WO2020090895A1 - Ophthalmic composition for suppressing degradation of soft contact lens - Google Patents

Ophthalmic composition for suppressing degradation of soft contact lens Download PDF

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Publication number
WO2020090895A1
WO2020090895A1 PCT/JP2019/042590 JP2019042590W WO2020090895A1 WO 2020090895 A1 WO2020090895 A1 WO 2020090895A1 JP 2019042590 W JP2019042590 W JP 2019042590W WO 2020090895 A1 WO2020090895 A1 WO 2020090895A1
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WO
WIPO (PCT)
Prior art keywords
salt
ophthalmic composition
composition according
epinastine
concentration
Prior art date
Application number
PCT/JP2019/042590
Other languages
French (fr)
Japanese (ja)
Inventor
隆司 森本
孝司 稲垣
敏弘 小川
雄介 桃川
Original Assignee
参天製薬株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Application filed by 参天製薬株式会社 filed Critical 参天製薬株式会社
Priority to CN201980071142.8A priority Critical patent/CN112969465A/en
Publication of WO2020090895A1 publication Critical patent/WO2020090895A1/en

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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
    • A61K9/08—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
    • 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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Abstract

The present invention provides: an ophthalmic composition which has an effect of suppressing the degradation of a soft contact lens, the ophthalmic composition containing a boric acid or a salt thereof and an epinastine or a salt thereof; and a pollen rupture inhibitor containing a specific concentration of a boric acid or a salt thereof and an epinastine or a salt thereof.

Description

ソフトコンタクトレンズの変質を抑制する眼科用組成物Ophthalmic composition for suppressing deterioration of soft contact lens
　本発明は、ほう酸又はその塩及びエピナスチン又はその塩を含有する、ソフトコンタクトレンズの変質を抑制する眼科用組成物に関する。また、ほう酸又はその塩及びエピナスチン又はその塩を含有し、ほう酸又はその塩の濃度が０．０１～２％（ｗ／ｖ）である、花粉破裂抑制剤に関する。 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).
　繰り返しの使用を想定した、水等の溶媒を含む眼科用組成物は、菌類等の繁殖を防止するために一定以上の防腐対策が要求される。そのため、そのような眼科用組成物には通常、防腐剤が配合されている。例えば、点眼液であれば、多くの場合、防腐剤として塩化ベンザルコニウムが使用される。塩化ベンザルコニウムは、水溶性であり、化学的に安定で、他の防腐剤と比較しても防腐効力が高い。しかし、塩化ベンザルコニウムは細胞障害性があり、また、ソフトコンタクトレンズに吸着することが知られている。塩化ベンザルコニウムがソフトコンタクトレンズに吸着するとソフトコンタクトレンズの変色や変形の原因になるだけではなく、角膜との接触時間が長くなることによって、角膜上皮障害を引き起こす可能性も増大する。そのため、防腐剤を含む点眼液は、ソフトコンタクトレンズ装用時には使用されていなかった。 -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. 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.
　非特許文献１には、現在、アレルギー性結膜炎治療剤として日本で上市されている、エピナスチン塩酸塩を有効成分とするアレジオン（登録商標）点眼液０．０５％について記載されている。この点眼液はソフトコンタクトレンズ装用時においても点眼可能であることが知られているが、これは防腐剤として塩化ベンザルコニウムを使用していないことによってソフトコンタクトレンズの変質が起こらないためである。 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. ..
　眼科用組成物に含まれる有効成分、添加物の種類及びこれらの含有量の組み合わせによっては、塩化ベンザルコニウム等の防腐剤を含有しない眼科用組成物であってもソフトコンタクトレンズの変質に影響を及ぼすことがあることは知られていない。さらに、エピナスチン又はその塩がソフトコンタクトレンズの変質を引き起こすこと、そして、ほう酸又はその塩が、その引き起こされたソフトコンタクトレンズの変質を抑制する効果を有することは知られていない。 Depending on the active ingredients contained in the ophthalmic composition, the type of additive and the combination of these contents, even 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.
　また、近年、アレルギー疾患について様々な検討がなされ、その発症機序について解明されつつある。例えば、非特許文献２および非特許文献３によると、スギ花粉によるアレルギー性結膜炎は、飛散した花粉粒子が結膜嚢内に侵入した後、涙液によって花粉外壁が破裂し、溶出したアレルゲンが結膜組織に移行して肥満細胞上の抗体へ結合することにより発症すると考えられている。涙液中では花粉外壁の破裂は起こりやすく、花粉外壁の破裂に影響を及ぼす因子には、ｐＨや温度といった物理化学的な影響に加えて、涙液中の成分（リゾチームやタンパク質、様々な分解酵素など）による影響があることが示唆されている。また、種々の抗アレルギー点眼液においても、その種類によっては、従来の薬理作用の他にも花粉外壁の破裂やアレルゲンの溶出に影響を及ぼす可能性があることが示唆されている。 Also, in recent years, various studies have been conducted on allergic diseases, and the mechanism of their onset is being elucidated. For example, according to 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.
　非特許文献４によると、点眼液に含まれる添加剤についても、花粉外壁の破裂やアレルゲンの溶出に影響を及ぼす可能性があり、例えば、ＰＢＳ（リン酸緩衝生理食塩水）は花粉外壁の破裂を促進する可能性が示唆されている。 According to Non-Patent Document 4, the additive contained in eye drops may also affect the rupture of the outer wall of pollen and the elution of allergen. For example, PBS (phosphate buffered saline) ruptures the outer wall of pollen. It has been suggested that it may promote
　したがって、ソフトコンタクトレンズの変質の抑制効果をもたらす、ソフトコンタクトレンズを装用したままであっても、安全に使用できるエピナスチン又はその塩を含有する眼科用組成物を提供することは興味深い課題である。さらに、本発明は、特定の濃度のほう酸又はその塩と、エピナスチン又はその塩を含有する花粉破裂抑制剤を提供することを目的とする。 Therefore, it is an interesting subject to provide an ophthalmic composition containing epinastine or a salt thereof that can be safely used even when the soft contact lens is worn, which brings about an effect of suppressing deterioration of the soft contact lens. 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.
　本発明者らは、エピナスチン又はその塩を含有する眼科用組成物について鋭意研究を行ったところ、エピナスチン又はその塩自体がソフトコンタクトレンズの変質を引き起こすこと、そして、エピナスチン又はその塩とほう酸又はその塩を含有させることによってソフトコンタクトレンズの変質を抑制できることを見出した。さらに、特定の濃度のほう酸又はその塩と、エピナスチン又はその塩を含有することによって、花粉の破裂が抑制され、アレルギー性疾患の治療効果に優れていることを見出し、本発明に至った。 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.
　具体的に、本発明は以下を提供する。
（１）ほう酸又はその塩を含有する、ソフトコンタクトレンズの変質を抑制する眼科用組成物であって、エピナスチン又はその塩を含有し、前記ソフトコンタクトレンズは最長１か月装用可能なソフトコンタクトレンズである、眼科用組成物。
（２）エピナスチン又はその塩の濃度が０．１％（ｗ／ｖ）以下である、（１）に記載の眼科用組成物。
（３）エピナスチン又はその塩の濃度が０．０５％（ｗ／ｖ）である、（１）又は（２）に記載の眼科用組成物。
（４）ほう酸又はその塩の濃度が、０．０１～２％（ｗ／ｖ）である、（１）～（３）のいずれか１つに記載の眼科用組成物。
（５）塩化ベンザルコニウムを含有しない、（１）～（４）のいずれか１つに記載の眼科用組成物。
（６）さらに緩衝剤を含有する、（１）～（５）のいずれか１つに記載の眼科用組成物。
（７）さらに等張化剤を含有する、（１）～（６）のいずれか１つに記載の眼科用組成物。
（８）さらに安定化剤を含有する、（１）～（７）のいずれか１つに記載の眼科用組成物。
（９）安定化剤がエデト酸又はその塩である、（８）に記載の眼科用組成物。
（１０）エデト酸又はその塩の濃度が、０．００５～０．１％（ｗ／ｖ）である、（９）に記載の眼科用組成物。
（１１）点眼剤である、（１）～（１０）のいずれか１つに記載の眼科用組成物。
（１２）ソフトコンタクトレンズが装用された眼に点眼されるように用いられる、（１）～（１１）のいずれか１つに記載の眼科用組成物。
（１３）ソフトコンタクトレンズ未装用の眼に点眼されるように用いられる、（１）～（１１）のいずれか１つに記載の眼科用組成物。
（１４）１眼あたり１滴又は２滴を１回として１日２回～４回点眼されるように用いられる、（１）～（１３）のいずれか１つに記載の眼科用組成物。
（１５）ソフトコンタクトレンズが、グループI、グループII、グループIII及びグループIVのいずれかに分類されるソフトコンタクトレンズである、（１）～（１４）のいずれか１つに記載の眼科用組成物。
（１６）０．０５～１％（ｗ／ｖ）の濃度のほう酸又はその塩、０．０１～０．０５％（ｗ／ｖ）の濃度のエデト酸又はその塩、及び等張化剤を含有する、ソフトコンタクトレンズの変質を抑制する眼科用組成物であって、さらに０．０５％～０．１（ｗ／ｖ）の濃度のエピナスチン又はその塩を含有し、前記ソフトコンタクトレンズは最長１か月装用可能なソフトコンタクトレンズである、眼科用組成物。
（１７）ほう酸又はその塩、及びエピナスチン又はその塩を含有する眼科用組成物をソフトコンタクトレンズが装用された眼に投与することにより、ソフトコンタクトレンズの変質を抑制する方法。
（１８）ほう酸又はその塩、及びエピナスチン又はその塩を含有し、前記ほう酸又はその塩の濃度が０．０１～２％（ｗ／ｖ）である、花粉破裂抑制剤。
（１９）エピナスチン又はその塩の濃度が０．０５％（ｗ／ｖ）以上である、（１８）に記載の花粉破裂抑制剤。
（２０）エピナスチン又はその塩の濃度が０．１％（ｗ／ｖ）である、（１８）に記載の花粉破裂抑制剤。
（２１）塩化ベンザルコニウムを含有しない、（１８）～（２０）のいずれか１つに記載の花粉破裂抑制剤。
（２２）さらに緩衝剤を含有する、（１８）～（２１）のいずれか１つに記載の花粉破裂抑制剤。
（２３）さらに等張化剤を含有する、（１８）～（２２）のいずれか１つに記載の花粉破裂抑制剤。
（２４）さらにｐＨ調節剤を含有する、（１８）～（２３）のいずれか１つに記載の花粉破裂抑制剤。
（２５）さらに安定化剤を含有する、（１８）～（２４）のいずれか１つに記載の花粉破裂抑制剤。
（２６）点眼用である、（１８）～（２５）のいずれか１つに記載の花粉破裂抑制剤。
（２７）ソフトコンタクトレンズが装用された眼に点眼されるように用いられる、（１８）～（２６）のいずれか１つに記載の花粉破裂抑制剤。
（２８）ソフトコンタクトレンズ未装用の眼に点眼されるように用いられる、（１８）～（２６）のいずれか１つに記載の花粉破裂抑制剤。
（２９）１眼あたり１滴又は２滴を１回として１日２回～４回点眼されるように用いられる、（１８）～（２８）のいずれか１つに記載の花粉破裂抑制剤。
（３０）ほう酸又はその塩、エピナスチン又はその塩、及び等張化剤を含有し、前記ほう酸又はその塩の濃度が０．０５～１％（ｗ／ｖ）であり、前記エピナスチン又はその塩の濃度が０．０５％～０．１（ｗ／ｖ）である、花粉破裂抑制剤。
（３１）エピナスチン又はその塩、及び０．０１～２％（ｗ／ｖ）の濃度のほう酸又はその塩を含有する眼科用組成物を、花粉と接触させることを特徴とする、花粉の破裂を抑制する方法。
（３２）ほう酸又はその塩、及びエピナスチン又はその塩を含有する眼科用組成物であって、エピナスチン又はその塩の濃度が０．１％（ｗ／ｖ）以下であり、ソフトコンタクトレンズが装用された眼に点眼されるように用いられることを特徴とする、眼科用組成物。
（３３）エピナスチン又はその塩の濃度が０．１％（ｗ／ｖ）である、（３２）に記載の眼科用組成物。
（３４）エピナスチン又はその塩の濃度が０．０５％（ｗ／ｖ）である、（３２）に記載の眼科用組成物。
（３５）ほう酸又はその塩の濃度が、０．０１～２％（ｗ／ｖ）である、（３２）～（３４）のいずれか１つに記載の眼科用組成物。
（３６）塩化ベンザルコニウムを含有しない、（３２）～（３５）のいずれか１つに記載の眼科用組成物。
（３７）さらに緩衝剤を含有する、（３２）～（３６）のいずれか１つに記載の眼科用組成物。
（３８）さらに等張化剤を含有する、（３２）～（３７）のいずれか１つに記載の眼科用組成物。
（３９）さらに安定化剤を含有する、（３２）～（３８）のいずれか１つに記載の眼科用組成物。
（４０）安定化剤がエデト酸又はその塩である、（３９）に記載の眼科用組成物。
（４１）エデト酸又はその塩の濃度が、０．００５～０．１％（ｗ／ｖ）である、（４０）に記載の眼科用組成物。
（４２）点眼剤である、（３２）～（４１）のいずれか１つに記載の眼科用組成物。
（４３）ソフトコンタクトレンズが、最長１か月装用可能なソフトコンタクトレンズである、（３２）～（４２）のいずれか１つに記載の眼科用組成物。
（４４）ほう酸又はその塩、及びエピナスチン又はその塩を含有する眼科用組成物であって、エピナスチン又はその塩の濃度が０．１％（ｗ／ｖ）以下である、眼科用組成物。
（４５）エピナスチン又はその塩の濃度が０．１％（ｗ／ｖ）である、（４４）に記載の眼科用組成物。
（４６）エピナスチン又はその塩の濃度が０．０５％（ｗ／ｖ）である、（４４）に記載の眼科用組成物。
（４７）ほう酸又はその塩の濃度が、０．０１～２％（ｗ／ｖ）である、（４４）～（４６）のいずれか１つに記載の眼科用組成物。
（４８）塩化ベンザルコニウムを含有しない、（４４）～（４７）のいずれか１つに記載の眼科用組成物。
（４９）さらに緩衝剤を含有する、（４４）～（４８）のいずれか１つに記載の眼科用組成物。
（５０）さらに等張化剤を含有する、（４４）～（４９）のいずれか１つに記載の眼科用組成物。
（５１）さらに安定化剤を含有する、（４４）～（５０）のいずれか１つに記載の眼科用組成物。
（５２）安定化剤がエデト酸又はその塩である、（５１）に記載の眼科用組成物。
（５３）エデト酸又はその塩の濃度が、０．００５～０．１％（ｗ／ｖ）である、（５２）に記載の眼科用組成物。
（５４）点眼剤である、（４４）～（５３）のいずれか１つに記載の眼科用組成物。
（５５）ほう酸又はその塩、及びエピナスチン又はその塩を含有する眼科用組成物であって、エピナスチン又はその塩の濃度が０．１％（ｗ／ｖ）である、眼科用組成物。
（５６）ほう酸又はその塩の濃度が、０．０１～２％（ｗ／ｖ）である、（５５）に記載の眼科用組成物。
（５７）緩衝剤としてほう酸又はその塩を含有する、（５５）または（５６）に記載の眼科用組成物。
（５８）緩衝剤としてほう酸又はその塩のみを含有する、（５５）～（５７）のいずれか１つに記載の眼科用組成物。
（５９）塩化ベンザルコニウムを含有しない、（５５）～（５８）のいずれか１つに記載の眼科用組成物。
（６０）リン酸又はその塩を含有しない、（５５）～（５９）のいずれか１つに記載の眼科用組成物。
（６１）点眼剤である、（５５）～（６０）のいずれか１つに記載の眼科用組成物。
（６２）アレルギー性結膜炎を治療するための、（５５）～（６１）のいずれか１つに記載の眼科用組成物。
（６３）１眼あたり１滴又は２滴を１回として１日２回点眼されるように用いられることを特徴とする、（５５）～（６２）のいずれか１つに記載の眼科用組成物。
　なお、前記（１）から（６３）の各構成は、任意に２以上を選択して組み合わせることができる。 Specifically, the present invention provides the following.
(1) An ophthalmic composition containing boric acid or a salt thereof for suppressing deterioration of a soft contact lens, comprising epinastine or a salt thereof, wherein the soft contact lens can be worn for up to 1 month. 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.
(3) The ophthalmic composition according to (1) or (2), wherein the concentration of epinastine or a salt thereof 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 according to 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 buffering agent.
(7) The ophthalmic composition according to any one of (1) to (6), which further contains a tonicity agent.
(8) The ophthalmic composition according to 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 according to (9), wherein the concentration of edetic acid or a salt thereof 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 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.
(13) 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.
(14) The ophthalmic composition according to any one of (1) to (13), which is used so as to be instilled once or twice per eye twice to four times a day.
(15) The ophthalmic composition according to any one of (1) to (14), wherein the soft contact lens is a soft contact lens classified into any one of Group I, Group II, Group III and Group IV. object.
(16) Boric acid or a salt thereof in a concentration of 0.05 to 1% (w / v), edetic acid or a salt thereof in a concentration of 0.01 to 0.05% (w / v), and an isotonicity agent. 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.
(17) 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.
(18) 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).
(19) The pollen burst inhibitor according to (18), wherein the concentration of epinastine or a salt thereof is 0.05% (w / v) or more.
(20) The pollen burst suppressor according to (18), wherein the concentration of epinastine or a salt thereof is 0.1% (w / v).
(21) The pollen burst inhibitor according to any one of (18) to (20), which does not contain benzalkonium chloride.
(22) The pollen burst suppressant according to any one of (18) to (21), which further contains a buffering agent.
(23) The pollen burst suppressor according to any one of (18) to (22), which further contains a tonicity agent.
(24) The pollen burst suppressor according to any one of (18) to (23), which further contains a pH adjuster.
(25) The pollen burst inhibitor according to any one of (18) to (24), which further contains a stabilizer.
(26) The pollen burst suppressant according to any one of (18) to (25), which is for eye drops.
(27) The pollen rupture inhibitor according to any one of (18) to (26), which is used so as to be instilled in an eye to which a soft contact lens is worn.
(28) The pollen rupture inhibitor as described in any one of (18) to (26), which is used so as to be instilled in an eye without a soft contact lens.
(29) The pollen burst inhibitor according to any one of (18) to (28), which is used so as to be instilled once or twice per eye twice to four times a day.
(30) Containing boric acid or a salt thereof, epinastine or a salt thereof, and an isotonicity agent, and the concentration of the boric acid or a salt thereof is 0.05 to 1% (w / v). A pollen burst inhibitor having a concentration of 0.05% to 0.1 (w / v).
(31) 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.
(32) An ophthalmic composition containing boric acid or a salt thereof and epinastine or a salt thereof, wherein the concentration of epinastine or a salt thereof is 0.1% (w / v) or less, and a soft contact lens is worn. An ophthalmic composition, which is used so as to be instilled into the eye.
(33) The ophthalmic composition according to (32), wherein the concentration of epinastine or a salt thereof is 0.1% (w / v).
(34) The ophthalmic composition according to (32), wherein the concentration of epinastine or a salt thereof 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 according to any one of (32) to (35), which does not contain benzalkonium chloride.
(37) The ophthalmic composition according to any one of (32) to (36), which further contains a buffering agent.
(38) The ophthalmic composition according to any one of (32) to (37), which further contains a tonicity agent.
(39) The ophthalmic composition according to 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 a salt thereof is 0.005 to 0.1% (w / v).
(42) The ophthalmic composition according to 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 up to 1 month.
(44) An ophthalmic composition containing boric acid or a salt thereof and epinastine or a salt thereof, wherein the concentration of epinastine or a salt thereof is 0.1% (w / v) or less.
(45) The ophthalmic composition according to (44), wherein the concentration of epinastine or a salt thereof is 0.1% (w / v).
(46) The ophthalmic composition according to (44), wherein the concentration of epinastine or a salt thereof 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 according to any one of (44) to (47), which does not contain benzalkonium chloride.
(49) The ophthalmic composition according to any one of (44) to (48), which further contains a buffering agent.
(50) The ophthalmic composition according to any one of (44) to (49), which further contains a tonicity agent.
(51) The ophthalmic composition according to 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 a salt thereof is 0.005 to 0.1% (w / v).
(54) The ophthalmic composition according to any one of (44) to (53), which is an eye drop.
(55) An ophthalmic composition containing boric acid or a salt thereof, and epinastine or a salt thereof, wherein the concentration of epinastine or the 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 to 2% (w / v).
(57) The ophthalmic composition according to (55) or (56), which contains boric acid or a salt thereof as a buffer.
(58) The ophthalmic composition according to any one of (55) to (57), which contains only boric acid or a salt thereof as a buffer.
(59) The ophthalmic composition according to any one of (55) to (58), which does not contain benzalkonium chloride.
(60) The ophthalmic composition according to any one of (55) to (59), which does not contain phosphoric acid or a salt thereof.
(61) The ophthalmic composition according to any one of (55) to (60), which is an eye drop.
(62) The ophthalmic composition according to any one of (55) to (61), for treating allergic conjunctivitis.
(63) The ophthalmic composition according to any one of (55) to (62), which is used so as to be instilled once or twice per eye twice a day. object.
It should be noted that each of the configurations (1) to (63) can be arbitrarily selected in combination of two or more.
さらに、本発明は以下も提供する。
（６４）治療が必要な患者に、治療上の有効量の（１８）～（３０）のいずれか１つに記載の花粉破裂抑制剤を投与することを特徴とする、アレルギー性疾患を治療および／または予防する方法。
（６５）アレルギー性疾患の治療および／または予防に使用する、（１８）～（３０）のいずれか１つに記載の花粉破裂抑制剤。
（６６）アレルギー性疾患を治療および／または予防するための医薬を製造するための、（１８）～（３０）のいずれか１つに記載の花粉破裂抑制剤の使用。
（６７）アレルギー性疾患がアレルギー性結膜炎である、（６４）に記載の方法、（６５）に記載の花粉破裂抑制剤または（６６）に記載の使用。
（６８）治療が必要な患者に、治療上の有効量の（１）～（１６）および（３２）～（６１）のいずれか１つに記載の眼科用組成物を投与することを特徴とする、アレルギー性疾患を治療および／または予防する方法。
（６９）アレルギー性疾患の治療および／または予防に使用する、（１）～（１６）および（３２）～（６１）のいずれか１つに記載の眼科用組成物。
（７０）アレルギー性疾患を治療および／または予防するための医薬を製造するための、（１）～（１６）および（３２）～（６１）のいずれか１つに記載の眼科用組成物の使用。
（７１）アレルギー性疾患がアレルギー性結膜炎である、（６８）に記載の方法、（６９）に記載の眼科用組成物または（７０）に記載の使用。
（７２）１眼あたり１滴又は２滴を１回として１日２回点眼されるように用いられることを特徴とする、（６８）に記載の方法、（６９）に記載の眼科用組成物または（７０）に記載の使用。 Further, the present invention also provides the following.
(64) 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.
(65) The pollen burst suppressor according to any one of (18) to (30), which is used for treating and / or preventing allergic diseases.
(66) Use of the pollen burst inhibitor according to any one of (18) to (30) for producing a medicament for treating and / or preventing an allergic disease.
(67) The method according to (64), the pollen burst inhibitor according to (65) or the use according to (66), wherein the allergic disease is allergic conjunctivitis.
(68) 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.
(71) The method according to (68), the ophthalmic composition according to (69) or the use according to (70), wherein the allergic disease is allergic conjunctivitis.
(72) 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).
　本発明は、ソフトコンタクトレンズの変質の抑制効果をもたらす、ソフトコンタクトレンズを装用したままであっても、安全に使用できるエピナスチン又はその塩を含有する眼科用組成物を得ることができる。また、特定の濃度のほう酸又はその塩と、エピナスチン又はその塩を含有することによって、花粉破裂抑制剤を得ることができる。 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. Further, 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.
　以下に、本発明について詳細に説明する。なお、本明細書において、「眼科用組成物」は、「花粉破裂抑制剤」と読み替えることもできる。 The present invention will be described in detail below. In addition, in this specification, an "ophthalmic composition" can also be read as a "pollen burst inhibitor."
　本発明の眼科用組成物において、「エピナスチン」とは、化学名（±）－３－Ａｍｉｎｏ－９，１３ｂ－ｄｉｈｙｄｒｏ－１Ｈ－ｄｉｂｅｎｚ［ｃ，ｆ］ｉｍｉｄａｚｏ［１，５－ａ］ａｚｅｐｉｎｅで表される化合物であり、また、下記式：
Figure JPOXMLDOC01-appb-C000001
 で表される化合物である。 In the ophthalmic composition of the present invention, “epinastine” is represented by the chemical name (±) -3-Amino-9,13b-dihydro-1H-dibenz [c, f] imidazo [1,5-a] azepine. And a compound of the following formula:
Figure JPOXMLDOC01-appb-C000001
 Is a compound represented by.
　本発明の眼科用組成物において、含有されるエピナスチンはラセミ体であってもよく、光学異性体であってもよい。 The epinastine contained in the ophthalmic composition of the present invention may be a racemate or an optical isomer.
　本発明の眼科用組成物において、含有されるエピナスチンは塩であってもよく、医薬として許容される塩であれば特に制限はない。塩としては例えば、無機酸との塩、有機酸との塩等が挙げられる。
　無機酸との塩としては、塩酸、臭化水素酸、ヨウ化水素酸、硝酸、硫酸、リン酸等との塩が挙げられる。
　有機酸との塩としては、酢酸、シュウ酸、フマル酸、マレイン酸、コハク酸、リンゴ酸、クエン酸、酒石酸、アジピン酸、グルコン酸、グルコヘプト酸、グルクロン酸、テレフタル酸、メタンスルホン酸、アラニン、乳酸、馬尿酸、１，２－エタンジスルホン酸、イセチオン酸、ラクトビオン酸、オレイン酸、没食子酸、パモ酸、ポリガラクツロン酸、ステアリン酸、タンニン酸、トリフルオロメタンスルホン酸、ベンゼンスルホン酸、ｐ－トルエンスルホン酸、硫酸ラウリル、硫酸メチル、ナフタレンスルホン酸、スルホサリチル酸等との塩が挙げられる。
　エピナスチンの塩としては、一塩酸塩（エピナスチン塩酸塩）が特に好ましい。 In the ophthalmic composition of the present invention, the epinastine contained may be a salt and is not particularly limited as long as it is a pharmaceutically acceptable salt. Examples of the salt include salts with inorganic acids and salts with organic acids.
Examples of the salt with an inorganic acid include salts with hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, phosphoric acid and the like.
As salts with organic acids, acetic acid, oxalic acid, fumaric acid, maleic acid, succinic acid, malic acid, citric acid, tartaric acid, adipic acid, gluconic acid, glucohepto 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- Examples thereof include salts with toluenesulfonic acid, lauryl sulfate, methyl sulfate, naphthalenesulfonic acid, sulfosalicylic acid and the like.
As the salt of epinastine, monohydrochloride (epinastine hydrochloride) is particularly preferable.
　本発明の眼科用組成物において、含有されるエピナスチン又はその塩は、水和物又は溶媒和物の形態をとってもよい。 In the ophthalmic composition of the present invention, epinastine or a salt thereof contained may be in the form of a hydrate or a solvate.
　本発明の眼科用組成物において、有効成分であるエピナスチン又はその塩の含有量は、０．１５％（ｗ／ｖ）未満が好ましく、０．１％（ｗ／ｖ）以下がより好ましい。例えば、その含有量は、０．１％（ｗ／ｖ）である。また、有効成分であるエピナスチン又はその塩の含有量は、濃度が低いと十分な薬効効果を得るために点眼量や点眼回数を増やさなければならないことから、その下限として０．０５％（ｗ／ｖ）が好ましく、０．０５％（ｗ／ｖ）以上がより好ましい。
　なお、本発明において、「％（ｗ／ｖ）」は、本発明の眼科用組成物１００ｍＬ中に含まれる対象成分の質量（ｇ）を意味する。本発明において、エピナスチンの塩が含有される場合、その値はエピナスチンの塩の含有量である。また、本発明において、エピナスチン又はその塩が水和物又は溶媒和物の形態をとって配合される場合、その値はエピナスチン又はその塩の、水和物又は溶媒和物の含有量である。以下、特に断りがない限り同様とする。 In the ophthalmic composition of the present invention, 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. For example, its content is 0.1% (w / v). In addition, 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.
In addition, in this invention, "% (w / v)" means the mass (g) of the target component contained in 100 mL of ophthalmic compositions of this invention. In the present invention, when the epinastine salt is contained, the value is the content of the epinastine salt. In the present invention, when epinastine or a salt thereof 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. The same applies hereinafter unless otherwise specified.
　本発明の眼科用組成物において、ほう酸又はその塩は、ソフトコンタクトレンズの変質の抑制に寄与するものであるが、医薬品の添加剤、例えば緩衝剤、防腐剤、安定化剤、ｐＨ調節剤等としての作用も有する。そのため、ほう酸又はその塩は、医薬品の添加剤として使用することができる。また、本発明において、ほう酸又はその塩は、エピナスチン又はその塩を含有する眼科用組成物に含有させることにより、薬効効果を高めることもできる。 In the ophthalmic composition of the present invention, 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.
　ほう酸又はその塩としては、ほう酸、ほう酸ナトリウム、ほう酸カリウム等が挙げられ、これらの水和物であってもよいが、好ましくは、ほう酸である。 Examples of boric acid or a salt thereof include boric acid, sodium borate, potassium borate and the like, and hydrates thereof may be used, but boric acid is preferable.
　本発明の眼科用組成物において、ほう酸又はその塩の含有量は適宜調整することができ、０．００１～５％（ｗ／ｖ）であればよく、０．０１～２％（ｗ／ｖ）が好ましく、０．０５～１％（ｗ／ｖ）がより好ましく、０．１～０．５％（ｗ／ｖ）がさらに好ましい。また、０．１％（ｗ／ｖ）、０．２％（ｗ／ｖ）、０．３％（ｗ／ｖ）、０．４％（ｗ／ｖ）、０．５％（ｗ／ｖ）もさらに好ましい。 In the ophthalmic composition of the present invention, 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.
　本発明の眼科用組成物には、必要に応じて医薬品の添加剤をさらに用いることができる。具体的には、緩衝剤、等張化剤、粘稠化剤、界面活性化剤、安定化剤、抗酸化剤、防腐剤、ｐＨ調節剤等を加えることができる。これらは、それぞれ単独で用いてもよく、また、２種以上を適宜組み合わせて用いてもよく、適量を配合することができる。 If necessary, the ophthalmic composition of the present invention may further contain pharmaceutical additives. Specifically, 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. Each of these may be used alone, or may be used in combination of two or more kinds as appropriate, and an appropriate amount can be blended.
　本発明の眼科用組成物に緩衝剤を配合する場合の緩衝剤は、医薬品の添加剤として使用可能な緩衝剤を適宜配合できる。緩衝剤として、例えば、トロメタモール、リン酸又はその塩、炭酸又はその塩あるいは有機酸又はその塩等が挙げられ、これらの水和物又は溶媒和物であってもよい。 When a buffering agent is added to the ophthalmic composition of the present invention, a buffering agent that can be used as a pharmaceutical additive can be appropriately added. Examples of 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.
　リン酸又はその塩としては、リン酸、リン酸三ナトリウム、リン酸二水素ナトリウム、リン酸水素ナトリウム（リン酸水素二ナトリウム）、リン酸三カリウム、リン酸二水素カリウム、リン酸水素二カリウム等が挙げられ、これらの水和物であってもよい。 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.
　炭酸又はその塩としては、炭酸ナトリウム、炭酸水素ナトリウム等が挙げられ、これらの水和物であってもよい。 Examples of carbonic acid or a salt thereof include sodium carbonate, sodium hydrogencarbonate and the like, and a hydrate of these may be used.
　有機酸又はその塩としては、クエン酸、酢酸、ε－アミノカプロン酸、グルコン酸、フマル酸、乳酸、アスコルビン酸、コハク酸、マレイン酸、リンゴ酸、アミノ酸類又はこれらのナトリウム塩、カリウム塩等が挙げられ、これらの水和物であってもよい。 Examples of the organic acid or its salt 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 their sodium salts and potassium salts. And may be hydrates of these.
　本発明の眼科用組成物に緩衝剤を配合する場合の緩衝剤としては、リン酸又はその塩がより好ましく、リン酸二水素ナトリウム、リン酸水素ナトリウムが特に好ましい。
　本発明の眼科用組成物に緩衝剤を配合する場合、緩衝剤を２種以上一緒に用いてもよい。 As a buffer when the buffer is added to the ophthalmic composition of the present invention, phosphoric acid or a salt thereof is more preferable, and sodium dihydrogen phosphate and sodium hydrogen phosphate are particularly preferable.
When a buffering agent is added to the ophthalmic composition of the present invention, two or more buffering agents may be used together.
　本発明の眼科用組成物に緩衝剤を配合する場合の緩衝剤の含有量は、緩衝剤の種類などにより適宜調整することができるが、０．００１～１０％（ｗ／ｖ）が好ましく、０．０１～５％（ｗ／ｖ）がより好ましく、０．１～５％（ｗ／ｖ）がさらに好ましく、０．１～１％（ｗ／ｖ）が特に好ましい。 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.
　本発明の眼科用組成物に等張化剤を配合する場合の等張化剤は、医薬品の添加剤として使用可能な等張化剤を適宜配合することができる。等張化剤として、例えば、イオン性等張化剤や非イオン性等張化剤等が挙げられる。 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. Examples of the tonicity agent include an ionic tonicity agent and a nonionic tonicity agent.
　イオン性等張化剤としては、塩化ナトリウム、塩化カリウム、塩化カルシウム、塩化マグネシウム等が挙げられる。 As the ionic tonicity agent, sodium chloride, potassium chloride, calcium chloride, magnesium chloride and the like can be mentioned.
　非イオン性等張化剤としては、グリセリン、プロピレングリコール、ポリエチレングリコール、ソルビトール、マンニトール、トレハロース、マルトース、スクロース、キシリトール等が挙げられる。 Examples of nonionic tonicity agents include glycerin, propylene glycol, polyethylene glycol, sorbitol, mannitol, trehalose, maltose, sucrose, xylitol and the like.
　本発明の眼科用組成物に等張化剤を配合する場合の等張化剤として、イオン性等張化剤がより好ましく、塩化ナトリウムが特に好ましい。
　本発明の眼科用組成物に等張化剤を配合する場合、等張化剤を２種以上一緒に用いてもよい。 When the isotonic agent is added to the ophthalmic composition of the present invention, the isotonic agent is more preferably an ionic tonicity agent, and sodium chloride is particularly preferable.
When the isotonic agent is added to the ophthalmic composition of the present invention, two or more isotonic agents may be used together.
　本発明の眼科用組成物に等張化剤を配合する場合の等張化剤の含有量は、等張化剤の種類などにより適宜調整することができるが、０．００１～１０％（ｗ／ｖ）が好ましく、０．０１％～５％（ｗ／ｖ）がより好ましく、０．１～３％（ｗ／ｖ）がさらに好ましく、０．５～２％（ｗ／ｖ）が特に好ましい。 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.
　本発明の眼科用組成物に粘稠化剤を配合する場合の粘稠化剤は、医薬品の添加剤として使用可能な粘稠化剤を適宜配合することができる。粘稠化剤として、例えば、メチルセルロース、エチルセルロース、ヒドロキシメチルセルロース、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシエチルメチルセルロース、ヒドロキシプロピルメチルセルロース、カルボキシメチルセルロース、カルボキシメチルセルロースナトリウム、ヒドロキシプロピルメチルセルロースアセテートサクシネート、ヒドロキシプロピルメチルセルロースフタレート、カルボキシメチルエチルセルロース、酢酸フタル酸セルロース、ポリビニルピロリドン、ポリビニルアルコール、カルボキシビニルポリマー、ポリエチレングリコール、ヒアルロン酸ナトリウム等が挙げられる。
　本発明の眼科用組成物に粘稠化剤を配合する場合、粘稠化剤を２種以上一緒に用いてもよい。 When the thickening agent is added to the ophthalmic composition of the present invention, a thickening agent that can be used as an additive for pharmaceuticals can be appropriately added. As 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.
When the thickening agent is added to the ophthalmic composition of the present invention, two or more thickening agents may be used together.
　本発明の眼科用組成物に粘稠化剤を配合する場合の粘稠化剤の含有量は、粘稠化剤の種類などにより適宜調整することができるが、０．００１～５％（ｗ／ｖ）が好ましく、０．０１％～３％（ｗ／ｖ）がより好ましく、０．１～２％（ｗ／ｖ）がさらに好ましい。 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.
　本発明の眼科用組成物に界面活性化剤を配合する場合の界面活性化剤は、医薬品の添加剤として使用可能な界面活性化剤を適宜配合することができる。界面活性化剤として、例えば、カチオン性界面活性化剤、アニオン性界面活性化剤、非イオン性界面活性化剤等が挙げられる。 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. Examples of the surfactant include a cationic surfactant, an anionic surfactant, a nonionic surfactant and the like.
　カチオン性界面活性化剤としては、アルキルアミン塩、アルキルアミンポリオキシエチレン付加物、脂肪酸トリエタノールアミンモノエステル塩、アシルアミノエチルジエチルアミン塩、脂肪酸ポリアミン縮合物、アルキルイミダゾリン、１－アシルアミノエチル－２－アルキルイミダゾリン、１－ヒドロキシルエチル－２－アルキルイミダゾリン等が挙げられる。ただし、塩化ベンザルコニウムはカチオン性界面活性化剤の性質を有しているが、これには含まれない。 Examples of the cationic surfactants 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.
　アニオン性界面活性化剤としては、レシチン等のリン酸脂質等が挙げられる。 Examples of anionic surfactants include phospholipids such as lecithin.
　非イオン性界面活性化剤としては、ステアリン酸ポリオキシル４０等のポリオキシエチレン脂肪酸エステル；ポリソルベート８０、ポリソルベート６０、ポリソルベート４０、ポリオキシエチレンソルビタンモノラウレート、ポリオキシエチレンソルビタントリオレート、ポリソルベート６５等のポリオキシエチレンソルビタン脂肪酸エステル；ポリオキシエチレン硬化ヒマシ油１０、ポリオキシエチレン硬化ヒマシ油４０、ポリオキシエチレン硬化ヒマシ油５０、ポリオキシエチレン硬化ヒマシ油６０等のポリオキシエチレン硬化ヒマシ油；ポリオキシル５ヒマシ油、ポリオキシル９ヒマシ油、ポリオキシル１５ヒマシ油、ポリオキシル３５ヒマシ油、ポリオキシル４０ヒマシ油等のポリオキシルヒマシ油；ポリオキシエチレン（１６０）ポリオキシプロピレン（３０）グリコール、ポリオキシエチレン（４２）ポリオキシプロピレン（６７）グリコール、ポリオキシエチレン（５４）ポリオキシプロピレン（３９）グリコール、ポリオキシエチレン（１９６）ポリオキシプロピレン（６７）グリコール、ポリオキシエチレン（２０）ポリオキシプロピレン（２０）グリコール等のポリオキシエチレンポリオキシプロピレングリコール；ショ糖ステアリン酸エステル等のショ糖脂肪酸エステル；トコフェロールポリエチレングリコール１０００コハク酸エステル（ビタミンＥ　ＴＰＧＳ）等が挙げられる。
　本発明の眼科用組成物に界面活性化剤を配合する場合、界面活性化剤を２種以上一緒に用いてもよい。 Examples of 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 ophthalmic composition of the present invention, two or more surfactants may be used together.
　本発明の眼科用組成物に界面活性化剤を配合する場合の界面活性化剤の含有量は、界面活性化剤の種類などにより適宜調整することができるが、０．０１～１％（ｗ／ｖ）が好ましく、０．０５～０．５％（ｗ／ｖ）がより好ましく、０．０５％～０．２％（ｗ／ｖ）がさらに好ましい。 When the surfactant is blended with the ophthalmic composition of the present invention, 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.
　本発明の眼科用組成物に安定化剤を配合する場合の安定化剤は、医薬品の添加剤として使用可能な安定化剤を適宜配合することができる。安定剤として、例えば、エデト酸又はその塩等が挙げられる。
　エデト酸又はその塩としては、エデト酸、エデト酸二ナトリウム、エデト酸四ナトリウム等が挙げられる。
　本発明の眼科用組成物に安定化剤を配合する場合、安定化剤を２種以上一緒に用いてもよい。 As the stabilizer when the stabilizer is added to the ophthalmic composition of the present invention, a stabilizer that can be used as an additive for pharmaceuticals can be appropriately added. Examples of the stabilizer include edetic acid or a salt thereof.
Examples of edetic acid or a salt thereof include edetic acid, disodium edetate, and tetrasodium edetate.
When a stabilizer is added to the ophthalmic composition of the present invention, two or more stabilizers may be used together.
　本発明の眼科用組成物に安定化剤を配合する場合の安定化剤の含有量は、安定化剤の種類などにより適宜調整することができるが、０．００１～１％（ｗ／ｖ）が好ましく、０．００５％～０．１％（ｗ／ｖ）がより好ましく、０．０１～０．０５％（ｗ／ｖ）がさらに好ましい。また、０．０１％（ｗ／ｖ）、０．０２％（ｗ／ｖ）、０．０３％（ｗ／ｖ）、０．０４％（ｗ／ｖ）、０．０５％（ｗ／ｖ）もさらに好ましい。 When the stabilizer is added to the ophthalmic composition of the present invention, 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.
　本発明の眼科用組成物に抗酸化剤を配合する場合の抗酸化剤は、医薬品の添加剤として使用可能な抗酸化剤を適宜配合することができる。抗酸化剤として、例えば、アスコルビン酸、トコフェロール、ジブチルヒドロキシトルエン、亜硫酸ナトリウム等が挙げられる。
　本発明の眼科用組成物に抗酸化剤を配合する場合、抗酸化剤を２種以上一緒に用いてもよい。 As the antioxidant when the antioxidant is added to the ophthalmic composition of the present invention, an antioxidant that can be used as an additive for pharmaceuticals can be appropriately added. Examples of the antioxidant include ascorbic acid, tocopherol, dibutylhydroxytoluene, sodium sulfite and the like.
When adding an antioxidant to the ophthalmic composition of the present invention, two or more antioxidants may be used together.
　本発明の眼科用組成物に抗酸化剤を配合する場合の抗酸化剤の含有量は、抗酸化剤の種類などにより適宜調整することができるが、０．００１～５％（ｗ／ｖ）が好ましく、０．０１％～３％（ｗ／ｖ）がより好ましく、０．１～２％（ｗ／ｖ）がさらに好ましい。 When the antioxidant is blended with the ophthalmic composition of the present invention, 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.
　本発明の眼科用組成物に防腐剤を配合する場合の防腐剤は、医薬品の添加剤として使用可能な防腐剤を適宜配合することができる。 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.
　本発明において、防腐剤としては、例えば、逆性石鹸類、パラベン類、アルコール類、および有機酸又はその塩が挙げられる。 In the present invention, examples of antiseptics include reverse soaps, parabens, alcohols, and organic acids or salts thereof.
　逆性石鹸類としては、例えば、塩化ベンザルコニウム、臭化ベンザルコニウム、塩化ベンゼトニウム、臭化ベンゼトニウム、グルコン酸クロルヘキシジン、塩酸クロルヘキシジンである。 Examples of reverse soaps include benzalkonium chloride, benzalkonium bromide, benzethonium chloride, benzethonium bromide, chlorhexidine gluconate, and chlorhexidine hydrochloride.
　パラベン類としては、例えば、パラオキシ安息香酸メチル、パラオキシ安息香酸エチル、パラオキシ安息香酸プロピル、パラオキシ安息香酸ブチルである。 Examples of parabens are methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate.
　アルコール類としては、例えば、クロロブタノールである。 Examples of alcohols include chlorobutanol.
　有機酸又はその塩としては、例えば、ソルビン酸又はその塩、デヒドロ酢酸ナトリウムであり、そのうちソルビン酸又はその塩としては、例えば、ソルビン酸ナトリウム、ソルビン酸カリウムである。 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.
　本発明の眼科用組成物に防腐剤を配合する場合の防腐剤の含有量は、防腐剤の種類などにより適宜調整することができる。防腐剤の含有量は、安全性に悪影響を及ぼさない程度の量があればよく、その上限は、例えば１％（ｗ／ｖ）であり、１％（ｗ／ｖ）以下が好ましく、０．５％（ｗ／ｖ）以下がより好ましく、０．１％（ｗ／ｖ）以下がさらに好ましく、０．０１％（ｗ／ｖ）以下がさらにより好ましい。また、防腐作用が発揮できる量があればよく、その下限は、例えば０．０００１％（ｗ／ｖ）であり、０．０００１％（ｗ／ｖ）以上が好ましく、０．００１％（ｗ／ｖ）以上がより好ましい。防腐剤の含有量としては、０．０００１～１％（ｗ／ｖ）が好ましく、０．００１～０．５％（ｗ／ｖ）がより好ましく、０．００１～０．１％（ｗ／ｖ）がさらに好ましい。 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. Further, 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.
　一般的に防腐剤はソフトコンタクトレンズの変質に影響を及ぼすことから、本発明の眼科用組成物は、ソフトコンタクトレンズが変質しない範囲で防腐剤を含有してもよいが、防腐剤を含有しないことがより好ましく、塩化ベンザルコニウムを含有しないことが特に好ましい。 In general, preservatives affect the deterioration of soft contact lenses, so 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.
　また、本発明の眼科用組成物には、ソフトコンタクトレンズの変質を抑制するためにほう酸又はその塩が含有されており、ほう酸又はその塩は防腐剤としての作用も有することから、上記の防腐剤を含有しなくてもよい。 Further, 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.
　本発明の眼科用組成物にｐＨ調節剤を配合する場合のｐＨ調節剤は、医薬品の添加剤として使用可能なｐＨ調節剤を適宜配合することができるが、例えば、酸又は塩基であり、酸としては例えば、塩酸、リン酸、クエン酸、酢酸等、塩基としては例えば、水酸化ナトリウム、水酸化カリウム、炭酸ナトリウム、炭酸水素ナトリウム等が挙げられる。 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. Examples thereof include hydrochloric acid, phosphoric acid, citric acid, acetic acid and the like, and examples of the base include sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate and the like.
　本発明の眼科用組成物のｐＨは、医薬品として許容される範囲内にあればよく、例えば４．０～８．５又は４．０～８．０の範囲内であり、６．０～８．０が好ましく、６．５～７．５がより好ましい。特に好ましいｐＨは、６．７～７．３であるが、６．７、６．８、６．９、７．０、７．１、７．２、７．３もさらにより好ましい。 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.
　本発明の眼科用組成物の浸透圧比は、医薬品として許容される範囲内にあればよく、例えば０．５～２．０であり、０．７～１．６が好ましく、０．８～１．４がより好ましく、０．９～１．２がさらに好ましい。 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.
　本発明の眼科用組成物は、コンタクトレンズ未装用の眼に使用することもできるが、ハードコンタクトレンズ装用時においても、ソフトコンタクトレンズ装用時においても使用することができる。 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.
　ソフトコンタクトレンズは、平成１１年３月３１日医薬審第６４５号「ソフトコンタクトレンズ及びソフトコンタクトレンズ用消毒剤の製造（輸入）承認申請に際し添付すべき資料の取扱い等について」に従い、４つに分類される。すなわち、グループI（含水率が５０％未満で非イオン性であるもの）、グループII（含水率が５０％以上で非イオン性であるもの）、グループIII（含水率が５０％未満でイオン性であるもの）、グループIV（含水率が５０％以上でイオン性であるもの）に分類され、原材料ポリマーの構成モノマーのうち陰イオンを有するモノマーのモル％が１％以上であるものをイオン性、１％未満であるものを非イオン性とされる。また、ソフトコンタクトレンズとしては、例えば、２－ヒドロキシエチルメタクリレート（ＨＥＭＡ）、（ポリエチレングリコール）モノメタクリレート（ＰＥＧＭＡ）、グリセロールメタクリレート（ＧＭＡ）、Ｎ，Ｎ－ジメチルアクリルアミド（ＤＭＡ）、ビニルアルコール（ＶＡ）、Ｎ－ビニルピロリドン（ＮＶＰ又はＶＰ）、メタクリル酸（ＭＡＡ）、フッ素系含有メタクリレート系化合物、ケイ素含有メタクリレート系化合物、シリコーンハイドロゲル、シクロアルキルメタクリレート等を主成分とするソフトコンタクトレンズ等が挙げられる。 There are four types of soft contact lenses in accordance with Pharmaceutical Affairs Trial No. 645 “Handling of materials to be attached when manufacturing (importing) approval application for soft contact lenses and disinfectants for soft contact lenses” on March 31, 1999. being classified. Group I (water content less than 50% non-ionic), group II (water content 50% or more non-ionic), group III (water content less than 50% ionic) ), Group IV (water content is 50% or more and is ionic), and those in which the mol% of monomers having anions among the constituent monomers of the raw material polymer is 1% or more are ionic Those less than 1% are considered nonionic. Examples of soft contact lenses 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. ..
　本発明におけるソフトコンタクトレンズは、上記のいずれの材質であってもよく、また、上記４つに分類されるソフトコンタクトレンズのいずれの種類であってもよく、イオン性又は非イオン性、含水性又は非含水性の別を問わない。 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.
　ソフトコンタクトレンズは、その装用の仕方によって、終日装用する（朝起きて目に装用し、寝る前に外す）レンズと連続装用する（定められた期間内で就寝中も装用する）レンズとに分類されるが、本発明におけるソフトコンタクトレンズは、上記のいずれの分類のレンズであってもよい。 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. However, the soft contact lens in the present invention may be a lens of any of the above categories.
　ソフトコンタクトレンズは、その交換のサイクルによって、コンベンショナルレンズ、ディスポーザブル（使い捨て）レンズ、頻回交換レンズ、定期交換レンズに分類される。ディスポーザブルレンズは、一度、眼から外したコンタクトレンズは再装用しないレンズであり、１日使い捨てレンズ、１週間使い捨てレンズ等がある。頻回交換レンズは、毎日レンズを外す度にレンズケアを行って保存し、定められた期間内であれば再装用が可能なレンズであり、その交換の期限は通常１週間又は２週間までである。定期交換レンズは、頻回交換レンズと同様にレンズケアを行うことにより再装用が可能なレンズであり、その交換の期限は通常１か月又は３か月までである。本発明におけるソフトコンタクトレンズは、上記のいずれの分類のレンズであってもよい。本発明の眼科用組成物は、ソフトコンタクトレンズの変質を抑制することから、１日使い捨てレンズが装用された眼に点眼されるように用いられることも好ましいが、２日以上装用可能なディスポーザブルレンズ、頻回交換レンズ又は定期交換レンズが装用された眼に点眼されるように用いられることがより好ましく、また、１週間以上、２週間以上又は１か月装用可能なソフトコンタクトレンズが装用された眼に点眼されるように用いられることがより好ましい。 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. Since 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.
　本発明において、「ソフトコンタクトレンズの変質」とは、ソフトコンタクトレンズが変形、変色等をすることを指す。コンタクトレンズの変質の原因は、例えばエピナスチン又はその塩等の有効成分や、塩化ベンザルコニウム等の添加剤がソフトコンタクトレンズ表面に吸着すること等が挙げられる。 In the present invention, “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.
　本発明の眼科用組成物によってソフトコンタクトレンズの変質の有無を確認する方法としては、例えば、ソフトコンタクトレンズに直接滴下する方法、ソフトコンタクトレンズを浸漬する方法などが挙げられる。本発明の眼科用組成物とソフトコンタクトレンズとの接触時間の観点から、ソフトコンタクトレンズを浸漬する方法は、ソフトコンタクトレンズに直接滴下する方法に比べて、ソフトコンタクトレンズをより変質させる。ソフトコンタクトレンズを浸漬する場合、浸漬する時間は、例えば５分間又は１０分間であるが、時間が長くなるほどソフトコンタクトレンズは変質しやすい。 As 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. 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 causes more deterioration of the soft contact lens than the method of directly dropping the soft contact lens. When the soft contact lens is immersed, 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.
　本発明の眼科用組成物において、その構成成分が全て溶解または一部懸濁していてもよいが、構成成分が全て溶解している液状がより好ましい。 In the ophthalmic composition of the present invention, 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.
　本発明の眼科用組成物は、特に断りのない限り、エピナスチン又はその塩以外の点眼剤に用いられる有効成分を含んでいてもよい。 Unless otherwise specified, the ophthalmic composition of the present invention may contain an active ingredient used for eye drops other than epinastine or a salt thereof.
　本発明の眼科用組成物は、エピナスチン又はその塩を含有することから、アレルギー性結膜炎およびその症状のあらゆる治療（例えば、改善、軽減、進行の抑制など）およびその予防に使用することができ、ソフトコンタクトレンズ装用眼に対してもソフトコンタクトレンズ未装用眼に対しても使用することができる。 Since 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.
　本発明の眼科用組成物は、眼科用製剤として用いることができ、その剤形は、医薬品として使用可能なものであれば特に制限されるものではない。剤形としては、例えば、点眼剤、軟膏剤、クリーム剤、ゲル剤、経皮吸収型製剤、貼付剤、注射剤等が挙げられる。特に好ましくは点眼剤である。 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. Examples of the dosage form include eye drops, ointments, creams, gels, transdermal preparations, patches, injections and the like. Particularly preferred is an eye drop.
　本発明の眼科用組成物は、適量を１日２回～４回に分けて投与することが好ましい。特に、眼科用組成物が点眼剤である場合には、１眼あたり１滴又は２滴を１回として１日２回～４回に分けて点眼することが好ましく、１眼あたり１滴を１回として１日２回～４回に分けて点眼することがさらに好ましい。なお、本発明の眼科用組成物を１日２回～４回に分けて点眼する場合には、その点眼間隔は少なくとも１時間以上がよく、２時間以上が好ましく、３時間以上がより好ましい。１滴は、通常、約０．０１～約０．１ｍＬであり、約０．０１５～約０．０７ｍＬが好ましく、約０．０２～約０．０５ｍＬがより好ましく、約０．０３ｍＬが特に好ましい。 The appropriate amount of the ophthalmic composition of the present invention is preferably administered in 2 to 4 divided doses per day. In particular, when the ophthalmic composition is an eye drop, it is preferable to apply 1 drop or 2 drops per eye once to twice to 4 times a day, and 1 drop per eye It is more preferable that the instillation is divided into 2 to 4 times a day. When the ophthalmic composition of the present invention is instilled twice to four 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. ..
　本発明の眼科用組成物を収容する容器は、マルチドーズ型容器、１回使い切りのユニットドーズ型容器またはＰＦＭＤ（Ｐｒｅｓｅｒｖａｔｉｖｅ　Ｆｒｅｅ　Ｍｕｌｔｉ　Ｄｏｓｅ）容器のいずれであってもよい。なお、容器の素材に特に制限はなく、一般に汎用される点眼剤の容器であればよいが、好ましくは樹脂製容器であり、例えば、ポリエチレン（ＰＥ）製、ポリプロピレン（ＰＰ）製、ポリエチレンテレフタレート（ＰＥＴ）製、ポリブチレンテレフタレート（ＰＢＴ）製、ポリプロピレン－ポリエチレンコポリマー製、ポリ塩化ビニル製、アクリル製、ポリスチレン製、ポリ環状オレフィンコポリマー製等の容器を用いることができる。また、樹脂製容器の材質が、例えばポリエチレンであれば、ポリエチレンはその密度によって分類され、低密度ポリエチレン（ＬＤＰＥ）製、中密度ポリエチレン（ＭＤＰＥ）製、高密度ポリエチレン（ＨＤＰＥ）製等の容器を用いることができる。 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.
　本発明の眼科用組成物は、汎用される方法により調製することができる。例えば、蒸留水に各成分を溶解又は懸濁させ、浸透圧、ｐＨ等を所定の範囲に調整し、濾過滅菌又は加熱滅菌処理することにより調製することができる。 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.
　本発明の眼科用組成物は、粘膜上に存在する花粉の破裂を抑制し、花粉によるアレルギー症状が生じるのを有効に抑制する効果を有することから、花粉破裂抑制剤として使用することができる。本発明の眼科用組成物を花粉破裂抑制剤として使用する場合、本発明の眼科用組成物は、アレルギー性疾患、特にアレルギー性結膜炎の治療剤として有用である。 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. When the ophthalmic composition of the present invention is used as a pollen burst inhibitor, the ophthalmic composition of the present invention is useful as a therapeutic agent for allergic diseases, particularly allergic conjunctivitis.
　本発明において、「アレルギー性疾患」とは、花粉外壁の破裂によって外部からの抗原に対する免疫反応によって引き起こされる疾患またはその症状を指す。アレルギー性疾患の例として、アレルギー性結膜炎が挙げられるが、これだけに限定されるものではない。本発明において、アレルギー性疾患の治療とは、アレルギー性疾患又はその症状のあらゆる治療（例えば、治癒、改善、軽減、進行の抑制等）及びその予防を指す。また、アレルギー性疾患の再発の阻止も含まれる。 In the present invention, “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. Examples of allergic diseases include, but are not limited to, allergic conjunctivitis. In the present invention, 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.
　本発明において、「患者」とは、ヒトのみに限らずその他の動物、例えば、イヌ、ネコ、ウマなども意味する。患者は、好ましくは哺乳動物であり、より好ましくはヒトである。本発明において、「治療上の有効量」とは、未治療対象と比べて、疾患およびその症状の治療効果をもたらす量、または疾患およびその症状の進行の遅延をもたらす量などを指す。 In the present invention, “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. In the present invention, 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.
　以下に、製剤例および試験例を示すが、これらは本発明をより良く理解するためのものであり、本発明の範囲を限定するものではない。 Formulation examples and test examples are shown below, but these are for better understanding of the present invention and do not limit the scope of the present invention.
製剤例
　以下に本発明の代表的な製剤例を示す。なお、下記製剤例において各成分の配合量は製剤１００ｍＬ中の含量である。 Formulation Example A representative formulation example of the present invention is shown below. In addition, in the following formulation examples, the blending amount of each component is the content in 100 mL of the formulation.
製剤例１
　エピナスチン塩酸塩　　　　　　　０．０５ｇ
　ほう酸　　　　　　　　　　　　　０．０５ｇ
　リン酸二水素ナトリウム２水和物　　１．０ｇ
　塩化ナトリウム　　　　　　　　　　０．５ｇ
　希塩酸　　　　　　　　　　　　　　　　適量
　水酸化ナトリウム　　　　　　　　　　　適量
　精製水　　　　　　　　　　　　　　　　適量
　ｐＨ　　　　　　　　　　　　　　　　７．０ Formulation example 1
Epinastine hydrochloride 0.05g
Boric acid 0.05g
Sodium dihydrogen phosphate dihydrate 1.0 g
Sodium chloride 0.5g
Dilute hydrochloric acid Appropriate amount Sodium hydroxide Appropriate amount Purified water Appropriate amount pH 7.0
製剤例２
　エピナスチン塩酸塩　　　　　　　　０．１ｇ
　ほう酸　　　　　　　　　　　　　　０．１ｇ
　リン酸二水素ナトリウム２水和物　　０．３ｇ
　リン酸水素ナトリウム１２水和物　　１．０ｇ
　塩化ナトリウム　　　　　　　　　　０．５ｇ
　希塩酸　　　　　　　　　　　　　　　　適量
　水酸化ナトリウム　　　　　　　　　　　適量
　精製水　　　　　　　　　　　　　　　　適量
　ｐＨ　　　　　　　　　　　　　　　　７．０ Formulation example 2
Epinastine hydrochloride 0.1 g
Boric acid 0.1g
Sodium dihydrogen phosphate dihydrate 0.3 g
Sodium hydrogen phosphate dodecahydrate 1.0 g
Sodium chloride 0.5g
Dilute hydrochloric acid Appropriate amount Sodium hydroxide Appropriate amount Purified water Appropriate amount pH 7.0
製剤例３
　エピナスチン塩酸塩　　　　　　　　０．１ｇ
　ほう酸　　　　　　　　　　　　　　０．１ｇ
　リン酸二水素ナトリウム２水和物　　０．３ｇ
　リン酸水素ナトリウム１２水和物　　１．０ｇ
　エデト酸ナトリウム　　　　　　　０．０１ｇ
　塩化ナトリウム　　　　　　　　　　０．５ｇ
　希塩酸　　　　　　　　　　　　　　　　適量
　水酸化ナトリウム　　　　　　　　　　　適量
　精製水　　　　　　　　　　　　　　　　適量
　ｐＨ　　　　　　　　　　　　　　　　７．０ Formulation example 3
Epinastine hydrochloride 0.1 g
Boric acid 0.1g
Sodium dihydrogen phosphate dihydrate 0.3 g
Sodium hydrogen phosphate dodecahydrate 1.0 g
Sodium edetate 0.01g
Sodium chloride 0.5g
Dilute hydrochloric acid Appropriate amount Sodium hydroxide Appropriate amount Purified water Appropriate amount pH 7.0
製剤例４
　エピナスチン塩酸塩　　　　　　　　０．１ｇ
　ほう酸　　　　　　　　　　　　　　１．０ｇ
　塩化ナトリウム　　　　　　　　　　０．５ｇ
　希塩酸　　　　　　　　　　　　　　　　適量
　水酸化ナトリウム　　　　　　　　　　　適量
　精製水　　　　　　　　　　　　　　　　適量
　ｐＨ　　　　　　　　　　　　　　　　７．０ Formulation Example 4
Epinastine hydrochloride 0.1 g
Boric acid 1.0g
Sodium chloride 0.5g
Dilute hydrochloric acid Appropriate amount Sodium hydroxide Appropriate amount Purified water Appropriate amount pH 7.0
試験例
１．滴下によるソフトコンタクトレンズ（ＳＣＬ）変形試験
（１）被験製剤の調製
　含有するエピナスチン塩酸塩の濃度が０．１％（ｗ／ｖ）となるように、エピナスチン塩酸塩、リン酸塩、塩化ナトリウムを水に溶解し、ｐＨ調節剤（塩酸および／または水酸化ナトリウム）と水を加えて全量を１０ｍＬとし、濾過滅菌を行うことにより、組成物１の被験製剤（ｐＨ７．０）を調製した。また、エピナスチン塩酸塩の濃度を０．１５％（ｗ／ｖ）にすること以外は、組成物１の被験製剤と同様の方法で、組成物２の被験製剤（ｐＨ７．０）を調製した。なお、組成物２の被験製剤中に含有されるリン酸塩及び塩化ナトリウムの量は、組成物１の被験製剤と同量である。 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.
（２）試験方法
　ソフトコンタクトレンズの凸面に各被験製剤１滴を滴下し、ソフトコンタクトレンズ全体に行き渡らせた。余りを振り落とし、４分後に生理食塩水ですすいで洗浄した。これを１サイクルとして、７サイクル繰り返した。ソフトコンタクトレンズの直径およびベースカーブを測定し、直径変形量及びベースカーブ変形量が－０．２０～＋０．２０の範囲を適合とした。なお、使用したソフトコンタクトレンズはグループIVに分類される２ウィークアキュビュー（登録商標）（ジョンソン・エンド・ジョンソン株式会社）である。
　直径変形量及びベースカーブ変形量は以下の計算式より算出した。
直径変形量（ｍｍ）＝（７サイクル後の直径）－（使用前の直径）
ベースカーブ変形量（ｍｍ）＝（７サイクル後のベースカーブ）－（使用前のベースカーブ） (2) Test method One drop of each test preparation was dropped on the convex surface of the soft contact lens and spread over the entire soft contact lens. The excess was shaken off, and after 4 minutes, rinsed with physiological saline and washed. This was set as one cycle, and 7 cycles were repeated. The diameter and the base curve of the soft contact lens were measured, and the range in which the diameter deformation amount and the base curve deformation amount were −0.20 to +0.20 was determined to be suitable. The soft contact lens used was 2 week ACCUVIEW (registered trademark) (Johnson & Johnson Co., Ltd.) classified into Group IV.
The diameter deformation amount and the base curve deformation amount were calculated by the following formulas.
Deformation amount (mm) = (diameter after 7 cycles)-(diameter before use)
Base curve deformation amount (mm) = (base curve after 7 cycles)-(base curve before use)
（３）試験結果及び考察
　試験結果を表１に示す。
Figure JPOXMLDOC01-appb-T000002
 (3) Test results and consideration Table 1 shows the test results.
Figure JPOXMLDOC01-appb-T000002
　表１に示されるように、組成物１をソフトコンタクトレンズに繰り返し滴下しても、ソフトコンタクトレンズの変形は見られなかったが、組成物２については繰り返しの滴下によりソフトコンタクトレンズの変形が見られた。 As shown in Table 1, even if composition 1 was repeatedly dropped onto the soft contact lens, no deformation of the soft contact lens was observed. However, regarding composition 2, repeated deformation was observed to cause deformation of the soft contact lens. Was given.
２．浸漬によるソフトコンタクトレンズ（ＳＣＬ）変形試験
（１）被験製剤の調製
　組成物１の調製方法と同様の方法にて、組成物３～８の被験製剤を調製した。各被験製剤中に含まれる各成分の濃度は、表２に示す通りである。なお、各被験製剤中に含有されるリン酸塩及び塩化ナトリウムの量は、各被験製剤間に差は無く同量含有される。
Figure JPOXMLDOC01-appb-T000003
 2. Soft Contact Lens (SCL) Deformation Test by Immersion (1) Preparation of Test Preparations 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.
Figure JPOXMLDOC01-appb-T000003
（２）試験方法
　各被験製剤中にソフトコンタクトレンズを室温で１０分間浸漬し、取り出した。ソフトコンタクトレンズの直径およびベースカーブを測定し、直径変形量及びベースカーブ変形量が－０．２０～＋０．２０の範囲を適合とした。なお、使用したソフトコンタクトレンズはグループIVに分類される２ウィークアキュビュー（登録商標）（ジョンソン・エンド・ジョンソン株式会社）である。
　直径変形量及びベースカーブ変形量は以下の計算式より算出した。
直径変形量（ｍｍ）＝（浸漬後の直径）－（浸漬前の直径）
ベースカーブ変形量（ｍｍ）＝（浸漬後のベースカーブ）－（浸漬前のベースカーブ） (2) Test method A soft contact lens was immersed in each test preparation at room temperature for 10 minutes and then taken out. The diameter and the base curve of the soft contact lens were measured, and the range in which the diameter deformation amount and the base curve deformation amount were −0.20 to +0.20 was determined to be suitable. The soft contact lens used was 2 week ACCUVIEW (registered trademark) (Johnson & Johnson Co., Ltd.) classified into Group IV.
The diameter deformation amount and the base curve deformation amount were calculated by the following formulas.
Deformation amount (mm) = (diameter after immersion)-(diameter before immersion)
Deformation amount of base curve (mm) = (base curve after immersion)-(base curve before immersion)
（３）試験結果及び考察
　試験結果を表３に示す。
Figure JPOXMLDOC01-appb-T000004
 (3) Test result and consideration Table 3 shows the test result.
Figure JPOXMLDOC01-appb-T000004
　表３に示されるように、ほう酸を含有しない組成物７、ほう酸を含有せずに塩化ベンザルコニウムを含有する組成物８については、被験製剤中に浸漬することによってソフトコンタクトレンズの変形が確認された。一方で、ほう酸を含有する組成物３～６については、被験製剤中に浸漬してもソフトコンタクトレンズの変形は見られなかった。 As shown in Table 3, for 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. On the other hand, for the compositions 3 to 6 containing boric acid, no deformation of the soft contact lens was observed even when immersed in the test preparation.
　以上の結果より、エピナスチン又はその塩、ほう酸又はその塩を含有する組成物に、ソフトコンタクトレンズの変形を抑制する作用があることが示唆された。 From the above results, it was suggested that the 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.
３．花粉外壁の破裂抑制試験（１）
（１）被験製剤の調製
　被験製剤として、上記の「２．浸漬によるソフトコンタクトレンズ（ＳＣＬ）変形試験」で使用した組成物５～７の被験製剤を使用した。 3. Burst suppression test of pollen outer wall (1)
(1) Preparation of Test Preparation As the test preparation, the test preparations of the compositions 5 to 7 used in the above “2. Soft contact lens (SCL) deformation test by immersion” were used.
（２）試験方法
　スギ花粉粒子を約３μＬずつ採取し、９６ウェルマイクロプレートに播種した。その後、各ウェルに被験製剤５０μＬを滴下し、直後に血球計算盤を用いて光学顕微鏡下でトータルの花粉数を計測した。さらに、経時的に滴下５分後および１０分後に破裂した花粉数を同様に顕微鏡下で計測した。
　花粉破裂率は以下の計算式より算出した。
花粉破裂率（％）＝（滴下５分後または１０分後までに破裂した花粉数）／（被験製剤滴下直後のトータル花粉数）×１００ (2) Test method About 3 μL of cedar pollen particles were collected and seeded in a 96-well microplate. Then, 50 μL of the test preparation was dropped into each well, and immediately after that, the total number of pollen was measured under an optical microscope using a hemocytometer. Furthermore, the number of pollen which burst 5 minutes after dropping and 10 minutes after dropping was similarly measured under the microscope.
The pollen burst rate was calculated by the following formula.
Pollen burst rate (%) = (number of pollens that burst 5 minutes or 10 minutes after dropping) / (total number of pollens immediately after dropping test formulation) x 100
（３）試験結果及び考察
　試験結果を表４に示す。
Figure JPOXMLDOC01-appb-T000005
 (3) Test results and consideration Table 4 shows the test results.
Figure JPOXMLDOC01-appb-T000005
　表４に示されるように、ほう酸を含有しない組成物７と比較して、ほう酸を含有する組成物５及び組成物６は花粉外壁の破裂を抑制する効果を示した。従って、エピナスチン又はその塩に、ほう酸又はその塩を含有させることによって、エピナスチン又はその塩が有する薬効作用を高める効果があることが示唆された。 As shown in Table 4, as compared with the composition 7 containing no boric acid, 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.
４．花粉外壁の破裂抑制試験（２）
（１）被験製剤の調製
　組成物１の調製方法と同様の方法にて、組成物９～１４の被験製剤を調製した。各被験製剤中に含まれる各成分の濃度は、表５に示す通りである。なお、各被験製剤中に含有されるリン酸塩及び塩化ナトリウムの量は、各被験製剤間に差は無く同量含有される。
Figure JPOXMLDOC01-appb-T000006
 4. Burst suppression test of pollen outer wall (2)
(1) Preparation of Test Preparations 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.
Figure JPOXMLDOC01-appb-T000006
（２）試験方法
　前述の「３．花粉外壁の破裂抑制試験（１）」と同様の方法を用いて、花粉破裂率を算出した。 (2) Test method The pollen burst rate was calculated using the same method as in "3. Pollen outer wall burst suppression test (1)".
（３）試験結果及び考察
　試験結果を表６に示す。
Figure JPOXMLDOC01-appb-T000007
 (3) Test results and consideration Table 6 shows the test results.
Figure JPOXMLDOC01-appb-T000007
　表６に示されるように、０．１％（ｗ／ｖ）の濃度のエピナスチン又はその塩、およびほう酸又はその塩を含有する組成物は花粉外壁の破裂を抑制する効果を示した。
　また、表４および表６より、０．１％（ｗ／ｖ）の濃度のエピナスチン又はその塩、およびほう酸又はその塩を含有する組成物は、０．０５％（ｗ／ｖ）の濃度のエピナスチン又はその塩、およびほう酸又はその塩を含有する組成物に比べて、花粉外壁の破裂を抑制することが示された。 As shown in Table 6, the composition 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.
Further, from Table 4 and Table 6, 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.
　本発明は、ほう酸又はその塩及びエピナスチン又はその塩を含有する、ソフトコンタクトレンズの変質を抑制する眼科用組成物を提供する。さらには、ほう酸又はその塩、及びエピナスチン又はその塩を含有し、ほう酸又はその塩の濃度が０．０１～２％（ｗ／ｖ）である、花粉破裂抑制剤も提供する。 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).

Claims (60)

  1. 　ほう酸又はその塩を含有する、ソフトコンタクトレンズの変質を抑制する眼科用組成物であって、エピナスチン又はその塩を含有し、前記ソフトコンタクトレンズは最長１か月装用可能なソフトコンタクトレンズである、眼科用組成物。 An ophthalmic composition containing boric acid or a salt thereof, which suppresses deterioration of a soft contact lens, containing epinastine or a salt thereof, wherein the soft contact lens is a soft contact lens that can be worn for up to 1 month. Ophthalmic composition.
  2. 　エピナスチン又はその塩の濃度が０．１％（ｗ／ｖ）以下である、請求項１に記載の眼科用組成物。 The ophthalmic composition according to claim 1, wherein the concentration of epinastine or a salt thereof is 0.1% (w / v) or less.
  3. 　エピナスチン又はその塩の濃度が０．０５％（ｗ／ｖ）である、請求項１又は２に記載の眼科用組成物。 The ophthalmic composition according to claim 1 or 2, wherein the concentration of epinastine or a salt thereof is 0.05% (w / v).
  4. 　ほう酸又はその塩の濃度が、０．０１～２％（ｗ／ｖ）である、請求項１～３のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 1 to 3, wherein the concentration of boric acid or its salt is 0.01 to 2% (w / v).
  5. 　塩化ベンザルコニウムを含有しない、請求項１～４のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 1 to 4, which does not contain benzalkonium chloride.
  6. 　さらに緩衝剤を含有する、請求項１～５のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 1 to 5, further comprising a buffering agent.
  7. 　さらに等張化剤を含有する、請求項１～６のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 1 to 6, further comprising a tonicity agent.
  8. 　さらに安定化剤を含有する、請求項１～７のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 1 to 7, further comprising a stabilizer.
  9. 　安定化剤がエデト酸又はその塩である、請求項８に記載の眼科用組成物。 The ophthalmic composition according to claim 8, wherein the stabilizer is edetic acid or a salt thereof.
  10. 　エデト酸又はその塩の濃度が、０．００５～０．１％（ｗ／ｖ）である、請求項９に記載の眼科用組成物。 The ophthalmic composition according to claim 9, wherein the concentration of edetic acid or a salt thereof is 0.005 to 0.1% (w / v).
  11. 　点眼剤である、請求項１～１０のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 1 to 10, which is an eye drop.
  12. 　ソフトコンタクトレンズが装用された眼に点眼されるように用いられる、請求項１～１１のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 1 to 11, which is used so as to be instilled in an eye to which a soft contact lens is worn.
  13. 　ソフトコンタクトレンズ未装用の眼に点眼されるように用いられる、請求項１～１１のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 1 to 11, which is used so as to be instilled in an eye without a soft contact lens.
  14. 　１眼あたり１滴又は２滴を１回として１日２回～４回点眼されるように用いられる、請求項１～１３のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 1 to 13, which is used so as to be instilled once or twice per eye twice to four times a day.
  15. 　ソフトコンタクトレンズが、グループI、グループII、グループIII及びグループIVのいずれかに分類されるソフトコンタクトレンズである、請求項１～１４のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 1 to 14, wherein the soft contact lens is a soft contact lens classified into any one of Group I, Group II, Group III and Group IV.
  16. 　０．０５～１％（ｗ／ｖ）の濃度のほう酸又はその塩、０．０１～０．０５％（ｗ／ｖ）の濃度のエデト酸又はその塩、及び等張化剤を含有する、ソフトコンタクトレンズの変質を抑制する眼科用組成物であって、さらに０．０５％～０．１（ｗ／ｖ）の濃度のエピナスチン又はその塩を含有し、前記ソフトコンタクトレンズは最長１か月装用可能なソフトコンタクトレンズである、眼科用組成物。 Containing boric acid or a salt thereof in a concentration of 0.05 to 1% (w / v), edetic acid or a salt thereof in a concentration of 0.01 to 0.05% (w / v), and an isotonicity agent, An ophthalmic composition for suppressing deterioration of a soft contact lens, which further contains epinastine or a salt thereof in a concentration of 0.05% to 0.1 (w / v), and the soft contact lens has a maximum length of 1 month. An ophthalmic composition which is a wearable soft contact lens.
  17. 　ほう酸又はその塩、及びエピナスチン又はその塩を含有する眼科用組成物をソフトコンタクトレンズが装用された眼に投与することにより、ソフトコンタクトレンズの変質を抑制する方法。 A method of suppressing deterioration 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.
  18. 　ほう酸又はその塩、及びエピナスチン又はその塩を含有し、前記ほう酸又はその塩の濃度が０．０１～２％（ｗ／ｖ）である、花粉破裂抑制剤。 A pollen burst inhibitor containing boric acid or a salt thereof and epinastine or a salt thereof, wherein the concentration of the boric acid or the salt is 0.01 to 2% (w / v).
  19. 　エピナスチン又はその塩の濃度が０．０５％（ｗ／ｖ）以上である、請求項１８に記載の花粉破裂抑制剤。 The pollen burst inhibitor according to claim 18, wherein the concentration of epinastine or a salt thereof is 0.05% (w / v) or more.
  20. 　エピナスチン又はその塩の濃度が０．１％（ｗ／ｖ）である、請求項１８に記載の花粉破裂抑制剤。 The pollen burst inhibitor according to claim 18, wherein the concentration of epinastine or a salt thereof is 0.1% (w / v).
  21. 　塩化ベンザルコニウムを含有しない、請求項１８～２０のいずれか１項に記載の花粉破裂抑制剤。 The pollen burst inhibitor according to any one of claims 18 to 20, which does not contain benzalkonium chloride.
  22. 　さらに緩衝剤を含有する、請求項１８～２１のいずれか１項に記載の花粉破裂抑制剤。 The pollen burst inhibitor according to any one of claims 18 to 21, which further comprises a buffering agent.
  23. 　さらに等張化剤を含有する、請求項１８～２２のいずれか１項に記載の花粉破裂抑制剤。 The pollen burst inhibitor according to any one of claims 18 to 22, which further contains an isotonicity agent.
  24. 　さらにｐＨ調節剤を含有する、請求項１８～２３のいずれか１項に記載の花粉破裂抑制剤。 The pollen burst inhibitor according to any one of claims 18 to 23, which further contains a pH adjuster.
  25. 　さらに安定化剤を含有する、請求項１８～２４のいずれか１項に記載の花粉破裂抑制剤。 The pollen burst inhibitor according to any one of claims 18 to 24, which further comprises a stabilizer.
  26. 　点眼用である、請求項１８～２５のいずれか１項に記載の花粉破裂抑制剤。 The pollen burst inhibitor according to any one of claims 18 to 25, which is for eye drops.
  27. 　ソフトコンタクトレンズが装用された眼に点眼されるように用いられる、請求項１８～２６のいずれか１項に記載の花粉破裂抑制剤。 The pollen burst suppressant according to any one of claims 18 to 26, which is used so as to be instilled in an eye to which a soft contact lens is worn.
  28. 　ソフトコンタクトレンズ未装用の眼に点眼されるように用いられる、請求項１８～２６のいずれか１項に記載の花粉破裂抑制剤。 The pollen rupture inhibitor according to any one of claims 18 to 26, which is used so as to be instilled in an eye without a soft contact lens.
  29. 　１眼あたり１滴又は２滴を１回として１日２回～４回点眼されるように用いられる、請求項１８～２８のいずれか１項に記載の花粉破裂抑制剤。 The pollen burst suppressor according to any one of claims 18 to 28, which is used such that one drop or two drops per eye is applied once to twice to four times a day.
  30. 　ほう酸又はその塩、エピナスチン又はその塩、及び等張化剤を含有し、前記ほう酸又はその塩の濃度が０．０５～１％（ｗ／ｖ）であり、前記エピナスチン又はその塩の濃度が０．０５％～０．１（ｗ／ｖ）である、花粉破裂抑制剤。 Boric acid or a salt thereof, epinastine or a salt thereof, and an isotonicity agent, the concentration of the boric acid or a salt thereof is 0.05 to 1% (w / v), and the concentration of the epinastine or a salt thereof is 0. A pollen burst inhibitor, which is 0.05% to 0.1 (w / v).
  31. 　エピナスチン又はその塩、及び０．０１～２％（ｗ／ｖ）の濃度のほう酸又はその塩を含有する組成物を、花粉と接触させることを特徴とする、花粉の破裂を抑制する方法。 A method for suppressing burst of pollen, which comprises contacting pollen with a composition containing epinastine or a salt thereof and boric acid or a salt thereof at a concentration of 0.01 to 2% (w / v).
  32. 　ほう酸又はその塩、及びエピナスチン又はその塩を含有する眼科用組成物であって、エピナスチン又はその塩の濃度が０．１％（ｗ／ｖ）以下であり、ソフトコンタクトレンズが装用された眼に点眼されるように用いられることを特徴とする、眼科用組成物。 An ophthalmic composition containing boric acid or a salt thereof, and epinastine or a salt thereof, wherein the concentration of epinastine or a salt thereof is 0.1% (w / v) or less, and the soft contact lens is applied to an eye. An ophthalmic composition, which is used as an eye drop.
  33. 　エピナスチン又はその塩の濃度が０．１％（ｗ／ｖ）である、請求項３２に記載の眼科用組成物。 33. The ophthalmic composition according to claim 32, wherein the concentration of epinastine or a salt thereof is 0.1% (w / v).
  34. 　エピナスチン又はその塩の濃度が０．０５％（ｗ／ｖ）である、請求項３２に記載の眼科用組成物。 33. The ophthalmic composition according to claim 32, wherein the concentration of epinastine or a salt thereof is 0.05% (w / v).
  35. 　ほう酸又はその塩の濃度が、０．０１～２％（ｗ／ｖ）である、請求項３２～３４のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 32 to 34, wherein the concentration of boric acid or its salt is 0.01 to 2% (w / v).
  36. 　塩化ベンザルコニウムを含有しない、請求項３２～３５のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 32 to 35, which does not contain benzalkonium chloride.
  37. 　さらに緩衝剤を含有する、請求項３２～３６のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 32 to 36, which further contains a buffering agent.
  38. 　さらに等張化剤を含有する、請求項３２～３７のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 32 to 37, which further contains a tonicity agent.
  39. 　さらに安定化剤を含有する、請求項３２～３８のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 32 to 38, which further contains a stabilizer.
  40. 　安定化剤がエデト酸又はその塩である、請求項３９に記載の眼科用組成物。 40. The ophthalmic composition according to claim 39, wherein the stabilizer is edetic acid or a salt thereof.
  41. 　エデト酸又はその塩の濃度が、０．００５～０．１％（ｗ／ｖ）である、請求項４０に記載の眼科用組成物。 The ophthalmic composition according to claim 40, wherein the concentration of edetic acid or a salt thereof is 0.005 to 0.1% (w / v).
  42. 　点眼剤である、請求項３２～４１のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 32 to 41, which is an eye drop.
  43. 　ソフトコンタクトレンズが、最長１か月装用可能なソフトコンタクトレンズである、請求項３２～４２のいずれか１項に記載の眼科用組成物。 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.
  44. 　ほう酸又はその塩、及びエピナスチン又はその塩を含有する眼科用組成物であって、エピナスチン又はその塩の濃度が０．１％（ｗ／ｖ）以下である、眼科用組成物。 An ophthalmic composition containing boric acid or a salt thereof and epinastine or a salt thereof, wherein the concentration of epinastine or a salt thereof is 0.1% (w / v) or less.
  45. 　エピナスチン又はその塩の濃度が０．１％（ｗ／ｖ）である、請求項４４に記載の眼科用組成物。 The ophthalmic composition according to claim 44, wherein the concentration of epinastine or a salt thereof is 0.1% (w / v).
  46. 　エピナスチン又はその塩の濃度が０．０５％（ｗ／ｖ）である、請求項４４に記載の眼科用組成物。 The ophthalmic composition according to claim 44, wherein the concentration of epinastine or a salt thereof is 0.05% (w / v).
  47. 　ほう酸又はその塩の濃度が、０．０１～２％（ｗ／ｖ）である、請求項４４～４６のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 44 to 46, wherein the concentration of boric acid or its salt is 0.01 to 2% (w / v).
  48. 　塩化ベンザルコニウムを含有しない、請求項４４～４７のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 44 to 47, which does not contain benzalkonium chloride.
  49. 　さらに緩衝剤を含有する、請求項４４～４８のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 44 to 48, which further contains a buffering agent.
  50. 　さらに等張化剤を含有する、請求項４４～４９のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 44 to 49, which further contains a tonicity agent.
  51. 　さらに安定化剤を含有する、請求項４４～５０のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 44 to 50, which further contains a stabilizer.
  52. 　安定化剤がエデト酸又はその塩である、請求項５１に記載の眼科用組成物。 The ophthalmic composition according to claim 51, wherein the stabilizer is edetic acid or a salt thereof.
  53. 　エデト酸又はその塩の濃度が、０．００５～０．１％（ｗ／ｖ）である、請求項５２に記載の眼科用組成物。 The ophthalmic composition according to claim 52, wherein the concentration of edetic acid or a salt thereof is 0.005 to 0.1% (w / v).
  54. 　点眼剤である、請求項４４～５３のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 44 to 53, which is an eye drop.
  55. 　ほう酸又はその塩、及びエピナスチン又はその塩を含有する眼科用組成物であって、エピナスチン又はその塩の濃度が０．１％（ｗ／ｖ）である、眼科用組成物。 An ophthalmic composition containing boric acid or a salt thereof and epinastine or a salt thereof, wherein the concentration of epinastine or a salt thereof is 0.1% (w / v).
  56. 　ほう酸又はその塩の濃度が、０．０１～２％（ｗ／ｖ）である、請求項５５に記載の眼科用組成物。 The ophthalmic composition according to claim 55, wherein the concentration of boric acid or its salt is 0.01 to 2% (w / v).
  57. 　緩衝剤としてほう酸又はその塩を含有する、請求項５５または５６に記載の眼科用組成物。 The ophthalmic composition according to claim 55 or 56, which contains boric acid or a salt thereof as a buffer.
  58. 　点眼剤である、請求項５５～５７のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 55 to 57, which is an eye drop.
  59. 　アレルギー性結膜炎を治療するための、請求項５５～５８のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 55 to 58, for treating allergic conjunctivitis.
  60. 　１眼あたり１滴又は２滴を１回として１日２回点眼されるように用いられることを特徴とする、請求項５５～５９のいずれか１項に記載の眼科用組成物。 The ophthalmic composition according to any one of claims 55 to 59, which is used so as to be instilled twice a day with 1 drop or 2 drops once per eye.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113608363A (en) * 2021-08-24 2021-11-05 江苏康耐特光学有限公司 Front bending degree design method for preparing high-refractive-index resin lens

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7118579B1 (en) 2020-04-16 2022-08-16 参天製薬株式会社 Aqueous composition containing epinastine or its salt
JP6963651B2 (en) * 2020-04-16 2021-11-10 参天製薬株式会社 Aqueous composition containing epinastine or a salt thereof
JP7114668B2 (en) * 2020-10-08 2022-08-08 参天製薬株式会社 Pollen burst inhibitor containing epinastine or its salt
CN116744904A (en) * 2020-12-24 2023-09-12 参天制药株式会社 Pharmaceutical composition for transdermal administration comprising epinastine or a salt thereof and a thio-antioxidant

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007088783A1 (en) * 2006-02-02 2007-08-09 Menicon Co., Ltd. Eye drop/wearing fluid for soft contact lenses
WO2015152155A1 (en) * 2014-03-31 2015-10-08 ロート製薬株式会社 Ophthalmologic or otorhinologic aqueous composition
JP2018102534A (en) * 2016-12-26 2018-07-05 小林製薬株式会社 Pollen rupture inhibitor
JP2018102535A (en) * 2016-12-26 2018-07-05 小林製薬株式会社 Pollen rupture inhibitor

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19954516A1 (en) * 1999-11-12 2001-05-17 Boehringer Ingelheim Int Solutions containing epinastine
CN107614018A (en) * 2015-05-28 2018-01-19 乐敦制药株式会社 Aqueous ophthalmic composition
JP6134853B1 (en) * 2016-10-28 2017-05-24 参天製薬株式会社 Epinastine-containing ophthalmic solution
JP7313181B2 (en) 2018-04-23 2023-07-24 ロート製薬株式会社 ophthalmic composition
JP7382731B2 (en) 2018-04-23 2023-11-17 ロート製薬株式会社 Ophthalmic composition
JP7355539B2 (en) * 2018-07-20 2023-10-03 ロート製薬株式会社 Ophthalmic composition
JP7458159B2 (en) * 2018-09-28 2024-03-29 ロート製薬株式会社 Ophthalmic Composition

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007088783A1 (en) * 2006-02-02 2007-08-09 Menicon Co., Ltd. Eye drop/wearing fluid for soft contact lenses
WO2015152155A1 (en) * 2014-03-31 2015-10-08 ロート製薬株式会社 Ophthalmologic or otorhinologic aqueous composition
JP2018102534A (en) * 2016-12-26 2018-07-05 小林製薬株式会社 Pollen rupture inhibitor
JP2018102535A (en) * 2016-12-26 2018-07-05 小林製薬株式会社 Pollen rupture inhibitor

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
"Antiallergic ophthalmic agent, Alesion (registered trademark) ophthalmic solution 0.05%, ' Composition and Properties', 'Usage and Dosage", 2017, pages 1 - 4 *
ALLERGOLOGY & IMMUNOLOGY, vol. 23, no. 10, 2016, pages 64 - 71 *
SUGIO, YOSHIHIRO ET AL.: "The Allergy in Practice", vol. 36, 2016, article "Pharmacological action and clinical result of epinastine hydrochloride ophthalmic solution", pages: 43 - 51 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113608363A (en) * 2021-08-24 2021-11-05 江苏康耐特光学有限公司 Front bending degree design method for preparing high-refractive-index resin lens
CN113608363B (en) * 2021-08-24 2023-04-14 江苏康耐特光学有限公司 Front bending degree design method for preparing high-refractive-index resin lens

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