Oral composition

Abstract

To provide an oral composition that can eliminate bacteria inside the oral cavity and that is capable of maintaining continuous moisturizing effect on the oral mucosa.SOLUTION: An oral composition contains (A) a quaternary ammonium salt and (B) hypromellose.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an oral composition that can sterilize the oral cavity and also has a sustained moisturizing effect on the oral mucosa. [Background technology]

[0002] In recent years, the number of people suffering from dry mouth has been increasing. Dry mouth, also known as xerostomia, is a symptom of reduced saliva secretion and dryness in the oral cavity. Dry mouth can be caused by a variety of factors, such as aging, stress, muscle weakness, diabetes, renal failure, menopausal disorders, and side effects of medication. These causes often cannot be completely eliminated, and treatment of dry mouth has no choice but to rely on symptomatic treatments that moisturize the oral cavity using oral compositions such as oral sprays, mouthwashes, mouthwashes, artificial saliva, and lozenges.

[0003] Various oral compositions effective for preventing or ameliorating 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 for preventing or treating dry mouth. Patent Document 2 discloses that an oral spray composition containing 0.05 to 5% by mass of polyglutamic acid, 2 to 6% by mass of an organic acid such as citric acid and its salt, 10 to 50% by mass of l-menthol, glycerin, a surfactant, and 0.01 to 0.3% by mass of monomenthyl succinate is effective for preventing or treating dry mouth. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2012-153677 [Patent Document 2] Japanese Patent Application Laid-Open No. 2011-105651 DISCLOSURE OF THE INVENTION [Problem to be solved by the invention]

[0005] For the prevention or treatment of dry mouth, it is important not only to temporarily moisturize the oral mucosa but also to sustain this effect. Furthermore, 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. Therefore, it is desirable for an oral composition effective for the prevention or treatment of dry mouth to not only moisturize the oral cavity but also have a bactericidal effect.

[0006] Therefore, an object of the present invention is to provide an oral composition that can sterilize the oral cavity and also has a sustained moisturizing effect on the oral mucosa. [Means for solving the problem]

[0007] The present inventors have conducted extensive research to solve the above problems and have found that the combined use of a quaternary ammonium salt and hypromellose in an oral composition provides a bactericidal effect while dramatically improving the durability of the moisturizing effect on the oral mucosa due to the synergistic action of these components.The present invention was completed through further research based on this finding.

[0008] That is, the present invention provides the following aspects. Item 1. An oral composition containing (A) a quaternary ammonium salt and (B) hypromellose. Item 2. The oral composition according to Item 1, further comprising (C) azulene sulfonic acid and / or a salt thereof. Item 3. The oral composition according to Item 1 or 2, wherein the component (A) is at least one selected from the group consisting of cetylpyridinium chloride, benzethonium chloride, and benzalkonium chloride. Item 4. The oral composition according to any one of Items 1 to 3, which is used for the prevention or treatment of dry mouth. [Effects of the Invention]

[0009] The oral composition of the present invention is effective for oral care because it can exert a bactericidal effect while also exerting a sustained moisturizing effect on the oral mucosa, and can be suitably used for applications such as the prevention or treatment of dry mouth. DETAILED DESCRIPTION OF THE INVENTION

[0010] The oral composition of the present invention is characterized by containing (A) a quaternary ammonium salt and (B) hypromellose. The oral composition of the present invention will be described below.

[0011] [(A) Quaternary ammonium salt] The oral composition of the present invention contains a quaternary ammonium salt (sometimes referred to as component (A)). By including a quaternary ammonium salt in the topical composition of the present invention, it is possible to achieve a bactericidal effect in the oral cavity.

[0012] The type of quaternary ammonium salt is not particularly limited as long as it is pharmaceutically acceptable. For example, quaternary ammonium salts 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, and lauroylcholaminoformylmethylpyridinium chloride. The quaternary ammonium salt may be in the form of a solvate such as a hydrate. These quaternary ammonium salts may be used alone or in combination of two or more. Among these quaternary ammonium salts, preferred are cetylpyridinium chloride, benzethonium chloride, and benzalkonium chloride, and more preferred are cetylpyridinium chloride.

[0013] Of the components (A), from the viewpoint of further improving the durability of the moisturizing effect on the oral mucosa, preferred are cetylpyridinium chloride, benzethonium chloride, and benzalkonium chloride, and more preferred is cetylpyridinium chloride.

[0014] As the component (A), one type of quaternary ammonium salt may be used alone, or two or more types may be used in combination.

[0015] 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., and may be, for example, 0.001 to 5 wt %, preferably 0.01 to 2 wt %, and more preferably 0.05 to 1.25 wt %.

[0016] [(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 two components can be significantly improved, thereby dramatically improving the durability of the moisturizing effect on the oral mucosa.

[0017] Hypromellose is a known cellulose derivative also known as hydroxypropyl methylcellulose.

[0018] The content of component (B) in the oral composition of the present invention may be appropriately set depending on the formulation of the oral composition, and may be, for example, 0.01 to 1.5 wt %, preferably 0.1 to 1.5 wt %, more preferably 0.2 to 1.5 wt %, and even more preferably 0.6 to 1.5 wt %. By ensuring that the content of component (B) falls within this range, the durability of the moisturizing effect on the oral mucosa can be dramatically improved without increasing the viscosity and thereby reducing the feel of use.

[0019] In the oral composition of the present invention, the ratio of component (A) to component (B) is determined depending on the respective contents of these two components, but for example, the ratio of component (B) is 0.1 to 20 parts by weight, preferably 0.5 to 6 parts by weight, more preferably 1 to 6 parts by weight, and even more preferably 2 to 6 parts by weight per 1 part by weight of component (A).

[0020] [(C) Azulene sulfonic acid and / or its salt] The oral composition of the present invention may contain azulene sulfonic acid and / or a salt thereof (sometimes referred to as component (C)) in addition to the components (A) and (B). By including azulene sulfonic acid and / or a salt thereof in the oral composition of the present invention, it becomes possible to achieve both anti-inflammatory and bactericidal effects in the oral cavity while further improving the durability of the moisturizing effect on the oral mucosa.

[0021] Azulene sulfonic acid, also known as 1,4-dimethyl-7-isopropylazulene-3-sulfonic acid, is a known anti-inflammatory ingredient.

[0022] The type of azulene sulfonic acid salt is not particularly limited as long as it is pharmaceutically 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, and 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; inorganic acid salts such as hydrochloride, sulfate, nitrate, hydrobromide, and phosphate. Among these salts, alkali metal salts are preferred, and sodium salts are more preferred.

[0023] Of the components (C), from the viewpoint of further improving the durability of the moisturizing effect on the oral mucosa, salts of azulene sulfonic acid are preferred, and sodium azulene sulfonate is more preferred.

[0024] As the component (C), one kind of azulene sulfonic acid and its salts may be used alone, or two or more kinds of components may be used in combination.

[0025] When the oral composition of the present invention contains component (C), its content may be appropriately set depending on the type of component (C) used, the formulation form of the oral composition, etc., but may be, for example, 0.0001 to 5 wt %, preferably 0.001 to 1 wt %, and more preferably 0.01 to 0.5 wt %.

[0026] When the oral composition of the present invention contains component (C), the ratio of component (A) to component (C) is determined according to the respective contents of these two components, but for example, the ratio of component (B) is 0.01 to 10 parts by weight, preferably 0.01 to 1 part by weight, more preferably 0.02 to 0.2 parts by weight per part by weight of component (A).

[0027] [(D) Monohydric lower alcohol] The oral composition of the present invention may contain a monohydric lower alcohol (sometimes referred to as component (D)) in addition to the aforementioned components (A) and (B). In the present invention, the monohydric lower alcohol refers to a monohydric alcohol having 1 to 5 carbon atoms.

[0028] The type of monohydric lower alcohol is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof 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.

[0029] Among these monohydric lower alcohols, ethanol is preferred.

[0030] When component (D) 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.

[0031] [(E) Polyhydric alcohol] The oral composition of the present invention may contain a polyhydric alcohol (sometimes referred to as component (E)) in addition to the above-mentioned components (A) and (B).

[0032] The type of polyhydric alcohol is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof 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.

[0033] Among these polyhydric alcohols, dihydric alcohols are preferred, and propylene glycol is more preferred.

[0034] When component (E) 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.

[0035] [water] The oral composition of the present invention may contain water as part of the base. When the oral composition of the present invention contains water, the content of water may be appropriately determined depending on the formulation, etc., and may be, for example, 1 to 90 wt %, preferably 10 to 70 wt %, more preferably 25 to 60 wt %.

[0036] [Other ingredients] The oral composition of the present invention may contain other medicinal ingredients in addition to the above-mentioned ingredients, if necessary. Such medicinal ingredients are not particularly limited as long as they can be incorporated into pharmaceuticals, oral care products, etc., and examples thereof include iodine-based antibacterial ingredients (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, hypersensitivity inhibitors, anti-tartar agents, antipyretics, antihistamines, bactericides (other than quaternary ammonium salts), gastric mucosa protectants, caffeine, vitamins, herbal medicines, and herbal ingredients.

[0037] The oral composition of the present invention may contain bases and additives to obtain a desired formulation. Such bases and additives are not particularly limited as 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, colorings, deodorizers, pigments, buffers, pH adjusters, etc.

[0038] [Shape / 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 liquid.

[0039] 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, and examples thereof include oral care products such as oral sprays (including throat sprays), mouthwashes, gargles, liquid dentifrices, toothpastes, mouth fresheners, oral pastes, and gum massage creams. Of these, oral sprays, mouthwashes, and gargles are preferred, and oral sprays are more preferred.

[0040] [How to use] When applied to the oral cavity, the oral composition of the present invention can anti-inflammate and / or disinfect the oral cavity, and can also exert a sustained moisturizing effect on the oral mucosa, making it suitable for use, for example, in the prevention or treatment of dry mouth.

[0041] The dosage and administration of the oral composition of the present invention are determined appropriately depending on the content of each compounded ingredient, the formulation form of the oral composition, the expected effect, etc., but for example, an appropriate amount may be applied to the oral cavity 1 to 6 times a day. [Example]

[0042] The present invention will be explained in more detail below by showing examples, but the present invention is not limited to these examples.

[0043] Test Example 1 Oral compositions (oral sprays) were prepared with the compositions shown in Tables 1 and 2. The resulting oral compositions were evaluated for their sustained moisturizing effect on the oral mucosa using the following method. First, an edible pig tongue (unsliced) excised as a pseudo-mucosa was lightly wetted with running water, lightly wiped, and left to stand at 30°C and 30% relative humidity until the measurement value using an oral moisture meter (Mucus Oral Moisture Meter, Yoshida Co., Ltd.) reached a dryness index value of 25 or less. Next, the resulting oral composition was placed in a spray container, and approximately 0.3 ml of the oral composition was sprayed onto a portion of the pig tongue slightly from the center to the tip, and then left to stand in an atmosphere of 30°C and 30% relative humidity for 6 hours. Immediately after application of the oral composition and 6 hours after application, the moisture content of the pig tongue area where the oral composition had been 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 formula. The value was rounded to one decimal place to obtain the moisture retention rate (%) 6 hours after application.

number

[0044] The results are shown in Tables 1 and 2. When cetylpyridinium chloride was used alone, the moisture retention rate was low 6 hours after application, and the moisturizing effect could not be sustained (Comparative Example 1). When hypromellose, hydroxyethyl cellulose, or carboxyvinyl polymer were used alone, the moisture retention rate was somewhat higher 6 hours after application, but was still insufficient (Comparative Examples 6 to 8). When cetylpyridinium chloride was used in combination with hydroxyethyl cellulose or carboxyvinyl polymer, only an additive improvement in the moisture retention rate 6 hours after application was observed (Comparative Examples 2 to 5, 9 to 13, and 15 to 18). In contrast, when cetylpyridinium chloride and hypromellose were used in combination, the moisture retention rate 6 hours after application was synergistically improved, and the moisturizing effect was significantly longer lasting (Examples 1 to 6). In particular, when cetylpyridinium chloride, hypromellose, and sodium azulene sulfonate were used in combination, the moisture retention rate was further improved 6 hours after application, and the moisturizing effect was significantly longer lasting (Examples 4 to 6). The oral compositions of Examples 1 to 3 contain cetylpyridinium chloride, and therefore have compositions capable of exerting a bactericidal effect. The oral compositions of Examples 4 to 6 contain cetylpyridinium chloride and sodium azulene sulfonate, and therefore have compositions capable of exerting a bactericidal effect and an anti-inflammatory effect.

[0045] [Table 1]

[0046] [Table 2]

[0047] Prescription example Oral compositions (oral sprays) were prepared with the compositions shown in Table 3. 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 the durability of their moisturizing effect using the same method 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 18. Furthermore, 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, for the durability of their moisturizing effect.

[0048] [Table 3]

Claims

1. An oral composition (excluding (i) those containing ethyl aminobenzoate and (ii) those containing glycerin and hydroxyethyl cellulose) which is in a liquid or solid form and which contains (A) at least one quaternary ammonium salt selected from the group consisting of cetylpyridinium chloride, benzethonium chloride, and benzalkonium chloride, (B) hypromellose, and (C) azulene sulfonic acid and / or a salt thereof.

2. The oral composition according to claim 1, which is used for the prevention or treatment of dry mouth.

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