JP6435172B2 - Liquid oral composition - Google Patents

Description

  The present invention relates to a liquid oral composition.

  In recent years, erosion teeth that dissolve teeth have become a problem. Carbonated beverages, wines, citrus juices and the like have a pH of about 2 to 4, and excessive intake thereof induces erosion. The higher the concentration of acid in the beverage, the higher the degree of damage it causes on the teeth (Non-Patent Document 1). In addition, other factors of erosion teeth are chemical action, tooth brushing with a cleaning agent containing abrasives, or gastric acid reflux due to vomiting and reflexes. In the oral cavity, the pH at rest is maintained at around 6.8 due to the buffering ability of bicarbonate contained in saliva. The surface of the tooth is covered with saliva and a saliva-derived coating (pellicle), and the saliva and the pellicle derived from saliva protect the tooth from erosion teeth. For this reason, it is said that if the buffering capacity of saliva is low, it will be easily applied to erosion teeth (Non-Patent Document 2).

  However, in recent years, the background of the problem of erosion has been due not only to an increase in the intake of acidic food and drink, but also due to a decrease in the amount of saliva secreted by modern people. Only the action of saliva cannot keep the oral cavity at a constant pH, and the progression of erosion teeth cannot be inhibited. For this reason, it is considered to suppress the progression of erosion by using a liquid oral composition.

  For liquid oral compositions, in addition to pH buffering agents (generally consisting of a combination of a weak acid and its salt) that are simply added to adjust the pH of the formulation to an appropriate range and stabilize the formulation quality, A component having an action may be blended.

  As an example of a liquid oral composition using a means for suppressing a decrease in pH, a method using a basic amino acid, peptide, or protein pH buffering action as a method not using a general pH buffering agent (Patent Document 1) To 4), those using chitin / chitosan (Patent Document 5) and those using coral powder (Patent Document 6) are known.

  In addition, the liquid oral composition contains a bactericidal agent for sterilizing microorganisms that cause caries (typically Streptococcus mutans, hereinafter referred to as mutans) for the prevention of caries. Yes. On the other hand, a solubilizer is blended in the liquid oral composition for the purpose of stabilizing the preparation and solubilizing the components. Since the solubilizer has an inactivating effect on the bactericidal agent, in order for the oral composition to exhibit a sufficient bactericidal effect, it is important to balance the blending amount of the bactericidal agent with the solubilizer and other additives. .

Japanese Patent Publication No.62-59093 JP-A-8-301742 JP 2002-255773 A JP 2011-88830 A Japanese Examined Patent Publication No. 6-84309 JP 10-45548 A

Lussi, Caries Res. 1995, Vol. 29, p. 349-354 Michael Edgar, Colin Dawes, Denis O'Mullane Saliva Teeth and oral health Original 3rd edition p102, p108

  However, when a large amount of a pH buffer consisting of a combination of a weak acid and its salt is added to the liquid oral composition to suppress pH fluctuations in the oral cavity, it may affect the taste by increasing the saltiness. There was a problem that the feeling was remarkably impaired. Due to such problems, the liquid oral composition cannot provide a large pH buffering capacity, and even if the liquid oral composition is used after ingestion of acidic food and drink, There is a problem that the pH cannot be brought close to the pH in the oral cavity at rest.

  In addition, when amino acids, peptides, proteins, chitin / chitosan and coral powder are used in the liquid oral composition as in other examples, the pH buffering ability of the liquid oral composition is not sufficient, so There is a problem that the pH inside cannot be brought close to the pH in the oral cavity at rest. Further, hydroxyapatite, chitin / chitosan, and coral powder have a problem of blending into liquid oral compositions because of their low solubility in aqueous solutions at neutral pH.

  Furthermore, when a bactericide is used in the liquid oral composition, the feeling of use is inferior due to the blending due to the irritation of the bactericide. In addition, it is necessary to add a solubilizing agent in order to dissolve insoluble components such as isopropylmethylphenol, but when the solubilizing agent is used, an unpleasant taste caused by the solubilizing agent (eg bitter taste) Therefore, the feeling of use is inferior due to the blending. Furthermore, sodium benzoate has a problem that its activity against microorganisms decreases in the neutral range. Therefore, it has been required to reduce the blending amount of the bactericide and the use amount of the solubilizing agent while exhibiting a sufficient bactericidal effect on the microorganisms causing caries.

  The present invention has been made in view of the above circumstances, and is a preparation that has a sufficient buffering capacity against acid at around pH 6.8, can stably maintain hydroxyapatite in a dissolved state, and a blending amount of a solubilizing agent It is an object of the present invention to provide a liquid oral composition having excellent usability in terms of sourness, salty taste, bitterness and irritation and having sufficient bactericidal activity against mutans bacteria.

The liquid oral composition of the present invention comprises a buffer containing citric acid and sodium citrate, disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium phosphate, sodium hydrogen carbonate, potassium hydroxide, sodium hydroxide. A pH adjuster comprising at least one of the following in the absence of sericin , the pH is in the range of 6.5 to 7.4 ,
The pH buffering capacity against the presence of acid is a buffering capacity capable of maintaining the pH in the range of 5.5 to 6.8 even when 0.1M hydrochloric acid is added dropwise to 20 mL of liquid oral composition liquid. It is what is.

The liquid oral composition of the present invention comprises a buffer containing citric acid and sodium citrate, and a pH adjuster containing at least one of disodium hydrogen phosphate, sodium dihydrogen phosphate, and dipotassium phosphate. In the absence of sericin, the pH is in the range of 6.5-7.4,
  The pH buffering capacity against the presence of acid is a buffering capacity capable of maintaining the pH in the range of 5.5 to 6.8 even when 0.1M hydrochloric acid is added dropwise to 20 mL of liquid oral composition liquid. It is what is.

The liquid oral compositions of the present invention, as a buffer, 0.05 to 0.5% citric acid, it is preferred that sodium citrate Ru with 0.4~8.8wt%.

  In the liquid oral composition of the present invention, the pH adjuster is preferably disodium hydrogen phosphate or dipotassium phosphate.

In the composition for liquid oral cavity of the present invention, when disodium hydrogen phosphate is selected as a pH adjuster, it is 0.19 to 4.0 wt%, and when dipotassium phosphate is selected, 0.2 Rukoto with ~5.0wt% is preferred.

  In the liquid oral composition of the present invention, it is preferable to dissolve calcium phosphate.

  In the liquid oral composition of the present invention, the calcium phosphate is preferably hydroxyapatite.

  The liquid oral composition of the present invention preferably comprises 0.001 to 0.2 wt% of hydroxyapatite.

  The liquid oral composition of the present invention preferably contains a bactericidal agent and a solubilizer.

  The composition for liquid oral cavity of the present invention comprises 0.009 wt% or more and 0.22 wt% of a bactericidal agent, 0.001 wt% to 0.02 wt% of cetylpyridinium chloride as a bactericidal agent, and 0.006 wt% of sodium benzoate -0.1 wt%, isopropylmethylphenol is preferably contained at 0.002 wt% -0.1 wt%, cetylpyridinium chloride is added at 0.001 wt% to 0.01 wt%, and sodium benzoate is added at 0.006 wt% to 0 wt%. It is preferable that 0.06 wt% or less and isopropylmethylphenol be 0.002 wt% or more and 0.03 wt% or less. It is preferable that 0.05% to 0.4% by weight of polyoxyethylene hydrogenated castor oil 60 is included as the solubilizer.

  In the liquid oral composition of the present invention, for example, citrus flavors such as lemon, orange, lime, grapefruit, bergamot, mandarin, limonene, citral, γ-terpinene, nootkaton, linalyl acetate, such as peppermint, spearmint, marine mint Mint flavors such as peppermint oil, carvone, menthone and L-menthol, floral fragrances such as roses such as rose and mussels such as jasmine, herbal flavors such as lavender, rosemary and thyme, green tea It preferably contains a fragrance selected from green fragrances such as green apple, green floral, fresh green, fruity green and floral green.

  In the composition for liquid oral cavity of the present invention, it is preferable to contain 0.01 to 0.05 wt% of L-menthol as a fragrance.

  The liquid composition for oral cavity of the present invention has sufficient buffering ability against acid at around pH 6.8, is excellent in use in terms of acidity, salty taste, bitterness and irritation, and can stably maintain calcium phosphate as a solution. It is a preparation and can have sufficient bactericidal activity against mutans by reducing the amount of solubilizing agent.

It is a graph which shows the buffer capacity with respect to the acid of the buffer systems 1-7 of this invention. It is a graph which shows the buffer capacity with respect to the acid of the buffer systems 8-11 of this invention. It is a graph which shows the buffer capacity with respect to the acid of the buffer systems 12-13 of this invention. It is a graph which shows the buffer capacity with respect to the acid of the buffer systems 14-20 of this invention. It is a graph which shows the buffering ability with respect to the acid of mouthwashes AG of this invention (liquid oral composition). It is a graph which shows the example of the comparison of the pH buffer ability of the mouthwash (liquid oral composition) of this invention, and a competitor's product. It is a graph which shows the comparison of the buffer capacity of the mouthwash (liquid oral composition) of this invention, and the mouthwash containing protein. It is a graph which shows the influence which the compounding quantity of a solubilizer has on the bactericidal activity of a mouthwash in the mouthwashes IL of this invention (liquid oral composition). It is a graph which shows the comparison of the buffer capacity of a mouthwash when dipotassium phosphate is used for a pH adjuster in the buffer system of the mouthwash (liquid oral cavity composition) of the present invention. It is a graph which shows the comparison of the buffer capacity of a mouthwash at the time of using sodium hydroxide for a pH adjuster in the buffer system of the mouthwash of this invention (liquid oral composition). It is a graph which shows the buffer system of a citrate buffer and a phosphate buffer in the buffer system of the mouthwash (liquid oral cavity composition) of this invention.

  The oral composition of the present invention is a liquid composition (liquid oral composition) for excellent usability, and if desired, a viscosity modifier or the like is further added to the aqueous composition to increase the viscosity. There may be. The liquid oral composition of the present invention is, for example, a mouthwash, a spray such as a mouse spray, a liquid such as a liquid dentifrice, a gel such as a toothpaste, a mouthwash, an oral cleansing agent, an impregnating agent for an oral cleaning sheet, etc. Can be provided. In addition to the components described above, the liquid oral composition can further contain appropriate components according to the form of the composition within a range not impairing the effects of the present invention.

  Here, the feeling of use refers to the flavor and mouthfeel caused by the use of a liquid composition such as a mouthwash. Flavor is defined as the total sense of taste and smell when food is put in the mouth, and the mouth feel is defined as the total sense of touch perceived in the mouth including the tongue, gums and teeth. be able to.

  Subsequently, the liquid oral composition of the embodiment is described with reference to an embodiment of the present invention. The liquid oral composition includes a buffer containing citric acid and sodium citrate, a pH adjusting agent for adjusting pH, and sterilization. It has an agent, a solubilizer, and a fragrance, and has a pH in the range of 5.6 to 8.0, and more preferably in the range of 6.5 to 7.4. In addition, calcium phosphate is dissolved in the liquid oral composition.

  As for the buffering agent, the amount of citric acid is 0.05 wt% to 0.5 wt% in the liquid oral composition, and the amount of sodium citrate is 0.4 wt% to 8.8 wt% in the liquid oral composition. It is as follows.

  Here, as the buffering agent, a combination of a weak acid and a salt of the weak acid can generally be used as a buffer system of the liquid oral composition, for example, acetic acid and acetate, phosphoric acid and phosphate, apple Examples include acid and malate, succinic acid and succinate, lactic acid and lactate, propionic acid and propionate, carbonate and bicarbonate. Moreover, the hydrate of the said buffering agent can be used for a buffering agent. When the hydrate is used, the blending amount can be appropriately calculated from the molecular weight of the buffer and the molecular weight of the buffer hydrate. On the other hand, acetic acid, succinic acid, lactic acid, and propionic acid are not suitable for a liquid oral composition from the viewpoint of a characteristic odor and a taste caused. In addition, a buffer system using carbonate has a buffering pH of 9.2 to 10.6, which is significantly different from the pH in the oral cavity, and is not suitable as a buffer for liquid oral compositions. Furthermore, when the blending amount of citric acid and sodium citrate is set to other ratios, it is difficult to maintain the buffer capacity in the pH range of 6.2 to 8.0, and the feeling of use is remarkably reduced. There is a problem of doing.

  The pH adjusting agent has a buffer action range of pH 3.0 to 6.2 by the combination of citric acid and sodium citrate as a buffering agent, while increasing the pH of the liquid oral composition at rest. Is selected from at least one of disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium phosphate, sodium bicarbonate, potassium hydroxide, and sodium hydroxide so as to adjust the pH to 6.8. . Moreover, the hydrate of the said pH adjuster can be used for a pH adjuster. The amount of the hydrate used can be appropriately calculated from the molecular weight of the pH adjuster and the molecular weight of the hydrate of the pH adjuster. Furthermore, disodium hydrogen phosphate is selected in the embodiment, and the blending amount is 0.19 to 4.0 wt% in the liquid oral composition. In another example of the embodiment, dipotassium phosphate is selected and the blending amount is 0.2 to 5.0 wt% in the liquid oral composition.

  Among the pH adjusters, disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium phosphate, sodium hydrogen carbonate, potassium hydroxide, sodium hydroxide, sodium hydroxide and potassium hydroxide are citrate buffer buffers Since the performance is reduced, the suitability is inferior compared to disodium hydrogen phosphate, sodium dihydrogen phosphate, and dipotassium phosphate. Furthermore, when the blending amount of the pH adjuster is out of the above range, there is a problem that it becomes difficult to maintain the pH in the range of 6.2 to 8.0.

  The disinfectant is selected from at least one of cetylpyridinium chloride, sodium benzoate, p-hydroxybenzoate ester, and isopropylmethylphenol, and the blending amount is 0.009 wt% or more and 0.22 wt% or less in the liquid oral composition. ing. In the embodiment, the blending amount of cetylpyridinium chloride is 0.001 wt% or more and 0.02 wt% or less in the liquid oral composition, and the blending amount of sodium benzoate is 0.006 wt% or more and 0 or more in the liquid oral composition. It is preferable that the blending amount of isopropylmethylphenol is not less than 0.002 wt% and not more than 0.1 wt% in the liquid oral composition, and the blending amount of cetylpyridinium chloride in the liquid oral composition is preferably 0.00. 001 wt% or more and 0.01 wt% or less, the amount of sodium benzoate in the liquid oral composition is 0.006 wt% or more and 0.06 wt% or less, and the amount of isopropylmethylphenol in the liquid oral composition is 0.002 wt% It is preferable to make it 0.03 wt% or less. Here, the bactericides include sodium dodecyl sulfate, alkyldiaminoethylglycine hydrochloride and the like in addition to cetylpyridinium chloride, sodium benzoate, paraoxybenzoate ester, and isopropylmethylphenol. Examples of the paraoxybenzoic acid ester include methyl paraoxybenzoate, ethyl paraoxybenzoate, butyl paraoxybenzoate, propyl paraoxybenzoate, and isopropyl paraoxybenzoate. However, sodium dodecyl sulfate and alkyldiaminoethyl glycine hydrochloride are inferior in the feeling of use because they give unpleasant irritation in the mouth and are not suitable for use in liquid oral compositions. Alkyldiaminoethylglycine hydrochloride, like sodium dodecyl sulfate, is inferior in use in terms of the taste it causes, and is not suitable for use in liquid oral compositions. In addition, when the blending amount is less than 0.009 wt%, the activity decreases due to the influence of the solubilizing agent in the preparation, so that microorganisms such as mutans bacteria grow and the liquid oral composition There is a problem that the quality of the product is deteriorated, and when the blending amount is more than 0.22 wt%, there is a problem that the feeling of use is impaired.

  The solubilizers are polyoxyethylene hydrogenated castor oil and polysorbate, and the blending amount is 0.05 wt% or more and 0.40 wt% or less in the liquid oral composition. Moreover, in the embodiment, it is preferable that the blending amount of the polyoxyethylene hydrogenated castor oil 60 is 0.10 wt% in the liquid oral composition. As the solubilizer, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 80, polyoxyethylene hydrogenated castor oil 100 are suitable as polyoxyethylene hydrogenated castor oil. Yes. As polysorbate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, and polysorbate 80 are suitable. In addition to polyoxyethylene hydrogenated castor oil 60, there are sodium dodecyl sulfate, alkyldiaminoethylglycine hydrochloride, polysorbate 20, and the like. However, sodium dodecyl sulfate and alkyldiaminoethyl glycine hydrochloride are inferior in use and are not suitable for use in liquid oral compositions. In addition, when the blending amount is less than 0.05 wt%, the solubilizer has a problem that a blending component having low solubility in water is precipitated and the quality stability of the liquid oral composition is impaired.

  The fragrance is selected from citrus fragrances, mint fragrances, floral fragrances, herbal fragrances, and green fragrances, and these may be blended in a single or a plurality of combinations in the liquid oral composition. 0.01 to 0.08 wt%. Examples of citrus flavors include lemon, orange, lime, grapefruit, bergamot, mandarin, limonene, citral, γ-turpinene, nootkaton, linalyl acetate, etc., and examples of mint flavors include peppermint, spearmint, Marine mint, mint oil, carvone, menthone, L-menthol and the like, and the floral fragrances are, for example, roses such as rose, and mossaceae such as jasmine, and herbal fragrances are, for example, lavender, rose Examples of the green flavor include green tea, green apple, green floral, fresh green, fruity green, and floral green. Further, L-menthol is included in the liquid oral composition in an amount of 0.01 to 0.05 wt%. The fragrance is not limited to citrus fragrances, mint fragrances, floral fragrances, herbal fragrances, and green fragrances, and is particularly limited as long as it maintains the effects of the present invention and enhances the feeling of use. Is not to be done.

  Calcium phosphate is hydroxyapatite and is provided in the liquid oral composition at 0.001 wt% or more and 0.2 wt% or less. When the blending amount of hydroxyapatite is greater than 0.2 wt% and pH 6.8, the liquid oral composition has the problem that the hydroxyapatite becomes cloudy and precipitates, and the usability and appearance are significantly impaired.

  Next, the pH of the liquid oral composition will be described.

  As for the pH of the liquid oral cavity composition, the lower limit of pH 5.6 is derived from the mechanism of erosion. That is, since erosion occurs when the enamel is decalcified at a pH of 5.5 or lower, the pH of the liquid oral composition needs to be maintained at a value greater than 5.5, so the lower limit is set at pH 5.6. did. In addition, when preparing the buffer solution with citric acid and sodium citrate, the citrate buffer solution has a buffer capacity in the range of pH 3.0 to 6.2. Get smaller. In the embodiment, although the liquid oral composition has a pH of 6.8, by adding disodium hydrogen phosphate, it is possible to maintain the feeling of use as a mouthwash and further maintain the buffer capacity. It is possible.

  Further, the pH of the liquid oral composition is derived from the characteristics of disodium hydrogen phosphate used as a pH adjuster, the upper limit value of pH 8.0. The buffer capacity when prepared with phosphoric acid and disodium hydrogen phosphate is pH 5.8 to 8.0, and the upper limit value of the pH control function by disodium hydrogen phosphate is changed to the upper limit value of the buffer capacity of the phosphate buffer. Set in anticipation of close. Further, when the pH is adjusted to be greater than 8.0 with disodium hydrogen phosphate, the feeling in use is inferior.

  Next, the buffer capacity of the liquid oral composition will be described.

  In the liquid composition for oral cavity according to the embodiment, the mouthwash whose pH is adjusted to 5.78 with citric acid and sodium citrate has a strong buffering capacity, and even when 5 mL of 0.1 M hydrochloric acid is added dropwise, the pH is 5. 5 is maintained. Since the pH buffering action of the citrate buffer system usually increases the buffering action in the weakly acidic region of pH 3.0 to 6.2, a pH adjuster is used when buffering in the neutral region.

  Further, when the mouthwash is raised to pH 7.00 with 0.1M potassium hydroxide and titrated with hydrochloric acid, the pH becomes 6.06 by dropwise addition of 5 mL of 0.1M hydrochloric acid. It has been shown that the buffer capacity of the citrate buffer system decreases with increasing pH of potassium hydroxide.

  Further, when the mouthwash is raised to pH 6.97 with disodium hydrogen phosphate and titrated with hydrochloric acid, the pH becomes 6.68 by dropwise addition of 5 mL of 0.1 M hydrochloric acid. This is higher than the buffer capacity of the mouthwash to which potassium hydroxide has been added, and has been shown to maintain the buffer capacity of the original citrate buffer system.

  Thus, according to the composition for liquid oral cavity of the embodiment, the preparation has a large buffering capacity against acid at around pH 6.8, can stably maintain hydroxyapatite in a dissolved state, and a solubilizing agent. It is possible to reduce the blending amount, and to have excellent usability and sufficient bactericidal activity against mutans bacteria.

  In addition, the liquid oral composition of the embodiment has a sufficient buffering capacity against acid, and does not adversely affect the taste and mouthfeel, and can enhance the feeling of use. Furthermore, the liquid oral composition of the embodiment can appropriately correspond the pH region where the pH buffering agent exhibits the optimum buffering action and the pH in the oral cavity at rest. Furthermore, the liquid oral composition of the embodiment has sufficient pH buffering capacity in the oral cavity compared to the case of using amino acids, peptides, proteins, chitin / chitosan, and coral powder, and the amino acid, peptide, protein Thus, it is possible to eliminate the low water solubility. Furthermore, formation of an insoluble precipitate of hydroxyapatite can be suppressed, and it can be appropriately blended in a state where hydroxyapatite is dissolved in the liquid oral composition. Furthermore, the liquid oral composition according to the embodiment reduces the blending amount of the bactericide and suppresses the progress of caries. Furthermore, by returning the mouth to neutrality, progression of erosion teeth can be suppressed, and remineralization of enamel can be promoted.

  In the composition for liquid oral cavity according to the embodiment, the pH buffering ability with respect to the presence of an acid is 5. Even if 0-50 mL of 0.1M hydrochloric acid is dropped with respect to 20 mL of liquid oral composition liquid. The buffering capacity that can be maintained in the range of 5 to 6.8 is a preparation that is excellent in feeling of use, can stably maintain hydroxyapatite in a dissolved state, and reduces the amount of the bactericide while reducing the amount of It can have a sufficient bactericidal activity against Tans bacteria.

  Moreover, in the composition for liquid oral cavity according to the embodiment, 0.05 to 0.5 wt% of citric acid and 0.4 to 8.8 wt% of sodium citrate are provided, and the pH is adjusted to 5.6 to 8 with a pH adjuster. When adjusted to 0.0, the buffering capacity against acid is high at around pH 6.8, excellent in the feeling of use, is a preparation that can stably maintain hydroxyapatite in a dissolved state, and reduces the amount of solubilizer, It can have sufficient bactericidal activity against mutans bacteria.

  In the liquid oral composition according to the embodiment, the pH adjuster is at least one of disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium phosphate, sodium bicarbonate, potassium hydroxide, and sodium hydroxide. In particular, the pH adjusting agent is disodium hydrogen phosphate, 0.19 to 4.0 wt% of disodium hydrogen phosphate is included in the liquid oral composition, and the pH is adjusted to 5.6 to 8.0. When adjusted, the formulation has a high acid buffering ability near pH 6.8, excellent usability, can stably maintain hydroxyapatite in a dissolved state, and reduces the amount of solubilizing agent. Can have sufficient bactericidal activity against.

  Further, in the liquid oral composition of the embodiment, when calcium phosphate is dissolved, calcium phosphate is hydroxyapatite, and 0.001 to 0.2 wt% of hydroxyapatite is mixed, the dissolved state of hydroxyapatite is appropriately maintained. be able to.

  Further, in the liquid oral composition according to the embodiment, the composition contains a bactericidal agent and a solubilizing agent, and as a bactericidal agent, cetylpyridinium chloride is 0.001 wt% or more and 0.02 wt% or less, and sodium benzoate is 0.006 wt% or more. When 0.1 wt% or less, 0.002 wt% or more and 0.1 wt% or less of isopropylmethylphenol are provided, and 0.05 wt% or more and 0.4 wt% or less of polyoxyethylene hydrogenated castor oil 60 is provided as the solubilizer, pH 6. It has a high acid buffering capacity near 8 and can maintain hydroxyapatite stably in a dissolved state. It reduces the amount of solubilizer, has a good feeling of use, and has a sufficient bactericidal activity against mutans bacteria. Can have.

  Moreover, the liquid oral composition of the embodiment can maintain L-menthol for a long period of time. Preferably, L-menthol is provided in the liquid oral composition in an amount of 0.01 to 0.05 wt%. ing. L-menthol can be suitably used for a long period of time in the amount of L-menthol in the liquid oral composition.

[Example 1] Among the combinations of a buffer and a pH adjuster that can be used in the mouthwash, the buffering capacity against acid was examined for disodium hydrogen phosphate, potassium hydroxide, and sodium hydrogen carbonate.
〔procedure〕
20 mL of a solution in which a pH adjusting agent was added to a citric acid (monohydrate) and sodium citrate (dihydrate) buffer at a ratio described in Tables 1 to 3 was prepared, and the pH was measured with a pH meter. . Further, 0.1M hydrochloric acid was added dropwise to the solution, and the change in pH was measured.
〔result〕
The buffer system (No. 1) has a pH of 5.78, and a buffer system (No. 2) to which 1 g of disodium hydrogen phosphate (anhydrous) is added as a pH adjuster is pH 6.59. 3) pH 6.97, 3 g added buffer system (No. 4) pH 7.22, 4 g added buffer system (No. 5) pH 7.39, 5 g added buffer system (No. 6) pH 7. 47 and 10 g added buffer system (No. 7) had a pH of 7.82. FIG. 1 shows a titration curve with 0.1 M hydrochloric acid.
No. The titer of 0.1M hydrochloric acid required for the pH of 1 to reach 5.5 was about 5 mL.
The titration amount of 0.1M hydrochloric acid when disodium hydrogen phosphate (anhydrous) was added as a pH adjuster was No. 2 is about 18 mL, No. 2 3 is about 30 mL. 4 is about 42 mL, No. 4 5 is about 57 mL, No. 5 6 is about 68 mL. In the case of 7, 100 mL was required up to pH 6.0.
On the other hand, a buffer system (No. 8) in which 2 mL of a solution obtained by adding 0.1 M potassium hydroxide as a pH adjuster to the buffer solution is added is pH 6.11, and a buffer system (No. 9) in which 3.2 mL is added has a pH of 6. 48, 4 mL added buffer system (No. 10) had pH 7.00, 4.4 mL added buffer system (No. 11) had pH 7.96. FIG. 2 shows a titration curve with 0.1 M hydrochloric acid. The titration amount of 0.1M hydrochloric acid when 0.1M potassium hydroxide was added as a pH adjuster was No. 8 is about 9 mL, no. 9 is about 12 mL. 10 is about 13 mL, No. 10 11 was about 14 mL.
In order to compare the buffer capacity, no. 2 and No. 9 and no. 3 and no. 10 were 18 mL and 12 mL, and 30 mL and 13 mL, respectively, and the buffer system to which disodium hydrogen phosphate (anhydrous) was added as a pH adjuster had a higher titration amount of 0.1N hydrochloric acid, and the buffer capacity was higher. It was shown to be big.
Furthermore, the buffer system in which sodium bicarbonate was added as a pH adjusting agent to the buffer solution was the buffer system (No. 13) in which 1 g of sodium bicarbonate was added, the buffer system (No. 13) in which pH 6.80 was added and 2 g of sodium bicarbonate was added. 12) was pH 7.17. FIG. 3 shows a titration curve with 0.1 M hydrochloric acid. The titration of 0.1M hydrochloric acid until the pH reached 5.5 when sodium bicarbonate was added was No. 13 is about 27 mL, No. 13 12 was about 42 mL. In order to compare the buffer capacity, no. 3 and no. 13 and no. 4 and no. 12 were 30 mL and 27 mL, and 42 mL and 42 mL, respectively, and it was shown that almost the same buffer capacity as that obtained when disodium hydrogen phosphate (anhydrous) was added was obtained.
The buffer system (No. 17) was pH 6.16, and the buffer system (No. 18) in which 0.5 g of disodium hydrogen phosphate (anhydrous) was added as a pH adjusting agent was added pH 6.80, 1 g. The buffer system (No. 19) was pH 7.31, and the buffer system (No. 20) added with 1 g was pH 7.59. FIG. 4 shows a titration curve with 0.1 M hydrochloric acid.
No. The titer of 0.1M hydrochloric acid required for the pH of 17 to reach 5.5 was about 5 mL. The titration amount of 0.1M hydrochloric acid when disodium hydrogen phosphate (anhydrous) was added as a pH adjuster was No. 18 is about 6 mL, No. 18 19 is about 15 mL. 20 was about 30 mL.

[Example 2] Examination of mouthwash (liquid oral composition) in which hydroxyapatite is dissolved to use hydroxyapatite as an adsorbent Hydroxyapatite (HAP) solution was examined for HAP precipitation over time. .
〔procedure〕
40 mg, 60 mg, 80 mg, 100 mg, 120 mg and 140 mg of HAP were blended in an aqueous citric acid solution in which 0.22 g of citric acid (monohydrate) was dissolved in 70 mL of purified water, respectively, and sodium citrate (dihydrate) was added after stirring. ) 2.86 g was dissolved and stored at pH 6.1, 5 ° C. for 18 days.
〔result〕
In 10 minutes of stirring, none of the samples dissolved and became cloudy, but in 20 minutes of stirring, the samples containing 40 mg and 60 mg were dissolved and became transparent. Furthermore, the sample which mix | blended 80 mg by 30 minutes stirring also melt | dissolved and became transparent. Even after 90 minutes of stirring, the 100 mg sample did not dissolve transparently, and the 120 mg and 140 mg samples did not dissolve and remained cloudy.
The stored samples maintained the solubility of HAP at 40 mg and 60 mg, but the samples of 80 mg, 100 mg, 120 mg, and 140 mg had white turbidity. Therefore, it was shown that HAP can be blended at a ratio of 60 mg / 70 mL, that is, 85.7 mg / 100 mL or less.
Since pH affects the solubility of HAP, there is concern about precipitation of HAP due to an increase in pH. Accordingly, when the HAP was dissolved at 1 mg / 100 mL, no HAP crystal precipitation was observed.

[Example 3] Preparation of mouthwash (liquid oral composition) Based on Example 1, mouthwashes A to G (Table 4) in which hydroxyapatite was dissolved were prepared.
〔procedure〕
After dissolving citric acid (monohydrate) in 70 mL of purified water, hydroxyapatite is dissolved, and then sodium citrate (dihydrate), sodium hydrogenphosphate (12 hydrate), and other ingredients are added. Dissolved and finally adjusted to 100 mL with purified water. Other components include solubilizers, bactericides, flavoring agents, fragrances, and wetting agents.

[Example 4] pH buffering ability test of mouthwash (liquid oral composition) The buffering ability of mouthwash to acid was examined.
〔procedure〕
20 mL of the mouthwash prepared in Example 3 was prepared, and the pH was measured with a pH meter. Further, 0.1M hydrochloric acid was added dropwise to the mouthwash, and the change in pH was measured.
〔result〕
Mouthwash A is pH 6.82, Mouthwash B is pH 6.79, Mouthwash C is pH 6.74, Mouthwash D is pH 6.79, Mouthwash E is pH 6.89, Mouthwash F is pH 7.02 and mouthwash G were pH 6.77 (see Table 4, FIG. 5). The amount of 0.1 M hydrochloric acid required to lower the pH of each mouthwash to 5.5 is about 25 mL for mouthwash A, about 25 mL for mouthwash B, about 20 mL for mouthwash C, Mouth solution D was 15 mL, Mouth solution E was about 20 mL, Mouth solution F was about 20 mL, and Mouth solution G was about 20 mL.

[Example 5] Comparison of pH buffering capacity of the present invention (liquid oral composition) and other company's products Shown by comparing the buffering strength of mouthwash (liquid oral composition) with other companies' products .
〔procedure〕
20 mL of mouthwash was prepared in the same manner as in Example 4, and the pH was measured with a pH meter. Furthermore, 0.01M hydrochloric acid was added dropwise to the mouthwash, and the change in pH was measured. The samples used were mouthwash B prepared with a composition of citric acid: 0.22 wt%, Na citrate: 2.86 wt%, and hydrogen phosphate Na: 2.2 wt%, as well as products of other companies.
〔result〕
As shown in FIG. 6, mouthwash B (pH 6.79) dropped to pH 5.75 when 200 mL of 0.01 M hydrochloric acid diluted 10-fold with 0.1 M hydrochloric acid was dropped, and the decrease in pH remained at 1.04.
On the other hand, as shown in FIG. 6, the competitor's product I (pH 5.95) was dropped to 4.84 (1.11 lower) by adding 4 mL of 0.01M hydrochloric acid 10-fold diluted with 0.1M hydrochloric acid, as shown in FIG. Product II (pH 6.07) has a pH of 5.56 (down 0.51), Competitor product III (pH 6.01) has a pH of 5.74 (down 0.27), Competitor product IV (pH 6.05) has a pH of 5.81 ( Competitor product V (pH 6.08) pH 5.84 (0.24 decrease), Competitor product VI (pH 5.92) pH 5.7 (0.22 decrease), Competitor product VII (pH 8. 88) is pH 8.60 (down 0.28), competitor VIII (pH 6.21) is pH 5.99 (down 0.22), and competitor IX (pH 6.30) is pH 6.01 (down 0.29) The other company's product X (pH6.13) is p It became 5.91 (0.22 decrease).
Competitor's product II is pH 5.12 with 9 mL of hydrochloric acid dropwise, Competitor's product III is pH 5.11 with 14 mL of hydrochloric acid dropwise, Competitor's product IV is pH 5.14 with 14 mL of hydrochloric acid, and Competitor's product V is pH 5 with 14 mL of hydrochloric acid. .32, Competitor's product VI is pH 5.11 with 14 mL of hydrochloric acid, Competitor's product VII is pH 5.54 with 120 mL of hydrochloric acid, Competitor's product VIII is pH 5.40 with 24 mL of hydrochloric acid, and Competitor's product IX is 19 mL of hydrochloric acid. The pH of the other company's product X was pH 5.40 when 14 mL of hydrochloric acid was added dropwise. Therefore, it was shown that the mouthwash B has an excellent buffering capacity compared with the products of other companies.

[Example 6] Comparison result of liquid mouth composition containing protein having buffer action and mouthwash [Procedure]
In the same manner as in Example 1, 10 mL of the sample solution was prepared, the pH was measured with a pH meter, and 0.1 M hydrochloric acid was titrated to measure the change in pH.
〔result〕
As shown in FIG. 7, mouthwash B in which disodium hydrogen phosphate was added to the citrate buffer (2.2% by mass) had a pH of 6.78, and sericin was added to the citrate buffer (5.0% by mass). ) Mouthwash H had a pH of 6.06 and the citrate buffer only control had a pH of 6.00. Mouthwash B was pH 6.20 when 5 mL of 0.1 M hydrochloric acid was added dropwise, while Mouthwash H was pH 5.42 when 5 mL of 0.1 M hydrochloric acid was added, and the control was pH 5.34. Comparing the slopes of the approximate curves for each mouthwash and subject drop curve, mouthwash B was -0.0933, mouthwash H was -0.1236, and control was -0.1254. Mouthwash H is almost the same as the slope of the control, whereas Mouthwash B showed a small value, so the pH drop due to the dropwise addition of 1M hydrochloric acid is slow. Furthermore, the mouthwash B showed a smaller approximate curve than the control despite the pH higher than the buffer range of the general citrate buffer system, and therefore, at a pH outside the buffer range of the citrate buffer system. Excellent buffer capacity. From this, it was shown that the mouthwash B had better buffering capacity than the mouthwash H, and further had a pH suitable for the oral composition.

[Example 7] Usability evaluation test [Procedure]
The buffer solution described in Tables 1 to 3 and Table 5 was included in about 3 mL mouth and rinsed, and the feeling of use (salt taste) was evaluated.
〔result〕
As shown in Tables 1 to 3 and Table 5, when 10 g of sodium citrate (dihydrate) was blended, any combination exhibited a very strong salty taste, and 10 g of disodium hydrogen phosphate (anhydrous) was blended. In some cases, the salty taste was very strong. In addition, when 5 g of sodium citrate (dihydrate) was blended, and when 3 g or more of disodium hydrogen phosphate (anhydrous) was blended with 3 g of sodium citrate (dihydrate), a strong salty taste was exhibited. . On the other hand, when 3 g or less of sodium citrate (dihydrate) and 2 g or less of disodium hydrogen phosphate (anhydrous) were blended, an appropriate salty taste was exhibited in any combination.

[Example 8] Comparison of the effects of the amount of solubilizer in the mouthwash (liquid oral composition) on bactericidal activity [Procedure]
After dissolving citric acid (monohydrate) in 70 mL of purified water, hydroxyapatite is dissolved, and then sodium citrate (dihydrate), sodium hydrogenphosphate (12 hydrate), and other ingredients are added. Dissolved and finally adjusted to 100 mL with purified water. Other ingredients include solubilizers such as bactericides, flavoring agents, fragrances, and wetting agents. As a disinfectant, 0.01 g of cetylpyridinium chloride, 0.06 g of sodium benzoate, and 0.02 g of isopropylmethylphenol are included, and as a solubilizer, polyoxyethylene hydrogenated castor oil 60 (HCO-60) is represented. A mouthwash contained at a ratio of 6 was used as a sample. Here, the composition of the mouthwash is citric acid: 0.135 wt%, citric acid Na: 1.85 wt%, and hydrogen phosphate Na: 1.2 wt%.
An overnight culture of Streptococcus mutans was diluted 10-fold with phosphate buffered saline to obtain a test bacterial solution. The test bacterial solution was added to the sample to a final concentration of 5% to start the action. Thereafter, part of the working fluid was collected over time, and the number of viable bacteria was measured by a culture method.
〔result〕
In all mouthwashes, the test bacteria were killed by 360 minutes after the start of action (see FIG. 8). And when the bactericidal activity of each sample is compared, when the polyoxyethylene hydrogenated castor oil 60 content is reduced from 0.2% to 0.075%, the bactericidal activity is improved, and the HCO-60 content is 0.075% and 0.0. In 1% of the samples, the test bacteria died by 20 minutes after the start of action.

[Example 9] Comparison of effects of mouthwash (liquid oral composition) on stability over time of L-menthol [Procedure]
Using mouthwash D prepared with a composition of citric acid: 0.135 wt%, sodium citrate: 1.85 wt%, hydrogen phosphate Na: 1.2 wt%, mouthwash D and water or phosphate buffer L-menthol remains in a solution containing 0.03% L-menthol in physiological saline at 40 ° C and 75% humidity for 1 month, 3 months and 6 months, and at 25 ° C for 6 months The rate was measured.
〔result〕
Mouthwash D is 109.3% (0 months), 110.0% (1 month), 107.5% (3 months), 106.5% (6 months) when stored at 40 ° C. and 75% humidity. )Met. When stored at 25 ° C., they were 109.3% (0 month) and 111.9% (6 months).

[Example 10] Buffering ability and feeling of use of mouthwash when dipotassium phosphate and sodium hydroxide are used as pH adjusters [Procedure and results]
The buffer system (No. 1) has a pH of 5.78, and a buffer system (No. 23) to which 1 g of dipotassium phosphate (anhydrous) is added as a pH adjuster has a pH of 6.52 and a buffer system (2 g) has been added. The pH of No. 24) is 6.93, 3 g added buffer system (No. 25) is 6.93, 4 g added buffer system (No. 26) is 7.32, 5 g added buffer system The pH of (No. 27) was 7.42. FIG. 9 shows a titration curve with 0.1 M hydrochloric acid.
No. The titer of 0.1M hydrochloric acid required for the pH of 1 to reach 5.5 was about 5 mL. The titration amount of 0.1M hydrochloric acid when dipotassium phosphate (anhydrous) was added as a pH adjuster was 23 is about 15 mL. 24 is about 25 mL, No. 24 25 is about 40 mL. 26 is about 45 mL, No. 26 27 was about 55 mL.
On the other hand, the pH of the buffer system (No. 28) in which 1.0 mL of 0.1 M sodium hydroxide was added as a pH adjuster to the buffer was 6.13, and the pH of the buffer system (No. 29) in which 3.2 mL was added was The pH of the buffer system (No. 30) added with 6.46, 4.0 mL was 6.88, and the pH of the buffer system (No. 31) added with 4.5 mL was 8.70. FIG. 10 shows a titration curve with 0.1 M hydrochloric acid.
The titration of 0.1M hydrochloric acid when sodium hydroxide is added as a pH adjuster is 28 is about 9 mL, No. 28 29 is about 11 mL, No. 29 30 is about 13 mL. 31 was about 14 mL. Table 7 shows the composition table and usability of each buffer system.

[Example 11] About buffer system of citrate buffer and phosphate buffer [Procedure and result]
Example 11 shows a buffer system of citrate buffer and phosphate buffer such as McKilben buffer, and corresponds to a reference example of the liquid oral composition of the present invention.
The buffer system (No. 1) has a pH of 5.78, a buffer system (No. 3-1) in which 2 g of sodium dihydrogen phosphate (P1) and 0.5 g of disodium hydrogen phosphate (P2) are added. The pH of the buffer system (No. 3-2) in which pH was 6.24, 2 g of P1 and 0.3 g of P2 were added (No. 3-2), and the buffer system (No. 3 in which 2 g of P1 and 0.7 g of P2 were added) was added. -3) has a pH of 6.17, a buffer system added with 3 g of P1 and 0.5 g of P2 (No. 4-1) has a pH of 6.44, a buffer system with 4 g of P1 and 0.5 g of P2. The pH of (No. 5-1) is 6.59, the pH of the buffer system (No. 5-2) to which 4 g of P1 and 0.3 g of P2 are added is 6.69, 4 g of P1 and 0.7 g of P2. The pH of the added buffer system (No. 5-3) was 6.50. The buffer system (No. 17) has a pH of 6.16, and the buffer system (No. 19-1) in which 1 g of P1 and 0.5 g of P2 are added has a pH of 6.37, 2 g of P1 and P2. The pH of the buffer system (No. 20-1) added with 0.5 g was 6.68. FIG. 11 shows a titration curve with 0.1 M hydrochloric acid.
No. The titer of 0.1M hydrochloric acid required for the pH of 1 to reach 5.5 was about 5 mL. The titration of 0.1M hydrochloric acid when P1 and P2 were added thereto was No. 3-1, about 15 mL, No.3. 3-2 is about 14 mL, No. 3-2. 3-3 is about 15 mL. 4-1 is about 35 mL, No. 4-1. 5-1, about 25 mL, No. 5-2 is about 25 mL, No. 5-3 was about 25 mL. No. 17 is about 5 mL. 19-1 is about 8 mL, No. 20-1 was about 13 mL. In addition, the feeling of use was slightly salty and bitter.

Claims (11)

A buffer containing citric acid and sodium citrate, and a pH adjusting agent containing at least one of disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium phosphate, sodium hydrogen carbonate, potassium hydroxide, sodium hydroxide ; In the absence of sericin , the pH is in the range of 6.5 to 7.4,
The pH buffering capacity against the presence of acid is a buffering capacity capable of maintaining the pH in the range of 5.5 to 6.8 even when 0.1M hydrochloric acid is added dropwise to 20 mL of liquid oral composition liquid. liquid oral compositions, characterized in that it. A buffer containing citric acid and sodium citrate, and a pH adjuster containing at least one of disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium phosphate in the absence of sericin; Is in the range of 6.5 to 7.4,
  The pH buffering capacity against the presence of acid is a buffering capacity capable of maintaining the pH in the range of 5.5 to 6.8 even when 0.1M hydrochloric acid is added dropwise to 20 mL of liquid oral composition liquid. A liquid oral composition characterized by the above. As a buffering agent, 0.05 to 0.5%, the liquid oral composition according to claim 1 or 2, characterized in that sodium citrate Ru with 0.4～8.8Wt% citric acid. The liquid oral composition according to any one of claims 1 to 3 , wherein the pH adjuster is disodium hydrogen phosphate or dipotassium phosphate. As pH adjusting agents, comprises 0.19～4.0Wt% if you choose the disodium hydrogen phosphate, if you select dipotassium phosphate is characterized Rukoto with 0.2～5.0Wt% The composition for liquid oral cavity according to any one of claims 1 to 4 . The liquid oral composition according to any one of claims 1 to 5 , wherein calcium phosphate is dissolved. The liquid oral composition according to claim 6 , wherein the calcium phosphate is hydroxyapatite. The composition for liquid oral cavity according to claim 7 , comprising 0.001 to 0.2 wt% of hydroxyapatite. The composition for liquid oral cavity according to any one of claims 1 to 8 , comprising a bactericidal agent and a solubilizing agent. 0.009 wt% or more and 0.22 wt% of a disinfectant, 0.001 wt% to 0.02 wt% of cetylpyridinium chloride, 0.006 wt% to 0.1 wt% of sodium benzoate, and isopropylmethylphenol as disinfectants includes 0.002wt% ~0.1wt%, to any one of claims 1 to 9, characterized in that it comprises a polyoxyethylene hydrogenated castor oil 60 0.05% ~0.4wt% as the solubilizer The composition for liquid oral cavity as described. The liquid oral cavity according to any one of claims 1 to 10 , comprising a fragrance selected from citrus fragrance, mint fragrance, floral fragrance, herbal fragrance, marine fragrance, and green fragrance. Composition.

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