JP2018118964A - Ophthalmic composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an ophthalmic composition for soft contact lenses that can reduce discomfort of soft contact lenses when being used, and that can reduce protein contamination of the soft contact lenses.SOLUTION: The ophthalmic composition for soft contact lenses comprises: (A) neostigmine methyl sulfate; (B) three or more of epsilon-aminocaproic acid, allantoin, berberine chloride or berberine sulfate, sodium azulene sulfonate, dipotassium glycyrrhizinate, and zinc sulfate or zinc lactate; (C) diphenhydramine hydrochloride or chlorpheniramine maleate; (D) three or more of flavin adenine dinucleotide sodium, cyanocobalamin, retinol acetate or retinol palmitate, pyridoxine hydrochloride, panthenol or calcium pantothenate or sodium pantothenate, and tocopherol acetate; and (E) potassium L-aspartate or magnesium L-aspartate or an equivalent mixture thereof, aminoethylsulfonic acid, and sodium chondroitin sulfate.SELECTED DRAWING: None

Description

  The present invention relates to an ophthalmic composition suitable for use with soft contact lenses.

Wearing contact lenses can easily cause secretions from the eyes such as proteins, lipids, and calcium, as well as pollen, dust, tobacco smoke, cosmetics, dirt on fingers, sweat, bacteria, mold, etc. . If the lens is left unclean, it may cause a foreign body sensation on the back of the eyelids, cause eyes to bleed, or cause infection. Therefore, in order to use the contact lens comfortably and prevent eye diseases, it is important to keep the lens clean.
Of the contact lenses, the soft contact lens contains a lot of moisture, so that dirt easily adheres to it. For this reason, if the soft contact lens is neglected, it may cause discomfort or cause eye disease.

In this regard, Patent Document 1 discloses an ophthalmic composition containing at least one of neostigmine methyl sulfate and a salt thereof and at least one of glycyrrhizic acid, aminoethylsulfonic acid, aspartic acid, chondroitin sulfate, and a salt thereof. In addition, it is disclosed that the adsorption of pollen protein to the irregularities on the surface of the silicone hydrogel soft contact lens can be suppressed.
However, patent document 1 does not mention adsorption suppression of proteins other than pollen protein, and does not mention protein adsorption suppression to hydrogel soft contact lenses.

  Soft contact lenses are often used because they are softer and more comfortable to wear than hard contact lenses. In particular, since disposable soft contact lenses have been sold, the number of users of soft contact lenses has increased greatly, and the elderly wear more. For this reason, an increasing number of people experience discomfort when wearing soft contact lenses. Accordingly, there is a need for an ophthalmic composition that can reduce discomfort when using contact lenses.

JP 2011-136888 A

  An object of the present invention is to provide an ophthalmic composition for a soft contact lens that can reduce discomfort when using the soft contact lens and can reduce protein contamination of the soft contact lens.

The present inventor repeated researches to solve the above-described problems, and obtained the following knowledge.
That is, in the ophthalmic composition,
(A) Methyl sulfate neostigmine;
(B) at least three selected from the group consisting of epsilon-aminocaproic acid, allantoin, berberine chloride or berberine sulfate, sodium azulenesulfonate, dipotassium glycyrrhizinate, and zinc sulfate or zinc lactate;
(C) diphenhydramine hydrochloride or chlorpheniramine maleate;
(D) at least three selected from the group consisting of sodium flavin adenine dinucleotide, cyanocobalamin, retinol acetate or retinol palmitate, pyridoxine hydrochloride, panthenol or calcium pantothenate or sodium pantothenate, and tocopherol acetate; and (E) By blending 11 or more kinds of components such as potassium L-aspartate or magnesium L-aspartate or an equivalent mixture thereof, aminoethylsulfonic acid and sodium chondroitin sulfate, the wettability with the soft contact lens is remarkably improved. To do.
In addition, the protein stain adsorbed on the soft contact lens can be effectively removed by bringing the ophthalmic composition containing the above 11 or more components into contact with the soft contact lens.

The present invention has been completed based on the above findings, and provides the following ophthalmic composition for soft contact lenses.
Item 1. (A) Methyl sulfate neostigmine;
(B) at least three selected from the group consisting of epsilon-aminocaproic acid, allantoin, berberine chloride or berberine sulfate, sodium azulenesulfonate, dipotassium glycyrrhizinate, and zinc sulfate or zinc lactate;
(C) diphenhydramine hydrochloride or chlorpheniramine maleate;
(D) at least three selected from the group consisting of sodium flavin adenine dinucleotide, cyanocobalamin, retinol acetate or retinol palmitate, pyridoxine hydrochloride, panthenol or calcium pantothenate or sodium pantothenate, and tocopherol acetate; and (E) An ophthalmic composition for soft contact lenses comprising potassium L-aspartate or magnesium L-aspartate or an equivalent mixture thereof, aminoethylsulfonic acid, and sodium chondroitin sulfate.
Item 2. Item 4. The ophthalmic composition according to Item 1, wherein the pH is 5.5 to 8.5.
Item 3. Item 3. The ophthalmic composition according to Item 1 or 2, further comprising a surfactant.
Item 4. Furthermore, the ophthalmic composition in any one of claim | item 1 -3 containing a cooling agent.
Item 5. Item 5. The ophthalmic composition according to any one of Items 1 to 4, which is contained in a polyethylene terephthalate container.
Item 6. Item 6. The ophthalmic composition according to any one of Items 1 to 5, which is used 3 to 6 times per day.

As mentioned above, soft contact lenses are softer than hard contact lenses and feel better to wear, but the number of users of soft contact lenses, including elderly people, has increased rapidly, so discomfort when wearing soft contact lenses. An increasing number of people are experiencing this.
The contact lens enters the tear water layer as a foreign substance when worn. To achieve this state, the affinity between the lens and the water layer is important. If the lens surface is difficult to get wet by the water layer, uncomfortable feelings such as dry feeling and foreign object feeling during contact lens wearing occur. Therefore, by using an ophthalmic composition having good wettability with respect to a contact lens during or at the time of wearing the contact lens, the discomfort associated with such contact lens wearing can be reduced.
In this regard, the ophthalmic composition for soft contact lenses of the present invention has very high wettability with respect to the soft contact lens by including 11 or more specific components. Therefore, unpleasant symptom such as dry feeling and foreign object feeling during wearing or wearing a soft contact lens can be alleviated.

  In addition, when the wettability of the contact lens is poor, the surface of the cornea is scratched, causing various eye diseases. In this regard, the ophthalmic composition of the present invention can improve the wettability of the soft contact lens by containing 11 or more specific components, so that the damage to the cornea and conjunctiva can be reduced.

  Soft contact lenses also contain a lot of moisture, so they can cause secretions from the eye such as proteins, lipids, and inorganic substances, pollen, dust, tobacco smoke, cosmetics, dirt on fingers, sweat, bacteria, mold, etc. Dirt from outside tends to adhere. In particular, protein stains secreted from the eye may cause a certain amount of adhesion due to wearing the contact lens, causing the lens to become cloudy or cause a rough feeling. Therefore, it is necessary to frequently wash with an enzyme agent or the like, which is troublesome. Moreover, since protein dirt adheres while using a disposable soft contact lens, in order to prolong the service life, it is desirable that the protein dirt adhere less.

  In this regard, the ophthalmic composition of the present invention contains 11 or more specific components, so that the protein stain adsorbed on the soft contact lens can be effectively washed away by using it in contact with the soft contact lens. be able to. Accordingly, it is possible to prevent or suppress uncomfortable feeling, clouding of the visual field, eye diseases and the like caused by wearing the soft contact lens.

  In addition, hydrogel soft contact lenses are less likely to adhere lipid stains than protein hydrogel soft contact lenses, but protein stains are more likely to adhere. The ophthalmic composition of the present invention can effectively remove not only the silicone hydrogel soft contact lens but also protein stains adsorbed on the hydrogel soft contact lens.

  A soft contact lens has a high water content, and therefore has a property of easily absorbing tears when the moisture in the lens decreases with use. Therefore, when a soft contact lens is worn, the conjunctiva is generally damaged by friction between the contact lens surface and the eyelid conjunctiva or friction between the edge of the contact lens and the eyeball conjunctiva. In this regard, the ophthalmic composition of the present invention can effectively suppress the drying of the soft contact lens over time by including 11 or more specific components. Therefore, it is possible to prevent or suppress conjunctival damage, dryness, and blurred vision due to wearing a soft contact lens.

  In addition, when the ophthalmic composition of the present invention is used by being dropped from a container mouth, for example, as an eye drop, the variation in the amount of one drop is small. Therefore, a predetermined drug amount can be accurately administered.

Moreover, the ophthalmic composition of this invention has a wide physiological activity by including 11 or more types of active ingredients. This reduces the discomfort when using soft contact lenses, dry eyes, tired eyes, blurred eyes, itchy eyes, eye inflammation caused by light rays, and prevents eye disease. Widely used for easy installation.
In general, the more the ophthalmic composition contains various types of components, the more various problems arise in formulation, and various problems are likely to occur due to interaction with contact lenses. In this regard, the ophthalmic composition of the present invention is useful in that the multifunctional ophthalmic composition can be used for soft contact lenses. In particular, by containing 11 to 17 species selected from specific components, while exhibiting the effects of the present invention described above and exhibiting a wide range of physiological activities, problems during formulation and problems due to interaction with contact lenses Is suppressed as much as possible, and is a practical ophthalmic composition.

It is a figure which shows the contact angle improvement rate of an Example and a comparative example. It is a figure which shows the protein adsorption amount of an Example and a comparative example.

Hereinafter, the present invention will be described in detail.
(A) Component The ophthalmic composition of the present invention contains neostigmine methylsulfate. Methyl sulfate neostigmine is an eye muscle regulator and has an action of improving the eye regulation function and alleviating discomfort caused by tired eyes.
The content of neostigmine methylsulfate is preferably 0.0002 w / v% or more, more preferably 0.0005 w / v% or more, particularly preferably 0.001 w / v% or more with respect to the total amount of the ophthalmic composition. / V% or less, preferably 0.01 w / v% or less, and more preferably 0.005 w / v% or less.

(B) Component The ophthalmic composition of the present invention is a compound selected from the group consisting of epsilon-aminocaproic acid, allantoin, berberine chloride or berberine sulfate, sodium azulenesulfonate, dipotassium glycyrrhizinate, and zinc sulfate or zinc lactate. Including more than one species, such as 3, 4, 5 or 6 species. These are components having an anti-inflammatory effect.
Among these, it is preferable to include 3 or more, for example, 3 or 4 compounds selected from the group consisting of epsilon-aminocaproic acid, allantoin, dipotassium glycyrrhizinate, and zinc sulfate or zinc lactate.
As the component (B), it is preferable that epsilon-aminocaproic acid, allantoin, and dipotassium glycyrrhizinate are included from the standpoint of significantly achieving the effects of the present invention. In addition, epsilon-aminocaproic acid has a good usability when instilled when wearing a soft contact lens, or a good usability when instilled when wearing a soft contact lens when it contains a cooling agent such as menthol. , Allantoin, and zinc sulfate.

  The total content of component (B) is preferably 0.0005 w / v% or more, more preferably 0.005 w / v% or more, particularly preferably 0.05 w / v% or more, and 10 w based on the total amount of the ophthalmic composition. / V% or less, in particular, 8 w / v% or less, especially 6 w / v% or less is preferable.

  When epsilon-aminocaproic acid is included, the content thereof is preferably 0.001 w / v% or more, more preferably 0.01 w / v% or more, particularly preferably 0.1 w / v% or more, based on the total amount of the ophthalmic composition. Further, it is preferably 10 w / v% or less, more preferably 7.5 w / v% or less, and particularly preferably 5 w / v% or less.

  When allantoin is contained, the content thereof is preferably 0.01 w / v% or more, more preferably 0.03 w / v% or more, particularly preferably 0.06 w / v% or more with respect to the total amount of the ophthalmic composition. / V% or less, in particular 0.75 w / v% or less, in particular 0.5 w / v% or less, in particular 0.3 w / v% or less.

  In the case of containing berberine chloride or berberine sulfate, the content thereof is preferably 0.0005 w / v% or more, more preferably 0.001 w / v% or more, particularly preferably 0.005 w / v% or more based on the total amount of the ophthalmic composition. Also, it is preferably 0.1 w / v% or less, especially 0.05 w / v% or less, especially 0.03 w / v% or less, especially 0.025 w / v% or less.

  When sodium azulene sulfonate is included, the content is preferably 0.0004 w / v% or more, more preferably 0.001 w / v% or more, particularly preferably 0.004 w / v% or more, based on the total amount of the ophthalmic composition. Further, it is preferably 0.1 w / v% or less, particularly 0.05 w / v% or less, particularly 0.025 w / v% or less, and particularly preferably 0.02 w / v% or less.

  When dipotassium glycyrrhizinate is included, the content thereof is preferably 0.0005 w / v% or more, more preferably 0.005 w / v% or more, particularly preferably 0.05 w / v% or more based on the total amount of the ophthalmic composition. Further, it is preferably 1.25 w / v% or less, particularly 0.75 w / v% or less, especially 0.3 w / v% or less, especially 0.25 w / v% or less.

  When zinc sulfate or zinc lactate is included, the content thereof is preferably 0.005 w / v% or more, more preferably 0.01 w / v% or more, and particularly preferably 0.05 w / v% or more with respect to the total amount of the ophthalmic composition. Further, it is preferably 1 w / v% or less, particularly 0.5 w / v% or less, particularly 0.3 w / v% or less, especially 0.25 w / v% or less.

(C) Component The ophthalmic composition of this invention contains diphenhydramine hydrochloride or chlorpheniramine maleate. These are compounds having an antihistaminic action.
(C) As a component, it is a point which has a good usability when instilled when wearing a soft contact lens, or a usability when instilled when wearing a soft contact lens when a cooling agent such as menthol is included. Preferably, chlorpheniramine maleate is included.

  The total content of component (C) is preferably 0.0001 w / v% or more, more preferably 0.001 w / v% or more, particularly preferably 0.01 w / v% or more, based on the total amount of the ophthalmic composition. 0.5 w / v% or less, especially 0.2 w / v% or less, especially 0.1 w / v% or less is preferable.

  When diphenhydramine hydrochloride is included, the content thereof is preferably 0.001 w / v% or more, more preferably 0.005 w / v% or more, particularly preferably 0.01 w / v% or more, based on the total amount of the ophthalmic composition. 0.1 w / v% or less, especially 0.075 w / v% or less, especially 0.06 w / v% or less, especially 0.05 w / v% or less is preferable.

  When chlorpheniramine maleate is included, the content thereof is preferably 0.0006 w / v% or more, more preferably 0.001 w / v% or more, particularly preferably 0.006 w / v% or more, based on the total amount of the ophthalmic composition. Also, it is preferably 0.1 w / v% or less, especially 0.075 w / v% or less, especially 0.05 w / v% or less, especially 0.03 w / v% or less.

(D) Component The ophthalmic composition of the present invention is selected from the group consisting of sodium flavin adenine dinucleotide, cyanocobalamin, retinol acetate or retinol palmitate, pyridoxine hydrochloride, pantenol or calcium pantothenate or sodium pantothenate, and tocopherol acetate. Contains 3 or more of the compounds, for example 3, 4, 5, or 6. These are compounds that act as vitamins.
Among them, it is preferable to include 3 or more, for example, 3 or 4 types of compounds selected from the group consisting of cyanocobalamin, pyridoxine hydrochloride, panthenol or calcium pantothenate or sodium pantothenate, and tocopherol acetate.
As the component (D), it is preferable that cyanocobalamin, panthenol, and tocopherol acetate are included from the standpoint that the effects of the present invention are remarkably exhibited. In addition, pyridoxine hydrochloride, pan, etc. have a good usability when instilled when wearing a soft contact lens, or a good usability when instilled when wearing a soft contact lens when a cooling agent such as menthol is included. It preferably contains tenol and tocopherol acetate.

  The total content of the component (D) is preferably 0.0002 w / v% or more, more preferably 0.002 w / v% or more, particularly preferably 0.02 w / v% or more with respect to the total amount of the ophthalmic composition. / V% or less, in particular 0.5 w / v% or less, especially 0.3 w / v% or less is preferable.

  When flavin adenine dinucleotide sodium is contained, the content thereof is preferably 0.0001 w / v% or more, more preferably 0.001 w / v% or more, and particularly preferably 0.01 w / v% or more with respect to the total amount of the ophthalmic composition. Further, it is preferably 0.25 w / v% or less, especially 0.1 w / v% or less, especially 0.06 w / v% or less, especially 0.05 w / v% or less.

  When cyanocobalamin is contained, the content thereof is preferably 0.0006 w / v% or more, more preferably 0.001 w / v% or more, particularly preferably 0.004 w / v% or more based on the total amount of the ophthalmic composition. 0.1 w / v% or less, especially 0.05 w / v% or less, especially 0.025 w / v% or less, especially 0.02 w / v% or less is preferable.

  In the case of containing retinol acetate or retinol palmitate, the content thereof is 0.01 million units / 100 mlL or more, especially 10,000 units / 100 mlL or more, especially 10,000 units / 100 mlL or more with respect to the total amount of the ophthalmic composition. In addition, 500,000 units / 100 mlL or less, particularly 250,000 units / 100 mlL or less, particularly 100,000 units / 100 mlL or less, especially 50,000 units / 100 mlL or less are preferred.

  When pyridoxine hydrochloride is included, the content thereof is preferably 0.001 w / v% or more, more preferably 0.005 w / v% or more, particularly preferably 0.01 w / v% or more based on the total amount of the ophthalmic composition. 1 w / v% or less, especially 0.5 w / v% or less, especially 0.2 w / v% or less, especially 0.1 w / v% or less is preferable.

  When pantenol, calcium pantothenate, or sodium pantothenate is contained, the content thereof is 0.001 w / v% or more, particularly 0.005 w / v% or more, especially 0.01 w, based on the total amount of the ophthalmic composition. / W% or more is preferable, and 1 w / v% or less, especially 0.5 w / v% or less, especially 0.2 w / v% or less, especially 0.1 w / v% or less is preferable.

  When tocopherol acetate is contained, the content thereof is preferably 0.0005 w / v% or more, more preferably 0.001 w / v% or more, particularly preferably 0.005 w / v% or more, based on the total amount of the ophthalmic composition. It is preferably 0.25 w / v% or less, especially 0.15 w / v% or less, especially 0.1 w / v% or less, especially 0.05 w / v% or less.

(E) Component The ophthalmic composition of the present invention contains three kinds of potassium L-aspartate or magnesium L-aspartate, or an equivalent mixture thereof, aminoethylsulfonic acid (taurine), and sodium chondroitin sulfate. These are compounds classified as amino acids.

  The total content of component (E) is preferably 0.005 w / v% or more, more preferably 0.1 w / v% or more, particularly preferably 0.2 w / v% or more, and 7 w based on the total amount of the ophthalmic composition. / V% or less, especially 5 w / v% or less, especially 3 w / v% or less is preferable.

  The content of potassium L-aspartate or magnesium L-aspartate or an equivalent mixture thereof is 0.001 w / v% or more, particularly 0.01 w / v% or more, based on the total amount of the ophthalmic composition. Among them, 0.1 w / v% or more, particularly 0.2 w / v% or more is preferable, and 5 w / v% or less, especially 3 w / v% or less, especially 2.5 w / v% or less, especially 2 w / v% or less. Is preferred.

  The content of aminoethylsulfonic acid is 0.001 w / v% or more, preferably 0.01 w / v% or more, more preferably 0.1 w / v% or more, and preferably 10 w / v with respect to the total amount of the ophthalmic composition. It is preferably v% or less, especially 5 w / v% or less, especially 2.5 w / v% or less, especially 1 w / v% or less.

  The content of sodium chondroitin sulfate is 0.001 w / v% or more, preferably 0.01 w / v% or more, more preferably 0.05 w / v% or more, and 5 w / v based on the total amount of the ophthalmic composition. % Or less, especially 3 w / v% or less, especially 1 w / v% or less, especially 0.5 w / v% or less is preferable.

Components other than essential components The ophthalmic composition of the present invention can contain other components to be blended in the ophthalmic composition as long as the effects of the present invention are not impaired.
Specifically, for example, an active ingredient in an ophthalmic drug described in the Occupational Drug Manufacturing and Sales Approval Standard 2012 Edition (supervised by the Japanese Society for Regulatory Science) can be blended.

  Ingredients that can be added include vasoconstrictor or decongestant, sulfa antibacterial agent, antibacterial or antiseptic other than sulfa, antiallergic agent, antioxidant, mucopolysaccharide, ocular muscle other than (A) component Examples include regulators, anti-inflammatory agents other than component (B), antihistamines other than component (C), vitamins other than component (D), and amino acids other than component (E).

  Examples of the vasoconstrictor or the decongestant include epinephrine, epinephrine hydrochloride, tetrahydrozoline hydrochloride, naphazoline hydrochloride, naphazoline nitrate, phenylephrine hydrochloride, methylephedrine hydrochloride, and the like. In addition, the ophthalmic composition of this invention can also be a thing which does not contain a vasoconstrictor or a decongestant, especially tetrahydrozoline and / or a tetrahydrozoline salt.

  Examples of the sulfa antibacterial agent include sulfamethoxazole, sulfamethoxazole sodium, sulfisoxazole, sulfisomidine sodium and the like.

  Antibacterial agents or preservatives other than sulfa series include alkyl polyaminoethyl glycine, boric acid, cetyl pyridinium, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, polyhexamethylene biguanide hydrochloride, alkyl polyaminoethyl glycine, chloro Lambphenicol, ofloxacin, norfloxacin, levofloxacin, lomefloxacin hydrochloride, acyclovir, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl parahydroxybenzoate, ethyl paraoxybenzoate Propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, Benzyl alcohol, polyhexamethylene biguanide (abbreviated: PHMB), Gurokiru (trade name) (manufactured by Rhodia), hydrochloric polyhexanide, Poridoroniumu chloride, phenylethyl alcohol, chlorobutanol, etc. can be mentioned.

  Antiallergic agents include sodium cromoglycate, tranilast, acitazanolast, tazanolast, amlexanox, ibudilast and the like.

Examples of the antioxidant include dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), nordihydroguaiaretic acid (NDGA), propyl gallate, sodium bisulfite, sodium sulfite, sodium thiosulfate and the like.
Examples of mucopolysaccharides include hyaluronic acid and sodium hyaluronate.

Examples of the ocular muscle modifier other than the component (A) include physostigmine salicylate, distigmine bromide, tropicamide, atropine helenien sulfate, pilocarpine hydrochloride, and the like.
Examples of anti-inflammatory agents other than the component (B) include monoammonium glycyrrhizinate, lysozyme chloride, indomethacin, silver nitrate, diclofenac sodium, bromfenac sodium, and licorice.
Examples of antihistamines other than the component (C) include chlorpheniramine fumarate, iproheptin, ketotifen fumarate, pemirolast potassium, and olopatadine hydrochloride.
Examples of vitamins other than the component (D) include ascorbic acid and ubiquinone derivatives.
Examples of amino acids other than the component (E) include sodium glutamate, creatinine, glycine, alanine, arginine, lysine, γ-aminobutyric acid, γ-aminovaleric acid, sodium hyaluronate, sodium alginate and the like.
Components other than the essential components of the present invention can be used alone or in combination of two or more.

Additives In addition, the ophthalmic composition of the present invention can contain various additives blended in the ophthalmic composition as long as the effects of the present invention are not impaired.
Specifically, for example, additives described in Pharmaceutical Additive Dictionary 2016 (edited by Japan Pharmaceutical Additives Association) can be blended.
Examples of additives include thickeners, surfactants, sugars, sugar alcohols, pH adjusters, buffers, stabilizers, fragrances or refreshing agents, inorganic salts, and the like.

  Examples of the thickener include polyvinyl alcohol, polyvinyl pyrrolidone, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, glucose, carboxyvinyl polymer, alginic acid, gum arabic powder, sodium alginate, propylene glycol alginate, macrogol and the like.

As the surfactant, polyoxyethylene (hereinafter also referred to as “POE”)-polyoxypropylene (hereinafter also referred to as “POP”) block copolymer (for example, Poloxamer 407, Poloxamer 235, Poloxamer 188), POE-POP block copolymer adduct of ethylenediamine (for example, poloxamine), POE sorbitan fatty acid ester (for example, polysorbate 20, polysorbate 60, polysorbate 80), POE hydrogenated castor oil (for example, POE (60) hydrogenated castor oil), POE castor Nonionic boundaries such as oils, POE alkyl ethers (eg, polyoxyethylene (9) lauryl ether, polyoxyethylene (20) polyoxypropylene (4) cetyl ether), and polyoxyl stearate Active agent;
Amphoteric surfactants such as glycine-type amphoteric surfactants (eg, alkyldiaminoethylglycine, alkylpolyaminoethylglycine) and betaine-type amphoteric surfactants (eg, lauryldimethylaminoacetic acid betaine, imidazolinium betaine); Cations such as alkyl quaternary ammonium salts (eg, benzalkonium chloride, benzethonium chloride, hexamethylene biguanide and its polymers (ie, polyhexamethylene biguanide (abbreviation: PHMB)), chlorhexidine, alexidine, hexidine, polydronium chloride) Surfactants and the like. The numbers in parentheses indicate the number of added moles.
Among these, nonionic surfactants, glycine-type amphoteric surfactants, and cationic surfactants are preferable. Among the nonionic surfactants, polyoxyethylene-polyoxypropylene block copolymer, POE sorbitan fatty acid ester, POE hydrogenated castor oil, POE castor oil, and polyoxyl stearate are preferable. Of the glycine-type amphoteric surfactants, alkylpolyaminoethylglycine is preferable. Among the cationic surfactants, benzalkonium chloride, benzethonium chloride, hexamethylene biguanide and its polymer, chlorhexidine, alexidine, and polydronium chloride are preferable.
Note that the ophthalmic composition of the present invention may not contain a surfactant.

Examples of the saccharide include glucose and cyclodextrin.
Examples of the sugar alcohol include xylitol, sorbitol, mannitol and the like.

  Examples of pH regulators include hydrochloric acid, boric acid, citric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium bicarbonate, sodium carbonate, borax, triethanolamine, monoethanolamine, Examples include diisopropanolamine, sulfuric acid, phosphoric acid, polyphosphoric acid, propionic acid, oxalic acid, gluconic acid, fumaric acid, lactic acid, tartaric acid, malic acid, succinic acid, gluconolactone, and ammonium acetate.

Examples of the buffer include borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, Tris buffer, and aspartate buffer. Among these, a boric acid buffer or a combined use of a boric acid buffer and a phosphate buffer is preferable from the viewpoint of storage efficacy or the point that the effects of the present invention are remarkably exhibited.
Examples of the components of the boric acid buffer include boric acid and borates (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.). 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). 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). Examples of the component of the tris buffer include tris (hydroxymethyl) aminomethane or a salt thereof (hydrochloride, acetate, sulfonate, etc.). Examples of the aspartic acid component include aspartic acid or a salt thereof (sodium aspartate, magnesium aspartate, potassium aspartate). These may be hydrates.

Examples of the stabilizer include trometamol, sodium formaldehyde sulfoxylate (Longalite), sodium pyrosulfite, monoethanolamine, aluminum monostearate, glyceryl monostearate and the like.
Examples of chelating agents include ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid (edetic acid, EDTA), N- (2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), and diethylenetriaminepentaacetic acid (DTPA). It is done.

  Examples of the fragrance or the refreshing agent include 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. These fragrances or refreshing agents may be formulated as essential oils such as peppermint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, bergamot oil, eucalyptus oil, and rose oil. Among terpenoids, menthol, camphor, geraniol, borneol, and agate are preferred. Among the essential oils, peppermint oil, cool mint oil, peppermint oil, fennel oil, cinnamon oil, bergamot oil and eucalyptus oil are preferred.

Inorganic salts include potassium chloride, sodium chloride, calcium chloride, sodium bicarbonate, sodium carbonate (including dry sodium carbonate), potassium bicarbonate, potassium carbonate, magnesium sulfate, sodium hydrogen phosphate, potassium hydrogen phosphate, phosphoric acid Examples thereof include sodium dihydrogen, potassium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, potassium acetate, sodium acetate, sodium thiosulfate and the like.
An additive can mix | blend 1 type (s) or 2 or more types.

As a base or carrier to be blended in the ophthalmic composition of the present invention, for example, water, an aqueous solvent such as ethanol, propylene glycol, concentrated glycerin, polyhydric alcohol such as glycerin, vegetable oil such as sesame oil, castor oil, etc. Is mentioned. A base or a support | carrier can be used individually by 1 type or in combination of 2 or more types.
The ophthalmic composition of the present invention is preferably an aqueous composition containing 80% by weight or more of water based on the total amount of the composition. Among them, 83% by weight or more, particularly 85% by weight or more, particularly 88% by weight or more, particularly 90% by weight or more can be included with respect to the total amount of the composition. Although the upper limit of water content changes with content of each component, it can be about 98 weight% with respect to the whole quantity of a composition.

pH
The pH of the ophthalmic composition of the present invention may be in a physiologically acceptable range, and can be, for example, about 5.5 to 8.5. Among them, it can be 5.8 or more, 6 or more, 6.5 or more, or 7 or more, and can be 8 or less, 7.5 or less, or 7 or less.

Osmotic pressure of the ophthalmic composition of the osmotic pressure present invention may be a range that is acceptable as an ophthalmic composition, e.g., 0.5 to 5, preferably 0.6 to 3, particularly preferably 0.7 to 2 It can be.
The osmotic pressure can be adjusted using an inorganic salt, a polyhydric alcohol, a sugar alcohol, a saccharide, or the like, if necessary. The osmotic pressure ratio is the ratio of the osmotic pressure of the sample to 286 mOsm (0.9 w / v% sodium chloride aqueous solution) based on the 17th revised Japanese Pharmacopoeia. Measure according to the freezing point method.

Properties The properties of the ophthalmic composition are not particularly limited, and examples thereof include liquid, fluid, gel, and 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.

The ophthalmic composition of the present invention for soft contact lenses is a composition for use in contact with soft contact lenses. For example, eyedrops for soft contact lenses that are eye drops that can be used while wearing soft contact lenses, eye wash agents for soft contact lenses that can be used while wearing soft contact lenses, soft contact lens mounting solutions, Examples include soft contact lens solutions (cleaning solution, preservative solution, disinfectant solution, multipurpose solution). Especially, it can be conveniently used as an eye drop for soft contact lenses.
The eye drop for soft contact lens and the eye wash for soft contact lens can be used when the soft contact lens is not worn or worn, but are suitable for use when the soft contact lens is worn or worn.

  The ophthalmic composition of the present invention can be applied to any soft contact lens. Soft contact lenses are contact lenses that have a higher moisture content than hard contact lenses.

  Soft contact lenses can be classified into four types of groups I to IV depending on the moisture content and the presence or absence of ionicity. The group I soft contact lens is a lens having a water content of less than 50% and a mole% of a monomer having an anion out of constituent monomers of the raw material polymer being less than 1%. Group II soft contact lenses are lenses having a water content of 50% or more and a mole% of the monomer of less than 1%. Group III soft contact lenses are lenses having a moisture content of less than 50% and a mole% of the monomer of 1% or more. Group IV soft contact lenses are lenses having a water content of 50% or more and a mole% of the monomer of 1% or more. The ophthalmic composition of the present invention can be applied to any group of soft contact lenses. Among them, a group I soft contact lens is preferable.

  Soft contact lenses include silicone hydrogel contact lenses and hydrogel contact lenses. Silicone hydrogel contact lenses are made of a material obtained by copolymerizing a silicone-containing material such as a polymer of silicone and acrylate with a hydrophilic monomer such as hydroxyethyl methacrylate or dimethylacrylamide. The ophthalmic composition of the present invention can be applied to both silicone hydrogel contact lenses and hydrogel contact lenses.

Efficacy / Effects Since the ophthalmic composition of the present invention contains 11 or more kinds of eye muscle regulators, anti-inflammatory agents, antihistamines, vitamins, and amino acids, it has many physiological activities derived therefrom. In addition, as described above, the wettability with the soft contact lens is good, protein stains of the soft contact lens can be effectively removed, and drying of the soft contact lens can be suppressed.
As a result, the ophthalmic composition of the present invention has dry eyes, tired eyes, blurred eyes, itchy eyes, eye inflammation due to light, ophthalmitis due to light, and poor use when using soft contact lenses. It can be used for alleviating, improving, or treating pleasure. Relieving, ameliorating, or treating dry eyes may be due to the aid of tears. In addition, the ophthalmic composition of the present invention can prevent eye diseases (such as when dust or sweat enters the eyes after swimming), or reduce, improve, or treat eye inflammation (such as snow eyes) caused by ultraviolet rays or other rays. Can be used for. It can also be used to facilitate the mounting of soft contact lenses.

  The ophthalmic composition of the present invention varies depending on the dosage form and application, but it is 1 to 2 times or more, 3 times or more per day, 4 times or less, 5 times or less, or 6 times or less, soft contact lens It is preferable to use it so as to come into contact with this, so that the wettability of the soft contact lens can be effectively improved and the protein soil can be effectively washed away.

When the ophthalmic composition of the present invention is an eye drop, 1 to 4 drops, for example, 1 to 3 drops can be used per time. When the ophthalmic composition of the present invention is an eye wash, for example, about 1 to 20 mL, particularly about 1 to 7 mL, especially about 1 to 5 mL can be used per time.
In addition, when the ophthalmic composition of the present invention is an eye drop or an eye wash, the use may be started at the same time or after the symptom appears, but about 1 to 14 days before the symptom appears, especially about 1 to 10 days before In particular, use may be started from about 1 to 7 days in advance, thereby effectively preventing symptoms.

  When the ophthalmic composition of the present invention is a contact lens mounting solution, at the time of mounting the contact lens, for example, 1 to 4 drops, especially 1 to 3 drops are dropped on one side and / or both sides of the contact lens. Contact lenses can be worn. Further, when removing the contact lens from the eyes, the contact lens can be removed while dropping, for example, 1 to 4 drops, especially 1 to 3 drops on the contact lens.

  When the ophthalmic composition of the present invention is a contact lens cleaning solution or a disinfecting solution, the ophthalmic composition of the present invention and the contact lens are contacted with each other, for example, for about 5 minutes to 12 hours, especially about 10 minutes to 8 hours. I can leave it to you. The same applies when the ophthalmic composition of the present invention is a multi-purpose solution used for cleaning or disinfecting contact lenses.

  When the ophthalmic composition of the present invention is a contact lens preservation solution, the ophthalmic composition of the present invention and the contact lens can be kept in contact, for example, for about 5 minutes to 10 days, particularly about 10 minutes to 7 days. . The same applies when the ophthalmic composition of the present invention is a multi-purpose solution and is used for contact lens storage purposes.

Container The ophthalmic composition of the present invention is usually housed or filled in an ophthalmic container. The material of the container is not particularly limited, and examples thereof include a plastic container, a metal container, and a glass container. Specifically, for example, polyolefin, acrylic resin, terephthalic acid ester, 2,6-naphthalenedicarboxylic acid ester, polycarbonate, polymethylpentene, fluorine resin, polyvinyl chloride, polyamide, ABS resin, AS resin, polyacetal, modified Examples include polyphenylene ether, polyarylate, polysulfone, polyimide, plastics such as cellulose acetate, metals such as aluminum, and glass. The container may be composed of one kind of material, or may be composed of two or more kinds of materials. In the case of plastic, it may be a mixture or a copolymer.
Among these, a plastic container is preferable, and a polyolefin container and a terephthalate container are more preferable.
In a container having a spout or a nozzle, the entire part including the spout or the nozzle may be molded from the above material, or only the main body portion other than the spout or the nozzle may be molded from the above material.

Examples of 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 ester include polystyrene-modified polyphenylene ester.
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.

EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated in detail, this invention is not limited to these.
(1) Preparation of ophthalmic composition Ophthalmic compositions having the compositions shown in Tables 1 and 2 were prepared according to a conventional method.

(2) Evaluation of wettability The wettability test was performed according to the following procedure in accordance with the method disclosed in Japanese Patent No. 5078254.
1. As a pretreatment, soft contact lenses (Group I; trade name “Medalist Plus”) were each immersed in 4 mL of physiological saline and stored at room temperature for 4 hours or more.
2. 5 μL of each ophthalmic composition was dropped on each pretreated lens, and 0.5 seconds later, the image was taken with a digital camera from the side of the lens. The focus of the camera was adjusted to the portion where the droplet was in contact with the contact lens and the apex of the droplet.
3. For the photographed image, the contact angle of the droplet in contact with the surface was measured using image analysis software.
4). The contact angle improvement rate with respect to the control was calculated by the following formula.

Contact angle improvement rate with respect to control (%)
= {1- (contact angle of each test solution / contact angle of control)} × 100

The results are shown in FIG. As shown in FIG. 1, the ophthalmic compositions of Comparative Examples 1 to 5 had the same contact angle as the control not including any of the components (A) to (E) of the present invention. On the other hand, the ophthalmic compositions of Examples 1 to 7 greatly decreased the contact angle compared to the control.
Comparative Examples 1 to 5 are compositions containing other similar components instead of the component (B), the component (D), or the component (E) of the present invention. Therefore, it can be seen that the wettability with the soft contact lens is improved by combining the components (A) to (E) of the present invention, thereby improving the feeling of use of the soft contact lens.

(3) Evaluation of washing power of adsorbed protein The protein washing test was performed according to the following procedure according to the method disclosed in Japanese Patent No. 5506357.
1. As a pretreatment, soft contact lenses (Group I; trade name “Medalist Plus”) were immersed one by one in 4 mL of physiological saline and stored at room temperature for 4 hours or more.
2. 1.0 mL of the protein solution having the composition shown in Table 3 was placed in each hole of the 12-well plate, and after wiping off excess moisture from the pretreated lens, it was immersed and shaken at 34 ° C. and 400 rpm for 14 hours.

3. The lens immersed in the protein solution is taken out, quickly immersed in 100 mL of physiological saline (about 1 second) to rinse the excess solution, wiped off the water, and then added to each 2.0 mL of each ophthalmic composition placed in a 12-well plate. It was immersed and shaken at 34 ° C. and 120 rpm for 4 hours.
4). After removing the lens and rinsing the excess liquid quickly by immersing it in 100 mL of physiological saline (about 1 second), using a beaker's edge, lightly drain the water and put it in a 12-well plate (1 % Sodium carbonate and 1% SDS-containing aqueous solution).
5. The mixture was shaken at 34 ° C. and 120 rpm for 3 hours to separate the protein adsorbed on the lens into the protein separation solution.
6). Using a micro BCA assay kit (Thermo Scientific, Pierce # 23235), the amount of protein present in the protein separation solution was quantified as an albumin equivalent value, and the amount of protein remaining in the lens (remaining amount of protein) Was calculated. In calculating the amount of remaining protein, the amount of remaining protein was determined by subtracting the absorbance of the blank group from the absorbance of each sample and calculating it as an albumin equivalent value.

The results are shown in FIG. As shown in FIG. 2, when washed with the ophthalmic compositions of Comparative Examples 1 to 5, the residual amount of protein was as high as 3 μg or more. On the other hand, when washed with the ophthalmic compositions of Examples 1 and 4 to 6, the remaining amount of protein was 2.5 μg or less, which was clearly less than the ophthalmic compositions of Comparative Examples 1 to 5.
The protein solution subjected to the test contains 4 types of proteins. Therefore, it can be seen that various protein stains adsorbed on the soft contact lens can be effectively washed and removed by combining the components (A) to (E) of the present invention.

  Formulation examples of the ophthalmic composition of the present invention are shown in Tables 4 to 11. The component concentration in the table is w / v% excluding retinol palmitate.

  The ophthalmic composition of the present invention has good wettability with respect to a soft contact lens by containing 11 or more specific components. Moreover, the protein dirt adsorb | sucked to the lens can be effectively removed by using it making it contact with a soft contact lens. Therefore, the use feeling of the soft contact lens is improved by using the ophthalmic composition of the present invention.

Claims (6)

(A) Methyl sulfate neostigmine;
(B) at least three selected from the group consisting of epsilon-aminocaproic acid, allantoin, berberine chloride or berberine sulfate, sodium azulenesulfonate, dipotassium glycyrrhizinate, and zinc sulfate or zinc lactate;
(C) diphenhydramine hydrochloride or chlorpheniramine maleate;
(D) at least three selected from the group consisting of sodium flavin adenine dinucleotide, cyanocobalamin, retinol acetate or retinol palmitate, pyridoxine hydrochloride, panthenol or calcium pantothenate or sodium pantothenate, and tocopherol acetate; and (E) An ophthalmic composition for soft contact lenses comprising potassium L-aspartate or magnesium L-aspartate or an equivalent mixture thereof, aminoethylsulfonic acid, and sodium chondroitin sulfate.   The ophthalmic composition according to claim 1, which has a pH of 5.5 to 8.5.   The ophthalmic composition according to claim 1, further comprising a surfactant.   Furthermore, the ophthalmic composition in any one of Claims 1-3 containing a cooling agent.   The ophthalmic composition according to any one of claims 1 to 4, which is contained in a polyethylene terephthalate container.   The ophthalmic composition according to any one of claims 1 to 5, which is used 3 to 6 times per day.