Mouthwash

Abstract

To provide a mouthwash that suppresses foaming, crystal precipitation, and dripping when using, and has an excellent flavor when gargling, in mouthwashes containing azulene sulfonic acid and / or a salt thereof, cetylpyridinium and / or a salt thereof, and l-menthol, and the like.SOLUTION: Provided is a mouthwash characterized by containing each of the following ingredients (A), (B), (C), and (D), in liquid compositions containing azulene sulfonic acid and / or a salt thereof, cetylpyridinium and / or a salt thereof, and l-menthol, and the like. (A) One or more flavoring agents selected from saccharin sodium and acesulfame potassium. (B) Polyhydric alcohol fatty acid ester. (C) Celluloses. (D) Polyoxyethylene hydrogenated castor oils.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a mouthwash (gargle) containing azulene sulfonic acid and / or a salt thereof. [Background technology]

[0002] Azulene sulfonic acid and its salts have been widely used as anti-inflammatory agents, and it is known that gargling with a diluted aqueous solution of this agent has the effect of soothing tonsillitis, pharyngitis, stomatitis, and gingivitis. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] JP 2020-105082 A Summary of the Invention [Problem to be solved by the invention]

[0004] Mouthwashes often contain anti-inflammatory agents such as azulene sulfonic acid and / or its salts to reduce throat swelling, antiseptics such as cetylpyridinium and / or its salts to suppress bacterial growth in the mucous membranes of the mouth and throat, and terpenes such as l-menthol, which give a cooling sensation in the mouth and remove bad breath. Of these, when azulene sulfonic acid and / or its salts are combined with cetylpyridinium and / or its salts, a large amount of foam is produced during use, and when azulene sulfonic acid and / or its salts are combined with terpenes such as l-menthol, crystals of one or both of these compounds are precipitated. Furthermore, when azulene sulfonic acid and / or its salts, cetylpyridinium and / or its salts are combined with terpenes such as l-menthol, dripping occurs during use and the feel when used (flavor when gargling) is poor.

[0005] Regarding the foaming, it has been proposed to incorporate glycyrrhizinic acid or its salts, which are known to have anti-inflammatory effects, into mouthwash as a foaming inhibitor (Patent Document 1). Although the proposal states that glycyrrhizinic acid or its salts are added to pharmaceuticals as flavoring agents or sweeteners, it is difficult to say that glycyrrhizinic acid or its salts have sufficient flavoring properties to improve the feel (flavor) of mouthwash when used.

[0006] The present invention provides a mouthwash containing azulene sulfonic acid and / or a salt thereof, cetylpyridinium and / or a salt thereof, 1-menthol, and the like, which suppresses foaming, crystal precipitation, and dripping during use and has an excellent flavor when rinsing. [Means for solving the problem]

[0007] That is, the present invention relates to the following [1] to [4]. [1] A mouthwash characterized in that the liquid composition contains azulene sulfonic acid and / or its salt, cetylpyridinium and / or its salt, and l-menthol, and further contains the following components (A), (B), (C), and (D): (A) one or more flavoring agents selected from sodium saccharin and potassium acesulfame; (B) polyhydric alcohol fatty acid ester, (C) Celluloses, (D) Polyoxyethylene hydrogenated castor oils. [2] The mouthwash according to [1], wherein the (B) polyhydric alcohol fatty acid ester is a glycerin fatty acid ester. [3] The mouthwash according to [1], wherein the (C) cellulose is one or more selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl cellulose, and hypromellose. [4] The mouthwash according to any one of [1] to [3], wherein the polyoxyethylene hydrogenated castor oil (D) is one or more selected from the group consisting of polyoxyethylene hydrogenated castor oil 5, polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60 and polyoxyethylene hydrogenated castor oil 100. Effect of the Invention

[0008] According to the present invention, it is possible to provide a mouthwash (liquid composition) containing azulene sulfonic acid and / or a salt thereof, cetylpyridinium and / or a salt thereof, and l-menthol, which suppresses foaming and dripping when the mouthwash is used, suppresses crystal precipitation of azulene sulfonic acid and / or a salt thereof, and l-menthol, and also suppresses unpleasant flavors such as bitterness when held in the mouth. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] [Mouthwash] The mouthwash of the present invention is characterized in that it is a liquid composition containing azulene sulfonic acid and / or a salt thereof, cetylpyridinium and / or a salt thereof, and l-menthol, and further contains the following ingredients: (A) a specific flavoring agent, (B) a polyhydric alcohol fatty acid ester, (C) a cellulose, and (D) a polyoxyethylene hydrogenated castor oil.

[0010] Azulene sulfonic acid and / or its salt The salt of azulene sulfonic acid refers to a pharmacologically acceptable salt of 1,4-dimethyl-7-isopropylazulene-3-sulfonic acid and a hydrate thereof. The azulene sulfonic acid and / or its salt are known to have anti-inflammatory and anti-allergic effects, and to promote granulation and epithelial formation. Examples of pharmacologically acceptable salts include sodium salts, potassium salts, ammonium salts, etc., and among these, sodium salts (usually referred to as sodium azulene sulfonate) are particularly preferred.

[0011] <Cetylpyridinium and / or its salt> The cetylpyridinium and / or its salts include, for example, cetylpyridinium hydrochloride, i.e., 1-hexadecylpyridinium chloride and its hydrate. This component has a bactericidal effect, and is known to have the effects of suppressing bacterial growth in mucous membranes, relieving throat inflammation, and preventing periodontal disease and bad breath.

[0012] <l-Menthol> As mentioned above, l-menthol has the effect of providing a cooling sensation in the mouth and eliminating bad breath, and also generally serves as a flavoring agent that corrects the flavor of oral medications to make them easier to take.

[0013] (A) Certain flavoring agents The mouthwash of the present invention contains (A) sodium saccharin and acesulfame as flavoring agents. The metal oxide contains at least one selected from potassium. The above-mentioned saccharin sodium and acesulfame potassium are known as non-carbohydrate synthetic sweeteners, and in the mouthwash of the present invention, they serve as sweeteners and flavoring agents, and when used in combination with (B) polyhydric alcohol fatty acid esters and (C) celluloses described below, they can also serve to suppress foaming when the mouthwash is used.

[0014] (B) polyhydric alcohol fatty acid ester, The mouthwash of the present invention contains (B) a polyhydric alcohol fatty acid ester. Polyhydric alcohol fatty acid esters are generally used as solubilizing agents, but in the mouthwash of the present invention, they can also play a role in suppressing foaming during use of the mouthwash. Among the (B) polyhydric alcohol fatty acid esters, glycerin fatty acid esters can be preferably used.

[0015] (C) Cellulose The mouthwash of the present invention contains (C) celluloses. Celluloses are generally added as thickeners to adjust (increase) the viscosity of the mouthwash, and can prevent dripping of the mouthwash when it is used, as well as suppress foaming when the mouthwash is used. Among the (C) celluloses, one or more selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl cellulose, and hypromellose (hydroxypropyl methylcellulose) can be preferably used. These celluloses are commercially available in various grades depending on the degree of substitution of hydroxyl groups in the cellulose, viscosity, etc., and can be selected in consideration of the solubility in the mouthwash and the viscosity as a mouthwash product. For example, in the case of hypromellose, one can select one with a degree of substitution of methoxyl groups of 22 to 30%, a molar number of substitution of hydroxyl groups of 7 to 12%, and a viscosity (20°C, 2% by weight aqueous solution): 3000 to 5600 mPa·s, but is not limited thereto.

[0016] (D) Polyoxyethylene hydrogenated castor oils The mouthwash of the present invention contains (D) polyoxyethylene hydrogenated castor oils, which act as solubilizers to inhibit crystallization of l-menthol, azulene sulfonic acid and / or its salts. Among the polyoxyethylene hydrogenated castor oils, one or more selected from the group consisting of polyoxyethylene hydrogenated castor oil 5, polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, and polyoxyethylene hydrogenated castor oil 100 can be preferably used.

[0017] <Other additives> The mouthwash according to the present invention may contain other additives as optional components other than those described above, provided that the effects of the present invention and the effects (pharmaceutical efficacy) of the mouthwash are not impaired. Representative examples of other additives are given below, but the present invention is not limited to these examples, and various additives commonly used in mouthwashes can be blended. The addition of these additives is also not limited to the following.

[0018] As an anti-inflammatory agent, for example, dipotassium glycyrrhizinate and the like can be used. As the disinfectant, for example, benzalkonium chloride, benzethonium chloride, etc. can be used. As flavoring agents other than the above-mentioned (A), for example, camphor, lemon oil, fennel oil, eucalyptus oil, cinnamon oil, clove oil, vanillin, flavors, etc. can be used. Stabilizers include, for example, ascorbic acid, polyvinyl alcohol, macrogol, etc. It can be used. Examples of the alcohols include monoalcohols such as ethanol and propyl alcohol, and polyhydric alcohols such as propylene glycol, polyethylene glycol, and sugar alcohols (mannitol, etc.). Examples of sugar alcohols that can be used include xylitol, sorbitol, and glycerin. As the chelating agent, for example, sodium edetate, calcium disodium edetate, and hydrates thereof can be used. As the surfactant, for example, sodium lauryl sulfate, sucrose fatty acid ester, etc. can be used. As the isotonicity agent, for example, inorganic salts such as sodium chloride and magnesium chloride, polyhydric alcohols such as propylene glycol and D-mannitol, and the like can be used. Preservatives that can be used include, for example, parabens, thymol, sorbic acid, and the like. As the solubilizing agent, for example, triacetin, sucrose, benzyl alcohol, polyvinylpyrrolidone, etc. can be used. As a thickening agent, for example, carboxyvinyl polymer, carmellose sodium, gelatin, etc. can be used. Examples of pH adjusters include citric acid, lactic acid, phosphoric acid, carbonic acid, salts thereof, and hydrates of the salts thereof. Examples of the salts and hydrates of the salts thereof include sodium citrate hydrate, citric acid hydrate, sodium lactate, sodium hydrogen phosphate, sodium hydrogen phosphate hydrate, and sodium hydrogen carbonate.

[0019] In the mouthwash of the present invention, the blending amount of each component is not particularly limited as long as it is within the blending amount range that can obtain the desired effect, and can be, for example, as follows. Note that the above concentrations are the concentrations of the mouthwash stock solution, and the mouthwash stock solution is usually diluted 1 to 300 times before use, and depending on the adjusted concentration, it can also be used as is (without dilution). Azulene sulfonic acid and / or its salts: 0.001-0.6 w / v% Cetylpyridinium and / or its salts: 0.001-10 w / v% l-Menthol: 0.001~10w / v% (A) One or more flavoring agents selected from sodium saccharin and potassium acesulfame: 0.05 to 20 w / v% (B) Polyhydric alcohol fatty acid ester: 0.001 to 5 w / v% (C) Cellulose: 0.001 to 5 w / v% (D) Polyoxyethylene hydrogenated castor oils: 0.001 to 5 w / v%

[0020] The mouthwash of the present invention can be stored in a container made of a conventional resin such as polyethylene (PE), polypropylene (PP), or polyethylene terephthalate (PET), or in a glass container. The shape of the container is not particularly limited.

[0021] [Manufacturing method of mouthwash] An example of a method for producing the mouthwash of the present invention will be described below, but the method is not particularly limited to this method. For example, cetylpyridinium and / or its salt, 1-menthol, (B) polyhydric alcohol fatty acid ester, and (D) polyoxyethylene hydrogenated castor oil are mixed to prepare the cetylpyridinium phase. When preparing the cetylpyridinium phase, heating may be performed as necessary, or alcohols may be added to increase the solubility. If water is present in the system during preparation, the cetylpyridinium phase tends to foam, and it may take time for the foaming to subside. Separately from the cetylpyridinium phase, (A) a specific flavoring agent and (C) a cellulose compound, and if necessary, water are added to form a flavoring agent phase. After the cetylpyridinium phase and the flavoring agent phase are mixed to form a homogeneous phase, azulene sulfonic acid and / or its salt, or an aqueous solution thereof, if necessary, is added and dissolved therein. The above-mentioned <other additives> may be added during the preparation of the cetylpyridinium phase or the flavoring agent phase, or may be added before or after the addition of the azulene sulfonic acids when they are mixed to form a homogeneous phase. By adding the azulene sulfonic acids after confirming the dissolution of each component, it is easy to check for undissolved or precipitated components and additives. In addition, when adding azulene sulfonic acids, it is expected that the stability of the azulene sulfonic acids can be increased (a decrease in content can be suppressed) by maintaining the pH of the system at a weak acidic level (pH 6.5 to 8.5), so the pH of the system can be adjusted as necessary. Thereafter, water is added to adjust the volume as necessary to obtain the mouthwash (undiluted solution). EXAMPLES

[0022] The present invention will be described in more detail below with reference to examples, although the present invention is not limited to these examples.

[0023] [Preparation of mouthwash concentrate and mouthwash (1)] Example 1 0.1g of polyoxyethylene hydrogenated castor oil 60 was dissolved by heating, and then dissolved in 55g of propylene glycol. 7.5mL of ethanol and glycerin fatty acid ester were added. 0.1 g of ethylhexyl phosphate, 1.25 g of cetylpyridinium chloride hydrate, and 5 g of 1-menthol were added and dissolved by stirring at room temperature to obtain a cetylpyridinium phase. Next, 2.5 g of sodium saccharin and 0.1 g of hydroxyethyl cellulose SE-600 were added to 30 g of purified water and dissolved by stirring at room temperature to obtain a flavoring agent phase. The flavoring agent phase was added to the cetylpyridinium phase and dissolved by stirring at room temperature, after which 0.5 g of sodium azulene sulfonate was added and dissolved, and purified water was added to make up a total volume of 100 mL to obtain the mouthwash concentrate of Example 1 (Table 1). 0.4 mL of the mouthwash concentrate was diluted with 100 mL of water to obtain the mouthwash of Example 1 (Table 2). Example 2 A mouthwash concentrate and a mouthwash of Example 2 were obtained in the same manner as in Example 1, except that the saccharin sodium in Example 1 was changed to acesulfame potassium.

[0024] Comparative Example 1 A mouthwash concentrate and mouthwash of Comparative Example 1 were obtained in the same manner as in Example 1, except that the sodium saccharin in Example 1 was changed to dipotassium glycyrrhizinate. Comparative Example 2 A mouthwash concentrate and mouthwash of Comparative Example 2 were obtained in the same manner as in Example 1, except that the saccharin sodium of Example 1 was not added. Comparative Example 3 A mouthwash concentrate and a mouthwash of Comparative Example 3 were obtained in the same manner as in Example 1, except that the hydroxyethyl cellulose SE-600 of Example 1 was not added. Comparative Example 4 A mouthwash concentrate and a mouthwash of Comparative Example 4 were obtained in the same manner as in Example 1, except that the glycerin fatty acid ester of Example 1 was not added. Comparative Example 5 A mouthwash concentrate and a mouthwash of Comparative Example 5 were obtained in the same manner as in Example 1, except that the hydroxyethyl cellulose SE-600 and glycerin fatty acid ester of Example 1 were not blended. Comparative Example 6 The same as in Example 1 except that the polyoxyethylene hydrogenated castor oil 60 in Example 1 was not added. In this manner, the mouthwash concentrate and mouthwash of Comparative Example 6 were obtained. Comparative Example 7 The mouthwash concentrate and mouthwash of Comparative Example 7 were obtained in the same manner as in Example 1, except that the saccharin sodium, hydroxyethyl cellulose SE-600, glycerin fatty acid ester, and polyoxyethylene hydrogenated castor oil 60 of Example 1 were not added.

[0025] The formulations of the undiluted mouthwash solutions prepared in Examples 1 and 2 and Comparative Examples 1 to 7 are shown in Table 1, and the formulations of the mouthwashes (after dilution) are shown in Table 2, respectively.

[0026] [Table 1]

[0027] [Test Example 1: Usability (flavor correction)] An appropriate amount of each of the mouthwashes of Examples 1 and 2 and Comparative Examples 1 to 7 was placed in the mouth, and a sensory evaluation was performed according to the following criteria. <Usability (flavor) evaluation criteria> 〇: Less bitter, easier to gargle (taste is corrected) △: Slightly bitter, difficult to gargle (slightly flavored) ×: Bitter taste, difficult to gargle (no taste)

[0028] [Test Example 2: Evaluation of foam suppression] Referring to the JIS foaming test (JIS K3362-2008 8.5 Foaming power and foam stability, Ross-Miles method), the mouthwashes of Examples 1 and 2 and Comparative Examples 1 to 7 were subjected to a foaming test according to the following procedure. Approximately 50 mL of each mouthwash (sample) was placed in a 50 mL burette, and approximately 20 mL of the sample was then added to a 100 mL measuring cylinder. The burette was then positioned so that the tip of the burette (the stopcock side) was approximately 45 cm from the liquid level of the test liquid in the measuring cylinder. The cock of the burette was fully opened and the entire amount was added to a measuring cylinder. The height of the foam that immediately formed was measured and the foaming inhibition was evaluated according to the following criteria. <Foam suppression evaluation criteria> 〇:0~20cm △:21~40cm ×: 41cm or more

[0029] [Test Example 3: Evaluation of dripping suppression] Generally, mouthwash is used by measuring an appropriate amount from a container containing the mouthwash (undiluted) into an attached cup or glass, diluting it with water, and then rinsing. The dripping property of mouthwash (undiluted) when pouring it into a glass or glass was evaluated using the following procedure. A plastic container (a commercially available mouthwash container) was filled with an appropriate amount of the mouthwash concentrate of Examples 1 to 2 and Comparative Examples 1 to 7. As in the case of using the mouthwash, the suppression of dripping when measuring out about 0.4 mL of the mouthwash concentrate into the attached cup was evaluated according to the following criteria. <Drip suppression evaluation criteria> 〇: Can measure without dripping ×: Dripping and difficult to use

[0030] [Test Example 4: Evaluation of Crystal Precipitation Inhibition] The mouthwashes of Examples 1 and 2 and Comparative Examples 1 to 7 were left at room temperature overnight, and the presence or absence of crystal precipitation was visually confirmed, and the inhibition of crystal precipitation was evaluated according to the following criteria. <Crystallization Suppression Evaluation Criteria> 〇: No crystallization occurs ×: Crystallization occurs

[0031] [Table 2]

[0032] As shown in Table 2, (A) the mouthwashes containing saccharin sodium (Example 1) and acesulfame potassium (Example 2) as flavoring agents were excellent in usability (ease of gargling (flavor masking (suppression of bitterness, etc.)) and suppressed foaming, dripping, and crystal precipitation, but the mouthwashes containing dipotassium glycyrrhizinate (Comparative Example 1), which has also been used as a flavoring agent in the past, were found to have a poor usability. The mouthwash (Comparative Example 2) that does not contain (A) flavoring agents (saccharin sodium, acesulfame potassium) had a very poor feel when used, and furthermore, even when it contained (C) celluloses described below and (B) polyhydric alcohol fatty acid esters, which are surfactants that are expected to contribute to foaming suppression, it did not suppress foaming. The mouthwash (Comparative Example 3) that does not contain (C) celluloses (hydroxyethyl cellulose) resulted in significant dripping and also had a low foaming suppression effect. The mouthwash (Comparative Example 4) that does not contain (B) polyhydric alcohol fatty acid esters (glycerin fatty acid esters) resulted in a low foaming suppression effect. Furthermore, the mouthwash (Comparative Example 5) that does not contain (C) celluloses (hydroxyethyl cellulose) and (B) polyhydric alcohol fatty acid esters (glycerin fatty acid esters) also As a result, the foam suppression effect was low. On the other hand, the mouthwash (Comparative Example 6) not containing the polyoxyethylene hydrogenated castor oil (D) which contributes to the inhibition of crystal precipitation had a low inhibitory effect on crystal precipitation. In addition, a mouthwash (Comparative Example 7) that did not contain any of (A) flavoring agents (saccharin sodium, acesulfame potassium), (B) polyhydric alcohol fatty acid esters (glycerin fatty acid esters), (C) celluloses (hydroxyethyl cellulose), and (D) polyoxyethylene hydrogenated castor oils had a poor feel when used and was poor in foaming, dripping, and crystal precipitation inhibitory effects. In addition, in order to clarify the foaming-inhibiting effect of sugar and the crystal precipitation-inhibiting effect of l-menthol, this formulation contains larger amounts of sugar and l-menthol than general formulations, and therefore the evaluation criteria for this series of tests may differ from the evaluation criteria for similar tests described below.

[0033] [Preparation of mouthwash concentrate and mouthwash (2)] Example 3 0.1g of polyoxyethylene hydrogenated castor oil 60 was dissolved by heating, and then dissolved in 50g of propylene glycol. 7.5mL of ethanol and glycerin fatty acid ester were added. 0.1 g of menthol, 1.25 g of cetylpyridinium chloride hydrate, and 1 g of 1-menthol were added and dissolved by stirring at room temperature to obtain a cetylpyridinium phase. Next, 1 g of sodium saccharin and 0.1 g of hypromellose 60SH-4000 were added to 30 g of purified water and dissolved by stirring at room temperature to prepare a flavoring agent phase. The flavoring agent phase was added to the cetylpyridinium phase and dissolved by stirring at room temperature, after which 0.5 g of sodium azulene sulfonate and an appropriate amount of pH adjuster were added and dissolved, and purified water was added to make up a total volume of 100 mL to obtain the mouthwash concentrate (pH 7.5) of Example 3 (Table 3). 0.4 mL of the mouthwash concentrate was diluted with 100 mL of water to obtain the mouthwash of Example 3 (Table 4). Example 4 The mouthwash concentrate and mouthwash of Example 4 were obtained in the same manner as in Example 3, except that the amount of hypromellose 60SH-4000 in Example 3 was changed to 0.12 g. Example 5 The mouthwash concentrate and mouthwash of Example 5 were obtained in the same manner as in Example 3, except that the hypromellose 60SH-4000 in Example 3 was changed to hypromellose 90SH-4000SR and the blended amount was changed to 0.15 g. Example 6 The mouthwash concentrate and mouthwash of Example 6 were obtained in the same manner as in Example 3, except that hypromellose 60SH-4000 in Example 3 was replaced with hydroxyethyl cellulose SE-900.

[0034] Comparative Example 8 A mouthwash concentrate and a mouthwash of Comparative Example 8 were obtained in the same manner as in Example 3, except that hypromellose 60SH-4000 of Example 3 was not added.

[0035] The formulations of the undiluted mouthwash solutions prepared in Examples 3 to 6 and Comparative Example 8 are shown in Table 3, and the formulations of the mouthwashes (after dilution) are shown in Table 4, respectively.

[0036] [Table 3]

[0037] [Test Example 5: Viscosity Evaluation] A 100 mL beaker containing 100 mL of the mouthwash concentrate of Examples 3 to 6 and Comparative Example 8 was prepared, and a test was performed using a rotational viscometer (VISCOMETER TV-10, Toki Sangyo Co., Ltd.) at room temperature (20±5°C). The rotor used was an M-1 rotor, and measurements were performed for 120 seconds at a rotation speed of 100 rpm. Furthermore, if the viscosity is less than 10 mPa·s, the viscosity will be low enough for use as an undiluted mouthwash solution, and there is concern that the liquid may drip when measured out.

[0038] Furthermore, for the undiluted mouthwash solutions of Examples 3 to 6 and Comparative Example 8, the suppression of dripping when the undiluted mouthwash solutions were measured out was evaluated according to the procedure of [Test Example 3: Evaluation of Dripping Suppression] described above. These results are shown together in Table 4.

[0039] [Table 4]

[0040] In this formulation, the viscosity and dripping suppression effect of the formulations containing different amounts of the thickening agents hydroxyethyl cellulose SE-900, hypromellose 60SH-4000, and hypromellose 90SH-4000SR were evaluated. In Comparative Example 8, which did not contain a thickener, the viscosity of the undiluted mouthwash solution was 10 mPa s or less, and the undiluted mouthwash solution dripped when measured out, making it difficult to use. In contrast, the undiluted mouthwash solutions of Examples 3 to 6, which contained 0.10% to 0.15% thickener, had a viscosity of 15 mPa s or more regardless of the type and grade of thickener used, and could be measured out without dripping.

[0041] [Preparation of mouthwash concentrate and mouthwash (3)] Example 7 0.5 g of polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was dissolved by heating, and then dissolved in 55 g of propylene glycol. 7.5 mL of ethanol, 0.1 g of glycerin fatty acid ester, 1.25 g of cetylpyridinium chloride hydrate, and 1 g of l-menthol were added and dissolved at room temperature with stirring to form a cetylpyridinium phase. Next, 1 g of sodium saccharin and hypromellose (Metholone) were added to 30 g of purified water. The mixture was stirred at room temperature to dissolve, forming a flavoring agent phase. The flavoring agent phase was added to the cetylpyridinium phase and dissolved by stirring at room temperature, after which 0.5 g of sodium azulene sulfonate was added and dissolved, and purified water was added to make up a total volume of 100 mL to obtain the mouthwash concentrate of Example 7 (Table 5). 0.4 mL of the mouthwash concentrate was diluted with 100 mL of water to obtain the mouthwash of Example 7 (Table 6). Example 8 A mouthwash concentrate and a mouthwash of Example 8 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was changed to polyoxyethylene hydrogenated castor oil 50 (Nikkol HCO-50). Example 9 The mouthwash concentrate and mouthwash of Example 9 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was changed to polyoxyethylene hydrogenated castor oil 60 (Nikkol HCO-60). Example 10 A mouthwash concentrate and mouthwash of Example 10 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was changed to polyoxyethylene hydrogenated castor oil 100 (Nikkol HCO-100).

[0042] Comparative Example 9 A mouthwash concentrate of Comparative Example A was obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was replaced with decaglyceryl polylaurate (Nikkol Decaglyn 1-L) (Table A). 0.4 mL of the mouthwash stock solution was diluted with 100 mL of water to obtain the mouthwash of Comparative Example A (Table B). Comparative Example 10 A mouthwash concentrate and mouthwash of Comparative Example 10 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was replaced with polysorbate 20 (Nikkol TL-10). Comparative Example 11 A mouthwash concentrate and a mouthwash of Comparative Example 11 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was replaced with polysorbate 40 (Nikkol TP-10EX). Comparative Example 12 A mouthwash concentrate and a mouthwash of Comparative Example 12 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was changed to polysorbate 60 (Nikkol TS-10MV). Comparative Example 13 A mouthwash concentrate and a mouthwash of Comparative Example 13 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was changed to polysorbate 80 (Nikkol TO-10MV). Comparative Example 14 A mouthwash concentrate and mouthwash of Comparative Example 14 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was changed to lauromacrogol (Nikkol BL-21). Comparative Example 15 A mouthwash concentrate and mouthwash of Comparative Example 15 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was changed to lauromacrogol (Nikkol BL-25). Comparative Example 16 A mouthwash concentrate and mouthwash of Comparative Example 16 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was changed to polyoxyethylene oleyl ether (Nikkol BO-20V). Comparative Example 17 A mouthwash concentrate and mouthwash of Comparative Example 17 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was changed to polyoxyethylene oleyl ether (Nikkol BO-50V).

[0043] The formulations of the undiluted mouthwash solutions prepared in Examples 7 to 10 and Comparative Examples 9 to 17 are shown in Table 5, and the formulations of the mouthwashes (after dilution) are shown in Table 6, respectively.

[0044] [Table 5]

[0045] [Table 6]

[0046] [Test Example 6: Appearance evaluation of mouthwash concentrate before the addition of sodium azulene sulfonate] When sodium azulene sulfonate was added, the color turned dark blue, and the appearance (turbidity, etc.) of the mouthwash concentrate could not be evaluated. Therefore, the appearance of the mouthwash concentrate was evaluated before adding sodium azulene sulfonate. Evaluated. The appearance of the mouthwash concentrates of Examples 7 to 10 and Comparative Examples 9 to 17 was visually evaluated according to the following criteria before the addition of sodium azulene sulfonate. The results are shown in Table 7. <Appearance of mouthwash concentrate before adding sodium azulene sulfonate Evaluation criteria> 〇: Clear △: Slightly cloudy ×: Cloudy

[0047] [Test Example 7: Sensitivity of mouthwash (after dilution) (sweetness)] An appropriate amount of each of the mouthwashes (diluted) of Examples 7 to 10 and Comparative Examples 9 to 17 was placed in the mouth, and the sensation of use (sweetness) was evaluated in a sensory test according to the following criteria. The results are shown in Table 7. <Evaluation criteria for sweetness of diluted mouthwash> 〇: Sweet and easy to gargle △: Slightly sweet, but difficult to gargle ×: No sweetness, difficult to gargle

[0048] [Test Example 8: Evaluation of crystal precipitation when dripping mouthwash concentrate (during dilution operation)] 50 mL of tap water was placed in a 50 mL beaker, and an appropriate amount of the mouthwash concentrate of Examples 7 to 10 and Comparative Examples 9 to 17 was dropped into it. After dropping and leaving it for 5 minutes, the presence or absence of crystal precipitation was visually confirmed and evaluated according to the following criteria. The obtained results are shown in Table 7. <Crystallization evaluation criteria when dripping undiluted mouthwash solution (during dilution)> 〇: No crystallization occurs ×: Crystals precipitated

[0049] [Test Example 9: Turbidity evaluation of mouthwash (after dilution)] After preparing the mouthwashes of Examples 7 to 10 and Comparative Examples 9 to 17, the turbidity (OD) at a wavelength of 660 nm was measured using an ultraviolet-visible spectrophotometer (UV-1600, Shimadzu Corporation). 660 ) was measured and evaluated according to the following criteria. The results are shown in Table 7. Note that since the occurrence of turbidity makes crystals more likely to precipitate, the turbidity measurement can be considered as an index of crystal precipitation. Turbidity of the diluted mouthwash solution (OD 660 ) Evaluation criteria> ○: 0.035 or less △:0.035~0.044 ×:0.045 or more

[0050] [Test Example 10: Evaluation of crystal precipitation of mouthwash (after dilution) at low temperatures] The mouthwashes of Examples 7 to 10 and Comparative Examples 9 to 17 were stored overnight at 5° C., and the presence or absence of crystal precipitation was visually confirmed, and the inhibition of crystal precipitation was evaluated according to the following criteria. The obtained results are shown in Table 7. <Crystallization criteria for mouthwash (after dilution) at low temperature (5℃)> ◯: No crystals were precipitated and the liquid was clear. △: No crystals were precipitated, but the solution became cloudy. ×: Crystals precipitate.

[0051] [Test Example 11: Evaluation of foam suppression of mouthwash (after dilution)] Referring to the JIS foaming test (JIS K3362-2008 8.5 Foaming power and foam stability, Ross-Miles method), the mouthwashes of Examples 7 to 10 and Comparative Examples 9 to 17 were subjected to a foaming test according to the following procedure. Approximately 50 mL of each mouthwash (sample) was placed in a 50 mL burette, and approximately 20 mL of the sample was then added to a 100 mL measuring cylinder. The burette was then positioned so that the tip of the burette (the stopcock side) was approximately 45 cm from the liquid level of the test liquid in the measuring cylinder. The cock of the burette was fully opened and the entire amount was added to a measuring cylinder. The height of the foam that immediately formed was measured and the foaming inhibition was evaluated according to the following criteria. The results are shown in Table 7. <Garment solution (diluted) foam suppression evaluation criteria> 〇:0~10cm △:10.5~12.5cm ×:13.0cm or more

[0052] [Table 7]

[0053] In this formulation, instead of polyoxyethylene hydrogenated castor oils, polyoxyethylene hydrogenated castor oils are used to suppress crystal precipitation in the undiluted mouthwash solution at room temperature (appearance of the undiluted solution), crystal precipitation when the undiluted mouthwash solution is dripped (during dilution), turbidity of the mouthwash solution (after dilution), and crystal precipitation at low temperatures (5°C). The effects of adding various surfactants, known as solubilizers, were evaluated. The mouthwash's feel after dilution (sweetness after dilution) and foam suppression (after dilution) were also evaluated. The polyoxyethylene hydrogenated castor oils, which are component (D) of the present invention, have some grades in which the crystal precipitation suppression effect during dilution (dropping of the original solution) and the feeling of use (sweetness) of the mouthwash (after dilution) are somewhat reduced, but the appearance of the original solution, the crystal precipitation suppression effect (turbidity of the solution, crystal precipitation at low temperatures) and the foaming suppression effect are good, and the results of all evaluations were generally satisfactory. (Examples 7 to 10) When decaglyceryl laurate was used as a solubilizer, crystal precipitation was confirmed when the mouthwash concentrate was dripped (during dilution), the appearance of the concentrate became cloudy, and the mouthwash (after dilution) also showed a tendency to have a reduced feel (sweetness) and foam suppression effect (comparative example 9). In addition, for all grades of polysorbates, crystal precipitation was observed when the undiluted mouthwash solution was dripped (during dilution), and some grades were found to be inferior in appearance of the undiluted solution, feeling of use (sweetness) of the mouthwash (after dilution), and foaming suppression effect (Comparative Examples 10 to 13). All grades of lauromacrogols crystallized when stored at low temperatures in diluted mouthwash, had low foaming suppression effects, and were slightly inferior in terms of usability (sweetness) of diluted mouthwash and crystal precipitation when dripping undiluted mouthwash (during dilution) (Comparative Examples 14 and 15). Polyoxyethylene oleyl ethers include grades that have a poor feel when used and grades in which crystal precipitation was observed when the mouthwash (after dilution) was stored at low temperatures (Comparative Examples 16 and 17). From the above results, it was found that polyoxyethylene hydrogenated castor oils are good solubilizers that can satisfy the following criteria: crystal precipitation in the undiluted mouthwash solution at room temperature (appearance of the undiluted solution), crystal precipitation inhibition at room temperature when the undiluted mouthwash solution is dripped (during the dilution process) (visual inspection), crystal precipitation inhibition based on turbidity evaluation of the mouthwash solution (diluted), and crystal precipitation inhibition at low temperatures (5°C) (visual inspection) without compromising the feel (sweetness) and foaming inhibition effect of the mouthwash (after dilution).

[0054] [Preparation of mouthwash concentrate and mouthwash (4)] Example 11 0.5g of polyoxyethylene hydrogenated castor oil 60 was dissolved by heating, and then dissolved in 55g of propylene glycol. 7.5mL of ethanol and glycerin fatty acid ester were added. 0.1 g of menthol, 1.25 g of cetylpyridinium chloride hydrate, and 1 g of 1-menthol were added and dissolved by stirring at room temperature to obtain a cetylpyridinium phase. Next, 1 g of sodium saccharin and 0.15 g of hypromellose 90SH-4000SR were added to 30 g of purified water and dissolved by stirring at room temperature to prepare a flavoring agent phase. The flavoring agent phase was added to the cetylpyridinium phase and dissolved by stirring at room temperature, after which 0.5 g of sodium azulene sulfonate and an appropriate amount of pH adjuster were added and dissolved, and purified water was added to make up a total volume of 100 mL to obtain the mouthwash concentrate (pH 7.5) of Example 11 (Table 8). 0.4 mL of the mouthwash concentrate was diluted with 100 mL of water to obtain the mouthwash of Example 11 (Table 9).

[0055] Comparative Example 18 The mouthwash concentrate and mouthwash of Comparative Example 18 were obtained in the same manner as in Example 11, except that the amount of glycerin fatty acid ester was changed to 0.05 g, the amount of polyoxyethylene hydrogenated castor oil 60 was changed to 0.10 g, and 0.30 g of polysorbate 80 was added to the cetylpyridinium phase. Comparative Example 19 The mouthwash concentrate and mouthwash of Comparative Example 19 were obtained in the same manner as in Example 11, except that the amount of polyoxyethylene hydrogenated castor oil 60 was changed to 0.10 g and 0.30 g of polysorbate 80 was added to the cetylpyridinium phase. Comparative Example 20 A mouthwash concentrate and mouthwash of Comparative Example 20 were obtained in the same manner as in Example 11, except that 0.05 g of polysorbate 80 was added to the cetylpyridinium phase. Comparative Example 21 A mouthwash concentrate and mouthwash of Comparative Example 21 were obtained in the same manner as in Example 11, except that 0.10 g of polysorbate 80 was added to the cetylpyridinium phase. Comparative Example 22 A mouthwash concentrate and mouthwash of Comparative Example 22 were obtained in the same manner as in Example 11, except that 0.30 g of polysorbate 80 was added to the cetylpyridinium phase.

[0056] The formulations of the mouthwash concentrates prepared in Example 11 and Comparative Examples 18 to 22 are shown in Table 8, and the formulations of the mouthwashes (after dilution) are shown in Table 9, respectively.

[0057] [Table 8]

[0058] [Test Example 12: Evaluation of crystal precipitation during dilution of stock solution] 50 mL of tap water was placed in a 50 mL beaker, and an appropriate amount of the mouthwash concentrate of Example 11 and Comparative Examples 18 to 22 was dropped into it. After leaving it for 5 minutes, the presence or absence of crystal precipitation was visually confirmed and evaluated according to the following criteria. <Crystallization criteria when diluting stock solution> 〇: No crystallization occurs ×: Crystals precipitated

[0059] [Test Example 13: Evaluation of turbidity upon dilution] After preparing the mouthwashes of Example 11 and Comparative Examples 18 to 22, the turbidity (OD 660 ) was measured and evaluated according to the following evaluation criteria. < Turbidity when diluted (OD 660 ) Evaluation criteria> ○: 0.020 or less △:0.020~0.025 ×:0.026 or more

[0060] [Test Example 14: Evaluation of crystal precipitation during low-temperature storage (5°C)] The mouthwashes (diluted) of Example 11 and Comparative Examples 18 to 22 were used and stored at 5° C. for 7 days, after which the presence or absence of crystal precipitation was visually confirmed and evaluated according to the following criteria. <Crystallization criteria during low-temperature storage> 〇: No crystallization occurs ×: Crystals precipitated

[0061] In addition, the mouthwashes of Example 11 and Comparative Examples 18 to 22 were evaluated for usability (taste masking) and foaming inhibition according to the procedures described above in [Test Example 1: Usability (taste masking)] and [Test Example 2: Foaming inhibition evaluation]. These results are shown together in Table 9.

[0062] [Table 9]

[0063] As shown in Tables 8 and 9, when the amount of polyoxyethylene hydrogenated castor oil 60 in the mouthwash concentrate was 0.1% and 0.30% polysorbate 80 was added instead, it was difficult to suppress the feel (flavor), crystal precipitation upon dilution, and crystal precipitation and foaming during storage at low temperatures, even if the amount of glycerin fatty acid ester was changed (Comparative Examples 18 and 19). In addition, when the amount of polyoxyethylene hydrogenated castor oil 60 in the mouthwash concentrate was increased to 0.5% (polysorbate: 0.30%, Comparative Example 22), the inhibition of crystal precipitation during dilution and low-temperature storage was improved compared to the above-mentioned Comparative Example 10, but the result was that the feeling of use (flavor) was still lacking, and when the amount of polysorbate 80 was 0.1% or less, the feeling of use (flavor) was improved, but turbidity occurred when diluted (Comparative Examples 20 and 21). In addition, in all of Comparative Examples 20 to 22, in which polysorbate 80 was blended in the range of 0.05 to 0.3%, foaming was not suppressed. From the above results, it was confirmed that the blending of polysorbate 80 is not preferable, even in small amounts, especially from the viewpoint of foaming inhibition. On the other hand, 0.1% glycerin fatty acid ester and 60% polyoxyethylene hydrogenated castor oil Example 11, which contained 0.5% of polysorbate 80 and no polysorbate 80, was excellent in terms of usability, precipitation upon dilution, turbidity upon dilution, crystal precipitation during low-temperature storage, and foaming inhibitory effect.

[0064] From the above results, it was confirmed that in a mouthwash containing azulene sulfonic acid and / or its salts, cetylpyridinium and / or its salts, and l-menthol, the combination of (A) a specific flavoring agent, (B) a polyhydric alcohol fatty acid ester, (C) celluloses, and (D) polyoxyethylene hydrogenated castor oils provides satisfactory effects in terms of the mouthwash's feel when used, as well as in terms of foaming suppression, dripping suppression, and crystal precipitation suppression. And when the above (B) to (D) ingredients were mixed and another compound introduced as a flavoring agent was mixed, the mouthwash did not have a satisfactory feeling when used, when the specific flavoring agent (A) was not used, no foaming suppression effect was obtained, when the specific flavoring agent (A) was used, a satisfactory foaming suppression effect was not obtained when either or both of the (B) and (C) ingredients were not mixed, and when the (C) ingredient was not mixed, no dripping suppression effect was obtained.And when the (D) ingredient was not mixed, no crystal precipitation suppression effect was obtained, and when the surfactants decaglyceryl laurate, polysorbates, lauromalgols, and polyoxyethylene oleyl ethers were used, all of the crystal precipitation suppression, foaming suppression, and feeling when used (flavoring and sweetness) were not satisfactory.

Claims

[Claim 1] A mouthwash characterized in that the liquid composition contains azulene sulfonic acid and / or a salt thereof, cetylpyridinium and / or a salt thereof, and 1-menthol, and further contains the following components (A), (B), (C), and (D) (excluding a betaine acetate surfactant and polysorbate 80): (A) one or more flavoring agents selected from saccharin sodium and acesulfame potassium; (B) glycerin fatty acid ester, (C) one or more celluloses selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl cellulose, and hypromellose; (D) Polyoxyethylene hydrogenated castor oils which are one or more selected from the group consisting of polyoxyethylene hydrogenated castor oil 5, polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60 and polyoxyethylene hydrogenated castor oil 100.

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