TW202228664A - Oral composition - Google Patents

Abstract

The objective of the present invention is to provide an oral composition that exhibits anti-inflammatory action inside the oral cavity and that is capable of maintaining continuous moisturizing effect on the oral mucosa. An oral composition containing (A) an azulene sulfonic acid and/or a salt thereof, and (B) hypromellose.

Description

Oral composition

The present invention relates to a composition for oral cavity, which can reduce inflammation in the oral cavity and can continuously exert moisturizing effect on the oral mucosa.

In recent years, there has been an increase in the number of patients with dry mouth. Also known as xerostomia, xerostomia is a symptom in which the secretion of saliva decreases and the inside of the mouth becomes dry. With regard to dry mouth, various reasons such as aging, stress, decreased muscle strength, diabetes, renal insufficiency, menopausal disorders, and side effects of medication can be considered, and in most cases, these reasons cannot be completely eliminated, so in the treatment of dry mouth, In the case of having to rely on symptomatic treatment for moisturizing the oral cavity with oral compositions such as oral sprays, gargles, mouthwashes, artificial saliva, and troche.

Conventionally, various reports have been made on oral compositions effective in preventing or improving dry mouth. For example, Patent Document 1 discloses that a composition for oral cavity containing a hydrophobically modified polyether urethane and a humectant is effective for prevention or treatment of dry mouth. In addition, Patent Document 2 discloses that 0.05% by mass to 5% by mass of polyglutamic acid salts, 2% by mass to 6% by mass of organic acids such as citric acid and salts thereof, 10% by mass to 10% by mass of 1-menthol and glycerin 50 mass %, surfactant, and 0.01 mass % - 0.3 mass % of the composition for oral spray of monomenthyl succinate are effective for prevention or treatment of dry mouth. [Prior Art Literature] [Patent Literature]

[Patent Document 1] Japanese Patent Laid-Open No. 2012-153677 [Patent Document 2] Japanese Patent Laid-Open No. 2011-105651

[The problem to be solved by the invention]

In the prevention or treatment of dry mouth, it is important not only to temporarily impart a moisturizing effect to the oral mucosa, but also to maintain the effect. In addition, xerostomia is caused by the drying of the oral mucosa, which reduces the barrier function against bacteria, and thus easily causes bacterial infection or inflammation in the oral cavity. Therefore, it is desirable for an oral composition to be effective in preventing or treating dry mouth not only to impart a moisturizing effect to the inside of the oral cavity, but also to have an anti-inflammatory effect.

Therefore, an object of the present invention is to provide a composition for oral cavity which can reduce inflammation in the oral cavity and can continuously exhibit the moisturizing effect on the oral mucosa. [Means of Solving Problems]

The inventors of the present invention have made diligent studies to solve the above-mentioned problems, and as a result, they have found that by using azulenic sulfonic acid and/or a salt thereof and hypromellose in combination in an oral composition, the anti-inflammatory effect is exhibited, and these The synergistic effect of the ingredients dramatically improves the sustainability of the moisturizing effect on the oral mucosa. The present invention has been completed by further repeated studies based on the above findings.

That is, this invention provides invention of the aspect disclosed below. 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, for preventing or treating dry mouth. [Effect of invention]

The oral composition of the present invention exhibits an anti-inflammatory effect and a sustained moisturizing effect on the oral mucosa, so it is effective for oral care, and can be suitably used, for example, for the prevention or treatment of dry mouth.

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

[(A) Azulene sulfonic acid and/or its salt] The oral composition of this invention contains azulene sulfonic acid and/or its salt (it may also be expressed as (A) component). The composition for external use of the present invention can exhibit an anti-inflammatory effect in the oral cavity by including azulene sulfonic acid and/or its salt.

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

There is no particular limitation on the type of the salt of azulene sulfonic acid to the extent that it is pharmaceutically acceptable, and examples thereof include alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as calcium salts and magnesium salts; aluminum salts and others. Metal salts; ammonium salts; acetate, trifluoroacetate, butyrate, palmitate, stearate, fumarate, maleate, succinate, malonate, lactate, tartaric acid Salts, citrates and other carboxylates; methanesulfonate, tosylate, p-toluenesulfonate and other organic sulfonates; methylamine salts, triethylamine salts, triethanolamine salts, morpholine salts, Organic amine salts such as piperazine salt, pyrrolidine salt, tripyridine salt, picoline salt; inorganic acid salt such as hydrochloride, sulfate, nitrate, hydrobromide, phosphate, etc. Among these salts, preferred examples include alkali metal salts, and more preferred examples include sodium salts.

Among the components (A), from the viewpoint of further improving the sustainability of the moisturizing effect on the oral mucosa, salts of azulene sulfonic acid are preferably used, and sodium azulene sulfonate is more preferably used.

As the component (A), one component may be used alone from azulene sulfonic acid and a salt thereof, or two or more components may be used in combination.

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

[(B) Hypromellose] The oral composition of this invention contains hypromellose (it may be expressed as (B) component) in addition to the said (A) component. By using the component (A) and hypromellose in combination, the continuation of the moisturizing effect on the oral mucosa can be dramatically improved by the synergistic effect of these.

The so-called hydroxypropyl cellulose is a well-known cellulose derivative also called hydroxypropyl methyl cellulose.

The content of the component (B) in the oral composition of the present invention may be appropriately set according to the formulation form of the oral composition, for example, 0.01% by weight to 1.5% by weight, preferably 0.1% by weight to 1.5% by weight % by weight, more preferably 0.2% by weight to 1.5% by weight, still more preferably 0.5% by weight to 1.5% by weight. When the content of the component (B) satisfies the above-mentioned range, the durability of the moisturizing effect on the oral mucosa can be remarkably improved without causing a decrease in the feeling of use due to an increase in the viscosity.

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

[(C) Monohydric lower alcohol] The oral cavity composition of this invention may contain a monovalent lower alcohol (it may be expressed as (C) component) in addition to the said (A) component and (B) component. 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 pharmaceutically acceptable, for example, ethanol, n-propanol, isopropanol, n-butanol, 2nd butanol, 3rd butanol, n-pentanol alcohol, second amyl alcohol, isoamyl alcohol, third amyl alcohol, neopentyl alcohol, etc. These monovalent lower alcohols may be used alone or in combination of two or more.

Among these monohydric lower alcohols, ethanol is preferably used.

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

[(D) Polyol] The oral cavity composition of this invention may contain a polyhydric alcohol (it may be expressed as (D) component) in addition to the said (A) component and (B) component.

The type of polyhydric alcohol is not particularly limited as long as it is pharmaceutically acceptable, for example, 1,3-butanediol, ethylene glycol, propylene glycol, isopropylene glycol, diethylene glycol, dipropylene glycol, polyethylene glycol Diols such as diols; glycerol, etc. These polyols may be used alone or in combination of two or more.

Among these polyhydric alcohols, dihydric alcohols are preferable, and propylene glycol is more preferable.

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

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

[other ingredients] The oral composition of the present invention may contain other medicinally effective components as necessary in addition to the above-mentioned components. Such a medicinal ingredient is not particularly limited as long as it can be formulated into pharmaceuticals, oral care products, etc., and examples thereof include iodine-based bactericidal ingredients (for example, iodine, povidone iodine, Phenyl alcohol ether iodine (nonoxynol iodine and phenoxy iodine, etc.), bronchodilators, antitussives, expectorants, anti-inflammatory agents (except azulene sulfonic acid and its salts), glucosyltransferase inhibitors, plaque inhibitors (plaque inhibitor), hyperesthesia inhibitors, calculus preventives, antipyretic analgesics, antihistamines, bactericides (except quaternary ammonium salts), gastric mucosal protective drugs, caffeine, vitamin drugs, traditional Chinese medicines, herbal ingredients, etc. .

Moreover, in order to make into a desired formulation form, a base or an additive may be contained in the oral composition of this invention. Such bases and additives are not particularly limited as long as they can be formulated into pharmaceuticals, oral care products, and the like, and examples thereof include oily components, surfactants, preservatives, thickeners (hypromellose) (excluding vegetarian), fragrances, flavoring agents, cooling agents, pigments, deodorants, pigments, buffers, pH adjusters, etc.

[Shape and Form of Preparation] The shape of the oral composition of the present invention is not particularly limited, and may be any of liquid, solid, semi-solid (gel, ointment, and paste), and preferably liquid .

The formulation form of the oral composition of the present invention is not limited as long as it can be applied to the oral cavity and remains in the oral cavity for a certain period of time, and examples thereof include oral spray (including throat spray), mouthwash, gargle Oral care products such as agent, liquid dentifrice, toothpaste, mouth cooling agent, oral paste, gum massage cream, etc. Among these, a spray for oral cavity, a mouthwash, and a gargle are preferably mentioned, and a spray for oral cavity is more preferably used.

[Instructions] By applying the oral composition of the present invention to the oral cavity, the oral cavity can be anti-inflammatory and/or sterilized, and furthermore, the oral mucosa can continue to have a moisturizing effect. Therefore, it can be suitably used, for example, for the prevention or treatment of dry mouth.

The usage and volume of the oral composition of the present invention can be appropriately set according to the content of each compounded component, the preparation form of the oral composition, the expected effect, etc., for example, the frequency of once to six times a day can be used in the oral cavity. Apply the right amount. [Example]

The present invention will be described more specifically with reference to examples below, but the present invention is not limited to these examples.

Test Example 1 Oral compositions (oral sprays) having the compositions shown in Table 1 were prepared. About the obtained composition for oral cavity, the sustainability of the moisturizing effect on the oral mucosa was evaluated by the following method. First, use running water to lightly wet the edible pig tongue (unsliced state) that has been excised as a suspected mucous membrane, wipe it gently, and let it stand at 30°C and a relative humidity of 30%RH until an oral moisture meter (oral moisture content) is used. The measured value measured by Mucus (Yoshida Co., Ltd.) becomes the dryness index value (25 or less). Then, the obtained composition for oral cavity was accommodated in a spray container, and about 0.3 ml of the composition for oral cavity was sprayed and applied to the position slightly from the center of the pig tongue to the front end, at 30° C. and relative humidity of 30% RH. in the environment for 6 hours. Immediately after application of the oral composition and 6 hours after application of the oral composition, the application of the oral composition was measured using an oral moisture meter (Mucus, Yoshida Co., Ltd.) The moisture value of the pig tongue was calculated according to the following formula, and the moisture retention rate (%) after 6 hours of application was calculated, and the value after rounding the value to the first decimal place was used as the moisture retention rate after 6 hours of application. Rate(%). [Number 1] Moisture retention rate (%) after 6 hours of coating = (Moisture value after 6 hours of coating/Moisture value just after coating) × 100

The results are shown in Table 1. When sodium azulene sulfonate was used alone, the water retention rate after 6 hours of application was low, and the moisturizing effect could not be sustained (Comparative Example 1). In addition, even if hypromellose, hydroxyethyl cellulose, and carboxyvinyl polymers were used alone, the water retention rate after 6 hours of coating was slightly improved, but still insufficient (Comparative Example 6 ~Comparative Example 8). Furthermore, even if hydroxyethyl cellulose or carboxyvinyl polymer was used together with sodium azulene sulfonate, the water retention rate after 6 hours of coating was only confirmed to increase in additivity (Comparative Examples 2 to 5) . On the other hand, when sodium azulene sulfonate and hypromellose were used in combination, the water retention rate after 6 hours of application was synergistically improved, and the sustainability of the moisturizing effect was significantly improved (Examples 1 to 3). ). In addition, since the oral compositions of Examples 1 to 3 contained sodium azulene sulfonate, they had compositions capable of exhibiting an anti-inflammatory effect.

[Table 1] Comparative example Example 1 2 3 4 5 6 7 8 1 2 3 Sodium azulene sulfonate 0.02 0.02 0.02 0.02 0.02 - - - 0.02 0.02 0.02 Hypromellose ^#1 - - - - - 0.3 - - 0.3 0.7 1.4 Hydroxyethyl cellulose - 0.3 1.4 - - - 0.3 - - - - Carboxy vinyl polymer - - - 0.3 1.4 - - 0.3 - - - Ethanol 1 1 1 1 1 1 1 1 1 1 1 Propylene Glycol 55 55 55 55 55 55 55 55 55 55 55 purified water The remaining part The remaining part The remaining part The remaining part The remaining part The remaining part The remaining part The remaining part The remaining part The remaining part The remaining part Total (wt%) 100 100 100 100 100 100 100 100 100 100 100 Moisture retention rate (%) after 6 hours of coating 3 12 18 14 20 10 9 10 34 38 40 #1 Hypromellose using the trade name "Metolose 60SH-4000" (manufactured by Shin-Etsu Chemical Co., Ltd.).

Prescription example Oral compositions (oral sprays) having the compositions shown in Table 2 were prepared. Moreover, for comparison, the composition for oral cavity for comparison which changed the hypromellose of prescription example 5 and prescription example 6 to purified water was also prepared. By the same method as in Test Example 1, the persistence of moisturizing effect was evaluated with respect to these oral compositions. Compared with Comparative Examples 1 to 8, the water retention ratios of formulation examples 1 to 4 after application for 6 hours were significantly improved in the sustainability of the moisturizing effect. In addition, in Recipe Example 5 and Recipe Example 6 in which cetylpyridinium chloride was replaced by benzalkonium chloride or benzethonium chloride, after 6 hours of application, the The water retention rate was also significantly improved compared with the oral compositions for comparison of the formulation examples 5 and 6, and the comparative examples 1 to 18.

[Table 2] Prescription example 1 2 3 4 5 6 Sodium azulene sulfonate 0.02 0.02 0.02 0.02 0.02 0.02 cetylpyridinium chloride 0.3 0.3 0.3 0.3 - - Benzylammonium chloride - - - - 0.3 - benzoxonine chloride - - - - - 0.3 Hypromellose 0.5 0.7 0.8 1.0 0.7 0.7 Ethanol 0.5 1.5 1.5 1.5 1.5 1.5 Propylene Glycol 60 60 60 60 55 55 Sodium Saccharin Hydrate 0.2 0.35 0.35 0.4 0.2 0.2 Menthol 0.1 0.2 0.2 0.2 0.2 0.2 Anhydrous sodium dihydrogen phosphate Moderate Moderate Moderate Moderate Moderate Moderate Sodium Phosphate Hydrate Moderate Moderate Moderate Moderate Moderate Moderate purified water The remaining part The remaining part The remaining part The remaining part The remaining part The remaining part Total (wt%) 100 100 100 100 100 100

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Claims (2)

An oral composition comprising (A) azulene sulfonic acid and/or a salt thereof, and (B) hypromellose. The oral composition according to claim 1, for preventing or treating dry mouth.