JP2021107464A - Ophthalmic composition - Google Patents

Abstract

To provide an ophthalmic composition capable of widely improving, alleviating, treating, or preventing various symptoms or abnormalities of the eye and being more effective for improvement, alleviation, treatment, or prevention than a conventional ophthalmic composition.SOLUTION: The present invention provides an ophthalmic composition for ameliorating, alleviating, treating, or preventing complex symptoms or abnormalities of the eyes. The composition comprises: (a) at least one selected from the group consisting of pranoprofen and a salt thereof; and B) at least one component selected from the group consisting of a decongestant, an eye muscle regulator, an anti-inflammatory agent other than pranoprofen or a salt thereof, an anti-histamine agent, vitamins, and amino acids.SELECTED DRAWING: None

Description

The present invention relates to ophthalmic compositions useful for ameliorating (including alleviating, treating, or preventing) various eye symptoms.

Blurred vision, itchy eyes, conjunctival congestion, blepharitis, eye inflammation caused by ultraviolet rays and other rays, discomfort when wearing contact lenses, and other eye discomfort, relieve eye fatigue, and prevent eye diseases. To this end, numerous ophthalmic compositions are commercially available and used.

These ophthalmic compositions are usually approved as active ingredients for over-the-counter ophthalmic agents, such as decongestants, ophthalmic muscle regulators, anti-inflammatory agents, antihistamines, vitamins, amino acids, and sulfa antibacterial agents. , Inorganic salts, high molecular weight thickeners, preservatives and other ingredients, and other additives are combined and blended.
However, although conventional ophthalmic compositions can alleviate or prevent various symptoms of the eye to some extent, it is often the case that only some of the symptoms can be sufficiently alleviated or prevented in practice. In addition, there are some eye symptoms that cannot be sufficiently alleviated or prevented by conventional ophthalmic compositions.
In particular, in recent years, it has become difficult to keep the eyes comfortable with conventional ophthalmic compositions due to the overuse of eyes due to the spread of personal computers, the spread of contact lenses, and the increase in scattering of antigenic substances.

An object of the present invention is to provide an ophthalmic composition which can broadly improve various symptoms or abnormalities of the eye and has a high improvement effect as compared with a conventional ophthalmic composition.

The present inventor has conducted repeated studies to solve the above problems, and contains at least one component selected from the group consisting of anticonjunctival agents, eye muscle regulators, anti-inflammatory agents, anti-histamine agents, vitamins, and amino acids. By adding pranoprofen and / or its pharmaceutically acceptable salt (hereinafter abbreviated as "salt") to the ophthalmic composition, eye strain, blurred vision, itchy eyes, conjunctival hyperemia, It was found that the effect of improving symptoms such as eye discomfort was widely and sufficiently achieved. It has also been found that the effect of improving (including alleviation, treatment, or prevention) of such symptoms or abnormalities is higher than that of conventional ophthalmic compositions.

The present invention has been completed based on the above findings, and provides the following ophthalmic compositions.
Item 1. At least one selected from the group consisting of (a) pranoprofen and its salts, and (b) decongestants, eye muscle regulators, anti-inflammatory agents other than pranoprofen or its salts, antihistamines, vitamins, and An ophthalmic composition for improving complex eye symptoms, which comprises at least one component selected from the group consisting of amino acids.
Item 2. (B) The composition according to Item 1, which contains a decongestant, an extraocular muscle regulator, an anti-inflammatory agent other than pranoprofen or a salt thereof, an antihistamine, vitamins, and amino acids.
Item 3. One or more compound eye symptoms selected from the group consisting of tired eyes, blurred vision, itchy eyes, conjunctival hyperemia, blepharitis, light-induced eye inflammation, foreign body sensation, swelling eyes, eye discomfort, and eye diseases. Item 2. The composition according to Item 1 or 2.
Item 4. Item 2. 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 a salt thereof is 0.001 to 1 w / v% with respect to the total amount of the composition. thing.
Item 5. Item 4. The composition according to any one of Items 1 to 4, further containing an antioxidant.

Since the ophthalmic composition of the present invention contains planoprofen and / or a salt thereof, eye fatigue, blurred vision such as when there are many eyes, itchy eyes, conjunctival congestion, eyelid inflammation (swelling of the eyelids), Eye discomfort due to ultraviolet rays or other rays (so-called snow eyes, etc.), foreign body sensation (rolling, tingling, etc.), slack eyes, discomfort when wearing contact lenses, and other eye discomfort, eye diseases (caused by swimming) The effects of alleviation, improvement, treatment, or prevention of eye diseases (eye diseases caused by getting dust or sweat into the eyes, etc.) are widely and sufficiently achieved.

Therefore, if the ophthalmic composition of the present invention is used, the condition of the eyes can be kept comfortable without using a plurality of ophthalmic compositions in combination. Therefore, the ophthalmic composition of the present invention is used for improving, alleviating, treating, or preventing general eye symptoms or abnormalities, improving, alleviating, treating, or preventing complex eye symptoms or abnormalities, for total eye care, or for general eye care. It can be a composition for chemical use. The ophthalmic composition of the present invention can also be a multifunctional composition for improving, alleviating, or preventing general eye symptoms.
Conditions with multiple symptoms or abnormalities of the eye may be more difficult to improve or prevent than conditions with a single symptomatology or abnormality. The ophthalmic composition of the present invention can effectively improve, alleviate, treat, or prevent those symptoms even in such a case.

In addition, the ophthalmic composition of the present invention includes eye fatigue, blurred vision when there are many eyes and eyes, itchy eyes, conjunctival congestion, eyelid inflammation, eye inflammation due to ultraviolet rays and other light rays, foreign body feeling, swelling eyes, contact lenses. It can also be used for improving, alleviating, treating, or preventing eye discomfort such as discomfort when wearing a lens, and one eye symptom or abnormality selected from eye diseases.

In addition, the ophthalmic composition of the present invention has a higher effect of improving, alleviating, treating, or preventing eye symptoms or abnormalities than conventional ophthalmic compositions.

Hereinafter, the present invention will be described in detail.
The ophthalmic composition of the present invention comprises (a) at least one selected from the group consisting of pranoprofen and salts thereof, (b) decongestants, eye muscle regulators, and (a) anti-inflammatory agents other than the components. It contains at least one component selected from the group consisting of antihistamines, vitamins, and amino acids.
The use of the ophthalmic composition of the present invention will be described later.

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

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, and 0.02 w, based on the total amount of the composition. / V% or more is even more preferable, and 0.03 w / v% or more is even more preferable. Further, it may be 0.04 w / v% or more, or 0.05 w / v% or more.
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, and 0.2 w, based on the total amount of the composition. / V% or less is even more preferable, and 0.1 w / v% or less is even more preferable. Further, it may 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%, 0.03 w / v%, 0.04 w / v%, 0.05 w / v%, and so on. Examples thereof include 0.06 w / v%, 0.07 w / v%, 0.08 w / v%, 0.09 w / v%, and 0.1 w / v%. 0.05 w / v% is particularly preferable.

Decongestant (component (b))
Decongestants cause eye anemia by constricting blood vessels, soothing local hyperemia, relieving pain and promoting tissue healing. For example, by stimulating α-adrenergic nerves, it has a vasoconstrictive effect, thereby contributing to the effects of the present invention.
The decongestant is, but is not limited to, ephedrine or a salt thereof (eg, ephedrine hydrochloride, ephedrine hydrogen tartrate), ephedrine or a salt thereof (eg, ephedrine hydrochloride), methylephedrine or a salt thereof (eg, methylephedrine hydrochloride, etc.). In particular, dl-methylephedrine hydrochloride), phenilephedrine or a salt thereof (eg, phenyleffrin hydrochloride), imidazoline-based vasoconstrictor [tetrahydrozoline or a salt thereof (eg, tetrahydrozoline hydrochloride), naphazoline or a salt thereof (eg, naphazoline hydrochloride, naphazoline nitrate). , Oxymethazoline or a salt thereof (for example, oxymethazoline hydrochloride)] and the like.
Among them, ephedrine or a salt thereof (particularly ephedrine 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), An imidazoline-based vasoconstrictor is preferable, an imidazoline-based vasoconstrictor is more preferable, tetrahydrozoline hydrochloride, naphazoline hydrochloride, and naphazoline nitrate are more preferable, and tetrahydrozoline hydrochloride is particularly preferable.
The decongestant can be used alone or in combination of two or more.

When the ophthalmic composition contains a decongestant, the total amount of the decongestant is 0.0006 w / v% or more, particularly 0.003 w / v% or more, based on the total amount of the composition. Among them, 0.01 w / v% or more, and above all, 0.02 w / v% or more can be mentioned. Further, it may be 0.03 w / v% or more, 0.04 w / v% or more, or 0.05 w / v% or more.
Further, the total amount of the decongestant with respect to the total amount of the composition is, for example, 0.2 w / v% or less, particularly 0.15 w / v% or less, particularly 0.1 w / v% or less, particularly 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%, 0.01 w / v%, 0.02 w / v%, 0.03 w / v%, 0.04 w /. Examples thereof include v% and 0.05 w / v%. 0.05 w / v% is particularly preferable.

Eye muscle regulator (component (b))
The eye muscle regulator stimulates the parasympathetic nerves of the iris sphincter muscle to constrict the pupil. For example, it contributes to the effect of the present invention by activating parasympathetic nerves by inhibiting cholinesterase, which has an active center similar to that of acetylcholine.
Eye muscle regulators include, but are not limited to, neostigmine or salts thereof (particularly neostigmine methylsulfate), physostigmine or salts thereof (eg, physostigmine salicylate, physostigmine sulfate), distigmine or salts thereof (eg, distigmine bromide), Examples thereof include tropicamide, atropine or a salt thereof (particularly, atropine helenien sulfate), pilocarpine or a salt thereof (for example, pilocarpine hydrochloride).
Of these, neostigmine or a salt thereof is preferable, and neostigmine methylsulfate is particularly preferable.
The eye muscle regulator may be used alone or in combination of two or more.

When the ophthalmic composition contains an eye muscle regulator, the total amount of the eye muscle regulator is, for example, 0.0002 w / v% or more, particularly 0.0005 w / v%, based on the total amount of the composition. Above all, 0.001 w / v% or more, and above all, 0.002 w / v% or more can be mentioned. Further, it may be 0.003 w / v% or more, 0.004 w / v% or more, or 0.005 w / v% or more.
Further, the total amount of the eye muscle regulator with respect to the total amount of the composition is, for example, 0.02 w / v% or less, particularly 0.01 w / v% or less, particularly 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 eye muscle regulator is preferably 0.001 to 0.005 w / v%, 0.001 w / v%, 0.002 w / v%, 0.003 w / v%, 0.004 w. / V%, 0.005 w / v% and the like can be mentioned. 0.005 w / v% is particularly preferable.

Anti-inflammatory agent (component (b))
The ophthalmic compositions of the present invention can include anti-inflammatory agents other than pranoprofen. The anti-inflammatory agent contributes to the effect of the present invention by suppressing inflammation or exerting an astringent action accordingly.
Anti-inflammatory agents other than planoprofen include, but are not limited to, epsilon-aminocaproic acid, allantin, berberine or salts thereof (eg, berberine chloride, berberine sulfate), azulene sulfonic acid or salts thereof. (For example, sodium azulene sulfonate, potassium azulene sulfonate, calcium azulene sulfonate, magnesium azulene sulfonate), glycyrrhizinic acid or a salt thereof (eg dipotassium glycyrrhizinate, monoammonium glycyrrhizinate), zinc salt (eg zinc sulfate) , Zinc lactate), lysoteam or a salt thereof (eg, lysoteam chloride), indomethacin, silver salt (eg, silver nitrate), diclofenacic acid or a salt thereof (eg, diclofenac sodium), bromufenacic acid or a salt thereof (eg, bromfenac sodium). ) And so on.
Among them, epsilon-aminocaproic acid, allantin, berberine or a salt thereof (particularly berberine chloride, berberine sulfate), azulene sulfonic acid or a salt thereof (particularly sodium azulene sulfonate), glycyrrhizinic acid or a salt thereof (particularly). In particular, dipotassium glycyrrhizinate), zinc salts (particularly zinc sulfate, zinc lactate), lysoteam or salts thereof (particularly lysoteam chloride) are preferable, and epsilon-aminocaproic acid and dipotassium glycyrrhizinate are more preferable.
The anti-inflammatory agent may be used alone or in combination of two or more.

When the ophthalmic composition contains an anti-inflammatory agent other than pranoprofen, the total amount of the anti-inflammatory agent other than pranoprofen is 0.0005 w / v% or more based on the total amount of the composition. , 0.005w / v% or more, 0.02w / v% or more, 0.1w / v% or more, 0.25w / v% or more, 0.3w / v% or more, 0.35w / v% or more, 0 .4 w / v% or more, 0.45 w / v% or more, or 0.5 w / v% or more.
The total amount of anti-inflammatory agents other than pranoprofen, for example, 10 w / v% or less, 2 w / v% or less, 1.5 w / v% or less, 1 w / v% or less, 0, based on the total amount of the composition. Examples include .5 w / v% or less, 0.25 w / v% or less, and 0.05 w / v% or less.
Within the above range, the effects of the present invention can be sufficiently obtained.
The total content of anti-inflammatory agents other than planoprofen is preferably 0.25 to 2 w / v%, 0.25 w / v%, 0.3 w / v%, 0.35 w / v%, 0. .4w / v%, 0.45w / v%, 0.5w / v%, 0.55w / v%, 0.6w / v%, 0.65w / v%, 0.7w / v%, 0. 75w / v%, 0.8w / v%, 0.85w / v%, 0.9w / v%, 0.95w / v%, 1w / v%, 1.05w / v%, 1.1w / v %, 1.15w / v%, 1.2w / v%, 1.25w / v%, 1.3w / v%, 1.35w / v%, 1.4w / v%, 1.45w / v% , 1.5w / v%, 1.55 / v%, 1.6w / v%, 1.65w / v%, 1.7w / v%, 1.75w / v%, 1.8w / v%, 1.85w / v%, 1.9w / v%, 1.95w / v%, 2w / v% and the like. 1.25 w / v% is particularly preferable.

Antihistamine (component (b))
The antihistamine contributes to the effect of the present invention by, for example, antagonizing the histamine receptor and suppressing the action of histamine.
Antihistamines include, but are not limited to, diphenhydramine or salts thereof (eg, diphenhydramine hydrochloride), chlorpheniramine or salts thereof (eg, chlorpheniramine maleate, chlorpheniramine fumarate), ketotifen or salts thereof (eg, chlorpheniramine fumarate). Ketotifen fumarate), olopatadine or a salt thereof (for example, olopatadine hydrochloride) and the like.
Among them, diphenhydramine or a salt thereof (particularly diphenhydramine hydrochloride), chlorpheniramine or a salt thereof (particularly chlorpheniramine maleate) are preferable, and chlorpheniramine maleate is more preferable.
The antihistamine can be used alone or in combination of two or more.

When the ophthalmic composition contains an antihistamine, the total amount of the antihistamine is, for example, 0.0006 w / v% or more, particularly 0.001 w / v% or more, and 0.006 w in particular, based on the total amount of the composition. / V% or more, especially 0.01 w / v% or more. Further, it may be 0.02 w / v% or more.
Further, the total amount of the antihistamine with respect 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%, 0.006 w / v%, 0.008 w / v%, 0.01 w / v%, 0.015 w / v%. , 0.02 w / v%, 0.03 w / v%, 0.05 w / v% and the like. 0.03 w / v% is particularly preferable.

Vitamins ((b) component)
Vitamins, in very small amounts, play a major role in the metabolic function of the body. For example, it contributes to the effect of the present invention by functioning as a coenzyme or by an antioxidant action.
Vitamins include, but are not limited to, flavin adenin dinucleotide or salts thereof (eg, flavin adenin dinucleotide sodium), cobalamine or salts thereof (eg, cyanocobalamin, methylcobalamin), retinol, derivatives thereof and / or theirs. Salts (eg, retinol acetate, retinol palmitate), pyridoxine or salts thereof (eg, pyridoxine hydrochloride), pantenol, pantothenic acid or salts thereof (eg, sodium pantothenate, potassium pantothenate, calcium pantothenate, magnesium pantothenate) , Tocopherols, derivatives thereof and / or salts thereof (eg tocopherol acetate, tocopherol succinate, tocopherol nicotinate), pyridoxal or salts thereof (eg pyridoxal phosphate), ascorbic acid or salts thereof (eg sodium ascorbate, ascorbate). Calcium acidate) and the like.
Among them, flavin adenin dinucleotide or a salt thereof (particularly flavin adenin dinucleotide sodium), cobalamine or a salt thereof (particularly cyanocobalamin), retinol, a derivative thereof and / or a salt thereof (particularly retinol acetate, retinol palmitate), Pyridoxine or salts thereof (particularly pyridoxine hydrochloride), pantenol, pantothenic acid or salts thereof (particularly sodium pantothenate, calcium pantothenate), tocopherols, derivatives thereof and / or salts thereof (particularly tocopherol acetate) are preferred. Pyridoxine hydrochloride and tocopherol acetate are more preferable.
One type of vitamins can be used alone, or two or more types can be used in combination.

When the ophthalmic composition contains vitamins (vitamins other than retinol, its derivatives and / or salts thereof), the content thereof is, for example, 0. 0002w / v% or more, in particular 0.002w / v% or more, in particular 0.005w / v% or more, in particular 0.01w / v%, in particular 0.03w / v% or more. Further, it may be 0.04 w / v% or more, or 0.05 w / v% or more.
Further, the total amount of these vitamins, 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. 6w / v% or less, 0.5w / v% or less, 0.4w / v% or less, 0.3w / v% or less, 0.2w / v% or less, 0.1w / v% or less, 0.09w / Examples thereof include 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 total amount of retinol, a derivative thereof and / or a salt thereof is, for example, 500 units / unit, based on the total amount of the composition. Examples include 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, and 10000 units / 100 mL or more.
In addition, the total amount of retinol, its derivatives and / or salts thereof with respect to the total amount of the composition is, 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, Examples thereof include 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, and 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 mean compounds or derivatives thereof having an amino group and a carboxyl group or a sulfo group in the molecule, and contribute to the effect of the present invention by metabolizing cells and repairing damaged tissues.
Amino acids include, but are not limited to, L-aspartic acid or salts thereof (eg, potassium L-aspartate, sodium L-aspartate, magnesium L-aspartate, calcium L-aspartate, magnesium L-aspartate). Potassium (equal mixture of magnesium L-aspartate and potassium L-aspartate), aminoethylsulfonic acid (taurine), sodium chondroitin sulfate, glutamate or a salt thereof (eg, sodium glutamate, magnesium glutamate), creatinine, Examples thereof include glycine, alanine, arginine, lysine, γ-aminobutyric acid, γ-aminovaleric acid, hyaluronic acid or a salt thereof (for example, sodium hyaluronate), aspartic acid or a salt thereof (for example, sodium alginate).
Aminoethyl sulfonic acid is a compound similar to an amino acid synthesized from a sulfur-containing amino acid, and is included in amino acids in the field of ophthalmic compositions, particularly in the field of ophthalmic compositions as over-the-counter drugs. In addition, sodium chondroitin sulfate is also included in amino acids in the field of ophthalmic compositions, particularly in the field of ophthalmic compositions as over-the-counter drugs.
Among them, L-aspartic acid or a salt thereof (particularly, potassium L-aspartate, magnesium L-aspartate, magnesium / potassium L-aspartate (equal mixture of magnesium L-aspartate and potassium L-aspartate)) , Aminoethyl sulfonic acid (taurine), sodium chondroitin sulfate is preferable, and potassium L-aspartate, aminoethyl sulfonic acid, sodium chondroitin sulfate is more preferable.
Amino acids may be used alone or in combination of two or more.

When the ophthalmic composition contains amino acids, the total amount of amino acids is, for example, 0.005 w / v% or more, 0.05 w / v% or more, 0.1 w with respect to the total amount of the composition. / 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.
In addition, the total amount of amino acids, 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 with respect to the total amount of the composition. % 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. Be done.

Total content of component (b) The total content of component (b) in the ophthalmic composition is, for example, 0.0002 w / v% or more, particularly 0.0006 w / v% or more, based on the total amount of the composition. Among them, 0.0007w / v% or more, especially 0.0008w / v% or more, especially 0.0009w / v% or more, especially 0.001w / v% or more, especially 0.002w / v% or more, especially 0.003w / V% or more, especially 0.004 w / v% or more, especially 0.005 w / v% or more, especially 0.006 w / v% or more, especially 0.01 w / v% or more, especially 0.05 w / v% or more, especially 0.1 w / v% or more, particularly 0.2 w / v% or more, and 1 w / v% or more in particular.
Further, with respect to the total amount of the composition, for example, 10 w / v% or less, especially 5 w / v% or less, especially 3 w / v% or less, especially 2 w / v% or less, especially 1 w / v% or less, especially 0.7 w / V% or less, especially 0.5 w / v% or less, especially 0.25 w / v% or less, especially 0.1 w / v% or less, especially 0.05 w / v% or less, especially 0.03 w / v% or less, among others 0.005 w / v% or less can be mentioned.
Within the above range, the effects of the present invention can be sufficiently obtained.

The ratio of the total content of the component (b) to the component (a) is, for example, 0.002 parts by weight or more, particularly 0.05 parts by weight or more, particularly 0, with respect to 1 part by weight of the component (a). 0.01 parts by weight or more, especially 0.05 parts by weight or more, especially 0.1 parts by weight or more, especially 0.2 parts by weight or more, especially 0.5 parts by weight or more, especially 1 part by weight or more, especially 5 parts by weight or more, Among them, 20 parts by weight or more can be mentioned.
Further, for 1 part by weight of the component (a), for example, 200 parts by weight or less, particularly 100 parts by weight or less, particularly 50 parts by weight or less, particularly 20 parts by weight or less, particularly 10 parts by weight or less, particularly 5 parts by weight or less, Among them, 2 parts by weight or less, particularly 1 part by weight or less, especially 0.6 parts by weight or less, particularly 0.1 part by weight or less can be mentioned.
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 a component having pharmacological activity or physiological activity.
The pharmacologically active ingredient or the physiologically active ingredient may be used alone or in combination of two or more.
Specific examples of the pharmacologically active ingredient or the physiologically active ingredient are illustrated below. The pharmacologically active ingredient or the physiologically active ingredient can be blended as either an active ingredient or an additive.

Antibacterial Ingredients The ophthalmic compositions of the present invention can further include antibacterial ingredients.
Antibacterial components include, but are not limited to, sulfamethoxazole or salts thereof (eg, sulfamethoxazole sodium, sulfamethoxazole potassium, sulfamethoxazole calcium, sulfamethoxazole magnesium). , Sulfa-based antibacterial agents such as sulfasoxazole, sulfisomidin or salts thereof (eg, sodium sulfisomidine, potassium sulfisomidin, calcium sulfisomidine, magnesium sulfisomidin), alkylpolyaminoethylglycine. , Chloramphenicol, ofloxacin, norfloxacin, levofloxacin, lomefloxacin hydrochloride, acyclovir and the like.
Among them, sulfamethoxazole or a salt thereof (particularly, sulfamethoxazole sodium), sulfamethoxazole, sulfisomidine or a salt thereof (particularly, sodium sulfisomidine), a sulfa antibacterial agent, alkylpolyamino. Ethylglycine is preferred, and sulfamethoxazole sodium is 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 total amount of the antibacterial component is, for example, 0.001 w / v% or more, particularly 0.005 w / v% or more, particularly 0, based on the total amount of the composition. .01 w / v% or more, especially 0.05 w / v% or more, especially 0.1 w / v% or more, especially 0.5 w / v% or more, especially 1 w / v% or more, especially 2 w / v% or more. .. Further, it may be 3 w / v% or more.
Further, the total amount of the antibacterial component with respect to the total amount of the composition is, for example, 5 w / v% or less, particularly 4 w / v% or less. Further, it may be 3 w / v% or less.
The total content of antibacterial components is 1w / v%, 1.5w / v%, 2w / v%, 2.5w / v%, 3w / v%, 3.5w / v%, 4w / v%, Examples include 4.5 w / v% and 5 w / v%.

Anti-allergic agents The ophthalmic compositions of the present invention can further include anti-allergic agents.
Antiallergic agents include, but are not limited to, cromoglycic acid or salts thereof (eg, sodium cromoglycate, potassium cromoglycate, calcium cromoglycate, magnesium cromoglycate), acitazanolast, amlexanox, ibudilast, tranilast, pemirolast. Examples include potassium.
Among them, cromoglycic acid or a salt thereof (particularly sodium cromoglycate) is preferable, and sodium cromoglycate is more preferable.
The antiallergic drug may be used alone or in combination of two or more.

When the ophthalmic composition contains an antiallergic drug, the total amount of the antiallergic drug is, for example, 0.01 w / v% or more, 0.05 w / v% or more, 0, based on the total amount of the composition. .1w / v% or more, 0.2w / v% or more, 0.3w / v% or more, 0.4w / v% or more, 0.5w / v% or more, 0.6w / v% or more, 0.7w / V% or more, 0.8 w / v% or more, 0.9 w / v% or more can be mentioned.
Further, the total amount of the antiallergic agent, 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, based on the total amount of the composition. 1.8w / v% or less, 1.7w / v% or less, 1.6w / v% or less, 1.5w / v% or less, 1.4w / v% or less, 1.3w / v% or less, 1. Examples thereof include 2 w / v% or less, 1.1 w / v% or less, and 1 w / v% or less.
The total content of antiallergic agents is 0.01w / v%, 0.05w / v% 0.1w / v%, 0.2w / v%, 0.3w / v%, 0.4w / v%. , 0.5w / v%, 0.6w / v%, 0.7w / v%, 0.8w / v%, 0.9w / v%, 1w / v%, 1.1 / v%, 1. 2w / v%, 1.3w / v%, 1.4w / v%, w / v%, 1.5w / v%, 1.6w / v%, 1.7w / v%, 1.8w / v %, 1.9w / v%, 2w / v%, 3w / v%, 4w / v% and the like.

Antioxidants The ophthalmic compositions of the present invention can contain antioxidants. Antioxidants stabilize pranoprofen and component (b), which are unstable to heat and light. The antioxidant significantly improves the effect of the present invention by improving the residual rate of pranoprofen and other medicinal ingredients contained in the ophthalmic composition and maintaining their medicinal effects high.
Fat-soluble antioxidants include butyl group-containing phenols such as dibutylhydroxytoluene (BHT) and butylhydroxyanisole (BHA); nordihydroguayaletic acid (NDGA); palmitate ascorbic acid, stearate ascorbic acid, ascorbin. Ascorbic acid esters such as aminopropyl acid phosphate, tocopherol ascorbate, triphosphate ascorbate, palmitate ascorbate; gallic acid esters such as ethyl cartic acid, propyl carpentate, octyl carnivorate, dodecyl carnivorate Propyl gallate; 3-butyl-4-hydroxyquinolin-2 on; carotenoids such as lutein and astaxanthin; polyphenols such as anthocyanins, catechins, tannins and curcumin; CoQ10 and the like.
In addition, as water-soluble antioxidants, ascorbic acid, ascorbic acid derivative (2 sodium ascorbic acid-2-sulfite, sodium ascorbate, magnesium ascorbic acid-2-phosphate, sodium ascorbic acid-2-phosphate, etc.) , Sodium hydrogen sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfite, edetonic acid or a salt thereof (sodium edetate, disodium edetate, tetrasodium edetate) and the like.
As the antioxidant, among the fat-soluble antioxidants, butyl group-containing phenol (particularly, dibutylhydroxytoluene and butylhydroxyanisole) is preferable, and dibutylhydroxytoluene is more preferable. Among the water-soluble antioxidants, edetic acid or a salt thereof (particularly sodium edetate) is preferable, and sodium edetate is more preferable. It is also preferable to use a fat-soluble antioxidant and a water-soluble antioxidant in combination, and a combination of dibutylhydroxytoluene and sodium edetate is more preferable.
One type of antioxidant may be used alone, or two or more types may be used in combination.

When the ophthalmic composition contains an antioxidant, the total amount of the antioxidant is 0.0001 w / v% or more, 0.0005 w / v% or more, and 0. Examples thereof include 001 w / v% or more, 0.002 w / v% or more, 0.003 w / v% or more, 0.004 w / v% or more, and 0.005 w / v% or more. Further, the total amount of the antioxidant is 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 with respect to the total amount of the composition. / 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, 0.005 w / v% or less.
The total content of the antioxidant is 0.0001 w / v%, 0.0005 w / v%, 0.001 w / v%, 0.002 w / v%, 0.003 w / relative to the total amount of the composition. v%, 0.004w / v%, 0.005w / v%, 0.006w / v%, 0.007w / v%, 0.008w / v%, 0.009w / v%, 0.01w / v %, 0.02 w / v%, 0.03 w / v%, 0.04 w / v%, 0.05 w / v%, 0.1 w / v%, 1 w / v% and the like.

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 painkillers such as procaine hydrochloride.

Among the components of the ophthalmic composition of the present invention, any of the d-form, l-form, or dl-form can be used as the component in which the d-form, l-form, or dl-form is present. Further, as the component having a hydrate, a hydrate can also be used.

The properties of the pharmaceutical ophthalmic composition are not particularly limited, and may be any properties such as liquid, fluid, gel, or semi-solid. In addition, those which have become liquid, fluid, gel, or semi-solid by preparation at the time of use are also included. The semi-solid state refers to a property having plasticity that can be deformed by applying a force, such as an ointment.

Further, the ophthalmic composition may be an aqueous composition (mainly containing an aqueous or hydrophilic composition as a base or carrier), and an oily composition (mainly an oily or hydrophobic composition as a base or carrier). Included in).
The water content in the case of the aqueous composition is preferably 50% by weight or more, more preferably 75% by weight or more, still more preferably 90% by weight or more, based on the total amount of the preparation. Further, it may be 95% by weight or more, or 98% by weight or more. Further, the base or carrier may consist only of water.
The water content of the oily composition is preferably less than 50% by weight, more preferably 30% by weight or less, still more preferably 20% by weight or less, based on the total amount of the preparation.
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 for example, an eye drop (also referred to as an eye drop or an eye drop; the eye drop includes an eye drop that can be instilled while wearing a contact lens), an eye wash. , Eye ointment (water-soluble eye ointment, oil-soluble eye ointment), contact lens wearing solution, intraocular injection (for example, intravital injection), contact lens solution (cleaning solution, preservative solution, disinfectant solution, multipurpose solution, Package solutions), preservatives for excised eye drops such as corneum for transplantation, perfusate during surgery, etc. Eye drops, eye wash agents, and eye ointments include those used when wearing contact lenses.
As the dosage form of the ophthalmic composition of the present invention, preferably, eye drops, eye wash agents, eye ointments (water-soluble eye ointments, oil-soluble eye ointments), contact lens wearing solutions, contact lens solutions (cleaning solutions, preservative solutions, disinfectants). Liquids, multi-purpose solutions, package solutions), and more preferably eye drops, eye wash agents, contact lens wearing liquids, contact lens liquids (cleaning liquids, preservatives, disinfectants, multi-purpose solutions, package solutions), etc. Examples thereof include eye drops and eye wash agents, and particularly preferably eye drops.

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

The ophthalmic composition of the present invention contains the above components (a) and (b) as a pharmaceutically acceptable base or carrier, and if necessary, a pharmaceutically acceptable additive for the ophthalmic composition or the like. By mixing with the active ingredient of, for example, it can be prepared by the conventional method described in the 16th revised Japanese Pharmacopoeia manual.

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

The ophthalmic composition of the present invention can be blended without limitation with those used as additives for the ophthalmic composition. Examples of the additive include a cooling 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.
As the additive, one type can be used alone, or two or more types can be used in combination. In addition, for each additive, one type can be used alone, or two or more types can be used in combination.
Specific examples of additives are illustrated below.

Cooling Agent The ophthalmic composition of the present invention may contain a refreshing agent.
Examples of the refreshing agent include, but are not limited to, terpenoids such as menthol, anethole, eugenol, camphor, geraniol, cineole, borneol, limonene, and ryuno. These may be d-form, l-form or dl-form. In addition, essential oils such as peppermint oil, cool mint oil, sparemint oil, peppermint oil, uikyo oil, kehi oil, bergamot oil, eucalyptus oil, and rose oil can also be mentioned.
Among them, terpenoids are preferable, among them, menthol, camphor, geraniol, cineol, borneol and ryuno are preferable, menthol, camphor and borneol are more preferable, and menthol is further preferable.
The refreshing agent may be used alone or in combination of two or more.

When the ophthalmic composition contains a refreshing agent, the total amount of the refreshing agent is, for example, 0.0001 w / v% or more, 0.0005 w / v% or more, based on the total amount of the composition. 0.001w / v% or more, 0.002w / v% or more, 0.003w / v% or more, 0.004w / v% or more, 0.005w / v% or more, 0.006w / v% or more, 0. 007w / v% or more, 0.008w / v% or more, 0.009w / v% or more, 0.01w / v% or more can be mentioned.
In addition, the total amount of the cooling agent is 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 with respect to the total amount of the composition. / 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, 0.02 w / v% or less.
The total content of the refreshing agent is 0.0001 w / v%, 0.0005%, 0.001 w / v%, 0.002 w / v%, 0.003 w / v% with respect to the total amount of the composition. , 0.004w / v%, 0.005w / v%, 0.006w / v%, 0.007w / v%, 0.008w / v%, 0.009w / v%, 0.01w / v%, 0.011w / v%, 0.012w / v%, 0.013w / v%, 0.014w / v%, 0.015w / v%, 0.016w / v%, 0.017w / v%, 0 .018w / v%, 0.019w / v%, 0.02w / v%, 0.03w / v%, 0.04w / v%, 0.05w / v%, 0.06w / v%, 0. Examples thereof include 07w / v%, 0.08w / v%, 0.09w / v%, 0.1w / v%, 1w / v% and the like.

Inorganic Salts The ophthalmic compositions of the present invention can further include inorganic salts.
Inorganic salts include, but are not limited to, potassium chloride, sodium chloride, calcium chloride, magnesium chloride, sodium hydrogen carbonate, sodium carbonate (including dry sodium carbonate), potassium hydrogen carbonate, potassium carbonate, magnesium sulfate, hydrogen phosphate. Sodium, potassium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, sodium hydrogen sulfite, sodium sulfite, potassium acetate, sodium acetate, sodium thiosulfate, etc. Be done.
Among them, potassium chloride, sodium chloride, calcium chloride, sodium hydrogen carbonate, sodium carbonate (including dry sodium carbonate), magnesium sulfate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate are preferable, and potassium chloride, Sodium chloride, calcium chloride, sodium hydrogen phosphate, and monosodium dihydrogen phosphate are more preferable, and potassium chloride and sodium chloride are even more preferable.
Inorganic salts may be used alone or in combination of two or more.

When the ophthalmic composition contains inorganic salts, the total amount of the inorganic salts is, for example, 0.05 w / v% or more, 0.1 w / v% or more, 0.2 w with respect to the total amount of the composition. / V% or more, 0.3 w / v% or more, 0.4 w / v% or more, 0.5 w / v% or more.
Further, the total amount of inorganic salts, 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, based on the total amount of the composition. , 0.7 w / v% or less, 0.6 w / v% or less, 0.5 w / v% or less.
The total content of the inorganic salts is 0.05 w / v%, 0.1 w / v%, 0.2 w / v%, 0.3 w / v%, 0.4 w / v with respect to the total amount of the composition. %, 0.5w / v%, 0.6w / v%, 0.7w / v%, 0.8w / v%, 0.9w / v%, 1w / v%, 2w / v%, 3w / v % And so on.

Polymer Viscosants or Thickeners The ophthalmic compositions of the present invention can further include polymeric thickeners or thickeners.
The polymer thickener or thickener is not limited to that, but is limited to cellulose derivatives (for example, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, carboxyethyl cellulose, carboxymethyl cellulose), polyvinyl-based. High molecular weight compounds (eg, polyvinyl alcohol (including fully or partially saponified products), polyvinylpyrrolidone, polyvinyl methacrylate), polyethylene glycol, dextran, α-cyclodextrin, dextrin, carboxyvinyl polymer, alginic acid, glucose, mucopolysaccharide (eg, alginic acid, glucose, mucopolysaccharide) For example, hyaluronic acid, hyaluronate (eg, sodium hyaluronate), heparin, heparin sulfate, heparan sulfate, keratosulfate, heparinoid), guar gum, arabic gum, karaya gum, xanthan gum, agar, starch, chitin and its derivatives, chitosan. And its derivatives, carrageenan, sorbitol, alkali metal salts of polyacrylic acid (eg, sodium polyacrylate, potassium polyacrylate), amine salts of polyacrylic acid (eg, polyacrylic acid monoethanolamine salt, polyacrylic acid diethanolamine) Salt, polyacrylate triethanolamine salt), casein, gelatin, collagen, pectin, elastin, ceramide, liquid paraffin, glycerin, macrogol, polyethyleneimine alginate (eg sodium alginate), alginate ester (eg propylene glycol alginate) Esther), tragant powder, etc.
In addition to the above-exemplified examples, these components may be salts (for example, sodium salt, potassium salt, calcium salt, magnesium salt).
Among them, cellulose derivatives (particularly hydroxyethyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose), polyvinyl alcohol (including completely or partially saponified products), polyvinylpyrrolidone, carboxyvinyl polymer, alginic acid, and glucose are preferable, and hydroxyethyl cellulose, hydroxypropyl methyl cellulose, Carboxyvinyl polymers are more preferred, and hydroxypropylmethyl celluloses are even more preferred.
The polymer thickener or thickener may be used alone or in combination of two or more.

When the ophthalmic composition contains a polymer thickener or a thickener, the content thereof is, for example, 0.001 w / v, which is the total amount of the polymer thickener or the thickener with respect to the total amount of the composition. % 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, 0.1 w / v% or more.
Further, the total amount of the polymer thickener or thickener, for example, 5 w / v% or less, 1 w / v% or less, 0.9 w / v% or less, 0.8 w / v% with respect to the total amount of the composition. Below, 0.7w / v% or less, 0.6w / v% or less, 0.5w / v% or less, 0.4w / v% or less, 0.3w / v% or less, 0.2w / v% or less, 0.1 w / v% or less can be mentioned.
The total content of the polymer thickener or thickener is 0.001 w / v%, 0.01 w / v%, 0.02 w / v%, 0.03 w / v with respect to the total amount of the composition. %, 0.04w / v%, 0.05w / v%, 0.06w / v%, 0.07w / v%, 0.08w / v%, 0.09w / v%, 0.1w / v% , 0.2w / v%, 0.3w / v%, 0.4w / v%, 0.5w / v%, 0.6w / v%, 0.7w / v%, 0.8w / v%, 0.9w / v%, 1w / v%, 2w / v%, 3w / v%, 4w / v%, 5w / v% and the like can be mentioned.

Preservatives The ophthalmic compositions of the present invention can further include preservatives.
Preservatives include, but are not limited to, boric acid, alkyldiaminoethylglycine and / or salts thereof (eg, alkyldiaminoethylglycine hydrochloride), benzoic acid and / or salts thereof (eg, sodium benzoate, potassium benzoate). ), Ethanol, quaternary ammonium salts (eg, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride), chlorhexidine and / or salts thereof (eg, chlorhexidine gluconate), chlorobutanol, sorbic acid and / or salts thereof (eg). For example, potassium sorbate), sodium dehydroacetate, paraoxybenzoic acid ester (eg, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate), oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, poly Examples thereof include bigamides such as hexamethylene biguanide and salts thereof (polyhexanide hydrochloride, etc.), glokill (trade name, Rhodia), polydronium chloride and the like.
Among them, boric acid, quaternary ammonium salts (particularly benzalkonium chloride, benzethonium chloride), chlorhexidine and / or salts thereof (particularly chlorhexidine gluconate), chlorobutanol, sorbic acid and / or salts thereof (eg, sorbin). Potassium acid), polyhexanide biguanide and salts thereof are preferred, alkylpolyaminoethylglycine, benzalkonium chloride, chlorhexidine gluconate, chlorobutanol, potassium sorbate, polyhexanide hydrochloride are more preferred, benzalkonium chloride, chlorobutanol, hydrochloric acid. Polyhexanide is more preferred.
The preservatives can be used alone or in combination of two or more.

When the ophthalmic composition contains a preservative, the total amount of the preservative is, for example, 0.00001 w / v% or more, 0.0001 w / v% or more, 0.0002 w with respect to the total amount of the composition. / V% or more, 0.0003w / v% or more, 0.0004w / v% or more, 0.0005w / v% or more, 0.0006w / v% or more, 0.0007w / v% or more, 0.0008w / v % Or more, 0.0009 w / v% or more, 0.001 w / v% or more.
Further, the total amount of the preservative is, 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 with respect to the total amount of the composition. 0.01w / v% or less, 0.009w / v% or less, 0.008w / v% or less, 0.007w / v% or less, 0.006w / v% or less, 0.005w / v% or less, 0.004w / V% or less, 0.003 w / v% or less, 0.002 w / v% or less, 0.001 w / v% or less.
The total content of the preservative is 0.00001w / v%, 0.0001w / v%, 0.0002w / v%, 0.0003w / v%, 0.0004w / v with respect to the total amount of the composition. %, 0.0005w / v%, 0.0006w / v%, 0.0007w / v%, 0.0008w / v%, 0.0009w / v%, 0.001w / v%, 0.002w / v% , 0.003w / v%, 0.004w / v%, 0.005w / v%, 0.006w / v%, 0.007w / v%, 0.008w / v%, 0.009w / v%, Examples thereof include 0.01 w / v%, 0.05 w / v%, 0.1 w / v%, 0.2 w / v%, 0.5 w / v% and the like.

Surfactants The ophthalmic compositions of the present invention can include surfactants.
Of the surfactants, nonionic surfactants are preferred.
Nonionic surfactants include monolauric acid POE (20) sorbitan (polysorbate 20), monopalmitate POE (20) sorbitan (polysolvate 40), monostearate POE (20) sorbitan (polysorbate 60), tristearate POE. (20) POE sorbitan fatty acid esters such as sorbitan (polysolvate 65) and monooleic acid POE (20) sorbitan (polysolvate 80); POP glycols; POE hardened castor oil 40, POE hardened castor oil 50, POE cured castor oil 60, POE cured castor oil 80, etc. POE cured castor oil; POE castor oil 3, POE castor oil 4, POE castor oil 6, POE POE castor oil such as 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, POE castor oil 50, etc. Polyethylene glycol monostearate (2EO), polyethylene glycol monostearate (4EO), polyethylene glycol monostearate (9EO), polyethylene glycol monostearate (10EO), mono Polyethylene Glycol Stearate (23EO), Polyethylene Glycol Monostearate (25EO), Polyethylene Glycol Monostearate (32EO), Polyethylene Glycol Monostearate (40EO, Polyoxyl 40 Stearate) ), Polyethylene glycol monostearate (45EO), Polyethylene glycol monostearate (55EO), Polyethylene glycol monostearate (75EO), Polyethylene glycol monostearate (140EO), etc. Polyethylene glycol monostearate; POE alkyl ethers such as POE (9) lauryl ether; POE-POP alkyl ethers such as POE (20) POP (4) cetyl ether; POE alkyl such as POE (10) nonylphenyl ether Examples include phenyl ethers. In the above-exemplified compounds, POE indicates polyoxyethylene, POP indicates polyoxypropylene, and the numbers in parentheses indicate the number of added moles.

Among them, non-ionic POE sorbitan fatty acid esters; POE / POP glycols; POE-cured castor oil; POE castor oil and polyethylene glycol monostearate are preferable, and polysorbate 80, porox summer 407, POE-cured castor oil 40, and POE-cured castor oil 60 are preferable. , POE castor oil 3, POE castor oil 10, POE castor oil 35, polyoxyl 40 stearate are more preferred, polysorbate 80, POE hardened castor oil 60 are even more preferred, and polysorbate 80 is particularly preferred.

Other amphoteric surfactants such as betaine-type amphoteric surfactants (eg, betaine lauryldimethylaminoacetate, imidazolinium betaine); such as alkyl quaternary ammonium salts (eg, benzalkonium chloride, benzethonium chloride). Cationic surfactants and the like can also be used.
One type of surfactant may be used alone, or two or more types may be used in combination.

When the ophthalmic composition of the present invention contains a surfactant, the total amount of the surfactant is, for example, 0.001 w / v% or more, particularly 0.005 w / /, based on the total amount of the composition. V% or more, particularly 0.01 w / v% or more, particularly 0.05 w / v% or more. Further, it may be 0.1 w / v% or more, 0.2 w / v% or more, 0.3 w / v% or more.
Further, the total amount of the surfactant with respect to the total amount of the composition is, for example, 5 w / v% or less, particularly 1 w / v% or less, particularly 0.5 w / v% or less, particularly 0.3 w / v% or less. Be done. Further, it may be 0.2 w / v% or less, 0.1 w / v% or less, and 0.05 w / v% or less.
The total content of the surfactant is 0.001 w / v%, 0.005 w / v%, 0.01 w / v%, 0.05 w / v%, 0.1 w / relative to the total amount of the composition. Examples thereof include v%, 0.2w / v%, 0.3w / v%, 0.5w / v%, 1w / v%, 5w / v% and the like.

Buffering Agent The ophthalmic composition of the present invention can contain a buffering agent.
Examples of the buffer include boric acid buffer, phosphoric acid buffer, carbonic acid buffer, citric acid buffer, acetate buffer and the like.
Examples of the components of the boric acid buffer include boric acid and borate (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.). The borate may be a hydrate.
Phosphate, phosphate (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, as components of the phosphate buffer (Calcium dihydrogen phosphate, etc.) and the like. The phosphate may be a hydrate.
Examples of the components of the carbonic acid buffer include carbonic acid and carbonates (potassium carbonate, sodium carbonate, calcium carbonate, potassium hydrogencarbonate, sodium hydrogencarbonate, magnesium carbonate, etc.).
Examples of the component of the citric acid buffer include citric acid and citrate (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.).
Examples of the components of the acetate buffer include acetic acid and acetates (ammonium acetate, potassium acetate, calcium acetate, sodium acetate, etc.).
Among them, a boric acid buffer and a phosphate buffer are preferable, and a boric acid buffer is more preferable, in that the effect of the present invention is further improved. As the boric acid buffer, a combination of boric acid and its salt is preferable, a combination of boric acid and an alkali metal salt of boric acid and / or an alkaline earth metal salt is more preferable, and a combination of boric acid and an alkali metal of boric acid is more preferable. The combination with salt is even more preferable, and the combination of boric acid and boric acid is even more preferable.
The buffer may be used alone or in combination of two or more.

When the ophthalmic composition of the present invention contains a buffer, the content thereof varies depending on the type of the buffer, the type and amount of other compounding components, and the like, and cannot be uniformly defined. The total amount of the buffering agent is 0.001 w / v% or more, particularly 0.01 w / v% or more, particularly 0.05 w / v% or more, and 0.1 w / v% or more in particular with respect to the total amount of the buffer. The total amount of the buffer is 10 w / v% or less, particularly 5 w / v% or less, particularly 3 w / v% or less, and 2 w / v% or less, based on the total amount of the composition.
The total content of the buffer is 0.001 w / v%, 0.01 w / v%, 0.05 w / v%, 0.1 w / v%, 0.5 w / v with respect to the total amount of the composition. %, 1w / v%, 2w / v%, 3w / v%, 5w / v%, 10w / v% and the like.

pH regulator The ophthalmic composition of the present invention can include a pH regulator.
Acidity regulators include hydrochloric acid, sulfuric acid, polyphosphate, organic acids (propionic acid, oxalic acid, gluconic acid, fumaric acid, lactic acid, tartaric acid, malic acid, succinic acid, etc.), sodium hydroxide, potassium hydroxide, hydroxide. Calcium, magnesium hydroxide, triethanolamine, monoethanolamine, diisopropanolamine and the like can be mentioned.

Isotonic Agent The ophthalmic composition of the present invention can contain an isotonic agent. Some of the above-exemplified inorganic salts are blended as isotonic agents.
Examples of the tonicity agent include sodium chloride, potassium chloride, calcium chloride, magnesium chloride, potassium acetate, sodium acetate, magnesium sulfate, glycerin, propylene glycol and the like.
Stabilizer Stabilizers include tromethamole, sodium formaldehyde sulfoxylate (longalit), monoethanolamine, aluminum monostearate, glycerin monostearate and the like.

Oils The ophthalmic compositions of the present invention may contain oils. Examples of the oil include animal oils such as squalane, liquid paraffin, mineral oils such as petrolatum, castor oil, and vegetable oils such as sesame oil.

Sugars The ophthalmic compositions of the present invention can contain sugars. Examples of the saccharide include monosaccharides and disaccharides, specifically glucose, maltose, trehalose, sucrose, cyclodextrin, xylitol, sorbitol, mannitol and the like. Some saccharides are compounded as polymer thickeners.

Polyhydric Alcohols The ophthalmic compositions of the present invention can include polyhydric alcohols. Examples of the polyhydric alcohol include polyethylene glycol, glycerin, propylene glycol, xylitol, diethylene glycol, mannitol, sorbitol, polyvinyl alcohol and the like. Some polyhydric alcohols are compounded as polymer thickeners.

Specific combinations of components that can be incorporated into the ophthalmic composition of the present invention are illustrated below. These combinations mean that those components are contained at a minimum, and various components can be included in addition to the indicated components.

(1) Pranoprofen, tetrahydrozoline hydrochloride, neostigmine methylsulfate, dipotassium glycyrrhizinate, chlorpheniramine maleate, pyridoxine hydrochloride, and potassium L-aspartate
(2) In (1), instead of potassium L-aspartate, aminoethyl sulfonic acid, chondroitin sulfate, potassium L-aspartate and aminoethyl sulfonic acid, potassium L-aspartate and chondroitin sulfate, or aminoethyl sulfonic acid. And a combination containing chondroitin sulfate
(3) In (1) or (2), instead of pyridoxin hydrochloride, tocopherol acetate, pantenol, cyanocobalamine, flavin adenine dinucleotide, pyridoxin hydrochloride and tocopherol acetate, pyridoxin hydrochloride and pantenol, pyridoxin hydrochloride and cyanocobalamine, pyridoxin hydrochloride And flavin adenin dinucleotide, tocopherol acetate and pantenol, tocopherol acetate and cyanocobalamine, tocopherol acetate and flavin adenin dinucleotide, pantenol and cyanocobalamine, pantenol and flavin adenin dinucleotide, cyanocopherol and flavin adenin dinucleotide, pyridoxin hydrochloride and tocopherol acetate. And pantenol, pyridoxin hydrochloride and tocopherol acetate and cyanocobalamine, pyridoxin hydrochloride and tocopherol acetate and flavin adenine dinucleotide, tocopherol acetate and pantenol and cyanocobalamine, tocopherol acetate and pantenol and flavin adenine dinucleotide, pantenol, cyanocopherol, flavin adenindi Nucleotides, pyridoxin hydrochloride and tocopherol acetate and pantenol and cyanocobalamine, pyridoxin hydrochloride and tocopherol acetate and pantenol and flavin adenine dinucleotide, tocopherol acetate and pantenol and cyanocopherol and flavin adenine dinucleotide, or pyridoxin hydrochloride and tocopherol acetate and pantenol Combination containing cyanocopherol and flavin adenin dinucleotide
(4) In (1) to (3), diphenhydramine hydrochloride or a combination containing chlorpheniramine maleate and diphenhydramine hydrochloride instead of chlorpheniramine maleate.
(5) In (1) to (4), instead of dipotassium glycyrrhizinate, epsilon aminocaproic acid, allantin, zinc sulfate, sodium azulene sulfonate, dipotassium glycyrrhizinate and epsilonaminocaproic acid, dipotassium glycyrrhizinate and allantin, Dipotassium glycyrrhizinate and zinc sulphate, dipotassium glycyrrhizinate and sodium azulene sulfonate, epsilon aminocaproic acid and allantin, epsilon aminocaproic acid and zinc sulfate, epsilon aminocaproic acid and sodium azulene sulphate, allantin and zinc sulfate, allantin and azulene sulfonic acid Sodium, zinc sulphate and sodium azulene sulfonate, dipotassium glycyrrhizinate and epsilon aminocaproic acid and allantin, dipotassium glycyrrhizinate and epsilon aminocaproic acid and zinc sulphate, dipotassium glycyrrhizinate and epsilon aminocaproic acid and sodium glycyrrhizinate Potassium and allantin and zinc sulfate, dipotassium glycyrrhizinate and allantin and sodium azulene sulfonate, dipotassium glycyrrhizinate and zinc sulfate and sodium azulene sulphate, epsilon aminocaproic acid and allantin and zinc sulfate, epsilon aminocaproic acid and allantin and azulene sulfonic acid Sodium, allantin and zinc sulfate and sodium azulene sulfonate, dipotassium glycyrrhizinate and epsilon aminocaproic acid and allantin and zinc sulfate, dipotassium glycyrrhizinate and epsilon aminocaproic acid and allantin and sodium azulene sulfonate, epsilon aminocaproic acid and allantin and zinc sulfate And sodium azulene sulfonate, or a combination containing dipotassium glycyrrhizinate, epsilon aminocaproic acid, allantin, zinc sulfate and sodium azulene sulfonate.
(6) In (1) to (5), instead of tetrahydrozoline hydrochloride, naphazoline hydrochloride or a combination containing tetrahydrozoline hydrochloride and naphazoline hydrochloride.

(7) In (1) to (6), combinations that do not contain amino acids
(8) In (1) to (6), combinations that do not contain vitamins
(9) Combinations (1) to (6) that do not contain antihistamines
(10) Combinations (1) to (6) that do not contain anti-inflammatory agents other than pranoprofen
(11) In (1) to (6), combinations that do not contain eye muscle regulators
(12) In (1) to (6), a combination that does not contain a decongestant

(13) In (1) to (6), a combination that does not contain amino acids and vitamins
(14) In (1) to (6), a combination that does not contain amino acids and antihistamines.
(15) In (1) to (6), a combination containing no amino acids and anti-inflammatory agents other than pranoprofen.
(16) In (1) to (6), a combination that does not contain amino acids and eye muscle regulators
(17) In (1) to (6), a combination that does not contain amino acids and decongestants
(18) In (1) to (6), a combination that does not contain vitamins and antihistamines
(19) In (1) to (6), a combination that does not contain vitamins and anti-inflammatory agents other than pranoprofen.
(20) In (1) to (6), a combination that does not contain vitamins and eye muscle regulators
(21) In (1) to (6), a combination that does not contain vitamins and decongestants
(22) In (1) to (6), a combination containing no antihistamine and an anti-inflammatory agent other than pranoprofen.
(23) In (1) to (6), a combination that does not contain an antihistamine and an eye muscle regulator
(24) In (1) to (6), a combination that does not contain an antihistamine and a decongestant
(25) In (1) to (6), a combination that does not contain an anti-inflammatory agent other than pranoprofen and an eye muscle regulator
(26) In (1) to (6), a combination that does not contain an anti-inflammatory agent other than pranoprofen and a decongestant.
(27) In (1) to (6), a combination that does not contain an eye muscle regulator and a decongestant

(28) In (1) to (6), a combination containing no amino acids, vitamins and antihistamines.
(29) In (1) to (6), a combination that does not contain amino acids, vitamins, and eye muscle regulators.
(30) In (1) to (6), a combination that does not contain amino acids, vitamins, and decongestants.
(31) In (1) to (6), a combination containing no amino acids, antihistamines, and anti-inflammatory agents other than pranoprofen.
(32) In (1) to (6), a combination that does not contain amino acids, antihistamines, and eye muscle regulators.
(33) In (1) to (6), a combination that does not contain amino acids, antihistamines, and decongestants.
(34) In (1) to (6), a combination that does not contain amino acids, anti-inflammatory agents other than pranoprofen, and eye muscle regulators.
(35) In (1) to (6), a combination that does not contain amino acids, anti-inflammatory agents other than pranoprofen, and decongestants.
(36) In (1) to (6), a combination that does not contain amino acids, eye muscle regulators, and decongestants.
(37) In (1) to (6), a combination containing vitamins, antihistamines and anti-inflammatory agents other than pranoprofen.
(38) In (1) to (6), a combination that does not contain vitamins, antihistamines, and eye muscle regulators.
(39) In (1) to (6), a combination that does not contain vitamins, antihistamines, and decongestants.
(40) In (1) to (6), a combination that does not contain vitamins, anti-inflammatory agents other than pranoprofen, and eye muscle regulators.
(41) In (1) to (6), a combination that does not contain vitamins, anti-inflammatory agents other than pranoprofen, and decongestants.
(42) In (1) to (6), a combination that does not contain vitamins, eye muscle regulators, and decongestants.
(43) In (1) to (6), a combination that does not contain an antihistamine, an anti-inflammatory agent other than pranoprofen, and an eye muscle regulator.
(44) In (1) to (6), a combination that does not contain an antihistamine, an anti-inflammatory agent other than pranoprofen, and a decongestant.
(45) In (1) to (6), a combination that does not contain an antihistamine, an eye muscle regulator, and a decongestant.
(46) In (1) to (6), a combination that does not contain an anti-inflammatory agent, an eye muscle regulator, and a decongestant.

(47) In (1) to (6), a combination containing no amino acids, vitamins, antihistamines, and anti-inflammatory agents other than pranoprofen.
(48) In (1) to (6), a combination that does not contain amino acids, vitamins, antihistamines, and eye muscle regulators.
(49) In (1) to (6), a combination that does not contain amino acids, vitamins, antihistamines, and decongestants.
(50) In (1) to (6), a combination that does not contain amino acids, vitamins, anti-inflammatory agents other than pranoprofen, and eye muscle regulators.
(51) In (1) to (6), a combination that does not contain amino acids, vitamins, anti-inflammatory agents other than pranoprofen, and decongestants.
(52) In (1) to (6), a combination that does not contain amino acids, vitamins, eye muscle regulators, and decongestants.
(53) In (1) to (6), a combination that does not contain vitamins, antihistamines, anti-inflammatory agents other than pranoprofen, and eye muscle regulators.
(54) In (1) to (6), a combination that does not contain vitamins, antihistamines, eye muscle regulators, and decongestants.
(55) In (1) to (6), a combination that does not contain an antihistamine, an anti-inflammatory agent other than pranoprofen, an eye muscle regulator, and a decongestant.

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

Compositions containing the components (1) to (62) include eye fatigue, blurred vision, itchy eyes, conjunctival congestion, eyelid inflammation, light-induced eye inflammation, foreign body sensation, blemishes, and contact lenses. Used for amelioration, alleviation, treatment, or prevention of one or more symptoms or abnormalities selected from the group consisting of discomfort and eye diseases (eye diseases caused by swimming, eye diseases caused by dust or sweat entering the eyes, etc.) be able to. Specific examples thereof include improvement, alleviation, treatment, or preventive use of the following symptoms or abnormalities.
If multiple symptoms or abnormalities are present, they may be a combination of symptoms or abnormalities.

Tired eyes, blurred vision, itchy eyes, conjunctival congestion, blepharitis, light-induced eye inflammation, foreign body sensation, loose eyes, discomfort when wearing contact lenses, or eye disease (eye disease caused by swimming, dust or sweat) Eye diseases caused by getting into the eyes, etc. The same applies to the applications of compositions containing the components (1) to (62) below.)

Eye strain and blurred vision, eye strain and itchy eyes, eye strain and conjunctival congestion, eye strain and eyelid inflammation, eye strain and ray-induced eye strain, eye strain and foreign body feeling, eye strain and nanami Eye strain and eye strain and discomfort when wearing contact lenses, eye strain and eye disease,
Blurred eyes and itchy eyes, blurred eyes and conjunctival congestion, blurred eyes and eyelids, blurred eyes and light rays, blurred eyes and foreign bodies, blurred eyes and blurred eyes, blurred eyes and contacts Discomfort when wearing the lens, blurred vision and eye disease,
Itching and conjunctival congestion of the eyes, itching and blepharitis of the eyes, itching of the eyes and eye inflammation caused by light rays, itching and foreign matter of the eyes, itching and swelling of the eyes, itching of the eyes and discomfort when wearing contact lenses, eyes Itching and eye disease,
Conjunctival congestion and blepharitis, conjunctival congestion and ray-induced eye inflammation, conjunctival congestion and foreign body sensation, conjunctival congestion and blemishes, conjunctival congestion and discomfort when wearing contact lenses, conjunctival congestion and eye disease,
Blepharitis and light-induced blepharitis, blepharitis and foreign body sensation, blepharitis and blepharitis, blepharitis and discomfort when wearing contact lenses, blepharitis and eye disease,
Ray-induced eye inflammation and foreign body sensation, ray-induced eye inflammation and blemishes, ray-induced eye inflammation and discomfort when wearing contact lenses, ray-induced eye inflammation and eye disease,
Foreign body sensation and loose eyes, foreign body sensation and discomfort when wearing contact lenses, foreign body sensation and eye disease,
Discomfort when wearing tears and contact lenses, tears and eye diseases,
Discomfort and eye disease when wearing contact lenses,

Eye strain and blurred vision and itchy eyes, tired eyes and blurred vision and conjunctival hyperemia,
Eye strain and blurred vision and blepharitis, tired eyes and blurred vision and eye inflammation due to light rays,
Eye strain and blurred vision and foreign body, tired eyes and blurred vision and blemishes, tired eyes and blurred vision and discomfort when wearing contact lenses, tired eyes and blurred vision and eye disease,
Eye fatigue and eye itch and conjunctival congestion, eye fatigue and eye itch and eyelid inflammation, eye fatigue and eye itch and ray-induced eye inflammation, eye fatigue and eye itch and foreign body sensation, eye fatigue Itchy and unpleasant eyes, tired eyes and itchy eyes and discomfort when wearing contact lenses, tired eyes and itchy eyes and eye diseases,
Eye strain and conjunctival congestion and eyelid inflammation, eye fatigue and conjunctival congestion and ray-induced eye inflammation, eye fatigue and conjunctival congestion and foreign body sensation, eye fatigue and conjunctival congestion and naive eyes, eye fatigue and conjunctival congestion and contact Discomfort when wearing the lens, eye strain, conjunctival congestion and eye disease,
Eye fatigue and blepharitis and ray-induced eye inflammation, eye fatigue and blepharitis and foreign body sensation, eye fatigue and blepharitis and blemishes, eye fatigue and blepharitis and discomfort when wearing contact lenses, eye fatigue And blepharitis and eye disease,
Eye fatigue and light-induced eye inflammation and foreign body feeling, eye fatigue and light-induced eye inflammation and sloppy eyes, eye fatigue and light-induced eye inflammation and discomfort when wearing contact lenses, eye fatigue and light-induced eye inflammation Eye disease,
Eye strain and foreign body sensation and unpleasant eyes, eyestrain and foreign body sensation and discomfort when wearing contact lenses, eyestrain and foreign body sensation and eye diseases,
Eye strain and swelling eyes and discomfort when wearing contact lenses, eyestrain and slack eyes and eye diseases,
Eye strain, discomfort when wearing contact lenses and eye disease,

Blurred eyes and itchy eyes and conjunctival congestion, blurred eyes and itchy eyes and eyelid inflammation, blurred eyes and itchy eyes and eye inflammation caused by light rays, blurred eyes and itchy eyes and foreign body feeling, blurred eyes Itchy and unpleasant eyes, blurred eyes and itchy eyes and discomfort when wearing contact lenses, blurred eyes and itchy eyes and eye diseases,
Blurred eyes and conjunctival congestion and blepharitis, blurred vision and conjunctival congestion and blepharitis due to light rays, blurred vision and conjunctival congestion and foreign body sensation, blurred vision and conjunctival congestion and blepharitis, blurred vision and conjunctival congestion and contact Discomfort when wearing the lens, blurred vision, conjunctival congestion and eye disease,
Blurred eyes and blepharitis and eye inflammation caused by light rays, blurred eyes and blepharitis and foreign body feeling, blurred eyes and blepharitis and blemishes, blurred eyes and blepharitis and discomfort when wearing contact lenses, blurred eyes And blepharitis and eye disease,
Blurred eyes and light rays cause eye inflammation and foreign body feeling, blurred eyes and light rays cause eye inflammation and blemishes, blurred eyes and light rays cause eye inflammation and discomfort when wearing contact lenses, blurred eyes and light rays cause eye inflammation and light rays Eye disease,
Blurred eyes and foreign body sensation and loose eyes, blurred eyes and foreign body sensation and discomfort when wearing contact lenses, blurred eyes and foreign body sensation and eye diseases,
Blurred eyes and dark eyes and discomfort when wearing contact lenses, blurred eyes and dark eyes and eye diseases,
Blurred eyes and discomfort when wearing contact lenses and eye diseases,

Eye itching and conjunctival hyperemia and blepharitis, eye itching and conjunctival hyperemia and ray-induced eye inflammation, eye itching and conjunctival hyperemia and foreign body sensation, eye itching and conjunctival hyperemia and blepharitis, eye itching and conjunctival hyperemia and contact Discomfort when wearing the lens, itching of the eyes, conjunctival hyperemia and eye disease,
Itching of the eyes and blepharitis and eye inflammation caused by light rays, itching of the eyes and blepharitis and foreign body feeling, itching of the eyes and blepharitis and swelling eyes, itching of the eyes and blepharitis and discomfort when wearing contact lenses, itching of the eyes And blepharitis and eye disease,
Itchy eyes and light rays cause eye inflammation and foreign body feeling, eye itching and light rays cause eye inflammation and swelling eyes, eye itching and light rays cause eye inflammation and discomfort when wearing contact lenses, eye itching and light rays cause eye inflammation and Eye disease,
Itching and foreign body sensation and loose eyes, itching and foreign body sensation and discomfort when wearing contact lenses, itching and foreign body sensation and eye diseases
Itching and swelling of the eyes Discomfort when wearing contact lenses, itch and swelling of the eyes and eye diseases,
Itching of the eyes, discomfort when wearing contact lenses and eye diseases,

Conjunctival hyperemia and blepharitis and light-induced eye inflammation, conjunctival hyperemia and blepharitis and foreign body sensation, conjunctival hyperemia and blepharitis and naive eyes, conjunctival hyperemia and blepharitis and discomfort when wearing contact lenses, conjunctival hyperemia and blepharitis and eye disease ,
Conjunctival hyperemia and ray-induced eye inflammation and foreign body sensation, conjunctival hyperemia and ray-induced eye inflammation and blemishes, conjunctival hyperemia and ray-induced eye inflammation and discomfort when wearing contact lenses, conjunctival hyperemia and ray-induced eye inflammation and eye disease,
Conjunctival hyperemia and foreign body sensation and blemishes, conjunctival hyperemia and foreign body sensation and discomfort when wearing contact lenses, conjunctival hyperemia and foreign body sensation and eye disease,
Conjunctival hyperemia and discomfort when wearing contact lenses, conjunctival hyperemia and nanami eyes and eye diseases,
Conjunctival hyperemia and discomfort and eye disease when wearing contact lenses,

Blepharitis and ray-induced eye inflammation and foreign body sensation, blepharitis and ray-induced eye inflammation and blepharitis, blepharitis and ray-induced eye inflammation and discomfort when wearing contact lenses, blepharitis and ray-induced eye inflammation and eye disease,
Blepharitis and foreign body sensation and loose eyes, blepharitis and foreign body sensation and discomfort when wearing contact lenses, blepharitis and foreign body sensation and eye disease,
Blepharitis and blepharitis and discomfort when wearing contact lenses, blepharitis and blepharitis and eye disease,
Blepharitis and discomfort and eye disease when wearing contact lenses,

Eyes caused by light rays and foreign body sensation and blemishes, eye inflammation and foreign body sensation caused by light rays and discomfort when wearing contact lenses, eye inflammation caused by light rays and foreign body sensation and eye diseases,
Ray-induced eye inflammation, blemishes and discomfort when wearing contact lenses, ray-induced eye inflammation, blemishes and eye diseases,
Eye inflammation caused by light rays, discomfort when wearing contact lenses, and eye diseases,

Foreign body sensation and blemishes and discomfort when wearing contact lenses, foreign body sensation and blemishes and eye diseases,
Foreign body sensation, discomfort when wearing contact lenses, eye disease,

Discomfort and eye disease when wearing tears and contact lenses,

Tired eyes and blurred eyes and itchy eyes and conjunctival congestion, tired eyes and blurred eyes and itchy eyes and eyelid inflammation, tired eyes and blurred eyes and itchy eyes and eye inflammation caused by light rays, tired eyes Blurred eyes and itchy eyes and foreign body feeling, tired eyes and blurred eyes and itchy eyes and sloppy eyes, tired eyes and blurred eyes and itchy eyes and discomfort when wearing contact lenses, tired eyes Blurred eyes, itchy eyes and eye diseases,
Eye fatigue and blurred vision and conjunctival congestion and eyelid inflammation, eye fatigue and blurred vision and conjunctival congestion and eye inflammation due to light rays, eye fatigue and blurred vision and conjunctival congestion and foreign body sensation, eye fatigue and eye fatigue and eye sensation. Haze and conjunctival congestion and blemishes, eye fatigue and eye haze and conjunctival congestion and discomfort when wearing contact lenses, eye fatigue and eye haze and conjunctival congestion and eye disease,
Eye fatigue and blurred vision and eyelid inflammation and light-induced eye inflammation, eye fatigue and blurred vision and eyelid inflammation and foreign body sensation, eye fatigue and blurred vision and conjunctival congestion and swelling eyes, eye fatigue and eye Haze and eyelid inflammation and discomfort when wearing contact lenses, eye fatigue and eye haze and eyelid inflammation and eye disease,
Eye fatigue and blurred vision and light rays cause eye inflammation and foreign body feeling, eye fatigue and blurred eyes and light rays cause eye inflammation and blemishes, eye fatigue and blurred eyes and light rays cause eye inflammation and contact lenses Discomfort, eye fatigue and blurred vision and light-induced eye inflammation and eye disease,
Eye strain, blurred vision, foreign body feeling, and unpleasant eyes, tired eyes, blurred vision, foreign body feeling, discomfort when wearing contact lenses, tired eyes, blurred vision, foreign body feeling, and eye disease.
Eye strain and blurred vision and unpleasant eyes and discomfort when wearing contact lenses, tired eyes and blurred eyes and blurred eyes and eye diseases,
Eye strain, blurred vision, discomfort when wearing contact lenses, eye disease,

Eye fatigue and eye itching and conjunctival congestion and eyelid inflammation, eye fatigue and eye itching and conjunctival congestion and ray-induced eye inflammation, eye fatigue and eye itching and conjunctival congestion and foreign body sensation, eye fatigue and eye Itching and conjunctival congestion and sick eyes, eye fatigue and eye itchiness and conjunctival congestion and discomfort when wearing contact lenses, eye fatigue and eye itchiness and conjunctival congestion and eye disease,
Eye fatigue and eye itch and blepharitis and ray-induced eye inflammation, eye fatigue and eye itch and blepharitis and foreign body sensation, eye fatigue and eye itch and blepharitis and blepharitis, eye fatigue and eyes Itching and blepharitis and discomfort when wearing contact lenses, eye fatigue and eye itch and blepharitis and eye disease,
Eye fatigue and eye itch and ray-induced eye inflammation and foreign body sensation, eye fatigue and eye itch and ray-induced eye inflammation and blemishes, eye fatigue and eye itch and ray-induced eye inflammation and contact lens wearing Discomfort, tired eyes and itchy eyes and eye inflammation and eye disease due to light rays,
Eye strain, itchy eyes, foreign body feeling and sick eyes, eye strain, itchy eyes, foreign body feeling, discomfort when wearing contact lenses, eye fatigue, itchy eyes, foreign body feeling, and eye diseases.
Eye strain and itchy eyes and unpleasant eyes and discomfort when wearing contact lenses, eyestrain and itchy eyes and unpleasant eyes and eye diseases,
Eye strain, itching of the eyes, discomfort when wearing contact lenses and eye diseases,

Eye fatigue and conjunctival congestion and blepharitis and ray-induced eye inflammation, eye fatigue and conjunctival congestion and blepharitis and foreign body sensation, eye fatigue and conjunctival congestion and blepharitis and naive eyes, eye fatigue and conjunctival congestion and eyelid inflammation And discomfort when wearing contact lenses, eye fatigue, conjunctival congestion, blepharitis and eye disease,
Eye fatigue and conjunctival congestion and ray-induced eye inflammation and foreign body sensation, eye fatigue and conjunctival congestion and ray-induced eye inflammation and blemishes, eye fatigue and conjunctival congestion and ray-induced eye inflammation and discomfort when wearing contact lenses, Eye fatigue, conjunctival congestion, light-induced eye inflammation and eye disease,
Eye strain, conjunctival hyperemia, foreign body feeling and sick eyes, eye fatigue, conjunctival hyperemia and foreign body feeling, discomfort when wearing contact lenses, eye fatigue, conjunctival hyperemia, foreign body feeling, and eye disease.
Eye strain and conjunctival hyperemia and discomfort when wearing contact lenses, eye strain and conjunctival hyperemia and naive eyes and eye disease,
Eye strain, conjunctival hyperemia, discomfort when wearing contact lenses and eye disease,

Eye fatigue and eyelid inflammation and light-induced eye inflammation and foreign body feeling, eye fatigue and eyelid inflammation and light-induced eye inflammation and blemishes, eye fatigue and eyelid inflammation and light-induced eye inflammation and discomfort when wearing contact lenses, Eye fatigue, eyelid inflammation, eye inflammation and eye disease caused by light rays,
Eye strain, blepharitis, foreign body sensation, and sick eyes, eye strain, blepharitis, foreign body sensation, discomfort when wearing contact lenses, eye fatigue, blepharitis, foreign body sensation, and eye disease.
Eye strain and blepharitis and blepharitis and discomfort when wearing contact lenses, eye strain and blepharitis and blepharitis and eye disease,
Eye strain, blepharitis, discomfort when wearing contact lenses and eye disease,

Eye strain and light rays cause eye inflammation and foreign body feeling and slack eyes, eye fatigue and light rays cause eye inflammation and foreign body feeling and discomfort when wearing contact lenses, eye fatigue and light rays cause eye inflammation and foreign body feeling and eye disease,
Eye strain and eye inflammation caused by light rays and discomfort when wearing contact lenses, eye strain and eye inflammation caused by light rays, and eye disease and eye disease
Eye strain, eye inflammation due to light rays, discomfort when wearing contact lenses, and eye diseases

Eye strain and foreign body sensation and unpleasant eyes and discomfort when wearing contact lenses, eyestrain and foreign body sensation and unpleasant eyes and eye diseases,
Eye strain, foreign body sensation, discomfort when wearing contact lenses, eye disease,

Eye strain, unpleasant eyes, discomfort when wearing contact lenses, and eye diseases

Blurred eyes and itchy eyes and conjunctival congestion and eyelid inflammation, blurred eyes and itchy eyes and conjunctival congestion and light-induced eye inflammation, blurred eyes and itchy eyes and conjunctival congestion and foreign body feeling, blurred eyes and eyes Itching and conjunctival congestion and blemishes, blurred vision and itching and conjunctival congestion and discomfort when wearing contact lenses, blurred vision and itchy eyes and conjunctival congestion and eye disease,

Blurred eyes, conjunctival congestion, blepharitis, and light-induced eye inflammation, blurred vision, conjunctival congestion, blepharitis, and foreign body sensation, blurred vision, conjunctival congestion, blepharitis, and blepharitis, blurred vision, conjunctival congestion, and blepharitis. And discomfort when wearing contact lenses, blurred vision, conjunctival congestion, blepharitis and eye disease,
Blurred eyes and blepharitis and light rays cause eye inflammation and foreign body feeling, blurred eyes and blepharitis and light rays cause eye inflammation and blemishes, blurred eyes and blepharitis and light rays cause eye inflammation and discomfort when wearing contact lenses, Blurred eyes, blepharitis, light-induced eye inflammation and eye disease,
Blurred eyes and light rays cause eye inflammation and foreign body sensation and bleeding eyes, blurred eyes and light rays cause eye inflammation and foreign body sensation and discomfort when wearing contact lenses, blurred eyes and light rays cause eye inflammation and foreign body sensation and eye diseases,
Blurred eyes and foreign body sensation and unpleasant eyes and discomfort when wearing contact lenses, blurred eyes and foreign body sensation and unpleasant eyes and eye diseases,
Blurred eyes, unpleasant eyes, discomfort when wearing contact lenses, and eye diseases

Blurred eyes and blepharitis and light rays cause eye inflammation and foreign body feeling, blurred eyes and blepharitis and light rays cause eye inflammation and blemishes, blurred eyes and blepharitis and light rays cause eye inflammation and discomfort when wearing contact lenses, Blurred eyes, blepharitis, light-induced eye inflammation and eye disease,
Blurred eyes and light rays cause eye inflammation and foreign body sensation and bleeding eyes, blurred eyes and light rays cause eye inflammation and foreign body sensation and discomfort when wearing contact lenses, blurred eyes and light rays cause eye inflammation and foreign body sensation and eye diseases,
Blurred eyes and foreign body sensation and unpleasant eyes and discomfort when wearing contact lenses, blurred eyes and foreign body sensation and unpleasant eyes and eye diseases,
Blurred eyes, unpleasant eyes, discomfort when wearing contact lenses, and eye diseases

Blurred eyes and light rays cause eye inflammation and foreign body sensation and bleeding eyes, blurred eyes and light rays cause eye inflammation and foreign body sensation and discomfort when wearing contact lenses, blurred eyes and light rays cause eye inflammation and foreign body sensation and eye diseases,

Blurred eyes and foreign body sensation and unpleasant eyes and discomfort when wearing contact lenses, blurred eyes and foreign body sensation and unpleasant eyes and eye diseases,
Blurred eyes, unpleasant eyes, discomfort when wearing contact lenses, and eye diseases

Blurred eyes and light rays cause eye inflammation and foreign body sensation and bleeding eyes, blurred eyes and light rays cause eye inflammation and foreign body sensation and discomfort when wearing contact lenses, blurred eyes and light rays cause eye inflammation and foreign body sensation and eye diseases,

Blurred eyes and foreign body sensation and unpleasant eyes and discomfort when wearing contact lenses, blurred eyes and foreign body sensation and unpleasant eyes and eye diseases,

Blurred eyes, unpleasant eyes, discomfort when wearing contact lenses, and eye diseases

Itching and conjunctival congestion of the eyes and blepharitis and light-induced eye inflammation, itching and conjunctival congestion of the eyes and blepharitis and foreign body sensation, itching of the eyes and conjunctival congestion and blepharitis and blepharitis, itching of the eyes and conjunctival congestion and eyelid inflammation And discomfort when wearing contact lenses, itching of the eyes, conjunctival congestion, blepharitis and eye diseases,
Itching of the eyes and blepharitis and light rays cause eye inflammation and foreign body feeling, itching of eyes and blepharitis and light rays cause eye inflammation and blemishes, itching of eyes and blepharitis and light rays cause eye inflammation and discomfort when wearing contact lenses, Itching of the eyes, blepharitis, eye inflammation and eye diseases caused by light rays,
Itchy eyes and foreign body sensation and sick eyes, itchy eyes and foreign body sensation and discomfort when wearing contact lenses, itchy eyes and foreign body sensation and eye diseases
Itching and foreign body sensation in the eyes and discomfort when wearing contact lenses, itching and foreign body sensation in the eyes and sick eyes and eye diseases
Itching and swelling of the eyes and discomfort and eye disease when wearing contact lenses,

Conjunctival congestion and blepharitis and light-induced eye inflammation and foreign body sensation, conjunctival congestion and blepharitis and light-induced eye inflammation and blemishes, conjunctival congestion and blepharitis and light-induced eye inflammation and discomfort when wearing contact lenses, conjunctival congestion and Blepharitis and ray-induced eye inflammation and eye disease,
Conjunctival hyperemia and light-induced eye inflammation and foreign body sensation and blemishes, conjunctival hyperemia and light-induced eye inflammation and foreign body sensation and discomfort when wearing contact lenses, conjunctival hyperemia and light-induced eye inflammation and foreign body sensation and eye disease,
Conjunctival hyperemia and foreign body sensation and discomfort when wearing contact lenses, conjunctival hyperemia and foreign body sensation and naive eyes and eye diseases,
Conjunctival hyperemia, discomfort and eye disease when wearing contact lenses

Blepharitis and light-induced eye inflammation and foreign body sensation and blemishes, blepharitis and light-induced eye inflammation and foreign body sensation and discomfort when wearing contact lenses, blepharitis and light-induced eye inflammation and foreign body sensation and eye disease,
Blepharitis and foreign body sensation and unpleasant eyes and discomfort when wearing contact lenses, blepharitis and foreign body sensation and unpleasant eyes and eye diseases,
Blepharitis, blepharitis, discomfort and eye disease when wearing contact lenses,

Eye inflammation and foreign body sensation caused by light rays and discomfort when wearing contact lenses, eye inflammation and foreign body sensation caused by light rays, and eye diseases and eye diseases
Eye inflammation caused by light rays, unpleasant eyes, discomfort when wearing contact lenses, and eye diseases

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

Eye fatigue, blurred vision, itchy eyes, conjunctival hyperemia and eyelid inflammation, tired eyes, blurred vision, itchy eyes, conjunctival congestion and light-induced eye inflammation, tired eyes, blurred vision, and itchy eyes. Conjunctival congestion and foreign body sensation, eye fatigue and blurred vision and itchy eyes and conjunctival congestion and blemishes, eye fatigue and blurred vision and eye itchiness and conjunctival congestion and discomfort when wearing contact lenses, eye fatigue Blurred eyes, itchy eyes, conjunctival congestion and eye diseases,
Eye fatigue, eye itching, blepharitis, blepharitis, and blepharitis, eye fatigue, eye itch, conjunctival congestion, blepharitis, and foreign body sensation, eye fatigue, eye itch, blepharitis, and blepharitis. Eyes, eye fatigue, eye itching, blepharitis, blepharitis, discomfort when wearing contact lenses, eye fatigue, eye itch, conjunctival congestion, blepharitis, and eye disease.
Eye fatigue and conjunctival congestion and eyelid inflammation and light-induced eye inflammation and foreign body sensation, eye fatigue and conjunctival congestion and eyelid inflammation and ray-induced eye inflammation and blemishes, eye fatigue and conjunctival congestion and eyelid inflammation and ray-induced eye inflammation Discomfort when wearing contact lenses, eye fatigue, conjunctival congestion, eyelid inflammation, eye inflammation and eye disease due to light rays,
Eye fatigue and blepharitis and light-induced eye inflammation and foreign body sensation and slack eyes, eye fatigue and blepharitis and light-induced eye inflammation and foreign body sensation and discomfort when wearing contact lenses, eye fatigue and blepharitis and light-induced Blepharitis, foreign body feeling and eye disease,
Eye strain and light rays cause eye inflammation and foreign body feeling and discomfort when wearing contact lenses, eye strain and light rays cause eye inflammation and foreign body feeling and naive eyes and eye diseases,
Eye strain, foreign body sensation, unpleasant eyes, discomfort when wearing contact lenses, and eye diseases

Blurred eyes, itchy eyes, conjunctival hyperemia, eyelid inflammation, and ray-induced ophthalmia, blurred eyes, itchy eyes, conjunctival hyperemia, eyelid inflammation, and foreign sensation, blurred vision, itchy eyes, conjunctival hyperemia, and eyelid inflammation. Eyes, blurred vision, itchy eyes, conjunctival congestion, eyelid inflammation, discomfort when wearing contact lenses, blurred vision, itchy eyes, conjunctival congestion, eyelid inflammation, and eye disease.
Blurred eyes, conjunctival congestion, blepharitis, and light-induced ophthalmia and foreign body sensation, blurred eyes, conjunctival congestion, blepharitis, and light-induced eye inflammation and blepharitis, blurred vision, conjunctival congestion, blepharitis, and light-induced eye inflammation. Discomfort when wearing contact lenses, blurred vision, conjunctival congestion, blepharitis, light-induced eye inflammation and eye disease,
Blurred eyes, blepharitis and light rays cause eye inflammation and foreign body feeling and slack eyes, blurred eyes and blepharitis and light rays cause eye inflammation and foreign body feeling and discomfort when wearing contact lenses, blurred eyes and blepharitis and light rays Blepharitis, foreign body feeling and eye disease,
Blurred eyes and light rays cause eye inflammation and foreign body sensation and discomfort when wearing contact lenses, blurred eyes and light rays cause eye inflammation and foreign body sensation, and eyes and eye diseases
Blurred eyes, foreign body sensation, unpleasant eyes, discomfort when wearing contact lenses, and eye diseases.

Itching of the eyes, conjunctival congestion, eyelid inflammation and light-induced eye inflammation and foreign body sensation, eye itching and conjunctival congestion and eyelid inflammation and light-induced eye inflammation and naive eyes, eye itching and conjunctival congestion and eyelid inflammation and light-induced eye inflammation Discomfort when wearing contact lenses, itching of the eyes, conjunctival congestion, eyelid inflammation, eye inflammation and eye disease caused by light rays,
Itching of the eyes, blepharitis and light rays cause eye inflammation and foreign body feeling and slack eyes, itchy eyes and blepharitis and light rays cause eye inflammation and foreign body feeling and discomfort when wearing contact lenses, itchy eyes and blepharitis and light rays Blepharitis, foreign body feeling and eye disease,
Itching of the eyes, eye inflammation caused by light rays, foreign body sensation, unpleasant eyes and discomfort when wearing contact lenses,
Itching of the eyes, eye inflammation caused by light rays, foreign body sensation, sick eyes and eye diseases,
Itching and foreign body sensation in the eyes, discomfort when wearing contact lenses and eye diseases,

Conjunctival hyperemia, blepharitis, light-induced eye inflammation, foreign body sensation, and blemishes, conjunctival hyperemia, blepharitis, light-induced eye inflammation, foreign body sensation, discomfort when wearing contact lenses, conjunctival hyperemia, blepharitis, and light-induced eye inflammation. Foreign body feeling and eye disease,
Conjunctival hyperemia and light-induced ophthalmia and foreign body sensation and discomfort when wearing contact lenses, conjunctival hyperemia and light-induced eye inflammation and foreign body sensation and nasty eyes and eye diseases
Conjunctival hyperemia, foreign body sensation, unpleasant eyes, discomfort when wearing contact lenses, and eye diseases

Blepharitis and foreign body sensation due to blepharitis and discomfort when wearing contact lenses, blepharitis and foreign body sensation and blemishes and eye diseases

Eye inflammation and foreign body sensation caused by light rays, unpleasant eyes, discomfort when wearing contact lenses, and eye diseases

Tired eyes, blurred eyes, itchy eyes, blepharitis, blepharitis and light-induced eye inflammation, tired eyes, blurred eyes, itchy eyes, conjunctival congestion, blepharitis and foreign bodies, tired eyes and eyes Blurred eyes, itchy eyes, blepharitis, blepharitis and naive eyes, tired eyes and blurred eyes, itchy eyes, conjunctival congestion, blepharitis and discomfort when wearing contact lenses, tired eyes and blurred eyes and eyes Itching and conjunctival congestion and blepharitis and eye disease Eye fatigue and eye itching and conjunctival congestion and blepharitis and light-induced blepharitis and foreign body sensation, eye fatigue and eye itching and conjunctival congestion and blepharitis and light-induced eye inflammation Tonamida eyes, eye fatigue, eye itching, blepharitis, blepharitis, ray-induced eye inflammation and discomfort when wearing contact lenses, eye fatigue, eye itching, conjunctival congestion, blepharitis, and ray-induced eye inflammation. Eye disease Eye fatigue, blepharitis, blepharitis, blepharitis and light-induced ophthalmia and foreign body sensation and blepharitis, eye fatigue and conjunctival blepharitis and blepharitis and light-induced blepharitis and foreign body sensation, discomfort when wearing contact lenses, eyes Tiredness, blepharitis, blepharitis, blepharitis, foreign body sensation, and eye disease Eye fatigue, blepharitis, blepharitis, foreign body sensation, blepharitis, discomfort when wearing contact lenses, eye fatigue and blepharitis Blepharitis and blepharitis caused by light rays Blepharitis and eye disease Eye fatigue and blepharitis caused by light rays and blepharitis and blepharitis and discomfort and eye disease when wearing contact lenses

Blurred eyes, itchy eyes, conjunctival hyperemia, eyelid inflammation, light-induced ophthalmitis and foreign body sensation, blurred eye, itchy eyes, conjunctival congestion, eyelid inflammation, light-induced eye inflammation and naive eyes, blurred vision and eyes. Itching, conjunctival congestion, eyelid inflammation, eye inflammation due to light rays, discomfort when wearing contact lenses, blurred vision, itching of eyes, conjunctival congestion, eyelid inflammation, eye inflammation and eye diseases, blurred vision, conjunctival congestion, and eyelid inflammation. Eye inflammation and foreign body feeling and blemishes due to light rays, blurred vision and conjunctival congestion and eyelids, eye inflammation and foreign body feeling due to light rays and discomfort when wearing contact lenses, blurred vision and conjunctival congestion and eyelid inflammation and light rays Eye inflammation, foreign body sensation, and eye disease Eye haze, eyelid inflammation, and light beam-induced eye inflammation and foreign body sensation. And eye disease Ophthalmitis and foreign body feeling due to blurred vision and light rays, unpleasant eyes and discomfort when wearing contact lenses and eye disease

Itching of the eyes, conjunctival congestion, eyelid inflammation, eye inflammation and foreign body feeling due to light rays, and swelling eyes, itching of eyes, conjunctival congestion, eyelid inflammation, eye inflammation and foreign body feeling due to light rays, discomfort when wearing contact lenses, itching of eyes Conjunctival congestion, eyelid inflammation, eye inflammation caused by light rays, foreign body sensation, and eye diseases Itchy eyes, eye blemishes, eye inflammation caused by light rays, foreign body feeling, unpleasant eyes and discomfort when wearing contact lenses, itchy eyes, eyelid inflammation, and light rays. Eye inflammation and foreign body sensation due to itchy eyes and light rays and foreign body sensation and blemishes and discomfort and eye disease when wearing contact lenses

Conjunctival hyperemia, blepharitis, light-induced eye inflammation, foreign body feeling, discomfort when wearing contact lenses, conjunctival hyperemia, blepharitis, light-induced eye inflammation, foreign body feeling, naive eyes, and eye disease

Blepharitis, eye inflammation caused by light rays, foreign body sensation, unpleasant eyes, discomfort when wearing contact lenses, and eye diseases

Eye fatigue, blurred vision, itchy eyes, conjunctival hyperemia, eyelid inflammation, eye inflammation and foreign body sensation, eye fatigue, blurred vision, itchy eyes, conjunctival congestion, eyelid inflammation, and ray-induced eye inflammation. Eye, eye fatigue, blurred vision, itchy eyes, conjunctival congestion, eyelid inflammation, eye inflammation due to light rays, discomfort when wearing contact lenses, tired eyes, blurred vision, itchy eyes, conjunctival congestion, and eyelid inflammation. Eye fatigue and eye disease Eye fatigue and eye itching and conjunctival congestion and eyelid inflammation and ray-induced eye inflammation and foreign body sensation and sick eyes, eye fatigue and eye itching and conjunctival congestion and eyelid inflammation and ray-induced eye inflammation And foreign body feeling and discomfort when wearing contact lenses, eye fatigue, itchy eyes, conjunctival congestion, eyelid inflammation, eye inflammation due to light rays, foreign body feeling, eye diseases, eye fatigue, conjunctival congestion, eyelid inflammation, and eye inflammation due to light rays. Foreign body feeling and discomfort when wearing contact lenses, eye fatigue and conjunctival hyperemia, eye inflammation and foreign body feeling due to eyelid inflammation and light rays Tonamida Eyes and discomfort when wearing contact lenses and eye diseases Blurred eyes, itchy eyes, conjunctival congestion, eyelid inflammation, eye inflammation caused by light rays, foreign body feeling, blurred eyes, blurred eyes, itchy eyes, conjunctival congestion, and eyelids Eye inflammation and foreign body feeling due to flame and light, discomfort when wearing contact lenses, blurred vision and itchy eyes and conjunctival congestion and eyelid inflammation and light beam eye inflammation and foreign body feeling and eye disease Blurred eye and conjunctival congestion and eye disease Eye inflammation and foreign body sensation caused by light rays and discomfort when wearing contact lenses, blurred vision and conjunctival congestion and eyelid inflammation and light rays caused eye inflammation and foreign body feeling Eye inflammation, foreign body feeling, discomfort and eye disease when wearing contact lenses, itchy eyes, conjunctival congestion, eyelid inflammation, eye inflammation and foreign body feeling due to light rays Itching, conjunctival congestion, eyelid inflammation, eye inflammation and foreign body sensation caused by light rays, bleeding eyes and eye diseases Itching and eye blemishes, eye blemishes and foreign body sensation caused by light rays Eyebrow inflammation, eye inflammation caused by light rays, foreign body feeling, unpleasant eyes, discomfort when wearing contact lenses, and eye diseases

Tired eyes, blurred vision, itchy eyes, conjunctival congestion, eye blemishes, eye inflammation due to light rays, foreign body feeling and blemishes, tired eyes, blurred eyes, itchy eyes, conjunctival congestion, eye blemishes and rays. Flame, foreign body feeling, discomfort when wearing contact lenses, eye fatigue, blurred vision, itchy eyes, conjunctival congestion, eyelid inflammation, eye inflammation due to light rays, foreign body feeling, eye diseases, eye fatigue, itchy eyes, and conjunctival congestion. Eye blemishes and light-induced eye inflammation and foreign body sensation and discomfort when wearing eyes and contact lenses, eye fatigue and eye itchiness and conjunctival congestion, eye blemishes and light-induced eye inflammation and foreign body sensation Tiredness, conjunctival congestion, eyelid inflammation, eye inflammation due to light rays, foreign body feeling, discomfort and eye diseases when wearing contact lenses Flames and discomfort and eye disease when wearing contact lenses Eye fatigue and blurred vision and itchy eyes and conjunctival congestion and eyelid inflammation and discomfort and eye disease when wearing contact lenses Eye fatigue and blurred vision and eyes Itching, conjunctival congestion, foreign body feeling, discomfort and eye disease when wearing contact lenses Pleasure and eye diseases Blurred eyes, itchy eyes, conjunctival congestion, eyelid inflammation, light-induced eye inflammation, foreign body feeling, unpleasant eyes and discomfort when wearing contact lenses, blurred vision, itchy eyes, conjunctival congestion, and eyelid inflammation Eye inflammation and foreign body sensation due to light rays and blemishes and eye diseases Blurred eyes and conjunctival congestion and eyelid inflammation and light rays eye inflammation and foreign body sensation and blemishes and discomfort and eye diseases when wearing contact lenses Eye itching and conjunctival congestion and eye diseases Eye inflammation caused by flames and light rays, feeling of foreign matter, unpleasant eyes, discomfort when wearing contact lenses, and eye diseases

Eye fatigue, blurred vision, itchy eyes, conjunctival hyperemia, eyelid inflammation, eye inflammation due to light rays, foreign body feeling, discomfort when wearing contact lenses, tired eyes, blurred vision, itchy eyes, and conjunctivitis. Congestion, eyelid inflammation, eye inflammation and foreign body feeling due to light rays, eye and eye disease Eye fatigue, itching of eyes, conjunctival congestion, eyelid inflammation, eye inflammation due to light rays, foreign body feeling, naive eyes and discomfort when wearing contact lenses Eye diseases Blurred eyes, itchy eyes, conjunctival congestion, eyelid inflammation, eye inflammation caused by light rays, foreign body feeling, unpleasant eyes and discomfort when wearing contact lenses, eye diseases Eye fatigue, blurred eyes, itchy eyes, and eye disease Eye inflammation and foreign body feeling due to light rays and discomfort and eye disease when wearing contact lenses Eye fatigue and blurred eyes and itching of eyes and conjunctival congestion and eye inflammation and foreign body feeling due to light rays and when wearing contact lenses Discomfort and eye disease Eye fatigue, blurred vision, itchy eyes, conjunctival congestion, eyelid inflammation, foreign body feeling, discomfort and eye disease when wearing contact lenses Eye fatigue, blurred vision, and itchy eyes Conjunctival congestion, eyelid inflammation, eye inflammation caused by light rays, discomfort and eye diseases when wearing contact lenses Eye fatigue, blurred vision, itchy eyes, conjunctival congestion, eyelid inflammation, eye inflammation caused by light rays, foreign body feeling, and contact Discomfort and eye disease when wearing the lens

Eye strain, blurred vision, itchy eyes, conjunctival hyperemia, blepharitis, light-induced eye inflammation, foreign body sensation, unpleasant eyes, discomfort when wearing contact lenses, and eye diseases

pH
The pH of the ophthalmic composition of the present invention is preferably 3 or more, more preferably 4 or more, even more preferably 5 or more, and even more preferably 6 or more. Further, 10 or less is preferable, 9 or less is more preferable, 8.5 or less is even more preferable, and 8 or less is even more preferable. Within the above range, irritation to the eyes can be suppressed and the above effects of the present invention can be obtained.

Osmotic pressure ratio of ophthalmic compositions of the osmotic pressure present invention is preferably 0.4 or more, more preferably 0.6 or more, even more preferably 0.8 or more. Further, 5 or less is preferable, 3 or less is more preferable, and 2 or less is even more preferable. Within the above range, irritation to the eyes can be suppressed and the above 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) based on the 16th revised Japanese Pharmacopoeia. The osmotic pressure is measured according to the osmotic pressure measurement method (freezing point drop method) described in the 16th revised Japanese Pharmacopoeia. The standard solution for measuring the osmotic pressure ratio (0.9w / v% sodium chloride aqueous solution) is released in a desiccator (silica) after drying sodium chloride (standard reagent of the Japanese Pharmacy) at 500 to 650 ° C for 40 to 50 minutes. Cool, weigh accurately 0.900 g, dissolve in purified water to prepare exactly 100 mL, or use a commercially available standard solution for measuring osmotic pressure ratio (0.9 w / v% sodium chloride aqueous solution).

Container The ophthalmic composition of the present invention is contained in a container.
The container refers to a packaging body having a surface that comes into contact with the pharmaceutical product, such as a container main body part that stores the liquid, a part (nozzle, inner plug) including an extraction port of the container, a suction tube, and a cap.
The material constituting the container containing the ophthalmic composition of the present invention can be selected from a wide range.
For example, at least part or all of the contact surface with the ophthalmic composition is plastic (eg, polyolefin, acrylic acid resin, terephthalic acid ester, 2,6-naphthalenedicarboxylic acid ester, polycarbonate, polymethylpentene, fluororesin, poly). Consists of vinyl chloride, polyamide, ABS resin, AS resin, polyacetal, modified polyphenylene ether, polyarylate, polysulfone, polyimide, cellulose acetate, hydrocarbons that may be substituted with halogen atoms, etc.), metals (aluminum, etc.), and glass. Examples include containers made of at least one material selected from the group.

Polyolefins include polyethylene (including high-density polyethylene, low-density polyethylene, ultra-low-density polyethylene, linear low-density polyethylene, ultra-high-density polyethylene, etc.), polypropylene (isotactic polypropylene, syndiotactic polypropylene, atactic polypropylene). Etc.), and ethylene / propylene copolymers and the like.

Examples of the acrylate resin include acrylate esters such as methyl acrylate, methacrylic acid esters such as methyl methacrylate, cyclohexyl methacrylate, and t-butylcyclohexyl methacrylate.

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

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

Fluororesin includes fluorine-substituted polyethylene (polytetrafluoroethylene, polychlorotrifluoroethylene, etc.), polyvinylidene fluoride, vinyl fluoride, perfluoroalkoxyfluororesin, ethylene tetrafluoride / propylene hexafluoride copolymer, ethylene / tetra. Examples thereof include a fluoroethylene copolymer and an ethylene / chlorotrifluoroethylene copolymer.

Examples of the polyamide include nylon and the like.

Examples of polyacetals include those consisting of only oxymethylene units and those containing some oxyethylene units.

Examples of the modified polyphenylene ether include polystyrene-modified polyphenylene ether.

Examples of polyarylate include amorphous polyarylate.

Examples of the polyimide include an aromatic polyimide obtained by polymerizing pyromellitic acid dianhydride and 4,4'-diaminodiphenyl ether.

Examples of cellulose acetate include cellulose diacetate and cellulose triacetate.
As the container for containing the ophthalmic composition of the present invention, polyolefin and terephthalic acid ester are preferable, terephthalic acid ester is more preferable, polyethylene terephthalate and polybutylene terephthalate are more preferable, and polyethylene terephthalate is even more preferable. From another point of view, polypropylene, polyethylene, polyethylene terephthalate and polybutylene terephthalate are preferable, polypropylene, polyethylene terephthalate, polyethylene and polybutylene terephthalate are more preferable, polyethylene terephthalate and polyethylene are even more preferable, and polyethylene terephthalate is further preferable.
As the container for accommodating the ophthalmic composition of the present invention, the container material may be a blend polymer with a polymer other than the polymer. When the container material of the container for accommodating the ophthalmic composition of the present invention is a blend polymer with the polymer, the mixing ratio of the polymer with a polymer other than the polymer is not particularly limited as long as the effect of the present invention is obtained. The total weight of the polymer is preferably 30 w / w% or more, more preferably 50 w / w% or more, still more preferably 65 w / w% or more, based on the total amount of the total constituent materials. It is particularly preferable that it is 80 w / w% or more.

The container may be made of the above-mentioned material at least a part of the surface in contact with the ophthalmic composition of the present application.
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.
Further, the constituent parts of the container (the main body of the container, the portion including the extraction port of the container (nozzle, inner plug), suction tube, cap, etc.) may be made of the above-mentioned material, and the entire part of the container may be made of the above-mentioned material. It may be composed of. In particular, it is preferable that the container body portion is made of the above material, and all of the container body portion is made of the above material (a part of the layers constituting the container body is made of the above material). (Not in a state) is more preferable.

In addition, the container may be a light-shielding container, which improves the stability of components such as pranoprofen or a salt thereof. Examples of the light-shielding container include a container made of the above-mentioned material covered with a light-shielding film, a container made of the above-mentioned material and a colorant, and the like.

Symptomatology or Abnormality of Interest The ophthalmic compositions of the present invention improve complex eye symptoms. Improvement of compound eye symptoms includes improvement, alleviation, treatment, or prevention of compound eye symptoms or abnormalities.
As compound eye symptoms or abnormalities, specifically, eye fatigue, blurred vision such as when there are many eyes, itchy eyes, conjunctival congestion, eyelid inflammation (swelling of the eyelids), eye inflammation caused by ultraviolet rays or other rays (so-called so-called eye inflammation). Snowy eyes, etc.), foreign body feeling (rolling, tingling, etc.), loose eyes, eye discomfort (including eye discomfort such as discomfort when wearing contact lenses), eye disease (caused by swimming) It is useful for ameliorating, alleviating, treating, or preventing one or more symptoms or abnormalities such as eye disease, eye disease caused by dust or sweat entering the eye).
Conditions with multiple symptoms or abnormalities of the eye may be more difficult to improve or prevent than conditions with a single symptomatology or abnormality. The ophthalmic composition of the present invention can effectively improve, alleviate, treat, or prevent those symptoms even in such a case.

In particular, with the spread of personal computers in recent years, the overuse of the eyes and the spread of contact lenses have led to the tiredness of the eyes, itching of the eyes, conjunctival hyperemia, blurred vision, and blindness of the eyes for modern consumers, consumers, and workers. There are many general or complex discomforts that present one or more of the pleasant sensations, but the present invention can effectively improve, alleviate, treat, or prevent such comprehensive or complex symptoms. ..
In particular, itching of the eyes, conjunctival hyperemia, 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.
In addition, itching of the eyes, conjunctival hyperemia, blurred vision due to rheumatism, swelling, and foreign body sensation are triggered by allergens such as house dust (indoor dust), yellow sand, PM2.5, and mites, and inflammation and allergic symptoms. In such a state, one or more symptoms are often presented in combination. The present invention can effectively improve, alleviate, treat, or prevent such complex symptoms.

The above-mentioned eye diseases include inflammatory diseases such as blepharitis, conjunctivitis, keratitis, scleritis, episcleritis, anterior uveitis, postoperative inflammation, lacrimal adenitis, lacrimal pouchitis, and lacrimal ductitis; Symptoms caused by bacterial infection such as conjunctivitis can be mentioned. Also included are eye diseases caused by swimming, eye diseases caused by dust or sweat getting into the eyes. Symptoms caused by inflammatory diseases and bacterial infections may be accompanied by the allergic symptoms described above.

As described above, eye discomfort includes eye discomfort when wearing contact lenses. Discomfort when wearing contact lenses also includes discomfort when wearing either hard contact lenses or soft contact lenses. In addition, although discomfort is great when wearing hard contact lenses, the ophthalmic composition of the present invention can effectively improve, alleviate, treat, or prevent such discomfort.

Therefore, the ophthalmic composition of the present invention is used for improving, alleviating, treating, or preventing general eye symptoms or abnormalities, improving, alleviating, treating, or preventing complex eye symptoms or abnormalities, for total eye care, or for general eye care. It can be a composition for chemical use. The ophthalmic composition of the present invention can also be a composition for ameliorating, alleviating, treating, or preventing multifunctional general 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 avoidance, delay, and reduction of onset rate, "alleviation" includes symptom relief and suppression of symptom progression, and "improvement" and "treatment" include symptomatology. Includes remission, suppression of symptom progression, cure or complete recovery.

Usage method When the ophthalmic composition of the present invention is a preparation to be applied to the eyes such as eye drops, eye wash agents, and eye ointments, the usage thereof varies depending on the target symptom, but for example, once or more or twice a day. It can be 3 times or more, 4 times or more, 5 times or more, or 6 times or more. Further, it can be 9 times or less, 8 times or less, 7 times or less, 6 times or less, 5 times or less, or 4 times or less per day. It is particularly preferable to administer 4 times a day.

The use may be started at the same time as or after the onset of symptoms, but the use may be started 1 day or more before the onset of symptoms, particularly 3 days or more, especially 7 days or more. In addition, the use can be started 10 days or more before the onset of symptoms. In addition, the use may be started within 30 days before the onset of symptoms, particularly within 20 days, particularly within 14 days. By using it before the symptoms appear, the symptoms can be effectively prevented.

When the ophthalmic composition of the present invention is an eye drop, an eye drop containing each component at the above concentration may be instilled in an amount of 1 to 3 drops, preferably 1 to 2 drops, for example. It can be one drop.
When the ophthalmic composition of the present invention is an eye wash, the eye wash containing each component at the above concentration may be washed using, for example, 1 to 30 mL at a time, preferably 1 to 20 mL, and more preferably 4 You can wash your eyes with ~ 6 mL.
When the ophthalmic composition of the present invention is an eye ointment, an eye ointment containing each component at the above concentration may be applied to, for example, 0.001 to 5 g of an eye at a time.

When the ophthalmic composition of the present invention is a contact lens wearing solution, when the contact lens is put on and taken off, for example, 1 to 3 drops, preferably 1 to 2 drops, are applied to one side of the contact lens and / Alternatively, the contact lens may be dropped on both sides and wet, and then worn, preferably after both sides of the contact lens are wet.

When the ophthalmic composition of the present invention is a contact lens solution, for example, the ophthalmic composition and the contact lens are in contact with each other for 1 hour or more, 2 hours or more, 4 hours or more, or 1 day or more. I can let you. In addition, contact can be made for 30 days or less, 14 days or less, 7 days or less, or 2 days or less.

表１中の各成分濃度の単位は、ｗ／ｖ％であり、残量は水（精製水）であり全量１００ｍＬである。なお、ｐＨは、必要に応じて適宜ｐＨ調整剤（塩酸、水酸化ナトリウム：適量）により調整した。 Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.
Test example 1. Evaluation of eye drops effect 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 these were sterilized. A PET eye drop container (13 mL volume) was filled with 10 mL.

The unit of each component concentration in Table 1 is w / v%, and the remaining amount is water (purified water), and the total volume is 100 mL. The pH was appropriately adjusted with a pH adjuster (hydrochloric acid, sodium hydroxide: appropriate amount) as needed.

As the subject, an office worker who routinely performs VDT (Visual Display Terminals) work for 4 hours or more a day was selected. Each subject conducted the test after confirming that there was no difference in the condition of the left and right eyes in advance.
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 as Example 1 except that it does not contain pranoprofen, and Test A is a test in which Example 1 and Comparative Example 1 are used as a set.
Five subjects (4 males and 1 female) instilled 1 drop each of the eye drops of the example into the right eye and the eye drops of the comparative example into the left eye for tests A to H, and set a scale of 0 to 100. About various eye symptoms (eye fatigue, itchy eyes, blurred vision, conjunctival hyperemia, eye discomfort) 30 seconds after instillation by "VAS method (Visual Analog Scale)" using the attached 10 cm straight line. The effects were compared. When conducting different tests in succession, the next instillation was performed after an interval of 1 hour or more after the instillation was completed.

The average value of the VAS score values of the five subjects was calculated, and the score increase value from each corresponding comparative example in each example was calculated by the following formula (1). Table 1 shows the results of the score increase value for each eye symptom. The higher the VAS score value, the stronger the eye symptoms (eye strain, itchy eyes, blurred eyes, conjunctival hyperemia, eye discomfort), and the higher the score increase value, the greater the improvement in eye symptoms. Is shown.

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

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

It was confirmed that the combination of planoprofen clearly suppressed all symptoms of eye strain, itching of eyes, blurred vision, conjunctival hyperemia, and discomfort of eyes, and improved compound eye symptoms.

The eye drops of Preparation Examples 1 to 8 whose compositions are shown in Table 3 below suppress eye strain, itching of the eyes, blurred vision, conjunctival hyperemia, and discomfort of the eyes, 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). Further, in Table 3, the remaining amount is water (purified water), and the total amount is 100 mL.
Pharmaceutical examples 1 to 8 are adjusted to 6 with a pH adjuster (appropriate amount of hydrochloric acid and sodium hydroxide), and pharmaceutical examples 1-1 to 1-8 are adjusted to 7 and pharmaceutical examples 1 to 8 are adjusted to 7 with a pH adjuster. The obtained product was designated as Formulation Examples 2-1 to 2-8, and the prepared product Examples 1 to 8 were adjusted to 8 with a pH adjusting agent, and the product was designated as Pharmaceutical Example 3-1 to 3-8.

The ophthalmic composition of the present invention can practically sufficiently improve, alleviate, treat, or prevent a wider variety of eye symptoms or abnormalities as compared with conventional ophthalmic compositions. Therefore, it is not necessary to use a plurality of ophthalmic compositions in combination. Therefore, the ophthalmic composition of the present invention is very useful industrially.

Claims (5)

At least one selected from the group consisting of (a) pranoprofen and its salts, and (b) decongestants, eye muscle regulators, anti-inflammatory agents other than pranoprofen or its salts, antihistamines, vitamins, and An ophthalmic composition for improving complex eye symptoms, which comprises at least one component selected from the group consisting of amino acids. (b) The composition according to claim 1, which contains a decongestant, an eye muscle regulator, an anti-inflammatory agent other than pranoprofen or a salt thereof, an antihistamine, vitamins, and amino acids. One or more compound eye symptoms selected from the group consisting of tired eyes, blurred vision, itchy eyes, conjunctival congestion, blepharitis, light-induced eye inflammation, foreign body sensation, swelling eyes, eye discomfort, and eye diseases. The composition according to claim 1 or 2. The content of any one of claims 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% with respect to the total amount of the composition. Composition. The composition according to any one of claims 1 to 4, further comprising an antioxidant.