JP2024067935A - Oral Composition - Google Patents

Abstract

[Problem] The object of the present invention is to provide an oral composition containing at least one component selected from the group consisting of azulene sulfonic acid, azulene sulfonic acid salts, and hinokitiol, and having improved storage stability of said component. [Solution] An oral composition containing (A) at least one component selected from the group consisting of azulene sulfonic acid, azulene sulfonic acid salts, and hinokitiol, and (B) water, the water content of (B) being 20% by weight or less, and having a pH of 8.0 or more. [Selected Figure] None

Description

The present invention relates to an oral composition that contains at least one component selected from the group consisting of azulene sulfonic acid, a salt of azulene sulfonic acid, and hinokitiol, and that has improved storage stability of the component.

Azulene sulfonic acid and its salts are known to have anti-inflammatory and epithelial tissue repairing effects, and are widely used in oral compositions such as dentifrices and mouthwashes. Hinokitiol is known to have low toxicity and a wide antibacterial spectrum, and is widely used in oral compositions. However, azulene sulfonic acid and its salts have the disadvantages of being easily decomposed by heat and having low storage stability. Hinokitiol is also known to have problems with storage stability.

Various formulation techniques for improving the storage stability of azulene sulfonic acid and its salts and hinokitiol have been studied. For example, Patent Document 1 describes that the storage stability of an azulene derivative can be improved by degassing a liquid drug containing an azulene derivative to remove dissolved oxygen in the solution and placing it in a filled container, replacing the head space of the container with an inert gas, and removing oxygen in the container. Patent Document 2 describes that the storage stability of a water-soluble azulene formulation can be improved by incorporating a nonionic surfactant, gelatin, a water-soluble polymer, and glycerin into an emulsified petroleum hydrocarbon, thereby containing water-soluble azulene. Patent Document 3 describes that the storage stability of hinokitiol can be improved by incorporating edetic acid. In recent years, consumer demands for oral compositions have become more diverse, and as a result, there is a demand for the development of a variety of formulations. In order to respond to the diversification of formulations, there is a demand for further development of formulation technology that improves the storage stability of oral compositions containing azulene sulfonic acid and/or its salts, or hinokitiol.

Japanese Patent Application Laid-Open No. 10-130141 Japanese Patent Application Laid-Open No. 7-89850 JP 2002-20253 A

The object of the present invention is to provide an oral composition that contains at least one component selected from the group consisting of azulene sulfonic acid, a salt of azulene sulfonic acid, and hinokitiol, and that has improved storage stability of the component.

The inventors conducted extensive research to solve the above problems and discovered that in an oral composition containing azulene sulfonic acid and/or a salt thereof, and hinokitiol, the storage stability of the components is improved by setting the water content to 20% by weight or less and the pH to 8.0 or more. The present invention was completed based on this knowledge and through further research.

That is, the present invention provides the following aspects.
Item 1. A composition comprising (A) at least one selected from the group consisting of azulene sulfonic acid, a salt of azulene sulfonic acid, and hinokitiol, and (B) water,
(B) An oral composition having a water content of 20% by weight or less and a pH of 8.0 or more.
Item 2. The oral composition according to Item 1, further comprising (C) a water-soluble aluminum salt.
Item 3. The oral composition according to Item 2, wherein the (C) water-soluble aluminum salt is aluminum lactate.
Item 4. The oral composition according to item 2 or 3, containing 0.5% by weight or more of the water-soluble aluminum salt (C).
Item 5. The oral composition according to item 1 or 2, which is a toothpaste.

According to the present invention, the decomposition during storage of at least one component selected from the group consisting of azulene sulfonic acid, azulene sulfonic acid salts, and hinokitiol can be suppressed, so that an oral composition containing azulene sulfonic acid and/or its salts, and hinokitiol can be provided with excellent storage stability.

1. Oral Composition The oral composition of the present invention contains at least one component selected from the group consisting of azulene sulfonic acid, a salt of azulene sulfonic acid, and hinokitiol, and water, and is characterized in that the water content is 20% by weight or less and the pH is 8.0 or more. The oral composition of the present invention will be described in detail below.

[(A) Azulene sulfonic acid, a salt of azulene sulfonic acid, and/or hinokitiol]
The oral composition of the present invention contains at least one component (sometimes referred to as component (A)) selected from the group consisting of azulene sulfonic acid, a salt of azulene sulfonic acid, and hinokitiol.

Azulene sulfonic acid is a known anti-inflammatory ingredient also known as 1,4-dimethyl-7-isopropylazulene-3-sulfonic acid. The type of salt of azulene sulfonic acid is not particularly limited as long as it is pharma- ceutically acceptable, but examples of the salt include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; other metal salts such as aluminum salt; ammonium salt; carboxylates such as acetate, trifluoroacetate, butyrate, palmitate, stearate, fumarate, maleate, succinate, malonate, lactate, tartrate, citrate; organic sulfonates such as methanesulfonate, toluenesulfonate, and tosylate; organic amine salts such as methylamine salt, triethylamine salt, triethanolamine salt, morpholine salt, piperazine salt, pyrrolidine salt, tripyridine salt, and picoline salt; and inorganic acid salts such as hydrochloride, sulfate, nitrate, hydrobromide, and phosphate.

Hinokitiol is a known fungicide.

The oral composition of the present invention may use one component selected from azulene sulfonic acid, azulene sulfonic acid salts, and hinokitiol as component (A) alone, or may use a combination of two or more components.

Among the (A) components, preferred are salts of azulene sulfonic acid and/or hinokitiol, more preferred are alkali metal salts of azulene sulfonic acid and/or hinokitiol, and even more preferred are sodium azulene sulfonate and/or hinokitiol.

The content of component (A) in the oral composition of the present invention may be appropriately set depending on the formulation form and use of the oral composition, and may be, for example, 0.0001 to 1% by weight, preferably 0.002 to 0.7% by weight, and more preferably 0.02 to 0.15% by weight, in terms of the total amount of component (A). More specifically, in the case of azulene sulfonic acid and/or a salt thereof, the content of azulene sulfonic acid and/or a salt thereof in the oral composition of the present invention is preferably 0.001 to 0.5% by weight, and more preferably 0.01 to 0.1% by weight. In the case of hinokitiol, the content of hinokitiol in the oral composition of the present invention is preferably 0.001 to 0.2% by weight, and more preferably 0.01 to 0.05% by weight.

[(B) pH of water and oral composition]
The oral composition of the present invention contains water in an amount of 20% by weight or less and has a pH of 8.0 or more. By satisfying these water content and pH requirements, it is possible to improve the storage stability of component (A).

The moisture content of the oral composition of the present invention may be 20% by weight or less, but from the viewpoint of more effectively improving the storage stability of component (A), the moisture content is preferably 5 to 19% by weight, more preferably 10 to 18% by weight, and even more preferably 12 to 17% by weight.

The pH of the oral composition of the present invention may be 8.0 or higher, but from the viewpoint of more effectively improving the storage stability of component (A), the pH is preferably 8.0 to 9.0, more preferably 8.1 to 8.5, and even more preferably 8.2 to 8.4. In the present invention, the pH of the oral composition is a value measured at a temperature condition of 25°C. To adjust the pH to the aforementioned range, a buffering agent, a pH adjusting agent, etc. may be used.

[(C) Water-soluble aluminum salt]
The oral cavity composition of the present invention may contain a water-soluble aluminum salt (sometimes referred to as component (C)) as necessary. When a water-soluble aluminum salt is contained, it becomes possible to more effectively improve the storage stability of component (A).

The type of water-soluble aluminum salt is not particularly limited, so long as it can be applied to the oral cavity. Examples include aluminum lactate, aluminum chlorohydrate, aluminum allantoin hydroxyaluminum, aluminum allantoin chlorhydroxyaluminum, aluminum allantoin dihydroxyaluminum, aluminum paraphenolsulfonate, aluminum chloride, alum, aluminum nitrate, etc.

These water-soluble aluminum salts may be used alone or in combination of two or more.

Among these (C) components, aluminum lactate is preferred from the viewpoint of more effectively improving the storage stability of (A) component.

When the oral composition of the present invention contains component (C), its content is not particularly limited, but may be, for example, 0.01 to 5% by weight. Furthermore, when the oral composition of the present invention contains 0.5% by weight or more of component (C), it becomes possible to remarkably improve the storage stability of component (A). From the viewpoint of remarkably improving the storage stability in this way, the content of component (C) in the oral composition of the present invention is preferably 0.5 to 5% by weight, more preferably 0.7 to 3% by weight, and even more preferably 0.8 to 1.5% by weight.

[(D) Quaternary ammonium salt]
The oral composition of the present invention may contain a quaternary ammonium salt (sometimes referred to as component (D)) as necessary. The type of quaternary ammonium salt used in the present invention is not particularly limited as long as it is applicable to the oral cavity, but for example, a quaternary ammonium salt having a bactericidal effect can be preferably used. Specific examples of such quaternary ammonium salts include cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, dequalinium chloride, alkyldimethylammonium chloride, alkyltrimethylammonium chloride, methylbenzethonium chloride, lauroylcollaminoformylmethylpyridinium chloride, etc. In addition, the quaternary ammonium salt used in the present invention may be in the form of a solvate such as a hydrate.

These (D) components may be used alone or in combination of two or more.

Among these (D) components, preferred are cetylpyridinium chloride, benzethonium chloride, and benzalkonium chloride, and more preferred are cetylpyridinium chloride.

When component (D) is contained in the oral composition of the present invention, its content may be appropriately set depending on the formulation form and use of the oral composition, but may be, for example, 0.001 to 5% by weight, preferably 0.005 to 2% by weight, and more preferably 0.01 to 1% by weight.

[(E) Fluorine compounds]
The oral composition of the present invention may contain a fluorine compound (sometimes referred to as component (E)) as necessary.

The type of fluorine compound used in the oral composition of the present invention is not particularly limited, but examples include alkali metal fluorides, fluorophosphates, and salts of fluorophosphates.

There are no particular limitations on the type of alkali metal fluoride, as long as it can be applied to the oral cavity, but examples include sodium fluoride, potassium fluoride, etc.

There are no particular limitations on the type of fluorophosphate, as long as it can be applied to the oral cavity, but examples include monofluorophosphate, difluorophosphate, etc.

The type of fluorophosphoric acid salt is not particularly limited, as long as it can be applied to the oral cavity, but examples include alkali metal salts of the fluorophosphoric acid, more specifically, sodium salts and potassium salts of the fluorophosphoric acid.

One of these components (E) may be selected and used alone, or two or more may be used in combination.

Among these components (E), preferred are salts of fluorophosphoric acid, more preferably sodium monofluorophosphate.

When component (E) is contained in the oral composition of the present invention, its content may be appropriately set depending on the formulation form and use of the oral composition, but may be, for example, 0.001 to 5% by weight, preferably 0.01 to 3% by weight, and more preferably 0.1 to 2% by weight.

[(F) Anionic Surfactant]
The oral composition of the present invention may contain an anionic surfactant (sometimes referred to as component (F)) as necessary.

The type of anionic surfactant used in the present invention is not particularly limited as long as it is applicable to the oral cavity, but examples thereof include salts of alkyl sulfate esters such as lauryl sulfate, myristyl sulfate, cetyl sulfate, and oleyl sulfate; salts of higher fatty acid amide sulfonic acids such as lauroyl methyl taurine, myristoyl methyl taurine, coconut oil fatty acid methyl taurine, and lauryl methyl taurine; salts of α-olefin sulfonic acid; salts of N-acyl amino acids such as N-myristoyl glutamic acid, cocoyl glutamic acid, N-lauroyl glutamic acid, N-stearoyl glutamic acid, and cocoyl glycine; salts of alkyl benzene sulfonic acids such as dodecyl benzene sulfonic acid; salts of polyoxyethylene alkyl ether sulfate esters such as polyoxyethylene lauryl ether sulfate; and salts of N-acyl sarcosine acids such as lauroyl sarcosine. Examples of the salt forms of these anionic surfactants include alkali metal salts such as sodium salts and potassium salts. One of these anionic surfactants may be selected and used alone, or two or more of them may be used in combination. Among these anionic surfactants, preferred are salts of alkyl sulfate esters, and more preferred are sodium lauryl sulfate.

When component (F) is contained in the oral composition of the present invention, its content may be appropriately set depending on the formulation form and use of the oral composition, but may be, for example, 0.001 to 5% by weight, preferably 0.01 to 3% by weight, and more preferably 0.1 to 2% by weight.

[(G) Amphoteric surfactant]
The oral composition of the present invention may contain an amphoteric surfactant (sometimes referred to as component (G)) as necessary.

The type of amphoteric surfactant used in the present invention is not particularly limited, provided that it is applicable to the oral cavity. Examples of such surfactants include imidazoline-type amphoteric surfactants such as N-coconut fatty acid acyl-N-carboxymethyl-N-hydroxyethylethylenediamine, N-coconut fatty acid acyl-N-carboxyethyl-N-hydroxyethylethylenediamine, N-coconut fatty acid-N-carboxymethoxyethyl-N-carboxymethylethylenediamine, N-coconut fatty acid acyl-N-carboxyethoxyethyl-N-carboxyethylethylenediamine, and salts thereof; lauryl dimethylaminoacetate betaine, myristyl dimethylaminoacetate betaine, palmityl dimethylaminoacetate betaine, stearyl dimethylaminoacetate betaine, etc. alkyl betaine type amphoteric surfactants such as betaine, coconut oil fatty acid dimethylaminoacetic acid betaine, palm kernel oil fatty acid dimethylaminoacetic acid betaine, lauryl dihydroxyethyl aminoacetic acid betaine, and salts thereof; amido betaine type amphoteric surfactants such as lauryl amidopropyl dimethylaminoacetic acid betaine, myristyl amidopropyl dimethylaminoacetic acid betaine, palmitylamidopropyl dimethylaminoacetic acid betaine, stearyl amidopropyl dimethylaminoacetic acid betaine, coconut oil fatty acid amidopropyl dimethylaminoacetic acid betaine (coconut oil fatty acid amidopropyl betaine solution), palm kernel oil fatty acid amidopropyl dimethylaminoacetic acid betaine lauryl amidopropyl dimethylaminoacetic acid betaine, and salts thereof. Examples of the salt form of these amphoteric surfactants include alkali metal salts such as sodium salts and potassium salts. Among these amphoteric surfactants, preferred are imidazoline type amphoteric surfactants, more preferred are N-coconut oil fatty acid acyl-N-carboxymethyl-N-hydroxyethyl ethylenediamine and its salts, and even more preferred are N-coconut oil fatty acid acyl-N-carboxymethyl-N-hydroxyethyl ethylenediamine sodium. These amphoteric surfactants may be used alone or in combination of two or more. Among these amphoteric surfactants, amidobetaine type amphoteric surfactants are preferred, and coconut oil fatty acid amidopropyl betaine solution is more preferred.

When component (G) is contained in the oral composition of the present invention, its content may be appropriately set depending on the formulation form and use of the oral composition, but may be, for example, 0.001 to 5% by weight, preferably 0.01 to 2% by weight, and more preferably 0.1 to 1% by weight.

[(H) Nonionic Surfactant]
The oral composition of the present invention may contain a nonionic surfactant (sometimes referred to as component (H)) as necessary.

The type of nonionic surfactant used in the present invention is not particularly limited, provided that it is applicable to the oral cavity. Examples of such surfactants include polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, sucrose fatty acid ester, polyalkylene glycol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbit fatty acid ester, etc. One of these nonionic surfactants may be selected and used alone, or two or more types may be used in combination. Of these nonionic surfactants, polyoxyethylene hydrogenated castor oil is preferred.

When component (H) is contained in the oral composition of the present invention, its content may be appropriately set depending on the formulation form and use of the oral composition, but may be, for example, 0.01 to 15% by weight, preferably 0.1 to 10% by weight, and more preferably 1 to 6% by weight.

[(I) Polyhydric alcohol]
The oral composition of the present invention may contain a polyhydric alcohol (sometimes referred to as component (I)) as necessary.

The type of polyhydric alcohol used in the present invention is not particularly limited, so long as it is applicable to the oral cavity, but examples include dihydric alcohols such as 1,3-butylene glycol, ethylene glycol, propylene glycol, isoprene glycol, diethylene glycol, dipropylene glycol, and polyethylene glycol; glycerin, etc. These polyhydric alcohols may be used alone or in combination of two or more. Among these polyhydric alcohols, propylene glycol and glycerin are preferred.

When component (I) is contained in the oral composition of the present invention, its content is not particularly limited, but may be, for example, 1 to 75% by weight, preferably 10 to 70% by weight, and more preferably 30 to 60% by weight of the total amount of component (I).

[(J) Sugar alcohol]
The oral composition of the present invention may contain a sugar alcohol (sometimes referred to as component (J)) as necessary.

The type of sugar alcohol used in the present invention is not particularly limited, so long as it is applicable to the oral cavity, and examples include sorbitol, mannitol, xylitol, erythritol, etc. These sugar alcohols may be used alone or in combination of two or more. Among these sugar alcohols, sorbitol is preferred.

When component (J) is contained in the oral composition of the present invention, its content is not particularly limited, but may be, for example, 0.1 to 20% by weight, preferably 0.5 to 15% by weight, and more preferably 3 to 10% by weight.

[(K) Monohydric lower alcohol]
The oral cavity composition of the present invention may contain a monohydric lower alcohol (sometimes referred to as component (K)) as necessary.

The monohydric lower alcohol used in the present invention is not particularly limited, so long as it is applicable to the oral cavity, but examples thereof include monohydric alcohols having 2 to 5 carbon atoms, specifically ethanol, propanol, isopropanol, butanol, etc. Among these monohydric lower alcohols, ethanol is preferable. These monohydric lower alcohols may be used alone or in combination of two or more.

When the oral composition of the present invention contains component (K), its content is not particularly limited, but may be, for example, 0.001 to 15% by weight, preferably 0.01 to 10% by weight, and more preferably 0.1 to 5% by weight.

[(L) Thickener]
The oral composition of the present invention may contain a thickener (sometimes referred to as component (L)) as necessary.

The thickener used in the present invention is not particularly limited, so long as it is applicable to the oral cavity. Examples of the thickener include cellulose-based thickeners such as hydroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, and carboxymethyl cellulose; thickening polysaccharides such as alginic acid, guar gum, tragacanth gum, karaya gum, locust bean gum, gum arabic, and carrageenan; and vinyl-based thickeners such as alkyl vinyl ether/maleic anhydride copolymer. Among these thickeners, cellulose-based thickeners are preferred, and hydroxyethyl cellulose is more preferred. These thickeners may be used alone or in combination of two or more.

When component (L) is contained in the oral composition of the present invention, its content is not particularly limited, but may be, for example, 0.001 to 15% by weight, preferably 0.01 to 10% by weight, and more preferably 0.1 to 5% by weight.

[Other ingredients]
In addition to the above-mentioned components, the oral composition of the present invention may contain components that are commonly used in the art, depending on the form of the oral composition, within a range that does not impair the effects of the present invention. Examples of such components include preservatives, bactericides, antibacterial agents, anti-inflammatory agents, abrasives, glucosyltransferase (GTase) inhibitors, plaque inhibitors, hypersensitivity inhibitors, tartar prevention agents, tooth strengthening/remineralization agents, local anesthetics, blood circulation promoters, humectants, sweeteners, colorants, deodorants, etc.

[Dosage form/shape]
The dosage form of the oral composition of the present invention is not particularly limited as long as it can be applied to the oral cavity, and may be, for example, liquid or semi-solid (gel, paste), although a semi-solid form is preferred.

The form of the oral composition of the present invention is not particularly limited as long as it can be applied to the oral cavity and remain there for a certain period of time, but examples include oral hygiene agents such as liquid dentifrice, toothpaste, mouthwash (liquid dentifrice and mouthwash are generally sometimes called mouth rinse, mouthwash, dental rinse, etc.), mouth fresheners (mouth spray, etc.), and oral ointments. Of these, toothpaste is preferred.

2. Method for Improving the Stability of Azulene Sulfonic Acid and/or a Salt Thereof, and Hinokitiol The present invention further provides a method for improving the stability of at least one component selected from the group consisting of azulene sulfonic acid, azulene sulfonic acid salts, and hinokitiol in an oral composition, which comprises blending (A) at least one component selected from the group consisting of azulene sulfonic acid, azulene sulfonic acid salts, and hinokitiol, and (B) 20% by weight or less of water into the oral composition, and adjusting the pH to 8.0 or higher.

In the stability improving method of the present invention, the type and amount of azulene sulfonic acid and/or its salt, the type and amount of hinokitiol, the amount of water, pH, and the dosage form and shape of the oral composition are as described in the section "1. Oral composition" above.

The present invention will be explained in more detail below with reference to examples, but the present invention is not limited to these.

Test Example 1
A paste-type dentifrice was prepared with the composition shown in Table 1. Approximately 40 g of the obtained paste-type dentifrice was filled into an aluminum laminate tube, sealed, and stored for one month under the conditions of 50°C and 60% RH. The contents of sodium azulene sulfonate and hinokitiol in the paste-type dentifrice before and after storage were measured by high performance liquid chromatography, and the content before storage was taken as 100%, and the percentage of the content after storage was calculated as the remaining rate.

The results are shown in Table 1. In a paste-type dentifrice containing sodium azulene sulfonate and hinokitiol, when the moisture content was 20% by weight or less and the pH was 8.0 or more, the residual rate of hinokitiol after storage was 97% or more and the residual rate of sodium azulene sulfonate after storage was 95% or more, and the storage stability was excellent (Examples 1 and 2). In contrast, when the moisture content was more than 20% by weight and the pH was less than 8.0, the residual rate of hinokitiol after storage was only about 95%, and the residual rate of sodium azulene sulfonate after storage further decreased to less than 90% (Comparative Example 1). In addition, even if the pH was 8.0 or more, when the moisture content was more than 20% by weight, the residual rates of sodium azulene sulfonate and hinokitiol after storage each decreased to around 90% (Comparative Example 2).

A paste-type dentifrice was prepared with the composition shown in Prescription Example Table 2. The storage stability of the obtained paste-type dentifrice was evaluated in the same manner as in Test Example 1. It was confirmed that the residual ratio of sodium azulene sulfonate and hinokitiol was high in each case, and that the paste-type dentifrice had excellent storage stability.

Claims (5)

(A) at least one selected from the group consisting of azulene sulfonic acid, a salt of azulene sulfonic acid, and hinokitiol, and (B) water;
(B) An oral composition having a water content of 20% by weight or less and a pH of 8.0 or more. The oral composition according to claim 1, further comprising (C) a water-soluble aluminum salt. The oral composition according to claim 2, wherein the water-soluble aluminum salt (C) is aluminum lactate. The oral composition according to claim 2 or 3, which contains 0.5% by weight or more of the water-soluble aluminum salt (C). The oral composition according to claim 1 or 2, which is a toothpaste.