JP7690280B2 - Nasal wash composition - Google Patents

Description

The present invention relates to a nasal irrigation composition that contains a preservative and a thickener and is suppressed from becoming cloudy.

The nasal mucosa is an epithelial tissue that is directly exposed to the outside world and is sensitive to stimuli from the outside world. It is known that when foreign matter such as pollen, microorganisms, and house dust adheres to the nasal mucosa, it can cause unbearable discomfort and lead to the development of various diseases such as allergies and infectious diseases. In order to prevent or improve such nasal mucosa symptoms, it is effective to remove the foreign matter adhered to the mucosa using a nasal cleansing composition.

Nasal irrigation compositions are required to have antiseptic properties because they may be used when going out or may be used repeatedly. Thus, various formulations of nasal irrigation compositions containing preservatives such as benzalkonium chloride have been reported (see, for example, Patent Document 1).

Japanese Patent Application Publication No. 11-92368

In order to improve the usability of the nasal cleansing composition and to control the particle size of the droplets formed when the nasal cleansing composition is introduced into the nasal cavity in droplet form, it is effective to add a thickener. Therefore, the present inventors conducted research to develop a nasal cleansing composition containing a preservative and a thickener, and found that a nasal cleansing composition containing a preservative and a thickener becomes cloudy and the appearance is deteriorated.

Therefore, the present invention aims to provide a nasal cleansing composition that contains a preservative and a thickener and is suppressed from becoming cloudy.

The inventors conducted extensive research to solve the above problems and discovered that by incorporating a nonionic surfactant together with a preservative and a thickener in a nasal cleansing composition, it is possible to suppress cloudiness and provide the composition with excellent appearance properties. The present invention was completed based on this knowledge and through further research.

That is, the present invention provides the following aspects.
Item 1. A nasal irrigation composition comprising a preservative, a thickener, and a nonionic surfactant.
Item 2. The composition for nasal washing according to Item 1, wherein the preservative is a paraoxybenzoic acid ester and/or a quaternary ammonium salt.
Item 3. The nasal rinsing 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 cleansing 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 cleansing 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.

The nasal cleansing composition of the present invention contains a preservative and a thickener, yet suppresses cloudiness and has excellent appearance properties.

The nasal cleansing composition of the present invention is characterized by containing a preservative, a thickener, and a nonionic surfactant. The nasal cleansing composition of the present invention will be described in detail below.

[Preservatives]
The nasal cleansing composition of the present invention contains a preservative. By containing a preservative, the nasal cleansing composition of the present invention can be endowed with antiseptic properties.

The preservatives used in the present invention are not particularly limited, so long as they are applicable to the nasal cavity. Examples of the preservatives include paraoxybenzoic acid esters, quaternary ammonium salts, chlorobutanol, chlorhexidine gluconate, chlorhexidine acetate, dehydroacetic acid or its salts, benzyl alcohol, zinc chloride, parachlormetaxylenol, chlorcresol, phenethyl alcohol, polydronium chloride, thimerosal, dibutylhydroxytoluene, etc.

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

Among these preservatives, paraoxybenzoic acid esters and quaternary ammonium salts are preferred.

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, and benzyl paraoxybenzoate. Among these paraoxybenzoic acid esters, methyl paraoxybenzoate, ethyl paraoxybenzoate, and propyl paraoxybenzoate are preferred.

Specific examples of quaternary ammonium salts include benzalkonium chloride, cetylpyridinium chloride, benzethonium chloride, dequalinium chloride, alkyldimethylammonium chloride, alkyltrimethylammonium chloride, methylbenzethonium chloride, lauroylcholaminoformylmethylpyridinium chloride, and the like. These quaternary ammonium salts may be in the form of a solvate such as a hydrate. Of these quaternary ammonium salts, benzalkonium chloride is preferred.

When a combination of paraoxybenzoic acid esters and quaternary ammonium salts is used as a preservative, there are no particular limitations on the ratio between them, but for example, the total amount of the quaternary ammonium salts is 0.01 to 20 parts by weight, preferably 0.1 to 10 parts by weight, and more preferably 1 to 5 parts by weight per 100 parts by weight of the total amount of the paraoxybenzoic acid esters.

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

[Thickener]
The nasal rinse composition of the present invention includes a thickening agent.

The thickener used in the present invention is not particularly limited, so long as it can be applied to the nasal cavity. Examples of the thickener include cellulose-based thickeners, polyvinyl-based thickeners, polysaccharide thickeners, and acrylic acid-based thickeners.

Specific examples of cellulose-based thickeners include carmellose, hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, and hydroxyethylcellulose. These cellulose-based thickeners may be in the form of a salt. Examples of cellulose-based thickeners in the form of a salt include carmellose sodium.

Specific examples of polyvinyl thickeners include carboxyvinyl polymer, polyvinylpyrrolidone, polyvinyl alcohol, and polyvinyl methyl ether.

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

Specific examples of acrylic acid-based thickeners include acrylic acid/alkyl methacrylate copolymers, sodium polyacrylate bentonite, etc.

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

Among these thickeners, preferred are cellulose-based thickeners and polyvinyl-based thickeners, and more preferred are carmellose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, and carboxyvinyl polymers.

The content of the thickener in the nasal cleansing composition of the present invention may be appropriately set depending on the type of thickener used, the viscosity to be imparted, etc., but may be, for example, 0.005 to 2% by weight, preferably 0.05 to 1% by weight, and more preferably 0.1 to 0.5% by weight in total of the thickener.

In the nasal cleansing composition of the present invention, the ratio of preservative to thickener is not particularly limited, but for example, the total amount of thickener is 0.01 to 50 parts by weight, preferably 0.1 to 25 parts by weight, and more preferably 0.5 to 5 parts by weight per 1 part by weight of the total amount of preservative.

[Nonionic Surfactant]
The nasal cleansing composition of the present invention contains a nonionic surfactant. In the prior art, the coexistence of a preservative and a thickener in a nasal cleansing composition causes cloudiness, but the nasal cleansing composition of the present invention contains a nonionic surfactant together with the preservative and the thickener, thereby suppressing cloudiness and providing the composition with excellent appearance properties.

The nonionic surfactant used in the present invention is not particularly limited, so long as it is applicable to the nasal cavity, but examples thereof include polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, sorbitan fatty acid esters, polyoxyethylene alkyl ethers, polyoxyethylene glycerin fatty acid esters, polyoxyethylene sorbitol fatty acid esters, glycerin fatty acid esters, sucrose fatty acid esters, etc. These nonionic surfactants may be used alone or in combination of two or more.

Among these nonionic surfactants, polyoxyethylene sorbitan fatty acid esters and polyoxyethylene hydrogenated castor oil are preferred from the viewpoint of more effectively suppressing cloudiness.

The average number of moles of ethylene oxide (EO) added that constitutes the polyoxyethylene sorbitan fatty acid ester is not particularly limited, but may be, for example, 5 to 40 moles, preferably 10 to 30 moles, and more preferably 15 to 25 moles. The number of carbon atoms in the fatty acid that constitutes the polyoxyethylene sorbitan fatty acid ester is not particularly limited, but may be, for example, 10 to 22, preferably 14 to 22, and more preferably 16 to 20. Specific examples of polyoxyethylene sorbitan fatty acid ester include polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan trioleate, polyoxyethylene sorbitan tristearate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monopalmitate, and polyoxyethylene sorbitan monolaurate. Among these polyoxyethylene sorbitan fatty acid esters, preferred are polyoxyethylene sorbitan monooleate (polysorbate 80), which has an average number of moles of ethylene oxide (EO) added of 20, and polyoxyethylene sorbitan monostearate (polysorbate 60), which has an average number of moles of ethylene oxide (EO) added of 20.

The average number of moles of ethylene oxide (EO) added in polyoxyethylene hydrogenated castor oil is not particularly limited, but may be, for example, 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 preferred.
Examples include:

The content of the nonionic surfactant in the nasal cleansing 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 cleansing composition of the present invention is preferably 0.01 to 2% by weight, more preferably 0.1 to 0.5% by weight.

In the nasal cleansing composition of the present invention, the ratio of the preservative to the nonionic surfactant is not particularly limited, but may be, for example, 0.01 to 50 parts by weight of the nonionic surfactant in total per 1 part by weight of the preservative in total. From the viewpoint of more effectively suppressing cloudiness, the nonionic surfactant in total 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 preservative in total.

[Inorganic salts of alkali metals]
The nasal cleansing composition of the present invention may contain an inorganic salt of an alkali metal, if necessary, for adjusting the osmotic pressure or the like.

The inorganic salt of an alkali metal is not particularly limited, as long as it can be applied to the nasal cavity, but examples thereof include chlorides of alkali metals and carbonates of alkali metals. Specific examples of chlorides of alkali metals include sodium chloride and potassium chloride. Specific examples of carbonates of alkali metals include sodium bicarbonate, sodium carbonate, potassium bicarbonate, and potassium carbonate. 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 an inorganic salt of an alkali metal is contained, the content of the inorganic salt is not particularly limited, but examples thereof include 0.01 to 5% by weight, preferably 0.1 to 3% by weight, and more preferably 0.3 to 2% by weight.

[Polyhydric alcohol]
The nasal cleansing composition of the present invention may contain a polyhydric alcohol, if necessary.

The polyhydric alcohol used in the present invention is not particularly limited, so long as it is applicable to the nasal cavity, and 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 preferred, and propylene glycol is more preferred. 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.

[Other ingredients]
In addition to the above-mentioned components, the nasal washing composition of the present invention may contain other bases and additives required for formulation, etc., within the scope of not impairing the effects of the present invention. Such bases and additives are not particularly limited as long as they are pharma- ceutically acceptable, and examples thereof include monohydric lower alcohols having 1 to 5 carbon atoms, surfactants other than nonionic surfactants, inorganic salts of alkaline earth metals, colorants, thickening agents, pH adjusters, wetting agents, stabilizers, antioxidants, UV absorbers, buffers, solubilizing agents, solubilizers, chelating agents, fragrances, inorganic salts, water, and other additives. These bases and additives may be used alone or in combination of two or more.

In addition to the above-mentioned components, the nasal cleansing composition of the present invention may contain other pharmacological components as necessary, provided that 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.

[Dosage form/Application/Product form]
The nasal wash composition of the present invention is a liquid preparation, and is prepared by adding and dissolving predetermined amounts of each of the components to be formulated in water, followed by sterilization as necessary.

The nasal cleaning composition of the present invention is used for cleaning the inside of the nasal cavity. Examples of methods for cleaning the inside of the nasal cavity using the nasal cleaning composition of the present invention include a method of introducing the nasal cleaning composition of the present invention into one nasal cavity and letting the nasal cleaning composition flow out of the nasal cavity as it is; a method of introducing the nasal cleaning composition of the present invention into the nasal cavity and letting the nasal cleaning composition flow out of the mouth; a method of introducing the nasal cleaning composition of the present invention into one nasal cavity and letting the nasal cleaning composition flow out of the other nasal cavity, and the like. When the nasal cleaning composition of the present invention is introduced into the nasal cavity, it may be introduced in the form of droplets (particularly in the form of a mist) or as a liquid flow.

The nasal cleansing composition of the present invention is used by being contained 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 dripping or spraying, or may be a container capable of discharging the contents as a liquid flow. Since the nasal cleansing composition of the present invention contains a thickener and thus has properties suitable for discharging the contents in the form of droplets (particularly as a mist), a suitable example of a container for containing the nasal cleansing composition of the present invention is a container capable of discharging the contents in the form of droplets by dripping or spraying into the nasal cavity.

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

Test Example 1
A nasal cleansing composition (liquid preparation) was prepared having the composition shown in Table 1. The obtained nasal cleansing composition was filled into a 200 ml glass bottle, and the appearance of the nasal cleansing composition was visually observed and the degree of cloudiness was scored from 1 to 15 points, with 15 points being "a clear state with absolutely no cloudiness observed throughout" and 1 point being "a state in which the entire composition is cloudy and completely opaque."

The results are shown in Table 1. Significant cloudiness was observed in the nasal cleansing compositions that contained a preservative (methyl paraoxybenzoate and/or benzalkonium chloride) and a thickener (carmellose sodium, hydroxypropyl methylcellulose, hydroxypropyl cellulose, or carboxyvinyl polymer) but did not contain a nonionic surfactant (Comparative Examples 1 to 6). When the composition of each of the nasal cleansing compositions of Comparative Examples 1 to 6 was changed so that the thickener was not blended, no cloudiness was observed and the composition had a clear appearance.

On the other hand, in the nasal cleansing composition containing a nonionic surfactant (polysorbate 80 or polyoxyethylene hydrogenated castor oil 60) together with a preservative and a thickener, opacity was suppressed and the composition had a clear appearance (Examples 1 to 7). In the nasal cleansing composition containing a preservative and carmellose sodium but no nonionic surfactant (Comparative Example 1), opacity was particularly noticeable, whereas in the nasal cleansing composition containing polysorbate 80 (Example 3), opacity was particularly significantly suppressed and the composition had a clear appearance. Furthermore, even when the content of carmellose sodium in the nasal cleansing composition of Example 3 was changed to 0.5% by weight, opacity was also significantly suppressed and the composition had a clear appearance.

Test Example 2
Nasal cleansing compositions were prepared by replacing methyl parahydroxybenzoate in the nasal cleansing compositions of Comparative Examples 1 to 5 and Examples 1 and 3 to 7 in Table 1 with ethyl parahydroxybenzoate or propyl parahydroxybenzoate, and the degree of cloudiness was evaluated in the same manner as in Test Example 1. In the nasal cleansing compositions not containing a nonionic surfactant, when ethyl parahydroxybenzoate or propyl parahydroxybenzoate was contained, cloudiness was observed as in Comparative Examples 1 to 5. In contrast, when a nonionic surfactant was contained together with ethyl parahydroxybenzoate or propyl parahydroxybenzoate, cloudiness was suppressed and the compositions had a clear appearance as in Examples 1 and 3 to 7.

Test Example 3
Nasal cleansing compositions were prepared by replacing the polysorbate 80 in the nasal cleansing compositions of Examples 1 to 6 in Table 1 with polyoxyethylene sorbitan monostearate (polysorbate 60) or polyoxyethylene hydrogenated castor oil 80, and the degree of cloudiness was evaluated in the same manner as in Test Example 1. As in Examples 1 to 6, cloudiness was suppressed and the composition had a clear appearance.

Nasal cleansing compositions were prepared according to the compositions shown in Formulation Example Table 2. The degree of turbidity of the obtained nasal cleansing compositions was evaluated in the same manner as in Test Example 1. All of the nasal cleansing compositions of Formulation Examples 1 to 5 had suppressed turbidity and had a clear appearance.

Claims (3)

Contains preservatives, thickeners, and nonionic surfactants ,
The preservative comprises a paraoxybenzoic acid ester,
the thickener is at least one selected from the group consisting of carmellose and its salts, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, ethyl cellulose, hydroxyethyl cellulose, carboxyvinyl polymer, polyvinylpyrrolidone, polyvinyl alcohol, and polyvinyl methyl ether;
A nasal cleansing composition , wherein the nonionic surfactant is a polyoxyethylene sorbitan fatty acid ester and/or a polyoxyethylene hydrogenated castor oil . The nasal rinse composition of claim 1 , wherein the preservative further comprises a quaternary ammonium salt. 3. The nasal cleansing composition according to claim 1 , which is contained in a container capable of discharging the contents in the form of droplets into the nasal cavity by dropping or spraying.