JP3070152B2 - Liquid oral composition - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION The present invention relates to a quaternary ammonium salt type cationic antibacterial agent which has almost no bitterness and excellent antibacterial activity, and is suitable for preventing and improving caries, periodontal diseases, bad breath and the like. It relates to an oral composition.

[0002]

2. Description of the Related Art
When a quaternary ammonium salt-type cationic antibacterial agent is incorporated into a composition for oral cavity, such an antibacterial agent has a disadvantage that bitterness due to the antibacterial agent is generated and taste is deteriorated.

[0003] Therefore, in order to reduce the bitterness derived from this antibacterial agent, a sweetener such as saccharin or dipotassium glycyrrhizinate is added to the oral composition, or the amount of the sweetening polyhydric alcohol such as glycerin or sorbite is increased. That is being done.

[0004] However, the addition of the former sweetener such as saccharin has a problem that a cation-anion complex is generated and the antibacterial activity of the above antibacterial agent is not sufficiently exerted. In addition, the latter sweetener such as glycerin cannot be used. The method of increasing the amount has a problem that the sticky feeling of the oral composition increases and the feeling of use is deteriorated.

[0005] Therefore, it is desired to develop an oral composition which has almost no bitterness derived from a quaternary ammonium salt type cationic antibacterial agent, has excellent antibacterial activity, and has a good feeling in use.

[0006]

Means for Solving the Problems and Actions The present inventors have made intensive studies in view of the above circumstances, and as a result, have found that a liquid oral composition containing a quaternary ammonium salt type cationic antibacterial agent has
When tranexamic acid and / or ε-aminocaproic acid are combined with a stevia-based sweetener, the two components unexpectedly act synergistically to reduce the bitterness derived from the quaternary ammonium salt-type cationic antibacterial agent. In addition to being masked, the taste can be improved, the antibacterial activity of the antibacterial agent is sufficiently exerted without inactivation, and the feeling of use is good, and a transparent liquid composition such as a mouthwash It was found that a preparation having a good appearance without white turbidity or the like can be obtained when prepared as follows, and the present invention has been accomplished.

That is, it has been known that tranexamic acid and ε-aminocaproic acid are conventionally added to an oral composition as a component capable of imparting antiplasmin and anti-inflammatory effects. However, even when such tranexamic acid or ε-aminocaproic acid is simply used in combination with a quaternary ammonium salt-type cationic antibacterial agent, the bitterness is not reduced. Rather, tranexamic acid itself has a bitter taste, and in fact, it has been an issue in the prior art to reduce the bitter taste of such tranexamic acid. On the other hand, stevia-based sweeteners are also known sweeteners, but even if they are added to quaternary ammonium salt-type cationic antibacterial agents at a low concentration, the effect of reducing bitterness is not sufficient. Further, when added at a high concentration, the bitter taste of the stevia-based sweetener itself appears.

However, when tranexamic acid or ε-aminocaproic acid and a stevia-based sweetener are combined with a quaternary ammonium salt type cationic antibacterial agent, a liquid oral composition with a reduced bitterness is surprisingly obtained. And a quaternary ammonium salt-type cationic antibacterial agent having a bitter taste, in which tranexamic acid or ε-
An unexpected new fact was discovered that aminocaproic acid acts as a bitter reducer in the presence of a stevia sweetener.

Hereinafter, the present invention will be described in more detail. The liquid oral composition of the present invention can be prepared, for example, as a mouthwash, mouthwash, etc., and comprises a quaternary ammonium salt type cationic antibacterial agent, Tranexamic acid and / or
Alternatively, it is obtained by mixing ε-aminocaproic acid and a stevia-based sweetener.

Examples of the quaternary ammonium salt type cationic antibacterial which is the first essential component of the present invention include alkylpyridinium salts such as benzethonium chloride, cetylpyridinium chloride and benzalkonium chloride, and mono-length such as cetyltrimethylammonium chloride. And the like. One of these can be used alone or two or more can be used in combination.

The compounding amount of the quaternary ammonium salt type cationic antibacterial agent is 0.005 to 0.2% of the whole composition.
(% By weight, the same applies hereinafter), particularly preferably 0.01 to 0.05%. If the compounding amount is less than 0.005%, a sufficient antibacterial effect may not be obtained, and 0.2% If it exceeds, irritation to the oral cavity increases, and it may not be suitable for use.

Next, the blending amount of the second essential component, tranexamic acid or ε-aminocaproic acid, is 0.0% of the total composition.
More preferably, the content is set to 0.05 to 0.3%, particularly 0.01 to 0.1%. If the amount is less than 0.005%, the bitterness derived from the antibacterial agent may not be reduced,
If the amount exceeds the above, bitterness itself may appear or the antibacterial activity may be adversely affected.

Further, examples of the stevia sweetener to be blended as the third essential component in the present invention include stevia extract, stevioside, rebaudioside, and the like. One of these can be used alone, or two or more can be mixed. Can be used.

Here, the amount of the stevia sweetener is 0.0005 to 0.3% of the whole composition, especially 0.001 to 0.3%.
0.1% is desirable, and the compounding amount is 0.0005.
%, The bitterness derived from the antibacterial agent may not be reduced, and if it exceeds 0.3%, the bitterness itself may appear.

The liquid oral composition of the present invention can be prepared into dosage forms such as mouth washes, mouthwashes, liquid dentifrices, etc. In addition to the above-mentioned components, various known components corresponding to the respective types are used. It can be blended as long as the effects of the invention are not impaired. For example, anionic surfactants such as α-sulfofatty acid alkyl esters or water-soluble salts thereof, alkyl sulfate salts, N-acyl amino acid salts, etc., fatty acid monoglycerides, fatty acid alkanolamides, polyoxyethylene sorbitan fatty acids, depending on the type of the composition, etc. Nonionic surfactants such as esters, polyoxyethylene hydrogenated castor oil, and sucrose fatty acid esters; amphoteric surfactants such as alkyl betaine, imidazolinium betaine and sulfobetaine; and semipolar surfactants such as alkylamine oxide. Various surfactants, abrasives such as dibasic calcium phosphate, calcium carbonate, calcium pyrophosphate, insoluble sodium metaphosphate, aluminum hydroxide, silicic anhydride, glycerin, sorbite, propylene glycol,
Wetting agents such as polyethylene glycol, binders such as sodium carboxymethylcellulose, carrageenan, sodium alginate, veegum, hydroxyethylcellulose, xanthan gum, sodium polyacrylate, aspartame, paramethoxycinnamic aldecht;
Non-Stevia sweeteners such as neohesperidyl dihydrochalcone and perillartin, and flavorings such as menthol, carvone, and anethole are used. Fungicides other than quaternary ammonium salt type antibacterial agents, anti-inflammatory agents such as allantoinate, phosphate compounds such as sodium phosphate, sodium pyrophosphate, sodium tripolyphosphate, sodium tetrapolyphosphate, and inorganic salts such as sodium chloride. Are used as appropriate. In addition, these liquid oral compositions can be prepared according to a conventional method.

[0016]

Industrial Applicability The liquid oral composition of the present invention has almost no bitterness derived from a quaternary ammonium salt type cationic antibacterial agent, has good taste, and can exhibit excellent antibacterial effect.
The feeling of use is also good. In addition, when the composition of the present invention is prepared as a transparent liquid composition such as a mouthwash, a preparation having a good appearance without clouding can be obtained. Therefore, the liquid oral composition of the present invention is suitable for prevention and improvement of caries, periodontal disease, bad breath and the like.

[0017]

EXAMPLES The present invention will be described in detail below with reference to examples and comparative examples, but the present invention is not limited to the following examples. In addition, all% in each example are weight%.

Examples 1 to 8, Comparative Examples 1 to 11
A mouthwash having the composition shown in No. 2 was prepared and subjected to a bitterness test, an antibacterial test and a comprehensive evaluation by the following methods. The results are shown in Tables 1 and 2.
It is described together. Bitterness test: Mouthwash was washed for about 30 seconds with 20 ml of mouthwash, and the degree of bitterness remaining in the mouth after ejection was sensory evaluated on a 5-point scale by five specialized panelists. The evaluation criteria are as follows. -: No bitterness ±: bitterness is difficult to understand +: bitterness ++: considerably bitterness +++: very bitterness Antibacterial activity test: about 10 ⁸ Escherichia coli / m in 10 ml of mouthwash
Immediately after incubating at 37 ° C. for 1 minute, 1 ml thereof is immediately inactivated with 1% polysorbate 80%.
And 0.1% lecithin) in 10-fold serial dilution with phosphate buffered saline, and the viable cell count in each dilution was determined by pour culture on an SCDLP agar medium (Daigo, manufactured by Nippon Pharmaceutical Co., Ltd.) (37 ° C.,
48 hours), the number of bacteria remaining in the mouthwash (cells / ml) was calculated, and the bactericidal activity of each mouthwash against Escherichia coli (U5 / 41 strain) was compared. Comprehensive evaluation: Comprehensive evaluation was performed according to the following criteria. ：: Evaluation of bitterness was-to ± and the number of residual bacteria was 0 (cells / m
In the case of l). ×: When the evaluation of bitterness is + to +++ or when the number of remaining bacteria is recognized.

[0019]

[Table 1]

[0020]

[Table 2]

From the results shown in Tables 1 and 2, the antibacterial activity was reduced when an amount of saccharin necessary to mask the bitterness of benzethonium chloride in the mouthwash was added (Comparative Examples 2 to 4).
4). In addition, Stevia extract composition (Comparative Examples 5 to 8)
Does not inactivate the antibacterial activity of benzethonium chloride,
With the addition composition of 0.01 to 0.1% (Comparative Examples 5 to 7), the bitterness masking effect of benzethonium chloride is not sufficient,
Conversely, with the 0.3% additive composition (Comparative Example 8), the bitterness of the stevia extract itself appeared. On the other hand, when glycyrrhizic acid, which is a sweet anti-inflammatory agent, was added (Comparative Example 11), the formation of a cation-anion complex inactivated the antibacterial activity.

Further, tranexamic acid was recognized as bitter at an aqueous solution concentration of more than 0.05%, and the composition of 0.05% (Comparative Example 9) did not show the bitterness masking effect of benzethonium chloride. The amount is 0.
Similarly, even with a composition of 2% (Comparative Example 10), no bitterness masking effect was observed.

On the other hand, when both stevia extract and tranexamic acid are used together (Examples 1 to 4), a composition in which the bitterness of benzethonium chloride is masked surprisingly and the antibacterial activity is not inactivated is obtained. It has been found. Also, the composition of ε-aminocaproic acid (Example 5)
8), a synergistic effect similar to that of tranexamic acid was observed. In addition, all of the mouthwashes of Examples 1 to 8 had good feeling in use.

Example 9 Mouthwash Ethanol 10.0% Sorbitol (60%) 10.0 Monosodium phosphate 0.12 Disodium phosphate 0.54 Ethylene glycol / propylene glycol condensed nonionic activator 2.0 Cetylpyridinium chloride 0.05 Tranexamic acid 0.1 Stevia extract 0.1 Sodium benzoate 0.2 Fragrance 0.2 Dye 0.0002 Purified water Balance meter 100.0%

Example 10 Mouthwash ethanol 7.0% propylene glycol 1.5 glycerin 7.5 citric acid 0.16 sodium citrate 0.32 benzethonium chloride 0.01 tranexamic acid 0.05 allantoin 0.2 Stevia extract 0.005 Perfume 0.05 Purified water Balance meter 100.0%

Example 11 Mouthwash Ethanol 6.5% Glycerin 5.0 Polyoxyethylene hydrogenated castor oil (60EO) 1.5 Cetylpyridinium chloride 0.02 ε-Aminocaproic acid 0.1 Sodium guaiazulene sulfonate 0 .02 Stevia extract 0.02 dl-malic acid 0.02 dl-sodium malate 0.06 Methyl paraoxybenzoate 0.1 Perfume 0.3 Purified water Balance meter 100.0%

Example 12 Mouthwash ethanol 1.0% glycerin 8.0 ethylene glycol / propylene glycol condensed nonionic activator 1.5 benzalkonium chloride 0.01 tranexamic acid 0.01 ε-aminocaproic acid 03 Lysozyme chloride 0.5 Monosodium phosphate 0.12 Disodium phosphate 0.54 Sodium benzoate 0.2 Stevioside 0.01 Fragrance 0.1 Purified water Balance meter 100.0%

Example 13 Mouthwash Ethanol 1.5% Glycerin 8.0 Polyoxyethylene hydrogenated castor oil (60EO) 2.0 Citric acid 0.16 Sodium citrate 0.32 Benzethonium chloride 0.01 Tranexamic acid 0.05 Dextranase 500 U / g Sodium fluoride 0.02 Methyl paraoxybenzoate 0.1 Propyl paraoxybenzoate 0.05 Rebaudioside 0.001 Fragrance 0.4 Dye 0.0004 Purified water Balance meter 100. 0%

Example 14 Diluted mouthwash ethanol 20.0% glycerin 15.0 benzethonium chloride 0.05 tranexamic acid 0.1 polyoxyethylene hydrogenated castor oil (40EO) 4.0 dl-α-tocopherol acetate 0.3 Stevia extract 0.1 Fragrance 0.8 Purified water Balance meter 100.0%

Example 15 Oral Freshener Ethanol 40.0% Glycerin 10.0 Cetylpyridinium chloride 0.01 ε-Aminocaproic acid 0.05 Polyoxyethylene hydrogenated castor oil (60EO) 3.0 1-Menthol 0 Stevia extract 0.1 Fragrance 1.5 Purified water Balance meter 100.0%

[0031]

[0032]

[0033]

[0034]

[0035]

[0036]

[0037]

[0038]

[0039]

Claims (1)

(57) [Claims] 1. A liquid oral composition comprising a quaternary ammonium salt-type cationic antibacterial agent, tranexamic acid and / or ε-aminocaproic acid, and a stevia sweetener.