Oral composition

Abstract

To provide a formulation technique that inhibits the formation of deposits due to cryopreservation in an oral composition containing a quaternary ammonium salt and monoterpene.SOLUTION: The present invention discloses an oral composition containing a quaternary ammonium salt and monoterpene as well as hypromellose, wherein the composition can inhibit the formation of deposits due to cryopreservation.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an oral composition which contains a quaternary ammonium salt and a monoterpene and which is inhibited from forming precipitates due to storage at low temperatures. [Background technology]

[0002] Quaternary ammonium salts such as cetylpyridinium chloride have a bactericidal effect and are therefore widely used in oral compositions. It is also known that the incorporation of monoterpenes such as menthol into oral compositions can provide a refreshing feeling and improve the feeling of use. Various oral compositions containing quaternary ammonium salts and monoterpenes have been reported.

[0003] For example, Patent Document 1 discloses that a liquid oral composition containing 0.02 to 0.1 mass% cetylpyridinium chloride, 0.0003 to 0.005 mass% ethyl maltol, and 0.0001 to 0.02 mass% l-menthol and having a pH of 5.5 or more and less than 7.5, exhibits sufficient bactericidal effect, is pleasant to eat, has low irritation, and is comfortable to use.

[0004] Furthermore, Patent Document 2 discloses that a liquid oral cavity medicine containing a predetermined amount of each of cetylpyridinium chloride, glycerin, 1-menthol, ethyl alcohol, and propylene glycol has reduced bitterness and irritation.

[0005] However, the low-temperature stability of oral compositions containing a quaternary ammonium salt and a monoterpene has not been sufficiently investigated. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] JP 2016-222556 A [Patent Document 2] JP 2018-108963 A Summary of the Invention [Problem to be solved by the invention]

[0007] The present inventors have discovered a new problem in that a precipitate is formed when an oral composition containing a quaternary ammonium salt and a monoterpene is stored at low temperature.

[0008] Therefore, an object of the present invention is to provide a formulation technology that suppresses the formation of precipitates due to low-temperature storage in an oral composition containing a quaternary ammonium salt and a monoterpene. [Means for solving the problem]

[0009] The present inventors conducted extensive research to solve the above problems and found that an oral composition containing hypromellose together with a quaternary ammonium salt and a monoterpene can suppress the formation of precipitates during storage at low temperatures (e.g., 4°C or lower). Furthermore, the present inventors also found that the oral composition has a dramatically improved effect of preventing or improving dry throat. The present invention was completed through further research based on these findings.

[0010] That is, the present invention provides the following aspects. Item 1. An oral composition comprising a quaternary ammonium salt, a monoterpene, and hypromellose. 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, while containing a quaternary ammonium salt and a monoterpene, is inhibited from forming precipitates during low-temperature storage and has excellent formulation stability, so that the components contained therein can be stably maintained during storage and a good external appearance can be maintained. In addition, the oral composition of the present invention has an excellent effect of preventing or improving dry throat, and can be suitably used as an oral care product. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] 1.Oral composition The oral composition of the present invention is characterized by containing a quaternary ammonium salt, a monoterpene, and hypromellose. The oral composition of the present invention will be described below.

[0013] [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.

[0014] Among these quaternary ammonium salts, preferred are cetylpyridinium chloride, benzethonium chloride, and benzalkonium chloride, and more preferred are cetylpyridinium chloride.

[0015] 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 %.

[0016] [Monoterpene] The oral composition of the present invention contains a monoterpene. In the conventional oral composition, when a quaternary ammonium salt and a monoterpene are present together, a precipitate is formed when the composition is stored at a low temperature. However, in the present invention, the composition contains hypromellose, which will be described later, and thus the formation of the precipitate when the composition is stored at a low temperature can be suppressed.

[0017] Monoterpenes are known compounds that have a structure containing two isoprene units in the molecule and have cooling and refreshing properties.

[0018] 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.

[0019] 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.

[0020] Among these monoterpenes, menthol is preferable, and 1-menthol is more preferable.

[0021] The content of monoterpene 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 1 wt %, preferably 0.01 to 1 wt %, and more preferably 0.1 to 0.5 wt %.

[0022] In the oral composition of the present invention, the ratio of the quaternary ammonium salt to the monoterpene is determined according to the respective contents of these two components, but for example, the monoterpene may be 0.05 to 50 parts by weight, preferably 0.1 to 10 parts by weight, and more preferably 0.2 to 1.5 parts by weight per 1 part by weight of the quaternary ammonium salt.

[0023] [Hypromellose] The oral composition of the present invention contains hypromellose in addition to the above-mentioned components. By using hypromellose in addition to the quaternary ammonium salt and monoterpene, it is possible to suppress the formation of precipitates due to low-temperature storage, and further improve the effect of preventing or improving dry throat.

[0024] Hypromellose is a known cellulose derivative also known as hydroxypropyl methylcellulose.

[0025] The content of hypromellose in the oral cavity composition of the present invention is, for example, 0.01 to 1.5% by weight. From the viewpoint of further improving the effect of suppressing the formation of precipitates due to low-temperature storage and the effect of preventing or improving dry throat, the content of hypromellose in the oral cavity composition of the present invention is preferably 0.1 to 1.5% by weight, more preferably 0.2 to 0.7% by weight, and even more preferably 0.4 to 0.7% by weight.

[0026] In the oral composition of the present invention, the ratio of the quaternary ammonium salt to hypromellose is determined depending on the respective contents of these two components, and may be, for example, 0.01 to 100 parts by weight of hypromellose per part by weight of the quaternary ammonium salt. From the viewpoint of further improving the effect of inhibiting the formation of precipitates due to low-temperature storage and the effect of preventing or improving dry throat, the ratio of the quaternary ammonium salt to hypromellose is preferably 0.05 to 10 parts by weight, more preferably 0.5 to 3 parts by weight, and even more preferably 1 to 3 parts by weight.

[0027] [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.

[0028] 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.

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

[0030] 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, 0.01 to 15% by weight, preferably 0.1 to 10% by weight, and more preferably 1 to 8% by weight.

[0031] [Polyhydric alcohol] The oral composition of the present invention may contain a polyhydric alcohol in addition to the above-mentioned components.

[0032] 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, propylene 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.

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

[0034] When a polyhydric alcohol is contained in the oral composition of the present invention, the content is not particularly limited, but may be, for example, 1 to 80% by weight, preferably 5 to 50% by weight, and more preferably 10 to 30% by weight.

[0035] [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, 5 to 90% by weight, preferably 20 to 90% by weight, more preferably 50 to 85% by weight, and further preferably 60 to 85% by weight.

[0036] [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.

[0037] In addition, 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 (other than hypromellose), flavors, flavorings, colorants, deodorants, pigments, buffers, pH adjusters, etc.

[0038] [Shape, formulation, and use] 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., with a liquid being preferred.

[0039] 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.

[0040] 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.

[0041] In addition, the oral composition of the present invention can be used for oral care, but since it has an excellent effect in preventing dry throat, it is preferably used as one embodiment of the oral composition of the present invention for preventing or improving dry throat.

[0042] 2. Methods for suppressing the formation of precipitates The method for inhibiting the formation of precipitates of the present invention is a method for inhibiting the formation of precipitates in an oral composition containing a quaternary ammonium salt and a monoterpene, and is characterized in that the oral composition contains a quaternary ammonium salt, a monoterpene, and hypromellose.

[0043] In the method of inhibiting the formation of precipitates of the present invention, 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

[0044] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these.

[0045] Test Example 1 An oral composition (oral spray) was prepared having the composition shown in Table 1. Using the obtained oral composition, a low-temperature storage test and an evaluation test for the effect of improving dry throat were carried out as described below. <Low temperature storage test> 3.0 ml of the oral composition was placed in a 13.5 ml container, sealed, and stored at 4° C. under light-shielded conditions for 3 days. After storage for 3 days, the appearance of each oral composition was observed, and the score was divided into 10 levels according to the amount of precipitate, with 10 points for no precipitate at all and 1 point for the amount of precipitate observed in Comparative Example 2. Note that no precipitate was observed in any of the oral compositions immediately after preparation.

[0046] <Evaluation test for improving dry throat> Twelve complainants who were aware of a dry throat were asked to apply 0.2-0.3 ml of the oral composition to their throats using a spray bottle before going to bed. The following morning, they were asked to rate their satisfaction with the improvement in their dry throat on a five-point scale: "satisfied," "somewhat satisfied," "neither satisfied nor dissatisfied," "somewhat dissatisfied," and "dissatisfied." The percentage of those who answered "satisfied" or "somewhat satisfied" was calculated, and the value was rounded off to the first decimal place and scored according to the following criteria. 1: The percentage of people who answered "Satisfied" or "Somewhat satisfied" is 0-9% 2: The percentage of people who answered "Satisfied" or "Somewhat Satisfied" is 10-19% 3: The percentage of people who answered "Satisfied" or "Somewhat satisfied" is 20-29% 4: The percentage of people who answered "Satisfied" or "Somewhat Satisfied" is 30-39% 5: The percentage of people who answered "Satisfied" or "Somewhat Satisfied" is 40-49% 6: The percentage of people who answered "Satisfied" or "Somewhat satisfied" is 50-59%. 7: The percentage of people who answered "Satisfied" or "Somewhat satisfied" is 60-69%. 8: The percentage of people who answered "Satisfied" or "Somewhat satisfied" is 70-79%. 9: The percentage of people who answered "Satisfied" or "Somewhat Satisfied" is 80-89%. 10: The percentage of people who answered "Satisfied" or "Somewhat satisfied" is 90% or more.

[0047] The results are shown in Table 1. In the oral compositions containing cetylpyridinium chloride and menthol (Comparative Examples 1 and 2), the formation of precipitates was observed after storage at 4° C. for 3 days. In contrast, in the oral compositions containing hypromellose together with cetylpyridinium chloride and menthol (Examples 1 to 6), the formation of precipitates was suppressed after storage at 4° C. for 3 days. Furthermore, the oral compositions containing cetylpyridinium chloride, menthol, and hypromellose (Examples 1 to 6) showed a dramatically improved effect on improving dry throat compared to the compositions not containing hypromellose.

[0048] [Table 1]

[0049] Prescription Examples Oral compositions (oral sprays) having the compositions shown in Table 2 were prepared. Formulation Examples 1 and 2 are oral compositions in which the pH of Example 6 is changed to 7.1 or 8.5. Formulation Examples 3 to 6 are oral compositions in which cetylpyridinium chloride is replaced with benzalkonium chloride or benzethonium chloride in Example 5 or 6. For each oral composition, a low-temperature storage test and an evaluation test for the effect of improving dry throat were performed in the same manner as in Test Example 1. As a result, in all oral compositions, the formation of precipitates after storage at 4°C for 3 days was suppressed, and the effect of improving dry throat was dramatically improved.

[0050] [Table 2]

Claims

[Claim 1] An oral composition containing 0.01 to 5% by weight of at least one quaternary ammonium salt selected from the group consisting of cetylpyridinium chloride, benzalkonium chloride, and benzethonium chloride, 0.1 to 1% by weight of an alcohol-based monoterpene, and 0.1 to 1.5% by weight of hypromellose (excluding those containing peppermint oil and a phosphocholine group-containing polymer, those containing hydroxypropyl cellulose and polyvinylpyrrolidone, those containing polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 10 or more and 30 or less, those containing glycerin and hydroxyethyl cellulose, and those containing a phosphocholine group-containing polymer and glycerin).

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