Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/02—Inorganic compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
  • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0048—Eye, e.g. artificial tears
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/08—Solutions
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P27/00—Drugs for disorders of the senses
  • A61P27/02—Ophthalmic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P27/00—Drugs for disorders of the senses
  • A61P27/02—Ophthalmic agents
  • A61P27/14—Decongestants or antiallergics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P37/00—Drugs for immunological or allergic disorders
  • A61P37/08—Antiallergic agents
• • G—PHYSICS
  • G02—OPTICS
  • G02C—SPECTACLES; SUNGLASSES OR GOGGLES INSOFAR AS THEY HAVE THE SAME FEATURES AS SPECTACLES; CONTACT LENSES
  • G02C13/00—Assembling; Repairing; Cleaning
• • G—PHYSICS
  • G02—OPTICS
  • G02C—SPECTACLES; SUNGLASSES OR GOGGLES INSOFAR AS THEY HAVE THE SAME FEATURES AS SPECTACLES; CONTACT LENSES
  • G02C7/00—Optical parts
  • G02C7/02—Lenses; Lens systems ; Methods of designing lenses
  • G02C7/04—Contact lenses for the eyes

Definitions

• the present invention relates to an ophthalmic composition containing boric acid or a salt thereof and epinastine or a salt thereof, which suppresses deterioration of soft contact lenses.
• the present invention also relates to a pollen burst inhibitor containing boric acid or a salt thereof and epinastine or a salt thereof, wherein the concentration of boric acid or the salt is 0.01 to 2% (w / v).
• -Ophthalmic compositions containing solvents such as water that are intended to be used repeatedly require antiseptic measures above a certain level to prevent the growth of fungi. Therefore, such an ophthalmic composition usually contains a preservative.
• a preservative for example, in the case of eye drops, benzalkonium chloride is often used as a preservative. Benzalkonium chloride is water-soluble, chemically stable, and has a high antiseptic effect as compared with other preservatives. However, benzalkonium chloride has cytotoxicity and is known to be adsorbed on soft contact lenses.
• Adsorption of benzalkonium chloride on a soft contact lens not only causes discoloration and deformation of the soft contact lens, but also increases the possibility of causing corneal epithelial damage by prolonging the contact time with the cornea. Therefore, eye drops containing a preservative have not been used when wearing soft contact lenses.
• Non-Patent Document 1 describes Alesion (registered trademark) eye drop 0.05% containing epinastine hydrochloride as an active ingredient, which is currently marketed in Japan as a therapeutic agent for allergic conjunctivitis. It is known that this ophthalmic solution can be applied even when wearing soft contact lenses, but this is because the deterioration of soft contact lenses does not occur because benzalkonium chloride is not used as a preservative. ..
• the ophthalmic composition containing no preservative such as benzalkonium chloride affects the deterioration of the soft contact lens. It is not known to cause Furthermore, it is not known that epinastine or a salt thereof causes deterioration of the soft contact lens, and that boric acid or a salt thereof has an effect of suppressing the caused deterioration of the soft contact lens.
• Non-Patent Document 2 and Non-Patent Document 3 allergic conjunctivitis due to Japanese cedar pollen is that after the scattered pollen particles invade the conjunctival sac, the outer wall of the pollen is ruptured by lacrimal fluid, and the allergen eluted into the conjunctival tissue. It is thought to develop by migrating and binding to antibodies on mast cells. Rupture of the outer wall of pollen is likely to occur in tear fluid.
• Factors that affect the outer wall of pollen are not only physicochemical effects such as pH and temperature, but also components of tear fluid (lysozyme, proteins, various degradations). It is suggested that there is an effect of the enzyme). In addition, it has been suggested that various anti-allergic eye drops may affect rupture of the outer wall of pollen and elution of allergen, in addition to the conventional pharmacological action, depending on the type.
• the additive contained in eye drops may also affect the rupture of the outer wall of pollen and the elution of allergen.
• PBS phosphate buffered saline
• a further object of the present invention is to provide a pollen burst inhibitor containing boric acid or a salt thereof at a specific concentration and epinastine or a salt thereof.
• the present inventors have conducted intensive studies on an ophthalmic composition containing epinastine or a salt thereof, and that epinastine or a salt itself causes alteration of a soft contact lens, and epinastine or a salt thereof and boric acid or a boric acid thereof. It was found that the deterioration of soft contact lenses can be suppressed by adding salt. Furthermore, the inventors have found that, by containing boric acid or a salt thereof at a specific concentration and epinastine or a salt thereof, bursting of pollen is suppressed and the therapeutic effect on allergic diseases is excellent, and the present invention has been completed.
• the present invention provides the following.
• An ophthalmic composition. (2) The ophthalmic composition according to (1), wherein the concentration of epinastine or a salt thereof is 0.1% (w / v) or less.
• (11) The ophthalmic composition according to any one of (1) to (10), which is an eye drop.
• (12) The ophthalmic composition according to any one of (1) to (11), which is used so as to be instilled in an eye to which a soft contact lens is worn.
• (12) The ophthalmic composition according to any one of (1) to (11), which is used so as to be applied to an eye without a soft contact lens.
• the soft contact lens is a soft contact lens classified into any one of Group I, Group II, Group III and Group IV. object.
• An ophthalmic composition for suppressing deterioration of a soft contact lens which further comprises epinastine or a salt thereof in a concentration of 0.05% to 0.1 (w / v), and the soft contact lens is the longest.
• An ophthalmic composition which is a soft contact lens that can be worn for one month.
• a method for suppressing alteration of a soft contact lens by administering an ophthalmic composition containing boric acid or a salt thereof and epinastine or a salt thereof to an eye in which the soft contact lens is worn.
• a pollen burst inhibitor which comprises boric acid or a salt thereof and epinastine or a salt thereof, and the concentration of the boric acid or the salt is 0.01 to 2% (w / v).
• a burst of pollen which comprises contacting an ophthalmic composition containing epinastine or a salt thereof and boric acid or a salt thereof at a concentration of 0.01 to 2% (w / v) with the pollen. How to suppress.
• the present invention also provides the following.
• Treating an allergic disease which comprises administering a therapeutically effective amount of the pollen burst suppressor according to any one of (18) to (30) to a patient in need thereof. / / How to prevent.
• a therapeutically effective amount of the ophthalmic composition according to any one of (1) to (16) and (32) to (61) is administered to a patient in need of treatment.
• a method of treating and / or preventing an allergic disease (69) The ophthalmic composition according to any one of (1) to (16) and (32) to (61), which is used for treatment and / or prevention of allergic diseases. (70) The ophthalmic composition according to any one of (1) to (16) and (32) to (61), for producing a medicament for treating and / or preventing an allergic disease. use.
• the ophthalmic composition according to (68) which is used so as to be instilled once or twice per eye twice a day. Or the use according to (70).
• the present invention can provide an ophthalmic composition containing epinastine or a salt thereof that can be used safely even while wearing a soft contact lens, which brings about an effect of suppressing deterioration of the soft contact lens.
• a pollen burst inhibitor can be obtained by containing boric acid or a salt thereof at a specific concentration and epinastine or a salt thereof.
• an "ophthalmic composition” can also be read as a “pollen burst inhibitor.”
• epinastine is represented by the chemical name ( ⁇ ) -3-Amino-9,13b-dihydro-1H-dibenz [c, f] imidazo [1,5-a] azepine.
• the epinastine contained in the ophthalmic composition of the present invention may be a racemate or an optical isomer.
• the epinastine contained may be a salt and is not particularly limited as long as it is a pharmaceutically acceptable salt.
• the salt include salts with inorganic acids and salts with organic acids.
• the salt with an inorganic acid include salts with hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, phosphoric acid and the like.
• salt of epinas As the salt of epin
• epinastine or a salt thereof contained may be in the form of a hydrate or a solvate.
• the content of epinastine or a salt thereof as an active ingredient is preferably less than 0.15% (w / v), more preferably 0.1% (w / v) or less.
• its content is 0.1% (w / v).
• the content of epinastine or a salt thereof as an active ingredient is 0.05% as a lower limit (w / w) since the amount of eye drops and the number of times of eye drops must be increased in order to obtain a sufficient medicinal effect when the concentration is low.
• v) is preferable, and 0.05% (w / v) or more is more preferable.
• % (w / v) means the mass (g) of the target component contained in 100 mL of ophthalmic compositions of this invention.
• the value is the content of the epinastine salt.
• the value is the content of the hydrate or solvate of epinastine or its salt. The same applies hereinafter unless otherwise specified.
• boric acid or a salt thereof contributes to suppression of deterioration of soft contact lenses, but is a pharmaceutical additive such as a buffer, a preservative, a stabilizer, and a pH adjuster. Also acts as. Therefore, boric acid or a salt thereof can be used as an additive for pharmaceuticals. In addition, in the present invention, boric acid or a salt thereof can be added to an ophthalmic composition containing epinastine or a salt thereof to enhance the medicinal effect.
• boric acid or a salt thereof examples include boric acid, sodium borate, potassium borate and the like, and hydrates thereof may be used, but boric acid is preferable.
• the content of boric acid or a salt thereof can be appropriately adjusted and may be 0.001 to 5% (w / v), 0.01 to 2% (w / v). ) Is preferable, 0.05 to 1% (w / v) is more preferable, and 0.1 to 0.5% (w / v) is further preferable. Also, 0.1% (w / v), 0.2% (w / v), 0.3% (w / v), 0.4% (w / v), 0.5% (w / v) ) Is more preferable.
• the ophthalmic composition of the present invention may further contain pharmaceutical additives.
• a buffering agent, an isotonicity agent, a thickening agent, a surfactant, a stabilizer, an antioxidant, an antiseptic, a pH adjusting agent and the like can be added.
• a surfactant e.g., sodium bicarbonate
• a stabilizer e.g., sodium bicarbonate
• an antioxidant e.g., sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate
• a buffering agent that can be used as a pharmaceutical additive can be appropriately added.
• the buffer include trometamol, phosphoric acid or a salt thereof, carbonic acid or a salt thereof, an organic acid or a salt thereof, and the like, and a hydrate or solvate thereof may be used.
• Examples of phosphoric acid or salts thereof include phosphoric acid, trisodium phosphate, sodium dihydrogen phosphate, sodium hydrogen phosphate (disodium hydrogen phosphate), tripotassium phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate. And the like, and may be a hydrate of these.
• carbonic acid or a salt thereof examples include sodium carbonate, sodium hydrogencarbonate and the like, and a hydrate of these may be used.
• organic acid or its salt examples include citric acid, acetic acid, ⁇ -aminocaproic acid, gluconic acid, fumaric acid, lactic acid, ascorbic acid, succinic acid, maleic acid, malic acid, amino acids or their sodium salts and potassium salts. And may be hydrates of these.
• phosphoric acid or a salt thereof is more preferable, and sodium dihydrogen phosphate and sodium hydrogen phosphate are particularly preferable.
• a buffering agent is added to the ophthalmic composition of the present invention, two or more buffering agents may be used together.
• the content of the buffer when the buffer is added to the ophthalmic composition of the present invention can be appropriately adjusted depending on the type of the buffer and the like, but is preferably 0.001 to 10% (w / v), 0.01 to 5% (w / v) is more preferable, 0.1 to 5% (w / v) is further preferable, and 0.1 to 1% (w / v) is particularly preferable.
• the isotonicity agent When the isotonicity agent is added to the ophthalmic composition of the present invention, the isotonicity agent that can be used as an additive for pharmaceuticals can be appropriately added.
• the tonicity agent include an ionic tonicity agent and a nonionic tonicity agent.
• sodium chloride, potassium chloride, calcium chloride, magnesium chloride and the like can be mentioned.
• nonionic tonicity agents examples include glycerin, propylene glycol, polyethylene glycol, sorbitol, mannitol, trehalose, maltose, sucrose, xylitol and the like.
• the isotonic agent is more preferably an ionic tonicity agent, and sodium chloride is particularly preferable.
• the isotonic agent is added to the ophthalmic composition of the present invention, two or more isotonic agents may be used together.
• the content of the tonicity agent when blending the tonicity agent in the ophthalmic composition of the present invention can be appropriately adjusted depending on the type of the tonicity agent and the like, but 0.001 to 10% (w / V) is preferable, 0.01% to 5% (w / v) is more preferable, 0.1 to 3% (w / v) is further preferable, and 0.5 to 2% (w / v) is particularly preferable. preferable.
• a thickening agent that can be used as an additive for pharmaceuticals can be appropriately added.
• the thickening agent 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, carboxy.
• Methyl ethyl cellulose, cellulose acetate phthalate, polyvinylpyrrolidone, polyvinyl alcohol, carboxyvinyl polymer, polyethylene glycol, sodium hyaluronate and the like can be mentioned.
• the thickening agent is added to the ophthalmic composition of the present invention, two or more thickening agents may be used together.
• the content of the thickening agent in the case of adding the thickening agent to the ophthalmic composition of the present invention can be appropriately adjusted depending on the kind of the thickening agent and the like, but 0.001 to 5% (w / V) is preferred, 0.01% to 3% (w / v) is more preferred, and 0.1 to 2% (w / v) is even more preferred.
• the surfactant When the surfactant is added to the ophthalmic composition of the present invention, the surfactant that can be used as a pharmaceutical additive can be appropriately added.
• the surfactant include a cationic surfactant, an anionic surfactant, a nonionic surfactant and the like.
• cationic surfactants examples include alkylamine salts, alkylamine polyoxyethylene adducts, fatty acid triethanolamine monoester salts, acylaminoethyldiethylamine salts, fatty acid polyamine condensates, alkylimidazolines, 1-acylaminoethyl-2. -Alkylimidazoline, 1-hydroxylethyl-2-alkylimidazoline and the like can be mentioned. However, although benzalkonium chloride has the property of a cationic surfactant, it is not included in this.
• anionic surfactants include phospholipids such as lecithin.
• nonionic surfactants include polyoxyethylene fatty acid esters such as polyoxyl 40 stearate; polysorbate 80, polysorbate 60, polysorbate 40, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan trioleate, polysorbate 65 and the like.
• Polyoxyethylene sorbitan fatty acid ester polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60 and other polyoxyethylene hydrogenated castor oil; polyoxyl 5 castor Polyoxyl castor oil such as oil, polyoxyl 9 castor oil, polyoxyl 15 castor oil, polyoxyl 35 castor oil, polyoxyl 40 castor oil; polyoxyethylene (160) Lioxypropylene (30) glycol, polyoxyethylene (42) polyoxypropylene (67) glycol, polyoxyethylene (54) polyoxypropylene (39) glycol, polyoxyethylene (196) polyoxypropylene (67) glycol, Examples include polyoxyethylene (20) polyoxypropylene (20) glycol and other polyoxyethylene polyoxypropylene glycol; sucrose stearate and other sucrose fatty acid esters; tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS) and the like. Be done. When a surfactant is added to the
• the content of the surfactant can be appropriately adjusted depending on the kind of the surfactant and the like, but is 0.01 to 1% (w / V) is preferable, 0.05 to 0.5% (w / v) is more preferable, and 0.05% to 0.2% (w / v) is further preferable.
• a stabilizer that can be used as an additive for pharmaceuticals can be appropriately added.
• the stabilizer include edetic acid or a salt thereof.
• edetic acid or a salt thereof include edetic acid, disodium edetate, and tetrasodium edetate.
• two or more stabilizers may be used together.
• the content of the stabilizer can be appropriately adjusted depending on the kind of the stabilizer, etc., but 0.001 to 1% (w / v) Is preferred, 0.005% to 0.1% (w / v) is more preferred, and 0.01 to 0.05% (w / v) is even more preferred. In addition, 0.01% (w / v), 0.02% (w / v), 0.03% (w / v), 0.04% (w / v), 0.05% (w / v ) Is more preferable.
• an antioxidant that can be used as an additive for pharmaceuticals can be appropriately added.
• the antioxidant include ascorbic acid, tocopherol, dibutylhydroxytoluene, sodium sulfite and the like.
• two or more antioxidants may be used together.
• the content of the antioxidant can be appropriately adjusted depending on the kind of the antioxidant, etc., but 0.001 to 5% (w / v) Is preferred, 0.01% to 3% (w / v) is more preferred, and 0.1 to 2% (w / v) is even more preferred.
• the antiseptic agent When the antiseptic agent is added to the ophthalmic composition of the present invention, the antiseptic agent that can be used as an additive for pharmaceuticals can be appropriately added.
• antiseptics examples include reverse soaps, parabens, alcohols, and organic acids or salts thereof.
• reverse soaps examples include benzalkonium chloride, benzalkonium bromide, benzethonium chloride, benzethonium bromide, chlorhexidine gluconate, and chlorhexidine hydrochloride.
• parabens examples include methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate.
• alcohols examples include chlorobutanol.
• the organic acid or a salt thereof is, for example, sorbic acid or a salt thereof, sodium dehydroacetate, and the sorbic acid or a salt thereof is, for example, sodium sorbate or potassium sorbate.
• the content of the antiseptic when the antiseptic is added to the ophthalmic composition of the present invention can be appropriately adjusted depending on the type of the antiseptic and the like.
• the content of the preservative may be such that the safety is not adversely affected, and the upper limit thereof is, for example, 1% (w / v), preferably 1% (w / v) or less, and 0. It is more preferably 5% (w / v) or less, still more preferably 0.1% (w / v) or less, even more preferably 0.01% (w / v) or less.
• the amount of antiseptic action is sufficient, and the lower limit thereof is, for example, 0.0001% (w / v), preferably 0.0001% (w / v) or more, and 0.001% (w / v). v) or more is more preferable.
• the content of the preservative is preferably 0.0001 to 1% (w / v), more preferably 0.001 to 0.5% (w / v), and 0.001 to 0.1% (w / v). v) is more preferred.
• the ophthalmic composition of the present invention may contain a preservative within the range in which the soft contact lens does not deteriorate, but does not contain a preservative. More preferably, and particularly preferably free of benzalkonium chloride.
• the ophthalmic composition of the present invention contains boric acid or a salt thereof in order to suppress deterioration of the soft contact lens, and boric acid or a salt thereof also has an action as an antiseptic, so that the above antiseptic It may not contain an agent.
• the pH adjusting agent in the case of adding the pH adjusting agent to the ophthalmic composition of the present invention can be appropriately added with a pH adjusting agent usable as an additive for pharmaceuticals, for example, an acid or a base.
• a pH adjusting agent usable as an additive for pharmaceuticals for example, an acid or a base.
• examples thereof include hydrochloric acid, phosphoric acid, citric acid, acetic acid and the like
• examples of the base include sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate and the like.
• the pH of the ophthalmic composition of the present invention may be in the range acceptable as a pharmaceutical product, for example, in the range of 4.0 to 8.5 or 4.0 to 8.0, and 6.0 to 8 0.0 is preferable, and 6.5 to 7.5 is more preferable.
• a particularly preferred pH is 6.7 to 7.3, but 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3 are even more preferred.
• the osmotic pressure ratio of the ophthalmic composition of the present invention may be within a range acceptable as a pharmaceutical product, and is, for example, 0.5 to 2.0, preferably 0.7 to 1.6, and 0.8 to 1. 0.4 is more preferable, and 0.9 to 1.2 is further preferable.
• the ophthalmic composition of the present invention can be used for eyes not wearing contact lenses, but can be used both when wearing hard contact lenses and when wearing soft contact lenses.
• soft contact lenses examples include 2-hydroxyethyl methacrylate (HEMA), (polyethylene glycol) monomethacrylate (PEGMA), glycerol methacrylate (GMA), N, N-dimethylacrylamide (DMA), vinyl alcohol (VA). , N-vinylpyrrolidone (NVP or VP), methacrylic acid (MAA), fluorine-containing methacrylate-based compounds, silicon-containing methacrylate-based compounds, silicone hydrogels, and soft contact lenses containing cycloalkyl methacrylate as a main component. ..
• HEMA 2-hydroxyethyl methacrylate
• PEGMA polyethylene glycol) monomethacrylate
• GMA glycerol methacrylate
• DMA N-dimethylacrylamide
• VA vinyl alcohol
• MAA methacrylic acid
• FEMA methacrylic acid
• fluorine-containing methacrylate-based compounds silicon-containing methacrylate-based compounds
• the soft contact lens in the present invention may be made of any of the above-mentioned materials, and may be any type of soft contact lens classified into the above-mentioned four, ionic or nonionic, and water-containing. It does not matter whether it is non-hydrated or not.
• Soft contact lenses are classified into lenses that are worn all day (wear in your eyes in the morning and remove before bed) and continuous wear (wear even during sleep within a set period), depending on how you wear them.
• the soft contact lens in the present invention may be a lens of any of the above categories.
• Soft contact lenses are classified into conventional lenses, disposable (disposable) lenses, frequent interchangeable lenses, and regular interchangeable lenses depending on the exchange cycle.
• the disposable lens is a lens that does not wear a contact lens once removed from the eye, such as a daily disposable lens and a weekly disposable lens.
• Frequent interchangeable lenses are lenses that can be re-used within a prescribed period by performing lens care every time the lens is removed and reserving the lens.
• the replacement period is usually one week or two weeks. is there.
• the regular replacement lens is a lens that can be re-weared by performing lens care like the frequent replacement lens, and the replacement period is usually up to 1 month or 3 months.
• the soft contact lens in the present invention may be a lens of any of the above categories.
• the ophthalmic composition of the present invention suppresses the deterioration of the soft contact lens, it is also preferable that the ophthalmic composition be used so as to be instilled in the eye to which the disposable lens for one day is worn, but the disposable lens that can be worn for two days or more. More preferably, it is used so as to be instilled in an eye to which a frequent interchangeable lens or a regular interchangeable lens is worn, and a soft contact lens that can be worn for 1 week or more, 2 weeks or more, or 1 month is worn. More preferably, it is used so as to be instilled into the eye.
• “degeneration of soft contact lens” means that the soft contact lens is deformed or discolored.
• the cause of the deterioration of the contact lens is, for example, that the active ingredient such as epinastine or a salt thereof and the additive such as benzalkonium chloride are adsorbed on the surface of the soft contact lens.
• a method for confirming whether or not the soft contact lens is deteriorated by the ophthalmic composition of the present invention for example, a method of directly dropping the soft contact lens or a method of immersing the soft contact lens can be mentioned.
• the method of immersing the soft contact lens causes more deterioration of the soft contact lens than the method of directly dropping the soft contact lens.
• the immersion time is, for example, 5 minutes or 10 minutes, but the longer the time, the more easily the soft contact lens is deteriorated.
• all the constituent components may be dissolved or partially suspended, but a liquid form in which all the constituent components are dissolved is more preferable.
• the ophthalmic composition of the present invention may contain an active ingredient used for eye drops other than epinastine or a salt thereof.
• the ophthalmic composition of the present invention contains epinastine or a salt thereof, it can be used for any treatment of allergic conjunctivitis and its symptoms (for example, improvement, alleviation, suppression of progression) and its prevention, It can be used for eyes with and 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 include eye drops, ointments, creams, gels, transdermal preparations, patches, injections and the like. Particularly preferred is an eye drop.
• the appropriate amount of the ophthalmic composition of the present invention is preferably administered in 2 to 4 divided doses per day.
• the ophthalmic composition is an eye drop
• the instillation is divided into 2 to 4 times a day.
• the instillation interval is preferably at least 1 hour or more, preferably 2 hours or more, and more preferably 3 hours or more.
• 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, particularly preferably about 0.03 mL. ..
• the container for accommodating the ophthalmic composition of the present invention may be a multi-dose type container, a single-use unit dose type container or a PFMD (Preservative Free Multi Dose) container.
• the material of the container is not particularly limited as long as it is a container for eye drops that is generally used, but a container made of resin is preferable, and examples thereof include polyethylene (PE), polypropylene (PP), and polyethylene terephthalate ( Containers made of PET, polybutylene terephthalate (PBT), polypropylene-polyethylene copolymer, polyvinyl chloride, acrylic, polystyrene, polycyclic olefin copolymer, or the like can be used. If the material of the resin container is polyethylene, for example, polyethylene is classified according to its density, and containers made of low density polyethylene (LDPE), medium density polyethylene (MDPE), high density polyethylene (HDPE), etc. Can be used.
• LDPE low density polyethylene
• MDPE medium density
• the ophthalmic composition of the present invention can be prepared by a commonly used method. For example, it can be prepared by dissolving or suspending each component in distilled water, adjusting the osmotic pressure, pH, etc. within a predetermined range, and subjecting to sterilization by filtration or heat sterilization.
• the ophthalmic composition of the present invention can be used as a pollen burst inhibitor because it has the effect of suppressing the burst of pollen existing on the mucous membrane and effectively suppressing the occurrence of allergic symptoms caused by pollen.
• the ophthalmic composition of the present invention is useful as a therapeutic agent for allergic diseases, particularly allergic conjunctivitis.
• allergic disease refers to a disease or a symptom thereof caused by an immune reaction to an antigen from the outside by rupture of the outer wall of pollen.
• allergic diseases include, but are not limited to, allergic conjunctivitis.
• the treatment of allergic disease refers to any treatment (for example, cure, improvement, alleviation, suppression of progression, etc.) of allergic disease or its symptoms and prevention thereof. It also includes the prevention of recurrence of allergic diseases.
• “patient” means not only humans but also other animals such as dogs, cats and horses.
• the patient is preferably a mammal, more preferably a human.
• the “therapeutically effective amount” refers to an amount that produces a therapeutic effect on the disease and its symptoms, or an amount that delays the progression of the disease and its symptoms, etc., as compared to an untreated subject.
• Formulation Example A representative formulation example of the present invention is shown below.
• the blending amount of each component is the content in 100 mL of the formulation.
• Test Example 1 Deformation test of soft contact lens (SCL) by dripping (1) Preparation of test preparation Epinastine hydrochloride, phosphate and sodium chloride were added so that the concentration of epinastine hydrochloride contained was 0.1% (w / v).
• a test preparation of Composition 1 (pH 7.0) was prepared by dissolving in water, adding a pH adjusting agent (hydrochloric acid and / or sodium hydroxide) and water to make the total amount 10 mL, and sterilizing by filtration.
• a test preparation of composition 2 (pH 7.0) was prepared in the same manner as the test preparation of composition 1 except that the concentration of epinastine hydrochloride was 0.15% (w / v).
• 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.
• Test preparations of Compositions 3 to 8 were prepared in the same manner as in the preparation method of Composition 1.
• the concentration of each component contained in each test preparation is as shown in Table 2.
• the amounts of phosphate and sodium chloride contained in each test preparation are the same, and there is no difference between the test preparations.
• composition 7 containing no boric acid and composition 8 containing no boric acid and containing benzalkonium chloride the deformation of the soft contact lens was confirmed by immersion in the test preparation. Was done.
• the compositions 3 to 6 containing boric acid no deformation of the soft contact lens was observed even when immersed in the test preparation.
• composition containing epinastine or a salt thereof, boric acid or a salt thereof has an action of suppressing the deformation of the soft contact lens.
• the compositions 5 and 6 containing boric acid showed the effect of suppressing the rupture of the outer wall of the pollen. Therefore, it was suggested that by incorporating boric acid or a salt thereof into epinastine or a salt thereof, there is an effect of enhancing the pharmacological action of epinastine or a salt thereof.
• Test preparations of Compositions 9 to 14 were prepared in the same manner as in the preparation method of Composition 1.
• the concentration of each component contained in each test preparation is as shown in Table 5.
• the amounts of phosphate and sodium chloride contained in each test preparation are the same, and there is no difference between the test preparations.
• compositions containing epinastine or a salt thereof and boric acid or a salt thereof at a concentration of 0.1% (w / v) showed an effect of suppressing the rupture of the outer wall of pollen.
• compositions containing epinastine or a salt thereof and boric acid or a salt thereof at a concentration of 0.1% (w / v) have a concentration of 0.05% (w / v). It was shown to suppress the rupture of the outer wall of pollen as compared with the composition containing epinastine or a salt thereof and boric acid or a salt thereof.
• the present invention provides an ophthalmic composition containing boric acid or a salt thereof and epinastine or a salt thereof, which suppresses deterioration of soft contact lenses. Further provided is a pollen burst inhibitor containing boric acid or a salt thereof and epinastine or a salt thereof, wherein the concentration of boric acid or the salt is 0.01 to 2% (w / v).

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