JP3460366B2 - Oral composition - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an oral composition for preventing dental caries, cleaning the oral cavity, that is, the teeth and gums, and preventing halitosis. The present invention can be applied to oral compositions in general, but is particularly suitable for liquid oral compositions.

[0002]

2. Description of the Related Art There are various bacteria in the oral cavity, and the growth of these oral bacteria is promoted by sugars contained in food waste and foods, and secretes substances that cause tooth decay and diseases around teeth. It causes caries and oral diseases. It is impossible to completely kill the bacteria in the oral cavity, and there is a concern that the bacterial balance in the oral cavity and digestive system may be lost. But,
Various compounds are known for effectively preventing the growth of harmful bacteria in the oral cavity, and mouthwashes, liquid toothpaste, liquid toothpaste and toothpaste such as toothpaste are used as oral compositions containing these as active ingredients. , Oral refreshing agents and mouthwashes (gargles) are prescribed. In particular, liquid oral compositions such as mouthwash and liquid toothpaste (liquid toothpaste) have been launched in recent years and have become a habit.

In this oral composition for liquid toothpaste or the like, cetylpyridinium chloride (C
PC), triclosan, chlorhexidine gluconate and the like are mixed, but in addition to them, a slightly water-soluble flavor such as menthol is added to obtain a refreshing feeling. In addition, a large amount (about 1
About 5% of ethanol is blended.

On the other hand, oral compositions such as liquid toothpaste have become established in the habit, so that the age group of users is widened or individual tastes are motivated to purchase products. For this reason, there is a demand for toothpaste that has a refreshing feeling and is less irritating, and it does not contain ethanol, which has been used to give a "feeling of use" among the constituents of toothpaste, and it has a refreshing feeling. Oral compositions are under consideration. Also, as a liquid toothpaste for children, the content of ethanol in the products that have been released before is less than half 7
% Blends are also on sale. However, according to the studies by the inventors, it is said that children still have a strong irritation and are difficult to use, and an oral composition having less irritation is desired.

The oral composition such as a liquid toothpaste containing less than half or no ethanol in the product, and thus having less irritation, has a better storability than the conventional oral composition having an ethanol content of about 15% or more. Since the (inhibition of the propagation of miscellaneous bacteria) is weak, it is considered to add an antiseptic agent to improve the preservability. Examples of the preservative used in the oral composition include isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, ethyl paraoxybenzoate, butyl paraoxybenzoate, propyl paraoxybenzoate, methyl paraoxybenzoate, benzoic acid, sodium benzoate, salicylic acid. Examples thereof include methyl, potassium sorbate, and sodium dehydroacetate, but sodium benzoate or sodium salicylate, which has less irritation during use, has been conventionally preferred.

As described above, it is already known to use an alkyl ester of paraoxybenzoic acid as a preservative for oral compositions, but what kind of alkyl ester compound exhibits an excellent effect as a preservative? It is not uniform depending on the composition of the composition for use. For example, JP-A-58-1
Japanese Patent No. 57714 discloses an oral composition comprising methyl paraoxybenzoate in an oral composition containing one or more sweeteners selected from natural sweeteners having a sugar residue and sweeteners having a peptide ester. Things are listed. Here, when the paraoxybenzoic acid alkyl ester is evaluated by the phenol coefficient, and when it is evaluated by the minimum inhibitory concentration against Gram-positive bacteria and Gram-negative bacteria, butyl paraoxybenzoate has the largest antibacterial activity, As a preservative of the oral composition containing a sweetener, the use of methyl ester alone is claimed to be particularly effective.

On the other hand, it has been already known that a quaternary ammonium-based bactericide is used as an oral composition for preventing tooth decay and periodontal diseases. For example, in Japanese Patent Publication No. 3-47245, thymol is used for an oral composition comprising a combination of one or more bactericides selected from cationic bactericides and zwitterionic bactericides and nonionic surfactants. , A biosol and butyl parahydroxybenzoate, and a composition for oral cavity containing one or more selected from them. And the fourth cationic bactericide
The case where it is a primary ammonium salt is described. Also,
Japanese Patent Publication No. 6-29177 discloses an oral composition comprising a combination of one or more bactericides selected from cationic bactericides and zwitterionic bactericides and nonionic surfactants. -Hydroxybenzoic acid (salicylic acid), ester products of m-hydroxybenzoic acid methyl, ethyl, propyl, butyl, etc. Ester products of methyl gallate, ethyl, propyl, etc., eugenol, isoeugenol,
It describes an oral composition containing one or two or more derivatives of banitrop, 4-ethylguaiacol phenol and polyhydric phenol. However, this publication does not describe addition of an alkyl ester of paraoxybenzoic acid, nor does it describe the necessity of a preservative.

[0008]

DISCLOSURE OF THE INVENTION The object of the present invention is to provide a liquid having extremely excellent storage stability, low irritation and excellent safety.
The present invention provides a composition for oral cavity. Further, in the present invention, not contained at all in ethanol or in the product or a content of less than half of conventional in the product, irritation less Ruki Shirito <br/> chromatography is most commonly used as a sweetener for liquid oral composition using sugar alcohols such as Le, and an object thereof is to provide a liquid oral composition having an optimal antiseptic effect. Incidentally, it has been conventionally said that sodium benzoate or sodium salicylate is preferable as described above in order to give an antiseptic effect to an oral composition having less irritation.

[0009]

The above objects are achieved by the oral composition of the present invention. That is, (1) a flavor-imparting and solubility-improving agent together with sugar alcohol
As a mixture, a mixture of propyl paraoxybenzoate and methyl paraoxybenzoate is blended in the oral composition, and the mixing ratio of both in the mixture is 1 part to 6 parts of methyl paraoxybenzoate to 1 part of propyl paraoxybenzoate.
And a liquid oral composition. (2) The mixing ratio of the two in the mixture is 1 part of propyl paraoxybenzoate to 4 parts of methyl paraoxybenzoate, wherein the ratio is (1).
Liquid oral composition. (3) The liquid oral composition according to the item (1) or (2), wherein 0.1% by weight or less of the mixture is blended with respect to the total amount of the liquid oral composition. (4) The liquid oral composition according to item (1) or (2), wherein the amount of the mixture is 0.05% by weight or less based on the total amount of the liquid oral composition. (5) of active ingredient to be blended in the liquid oral composition wherein (1) term, which is a quaternary ammonium-based disinfectant (4) liquid according to any one of items <br/> Oral composition. (6) Item (1) to (5), wherein a nonionic surfactant is added to the liquid oral composition.
The liquid oral composition according to any one of items. (7) Item (1) to (6) above, wherein the base of the liquid oral composition is water and / or a lower alcohol having 2 or more carbon atoms, and its formulation is liquid. The liquid oral composition according to any one of 1.

As already mentioned above, in the conventional oral composition, a large amount (about 15%) of ethanol is blended in order to obtain a refreshing sensation called "feeling of use" due to irritation. Insufficient examination of storability,
It has been considered sufficient to use butyl paraoxybenzoate or sodium benzoate alone. Further, as described above, the effect of preservative effect due to the antiseptic action varies depending on the composition of the oral composition, and therefore it is necessary to select and use an antiseptic effect suitable for the composition. Gist of the present invention, ethanol in the product is not included or no a content of less than half of conventional stimulation is small, and use the most universally used have sugar alcohols such as Ruki xylitol as a sweetener Among the liquid oral compositions, the one which gives the optimum antiseptic effect has been found in a mixture of conventional antiseptics which has not been sufficiently studied.
The mixture of propyl paraoxybenzoate and methyl paraoxybenzoate (hereinafter referred to as the mixture of the present invention) not only has an excellent antiseptic effect and improves the preservability of the liquid oral composition, but i) has a stimulating taste. It has a good usability. ii) Good solubility because it is a mixture of similar esters,
It dissolves well with a small amount of alcohol. Therefore, it can be said that it is an additive having a function of imparting flavor and a function of improving solubility rather than a simple preservative.
Among the examined mixture of preservatives, the one which gives an excellent antiseptic effect is a mixture of 1 part to 6 parts of methyl paraoxybenzoate with 1 part of propyl paraoxybenzoate. The mixture giving the best antiseptic effect is a mixture of 1 part propyl paraoxybenzoate and 4 parts methyl paraoxybenzoate. The composition for oral cavity in which the mixture of methyl paraoxybenzoate and propyl paraoxybenzoate provides a particularly excellent antiseptic effect, the active ingredient is a quaternary ammonium-based bactericide, and the composition for oral cavity is nonionic. It is preferable that a surfactant is blended. That is.

Therefore, the "mixture of the present invention" means a mixture of 1 part to 6 parts of methyl paraoxybenzoate with 1 part of propyl paraoxybenzoate, preferably 1 part of propyl paraoxybenzoate with paraoxybenzoic acid. It refers to a mixture of 1 part to 4 parts of methyl acid. In other words, in the liquid oral composition of the above composition of the present invention, any of the compounds of methyl, ethyl, propyl and butyl of paraoxybenzoic acid, which has been regarded as a preservative which gives an excellent antiseptic effect, is also benzoic acid. This means that sodium and sodium salicylate alone did not provide the antiseptic effect, which is good in the case where the liquid oral composition has less than half the conventional alcohol.

[0012] In the present invention, the liquid oral compositions of interest, Mausuwoshu, liquid dentifrice, liquid dentifrice such as-out liquid tooth <br/> polishing, breath fresheners and mouthwashes (gargle) , Troches, chewing gum and the like, and the effect is particularly clear and preferable when the dosage form is liquid such as mouthwash, liquid toothpaste, liquid toothpaste mouthwash and mouthwash. Examples of the sugar alcohol of the artificial sweetener to be mixed in the liquid oral composition of the present invention include xylitol, sorbitol, mannitol, erythritol and the like. Further, as an active ingredient to be mixed in the liquid oral composition of the present invention, dextranase, lytic enzyme (lysozyme chloride etc.), mutanase, chlorhexidine hydrochloride, chlorhexidine gluconate, sorbic acid, alexidine, hinokitiol, alkylglycine, Triclosan, alkyldiaminoethylglycine salt, β-aminocaproic acid, tranexamic acid, vitamin E, sodium monofluorophosphate, sodium fluoride, cuprous fluoride, water-soluble primary or secondary phosphate, quaternary ammonium salt Compounds, allantoin, potassium nitrate, aluminum lactate, sodium pyrophosphate, sodium polyphosphate, potassium phosphate, glycyrrhizinate, glycyrrhizic acid, β-glycyrrhetinic acid, ascorbic acid, isopropylmethylphenol, sodium chloride Examples thereof include triumnium and the like, but quaternary ammonium compounds are preferable. Examples of the quaternary ammonium compound include cetylpyridinium chloride (CPC), benzalkonium chloride, benzethonium chloride, benzenium chloride, decalinium chloride and the like, and mixtures thereof, with cetylpyridinium chloride being particularly preferred. If the concentration of cetylpyridinium chloride contained in the oral composition is 100 ppm, that is, 0.01% or less, the antibacterial activity is significantly reduced. Cetylpyridinium chloride may be usually added in an effective amount, but since it has bitterness, its content is preferably low, and in this case, the upper limit is 0.05%.

In the present invention, as the surfactant, when a quaternary ammonium compound such as cetylpyridinium chloride is used as an active ingredient, a substance which does not inhibit the bactericidal activity of the quaternary ammonium compound such as cetylpyridinium chloride is used. Are preferred, and examples thereof include polyoxyethylene polyoxypropylene glycol and polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 40 to 100. Furthermore, considering the fact that the object of the present invention is no taste, that is, bitterness, and proper foaming, the nonionic surfactants as described above are preferable, and polyoxyethylene (160) polyoxypropylene glycol ( 30), polyoxyethylene hydrogenated castor oil (60 to 100) is good, and also in terms of pH stability, polyoxyethylene (160) polyoxypropylene glycol (30), polyoxyethylene hydrogenated castor oil (60 to 100) Is preferred. Further, the amount of the surfactant blended may be an amount of foaming during use, and may be in the range of 0.01 to 1.0%.

As other components of the present invention, appropriate components are used depending on the kind of the oral composition. For example, as the thickener, brown algae extract, carrageenan, carboxyvinyl polymer, sodium carboxymethyl cellulose, licorice extract, agar, gelatin, sodium fibrin glycolate, sodium polyacrylate, hydroxyethyl cellulose, polyethylene glycol 400, polyethylene glycol 600, polyethylene Glycol 1
500, polyethylene glycol 6000, etc., as a pH adjusting agent, tartaric acid, sodium hydroxide, sodium monohydrogen phosphate, sodium dihydrogen phosphate, sodium phosphate, citric acid, dilute hydrochloric acid, etc. Other buffering agents or neutral salts Is sodium N-acyl-L-glutamate, ascorbic acid, sodium alginate, disodium edetate, tetrasodium edetate dihydrate, zinc chloride, sodium chloride, tartaric acid, sodium cetyl sulfate, sorbit, sodium hydrogencarbonate, copper chlorophyllin. Fragrance ingredients such as sodium, sodium lactate, sodium hydroxide, sodium citrate, menthol, thymol,
Carvacrol, anethole, eucalyptus oil, methyl salicylate, cinnaldehyde, eugenol, d-
As a water-soluble organic solvent such as borneol, glycerin,
Propanol, propylene glycol, other additives such as crystalline cellulose, aluminum oxide, calcium hydrogen phosphate for toothpaste, methyl cellulose, liquid paraffin, calcium hydrogen phosphate and magnesium phosphate,
Examples include calcium pyrophosphate and ground calcium carbonate.

[0015]

[Action] ethanol are not included or no a content of less than half of conventional in the product, the liquid oral composition using sugar alcohols such as key Shirito <br/> Le as a sweetener, the optimal The mixture of the present invention which imparts the antiseptic effect is, as will be apparent from the following examples, 1 part to 6 parts of methyl paraoxybenzoate to 1 part of propyl paraoxybenzoate.
1 part of propyl paraoxybenzoate and 4 parts of methyl paraoxybenzoate are mixed with 1 part of propyl paraoxybenzoate. The reason for this is not clear yet.

[0016]

EXAMPLES The present invention will be described in detail below with reference to test examples and examples, but the present invention is not limited to these examples.

The liquid oral composition of the present invention or the oral composition for comparison is based on a mouthwash formulation consisting of polyoxyethylene hydrogenated castor oil, glycerin, monosodium phosphate and disodium phosphate. , alcohols and a small amount or not used, select the cetylpyridinium chloride as an active ingredient, using the key xylitol as a sweetener, a base as the oral composition of water and and dosage form liquid, to which p-hydroxybenzoate Propyl acid salt, methyl paraoxybenzoate, sodium benzoate and the like were added alone or in combination and adjusted. In addition, as a reference example
It also shows the case where the soda is used. Examples , reference
For Reference Example Alternatively comparative example, the taste of the liquid, the germicidal and antiseptic were evaluated as follows with evaluating the stability (sediment generation degree). That is, the sterilizing power was obtained by taking 0.4 ml of the test solution in a sterilized test tube and adding the test solution to Streptococcus.
Bacterial fluid 0.1 obtained by culturing mutans MT 8148R
ml was added, and the mixture was immediately stirred, and after 30 seconds, 0.
1 ml of SCDLP (Soybeen casein digest broth wi
th lectin and polysorbate (80)) liquid medium, 0.1 ml of the diluted solution was smeared on the medium for SCDLP measurement, and after culturing, the number of surviving bacteria was measured to evaluate the bactericidal activity. As for the antiseptic activity, 1 ml of each of the four kinds of bacteria (Escherichia coli, Bacillus subtilis, Staphylococcus aureus and Pseudomonas aeruginosa) cultured up to 1 × 10 ⁸ cells with BHI broth was added to each formulation solution 50
Add to ml and leave at 36 ° C for 1 day. Then, 0.1 ml of the formulation solution containing the bacterial solution is appropriately diluted with SCDLP liquid medium, and 0.1 ml of the diluted solution is used for SCDLP.
After smearing on the measuring medium and measuring the number of surviving bacteria after culturing,
The antiseptic power was evaluated.

In the following Examples , Reference Examples and Comparative Examples, the evaluation results of the liquid properties of the test liquids are shown in Tables 1 to 9, and the meanings of the symbols in the tables are as follows. Taste: ○ Good taste, △ No change, × Poor Ori formation: ＋＋ ＋ ＋ ＋ ＋ ＋ Slightly − No sterilizing power ： ○ Surviving bacterial count is 10 ^-5 or less compared to physiological saline △ 10 ^-5 〜 10 ^-3 × 10 ^-3 or more Preservative power: ○ The number of ^surviving bacteria is 10 ^-5 or less compared to physiological saline △ 10 ^-5 -10 ^-3 × 10 ^-3 or more

In Reference Examples 1 to 6, alcohol was not included,
Liquid oral composition when saccharin soda is used as a sweetener (other liquid oral compositions include polyoxyethylene hydrogenated castor oil, glycerin, monosodium phosphate and disodium phosphate) and it includes a mixture or a conventional preservative present invention. However, reference example 8 the following references
In the examples and all the comparative examples, the compounding components described in the parentheses are described in the table and omitted in the description. ) Was evaluated for the properties of the preparation liquid. The prescriptions and the evaluation results are shown in Tables 1 and 2.

[0020]

[Table 1]

[0021]

[Table 2]

Reference Examples 7 to 14 contain alcohol,
The properties of the formulation liquid were evaluated for the oral composition using saccharin soda as the sweetener. The formulations and the evaluation results are shown in Table 2 and Table 3 below.

[0023]

[Table 3]

In Comparative Examples 1 to 13, the properties of the preparation liquids were evaluated in the case where saccharin soda was used as a sweetener without containing alcohol and the conventional preservative, which was not the mixture of the present invention, was added. . The prescriptions and the evaluation results are shown in Tables 4, 5, and 6.

[0025]

[Table 4]

[0026]

[Table 5]

[0027]

[Table 6]

In Comparative Examples 14 to 19, the properties of the liquid preparations containing alcohol and using saccharin soda as a sweetener and containing a conventional preservative were evaluated. The formulations and the evaluation results are shown in Table 6 above and Table 7 below.

[0029]

[Table 7]

In Examples 1 to 5 , the properties of the liquid preparations were evaluated for liquid oral compositions in which xylitol was used as a sweetener as a typical example of sugar alcohol, with and without alcohol. Table 8 shows the formulations and the evaluation results. Other examples of sugar alcohols, for example, sorbitol, mannitol, and erythritol were also evaluated, and the same formulation liquids showed excellent properties when xylitol was used in Examples 1 to 5 , but they are described here. Absent.

[0031]

[Table 8]

In Comparative Examples 20 to 25, the case of using xylitol as a sweetener as a representative example of sugar alcohol in the case of containing alcohol and the case of not containing alcohol, and the preservative is not the one of the present invention Was evaluated. Table 9 shows the prescriptions and the evaluation results.

[0033]

[Table 9]

[0034] The respective embodiments, from the results of Reference Examples and Comparative Examples, using an artificial sweetener der Ru sugar alcohol as a sweetener, and a base with water, the dosage form is oral composition of liquid , A mixture of 1 part to 6 parts of methyl paraoxybenzoate with 1 part of propyl paraoxybenzoate, in particular, a mixture of 1 part of propyl paraoxybenzoate with 4 parts of methyl paraoxybenzoate has excellent storage stability. It shows and tastes good.

[0035]

【The invention's effect】

1) Since the mixture of propyl paraoxybenzoate and methyl paraoxybenzoate used in the present invention has good solubility, it can be dissolved well even if the alcohol content is low, and the oral composition has a liquid dosage form. Suitable for things. 2) The composition for oral cavity of the present invention is excellent in safety and contributes to improving the feeling of use (flavor). 3) The mixture of propyl paraoxybenzoate and methyl paraoxybenzoate according to the present invention has an excellent antiseptic effect and an effect equal to or higher than that of butyl paraoxybenzoate alone.

─────────────────────────────────────────────────── ─── Continuation of the front page (56) Reference JP-A-7-25734 (JP, A) JP-A-4-159212 (JP, A) JP-A-5-931 (JP, A) JP-A-5- 929 (JP, A) JP 64-85909 (JP, A) (58) Fields investigated (Int.Cl. ⁷ , DB name) A61K ^7/ 00-7/50

Claims (7)

(57) [Claims] 1. A flavor-imparting and dissolving with sugar alcohol.
As a sex improving agent, a mixture of propyl paraoxybenzoate and methyl paraoxybenzoate is mixed in the oral composition,
The mixing ratio of the two in the mixture is 1 part of propyl paraoxybenzoate to 1 part of methyl paraoxybenzoate.
Liquid composition for oral cavity, characterized in that it is from 6 parts to 6 parts. Wherein the mixing ratio of the two in the mixture, according to claim 1, characterized in that to 1 part propyl parahydroxybenzoate is 4 parts of methyl parahydroxybenzoate
The liquid oral composition according to item 4. 3. The liquid oral composition according to claim 1, wherein 0.1% by weight or less of the mixture is blended with respect to the total amount of the liquid oral composition. 4. The liquid oral composition according to claim 1, wherein 0.05% by weight or less of the mixture is blended with respect to the total amount of the liquid oral composition. 5. A liquid according to any one of claims 1 to 4, characterized in that the active ingredient be incorporated into the liquid oral composition is a quaternary ammonium fungicides
Body- oral composition. 6. The liquid oral composition according to any one of claims 1 to 5, wherein a nonionic surfactant is added to the liquid oral composition. 7. The liquid oral composition base material is water and / or a lower alcohol having 2 or more carbon atoms, and its dosage form is a liquid.
The liquid oral composition according to any one of 1.