JP7601374B2 - Oral Composition - Google Patents

Description

The present invention relates to an oral composition.

Biofilms are one of the causes of dental caries and periodontal disease. Biofilms, also known as bacterial membranes, are structures formed by microorganisms such as bacteria. Generally, a biofilm is a film formed by bacterial aggregates covered with glycocalyx, which is made of exopolysaccharides, attached to the surface of a material. Because biofilms have a barrier function on their surface, it is difficult for antibacterial agents to penetrate deep into the biofilm, making it difficult to kill the bacteria inside the biofilm using conventional antibacterial agents alone.

Accordingly, various oral compositions that exhibit a high penetrating effect into biofilms have been developed (see, for example, Patent Documents 1 to 3).
Patent Documents 1 to 3 describe preparations that use isopropylmethylphenol as one of the biofilm bactericidal components.

JP 2011-098919 A JP 2012-131769 A JP 2013-245187 A

However, conventional oral compositions do not yet have sufficient penetrating bactericidal activity against biofilms, and oral compositions with high penetrating bactericidal activity are in demand.

The present invention aims to provide an oral composition that has a high penetrating bactericidal effect against biofilms.

The oral composition according to the present invention comprises camphor and
A phenolic antibacterial agent,
A betaine surfactant,
The camphor content is 0.05 to 5% by mass,
The content of the phenol-based antibacterial agent is 0.0005 to 2% by mass,
The content of the betaine surfactant is 0.01 to 20% by mass,
The phenolic antibacterial agent is isopropyl methylphenol .

In the oral composition according to the present invention, the content of the phenol-based antibacterial agent is preferably 1/10,000 parts by mass or more and 40 parts by mass or less when the content of the camphor is 1 part by mass.
In the oral composition according to the present invention, it is preferable that the content of the betaine surfactant is 1/500 part by mass or more and 400 parts by mass or less when the content of the camphor is 1 part by mass.

In the oral composition according to the present invention, the betaine surfactant is preferably cocamidopropyl betaine.
In addition, the oral composition according to the present invention is preferably a biofilm inhibitor.

The present invention provides an oral composition that has a high penetrating bactericidal effect against biofilms.

Preferred embodiments of the oral composition of the present invention will be described in detail below.
The oral composition according to the present invention comprises camphor, a phenol-based antibacterial agent, and a betaine-based surfactant.
The oral composition according to the present invention is characterized in that the camphor content is 0.05 to 5% by mass, the phenol-based antibacterial agent content is 0.0005 to 2% by mass, and the betaine surfactant content is 0.01 to 20% by mass.
By containing each of the above components in the above-mentioned specified amounts, the permeability into the biofilm is improved, and the biofilm can be effectively sterilized and removed.

In this specification, the oral compositions include dentifrices such as toothpaste, powdered toothpaste, liquid toothpaste, and liquid toothpaste, as well as lozenges, tablets, creams, ointments, patches, mouthwashes, and chewing gums.

<CAMPHOR>
The oral composition of the present invention contains camphor.
Camphor is an ingredient that has effects such as promoting blood circulation, relieving pain, and anti-inflammatory properties.
Examples of camphor include d-camphor and dl-camphor, and these can be used alone or in mixtures.

The camphor content is 0.05 to 5% by mass, preferably 0.1 to 2% by mass, and more preferably 0.3 to 1% by mass. This allows the penetrating bactericidal effect on biofilms to be more effective.

<Phenol-based antibacterial agents>
The oral composition of the present invention contains a phenolic antibacterial agent.
Phenol-based antibacterial agents are components that have antibacterial and bactericidal effects against biofilms.
Examples of phenol-based antibacterial agents include isopropylmethylphenol, triclosan, hinokitiol, thymol, etc., and these can be used alone or in combination of two or more. Among these, isopropylmethylphenol is preferably used because it has a particularly high bactericidal activity against biofilms.

The content of the phenol-based antibacterial agent is 0.0005 to 2% by mass, preferably 0.01 to 1% by mass, and more preferably 0.02 to 0.1% by mass. This allows the agent to more effectively exert its penetrating bactericidal effect on biofilms.

When the above-mentioned camphor content is taken as 1 part by mass, the content of the phenol-based antibacterial agent is preferably 1/10,000 parts by mass or more and 40 parts by mass or less, more preferably 1/200 parts by mass or more and 10 parts by mass or less, and even more preferably 1/50 parts by mass or more and 1/3 parts by mass or less. When the camphor content ratio is within the above range, the permeability of the phenol-based antibacterial agent (particularly isopropyl methylphenol) into the biofilm is increased, and the bactericidal properties against the biofilm can be further enhanced.

<Betaine-based surfactants>
The oral composition according to the present invention further contains a betaine surfactant.
Betaine surfactants are a type of amphoteric surfactant.
Examples of betaine surfactants include cocamidopropyl betaine, lauryl dimethylaminoacetate betaine, lauryl dimethylamine oxide, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolium betaine, N-lauryl diaminoethyl glycine, N-myristyl diaminoethyl glycine, and N-alkyl-1-hydroxyethyl imidazoline betaine sodium, and one or more of these surfactants may be used in combination. Among these surfactants, it is preferable to use cocamidopropyl betaine. This can further improve the bactericidal properties against biofilms.

The content of the betaine surfactant is 0.01 to 20% by mass, preferably 0.1 to 10% by mass, and more preferably 0.4 to 5% by mass. This allows the penetrating bactericidal effect on biofilms to be exerted more effectively.

When the above-mentioned camphor content is taken as 1 part by mass, the content of the betaine surfactant is preferably 1/500 parts by mass or more and 400 parts by mass or less, more preferably 1/20 parts by mass or more and 100 parts by mass or less, and even more preferably 2/5 parts by mass or more and 50/3 parts by mass or less. When the camphor content ratio is within the above range, the bactericidal properties against biofilms can be further improved.

<Other ingredients>
The oral cavity composition of the present invention may contain various ingredients depending on its dosage form, etc. For example, when the oral cavity composition of the present invention is applied to a toothpaste, it may contain abrasives, humectants, binders, foaming agents, sweeteners, preservatives, flavoring ingredients, medicinal ingredients, etc.
Examples of the abrasive include silica-based abrasives such as silica gel, precipitated silica, pyrogenic silica, hydrous silicic acid, anhydrous silicic acid, zeolite, aluminosilicate, and zirconosilicate; crystalline cellulose, dibasic calcium phosphate dihydrate, dibasic calcium phosphate anhydrate, calcium pyrophosphate, tribasic magnesium phosphate, tribasic calcium phosphate, aluminum hydroxide, alumina, light calcium carbonate, heavy calcium carbonate, magnesium carbonate, zirconium silicate, and synthetic resin abrasives; and these can be used alone or in combination of two or more.
The amount of the abrasive blended is not particularly limited, but is preferably 3 to 60% by mass, and more preferably 10 to 45% by mass.

Examples of the humectant include polyhydric alcohols such as glycerin, diglycerin, polyglycerin, 1,3-butylene glycol, polyethylene glycol, 1,2-pentanediol, 1,3-hexanediol, propylene glycol, dipropylene glycol, isopropylene glycol, polypropylene glycol, ethylene glycol, diethylene glycol, triethylene glycol, maltitol, reduced starch syrup, lactitol, palatinit, erythritol, sorbitol, mannitol, xylitol, xylose, trehalose, glucose, lactose, mannose, maltose, fructose, inositol, pentaerythritol, maltotriose, starch decomposition sugar, and starch decomposition sugar reduced alcohol, and these can be used alone or in combination of two or more kinds.
The amount of the wetting agent is not particularly limited, but is preferably from 1 to 60% by mass, and more preferably from 5 to 50% by mass.

Examples of binders include carrageenan (ι, λ, κ), alginic acid, sodium alginate, propylene glycol alginate, calcium-containing sodium alginate, potassium alginate, calcium alginate, ammonium alginate, and other alginic acid and derivatives thereof, xanthan gum, guar gum, gelatin, agar, sodium carboxymethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, sodium polyacrylate, and the like, and one or more of these can be used in combination.
The amount of the binder is not particularly limited, but is preferably 0.1 to 5.0% by mass, and more preferably 0.5 to 3.0% by mass.

Examples of the foaming agent include sodium lauryl sulfate, sodium lauroyl sarcosine, sodium alkyl sulfosuccinate, sodium coconut oil fatty acid monoglycerin sulfonate, sodium α-olefin sulfonate, N-acylamino acid salts such as N-acyl glutamate, maltitol fatty acid esters, sucrose fatty acid esters, glycerin fatty acid esters, fatty acid diethanolamides, polyoxyethylene sorbitan monostearate, polyoxyethylene hydrogenated castor oil, polyoxyethylene fatty acid esters, and the like, and one or more of these can be used in combination.
The amount of the foaming agent is not particularly limited, but is preferably 0.1 to 10.0% by mass, and more preferably 0.5 to 5.0% by mass.

Examples of sweeteners include saccharin sodium, aspartame, trehalose, stevioside, stevia extract, paramethoxycinnamic aldehyde, neohesperidyl dihydrochalcone, perillartine, and the like, and one or more of these can be used in combination.
The amount of the sweetener to be added is not particularly limited, but is preferably 0.005 to 5.0% by mass, and more preferably 0.01 to 3.0% by mass.

Examples of preservatives include parabens such as methylparaben, ethylparaben, propylparaben, and butylparaben, sodium benzoate, phenoxyethanol, and alkyldiaminoethylglycine hydrochloride, and these can be used alone or in combination of two or more kinds.
The amount of the preservative to be added varies depending on the type, etc., but is preferably 0.005 to 5.0% by mass, and more preferably 0.01 to 3.0% by mass.

As the fragrance component, one or more of 1-menthol, anethole, menthone, cineol, limonene, carvone, methyl salicylate, ethyl butyrate, eugenol, cinnamic aldehyde, trans-2-hexenal, etc. may be used in combination. These components may be blended alone, or essential oils containing these may be used.
In addition to the above-mentioned fragrance components, fragrance components such as aliphatic alcohols and their esters, terpene hydrocarbons, phenol ethers, aldehydes, ketones, lactones, and essential oils may be blended within a range that does not impair the effects of the present invention. The blending amount of the above-mentioned fragrances is generally in the range of 0.02 to 2% by mass.

The oral composition of the present invention may further contain active ingredients in addition to those mentioned above. Such active ingredients include lysozyme chloride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, polyethylene glycol, polyvinylpyrrolidone, zeolite, ascorbic acid, ascorbate salts, chlorhexidine salts, cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, dequalinium chloride, bisabolol, ascorbic acid and/or its derivatives, tocopherol acetate, ε-aminocaproic acid, tranexamic acid, aluminum hydroxyl allantoin, aluminum lactate, potassium nitrate, dihydrocholesterol, glycyrrhetinic acid, glycyrrhizinate salts, copper chlorophyllin salt, sodium chloride, guaiazulene sulfonate, dextranase, pyridoxine hydrochloride, and the like. One or more of these may be contained.

In addition to the above-mentioned ingredients, the product may also contain, for example, colorants such as Blue No. 1, pigments such as titanium oxide, antioxidants such as dibutylhydroxytoluene, chelating agents such as edetate, and flavoring agents such as tea extract and tea distillate.

In addition to the above, the oral composition of the present invention may also contain herbal extracts.
Examples of herbal extracts include chamomile extract, valerian extract, jujube extract, hop extract, lamenda extract, linden extract, quince extract, goldenrod extract, kumazasa extract, oleander extract, clove extract, ginseng extract, salvia extract, soapberry extract, platycodon extract, rehmannia extract, peony extract, hawthorn extract, angelica extract, tea extract, oak salicylate extract, bark extract, white birch extract, carrot extract, acacia extract, turmeric extract, and rosemary extract. These may be used alone or in combination of two or more.
In addition to the above-mentioned components, the composition may contain, for example, coloring matter such as Blue No. 1, pigments such as titanium oxide, tea dry distillate, flavoring agents such as sodium glutamate, and the like.

The oral composition of the present invention can be produced in accordance with a conventional method, and the production method is not particularly limited.
The resulting toothpaste or other composition can be filled into an aluminum tube, a laminate tube, a glass-deposited tube, a plastic tube, a plastic bottle, an aerosol container, or the like for use.

Although the oral composition of the present invention has been described above, the present invention is not limited thereto. For example, in addition to the components described above, components having any desired function can be blended into the oral composition of the present invention.

Next, specific examples of the present invention will be described.
1. Production of oral compositions (Examples 1 to 4, Comparative Examples 1 to 8)
The components shown in Table 1 were mixed in the amounts shown in Table 1, and liquid oral compositions were produced in the usual manner.

Table 1 shows the ingredients and amounts thereof for each of the examples and comparative examples.
In the table, isopropylmethylphenol is abbreviated as IMP, cetylpyridinium chloride as CPC, and cocamidopropyl betaine as CPB.

2. Biofilm Penetration Bactericidal Test [Preparation of Biofilm]
Streptococcus mutans (Streptococcus mutans JCM5705) was pre-cultured in SCD medium for 24 hours at 32.5 ° C. to obtain a pre-cultured bacterial solution. The obtained pre-cultured bacterial solution was added to 1% sucrose-containing SCD medium so that the number of bacteria was 10 ⁷ CFU / mL to obtain a cultured bacterial solution, and 2 mL of the cultured bacterial solution was seeded on a 24-well plate. The seeded culture pestle was anaerobically cultured at 37 ° C. for 48 hours to obtain a biofilm.

[Biofilm Penetration Bactericidal Test]
The prepared biofilm was washed twice with 0.01 mL/L phosphate buffered saline (PBS) to remove floating bacteria. 2 mL of the oral composition of each Example and Comparative Example was added to the biofilm of a 24-well plate, left for 10 minutes, and all the supernatant was sucked and removed, and then 2 mL of LP dilution solution was added to the residue and used in an ultrasonic homogenizer to peel off the biofilm from the well plate. 1 mL of the bacterial liquid containing the peeled biofilm was serially diluted with 9 mL of LP dilution solution, and 1 mL of the diluted solution of the obtained bacterial liquid was smeared on a TSA medium, and the viable bacterial count was determined by the pour culture method. Here, in the pour culture method, the sample liquid and the agar medium were mixed and solidified in a petri dish, and cultured under aerobic conditions at 32.5 ° C., and the number of colonies generated after culture was measured visually, and multiplied by a multiplier to obtain the viable bacterial count.

The test results are shown in Table 1.
As can be seen from the test results of Comparative Examples 1 to 4 in Table 1, no penetrating bactericidal effect was observed in the case of cocamidopropyl betaine alone, or in the case of cocamidopropyl betaine and dl-camphor or isopropyl methylphenol.
On the other hand, as can be seen from the test results of Examples 1 to 4 and Comparative Examples 5 to 8, it was confirmed that the addition of three types of dl-camphor, isopropylmethylphenol, and cocamidopropyl betaine in the amounts specified in the present application exerted a penetrating bactericidal effect.
Moreover, as can be seen from the test results of Comparative Example 8, when cetylpyridinium chloride, a cationic bactericide, was used instead of isopropylmethylphenol, no penetrative bactericidal effect was observed.

Claims (5)

Camphor and
A phenolic antibacterial agent,
A betaine surfactant,
The camphor content is 0.05 to 5% by mass,
The content of the phenol-based antibacterial agent is 0.0005 to 2% by mass,
The content of the betaine surfactant is 0.01 to 20% by mass,
The oral composition wherein the phenolic antibacterial agent is isopropyl methylphenol . The oral composition according to claim 1, wherein the content of the phenol-based antibacterial agent is 1/10,000 parts by mass or more and 40 parts by mass or less when the content of the camphor is 1 part by mass. The oral composition according to claim 1 or 2, wherein the content of the betaine surfactant is 1/500 parts by mass or more and 400 parts by mass or less when the content of the camphor is 1 part by mass. 4. The oral composition according to claim 1, wherein the betaine surfactant is cocamidopropyl betaine. The oral composition according to any one of claims 1 to 4, which is a biofilm inhibitor.