JP2021134193A - Oral composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an oral composition which has almost no bitterness at the time of use, is excellent in usability, and can obtain a sufficient osmotic bactericidal effect. SOLUTION: This contains (A) cetylpyridinium chloride and (B) a compound having one or more hydroxyl groups selected from the group consisting of thymol, menthol, and borneol, and has the above (B) with respect to the above (A). An oral composition having a content of more than double. [Selection diagram] None

Description

The present invention relates to oral compositions.

Discomfort such as stickiness and bad breath in the oral cavity is caused by oral bacteria and proteins, and it is considered that saliva-derived proteins are particularly responsible for the stickiness. Bacteria in the oral cavity multiply in the oral cavity to form plaque, and stains in the oral cavity caused by saliva-derived proteins and viscous substances such as plaque form a biofilm, which also causes caries and periodontal disease. ..

In order to reduce such discomfort in the oral cavity and prevent or improve periodontal disease, oral compositions such as dentifrices and mouthwashes containing various components have been studied. In the oral composition, for example, cetylpyridinium chloride (CPC), which is a cationic bactericidal agent, is often used in order to obtain a bactericidal effect.

For example, Patent Document 1 discloses an oral composition having an excellent antibacterial effect and a halitosis removing effect by using a specific copper compound in combination with a bactericidal agent such as cetylpyridinium chloride.

Japanese Unexamined Patent Publication No. 1-153620

However, the biofilm formed by the oral bacteria has a problem that the drug does not easily permeate and the bactericidal effect cannot be obtained, and the conventional oral composition cannot sufficiently obtain the bactericidal effect.
In addition, increasing the amount of cetylpyridinium chloride in the oral composition in order to enhance the bactericidal effect causes bitterness, and the compatibility of cetylpyridinium chloride with other components in the oral composition is poor. Due to the problem, it was difficult to examine the amount of cetylpyridinium chloride compounded.

Therefore, the present invention has been made in view of the above-mentioned conventional circumstances, and provides an oral composition which has almost no bitterness at the time of use, is excellent in usability, and has a sufficient osmotic bactericidal effect. Is the subject.

As a result of diligent studies, the present inventors have found that (A) cetylpyridinium chloride and (B) a compound having one or more hydroxyl groups selected from the group consisting of thymol, menthol, and borneol are contained. We have found that the above problems can be solved by doubling or more the content of (B) with respect to A) in terms of mass ratio, and have completed the present invention.
That is, the present invention relates to the following.

[1]
(A) Cetylpyridinium chloride and
(B) Containing a compound having one or more hydroxyl groups selected from the group consisting of thymol, menthol, and borneol,
An oral composition in which the content of (B) with respect to (A) is at least twice the mass ratio.
[2]
The oral composition according to [1], wherein the content of (A) is 0.005 to 1% by mass.

According to the present invention, it is possible to provide an oral composition that has almost no bitterness during use, is excellent in usability, and has a sufficient osmotic bactericidal effect.

Hereinafter, the present invention will be described in detail, but these show examples of desirable embodiments, and the present invention is not specified in these contents.

The oral composition according to the embodiment of the present invention includes (A) cetylpyridinium chloride and
(B) Containing a compound having one or more hydroxyl groups selected from the group consisting of thymol, menthol, and borneol,
The content of (B) with respect to (A) is more than twice the mass ratio.

<(A) Cetylpyridinium chloride>
In the present invention, (A) cetylpyridinium chloride (hereinafter, may be simply referred to as component (A)) is a cationic fungicide classified as a quaternary ammonium compound having an IUPAC name of 1-hexadecylpyridinium chloride. It is an agent. It has excellent bactericidal activity against oral pathogenic bacteria that cause periodontal disease and caries, and is widely used as a medicinal ingredient in oral compositions.
The blending amount of the component (A) cetylpyridinium chloride is preferably in the range of 0.005% by mass or more and 1% by mass or less, more preferably 0.5% by mass or less, and further preferably 0.01% by mass of the entire oral composition. It is in the range of% or more and 0.3% by mass or less. The larger the blending amount, the higher the bactericidal activity against orally pathogenic bacteria, and when it is 0.005% by mass or more, sufficient bactericidal activity against orally pathogenic bacteria can be exhibited. Further, preferably 1% by mass or less, more preferably 0.5% by mass or less, still more preferably 0.3% by mass or less, in order to make the bitterness of cetylpyridinium chloride less noticeable, it becomes cloudy in low temperature storage. It is also suitable in terms of appearance stability without causing such problems.

<(B) A compound having one or more hydroxyl groups selected from the group consisting of thymol, menthol, and borneol>
The oral composition according to the embodiment of the present invention is a compound having one or more hydroxyl groups selected from the group consisting of (B) thymol, menthol, and borneol (hereinafter, may be simply referred to as component (B)). Contains.
Thymol (2-isopropyl-5-methylphenol) is a nonionic bactericidal agent having a high penetrating bactericidal effect on biofilms that cause periodontal disease and caries.
Menthol and borneol are volatile essential oil components, and are widely used as fragrance components, pest repellent components, insecticidal components, sterilizing components, and deodorizing components.
When the oral composition according to the embodiment of the present invention contains the component (B), the component (B) permeates the biofilm and sterilizes deep bacteria.

The component (B) is a compound that has relatively low solubility in water and is difficult to solubilize. However, in the case of the composition of the present invention, the component (B) contained in the oral composition can be used. Even if the content is more than twice that of the component (A), it is possible to prepare a highly stable oral composition without impairing the appearance stability such as forming agglomerates (aggregates) and causing cloudiness. can. In addition, it is possible to suppress the bitterness of cetylpyridinium chloride and bring about a good refreshing sensation without impairing the flavor, and it is possible to sufficiently impart the performance derived from the component (B). One of the performances derived from the component (B) in the present invention is an action of assisting the improvement of the adsorptivity of the component (A) on the tooth surface. In the oral composition according to the embodiment of the present invention, the adsorption of the component (A) on the tooth surface is improved by setting the content of the component (B) to twice or more the content of the component (A). It is preferable because the effect of the above can be further enhanced.

The blending amount of the component (B) in the oral composition according to the embodiment of the present invention is preferably 0.005% by mass or more, and preferably 0.01% by mass or more of the entire oral composition. More preferably, it is 0.05% by mass or more. When it is 0.005% by mass or more, sufficient osmotic bactericidal activity can be exerted on the biofilm in the oral cavity. Further, if it exceeds 1% by mass, the flavor may deteriorate. Therefore, it is preferably 1% by mass or less, more preferably 0.5% by mass or less, and preferably 0.1% by mass or less. More preferred.

<About the blending ratio of ingredients (A) and (B)>
In the oral composition according to the embodiment of the present invention, the compounding ratio of the component (B) to the component (A) is set to be twice or more by mass ratio, so that the component (A) cetylpyridinium chloride can be added to the tooth surface. It is possible to improve the adsorptivity and suppress the bitterness and irritation to improve the usability.
In particular, the blending ratio of the component (B) to the component (A) is an indispensable factor for further improving the adsorptivity of the component (A) cetylpyridinium chloride to the tooth surface.
By setting the blending ratio of the component (B) to the component (A) to preferably 2 times or more, more preferably 2.5 times or more in terms of mass ratio, the adsorptivity of the component (A) cetylpyridinium chloride to the tooth surface. Can be further improved, which is preferable. The blending ratio of the component (B) to the component (A) is preferably 200 times or less, more preferably 10 times or less in terms of mass ratio.

[Oral composition]
The oral composition according to the embodiment of the present invention may be a liquid oral composition, and a solvent can be used.
When a solvent is used in the oral composition according to the embodiment of the present invention, an aqueous solvent is preferable from the viewpoint of application to the oral cavity, and examples of the aqueous solvent include water, polyethylene glycol, glycerin and a mixture thereof. Examples include liquids.
Among these, water or a water mixture is preferable. As the water, purified water, ionized water, distilled water or the like can be used.

The content of water contained in the solvent is usually preferably 50% by mass or more. When the content of water in the solvent is within the above range, the component (A) and the component (B) are likely to be dissolved in the solvent.

The pH of the oral composition is 4-9. If the pH deviates from the above range, the irritation in the oral cavity becomes strong and the usability deteriorates.

Examples of pH adjusting agents that can be used to adjust the pH to the above range include acetic acid, hydrochloric acid, sulfuric acid, nitrate, citric acid, malic acid, lactic acid, phosphoric acid, benzoic acid, sodium hydroxide, potassium hydroxide and acetic acid. Examples thereof include sodium, sodium carbonate, sodium hydrogen carbonate, sodium citrate, sodium hydrogen citrate, sodium lactate, calcium lactate, sodium phosphate, sodium hydrogen phosphate and the like.

In addition, various components applicable to the oral cavity can be blended in the oral composition according to the embodiment of the present invention as long as the effects of the present invention are not impaired.

For example, in addition to improving the solubility of the component (A) and the component (B) in the solvent, it has the effect of lowering the skin temperature in the oral cavity and the effect of suppressing unnecessary foaming of the entire oral composition. Commercially available alcohols such as fermented alcohols and synthetic alcohols can be used.
Examples of the alcohol include ethanol.
The blending amount of the alcohol is preferably 1% by mass or more, and more preferably 2% by mass or more of the entire oral composition from the viewpoint of assisting the solubility of the component (A) and the component (B) in the solvent. , More preferably 3% by mass or more. Further, in order to suppress the irritation of alcohol and maintain a good feeling of use, the total amount of the oral composition is preferably 30% by mass or less, more preferably 28% by mass or less, still more preferably 25. It is less than mass%.

Ingredients other than alcohol include, for example, wetting agents such as glycerin and propylene glycol, foaming agents such as sodium lauryl sulfate, sweeteners such as stebioside, xylitol, erythritol, sorbitol, sodium saccharin, scullose and trehalose, triclosan and isopropylmethylphenol. Bactericides such as cetylpyridinium chloride, benzethonium chloride, chlorhexidine hydrochloride, enzymes such as protease, fluorine ion sources such as sodium fluoride, fluorophosphate, fluoroborate, calcium sources such as calcium phosphate, hydroxyapatite, calcium gluconate, Preservatives such as methylparaben, ethylenediamine tetraacetate (EDTA-2Na), parahydroxybenzoic acid ester, sodium benzoate, essential oil components such as peppermint oil, peppermint oil, carbachlor, eucalyptus oil, eugenol, anator, cineole, hinokithiol, etc. Examples thereof include crude drugs such as Oubaku extract and Touki extract, pigments such as Blue No. 1, Yellow No. 4, Red No. 102, and Green No. 201, and fragrances such as sage, cloves, cinnamon, and camphor.

In addition, lysoteam chloride, dextranase, mutanase, glycyrrhizinate and its derivatives, glycyrrhetinate and its derivatives, azulene, azulene sulfonic acid, dihydrocholesterol, epidihydrocholesterin, allantin, allantinchlorohydroxyaluminum, sodium chloride, acetic acid. dl-α-tocopherol, dl-α-tocopherol nicotinate, epsilon aminocaproic acid, tranexamic acid, polyphosphate, sodium copper chlorophyllin, vitamins, amino acids and the like can be blended.

In addition, the oral composition may further contain a surfactant.
Examples of the surfactant include polyoxyethylene (POE) hardened castor oil, polyoxyethylene / polyoxypropylene (POE / POP) block polymer, POE / POP alkyl ether, POE alkyl ether, POE alkylphenyl ether, and POE fatty acid. Nonionic surfactants such as esters, POE higher alcohol ethers, POE / POP fatty acid esters, POE sorbitan fatty acid esters, sorbitan fatty acid esters, glycerin fatty acid esters, propylene glycol fatty acid esters, sodium lauryl sulfate, sodium myristyl sulfate, POE alkyl ethers. Sulfate, sodium lauroyl sarcosin, sodium myristyl sarcosin, alkyl ether carboxylate, alkyl phosphate, POE alkyl ether phosphate, N-acyl taurine salt, POE alkyl ether phosphate or phosphate, sulfonate, etc. Anionic surfactants, cationic surfactants such as alkyltrimethylammonium chloride, dialkyldimethylammonium chloride, polyoxyethylene alkylamine fatty acid amides, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine, Examples thereof include amphoteric surfactants such as coconut oil fatty acid amide propyl betaine, lauryl diaminoethylglycine sodium, and lauryl dimethylamino acetate betaine.

From the viewpoint of dissolving the composition components, the blending amount of the surfactant is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, and further preferably 0.1 by mass of the entire oral composition. It is mass% or more. Further, in order to suppress solidification of the composition, the total amount of the oral composition is preferably 30% by mass or less, more preferably 10% by mass or less, and further preferably 1% by mass or less.

<Mouth cleaning method>
The oral cleaning method according to the embodiment of the present invention is a method of cleaning the oral cavity using the above-mentioned oral composition. As described above, the oral composition according to the embodiment of the present invention has almost no bitterness during use, is excellent in usability, and exhibits a sufficient osmotic bactericidal effect. Therefore, by cleaning the oral cavity with such an oral composition, the user can keep the oral cavity clean and is less likely to feel bitterness or the like during use.
In addition, the liquid oral composition according to the embodiment of the present invention can be used by containing an appropriate amount in the oral cavity as a mouthwash, a mouthwash, or the like to wash the mouth. Further, it can also be used as a liquid dentifrice, including an abrasive containing calcium hydrogen phosphate, aluminum hydroxide, silicic anhydride, calcium carbonate and the like, if necessary.

Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited to these examples. Unless otherwise specified, "%" means "mass%" and "part" means "parts by mass".

[Examples 1 to 5, Comparative Examples 1 to 6]
Ingredients (A), Ingredients (B) and other materials and purified water were mixed according to the formulations shown in Table 1 to prepare the respective liquid oral compositions. In addition, the osmotic sterilization test appearance observation evaluation and the cetylpyridinium chloride adsorption test were carried out by the following methods.

(Penetration sterilization test)
The oral compositions prepared in Examples 1 to 5 and Comparative Examples 1 to 6 were subjected to an osmotic sterilization test as follows.
Streptococcus mutans (S. mutans (MT8148R)) was pre-cultured in BHI medium (BD, Bacto (TM) Brain Heart Infusion) at 37 ° C. under anaerobic conditions for 24 hours. The cultured mutans bacteria were washed with phosphate buffered saline (PBS) and centrifuged once to remove the medium.
The obtained mutans bacterium was suspended in 10 mL of PBS, and then OD660 (turbidity at 660 nm) (Thermo Fisher Scientific, Multiskan GO) was measured.
Diluted with 1% sucrose-added BHI medium so that OD660 became 0.0005 to obtain a diluted solution 1 of mutans bacteria.
The obtained diluted solution 1 was added dropwise to a container containing a cell disk (Sumitomo Bakelite Co., Ltd., Celldesk LF1) in an amount of 1 mL each, and the mutans bacteria were cultured under 37 ° C. anaerobic conditions for 17 hours.

The step of immersing the mutans bacteria cultured on the cell disk in 2 mL of PBS in a 24-well plate (IWAKI, a microplate for culturing 24-well cells) for 3 minutes was performed twice. Further, the mutans bacteria cultured in 1 mL of each oral composition and physiological saline prepared in Examples 1 to 5 and Comparative Examples 1 to 6 were immersed together with the cell disk for 3 minutes.
The soaked cell disk was taken out from each oral composition and placed in 10 mL of SCDLP liquid medium (Fujifilm Wako Pharmaceutical Co., Ltd., SCDLP medium "Daigo") to inactivate the bactericide.
The mutans bacteria were dispersed in a SCDLP liquid medium for 1 minute with an ultrasonic crusher (Tomy Seiko Co., Ltd., UD-201) to obtain a diluted solution 2 of the mutans bacteria. 0.1 mL of diluted solution 2 of mutans bacteria was sprinkled on a separately prepared SCDLP agar medium (Fuji Film Wako Pharmaceutical Co., Ltd., SCDLP agar medium "Daigo"), and the number of colonies was counted to determine the number of LOG surviving bacteria.
Table 2 shows the results (average value of n = 3) of each Example and Comparative Example measured by the above operation.
In addition, those with a decrease of 2 or more from the number of surviving LOG bacteria in physiological saline were evaluated as "○", and those with a decrease of less than 2 were evaluated as "x" and are shown in Table 1.

(Appearance observation evaluation)
The appearance of the liquid oral composition prepared above was visually confirmed, and those in which no agglutination (turbidity) was generated were evaluated as "○", and those in which agglutination (turbidity) was generated were evaluated as "x". .. The results are shown in Table 1.

From the results of Tables 1 and 2, the oral compositions of Examples 1 to 5 in which the blending ratio of the component (B) to the component (A) is more than twice the mass ratio contains the component (B). It is clear that the osmotic bactericidal effect is superior to the oral compositions of Comparative Examples 3 to 5 in which the compounding ratio of the component (B) to the components (A) is less than twice that of Comparative Examples 1, 2 and 6 and the component (A). It became.

(Cetylpyridinium chloride (CPC) adsorption test)
A CPC adsorption test was performed on Examples 1-5.
200 mg of hydroxyapatite powder (Bio-Gel HTP Hydroxyapatite; Bio-Rad) was weighed in a 50 mL centrifuge tube, 10 mL of the test product was added, and the mixture was stirred with a vortex mixer for 30 seconds.
Centrifugation (3,000 rpm × 10 min) was performed, and the CPC concentration in the supernatant was measured by HPLC (high performance liquid chromatography) (manufactured by Shimadzu Corporation).
CPC adsorption rate (%) = (CPC amount before adsorption-CPC amount in supernatant) / CPC amount before adsorption

Table 3 shows the measurement results of the CPC adsorption rate (%) of each Example and Comparative Example measured as described above.

From the results in Table 3, the oral use of Examples 1 to 5 which contains the component (A) and the component (B) and the compounding ratio of the component (B) to the component (A) is more than twice by mass ratio. In the composition, it was revealed that the component (A) has high adsorptivity to the tooth surface.
From this result, it is important to double or more the blending ratio of the component (B) to the component (A) in order to improve the adsorptivity of the component (A) to the tooth surface and obtain an excellent osmotic sterilization effect. It was also confirmed that this range has a critical significance.

Claims (2)

(A) Cetylpyridinium chloride and
(B) Containing a compound having one or more hydroxyl groups selected from the group consisting of thymol, menthol, and borneol,
An oral composition in which the content of (B) with respect to (A) is at least twice the mass ratio. The oral composition according to claim 1, wherein the content of (A) is 0.005 to 1% by mass.