HK1220913B - Aqueous composition for ophthalmological use or otolaryngological use - Google Patents

Description

Aqueous composition for ophthalmology or otolaryngology

Technical Field

The present invention relates to an aqueous composition for ophthalmology or otolaryngology.

Background Art

It is known that allergies can be caused by a variety of factors, including pollen, dust, mites, mold, pet hair, contact lenses, and cosmetics. Among these, pollen-induced allergies are known as hay fever, which is caused by pollen proteins contained in pollen acting as antigens and coming into contact with mucous membranes. In recent years, with the increasing number of allergy sufferers, there has been a desire to develop compositions that can prevent hay fever or inhibit its progression. For example, Patent Document 1 discloses an eyewash containing a carboxyvinyl polymer and a monoterpene, with a single application volume of 500 μl or more for contact with the area being cleaned.

Prior art literature

Patent Literature

Patent Document 1: Japanese Patent Application Laid-Open No. 2011-093889

Summary of the Invention

Technical Problems to be Solved by the Invention

The eyewash described in Patent Document 1 can remove dirt such as pollen, dust, and cosmetics (mascara, eyeliner, eye shadow, lotion, emulsion, eye cream, etc.) attached to the eyeball (particularly the cornea). On the other hand, people are still seeking a method for removing pollen and the like more simply and effectively.

The technical problem of the present invention is to provide an aqueous composition for ophthalmology or otolaryngology having an excellent pollen removal effect.

Technical means to solve technical problems

The present inventors have discovered that an aqueous composition containing (A) vaseline and two or more (B) nonionic surfactants can simply and effectively remove pollen attached to the ocular mucosa or nasal mucosa.

However, vaseline is a non-polar oil that has been widely used for many years as a base for ointments. It is also widely used as a base for eye ointments in the field of ophthalmology, but its aqueous composition is not fully known in the fields of ophthalmology or otolaryngology. The inventors have discovered a new technical problem in the preparation of an aqueous composition containing vaseline. For example, even if a surfactant is used as a dissolution aid, separation or precipitation of the oil layer will still occur, making it impossible to fully dissolve the vaseline. In response to this, the inventors have found that an aqueous composition containing (A) vaseline and two or more (B) nonionic surfactants can suppress the separation or precipitation of the oil layer, and the solubility of vaseline is significantly improved.

The present inventors have further discovered that an aqueous composition containing (A) petrolatum and two or more (B) nonionic surfactants can alleviate cellular damage (sicca syndrome) caused by dryness stress in mucous membrane cells of the eyes, nose, and the like.

The present invention has been accomplished based on the above findings, and relates to, for example, the following inventions.

[1] An aqueous composition for ophthalmology or otolaryngology, comprising (A) vaseline and two or more (B) nonionic surfactants.

[2] The aqueous composition according to [1], further comprising (C) fat-soluble vitamins or vegetable oil.

[3] The aqueous composition according to [1] or [2], comprising (B-1) a nonionic surfactant having an HLB value of 10 or greater, and (B-2) a nonionic surfactant having an HLB value of less than 10.

[4] The aqueous composition according to any one of [1] to [3], wherein (A) vaseline is white vaseline.

[5] The aqueous composition according to any one of [2] to [4], wherein (C) the fat-soluble vitamins or vegetable oils are vitamins E, vitamins A, sesame oil, castor oil, olive oil, soybean oil, peanut oil, almond oil, wheat germ oil, camellia oil, corn oil, rapeseed oil, sunflower oil, cottonseed oil or coconut oil.

[6] The aqueous composition according to any one of [1] to [5], further comprising (D) a buffer.

[7] The aqueous composition according to any one of [1] to [6], wherein the transmittance of light at a wavelength of 660 nm is 60% or more.

[8] The aqueous composition according to any one of [1] to [7], wherein the content of (A) vaseline is 0.0001 to 1 w/v% based on the total amount of the aqueous composition.

[9] The aqueous composition according to any one of [1] to [8], which is used for preventing, treating, improving or allergic symptoms.

[10] An agent for preventing, treating, ameliorating or allergic symptoms, comprising an aqueous composition for ophthalmology or otolaryngology containing (A) vaseline and two or more (B) nonionic surfactants.

[11] Use of (A) vaseline and two or more (B) nonionic surfactants in the preparation of an aqueous composition for ophthalmology or otolaryngology for preventing, treating, improving or allergic symptoms.

[12] A method for imparting to an ophthalmic or otolaryngological aqueous composition a preventive, therapeutic, ameliorative or allergic symptom-relieving effect, the method comprising preparing an ophthalmic or otolaryngological aqueous composition containing (A) vaseline and two or more (B) nonionic surfactants.

[13] A method for preparing an aqueous composition for ophthalmology or otolaryngology in which (A) vaseline does not separate and is soluble, the method comprising making the aqueous composition contain (A) vaseline and two or more (B) nonionic surfactants.

[14] An agent for preventing, treating, ameliorating or alleviating dry eye symptoms, comprising an ophthalmic aqueous composition containing (A) vaseline and two or more (B) nonionic surfactants.

[15] Use of (A) vaseline and two or more (B) nonionic surfactants in the preparation of an ophthalmic aqueous composition for preventing, treating, improving or alleviating the symptoms of dry eye.

[16] A method for imparting to an ophthalmic aqueous composition a preventive, therapeutic, ameliorative or alleviating effect on dry eye symptoms, the method comprising preparing an ophthalmic aqueous composition containing (A) vaseline and two or more (B) nonionic surfactants.

[2-1] An aqueous composition for otolaryngology, comprising (A) vaseline and contained in a container having a spray nozzle.

[2-2] The aqueous otorhinolaryngologic composition according to [2-1], further comprising one or more (B) nonionic surfactants.

[2-3] The otorhinolaryngology aqueous composition according to [2-1] or [2-2], wherein the otorhinolaryngology aqueous composition is the aqueous composition according to any one of [1] to [9].

[2-4] The otorhinolaryngology aqueous composition according to any one of [2-1] to [2-3], which is a nasal drop or a nasal wash.

[2-5] An agent for improving or alleviating irritation during use, comprising the otorhinolaryngology aqueous composition according to any one of [2-1] to [2-4].

[2-6] (A) Use of vaseline in the preparation of an aqueous otorhinolaryngological composition contained in a container having a spray nozzle for improving or alleviating irritation during use.

[2-7] The use according to [2-6], wherein the otorhinolaryngology aqueous composition is the otorhinolaryngology aqueous composition according to any one of [2-1] to [2-4].

[2-8] A method for imparting an ameliorative or alleviating effect on irritation during use to an otorhinolaryngology aqueous composition, the method comprising preparing the otorhinolaryngology aqueous composition according to any one of [2-1] to [2-4].

The present invention may also include the following methods.

[3-1] A method for preventing, treating, improving or allergic symptoms, comprising the step of washing the ocular mucosa or nasal mucosa with an aqueous composition containing (A) vaseline and two or more (B) nonionic surfactants.

[3-2] A method for alleviating xerosis in ocular mucosal cells, comprising the step of bringing an aqueous composition containing (A) vaseline and two or more (B) nonionic surfactants into contact with the ocular mucosa.

[3-3] A method for preventing, treating, improving or alleviating dry eye symptoms, comprising the step of bringing an aqueous composition containing (A) vaseline and two or more (B) nonionic surfactants into contact with an ocular mucosa.

[3-4] A method for improving or alleviating irritation when the aqueous composition is applied to the nasal mucosa or ear, comprising the step of adding (A) vaseline to the aqueous composition.

[3-5] The method according to [3-4], further comprising the step of storing the aqueous composition in a container having a spray nozzle.

Effects of the Invention

According to the present invention, allergens such as pollen adhering to the cornea and other ocular surfaces, or to local mucous membranes such as the nasal cavity, can be easily and effectively removed. Therefore, allergic symptoms caused by allergens adhering to local mucous membranes such as the eyes and nose, such as hay fever, can be effectively prevented, treated, improved, or alleviated.

Furthermore, according to the present invention, there can be provided an aqueous composition for ophthalmology or otolaryngology, which, although containing vaseline, suppresses separation or precipitation of the oil layer and furthermore significantly improves the solubility of vaseline.

Furthermore, the present invention can suppress cellular damage caused by dryness stress reactions in cells of the ocular mucosa, such as corneal cells, and nasal mucosa. Consequently, it is possible to suppress irritation and dry eyes (dry eyes) caused by dryness symptoms, as well as the release of allergens such as histamine due to cellular damage, thereby alleviating the exacerbation of allergic symptoms. Thus, it is possible to provide an aqueous composition for ophthalmology or otolaryngology that has an excellent feel and is particularly effective for treating dry eyes and allergies.

Furthermore, the present invention can provide an otorhinolaryngological aqueous composition containing vaseline in a container having a spray nozzle, thereby reducing irritation during use and providing an excellent feeling during use.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG1 is a photograph showing the appearance of an aqueous composition of Reference Example 1 (left) and an aqueous composition of Reference Example 2 (right) of Reference Test Example 1;

FIG. 2 is a graph showing the cell viability in Test Example 3. FIG.

DETAILED DESCRIPTION

Hereinafter, the embodiment for implementing the present invention will be described in detail, but the present invention is not limited to the following embodiment.

In this specification, the unit "%" of content means "w/v%", which has the same meaning as "g/100 mL".

In this specification, unless otherwise specified, the abbreviation "POE" means polyoxyethylene.

In this specification, unless otherwise specified, the abbreviation "POP" means polyoxypropylene.

In this specification, unless otherwise specified, ophthalmic compositions include those applied to ocular mucosa, and otolaryngological compositions include those applied to at least one of the nasal mucosa and the ear. Otolaryngological compositions are preferably applied to the nasal mucosa.

[1. Aqueous composition for ophthalmology or otolaryngology]

The ophthalmic or otolaryngological aqueous composition of this embodiment contains (A) vaseline (hereinafter simply referred to as "component (A)") and two or more (B) nonionic surfactants (hereinafter simply referred to as "component (B)").

(A)Ingredients

In this specification, "vaseline" includes both "yellow vaseline" purified from a hydrocarbon mixture obtained from petroleum and "white vaseline" decolorized and purified.

As petroleum jelly, commercially available petroleum jelly can be used without limitation. Specific examples of petroleum jelly include Perfecta, Protopet Alba, Protopet White 1S, White Fonoline, Protopet White 2L, Protopet White 3C, Yellow Fonoline, Protopet Yellow 1E, Protopet Yellow 2A, Protopet Super White (all manufactured by Witco), Penreco Ultima, Penreco Super, Penreco Snow, Penreco Regent, Penreco Lily, Penreco Cream, Penreco Royal, Penreco Blond, Penreco Amber, Penreco 4650, Penreco Snow V, and Ointment. Base No. 4, No. 6, No. 8 (all manufactured by Penreco), Perlatum 330, Perlatum 310/410, Perlatum 320/420, Perlatum 321, Perlatum 325/425, Perlatum 325/415 (all manufactured by IGI), Snowwhite Special, Snowwhite A4 and other Snowwhite series, Microwax MA, Sonnecone CM, Sonnecone DM, White Fonoline H, White Protopetl SH (all manufactured by Sonnebom), Japanese Pharmacopoeia White Vaseline (manufactured by Maruishi Pharmaceutical Co., Ltd., Nikko Pharmaceutical Co., Ltd., etc.), Japanese Pharmacopoeia Yellow Vaseline (manufactured by Maruishi Pharmaceutical Co., Ltd., Nikko Pharmaceutical Co., Ltd., etc.), Crolatum V (manufactured by Croda Japan Co., Ltd.), Sunwhite P-1, Sunwhite P-150, Sunwhite P-200, Sunwhite Further purified petrolatum such as S-200 (manufactured by Nikko Rica Co., Ltd.), Nomucota W (manufactured by The Nisshin Oilliogroup Co., Ltd.), and Propeto (manufactured by Maruishi Pharmaceutical Co., Ltd.) can be used. These petrolatums may be used alone or in any combination of two or more.

Among them, white vaseline that complies with the specifications of the 16th revision of the Japanese Pharmacopoeia is preferred from the viewpoint of more significantly exerting the pollen removal effect of the present invention, the effect of inhibiting the separation and precipitation of the oil layer, the effect of inhibiting the drying barrier of cells, and the effect of inhibiting irritation during nasal instillation.

The content of component (A) in the ophthalmic or otolaryngological aqueous composition of this embodiment is not particularly limited and can be appropriately set depending on the application of the ophthalmic or otolaryngological aqueous composition, the formulation form, etc. As the lower limit of the content of component (A), from the viewpoint of more significantly exerting the pollen removal effect of the present invention, the effect of inhibiting the separation and precipitation of the oil layer, the effect of inhibiting the drying disorder of cells, and the effect of inhibiting irritation during nasal instillation, for example, the total content of component (A) can be 0.00001 w/v% or more, preferably 0.0001 w/v% or more, more preferably 0.0005 w/v% or more, further preferably 0.001 w/v% or more, and particularly preferably 0.005 w/v% or more, based on the total amount of the ophthalmic or otolaryngological aqueous composition. There is no particular upper limit on the content of component (A). For example, based on the total amount of the ophthalmic or otolaryngological aqueous composition, the total content of component (A) may be 10 w/v% or less, preferably 5 w/v% or less, more preferably 1 w/v% or less, even more preferably 0.1 w/v% or less, even more preferably 0.05 w/v% or less, and particularly preferably 0.02 w/v% or less. These upper and lower limits may be arbitrarily combined.

The specific range of the content of component (A) is, from the viewpoint of more significantly exhibiting the pollen removal effect of the present invention, the effect of inhibiting separation and precipitation of the oil layer, the effect of inhibiting the desiccation of cells, and the effect of inhibiting irritation during nasal instillation, and the like. For example, the total content of component (A) can be 0.00001 to 10 w/v%, preferably 0.0001 to 1 w/v%, more preferably 0.0005 to 1 w/v%, and even more preferably 0.001 to 0.1 w/v%, based on the total amount of the ophthalmic or otolaryngological aqueous composition.

(B) Ingredients

The nonionic surfactant is not particularly limited as long as it is medically, pharmacologically (pharmaceutically) or physiologically acceptable. Specific examples of the nonionic surfactant include POE sorbitan fatty acid esters such as monolaurate POE (20) sorbitan (polysorbate 20), monooleate POE (20) sorbitan (polysorbate 80), POE sorbitan monostearate (polysorbate 60), and POE sorbitan tristearate (polysorbate 65); POE hydrogenated castor oil 5, POE hydrogenated castor oil 10, and POE POE hydrogenated castor oil 20, POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, POE hydrogenated castor oil 100, POE hydrogenated castor oil 3, POE castor oil 4, POE castor oil 6, POE castor oil 7, POE castor oil 10, POE castor oil 13.5, POE castor oil 17, POE castor oil 20, POE castor oil 25, POE castor oil 30, POE E castor oil 35, POE castor oil 50, etc. POE castor oil; polyethylene glycol monostearate (2E.O.), polyethylene glycol monostearate (4E.O.), polyethylene glycol monostearate (9E.O.), polyethylene glycol monostearate (10E.O.), polyethylene glycol monostearate (23E.O.), polyethylene glycol monostearate (25E.O.), polyethylene glycol monostearate (32E.O.), polyethylene glycol monostearate Monostearate polyethylene glycol esters (40E.O., polyoxyethylene stearate (40)), monostearate polyethylene glycol ester (45E.O.), monostearate polyethylene glycol ester (55E.O.), monostearate polyethylene glycol ester (75E.O.), monostearate polyethylene glycol ester (140E.O., polyoxyethylene stearate (140)); POE (196) POP (67) glycol (poloxamer 407, Pluronic F127), polyoxyethylene-polyoxypropylene block copolymers such as POE(200)POP(70) glycol; POE-POP block copolymer adducts of ethylenediamine such as poloxamine; POE alkyl ethers such as POE(9) lauryl ether; POE-POP alkyl ethers such as POE(20)POP(4) hexadecyl ether; POE alkylphenyl ethers such as POE(10) nonylphenyl ether, etc. In addition, the numbers in parentheses represent the number of added moles.

The ophthalmic or otolaryngological aqueous composition of this embodiment contains two or more (B) nonionic surfactants. The combination of the (B) nonionic surfactants is not particularly limited. From the perspective of more significantly exerting the effects of the present invention, a combination of one or more (B-1) nonionic surfactants having an HLB value of 10 or greater and one or more (B-2) nonionic surfactants having an HLB value of less than 10 is preferred. In this case, the nonionic surfactant (B-1) preferably has an HLB value of 11 or greater, and more preferably has an HLB value of 13 or greater. The nonionic surfactant (B-2) preferably has an HLB value of 8 or less, and more preferably has an HLB value of 6 or less.

Examples of the (B-1) nonionic surfactant having an HLB value of 10 or more (hereinafter simply referred to as "component (B-1)") include POE sorbitan fatty acid esters such as POE (20) sorbitan monolaurate (polysorbate 20), POE (20) sorbitan monooleate (polysorbate 80), POE sorbitan monostearate (polysorbate 60), and POE sorbitan tristearate (polysorbate 65); POE hydrogenated castor oils having an average added mole number of ethylene oxide of 20 or more such as POE hydrogenated castor oil 20, POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, and POE hydrogenated castor oil 100; and POE castor oil 25, POE castor oil 30, POE castor oil 35, and POE castor oil 50. POE castor oil with an average added mole number of ethylene of 23 or more; polyethylene glycol monostearate (9E.O.), polyethylene glycol monostearate (10E.O.), polyethylene glycol monostearate (23E.O.), polyethylene glycol monostearate (25E.O.), polyethylene glycol monostearate (32E.O.), polyethylene glycol monostearate (40E.O.), polyethylene glycol monostearate (4 0) ester), polyethylene glycol monostearate (45E.O.), polyethylene glycol monostearate (55E.O.), polyethylene glycol monostearate (75E.O.), polyethylene glycol monostearate (140E.O.), etc., polyethylene glycol monostearate with an average added mole number of ethylene oxide of 7 or more; POE (196) POP (67) diol (Poloxamer 407, Pluronic F127), POE (200) POP (70) diol, poloxamine, POE (20) POP (4) hexadecyl ether, POE (10) nonylphenyl ether. Among them, from the viewpoint of more significantly exerting the pollen removal effect of the present invention, the separation and precipitation inhibitory effect of the oil layer, the drying barrier inhibitory effect of cells, and the irritation inhibitory effect during nasal drops, POE (20) monooleate sorbitan (polysorbate 80), POE hydrogenated castor oil 40, POE hydrogenated castor oil 60, POE castor oil 35, polyoxyl stearate (40), polyoxyl stearate (140), POE (196) POP (67) diol (poloxamer 407, Pluronic F127), POE (200) POP (70) diol are preferred, and POE (20) monooleate sorbitan (polysorbate 80) and POE hydrogenated castor oil 60 are more preferred.

Examples of the nonionic surfactant (B-2) having an HLB value of less than 10 (hereinafter simply referred to as "component (B-2)") include POE hydrogenated castor oils such as POE hydrogenated castor oil 5 and POE hydrogenated castor oil 10, wherein the average number of moles of ethylene oxide added is less than 20; POE castor oil 3, POE castor oil 4, POE castor oil 6, POE castor oil 7, POE castor oil 10, POE castor oil 13.5, POE castor oil 17, and POE castor oil 20, wherein the average number of moles of ethylene oxide added is less than 23; polyethylene glycol monostearate (2E.O.), monostearate Monostearate polyethylene glycol esters such as polyethylene glycol ester (4E.O.) having an average number of added ethylene oxide moles of less than 7 are preferred. From the viewpoint of more significantly exhibiting the pollen removal effect, the oil layer separation and precipitation inhibitory effect, the cell drying disorder inhibitory effect, and the irritation inhibitory effect during nasal instillation of the present invention, POE hydrogenated castor oil having an average number of added ethylene oxide moles of less than 20 and POE castor oil having an average number of added ethylene oxide moles of less than 23 are preferred. POE castor oil having an average number of added ethylene oxide moles of less than 23 is more preferred. POE castor oil 3 and POE castor oil 10 are further preferred, and POE castor oil 3 is particularly preferred.

The content of component (B) in the ophthalmic or otolaryngological aqueous composition of this embodiment is not particularly limited and can be appropriately set according to the application and formulation form of the ophthalmic or otolaryngological aqueous composition. As the lower limit of the content of component (B), from the perspective of more significantly exerting the pollen removal effect of the present invention, the effect of inhibiting the separation and precipitation of the oil layer, the effect of inhibiting the drying of cells, and the effect of inhibiting irritation during nasal instillation, for example, the total content of component (B) is 0.0001 w/v% or more, preferably 0.001 w/v% or more, more preferably 0.01 w/v% or more, and even more preferably 0.1 w/v% or more, based on the total amount of the ophthalmic or otolaryngological aqueous composition. The upper limit of the content of component (B) is not particularly limited, for example, the total content of component (B) can be 20 w/v% or less, preferably 10 w/v% or less, more preferably 5 w/v% or less, and even more preferably 1 w/v% or less, based on the total amount of the ophthalmic or otolaryngological aqueous composition.

The specific range of the content of component (B) is, from the viewpoint of more significantly exhibiting the pollen removal effect of the present invention, the effect of inhibiting separation and precipitation of the oil layer, the effect of inhibiting the desiccation of cells, and the effect of inhibiting irritation during nasal instillation, and the like. For example, the total content of component (B) can be 0.0001 to 20 w/v%, preferably 0.001 to 10 w/v%, more preferably 0.01 to 5 w/v%, and even more preferably 0.1 to 1 w/v%, based on the total amount of the ophthalmic or otolaryngological aqueous composition.

When a nonionic surfactant (B-1) having an HLB value of 10 or greater is combined with a surfactant (B-2) having an HLB value of less than 10, the contents of the components (B-1) and (B-2) are exemplified below in order to more significantly exhibit the pollen removal effect of the present invention, the effect of inhibiting the separation and precipitation of the oil layer, the effect of inhibiting the drying disorder of cells, and the effect of inhibiting irritation during nasal instillation.

(B-1) Nonionic surfactant having an HLB value of 10 or greater: Based on the total amount of the aqueous ophthalmic or otolaryngological composition, the total content of component (B-1) may be 0.0001 to 10 w/v%, preferably 0.001 to 7 w/v%, more preferably 0.01 to 4 w/v%, and further preferably 0.1 to 1 w/v%.

(B-2) Nonionic surfactant having an HLB value of less than 10: Based on the total amount of the aqueous ophthalmic or otolaryngological composition, the total content of component (B-2) may be 0.0001 to 10 w/v%, preferably 0.001 to 5 w/v%, more preferably 0.005 to 1 w/v%, and further preferably 0.01 to 0.5 w/v%.

From the viewpoint of more significantly exerting the pollen removal effect of the present invention, the effect of inhibiting separation and precipitation of the oil layer, the effect of inhibiting the drying disorder of cells, and the effect of inhibiting irritation during nasal instillation, the ratio of component (A) to component (B) in the aqueous ophthalmic or otolaryngological composition of this embodiment can be, for example, 1 to 1,000,000 parts by mass, preferably 10 to 100,000 parts by mass, and more preferably 100 to 10,000 parts by mass, relative to 100 parts by mass of the total amount of component (A).

When a nonionic surfactant (B-1) having an HLB value of 10 or greater is combined with a surfactant (B-2) having an HLB value of less than 10, the ratios of component (A) and component (B) are exemplified below in order to more significantly exhibit the pollen removal effect, the effect of inhibiting the separation and precipitation of the oil layer, the effect of inhibiting the drying disorder of cells, and the effect of inhibiting irritation during nasal instillation of the present invention.

The ratio of the components (B-1) and (B-2) in the ophthalmic or otolaryngological aqueous composition of the present embodiment can be, for example, 0.1 to 100,000 parts by mass, preferably 1 to 10,000 parts by mass, and more preferably 10 to 1,000 parts by mass of the total amount of the component (B-1), relative to 100 parts by mass of the total amount of the component (B-2).

From the viewpoint of more significantly exerting the pollen removal effect of the present invention, the effect of inhibiting separation and precipitation of the oil layer, the effect of inhibiting the drying disorder of cells, and the effect of inhibiting irritation during nasal instillation, the ratio of the components (A) and (B-1) in the ophthalmic or otolaryngological aqueous composition of this embodiment can be, for example, 1 to 1,000,000 parts by mass, preferably 10 to 100,000 parts by mass, and more preferably 100 to 10,000 parts by mass, relative to 100 parts by mass of the total amount of the components (A).

From the viewpoint of more significantly exerting the pollen removal effect of the present invention, the effect of inhibiting separation and precipitation of the oil layer, the effect of inhibiting the drying disorder of cells, and the effect of inhibiting irritation during nasal instillation, the ratio of the components (A) and (B-2) in the ophthalmic or otolaryngological aqueous composition of this embodiment can be, for example, 1 to 1,000,000 parts by mass, preferably 10 to 100,000 parts by mass, and more preferably 100 to 10,000 parts by mass, relative to 100 parts by mass of the total amount of the component (A).

(C) Ingredients

The ophthalmic or otolaryngological aqueous composition of this embodiment preferably further contains at least one selected from the group consisting of (C) fat-soluble vitamins and vegetable oils (hereinafter simply referred to as "component (C)"). By further containing component (C), the pollen removal effect, the effect of inhibiting the separation and precipitation of the oil layer, the effect of inhibiting cellular drying disorders, and the effect of inhibiting irritation during nasal instillation of the present invention can be more significantly exerted.

Specific examples of fat-soluble vitamins include vitamins E, vitamins A, derivatives thereof, and salts thereof.

As vitamin E, there is no particular limitation as long as it is a substance that is pharmaceutically, pharmacologically (pharmaceutically) or physiologically permitted. Specifically, vitamin E includes, for example, tocopherol, tocotrienol and their derivatives, and their salts. Tocopherol and tocotrienol may be any of α-, β-, γ-, and δ-, and may be any of d- and dl-forms. Examples of their salts include organic acid salts (lactates, acetates, butyrates, trifluoroacetates, fumarates, maleates, tartrates, citrates, succinates, malonates, methanesulfonates, toluenesulfonates, toluenesulfonates, palmitates, stearates, etc.), inorganic salts (e.g., hydrochlorides, sulfates, nitrates, hydrobromides, phosphates, etc.), salts with organic bases (e.g., salts with organic amines such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, amino acids, tripyridine, and methylpyridine), and salts with inorganic bases (e.g., ammonium salts, salts with alkali metals such as sodium and potassium, with alkaline earth metals such as calcium and magnesium, and with metals such as aluminum). Examples of their derivatives include esters such as acetates, nicotinates, succinates, and linolenates. Vitamin E can be either natural or synthetic.

More specifically, examples of vitamin E include α-tocopherols such as D-α-tocopherol and dl-α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, vitamin E acetate (e.g., tocopheryl acetate), vitamin E nicotinate, vitamin E succinate, and vitamin E linolenate. Of these, tocopheryl acetate (e.g., d-α-tocopheryl acetate, dl-α-tocopheryl acetate, etc.) is preferred.

These vitamin E compounds may be used alone or in any combination of two or more.

As vitamin A, there is no particular limitation as long as it is a substance that is medically, pharmacologically (pharmaceutically) or physiologically allowed. As vitamin A, for example, vitamin A, a mixture containing vitamin A (for example, vitamin A oil), and a derivative with vitamin A activity can be listed. In addition, vitamin A oil refers to a fatty oil or a concentrate thereof obtained from aquatic animal tissue containing retinol, or a substance to which vegetable oil is appropriately added. As vitamin A, specifically, for example, retinal, retinol, retinoic acid, carotene, dehydroretinal, lycopene and their derivatives, and their salts (for example, retinol acetate, retinol palmitate, etc.) can be listed. Among them, retinol acetate and retinol palmitate are preferred. Vitamin A can be any of natural products and synthetic products.

Examples of vitamin A include retinyl palmitate manufactured by DSM, where 0.550 μg is equivalent to 1 IU of vitamin A. IU represents an international unit determined by methods such as those described in the 16th revision of the Japanese Pharmacopoeia Vitamin A Quantitative Method.

These vitamin A compounds may be used alone or in any combination of two or more.

Examples of vegetable oils include sesame oil, castor oil, olive oil, soybean oil, peanut oil, almond oil, wheat germ oil, camellia oil, corn oil, rapeseed oil, sunflower oil, cottonseed oil, and coconut oil. Commercially available vegetable oils can be used. These vegetable oils may be used alone or in any combination of two or more.

Sesame oil refers to a vegetable oil obtained from the seeds of plants of the genus Sesamum (Pedaliaceae, etc.) of the family Pedaliaceae. Sesame oil can be obtained from the seeds using known extraction and purification methods. For example, sesame oil listed in the Japanese Pharmacopoeia (see the 16th revised Japanese Pharmacopoeia, references C-1660 to 1662) can be obtained by purifying oil extracted by cold pressing.

Castor oil refers to a vegetable oil obtained from the seeds of plants of the genus Ricinus (Euphorbiaceae, etc.) of the Euphorbiaceae family. Castor oil can be obtained from the seeds using known extraction methods and known purification methods. For example, castor oil listed in the Japanese Pharmacopoeia (see the 16th revised Japanese Pharmacopoeia, references C-3748 to 3751) can be obtained by extracting the oil using a conventional pressing method, centrifuging the oil residue, decolorizing it with activated clay, steam distilling it at high temperature (200 to 220°C) under high vacuum, deoxidizing and deodorizing it, and then purifying it.

Olive oil refers to a vegetable oil obtained from the fruit of plants of the genus Olive (Olea europaea Linne) of the family Oleaceae (Oleaceae, etc.). It can be obtained from the fruit using known extraction methods and known purification methods. For example, olive oil listed in the Japanese Pharmacopoeia (see the 16th revised Japanese Pharmacopoeia, references C-1036 to 1039) can be obtained by directly cold-pressing (pressing the oil without heating) the ripe fruit, followed by physical filtration or centrifugal separation, and using conventional purification methods.

Soybean oil refers to a vegetable oil obtained from the seeds of plants of the genus Glycine max Merrill (Leguminosae, etc.) in the Leguminosae family. Soybean oil can be obtained from the seeds using known extraction methods and known purification methods. For example, soybean oil listed in the Japanese Pharmacopoeia (see the 16th revised Japanese Pharmacopoeia, Reference C-2617-2618) can be obtained by crushing and flattening soybeans (cold pressing or warm pressing can be used to produce oil) and then extracting the oil using a solvent (hexane).

Peanut oil refers to a vegetable oil obtained from the seeds of plants of the genus Arachis (such as Arachis hypogaea Linne) in the Leguminosae family. Peanut oil can be obtained from the seeds using a known extraction method or a known purification method. For example, peanut oil listed in the Japanese Pharmacopoeia (see the 16th revised Japanese Pharmacopoeia, references C-5093 to 5095) can be obtained by crushing the seeds with a roller, heating, and pressing, and filtering and purifying the resulting oil.

Almond oil is a vegetable oil obtained from the kernels of plants of the genus Prunus in the Rosaceae family (such as Prunus amygdalus Batsch, a variety of the Rosaceae family, and sweet almonds). It can be obtained from the kernels using known extraction and purification methods (see, for example, Pharmaceutical Additives Standards 2003, p. 93).

Wheat germ oil refers to a vegetable oil obtained from the germ of plants of the genus Triticum (common wheat (Triticum aestivum Linne)) (Gramdneae, etc.) of the Poaceae family. It can be obtained from the germ using known extraction methods and known purification methods (see Pharmaceutical Additives Standard 2003, p. 306, etc.).

Camellia oil refers to a vegetable oil obtained from the seeds of Camellia japonica Linne (Theaceae, etc.). It can be obtained from the seeds using known extraction and purification methods. For example, camellia oil listed in the Japanese Pharmacopoeia (see the 16th revised Japanese Pharmacopoeia, references C-2819-2820) can be obtained by pulverizing, steaming, and pressing sun-dried or artificially dried seeds, followed by filtration and purification.

Corn oil refers to a vegetable oil obtained from the germ of Zea mays Linne (Gramineae, etc.) of the grass family. It can be obtained from the germ using a known extraction method or a known purification method. For example, corn oil listed in the Japanese Pharmacopoeia (refer to the 16th revised Japanese Pharmacopoeia, reference C-2986 to 2988) is obtained by separating the germ from the grain, washing it with water, drying it by heating, and then pressing it. The pressing residue is then extracted with hexane to extract the oil.

Rapeseed oil is a vegetable oil obtained from the seeds of plants belonging to the genus Brassica (Brassica campestris Linne subsp. napus, Hooker filiuset Anderson var. nippo-oleifera Makino, etc.) of the Cruciferae family. It can be obtained from the seeds using known extraction and purification methods. For example, rapeseed oil listed in the Japanese Pharmacopoeia (see the 16th revised Japanese Pharmacopoeia, References C-3239-3240) is typically obtained by heating and pressing the seeds. The resulting residue is then subjected to solvent extraction and the extracted oil is used as crude oil. The resulting crude oil is then purified and used.

Sunflower oil is a vegetable oil obtained from the seeds of plants of the genus Helianthus (Compositae, etc.) in the Asteraceae family. It can be obtained from the seeds using known extraction and purification methods (see Pharmaceutical Additives Standards 2003, p. 523, etc.).

Cottonseed oil refers to a vegetable oil obtained from the seeds of plants of the genus Gossypium (Gossypium hirsutum Linne) in the Malvaceae family or plants of its genus (Malvaceae, etc.). Cottonseed oil can be obtained from the seeds using a known extraction method or a known purification method, for example, by purifying a fixed fatty oil obtained from the seeds by pressing or extraction (see, for example, Pharmaceutical Additives Standard 2003, p. 710).

Coconut oil refers to a vegetable oil obtained from the seeds of the plant Cocos nucifera Linne (Palmae, etc.) of the palm family. It can be obtained from the seeds using known extraction methods and known purification methods. For example, coconut oil listed in the Japanese Pharmacopoeia (see the 16th revised Japanese Pharmacopoeia, References C-5017 to 5019) can be obtained by pulverizing dried coconut meat, further pulverizing it, steaming and pressing it, removing suspended matter, and then purifying it.

Component (C) may be used alone or in any combination of two or more. Component (C) is preferably vitamin E, vitamin A, sesame oil, or castor oil, more preferably vitamin E, sesame oil, or castor oil, and even more preferably tocopheryl acetate or sesame oil.

When the component (C) is used, the lower limit of the content of the component (C) in the ophthalmic or otolaryngological aqueous composition of the present embodiment is not particularly limited. However, from the viewpoint of more significantly exhibiting the pollen removal effect, the oil layer separation and precipitation inhibitory effect, the cell drying disorder inhibitory effect, and the irritation inhibitory effect during nasal instillation of the present invention, the total content of the component (C) can be, for example, 0.00001 w/v% or more, preferably 0.0001 w/v% or more, more preferably 0.0005 w/v% or more, and even more preferably 0.005 w/v% or more, based on the total amount of the ophthalmic or otolaryngological aqueous composition. The upper limit of the content of component (C) is not particularly limited. However, from the viewpoint of more significantly exerting the pollen removal effect of the present invention, the effect of inhibiting separation and precipitation of the oil layer, the effect of inhibiting the desiccation of cells, and the effect of inhibiting irritation during nasal instillation, the total content of component (C) may be, for example, 10 w/v% or less, preferably 5 w/v% or less, more preferably 1 w/v% or less, and even more preferably 0.5 w/v% or less, based on the total amount of the ophthalmic or otolaryngological aqueous composition.

The specific range of the content of component (C) is, from the viewpoint of more significantly exhibiting the pollen removal effect of the present invention, the effect of inhibiting separation and precipitation of the oil layer, the effect of inhibiting the desiccation of cells, and the effect of inhibiting irritation during nasal instillation, and the like. For example, the total content of component (C) can be 0.00001 to 10 w/v%, preferably 0.0001 to 1 w/v%, more preferably 0.0005 to 1 w/v%, and even more preferably 0.001 to 0.1 w/v%, based on the total amount of the ophthalmic or otolaryngological aqueous composition.

From the viewpoint of more significantly exerting the pollen removal effect of the present invention, the effect of inhibiting separation and precipitation of the oil layer, the effect of inhibiting the drying disorder of cells, and the effect of inhibiting irritation during nasal instillation, the ratio of component (A) to component (C) in the aqueous ophthalmic or otolaryngological composition of this embodiment can be, for example, 1 to 1,000,000 parts by mass, preferably 10 to 100,000 parts by mass, and more preferably 100 to 10,000 parts by mass relative to 100 parts by mass of the total amount of component (A).

(D) Ingredients

The ophthalmic or otolaryngological aqueous composition of this embodiment preferably further contains (D) a buffer (hereinafter simply referred to as "component (D)"). By further containing component (D), the effects of the present invention can be more significantly exhibited.

The buffer (D) is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically), or physiologically acceptable. Specific examples of the buffer (D) include boric acid buffers, phosphate buffers, carbonate buffers, citric acid buffers, acetic acid buffers, ε-aminocaproic acid, aspartic acid, and aspartate. Among these, boric acid buffers, phosphate buffers, carbonate buffers, and citric acid buffers are preferred.

Examples of boric acid buffers include boric acid, alkali metal borates, and alkaline earth metal borates. Examples of phosphate buffers include phosphoric acid, alkali metal phosphates, and alkaline earth metal phosphates. Examples of carbonate buffers include carbonates such as carbonic acid, alkali metal carbonates, and alkaline earth metal carbonates. Examples of citric acid buffers include citric acid, alkali metal citrates, and alkaline earth metal citrates. Hydrates of borates or phosphates can be used as boric acid buffers or phosphate buffers. More specifically, boric acid buffers include boric acid or its salts (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.); phosphate buffers include phosphoric acid or its salts (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.); carbonate buffers include carbonic acid or its salts (sodium bicarbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium bicarbonate, magnesium carbonate, etc.); citric acid buffers include citric acid or its salts (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.); acetic acid buffers include acetic acid or its salts (ammonium acetate, potassium acetate, calcium acetate, sodium acetate, etc.), aspartic acid or its salts (sodium aspartate, magnesium aspartate, potassium aspartate, etc.). These buffers may be used alone or in any combination of two or more.

Among the above-mentioned buffers, boric acid buffers and phosphate buffers are particularly preferred. As the boric acid buffer, a combination of boric acid and a salt thereof is preferred, more preferably a combination of boric acid and an alkali metal salt and/or alkaline earth metal salt thereof, further preferably a combination of boric acid and an alkali metal salt thereof, and even more preferably a combination of boric acid and borax. As the phosphate buffer, a combination of a first phosphate and a second phosphate is preferred, more preferably a combination of an alkali metal salt of the first phosphate and an alkali metal salt of the second phosphate, and even more preferably a combination of sodium dihydrogen phosphate and disodium hydrogen phosphate. From the perspective of more significantly exerting the effects of the present invention, the boric acid buffer is particularly preferred.

When the component (D) is used, the content of the component (D) in the ophthalmic or otolaryngological aqueous composition of the present embodiment varies depending on the type of component (D) used, the types and amounts of other ingredients, the application of the ophthalmic or otolaryngological aqueous composition, the formulation form, etc., and cannot be specified in general. However, for example, the total content of the component (D) can be 0.01 to 10 w/v%, preferably 0.1 to 5 w/v%, and more preferably 0.2 to 2 w/v%, based on the total amount of the ophthalmic or otolaryngological aqueous composition.

The ophthalmic or otolaryngological aqueous composition of the present embodiment preferably further contains terpenoids. As terpenoids, there are no particular limitations as long as they are pharmaceutically, pharmacologically (pharmaceutically) or physiologically permitted substances. As terpenoids, specifically, for example, menthol, camphor, borneol, geraniol, eucalyptol, citronellol, menthone, carvone, anethole, eugenol, limonene, linalool, linalyl acetate and their derivatives can be listed. Terpenoids can be any of the d-isomer, l-isomer or dl-isomer. In addition, as terpenoids, essential oils containing terpenoids can be used. As the essential oils, for example, lemon eucalyptus oil, bergamot oil, peppermint oil (peppermint oil), ice mint oil, spearmint oil, peppermint oil (hatsuri oil), anise oil, cinnamon oil and rose oil can be listed. These terpenoids can be used alone or in any combination of two or more.

Among terpenoids, dl-menthol, l-menthol, dl-camphor, d-camphor, d-borneol, or geraniol are preferred because they can more significantly exert the effects of the present invention. Examples of essential oils containing these terpenoids include ice mint oil, peppermint oil, peppermint oil, and camphor oil. Terpenoids are more preferably dl-menthol, l-menthol, dl-camphor, d-camphor, and d-borneolgeraniol, more preferably l-menthol, d-camphor, and dl-camphor, and even more preferably l-menthol.

When terpenoid compounds are used, the content of terpenoid compounds in the ophthalmic or otolaryngological aqueous composition of this embodiment varies depending on the type of terpenoid compound used, the type and amount of other ingredients, the purpose of the ophthalmic or otolaryngological aqueous composition and the formulation form, and cannot be specified in general. However, for example, based on the total amount of the ophthalmic or otolaryngological aqueous composition, the total content of terpenoid compounds can be 0.0001 to 10 w/v%, preferably 0.0001 to 5 w/v%, more preferably 0.0005 to 5 w/v%, further preferably 0.001 to 3 w/v%, further preferably 0.001 to 1 w/v%, and particularly preferably 0.001 to 0.1 w/v%.

The ophthalmic or otolaryngological aqueous composition of the present embodiment preferably further contains a thickener. As a thickener, as long as it is a material that is medically, pharmacologically (pharmaceutically) or physiologically allowed, there is no particular limitation. As a thickener, specifically, for example, vinyl thickeners [for example, polyvinyl alcohol (complete or partial saponification), polyvinyl pyrrolidone (K25, K30, K90, etc.), carboxyvinyl polymers, etc.], cellulose thickeners [for example, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose (2208, 2906, 2910, etc.), carboxymethylcellulose, carboxyethylcellulose, nitrocellulose or their salts, etc.], polyethylene glycol (Macrogol 300, Macrogol 400, Macrogol 1500, Macrogol 4000, etc.) or mucopolysaccharides [for example, chondroitin sulfate, alginic acid, hyaluronic acid, or salts thereof], polysaccharides [for example, guar gum, hydroxypropyl guar gum, gum arabic, karaya gum, xanthan gum, carrageenan, agar, alginic acid, α-cyclodextrin, dextrin, dextran, starch, chitin and its derivatives, chitosan and its derivatives]. Examples of thickener salts include salts with inorganic bases. Thickener salts are preferably alkali metal salts or alkaline earth metal salts, more preferably sodium salts, potassium salts, calcium salts, or magnesium salts, and even more preferably sodium salts. These thickeners may be used alone or in any combination of two or more.

Among thickeners, vinyl thickeners, cellulosic thickeners, polyethylene glycol, or mucopolysaccharides are preferred because they can more significantly demonstrate the effects of the present invention. Examples of vinyl thickeners include polyvinyl alcohol, polyvinyl pyrrolidone, and carboxyvinyl polymers. Examples of cellulosic thickeners include methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, or salts thereof. Examples of polyethylene glycol include Macrogol 300 and Macrogol 400. Examples of mucopolysaccharides include chondroitin sulfate or salts thereof, alginic acid or salts thereof, and hyaluronic acid or salts thereof. As the thickening agent, carboxyvinyl polymer, hydroxypropyl methylcellulose, hydroxyethyl cellulose, polyvinyl pyrrolidone, polyvinyl alcohol, alginic acid or sodium hyaluronate is more preferred, polyvinyl pyrrolidone (K25, K90), carboxyvinyl polymer, hydroxyethyl cellulose, hydroxypropyl methylcellulose (2208, 2906, 2910), sodium chondroitin sulfate or sodium hyaluronate is further preferred, and hydroxypropyl methylcellulose, sodium chondroitin sulfate or sodium hyaluronate is even more preferred.

When a thickener is used, the content of the thickener in the ophthalmic or otolaryngological aqueous composition of this embodiment varies depending on the type of thickener used, the type and amount of other ingredients, the application of the ophthalmic or otolaryngological aqueous composition, the formulation form, etc., and cannot be specified in general. However, for example, the total content of the thickener can be 0.01 to 10 w/v%, preferably 0.01 to 5 w/v%, more preferably 0.05 to 3 w/v%, and even more preferably 0.1 to 1 w/v%, based on the total amount of the ophthalmic or otolaryngological aqueous composition.

The ophthalmic or otolaryngological aqueous composition of this embodiment may further contain a tonicity agent. As a tonicity agent, there is no particular limitation as long as it is a substance that is medically, pharmacologically (pharmaceutically) or physiologically acceptable. As a tonicity agent, specifically, for example, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium bisulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, potassium acetate, sodium acetate, sodium bicarbonate, sodium carbonate, sodium thiosulfate and magnesium sulfate can be listed. Among the tonicity agents, potassium chloride, calcium chloride, sodium chloride or magnesium chloride are preferred. These tonicity agents can be used alone or in any combination of two or more.

When a tonicity agent is used, the content of the tonicity agent in the ophthalmic or otolaryngological aqueous composition of this embodiment varies depending on the type of tonicity agent used, the types and amounts of other ingredients, the application of the ophthalmic or otolaryngological aqueous composition, the formulation form, etc., and cannot be specified in general. However, for example, the total content of the tonicity agent can be 0.01 to 10 w/v%, preferably 0.05 to 5 w/v%, and more preferably 0.1 to 2 w/v%, based on the total amount of the ophthalmic or otolaryngological aqueous composition.

The pH of the ophthalmic or otolaryngological aqueous composition of this embodiment is not particularly limited as long as it is within a pharmaceutically, pharmacologically (pharmaceutically), or physiologically acceptable range. The pH of the ophthalmic or otolaryngological aqueous composition of this embodiment can be, for example, 4.0 to 9.5, preferably 4.5 to 8.5, more preferably 5.0 to 8.5, and even more preferably 5.5 to 7.5.

The ophthalmic or otolaryngological aqueous composition of this embodiment can be adjusted to an osmotic pressure ratio within the range allowed by the organism as needed. The appropriate osmotic pressure ratio varies depending on the applicable site, dosage form, etc., but can be, for example, 0.7 to 5.0, preferably 0.9 to 3.0, and more preferably 1.0 to 2.0. The adjustment of osmotic pressure can be carried out using inorganic salts, polyols, etc., using known methods in this technical field. The osmotic pressure ratio is the ratio of the osmotic pressure of a sample relative to 286mOsm (the osmotic pressure of a 0.9w/v% sodium chloride aqueous solution) according to the sixteenth revision of the Japanese Pharmacopoeia, and the osmotic pressure is measured with reference to the osmotic pressure determination method (freezing point depression method) recorded in the Japanese Pharmacopoeia. Alternatively, as a standard solution for osmotic pressure ratio measurement (0.9 w/v% sodium chloride aqueous solution), sodium chloride (Japanese Pharmacopoeia standard reagent) can be dried at 500-650°C for 40-50 minutes, then naturally cooled in a desiccator (silica gel), and 0.900 g of this sodium chloride accurately weighed and dissolved in pure water to accurately prepare 100 mL. Alternatively, a commercially available standard solution for osmotic pressure ratio measurement (0.9 w/v% sodium chloride aqueous solution) can be used.

The ophthalmic or otolaryngological aqueous composition of the present embodiment can contain the component of the multiple pharmacologically active ingredients and physiologically active ingredients selected from the above-mentioned components in the scope of not damaging the effect of the present invention in appropriate amount combination. This component is not particularly limited, and for example, the active ingredient in the ophthalmic or otolaryngological medicine recorded in the 2012 edition of the conventional pharmaceutical manufacturing and sales approval benchmark (general corporate body Regulatory Science Society Supervision) can be illustrated. As the component used in ophthalmic or otolaryngological medicine, specifically, for example, the following components can be listed.

Antihistamines: for example, iprohydramine, diphenhydramine, chlorpheniramine maleate, ketotifen fumarate, olopatadine hydrochloride, levocabastine hydrochloride, etc.

Antiallergic agents: for example, sodium cromoglycate, tranilast, pemirolast potassium, etc.

Steroid agents: for example, fluticasone propionate, fluticasone furoate, mometasone furoate, beclomethasone propionate, flunisolide, etc.

Vasoconstrictors (decongestants): for example, tetrahydrozoline, naphazoline, epinephrine, ephedrine, methylephedrine, phenylephrine, etc.

Bactericides: for example, rivanol, cetylpyridine, benzalkonium chloride, benzethonium chloride, chlorhexidine, polyhexamethylene biguanide, etc.

Vitamins: for example, sodium flavin adenine dinucleotide, cyanocobalamin, pyridoxine hydrochloride, panthenol, calcium pantothenate, etc.

Amino acids: for example, potassium aspartate, magnesium aspartate, magnesium and potassium aspartate, aminoethanesulfonic acid, etc.

Anti-inflammatory agents: for example, glycyrrhetinic acid, glycyrrhizic acid, pranoprofen, methyl salicylate, glycol salicylate, allantoin, tranexamic acid, ε-aminocaproic acid, berberine, sodium azulenesulfonate lysozyme, licorice, etc.

Astringents: for example, zinc oxide, zinc lactate, zinc sulfate, etc.

Local anesthetics: for example, lidocaine, etc.

Others: for example, sulfamethoxazole, indomethacin, ibuprofen, ibuprofen pyridine methanol, bufenac, flufenamic acid butyl ester, bendazolic acid, piroxicam, ketoprofen, felbinac, lithospermum parkii root, horse chestnut, and their salts.

The ophthalmic or otolaryngological aqueous composition of this embodiment can contain various additives as appropriate according to the conventional method, within the scope that does not impair the effects of the present invention, depending on its application and formulation form, and can contain one or more additives in appropriate amounts and use them simultaneously. Examples of such additives include the various additives listed in the Encyclopedia of Pharmaceutical Additives 2007 (edited by the Japan Pharmaceutical Additives Association). Representative ingredients include the following additives.

Carrier: An aqueous solvent such as water or aqueous ethanol.

Sugars: For example, glucose, etc.

Sugar alcohols: for example, xylitol, sorbitol, mannitol, etc. They can be any of the d-isomer, l-isomer or dl-isomer.

Preservatives, bactericides, or antimicrobial agents: for example, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, casethonium chloride, chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, hydroxyquinoline sulfate, phenylethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexamethylene biguanide, etc.), Grokil (trade name of RHODIA Co., Ltd.), etc.

Chelating agents: for example, ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid (EDTA), N-(2-hydroxyethyl)ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA), etc.

Stabilizers: for example, butylated hydroxytoluene, tromethamine, sodium formaldehyde sulfoxylate (rongalite), tocopherol, sodium metabisulfite, monoethanolamine, aluminum monostearate, glyceryl monostearate, etc.

Primer: for example, octyldodecanol, titanium dioxide, potassium bromide, liquid paraffin, Plastibase, lanolin, propylene glycol, etc.

In the present embodiment, the aqueous composition refers to a composition in which the content of water is 50w/v% or more relative to the total amount of the aqueous composition. The content of water in the aqueous composition is preferably 80w/v% or more relative to the total amount of the aqueous composition, more preferably 90w/v% or more, further preferably 95w/v% or more, and further preferably 97w/v% or more. In addition, when the aqueous composition is an otolaryngology composition, the content of water may be 60w/v% or more, or 70w/v% or more relative to the total amount of the aqueous composition. The water used in the aqueous composition can be any water that is medically, pharmacologically (pharmaceutically) or physiologically permitted. Examples of such water include distilled water, ordinary water, pure water, sterilized pure water, water for injection, and distilled water for injection. Their definitions are based on the sixteenth revision of the Japanese Pharmacopoeia.

In the present embodiment, the aqueous composition is preferably an ophthalmic or otolaryngological aqueous composition used in the ophthalmic field or the otolaryngological field.

The ophthalmic or otolaryngological aqueous composition of this embodiment can be prepared to a desired concentration by adding and mixing the desired amounts of component (A), component (B), and other components as needed. For example, it can be prepared by dissolving or suspending these components in pure water, adjusting the pH and osmotic pressure to a predetermined value, and sterilizing by filtration or the like as needed. To dissolve component (A) and other highly hydrophobic components, component (B) or a component that assists in dissolution can be stirred in advance before adding pure water to dissolve them.

The ophthalmic or otolaryngological aqueous composition of this embodiment can be prepared in various formulation forms depending on the intended purpose. Examples of formulation forms include liquid preparations and semisolid preparations (ointments, etc.). The ophthalmic or otolaryngological aqueous composition of this embodiment is preferably a liquid preparation.

The ophthalmic or otolaryngological aqueous composition of this embodiment can be used as, for example, eye drops (referring to eye drops or eye drops. In addition, eye drops include eye drops that can be instilled into the eyes while wearing contact lenses), artificial tears, eye washes (referring to eye washes or eye washes. In addition, eye washes include eye washes that can be used to wash the eyes while wearing contact lenses), contact lens wearing solutions, contact lens care agents (including contact lens disinfectants, contact lens preservatives, contact lens cleaning agents, contact lens cleaning and preservatives, etc.), eye ointments, nasal drops, nasal washes (referring to nasal wash solutions), ear drops, etc. In addition, "contact lenses" include hard contact lenses, soft contact lenses (including both ionic and non-ionic types, and including both silicone hydrogel contact lenses and non-silicone hydrogel contact lenses).

Among them, the single usage amount of eye drops is extremely small. Therefore, due to the influence of the content change of the components in the preparation used once, such as separation, it is particularly strongly required to stably maintain the added components. According to the ophthalmic or otolaryngological aqueous composition of this embodiment, vaseline can be contained, but the separation or precipitation of the oil layer can be suppressed, further significantly improving the solubility of vaseline. In view of this effect, the ophthalmic or otolaryngological aqueous composition of this embodiment can be used as eye drops.

The ophthalmic or otolaryngological aqueous composition of the present embodiment can be provided in a container commonly used in the medical field. The container can be made of glass or plastic. The container can be a transparent container so that the interior of the container can be identified, or an opaque container so that the interior of the container is difficult to identify. Here, "transparent container" includes both colorless transparent containers and colored transparent containers. There is no particular limitation on the material of the plastic container. For example, any one of polyethylene naphthalate, polyacrylate, polyethylene terephthalate, polypropylene, polyethylene, and polyimide, their copolymers, or a mixture of two or more of these materials can be listed. As the above-mentioned copolymer, any one of a copolymer containing ethylene-2,6-naphthalene dicarboxylic acid unit, an acrylate unit, an ethylene terephthalate unit, a propylene unit, an ethylene unit, and an imide unit can be listed.

The ophthalmic or otolaryngological aqueous composition of this embodiment has high solubility in petrolatum and exhibits high light transmittance. Therefore, in order to visually confirm that it is a preparation with high light transmittance, a transparent container is suitable as a container for storing the ophthalmic or otolaryngological aqueous composition of this embodiment. Due to the high light transmittance of the preparation, storing it in a transparent container allows for easy visual inspection of foreign matter. Therefore, the aqueous composition of the present invention is preferably used as an eye drop or eye wash, which particularly requires foreign matter inspection. The light transmittance of the ophthalmic or otolaryngological aqueous composition of this embodiment, for example, at a wavelength of 660 nm, can be 20% or more, preferably 30% or more, more preferably 50% or more, further preferably 60% or more, even more preferably 70% or more, even more preferably 75% or more, particularly preferably 80% or more, even more preferably 85% or more, and even more preferably 90% or more.

〔2. Prevention, treatment, improvement or relief of allergic symptoms〕

The ophthalmic or otolaryngological aqueous composition of this embodiment has a cleansing effect on allergens such as pollen adhering to the surface of the ocular or nasal mucosa. Therefore, the ophthalmic or otolaryngological aqueous composition of this embodiment is effective in preventing, treating, ameliorating, or allergic symptoms.

Therefore, as one embodiment of the present invention, there is provided a preventive, therapeutic, ameliorative or allergic symptom agent, which is composed of an ophthalmic or otolaryngological aqueous composition containing (A) vaseline and two or more (B) nonionic surfactants. In addition, as one embodiment of the present invention, there is provided the use of (A) vaseline and two or more (B) nonionic surfactants in the preparation of an ophthalmic or otolaryngological aqueous composition for the prevention, treatment, amelioration or alleviation of allergic symptoms. In addition, as one embodiment of the present invention, there is provided a method for imparting an ophthalmic or otolaryngological aqueous composition with a preventive, therapeutic, ameliorative or allergic symptom effect, which comprises preparing an ophthalmic or otolaryngological aqueous composition containing (A) vaseline and two or more (B) nonionic surfactants. In addition, as one embodiment of the present invention, there is provided a method for preventing, treating, ameliorative or allergic symptoms, which comprises the step of washing the ocular mucosa or nasal mucosa of the object with an ophthalmic or otolaryngological aqueous composition containing (A) vaseline and two or more (B) nonionic surfactants. This washing step can effectively remove allergy-causing substances (eg, pollen, dust, mites, mold, pet hair, contact lenses, cosmetics, etc.) present in the target ocular mucosa or nasal mucosa.

In addition, the types and contents of components (A) and (B), the types and contents of other components, the formulation form and uses of the aqueous composition in each of the above embodiments are as described in [1. Aqueous composition for ophthalmology or otolaryngology].

〔3. Alleviation of dryness disorder of ocular mucosal cells〕

The ophthalmic or otolaryngological aqueous composition of this embodiment has the effect of suppressing cell disorders (siccatility) caused by dry stress response. Therefore, as one embodiment of the present invention, there is provided a kind of ophthalmic aqueous composition containing (A) vaseline, two or more (B) nonionic surfactants, comprising a dry barrier alleviating agent for ocular mucosal cells. In addition, as one embodiment of the present invention, there is provided a kind of ophthalmic aqueous composition for alleviating the dry barrier of ocular mucosal cells. In addition, as one embodiment of the present invention, there is provided a kind of ophthalmic aqueous composition for alleviating the dry barrier of ocular mucosal cells, the method comprising preparing an ophthalmic aqueous composition containing (A) vaseline and two or more (B) nonionic surfactants ... there is provided a kind of ophthalmic aqueous composition for alleviating the dry barrier of ocular mucosal cells, the method comprising making an ophthalmic aqueous composition containing (A) vaseline, two or more (B) nonionic surfactants contact with the ocular mucosa.

The ophthalmic aqueous composition of this embodiment can reduce the dryness barrier of ocular mucosal cells such as corneal epithelial cells, and is therefore useful for dry eyes (dry eyes). Therefore, as one embodiment of the present invention, there is provided a kind of prevention, treatment, improvement or relief agent for dry eye symptoms, which is composed of an ophthalmic aqueous composition containing (A) vaseline, two or more (B) nonionic surfactants. In addition, as one embodiment of the present invention, there is provided a kind of (A) vaseline and two or more (B) nonionic surfactants for the preparation of ophthalmic aqueous compositions for preventing, treating, improving or alleviating dry eyes. In addition, as one embodiment of the present invention, there is provided a kind of method for giving ophthalmic aqueous compositions dry eye symptoms, treatment, improvement or relief effect, which includes preparing an ophthalmic aqueous composition containing (A) vaseline and two or more (B) nonionic surfactants. In addition, as one embodiment of the present invention, there is provided a kind of prevention, treatment, improvement or relief method for dry eye symptoms, which includes the step of contacting an ophthalmic aqueous composition containing (A) vaseline, two or more (B) nonionic surfactants with an ocular mucosa.

In addition, the types and contents of components (A) and (B), the types and contents of other components, the formulation form and uses of the aqueous composition in each of the above embodiments are as described in [1. Aqueous composition for ophthalmology or otolaryngology].

[4. Aqueous otolaryngological composition contained in a container having a nozzle]

The otorhinolaryngological aqueous composition can be contained in a container having a nozzle. In this embodiment, the otorhinolaryngological aqueous composition only needs to contain (A) vaseline, and preferably further contains one or more (B) nonionic surfactants, more preferably two or more (B) nonionic surfactants.

The container for storing the aqueous composition for otorhinolaryngology can be made into various forms such as drop-type, coating type, spray type, etc., depending on the shape of the nozzle. In the case of the spray type, there are manual pump nasal drops with a structure in which the aqueous composition is sprayed by manually operating a pump attached to the container, and aerosol nasal drops with a structure in which a spray of compressed gas (air, oxygen, nitrogen, carbonic acid, or a mixed gas) is filled in the container and the aqueous composition is automatically sprayed by operating a valve attached to the container. From the perspective of more significantly exerting the effect of removing allergic substances, the effect of suppressing cell disorders caused by dryness stress reaction, and the effect of reducing or alleviating irritation during use, the spray type is preferred, and the manual pump type is more preferred.

Therefore, as one embodiment of the present invention, there is provided an improvement or relief agent for irritation during use, which contains (A) vaseline, is contained in a container with a spray nozzle, and is composed of an aqueous composition for otorhinolaryngology. In addition, as one embodiment of the present invention, there is provided an application of (A) vaseline in the preparation of an aqueous composition for otorhinolaryngology, which is contained in a container with a spray nozzle and is used for improvement or relief of irritation during use. In addition, as one embodiment of the present invention, there is provided a method for improving or alleviating irritation when the otorhinolaryngology aqueous composition is used, which includes preparing an otorhinolaryngology aqueous composition containing (A) vaseline and contained in a container with a spray nozzle. In addition, as one embodiment of the present invention, there is provided a method for improving or alleviating irritation when the aqueous composition is applied to the nasal mucosa or ear, the method including adding (A) vaseline to the aqueous composition. The method may further include the step of containing the aqueous composition in a container with a spray nozzle.

The ophthalmic or otolaryngological aqueous composition of this embodiment has the effect of suppressing the cell disorder (dryness disorder) caused by the dry stress reaction. Therefore, as one embodiment of the present invention, there is provided a dryness disorder alleviating agent for nasal mucosal cells composed of an otolaryngological aqueous composition containing (A) vaseline and two or more (B) nonionic surfactants. In addition, as one embodiment of the present invention, there is provided an application of (A) vaseline and two or more (B) nonionic surfactants in the preparation of an otolaryngological aqueous composition for alleviating the dryness disorder of nasal mucosal cells. In addition, as one embodiment of the present invention, there is provided a method for imparting an otolaryngological aqueous composition to a dryness disorder alleviating effect on nasal mucosal cells, which includes preparing an otolaryngological aqueous composition containing (A) vaseline and two or more (B) nonionic surfactants. In addition, as one embodiment of the present invention, there is provided a method for alleviating the dryness disorder of nasal mucosal cells, which includes contacting an otolaryngological aqueous composition containing (A) vaseline and two or more (B) nonionic surfactants with the nasal mucosa.

In addition, the types and contents of the components (A) and (B) and the types and contents of other components in each of the above embodiments are as described in [1. Aqueous composition for ophthalmology or otolaryngology].

Example

The present invention will be specifically described below based on test examples, but the present invention is not limited thereto.

[Test Example 1. Pollen Cleaning Test]

Prepare an aqueous composition with the composition shown in Table 1. First, stir the oily component and surfactant with a stirrer while heating to 60°C. Then, add pure water heated to 60°C and stir to mix. Allow to cool naturally to room temperature, then add and dissolve the other components. Adjust the pH, and add pure water to the final volume. Sunwhite P200 manufactured by Nikko-Rica Co., Ltd. was used as the white vaseline.

Human corneal epithelial cell line HCE-T (RIKEN BioResource Center, No. RCB1384) was seeded on a 24-well culture plate (manufactured by Corning, Japan) and cultured until confluent at 37°C, 5% CO ₂ , and 90% humidity. A growth medium containing 5% FCS (manufactured by DS-Pharma), 0.5% DMSO (manufactured by Wako Pure Chemical Industries, Ltd.), 10 ng/mL recombinant human EGF (manufactured by R&D), and 5 μg/mL human insulin solution (manufactured by SIGMA) was used.

The growth medium was removed from each well by aspiration, and 0.5 mL of growth medium containing 0.2 mg/mL suspension of mugwort pollen (Sigma, Cat. P9395-1G) was added to each well. The cells were then incubated at 37°C and 5% _CO₂ for 4 hours to allow the pollen to adhere to the cells.

The supernatant was removed from each well by aspiration, and 500 μL of each aqueous composition (Examples 1 to 3 and Comparative Example 1) with the composition shown in Table 1 was added to each well, followed by shaking at 400 rpm for 30 seconds. After aspiration, each aqueous composition was removed from each well. Microscopic photographs were taken at five random locations in each well, and the total area of remaining pollen was calculated using image analysis software (WinROOF).

The average value of the total area of remaining pollen measured for each aqueous composition (4 wells) was determined. The ratio of the total area of remaining pollen in each example to the total area of remaining pollen in Comparative Example 1 is shown in Table 1 as the remaining pollen amount (%).

[Table 1]

Unit (w/v%) Comparative Example 1 Example 1 Example 2 Example 3 White Vaseline - 0.01 0.01 0.03 sesame oil - - 0.05 0.05 Polysorbate 80 (HLB15) 0.2 0.2 0.2 0.2 Polyoxyethylene castor oil 3 (HLB3) 0.2 0.2 0.2 0.2 Sodium chloride 0.6 0.6 0.6 0.6 Boric acid 1.2 1.2 1.2 1.2 Borax 0.2 0.2 0.2 0.2 pure water margin margin margin margin pH 7.25 7.26 7.28 7.26 Pollen residue (%) - 90.6 43.0 24.1

Compared to an aqueous composition containing only two surfactants, the aqueous composition that further added white petrolatum showed a striking decrease in the amount of pollen remaining in corneal epithelial cells. The aqueous composition that further added sesame oil showed an even more significant decrease in the amount of pollen remaining, confirming an enhanced pollen cleansing effect.

[Reference Test Example 1. Solubility Test (1)]

Prepare an aqueous composition with the composition shown in Table 2. First, stir white petrolatum or liquid paraffin and polysorbate 80 at 60°C with a stirrer. Add purified water, also heated to 60°C, and stir to mix. Allow the mixture to cool naturally to room temperature, and then add purified water to the final volume.

The presence or absence of separation of the oil layer was visually evaluated for each aqueous composition of Reference Examples 1 and 2 according to the following criteria immediately after preparation. The results are shown in Table 2 and Figure 1.

<Criteria for judging whether there is separation of oil layer>

◎: The oil layer and the water layer do not separate when standing still

○: The oil layer and the water layer separate when standing still, but become one by inverting and mixing

×: The oil layer and the water layer are separated and do not mix at all even when mixed upside down.

[Table 2]

Unit (w/v%) Reference Example 1 Reference Example 2 White Vaseline - 0.01 liquid paraffin 0.01 - Polysorbate 80 0.5 0.5 pure water margin margin Separation of oil layers ◎ ×

Both petrolatum and liquid paraffin are known non-polar oils, commercially available for use in eye drops. As shown in Table 2, the aqueous composition containing liquid paraffin exhibited no separation of the oil layer and remained clear when polysorbate 80 was used as a surfactant. On the other hand, the aqueous composition containing white petrolatum showed little solubility of polysorbate 80 alone. In other words, even though both are non-polar oils, white petrolatum exhibited a technical solubility issue not encountered with liquid paraffin.

[Test Example 2. Solubility Test]

Aqueous compositions with the compositions shown in Tables 3 and 4 were prepared. First, the oily component and surfactant were stirred with a stirrer while heated to 60°C. Pure water, also heated to 60°C, was added and stirred to mix. The mixture was allowed to cool naturally to room temperature, and then the other components were added and dissolved. The pH was then adjusted, and pure water was added to the volume. Sunwhite P200 manufactured by Nikko-Rica Co., Ltd. was used as the white vaseline.

The presence or absence of oil layer separation was evaluated for each aqueous composition (Examples 4 to 11) using the same procedure as in Reference Test Example 1. Furthermore, the transmittance of each aqueous composition at a wavelength of 660 nm was measured using a spectrophotometer (UV-2450 UV-visible spectrophotometer, manufactured by Shimadzu Corporation) one day after preparation. This transmittance serves as an indicator of the clarity of each aqueous composition. The results are shown in Tables 3 and 4.

[Table 3]

[Table 4]

Unit (w/v%) Example 8 Example 9 Example 10 Example 11 White Vaseline 0.01 0.01 0.01 0.01 Polyoxyethylene hydrogenated castor oil 60 (HLB 14.0) 0.2 0.1 0.3 0.2 Polyoxyethylene castor oil 3 (HLB3) 0.2 - 0.1 - Polyoxyethylene castor oil 10 (HLB 6.5) - 0.3 - 0.2 sesame oil 0.05 0.05 0.05 0.05 pure water margin margin margin margin pH 8.2 8.0 8.3 8.2 Separation of oil layers ◎ ◎ ◎ ◎ Transmittance (%T: 660nm) 75.6 25.6 52.7 29.6

As shown in Table 3, by including polyoxyethylene castor oil 3 or polyoxyethylene castor oil 10 in addition to polysorbate 80, a clear, separated aqueous composition without an oil layer can be prepared. Furthermore, a comparison of Examples 4 and 5 shows that by further including a boric acid buffer, a clearer aqueous composition can be prepared. As shown in Table 4, even when polyoxyethylene castor oil 60 is used in place of polysorbate 80, a clear, separated aqueous composition without an oil layer can be prepared by including polyoxyethylene castor oil 3 or polyoxyethylene castor oil 10.

[Test Example 3. Cell Drying Test]

Prepare an aqueous composition with the composition shown in Table 5. First, stir the oil component and surfactant with a stirrer while heating to 60°C. Then, add pure water heated to 60°C and stir to mix. Allow to cool naturally to room temperature, then add and dissolve the other ingredients. Then, adjust the pH and add pure water to the volume. Nikko-rica sunwhite P200 was used as white vaseline. Penreco 4650 was used as yellow vaseline.

[Table 5]

Unit (w/v%) Comparative Example 2 Example 12 Example 13 Yellow Vaseline - 0.01 - White Vaseline - - 0.01 sesame oil 0.05 0.05 0.05 Polysorbate 80 (HLB15) 0.3 0.3 0.3 Polyoxyethylene castor oil 3 (HLB3) 0.15 0.15 0.15 Polyoxyl (140) Stearate (HLB 17.5) 0.1 0.1 0.1 Sodium chloride 0.6 0.6 0.6 Boric acid 1.2 1.2 1.2 Borax 0.2 0.2 0.2 pure water margin margin margin pH 7.2 7.2 7.2

Human corneal epithelial cell line HCE-T (RIKEN BioResource Center, No. RCB1384) was seeded on a culture plate (96-well, Corning, Japan) and cultured until confluent at 37°C, 5% CO ₂ , and 90% humidity. A growth medium containing 5% FCS (DS-pharma), 0.5% DMSO (Wako Pure Chemical Industries, Ltd.), 10 ng/mL recombinant human EGF (R&D), and 5 μg/mL human insulin solution (SIGMA) was used in DMEM/F12 (INVITROGEN).

The proliferation medium was removed by suction from each well, and 50 μL of each aqueous composition (Examples 12 to 13 and Comparative Example 2) of the composition shown in Table 5 was added to each well, and incubated at 37°C, 5% CO ₂ for 15 minutes. After removing each aqueous composition from each well by suction, it was placed in a clean bench for 20 minutes to give a drying stress reaction, and then the number of live cells was measured. The number of live cells was determined by adding a cell number determination drug Cell Counting Kit-8 (manufactured by DOJINDO) to each well, incubating at 37°C, 5% CO ₂ for 1 hour, and then measuring the absorbance at 450 nm. The cell survival rate was calculated using the ratio of the measured number of live cells to the blank group treated in the same manner as above except that no drying stress reaction was given. The results are shown in Figure 2.

As shown in Figure 2, the addition of vaseline to the aqueous composition of Comparative Example 2 significantly suppressed cell death caused by dryness stress. Furthermore, it was confirmed that the use of white vaseline significantly suppressed cell death compared to yellow vaseline.

[Test Example 4. Evaluation of Usage]

Aqueous compositions of the composition shown in Table 6 were prepared. First, the oily component and the surfactant were stirred with a stirrer while being heated to 60°C, and pure water heated to 60°C was added thereto and stirred and mixed. After being cooled naturally and the temperature dropped to room temperature, the other components were added and dissolved. The pH was then adjusted, and pure water was further added to make up the volume. Sunwhite P200 manufactured by Nikko-rica was used as white vaseline. Each of the prepared aqueous compositions was filled into a quantitative spray-type nasal spray container (manual type). In addition, the viscosity of each aqueous composition was measured using the "cone-plate type viscometer" test method described in the 16th revised Japanese Pharmacopoeia - General Test Methods - Viscosity Determination - Method 2 Rotational Viscometer Method. The measurement conditions are as follows.

Measurement temperature: 25°C

Measuring device: TV-20 (manufactured by Toki Sangyo Co., Ltd.)

Rotation speed: 50rpm

Rotor: Standard conical rotor (1°34'×R24)

Setting time: viscosity after 3 minutes

Furthermore, the aqueous composition of Example 14 was evaluated for the presence or absence of separation of the oil layer by the same procedure as in Reference Test Example 1, and the transmittance of light at a wavelength of 660 nm was measured by the same procedure as in Test Example 2.

[Table 6]

Using the Visual Analog Scale (VAS) method as the standard, an evaluation test of the irritation of each aqueous composition was performed on five test subjects with healthy nasal mucosal conditions. Specifically, the nasal drops of Comparative Example 3 and Example 14 were pressed into each nostril twice to evaluate the irritation after nasal instillation. The evaluation was carried out in the following manner. In the subjective symptom questionnaire with a 100mm line, a completely non-irritating condition was recorded as 0mm, and a very irritating condition was recorded as 100mm. The portion of the symptom felt by the test subject was examined and used as the subjective symptom score. The length (mm) was measured. The average score of the five test subjects was calculated.

The results are shown in Table 6. The inclusion of vaseline in the aqueous composition was confirmed to improve irritation during nasal drip. Therefore, it was confirmed that the inclusion of vaseline in the aqueous composition for otorhinolaryngology filled in a spray container suppressed irritation (irritation) during nasal drip, resulting in a formulation with an excellent feel during use.

[Test Example 5. Solubility Test]

Aqueous compositions with the compositions shown in Tables 7 and 8 were prepared. First, the oily component and surfactant were stirred with a stirrer while heated to 60°C. Pure water, also heated to 60°C, was added and stirred to mix. The mixture was allowed to cool naturally to room temperature, and then the other components were added and dissolved. The pH was then adjusted, and pure water was added to the volume. Sunwhite P200 manufactured by Nikko-Rica Co., Ltd. was used as the white vaseline.

The presence or absence of an oil layer was evaluated for each aqueous composition (Examples 15-27) using the same procedure as Reference Test Example 1. Furthermore, the transmittance of each aqueous composition at a wavelength of 660 nm was measured using a spectrophotometer (UV-2450 UV-visible spectrophotometer, manufactured by Shimadzu Corporation) one day after preparation. This transmittance serves as an indicator of the clarity of each aqueous composition. The results are shown in Tables 7 and 8.

[Table 7]

[Table 8]

[Preparation Example]

Eye drops (including drops for contact lens wear), eyewash, multi-purpose care solution (MPS), contact lens wearing solution, and nasal drops were prepared using the formulations described in Tables 9 to 11. All units in the tables are (w/v%).

[Table 9]

[Table 10]

[Table 11]

Claims (12)

1. An ophthalmic or otolaryngological aqueous composition comprising (A) white petrolatum, one or more (B-1) nonionic surfactants with an HLB value of 10 or higher, one or more (B-2) nonionic surfactants with an HLB value of less than 10, and (C) sesame oil, wherein the (B-1) nonionic surfactant with an HLB value of 10 or higher is a nonionic surfactant selected from the group consisting of polysorbate 80, POE hydrogenated castor oil 60, and stearic acid polyoxyethylene (140) ester, and the (B-2) nonionic surfactant with an HLB value of less than 10 is a nonionic surfactant selected from the group consisting of POE castor oil 3 and POE castor oil 10, wherein, based on the total amount of the ophthalmic or otolaryngological aqueous composition, the total content of component (A) is 0.0005 to 1 w/v%, the total content of component (B) is 0.1 to 1 w/v%, and the water content is 70 w/v or higher. 2. The aqueous composition according to claim 1, further comprising vitamin E, vitamin A, castor oil, olive oil, soybean oil, peanut oil, almond oil, wheat germ oil, camellia oil, corn oil, rapeseed oil, sunflower seed oil, cottonseed oil, or coconut oil, wherein the vitamin E comprises tocopherols, tocotrienols and their salts, as well as their acetates, nicotinic acid esters, succinates, and linolenic acid esters; and the vitamin A comprises vitamin A, retinaldehyde, retinol, retinoic acid, carotene, dehydroretinaldehyde, lycopene and their salts, as well as their esters. 3. The aqueous composition according to claim 1 or 2, wherein it further comprises (D) a buffer. 4. The aqueous composition according to claim 1 or 2, wherein the transmittance of light with a wavelength of 660 nm is 60% or more. 5. The aqueous composition according to claim 1 or 2, used for the prevention, treatment, improvement or relief of allergic symptoms. 6. The aqueous composition according to claim 1 or 2, further comprising a thickener. 7. The use of the ophthalmic or otolaryngological aqueous composition of claim 1 in the preparation of an ophthalmic or otolaryngological aqueous composition for the prevention, treatment, improvement or relief of allergic symptoms. 8. The application according to claim 7, wherein the transmittance of light with a wavelength of 660 nm of the aqueous composition is 60% or more. 9. A method for preparing an ophthalmic or otolaryngological aqueous composition of claim 1 that is non-separable and soluble with (A) white petrolatum, comprising making the aqueous composition contain (A) white petrolatum, one or more (B-1) nonionic surfactants with an HLB value of 10 or more, one or more (B-2) nonionic surfactants with an HLB value of less than 10, and (C) sesame oil, wherein the (B-1) nonionic surfactant with an HLB value of 10 or more is a nonionic surfactant selected from the group consisting of polysorbate 80, POE hydrogenated castor oil 60, and stearic acid polyoxyethylene (140) ester, and the (B-2) nonionic surfactant with an HLB value of less than 10 is a nonionic surfactant selected from the group consisting of POE castor oil 3 and POE castor oil 10. 10. The method according to claim 9, wherein the transmittance of light with a wavelength of 660 nm of the aqueous composition is 60% or more. 11. The use of the ophthalmic or otolaryngological aqueous composition of claim 1 in the preparation of an ophthalmic aqueous composition for the prevention, treatment, improvement or relief of symptoms of dry eye. 12. The application according to claim 11, wherein the transmittance of light with a wavelength of 660 nm of the aqueous composition is 60% or more.