JP7634963B2 - Oral Composition - Google Patents

Description

The present invention relates to an oral composition that can reduce inflammation in the oral cavity and provide sustained moisturizing effects on the oral mucosa.

In recent years, the number of people suffering from dry mouth has been increasing. Dry mouth, also known as xerostomia, is a symptom in which the amount of saliva secreted is reduced, causing the mouth to become dry. Dry mouth can be caused by a variety of factors, including aging, stress, muscle weakness, diabetes, renal failure, menopausal disorders, and side effects of medication, and these causes often cannot be completely eliminated. In order to treat dry mouth, patients have no choice but to rely on symptomatic treatments that moisturize the mouth using oral compositions such as oral sprays, mouthwashes, mouthwashes, artificial saliva, and lozenges.

Various oral compositions effective in preventing or improving dry mouth have been reported. For example, Patent Document 1 discloses that an oral composition containing a hydrophobically modified polyether urethane and a humectant is effective in preventing or treating dry mouth. Patent Document 2 discloses that an oral spray composition containing 0.05-5% by mass of polyglutamic acid, 2-6% by mass of an organic acid such as citric acid and its salt, 10-50% by mass of l-menthol, glycerin, a surfactant, and 0.01-0.3% by mass of monomenthyl succinate is effective in preventing or treating dry mouth.

JP 2012-153677 A JP 2011-105651 A

To prevent or treat dry mouth, it is important not only to provide a temporary moisturizing effect to the oral mucosa, but also to sustain this effect. In addition, dry mouth is caused by a decrease in the barrier function against bacteria due to the dryness of the oral mucosa, making the oral cavity more susceptible to bacterial infection and inflammation. For this reason, it is desirable for an oral composition that is effective in preventing or treating dry mouth to not only provide a moisturizing effect to the oral cavity, but also to have an anti-inflammatory effect.

Therefore, the present invention aims to provide an oral composition that can reduce inflammation in the oral cavity and provide a sustained moisturizing effect on the oral mucosa.

The inventors conducted extensive research to solve the above problems and discovered that the use of azulene sulfonic acid and/or a salt thereof in combination with hypromellose in an oral composition provides an anti-inflammatory effect while dramatically improving the durability of the moisturizing effect on the oral mucosa through the synergistic action of these components. The present invention was completed through further research based on this knowledge.

That is, the present invention provides the following aspects.
Item 1. An oral composition comprising (A) azulene sulfonic acid and/or a salt thereof, and (B) hypromellose.
Item 2. The oral composition according to Item 1, which is used for the prevention or treatment of dry mouth.

The oral composition of the present invention has an anti-inflammatory effect while providing a sustained moisturizing effect on the oral mucosa, making it effective for oral care and suitable for use in preventing or treating dry mouth, for example.

The oral composition of the present invention is characterized by containing (A) azulene sulfonic acid and/or a salt thereof, and (B) hypromellose. The oral composition of the present invention is described below.

[(A) Azulene sulfonic acid and/or its salt]
The oral composition of the present invention contains azulene sulfonic acid and/or a salt thereof (sometimes referred to as component (A)). By including azulene sulfonic acid and/or a salt thereof in the topical composition of the present invention, it becomes possible to exert an anti-inflammatory effect in the oral cavity.

Azulene sulfonic acid is a known anti-inflammatory ingredient that is 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, and examples thereof 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. Among these salts, alkali metal salts are preferred, and sodium salt is more preferred.

Among the (A) components, from the viewpoint of further improving the durability of the moisturizing effect on the oral mucosa, a salt of azulene sulfonic acid is preferred, and sodium azulene sulfonate is more preferred.

As component (A), one component selected from azulene sulfonic acid and its salts may be used alone, or two or more components may be used in combination.

The content of component (A) in the oral composition of the present invention may be appropriately set depending on the type of component (A) used, the formulation form of the oral composition, etc., but may be, for example, 0.0001 to 5% by weight, preferably 0.001 to 1% by weight, and more preferably 0.01 to 0.5% by weight.

[(B) Hypromellose]
The oral composition of the present invention contains hypromellose (sometimes referred to as component (B)) in addition to component (A). By using component (A) in combination with hypromellose, the synergistic effect of these components can be achieved, dramatically improving the duration of the moisturizing effect on the oral mucosa.

Hypromellose is a well-known cellulose derivative also known as hydroxypropyl methylcellulose.

The content of component (B) in the oral composition of the present invention may be set appropriately depending on the formulation form of the oral composition, and may be, for example, 0.01 to 1.5% by weight, preferably 0.1 to 1.5% by weight, more preferably 0.2 to 1.5% by weight, and even more preferably 0.5 to 1.5% by weight. By ensuring that the content of component (B) falls within the above range, the durability of the moisturizing effect on the oral mucosa can be dramatically improved without causing a decrease in the feel of use due to an increase in viscosity.

In the oral composition of the present invention, the ratio of component (A) to component (B) is determined according to the respective contents of these two components, but for example, the ratio of component (B) is 1 to 300 parts by weight, preferably 5 to 80 parts by weight, more preferably 10 to 80 parts by weight, and even more preferably 30 to 80 parts by weight per 1 part by weight of component (A).

[(C) Monohydric lower alcohol]
The oral cavity composition of the present invention may contain a monohydric lower alcohol (sometimes referred to as component (C)) in addition to the above-mentioned components (A) and (B). In the present invention, the monohydric lower alcohol refers to a monohydric alcohol having 1 to 5 carbon atoms.

The type of monohydric lower alcohol is not particularly limited as long as it is pharma- ceutically acceptable, but examples include ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, tert-butanol, n-amyl alcohol, sec-amyl alcohol, isoamyl alcohol, tert-amyl alcohol, neopentyl alcohol, etc. These monohydric lower alcohols may be used alone or in combination of two or more.

Among these monohydric lower alcohols, ethanol is preferred.

When component (C) is contained in the oral composition of the present invention, its content is not particularly limited, but may be, for example, 0.01 to 10% by weight, preferably 0.1 to 5% by weight, and more preferably 0.5 to 3% by weight.

[(D) Polyhydric alcohol]
The oral composition of the present invention may contain a polyhydric alcohol (sometimes referred to as component (D)) in addition to the above-mentioned components (A) and (B).

The type of polyhydric alcohol is not particularly limited as long as it is pharma- ceutically acceptable, 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, dihydric alcohols are preferred, and propylene glycol is more preferred.

When component (D) is contained in the oral composition of the present invention, its content is not particularly limited, but may be, for example, 1 to 80% by weight, preferably 10 to 75% by weight, and more preferably 30 to 70% by weight.

[water]
The oral composition of the present invention may contain water as a part of the base. When the oral composition of the present invention contains water, the content of water may be appropriately set depending on the formulation form, etc., and may be, for example, 1 to 90% by weight, preferably 10 to 70% by weight, more preferably 25 to 60% by weight.

[Other ingredients]
The oral cavity composition of the present invention may contain other medicinal components as necessary, in addition to the above-mentioned components. Such medicinal components are not particularly limited, as long as they can be incorporated into medicines, oral care products, etc., and include, for example, iodine-based bactericidal components (e.g., iodine, povidone iodine, nonoxynol iodine, phenoxy iodine, etc.), bronchodilators, antitussives, expectorants, anti-inflammatory agents (other than azulene sulfonic acid and its salts), glucosyltransferase inhibitors, plaque inhibitors, dentin hypersensitivity inhibitors, tartar prevention agents, antipyretics, analgesics, antihistamines, bactericides (other than quaternary ammonium salts), gastric mucosa protective agents, caffeines, vitamins, Chinese herbal medicines, herbal medicine components, etc.

The oral composition of the present invention may also contain bases and additives to obtain the desired formulation. There are no particular limitations on such bases and additives, so long as they can be incorporated into pharmaceuticals, oral care products, etc. Examples of such bases and additives include oily components, surfactants, preservatives, thickeners (other than hypromellose), fragrances, flavorings, cooling agents, colorants, deodorants, pigments, buffers, pH adjusters, etc.

[Shape and dosage form]
The form of the oral composition of the present invention is not particularly limited and may be any of liquid, solid, semi-solid (gel, ointment, paste), etc., but is preferably a liquid.

The formulation of the oral composition of the present invention is not limited as long as it can be applied to the oral cavity and remain there for a certain period of time, but examples of oral care products include oral sprays (including throat sprays), mouthwashes, gargles, liquid dentifrices, toothpastes, mouth fresheners, oral pastes, and gum massage creams. Among these, oral sprays, mouthwashes, and gargles are preferred, and oral sprays are more preferred.

[How to use]
The oral composition of the present invention can anti-inflammation and/or sterilization in the oral cavity by application to the oral cavity, and can also exert a sustained moisturizing effect on the oral mucosa, and is therefore suitable for use, for example, in the prevention or treatment of dry mouth.

The dosage and volume of the oral composition of the present invention are appropriately determined depending on the content of each compounded ingredient, the formulation form of the oral composition, the expected effects, etc., but for example, an appropriate amount may be applied to the oral cavity 1 to 6 times a day.

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
An oral composition (oral spray) having the composition shown in Table 1 was prepared. The obtained oral composition was evaluated for the duration of the moisturizing effect on the oral mucosa by the following method. First, an edible pig tongue (not sliced) excised as a pseudo-mucosa was lightly wetted with running water, lightly wiped, and left to stand in an environment of 30°C and 30% RH relative humidity until the measurement value of an oral moisture meter (Oral Moisture Meter Mucus, Yoshida Co., Ltd.) reached the dryness index value (25 or less). Next, the obtained oral composition was placed in a spray container, and about 0.3 ml of the oral composition was sprayed and applied to a part of the pig tongue slightly from the center to the tip, and left to stand in an atmosphere of 30°C and 30% RH relative humidity for 6 hours. Immediately after application of the oral composition and 6 hours after application, the moisture value of the pig tongue area where the oral composition was applied was measured using an oral moisture meter (Oral Moisture Meter Mucus, Yoshida Co., Ltd.), and the moisture retention rate (%) 6 hours after application was calculated according to the following calculation formula. The value was rounded off to one decimal place to obtain the moisture retention rate (%) 6 hours after application.

The results are shown in Table 1. When sodium azulene sulfonate was used alone, the moisture retention rate was low after 6 hours of application, and the moisturizing effect could not be sustained (Comparative Example 1). When hypromellose, hydroxyethyl cellulose, and carboxyvinyl polymer were used alone, the moisture retention rate after 6 hours of application was somewhat high, but still insufficient (Comparative Examples 6 to 8). When sodium azulene sulfonate was used in combination with hydroxyethyl cellulose or carboxyvinyl polymer, only an additive improvement in the moisture retention rate after 6 hours of application was observed (Comparative Examples 2 to 5). In contrast, when sodium azulene sulfonate was used in combination with hypromellose, the moisture retention rate after 6 hours of application was synergistically improved, and the moisturizing effect was significantly longer lasting (Examples 1 to 3). The oral compositions of Examples 1 to 3 contain sodium azulene sulfonate, and therefore have a composition capable of exerting an anti-inflammatory effect.

Oral compositions (oral sprays) having the compositions shown in Table 2 of Formulation Examples were prepared. For comparison, comparative oral compositions were also prepared in which the hypromellose in Formulation Examples 5 and 6 was replaced with purified water. These oral compositions were evaluated for durability of moisturizing effect in the same manner as in Test Example 1. In all of Formulation Examples 1 to 4, the moisture retention rate after 6 hours of application was significantly higher than that of Comparative Examples 1 to 8. In addition, in Formulation Examples 5 and 6 in which cetylpyridinium chloride was replaced with benzalkonium chloride or benzethonium chloride, the moisture retention rate after 6 hours of application was also significantly higher than that of the comparative oral compositions of Formulation Examples 5 and 6 and Comparative Examples 1 to 18.

Claims (2)

An oral composition (excluding those containing ethyl aminobenzoate) which contains (A) azulene sulfonic acid and/or a salt thereof, and (B) hypromellose, and which is in a liquid or solid form. The oral composition according to claim 1 , which is used for the prevention or treatment of dry mouth.