JP2017075145A - Ophthalmic composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: 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 the improvement (including relief, treatment, or prevention) of various eye symptoms.

  Reducing eye discomfort, eye fatigue, and preventing eye disease such as blurred vision, itchy eyes, conjunctival redness, blepharitis, ophthalmitis caused by ultraviolet rays and other rays, and discomfort when wearing contact lenses To do so, a large number of ophthalmic compositions are commercially available and used.

These ophthalmic compositions are usually approved as active ingredients of ophthalmic preparations for over-the-counter medicines. Decongestants, eye muscle regulators, anti-inflammatory agents, antihistamines, vitamins, amino acids, sulfa antibacterial agents It is prepared by combining components such as inorganic salts, polymer thickeners, preservatives, and other additives in combination.
However, although conventional ophthalmic compositions can relieve or prevent various symptoms of the eye to some extent, it is often only some symptoms that can be sufficiently relieved or prevented in practice. In addition, there are eye symptoms that cannot be sufficiently relieved or prevented with conventional ophthalmic compositions.
In particular, in recent years, it has been difficult to keep the eyes comfortable with conventional ophthalmic compositions due to the overuse of the eyes due to the spread of personal computers, the spread of contact lenses, and the increased scattering of antigenic substances.

  An object of the present invention is to provide an ophthalmic composition that can broadly improve various symptoms or abnormalities of the eye and has a higher improvement effect than conventional ophthalmic compositions.

  The present inventor has conducted research to solve the above-described problems, and contains at least one component selected from the group consisting of a decongestant, an eye muscle regulator, an anti-inflammatory agent, an antihistamine, vitamins, and amino acids. By blending pranoprofen and / or a pharmaceutically acceptable salt thereof (hereinafter abbreviated as “salt”) into the ophthalmic composition, eye fatigue, blurred vision, itchy eyes, conjunctival hyperemia, It has been found that the effect of improving symptoms such as eye discomfort is wide and sufficient. Moreover, it discovered that the improvement (including relief, treatment, or prevention) of such a symptom or abnormality was high compared with the conventional ophthalmic composition.

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

  Since the ophthalmic composition of the present invention contains pranoprofen and / or a salt thereof, it may cause eye fatigue, blurred vision, itching of the eyes, itching of the eyes, conjunctival redness, blepharitis (acupuncture). Ocular inflammation due to ultraviolet rays or other rays (so-called snow eyes, etc.), foreign body sensation (colossal feeling, tingling sensation, etc.), lax eyes, discomfort when wearing contact lenses, eye discomfort, eye disease (caused by swimming The effect of alleviating, ameliorating, treating, or preventing eye diseases (eg, eye diseases caused by dust or sweat entering the eyes) is widely and sufficiently exerted.

For this reason, if the ophthalmic composition of this invention is used, the state of eyes can be kept comfortable, without using together several ophthalmic compositions. Therefore, the ophthalmic composition of the present invention is used for improving, alleviating, treating, or preventing general eye symptoms or abnormalities, for improving, alleviating, treating, or preventing complex eye symptoms or abnormalities, for total eye care, or for normal total eyes. It can be a composition for chemical use. In addition, the ophthalmic composition of the present invention can be a multifunctional composition for improving, alleviating, or preventing general eye symptoms.
A condition that exhibits multiple symptoms or abnormalities of the eye may be more difficult to improve or prevent than a condition that exhibits a single symptom or abnormality. Even in such a case, the ophthalmic composition of the present invention can effectively improve, alleviate, treat, or prevent those symptoms.

  In addition, the ophthalmic composition of the present invention is composed of eye fatigue, blurred vision, itchy eyes, itchy eyes, conjunctival redness, blepharitis, ophthalmitis due to ultraviolet rays and other rays, foreign body sensation, sloppy eyes, contact It can also be used for improving, alleviating, treating, or preventing one eye symptom or abnormality selected from eye discomfort such as discomfort when wearing a lens, and eye disease.

  In addition, the ophthalmic composition of the present invention has a higher effect, alleviation, treatment, or prevention of 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 a salt thereof, (b) a decongestant, an eye muscle modulator, (a) an anti-inflammatory agent other than the component, And 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.

Planoprofen and / or its salt (component (a))
The planoprofen salt may be a pharmaceutically or physiologically acceptable salt, such as an alkali metal salt (sodium salt, potassium salt, etc.), an alkaline earth metal salt (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, And salts with organic bases such as picoline salts).
Planoprofen and its salts include those in the form of hydrates.
Planoprofen and its salt can be used singly or in combination of two or more.
Of the pranoprofen and / or its salt, 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 with respect to the total amount of the composition. / V% or more is even more preferable, and 0.03 w / v% or more is even more preferable. Moreover, 0.04 w / v% or more, or 0.05 w / v% or more may be sufficient.
Further, 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 more preferably 0.2 w with respect to the total amount of the composition. / V% or less is even more preferable, and 0.1 w / v% or less is even more preferable. Moreover, 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 may be sufficient.
If it is the said range, the effect of this invention will fully be acquired.
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%, Examples 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 anemia of the eye by constricting blood vessels, relieve local hyperemia, relieve pain and promote tissue healing. For example, by stimulating α-adrenergic nerves, it has a vasoconstrictive action, thereby contributing to the effects of the present invention.
Examples of the decongestant include, but are not limited to, epinephrine or a salt thereof (eg, epinephrine hydrochloride, epinephrine hydrogen tartrate), ephedrine or a salt thereof (eg, ephedrine hydrochloride), methylephedrine or a salt thereof (eg, methylephedrine hydrochloride, In particular, dl-methylephedrine hydrochloride), phenylephrine or a salt thereof (eg phenylephrine hydrochloride), imidazoline vasoconstrictor [tetrahydrozoline or a salt thereof (eg tetrahydrozoline hydrochloride), naphazoline or a salt thereof (eg naphazoline hydrochloride, naphazoline nitrate) And oxymetazoline or a salt thereof (for example, oxymetazoline hydrochloride).
Among them, epinephrine or a salt thereof (particularly epinephrine hydrochloride), ephedrine or a salt thereof (particularly ephedrine hydrochloride), methylephedrine or a salt thereof (particularly dl-methylephedrine hydrochloride), phenylephrine or a salt thereof (particularly phenylephrine hydrochloride), Imidazoline vasoconstrictors are preferred, imidazoline vasoconstrictors are more preferred, tetrahydrozoline hydrochloride, naphazoline hydrochloride, and naphazoline nitrate are more preferred, and tetrahydrozoline hydrochloride is particularly preferred.
One decongestant can be used alone, or two or more can be used in combination.

When the ophthalmic composition contains a decongestant, the total amount of the decongestant is, for example, 0.0006 w / v% or more, particularly 0.003 w / v% or more, with respect to the total amount of the composition. Of these, 0.01 w / v% or more, and 0.02 w / v% or more are particularly preferable. Moreover, 0.03 w / v% or more, 0.04 w / v% or more, or 0.05 w / v% or more may be sufficient.
Further, the total amount of the decongestant is, for example, 0.2 w / v% or less, particularly 0.15 w / v% or less, especially 0.1 w / v% or less, especially 0.05 w / v with respect to the total amount of the composition. % Or less.
If it is the said range, the effect of this invention will fully be acquired.
The total content of the decongestant is preferably 0.01 to 0.05 w / v%, preferably 0.01 w / v%, 0.02 w / v%, 0.03 w / v%, 0.04 w / v. v%, 0.05 w / v% and the like. 0.05 w / v% is particularly preferable.

Eye muscle modifier (component (b))
The eye muscle modulating agent stimulates the parasympathetic nerve of the pupil sphincter to contract the pupil. For example, by inhibiting the cholinesterase having an active center similar to acetylcholine, the parasympathetic nerve is activated, thereby contributing to the effect of the present invention.
Examples of the eye muscle modulator include, but are not limited to, neostigmine or a salt thereof (particularly neostigmine methyl sulfate), physostigmine or a salt thereof (eg, physostigmine salicylate, physostigmine sulfate), distigmine or a salt thereof (eg, distigmine bromide), Examples include tropicamide, atropine or a salt thereof (particularly, atropine of helenien sulfate), pilocarpine or a salt thereof (for example, pilocarpine hydrochloride) and the like.
Of these, neostigmine or a salt thereof is preferable, and neostigmine methylsulfate is particularly preferable.
The eye muscle modifiers can be used alone or in combination of two or more.

When the ophthalmic composition contains an eye muscle modifier, the total amount of the eye muscle modifier is, for example, 0.0002 w / v% or more, particularly 0.0005 w / v% with respect to the total amount of the composition. Above all, 0.001 w / v% or more, especially 0.002 w / v% or more can be mentioned. Moreover, 0.003 w / v% or more, 0.004 w / v% or more, or 0.005 w / v% or more may be sufficient.
In addition, the total amount of the eye muscle regulating agent is, for example, 0.02 w / v% or less, particularly 0.01 w / v% or less, especially 0.005 w / v% or less with respect to the total amount of the composition.
If it is the said range, the effect of this invention will fully be acquired.
The total content of the eye muscle modifier 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. 0.005 w / v% is particularly preferable.

Anti-inflammatory agent (component (b))
The ophthalmic composition of the present invention can contain an anti-inflammatory agent other than pranoprofen. The anti-inflammatory agent contributes to the effect of the present invention by suppressing inflammation or producing a converging action accordingly.
Anti-inflammatory agents other than pranoprofen include, but are not limited to, epsilon-aminocaproic acid, allantoin, berberine or a salt thereof (eg, berberine chloride, berberine sulfate), azulene sulfonic acid or a salt thereof (Eg, sodium azulene sulfonate, potassium azulene sulfonate, calcium azulene sulfonate, magnesium azulene sulfonate), glycyrrhizic acid or a salt thereof (eg, dipotassium glycyrrhizinate, monoammonium glycyrrhizate), zinc salt (eg, zinc sulfate) Zinc lactate), lysozyme or a salt thereof (eg lysozyme chloride), indomethacin, silver salt (eg silver nitrate), diclofenac acid or a salt thereof (eg diclofenac sodium), bromfenac acid or a salt thereof (eg bromfena ).
Among them, epsilon-aminocaproic acid, allantoin, berberine or a salt thereof (especially berberine chloride, berberine sulfate), azulenesulfonic acid or a salt thereof (particularly sodium azulenesulfonate), glycyrrhizic acid or a salt thereof ( In particular, dipotassium glycyrrhizinate), zinc salts (particularly zinc sulfate, zinc lactate), lysozyme or salts thereof (particularly lysozyme chloride) are preferred, and epsilon-aminocaproic acid and dipotassium glycyrrhizinate are more preferred.
An anti-inflammatory agent can be used individually by 1 type or in combination of 2 or more types.

When the ophthalmic composition contains an anti-inflammatory agent other than pranoprofen, the content thereof is, for example, 0.0005 w / v% or more in the total amount of the anti-inflammatory agent other than pranoprofen with respect to the total amount of the composition 0.005 w / v% or more, 0.02 w / v% or more, 0.1 w / v% or more, 0.25 w / v% or more, 0.3 w / v% or more, 0.35 w / v% or more, 0 4 w / v% or more, 0.45 w / v% or more, or 0.5 w / v% or more.
The total amount of anti-inflammatory agents other than pranoprofen is, for example, 10 w / v% or less, 2 w / v% or less, 1.5 w / v% or less, 1 w / v% or less, 0, 0.5 w / v% or less, 0.25 w / v% or less, 0.05 w / v% or less.
If it is the said range, the effect of this invention will fully be acquired.
The total content of anti-inflammatory agents other than pranoprofen is preferably 0.25 to 2 w / v%, and is preferably 0.25 w / v%, 0.3 w / v%, 0.35 w / v%, 0 .4 w / v%, 0.45 w / v%, 0.5 w / v%, 0.55 w / v%, 0.6 w / v%, 0.65 w / v%, 0.7 w / v%,. 75 w / v%, 0.8 w / v%, 0.85 w / v%, 0.9 w / v%, 0.95 w / v%, 1 w / v%, 1.05 w / v%, 1.1 w / v %, 1.15 w / v%, 1.2 w / v%, 1.25 w / v%, 1.3 w / v%, 1.35 w / v%, 1.4 w / v%, 1.45 w / v% 1.5w / v%, 1.55 / v%, 1.6w / v%, 1.65w / v%, 1.7w / v%, 1.75w / v%, 1.8w / v%, 1.85 w / v%, 1.9 w / v%, 1. 5w / v%, and the like 2w / v%. 1.25 w / v% is particularly preferred.

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.
Examples of the antihistamine include, but are not limited to, diphenhydramine or a salt thereof (for example, diphenhydramine hydrochloride), chlorpheniramine or a salt thereof (for example, chlorpheniramine maleate, chlorpheniramine fumarate), ketotifen or a salt thereof (for example, 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) is preferable, and chlorpheniramine maleate is more preferable.
An antihistamine can be used individually by 1 type or in combination of 2 or more types.

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, especially 0.006 w, based on the total amount of the composition. / V% or more, especially 0.01 w / v% or more. Moreover, 0.02 w / v% or more may be sufficient.
Further, the total amount of the antihistamine is, for example, 0.1 w / v% or less, particularly 0.05 w / v% or less, especially 0.03 w / v% or less, based on the total amount of the composition.
If it is the said range, the effect of this invention will fully be acquired.
The total content of antihistamines 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%, among others. 0.02 w / v%, 0.03 w / v%, 0.05 w / v%, and the like. 0.03 w / v% is particularly preferred.

Vitamins (component (b))
Vitamins play a major role in the metabolic function of the body in very small amounts. 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 adenine dinucleotide or a salt thereof (eg, flavin adenine dinucleotide sodium), cobalamin or a salt thereof (eg, cyanocobalamin, methylcobalamin), retinol, a derivative thereof and / or a derivative thereof. Salt (eg, retinol acetate, retinol palmitate), pyridoxine or a salt thereof (eg, pyridoxine hydrochloride), panthenol, pantothenic acid or a salt thereof (eg, sodium pantothenate, potassium pantothenate, calcium pantothenate, magnesium pantothenate) , Tocopherol, derivatives thereof and / or their salts (eg, tocopherol acetate, tocopherol succinate, tocopherol nicotinate), pyridoxal or salts thereof (eg, pyrophosphate) Dokisaru), ascorbic acid or a salt thereof (e.g., sodium ascorbate, calcium ascorbate) and the like.
Among them, flavin adenine dinucleotide or a salt thereof (particularly flavin adenine dinucleotide sodium), cobalamin or a salt thereof (particularly cyanocobalamin), retinol, a derivative thereof and / or a salt thereof (particularly retinol acetate, retinol palmitate), Pyridoxine or a salt thereof (particularly pyridoxine hydrochloride), panthenol, pantothenic acid or a salt thereof (particularly sodium pantothenate, calcium pantothenate), a tocopherol, a derivative thereof and / or a salt thereof (particularly a tocopherol acetate) is preferable. Pyridoxine hydrochloride and tocopherol acetate are more preferred.
Vitamins can be used singly or in combination of two or more.

When the ophthalmic composition contains vitamins (vitamins other than retinol, derivatives thereof and / or salts thereof), the content thereof is, for example, 0.8% in terms of the total amount of the vitamins relative to the total amount of the composition. 0002 w / v% or more, especially 0.002 w / v% or more, especially 0.005 w / v% or more, especially 0.01 w / v%, especially 0.03 w / v% or more. Moreover, 0.04 w / v% or more, or 0.05 w / v% or more may be sufficient.
In addition, the total amount of vitamins relative to the total amount of the composition is, for example, 1 w / v% or less, 0.9 w / v% or less, 0.8 w / v% or less, 0.7 w / v% or less, 0. 6 w / v% or less, 0.5 w / v% or less, 0.4 w / v% or less, 0.3 w / v% or less, 0.2 w / v% or less, 0.1 w / v% or less, 0.09 w / v% or less, 0.08 w / v% or less, 0.07 w / v% or less, 0.06 w / v% or less, or 0.05 w / v% or less.

When the ophthalmic composition contains retinol, a derivative thereof and / or a salt thereof, the content thereof is, for example, 500 units / unit in terms of the total amount of retinol, a derivative thereof and / or a salt thereof relative to the total amount of the composition. 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, 10000 units / 100 mL or more.
Further, the total amount of retinol, a derivative thereof and / or a salt thereof, for example, 100000 units / 100 mL) or less, 90000 units / mL or less, 80000 units / mL or less, 70000 units / mL or less, Examples include 60000 units / mL or less, 50000 units / 100 mL or less, 40000 units / 100 mL or less, 30000 units / 100 mL or less, 20000 units / 100 mL or less.
If it is the said range, the effect of this invention will fully be acquired.

Amino acids (component (b))
Amino acids mean a compound having an amino group and a carboxyl group or a sulfo group in the molecule or a derivative thereof, and contributes to the effects of the present invention by metabolizing cells and repairing damaged tissue.
Examples of amino acids include, but are not limited to, L-aspartic acid or a salt thereof (eg, potassium L-aspartate, sodium L-aspartate, magnesium L-aspartate, calcium L-aspartate, magnesium L-aspartate). -Potassium (a mixture of equal amounts of magnesium L-aspartate and potassium L-aspartate), aminoethyl sulfonic acid (taurine), sodium chondroitin sulfate, glutamic acid or a salt thereof (for example, 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), alginic acid or a salt thereof (for example, sodium alginate), and the like.
Aminoethylsulfonic 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. 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 (in particular, potassium L-aspartate, magnesium L-aspartate, magnesium L-aspartate / potassium (equivalent mixture of magnesium L-aspartate and potassium L-aspartate)) Aminoethylsulfonic acid (taurine) and sodium chondroitin sulfate are preferable, and potassium L-aspartate, aminoethylsulfonic acid, and sodium chondroitin sulfate are more preferable.
Amino acids can be used singly 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.
Also, the total amount of amino acids relative to the total amount of the composition, for example, 7 w / v% or less, 6 w / v% or less, 5 w / v% or less, 4 w / v% or less, 3 w / v% or less, 2 w / v % Or less, 1 w / v% or less, 0.9 w / v% or less, 0.8 w / v% or less, 0.7 w / v% or less, 0.6 w / v% or less, 0.5 w / v% or less. It is done.

(b) Total content of component 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, Especially 0.0007 w / v% or more, especially 0.0008 w / v% or more, especially 0.0009 w / v% or more, especially 0.001 w / v% or more, especially 0.002 w / v% or more, especially 0.003 w / 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, 0.1 w / v% or more, especially 0.2 w / v% or more, especially 1 w / v% or more.
The total amount of the composition is, 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. 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, 0.005 w / v% or less is mentioned.
If it is the said range, the effect of this invention will fully be acquired.

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, especially 0, relative 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, Of these, 20 parts by weight or more can be mentioned.
Further, for example, 200 parts by weight or less, especially 100 parts by weight or less, especially 50 parts by weight or less, especially 20 parts by weight or less, especially 10 parts by weight or less, especially 5 parts by weight or less, relative to 1 part by weight of the component (a) Among them, 2 parts by weight or less, especially 1 part by weight or less, especially 0.6 part by weight or less, especially 0.1 part by weight or less can be mentioned.
If it is the said range, the effect of this invention will fully be acquired.

In addition to the components (a) and (b), the ophthalmic composition of the present invention may contain a component having pharmacological activity or physiological activity.
A pharmacologically active ingredient or a physiologically active ingredient can be used individually by 1 type or in combination of 2 or more types.
Specific examples of the pharmacologically active ingredient or physiologically active ingredient are illustrated below. The pharmacologically active ingredient or physiologically active ingredient can be blended as either an active ingredient or additive.

Antibacterial component The ophthalmic composition of the present invention may further comprise an antibacterial component.
Antibacterial components include, but are not limited to, sulfamethoxazole or salts thereof (eg, sulfamethoxazole sodium, sulfamethoxazole potassium, sulfamethoxazole calcium, sulfamethoxazole magnesium) Sulfaxazole, sulfisomidine, sulfisomidine or a salt thereof (for example, sulfisomidine sodium, sulfisomidine potassium, sulfisomidine calcium, sulfisomidine magnesium), sulfa antibacterial agent, alkylpolyaminoethylglycine Chloramphenicol, ofloxacin, norfloxacin, levofloxacin, lomefloxacin hydrochloride, acyclovir and the like.
Among them, sulfamethoxazole or its salt (especially sulfamethoxazole sodium), sulfisoxazole, sulfisomidine or its salt (especially sulfisomidine sodium), sulfa antibacterial agent, alkylpolyamino Ethylglycine is preferred, and sulfamethoxazole sodium is more preferred.
An antimicrobial component can be used individually by 1 type or in combination of 2 or more types.

When the ophthalmic composition contains an antibacterial component, the total content of the antibacterial component is, for example, 0.001 w / v% or more, especially 0.005 w / v% or more, especially 0, relative to the total amount of the composition 0.01 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. . Moreover, 3 w / v% or more may be sufficient.
The total amount of the antibacterial component is, for example, 5 w / v% or less, particularly 4 w / v% or less, based on the total amount of the composition. Moreover, 3 w / v% or less may be sufficient.
The total content of antibacterial components is 1 w / v%, 1.5 w / v%, 2 w / v%, 2.5 w / v%, 3 w / v%, 3.5 w / v%, 4 w / v%, 4.5 w / v%, 5 w / v%, etc. are mentioned.

Antiallergic Agent The ophthalmic composition of the present invention can further contain an antiallergic agent.
Anti-allergic agents include, but are not limited to, cromoglycic acid or its salts (eg, sodium cromoglycate, potassium cromoglycate, calcium cromoglycate, magnesium cromoglycate), acitazanolast, amlexanox, ibudilast, tranilast, pemirolast Potassium etc. are mentioned.
Among them, cromoglycic acid or a salt thereof (particularly sodium cromoglycate) is preferable, and sodium cromoglycate is more preferable.
An antiallergic agent can be used individually by 1 type or in combination of 2 or more types.

When the ophthalmic composition contains an antiallergic agent, the content thereof is, for example, 0.01 w / v% or more, 0.05 w / v% or more, 0 in terms of the total amount of the antiallergic agent with respect to the total amount of the composition. .1 w / v% or more, 0.2 w / v% or more, 0.3 w / v% or more, 0.4 w / v% or more, 0.5 w / v% or more, 0.6 w / v% or more, 0.7 w / V% or more, 0.8 w / v% or more, 0.9 w / v% or more.
Further, the total amount of the antiallergic agent is, for example, 5 w / v% or less, 4 w / v% or less, 3 w / v% or less, 2 w / v% or less, 1.9 w / v% or less, 1.8 w / v% or less, 1.7 w / v% or less, 1.6 w / v% or less, 1.5 w / v% or less, 1.4 w / v% or less, 1.3 w / v% or less 2 w / v% or less, 1.1 w / v% or less, 1 w / v% or less.
The total content of antiallergic drugs is 0.01 w / v%, 0.05 w / v% 0.1 w / v%, 0.2 w / v%, 0.3 w / v%, 0.4 w / v% 0.5 w / v%, 0.6 w / v%, 0.7 w / v%, 0.8 w / v%, 0.9 w / v%, 1 w / v%, 1.1 / v%, 2 w / v%, 1.3 w / v%, 1.4 w / v%, w / v%, 1.5 w / v%, 1.6 w / v%, 1.7 w / v%, 1.8 w / v %, 1.9 w / v%, 2 w / v%, 3 w / v%, 4 w / v%, and the like.

Antioxidant The ophthalmic composition of the present invention may contain an antioxidant. Antioxidants stabilize pranoprofen and component (b), which are unstable to heat and light. Antioxidants improve the residual rate of pranoprofen and other medicinal ingredients contained in the ophthalmic composition and maintain their medicinal effects high, thereby significantly improving the effects of the present invention.
Examples of fat-soluble antioxidants include butyl group-containing phenols such as dibutylhydroxytoluene (BHT) and butylhydroxyanisole (BHA); nordihydroguaiaretic acid (NDGA); ascorbyl palmitate, ascorbyl stearate, ascorbine Ascorbic acid esters such as aminopropyl phosphate, tocopherol ascorbate phosphate, ascorbyl triphosphate, ascorbyl phosphate palmitate; ethyl gallate, propyl gallate, octyl gallate, gallic acid esters such as dodecyl gallate Propyl gallate; 3-butyl-4-hydroxyquinolin-2one; carotenoids such as lutein and astaxanthin; polyphenols such as anthocyanins, catechin, tannin and curcumin; CoQ 0 and the like.
Water-soluble antioxidants include ascorbic acid and ascorbic acid derivatives (ascorbic acid-2-sodium sulfate, sodium ascorbate, ascorbic acid-2-magnesium phosphate, ascorbic acid-2-sodium phosphate, etc.) Sodium bisulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, edetic 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 phenols (particularly dibutylhydroxytoluene and butylhydroxyanisole) are 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. Moreover, 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.
An antioxidant can be used individually by 1 type or in combination of 2 or more types.

When the ophthalmic composition contains an antioxidant, the content of the antioxidant is 0.0001 w / v% or more, 0.0005 w / v% or more, and 0.005 w / v% or more based on the total amount of the composition. 001 w / v% or more, 0.002 w / v% or more, 0.003 w / v% or more, 0.004 w / v% or more, 0.005 w / v% or more. In addition, the total amount of 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 and 0.005 w / v% or less.
The total content of antioxidants is 0.0001 w / v%, 0.0005 w / v%, 0.001 w / v%, 0.002 w / v%, 0.003 w / v based on the total amount of the composition. v%, 0.004 w / v%, 0.005 w / v%, 0.006 w / v%, 0.007 w / v%, 0.008 w / v%, 0.009 w / v%, 0.01 w / v %, 0.02 w / v%, 0.03 w / v%, 0.04 w / v%, 0.05 w / v%, 0.1 w / v%, 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 soothing agents such as procaine hydrochloride.

  Among the components of the ophthalmic composition of the present invention, any of d-form, l-form, or dl-form can be used as the component in which d-form, l-form, or dl-form exists. Moreover, a hydrate can also be used for the component which has a hydrate.

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

The ophthalmic composition may be an aqueous composition (mainly containing an aqueous or hydrophilic base or carrier), and an oily composition (an oil or hydrophobic base or carrier). Included).
The content of water in the case of the aqueous composition is preferably 50% by weight or more, more preferably 75% by weight or more, and still more preferably 90% by weight or more based on the total amount of the preparation. Moreover, 95 weight% or more or 98 weight% or more may be sufficient. In addition, the base or carrier may be composed only of water.
The water content in the case of an oily composition is preferably less than 50% by weight, more preferably 30% by weight or less, and even more preferably 20% by weight or less, based on the total 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. For example, eye drops (also referred to as eye drops or eye drops. Eye drops include eye drops that can be applied while wearing contact lenses), eye wash , Eye ointment (water-soluble eye ointment, oil-soluble eye ointment), contact lens mounting solution, intraocular injection (eg, intravitreal injection), contact lens solution (cleaning solution, preservation solution, disinfectant solution, multi-purpose solution, Package solutions), preservatives for isolated ocular tissues such as the cornea for transplantation, and perfusate during surgery. Eye drops, eye washes and eye ointments include those used when wearing contact lenses.
The dosage form of the ophthalmic composition of the present invention is preferably eye drops, eye wash, eye ointment (water-soluble eye ointment, oil-soluble eye ointment), contact lens mounting solution, contact lens solution (cleaning solution, preservative solution, disinfectant) Liquid, multipurpose solution, package solution), and more preferably eye drops, eye wash, contact lens mounting liquid, contact lens liquid (cleaning liquid, preservative liquid, disinfectant liquid, multipurpose solution, package solution), etc. Even more preferred are eye drops and eye wash, and particularly preferred are eye drops.

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

  The ophthalmic composition of the present invention comprises the above components (a) and (b), a pharmaceutically acceptable base or carrier, and optionally, a pharmaceutically acceptable additive of the ophthalmic composition, and others. For example, it can be prepared by a conventional method described in the 16th revised Japanese Pharmacopoeia Manual.

Examples of the base or carrier base or carrier include water; polar solvents such as ethanol; oily bases and the like.
A base or a support | carrier can be used individually by 1 type or in combination of 2 or more types.

What is used as an additive of an ophthalmic composition can be mix | blended with the ophthalmic composition of this invention without a restriction | limiting. Examples of additives include refreshing agents, inorganic salts, preservatives, surfactants, buffers, pH adjusters, isotonic agents, stabilizers, oils, saccharides, polyhydric alcohols and the like.
An additive can be used individually by 1 type or in combination of 2 or more types. Moreover, about each additive, 1 type can be used individually or in combination of 2 or more types.
Specific examples of the additive are exemplified below.

Cooling Agent The ophthalmic composition of the present invention can include a cooling agent.
Examples of the refreshing agent include, but are not limited to, terpenoids such as menthol, anethole, eugenol, camphor, geraniol, cineol, borneol, limonene, and agate. These may be any of d-form, l-form or dl-form. Moreover, essential oils such as mint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, bergamot oil, eucalyptus oil, rose oil and the like can also be mentioned.
Among these, terpenoids are preferable, and among these, menthol, camphor, geraniol, cineol, borneol, and agate are preferable, menthol, camphor, and borneol are more preferable, and menthol is more preferable.
A refreshing agent can be used individually by 1 type or in combination of 2 or more types.

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

Inorganic Salts The ophthalmic composition of the present invention can further contain inorganic salts.
Inorganic salts include, but are not limited to, potassium chloride, sodium chloride, calcium chloride, magnesium chloride, sodium bicarbonate, sodium carbonate (including dry sodium carbonate), potassium bicarbonate, potassium carbonate, magnesium sulfate, hydrogen phosphate Examples include 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. It is 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, potassium chloride, Sodium chloride, calcium chloride, sodium hydrogen phosphate, and sodium dihydrogen phosphate are more preferable, and potassium chloride and sodium chloride are still more preferable.
Inorganic salts can be used singly 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.
Also, the total amount of inorganic salts relative to the total amount of the composition, for example, 3 w / v% or less, 2 w / v% or less, 1 w / v% or less, 0.9 w / v% or less, 0.8 w / v% or less 0.7 w / v% or less, 0.6 w / v% or less, 0.5 w / v% or less.
The total content of 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. %, 0.5 w / v%, 0.6 w / v%, 0.7 w / v%, 0.8 w / v%, 0.9 w / v%, 1 w / v%, 2 w / v%, 3 w / v %.

Polymer thickener or thickener The ophthalmic composition of the present invention may further comprise a polymer thickener or thickener.
Examples of the polymer thickener or thickener include, but are not limited to, cellulose derivatives (for example, hydroxyethylcellulose, hydroxypropylmethylcellulose, methylcellulose, ethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, carboxyethylcellulose, carboxymethylcellulose), polyvinyl type High molecular compounds (for example, polyvinyl alcohol (including completely or partially saponified product), polyvinylpyrrolidone, polyvinyl methacrylate), polyethylene glycol, dextran, α-cyclodextrin, dextrin, carboxyvinyl polymer, alginic acid, glucose, mucopolysaccharide ( For example, hyaluronic acid, hyaluronic acid salt (eg hyaluronic acid sodium salt), heparin, heparin sulfate , Heparan sulfate, keratosulfate, heparinoid), guar gum, gum arabic, karaya gum, xanthan gum, agar, starch, chitin and its derivatives, chitosan and its derivatives, carrageenan, sorbitol, alkali metal salts of polyacrylic acid (for example, polyacrylic acid Sodium, potassium polyacrylate), amine salt of polyacrylic acid (eg, polyacrylic acid monoethanolamine salt, polyacrylic acid diethanolamine salt, polyacrylic acid triethanolamine salt), casein, gelatin, collagen, pectin, elastin, Ceramide, liquid paraffin, glycerin, macrogol, polyethyleneimine alginate (for example, sodium alginate), alginate (for example, propylene glycol alginate) And Tragant powder.
These components may be salts (eg, sodium salt, potassium salt, calcium salt, magnesium salt) other than those exemplified above.
Among these, cellulose derivatives (particularly, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose), polyvinyl alcohol (including completely or partially saponified product), polyvinyl pyrrolidone, carboxyvinyl polymer, alginic acid, and glucose are preferable, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, Carboxyvinyl polymer is more preferable, and hydroxypropylmethylcellulose is more preferable.
A polymeric thickener or a thickener can be used individually by 1 type or in combination of 2 or more types.

When the ophthalmic composition contains a polymer thickener or thickener, the total amount of the polymer thickener or thickener is, for example, 0.001 w / v 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, or 0.1 w / v% or more.
The total amount of the polymer thickener or thickener is, 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, 0.7 w / v% or less, 0.6 w / v% or less, 0.5 w / v% or less, 0.4 w / v% or less, 0.3 w / v% or less, 0.2 w / v% or less, 0.1 w / v% or less is 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. %, 0.04 w / v%, 0.05 w / v%, 0.06 w / v%, 0.07 w / v%, 0.08 w / v%, 0.09 w / v%, 0.1 w / v% 0.2 w / v%, 0.3 w / v%, 0.4 w / v%, 0.5 w / v%, 0.6 w / v%, 0.7 w / v%, 0.8 w / v%, 0.9 w / v%, 1 w / v%, 2 w / v%, 3 w / v%, 4 w / v%, 5 w / v% and the like.

Preservative The ophthalmic composition of the present invention may further contain a preservative.
Preservatives include, but are not limited to, boric acid, alkyldiaminoethyl glycine and / or its salts (eg, alkyldiaminoethyl glycine hydrochloride), benzoic acid and / or its salts (eg, sodium benzoate, potassium benzoate) ), Ethanol, quaternary ammonium salts (eg benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride), chlorhexidine and / or its salts (eg chlorhexidine gluconate), chlorobutanol, sorbic acid and / or its salts ( For example, potassium sorbate), sodium dehydroacetate, paraoxybenzoate (eg, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate), oxyquinoline sulfate, fe Chill alcohol, benzyl alcohol, Biguamido, such as poly hexamethylene biguanide and its salts (such as hydrochloride polyhexanide), Gurokiru (trade name, Rhodia), such as chloride Poridoroniumu the like.
Among them, boric acid, quaternary ammonium salt (especially benzalkonium chloride, benzethonium chloride), chlorhexidine and / or a salt thereof (particularly chlorhexidine gluconate), chlorobutanol, sorbic acid and / or a salt thereof (eg sorbine) Acid potassium), polyhexamethylene biguanide and salts thereof, alkyl polyaminoethylglycine, benzalkonium chloride, chlorhexidine gluconate, chlorobutanol, potassium sorbate, polyhexanide hydrochloride are more preferable, benzalkonium chloride, chlorobutanol, hydrochloric acid More preferred is polyhexanide.
A preservative can be used individually by 1 type or in combination of 2 or more types.

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, 0.0003 w / v% or more, 0.0004 w / v% or more, 0.0005 w / v% or more, 0.0006 w / v% or more, 0.0007 w / v% or more, 0.0008 w / v % Or more, 0.0009 w / v% or more, 0.001 w / v% or more.
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, .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 0.00001 w / v%, 0.0001 w / v%, 0.0002 w / v%, 0.0003 w / v%, 0.0004 w / v with respect to the total amount of the composition. %, 0.0005 w / v%, 0.0006 w / v%, 0.0007 w / v%, 0.0008 w / v%, 0.0009 w / v%, 0.001 w / v%, 0.002 w / v% 0.003 w / v%, 0.004 w / v%, 0.005 w / v%, 0.006 w / v%, 0.007 w / v%, 0.008 w / v%, 0.009 w / v%, 0.01 w / v%, 0.05 w / v%, 0.1 w / v%, 0.2 w / v%, 0.5 w / v%, etc. are mentioned.

Surfactant The ophthalmic composition of the present invention can comprise a surfactant.
Among the surfactants, nonionic surfactants are preferable.
Nonionic surfactants include monolauric acid POE (20) sorbitan (polysorbate 20), monopalmitic acid POE (20) sorbitan (polysorbate 40), monostearic acid POE (20) sorbitan (polysorbate 60), and tristearic acid POE. (20) POE sorbitan fatty acid esters such as sorbitan (polysorbate 65) and monooleic acid POE (20) sorbitan (polysorbate 80); POP glycols: POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, POE hydrogenated castor oil 80, etc .; POE castor oil 3, POE castor oil 4, POE castor oil 6, POE castor oil 6, POE Castor oil 7, POE castor oil 1 POE castor oil such as 0, 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; polyethylene glycol monostearate ( 2E.O.), polyethylene glycol monostearate (4E.O.), polyethylene glycol monostearate (9E.O.), polyethylene glycol monostearate (10E.O.), polyethylene glycol monostearate (23E.O.). O.), polyethylene glycol monostearate (25E.O.), polyethylene glycol monostearate (32E.O.), polyethylene glycol monostearate (40E.O., polyoxyl 40 stearate), polyethylene monostearate Polyglycol monostearate such as Recall (45E.O.), Polyethylene glycol monostearate (55E.O.), Polyethylene glycol monostearate (75E.O.), Polyethylene glycol monostearate (140E.O.) POE alkyl ethers such as POE (9) lauryl ether; POE-POP alkyl ethers such as POE (20) POP (4) cetyl ether; POE alkyl phenyl ethers such as POE (10) nonyl phenyl ether It is done. In the compounds exemplified above, POE is polyoxyethylene, POP is polyoxypropylene, and the numbers in parentheses indicate the number of moles added.

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

In addition, amphoteric surfactants such as betaine-type amphoteric surfactants (eg, lauryldimethylaminoacetic acid betaine, imidazolinium betaine); alkyl quaternary ammonium salts (eg, benzalkonium chloride, benzethonium chloride) A cationic surfactant can also be used.
Surfactant can be used individually by 1 type or in combination of 2 or more types.

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

Buffering Agent The ophthalmic composition of the present invention may contain a buffering agent.
Examples of the buffer include borate buffer, phosphate buffer, carbonate buffer, citrate buffer, and acetate buffer.
Examples of the components of the boric acid buffer include boric acid and borates (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.). The borate may be a hydrate.
Phosphate buffer components include phosphoric acid, phosphate (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, And calcium dihydrogen phosphate). The phosphate may be a hydrate.
Examples of the component of the carbonate buffer include carbonic acid and carbonate (such as potassium carbonate, sodium carbonate, calcium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, magnesium carbonate).
Examples of the citrate buffer component include citric acid and citrate (such as sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, and disodium citrate).
Examples of the component of the acetate buffer include acetic acid and acetate (such as ammonium acetate, potassium acetate, calcium acetate, and sodium acetate).
Among these, a borate buffer and a phosphate buffer are preferable, and a borate buffer is more preferable in that the effect of the present invention is further improved. The boric acid buffer is preferably a combination of boric acid and its salt, more preferably a combination of boric acid and an alkali metal salt of boric acid and / or an alkaline earth metal salt, and an alkali metal of boric acid and boric acid. A combination with a salt is further preferred, and a combination of boric acid and borax is even more preferred.
A buffering agent can be used individually by 1 type or in combination of 2 or more types.

When the ophthalmic composition of the present invention contains a buffering agent, the content varies depending on the type of buffering agent, the type and amount of other compounding components, and cannot be uniformly defined. The total amount of the buffering agent is 0.001 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. Further, the total amount of the buffering agent is 10 w / v% or less, particularly 5 w / v% or less, especially 3 w / v% or less, especially 2 w / v% or less with respect to 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. %, 1 w / v%, 2 w / v%, 3 w / v%, 5 w / v%, 10 w / v%, and the like.

pH adjuster The ophthalmic composition of the present invention may contain a pH adjuster.
Examples of pH regulators include hydrochloric acid, sulfuric acid, polyphosphoric acid, organic acids (propionic acid, oxalic acid, gluconic acid, fumaric acid, lactic acid, tartaric acid, malic acid, succinic acid, etc.), sodium hydroxide, potassium hydroxide, hydroxide Examples include calcium, magnesium hydroxide, triethanolamine, monoethanolamine, and diisopropanolamine.

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

Oil content The ophthalmic composition of the present invention may contain an oil content. Examples of the oil include animal oil such as squalane, liquid paraffin, mineral oil such as petrolatum, vegetable oil such as castor oil and sesame oil.

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

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

  Specific combinations of components that can be blended in the ophthalmic composition of the present invention are exemplified below. These combinations mean that these components are included at the minimum, and various components can be included in addition to the displayed components.

(1) Planoprofen, tetrahydrozoline hydrochloride, neostigmine methyl sulfate, dipotassium glycyrrhizinate, chlorpheniramine maleate, pyridoxine hydrochloride, and potassium L-aspartate
(2) In (1), in place of potassium L-aspartate, aminoethylsulfonic acid, chondroitin sulfate, potassium L-aspartate and aminoethylsulfonic acid, potassium L-aspartate and chondroitin sulfate, or aminoethylsulfonic acid With chondroitin sulfate
(3) In (1) or (2), instead of pyridoxine hydrochloride, tocopherol acetate, panthenol, cyanocobalamin, flavin adenine dinucleotide, pyridoxine hydrochloride and tocopherol acetate, pyridoxine hydrochloride and panthenol, pyridoxine hydrochloride and cyanocobalamin hydrochloride, pyridoxine hydrochloride And flavin adenine dinucleotide, tocopherol acetate and panthenol, tocopherol acetate and cyanocobalamin, tocopherol acetate and flavin adenine dinucleotide, panthenol and cyanocobalamin, panthenol and flavin adenine dinucleotide, cyanocobalamin and flavin adenine dinucleotide, pyridoxine hydrochloride and tocopherol acetate And panthenol, pyridoxine hydrochloride, tocopherol acetate and cyanocobalamin, pyridoxine hydrochloride and vinegar Tocopherol acid and flavin adenine dinucleotide, tocopherol acetate and panthenol and cyanocobalamin, tocopherol acetate and panthenol and flavin adenine dinucleotide, panthenol, cyanocobalamin, flavin adenine dinucleotide, pyridoxine hydrochloride, tocopherol acetate and pantenol and cyanocobalamin hydrochloride, pyridoxine hydrochloride And a combination comprising tocopherol acetate, panthenol and flavin adenine dinucleotide, tocopherol acetate and panthenol and cyanocobalamin and flavin adenine dinucleotide, or pyridoxine hydrochloride, tocopherol acetate, panthenol, cyanocobalamin and flavin adenine dinucleotide
(4) In (1) to (3), instead of chlorpheniramine maleate, diphenhydramine hydrochloride, or a combination comprising chlorpheniramine maleate and diphenhydramine hydrochloride
(5) In (1) to (4), instead of dipotassium glycyrrhizinate, epsilon aminocaproic acid, allantoin, zinc sulfate, sodium azulene sulfonate, dipotassium glycyrrhizinate and epsilon aminocaproic acid, dipotassium glycyrrhizinate and allantoin, Dipotassium glycyrrhizinate and zinc sulfate, Dipotassium glycyrrhizinate and sodium azulene sulfonate, Epsilon aminocaproic acid and allantoin, Epsilon aminocaproic acid and zinc sulfate, Epsilon aminocaproic acid and sodium azulene sulfonate, Allantoin and zinc sulfate, Allantoin and azulene sulfonic acid Sodium, zinc sulfate and sodium azulene sulfonate, dipotassium glycyrrhizinate and epsilon aminocaproic acid and allantoin, dicalylic acid dicarbonate Lithium and epsilon aminocaproic acid and zinc sulfate, dipotassium glycyrrhizinate and epsilon aminocaproic acid and sodium azulene sulfonate, dipotassium glycyrrhizinate and allantoin and zinc sulfate, dipotassium glycyrrhizinate and allantoin and sodium azulene sulfonate, dipotassium glycyrrhizinate Zinc sulfate and sodium azulenesulfonate, epsilon aminocaproic acid and allantoin and zinc sulfate, epsilon aminocaproic acid and allantoin and sodium azulenesulfonate, allantoin and zinc sulfate and sodium azulenesulfonate, dipotassium glycyrrhizinate and epsilon aminocaproic acid and allantoin and sulfuric acid Zinc, dipotassium glycyrrhizinate, epsilon aminocaproic acid, allantoin and azulenesulfo Combination comprising sodium acid, epsilon aminocaproic acid and allantoin and zinc and sodium azulene sulfonate sulfate, or dipotassium glycyrrhizinate and epsilon aminocaproic acid and allantoin and zinc and sodium azulene sulfonate sulfate
(6) In (1) to (5), instead of tetrahydrozoline hydrochloride, naphazoline hydrochloride, or a combination comprising tetrahydrozoline hydrochloride and naphazoline hydrochloride

(7) A combination not containing amino acids in (1) to (6)
(8) A combination not containing vitamins in (1) to (6)
(9) A combination not containing an antihistamine in (1) to (6)
(10) In (1) to (6), a combination containing no anti-inflammatory agent other than pranoprofen
(11) In (1) to (6), a combination not containing an eye muscle modifier
(12) In (1) to (6), a combination containing no decongestant

(13) A combination that does not contain amino acids and vitamins in (1) to (6)
(14) In (1) to (6), a combination not containing an amino acid and an antihistamine
(15) In (1) to (6), a combination containing no amino acid and an anti-inflammatory agent other than pranoprofen
(16) In (1) to (6), a combination not containing an amino acid and an eye muscle modulator
(17) In (1) to (6), a combination containing no amino acids and a decongestant
(18) A combination not containing vitamins and antihistamines in (1) to (6)
(19) In (1) to (6), a combination containing no vitamins and an anti-inflammatory agent other than pranoprofen
(20) Combinations of (1) to (6) that do not contain vitamins and eye muscle modifiers
(21) A combination that does not contain vitamins and a decongestant in (1) to (6)
(22) In (1) to (6), a combination containing no anti-inflammatory agent other than antihistamine and pranoprofen
(23) A combination that does not contain an antihistamine and an eye muscle modulator in (1) to (6)
(24) A combination that does not contain an antihistamine and a decongestant in (1) to (6)
(25) In (1) to (6), a combination containing no anti-inflammatory agent other than pranoprofen and an eye muscle modulating agent
(26) In (1) to (6), a combination not containing an anti-inflammatory agent other than pranoprofen and a decongestant
(27) In (1) to (6), a combination not containing an eye muscle modulator and a decongestant

(28) A combination of (1) to (6) that does not contain amino acids, vitamins, and antihistamines
(29) Combinations of (1) to (6) that do not contain amino acids, vitamins, and eye muscle modulators
(30) Combinations of (1) to (6) that do not contain amino acids, vitamins, and a decongestant
(31) A combination not containing an amino acid, an antihistamine, and an anti-inflammatory agent other than pranoprofen in (1) to (6)
(32) In (1) to (6), a combination not containing an amino acid, an antihistamine, and an eye muscle modulator
(33) A combination not containing an amino acid, an antihistamine, and a decongestant in (1) to (6)
(34) In (1) to (6), a combination not containing an amino acid and an anti-inflammatory agent other than pranoprofen and an eye muscle modulator
(35) A combination of (1) to (6) that does not contain an anti-inflammatory agent other than amino acids and pranoprofen and a decongestant
(36) In (1) to (6), a combination not containing an amino acid, an eye muscle modulator, and a decongestant
(37) In (1) to (6), a combination containing no vitamins, antihistamines and anti-inflammatory agents other than pranoprofen
(38) A combination that does not contain vitamins, antihistamines, and eye muscle modifiers in (1) to (6)
(39) Combinations of (1) to (6) that do not contain vitamins, antihistamines and decongestants
(40) A combination of (1) to (6) that does not contain an anti-inflammatory agent other than vitamins and pranoprofen and an eye muscle modulator
(41) Combinations of (1) to (6) that do not contain an anti-inflammatory agent other than vitamins and pranoprofen and a decongestant
(42) Combinations of (1) to (6) that do not contain vitamins, eye muscle modifiers and decongestants
(43) In (1) to (6), a combination not containing an anti-histamine and an anti-inflammatory agent other than pranoprofen and an eye muscle modulator
(44) In (1) to (6), a combination not containing an anti-histamine and an anti-inflammatory agent other than pranoprofen and a decongestant
(45) The combination of (1) to (6), which does not contain an antihistamine, an eye muscle modulator, and a decongestant
(46) The combination of (1) to (6), which does not contain an anti-inflammatory agent, an eye muscle modulator, 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 containing no amino acids, vitamins, antihistamines and eye muscle modulators
(49) A combination that does not contain amino acids, vitamins, antihistamines and decongestants in (1) to (6)
(50) Combinations of (1) to (6) that do not contain an anti-inflammatory agent other than amino acids, vitamins, and pranoprofen and an eye muscle modulator
(51) In (1) to (6), a combination not containing an anti-inflammatory agent and a decongestant other than amino acids, vitamins and pranoprofen
(52) Combinations of (1) to (6) that do not contain amino acids, vitamins, eye muscle modulators and decongestants
(53) Combinations of (1) to (6) that do not contain vitamins, antihistamines, anti-inflammatory agents other than pranoprofen, and eye muscle modulators
(54) Combinations of (1) to (6) that do not contain vitamins, antihistamines, eye muscle regulators, and decongestants
(55) The combination of (1) to (6), which does not contain an anti-inflammatory agent other than an antihistamine and pranoprofen, an eye muscle modulator, and a decongestant

(56) The combination further comprising dibutylhydroxytoluene and / or sodium edetate in (1) to (55)
(57) In (1) to (55), a combination further comprising menthol and / or camphor
(58) The combination according to (1) to (55), further comprising hydroxypropylmethylcellulose
(59) In (1) to (55), a combination further comprising dibutylhydroxytoluene and / or sodium edetate and menthol and / or camphor
(60) In (1) to (55), a combination further comprising dibutylhydroxytoluene and / or sodium edetate and hydroxypropylmethylcellulose
(61) In (1) to (55), a combination further comprising menthol and / or camphor and hydroxypropylmethylcellulose
(62) In (1) to (55), a combination further comprising dibutylhydroxytoluene and / or sodium edetate, menthol and / or camphor, and hydroxypropylmethylcellulose

The composition containing the components (1) to (62) is used for eye fatigue, blurred vision, itchy eyes, conjunctival hyperemia, blepharitis, ophthalmitis due to light, foreign body sensation, sleek eyes, and contact lenses. Used to ameliorate, relieve, treat, or prevent one or more symptoms or abnormalities selected from the group consisting of discomfort and eye disease (such as eye disease caused by swimming, eye disease caused by dust or sweat entering the eye, etc.) be able to. Specifically, the following symptom or abnormality can be improved, alleviated, treated, or prevented.
When a plurality of symptoms or abnormalities are exhibited, the symptoms or abnormalities may be combined.

  Eye fatigue, blurred vision, itchy eyes, conjunctival congestion, blepharitis, light-induced ophthalmitis, foreign body sensation, sore eyes, discomfort when wearing contact lenses, or eye disease (eye disease caused by swimming, dust or sweat (The same applies to the use of the composition containing the components (1) to (62) below.)

Eye fatigue and blurred vision, eye fatigue and itchy eyes, eye fatigue and conjunctival hyperemia, eye fatigue and blepharitis, eye fatigue and light-induced eye inflammation, eye fatigue and foreign body sensation, eye fatigue and stains Eyes, eye fatigue and discomfort when wearing contact lenses, eye fatigue and eye disease,
Blurred eyes and itchy eyes, blurred eyes and conjunctival redness, blurred eyes and blepharitis, blurred eyes and light-induced ophthalmitis, blurred eyes and foreign objects, blurred and blurred eyes, blurred eyes and contact with eyes Discomfort when wearing lenses, blurred vision and eye disease,
Eye itching and conjunctival redness, eye itching and blepharitis, eye itching and light-induced eye inflammation, eye itching and foreign body sensation, eye itching and freckles, eye itching and discomfort when wearing contact lenses, eyes Itching and eye disease,
Conjunctival congestion and blepharitis, Conjunctival congestion and light-induced ophthalmitis, Conjunctival congestion and foreign body sensation, Conjunctival congestion and discoloration, Conjunctival congestion and discomfort when wearing contact lenses, Conjunctival congestion and eye disease,
Blepharitis and light-induced blaze, blistering and foreign body sensation, blistering and freckles, blistering and discomfort when wearing contact lenses, blepharitis and eye disease,
Ophthalmia and foreign body sensation caused by light rays, ophthalmia and freckles caused by light rays, ophthalmitis caused by light rays and discomfort when wearing contact lenses, ophthalmitis and eye diseases caused by light rays,
Foreign body sensation and freckles, foreign body sensation and discomfort when wearing contact lenses, foreign body sensation and eye disease,
Nasty eyes and discomfort when wearing contact lenses, nasty eyes and eye diseases,
Discomfort and eye disease when wearing contact lenses,

Eye fatigue, blurred vision and itchy eyes, fatigue, blurred vision and conjunctival redness,
Eye fatigue, blurred vision and blepharitis, eye strain, blurred vision and light-induced ophthalmitis,
Eye fatigue, blurred vision and foreign body feeling, eye fatigue and blurred vision and eyes, eye fatigue, blurred vision and discomfort when wearing contact lenses, eye fatigue, blurred vision and eye disease,
Eye fatigue, itchy eyes and conjunctival redness, eye fatigue, itchy eyes and blepharitis, eye fatigue, eye itching and light-induced eye inflammation, eye fatigue, eye itching and foreign body sensation, eye fatigue Eye itching and eyelids, eye fatigue and itching and discomfort when wearing contact lenses, eye fatigue and itching and eye disease,
Eye fatigue and conjunctival redness and blepharitis, eye fatigue and conjunctival redness and light-induced ophthalmitis, eye fatigue and conjunctival redness and foreign body sensation, eye fatigue and conjunctival redness and discoloration, eye fatigue and conjunctival redness and contact Discomfort when wearing lenses, eye fatigue and conjunctival congestion and eye disease,
Eye fatigue, blepitis and light-induced eye inflammation, eye fatigue and blepitis and foreign body sensation, eye fatigue and blepharitis and freckles, eye fatigue and blepitis and discomfort when wearing contact lenses, eye fatigue And blepharitis and eye disease,
Eye fatigue caused by eye fatigue and light, foreign body sensation, eye fatigue caused by light and eye flames and freckles, eye fatigue caused by light rays and discomfort when wearing contact lenses, eye fatigue caused by eye fatigue and light rays Eye disease,
Eye fatigue, foreign body sensation and freckles, eye fatigue, foreign body sensation, discomfort when wearing contact lenses, eye fatigue, foreign body sensation, and eye disease
Tired eyes and discomfort when wearing contact lenses, tired eyes and eyes and eye disease,
Eye fatigue, discomfort and eye disease when wearing contact lenses,

Blurred eyes, itchy eyes and conjunctival redness, blurred eyes, itchy eyes and blepharitis, blurred eyes, itchy eyes and rays of eyes, blurred eyes, itchy eyes and foreign bodies, blurred eyes Itchy eyes and itchy eyes, blurred eyes and itchy eyes and discomfort when wearing contact lenses, blurred eyes and itchy eyes and eye disease,
Eye haze and conjunctival redness and blepharitis, eye haze and conjunctival redness and light-induced ophthalmitis, eye haze and conjunctival redness and foreign body sensation, eye haze and conjunctival redness and blemishes, eye haze and conjunctival redness and contact Discomfort when wearing lenses, blurred vision and conjunctival congestion and eye disease,
Blurred eyes, blepharitis and light-induced ophthalmitis, blurred vision, blepharitis and foreign body sensation, blurred vision and blisters, blurred vision, blurred vision, blepitis and discomfort when wearing contact lenses, blurred vision And blepharitis and eye disease,
Ocular inflammation and foreign body sensation due to blurred vision and light, ophthalmic and blemishes due to blurred vision and light, ophthalmic inflammation due to blurred vision and light and discomfort when wearing contact lenses, blurred vision and ophthalmic inflammation due to light Eye disease,
Blurred eyes and foreign body sensation and freckles, blurred vision and foreign body sensation and discomfort when wearing contact lenses, blurred vision and foreign body sensation and eye disease,
Blurred eyes and blemishes and discomfort when wearing contact lenses, blurred vision and blemishes and eye disease,
Blurred eyes and discomfort and eye disease when wearing contact lenses,

Eye itching and conjunctival redness and blepharitis, eye itching and conjunctival redness and light-induced ophthalmitis, eye itching and conjunctival redness and foreign body sensation, eye itching and conjunctival redness and blemishes, eye itching and conjunctival redness and contact Discomfort when wearing lenses, itchy eyes and conjunctival congestion and eye disease,
Itchy eyes, blepharitis and light-induced ophthalmitis, itchy eyes, blepharitis and foreign body sensation, itchy eyes, blepharitis and blemishes, itchy eyes, blepitis and discomfort when wearing contact lenses, itchy eyes And blepharitis and eye disease,
Eye itch and foreign body sensation due to eye itch and light, eye itch and light eye due to eye itch and light, eye inflammation due to eye itch and light and discomfort when wearing contact lenses, eye inflammation due to eye itch and light Eye disease,
Itchy eyes, foreign body sensations and freckles, itchy eyes, foreign body sensations, and discomfort when wearing contact lenses, itchy eyes, foreign body sensations, and eye diseases,
Itchy eyes and eyebrows and discomfort when wearing contact lenses, itchy eyes and eyebrows and eye diseases,
Itchy eyes and discomfort and eye disease when wearing contact lenses,

Conjunctival redness, blepharitis and light-induced ophthalmitis, conjunctival redness and blepharitis and foreign body sensation, conjunctival redness and blepharitis and freckles, conjunctival redness and blepharitis and discomfort when wearing contact lenses, conjunctival redness and blepharitis and eye disease ,
Ophthalmia and foreign body sensation due to conjunctival redness and light, ophthalmia and discoloration due to conjunctival redness and light, ophthalmia due to conjunctival redness and light and discomfort when wearing contact lenses, ophthalmia and eye disease due to conjunctival redness and light,
Conjunctival redness and foreign body sensation and discoloration, Conjunctival redness and foreign body sensation and discomfort when wearing contact lenses, Conjunctival redness and foreign body sensation and eye disease,
Conjunctival hyperemia and blemishes and discomfort when wearing contact lenses, conjunctival hyperemia and blemishes and eye diseases,
Conjunctival hyperemia and discomfort and eye disease when wearing contact lenses,

Eyelids and foreign body sensation due to blepharitis and light, eyeitis and freckles due to blepharitis and light, eye inflammation due to blepharitis and light and discomfort when wearing contact lenses, eye inflammation and eye disease due to blepharitis and light,
Blepharitis and foreign body sensation and freckles, blepharitis and foreign body sensation and discomfort when wearing contact lenses, blepharitis and foreign body sensation and eye disease,
Discomfort associated with blepitis and blemishes and contact lenses, blepharitis and blemishes and eye diseases,
Discomfort and eye disease when wearing blister and contact lenses,

Ophthalmitis and foreign body sensation and freckles due to light rays, ophthalmia and foreign body sensations due to light rays and discomfort when wearing contact lenses, ophthalmitis due to light rays and foreign body sensation and eye diseases,
Ophthalmitis and blemishes due to light rays and discomfort when wearing contact lenses, ophthalmitis and blemishes and eye diseases caused by light rays,
Ophthalmitis due to light rays and discomfort and eye disease when wearing contact lenses,

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

  Discomfort and eye disease when wearing nasty eyes and contact lenses,

Eye fatigue, blurred eyes, itchy eyes and conjunctival redness, blurred eyes, blurred eyes, itchy eyes and blepharitis, blurred eyes, blurred eyes, itchy eyes and eye inflammation caused by light rays, tired eyes And blurred eyes, itchy eyes and foreign body feeling, tired eyes and blurred eyes and itchy eyes, tired eyes and blurred eyes, itchy eyes and discomfort when wearing contact lenses, tired eyes And blurred vision, itchy eyes and eye disease,
Eye fatigue, blurred vision, conjunctival redness and blepharitis, eye fatigue, blurred vision, conjunctival congestion and light-induced ophthalmitis, eye fatigue, blurred vision, conjunctival congestion, foreign body sensation, tired eyes and eyes Haze and conjunctival redness and freckles, eye fatigue and blurred vision and conjunctival redness and discomfort when wearing contact lenses, eye fatigue and blurred vision and conjunctival redness and eye disease,
Eye fatigue, blurred vision, blepitis and light-induced ophthalmitis, eye fatigue, blurred vision, blepharitis and foreign body sensation, blurred eyes, blurred vision and eyes Haze and blepharitis and discomfort when wearing contact lenses, eye fatigue and blurred vision and blepharitis and eye disease,
Eye fatigue and blurred vision due to eye fatigue and blurred vision, eye fatigue and blurred vision due to eye fatigue and blurred vision, eye fatigue caused by eye fatigue and blurred vision and contact lenses Discomfort, eye fatigue and blurred vision and ophthalmitis and eye disease
Eye fatigue, blurred vision, foreign body sensation and freckles, eye fatigue, blurred vision, foreign body sensation, discomfort when wearing contact lenses, eye fatigue, blurred vision, foreign body sensation, and eye disease,
Eye fatigue and blurred vision and discomfort when wearing contact lenses, eye fatigue and blurred vision and blurred eyes and eye disease,
Eye fatigue, blurred vision, discomfort and eye disease when wearing contact lenses,

Eye fatigue, itchy eyes, conjunctival redness and blepharitis, eye fatigue, itchy eyes, conjunctival redness and light-induced ophthalmitis, eye fatigue, itchy eyes, conjunctival redness and foreign body sensation, eye fatigue and eyes Itching and conjunctival redness and freckles, eye fatigue and itching and conjunctival redness and discomfort when wearing contact lenses, eye fatigue and itching and conjunctival redness and eye disease,
Eye fatigue, itchy eyes, blepitis and light-induced eye inflammation, eye fatigue, itchy eyes, blepitis and foreign body sensation, eye fatigue, itchy eyes, blistering and blisters, eye fatigue and eyes Itching, blepharitis and discomfort when wearing contact lenses, eye fatigue, itching, blepharitis and eye disease,
Eye fatigue due to eye fatigue, itchy eyes and light, ocular sensation, foreign body feeling, eye fatigue due to eye fatigue, itchy eyes and light, ocular inflammation due to eye fatigue, eye itching, light rays, and contact lenses Discomfort, eye fatigue and itching and eye damage caused by light and eye disease,
Eye fatigue, itchy eyes, foreign body sensation and freckles, eye fatigue, itchy eyes, foreign body sensation, discomfort when wearing contact lenses, eye fatigue, itchy eyes, foreign body sensation, and eye disease,
Eyestrain and itchy eyes and discomfort when wearing contact lenses and contact lenses, eye fatigue and itchy eyes and eyes and eye disease,
Eye fatigue, itching, discomfort and eye disease when wearing contact lenses,

Eye fatigue, conjunctival redness, blepharitis and light-induced ophthalmitis, eye fatigue, conjunctival redness, blepharitis and foreign body sensation, eye fatigue, conjunctival redness and blepharitis and discoloration, eye fatigue, conjunctival redness and blepharitis And discomfort when wearing contact lenses, eye fatigue and conjunctival hyperemia, blepharitis and eye disease,
Eye fatigue and conjunctival redness and light-induced ophthalmia and foreign body sensation, eye fatigue and conjunctival redness and light-induced ophthalmia and freckles, eye fatigue and conjunctival redness and light-induced ophthalmia and discomfort when wearing contact lenses, Eye fatigue, conjunctival redness, and ophthalmitis and eye disease caused by light rays
Eye fatigue, conjunctival redness and foreign body sensation and discoloration;
Tired eyes and conjunctival redness and discoloration and discomfort when wearing contact lenses, eye fatigue and conjunctival redness and frowning and eye disease,
Eye fatigue, conjunctival redness, discomfort and eye disease when wearing contact lenses,

Eye fatigue, blepitis and light-induced eye inflammation and foreign body sensation, eye fatigue and blepharitis and light-induced eye inflammation and freckles, eye fatigue and blepitis and light-induced eye inflammation and discomfort when wearing contact lenses, Eye fatigue, blepharitis and eye ocular inflammation and eye disease
Eye fatigue, blepharitis, foreign body sensation and freckles, eye fatigue, blepitis, foreign body sensation, discomfort when wearing contact lenses, eye fatigue, blepitis, foreign body sensation, and eye disease,
Tired eyes and blepharitis and discomfort when wearing eye and contact lenses, eye fatigue and blepharitis and frown and eye disease,
Eye fatigue, blepharitis, discomfort and eye disease when wearing contact lenses,

Eye fatigue and light-induced ophthalmia and foreign body sensation and freckles, eye fatigue and light-induced ophthalmitis and foreign body sensation and discomfort when wearing contact lenses, eye fatigue and light-induced ophthalmitis and foreign body sensation and eye disease,
Eye fatigue due to eye fatigue and light rays and discomfort when wearing contact lenses and contact lenses, eye inflammation due to eye fatigue and light rays and eye spots and eye diseases,
Eye fatigue, light-induced ophthalmitis, contact discomfort and eye disease,

Tired eyes and foreign body sensations and freckles and discomfort when wearing contact lenses, eye fatigue and foreign body sensations and freckles and eye diseases,
Eye fatigue, foreign body sensation, discomfort and eye disease when wearing contact lenses,

  Discomfort and eye disease when wearing eye contact and contact lenses

  Blurred eyes, itchy eyes, conjunctival redness and blepharitis, blurred eyes, itchy eyes, conjunctival redness and light-induced ophthalmitis, blurred eyes, itchy eyes, conjunctival redness and foreign body sensation, blurred vision and eyes Itching and conjunctival redness and freckles, blurred vision and itching of eyes and conjunctival redness and discomfort when wearing contact lenses, blurred vision and itching of eyes and conjunctival redness and eye disease,

Blurred eyes, conjunctival redness, blepharitis and light-induced ophthalmitis, blurred vision, conjunctival redness, blepharitis and foreign body sensation, blurred vision, blurred vision, blistering eyes, conjunctival redness and blepharitis And discomfort when wearing contact lenses, blurred vision and conjunctival hyperemia, blepharitis and eye disease,
Eye haze, blepitis and light-induced ophthalmia and foreign body sensation, eye haze, blepitis and light-induced ophthalmia and blemishes, eye haze, blepitis and light-induced eye inflammation and discomfort when wearing contact lenses, Blurred eyes, blepharitis and light-induced eye inflammation and eye disease,
Eye haze and light-induced ophthalmia and foreign body sensation and blemishes, eye haze and light-induced eye inflammation and foreign body sensation and discomfort when wearing contact lenses, eye haze and light-induced ophthalmia and foreign body sensation and eye disease,
Blurred eyes and foreign body sensation and blemishes and discomfort when wearing contact lenses, blurred vision and foreign body sensation and blemishes and eye disease,
Discomfort and eye disease when wearing blurred eyes and contact lenses and contact lenses,

Eye haze, blepitis and light-induced ophthalmia and foreign body sensation, eye haze, blepitis and light-induced ophthalmia and blemishes, eye haze, blepitis and light-induced eye inflammation and discomfort when wearing contact lenses, Blurred eyes, blepharitis and light-induced eye inflammation and eye disease,
Eye haze and light-induced ophthalmia and foreign body sensation and blemishes, eye haze and light-induced eye inflammation and foreign body sensation and discomfort when wearing contact lenses, eye haze and light-induced ophthalmia and foreign body sensation and eye disease,
Blurred eyes and foreign body sensation and blemishes and discomfort when wearing contact lenses, blurred vision and foreign body sensation and blemishes and eye disease,
Discomfort and eye disease when wearing blurred eyes and contact lenses and contact lenses,

  Eye haze and light-induced ophthalmia and foreign body sensation and blemishes, eye haze and light-induced eye inflammation and foreign body sensation and discomfort when wearing contact lenses, eye haze and light-induced ophthalmia and foreign body sensation and eye disease,

Blurred eyes and foreign body sensation and blemishes and discomfort when wearing contact lenses, blurred vision and foreign body sensation and blemishes and eye disease,
Discomfort and eye disease when wearing blurred eyes and contact lenses and contact lenses,

  Eye haze and light-induced ophthalmia and foreign body sensation and blemishes, eye haze and light-induced eye inflammation and foreign body sensation and discomfort when wearing contact lenses, eye haze and light-induced ophthalmia and foreign body sensation and eye disease,

  Blurred eyes and foreign body sensation and blemishes and discomfort when wearing contact lenses, blurred vision and foreign body sensation and blemishes and eye disease,

  Discomfort and eye disease when wearing blurred eyes and contact lenses and contact lenses,

Itchy eyes, conjunctival redness, blepharitis and light-induced ophthalmitis, itchy eyes, conjunctival redness, blepharitis and foreign body sensation, itchy eyes, conjunctival redness and blepharitis, freckles, itchy eyes, conjunctival redness and blepharitis And discomfort when wearing contact lenses, itchy eyes and conjunctival hyperemia, blepharitis and eye diseases,
Eye itching and blepitis and light irritation and foreign body sensation, eye itching and blepitis and light eye irritation and freckles, eye itching and blepitis and light eye irritation and discomfort when wearing contact lenses, Itchy eyes, blepharitis and light-induced eye inflammation and eye disease,
Eye itching and rays caused by eye irritation and foreign body sensation and blemishes, eye itching and light rays caused by eye inflammation and foreign body sensation and discomfort when wearing contact lenses, eye itch and light ocular inflammation and foreign body sensation and eye disease,
Itchy eyes and foreign body sensations and blemishes and discomfort when wearing contact lenses, itchiness and foreign body sensations and blemishes and eye diseases,
Discomfort and eye disease when wearing itchy eyes and contact eyes and contact lenses,

Conjunctival redness, blepharitis and light-induced ophthalmia and foreign body sensation, conjunctival redness, blepharitis and light-induced ophthalmia and discoloration, conjunctival redness, blepharitis and light-induced ophthalmia, discomfort when wearing contact lenses, conjunctival redness Blepharitis and light-induced eye inflammation and eye disease,
Conjunctival redness and light-induced ophthalmia and foreign body sensation and freckles, conjunctival redness and light-induced ophthalmia and foreign body sensation and discomfort when wearing contact lenses, conjunctival redness and light-induced ophthalmia and foreign body sensation and eye disease,
Conjunctival redness and foreign body sensation and discoloration and discomfort when wearing contact lenses, conjunctival redness and foreign body sensation and frowning and eye disease,
Conjunctival hyperemia and discomfort and eye disease when wearing contact lenses,

Blaze and light-induced eye inflammation and foreign body sensation and freckles, 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 freckles and discomfort when wearing contact lenses, blepharitis and foreign body sensation and freckles and eye diseases,
Discomfort and eye disease when wearing blisters and freckles and contact lenses,

Ophthalmitis and foreign body sensation caused by light rays and discomfort when wearing contact lenses and contact lenses;
Discomfort and eye disease when wearing ophthalmia, freckles and contact lenses due to light rays,

  Discomfort and eye disease when wearing a contact lens with a foreign body sensation

Eye fatigue, blurred eyes, itchy eyes, conjunctival congestion and blepharitis, eye fatigue, blurred eyes, itchy eyes, and conjunctival congestion, light-induced eye inflammation, blurred eyes, blurred eyes and itchy eyes Conjunctival redness and foreign body sensation, eyestrain and blurring of eyes and itching of eyes and conjunctival redness and freckles, eyestrain and blurring of eyes and itching of eyes, conjunctival redness and discomfort when wearing contact lenses, eye fatigue And blurred eyes, itchy eyes, conjunctival hyperemia and eye disease,
Eye fatigue, itchy eyes, conjunctival redness, blepharitis and light-induced ophthalmitis, eye fatigue, itchy eyes, conjunctival redness, blepharitis and foreign body sensation, eye fatigue, itchy eyes, conjunctival redness and blepharitis Eye fatigue, itchy eyes, itchy conjunctiva, blepharitis and discomfort when wearing contact lenses, eye fatigue, itchy eyes, conjunctival redness, blepharitis and eye disease,
Eye fatigue, conjunctival redness, blepharitis and light-induced ophthalmia and foreign body sensation, eye fatigue and conjunctival redness, blepharitis and light-induced ophthalmia And discomfort when wearing contact lenses, eye fatigue and conjunctival hyperemia, blepharitis and light-induced eye inflammation and eye disease,
Eye fatigue, blepharitis and light-induced eye inflammation and foreign body sensation and freckles, 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 rays Ophthalmitis, foreign body sensation and eye disease,
Eye fatigue and rays caused by eye inflammation and foreign body sensation and discomfort when wearing eye and contact lenses, eye fatigue and light caused by eye inflammation and foreign body sensation and blind eyes and eye disease,
Discomfort and eye disease when wearing eyes and contact lenses

Blurred eyes, itchy eyes, conjunctival congestion, blepharitis and light-induced ophthalmitis, blurred vision, itchy eyes, conjunctival redness, blepharitis and foreign body sensation, blurred vision, itchy eyes, itchy conjunctiva and blepharitis Discoloration, blurred vision, itchy eyes, conjunctival congestion, blepharitis and discomfort when wearing contact lenses, blurred vision, itchy eyes, conjunctival congestion, blepharitis and eye disease,
Eye haze and conjunctival redness and blepharitis and light-induced ophthalmitis and foreign body sensation And discomfort when wearing contact lenses, blurred vision and conjunctival congestion, blepharitis and light-induced ophthalmitis and eye disease,
Blurred eyes, blepharitis and light-induced ophthalmia and foreign body sensation and blemishes, blurred vision, blistering eyes and foreign-light sensation and discomfort when wearing contact lenses, blurred vision and blepharitis and light rays Ophthalmitis, foreign body sensation and eye disease
Ocular inflammation and foreign body sensation due to blurred vision and light rays, discomfort when wearing eye and contact lenses, ophthalmic inflammation and foreign body sensation due to blurred vision and light rays, and blurred eye and eye disease,
Blurred eyes, foreign body sensation, freckles, discomfort and eye disease when wearing contact lenses,

Eye itching and conjunctival redness and blepharitis and light irritation and foreign body sensation And discomfort when wearing contact lenses, eye itching and conjunctival hyperemia, blepharitis and light-induced eye inflammation and eye disease,
Eye itch, blepitis and light caused by eye inflammation and foreign body sensation and blemishes, eye itch and blepitis and light caused by eye inflammation and foreign sensation and discomfort when wearing contact lenses, eye itch, blepitis and light rays Ophthalmitis, foreign body sensation and eye disease,
Eye irritation and rays caused by itchy eyes and foreign bodies, and discomfort when wearing eyebrows and contact lenses,
Eye irritation and foreign body sensation due to itchy eyes and rays
Discomfort and eye disease when wearing eye contact and contact lenses

Conjunctival redness, blepharitis and light-induced ophthalmia and foreign body sensation and discoloration, conjunctival redness and blepharitis and light-induced ophthalmia and foreign body sensation and discomfort when wearing contact lenses, conjunctival redness and blepharitis and light-induced ophthalmia Foreign body sensation and eye disease,
Conjunctival redness and light-induced ophthalmia and foreign body sensation and freckles and discomfort when wearing contact lenses;
Conjunctival redness, foreign body sensation, freckles, discomfort and eye disease when wearing contact lenses,

  Blaze and light-induced eye inflammation and foreign body sensation and discoloration and discomfort when wearing contact lenses, blepharitis and light-induced eye inflammation and foreign body sensation and frown and eye disease,

  Discomfort and eye disease when wearing eye contact with contact lenses, ocular inflammation and foreign body sensation due to light rays,

Eye fatigue, blurred vision, itchy eyes, conjunctival redness, blepharitis and light-induced ophthalmitis, eye fatigue, blurred vision, itchy eyes, conjunctival redness, blepharitis, foreign body feeling, tired eyes and eyes Blurred eyes, itchy eyes, conjunctival redness and blisters and blisters, eye fatigue, blurred eyes, itchy eyes, conjunctival redness, blepharitis, discomfort when wearing contact lenses, tired eyes, blurred eyes and eyes Itchy eyes, conjunctival redness, blepharitis and eye disease Eye fatigue, itchy eyes, conjunctival redness, blepharitis and light irritation and foreign body sensation, eye fatigue, itchy eyes, conjunctival redness, blepharitis and light irritation Disorder eyes, eye fatigue, itchy eyes, conjunctival redness, blepharitis and eye irritation caused by light rays and discomfort when wearing contact lenses, eye fatigue, itchy eyes, conjunctival redness, blepharitis and eye drops caused by light rays Eye disease Eye fatigue, conjunctival hyperemia, blepharitis, light-induced ophthalmitis and foreign body sensation Eyes, eye fatigue, conjunctival redness, blepharitis, light-induced ophthalmitis, foreign body sensation, discomfort when wearing contact lenses, eye fatigue, conjunctival redness, blepharitis, light-induced ophthalmitis, foreign body sensation, and eye disease Eye fatigue Ophthalmitis due to eyelids and blisters and rays and sensation of foreign objects and discomfort when wearing contact lenses, eye fatigue and blepharitis and irritations due to rays and foreign objects and eyebrows and eye diseases Eye fatigue and eye inflammation due to rays Discomfort and eye disease when wearing contact lenses

Blurred eyes, itchy eyes, conjunctival redness, blepharitis and light irritation and foreign body sensation, blurred eyes, itchy eyes and conjunctival redness, blistering eyes and blistering eyes, blistering eyes and eyes Itching, conjunctival redness, blepharitis, light-induced ophthalmitis, discomfort when wearing contact lenses, blurred vision, itchy eyes, conjunctival redness, blepharitis, light-induced ophthalmitis and eye disease, blurred vision, conjunctival redness, and blepharitis Ophthalmitis and foreign body sensation and freckles caused by light and light, blurring of eyes and conjunctival redness and blepharitis and sensation of foreign bodies and discomfort when wearing contact lenses, blurred vision and conjunctival redness and blepharitis and light rays Ophthalmitis, foreign body sensation and eye disease Eye haze, blepitis and light-induced eye inflammation and foreign body sensation and discoloration and discomfort when wearing contact lenses, eye haze and blepitis and light-induced eye inflammation and foreign body sensation and frowning And eye disease Ocular inflammation caused by blurred vision and light Foreign body sensation and tears eyes and contact lens discomfort when wearing and eye diseases

Eye itching and conjunctival redness and blepharitis and light irritation and foreign body sensation and freckles, eye itching and conjunctival redness and blepharitis and light irritation and foreign body feeling and discomfort when wearing contact lenses, eye itching Conjunctival hyperemia, blepharitis, light-induced eye inflammation, foreign body sensation, and eye disease Eye itch, blepharitis, light-induced eye inflammation, foreign body sensation, discoloration, discomfort when wearing contact lenses, eye itch, blepharitis, and light Ophthalmitis, foreign body sensation, and blemishes and eye disease due to eye itching and ray irritations, foreign body sensation, blemishes, and discomfort and eye diseases when wearing contact lenses

  Conjunctival hyperemia, blepharitis and light-induced ophthalmia and foreign body sensation and discoloration and discomfort when wearing contact lenses, conjunctival redness and blepharitis and light-induced ophthalmitis and foreign body sensation and frown and eye disease

  Blaze, light-induced ophthalmia, foreign body sensation, freckles, discomfort and eye disease when wearing contact lenses

Eye fatigue, blurring of eyes, itching of eyes, conjunctival redness, blepharitis and light irritation and foreign body sensation, eye fatigue, blurring of eyes, itching of eyes, conjunctival redness, blepharitis and rays of light Eyes, eye fatigue, itchy eyes, itchy eyes, conjunctival redness, blepharitis, eye inflammation caused by light rays, discomfort when wearing contact lenses, eye fatigue, blurred eyes, itchy eyes, conjunctival hyperemia and blepharitis Ophthalmitis and eye disease caused by eye and light Eye fatigue, itchy eyes and conjunctival redness and blepharitis and eye irritation and foreign body feeling caused by light rays, eye fatigue, eye itching and conjunctival redness and blepharitis and eye inflammation caused by light rays Feeling of foreign body and discomfort when wearing contact lenses, eye fatigue, itching of eyes, conjunctival redness, blepharitis and light irritation, foreign body sensation and eye disease Eye fatigue, conjunctival redness, blepharitis and eye inflammation due to light Foreign body sensation, freckles, discomfort when wearing contact lenses, eye fatigue And conjunctival hyperemia, blepharitis, light-induced ophthalmia, foreign body sensation, blemishes and eye disease eye fatigue, blepharitis, light-induced ophthalmitis, foreign body sensations, blemishes, discomfort and eye disease with eye contact Eye itching, conjunctival redness, blepharitis, light-induced ophthalmitis, foreign body sensation, and blemishes, eye blemishes, eye itching, conjunctival redness, blepharitis, light-induced eye inflammation, foreign body sensations, and discomfort when wearing contact lenses Eye haze, eye itching, conjunctival redness, blepharitis, light irritation, foreign body sensation, and eye disease Eye haze, conjunctival redness, blepharitis, light irritation, foreign body sensation, freckles, and contact lenses Discomfort, haze and conjunctival redness, blepharitis and light-induced ophthalmitis and foreign body sensation and blemishes and eye disease Eye haze and blistering and light-induced ophthalmitis and foreign sensations and discomfort when wearing contact lenses And eye disease Itchy eyes and conjunctival filling Ophthalmitis and foreign body sensation due to eyelids and blepharitis and rays and discoloration and discomfort when wearing contact lenses, eye itch and conjunctival hyperemia and blepharitis and rays sensation and foreign body sensation and blemishes and eye diseases eye itch and eyelids Discomfort and eye disease when wearing ophthalmitis and foreign body feeling and contact lens wearing by flame and light. Conjunctival hyperemia and blepharitis and eye inflammation and foreign body feeling caused by light ray and discomfort and eye disease when wearing eye and contact lens.

Eye fatigue, blurred vision, itchy eyes, conjunctival redness, blepharitis, light irritation, foreign body sensation, freckles, eye fatigue, blurred vision, itchy eyes, conjunctival hyperemia, blepharitis, and eyes with light rays Flame, foreign body sensation, discomfort when wearing contact lenses, eye fatigue, blurred vision, itchy eyes, conjunctival redness, blepharitis, light-induced eye inflammation, foreign body sensation, and eye disease Eye fatigue, itchy eyes, and conjunctival redness Ophthalmitis and foreign body sensation with eyelids and blisters and rays and discomfort when wearing eye and contact lenses, eye fatigue and itching of eyes and conjunctival redness Tiredness, conjunctival redness, blepharitis, light-induced ophthalmia, foreign body sensation, discomfort and eye disease when wearing eye contact lenses, eye fatigue, eye itchiness, eye itching, conjunctival redness, blepharitis, and light-induced eyes Discomfort and eye disease when wearing flames and contact lenses Tiredness, blurred vision, itchy eyes, conjunctival redness, blepharitis, freckles, discomfort and eye disease when wearing contact lenses Eye fatigue, blurred eyes, itchy eyes, conjunctival redness, foreign body sensations, blisters and contact Discomfort and eye disease when wearing lenses Eye fatigue, blurring of eyes and itching of eyes, ocular inflammation and foreign body feeling due to light rays, discomfort and eye diseases when wearing contact lenses, blurred vision and itching of eyes and conjunctival redness Ophthalmitis and foreign body sensation due to eyelids and blepharitis and light rays Discoloration and discomfort when wearing contact lenses, blurring of eyes and itchiness of eyes, conjunctival hyperemia, blepharitis and sensation of foreign bodies and light spots and eye diseases Blurring, conjunctival redness, blepharitis, light-induced ophthalmia, foreign body sensation, freckles, discomfort and eye disease when wearing contact lenses Eye itching, conjunctival redness, blepharitis, light-induced ophthalmitis, foreign body sensation, and freckles Contact Ren Discomfort when wearing and eye diseases

Eye fatigue, blurred vision, itchy eyes, conjunctival hyperemia, blepharitis, light-induced ophthalmitis, foreign body sensation, discomfort when wearing eyes and contact lenses, eye fatigue, blurred vision, itchy eyes and conjunctiva Redness, blepharitis, light-induced ophthalmia, foreign body sensation, blemishes and eye disease Eye fatigue, itchiness, conjunctival redness, blepharitis, light-induced ophthalmitis, foreign body sensation, discomfort when wearing eye and contact lenses Eye disease Blurred eyes, itchy eyes, conjunctival redness, blepharitis, light-induced eye inflammation, foreign body sensation, discomfort and eye disease when wearing contact lenses, eye fatigue, blurred eyes, itchy eyes and blepharitis Ocular inflammation, foreign body sensation due to light rays, discomfort and eye diseases when wearing eye contact lenses, contact sickness Eye fatigue, blurred vision, itching eyes, conjunctival redness, ophthalmic inflammation due to light rays, foreign body sensations, eye contact and wearing contact lenses Discomfort and eye disease eye fatigue Eye blur, eye itch, conjunctival redness, blepharitis, foreign body sensation, freckles, discomfort and eye disease when wearing contact lenses Eye fatigue, eye blur, eye itch, conjunctival redness, blepharitis and light rays Discomfort and eye disease when wearing ophthalmitis, blind eyes and contact lenses Eye fatigue, blurred vision, itching of eyes, conjunctival hyperemia, blepharitis, light-induced eye inflammation, foreign body feeling, discomfort and eye disease when wearing contact lenses

  Eye fatigue, blurred vision, itchy eyes, conjunctival hyperemia, blepharitis, light-induced ophthalmitis, foreign body sensation, discomfort and eye disease when wearing contact lenses

pH
The pH of the ophthalmic composition of the present invention is preferably 3 or more, more preferably 4 or more, still more preferably 5 or more, and even more preferably 6 or more. Moreover, 10 or less is preferable, 9 or less is more preferable, 8.5 or less is further more preferable, and 8 or less is still more preferable. If it is the said range, irritation | stimulation to eyes will be suppressed and the said effect of this invention will be acquired.

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. Moreover, 5 or less is preferable, 3 or less is more preferable, and 2 or less is still more preferable. If it is the said range, irritation | stimulation to eyes will be suppressed and the said effect of this invention will be acquired.
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 depression method) described in the 16th revision Japanese Pharmacopoeia. The standard solution for measuring the osmotic pressure ratio (0.9 w / v% sodium chloride aqueous solution) was dried in sodium chloride (Japanese Pharmacopoeia standard reagent) at 500 to 650 ° C. for 40 to 50 minutes and then released in a desiccator (silica gel). Cool and accurately measure 0.900 g and dissolve in purified water to make exactly 100 mL, or use a commercially available standard solution for osmotic pressure ratio measurement (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 package body having a surface that comes into contact with the preparation, such as a container main body part for storing a liquid, a part including an extraction port of the container (nozzle, inner plug), a suction tube, and a cap.
The material which comprises the container which accommodates the ophthalmic composition of this invention can be selected from a wide range.
For example, at least part or all of the contact surface with the ophthalmic composition is made of plastic (for example, polyolefin, acrylic acid resin, terephthalic acid ester, 2,6-naphthalenedicarboxylic acid ester, polycarbonate, polymethylpentene, fluororesin, Vinyl chloride, polyamide, ABS resin, AS resin, polyacetal, modified polyphenylene ether, polyarylate, polysulfone, polyimide, cellulose acetate, hydrocarbons optionally substituted with halogen atoms), metal (such as aluminum), and glass Examples thereof include a container composed 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 molecular weight polyethylene, etc.), polypropylene (isotactic polypropylene, syndiotactic polypropylene, atactic polypropylene). And ethylene-propylene copolymer.

  Examples of the acrylic resin include an acrylic ester such as methyl acrylate, a methacrylic ester 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 2,6-naphthalenedicarboxylic acid esters include polyethylene naphthalate and polybutylene naphthalate.

  Fluorine resins include fluorine-substituted polyethylene (polytetrafluoroethylene, polychlorotrifluoroethylene, etc.), polyvinylidene fluoride, polyvinyl fluoride, perfluoroalkoxy fluororesin, tetrafluoroethylene / hexafluoropropylene copolymer, ethylene / tetra Examples thereof include a fluorinated ethylene copolymer and an ethylene / chlorotrifluoroethylene copolymer.

  Examples of the polyamide include nylon.

  Examples of the polyacetal include those composed only of oxymethylene units and those partially containing oxyethylene units.

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

  Examples of polyarylate include amorphous polyarylate.

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

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

The container should just be comprised with the said material at least one part of the surface which contacts the ophthalmic composition of this 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.
In addition, the parts constituting the container (the container body part, the part including the extraction port of the container (nozzle, inner plug), suction tube, cap, etc.) may be made of the above materials, and the whole part of the container may be made of the above materials. It may be comprised. In particular, it is preferable that the container main body portion is made of the above material, and that all of the container main body portion is made of the above material (some layers constituting the container main body are made of the above material. Is not preferred).

  Further, 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 material covered with a light shielding film, a container made of the above material and a colorant, and the like.

Subject Symptoms or Abnormalities The ophthalmic composition of the present invention improves complex eye symptoms. Improvement of complex eye symptoms includes amelioration, alleviation, treatment, or prevention of complex eye symptoms or abnormalities.
As complex eye symptoms or abnormalities, specifically, eye fatigue, blurred vision, itchy eyes, itching of the eyes, conjunctival hyperemia, blepharitis (sores of eyelids), ophthalmitis caused by ultraviolet rays or other rays (so-called Snow etc.), foreign body sensation (colossal feeling, tingling sensation, etc.), sore eyes, eye discomfort (including eye discomfort when wearing contact lenses), eye disease (caused by swimming Useful for ameliorating, alleviating, treating, or preventing one or more symptoms or abnormalities such as eye disease, dust or sweat caused by eye contact).
A condition that exhibits multiple symptoms or abnormalities of the eye may be more difficult to improve or prevent than a condition that exhibits a single symptom or abnormality. Even in such a case, the ophthalmic composition of the present invention can effectively improve, alleviate, treat, or prevent those symptoms.

In particular, with the widespread use of eyes and contact lenses due to the spread of personal computers in recent years, it has become a problem for modern consumers, consumers, and workers for eye fatigue, itchy eyes, conjunctival redness, blurred vision, and blindness. Many comprehensive or complex discomfort symptoms exhibiting one or more pleasant feelings are also observed, but the present invention can effectively improve, alleviate, treat, or prevent such comprehensive or complex symptoms. .
In particular, itchy eyes, conjunctival redness, and blurred vision are symptoms that frequently appear in various eye diseases. These symptoms may be comprehensive or complex symptoms. The present invention can effectively improve, alleviate, treat or prevent these symptoms.
In addition, itchy eyes, conjunctival redness, blurring of the eyes due to eyes and burrs, flutes, and foreign body sensations are triggered by allergens such as house dust, indoor dust, PM2.5, ticks, inflammation and allergic symptoms In such a state, one or more symptoms are often presented in combination. The present invention can also effectively improve, alleviate, treat or prevent such complex symptoms.

  As the above eye diseases, inflammatory diseases such as blepharitis, conjunctivitis, keratitis, scleritis, suprasclerosis, anterior uveitis, postoperative inflammation, lacrimal inflammation, lacrimal cystitis, lacrimal canalitis, etc. Symptoms resulting from bacterial infection such as conjunctivitis are included. Also included are eye diseases caused by swimming, eye diseases caused by dust or sweat entering the eyes, and the like. Symptoms resulting from inflammatory diseases and bacterial infections may be accompanied by the allergic symptoms described above.

  As described above, eye discomfort includes eye discomfort when wearing a contact lens. Discomfort when wearing a contact lens includes discomfort when wearing either a hard contact lens or a soft contact lens. In addition, although discomfort is great when the hard contact lens is worn, 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, for improving, alleviating, treating, or preventing complex eye symptoms or abnormalities, for total eye care, or for normal total eyes. It can be a composition for chemical use. In addition, the ophthalmic composition of the present invention can also be a composition for use in improving, alleviating, treating, or preventing a multifunctional general eye symptom or abnormality.

  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 of the onset, delay, reduction of the incidence, “relief” includes amelioration of symptoms, suppression of progression of symptoms, “improvement” and “treatment” are symptoms Amelioration of symptoms, suppression of symptom progression, healing or completeness.

Method of Use When the ophthalmic composition of the present invention is a preparation to be applied to the eye, such as eye drops, eye wash, eye ointment, etc., the usage varies depending on the intended symptoms, but for example, once or more twice a day As mentioned above, it can be 3 times or more, 4 times or more, 5 times or more, or 6 times or more. Also, 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 preferred to administer 4 times a day.

  Further, the use may be started at the same time or after the symptom appears, but the use may be started 1 day or more before the symptom appears, particularly 3 days or more before, especially 7 days or more before. In addition, use can be started from 10 days or more before symptoms appear. In addition, use may be started within 30 days before the symptoms appear, particularly within 20 days, especially within 14 days. Symptoms can be effectively prevented by using before symptoms appear.

When the ophthalmic composition of the present invention is an eye drop, the eye drop containing each component at the above concentration may be instilled, for example, 1 to 3 drops, preferably 1 to 2 drops. One drop can also be used.
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, preferably 1 to 20 mL, more preferably 4 What is necessary is just to wash eyes using ~ 6mL.
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 eyes per time.

  When the ophthalmic composition of the present invention is a contact lens mounting solution, at the time of wearing or removing the contact lens, for example, 1 to 3 drops, preferably 1 to 2 drops per side, Alternatively, it may be worn after being dropped on both sides and wetted, and is preferably worn after wetting both sides of the contact lens.

  When the ophthalmic composition of the present invention is a contact lens solution, it is not limited thereto. For example, the ophthalmic composition and the contact lens are contacted for 1 hour or more, 2 hours or more, 4 hours or more, or 1 day or more. I can leave it to you. Moreover, 30 days or less, 14 days or less, 7 days or less, or 2 days or less can be made to contact.

EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated in detail, this invention is not limited to these.
Test Example 1 Evaluation of ophthalmic effects relating to various symptoms of the eye The eye drops of Examples 1 to 8 and Comparative Examples 1 to 8 having the compositions shown in Table 1 were prepared and sterilized with a filtration filter (0.2 μm). 10 mL of a PET eye drop container (13 mL capacity) was filled.
The unit of each component concentration in Table 1 is w / v%, the remaining amount is water (purified water), and the total amount is 100 mL. The pH was appropriately adjusted with a pH adjuster (hydrochloric acid, sodium hydroxide: appropriate amount) as necessary.

As a test subject, an office worker who routinely performs VDT (Visual Display Terminals) work for 4 hours or more per day was selected. Each subject confirmed that there was no difference in the state of the left and right eyes in advance, and then performed the test.
As shown in Table 2, 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 the test using Example 1 and Comparative Example 1 as a set is designated as Test A.
Five subjects (4 men and 1 woman) instilled one drop each in the eye drops of the example and the eye drop of the comparative example in the right eye and the scale from 0 to 100 for tests A to H. About various symptoms (eye fatigue, itchy eyes, blurred vision, conjunctival redness, eye discomfort) after 30 seconds of instillation with the “VAS method (Visual Analog Scale)” using a 10 cm straight line attached The effect was compared. When different tests were subsequently performed, the next instillation was performed after an interval of 1 hour or longer after the instillation was completed.

The average value of the VAS score values of 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 values for each symptom of the eye. The higher the VAS score value, the stronger the eye symptoms (eye fatigue, itchy eyes, blurred vision, conjunctival redness, eye discomfort), and the higher the score increase value, the greater the improvement in eye symptoms. Indicates.

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

Corresponding comparative examples refer to eye drops that were instilled as a set in tests A to H. For example, Comparative Example 1 indicates the case of Example 1, and Comparative Example 2 indicates the case of Example 2.
The results are shown in Table 2.

  It was confirmed that the combination of pranoprofen significantly suppressed all symptoms of eye fatigue, itchy eyes, blurred vision, conjunctival hyperemia, and eye discomfort, and improved complex eye symptoms.

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

  Compared with conventional ophthalmic compositions, the ophthalmic composition of the present invention can sufficiently improve, alleviate, treat, or prevent more various eye symptoms or abnormalities. For this reason, 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)

  (a) at least one member selected from the group consisting of pranoprofen and a salt thereof; and (b) an anti-decongestant, an eye muscle regulator, an anti-inflammatory agent other than pranoprofen or a salt thereof, an antihistamine, vitamins, and An ophthalmic composition for improving complex eye symptoms, comprising at least one component selected from the group consisting of amino acids.   (b) The composition according to claim 1, comprising a decongestant, an eye muscle regulator, an anti-inflammatory agent other than pranoprofen or a salt thereof, an antihistamine, vitamins, and amino acids.   Compound eye symptom is one or more selected from the group consisting of eye fatigue, blurred vision, itchy eyes, conjunctival redness, blepharitis, light-induced ophthalmitis, foreign body sensation, smooth eyes, eye discomfort, and eye disease The composition according to claim 1 or 2, 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, according to any one of claims 1 to 3. Composition.   Furthermore, the composition in any one of Claims 1-4 containing an antioxidant.