Composition for nasal irrigation

Abstract

To provide a composition for washing a nasal cavity that contains a preservative and a thickener and has reduced white turbidness.SOLUTION: A composition for washing a nasal cavity has a preservative and a thickener blended with a nonionic surfactant, so that the composition achieves reduced white turbidness and superior appearance properties.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a nasal irrigation composition containing a preservative and a thickener, with turbidity suppressed.

Background Art

[0002] The nasal mucosa is an epithelial tissue that is directly exposed to the outside world and reacts sensitively to external stimuli. When foreign substances such as pollen, microorganisms, and house dust adhere to the nasal mucosa, it is known to cause intolerable discomfort or various diseases such as allergic diseases and infectious diseases. To prevent or improve such nasal mucosal symptoms, it is effective to remove foreign substances adhering to the mucosa with a nasal irrigation composition.

[0003] Since nasal irrigation compositions may be used when going out or used repeatedly, they are required to have preservative performance. Therefore, conventionally, various formulations of nasal irrigation compositions containing preservatives such as benzalkonium chloride have been reported (see, for example, Patent Document 1).

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] To improve the usability of the nasal irrigation composition and control the particle size of the droplets formed when introducing the nasal irrigation composition into the nasal cavity in the form of droplets, it is effective to blend a thickener. Therefore, the present inventor proceeded with studies to develop a nasal irrigation composition containing a preservative and a thickener, and found that turbidity occurs and the appearance properties deteriorate in the nasal irrigation composition containing a preservative and a thickener.

[0006] Therefore, an object of the present invention is to provide a nasal irrigation composition containing a preservative and a thickener and having suppressed cloudiness.

Means for Solving the Problems

[0007] As a result of intensive studies to solve the above problems, the present inventor has found that by blending a nonionic surfactant together with a preservative and a thickener in a nasal irrigation composition, cloudiness can be suppressed and excellent appearance properties can be obtained. The present invention has been completed by further studies based on such findings.

[0008] That is, the present invention provides inventions in the following aspects. Item 1. A nasal irrigation composition containing a preservative, a thickener, and a nonionic surfactant. Item 2. The nasal irrigation composition according to Item 1, wherein the preservative is a paraoxybenzoic acid ester and / or a quaternary ammonium salt. Item 3. The nasal irrigation composition according to Item 1 or 2, wherein the thickener is a cellulose-based thickener and / or a polyvinyl-based thickener. Item 4. The nasal irrigation composition according to any one of Items 1 to 3, wherein the nonionic surfactant is a polyoxyethylene sorbitan fatty acid ester and / or a polyoxyethylene hydrogenated castor oil. Item 5. The nasal irrigation composition according to any one of Items 1 to 4, which is contained in a container capable of discharging the contents in the form of droplets into the nasal cavity by dropping or spraying.

Effects of the Invention

[0009] The nasal irrigation composition of the present invention can suppress cloudiness and has excellent appearance properties while containing a preservative and a thickener.

Modes for Carrying Out the Invention

[0010] 1. Composition for nasal irrigation The nasal irrigation composition of the present invention is characterized by containing a preservative, a thickener, and a nonionic surfactant. Hereinafter, the nasal irrigation composition of the present invention will be described in detail.

[0011] [Preservative] The nasal irrigation composition of the present invention contains a preservative. By including a preservative in the nasal irrigation composition of the present invention, it is possible to have preservative performance.

[0012] The preservative used in the present invention is not particularly limited as long as it is applicable to the nasal cavity. For example, paraoxybenzoic acid esters, quaternary ammonium salts, chlorobutanol, chlorhexidine gluconate, chlorhexidine acetate, dehydroacetic acid or its salts, benzyl alcohol, zinc chloride, parachlorometaxylenol, chlorocresol, phenethyl alcohol, poly(dronium) chloride, thimerosal, dibutylhydroxytoluene, etc. can be mentioned.

[0013] These preservatives may be used alone or in combination of two or more.

[0014] Among these preservatives, paraoxybenzoic acid esters and quaternary ammonium salts are preferably mentioned.

[0015] Paraoxybenzoic acid esters are alkyl esters or benzyl esters of paraoxybenzoic acid. Examples of the alkyl group in the alkyl ester of paraoxybenzoic acid include linear or branched alkyl groups having 1 to 5 carbon atoms. Specific examples of paraoxybenzoic acid esters include methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, isopropyl paraoxybenzoate, butyl paraoxybenzoate, isobutyl paraoxybenzoate, benzyl paraoxybenzoate, etc. Among these paraoxybenzoic acid esters, methyl paraoxybenzoate, ethyl paraoxybenzoate, and propyl paraoxybenzoate can be mentioned.

[0016] Examples of the quaternary ammonium salts include benzalkonium chloride, cetylpyridinium chloride, benzethonium chloride, decalinium chloride, alkyldimethylammonium chloride, alkyltrimethylammonium chloride, methylbenzethonium chloride, lauroylcolaminomethylpyridinium chloride, and the like. These quaternary ammonium salts may be in the form of solvates such as hydrates. Among these quaternary ammonium salts, benzalkonium chloride is preferably used.

[0017] When a paraoxybenzoic acid ester and a quaternary ammonium salt are used in combination as preservatives, the ratio between them is not particularly limited. For example, per 100 parts by weight of the total amount of the paraoxybenzoic acid ester, the total amount of the quaternary ammonium salt is 0.01 to 20 parts by weight, preferably 0.1 to 10 parts by weight, more preferably 1 to 5 parts by weight.

[0018] The content of the preservative in the nasal irrigation composition of the present invention may be appropriately set according to the type of the preservative used, the preservative performance to be provided, etc. For example, the total amount of the preservative is 0.00005 to 0.6% by weight, preferably 0.0001 to 0.5% by weight, more preferably 0.001 to 0.35% by weight. More specifically, when a paraoxybenzoic acid ester is used as the preservative, the content of the paraoxybenzoic acid ester is 0.005 to 0.5% by weight, preferably 0.01 to 0.4% by weight, more preferably 0.05 to 0.2% by weight. Further, when a quaternary ammonium salt is used as the preservative, the content of the quaternary ammonium salt is, for example, 0.00005 to 0.1% by weight, preferably 0.0001 to 0.1% by weight, more preferably 0.001 to 0.01% by weight.

[0019] [Thickener] The nasal irrigation composition of the present invention contains a thickener.

[0020] The thickener used in the present invention is not particularly limited as long as it can be applied into the nasal cavity. Examples thereof include cellulose-based thickeners, polyvinyl-based thickeners, thickening polysaccharides, acrylic acid-based thickeners, and the like.

[0021] Specific examples of the cellulose-based thickeners include carmellose, hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethyl cellulose, etc. These cellulose-based thickeners may be in the form of salts. Examples of the cellulose-based thickeners in the form of salts include sodium carmellose, etc.

[0022] Specific examples of the polyvinyl-based thickeners include carboxyvinyl polymer, polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl methyl ether.

[0023] Specific examples of the thickening polysaccharides include xanthan gum, guar gum, locust bean gum, carrageenan, alginic acid, etc. These thickening polysaccharides may be in the form of salts. Examples of the thickening polysaccharides in the form of salts include sodium alginate, etc.

[0024] Specific examples of the acrylic acid-based thickeners include alkyl acrylate-methacrylate copolymer, sodium polyacrylate bentonite, etc.

[0025] These thickeners may be used alone or in combination of two or more.

[0026] Among these thickeners, cellulose-based thickeners and polyvinyl-based thickeners are preferred, and carmellose, hydroxypropylmethylcellulose, hydroxypropylcellulose, and carboxyvinyl polymer are more preferred.

[0027] Regarding the content of the thickener in the nasal irrigation composition of the present invention, it may be appropriately set according to the type of thickener used, the viscosity to be imparted, etc. For example, the total amount of the thickener is 0.005 to 2% by weight, preferably 0.05 to 1% by weight, more preferably 0.1 to 0.5% by weight.

[0028] In the nasal irrigation composition of the present invention, the ratio of the preservative to the thickener is not particularly limited. For example, per 1 part by weight of the total amount of the preservative, the thickener is 0.01 to 50 parts by weight in total, preferably 0.1 to 25 parts by weight, more preferably 0.5 to 5 parts by weight.

[0029] [Nonionic surfactant] The nasal irrigation composition of the present invention contains a nonionic surfactant. In the prior art, when a preservative and a thickener coexist in a nasal irrigation composition, turbidity occurs. However, in the nasal irrigation composition of the present invention, by containing a nonionic surfactant together with the preservative and the thickener, it is possible to suppress turbidity and provide excellent appearance properties.

[0030] The nonionic surfactant used in the present invention is not particularly limited as long as it is applicable to the nasal cavity. For example, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, sorbitan fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene glycerin fatty acid ester, polyoxyethylene sorbitol fatty acid ester, glycerin fatty acid ester, sucrose fatty acid ester, etc. may be mentioned. These nonionic surfactants may be used alone or in combination of two or more.

[0031] Among these nonionic surfactants, from the viewpoint of more effectively suppressing turbidity, polyoxyethylene sorbitan fatty acid ester and polyoxyethylene hydrogenated castor oil are preferably mentioned.

[0032] The average number of moles of ethylene oxide (EO) added to form the polyoxyethylene sorbitan fatty acid ester is not particularly limited, and examples thereof include 5 to 40 moles, preferably 10 to 30 moles, and more preferably 15 to 25 moles. The number of carbon atoms of the fatty acid that constitutes the polyoxyethylene sorbitan fatty acid ester is not particularly limited, and examples thereof include 10 to 22, preferably 14 to 22, and more preferably 16 to 20. Specific examples of the polyoxyethylene sorbitan fatty acid ester include polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan trioleate, polyoxyethylene sorbitan tristearate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monolaurate, and the like. Among these polyoxyethylene sorbitan fatty acid esters, polyoxyethylene sorbitan monooleate (polysorbate 80) having an average number of moles of ethylene oxide (EO) added of 20 and polyoxyethylene sorbitan monostearate (polysorbate 60) having an average number of moles of ethylene oxide (EO) added of 20 are preferably mentioned.

[0033] The average number of moles of ethylene oxide (EO) added to the polyoxyethylene hydrogenated castor oil is not particularly limited, and examples thereof include 5 to 100 moles, preferably 20 to 80 moles, and more preferably 40 to 80 moles. Among these, polyoxyethylene hydrogenated castor oil 60 and polyoxyethylene hydrogenated castor oil 80 are preferably mentioned. may be mentioned.

[0034] The content of the nonionic surfactant in the nasal irrigation composition of the present invention is, for example, 0.005 to 5% by weight. From the viewpoint of more effectively suppressing cloudiness, the content of the nonionic surfactant in the nasal irrigation composition of the present invention is preferably 0.01 to 2% by weight, and more preferably 0.1 to 0.5% by weight.

[0035] In the nasal cavity irrigation composition of the present invention, the ratio of the preservative to the nonionic surfactant is not particularly limited. For example, the total amount of the nonionic surfactant is 0.01 to 50 parts by weight per 1 part by weight of the total amount of the preservative. From the viewpoint of more effectively suppressing cloudiness, the total amount of the nonionic surfactant is preferably 0.1 to 25 parts by weight, more preferably 0.5 to 5 parts by weight per 1 part by weight of the total amount of the preservative.

[0036] [Inorganic salts of alkali metals] The nasal cavity irrigation composition of the present invention may contain inorganic salts of alkali metals as necessary for adjusting the osmotic pressure and the like.

[0037] The inorganic salts of alkali metals are not particularly limited as long as they are applicable to the nasal cavity. For example, chlorides of alkali metals, carbonates of alkali metals, etc. may be mentioned. Specific examples of the chlorides of alkali metals include sodium chloride, potassium chloride, etc. Specific examples of the carbonates of alkali metals include sodium hydrogen carbonate, sodium carbonate, potassium hydrogen carbonate, potassium carbonate, etc. These inorganic salts may be used alone or in combination of two or more. Among these inorganic salts of alkali metals, chlorides of alkali metals are preferred, and sodium chloride is more preferred. When the inorganic salts of alkali metals are contained, the content of the inorganic salts is not particularly limited. For example, 0.01 to 5% by weight, preferably 0.1 to 3% by weight, more preferably 0.3 to 2% by weight may be mentioned.

[0038] [Polyhydric alcohol] The nasal cavity irrigation composition of the present invention may contain polyhydric alcohol as necessary.

[0039] The polyhydric alcohols used in the present invention are not particularly limited as long as they can be applied into the nasal cavity. Examples thereof include dihydric alcohols such as propylene glycol and 1,3-butylene glycol; and trihydric alcohols such as glycerin. These polyhydric alcohols 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 a polyhydric alcohol is contained, its content is not particularly limited, and examples thereof include 0.01 to 10% by weight, preferably 0.1 to 5% by weight, and more preferably 0.3 to 2% by weight.

[0040] [Other components] In addition to the above components, the nasal cavity irrigation composition of the present invention may contain other bases and additives required for formulation and the like as long as the effects of the present invention are not impaired. Such bases and additives are not particularly limited as long as they are pharmaceutically acceptable. Examples thereof include monohydric lower alcohols having 1 to 5 carbon atoms, surfactants other than nonionic surfactants, inorganic salts of alkaline earth metals, coloring agents, thickeners, pH adjusters, wetting agents, stabilizers, antioxidants, ultraviolet absorbers, buffers, solubilizing aids, solubilizers, chelating agents, fragrances, inorganic salts, water and other additives. These base materials and additives may be used alone or in combination of two or more.

[0041] In addition to the above components, the nasal cavity irrigation composition of the present invention may contain other pharmacological components as needed as long as the effects of the present invention are not impaired. Examples of such pharmacological components include vitamins, amino acids, antihistamines, antiallergic agents, local anesthetics, anti-inflammatory agents, blood circulation promoting components, astringents, cooling agents, mucopolysaccharides and the like. These pharmacological components may be used alone or in combination of two or more.

[0042] [Dosage form, use, product form] The nasal cavity cleansing composition of the present invention is a liquid preparation, which is prepared by adding a predetermined amount of each component to be blended to water, dissolving them, and subjecting them to a sterilization treatment as necessary.

[0043] The nasal cavity cleansing composition of the present invention is used for cleansing the nasal cavity. As a method for cleansing the nasal cavity using the nasal cavity cleansing composition of the present invention, for example, a method of introducing the nasal cavity cleansing composition of the present invention into one nasal cavity and allowing the nasal cavity cleansing composition to flow out as it is from the nasal cavity; a method of introducing the nasal cavity cleansing composition of the present invention into the nasal cavity and allowing the nasal cavity cleansing composition to flow out from the mouth; a method of introducing the nasal cavity cleansing composition of the present invention into one nasal cavity and allowing the nasal cavity cleansing composition to flow out from the other nasal cavity, etc. can be mentioned. Further, when introducing the nasal cavity cleansing composition of the present invention into the nasal cavity, it may be introduced in the form of droplets (particularly, mist), or may be introduced as a liquid flow.

[0044] The nasal cavity cleansing composition of the present invention is used by being housed in a container capable of discharging the contents into the nasal cavity. The container may be a container capable of discharging the contents in the form of droplets by dropping or spraying, or may be a container capable of discharging the contents as a liquid flow. Since the nasal cavity cleansing composition of the present invention has properties suitable for discharging in the form of droplets (particularly, mist) by containing a thickening agent, as a suitable example of the container for housing the nasal cavity cleansing composition of the present invention, a container capable of discharging the contents in the form of droplets into the nasal cavity by dropping or spraying can be mentioned.

Examples

[0045] Examples are shown below to more specifically explain the present invention, but the present invention is not limited thereto.

[0046] Test Example 1 A nasal cavity cleansing composition (liquid preparation) having the composition shown in Table 1 was prepared. The obtained nasal cavity cleansing composition was filled into a 200 ml glass bottle, and the appearance of the nasal cavity cleansing composition was visually observed. With "no turbidity was observed throughout and it was in a clear state" being 15 points and "the whole was turbid and in a completely opaque state" being 1 point, the degree of turbidity was scored between 1 and 15 points.

[0047] The results are shown in Table 1. In the nasal irrigation compositions containing a preservative (methyl paraoxybenzoate and / or benzalkonium chloride) and a thickener (sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, or carboxyvinyl polymer) and not containing a nonionic surfactant, significant cloudiness was observed (Comparative Examples 1 to 6). When the composition of each nasal irrigation composition of Comparative Examples 1 to 6 was changed so as not to contain a thickener, no cloudiness was observed and the appearance was clear.

[0048] On the other hand, in the nasal irrigation compositions containing a nonionic surfactant (polysorbate 80 or polyoxyethylene hydrogenated castor oil 60) together with a preservative and a thickener, cloudiness was suppressed and the appearance was clear (Examples 1 to 7). In the nasal irrigation composition containing a preservative and sodium carboxymethyl cellulose and not containing a nonionic surfactant (Comparative Example 1), significant cloudiness was particularly observed, whereas in the nasal irrigation composition containing polysorbate 80 in this (Example 3), cloudiness was particularly significantly suppressed and the appearance was clear. Further, even when the content of sodium carboxymethyl cellulose in the nasal irrigation composition of Example 3 was changed to 0.5% by weight, cloudiness was significantly suppressed and the appearance was clear.

[0049] [Table 1]

[0050] Test Example 2 The nasal irrigation compositions of Comparative Examples 1 to 5 and Examples 1 and 3 to 7 in Table 1 were prepared by changing methyl paraben to ethyl paraben or propyl paraben, and the degree of turbidity was evaluated in the same manner as in Test Example 1. In the nasal irrigation composition containing no nonionic surfactant, turbidity was observed in the same manner as in Comparative Examples 1 to 5 when ethyl paraben or propyl paraben was included. On the other hand, when a nonionic surfactant was included together with ethyl paraben or propyl paraben, turbidity was suppressed and a clear appearance was obtained in the same manner as in Examples 1 and 3 to 7.

[0051] Test Example 3 The nasal irrigation compositions of Examples 1 to 6 in Table 1 were prepared by changing polysorbate 80 to polyoxyethylene sorbitan monostearate (polysorbate 60) or polyoxyethylene hydrogenated castor oil 80, and the degree of turbidity was evaluated in the same manner as in Test Example 1. As a result, turbidity was suppressed and a clear appearance was obtained in the same manner as in Examples 1 to 6.

[0052] Formulation Example Nasal irrigation compositions having the compositions shown in Table 2 were prepared. The degree of turbidity of the obtained nasal irrigation compositions was evaluated in the same manner as in Test Example 1. As a result, the nasal irrigation compositions of Formulation Examples 1 to 5 all had suppressed turbidity and a clear appearance.

[0053]

Table 2

Claims

1. A nasal irrigation composition containing a preservative, a thickener, and a nonionic surfactant, wherein the preservative includes a paraoxybenzoic acid ester, the thickener is at least one selected from the group consisting of carmellose and its salts, hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, carboxyvinyl polymer, polyvinylpyrrolidone, polyvinyl alcohol, and polyvinyl methyl ether, and the nonionic surfactant is polyoxyethylene sorbitan fatty acid ester and / or polyoxyethylene hydrogenated castor oil.

2. The nasal irrigation composition according to claim 1, wherein the preservative further includes a quaternary ammonium salt.

3. The nasal irrigation composition according to claim 1 or 2, which is contained in a container capable of discharging the content in droplet form into the nasal cavity by dropping or spraying.

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