TW202031263A - Ophthalmic composition for preventing deterioration of soft contact lenses - Google Patents

Abstract

The present invention provides an ophthalmic composition comprising boric acid or a salt thereof and epinastine or a salt thereof which produces the effect for preventing the deterioration of soft contact lenses as well as an agent for preventing the burst of pollens comprising boric acid and a salt in a specific concentration and epinastine or a salt thereof.

Description

Ophthalmic composition for inhibiting deterioration of soft contact lens

The present invention relates to an ophthalmic composition containing boric acid or its salt and epinastine or its salt for inhibiting the deterioration of soft contact lenses. In addition, it relates to a pollen break inhibitor containing boric acid or its salt and epinastine or its salt, and the concentration of boric acid or its salt is 0.01-2% (w/v).

An ophthalmic composition containing water and other solvents, which is supposed to be used repeatedly, requires a certain level of anti-corrosion measures to prevent the growth of fungi. Therefore, preservatives are usually blended in such ophthalmic compositions. For example, in the case of eye drops, in most cases, benzalkonium chloride (benzalkonium chloride) is used as a preservative. Benzyldimethylammonium chloride is water-soluble and chemically stable. Even when compared with other preservatives, it has high preservative effectiveness. However, it is known that benzalkonium chloride is cytotoxic and will adsorb on soft contact lenses. If the benzalkonium chloride is adsorbed on the soft contact lens, it will not only become the cause of the discoloration and deformation of the soft contact lens, but also the possibility of causing corneal epithelium disorder as the contact time with the cornea becomes longer. Increase. Therefore, eye drops containing preservatives are not used when wearing soft contact lenses.

Non-Patent Document 1 describes that Alesion ^{( registered trademark )} ophthalmic solution containing epinastine hydrochloride as an active ingredient, which is currently marketed in Japan as a therapeutic agent for allergic conjunctivitis, 0.05%. It is known that this ophthalmic solution can be used when wearing soft contact lenses, but this is because it does not use benzalkonium chloride as a preservative and does not cause deterioration of soft contact lenses.

It is not known that based on the combination of the active ingredients contained in the ophthalmic composition, the type of additives and the content of these, even the ophthalmic composition that does not contain preservatives such as benzalkonium chloride is still invisible to softness. The deterioration of the glasses has an impact. In addition, it is not known that epinastine or its salt causes the deterioration of soft contact lenses, and boric acid or its salt has the effect of inhibiting the deterioration of soft contact lenses caused by it.

In addition, various reviews have been conducted on allergic diseases in recent years, and their pathogenesis is gradually being clarified. For example, according to Non-Patent Document 2 and Non-Patent Document 3, it can be considered that allergic conjunctivitis caused by cedar pollen is an allergy caused by the dissolution of the outer wall of the pollen after the scattered pollen particles penetrate into the conjunctival sac. The original migrates to the conjunctival tissue and binds to the antibodies on the obese cells, thereby causing the disease. The rupture of the outer wall of the pollen easily occurs in the sludge. This implies that the factors that affect the rupture of the outer wall of the pollen are not only due to the physical and chemical effects such as pH and temperature, but also due to the components in the sludge (lysozyme or protein, Various decomposing enzymes, etc.). Furthermore, it is implied that in various anti-allergic eye drops, in addition to the previous pharmacological effects, it may also affect the rupture of the outer wall of pollen or the dissolution of allergens, depending on the type.

According to Non-Patent Document 4, it is suggested that the additives contained in eye drops may also affect the rupture of the outer wall of pollen or the elution of allergens. For example, PBS (phosphate buffered physiological saline) promotes the rupture of the outer wall of pollen. Possibility. [Prior Technical Literature] [Non-Patent Literature]

[Non-Patent Document 1] Alesion ^{( registered trademark )} eye drops 0.05% copy sheet [Non-Patent Document 2] Allergy and Immunity 2010, Vol.17, No. 2, 124-129 [Non-Patent Document 3] Allergy and Immunity 2011 , Vol.18, No.2, 82-87 [Non-Patent Document 4] Allergy and Immunity 2016, Vol.23, No.2, 124-130

[The problem to be solved by the invention]

Therefore, it is an intriguing issue to provide an ophthalmic composition containing epinastine or its salt that can be used safely even when the soft contact lens is worn with the effect of suppressing deterioration of the soft contact lens. Furthermore, the object of the present invention is to provide a pollen rupture inhibitor containing boric acid or its salt and epinastine or its salt in a specific concentration. [Means to solve the problem]

As a result of intensive research on ophthalmic compositions containing epinastine or its salt, the inventors found that epinastine or its salt itself caused the deterioration of soft contact lenses, and then found that by containing epinastine or Its salt and boric acid or its salt can inhibit the deterioration of soft contact lenses. Furthermore, it was found that by containing boric acid or its salt, and epinastine or its salt in a specific concentration, the rupture of pollen is inhibited and the therapeutic effect on allergic diseases is excellent, and the present invention has been completed.

Specifically, the present invention provides the following items. (1) An ophthalmic composition containing boric acid or a salt thereof and suppressing deterioration of soft contact lenses, wherein the composition contains epinastine or its salt, and the soft contact lens is the longest Wear soft contact lenses for 1 month. (2) The ophthalmic composition as described in (1), wherein the concentration of epinastine or its salt is 0.1% (w/v) or less. (3) The ophthalmic composition as described in (1) or (2), wherein the concentration of epinastine or its salt is 0.05% (w/v). (4) The ophthalmic composition according to any one of (1) to (3), wherein the concentration of boric acid or its salt is 0.01 to 2% (w/v). (5) The ophthalmic composition as described in any one of (1) to (4), which does not contain benzalkonium chloride. (6) The ophthalmic composition according to any one of (1) to (5), which further contains a buffer. (7) The ophthalmic composition according to any one of (1) to (6), which further contains an isotonicity agent. (8) The ophthalmic composition described in any one of (1) to (7), which further contains a stabilizer. (9) The ophthalmic composition according to (8), wherein the stabilizer is edetic acid or a salt thereof. (10) The ophthalmic composition described in (9), wherein the concentration of edetic acid or its salt is 0.005 to 0.1% (w/v). (11) The ophthalmic composition according to any one of (1) to (10), which is an eye drop. (12) The ophthalmic composition as described in any one of (1) to (11), which is used in a way that is applied to the eyes wearing soft contact lenses. (13) The ophthalmic composition as described in any one of (1) to (11), which is used in a way that is applied to the eyes without soft contact lenses. (14) The ophthalmic composition described in any one of (1) to (13), which is used in a form of 1 or 2 drops per eye, and 2 to 4 drops per day . (15) The ophthalmic composition according to any one of (1) to (14), wherein the soft contact lens is classified into any of the first, second, third, and fourth types Of soft contact lenses. (16) An ophthalmic composition containing boric acid or its salt at a concentration of 0.05 to 1% (w/v), edetic acid or its salt at a concentration of 0.01 to 0.05% (w/v), and the like A tonicity agent and an ophthalmic composition that inhibits the deterioration of soft contact lenses, wherein the composition further contains epinastine or its salt at a concentration of 0.05% to 0.1 (w/v), and the soft contact lens is the longest Wear soft contact lenses for 1 month. (17) A method for inhibiting deterioration of soft contact lenses by administering an ophthalmic composition containing boric acid or its salt, and epinastine or its salt to the eye wearing the soft contact lens. (18) A pollen rupture inhibitor comprising boric acid or its salt, and epinastine or its salt, and the concentration of the aforementioned boric acid or its salt is 0.01-2% (w/v). (19) The pollen rupture inhibitor as described in (18), wherein the concentration of epinastine or its salt is 0.05% (w/v) or more. (20) The pollen rupture inhibitor as described in (18), wherein the concentration of epinastine or its salt is 0.1% (w/v). (21) The pollen rupture inhibitor according to any one of (18) to (20), which does not contain benzalkonium chloride. (22) The pollen rupture inhibitor according to any one of (18) to (21), which further contains a buffer. (23) The pollen rupture inhibitor according to any one of (18) to (22), which further contains an isotonicity agent. (24) The pollen breakdown inhibitor according to any one of (18) to (23), which further contains a pH adjuster. (25) The pollen rupture inhibitor according to any one of (18) to (24), which further contains a stabilizer. (26) The pollen rupture inhibitor according to any one of (18) to (25), which is for ophthalmic use. (27) The pollen rupture inhibitor as described in any one of (18) to (26), which is used in a way that is applied to the eyes wearing soft contact lenses. (28) The pollen rupture inhibitor as described in any one of (18) to (26), which is used in a way that is applied to eyes that are not wearing soft contact lenses. (29) The pollen rupture inhibitor as described in any one of (18) to (28), which is used in the form of 1 or 2 drops per eye, and 2 to 4 drops a day . (30) A pollen rupture inhibitor comprising boric acid or its salt, epinastine or its salt, and an isotonicity agent, the concentration of the aforementioned boric acid or its salt is 0.05-1% (w/v), the aforementioned The concentration of pistine or its salt is 0.05% to 0.1 (w/v). (31) A method for inhibiting pollen breakdown, which is characterized in that an ophthalmic composition containing epinastine or its salt and boric acid or its salt at a concentration of 0.01 to 2% (w/v) is brought into contact with pollen. (32) An ophthalmic composition, which is an ophthalmic composition containing boric acid or its salt, and epinastine or its salt, characterized in that the concentration of epistatine or its salt is 0.1% (w/v ) The following, and use it in a way that points to the eyes wearing soft contact lenses. (33) The ophthalmic composition as described in (32), wherein the concentration of epinastine or its salt is 0.1% (w/v). (34) The ophthalmic composition as described in (32), wherein the concentration of epistin or its salt is 0.05% (w/v). (35) The ophthalmic composition according to any one of (32) to (34), wherein the concentration of boric acid or its salt is 0.01 to 2% (w/v). (36) The ophthalmic composition described in any one of (32) to (35), which does not contain benzalkonium chloride. (37) The ophthalmic composition described in any one of (32) to (36), which further contains a buffer. (38) The ophthalmic composition according to any one of (32) to (37), which further contains an isotonicity agent. (39) The ophthalmic composition described in any one of (32) to (38), which further contains a stabilizer. (40) The ophthalmic composition according to (39), wherein the stabilizer is edetic acid or a salt thereof. (41) The ophthalmic composition according to (40), wherein the concentration of edetic acid or its salt is 0.005 to 0.1% (w/v). (42) The ophthalmic composition described in any one of (32) to (41), which is an eye drop. (43) The ophthalmic composition according to any one of (32) to (42), wherein the soft contact lens is a soft contact lens that can be worn for a maximum of one month. (44) An ophthalmic composition, which is an ophthalmic composition containing boric acid or its salt, and epinastine or its salt, wherein the concentration of the epinastine or its salt is 0.1% (w/v) or less . (45) The ophthalmic composition as described in (44), wherein the concentration of epistin or its salt is 0.1% (w/v). (46) The ophthalmic composition as described in (44), wherein the concentration of epinastine or its salt is 0.05% (w/v). (47) The ophthalmic composition according to any one of (44) to (46), wherein the concentration of boric acid or its salt is 0.01 to 2% (w/v). (48) The ophthalmic composition described in any one of (44) to (47), which does not contain benzalkonium chloride. (49) The ophthalmic composition described in any one of (44) to (48), which further contains a buffer. (50) The ophthalmic composition described in any one of (44) to (49), which further contains an isotonicity agent. (51) The ophthalmic composition described in any one of (44) to (50), which further contains a stabilizer. (52) The ophthalmic composition according to (51), wherein the stabilizer is edetic acid or a salt thereof. (53) The ophthalmic composition according to (52), wherein the concentration of edetic acid or its salt is 0.005 to 0.1% (w/v). (54) The ophthalmic composition described in any one of (44) to (53), which is an eye drop. (55) An ophthalmic composition, which is an ophthalmic composition containing boric acid or its salt, and epinastine or its salt, wherein the concentration of the epinastine or its salt is 0.1% (w/v). (56) The ophthalmic composition according to (55), wherein the concentration of boric acid or its salt is 0.01-2% (w/v). (57) The ophthalmic composition according to (55) or (56), which contains boric acid or its salt as a buffer. (58) The ophthalmic composition described in any one of (55) to (57), which contains only boric acid or a salt thereof as a buffer. (59) The ophthalmic composition described in any one of (55) to (58), which does not contain benzalkonium chloride. (60) The ophthalmic composition described in any one of (55) to (59), which does not contain phosphoric acid or its salt. (61) The ophthalmic composition described in any one of (55) to (60), which is an eye drop. (62) The ophthalmic composition described in any one of (55) to (61), which is used for the treatment of allergic conjunctivitis. (63) The ophthalmic composition described in any one of (55) to (62), which is characterized by using 1 or 2 drops per eye once and instilling eyes twice a day. In addition, for each of the aforementioned (1) to (63), a combination of two or more items can be arbitrarily selected.

Furthermore, the present invention also provides the following items. (64) A method for treating and/or preventing allergic diseases, characterized by administering a therapeutically effective amount of the pollen rupture inhibitor described in any one of (18) to (30) to a patient in need of treatment. (65) The pollen rupture inhibitor according to any one of (18) to (30), which is used for the treatment and/or prevention of allergic diseases. (66) A use of the pollen rupture inhibitor as described in any one of (18) to (30), which is used to manufacture a medicine for the treatment and/or prevention of allergic diseases. (67) The method described in (64), the pollen rupture inhibitor described in (65), or the use described in (66), wherein the allergic disease is allergic conjunctivitis. (68) A method for treating and/or preventing allergic diseases, characterized by adding a therapeutically effective amount of the ophthalmic composition described in any one of (1) to (16) and (32) to (61) Give to patients in need of treatment. (69) The ophthalmic composition described in any one of (1) to (16) and (32) to (61), which is used for the treatment and/or prevention of allergic diseases. (70) A use of the ophthalmic composition described in any one of (1) to (16) and (32) to (61), which is used to manufacture a medicine for the treatment and/or prevention of allergic diseases. (71) The method described in (68), the ophthalmic composition described in (69), or the use described in (70), wherein the allergic disease is allergic conjunctivitis. (72) The method described in (68), the ophthalmic composition described in (69), or the use described in (70), characterized by taking 1 or 2 drops per eye as one time, 1 day Use the eye twice. [Effects of Invention]

The present invention can obtain an ophthalmic composition containing epinastine or its salt, which has the effect of inhibiting the deterioration of soft contact lenses, and can be used safely even in the state of wearing soft contact lenses. In addition, by containing boric acid or its salt, and epinastine or its salt in a specific concentration, a pollen rupture inhibitor can be obtained.

[Form to implement the invention]

Hereinafter, the present invention will be described in detail. In addition, in this specification, "ophthalmic composition" may be replaced with "pollen rupture inhibitor".

。In the ophthalmic composition of the present invention, "epistin" is the chemical name (±)-3-amino-9,13b-dihydro-1H-dibenzo[c,f]imidazo[1, 5-a] A compound represented by nitrogen, which is a compound represented by the following formula:

.

In the ophthalmic composition of the present invention, the epinastine contained may be a racemate or an optical isomer.

In the ophthalmic composition of the present invention, the epinastine contained may be a salt, and it is not particularly limited as long as it is a salt that is acceptable as a medicine. As for the salt, for example, a salt with an inorganic acid, a salt with an organic acid, etc. can be cited. As for the salts with inorganic acids, salts with hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, phosphoric acid and the like can be cited. In terms of salts with organic acids, examples include acetic acid, oxalic acid, fumaric acid, maleic acid, succinic acid, malic acid, citric acid, tartaric acid, adipic acid, gluconic acid, glucoheptonic acid (glucoheptonic acid) , Glucuronic acid, terephthalic acid, methanesulfonic acid, alanine, lactic acid, hippuric acid, 1,2-ethanedisulfonic acid, isethionic acid, lactobionic acid, oleic acid, gallic acid , Pamoic acid, polygalacturonic acid, stearic acid, tannic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, lauryl sulfate, methyl sulfate, naphthalenesulfonic acid, sulfonic acid Salicylic acid and other salts. As far as the salt of epinastine is concerned, monohydrochloride (epistin hydrochloride) is particularly preferred.

In the ophthalmic composition of the present invention, the epinastine or its salt contained in it may be in the form of a hydrate or a solvate.

In the ophthalmic composition of the present invention, the content of the effective ingredient of epinastine or its salt is preferably less than 0.15% (w/v), more preferably less than 0.1% (w/v). For example, its content is 0.1% (w/v). In addition, if the content of epinastine or its salt, which is an active ingredient, is low, in order to obtain a sufficient medicinal effect, the amount or frequency of eye drops must be increased. Therefore, the lower limit is 0.05% ( w/v) is preferred, and 0.05% (w/v) or more is more preferred. In addition, in the present invention, "%(w/v)" means the mass (g) of the target component contained in 100 mL of the ophthalmic composition of the present invention. In the present invention, in the case of containing the salt of epinastine, the value is the content of the salt of epinastine. Furthermore, in the present invention, when epinastine or its salt is blended in the form of a hydrate or solvate, the value is the content of the hydrate or solvate of epinastine or its salt. Hereinafter, unless otherwise specified, it is the same.

In the ophthalmic composition of the present invention, boric acid or its salt is helpful in inhibiting the deterioration of soft contact lenses, but also has a role as an additive for medicines, such as buffers, preservatives, Stabilizer, pH adjuster, etc. Therefore, boric acid or its salt can be used as an additive for medicines. Furthermore, in the present invention, by including boric acid or its salt in an ophthalmic composition containing epinastine or its salt, the medicinal effect can also be improved.

Examples of boric acid or its salts include boric acid, sodium borate, potassium borate, and the like. Although hydrates thereof may also be used, boric acid is preferred.

In the ophthalmic composition of the present invention, the content of boric acid or its salt can be adjusted appropriately, as long as it is 0.001 to 5% (w/v), preferably 0.01 to 2% (w/v), and 0.05 -1% (w/v) is more preferable, and 0.1-0.5% (w/v) is still more preferable. Furthermore, 0.1% (w/v), 0.2% (w/v), 0.3% (w/v), 0.4% (w/v), and 0.5% (w/v) are further preferred.

In the ophthalmic composition of the present invention, additives for pharmaceuticals can be further used as necessary. Specifically, buffers, isotonic agents, thickeners, surfactants, stabilizers, antioxidants, preservatives, pH adjusters, etc. can be added. These may be used alone, or two or more of them may be appropriately combined and used, and an appropriate amount may be blended.

The buffer in the case of blending a buffer in the ophthalmic composition of the present invention can be suitably blended with a buffer that can be used as an additive to pharmaceuticals. As for the buffering agent, for example, trometamol, phosphoric acid or its salt, carbonic acid or its salt, or organic acid or its salt, etc., may be hydrates or solvates thereof.

Phosphoric acid or its salts include phosphoric acid, trisodium phosphate, sodium dihydrogen phosphate, sodium hydrogen phosphate (disodium hydrogen phosphate), tripotassium phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, etc. And other hydrates.

As for carbonic acid or its salt, sodium carbonate, sodium bicarbonate, etc. may be mentioned, and hydrates thereof may also be used.

Organic acids or their salts include citric acid, acetic acid, ε-aminocaproic acid, gluconic acid, fumaric acid, lactic acid, ascorbic acid, succinic acid, maleic acid, malic acid, amino acids or the like The sodium salt, potassium salt, etc., can also be the hydrate of this.

As for the buffer in the case of blending the buffer in the ophthalmic composition of the present invention, phosphoric acid or its salt is more preferred, and sodium dihydrogen phosphate and sodium hydrogen phosphate are particularly preferred. When a buffer is blended in the ophthalmic composition of the present invention, two or more buffers may be used together.

The content of the buffer when the buffer is blended in the ophthalmic composition of the present invention can be appropriately adjusted according to the type of the buffer, etc., but is preferably 0.001 to 10% (w/v), and 0.01 to 5% (w/v) is more preferred, 0.1 to 5% (w/v) is further preferred, and 0.1 to 1% (w/v) is particularly preferred.

In the case of blending an isotonicizer in the ophthalmic composition of the present invention, an isotonicizer that can be used as an additive for pharmaceuticals can be appropriately blended. Examples of isotonic agents include ionic isotonic agents and nonionic isotonic agents.

Examples of the ionic isotonicizer include sodium chloride, potassium chloride, calcium chloride, magnesium chloride, and the like.

Examples of nonionic isotonic agents include glycerin, propylene glycol, polyethylene glycol, sorbitol, mannitol, trehalose, maltose, sucrose, and xylitol.

In the case of blending an isotonicizer in the ophthalmic composition of the present invention, an ionic isotonic agent is more preferred, and sodium chloride is particularly preferred. When an isotonicity agent is blended in the ophthalmic composition of the present invention, two or more kinds of isotonicity agents may be used together.

The content of the isotonizing agent in the case of blending the isotonizing agent in the ophthalmic composition of the present invention can be appropriately adjusted according to the type of the isotonizing agent, etc., but is 0.001-10% (w/v) Preferably, 0.01% to 5% (w/v) is more preferred, 0.1 to 3% (w/v) is further preferred, and 0.5 to 2% (w/v) is particularly preferred.

When the thickener is blended in the ophthalmic composition of the present invention, the thickener can be suitably blended with a thickener that can be used as an additive for pharmaceuticals. As for the thickener, for example, methyl cellulose, ethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl Methyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose phthalate, carboxymethyl ethyl cellulose, acetic acid Cellulose phthalate, polyvinylpyrrolidone, polyvinyl alcohol, carboxyvinyl polymer, polyethylene glycol, sodium hyaluronate, etc. When a thickener is blended in the ophthalmic composition of the present invention, two or more thickeners may be used together.

When a thickener is blended in the ophthalmic composition of the present invention, the content of the thickener can be appropriately adjusted according to the type of thickener, etc., but 0.001 to 5% (w/v) is preferred. It is more preferably 0.01% to 3% (w/v), and more preferably 0.1 to 2% (w/v).

In the case of blending a surfactant in the ophthalmic composition of the present invention, the surfactant can be suitably blended with a surfactant that can be used as an additive for pharmaceuticals. Surfactants include, for example, cationic surfactants, anionic surfactants, and nonionic surfactants.

For cationic surfactants, alkylamine salts, alkylamine polyoxyethylene adducts, fatty acid triethanolamine monoester salts, acylaminoethyldiethylamine salts, fatty acid polyamine condensates, Alkyl imidazoline, 1-aminoethyl-2-alkylimidazoline, 1-hydroxyethyl-2-alkylimidazoline, etc. However, although benzalkonium chloride has the properties of a cationic surfactant, it is not included in it.

Examples of anionic surfactants include phospholipids such as lecithin.

Nonionic surfactants include polyoxyethylene fatty acid esters such as polyoxyl 40 stearate; polysorbate 80, polysorbate 60, polyoxyethylene 40 stearate, etc. Sorbitan 40, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan trioleate, polysorbate 65 and other polyoxyethylene sorbitan fatty acid esters; polyoxyethylene hardened castor oil 10 , Polyoxyethylene hardened castor oil 40, polyoxyethylene hardened castor oil 50, polyoxyethylene hardened castor oil 60 and other polyoxyethylene hardened castor oil; polyoxyl 5 castor oil (polyoxyl 5 castor oil), polyoxyethylene 9 Castor oil, polyoxyethylene 15 castor oil, polyoxyethylene 35 castor oil, polyoxyethylene 40 castor oil and other polyoxyethylene castor oil; polyoxyethylene (160) polyoxypropylene (30) glycol, polyoxyethylene (42 ) Polyoxypropylene (67) glycol, polyoxyethylene (54) polyoxypropylene (39) glycol, polyoxyethylene (196) polyoxypropylene (67) glycol, polyoxyethylene (20) polyoxypropylene ( 20) Polyoxyethylene polyoxypropylene glycol such as glycol; sucrose fatty acid ester such as sucrose stearate; Tocopherol polyethylene glycol 1000 succinate (Vitamin E TPGS), etc. When a surfactant is blended in the ophthalmic composition of the present invention, two or more surfactants may be used together.

When a surfactant is blended in the ophthalmic composition of the present invention, the content of the surfactant can be appropriately adjusted according to the type of the surfactant, etc., but 0.01 to 1% (w/v) is preferred. It is more preferably 0.05 to 0.5% (w/v), and more preferably 0.05 to 0.2% (w/v).

In the case of blending a stabilizer in the ophthalmic composition of the present invention, the stabilizer can be suitably blended with a stabilizer that can be used as an additive for pharmaceuticals. As the stabilizer, for example, edetic acid or a salt thereof can be used. Edetic acid or a salt thereof includes edetic acid, disodium edetate, tetrasodium edetate, and the like. When a stabilizer is blended in the ophthalmic composition of the present invention, two or more stabilizers can be used together.

When the stabilizer is blended in the ophthalmic composition of the present invention, the content of the stabilizer can be appropriately adjusted according to the type of stabilizer, etc., but 0.001 to 1% (w/v) is preferred. It is more preferably 0.005% to 0.1% (w/v), and more preferably 0.01 to 0.05% (w/v). In addition, 0.01% (w/v), 0.02% (w/v), 0.03% (w/v), 0.04% (w/v), and 0.05% (w/v) are more preferable.

When an antioxidant is blended in the ophthalmic composition of the present invention, an antioxidant that can be used as an additive for pharmaceuticals can be suitably blended. Examples of antioxidants include ascorbic acid, tocopherol, dibutylhydroxytoluene, sodium sulfite, and the like. When an antioxidant is blended in the ophthalmic composition of the present invention, two or more antioxidants can be used together.

The content of the antioxidant when the antioxidant is blended in the ophthalmic composition of the present invention can be appropriately adjusted according to the type of the antioxidant, but it is preferably 0.001 to 5% (w/v), and 0.01% ~3% (w/v) is more preferable, and 0.1 to 2% (w/v) is more preferable.

When the preservative is blended in the ophthalmic composition of the present invention, the preservative can be suitably blended with a preservative that can be used as an additive for pharmaceuticals.

In the present invention, the preservatives include, for example, conversion soaps, parabens, alcohols, and organic acids or their salts.

In terms of transformed soaps, for example, benzalkonium chloride, benzalkonium bromide, benzethonium chloride, benzethonium bromide, loch gluconate Cetidine (chlorhexidine gluconate), lohexidine hydrochloride.

The parabens are, for example, methyl paraben, ethyl paraben, propyl paraben, and butyl paraben.

For alcohols, for example, it is chlorobutanol.

The organic acid or its salt is, for example, sorbic acid or its salt, sodium dehydroacetate, and the sorbic acid or its salt is, for example, sodium sorbate and potassium sorbate.

The content of the preservative when the preservative is blended in the ophthalmic composition of the present invention can be appropriately adjusted according to the type of the preservative and the like. The content of the preservative is sufficient as long as it does not adversely affect the safety. The upper limit is, for example, 1% (w/v), preferably 1% (w/v) or less, and 0.5% (w/ v) or less is more preferable, 0.1% (w/v) or less is more preferable, and 0.01% (w/v) or less is still more preferable. Moreover, as long as the amount can exert the anticorrosive effect, the lower limit is, for example, 0.0001% (w/v), preferably 0.0001% (w/v) or more, and more preferably 0.001% (w/v) or more. As far as the content of preservative is concerned, 0.0001 to 1% (w/v) is preferred, 0.001 to 0.5% (w/v) is more preferred, and 0.001 to 0.1% (w/v) is more preferred .

Generally speaking, preservatives are involved in the effect of deterioration of soft contact lenses. Therefore, although the ophthalmic composition of the present invention may contain preservatives in the range where soft contact lenses does not deteriorate, it is better not to contain preservatives. Benzyldimethylammonium chloride is particularly preferred.

In addition, the ophthalmic composition of the present invention contains boric acid or its salt in order to inhibit the deterioration of soft contact lenses. Since boric acid or its salt also functions as a preservative, the above-mentioned preservative may not be included.

In the case of blending a pH regulator in the ophthalmic composition of the present invention, the pH regulator can be suitably blended with a pH regulator that can be used as an additive for pharmaceuticals, for example, an acid or a base; for an acid, for example, Examples include hydrochloric acid, phosphoric acid, citric acid, acetic acid, and the like; in terms of alkali, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, and the like can be cited.

The pH of the ophthalmic composition of the present invention may be within the acceptable range as a pharmaceutical product, for example within the range of 4.0-8.5 or 4.0-8.0, preferably 6.0-8.0, more preferably 6.5-7.5 good. The particularly preferred pH is 6.7 to 7.3, and 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, and 7.3 are further preferred.

The osmotic pressure ratio of the ophthalmic composition of the present invention may be within the acceptable range as a pharmaceutical product, for example, 0.5 to 2.0, preferably 0.7 to 1.6, more preferably 0.8 to 1.4, and 0.9 to 0.9. 1.2 is further preferred.

The ophthalmic composition of the present invention can also be used for eyes that are not wearing contact lenses, but can also be used even when wearing hard contact lenses or when wearing soft contact lenses.

Soft contact lenses are classified in accordance with the Japanese Medical Review No. 645 dated March 31, Heisei 11, "About the processing methods of the materials that should be attached to the application for the manufacture (import) of soft contact lenses and disinfectants for soft contact lenses", etc. 4 kinds. That is, it is classified into the first category (group I) (the water content is less than 50% and is non-ionic), the second category (group II) (the water content is more than 50% and the non-ionic), and the third Type (group III) (the water content is less than 50% and is ionic), the fourth type (group IV) (the water content is more than 50% and is ionic), the raw material polymer has anionic monomers The monomer whose molar% is 1% or more is regarded as ionic, and the monomer with less than 1% is regarded as non-ionic. In addition, for soft contact lenses, for example, 2-hydroxyethyl methacrylate (HEMA), (polyethylene glycol) monomethacrylate (PEGMA), glycerol methacrylate (GMA), N,N-Dimethacrylamide (DMA), vinyl alcohol (VA), N-vinylpyrrolidone (NVP or VP), methacrylic acid (MAA), fluorine-containing methacrylate compounds , Silicon-containing methacrylate compounds, polysiloxane hydrogels, cycloalkyl methacrylate and other soft contact lenses as main components.

The soft contact lens of the present invention can be any of the above-mentioned materials, and can be classified into any one of the above-mentioned 4 types of soft contact lenses, regardless of the difference between ionic or non-ionic, hydrated or non-hydrated.

Soft contact lenses can be classified into lenses that are worn all day (worn out in the morning and worn on the eyes, and removed before going to bed) according to the way they are worn, and lenses that are worn continuously (worn in bed for a certain period of time) The soft contact lens of the present invention can be any of the above-mentioned categories of lenses.

Soft contact lenses can be classified into traditional lenses, disposable (discarded after use) lenses, frequent replacement lenses, and regular replacement lenses according to their replacement cycle. Disposable lenses are lenses that are no longer worn after the contact lens is removed from the eye. There are daily disposable lenses and weekly disposable lenses. Frequent replacement lenses are maintained and stored when the lenses are removed every day. For lenses that can be worn again within a certain period of time, the replacement period is usually 1 week or 2 weeks. Regular replacement lenses are lenses that can be re-worn by performing lens maintenance in the same way as frequent replacement lenses. The replacement period is usually 1 month to 3 months. The soft contact lens of the present invention may be any of the above-mentioned categories of lenses. The ophthalmic composition of the present invention can inhibit the deterioration of soft contact lenses, although it is also preferable to use the eye drops on the eyes with daily disposable lenses, but it is more preferable that the eye drops can be worn for 2 days The above disposable lenses, frequent replacement lenses, or regular replacement lenses are used for the eyes. Also, it is more preferable to wear soft contact lenses that can be worn for more than 1 week, more than 2 weeks or 1 month. The way to use the eyes.

In the present invention, "deterioration of soft contact lenses" refers to deformation and discoloration of soft contact lenses. The reasons for the deterioration of contact lenses include, for example, active ingredients such as epinastine or its salts, or additives such as benzalkonium chloride adsorbed on the surface of soft contact lenses.

The method of confirming the presence or absence of deterioration of the soft contact lens by the ophthalmic composition of the present invention includes, for example, a method of directly dropping onto a soft contact lens, a method of immersing a soft contact lens, and the like. From the viewpoint of the contact time between the ophthalmic composition of the present invention and the soft contact lens, the method of immersing the soft contact lens deteriorates the soft contact lens more than the method of directly dropping it onto the soft contact lens. In the case of dipping soft contact lenses, the dipping time is, for example, 5 minutes or 10 minutes. However, the longer the time, the more easily the soft contact lenses deteriorate.

In the ophthalmic composition of the present invention, the constituent components may be completely dissolved or partly suspended, but it is more preferable to use a liquid form in which all the constituent components are dissolved.

Unless otherwise specified, the ophthalmic composition of the present invention may also contain active ingredients for eye drops other than epistin or its salt.

The ophthalmic composition of the present invention, since it contains epinastine or its salt, can be used for all the treatments (for example, improvement, alleviation, inhibition of progress, etc.) and prevention of allergic conjunctivitis and its symptoms. It can be used for eyes with contact lenses, or for eyes without soft contact lenses.

The ophthalmic composition of the present invention can be used as an ophthalmic preparation, and its dosage form is not particularly limited as long as it can be used as a pharmaceutical product. The dosage form includes, for example, eye drops, ointments, creams, gels, transdermal preparations, patches, injections, and the like. Especially good for eye drops.

The ophthalmic composition of the present invention is preferably divided into an appropriate amount and administered twice to four times a day. In particular, when the ophthalmic composition is an eye drop, it is better to divide 1 drop or 2 drops per eye into 1 time and divide the eye into 2 to 4 times a day, so that 1 drop per eye It is more preferable to divide the eyedrops into two to four times a day as one time. In addition, when the ophthalmic composition of the present invention is divided into two to four infusions a day, it is preferable that the instillation interval is at least 1 hour or more, preferably 2 hours or more, and more preferably 3 hours or more. good. One drop is usually about 0.01 to about 0.1 mL, preferably about 0.015 to about 0.07 mL, more preferably about 0.02 to about 0.05 mL, and particularly preferably about 0.03 mL.

The container containing the ophthalmic composition of the present invention may be any one of a multi-dose type container, a single-dose type container for a single use, or a PFMD (Preservative Free Multi Dose) container. In addition, the material of the container is not particularly limited, as long as it is a container for general eye drops, preferably a resin container. For example, polyethylene (PE), polypropylene (PP), or polymer can be used. Polyethylene phthalate (PET), polybutylene terephthalate (PBT), polypropylene-polyethylene copolymer, polyvinyl chloride, acrylic, polystyrene, polycyclic Containers made of olefin copolymer. In addition, if the material of the resin container is polyethylene, for example, polyethylene is classified according to its density. Low-density polyethylene (LDPE), medium-density polyethylene (MDPE), or high-density polyethylene (HDPE) can be used. Wait for the container.

The ophthalmic composition of the present invention can be prepared according to general methods. For example, it is prepared by dissolving or suspending each component in distilled water, adjusting the osmotic pressure, pH, etc. to a specified range, and performing filter sterilization or heat sterilization treatment.

The ophthalmic composition of the present invention has an effect of effectively suppressing allergic symptoms caused by pollen because it inhibits the rupture of pollen existing on the mucosa, and can be used as a pollen rupture inhibitor. When the ophthalmic composition of the present invention is used as a pollen rupture inhibitor, the ophthalmic composition of the present invention is useful as a therapeutic agent for allergic diseases, especially allergic conjunctivitis.

In the present invention, "allergic disease" refers to a disease or its symptoms caused by an immune response to an antigen from the outside due to the rupture of the outer wall of pollen. Examples of allergic diseases include allergic conjunctivitis, but it is not limited to this. In the present invention, the treatment of allergic diseases refers to all the treatments of allergic diseases or their symptoms (for example, cure, amelioration, alleviation, suppression of progress, etc.) and prevention thereof. It also includes the prevention of the recurrence of allergic diseases.

In the present invention, "patient" is not limited to humans, but also refers to other animals, such as dogs, cats, horses, etc. The patient is preferably a mammal, more preferably a human. In the present invention, the "therapeutically effective amount" refers to the amount that brings about the therapeutic effect of the disease and its symptoms, or the amount that causes the delay in the progress of the disease and its symptoms, etc., compared to an untreated subject. [Example]

Hereinafter, preparation examples and test examples are shown, but these are used to better understand the present invention and do not limit the scope of the present invention.

Preparation Examples The following shows representative preparation examples of the present invention. In addition, in the following formulation examples, the blending amount of each component is the content in 100 mL of the formulation.

Preparation example 1 Epinastine hydrochloride 0.05g Boric acid 0.05g Sodium dihydrogen phosphate dihydrate 1.0g Sodium chloride 0.5g Dilute hydrochloric acid Appropriate amount of sodium hydroxide Appropriate amount of purified water Appropriate amount of pH 7.0

Preparation example 2 Epinastine hydrochloride 0.1g boric acid 0.1g sodium dihydrogen phosphate dihydrate 0.3g sodium hydrogen phosphate dodecahydrate 1.0g sodium chloride 0.5g dilute hydrochloric acid appropriate amount of sodium hydroxide appropriate amount of purified water appropriate amount of pH 7.0

Preparation example 3 Epinastine hydrochloride 0.1g Boric acid 0.1g Sodium dihydrogen phosphate dihydrate 0.3g Sodium hydrogen phosphate dodecahydrate 1.0g Sodium edetate 0.01g Sodium chloride 0.5g Dilute hydrochloric acid appropriate amount of sodium hydroxide Right amount of refined water Right amount pH 7.0

Preparation example 4 Epinastine hydrochloride 0.1g Boric acid 1.0g Sodium chloride 0.5g Dilute hydrochloric acid Right amount of sodium hydroxide Right amount of purified water Right amount of pH 7.0

Test Example 1. Deformation test of soft contact lens (SCL) by dropping (1) Preparation of the test formulation so that the concentration of the contained epinastine hydrochloride becomes 0.1% (w/v) Pistatin hydrochloride, phosphate, and sodium chloride are dissolved in water, and pH adjusters (hydrochloric acid and/or sodium hydroxide) and water are added to make the total amount to 10 mL, and filter and sterilize to prepare composition 1 Test preparation (pH7.0). In addition, except that the concentration of epinastine hydrochloride was 0.15% (w/v), the test preparation (pH 7.0) of composition 2 was prepared in the same manner as the test preparation of composition 1. In addition, the amounts of phosphate and sodium chloride contained in the test preparation of composition 2 are the same as those of the test preparation of composition 1.

(2) Test method One drop of each test preparation was dropped on the convex surface of the soft contact lens to spread over the entire soft contact lens. Shake off the remaining part, and rinse with physiological saline after 4 minutes. Take this as 1 cycle and repeat 7 cycles. To measure the diameter and base curve of soft contact lenses, it is appropriate that the diameter deformation and the base curve deformation are in the range of -0.20～+0.20. In addition, the soft contact lens used is 2 Week ACUVUE ^{( registered trademark )} (Johnson & Johnson Co., Ltd.) classified into the fourth category. Diameter deformation and base arc deformation are calculated by the following calculation formulas. Diameter deformation (mm) = (diameter after 7 cycles)-(diameter before use) Base arc deformation (mm) = (base arc after 7 cycles)-(base arc before use)

(3) Test results and investigation The test results are shown in Table 1. [Table 1] Test preparation Composition 1 Composition 2 Diameter deformation (mm) 0.09 0.28 Base arc deformation (mm) 0.07 -0.04 determination Suitable for Not suitable

As shown in Table 1, even if the composition 1 was repeatedly dropped onto the soft contact lens, no deformation of the soft contact lens was seen. However, with regard to the composition 2, the deformation of the soft contact lens was seen by repeated dropping.

2. Deformation test of soft contact lens (SCL) by immersion (1) Preparation of test preparation The test preparation of composition 3-8 was prepared in the same way as the preparation method of composition 1. The concentration of each component contained in each test preparation is shown in Table 2. In addition, the amounts of phosphate and sodium chloride contained in each test preparation did not differ among the test preparations and contained the same amount. [Table 2] Test preparation Composition 3 4 5 6 7 8 Epistin hydrochloride [%(w/v)] 0.05 0.05 0.05 0.05 0.05 0.05 Boric acid [%(w/v)] 0.05 0.1 0.5 1 - - Benzyldimethylammonium chloride [%(w/v)] - - - - - 0.003 Sodium Edetate [%(w/v)] 0.01 0.01 0.01 0.01 0.01 0.01 Phosphate Right amount Sodium chloride Right amount Dilute hydrochloric acid/sodium hydroxide Right amount Refined water Right amount pH 7.0

(2) Test method The soft contact lens was immersed in each test preparation at room temperature for 10 minutes, and then taken out. To measure the diameter and base curve of soft contact lenses, it is appropriate that the diameter deformation and base curve deformation are in the range of -0.20～+0.20. In addition, the soft contact lens used is classified as the fourth category 2 Week ACUVUE ^{( registered trademark )} (Johnson & Johnson Co., Ltd.). Diameter deformation and base arc deformation are calculated by the following calculation formulas. Diameter deformation (mm) = (diameter after immersion)-(diameter before immersion) base arc deformation (mm) = (base arc after immersion)-(base arc before immersion)

(3) Test results and investigation The test results are shown in Table 3. [table 3] Test preparation Composition 3 Composition 4 Composition 5 Composition 6 Composition 7 Composition 8 Diameter deformation (mm) 0.01 0.00 0.00 0.02 -0.49 0.44 Base arc deformation (mm) -0.04 0.05 0.14 -0.20 0.90 0.53 determination Suitable for Suitable for Suitable for Suitable for Not suitable Not suitable

As shown in Table 3, regarding composition 7 containing no boric acid and composition 8 containing no boric acid and containing benzalkonium chloride, the deformation of the soft contact lens can be confirmed by immersing in the test formulation. On the other hand, with regard to compositions 3 to 6 containing boric acid, no deformation of the soft contact lens was seen even when immersed in the test formulation.

From the above results, it is suggested that the composition containing epinastine or its salt, boric acid or its salt has the effect of suppressing the deformation of soft contact lenses.

3. Inhibition test of pollen outer wall cracking (1) (1) Preparation of test preparation The test preparations of the compositions 5-7 used in the above-mentioned "2. Soft contact lens (SCL) deformation test by immersion" were used as the test preparations.

(2) Test method Collect about 3μL of cedar pollen particles and inoculate them in 96-well microplates. Then, 50 μL of the test preparation was dropped into each well, and then the total pollen count was counted under an optical microscope using a hemocytometer. In addition, 5 minutes and 10 minutes after dropping with time, the number of broken pollen was similarly counted under a microscope. Pollen rupture rate is calculated by the following calculation formula. Pollen rupture rate (%) = (number of pollen ruptured 5 minutes or 10 minutes after instillation)/(total pollen number immediately after instillation of the test formulation)×100

(3) Test results and investigation The test results are shown in Table 4. [Table 4] Test preparation Composition 5 Composition 6 Composition 7 Pollen rupture rate after 5 minutes twenty one% 20% 28% Pollen rupture rate after 10 minutes 36% 41% 66%

As shown in Table 4, compared with the composition 7 containing no boric acid, the composition 5 and the composition 6 containing the boric acid showed the effect of suppressing the cracking of the outer wall of pollen. Therefore, it is suggested that by containing boric acid or its salt in epinastine or its salt, there is an effect of enhancing the medicinal effect possessed by epinastine or its salt.

4. Pollen outer wall rupture inhibition test (2) (1) Preparation of test preparations The test preparations of compositions 9-14 were prepared in the same way as the preparation method of composition 1. The concentration of each component contained in each test preparation is shown in Table 5. In addition, the amounts of phosphate and sodium chloride contained in each test preparation did not differ among the test preparations and contained the same amount. [table 5] Test preparation Composition 9 10 11 12 13 14 Epistin hydrochloride [%(w/v)] 0.1 0.1 0.1 0.1 0.1 0.1 Boric acid [%(w/v)] 0.05 0.5 0.5 0.5 2 2 Sodium Edetate [%(w/v)] - - 0.01 0.01 - 0.01 Phosphate Right amount Right amount Right amount - - - Sodium chloride Right amount Dilute hydrochloric acid/sodium hydroxide Right amount Refined water Right amount pH 7.0

(2) Test method Calculate the pollen rupture rate using the same method as the aforementioned "3. Pollen outer wall cracking suppression test (1)".

(3) Test results and investigation The test results are shown in Table 6. [Table 6] Test preparation Composition 9 Composition 10 Composition 11 Composition 12 Composition 13 Composition 14 Pollen rupture rate after 5 minutes 17% 3% 3% 0.4% 0.2% 1% Pollen rupture rate after 10 minutes 42% 16% 13% 1% 1% 3%

As shown in Table 6, the composition containing epinastine or its salt, and boric acid or its salt at a concentration of 0.1% (w/v) showed the effect of suppressing the cracking of the outer wall of pollen. In addition, from Table 4 and Table 6, it is shown that compared with the composition containing 0.05% (w/v) concentration of epistatine or its salt, and boric acid or its salt, the concentration of 0.1% (w/v) The composition of epinastine or its salt and boric acid or its salt more inhibits the rupture of the outer wall of pollen. [Possibility of Industrial Use]

The present invention provides an ophthalmic composition containing boric acid or its salt and epinastine or its salt, and inhibiting the deterioration of soft contact lenses. Furthermore, it also provides a pollen rupture inhibitor containing boric acid or its salt, and epinastine or its salt, and the concentration of boric acid or its salt is 0.01-2% (w/v).

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Claims (60)

An ophthalmic composition containing boric acid or its salt and inhibiting the deterioration of soft contact lenses, wherein the composition contains epinastine or its salt, and the soft contact lens is the longest Wear soft contact lenses for 1 month. The ophthalmic composition of claim 1, wherein the concentration of epinastine or its salt is 0.1% (w/v) or less. The ophthalmic composition of claim 1 or 2, wherein the concentration of epinastine or its salt is 0.05% (w/v). The ophthalmic composition according to any one of claims 1 to 3, wherein the concentration of boric acid or its salt is 0.01-2% (w/v). Such as the ophthalmic composition of any one of claims 1 to 4, which does not contain benzalkonium chloride (benzalkonium chloride). The ophthalmic composition according to any one of claims 1 to 5, which further contains a buffer. The ophthalmic composition according to any one of claims 1 to 6, which further contains an isotonicity agent. The ophthalmic composition according to any one of claims 1 to 7, which further contains a stabilizer. The ophthalmic composition of claim 8, wherein the stabilizer is edetic acid or a salt thereof. Such as the ophthalmic composition of claim 9, wherein the concentration of edetic acid or its salt is 0.005 to 0.1% (w/v). The ophthalmic composition according to any one of claims 1 to 10, which is an eye drop. Such as the ophthalmic composition of any one of claims 1 to 11, which is used in a way that it is applied to the eyes wearing soft contact lenses. For example, the ophthalmic composition of any one of claims 1 to 11, which is used in a way that it is applied to the eyes without soft contact lenses. The ophthalmic composition according to any one of claims 1 to 13, which is used in a form of 1 drop or 2 drops per eye once, and instillation of the eyes 2 to 4 times a day. The ophthalmic composition according to any one of claims 1 to 14, wherein the soft contact lens is classified into any one of the first type, the second type, the third type, and the fourth type. An ophthalmic composition containing boric acid or its salt in a concentration of 0.05 to 1% (w/v), edetic acid or its salt in a concentration of 0.01 to 0.05% (w/v), and an isotonicity agent, and An ophthalmic composition for inhibiting deterioration of soft contact lenses, wherein the composition further contains epistine or its salt at a concentration of 0.05% to 0.1 (w/v), and the soft contact lens is a soft contact lens that can be worn for up to 1 month Contact lenses. A method for inhibiting the deterioration of soft contact lenses is by administering an ophthalmic composition containing boric acid or its salt, and epistin or its salt to the eyes wearing soft contact lenses. A pollen rupture inhibitor contains boric acid or its salt, and epinastine or its salt, and the concentration of the boric acid or its salt is 0.01-2% (w/v). Such as the pollen rupture inhibitor of claim 18, wherein the concentration of epinastine or its salt is 0.05% (w/v) or more. Such as the pollen rupture inhibitor of claim 18, wherein the concentration of epistin or its salt is 0.1% (w/v). Such as the pollen rupture inhibitor of any one of claims 18 to 20, which does not contain benzalkonium chloride. The pollen rupture inhibitor according to any one of claims 18 to 21, which further contains a buffer. The pollen rupture inhibitor according to any one of claims 18 to 22, which further contains an isotonicity agent. The pollen rupture inhibitor according to any one of claims 18 to 23, which further contains a pH adjusting agent. The pollen rupture inhibitor according to any one of claims 18 to 24, which further contains a stabilizer. Such as the pollen rupture inhibitor of any one of claims 18 to 25, which is ophthalmic. Such as the pollen rupture inhibitor according to any one of claims 18 to 26, which is used in a way that is applied to the eyes wearing soft contact lenses. Such as the pollen rupture inhibitor of any one of claims 18 to 26, which is used in a way that is applied to the eyes without soft contact lenses. For example, the pollen rupture inhibitor according to any one of claims 18 to 28 is used in a manner of 1 or 2 drops per eye as one time, and instillation of the eyes 2 to 4 times a day. A pollen rupture inhibitor, which contains boric acid or its salt, epinastine or its salt, and an isotonicity agent, the concentration of the boric acid or its salt is 0.05 to 1% (w/v), and the epinastine The concentration of its salt is 0.05%～0.1(w/v). A method for inhibiting pollen breakdown, which is characterized by contacting a composition containing epinastine or its salt and boric acid or its salt at a concentration of 0.01-2% (w/v) with pollen. An ophthalmic composition, which is an ophthalmic composition containing boric acid or its salt, and epistin or its salt, characterized in that the concentration of epinastine or its salt is 0.1% (w/v) or less, And it is used in a way that points to the eyes wearing soft contact lenses. For example, the ophthalmic composition of claim 32, wherein the concentration of epinastine or its salt is 0.1% (w/v). Such as the ophthalmic composition of claim 32, wherein the concentration of epinastine or its salt is 0.05% (w/v). The ophthalmic composition according to any one of claims 32 to 34, wherein the concentration of boric acid or its salt is 0.01-2% (w/v). Such as the ophthalmic composition of any one of claims 32 to 35, which does not contain benzalkonium chloride. The ophthalmic composition according to any one of claims 32 to 36, which further contains a buffer. The ophthalmic composition according to any one of claims 32 to 37, which further contains an isotonicity agent. The ophthalmic composition according to any one of claims 32 to 38, which further contains a stabilizer. The ophthalmic composition of claim 39, wherein the stabilizer is edetic acid or a salt thereof. Such as the ophthalmic composition of claim 40, wherein the concentration of edetic acid or its salt is 0.005 to 0.1% (w/v). Such as the ophthalmic composition of any one of claims 32 to 41, which is an eye drop. The ophthalmic composition according to any one of claims 32 to 42, wherein the soft contact lens is a soft contact lens that can be worn for up to 1 month. An ophthalmic composition, which is an ophthalmic composition containing boric acid or its salt, and epinastine or its salt, wherein the concentration of epinastine or its salt is less than 0.1% (w/v). For example, the ophthalmic composition of claim 44, wherein the concentration of epinastine or its salt is 0.1% (w/v). For example, the ophthalmic composition of claim 44, wherein the concentration of epinastine or its salt is 0.05% (w/v). The ophthalmic composition according to any one of claims 44 to 46, wherein the concentration of boric acid or its salt is 0.01-2% (w/v). Such as the ophthalmic composition of any one of claims 44 to 47, which does not contain benzalkonium chloride. The ophthalmic composition according to any one of claims 44 to 48, which further contains a buffer. The ophthalmic composition according to any one of claims 44 to 49, which further contains an isotonicity agent. The ophthalmic composition according to any one of claims 44 to 50, which further contains a stabilizer. The ophthalmic composition of claim 51, wherein the stabilizer is edetic acid or a salt thereof. For example, the ophthalmic composition of claim 52, wherein the concentration of edetic acid or its salt is 0.005 to 0.1% (w/v). Such as the ophthalmic composition of any one of claims 44 to 53, which is an eye drop. An ophthalmic composition, which is an ophthalmic composition containing boric acid or its salt, and epistin or its salt, wherein the concentration of the epinastine or its salt is 0.1% (w/v). Such as the ophthalmic composition of claim 55, wherein the concentration of boric acid or its salt is 0.01-2% (w/v). Such as the ophthalmic composition of claim 55 or 56, which contains boric acid or a salt thereof as a buffer. The ophthalmic composition according to any one of claims 55 to 57, which is an eye drop. The ophthalmic composition of any one of Claims 55 to 58, which is used for the treatment of allergic conjunctivitis. An ophthalmic composition according to any one of Claims 55 to 59, which is characterized by using 1 or 2 drops per eye as one time, and instilling the eyes twice a day.