JP2009001511A - Liquid oral composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a liquid oral composition in which a calcium ion can be stably formulated, and which can effectively prevent dental caries and periodontal disease by improving retentivity of a cationic bactericide on the surface of the oral tissue. <P>SOLUTION: The liquid oral composition contains the following components (A) to (C): (A) 0.005-1 mass% calcium ion-supplying compound, (B) a cationic bactericide and (C) a nonionic surfactant containing (C1) a fatty acid ester of a polyglycerol and (C2) a nonionic surfactant having 16-20 HLB except the component (C1). <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a liquid oral composition having good stability and excellent caries and periodontal disease prevention effects.

  Calcium ions are known to promote tooth remineralization, eliminate white spots (white spots) generated in the early stages of the cavity, and re-enamelize the enamel (Non-patent Document 1). Therefore, calcium ions are widely used in oral compositions aimed at promoting remineralization. However, in the composition, calcium ions are inactivated due to the interaction with various other compounding components, and the properties of the calcium ions may not be sufficiently exhibited. In particular, in the case of a liquid oral composition, it is caused by precipitation of an inactivated calcium salt. For this reason, in order to stabilize calcium ions, a larger amount of nonionic surfactant than anionic surfactant is used in combination (Patent Document 1).

On the other hand, cationic bactericides such as benzethonium chloride and cetylpyridinium chloride have high bactericidal activity against oral bacteria and prevent the formation of biofilms such as dental plaque and tongue coating, thus preventing caries, periodontal diseases, bad breath, etc. -It is blended in many oral compositions for improvement. However, when a larger amount of a nonionic surfactant than that of an anionic surfactant is added as a solubilizer for a calcium ion supply compound as in Patent Document 1, the bactericidal activity of the cationic bactericide and the teeth, oral mucosa, etc. It may reduce the adsorptivity to the oral tissue surface. Especially in liquid oral compositions such as mouthwashes, the application time to the oral cavity is shorter than general toothpastes (low retention in the oral cavity). It is difficult for chemicals such as bactericides to stay in the interior. Therefore, there has been a demand for a liquid oral composition capable of exhibiting effective bactericidal action in the oral cavity by allowing calcium ions to stably coexist and improving the adsorptivity of the bactericidal agent to the surface of oral tissues such as teeth and oral mucosa. .
Koulourides. T. et. Al, "Rehardening of softened enamel surface of human teeth by solution of calcium phosphates", 1961, 189, 226 JP 2005-187437 A

  An object of the present invention is a liquid oral composition that can stably contain calcium ions and can effectively prevent dental caries and periodontal disease by improving the retention of a cationic bactericide on the oral tissue surface. Is to provide.

  As a result of intensive studies to solve the above problems, the present inventors have combined the cationic bactericidal agent with a specific nonionic surfactant to stabilize the calcium ion and the oral tissue of the cationic bactericidal agent. It has been found that the retention on the surface can be achieved, and the present invention has been completed.

That is, this invention provides the liquid oral cavity composition containing the following component (A)-(C).
(A) Calcium ion supply compound 0.005 to 1% by mass,
(B) a cationic fungicide,
(C) a nonionic surfactant containing the following (C1) and (C2),
(C1) Nonionic surfactant of HLB16-20 other than polyglycerin fatty acid ester (C2) (C1).

  The liquid oral composition of the present invention can stably contain calcium ions, improve the retention of the cationic bactericide on the oral tissue surface, and can effectively prevent caries and periodontal disease. .

  The (A) calcium ion supply compound of the present invention is a water-soluble compound that dissolves in water and releases calcium ions, and preferably has a solubility in water of 3% by mass or more at 20 ° C. Specific examples include calcium chloride, calcium acetate, calcium formate, calcium lactate, calcium nitrate, calcium gluconate, calcium isobutyrate, calcium propionate, calcium salicylate, calcium glycerophosphate, and hydrates and mixtures thereof. Further, seawater containing a water-soluble calcium salt, deep ocean water, or the like can be used as an aqueous solution form. Among these, from the viewpoint of solubility, water-soluble calcium salts such as calcium lactate, calcium gluconate and calcium glycerophosphate are preferable. The content of the calcium ion supply is 0.005 to 1% by mass in terms of calcium ion with respect to the whole oral composition from the viewpoint of caries / periodontal disease prevention effect, but preferably 0.01 to 1% by mass, particularly 0.01 to 0.8% by mass is preferred.

  The (B) cationic bactericidal agent of the present invention adsorbs on oral tissue surfaces such as tooth surfaces, oral mucosa (including gums), etc., and is bactericidal against bacteria that cause caries, periodontal disease, bad breath and the like. For example, quaternary ammonium compounds, biguanide compounds and the like are included. Specifically, the bactericides belonging to quaternary ammonium compounds include cetylpyridinium chloride, decalinium chloride, benzethonium chloride, benzalkonium chloride, alkyldimethylammonium chloride, alkyltrimethylammonium chloride, methylbenzethonium chloride, lauroyl colamino chloride. And formylmethylpyridinium. Examples of the bactericides belonging to the biguanide compounds include chlorhexidine and salts thereof, and preferably chlorhexidine gluconate and chlorhexidine hydrochloride. As the component (B), 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. It is preferable to contain, and it is especially preferable to contain 0.005-0.2 mass%.

  Moreover, the liquid oral composition of this invention is a nonionic surfactant of HLB16-20 other than (C1) polyglycerin fatty acid ester and (C2) polyglycerin fatty acid ester at least in order to stabilize calcium ion. Two types of nonionic surfactants are used in combination.

  Examples of the (C1) polyglycerol fatty acid ester of the present invention include decaglycerol esters having a glycerol polymerization degree of 2 to 30, preferably 8 to 20, and more preferably a glycerol polymerization degree of 10. Moreover, as a fatty acid part, C6-C24 saturated or unsaturated fatty acid is mentioned, Specifically, lauric acid, myristic acid, palmitic acid, oleic acid, stearic acid, etc. are mentioned. Moreover, the thing whose HLB value is 12-15 is preferable. Here, the HLB value is obtained by the following Griffin equation.

HLB value = 20 (1-S / A)
(S: Saponification value, A: Acid value of fatty acid used)

  Polyglycerin fatty acid ester is contained in a liquid oral composition in an amount of 0.001 to 2% by mass from the viewpoint of improving the stability of calcium ions and the retention of cationic bactericides on the oral tissue surface and increasing the amount of adsorption. It is preferable to contain 0.005-1 mass% especially 0.01-0.5 mass%.

  The second nonionic surfactant of the present invention is a nonionic surfactant having an HLB of 16 to 20 other than (C2) polyglycerin fatty acid ester, and an HLB value of 18 to 20 is particularly preferable. Specific examples include sucrose fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, and the like. These nonionic surfactants are preferably saturated or unsaturated fatty acids having 6 to 24 carbon atoms as the fatty acid moiety of the fatty acid ester. Among these, as a component (C2), a sucrose fatty acid ester is preferable and the sucrose fatty acid ester whose HLB value is 18-20 is the most preferable. The component (C2) is preferably contained in the liquid oral composition in an amount of 0.001 to 2% by mass, particularly 0.005 to 1% by mass, more preferably 0.01 to 0, from the viewpoint of calcium ion stability. It is preferable to contain 5 mass%.

  In a liquid composition containing calcium ions, it is effective to add a highly hydrophilic nonionic surfactant (for example, HLB of 16 or more) to stabilize the calcium ion supply compound. When the amount of the active agent is increased, the cationic fungicide is taken into the micelle, and the cationic fungicide is prevented from adsorbing on the surface of oral tissues such as teeth and oral mucosa, resulting in a decrease in adsorbability. There is a possibility. Polyglycerin fatty acid ester has a closely-oriented fatty acid part interacting with the bactericide, and the terminal ester bond becomes a hydrophilic part and is oriented in water, but the hydrophilic part is an ester bond and the polarity is not so large. As a result, the hydrophilicity of the micelles is considered to be increased, and as a result, the adsorptivity of the micelle containing the cationic bactericide on the oral tissue surface is increased.

In the present invention, considering the stability of calcium ions and the improvement of adsorbability and retention of the cationic bactericidal agent on the oral tissue surface, the above (C1) and (C2) are (C1) :( C2) in mass ratio. ) Is preferably 10: 1 to 1: 1, particularly preferably 5: 1 to 1: 1.
Moreover, the total amount of the nonionic surfactant containing these (C1) and (C2) is 0.01-5 mass% in the liquid oral cavity composition of this invention from the point of stability and an adsorption power improvement effect. In particular, 0.05 to 2% by mass, more preferably 0.05 to 0.8% by mass.

The liquid oral cavity composition of the present invention may further contain (D) an acyl taurine salt from the viewpoint of improving detergency in addition to retention. (D) Examples of the acyl taurine salt include N-acyl-N-alkyl taurine or a salt thereof, and examples of the acyl group include a long chain acyl group having 12 to 20 carbon atoms. Twenty alkanoyl groups, alkenoyl groups, and hydroxyalkanoyl groups are preferred. Specific examples of the acyl group include lauroyl group, palmitoyl group, stearoyl group, oleoyl group, acyl group derived from coconut oil fatty acid (cocoyl group), and the like. Moreover, as an alkyl group, C1-C5 alkyl groups, such as a methyl group, an ethyl group, a propyl group, are mentioned, More preferably, it is a C1-C3 alkyl group. Examples of the salt of N-acyl-N-alkyltaurine include alkali metal salts such as sodium, potassium and lithium, and amine salts such as triethanolamine, diethanolamine and monoethanolamine. More specifically, caproyl methyl taurine salt, lauroyl methyl taurine salt, myristoyl methyl taurine salt, palmitoyl methyl taurine salt, oleoyl methyl taurine salt and the like can be mentioned. Here, the salt is preferably an alkali metal salt such as a sodium salt. The content is preferably 0.01 to 5% by mass, particularly preferably 0.05 to 2% by mass in the liquid oral composition of the present invention from the viewpoint of detergency.
Further, the component (D) acyl taurine salt is preferably 1 part by mass or more from the viewpoint of the calcium ion stabilizing effect, and 10 parts by mass from the point of taste with respect to 1 part by mass of the component (C) nonionic surfactant. The following is preferable, and more preferably 1 to 5 parts by mass.

  It is preferable to mix | blend ethanol with the liquid oral cavity composition of this invention from the point which improves a bactericidal effect and a refreshing feeling further. The content of ethanol is preferably 0.5 to 30% by mass, more preferably 1 to 20% by mass, and particularly preferably 3 to 15% by mass in the liquid oral composition.

Furthermore, the liquid oral cavity composition of the present invention can contain sugar alcohols, binders, polyhydric alcohols, buffers, other medicinal agents, sweeteners, fragrances and the like. Furthermore, a nonionic surfactant other than the component (C) and an anionic surfactant other than the component (D) can be blended as long as the effects of the present invention are not impaired.
Examples of the anionic surfactant include alkyl sulfate salts such as sodium lauryl sulfate and sodium myristyl sulfate; N-acyl amino acid salts such as sodium lauroyl sarcosine; N-acyl glutamate such as sodium N-lauroyl-L-glutamate; coconut oil And fatty acid ester sulfonates such as fatty acid ethyl ester sulfonate sodium salt. The content of these anionic surfactants is 0.01% by mass or less, particularly 0 to 0.01% by mass in the liquid oral composition from the viewpoint of stimulation and adsorption of the cationic bactericide on the teeth. preferable.

  Sugar alcohols include erythritol, xylitol, ribitol, arabitol, galactitol, sorbitol, mannitol, maltitol, palatinit, lactitol, maltotriitol, isomaltotetriitol, maltotetriitol, isomaltotetriitol, reduced water candy Etc. These sugar alcohols are preferably incorporated in the liquid oral composition of the present invention in an amount of 1 to 30% by mass from the viewpoint of obtaining a calcium ion stabilizing effect. More preferably, it is a liquid oral composition containing 1 to 30% by mass of one or more sugar alcohols selected from xylitol, erythritol and paratinite. Of these sugar alcohols, xylitol is preferably blended in an amount of 1 to 30% by mass from the standpoint of further superior caries prevention effects.

  As a binder, cellulose derivatives such as sodium carboxymethylcellulose and hydroxyethylcellulose, 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 the polyhydric alcohol include propylene glycol, glycerin, and polyethylene glycol. Examples of the buffer include citric acid and its salt, malic acid and its salt, phosphoric acid and its salt, 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; plant extracts such as glycyrrhizin salts, allantoins, buckwheat, ogon, chamomile, latania and myrrh; Enzymes such as stranase, mutanase and lysozyme chloride; alkali metal monofluorophosphates such as sodium monofluorophosphate; fluorides such as sodium fluoride and stannous fluoride; sodium chloride, potassium nitrate, carbonate and bicarbonate , Salts such as sesquicarbonate; one or more of copper chlorophyllin sodium, copper gluconate, zinc chloride, zeolite, water-soluble inorganic phosphate compound, aluminum lactate and the like.

  Examples of the sweetener include saccharin sodium, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perilartine, somatin, asparatylphenylalanyl methyl ester, sucralose and the like. The content of the sweetener is preferably 0.001 to 1% by mass, particularly preferably 0.005 to 0.05% by mass, in the liquid oral composition of the present invention, from the viewpoint of sweetness.

  As a fragrance, in addition to synthetic fragrances such as menthol, carvone, anethole, eugenol, cineol, thymol, methyl salicylate, pregon, menthone, pinene, limonene, menthyl acetate, mint oil such as peppermint oil, spearmint oil, mint oil, Citrus oils such as lemon, orange, grapefruit, lime, eucalyptus, sage, rosemary, thyme, laurel, basil, perilla, bay, estragon, parsley, celery, coriander, herb oil, cinnamon, pepper, nutmeg, mace, clove Natural essential oils, such as spice oil, ginger, cardamom, anise, apple, banana, melon, grape, peach, strawberry, blueberry, raspberry, blackcurrant, lychee, starfruit, passion Roots, can be used plum, pineapple, and fruit flavors, such as Muscat. In particular, when using cationic fungicides, oil-soluble fragrances such as menthol, carvone, peppermint oil, spearmint oil, peppermint oil, cineole, limonene, and pinene are used in order to obtain the masking effect of the cationic fungicide. It is preferable. The content of the fragrance is preferably 0.01 to 2% by mass, particularly preferably 0.1 to 1.5% by mass, in the liquid oral composition of the present invention, from the viewpoint of refreshing feeling and aftertaste.

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

The liquid oral cavity composition of the present invention is prepared by dissolving a cationic bactericide in water, adding a polyglycerin fatty acid ester and mixing, and then adding an acyl taurine salt and a calcium ion supply compound as necessary, and other than (C1) It is preferable to produce by adding the nonionic surfactant.
Further, the liquid oral composition of the present invention is prepared by dissolving a cationic bactericidal agent in water, adding a polyglycerin fatty acid ester and mixing, then adding ethanol, an acyl taurine salt, a calcium ion supply compound, It is preferable to manufacture by mixing nonionic surfactants of HLB 16 to 20 other than (C1).

Example 1
The mouthwash shown in Table 1 was prepared. First, after adding benzethonium chloride dissolved in purified water to a mixture of purified water and concentrated glycerin, polyglycerin fatty acid ester dissolved in purified water is added, and ethanol, acyl taurine salt (D), saccharin sodium After mixing with calcium lactate and xylitol, a mixture of ethyl paraoxybenzoate and sucrose fatty acid ester dissolved at 20 ° C. or higher was added to the fragrance.

  Each mouthwash in Table 1 is subjected to a bactericidal evaluation test, a calcium ion stability test, a low temperature stability test (5 ° C.) and a detergency test according to the following methods, and the results are shown in Table 1. . Moreover, about this invention product 1 and the comparative product 2, the adsorption test to the oral mucosa of a bactericidal agent was done, and a result is shown in FIG.

[Bactericidal evaluation test]
400 μL of the mouthwash of Example 1 in Table 1 is added to 100 μL of mouthwash saliva (containing 10 mL of ion-exchanged water for 1 minute) and stirred for 30 seconds with a tube mixer. 50 μL of this solution is mixed with 450 μL of SCDLP (SOYBEAN-CASEIN DIGEST BROTH with POCISORBATE 80) medium to stop the effect of the disinfectant (SCDLP is a component polysorbate: polyoxyethylene sorbitan oleate and surface activity of lecithin) Inactivate preservatives and fungicides by action).
The solution was diluted with SCDLP medium to an appropriate concentration at which colonies could be counted, sprayed onto a modified GAM (Gifu Anaerobic Medium) medium using a spiral system, and cultured at 37 ° C. for 48 hours under anaerobic conditions. The number of colonies after the culture was counted, and the increase / decrease was calculated based on the comparative product 1. The results are shown in Table 1.

[Bactericide adsorption test]
15 g of each mouthwash of the product 1 of the present invention and comparative product 2 was sprinkled after squeezing for 30 seconds. / Min, measurement wavelength: 210 nm). The amount of adsorption was calculated from the difference in the concentration of the bactericide before and after gargling and the discharge amount. The results are shown in FIG.

[Calcium stability]
The prepared composition was put in a glass container that can be sealed, and stored at 5 ° C. for 1 week, and the state of formation of suspended matter / precipitate was visually judged based on the following criteria.

Judgment criteria No suspended matter / sediment: 1
Only a few floats are seen: 2
A small amount of suspended matter and sediment can be seen: 3
Many floating and sediments are seen: 4

[Low temperature stability test of composition]
After adjusting the mouthwash, the properties of the liquid when allowed to stand at 5 ° C. for 2 weeks were visually evaluated according to the following criteria.

Criteria ◎: Transparent ○: Slightly opaque (transparent at room temperature)
Δ: Opaque (opaque even at room temperature)
×: Precipitation

[Detergency]
Five glass tubes with a diameter of 7 mm are arranged and fixed with an adhesive. Apply red lipstick (model dirt) to the groove between Pasteur pipettes. Pour 10 mL of the prepared composition onto a Pasteur pipette, brush with a toothbrush for 60 seconds, and then wash with water. Place a Pasteur pipette on 100 g of methanol and ultrasonically wash for 10 minutes. Absorbance is measured at 540 nm to calculate the amount of residual dirt. Based on the case of washing with water alone, the following criteria were used for evaluation.

More than 15% effect: 1
10-15% effect: 2
5-10% effect: 3
Effect of 5% or less: 4

Example 2
The mouthwash shown in Table 2 was prepared according to the method of Example 1. About each obtained mouthwash, a bactericidal power evaluation test, a calcium ion stability test, the low temperature stability test (5 degreeC) of a composition, and a detergency test were done, and it shows in Table 2 together with a result. The standard for evaluation of sterilizing power was Comparative product 4.

  As is apparent from Tables 1 and 2 and FIG. 1, the liquid oral composition of the present invention has excellent bactericidal power due to the cationic bactericidal agent and is stable in calcium ions. On the other hand, when (C1) polyglycerin fatty acid ester is not contained (Comparative product 1 and Comparative product 4), (C2) when the nonionic surfactant of HLB 16-20 is not contained (Comparative product 2), and When a nonionic surfactant other than HLB16-20 was used (Comparative product 3), either of these effects was poor.

It is a figure which shows the adsorption amount to the hydroxyapatite of the benzethonium chloride (BTC) of this invention liquid oral composition.

Claims (5)

A liquid oral composition containing the following components (A) to (C).
(A) Calcium ion supply compound 0.005 to 1% by mass,
(B) a cationic fungicide,
(C) a nonionic surfactant containing the following (C1) and (C2),
(C1) Nonionic surfactant of HLB16-20 other than polyglycerin fatty acid ester (C2) (C1).   Furthermore, the liquid oral cavity composition of Claim 1 which contains 1-10 mass parts of (D) acyl taurine salts with respect to 1 weight part of (C).   The composition for liquid oral cavity according to claim 1 or 2, wherein (C1) :( C2) (mass ratio) = 10: 1 to 1: 1.   The composition for liquid oral cavity according to any one of claims 1 to 3, wherein the component (C2) is a sucrose fatty acid ester.   A liquid in which a cationic bactericide is dissolved in water, and then a polyglycerin fatty acid ester is added and mixed, followed by addition of a calcium ion supply compound and further addition of a nonionic surfactant of HLB 16-20 other than (C1) A method for producing an oral composition.

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