JP5683389B2 - Transparent liquid oral composition - Google Patents

Description

  The present invention relates to a transparent liquid oral composition.

  Conventionally, allantoin and its salts are known to be useful medicinal ingredients that activate cell functions and have anti-inflammatory, hemostatic, bactericidal, anti-ulcer, etc. It is also used in other fields. For example, Patent Document 1 discloses an oral composition that improves the periodontal disease and bad breath suppression effect by combining with a metal compound having antibacterial properties.

  On the other hand, since allantoin has a property of being easily hydrolyzed, it is important to keep it stable, and various studies have been conducted in various fields. For example, Patent Document 2 discloses an aqueous preparation in which an allantoin is combined with an organic acid, an inorganic acid, or the like, and a specific example in which citric acid or lactic acid is combined as an organic acid is shown. Patent Document 3 discloses a liquid oral composition in which hydrolysis of allantoin is suppressed by containing citric acid and citrate.

JP 2010-189358 A JP 2010-143889 A JP-A 63-159317

  However, it has been found that, depending on the type of organic acid used in combination, allantoin may generate a precipitate due to allantoin as the pH varies, and the pH varies depending on the storage temperature. Therefore, in order to maintain the pH within the pH range that maintains the stability of allantoin while ensuring the stability of allantoin, further studies are required in selecting an appropriate organic acid, and transparency is particularly strongly demanded. In blending allantoin into the liquid oral composition, the trade-off with such pH must be fully taken into consideration.

  Accordingly, an object of the present invention is to provide a transparent liquid oral composition that has excellent transparency and good usability by suppressing the fluctuation of pH and stabilizing allantoin within the stable pH range of allantoin. There is to do.

  Therefore, the present inventors have made various studies to develop a stable transparent liquid oral composition containing allantoin, and when an organic acid such as citric acid or malic acid is blended, the pH varies with the change. Since a precipitate due to allantoin is generated, further examination of the blending of other organic acids, and by containing lactic acid and its alkali metal salt and a specific amount of water, within the stable pH range of allantoin, It has been found that a transparent liquid oral composition having excellent transparency and good flavor can be obtained by suppressing pH fluctuation to suppress hydrolysis and precipitation of allantoin.

That is, the present invention includes the following components (A), (B) and (C):
(A) Allantoin or salt thereof 0.01 to 0.3% by mass in terms of allantoin,
(B) Lactic acid and alkali metal salts thereof 0.08 to 0.12% by mass in terms of lactic acid, and (C) 75 to 99% by mass of water
And a transparent liquid oral composition having a pH of 4.5-6.

  ADVANTAGE OF THE INVENTION According to this invention, the fluctuation | variation of pH can be suppressed in the stable limited pH range of allantoin, and the hydrolysis and precipitation of allantoin can be suppressed. Therefore, it is possible to obtain a transparent liquid oral composition having excellent transparency and good taste while sufficiently exhibiting the action as a medicinal component of allantoin, and having excellent storage stability.

Hereinafter, the present invention will be described in detail.
The composition for transparent liquid oral cavity of this invention contains allantoin or its salt (A). Component (A) is a medicinal component that activates cell functions and has anti-inflammatory, hemostatic, bactericidal, and anti-ulcer effects.

  Allantoin has a chemical name of 5-ureidohydantoin, and its salts include allantoin acetyl-DL-methionine, allantoin polygalacturonic acid, allantoin ascorbic acid, allantoinglycyl, allantoindihydroxyaluminum (aldioxa), allantoinchlorohydroxyaluminum. (Alcloxa) and the like. Of these, metal salts of allantoin are preferable, and allantoinchlorohydroxyaluminum is particularly preferable.

  The content of allantoin or a salt thereof (A) is 0.01 to 0.00 in terms of allantoin in the transparent liquid oral composition of the present invention, from the viewpoint of maintaining good stability in a specific pH range described later. 3 mass%, preferably 0.02 to 0.2 mass%, more preferably 0.03 to 0.15 mass%.

  The composition for transparent liquid oral cavity of this invention contains lactic acid and its alkali metal salt (B). Ingredient (B) suppresses fluctuations in pH and exhibits sufficient buffering ability as a pH adjuster, and does not cause allantoin to precipitate in a pH range applicable for oral use, and provides a good flavor. be able to.

  Examples of the alkali metal lactate include sodium lactate and potassium lactate, and sodium lactate is preferable from the viewpoint of taste. In addition, for example, by blending a compound containing an alkali metal ion and lactic acid and forming a salt between a part of lactic acid and the alkali metal, lactic acid of component (B) and an alkali metal salt of lactic acid are obtained. You may make it contain.

  The content of lactic acid and its alkali metal salt (B) allows the adjustment to a specific pH range described later, while maintaining a stable pH over a long period of time, and suppressing the formation of precipitates due to allantoin. It is 0.08-0.12 mass% in the amount of lactic acid in the transparent liquid oral cavity composition of this invention, Preferably it is 0.085-0.115 mass%, More preferably, it is 0.085-0. 11% by mass. In addition, the blending amount of lactic acid and its alkali metal salt (B) into the transparent liquid oral composition of the present invention is the transparent of the present invention from the viewpoint of stability of pH, suppression of precipitate formation by allantoin, and flavor. In a liquid oral cavity composition, Preferably it is 0.095-0.135 mass%, More preferably, it is 0.1-0.13 mass%.

  The mass ratio of the blending amount of lactic acid and the blending amount of the alkali metal lactate salt (alkali metal lactate / lactic acid) is preferably 2.2 to 5 from the viewpoint of achieving both stability of pH and good flavor. Yes, more preferably 2.4-4. In addition, the molar ratio of the blending amount of lactic acid and the blending amount of the lactic acid alkali metal salt (alkali lactic acid metal salt / lactic acid) is preferably 1.8 to 4.5 from the viewpoint of improving pH stability and flavor. More preferably, it is 1.9-4, More preferably, it is 2-3.5.

  The content of the organic acid other than lactic acid in the transparent liquid oral composition of the present invention is preferably 0.05% by mass from the viewpoint of suppressing the formation of precipitates by allantoin within a specific pH range and flavor. Or less, more preferably 0.01% by mass or less, further preferably 0.001% by mass or less, and further preferably not contained. Specific examples of organic acids other than lactic acid include monobasic acids such as formic acid, acetic acid and propionic acid; dibasic acids such as oxalic acid, succinic acid, fumaric acid, adipic acid and maleic acid; glycolic acid, Hydroxycarboxylic acids other than lactic acid such as tartaric acid, malic acid, citric acid, ascorbic acid, gluconic acid and glyceric acid; acidic amino acids such as glutamic acid and aspartic acid; keto acids such as pyruvic acid, acetoacetic acid and levulinic acid; benzoic acid, Examples include aromatic carboxylic acids such as salicylic acid; polycarboxylic acids such as ethylenediaminetetraacetic acid; and other isocitric acid, malonic acid, glutaric acid, glucuronic acid, kojic acid, phytic acid, aconitic acid, and glycerophosphoric acid.

  In addition, the content of the inorganic acid in the transparent liquid oral composition of the present invention is preferably 0.01% by mass or less, more preferably from the viewpoint of suppressing the formation of precipitates due to allantoin within a specific pH range. It is 0.001 mass% or less, and it is preferable not to contain further. Specific examples of the inorganic acid include hydrochloric acid, sulfuric acid, carbonic acid, and phosphoric acid.

  The transparent liquid oral composition of the present invention contains 75 to 99% by mass of water (C) in the transparent liquid oral composition of the present invention. The content of water (C) is preferably 80 to 97% by mass, more preferably 85 to 95% by mass, from the viewpoints of use feeling and taste. The content of water (C) is the same as the blending amount, and the component (C) includes water contained in each component in addition to purified water and ion exchange water.

  The transparent liquid oral cavity composition of the present invention has a pH of 4.5-6. If it is such a pH range, while being applicable for oral cavity, it can hold | maintain allantoin stably in a composition and can suppress effectively that a residual rate falls. Specifically, for example, when the content of allantoin when stored at 5 ° C. is used as a reference, the remaining rate of allantoin after storage at 50 ° C. for one month is desirably 95% or more. From the viewpoint of further increasing the residual rate of allantoin, the pH is preferably 4.7 to 5.8, and more preferably 4.7 to 5.5.

  The transparent liquid oral cavity composition of the present invention preferably further contains β-glycyrrhetinic acid or a salt thereof (D). Since β-glycyrrhetinic acid or a salt thereof (D) has an anti-inflammatory action, an alveolar bone resorption inhibitory action, a histamine release inhibitory action, etc., it is further added to the periodontitis by blending with the transparent liquid oral composition of the present invention. In addition, it can prevent and improve periodontal diseases.

  β-glycyrrhetinic acid is 3β-hydroxy-11-oxooleana-12-ene-30-carboxylic acid obtained by hydrolyzing glycyrrhizic acid obtained from licorice or the like. Examples of the salt of β-glycyrrhetinic acid include alkali metal salts such as sodium salt and potassium salt, and alkaline earth metal salts such as calcium salt. Of these, β-glycyrrhetinic acid is preferred.

  The content of β-glycyrrhetinic acid or a salt thereof (D) is preferably 0 in terms of glycyrrhetinic acid in the transparent liquid oral composition of the present invention from the viewpoint of pharmacological action, dispersibility, stability and transparency. 0.006 to 0.06% by mass. The more preferable content of the component (D) is that the transparent liquid of the present invention has a sufficient pharmacological action and prevents the formation of precipitates and precipitates due to the decrease in dispersibility of the component (D). In the composition for oral cavity, it is 0.008-0.055 mass% in conversion amount of glycyrrhetic acid, More preferably, it is 0.01-0.05 mass%. The compounding quantity of (beta) -glycyrrhetic acid or its salt (D) is the same as said content.

  In addition, when β-glycyrrhetinic acid or a salt thereof (D) is contained, the content of allantoin or a salt thereof (A) is improved in transparency and flavor by improving dispersibility of β-glycyrrhetinic acid or a salt thereof (D). From the point of improvement, in the transparent liquid oral cavity composition of the present invention in terms of allantoin, preferably 0.01 to 0.3% by mass, more preferably 0.02 to 0.25% by mass, More preferably, it is 0.03-0.2 mass%. Furthermore, the molar ratio (A / D) between the content of allantoin or its salt (A) and the content of β-glycyrrhetinic acid or its salt (D) in the transparent liquid oral cavity composition of the present invention is the component ( From the viewpoint of the dispersibility of D), the transparency of the composition, and the flavor, it is preferably 0.8 to 75, more preferably 1.5 to 50, and even more preferably 2 to 25.

  The transparent liquid oral composition of the present invention preferably further contains a nonionic fungicide (E) selected from triclosan and isopropylmethylphenol. These components (E) may be used individually by 1 type, and may be used in combination of 2 types. When a cationic bactericide such as cetylpyridinium chloride is added to the transparent liquid oral cavity composition of the present invention, there is a possibility that the pH tends to fluctuate. A nonionic bactericide selected from triclosan and isopropylmethylphenol (E ), The fluctuation of pH can be suppressed, and the bactericidal effect can be effectively exhibited while maintaining these components (E) stably. Of these, triclosan is preferable from the viewpoint of ensuring transparency and bactericidal effect.

  When the transparent liquid oral composition of the present invention contains a nonionic fungicide (E), the content of the component (E) is preferably 0.001 to 0 in the transparent liquid oral composition of the present invention. 0.1% by mass, and more preferably 0.01 to 0.08% by mass.

  The transparent liquid oral composition of the present invention may further contain a binder in the transparent liquid oral composition of the present invention at 0.1% by mass or less, preferably 0.05% by mass or less. It is a quantity, More preferably, it is a content of 0.01 mass% or less, or it does not need to contain a binder. When the binder is contained in a small amount such as the content within the above range, an appropriate thick feeling can be realized. Even if the transparent liquid composition for oral cavity of the present invention does not contain a binder or is contained at 0.1% by mass or less, it can improve transparency and stability.

  Examples of the binder include sodium carboxymethylcellulose, hydroxyethylcellulose, carboxyvinyl polymer, xanthan gum, carrageenan, sodium alginate, hydroxypropylcellulose, sodium chondroitin sulfate and the like.

  The transparent liquid oral cavity composition of the present invention further contains a nonionic surfactant from the viewpoint of dispersibility, flavor and feeling of use of an oil-soluble component such as β-glycyrrhetinic acid or a salt thereof (D). Is preferred.

  Examples of such nonionic surfactants include polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene copolymer, sucrose fatty acid ester, sorbitan fatty acid ester, glycerin fatty acid ester, and polyglycerin fatty acid ester. , Polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbit fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene glycol fatty acid ester, polyoxyethylene phytosterol and phytostanol, polyoxyethylene lanolin and lanolin alcohol, polyoxyethylene alkylamine Fatty acid amide, polyoxyethylene alkylphenyl formaldehyde condensate, polyoxyethylene poly Polyoxypropylene alkyl ethers, polyoxyethylene alkyl phenyl ethers, polyoxyethylene alkyl phenyl ether and fatty ethanol amides. Among these, what has a C14-C20 fatty acid residue, an alkyl group, or an alkenyl group from the point of the dispersibility of the oil-soluble component, such as a component (D), stability, and flavor is preferable. Moreover, the thing of HLB 10-20 is preferable from the point of the dispersibility of oil-soluble components, such as a component (D), and the thing of HLB 12-19 is especially preferable. These nonionic surfactants are used alone or in combination of two or more. Here, the HLB is obtained by the Griffin equation (J. Soc. Cosmet. Chem., 1, 311 (1949)).

  In addition to the above components, the transparent liquid oral composition of the present invention includes sugar alcohols, polyhydric alcohols, sweeteners, lower alcohols such as ethanol, wetting agents, preservatives, fluorides, other medicinal agents, enzymes, dyes , Fragrances and the like can be included.

  Examples of sugar alcohols include erythritol, xylitol, ribitol, arabitol, galactitol, sorbitol, mannitol, maltitol, reduced palatinose, lactitol, maltotriitol, isomaltotetriitol, maltotetriitol, isomaltotetriitol, Reduced water candy etc. are mentioned. Of these, erythritol, xylitol, and maltitol are preferable from the viewpoint of flavor, and erythritol and xylitol are more preferable. 0.5-10 mass% is preferable, as for content of the sugar alcohol in the composition for transparent liquid oral cavity of this invention, 1-8 mass% is more preferable, and 3-7 mass% is further more preferable.

  Examples of the polyhydric alcohol include propylene glycol, glycerin, polyethylene glycol and the like. Especially, glycerin is preferable from the point of flavor. The content of the polyhydric alcohol is preferably 8% by mass or less, more preferably 6% by mass or less, and further preferably 4% by mass or less in the transparent liquid oral cavity composition of the present invention from the viewpoint of flavor. It is.

  Specific examples of the sweetening agent include saccharin sodium, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perilartin, somatin, asparatylphenylalanyl methyl ester, sucralose, and the like. Among these, sucralose is preferable from the viewpoint of imparting a better flavor.

  The transparent liquid oral cavity composition of the present invention has excellent transparency. Having transparency means that the sediment is settled, two layers separated, or turbid state is not visually confirmed, preferably transparent or translucent, It may be colored. In the present invention, being transparent or translucent means that the transmittance of light having an absorption wavelength of 550 nm in a cell having an optical path length of 10 mm is 80% or more, and more preferably 90% or more. Such a composition for transparent liquid oral cavity according to the present invention can be applied as a liquid dentifrice, water dentifrice, mouthwash, mouth spray, mouthwash, etc., and particularly preferably a liquid dentifrice and mouthwash. .

  The method for producing a transparent liquid oral composition of the present invention comprises a first water-soluble component mixed liquid production step of mixing purified alcohol with a polyhydric alcohol such as sugar alcohol and glycerin as necessary, and purified water with lactic acid and its Allantoin-containing liquid production process for mixing alkali metal salt and allantoin or its salt, and nonionic disinfectant, nonionic surfactant, fragrance, β- A process for producing an oil-soluble component-containing liquid in which oil-soluble components such as glycyrrhetinic acid and α-tocopherol are mixed and mixed, and a first water-soluble component mixed liquid and an allantoin-containing liquid are produced. And a step of mixing the water-soluble component mixture and the oil-soluble component-containing liquid. The first water-soluble component mixture production process is preferably mixed at 10 to 40 ° C., and the allantoin-containing liquid production process is 10 to 65 ° C., preferably 20 to 55 ° C. More preferably, the mixing is preferably performed at 40 to 55 ° C., and the mixing time is preferably 8 to 12 minutes. The production process of the oil-soluble component-containing liquid is preferably mixed at 10 to 40 ° C.

  Hereinafter, the present invention will be specifically described based on examples. In addition, unless otherwise indicated in a table | surface, content of each component shows the mass%.

[Example 1, Comparative Examples 1 to 5]
According to the formulation shown in Table 1, each liquid oral composition (mouthwash) was prepared. Each evaluation was performed according to the following method using the obtained composition for liquid oral cavity. The results are shown in Table 1.

<< pH immediately after preparation >>
The pH of each liquid oral composition immediately after preparation was measured.

《Presence or absence of precipitates》
Each liquid oral composition immediately after preparation was visually observed, and the case where no precipitate due to allantoin was generated was evaluated as “no”, and the case where a precipitate was generated was evaluated as “present”.

<Flavor>
Using each liquid oral composition, three panelists rinsed for 1 minute and evaluated astringency and salty taste. `` Good '' when no astringency or salty taste is felt, `` Generally good '' when almost no astringency or salty taste is felt, `` Slightly good '' when astringency or salty taste is somewhat satisfactory When astringency, salty taste or acid odor was felt, the felt flavor was shown and evaluated. The table shows the evaluation by the three persons.

"transparency"
Each liquid oral composition immediately after the preparation is visually observed, and the case where the cell having an optical path of 10 mm or more and the transmittance of light having an absorption wavelength of 550 nm is 90% or more is “transparent”, and the case where turbidity is generated is “ It was evaluated as “turbidity”.

  From the results in Table 1, in Comparative Example 1 containing citric acid and its sodium salt instead of lactic acid and its sodium salt, and Comparative Example 2 containing malic acid and its sodium salt, precipitates were produced and clear. It turns out that it is inferior. Moreover, although the comparative examples 3-5 containing an acetic acid and its sodium salt did not produce | generate a precipitate, even if it reduces the content, flavor evaluation is inferior by acetic acid odor, and it is unsuitable for oral use. I understand.

[Examples 2 to 4, Comparative Examples 6 to 8]
In Examples 2 to 4 and Comparative Examples 6 to 8, the content of lactic acid was varied according to the content shown in Table 2, and sodium lactate was contained in Table 2 so that the pH was 5.0 to 5.3. Except for the amount, each liquid oral composition was prepared by adjusting the content of purified water according to the formulation of Example 1. It preserve | saved for one month at -5 degreeC and 50 degreeC, pH after the preservation | save at each temperature was measured, the difference was calculated | required, and flavor was evaluated similarly to the above. The results are shown in Table 2, including the evaluation of Example 1.

  According to Table 2, the difference in pH value between −5 ° C. and 50 ° C. after storage for 1 month between Examples 1 to 4 and Comparative Examples 6 and 7 is 0.5 or less, and the big difference is There was no significant effect in terms of buffer capacity. However, Comparative Examples 6 to 7 were inferior in evaluation in terms of flavor as compared with Examples 1 to 4, and particularly salty taste was strongly felt under a high temperature environment of 50 ° C. On the other hand, although Comparative Example 8 is generally good in terms of flavor, the difference in pH value between −5 ° C. and 50 ° C. is greater than 0.5, so it is considered that there is a problem in the stability of allantoin after long-term storage. It is done.

[Examples 5 to 7]
In Examples 5 to 7, each liquid oral composition was prepared in the same manner as Example 1. The transparency and flavor were evaluated in the same manner as described above. The results are shown in Table 3. Although content of the component (A) and the component (D) was changed, precipitation was not recognized and evaluation that a flavor is favorable was obtained.

Claims (7)

The following components (A), (B) and (C):
(A) Allantoin or salt thereof 0.01 to 0.3% by mass in terms of allantoin,
(B) Lactic acid and alkali metal salts thereof 0.08 to 0.12% by mass in terms of lactic acid, and (C) 75 to 99% by mass of water
And a transparent liquid composition for oral cavity having a pH of 4.5-6.   The transparent liquid oral cavity composition according to claim 1, further comprising (D) β-glycyrrhetinic acid or a salt thereof.   (D) Transparent liquid oral cavity composition of Claim 2 whose content of (beta) -glycyrrhetic acid or its salt is 0.006-0.06 mass% in conversion amount of glycyrrhetic acid.   The transparent liquid oral cavity according to any one of claims 1 to 3, wherein a mass ratio of the blending amount of lactic acid and the blending amount of the alkali metal lactate (alkali metal lactate / lactic acid) is 2.2 to 5. Composition.   Furthermore, the transparent liquid oral cavity composition of any one of Claims 1-4 containing the nonionic disinfectant chosen from (E) triclosan and isopropylmethylphenol.   The transparent liquid oral cavity composition according to any one of claims 1 to 5, wherein the content of the binder is 0.1% by mass or less or does not contain the binder.   Furthermore, the transparent liquid oral cavity composition of any one of Claims 1-6 containing a nonionic surfactant.