Oral composition

Abstract

To provide a formulation technique that inhibits the formation of insoluble matter in an oral composition containing azulene sulfonic acid and / or a salt thereof, a quaternary ammonium salt, and monoterpene 0.5 wt.% or more.SOLUTION: The present invention discloses an oral composition containing azulene sulfonic acid and / or a salt thereof, a quaternary ammonium salt, and monoterpene 0.5 wt.% or more, as well as propyleneglycol 25 pts.wt. or more relative to the monoterpene 1 pt.wt., so that the composition can inhibit the formation of insoluble matter.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an oral composition which contains azulene sulfonic acid and / or a salt thereof, a quaternary ammonium salt, and 0.5% by weight or more of a monoterpene, and in which the formation of insoluble matter is suppressed. [Background technology]

[0002] Azulene sulfonic acid and its salts, and quaternary ammonium salts, each have anti-inflammatory and bactericidal effects, and are therefore widely used in oral compositions. Various oral compositions containing both azulene sulfonic acid or its salts and quaternary ammonium salts have been reported.

[0003] For example, Patent Document 1 discloses that a liquid preparation for oral and throat diseases containing sodium azulene sulfonate and 0.4 to 2 w / v % cetylpyridinium chloride does not become cloudy, precipitate, discolor, etc. even when stored for a long period of time, and can exert bactericidal and anti-inflammatory effects.

[0004] Patent Document 2 also discloses that a liquid formulation containing 0.001 to 1.0 mass% of an alkali metal salt of azulene sulfonate and 0.05 to 5.0 mass% of cetylpyridinium chloride and no bicarbonate and having a pH of 3.0 to 6.5 has excellent formulation stability.

[0005] On the other hand, it is known that the incorporation of a monoterpene such as menthol into an oral composition can provide a refreshing feeling and improve the feeling of use. However, there has been no sufficient study on the formulation technology for an oral composition containing a monoterpene together with azulene sulfonic acid and / or its salt and a quaternary ammonium salt. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] JP 2009-62285 A [Patent Document 2] JP 2003-81822 A Summary of the Invention [Problem to be solved by the invention]

[0007] In order to provide an oral composition containing azulene sulfonic acid and / or its salt and a quaternary ammonium salt with a greater cooling sensation and usability, the inventors considered incorporating a high content of monoterpene. However, they discovered a new problem: when the monoterpene content is 0.5% by weight or more, insoluble matter is generated that is not solubilized and separates after storage, resulting in reduced formulation stability.

[0008] Therefore, an object of the present invention is to provide a formulation technology that suppresses the formation of insoluble matter in an oral composition containing azulene sulfonic acid and / or its salt, a quaternary ammonium salt, and 0.5% by weight or more of monoterpene. [Means for solving the problem]

[0009] The present inventors have conducted extensive research to solve the above problems, and have found that the formation of insoluble matters can be suppressed by blending 25 parts by weight or more of propylene glycol per part by weight of monoterpene together with azulene sulfonic acid and / or its salt, quaternary ammonium salt, and 0.5% by weight or more of monoterpene in an oral composition. The present invention was completed through further research based on this finding.

[0010] That is, the present invention provides the following aspects. Item 1. A composition comprising azulene sulfonic acid and / or its salt, a quaternary ammonium salt, a monoterpene, and propylene glycol, The monoterpene content is 0.5% by weight or more, An oral composition comprising 25 or more parts by weight of propylene glycol per 1 part by weight of monoterpene. Item 2. The oral composition according to Item 1, wherein the quaternary ammonium salt is at least one selected from the group consisting of cetylpyridinium chloride, benzalkonium chloride, and benzethonium chloride. Effect of the Invention

[0011] The oral composition of the present invention contains 0.5% by weight or more of azulene sulfonic acid and / or its salt, quaternary ammonium salt, and monoterpene, but can suppress the generation of insoluble matter that is not solubilized and separated after storage, and has excellent formulation stability, so that the components contained therein can be stably maintained during storage and a good appearance shape can be maintained.In addition, the oral composition of the present invention contains 0.5% by weight or more of monoterpene, so that it has an enhanced refreshing feeling and usability, and can give consumers a high level of satisfaction in use. [Brief description of the drawings]

[0012] [Figure 1] 1 shows photographs of the appearance of the oral compositions of Example 4 and Comparative Example 3 observed from above the container after storage for 7 days. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] 1. Oral composition The oral composition of the present invention is characterized by comprising azulene sulfonic acid and / or its salt, quaternary ammonium, monoterpene, and propylene glycol, the monoterpene content being 0.5% by weight or more, and the propylene glycol being 25 parts by weight or more per part by weight of monoterpene. The oral composition of the present invention will be described below.

[0014] [Azulene sulfonic acid and / or its salt] The oral composition of the present invention contains azulene sulfonic acid and / or a salt thereof.

[0015] Azulene sulfonic acid, also known as 1,4-dimethyl-7-isopropylazulene-3-sulfonic acid, is a known anti-inflammatory ingredient.

[0016] 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 sulfonate salts such as methanesulfonate, toluenesulfonate, tosylate; organic amine salts such as methylamine salt, triethylamine salt, triethanolamine salt, morpholine salt, piperazine salt, pyrrolidine salt, tripyridine salt, picoline salt; and inorganic acid salts such as hydrochloride, sulfate, nitrate, hydrobromide, phosphate.

[0017] The oral cavity composition of the present invention may contain one kind of azulene sulfonic acid and its salts alone or two or more kinds of azulene sulfonic acid and its salts in combination.

[0018] Among azulene sulfonic acid and salts thereof, preferred are salts of azulene sulfonic acid, more preferred are alkali metal salts of azulene sulfonic acid, and even more preferred is sodium azulene sulfonate.

[0019] The content of azulene sulfonic acid and / or its salt 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 5 wt %, preferably 0.001 to 1 wt %, and more preferably 0.01 to 0.5 wt %. [Quaternary ammonium salts] The oral composition of the present invention contains a quaternary ammonium. The type of quaternary ammonium salt used in the present invention is not particularly limited as long as it is pharmacologic acceptable, but for example, a quaternary ammonium salt having a bactericidal action 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 quaternary ammonium salts may be used alone or in combination of two or more.

[0020] Among these quaternary ammonium salts, preferred are cetylpyridinium chloride, benzethonium chloride, and benzalkonium chloride, and more preferred are cetylpyridinium chloride.

[0021] The content of the quaternary ammonium salt 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, 0.001 to 5 wt %, preferably 0.01 to 2 wt %, and more preferably 0.05 to 1.25 wt %.

[0022] In the oral composition of the present invention, the ratio of azulene sulfonic acid and / or its salt to the quaternary ammonium salt is determined according to the respective contents of these two components, but for example, the quaternary ammonium salt may be 0.1 to 1000 parts by weight, preferably 1 to 100 parts by weight, and more preferably 5 to 50 parts by weight per 1 part by weight of azulene sulfonic acid and / or its salt.

[0023] [Monoterpene] The oral composition of the present invention contains 0.5% by weight or more of monoterpene. In the prior art, when azulene sulfonic acid and / or its salt, quaternary ammonium salt, and 0.5% by weight or more of monoterpene are present in the oral composition, insoluble matter is generated during storage. However, in the present invention, the generation of insoluble matter can be suppressed by including a predetermined amount of propylene glycol, which will be described later.

[0024] Monoterpenes are known compounds that have a structure containing two isoprene units in the molecule and have cooling and refreshing properties.

[0025] The type of monoterpene used in the present invention is not particularly limited as long as it is pharma- ceutically acceptable, and examples thereof include alcohol monoterpenes such as menthol, thymol, geraniol, linalool, borneol, cineole, and terpineol; aldehyde monoterpenes such as citral, citronellal, perillaldehyde, and safranal; and ketone monoterpenes such as camphor, menthone, carbomenthone, and ionone. When optical isomers exist, these monoterpenes may be d-, l-, or dl-isomers. These monoterpenes may be used alone or in combination of two or more kinds.

[0026] In addition, in the present invention, as the monoterpene, an essential oil containing monoterpene may be used. The essential oil containing monoterpene can be appropriately selected from known ones and used, and for example, essential oil containing menthol includes peppermint oil, peppermint oil, spearmint oil, etc. In addition, the description of the content and ratio of monoterpene in this specification is the value converted into the amount of monoterpene contained in the essential oil when an essential oil containing monoterpene is used.

[0027] Among these monoterpenes, menthol is preferable, and 1-menthol is more preferable.

[0028] The content of the monoterpene in the oral cavity composition of the present invention may be 0.5% by weight or more, specifically 0.5 to 1% by weight, and preferably 0.5 to 0.8% by weight.

[0029] In the oral composition of the present invention, the ratio of azulene sulfonic acid and / or its salt to monoterpene is determined according to the respective contents of these two components, but for example, the ratio may be 1 to 1,000 parts by weight, preferably 5 to 100 parts by weight, and more preferably 20 to 60 parts by weight of monoterpene per 1 part by weight of azulene sulfonic acid and / or its salt.

[0030] [Propylene glycol] The oral composition of the present invention contains 25 parts by weight or more of propylene glycol per part by weight of monoterpene. By containing propylene glycol in such a ratio, it is possible to suppress the formation of insoluble matter during storage in the oral composition containing azulene sulfonic acid and / or its salt, a quaternary ammonium salt, and 0.5% by weight or more of monoterpene.

[0031] The amount of propylene glycol contained may be 25 parts by weight or more per part by weight of monoterpene, but from the viewpoint of more effectively suppressing the formation of insoluble matter, the amount of propylene glycol contained per part by weight of monoterpene is 25 to 500 parts by weight, preferably 30 to 100 parts by weight, more preferably 35 to 60 parts by weight, and even more preferably 40 to 60 parts by weight.

[0032] The content of propylene glycol in the present invention may be appropriately set within a range that satisfies the ratio to the monoterpene described above, and may be, for example, 12.5 to 70% by weight, preferably 12.5 to 60% by weight, and more preferably 20 to 50% by weight.

[0033] [Monohydric lower alcohol] The oral cavity composition of the present invention may contain a monohydric lower alcohol in addition to the above-mentioned components. In the present invention, the monohydric lower alcohol refers to a monohydric alcohol having 1 to 5 carbon atoms.

[0034] The type of monohydric lower alcohol is not particularly limited as long as it is pharma- ceutically 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.

[0035] Among these monohydric lower alcohols, ethanol is preferable.

[0036] When a monohydric lower alcohol is contained in the oral composition of the present invention, the content is not particularly limited, but may be, for example, 0.1 to 20% by weight, preferably 1 to 20% by weight, and more preferably 5 to 15% by weight.

[0037] [Polyhydric alcohol other than propylene glycol] The oral cavity composition of the present invention may contain a polyhydric alcohol other than propylene glycol in addition to the above-mentioned components. In the present invention, the monohydric lower alcohol refers to a monohydric alcohol having 1 to 5 carbon atoms.

[0038] The type of polyhydric alcohol is not particularly limited as long as it is pharma- ceutically acceptable, and examples thereof include dihydric alcohols such as 1,3-butylene glycol, ethylene glycol, isoprene glycol, diethylene glycol, dipropylene glycol, polyethylene glycol, etc.; glycerin, etc. These polyhydric alcohols may be used alone or in combination of two or more.

[0039] Among these polyhydric alcohols, glycerin is preferred.

[0040] When the oral composition of the present invention contains a polyhydric alcohol other than propylene glycol, the content is not particularly limited, but may be, for example, 0.1 to 50% by weight, preferably 1 to 50% by weight, and more preferably 10 to 40% by weight.

[0041] [Sugar alcohol] The oral composition of the present invention may contain a sugar alcohol in addition to the above-mentioned components.

[0042] The type of sugar alcohol is not particularly limited as long as it is pharma- ceutically acceptable, and examples thereof 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.

[0043] When a sugar alcohol is contained in the oral composition of the present invention, the 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 1 to 10% by weight.

[0044] [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, 0.01 to 60% by weight, preferably 0.1 to 50% by weight, more preferably 0.1 to 40% by weight.

[0045] [Other ingredients] The oral cavity composition of the present invention may contain other medicinal ingredients as necessary, in addition to the above-mentioned ingredients. Such medicinal ingredients are not particularly limited, as long as they can be incorporated into medicines, oral care products, etc., and include, for example, iodine-based bactericidal ingredients (e.g., iodine, povidone iodine, nonoxynol iodine, phenoxy iodine, etc.), bronchodilators, antitussives, expectorants, anti-inflammatory agents, glucosyltransferase inhibitors, plaque inhibitors, dentin hypersensitivity inhibitors, tartar prevention agents, antipyretics, analgesics, antihistamines, bactericides (other than quaternary ammonium salts), gastric mucosa protective drugs, caffeines, vitamins, Chinese herbal medicines, herbal ingredients, etc.

[0046] The oral cavity composition of the present invention may contain a base or additive to obtain a desired formulation. Such base or additive is not particularly limited as long as it can be incorporated into pharmaceuticals, oral care products, etc., and examples thereof include oily components, surfactants, preservatives, thickeners, fragrances, flavorings, colorants, deodorants, pigments, buffers, pH adjusters, etc.

[0047] [Shape / Form of preparation] 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.

[0048] When the oral composition of the present invention is liquid or semi-solid, its pH may be appropriately set within a range acceptable for application to the oral cavity, for example, 6.0 to 9.5, preferably 7.0 to 9.0, and more preferably 7.5 to 8.5.

[0049] 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. Among these, preferred are oral sprays, mouthwashes, and gargles, and more preferred are oral sprays.

[0050] 2. Method for preventing the formation of insoluble matter The method of the present invention for inhibiting the formation of insoluble matter is a method for inhibiting the formation of insoluble matter in an oral composition containing azulene sulfonic acid and / or its salt, a quaternary ammonium salt, and 0.5 wt% or more of monoterpene, and is characterized in that the oral composition contains 25 weight parts or more of propylene glycol per weight part of monoterpene, in addition to azulene sulfonic acid and / or its salt, a quaternary ammonium salt, and 0.5 weight% or more of monoterpene.

[0051] In the method of the present invention for inhibiting the formation of insoluble matter, the types and amounts of the components used, the shape and formulation of the oral composition, etc. are as shown in the section "1. Oral composition" above. EXAMPLES

[0052] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these.

[0053] Test Example 1 Oral compositions (oral sprays) having the compositions shown in Tables 1 to 3 were prepared. 10.0 ml of the obtained oral compositions were placed in a 13.5 ml container with the lid open (area of ​​the opening: approximately 1.7 cm 2) at 25°C for 7 days. After storage for 7 days, the appearance of each oral composition was observed, and a score was assigned to each of the following 10 levels according to the amount of insoluble matter: 10 points for no insoluble matter that was not solubilized and separated, 1 point for the same amount of insoluble matter as in Comparative Example 3. Note that no insoluble matter was found in any of the oral compositions immediately after preparation.

[0054] The results are shown in Tables 1 to 3. Photographs of the appearance of the oral compositions of Example 4 and Comparative Example 3 after storage for 7 days, observed from above the container, are shown in Fig. 1. Within the dotted frame in the photograph of Comparative Example 3 in Fig. 1, insoluble matter that was not solubilized and was in a separated state is observed.

[0055] In an oral composition containing sodium azulene sulfonate, cetylpyridinium chloride, 0.1% by weight of menthol, and propylene glycol, even if the amount of propylene glycol was 20 parts by weight per 1 part by weight of menthol, no insoluble matter was generated after storage (Reference Example 1). On the other hand, in an oral composition containing sodium azulene sulfonate, cetylpyridinium chloride, 0.5% by weight or more of menthol, and propylene glycol, when the amount of propylene glycol was less than 25 parts by weight per 1 part by weight of menthol, insoluble matter was generated after storage (Comparative Examples 1 to 4). On the other hand, in an oral composition containing sodium azulene sulfonate, cetylpyridinium chloride, 0.5% by weight or more of menthol, and propylene glycol, when the amount of propylene glycol was 25 parts by weight or more per 1 part by weight of menthol, the generation of insoluble matter after storage was effectively suppressed (Examples 1 to 10). In particular, when the amount of propylene glycol was 40 to 60 parts by weight per part by weight of menthol, no formation of insoluble matter was observed after storage, and the effect of inhibiting the formation of insoluble matter was remarkable (Examples 2 to 4, 6, 8 and 10).

[0056] [Table 1]

[0057] [Table 2]

[0058] [Table 3]

[0059] Prescription Examples

[0060] The oral compositions (oral sprays) shown in Table 4 were prepared. Formulation Examples 1 and 2 are oral compositions in which cetylpyridinium chloride in Examples 1 and 2 was replaced with benzalkonium chloride, respectively. Formulation Examples 3 and 4 are oral compositions in which cetylpyridinium chloride in Examples 1 and 2 was replaced with benzethonium chloride, respectively. For comparison, comparative oral compositions were also prepared in which propylene glycol in Formulation Examples 1 and 3 was changed to 20 parts by weight per 1 part by weight of menthol. The insoluble matter after storage of these oral compositions was also confirmed under the same conditions as in Test Example 1. As a result, the formation of insoluble matter after storage was observed in the comparative oral compositions corresponding to each of the oral compositions shown in Table 4. In contrast, the formation of insoluble matter after storage was effectively suppressed in all of the oral compositions shown in Table 4.

[0061] [Table 4]

Claims

[Claim 1] At least one quaternary ammonium salt selected from the group consisting of azulene sulfonate, cetylpyridinium chloride, benzalkonium chloride, and benzethonium chloride, an alcohol monoterpene, and propylene glycol; The content of alcohol monoterpene is 0.5% by weight or more, The content of azulene sulfonate is 0.0001 to 0.5% by weight, An oral composition (excluding those containing ethyl aminobenzoate) comprising 25 parts by weight or more of propylene glycol per 1 part by weight of an alcohol-based monoterpene.

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