experiment method of adsorption amount of cetylpyridinium chloride (CPC) on tooth surface:
HAP powder (60 mg, ceramic hydroxyapatite, manufactured by BioRad) is weighed into a 5 ml microtube (manufactured by Argos), 2 ml of centrifugal supernatant saliva is added, and stirred at room temperature for 30 minutes using a rotator to treat saliva Went. Next, saliva was removed, 4 ml of the sample was added and stirred for 30 seconds, and then the sample was removed. The operation of adding 4 ml of pure water and stirring for 30 seconds to remove the washing solution was repeated twice. To this HAP powder, 3 ml of ethanol was added and stirred for 30 seconds to dissolve CPC adsorbed on HAP, and the supernatant was collected.
Using high-performance liquid chromatography (HPLC), the concentration (%) of CPC was determined by the absolute calibration curve method, and the amount of CPC adsorbed per mg of HAP powder (μg / HAP mg) was determined from the concentration of CPC.
From the CPC adsorption amount, the adsorption amount of CPC on the tooth surface was evaluated according to the following evaluation criteria.
Criteria for evaluating the amount of CPC adsorbed on the tooth surface ◎: CPC adsorption amount is 2.5 μg / HAP mg or more ○: CPC adsorption amount is 1.5 μg / HAP mg or more and less than 2.5 μg / HAP mg ×: CPC adsorption The amount is less than 1.5 μg / HAPmg

(2) Flavor Evaluation After 10 subjects included about 10 ml of sample in their mouth and rinsed for 30 seconds, the flavor in the mouth after mouthwash was determined based on the following four grades. From the average score of 10 persons, the flavor (astringency / no taste) was evaluated according to the following evaluation criteria, and indicated by ◎, ○, Δ, ×.
Rating criteria 4 points: No astringency / unpleasant 3 points: Slightly astringent / disgusting 2 points: Slightly astringent / disgusting 1 point: Astringent / disgusting Evaluation criteria ◎: Average Point is 3.5 or more and 4.0 or less ○: Average point is 3.0 or more and less than 3.5 △: Average point is 2.0 or more and less than 3.0 ×: Average point is less than 2.0

Details of the raw materials used are shown below.
(A) Cetylpyridinium chloride (CPC); Wako Pure Chemical Industries, Ltd. (B) Citric acid monohydrate; Fuso Chemical Industry Co., Ltd. Trisodium citrate monohydrate; Fuso Chemical Industry Co., Ltd. (C) sodium tartrate dihydrate; L-sodium tartrate, manufactured by Komatsuya Co., Ltd. sodium malate 1/2 hydrate; DL-sodium malate, Fuso Chemical Industries, Ltd.
) Sodium lactate; 50% aqueous solution, manufactured by Pure Chemical Co., Ltd. Monosodium succinate; manufactured by Tokyo Chemical Industry Co., Ltd.

＊；（Ｂ）／（比較品）のモル比
＊＊：（Ｂ）＋（比較品）の合計量（％）

*: (B) / (comparative product) molar ratio **: (B) + (comparative product) total amount (%)

  As shown in Table 1, even when the components (A), (B), and (C) are blended, if the amount of the component (B) or the amount of the component (C) is too small, the amount of adsorption of CPC on the tooth surface is reduced. Less (Comparative Examples 1 and 2), if the total amount of (B) + (C) is too much, astringency and off-flavor are produced and the flavor is inferior (Comparative Example 3), and the component (C) is not blended. And even if sodium lactate or monosodium succinate is blended together with component (B), the amount of CPC adsorbed on the tooth surface is small (Comparative Examples 4 and 5), as shown in Table 2 (A The composition for liquid oral cavity of the present invention (Example) in which the components (B) and (C) are used in appropriate amounts in combination with the component (A)) increases the amount of CPC adsorbed on the tooth surface, and has astringency. -Off-flavor was suppressed and flavor was good. And it turned out that the composition for liquid oral cavity of these Examples is suitable for provision of the plaque formation inhibitory effect.

Claims (6)

(A) a liquid oral composition containing cetylpyridinium chloride,
(B) 0.20% by mass or more of citric acid and / or a salt thereof,
(C) 0.4-0.8 mass % of 1 type (s) or 2 or more types chosen from tartaric acid, malic acid, and its salt
(B) / (which shows the ratio of the compounding quantity of (B) component and (C) component and 0.84-1.24 mass% and the total compounding quantity of (B) component and (C) component. A liquid oral composition , wherein C) is 0.7 to 2.0 as a molar ratio, and pH at 25 ° C. is 6.0 to 7.0 . The composition for liquid oral cavity according to claim 1 , wherein the blending amount of component (B) is 0.20 to 1.35 % by mass.   The composition for liquid oral cavity according to claim 1 or 2, wherein the amount of component (A) is 0.01 to 0.1% by mass.   The liquid oral composition according to claim 1, 2 or 3, wherein the component (B) is citric acid and citrate. (B) / (C) is 0.7-0.9 as a molar ratio, The composition for liquid oral cavity of any one of Claims 1-4. Furthermore, the composition for liquid oral cavity of any one of Claims 1-5 which mix | blended nonionic surfactant.