JP7787129B2 - Ophthalmic composition - Google Patents

Description

The present invention relates to an ophthalmic composition useful for improving (including alleviating, treating, or preventing) various ocular conditions.

A large number of ophthalmic compositions are commercially available and used to relieve eye discomfort such as blurred vision, itchy eyes, conjunctival congestion, blepharitis, ophthalmitis caused by ultraviolet or other light, and discomfort when wearing contact lenses, as well as to relieve eye fatigue and prevent eye diseases.

These ophthalmic compositions are usually prepared by combining and blending ingredients approved as active ingredients in over-the-counter ophthalmic drugs, such as decongestants, ocular muscle regulating agents, anti-inflammatory agents, antihistamines, vitamins, amino acids, sulfa-based antibacterial agents, inorganic salts, polymeric thickeners, and preservatives, as well as other additives.
However, although conventional ophthalmic compositions can alleviate or prevent a wide variety of eye symptoms to some extent, they often only adequately alleviate or prevent a portion of the symptoms in practice, and there are also eye symptoms that cannot be adequately alleviated or prevented by conventional ophthalmic compositions.
In particular, in recent years, due to the widespread use of personal computers, which has led to overuse of the eyes, the widespread use of contact lenses, and the increased dispersion of antigenic substances, it has become difficult to keep the eyes comfortable with conventional ophthalmic compositions.

The objective of the present invention is to provide an ophthalmic composition that can broadly improve a variety of eye symptoms or abnormalities and that has a greater improvement effect than conventional ophthalmic compositions.

The inventors conducted extensive research to solve the above-mentioned problems and discovered that by incorporating pranoprofen and/or a pharmaceutically acceptable salt thereof (hereinafter referred to as "salt") into an ophthalmic composition containing at least one component selected from the group consisting of decongestants, ocular muscle regulating agents, anti-inflammatory agents, antihistamines, vitamins, and amino acids, the present invention can broadly and satisfactorily alleviate symptoms such as eye fatigue, blurred vision, itchy eyes, conjunctival congestion, and eye discomfort. Furthermore, the inventors discovered that the present invention is more effective in alleviating (including alleviating, treating, or preventing) such symptoms or abnormalities than conventional ophthalmic compositions.

The present invention has been completed based on the above findings, and provides the following ophthalmic composition.
Item 1. An ophthalmic composition for improving complex eye symptoms, comprising (a) at least one component selected from the group consisting of pranoprofen and salts thereof, and (b) at least one component selected from the group consisting of decongestants, ocular muscle regulating agents, anti-inflammatory agents other than pranoprofen or salts thereof, antihistamines, vitamins, and amino acids.
Item 2. The composition according to Item 1, further comprising (b) a decongestant, an eye muscle adjusting agent, an anti-inflammatory agent other than pranoprofen or a salt thereof, an antihistamine, vitamins, and amino acids.
Item 3. The composition according to Item 1 or 2, wherein the complex eye symptom is one or more selected from the group consisting of eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, eye discomfort, and eye disease.
Item 4. The composition according to any one of Items 1 to 3, wherein the content of at least one selected from the group consisting of pranoprofen and salts thereof is 0.001 to 1 w/v % based on the total amount of the composition.
Item 5. The composition according to any one of Items 1 to 4, further comprising an antioxidant.

The ophthalmic composition of the present invention, containing pranoprofen and/or a salt thereof, is widely and satisfactorily effective in alleviating, improving, treating, or preventing eye discomfort such as eye fatigue, blurred vision due to excessive eye discharge, itchy eyes, conjunctival congestion, blepharitis (sore eyelids), eye inflammation caused by ultraviolet light or other light (such as so-called snow blindness), foreign body sensation (such as a gritty sensation or tingling sensation), watery eyes, and discomfort when wearing contact lenses, as well as eye diseases (such as eye diseases caused by swimming or eye diseases caused by dust or sweat getting into the eyes).

Therefore, by using the ophthalmic composition of the present invention, it is possible to maintain a comfortable eye condition without using multiple ophthalmic compositions in combination. Therefore, the ophthalmic composition of the present invention can be used as a composition for improving, alleviating, treating, or preventing comprehensive eye symptoms or abnormalities, improving, alleviating, treating, or preventing complex eye symptoms or abnormalities, for total eye care, or for comprehensive eye normalization. Furthermore, the ophthalmic composition of the present invention can also be used as a multifunctional composition for improving, alleviating, or preventing comprehensive eye symptoms.
Conditions presenting multiple eye symptoms or abnormalities may be more difficult to improve or prevent than conditions presenting a single symptom or abnormality, and the ophthalmic composition of the present invention can effectively improve, alleviate, treat, or prevent those symptoms even in such cases.

The ophthalmic composition of the present invention can also be used to improve, alleviate, treat, or prevent one of the following eye symptoms or abnormalities: eye discomfort, such as eye fatigue, blurred vision due to excessive eye discharge, itchy eyes, conjunctival congestion, blepharitis, ophthalmia caused by ultraviolet rays or other light, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, as well as eye diseases.

Furthermore, the ophthalmic composition of the present invention is more effective in improving, alleviating, treating, or preventing eye symptoms or abnormalities than conventional ophthalmic compositions.

The present invention will be described in detail below.
The ophthalmic composition of the present invention contains (a) at least one component selected from the group consisting of pranoprofen and salts thereof, and (b) at least one component selected from the group consisting of a decongestant, an ocular muscle regulating agent, an anti-inflammatory agent other than component (a), an antihistamine, vitamins, and amino acids.
Uses of the ophthalmic composition of the present invention will be described later.

Pranoprofen and/or its salt (component (a))
The salt of pranoprofen may be any pharmaceutically or physiologically acceptable salt, and examples thereof include salts with inorganic bases such as alkali metal salts (sodium salt, potassium salt, etc.), alkaline earth metal salts (calcium salt, magnesium salt, etc.), ammonium salts, and metal salts (aluminum salt, etc.), and salts with organic bases such as organic amine salts (methylamine salt, triethylamine salt, diethylamine salt, triethanolamine salt, morpholine salt, piperazine salt, pyrrolidine salt, tripyridine salt, picoline salt, etc.).
Pranoprofen and its salts also include those in the form of hydrates.
Pranoprofen and salts thereof can be used singly or in combination of two or more.
Among pranoprofen and/or a salt thereof, pranoprofen is most preferred.

The content of pranoprofen and/or a salt thereof in the ophthalmic composition is preferably 0.001 w/v% or more, more preferably 0.01 w/v% or more, even more preferably 0.02 w/v% or more, even more preferably 0.03 w/v% or more, and may also be 0.04 w/v% or more, or 0.05 w/v% or more, based on the total amount of the composition.
The content of pranoprofen and/or a salt thereof in the ophthalmic composition is preferably 1 w/v% or less, more preferably 0.5 w/v% or less, even more preferably 0.2 w/v% or less, and even more preferably 0.1 w/v% or less, based on the total amount of the composition, and may also be 0.09 w/v% or less, 0.08 w/v% or less, 0.07 w/v% or less, 0.06 w/v% or less, or 0.05 w/v% or less.
Within the above range, the effects of the present invention can be sufficiently obtained.
The content of pranoprofen and/or a salt thereof is preferably 0.03 to 0.1 w/v%, and examples thereof include 0.03 w/v%, 0.04 w/v%, 0.05 w/v%, 0.06 w/v%, 0.07 w/v%, 0.08 w/v%, 0.09 w/v%, and 0.1 w/v%, with 0.05 w/v% being particularly preferred.

Decongestant (ingredient (b))
Decongestants cause ocular anemia by constricting blood vessels, relieve local congestion, relieve pain, and promote tissue healing. For example, stimulating α-adrenergic nerves can have a vasoconstrictive effect, thereby contributing to the effects of the present invention.
Decongestants include, but are not limited to, epinephrine or a salt thereof (e.g., epinephrine hydrochloride, epinephrine bitartrate), ephedrine or a salt thereof (e.g., ephedrine hydrochloride), methylephedrine or a salt thereof (e.g., methylephedrine hydrochloride, particularly dl-methylephedrine hydrochloride), phenylephrine or a salt thereof (e.g., phenylephrine hydrochloride), imidazoline vasoconstrictors [tetrahydrozoline or a salt thereof (e.g., tetrahydrozoline hydrochloride), naphazoline or a salt thereof (e.g., naphazoline hydrochloride, naphazoline nitrate), oxymetazoline or a salt thereof (e.g., oxymetazoline hydrochloride)], and the like.
Among these, epinephrine or a salt thereof (particularly epinephrine hydrochloride), ephedrine or a salt thereof (particularly ephedrine hydrochloride), methylephedrine or a salt thereof (particularly dl-methylephedrine hydrochloride), phenylephrine or a salt thereof (particularly phenylephrine hydrochloride), and imidazoline vasoconstrictors are preferred, imidazoline vasoconstrictors are more preferred, tetrahydrozoline hydrochloride, naphazoline hydrochloride, and naphazoline nitrate are even more preferred, and tetrahydrozoline hydrochloride is particularly preferred.
Decongestants may be used singly or in combination of two or more.

When the ophthalmic composition contains a decongestant, the content thereof may be, for example, 0.0006 w/v % or more, preferably 0.003 w/v % or more, preferably 0.01 w/v % or more, preferably 0.02 w/v % or more, based on the total amount of the composition, or 0.03 w/v % or more, 0.04 w/v % or more, or 0.05 w/v % or more.
Furthermore, the total amount of the decongestant relative to the total amount of the composition is, for example, 0.2 w/v % or less, preferably 0.15 w/v % or less, preferably 0.1 w/v % or less, more preferably 0.05 w/v % or less.
Within the above range, the effects of the present invention can be sufficiently obtained.
The total content of the decongestant is preferably 0.01 to 0.05 w/v%, and examples thereof include 0.01 w/v%, 0.02 w/v%, 0.03 w/v%, 0.04 w/v%, and 0.05 w/v%, with 0.05 w/v% being particularly preferred.

Ocular muscle adjuster (ingredient (b))
The ocular muscle accommodating agent stimulates the parasympathetic nerves in the pupillary sphincter to constrict the pupil. For example, it has an active center similar to acetylcholine and inhibits cholinesterase, thereby activating the parasympathetic nerves and contributing to the effects of the present invention.
Examples of ocular muscle accommodating agents include, but are not limited to, neostigmine or a salt thereof (particularly, neostigmine methylsulfate), physostigmine or a salt thereof (e.g., physostigmine salicylate, physostigmine sulfate), distigmine or a salt thereof (e.g., distigmine bromide), tropicamide, atropine or a salt thereof (particularly, atropine heleniensulfate), and pilocarpine or a salt thereof (e.g., pilocarpine hydrochloride).
Of these, neostigmine or a salt thereof is preferred, and neostigmine methylsulfate is particularly preferred.
The ocular muscle adjusting agents can be used alone or in combination of two or more.

When the ophthalmic composition contains an ocular muscle accommodating agent, the content thereof, relative to the total amount of the composition, may be, for example, 0.0002 w/v% or more, preferably 0.0005 w/v% or more, preferably 0.001 w/v% or more, preferably 0.002 w/v% or more, or may be 0.003 w/v% or more, 0.004 w/v% or more, or 0.005 w/v% or more.
The total amount of the ocular muscle accommodating agent relative to the total amount of the composition is, for example, 0.02 w/v % or less, preferably 0.01 w/v % or less, and more preferably 0.005 w/v % or less.
Within the above range, the effects of the present invention can be sufficiently obtained.
The total content of the ocular muscle adjusting agent is preferably 0.001 to 0.005 w/v%, and examples thereof include 0.001 w/v%, 0.002 w/v%, 0.003 w/v%, 0.004 w/v%, and 0.005 w/v%, with 0.005 w/v% being particularly preferred.

Anti-inflammatory agent (ingredient (b))
The ophthalmic composition of the present invention may contain an anti-inflammatory agent other than pranoprofen. The anti-inflammatory agent suppresses inflammation and/or exhibits an accompanying astringent effect, thereby contributing to the effects of the present invention.
Anti-inflammatory agents other than pranoprofen include, but are not limited to, epsilon-aminocaproic acid, allantoin, berberine or a salt thereof (e.g., berberine chloride, berberine sulfate), azulene sulfonic acid or a salt thereof (e.g., sodium azulene sulfonate, potassium azulene sulfonate, calcium azulene sulfonate, magnesium azulene sulfonate), glycyrrhizic acid or a salt thereof (e.g., dipotassium glycyrrhizinate, monoammonium glycyrrhizinate), zinc salts (e.g., zinc sulfate, zinc lactate), lysozyme or a salt thereof (e.g., lysozyme chloride), indomethacin, silver salts (e.g., silver nitrate), diclofenac acid or a salt thereof (e.g., diclofenac sodium), bromfenac acid or a salt thereof (e.g., bromfenac sodium), and the like.
Among these, epsilon-aminocaproic acid, allantoin, berberine or a salt thereof (particularly berberine chloride and berberine sulfate), azulene sulfonic acid or a salt thereof (particularly sodium azulene sulfonate), glycyrrhizic acid or a salt thereof (particularly dipotassium glycyrrhizinate), zinc salts (particularly zinc sulfate and zinc lactate), and lysozyme or a salt thereof (particularly lysozyme chloride) are preferred, with epsilon-aminocaproic acid and dipotassium glycyrrhizinate being more preferred.
The anti-inflammatory agents can be used alone or in combination of two or more.

When the ophthalmic composition contains an anti-inflammatory agent other than pranoprofen, the content thereof may be, for example, 0.0005 w/v% or more, 0.005 w/v% or more, 0.02 w/v% or more, 0.1 w/v% or more, 0.25 w/v% or more, 0.3 w/v% or more, 0.35 w/v% or more, 0.4 w/v% or more, 0.45 w/v% or more, or 0.5 w/v% or more, in terms of the total amount of the anti-inflammatory agent other than pranoprofen, relative to the total amount of the composition.
Furthermore, the total amount of anti-inflammatory agents other than pranoprofen relative to the total amount of the composition may be, for example, 10 w/v% or less, 2 w/v% or less, 1.5 w/v% or less, 1 w/v% or less, 0.5 w/v% or less, 0.25 w/v% or less, or 0.05 w/v% or less.
Within the above range, the effects of the present invention can be sufficiently obtained.
The total content of the anti-inflammatory agent other than pranoprofen is preferably 0.25 to 2 w/v%, and more preferably 0.25 w/v%, 0.3 w/v%, 0.35 w/v%, 0.4 w/v%, 0.45 w/v%, 0.5 w/v%, 0.55 w/v%, 0.6 w/v%, 0.65 w/v%, 0.7 w/v%, 0.75 w/v%, 0.8 w/v%, 0.85 w/v%, 0.9 w/v%, 0.95 w/v%, 1 w/v%, %, 1.05 w/v%, 1.1 w/v%, 1.15 w/v%, 1.2 w/v%, 1.25 w/v%, 1.3 w/v%, 1.35 w/v%, 1.4 w/v%, 1.45 w/v%, 1.5 w/v%, 1.55 w/v%, 1.6 w/v%, 1.65 w/v%, 1.7 w/v%, 1.75 w/v%, 1.8 w/v%, 1.85 w/v%, 1.9 w/v%, 1.95 w/v%, 2 w/v%, etc. 1.25 w/v% is particularly preferred.

Antihistamine (ingredient (b))
Antihistamines contribute to the effects of the present invention by, for example, antagonizing histamine receptors and suppressing the action of histamine.
Antihistamines include, but are not limited to, diphenhydramine or a salt thereof (e.g., diphenhydramine hydrochloride), chlorpheniramine or a salt thereof (e.g., chlorpheniramine maleate, chlorpheniramine fumarate), ketotifen or a salt thereof (e.g., ketotifen fumarate), olopatadine or a salt thereof (e.g., olopatadine hydrochloride), and the like.
Of these, diphenhydramine or a salt thereof (particularly diphenhydramine hydrochloride) and chlorpheniramine or a salt thereof (particularly chlorpheniramine maleate) are preferred, with chlorpheniramine maleate being more preferred.
The antihistamines can be used alone or in combination of two or more.

When the ophthalmic composition contains an antihistamine, the content thereof is, for example, 0.0006 w/v % or more, preferably 0.001 w/v % or more, more preferably 0.006 w/v % or more, more preferably 0.01 w/v % or more, and may also be 0.02 w/v % or more, in terms of the total amount of the antihistamine relative to the total amount of the composition.
The total amount of antihistamines relative to the total amount of the composition is, for example, 0.1 w/v % or less, particularly 0.05 w/v % or less, particularly 0.03 w/v % or less.
Within the above range, the effects of the present invention can be sufficiently obtained.
The total content of the antihistamine is preferably 0.006 to 0.05 w/v%, and examples thereof include 0.006 w/v%, 0.008 w/v%, 0.01 w/v%, 0.015 w/v%, 0.02 w/v%, 0.03 w/v%, and 0.05 w/v%, with 0.03 w/v% being particularly preferred.

Vitamins (component (b))
Vitamins play a major role in the metabolic functions of the living body even in very small amounts, and contribute to the effects of the present invention by, for example, functioning as coenzymes or by having antioxidant effects.
Vitamins include, but are not limited to, flavin adenine dinucleotide or a salt thereof (e.g., flavin adenine dinucleotide sodium), cobalamin or a salt thereof (e.g., cyanocobalamin, methylcobalamin), retinol, a derivative thereof and/or a salt thereof (e.g., retinol acetate, retinol palmitate), pyridoxine or a salt thereof (e.g., pyridoxine hydrochloride), panthenol, pantothenic acid or a salt thereof (e.g., sodium pantothenate, potassium pantothenate, calcium pantothenate, magnesium pantothenate), tocopherol, a derivative thereof and/or a salt thereof (e.g., tocopherol acetate, tocopherol succinate, tocopherol nicotinate), pyridoxal or a salt thereof (e.g., pyridoxal phosphate), ascorbic acid or a salt thereof (e.g., sodium ascorbate, calcium ascorbate), etc.
Among these, flavin adenine dinucleotide or a salt thereof (particularly, sodium flavin adenine dinucleotide), cobalamin or a salt thereof (particularly, cyanocobalamin), retinol, a derivative thereof and/or a salt thereof (particularly, retinol acetate, retinol palmitate), pyridoxine or a salt thereof (particularly, pyridoxine hydrochloride), panthenol, pantothenic acid or a salt thereof (particularly, sodium pantothenate, calcium pantothenate), tocopherol, a derivative thereof and/or a salt thereof (particularly, tocopherol acetate) are preferred, and pyridoxine hydrochloride and tocopherol acetate are more preferred.
The vitamins can be used alone or in combination of two or more.

When the ophthalmic composition contains vitamins (vitamins other than retinol, its derivatives, and/or salts thereof), the content of the vitamins relative to the total amount of the composition is, for example, 0.0002 w/v% or more, preferably 0.002 w/v% or more, preferably 0.005 w/v% or more, preferably 0.01 w/v% or more, preferably 0.03 w/v% or more, or may be 0.04 w/v% or more, or 0.05 w/v% or more.
Furthermore, the total amount of these vitamins relative to the total amount of the composition may be, for example, 1 w/v% or less, 0.9 w/v% or less, 0.8 w/v% or less, 0.7 w/v% or less, 0.6 w/v% or less, 0.5 w/v% or less, 0.4 w/v% or less, 0.3 w/v% or less, 0.2 w/v% or less, 0.1 w/v% or less, 0.09 w/v% or less, 0.08 w/v% or less, 0.07 w/v% or less, 0.06 w/v% or less, or 0.05 w/v% or less.

When the ophthalmic composition contains retinol, a derivative thereof, and/or a salt thereof, the content thereof, in terms of the total amount of retinol, a derivative thereof, and/or a salt thereof relative to the total amount of the composition, can be, for example, 500 units/100 mL or more, 1000 units/100 mL or more, 5000 units/100 mL or more, 6000 units/mL or more, 7000 units/mL or more, 8000 units/mL or more, 9000 units/mL or more, or 10000 units/100 mL or more.
Further, the total amount of retinol, its derivatives, and/or salts thereof relative to the total amount of the composition may be, for example, 100,000 units/100 mL or less, 90,000 units/mL or less, 80,000 units/mL or less, 70,000 units/mL or less, 60,000 units/mL or less, 50,000 units/100 mL or less, 40,000 units/100 mL or less, 30,000 units/100 mL or less, or 20,000 units/100 mL or less.
Within the above range, the effects of the present invention can be sufficiently obtained.

Amino acids (component (b))
Amino acids refer to compounds or derivatives thereof having an amino group and a carboxyl group or a sulfo group in the molecule, and contribute to the effects of the present invention by metabolizing cells and repairing damaged tissues.
Examples of amino acids include, but are not limited to, L-aspartic acid or a salt thereof (e.g., potassium L-aspartate, sodium L-aspartate, magnesium L-aspartate, calcium L-aspartate, magnesium potassium L-aspartate (a mixture of equal parts of magnesium L-aspartate and potassium L-aspartate)), aminoethylsulfonic acid (taurine), sodium chondroitin sulfate, glutamic acid or a salt thereof (e.g., sodium glutamate, magnesium glutamate), creatinine, glycine, alanine, arginine, lysine, γ-aminobutyric acid, γ-aminovaleric acid, hyaluronic acid or a salt thereof (e.g., sodium hyaluronate), and alginic acid or a salt thereof (e.g., sodium alginate).
Aminoethylsulfonic acid is a compound similar to an amino acid synthesized from a sulfur-containing amino acid, and is included in the category of amino acids in the field of ophthalmic compositions, particularly in the field of over-the-counter ophthalmic compositions. Sodium chondroitin sulfate is also included in the category of amino acids in the field of ophthalmic compositions, particularly in the field of over-the-counter ophthalmic compositions.
Among these, L-aspartic acid or a salt thereof (particularly potassium L-aspartate, magnesium L-aspartate, magnesium potassium L-aspartate (a mixture of equal parts of magnesium L-aspartate and potassium L-aspartate)), aminoethylsulfonic acid (taurine), and sodium chondroitin sulfate are preferred, with potassium L-aspartate, aminoethylsulfonic acid, and sodium chondroitin sulfate being more preferred.
The amino acids can be used alone or in combination of two or more.

When the ophthalmic composition contains amino acids, the content thereof may be, for example, 0.005 w/v% or more, 0.05 w/v% or more, 0.1 w/v% or more, 0.2 w/v% or more, 0.3 w/v% or more, 0.4 w/v% or more, or 0.5 w/v% or more in terms of the total amount of amino acids relative to the total amount of the composition.
Furthermore, the total amount of amino acids relative to the total amount of the composition may be, for example, 7 w/v% or less, 6 w/v% or less, 5 w/v% or less, 4 w/v% or less, 3 w/v% or less, 2 w/v% or less, 1 w/v% or less, 0.9 w/v% or less, 0.8 w/v% or less, 0.7 w/v% or less, 0.6 w/v% or less, or 0.5 w/v% or less.

Total Content of Component (b) The total content of component (b) in the ophthalmic composition, relative to the total amount of the composition, can be, for example, 0.0002 w/v% or more, preferably 0.0006 w/v% or more, preferably 0.0007 w/v% or more, preferably 0.0008 w/v% or more, preferably 0.0009 w/v% or more, preferably 0.001 w/v% or more, preferably 0.002 w/v% or more, preferably 0.003 w/v% or more, preferably 0.004 w/v% or more, preferably 0.005 w/v% or more, preferably 0.006 w/v% or more, preferably 0.01 w/v% or more, preferably 0.05 w/v% or more, preferably 0.1 w/v% or more, preferably 0.2 w/v% or more, and preferably 1 w/v% or more.
Further, the amount relative to the total amount of the composition may be, for example, 10 w/v% or less, preferably 5 w/v% or less, preferably 3 w/v% or less, preferably 2 w/v% or less, preferably 1 w/v% or less, preferably 0.7 w/v% or less, preferably 0.5 w/v% or less, preferably 0.25 w/v% or less, preferably 0.1 w/v% or less, preferably 0.05 w/v% or less, preferably 0.03 w/v% or less, and preferably 0.005 w/v% or less.
Within the above range, the effects of the present invention can be sufficiently obtained.

The ratio of the total content of component (b) to component (a) may be, for example, 0.002 parts by weight or more, preferably 0.05 parts by weight or more, preferably 0.01 parts by weight or more, preferably 0.05 parts by weight or more, preferably 0.1 parts by weight or more, preferably 0.2 parts by weight or more, preferably 0.5 parts by weight or more, preferably 1 part by weight or more, preferably 5 parts by weight or more, and preferably 20 parts by weight or more, per 1 part by weight of component (a).
Furthermore, for example, the amount per 1 part by weight of component (a) is 200 parts by weight or less, preferably 100 parts by weight or less, preferably 50 parts by weight or less, preferably 20 parts by weight or less, preferably 10 parts by weight or less, preferably 5 parts by weight or less, preferably 2 parts by weight or less, preferably 1 part by weight or less, preferably 0.6 parts by weight or less, preferably 0.1 parts by weight or less.
Within the above range, the effects of the present invention can be sufficiently obtained.

In addition to the above-mentioned components (a) and (b), the ophthalmic composition of the present invention may contain other components having pharmacological or physiological activity.
The pharmacologically active ingredient or physiologically active ingredient can be used alone or in combination of two or more.
Specific examples of pharmacologically active ingredients or physiologically active ingredients are given below. The pharmacologically active ingredients or physiologically active ingredients can be incorporated either as an active ingredient or as an additive.

Antibacterial Component The ophthalmic compositions of the present invention may further comprise an antibacterial component.
Antibacterial components include, but are not limited to, sulfa-based antibacterial agents such as sulfamethoxazole or a salt thereof (e.g., sulfamethoxazole sodium, sulfamethoxazole potassium, sulfamethoxazole calcium, sulfamethoxazole magnesium), sulfisoxazole, sulfisomidine or a salt thereof (e.g., sulfisomidine sodium, sulfisomidine potassium, sulfisomidine calcium, sulfisomidine magnesium), alkylpolyaminoethylglycine, chloramphenicol, ofloxacin, norfloxacin, levofloxacin, lomefloxacin hydrochloride, and acyclovir.
Among these, sulfa-based antibacterial agents such as sulfamethoxazole or a salt thereof (particularly sulfamethoxazole sodium), sulfisoxazole, sulfisomidine or a salt thereof (particularly sulfisomidine sodium), and alkylpolyaminoethylglycine are preferred, with sulfamethoxazole sodium being more preferred.
The antibacterial component may be used alone or in combination of two or more.

When the ophthalmic composition contains an antibacterial component, the content thereof may be, for example, 0.001 w/v % or more, preferably 0.005 w/v % or more, preferably 0.01 w/v % or more, preferably 0.05 w/v % or more, preferably 0.1 w/v % or more, preferably 0.5 w/v % or more, preferably 1 w/v % or more, preferably 2 w/v % or more, or may be 3 w/v % or more, in terms of the total amount of the antibacterial component relative to the total amount of the composition.
The total amount of the antibacterial components relative to the total amount of the composition is, for example, 5 w/v % or less, preferably 4 w/v % or less, and may also be 3 w/v % or less.
Examples of the total content of the antibacterial component include 1 w/v%, 1.5 w/v%, 2 w/v%, 2.5 w/v%, 3 w/v%, 3.5 w/v%, 4 w/v%, 4.5 w/v%, and 5 w/v%.

Antiallergic Agent The ophthalmic composition of the present invention may further comprise an antiallergic agent.
Antiallergic drugs include, but are not limited to, cromoglycic acid or a salt thereof (e.g., sodium cromoglycate, potassium cromoglycate, calcium cromoglycate, magnesium cromoglycate), ashitazanolast, amlexanox, ibudilast, tranilast, pemirolast potassium, and the like.
Of these, cromoglycic acid or a salt thereof (particularly sodium cromoglycate) is preferred, with sodium cromoglycate being more preferred.
The antiallergic drugs can be used singly or in combination of two or more.

When the ophthalmic composition contains an antiallergic drug, the content thereof may be, in terms of the total amount of the antiallergic drug relative to the total amount of the composition, for example, 0.01 w/v% or more, 0.05 w/v% or more, 0.1 w/v% or more, 0.2 w/v% or more, 0.3 w/v% or more, 0.4 w/v% or more, 0.5 w/v% or more, 0.6 w/v% or more, 0.7 w/v% or more, 0.8 w/v% or more, or 0.9 w/v% or more.
Furthermore, the total amount of the antiallergic drug relative to the total amount of the composition may be, for example, 5 w/v% or less, 4 w/v% or less, 3 w/v% or less, 2 w/v% or less, 1.9 w/v% or less, 1.8 w/v% or less, 1.7 w/v% or less, 1.6 w/v% or less, 1.5 w/v% or less, 1.4 w/v% or less, 1.3 w/v% or less, 1.2 w/v% or less, 1.1 w/v% or less, or 1 w/v% or less.
Examples of the total content of the antiallergic drug include 0.01 w/v%, 0.05 w/v%, 0.1 w/v%, 0.2 w/v%, 0.3 w/v%, 0.4 w/v%, 0.5 w/v%, 0.6 w/v%, 0.7 w/v%, 0.8 w/v%, 0.9 w/v%, 1 w/v%, 1.1 w/v%, 1.2 w/v%, 1.3 w/v%, 1.4 w/v%, w/v%, 1.5 w/v%, 1.6 w/v%, 1.7 w/v%, 1.8 w/v%, 1.9 w/v%, 2 w/v%, 3 w/v%, and 4 w/v%.

The ophthalmic composition of the present invention may contain an antioxidant . The antioxidant stabilizes pranoprofen and component (b), which are unstable to heat and light. The antioxidant improves the retention rate of pranoprofen and other active ingredients contained in the ophthalmic composition and maintains their high pharmacological efficacy, thereby significantly improving the effects of the present invention.
Examples of fat-soluble antioxidants include butyl-containing phenols such as dibutylhydroxytoluene (BHT) and butylhydroxyanisole (BHA); nordihydroguaiaretic acid (NDGA); ascorbic acid esters such as ascorbyl palmitate, ascorbyl stearate, aminopropyl ascorbyl phosphate, tocopherol ascorbyl phosphate, ascorbyl triphosphate, and ascorbyl phosphate palmitate; gallic acid esters such as ethyl gallate, propyl gallate, octyl gallate, and dodecyl gallate; propyl gallate; 3-butyl-4-hydroxyquinolin-2-one; carotenoids such as lutein and astaxanthin; polyphenols such as anthocyanins, catechin, tannin, and curcumin; and CoQ10.
Examples of water-soluble antioxidants include ascorbic acid, ascorbic acid derivatives (disodium ascorbyl 2-sulfate, sodium ascorbate, magnesium ascorbyl 2-phosphate, sodium ascorbyl 2-phosphate, etc.), sodium bisulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, edetic acid or a salt thereof (sodium edetate, disodium edetate, tetrasodium edetate), etc.
As the antioxidant, among fat-soluble antioxidants, butyl group-containing phenols (particularly, dibutylhydroxytoluene and butylhydroxyanisole) are preferred, with dibutylhydroxytoluene being more preferred. Among water-soluble antioxidants, edetic acid or a salt thereof (particularly, sodium edetate) is preferred, with sodium edetate being more preferred. It is also preferred to use a fat-soluble antioxidant and a water-soluble antioxidant in combination, with the combination of dibutylhydroxytoluene and sodium edetate being more preferred.
The antioxidants can be used alone or in combination of two or more.

When the ophthalmic composition contains an antioxidant, the content thereof may be, relative to the total amount of the composition, 0.0001 w/v% or more, 0.0005 w/v% or more, 0.001 w/v% or more, 0.002 w/v% or more, 0.003 w/v% or more, 0.004 w/v% or more, or 0.005 w/v% or more. Also, the content of the antioxidant may be, relative to the total amount of the composition, 1 w/v% or less, 0.1 w/v% or less, 0.05 w/v% or less, 0.04 w/v% or less, 0.03 w/v% or less, 0.02 w/v% or less, 0.01 w/v% or less, 0.009 w/v% or less, 0.008 w/v% or less, 0.007 w/v% or less, 0.006 w/v% or less, or 0.005 w/v% or less.
The total content of the antioxidants relative to the total amount of the composition may be 0.0001 w/v%, 0.0005 w/v%, 0.001 w/v%, 0.002 w/v%, 0.003 w/v%, 0.004 w/v%, 0.005 w/v%, 0.006 w/v%, 0.007 w/v%, 0.008 w/v%, 0.009 w/v%, 0.01 w/v%, 0.02 w/v%, 0.03 w/v%, 0.04 w/v%, 0.05 w/v%, 0.1 w/v%, or 1 w/v%.

Other pharmacologically active ingredients that can be incorporated into the ophthalmic composition of the present invention include local anesthetic ingredients such as procaine hydrochloride and lidocaine hydrochloride, and analgesics such as procaine hydrochloride.

Among the components of the ophthalmic composition of the present invention, if a component exists in the d-, l-, or dl-form, any of the d-, l-, or dl-forms can be used. Furthermore, if a component has a hydrate, the hydrate can also be used.

The state of the ophthalmic preparation is not particularly limited and may be, for example, a liquid, fluid, gel, or semi-solid. It also includes those that are prepared just before use in a liquid, fluid, gel, or semi-solid state. A semi-solid state refers to a state that has plasticity that can be deformed by applying force, such as an ointment.

In addition, the ophthalmic composition may be an aqueous composition (mainly containing an aqueous or hydrophilic base or carrier) or an oily composition (mainly containing an oily or hydrophobic base or carrier).
In the case of an aqueous composition, the water content is preferably 50% by weight or more, more preferably 75% by weight or more, and even more preferably 90% by weight or more, based on the total weight of the formulation. It may also be 95% by weight or more, or 98% by weight or more. The base or carrier may also consist solely of water.
In the case of an oily composition, the water content is preferably less than 50% by weight, more preferably 30% by weight or less, and even more preferably 20% by weight or less, based on the total weight of the formulation.
The ophthalmic composition of the present invention is preferably an aqueous composition.

The dosage form of the ophthalmic composition of the present invention is not particularly limited, and examples thereof include eye drops (also called eye drops or eye drops; eye drops include eye drops that can be applied while wearing contact lenses), eyewash, eye ointment (water-soluble eye ointment, oil-soluble eye ointment), contact lens wetting solution, intraocular injection (e.g., intravitreal injection), contact lens solution (cleaning solution, storage solution, disinfectant solution, multi-purpose solution, package solution), preservatives for excised eye tissues such as corneas for transplantation, and surgical irrigation solutions. Eye drops, eyewashes, and eye ointments also include those used while wearing contact lenses.
Preferred dosage forms of the ophthalmic composition of the present invention include eye drops, eye washes, eye ointments (water-soluble eye ointments, oil-soluble eye ointments), contact lens wetting solutions, and contact lens solutions (cleaning solutions, storage solutions, disinfectants, multi-purpose solutions, and packaged solutions), more preferred are eye drops, eye washes, contact lens wetting solutions, and contact lens solutions (cleaning solutions, storage solutions, disinfectants, multi-purpose solutions, and packaged solutions), even more preferred are eye drops and eye washes, and particularly preferred are eye drops.

In the present invention, "contact lenses" includes hard contact lenses and soft contact lenses (including both ionic and non-ionic contact lenses, and both silicone hydrogel contact lenses and non-silicone hydrogel contact lenses).
The ophthalmic composition of the present invention may be in the form of a single-use unit dose or a multi-dose that can be used repeatedly, but is preferably stored and used in the form of a multi-dose because it has excellent preservative effectiveness.

The ophthalmic composition of the present invention can be prepared by mixing the above-mentioned components (a) and (b) with a pharmaceutically acceptable base or carrier, and, if necessary, with pharmaceutically acceptable additives and other active ingredients for the ophthalmic composition, using a conventional method, for example, as described in the 16th Edition of the Japanese Pharmacopoeia.

Base or Carrier Examples of the base or carrier include water; polar solvents such as ethanol; and oily bases.
The base or carrier may be used alone or in combination of two or more.

The ophthalmic composition of the present invention can contain any additives that are used in ophthalmic compositions, such as, for example, a refreshing agent, an inorganic salt, a preservative, a surfactant, a buffer, a pH adjuster, an isotonic agent, a stabilizer, an oil, a sugar, and a polyhydric alcohol.
The additives may be used alone or in combination of two or more. Furthermore, each additive may be used alone or in combination of two or more.
Specific examples of the additives are given below.

Cooling Agents The ophthalmic compositions of the present invention may include a cooling agent.
Examples of the cooling agent include, but are not limited to, terpenoids such as menthol, anethole, eugenol, camphor, geraniol, cineole, borneol, limonene, and rhubarb, which may be in the d-, l-, or dl-isomer. Other examples include essential oils such as peppermint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, bergamot oil, eucalyptus oil, and rose oil.
Of these, terpenoids are preferred, and among these, menthol, camphor, geraniol, cineol, borneol, and rhubarb are preferred, with menthol, camphor, and borneol being more preferred, and menthol being even more preferred.
The cooling agents may be used alone or in combination of two or more.

When the ophthalmic composition contains a cooling agent, the content thereof may be, in terms of the total amount of cooling agent relative to the total amount of the composition, for example, 0.0001 w/v% or more, 0.0005 w/v% or more, 0.001 w/v% or more, 0.002 w/v% or more, 0.003 w/v% or more, 0.004 w/v% or more, 0.005 w/v% or more, 0.006 w/v% or more, 0.007 w/v% or more, 0.008 w/v% or more, 0.009 w/v% or more, or 0.01 w/v% or more.
Further, the total amount of the cooling agent relative to the total amount of the composition may be 1 w/v% or less, 0.1 w/v% or less, 0.09 w/v% or less, 0.08 w/v% or less, 0.07 w/v% or less, 0.06 w/v% or less, 0.05 w/v% or less, 0.04 w/v% or less, 0.03 w/v% or less, or 0.02 w/v% or less.
The total content of the cooling agent relative to the total amount of the composition is 0.0001 w/v%, 0.0005%, 0.001 w/v%, 0.002 w/v%, 0.003 w/v%, 0.004 w/v%, 0.005 w/v%, 0.006 w/v%, 0.007 w/v%, 0.008 w/v%, 0.009 w/v%, 0.01 w/v%, 0.011 w/v%, 0.012 w/v%, Examples include 0.013 w/v%, 0.014 w/v%, 0.015 w/v%, 0.016 w/v%, 0.017 w/v%, 0.018 w/v%, 0.019 w/v%, 0.02 w/v%, 0.03 w/v%, 0.04 w/v%, 0.05 w/v%, 0.06 w/v%, 0.07 w/v%, 0.08 w/v%, 0.09 w/v%, 0.1 w/v%, and 1 w/v%.

Inorganic Salts The ophthalmic compositions of the present invention may further comprise inorganic salts.
Inorganic salts include, but are not limited to, potassium chloride, sodium chloride, calcium chloride, magnesium chloride, sodium bicarbonate, sodium carbonate (including dry sodium carbonate), potassium bicarbonate, potassium carbonate, magnesium sulfate, sodium hydrogen phosphate, potassium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, sodium bisulfite, sodium sulfite, potassium acetate, sodium acetate, sodium thiosulfate, and the like.
Among these, potassium chloride, sodium chloride, calcium chloride, sodium hydrogen carbonate, sodium carbonate (including dry sodium carbonate), magnesium sulfate, sodium hydrogen phosphate, sodium dihydrogen phosphate, and potassium dihydrogen phosphate are preferred, potassium chloride, sodium chloride, calcium chloride, sodium hydrogen phosphate, and sodium dihydrogen phosphate are more preferred, and potassium chloride and sodium chloride are even more preferred.
The inorganic salts may be used alone or in combination of two or more.

When the ophthalmic composition contains inorganic salts, the content thereof may be, for example, 0.05 w/v% or more, 0.1 w/v% or more, 0.2 w/v% or more, 0.3 w/v% or more, 0.4 w/v% or more, or 0.5 w/v% or more in terms of the total amount of inorganic salts relative to the total amount of the composition.
Furthermore, the total amount of inorganic salts relative to the total amount of the composition may be, for example, 3 w/v% or less, 2 w/v% or less, 1 w/v% or less, 0.9 w/v% or less, 0.8 w/v% or less, 0.7 w/v% or less, 0.6 w/v% or less, or 0.5 w/v% or less.
The total content of inorganic salts may be 0.05 w/v%, 0.1 w/v%, 0.2 w/v%, 0.3 w/v%, 0.4 w/v%, 0.5 w/v%, 0.6 w/v%, 0.7 w/v%, 0.8 w/v%, 0.9 w/v%, 1 w/v%, 2 w/v%, 3 w/v%, and the like, relative to the total amount of the composition.

Polymeric Thickeners or Viscosifiers The ophthalmic compositions of the present invention may further comprise a polymeric thickener or viscosity enhancer.
Examples of polymeric thickening agents or viscosity-increasing agents include, but are not limited to, cellulose derivatives (e.g., hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, carboxyethyl cellulose, carboxymethyl cellulose), polyvinyl polymer compounds (e.g., polyvinyl alcohol (including fully or partially saponified products), polyvinylpyrrolidone, polyvinyl methacrylate), polyethylene glycol, dextran, α-cyclodextrin, dextrin, carboxyvinyl polymer, alginic acid, glucose, mucopolysaccharides (e.g., hyaluronic acid, hyaluronate salts (e.g., hyaluronic acid sodium salt), heparin, heparin sulfate, heparan sulfate), , keratosulfuric acid, heparinoid), guar gum, gum arabic, karaya gum, xanthan gum, agar, starch, chitin and its derivatives, chitosan and its derivatives, carrageenan, sorbitol, alkali metal salts of polyacrylic acid (e.g., sodium polyacrylate, potassium polyacrylate), amine salts of polyacrylic acid (e.g., monoethanolamine polyacrylate, diethanolamine polyacrylate, triethanolamine polyacrylate), casein, gelatin, collagen, pectin, elastin, ceramide, liquid paraffin, glycerin, macrogol, polyethyleneimine alginate (e.g., sodium alginate), alginate esters (e.g., propylene glycol alginate), tragacanth powder, and the like.
In addition to the above examples, these components may also be salts (for example, sodium salts, potassium salts, calcium salts, magnesium salts).
Among these, cellulose derivatives (particularly hydroxyethyl cellulose, hydroxypropyl methyl cellulose, and carboxymethyl cellulose), polyvinyl alcohol (including fully or partially saponified products), polyvinylpyrrolidone, carboxyvinyl polymers, alginic acid, and glucose are preferred, with hydroxyethyl cellulose, hydroxypropyl methyl cellulose, and carboxyvinyl polymers being more preferred, and hydroxypropyl methyl cellulose being even more preferred.
The polymeric thickeners or thickeners may be used singly or in combination of two or more.

When the ophthalmic composition contains a polymeric thickener or thickener, the content thereof may be, for example, 0.001 w/v% or more, 0.01 w/v% or more, 0.02 w/v% or more, 0.03 w/v% or more, 0.04 w/v% or more, 0.05 w/v% or more, 0.06 w/v% or more, 0.07 w/v% or more, 0.08 w/v% or more, 0.09 w/v% or more, or 0.1 w/v% or more in terms of the total amount of polymeric thickener or thickener relative to the total amount of the composition.
Furthermore, the total amount of polymeric thickeners or thickeners relative to the total amount of the composition may be, for example, 5 w/v% or less, 1 w/v% or less, 0.9 w/v% or less, 0.8 w/v% or less, 0.7 w/v% or less, 0.6 w/v% or less, 0.5 w/v% or less, 0.4 w/v% or less, 0.3 w/v% or less, 0.2 w/v% or less, or 0.1 w/v% or less.
The total content of the polymeric thickener or thickener, relative to the total amount of the composition, may be 0.001 w/v%, 0.01 w/v%, 0.02 w/v%, 0.03 w/v%, 0.04 w/v%, 0.05 w/v%, 0.06 w/v%, 0.07 w/v%, 0.08 w/v%, 0.09 w/v%, 0.1 w/v%, 0.2 w/v%, 0.3 w/v%, 0.4 w/v%, 0.5 w/v%, 0.6 w/v%, 0.7 w/v%, 0.8 w/v%, 0.9 w/v%, 1 w/v%, 2 w/v%, 3 w/v%, 4 w/v%, 5 w/v%, and the like.

Preservatives The ophthalmic compositions of the present invention may further comprise a preservative.
Examples of preservatives include, but are not limited to, boric acid, alkyldiaminoethylglycine and/or its salts (e.g., alkyldiaminoethylglycine hydrochloride), benzoic acid and/or its salts (e.g., sodium benzoate, potassium benzoate), ethanol, quaternary ammonium salts (e.g., benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride), chlorhexidine and/or its salts (e.g., chlorhexidine gluconate), chlorobutanol, sorbic acid and/or its salts (e.g., potassium sorbate), sodium dehydroacetate, parahydroxybenzoic acid esters (e.g., methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate), oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguamides such as polyhexamethylene biguanide and its salts (e.g., polyhexanide hydrochloride), Gloquil (trade name, Rhodia), and polydronium chloride.
Among these, boric acid, quaternary ammonium salts (particularly, benzalkonium chloride and benzethonium chloride), chlorhexidine and/or its salts (particularly, chlorhexidine gluconate), chlorobutanol, sorbic acid and/or its salts (e.g., potassium sorbate), and polyhexamethylene biguanide and its salts are preferred, alkylpolyaminoethylglycine, benzalkonium chloride, chlorhexidine gluconate, chlorobutanol, potassium sorbate, and polyhexanide hydrochloride are more preferred, and benzalkonium chloride, chlorobutanol, and polyhexanide hydrochloride are even more preferred.
The preservatives can be used alone or in combination of two or more.

When the ophthalmic composition contains a preservative, the content thereof may be, for example, 0.00001 w/v% or more, 0.0001 w/v% or more, 0.0002 w/v% or more, 0.0003 w/v% or more, 0.0004 w/v% or more, 0.0005 w/v% or more, 0.0006 w/v% or more, 0.0007 w/v% or more, 0.0008 w/v% or more, 0.0009 w/v% or more, or 0.001 w/v% or more in terms of the total amount of preservative relative to the total amount of the composition.
Furthermore, the total amount of preservatives relative to the total amount of the composition may be, for example, 0.5 w/v% or less, 0.2 w/v% or less, 0.1 w/v% or less, 0.05 w/v% or less, 0.01 w/v% or less, 0.009 w/v% or less, 0.008 w/v% or less, 0.007 w/v% or less, 0.006 w/v% or less, 0.005 w/v% or less, 0.004 w/v% or less, 0.003 w/v% or less, 0.002 w/v% or less, or 0.001 w/v% or less.
The total content of preservatives is 0.00001 w/v%, 0.0001 w/v%, 0.0002 w/v%, 0.0003 w/v%, 0.0004 w/v%, 0.0005 w/v%, 0.0006 w/v%, 0.0007 w/v%, 0.0008 w/v%, 0.0009 w/v%, and 0. Examples include 0.001 w/v%, 0.002 w/v%, 0.003 w/v%, 0.004 w/v%, 0.005 w/v%, 0.006 w/v%, 0.007 w/v%, 0.008 w/v%, 0.009 w/v%, 0.01 w/v%, 0.05 w/v%, 0.1 w/v%, 0.2 w/v%, and 0.5 w/v%.

Surfactants The ophthalmic compositions of the present invention may contain a surfactant.
Among the surfactants, nonionic surfactants are preferred.
Nonionic surfactants include POE sorbitan fatty acid esters such as POE (20) sorbitan monolaurate (polysorbate 20), POE (20) sorbitan monopalmitate (polysorbate 40), POE (20) sorbitan monostearate (polysorbate 60), POE (20) sorbitan tristearate (polysorbate 65), and POE (20) sorbitan monooleate (polysorbate 80); poloxamer 407, poloxamer 235, poloxamer 188, poloxamer 403, and poloxamer 235; POE/POP glycols such as Summer 237 and Poloxamer 124; POE hydrogenated castor oils such as POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, and POE hydrogenated castor oil 80; POE castor oils such as 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, POE castor oil 20, POE castor oil 25, POE castor oil 30, POE castor oil 35, and POE castor oil 50; polyethylene monostearate Recall (2 E.O.), polyethylene glycol monostearate (4 E.O.), polyethylene glycol monostearate (9 E.O.), polyethylene glycol monostearate (10 E.O.), polyethylene glycol monostearate (23 E.O.), polyethylene glycol monostearate (25 E.O.), polyethylene glycol monostearate (32 E.O.), polyethylene glycol monostearate (40 E.O., Polyoxyl 40 stearate), polyethylene monostearate polyethylene glycol monostearate such as polyethylene glycol (45 E.O.), polyethylene glycol monostearate (55 E.O.), polyethylene glycol monostearate (75 E.O.), polyethylene glycol monostearate (140 E.O.); POE alkyl ethers such as POE (9) lauryl ether; POE-POP alkyl ethers such as POE (20) POP (4) cetyl ether; POE alkyl phenyl ethers such as POE (10) nonylphenyl ether. In the compounds exemplified above, POE stands for polyoxyethylene, POP stands for polyoxypropylene, and the numbers in parentheses indicate the number of moles added.

Among these, nonionic POE sorbitan fatty acid esters; POE/POP glycols; POE hydrogenated castor oil; POE castor oil, and polyethylene glycol monostearate are preferred, with polysorbate 80, poloxamer 407, POE hydrogenated castor oil 40, POE hydrogenated castor oil 60, POE castor oil 3, POE castor oil 10, POE castor oil 35, and polyoxyl stearate 40 being more preferred, with polysorbate 80 and POE hydrogenated castor oil 60 being even more preferred, and polysorbate 80 being particularly preferred.

Other usable surfactants include amphoteric surfactants such as betaine-type amphoteric surfactants (e.g., lauryldimethylaminoacetic acid betaine, imidazolinium betaine); and cationic surfactants such as alkyl quaternary ammonium salts (e.g., benzalkonium chloride, benzethonium chloride).
The surfactants can be used alone or in combination of two or more.

When the ophthalmic composition of the present invention contains a surfactant, the content thereof is, for example, 0.001 w/v % or more, preferably 0.005 w/v % or more, preferably 0.01 w/v % or more, preferably 0.05 w/v % or more, based on the total amount of the composition. It may also be 0.1 w/v % or more, 0.2 w/v % or more, or 0.3 w/v % or more.
The total amount of surfactants relative to the total amount of the composition may be, for example, 5 w/v % or less, preferably 1 w/v % or less, preferably 0.5 w/v % or less, preferably 0.3 w/v % or less, or may be 0.2 w/v % or less, 0.1 w/v % or less, or 0.05 w/v % or less.
The total content of the surfactant may be, for example, 0.001 w/v%, 0.005 w/v%, 0.01 w/v%, 0.05 w/v%, 0.1 w/v%, 0.2 w/v%, 0.3 w/v%, 0.5 w/v%, 1 w/v%, or 5 w/v% relative to the total amount of the composition.

Buffering Agents The ophthalmic compositions of the present invention may contain a buffering agent.
Examples of the buffer include borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, and the like.
Examples of components of the borate buffer include boric acid, borate salts (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.), etc. The borate salts may be hydrates.
Examples of components of phosphate buffers include phosphoric acid and phosphate salts (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.). The phosphate salts may be hydrates.
Examples of components of carbonate buffers include carbonic acid and carbonate salts (potassium carbonate, sodium carbonate, calcium carbonate, potassium bicarbonate, sodium bicarbonate, magnesium carbonate, etc.).
Components of citrate buffers include citric acid, citrate salts (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.), and the like.
Components of acetate buffers include acetic acid, acetate salts (ammonium acetate, potassium acetate, calcium acetate, sodium acetate, etc.), and the like.
Among these, boric acid buffers and phosphate buffers are preferred, with boric acid buffers being more preferred, as they further improve the effects of the present invention. As the boric acid buffer, a combination of boric acid and its salts is preferred, a combination of boric acid and an alkali metal salt and/or an alkaline earth metal salt of boric acid is more preferred, a combination of boric acid and an alkali metal salt of boric acid is even more preferred, and a combination of boric acid and borax is even more preferred.
The buffering agents can be used alone or in combination of two or more.

When the ophthalmic composition of the present invention contains a buffer, its content varies depending on the type of buffer and the types and amounts of other ingredients, and cannot be uniformly defined, but examples thereof include a total amount of buffer of 0.001 w/v % or more, preferably 0.01 w/v % or more, preferably 0.05 w/v % or more, and preferably 0.1 w/v % or more, relative to the total amount of the composition, and a total amount of buffer of 10 w/v % or less, preferably 5 w/v % or less, preferably 3 w/v % or less, and preferably 2 w/v % or less, relative to the total amount of the composition.
The total content of the buffering agent may be 0.001 w/v%, 0.01 w/v%, 0.05 w/v%, 0.1 w/v%, 0.5 w/v%, 1 w/v%, 2 w/v%, 3 w/v%, 5 w/v%, 10 w/v%, and the like, relative to the total amount of the composition.

pH Adjusting Agents The ophthalmic compositions of the present invention may include a pH adjusting agent.
Examples of pH adjusters include hydrochloric acid, sulfuric acid, polyphosphoric acid, organic acids (propionic acid, oxalic acid, gluconic acid, fumaric acid, lactic acid, tartaric acid, malic acid, succinic acid, etc.), sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, monoethanolamine, and diisopropanolamine.

The ophthalmic composition of the present invention may contain a tonicity agent. Some of the inorganic salts exemplified above may be incorporated as a tonicity agent.
The tonicity agent includes sodium chloride, potassium chloride, calcium chloride, magnesium chloride, potassium acetate, sodium acetate, magnesium sulfate, glycerin, propylene glycol, and the like.
stabilizers
Stabilizers include trometamol, sodium formaldehyde sulfoxylate (Rongalit), monoethanolamine, aluminum monostearate, and glyceryl monostearate.

The ophthalmic composition of the present invention may contain an oil component, such as animal oils like squalane, mineral oils like liquid paraffin and vaseline, and vegetable oils like castor oil and sesame oil.

The ophthalmic composition of the present invention may contain a sugar. Examples of the sugar include monosaccharides and disaccharides, specifically glucose, maltose, trehalose, sucrose, cyclodextrin, xylitol, sorbitol, and mannitol. Some sugars are incorporated as polymer thickeners.

The ophthalmic composition of the present invention may contain a polyhydric alcohol. Examples of polyhydric alcohols include polyethylene glycol, glycerin, propylene glycol, xylitol, diethylene glycol, mannitol, sorbitol, and polyvinyl alcohol. Some polyhydric alcohols are used as polymeric thickeners.

Specific combinations of ingredients that can be incorporated into the ophthalmic composition of the present invention are exemplified below. These combinations are meant to contain at least those ingredients, and various other ingredients in addition to the listed ingredients may also be included.

(1) Pranoprofen, tetrahydrozoline hydrochloride, neostigmine methylsulfate, dipotassium glycyrrhizinate, chlorpheniramine maleate, pyridoxine hydrochloride, and potassium L-aspartate
(2) In (1), a combination containing aminoethylsulfonic acid, chondroitin sulfate, potassium L-aspartate and aminoethylsulfonic acid, potassium L-aspartate and chondroitin sulfate, or aminoethylsulfonic acid and chondroitin sulfate is used instead of potassium L-aspartate.
(3) In (1) or (2), the following may be substituted for pyridoxine hydrochloride: tocopherol acetate, panthenol, cyanocobalamin, flavin adenine dinucleotide, pyridoxine hydrochloride and tocopherol acetate, pyridoxine hydrochloride and panthenol, pyridoxine hydrochloride and cyanocobalamin, pyridoxine hydrochloride and flavin adenine dinucleotide, tocopherol acetate and panthenol, tocopherol acetate and cyanocobalamin, tocopherol acetate and flavin adenine dinucleotide, panthenol and cyanocobalamin, panthenol and flavin adenine dinucleotide, cyanocobalamin and flavin adenine dinucleotide, pyridoxine hydrochloride, tocopherol acetate and panthenol, pyridoxine hydrochloride and tocopherol acetate and cyanocobalamin, pyridoxine hydrochloride, tocopherol acetate, and flavin adenine dinucleotide, tocopherol acetate, panthenol, and cyanocobalamin, panthenol, cyanocobalamin, flavin adenine dinucleotide, pyridoxine hydrochloride, tocopherol acetate, panthenol, and cyanocobalamin, pyridoxine hydrochloride, tocopherol acetate, panthenol, and flavin adenine dinucleotide, tocopherol acetate, panthenol, cyanocobalamin, and flavin adenine dinucleotide, or pyridoxine hydrochloride, tocopherol acetate, panthenol, cyanocobalamin, and flavin adenine dinucleotide.
(4) In (1) to (3), diphenhydramine hydrochloride or a combination containing chlorpheniramine maleate and diphenhydramine hydrochloride is used instead of chlorpheniramine maleate.
(5) In (1) to (4), epsilon aminocaproic acid, allantoin, zinc sulfate, sodium azulene sulfonate, dipotassium glycyrrhizinate and epsilon aminocaproic acid, dipotassium glycyrrhizinate and allantoin, dipotassium glycyrrhizinate and zinc sulfate, dipotassium glycyrrhizinate and sodium azulene sulfonate, epsilon aminocaproic acid and allantoin, epsilon aminocaproic acid and zinc sulfate, epsilon aminocaproic acid and sodium azulene sulfonate, allantoin and zinc sulfate, allantoin and sodium azulene sulfonate, zinc sulfate and sodium azulene sulfonate, dipotassium glycyrrhizinate, epsilon aminocaproic acid and allantoin, dipotassium glycyrrhizinate, epsilon aminocaproic acid and zinc sulfate, dipotassium glycyrrhizinate, epsilon aminocaproic acid and azulene Sodium sulfonate, dipotassium glycyrrhizinate, allantoin, and zinc sulfate, dipotassium glycyrrhizinate, allantoin, and sodium azulene sulfonate, dipotassium glycyrrhizinate, zinc sulfate, and sodium azulene sulfonate, epsilon aminocaproic acid, allantoin, and zinc sulfate, epsilon aminocaproic acid, allantoin, and sodium azulene sulfonate, allantoin, zinc sulfate, and sodium azulene sulfonate, dipotassium glycyrrhizinate, epsilon aminocaproic acid, allantoin, and zinc sulfate, dipotassium glycyrrhizinate, epsilon aminocaproic acid, allantoin, and sodium azulene sulfonate, epsilon aminocaproic acid, allantoin, zinc sulfate, and sodium azulene sulfonate, or combinations including dipotassium glycyrrhizinate, epsilon aminocaproic acid, allantoin, zinc sulfate, and sodium azulene sulfonate.
(6) In (1) to (5), naphazoline hydrochloride or a combination containing tetrahydrozoline hydrochloride and naphazoline hydrochloride is used instead of tetrahydrozoline hydrochloride.

(7) Combinations of (1) to (6) that do not contain amino acids
(8) Combinations of (1) to (6) that do not contain vitamins
(9) Combinations of (1) to (6) that do not contain antihistamines
(10) Combinations of (1) to (6) that do not contain anti-inflammatory drugs other than pranoprofen
(11) Combinations of (1) to (6) that do not contain an ophthalmologic adjustor
(12) Combinations of (1) to (6) that do not include a decongestant

(13) Combinations of (1) to (6) that do not contain amino acids or vitamins
(14) Combinations of (1) to (6) that do not contain amino acids or antihistamines
(15) Combinations of (1) to (6) that do not contain anti-inflammatory drugs other than amino acids and pranoprofen
(16) Combinations of (1) to (6) that do not include amino acids and eye muscle adjusters
(17) Combinations of (1) to (6) that do not contain amino acids or decongestants
(18) Combinations of (1) to (6) that do not include vitamins and antihistamines
(19) Combinations of (1) to (6) that do not contain anti-inflammatory drugs other than vitamins and pranoprofen
(20) Combinations of (1) to (6) that do not include vitamins and eye muscle adjusters
(21) Combinations of (1) to (6) that do not include vitamins and decongestants
(22) Combinations of (1) to (6) that do not include antihistamines and anti-inflammatory drugs other than pranoprofen
(23) Combinations of (1) to (6) that do not include antihistamines and ophthalmologic adjusters
(24) Combinations of (1) to (6) that do not include antihistamines or decongestants
(25) Combinations of (1) to (6) that do not include anti-inflammatory drugs other than pranoprofen and ophthalmologic adjusters
(26) Combinations of (1) to (6) that do not include anti-inflammatory drugs and decongestants other than pranoprofen
(27) Combinations of (1) to (6) that do not include an ophthalmic muscle adjuster and a decongestant.

(28) Combinations of (1) to (6) that do not contain amino acids, vitamins, or antihistamines
(29) Combinations of (1) to (6) that do not include amino acids, vitamins, and eye muscle adjusters
(30) Combinations of (1) to (6) that do not contain amino acids, vitamins, or decongestants
(31) Combinations of (1) to (6) that do not include amino acids, antihistamines, and anti-inflammatory drugs other than pranoprofen
(32) Combinations of (1) to (6) that do not include amino acids, antihistamines, and ophthalmologic adjusters
(33) Combinations of (1) to (6) that do not include amino acids, antihistamines, and decongestants.
(34) Combinations of (1) to (6) that do not include amino acids, anti-inflammatory drugs other than pranoprofen, and ophthalmologic adjusters.
(35) Combinations of (1) to (6) that do not include anti-inflammatory and decongestant drugs other than amino acids and pranoprofen.
(36) Combinations of (1) to (6) that do not include amino acids, eye muscle adjusters, and decongestants
(37) Combinations of (1) to (6) that do not include vitamins, antihistamines, and anti-inflammatory drugs other than pranoprofen
(38) Combinations of (1) to (6) that do not include vitamins, antihistamines, and eye muscle adjusters
(39) Combinations of (1) to (6) that do not include vitamins, antihistamines, and decongestants.
(40) Combinations of (1) to (6) that do not include vitamins, anti-inflammatory drugs other than pranoprofen, and eye muscle adjusters
(41) Combinations of (1) to (6) that do not include vitamins and anti-inflammatory and decongestant drugs other than pranoprofen.
(42) Combinations of (1) to (6) that do not include vitamins, eye muscle adjusters, and decongestants.
(43) Combinations of (1) to (6) that do not include antihistamines, anti-inflammatory drugs other than pranoprofen, and ophthalmologic adjusters
(44) Combinations of (1) to (6) that do not include antihistamines, anti-inflammatory drugs other than pranoprofen, and decongestants.
(45) Combinations of (1) to (6) that do not include antihistamines, ophthalmic muscle adjusters, and decongestants
(46) Combinations of (1) to (6) that do not include an anti-inflammatory agent, an ophthalmic muscle adjuster, and a decongestant.

(47) Combinations of (1) to (6) that do not contain amino acids, vitamins, antihistamines, or anti-inflammatory drugs other than pranoprofen.
(48) Combinations of (1) to (6) that do not include amino acids, vitamins, antihistamines, and eye muscle adjusters.
(49) Combinations of (1) to (6) that do not contain amino acids, vitamins, antihistamines, or decongestants.
(50) Combinations of (1) to (6) that do not include amino acids, vitamins, anti-inflammatory agents other than pranoprofen, and eye muscle adjusters.
(51) Combinations of (1) to (6) that do not include amino acids, vitamins, and anti-inflammatory and decongestant drugs other than pranoprofen.
(52) Combinations of (1) to (6) that do not include amino acids, vitamins, eye muscle adjusters, and decongestants.
(53) Combinations of (1) to (6) that do not include vitamins, antihistamines, anti-inflammatory drugs other than pranoprofen, and ophthalmologic adjusters.
(54) Combinations of (1) to (6) that do not include vitamins, antihistamines, eye muscle adjusters, and decongestants.
(55) Combinations of (1) to (6) that do not include antihistamines, anti-inflammatory drugs other than pranoprofen, ocular muscle adjusters, and decongestants.

(56) A combination of (1) to (55) further comprising dibutylhydroxytoluene and/or sodium edetate.
(57) Combination of (1) to (55) further containing menthol and/or camphor
(58) A combination of (1) to (55) further comprising hydroxypropyl methylcellulose.
(59) In any of (1) to (55), a combination further comprising dibutylhydroxytoluene and/or sodium edetate, and menthol and/or camphor.
(60) In any of (1) to (55), a combination further comprising dibutylhydroxytoluene and/or sodium edetate and hydroxypropylmethylcellulose.
(61) In any of (1) to (55), a combination further comprising menthol and/or camphor and hydroxypropyl methylcellulose.
(62) In any of (1) to (55), a combination further comprising dibutylhydroxytoluene and/or sodium edetate, menthol and/or camphor, and hydroxypropylmethylcellulose.

The composition containing the components (1) to (62) can be used for improving, alleviating, treating, or preventing one or more symptoms or abnormalities selected from the group consisting of eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases (eye diseases caused by swimming, eye diseases caused by dust or sweat getting into the eyes, etc.). Specific examples include the improvement, alleviation, treatment, or prevention of the following symptoms or abnormalities:
When multiple symptoms or abnormalities are present, they may be a combination of symptoms or abnormalities.

Eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, discomfort when wearing contact lenses, or eye diseases (such as eye diseases caused by swimming or eye diseases caused by dust or sweat getting into the eyes. The same applies below to the uses of compositions containing ingredients (1) to (62)).

Eye fatigue and blurred vision, eye fatigue and itchy eyes, eye fatigue and conjunctival congestion, eye fatigue and blepharitis, eye fatigue and light-induced ophthalmitis, eye fatigue and foreign body sensation, eye fatigue and watery eyes, eye fatigue and discomfort when wearing contact lenses, eye fatigue and eye diseases,
Blurred vision and itchy eyes, Blurred vision and conjunctival congestion, Blurred vision and blepharitis, Blurred vision and photoophthalmia, Blurred vision and foreign body sensation, Blurred vision and watery eyes, Blurred vision and discomfort when wearing contact lenses, Blurred vision and eye diseases,
Itchy eyes and conjunctival congestion, itchy eyes and blepharitis, itchy eyes and photoophthalmia, itchy eyes and foreign body sensation, itchy eyes and watery eyes, itchy eyes and discomfort when wearing contact lenses, itchy eyes and eye diseases,
Conjunctival congestion and blepharitis, conjunctival congestion and photoophthalmia, conjunctival congestion and foreign body sensation, conjunctival congestion and watery eyes, conjunctival congestion and discomfort when wearing contact lenses, conjunctival congestion and eye diseases,
Blepharitis and photoophthalmia, blepharitis and foreign body sensation, blepharitis and watery eyes, blepharitis and discomfort when wearing contact lenses, blepharitis and eye diseases,
Photoophthalmia and foreign body sensation, photoophthalmia and watery eyes, photoophthalmia and discomfort when wearing contact lenses, photoophthalmia and eye diseases,
Foreign body sensation and watery eyes, foreign body sensation and discomfort when wearing contact lenses, foreign body sensation and eye diseases,
Watery eyes and discomfort when wearing contact lenses, Watery eyes and eye diseases,
Discomfort and eye diseases when wearing contact lenses,

Eye fatigue, blurred vision and itchy eyes, eye fatigue, blurred vision and conjunctival congestion,
Eye fatigue, blurred vision and blepharitis, Eye fatigue, blurred vision and photoophthalmia,
Eye fatigue, blurred vision and foreign body sensation, Eye fatigue, blurred vision and watery eyes, Eye fatigue, blurred vision and discomfort when wearing contact lenses, Eye fatigue, blurred vision and eye diseases,
Eye fatigue, itchy eyes and conjunctival congestion, eye fatigue, itchy eyes and blepharitis, eye fatigue, itchy eyes and light-induced ophthalmitis, eye fatigue, itchy eyes and foreign body sensation, eye fatigue, itchy eyes and watery eyes, eye fatigue, itchy eyes and discomfort when wearing contact lenses, eye fatigue, itchy eyes and eye diseases,
Eye fatigue, conjunctival congestion and blepharitis, Eye fatigue, conjunctival congestion and photoophthalmia, Eye fatigue, conjunctival congestion and foreign body sensation, Eye fatigue, conjunctival congestion and watery eyes, Eye fatigue, conjunctival congestion and discomfort when wearing contact lenses, Eye fatigue, conjunctival congestion and eye diseases,
Eye fatigue, blepharitis and photoophthalmia, Eye fatigue, blepharitis and foreign body sensation, Eye fatigue, blepharitis and watery eyes, Eye fatigue, blepharitis and discomfort when wearing contact lenses, Eye fatigue, blepharitis and eye diseases,
Eye fatigue, light-induced ophthalmia and foreign body sensation, Eye fatigue, light-induced ophthalmia and watery eyes, Eye fatigue, light-induced ophthalmia and discomfort when wearing contact lenses, Eye fatigue, light-induced ophthalmia and eye diseases,
Eye fatigue, foreign body sensation and watery eyes, Eye fatigue, foreign body sensation and discomfort when wearing contact lenses, Eye fatigue, foreign body sensation and eye diseases,
Eye fatigue, watery eyes, and discomfort when wearing contact lenses, Eye fatigue, watery eyes, and eye diseases,
Eye fatigue, discomfort when wearing contact lenses, and eye diseases,

Blurred vision, itchy eyes and conjunctival congestion, Blurred vision, itchy eyes and blepharitis, Blurred vision, itchy eyes and photoophthalmia, Blurred vision, itchy eyes and foreign body sensation, Blurred vision, itchy eyes and watery eyes, Blurred vision, itchy eyes and discomfort when wearing contact lenses, Blurred vision, itchy eyes and eye diseases,
Blurred vision, conjunctival congestion and blepharitis, Blurred vision, conjunctival congestion and photoophthalmia, Blurred vision, conjunctival congestion and foreign body sensation, Blurred vision, conjunctival congestion and watery eyes, Blurred vision, conjunctival congestion and discomfort when wearing contact lenses, Blurred vision, conjunctival congestion and eye disease,
Blurred vision, blepharitis and photoophthalmia, Blurred vision, blepharitis and foreign body sensation, Blurred vision, blepharitis and watery eyes, Blurred vision, blepharitis and discomfort when wearing contact lenses, Blurred vision, blepharitis and eye diseases,
Blurred vision, light-induced ophthalmia and foreign body sensation, Blurred vision, light-induced ophthalmia and watery eyes, Blurred vision, light-induced ophthalmia and discomfort when wearing contact lenses, Blurred vision, light-induced ophthalmia and eye disease,
Blurred vision, foreign body sensation and watery eyes, Blurred vision, foreign body sensation and discomfort when wearing contact lenses, Blurred vision, foreign body sensation and eye diseases,
Blurred vision, watery eyes and discomfort when wearing contact lenses, Blurred vision, watery eyes and eye diseases,
Blurred vision, discomfort when wearing contact lenses, and eye diseases

Itchy eyes, conjunctival congestion and blepharitis, itchy eyes, conjunctival congestion and photoophthalmia, itchy eyes, conjunctival congestion and foreign body sensation, itchy eyes, conjunctival congestion and watery eyes, itchy eyes, conjunctival congestion and discomfort when wearing contact lenses, itchy eyes, conjunctival congestion and eye diseases,
Itchy eyes, blepharitis and photoophthalmia, Itchy eyes, blepharitis and foreign body sensation, Itchy eyes, blepharitis and watery eyes, Itchy eyes, blepharitis and discomfort when wearing contact lenses, Itchy eyes, blepharitis and eye diseases,
Itchy eyes, photophlegm and foreign body sensation, itchy eyes, photophlegm and watery eyes, itchy eyes, photophlegm and discomfort when wearing contact lenses, itchy eyes, photophlegm and eye disease,
Itchy eyes, foreign body sensation and watery eyes, Itchy eyes, foreign body sensation and discomfort when wearing contact lenses, Itchy eyes, foreign body sensation and eye diseases,
Itchy eyes, watery eyes and discomfort when wearing contact lenses, Itchy eyes, watery eyes and eye diseases,
Itchy eyes, discomfort when wearing contact lenses, and eye diseases

Conjunctival congestion, blepharitis and photoophthalmia, conjunctival congestion, blepharitis and foreign body sensation, conjunctival congestion, blepharitis and watery eyes, conjunctival congestion, blepharitis and discomfort when wearing contact lenses, conjunctival congestion, blepharitis and eye diseases,
Conjunctival congestion, photophlegm and foreign body sensation, conjunctival congestion, photophlegm and watery eyes, conjunctival congestion, photophlegm and discomfort when wearing contact lenses, conjunctival congestion, photophlegm and eye disease,
Conjunctival congestion, foreign body sensation and watery eyes, Conjunctival congestion, foreign body sensation and discomfort when wearing contact lenses, Conjunctival congestion, foreign body sensation and eye diseases,
Conjunctival congestion, watery eyes, and discomfort when wearing contact lenses, Conjunctival congestion, watery eyes, and eye diseases,
Conjunctival congestion and discomfort when wearing contact lenses and eye diseases,

Blepharitis, photoophthalmia and foreign body sensation, Blepharitis, photoophthalmia and watery eyes, Blepharitis, photoophthalmia and discomfort when wearing contact lenses, Blepharitis, photoophthalmia and eye disease,
Blepharitis, foreign body sensation and watery eyes, Blepharitis, foreign body sensation and discomfort when wearing contact lenses, Blepharitis, foreign body sensation and eye diseases,
Blepharitis, watery eyes and discomfort when wearing contact lenses, Blepharitis, watery eyes and eye diseases,
Blepharitis, discomfort when wearing contact lenses, and eye diseases

Photoophthalmia, foreign body sensation and watery eyes, Photoophthalmia, foreign body sensation and discomfort when wearing contact lenses, Photoophthalmia, foreign body sensation and eye diseases,
Photoophthalmia, watery eyes, and discomfort when wearing contact lenses, Photoophthalmia, watery eyes, and eye diseases,
Photoophthalmia and discomfort and eye diseases when wearing contact lenses,

Foreign body sensation, watery eyes, and discomfort when wearing contact lenses, Foreign body sensation, watery eyes, and eye diseases,
Foreign body sensation, discomfort when wearing contact lenses, and eye diseases

Watery eyes, discomfort when wearing contact lenses, and eye diseases,

Eye fatigue, blurred vision, itchy eyes and conjunctival congestion, eye fatigue, blurred vision, itchy eyes and blepharitis, eye fatigue, blurred vision, itchy eyes and light-induced ophthalmia, eye fatigue, blurred vision, itchy eyes and foreign body sensation, eye fatigue, blurred vision, itchy eyes and watery eyes, eye fatigue, blurred vision, itchy eyes and discomfort when wearing contact lenses, eye fatigue, blurred vision, itchy eyes and eye diseases,
Eye fatigue, blurred vision, conjunctival congestion and blepharitis, eye fatigue, blurred vision, conjunctival congestion and photoophthalmia, eye fatigue, blurred vision, conjunctival congestion and foreign body sensation, eye fatigue, blurred vision, conjunctival congestion and watery eyes, eye fatigue, blurred vision, conjunctival congestion and discomfort when wearing contact lenses, eye fatigue, blurred vision, conjunctival congestion and eye diseases,
Eye fatigue, blurred vision, blepharitis, and photoophthalmia, eye fatigue, blurred vision, blepharitis, and foreign body sensation, eye fatigue, blurred vision, conjunctival congestion, and watery eyes, eye fatigue, blurred vision, blepharitis, and discomfort when wearing contact lenses, eye fatigue, blurred vision, blepharitis, and eye diseases,
Eye fatigue, blurred vision, light-induced ophthalmia and foreign body sensation, Eye fatigue, blurred vision, light-induced ophthalmia and watery eyes, Eye fatigue, blurred vision, light-induced ophthalmia and discomfort when wearing contact lenses, Eye fatigue, blurred vision, light-induced ophthalmia and eye diseases,
Eye fatigue, blurred vision, foreign body sensation and watery eyes, Eye fatigue, blurred vision, foreign body sensation and discomfort when wearing contact lenses, Eye fatigue, blurred vision, foreign body sensation and eye diseases,
Eye fatigue, blurred vision, watery eyes, and discomfort when wearing contact lenses, Eye fatigue, blurred vision, watery eyes, and eye diseases,
Eye fatigue, blurred vision, discomfort when wearing contact lenses, and eye diseases

Eye fatigue, itchy eyes, conjunctival congestion and blepharitis, eye fatigue, itchy eyes, conjunctival congestion and photoophthalmia, eye fatigue, itchy eyes, conjunctival congestion and foreign body sensation, eye fatigue, itchy eyes, conjunctival congestion and watery eyes, eye fatigue, itchy eyes, conjunctival congestion and discomfort when wearing contact lenses, eye fatigue, itchy eyes, conjunctival congestion and eye diseases,
Eye fatigue, itchy eyes, blepharitis, and photoophthalmia, eye fatigue, itchy eyes, blepharitis, and foreign body sensation, eye fatigue, itchy eyes, blepharitis, and watery eyes, eye fatigue, itchy eyes, blepharitis, and discomfort when wearing contact lenses, eye fatigue, itchy eyes, blepharitis, and eye diseases,
Eye fatigue, itchy eyes, light-induced ophthalmia and foreign body sensation, Eye fatigue, itchy eyes, light-induced ophthalmia and watery eyes, Eye fatigue, itchy eyes, light-induced ophthalmia and discomfort when wearing contact lenses, Eye fatigue, itchy eyes, light-induced ophthalmia and eye diseases,
Eye fatigue, itchy eyes, foreign body sensation and watery eyes, Eye fatigue, itchy eyes, foreign body sensation and discomfort when wearing contact lenses, Eye fatigue, itchy eyes, foreign body sensation and eye diseases,
Eye fatigue, itchy eyes, watery eyes and discomfort when wearing contact lenses, eye fatigue, itchy eyes, watery eyes and eye diseases,
Eye fatigue, itchy eyes, discomfort when wearing contact lenses, and eye diseases,

Eye fatigue, conjunctival congestion, blepharitis, and photoophthalmia, Eye fatigue, conjunctival congestion, blepharitis, and foreign body sensation, Eye fatigue, conjunctival congestion, blepharitis, and watery eyes, Eye fatigue, conjunctival congestion, blepharitis, and discomfort when wearing contact lenses, Eye fatigue, conjunctival congestion, blepharitis, and eye diseases,
Eye fatigue, conjunctival congestion, photophlegm and foreign body sensation, Eye fatigue, conjunctival congestion, photophlegm and watery eyes, Eye fatigue, conjunctival congestion, photophlegm and discomfort when wearing contact lenses, Eye fatigue, conjunctival congestion, photophlegm and eye disease,
Eye fatigue, conjunctival congestion, foreign body sensation and watery eyes, Eye fatigue, conjunctival congestion, foreign body sensation and discomfort when wearing contact lenses, Eye fatigue, conjunctival congestion, foreign body sensation and eye disease,
Eye fatigue, conjunctival congestion, watery eyes, and discomfort when wearing contact lenses, Eye fatigue, conjunctival congestion, watery eyes, and eye diseases,
Eye fatigue, conjunctival congestion, discomfort when wearing contact lenses, and eye diseases,

Eye fatigue, blepharitis, photophthamitis and foreign body sensation, Eye fatigue, blepharitis, photophthamitis and watery eyes, Eye fatigue, blepharitis, photophthamitis and discomfort when wearing contact lenses, Eye fatigue, blepharitis, photophthamitis and eye diseases,
Eye fatigue, blepharitis, foreign body sensation and watery eyes, Eye fatigue, blepharitis, foreign body sensation and discomfort when wearing contact lenses, Eye fatigue, blepharitis, foreign body sensation and eye diseases,
Eye fatigue, blepharitis, watery eyes, and discomfort when wearing contact lenses, Eye fatigue, blepharitis, watery eyes, and eye diseases,
Eye fatigue, blepharitis, discomfort when wearing contact lenses, and eye diseases,

Eye fatigue, light-induced ophthalmia, foreign body sensation and watery eyes, Eye fatigue, light-induced ophthalmia, foreign body sensation and discomfort when wearing contact lenses, Eye fatigue, light-induced ophthalmia, foreign body sensation and eye disease,
Eye fatigue, light-induced ophthalmia, watery eyes, and discomfort when wearing contact lenses, Eye fatigue, light-induced ophthalmia, watery eyes, and eye diseases,
Eye fatigue, light-induced ophthalmitis, discomfort when wearing contact lenses, and eye diseases,

Eye fatigue, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, Eye fatigue, foreign body sensation, watery eyes, and eye diseases,
Eye fatigue, foreign body sensation, discomfort when wearing contact lenses, and eye diseases,

Eye fatigue, watery eyes, discomfort when wearing contact lenses, and eye diseases,

Blurred vision, itchy eyes, conjunctival congestion, and blepharitis; Blurred vision, itchy eyes, conjunctival congestion, and photoophthalmia; Blurred vision, itchy eyes, conjunctival congestion, and foreign body sensation; Blurred vision, itchy eyes, conjunctival congestion, and watery eyes; Blurred vision, itchy eyes, conjunctival congestion, and discomfort when wearing contact lenses; Blurred vision, itchy eyes, conjunctival congestion, and eye disease;

Blurred vision, conjunctival congestion, blepharitis, and photoophthalmia; Blurred vision, conjunctival congestion, blepharitis, and foreign body sensation; Blurred vision, conjunctival congestion, blepharitis, and watery eyes; Blurred vision, conjunctival congestion, blepharitis, and discomfort when wearing contact lenses; Blurred vision, conjunctival congestion, blepharitis, and eye diseases;
Blurred vision, blepharitis, photoophthalmia and foreign body sensation, Blurred vision, blepharitis, photoophthalmia and watery eyes, Blurred vision, blepharitis, photoophthalmia and discomfort when wearing contact lenses, Blurred vision, blepharitis, photoophthalmia and eye disease,
Blurred vision, light-induced ophthalmia, foreign body sensation and watery eyes, Blurred vision, light-induced ophthalmia, foreign body sensation and discomfort when wearing contact lenses, Blurred vision, light-induced ophthalmia, foreign body sensation and eye disease,
Blurred vision, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, Blurred vision, foreign body sensation, watery eyes, and eye diseases,
Blurred vision, watery eyes, discomfort when wearing contact lenses, and eye diseases,

Blurred vision, blepharitis, photoophthalmia and foreign body sensation, Blurred vision, blepharitis, photoophthalmia and watery eyes, Blurred vision, blepharitis, photoophthalmia and discomfort when wearing contact lenses, Blurred vision, blepharitis, photoophthalmia and eye disease,
Blurred vision, light-induced ophthalmia, foreign body sensation and watery eyes, Blurred vision, light-induced ophthalmia, foreign body sensation and discomfort when wearing contact lenses, Blurred vision, light-induced ophthalmia, foreign body sensation and eye disease,
Blurred vision, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, Blurred vision, foreign body sensation, watery eyes, and eye diseases,
Blurred vision, watery eyes, discomfort when wearing contact lenses, and eye diseases,

Blurred vision, light-induced ophthalmia, foreign body sensation, and watery eyes; Blurred vision, light-induced ophthalmia, foreign body sensation, and discomfort when wearing contact lenses; Blurred vision, light-induced ophthalmia, foreign body sensation, and eye disease;

Blurred vision, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, Blurred vision, foreign body sensation, watery eyes, and eye diseases,
Blurred vision, watery eyes, discomfort when wearing contact lenses, and eye diseases,

Blurred vision, light-induced ophthalmia, foreign body sensation, and watery eyes; Blurred vision, light-induced ophthalmia, foreign body sensation, and discomfort when wearing contact lenses; Blurred vision, light-induced ophthalmia, foreign body sensation, and eye disease;

Blurred vision, foreign body sensation, watery eyes, and discomfort when wearing contact lenses; Blurred vision, foreign body sensation, watery eyes, and eye diseases;

Blurred vision, watery eyes, discomfort when wearing contact lenses, and eye diseases,

Itchy eyes, conjunctival congestion, blepharitis, and photoophthalmia; Itchy eyes, conjunctival congestion, blepharitis, and foreign body sensation; Itchy eyes, conjunctival congestion, blepharitis, and watery eyes; Itchy eyes, conjunctival congestion, blepharitis, and discomfort when wearing contact lenses; Itchy eyes, conjunctival congestion, blepharitis, and eye diseases;
Itchy eyes, blepharitis, photoophthalmia and foreign body sensation, Itchy eyes, blepharitis, photoophthalmia and watery eyes, Itchy eyes, blepharitis, photoophthalmia and discomfort when wearing contact lenses, Itchy eyes, blepharitis, photoophthalmia and eye diseases,
Itchy eyes, photophlegm, foreign body sensation and watery eyes, itchy eyes, photophlegm, foreign body sensation and discomfort when wearing contact lenses, itchy eyes, photophlegm, foreign body sensation and eye disease,
Itchy eyes, foreign body sensation, watery eyes and discomfort when wearing contact lenses, Itchy eyes, foreign body sensation, watery eyes and eye diseases,
Itchy eyes, watery eyes, discomfort when wearing contact lenses, and eye diseases

Conjunctival congestion and blepharitis and photoophthalmia and foreign body sensation, Conjunctival congestion and blepharitis and photoophthalmia and watery eyes, Conjunctival congestion and blepharitis and photoophthalmia and discomfort when wearing contact lenses, Conjunctival congestion and blepharitis and photoophthalmia and eye disease,
Conjunctival congestion, photophlegm, foreign body sensation and watery eyes, conjunctival congestion, photophlegm, foreign body sensation and discomfort when wearing contact lenses, conjunctival congestion, photophlegm, foreign body sensation and eye disease,
Conjunctival congestion, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, Conjunctival congestion, foreign body sensation, watery eyes, and eye diseases,
Conjunctival congestion, watery eyes, discomfort when wearing contact lenses, and eye diseases

Blepharitis, photophthamitis, foreign body sensation and watery eyes, Blepharitis, photophthamitis, foreign body sensation and discomfort when wearing contact lenses, Blepharitis, photophthamitis, foreign body sensation and eye disease,
Blepharitis, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, Blepharitis, foreign body sensation, watery eyes, and eye diseases,
Blepharitis, watery eyes, discomfort when wearing contact lenses, and eye diseases

Photoophthalmia, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, Photoophthalmia, foreign body sensation, watery eyes, and eye diseases,
Photoophthalmia, watery eyes, discomfort when wearing contact lenses, and eye diseases

Foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases,

Eye fatigue, blurred vision, itchy eyes, conjunctival congestion and blepharitis, eye fatigue, blurred vision, itchy eyes, conjunctival congestion and photoophthalmia, eye fatigue, blurred vision, itchy eyes, conjunctival congestion and foreign body sensation, eye fatigue, blurred vision, itchy eyes, conjunctival congestion and watery eyes, eye fatigue, blurred vision, itchy eyes, conjunctival congestion and discomfort when wearing contact lenses, eye fatigue, blurred vision, itchy eyes, conjunctival congestion and eye diseases,
Eye fatigue, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, eye fatigue, itchy eyes, conjunctival congestion, blepharitis, foreign body sensation, eye fatigue, itchy eyes, conjunctival congestion, blepharitis, watery eyes, eye fatigue, itchy eyes, conjunctival congestion, blepharitis, discomfort when wearing contact lenses, eye fatigue, itchy eyes, conjunctival congestion, blepharitis, eye diseases,
Eye fatigue, conjunctival congestion, blepharitis, photoophthalmia and foreign body sensation, Eye fatigue, conjunctival congestion, blepharitis, photoophthalmia and watery eyes, Eye fatigue, conjunctival congestion, blepharitis, photoophthalmia and discomfort when wearing contact lenses, Eye fatigue, conjunctival congestion, blepharitis, photoophthalmia and eye diseases,
Eye fatigue, blepharitis, photophthamitis, foreign body sensation and watery eyes, Eye fatigue, blepharitis, photophthamitis, foreign body sensation and discomfort when wearing contact lenses, Eye fatigue, blepharitis, photophthamitis, foreign body sensation and eye diseases,
Eye fatigue, light-induced ophthalmia, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, Eye fatigue, light-induced ophthalmia, foreign body sensation, watery eyes, and eye diseases,
Eye fatigue, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases,

Blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, blurred vision, itchy eyes, conjunctival congestion, blepharitis, foreign body sensation, blurred vision, itchy eyes, conjunctival congestion, blepharitis, watery eyes, blurred vision, itchy eyes, conjunctival congestion, blepharitis, discomfort when wearing contact lenses, blurred vision, itchy eyes, conjunctival congestion, blepharitis, eye diseases,
Blurred vision, conjunctival congestion, blepharitis, photoophthalmia and foreign body sensation, Blurred vision, conjunctival congestion, blepharitis, photoophthalmia and watery eyes, Blurred vision, conjunctival congestion, blepharitis, photoophthalmia and discomfort when wearing contact lenses, Blurred vision, conjunctival congestion, blepharitis, photoophthalmia and eye disease,
Blurred vision, blepharitis, photophthamitis, foreign body sensation and watery eyes, Blurred vision, blepharitis, photophthamitis, foreign body sensation and discomfort when wearing contact lenses, Blurred vision, blepharitis, photophthamitis, foreign body sensation and eye diseases,
Blurred vision, light-induced ophthalmia, foreign body sensation, watery eyes, and discomfort when wearing contact lenses; Blurred vision, light-induced ophthalmia, foreign body sensation, watery eyes, and eye diseases;
Blurred vision, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases,

Itchy eyes, conjunctival congestion, blepharitis, photoophthalmia and foreign body sensation, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia and watery eyes, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia and discomfort when wearing contact lenses, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia and eye diseases,
Itchy eyes, blepharitis, photoophthalmia, foreign body sensation and watery eyes, Itchy eyes, blepharitis, photoophthalmia, foreign body sensation and discomfort when wearing contact lenses, Itchy eyes, blepharitis, photoophthalmia, foreign body sensation and eye diseases,
Itchy eyes, light-induced ophthalmitis, foreign body sensation, watery eyes, and discomfort when wearing contact lenses,
Itchy eyes, photoophthalmia, foreign body sensation, watery eyes, and eye diseases,
Itchy eyes, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases.

Conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation and watery eyes, Conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation and discomfort when wearing contact lenses, Conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation and eye disease,
Conjunctival congestion, photophthisis, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, Conjunctival congestion, photophthisis, foreign body sensation, watery eyes, and eye diseases,
Conjunctival congestion, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases,

Blepharitis, photoophthalmia, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, blepharitis, photoophthalmia, foreign body sensation, watery eyes, and eye diseases,

Photoophthalmia, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases,

Eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, foreign body sensation, eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, watery eyes, eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, discomfort when wearing contact lenses, eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, and eye diseases Eye fatigue, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, eye fatigue, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, watery eyes, eye fatigue, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, discomfort when wearing contact lenses, eye fatigue, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, and eye diseases, eye fatigue, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, eye fatigue, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, discomfort when wearing contact lenses, eye fatigue, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, and eye diseases Eye fatigue, blepharitis, photophthamitis, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, Eye fatigue, blepharitis, photophthamitis, foreign body sensation, watery eyes, and eye diseases Eye fatigue, photophthamitis, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, and eye diseases

Blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, watery eyes, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, discomfort when wearing contact lenses, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, and eye diseases, blurred vision, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, blurred vision, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, discomfort when wearing contact lenses, blurred vision, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, and eye diseases Blurred vision, blepharitis, photoophthalmia, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, Blurred vision, blepharitis, photoophthalmia, foreign body sensation, watery eyes, and eye diseases Blurred vision, photoophthalmia, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, and eye diseases

Itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, and discomfort when wearing contact lenses, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, itchy eyes, blepharitis, photoophthalmia, foreign body sensation, watery eyes, and eye diseases, itchy eyes, photoophthalmia, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, itchy eyes, blepharitis, photoophthalmia, foreign body sensation, watery eyes, and eye diseases, itchy eyes, photoophthalmia, foreign body sensation, watery eyes, and discomfort when wearing contact lenses and eye diseases

Conjunctival hyperemia, blepharitis, photoophthalmia, foreign body sensation, watery eyes, and discomfort when wearing contact lenses; Conjunctival hyperemia, blepharitis, photoophthalmia, foreign body sensation, watery eyes, and eye diseases

Blepharitis, photoophthalmia, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases

Eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, watery eyes, eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, discomfort when wearing contact lenses, eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, and eye diseases, eye fatigue, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, eye fatigue, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, discomfort when wearing contact lenses, eye fatigue, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, and eye diseases Eye fatigue, conjunctival congestion, blepharitis, photophlegm, foreign body sensation, watery eyes, discomfort when wearing contact lenses, eye fatigue, conjunctival congestion, blepharitis, photophlegm, foreign body sensation, watery eyes, and eye diseases, eye fatigue, blepharitis, photophlegm, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photophlegm, foreign body sensation, watery eyes, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photophlegm, foreign body sensation, discomfort when wearing contact lenses, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photophlegm, foreign body sensation, and eye diseases Blurred vision, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, discomfort when wearing contact lenses, Blurred vision, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, and eye diseases, Blurred vision, blepharitis, photoophthalmia, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases, Itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, and discomfort when wearing contact lenses, Itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, and eye diseases, Itchy eyes, blepharitis, photoophthalmia, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases Conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases

Eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, discomfort when wearing contact lenses, eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, discomfort when wearing contact lenses, eye fatigue, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, discomfort when wearing contact lenses, eye fatigue, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, eye diseases, eye fatigue, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, discomfort when wearing contact lenses, eye diseases Eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, discomfort when wearing contact lenses, and eye diseases. Eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, watery eyes, discomfort when wearing contact lenses, and eye diseases. Eye fatigue, blurred vision, itchy eyes, conjunctival congestion, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases. Eye fatigue, blurred vision, itchy eyes, photoophthalmia, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases. Blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases. Blurred vision, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases. Itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases.

Eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photophlegm, foreign body sensation, watery eyes, discomfort when wearing contact lenses, eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photophlegm, foreign body sensation, watery eyes, and eye diseases. Eye fatigue, itchy eyes, conjunctival congestion, blepharitis, photophlegm, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases. Blurred vision, itchy eyes, conjunctival congestion, blepharitis, photophlegm, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases. Eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photophlegm, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases. Eye fatigue, blurred vision, itchy eyes, conjunctival congestion, photophlegm, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases. Eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases. Eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photophlegm, watery eyes, discomfort when wearing contact lenses, and eye diseases. Eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photophlegm, foreign body sensation, discomfort when wearing contact lenses, and eye diseases.

Eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, photoophthalmia, foreign body sensation, watery eyes, discomfort when wearing contact lenses, and eye diseases

pH
The pH of the ophthalmic composition of the present invention is preferably 3 or higher, more preferably 4 or higher, even more preferably 5 or higher, and even more preferably 6 or higher. The pH is also preferably 10 or lower, more preferably 9 or lower, even more preferably 8.5 or lower, and even more preferably 8 or lower. If the pH is within the above range, eye irritation is suppressed and the above-mentioned effects of the present invention can be obtained.

The osmotic pressure ratio of the ophthalmic composition of the present invention is preferably 0.4 or more, more preferably 0.6 or more, and even more preferably 0.8 or more. Also, it is preferably 5 or less, more preferably 3 or less, and even more preferably 2 or less. If it is within the above range, eye irritation can be suppressed and the above-mentioned effects of the present invention can be obtained.
The osmotic pressure ratio is the ratio of the osmotic pressure of the sample to the osmotic pressure of 286 mOsm (0.9 w/v% sodium chloride aqueous solution) according to the 16th edition of the Japanese Pharmacopoeia. Osmotic pressure is measured according to the osmotic pressure measurement method (freezing point depression method) described in the 16th edition of the Japanese Pharmacopoeia. The standard solution for measuring the osmotic pressure ratio (0.9 w/v% sodium chloride aqueous solution) is prepared by drying sodium chloride (Japanese Pharmacopoeia standard reagent) at 500-650°C for 40-50 minutes, allowing it to cool in a desiccator (silica gel), accurately weighing 0.900 g, dissolving it in purified water, and preparing a solution of exactly 100 mL. Alternatively, a commercially available standard solution for measuring the osmotic pressure ratio (0.9 w/v% sodium chloride aqueous solution) can be used.

Container The ophthalmic composition of the present invention is housed in a container.
The container refers to a packaging body having a surface that comes into contact with the formulation, such as the container body that contains the liquid, the portion including the extraction port of the container (nozzle, inner plug), the suction tube, and the cap.
The material for composing the container for storing the ophthalmic composition of the present invention can be selected from a wide range of materials.
For example, at least a part or all of the surface that comes into contact with the ophthalmic composition may be made of at least one material selected from the group consisting of plastics (e.g., polyolefins, acrylic acid resins, terephthalic acid esters, 2,6-naphthalenedicarboxylic acid esters, polycarbonates, polymethylpentene, fluororesins, polyvinyl chloride, polyamides, ABS resins, AS resins, polyacetals, modified polyphenylene ethers, polyarylates, polysulfones, polyimides, cellulose acetates, hydrocarbons that may be substituted with halogen atoms, etc.), metals (e.g., aluminum), and glass.

Polyolefins include polyethylene (including high-density polyethylene, low-density polyethylene, very-low-density polyethylene, linear low-density polyethylene, and ultra-high-molecular-weight polyethylene), polypropylene (including isotactic polypropylene, syndiotactic polypropylene, and atactic polypropylene), and ethylene-propylene copolymers.

Acrylic acid resins include acrylic acid esters such as methyl acrylate, and methacrylic acid esters such as methyl methacrylate, cyclohexyl methacrylate, and t-butylcyclohexyl methacrylate.

Examples of terephthalic acid esters include polyethylene terephthalate, polytrimethylene terephthalate, and polybutylene terephthalate.

Examples of 2,6-naphthalenedicarboxylic acid esters include polyethylene naphthalate and polybutylene naphthalate.

Examples of fluororesins include fluorine-substituted polyethylene (polytetrafluoroethylene, polychlorotrifluoroethylene, etc.), polyvinylidene fluoride, polyvinyl fluoride, perfluoroalkoxy fluororesin, tetrafluoroethylene-hexafluoropropylene copolymer, ethylene-tetrafluoroethylene copolymer, and ethylene-chlorotrifluoroethylene copolymer.

Examples of polyamides include nylon.

Polyacetals include those consisting only of oxymethylene units, as well as those that partially contain oxyethylene units.

Examples of modified polyphenylene ethers include polystyrene-modified polyphenylene ethers.

Examples of polyarylates include amorphous polyarylates.

Examples of polyimides include aromatic polyimides, such as those obtained by polymerizing pyromellitic dianhydride and 4,4'-diaminodiphenyl ether.

Examples of cellulose acetate include cellulose diacetate and cellulose triacetate.
The container for storing the ophthalmic composition of the present invention is preferably made of polyolefin or terephthalic acid ester, more preferably terephthalic acid ester, further preferably polyethylene terephthalate or polybutylene terephthalate, and even more preferably polyethylene terephthalate. From another viewpoint, polypropylene, polyethylene, polyethylene terephthalate, or polybutylene terephthalate is preferred, more preferably polypropylene, polyethylene terephthalate, polyethylene, or polybutylene terephthalate, further more preferably polyethylene terephthalate or polyethylene, and even more preferably polyethylene terephthalate.
The container for storing the ophthalmic composition of the present invention may be made of a material that is a blend polymer with a polymer other than the above-mentioned polymer. When the container for storing the ophthalmic composition of the present invention is made of a blend polymer with the above-mentioned polymer, the mixing ratio of the above-mentioned polymer to the other polymer is not particularly limited as long as the effects of the present invention are achieved, but the total weight of the polymers relative to the total amount of all constituent materials is preferably 30 wt% or more, more preferably 50 wt% or more, even more preferably 65 wt% or more, and particularly preferably 80 wt% or more.

At least a portion of the surface of the container that comes into contact with the ophthalmic composition of the present application may be made of the above material.
For example, a layer or film made of the above material may be formed on the inner surface of the container, or the container itself may be molded from the above material.
Furthermore, the components of the container (such as the container body, the container's portion including the extraction port (nozzle, inner plug), suction tube, and cap) may be made of the above materials, or the entire container may be made of the above materials. In particular, it is preferable that the container body be made of the above materials, and it is more preferable that the entire container body be made of the above materials (a state in which some layers constituting the container body are not made of the above materials).

The container may also be a light-shielding container, which improves the stability of ingredients such as pranoprofen or its salts. Examples of light-shielding containers include containers made of the above materials covered with a light-shielding film, and containers made of the above materials and a colorant.

The ophthalmic composition of the present invention improves a complex ocular condition. Improvement of a complex ocular condition includes improvement, alleviation, treatment, or prevention of a complex ocular condition or condition.
The compound is useful for improving, alleviating, treating, or preventing one or more of the following complex eye symptoms or abnormalities: eye fatigue, blurred vision due to excessive eye discharge, itchy eyes, conjunctival congestion, blepharitis (sore eyelids), eye inflammation due to ultraviolet light or other light (so-called snow blindness, etc.), foreign body sensation (gritty sensation, tingling sensation, etc.), watery eyes, eye discomfort (including eye discomfort such as discomfort when wearing contact lenses), and eye diseases (eye diseases caused by swimming, eye diseases caused by dust or sweat getting into the eyes, etc.).
Conditions presenting multiple eye symptoms or abnormalities may be more difficult to improve or prevent than conditions presenting a single symptom or abnormality, and the ophthalmic composition of the present invention can effectively improve, alleviate, treat, or prevent those symptoms even in such cases.

In particular, with the recent widespread use of personal computers, which has led to heavy eye strain, and the widespread use of contact lenses, modern consumers, residents, and workers are increasingly experiencing comprehensive or complex unpleasant symptoms, including one or more of eye fatigue, itchy eyes, conjunctival congestion, blurred vision, and eye discomfort. The present invention can effectively improve, alleviate, treat, or prevent such comprehensive or complex symptoms.
In particular, itchy eyes, conjunctival congestion, and blurred vision are symptoms that frequently appear in various eye diseases. These symptoms may be comprehensive or complex. The present invention can effectively improve, alleviate, treat, or prevent these symptoms.
Furthermore, itchy eyes, conjunctival congestion, blurred vision due to eye discharge, watery eyes, and a foreign body sensation are often present as a combination of one or more symptoms in inflammation and allergic conditions triggered by allergens such as house dust, yellow sand, PM2.5, and mites. The present invention can effectively improve, alleviate, treat, or prevent such combination symptoms.

The above-mentioned eye diseases include inflammatory diseases such as blepharitis, conjunctivitis, keratitis, scleritis, episcleritis, anterior uveitis, postoperative inflammation, dacryoadenitis, dacryocystitis, and canaliculitis; and symptoms caused by bacterial infections such as styes and conjunctivitis. Other examples include eye diseases caused by swimming and eye diseases caused by dust or sweat getting into the eyes. Inflammatory diseases and symptoms caused by bacterial infections may also be accompanied by the allergic symptoms mentioned above.

As mentioned above, eye discomfort also includes eye discomfort experienced when wearing contact lenses. Discomfort experienced when wearing contact lenses encompasses discomfort experienced when wearing either hard or soft contact lenses. Furthermore, while wearing hard contact lenses can be quite uncomfortable, the ophthalmic composition of the present invention can effectively improve, alleviate, treat, or prevent such discomfort.

Accordingly, the ophthalmic composition of the present invention can be a composition for use in improving, alleviating, treating, or preventing comprehensive eye symptoms or abnormalities, for use in improving, alleviating, treating, or preventing complex eye symptoms or abnormalities, for use in total eye care, or for use in comprehensive eye normalization. The ophthalmic composition of the present invention can also be a multifunctional composition for use in improving, alleviating, treating, or preventing comprehensive eye symptoms or abnormalities.

The ophthalmic composition of the present invention can also be used to improve, alleviate, treat, or prevent one of the above symptoms or abnormalities.

In the present invention, "prevention" includes avoiding or delaying the onset of the disease or reducing the incidence rate, "alleviation" includes alleviating symptoms or inhibiting the progression of symptoms, and "improvement" and "treatment" include alleviating symptoms, inhibiting the progression of symptoms, and curing or complete recovery.

When the ophthalmic composition of the present invention is a preparation to be applied to the eyes, such as eye drops, eyewash, or eye ointment, its dosage varies depending on the target symptoms, but can be, for example, one or more, two or more, three or more, four or more, five or more, or six or more times per day. It can also be nine or fewer, eight or fewer, seven or fewer, six or fewer, five or fewer, or four or fewer times per day. Administration four times per day is particularly preferred.

Use may begin simultaneously with or after the onset of symptoms, but may also begin at least one day, particularly three or more days, and especially seven or more days, before the onset of symptoms. Use may also begin at least ten days before the onset of symptoms. Use may also begin within 30 days, particularly within 20 days, and especially within 14 days, before the onset of symptoms. By using the product before symptoms appear, symptoms can be effectively prevented.

When the ophthalmic composition of the present invention is in the form of eye drops, the eye drops containing the components at the above concentrations may be administered in an amount of, for example, 1 to 3 drops, preferably 1 to 2 drops, per administration. Alternatively, the amount may be 1 drop.
When the ophthalmic composition of the present invention is an eyewash, the eyewash containing each component at the above-mentioned concentrations may be used, for example, in an amount of 1 to 30 mL, preferably 1 to 20 mL, and more preferably 4 to 6 mL, per use.
When the ophthalmic composition of the present invention is an eye ointment, the eye ointment containing each component at the above-mentioned concentrations may be applied to the eye in an amount of, for example, 0.001 to 5 g per application.

When the ophthalmic composition of the present invention is a contact lens wetting solution, it can be applied, for example, 1 to 3 drops, preferably 1 to 2 drops, to one and/or both sides of the contact lens each time it is worn or removed, and preferably both sides of the contact lens are wetted before wearing.

When the ophthalmic composition of the present invention is a contact lens solution, the ophthalmic composition may be left in contact with the contact lens for, but not limited to, at least 1 hour, at least 2 hours, at least 4 hours, or at least 1 day. Also, the contact may be left for up to 30 days, up to 14 days, up to 7 days, or up to 2 days.

The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.
Test Example 1. Evaluation of the effect of eye drops on various eye symptoms
The eye drops of Examples 1 to 8 and Comparative Examples 1 to 8 having the compositions shown in Table 1 were prepared, sterilized with a filtration filter (0.2 μm), and then filled in 10 mL amounts into PET eye drop containers (13 mL capacity).
The unit of each component concentration in Table 1 is w/v %, the remainder is water (purified water), and the total volume is 100 mL. The pH was adjusted as needed with a pH adjuster (hydrochloric acid, sodium hydroxide: appropriate amount).

The subjects were office workers who regularly worked at visual display terminals (VDTs) for four hours or more per day. Each subject was tested after confirming that there was no difference in the condition of their left and right eyes.
As shown in Table 2, the tests using Examples 1 to 8 and Comparative Examples 1 to 8 as a set were designated as Tests A to H. For example, Comparative Example 1 is the same eye drop preparation as Example 1 except that it does not contain pranoprofen, and the test using Example 1 and Comparative Example 1 as a set was designated as Test A.
For tests A to H, five subjects (four males and one female) instilled one drop of the eye drops of the Example into their right eye and one drop of the eye drops of the Comparative Example into their left eye, and the effects on various ocular symptoms (eye fatigue, eye itching, blurred vision, conjunctival congestion, and eye discomfort) 30 seconds after instillation were compared using the "VAS (Visual Analog Scale)" method, which uses a 10 cm line graduated from 0 to 100. When different tests were conducted consecutively, an interval of at least one hour was allowed after the completion of instillation before the next instillation.

The average VAS score values of the five subjects were calculated, and the score increase value for each Example from the corresponding Comparative Example was calculated using the following formula (1). The results of the score increase value for each eye symptom are shown in Table 1. The higher the VAS score value, the stronger the eye symptom (eye fatigue, eye itchiness, blurred vision, conjunctival congestion, eye discomfort), and the higher the score increase value, the greater the improvement in the eye symptom.

Score increase value = average VAS score value of each example - average VAS score value of corresponding comparative example Formula (1)

The corresponding comparative example refers to the eye drops administered as a set in Tests A to H; for example, Example 1 corresponds to Comparative Example 1, and Example 2 corresponds to Comparative Example 2.
The results are shown in Table 2.

It has been confirmed that the inclusion of pranoprofen significantly suppresses all symptoms of eye fatigue, itchy eyes, blurred vision, conjunctival congestion, and eye discomfort, improving complex eye symptoms.

The eye drops of Preparation Examples 1 to 8, the compositions of which are shown in Table 3 below, suppress eye fatigue, eye itching, blurred vision, conjunctival congestion, and eye discomfort, and improve complex eye symptoms.
The unit of each component concentration in Table 3 is w/v % (the unit of 50 w/v % benzalkonium chloride solution is mL). In Table 3, the remaining amount is water (purified water), and the total amount is 100 mL.
Formulation Examples 1 to 8 were adjusted to pH 6 using a pH adjuster (hydrochloric acid, appropriate amount of sodium hydroxide) to form Formulation Examples 1-1 to 1-8, Formulation Examples 1 to 8 were adjusted to pH 7 using a pH adjuster to form Formulation Examples 2-1 to 2-8, and Formulation Examples 1 to 8 were adjusted to pH 8 using a pH adjuster to form Formulation Examples 3-1 to 3-8.

The ophthalmic composition of the present invention can practically and satisfactorily improve, alleviate, treat, or prevent a wider variety of eye symptoms or abnormalities than conventional ophthalmic compositions. Therefore, there is no need to use multiple ophthalmic compositions in combination. Therefore, the ophthalmic composition of the present invention is extremely useful industrially.

Claims (10)

(b) A method for imparting the effect of improving eye fatigue, blurred vision, itchy eyes, and conjunctival congestion by blending at least one component selected from the group consisting of pranoprofen and its salts with an ophthalmic composition containing at least one component selected from the group consisting of tetrahydrozoline hydrochloride, epsilon-aminocaproic acid, dipotassium glycyrrhizinate, chlorpheniramine maleate, pyridoxine hydrochloride , tocopherol acetate, potassium L-aspartate, aminoethylsulfonic acid, and sodium chondroitin sulfate . The method according to claim 1, wherein component (b) comprises tetrahydrozoline hydrochloride, epsilon-aminocaproic acid and/or dipotassium glycyrrhizinate, chlorpheniramine maleate, pyridoxine hydrochloride and/or tocopherol acetate, potassium L-aspartate, aminoethylsulfonic acid, and/or sodium chondroitin sulfate . 2. The method according to claim 1 , wherein component (b) comprises at least one selected from tetrahydrozoline hydrochloride , chlorpheniramine maleate, pyridoxine hydrochloride, tocopherol acetate, aminoethylsulfonic acid, and sodium chondroitin sulfate. The ophthalmic composition comprises:
When tetrahydrozoline hydrochloride is contained, the content is 0.0006 w/v% or more and 0.2 w/v% or less based on the total amount of the composition,
When epsilon-aminocaproic acid and/or dipotassium glycyrrhizinate is contained, the content is 0.0005 w/v% or more and 10 w/v% or less based on the total amount of the composition,
When chlorpheniramine maleate is contained, the content is 0.0006 w/v % or more and 0.1 w/v % or less based on the total amount of the composition;
When pyridoxine hydrochloride and/or tocopherol acetate are contained, the amount thereof is 0.0002 w/v% or more and 1 w/v% or less based on the total amount of the composition,
The method according to any one of claims 1 to 3 , wherein when potassium L-aspartate, aminoethylsulfonic acid, and/or sodium chondroitin sulfate are contained, the amount of each of them is 0.005 w/v% or more and 7 w/v% or less, based on the total amount of the composition. The method according to any one of claims 1 to 4 , wherein the total content of the component (b) in the ophthalmic composition is 0.0002 w/v % or more and 10 w/v % or less based on the total amount of the composition. The method according to any one of claims 1 to 5 , wherein the ophthalmic composition further comprises at least one selected from the group consisting of antioxidants and cooling agents. The method according to any one of claims 1 to 6 , wherein the ophthalmic composition further comprises at least one selected from the group consisting of butyl group-containing phenols and menthol. The method of any one of claims 1 to 7 , wherein the ophthalmic composition further comprises dibutylhydroxytoluene and menthol. The ophthalmic composition comprises:
When an antioxidant is contained, the total amount of the antioxidant is 0.0001 w/v % or more and 1 w/v % or less based on the total amount of the composition,
The method according to any one of claims 1 to 8 , wherein when a cooling agent is contained, the total amount of the cooling agent is 0.0001 w/v % or more and 1 w/v % or less relative to the total amount of the composition. The method according to any one of claims 1 to 9 , wherein the ophthalmic composition is formulated in an amount of 0.001 w/v % or more and 1 w/v % or less based on the total amount of the ophthalmic composition.