JP2024089892A - Oral Composition - Google Patents

Abstract

To improve the retentivity of dodecylpyridinium chloride on a tooth surface.SOLUTION: An oral composition contains dodecylpyridinium chloride and PCA ethyl cocoyl arginate.SELECTED DRAWING: None

Description

The present invention relates to an oral composition.

2. Description of the Related Art Conventionally, oral compositions intended for the prevention and treatment of periodontitis and stomatitis have been known.
Patent Document 1 discloses a composition for inhibiting plaque formation, which contains a quaternary ammonium salt having a C10 to C14 alkyl group, and cites dodecylpyridinium chloride as an example of the quaternary ammonium salt.

JP 2022-58280 A

Dodecylpyridinium chloride is known to exert its antibacterial activity while remaining on the tooth surface. In oral compositions such as those described in Patent Document 1, there is a demand for improved retention of dodecylpyridinium chloride on the tooth surface in order to allow the antibacterial activity of dodecylpyridinium chloride to be exerted for a longer period of time.

The oral composition for solving the above problems comprises dodecylpyridinium chloride and ethyl cocoyl arginine PCA.
The oral composition preferably contains the dodecylpyridinium chloride in an amount of 0.01% by mass or more and 0.1% by mass or less, and the cocoyl arginine ethyl PCA in an amount of 0.01% by mass or more and 0.1% by mass or less.

The oral composition of the present invention can improve the retention of DPC on the tooth surface.

An embodiment of the oral cavity composition according to the present invention will be described.
The oral composition contains dodecylpyridinium chloride (hereinafter also referred to as "DPC") and ethyl cocoyl arginine PCA. By containing DPC and ethyl cocoyl arginine PCA, the oral composition can improve the retention of DPC on the tooth surface.

Each component constituting the oral composition will be described below.
<DPC>
DPC is generally used as a cationic bactericide. The DPC is not particularly limited, and any known DPC can be used.

The content of DPC is not particularly limited. The lower limit of the content of DPC is preferably 0.01% by mass, more preferably 0.03% by mass. The upper limit of the content of DPC is preferably 0.1% by mass, more preferably 0.07% by mass. The upper or lower limit of the range may be, for example, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, or 0.09% by mass.

By ensuring that the content of DPC is within the above range, the dispersibility of DPC in the oral composition can be improved, while the bactericidal action of DPC can be suitably exerted.
<Cocoyl arginine ethyl PCA>
Cocoyl arginine ethyl PCA is a type of cationic surfactant, and is also called N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate or CAE (registered trademark). There is no particular limitation on the cocoyl arginine ethyl PCA, and any known cocoyl arginine ethyl PCA can be used.

The content of cocoyl arginine ethyl PCA is not particularly limited. The lower limit of the content of cocoyl arginine ethyl PCA is preferably 0.01% by mass, more preferably 0.03% by mass. The upper limit of the content of cocoyl arginine ethyl PCA is preferably 0.1% by mass, more preferably 0.07% by mass. The upper or lower limit of the range may be, for example, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, or 0.09% by mass.

<Other ingredients>
The oral cavity composition may contain other components other than those described above, such as medicinal components, surfactants, abrasives, humectants, thickeners, stabilizers, preservatives, sweeteners, pH adjusters, antioxidants, flavors, colorants, etc., depending on the application purpose, form, use, etc. Each of these components may be any known component that is contained in an oral cavity composition. Each of these components may be used alone or in combination of two or more.

Examples of the medicinal components include bactericides, blood circulation promoters, anti-inflammatory agents, bleeding improving agents, tissue repair agents, and remineralization agents.
Specific examples of medicinal ingredients include bactericides such as cationic bactericides such as cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, chlorhexidine gluconate, and chlorhexidine hydrochloride, amphoteric bactericides such as dodecyldiaminoethylglycine, halogenated diphenyl ethers such as triclosan (2',4,4'-trichloro-2-hydroxy-diphenyl ether), phenolic bactericides such as isopropylmethylphenol, and hinokitiol.

Examples of blood circulation promoters include vitamin E such as dl-α-tocopherol acetate, tocopherol succinate, and tocopherol nicotinate, and enzymes such as dextranase, amylase, protease, mutanase, lysozyme, and bacteriolytic enzyme (retic enzyme).

Anti-inflammatory agents include epsilon aminocaproic acid, dipotassium glycyrrhizinate, and the like.
Examples of bleeding improving agents include tranexamic acid and ascorbic acid.

Examples of tissue repair agents include allantoin.
Remineralizing agents include fluorine compounds such as sodium fluoride.
Other examples include plant extracts extracted with water-soluble solvents, chlorophyll, sodium chloride, zinc chloride, potassium nitrate, etc.

Specific examples of the surfactant include nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants.
(Nonionic Surfactant)
Specific examples of nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid esters and maltose fatty acid esters, sugar alcohol fatty acid esters such as maltitol fatty acid esters, sorbitan fatty acid esters such as sorbitan stearate and sorbitan monolaurate, polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan laurate (also called polysorbate 20), polyoxyethylene sorbitan stearate (also called polysorbate 60), and polyoxyethylene sorbitan oleate (also called polysorbate 80), fatty acid alkanolamides such as lauric acid diethanolamide, polyoxyethylene sorbitan fatty acid esters such as sorbitan stea ... fatty acid esters such as sorbitan stearate (also called polysorbate 60), and polyoxyethylene sorbitan fatty acid esters such as sorbitan stearate (also called polysorbate 60), and polyoxyethylene sorbitan fatty acid esters such as sorbitan stearate (also called polysorbate 60), and polyoxyethylene sorbitan fatty Examples of the polyoxyethylene alkyl ethers include polyoxyethylene stearyl ether and polyoxyethylene oleyl ether; polyethylene glycol fatty acid esters such as polyethylene glycol monooleate and polyethylene glycol monolaurate; alkyl glycosides such as lauryl glycoside and decyl glycoside; polyglycerin fatty acid esters, polyoxyethylene glycerin fatty acid esters, polyoxyethylene fatty acid esters, alkyl glucosides, polyoxyethylene hydrogenated castor oil (those having an average number of moles of ethylene oxide added of 10, 20, 40, or 60), glycerin fatty acid esters, and polyoxyethylene propylene block copolymers.

(Anionic Surfactant)
Specific examples of anionic surfactants include sulfate salts such as sodium lauryl sulfate and sodium polyoxyethylene lauryl ether sulfate, sulfosuccinates such as sodium lauryl sulfosuccinate and sodium polyoxyethylene lauryl ether sulfosuccinate, acylamino acid salts such as sodium cocoyl sarcosine and sodium lauroyl methyl alanine, and sodium cocoyl methyl taurate.

(Cationic Surfactant)
Specific examples of cationic surfactants include, in addition to the above-mentioned cocoyl arginine ethyl PCA, quaternary alkyl ammonium salts such as cetyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, and stearyltrimethylammonium chloride, and chlorhexidine gluconate.

(Amphoteric surfactant)
Specific examples of amphoteric surfactants include amino acid type amphoteric surfactants such as N-lauryldiaminoethylglycine and N-myristyldiethylglycine, betaine type amphoteric surfactants such as alkyldimethylaminoacetic acid betaine, N-alkyl-N'-carboxymethyl-N'-hydroxyethylethylenediamine salt, and 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine.

Specific examples of abrasives include calcium carbonate, calcium phosphate, dibasic calcium phosphate, calcium pyrophosphate, insoluble sodium metaphosphate, titanium oxide, amorphous silica, crystalline silica, abrasive silica, thickening silica, aluminosilicate, aluminum oxide, titanium oxide, aluminum hydroxide, resin, hydroxyapatite, etc. The above-mentioned silica is also called silicic anhydride.

Specific examples of humectants include propylene glycol, glycerin, sorbitol, polyethylene glycol, 1,3-butylene glycol, water, alcohol, etc. Specific examples of water include distilled water, pure water, ultrapure water, purified water, tap water, etc. Specific examples of alcohol include ethanol.

Specific examples of thickeners include sodium polyacrylate, carrageenan, sodium carboxymethylcellulose, sodium alginate, xanthan gum, hydroxyethyl cellulose, crystalline cellulose, hydroxypropyl methylcellulose, methylcellulose, propylene glycol alginate, etc. Thickeners are also called binders.

Specific examples of stabilizers include sodium edetate, sodium thiosulfate, sodium sulfite, calcium lactate, lanolin, triacetin, castor oil, magnesium sulfate, etc.

Specific examples of preservatives include 1,2-dibromo-2,4-dicyanobutane, photosensitizers, isothiazolone derivatives, hydantoin derivatives, parabens, sodium benzoate, phenol, and methyl paraoxybenzoate.

Specific examples of sweeteners include saccharin, saccharin sodium, acesulfame potassium, stevia extract, palatinose, palatinit, erythritol, maltitol, xylitol, lactitol, etc.

Specific examples of pH adjusters include citric acid, phosphoric acid, malic acid, pyrophosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, or chemically possible salts thereof, sodium hydroxide, etc.

Specific examples of the antioxidant include tocopherols, dibutylhydroxytoluene, butylhydroxyanisole, and gallic acid esters.
The flavoring may be a natural flavoring or a synthetic flavoring, and may be a single flavoring or a blend of flavorings.

Specific examples of fragrances include l-menthol, d-carvone, anethole, eugenol, methyl salicylate, limonene, ocimene, n-decyl alcohol, citronellol, α-terpineol, methyl acetate, citronellyl acetate, methyl eugenol, cineole, linalool, ethyl linalool, thymol, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, perilla oil, wintergreen oil, clove oil, eucalyptus oil, pimento oil, d-camphor, d-borneol, fennel oil, cinnamon oil, cinnamaldehyde, peppermint oil, and vanillin.

Specific examples of colorants include legal dyes such as Green No. 1, Green No. 3, Blue No. 1, Yellow No. 4, Yellow No. 5, Red No. 102, and Red No. 3, sodium copper chlorophyll, and titanium oxide.

The content of the other components is not particularly limited. The content of the other components is preferably 90% by mass or less in total, more preferably 85% by mass or less in total, and even more preferably 70% by mass or less in total. Furthermore, the content of the other components excluding the wetting agent is preferably 60% by mass or less in total, more preferably 55% by mass or less in total, and even more preferably 50% by mass or less in total.

<Application form, dosage form, and use of oral composition>
The application form of the oral composition is not particularly limited, and it can be used, for example, as a medicine, a designated quasi-drug, a quasi-drug, or a cosmetic.

The dosage form of the oral composition is not particularly limited, and it can be prepared as appropriate in a solid, semi-solid (hereinafter also referred to as a gel), liquid, etc. Examples of solid or semi-solid forms include powder, paste, liquid, etc., which conform to the dosage forms of dentifrice stipulated by the Japan Toothpaste Manufacturers Association.

The use of the oral composition is not particularly limited, and any known use may be appropriately adopted. Examples of uses of the oral composition include an agent for application to the oral cavity, including the tongue, an anti-inflammatory agent for gums, a treatment for periodontal disease, a denture wearing agent, an implant care agent, a toothpaste, a tooth powder, a liquid toothpaste, a moisturizing toothpaste, and a mouthwash.

<Action and Effects>
The action of the oral composition of this embodiment will be described.
The oral composition of the present invention contains ethyl cocoyl arginine PCA, which is a cationic surfactant, and thus makes it easier for DPC to remain on the tooth surface. In other words, the retention of DPC can be improved.

The effects of the oral composition of this embodiment will be described.
(1) The oral composition contains DPC and cocoyl arginine ethyl PCA.
This improves the retention of DPC on the tooth surface, thereby enabling the antibacterial activity of DPC to be exerted for a longer period of time.

(2) Contains DPC at a ratio of 0.01% by mass to 0.1% by mass and ethyl cocoyl arginine PCA at a ratio of 0.01% by mass to 0.1% by mass. Therefore, it is possible to improve the dispersibility of DPC in the oral composition while suitably improving the retention of DPC on the tooth surface.

In the following, examples will be given in order to more specifically explain the configuration and effects of the present invention, but the present invention is not limited to these examples.
The oral compositions of Examples 1 to 16 and Comparative Examples 1 to 4 shown in Tables 1 and 2 were produced by mixing the components in a conventional manner. In Tables 1 and 2, the numbers written to the right of each component indicate the content (mass%) of each component, which were mixed so that the total was 100 mass%.

In Tables 1 and 2, Mekxance (registered trademark) M means methyl paraoxybenzoate manufactured by Ueno Pharmaceutical Co., Ltd. PEG-60 means polyoxyethylene hydrogenated castor oil with an average number of moles of ethylene oxide added of 60. A commercially available synthetic fragrance was used as the fragrance.

(Evaluation test)
The retention of DPC on the tooth surface was evaluated for the oral compositions (hereinafter also referred to as test specimens) of Examples 1 to 16 and Comparative Examples 1 to 4. The evaluation method and evaluation results are shown below.

(Method of Evaluating Retention of DPC)
A pretreated hydroxyapatite (hereinafter also referred to as HAP carrier) was prepared and an adsorption test was carried out according to the following procedure.

[Preparation of pretreatment solution]
Bovine serum albumin (Sigma-Aldrich) was added to Dulbecco's Phosphate Buffered Saline (Sigma-Aldrich) to a concentration of 0.3% by mass. The mixture was stirred with a touch mixer until completely dissolved to prepare a pretreatment solution. The pretreatment solution was refrigerated until it was used for testing.

[Preparation of HAP carrier]
A HAP carrier that behaves similarly to a tooth surface was prepared according to the following procedure.
50 mg of hydroxyapatite powder (Bio-Gel HTP Gel; manufactured by BIO-RAD Lab.) was weighed into a PP tube (Falcon 2059). 2 mL of the above pretreatment solution was added to this hydroxyapatite powder, and the mixture was homogenized using a touch mixer, after which it was shaken for about 15 hours in a thermostatic chamber set at 37°C. Thereafter, it was centrifuged again at room temperature, 3000 rpm, and 5 minutes, and the supernatant was removed to obtain a HAP carrier.

[Adsorption test]
About 50 mg of the HAP carrier obtained above was weighed, and 2 mL of each test sample was added. After homogenizing with a touch mixer, the mixture was shaken for 15 minutes in a thermostatic chamber set at 37°C. Then, centrifugation was performed at room temperature, 3000 rpm, and 5 minutes to remove the supernatant. 2 mL of distilled water was added to the residue obtained. After homogenizing with a touch mixer, the mixture was centrifuged at room temperature, 3000 rpm, and 5 minutes to remove the supernatant. The residue obtained was washed with distilled water under the same conditions as above, and the HAP carrier after adsorption treatment was obtained as the residue.

[Measurement of adsorption amount]
5 mL of extraction solvent (a solution containing 2.88 g of sodium lauryl sulfate dissolved per 1 L of 0.02 M citrate buffer at pH 3: acetonitrile = 1:3) was added to the HAP carrier after the adsorption treatment obtained above, and the DPC adsorbed on the HAP carrier was extracted. The amount of DPC adsorbed on 50 mg of HAP carrier was determined by a known quantitative method using liquid chromatography. The same test was performed three times to determine the average amount of DPC adsorbed.

In addition, the average DPC adsorption amount of Comparative Examples 1 to 4, which do not contain cocoyl arginine ethyl PCA, was used as the standard, in other words, 100%, to determine the rate of change in the average DPC adsorption amount of each Example with the same DPC content. Specifically, the rate of change in the average DPC adsorption amount of Examples 1 to 4 was determined based on the average DPC adsorption amount of Comparative Example 1. The rate of change in the average DPC adsorption amount of Examples 5 to 8 was determined based on the average DPC adsorption amount of Comparative Example 2. The rate of change in the average DPC adsorption amount of Examples 9 to 12 was determined based on the average DPC adsorption amount of Comparative Example 3. The rate of change in the average DPC adsorption amount of Examples 13 to 16 was determined based on the average DPC adsorption amount of Comparative Example 4. The results are shown in the column of the rate of change in adsorption amount (%) in Tables 1 and 2.

The retention of DPC was evaluated according to the following criteria.
Evaluation criteria for DPC retention ◎◎ (particularly excellent): When the rate of change in the average DPC adsorption amount exceeds 220% ◎ (excellent): When the rate of change in the average DPC adsorption amount exceeds 180% and is 220% or less ○○ (good): When the rate of change in the average DPC adsorption amount exceeds 140% and is 180% or less ○ (acceptable): When the rate of change in the average DPC adsorption amount exceeds 100% and is 140% or less × (unacceptable): When the rate of change in the average DPC adsorption amount is 100% or less (Evaluation results)
As seen from Table 1, in all of Examples 1 to 16, the retention of DPC was "fair" or better, confirming that the retention of DPC was improved.

In Examples 1 and 6 to 8, it was confirmed that the retention of DPC was "good." In addition, in Examples 2 to 4, it was confirmed that the retention of DPC was "particularly excellent." This makes it possible to maintain the antibacterial activity of DPC for a longer period of time.

In addition, it was confirmed that when the DPC content is, for example, 0.01% by mass or more and 0.03% by mass or less, and the cocoyl arginine PCA content is 0.03% by mass or more and 0.1% by mass or less, the retention of DPC is "good" or better.

Table 3 below shows formulation examples 1 to 10 when the oral composition of the present invention is used in a liquid or gel form. Table 4 shows formulation examples 11 to 17 when the oral composition of the present invention is used as a toothpaste.

Claims (2)

An oral composition characterized by containing dodecylpyridinium chloride and ethyl cocoyl arginine PCA. The dodecylpyridinium chloride is 0.01% by mass or more and 0.1% by mass or less,
The oral composition according to claim 1, containing the cocoyl arginine ethyl PCA in an amount of 0.01% by mass or more and 0.1% by mass or less.