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WO2011040572A1 - Composition ophtalmique - Google Patents

Composition ophtalmique Download PDF

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Publication number
WO2011040572A1
WO2011040572A1 PCT/JP2010/067153 JP2010067153W WO2011040572A1 WO 2011040572 A1 WO2011040572 A1 WO 2011040572A1 JP 2010067153 W JP2010067153 W JP 2010067153W WO 2011040572 A1 WO2011040572 A1 WO 2011040572A1
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Prior art keywords
ophthalmic composition
shcl
item
present
contact lens
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
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PCT/JP2010/067153
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English (en)
Japanese (ja)
Inventor
江利 松本
一宏 福嶋
千夏 古宮
健一 春名
雅美 東田
元気 飯塚
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Rohto Pharmaceutical Co Ltd
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Rohto Pharmaceutical Co Ltd
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Priority to HK12112234.7A priority Critical patent/HK1171380B/xx
Priority to CN201080042077.5A priority patent/CN102548562B/zh
Publication of WO2011040572A1 publication Critical patent/WO2011040572A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • 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
    • A61K31/74—Synthetic polymeric materials
    • A61K31/765—Polymers containing oxygen
    • A61K31/78—Polymers containing oxygen of acrylic acid or derivatives thereof
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A61P23/02—Local anaesthetics
    • 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
    • A61P27/04—Artificial tears; Irrigation 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
    • A61P27/06—Antiglaucoma agents or miotics
    • 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
    • A61P27/12—Ophthalmic agents for cataracts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/14—Decongestants or antiallergics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to an ophthalmic composition exhibiting a histamine release inhibitory action. Moreover, this invention relates to the ophthalmic composition for silicone hydrogel contact lenses which can suppress adsorption
  • a polymer having a phosphorylcholine-like group in the side chain is known as a compound having high biocompatibility.
  • the polymer is known to be effective for skin care because it has functions such as keratin protection and moisture retention (see Patent Document 1).
  • Patent Document 2 it has been found that the polymer is effective in prevention or treatment of dry eye (see Patent Document 2) and improvement in retention of active ingredients (see Patent Document 3) in the ophthalmic field.
  • the polymer has not only biocompatibility but also various actions, and has attracted attention as a functional material.
  • the use of the polymer in the ophthalmic field has been actively attempted, and a prescription of an ophthalmic composition containing the polymer has also been reported (see Patent Documents 4-5).
  • terpenoids such as menthol are used as a refreshing agent in the ophthalmic field. Furthermore, the refreshing action of terpenoids is expected to have an effect of improving eye discomfort and imparting a sense of relaxation and refreshment.
  • JP-A-9-52848 Japanese Patent Laid-Open No. 10-324634 JP 11-335301 A JP 2008-273959 A JP 7-166154 A
  • a silicone hydrogel contact lens (hereinafter also referred to as “SHCL”) has a property of easily adsorbing terpenoids.
  • SHCL silicone hydrogel contact lens
  • an object of the present invention is to provide an ophthalmic composition exhibiting a histamine release-inhibiting action with a novel formulation that has not been conventionally used.
  • Another object of the present invention is to provide an ophthalmic composition for SHCL that can suppress adsorption of terpenoids to SHCL.
  • the inventors of the present invention tried to create an ophthalmic composition exhibiting a histamine release-inhibiting action and conducted extensive studies. Surprisingly, in the polymer and menthol having a phosphorylcholine-like group in the side chain, each histamine alone was used. It has been found that when these are used in combination at a specific blending ratio, a particularly excellent histamine release inhibitory effect is exhibited by a synergistic action, although the release inhibitory action is weak or absent.
  • SHCL has a property of easily adsorbing terpenoids, and as a means for solving this, a combination of a polymer having a phosphorylcholine-like group in the side chain and a terpenoid is used for SHCL. It was also found that it is effective in suppressing adsorption of terpenoids.
  • nonionic silicone hydrogel contact lenses (hereinafter sometimes referred to as “nonionic SHCL”) have extremely high adhesion of corneal epithelial cells.
  • nonionic SHCL nonionic silicone hydrogel contact lenses
  • the inventors have also found that a combination of a polymer having a phosphorylcholine-like group in the side chain and a terpenoid can effectively suppress the adhesion of corneal cells to the nonionic SHCL surface.
  • the present invention has been completed by further studies based on this finding.
  • the present invention provides the following ophthalmic compositions.
  • Item 1-1 (A) 0.001 to 2 w / v% of a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization;
  • n1 is an integer of 2 to 4
  • R 1 is a hydrogen atom or a methyl group
  • R 2 is a group represented by — (R 6 O) n2 —R 6 — (R 6 has 1 to 4 carbon atoms)
  • n2 represents an integer of 0 to 5
  • R 3 to R 5 are the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.
  • the component (A) is a polymer of a monomer represented by the general formula (I), or a copolymer of a monomer represented by the general formula (I) and a monomer represented by the following general formula (II).
  • Item 1-3 Item 1. The ophthalmic composition according to Item 1-1 or 1-2, wherein the component (A) is a copolymer of 2-methacryloyloxyethyl phosphorylcholine and butyl methacrylate. Item 1-4. Item 4. The ophthalmic composition according to any one of Items 1-1 to 1-3, comprising 0.02 to 20000 parts by weight of the total amount of component (B-1) per 100 parts by weight of component (A). Item 1-5. Item 5.
  • Item 5. The ophthalmic composition according to any one of Items 1-1 to 1-4, which is an eye wash.
  • Item 5. The ophthalmic composition according to any one of Items 1-1 to 1-4, which is a contact lens mounting solution.
  • Item 5. The ophthalmic composition according to any one of Items 1-1 to 1-4, which is an eye drop for contact lenses.
  • the ophthalmic composition according to any one of Items 1-1 to 1-4 which is an eye drop for a silicone hydrogel contact lens. Item 1-11. Item 5. The ophthalmic composition according to any one of Items 1-1 to 1-4, which is an eye drop for an ionic silicone hydrogel contact lens. Item 1-12. Item 5. The ophthalmic composition according to any one of Items 1-1 to 1-4, which is an eye drop for a nonionic silicone hydrogel contact lens.
  • this invention provides the ophthalmic composition for silicone hydrogel contact lenses hung up below.
  • Item 2-1. a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization;
  • n1 is an integer of 2 to 4
  • R 1 is a hydrogen atom or a methyl group
  • R 2 is a group represented by — (R 6 O) n2 —R 6 — (R 6 has 1 to 4 carbon atoms)
  • n2 represents an integer of 0 to 5
  • R 3 to R 5 are the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.
  • the component (A) is a polymer of a monomer represented by the general formula (I), or a copolymer of a monomer represented by the general formula (I) and a monomer represented by the following general formula (II).
  • Item 2-3 The ophthalmic composition for a silicone hydrogel contact lens according to Item 2-1 or 2-2, wherein the component (A) is a copolymer of 2-methacryloyloxyethyl phosphorylcholine and butyl methacrylate.
  • Item 2-4 The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 2-1 to 2-3, containing menthol as a component. Item 2-5. Item 5.
  • Item (B-2) The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 2-1 to 2-5, wherein the blending ratio of the component is 0.0001 to 1 w / v%.
  • Item 2-7 The ophthalmic composition for a silicone hydrogel contact lens according to any one of Items 2-1 to 2-6, wherein the total amount of the component (B-2) is 0.0002 to 50000 parts by weight per 100 parts by weight of the component (A) .
  • the ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 2-1 to 2-7 which is an eye drop for silicone hydrogel contact lenses.
  • Item 2-9. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 2-1 to 2-7, which is an eye wash for silicone hydrogel contact lenses.
  • Item 2-10. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 2-1 to 2-7, which is a contact lens mounting liquid for silicone hydrogel contact lenses.
  • Item 2-12. Item 9. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 2-1 to 2-8, which is an eye drop for a nonionic silicone hydrogel contact lens.
  • the present invention provides the following methods.
  • Item 3. In the ophthalmic composition, (A) 0.001 to 2 w / v% of a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another copolymerizable monomer, and (B-1) menthol 0.001 to 0.02 A method for imparting histamine release inhibitory action to an ophthalmic composition, characterized by using w / v% in combination.
  • Item 4. (A) a polymer obtained by polymerizing a monomer represented by the general formula (I) alone or with another monomer capable of copolymerization and (B-2) an ophthalmic composition containing a terpenoid, and a silicone hydrogel contact lens.
  • a method for suppressing adsorption of a terpenoid to a silicone hydrogel contact lens which is characterized in that it is contacted.
  • the ophthalmic composition is characterized in that (B) a terpenoid is blended with a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, A method of imparting to the ophthalmic composition an action of suppressing adsorption of terpenoids to a silicone hydrogel contact lens.
  • (A) a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, and (B-2) an ophthalmic composition containing a terpenoid, and a nonionic silicone hydrogel contact
  • the ophthalmic composition is characterized in that (B) a terpenoid is blended with a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, A method of imparting to the ophthalmic composition an action of suppressing adhesion of corneal epithelial cells to a nonionic silicone hydrogel contact lens.
  • Item 8-1 A polymer obtained by polymerizing 0.001 to 2 w / v% of the monomer represented by (A) the general formula (I) alone or with another monomer capable of copolymerization,
  • n1 is an integer of 2 to 4
  • R 1 is a hydrogen atom or a methyl group
  • R 2 is a group represented by — (R 6 O) n2 —R 6 — (R 6 has 1 to 4 carbon atoms
  • n2 represents an integer of 0 to 5
  • R 3 to R 5 are the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.
  • Item 8-1 wherein the ophthalmic composition is an eye wash.
  • Item 8-4. Item 9. The use according to Item 8-1, wherein the ophthalmic composition is a contact lens mounting solution.
  • Item 8-5. Item 9. The use according to Item 8-1, wherein the ophthalmic composition is an eye drop for contact lenses.
  • Item 8-6. Item 9. The use according to Item 8-1, wherein the ophthalmic composition is an eye drop for soft contact lenses.
  • Item 8-7 Item 9. The use according to Item 8-1, wherein the ophthalmic composition is an eye drop for a silicone hydrogel contact lens.
  • Item 8-8. Item 8.
  • n1 is an integer of 2 to 4
  • R 1 is a hydrogen atom or a methyl group
  • R 2 is a group represented by — (R 6 O) n2 —R 6 — (R 6 has 1 to 4 carbon atoms)
  • n2 represents an integer of 0 to 5
  • R 3 to R 5 are the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.
  • Item 9-3 Item 9. The use according to Item 9-1, wherein the ophthalmic composition for a silicone hydrogel contact lens is an eyewash for a silicone hydrogel contact lens.
  • Item 9-4 Item 9. The use according to Item 9-1, wherein the ophthalmic composition for a silicone hydrogel contact lens is a contact lens mounting liquid for a silicone hydrogel contact lens.
  • Item 9-5 The use according to Item 9-1, wherein the ophthalmic composition is a histamine release inhibitor.
  • Item 9-6 Item 9. The use according to Item 9-1, wherein the ophthalmic composition is an antiallergic agent, an eye itching inhibitor, or a discomfort inhibitor when wearing a contact lens.
  • the ophthalmic composition of the present invention exhibits an excellent histamine release inhibitory action, it is useful for ophthalmic preparations for uses such as antiallergy, itching, and discomfort when wearing contact lenses.
  • SHCL has a property of easily adsorbing terpenoids, but according to the ophthalmic composition for SHCL of the present invention, it suppresses the adsorption of terpenoids to SHCL. It is possible to secure sufficient safety in using SHCL.
  • nonionic SHCL has a unique property that corneal cells easily adhere, but according to the ophthalmic composition for SHCL of the present invention, non-ionic SHCL Corneal cell adhesion to ionic SHCL can be effectively suppressed. Therefore, according to the ophthalmic composition for SHCL of the present invention, it is possible to reduce damage to the corneal surface even when the lens is removed from the eye, and it is possible to wear nonionic SHCL with high safety. To do.
  • Test Example 1 it is a figure which shows the result of having evaluated the histamine release inhibitory effect of the test substance (Examples 1-1 to 1-6 and Comparative Examples 1-1 to 1-9) of various density
  • Test Example 1 the results of evaluating the histamine release inhibitory effect of various concentrations of test substances (Examples 1-7 to 1-10 and Comparative Examples 1-3 to 1-5, 1-8 and 1-10) FIG.
  • Test Example 1 the results of evaluating the histamine release inhibitory effect of various concentrations of test substances (Examples 1-11 to 1-14 and Comparative Examples 1-4 to 1-6, 1-8 and 1-11) FIG.
  • Test Example 1 it is a figure which shows the result of having evaluated the histamine release inhibitory effect of the test substance (Comparative Examples 1-4-1-5 and 1-12-1-14) of various density
  • the reference test example 1 it is a figure which shows the result of having evaluated the histamine release inhibitory effect about the pyridoxine hydrochloride single (reference example 1) and the combination (reference example 2) of the pyridoxine hydrochloride and MPC polymer.
  • Experiment 2 it is a figure which shows the result of having measured the adsorption amount of the menthol to SHCL using each prescription liquid (Example 2-1 and Comparative Example 2-1).
  • Experiment 2 it is a figure which shows the result of having measured the adsorption amount of the camphor to SHCL using each prescription liquid (Example 2-1 and Comparative Example 2-1).
  • the reference test example 2 it is a figure which shows the result of having evaluated the adhesiveness of the corneal epithelial cell to various soft contact lenses.
  • Experiment 3 it is a figure which shows the result of having evaluated the corneal epithelial cell adhesion inhibitory effect with respect to nonionic SHCL of each prescription liquid (Example 3-1 and Comparative Examples 3-1 and 3-3).
  • Test Example 3 it is a figure which shows the result of having evaluated the corneal epithelial cell adhesion inhibitory effect with respect to nonionic SHCL of each prescription liquid (Example 3-2, Comparative Examples 3-2, 3-4).
  • Experiment 3 it is a figure which shows the result of having evaluated the corneal epithelial cell adhesion inhibitory effect with respect to nonionic SHCL of each prescription liquid (Example 3-3, Comparative Examples 3-5, 3-6).
  • Experiment 3 it is a figure which shows the result of having evaluated the corneal epithelial cell adhesion inhibitory effect with respect to nonionic SHCL of each prescription liquid (Example 3-4, Comparative Examples 3-1 and 3-7).
  • the present invention relates to an ophthalmic composition that exhibits an excellent inhibitory effect on histamine release (hereinafter sometimes referred to as ophthalmic composition-1), and an ophthalmic composition for SHCL that can suppress adsorption of terpenoids to SHCL (hereinafter referred to as ophthalmic composition). In some cases) and various methods.
  • ophthalmic composition-1 an ophthalmic composition that exhibits an excellent inhibitory effect on histamine release
  • ophthalmic composition for SHCL that can suppress adsorption of terpenoids to SHCL
  • Ophthalmic composition-1 The ophthalmic composition-1 of the present invention is a polymer obtained by polymerizing a monomer represented by the following general formula (I) with another monomer that can be copolymerized alone or copolymerized (hereinafter, simply referred to as “component (A)”) May be included) at a rate of 0.001 to 2 w / v%.
  • n1 represents an integer of 2 to 4, preferably 2 or 3, and more preferably 2.
  • R 1 represents a hydrogen atom or a methyl group, preferably a methyl group.
  • R 2 represents a group represented by — (R 6 O) n2 —R 6 —.
  • R 6 represents an alkylene group having 1 to 4 carbon atoms. Specific examples of such an alkylene group include a methylene group, an ethylene group, a propylene group, and a butylene group.
  • R 6 is preferably an alkylene group having 1 to 3 carbon atoms, more preferably an alkylene group having 2 carbon atoms (ethylene group).
  • N2 represents an integer of 0 to 5, preferably an integer of 0 to 2, and more preferably 0.
  • R 3 to R 5 are the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.
  • Examples of such an alkyl group include a methyl group, an ethyl group, an n-propyl group, and an n-butyl group.
  • R 3 to R 5 are preferably a hydrogen atom or an alkyl group having 1 to 2 carbon atoms, more preferably an alkyl group having 1 carbon atom (methyl group).
  • the component (A) is a polymer of a monomer represented by the general formula (I) (hereinafter sometimes simply referred to as “monomer (I)”). It may also be a copolymer of monomer (I) and another monomer, or a mixture of a polymer of monomer (I) and a copolymer of monomer (I) and another monomer. There may be.
  • the finally obtained copolymer is pharmaceutically, pharmacologically (pharmaceutically) or physiologically.
  • the monomer hereinafter only described as “monomer (II)" represented by the following general formula (II) is illustrated.
  • R 7 represents a hydrogen atom or a methyl group, preferably a methyl group.
  • R 8 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms.
  • alkyl group examples include a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group, and an n-hexyl group.
  • R 8 is preferably an alkyl group having 1 to 5 carbon atoms, more preferably an alkyl group having 1 to 4 carbon atoms, and particularly preferably an alkyl group having 4 carbon atoms (n-butyl group).
  • Preferred examples of the monomer (II) include butyl methacrylate (BMA; R 7 is methyl group, R 8 is n-butyl group), methyl methacrylate (MMA; R 7 is methyl group, R 8 is methyl group), 2- Examples thereof include hydroxyethyl methacrylate (HEMA; R 7 is methyl group, R 8 is hydroxyethyl group); more preferably, 2-hydroxyethyl methacrylate, butyl methacrylate; and particularly preferably butyl methacrylate.
  • BMA butyl methacrylate
  • MMA methyl methacrylate
  • 2- Examples thereof include hydroxyethyl methacrylate (HEMA; R 7 is methyl group, R 8 is hydroxyethyl group); more preferably, 2-hydroxyethyl methacrylate, butyl methacrylate; and particularly preferably butyl methacrylate.
  • monomer (II) when monomer (II) can take the form of a salt (for example, when R 7 is a hydrogen atom), monomer (II) may be a salt.
  • examples of the salt form of monomer (II) include alkali metal salts such as sodium and potassium.
  • the composition ratio of the monomer (I) and other monomers varies depending on the structure of the monomer used, etc., but effectively exerts a preventive or therapeutic effect on dry eye.
  • the monomer (I) is usually 50 to 95 mol%, preferably 60 to 90 mol%, more preferably 75 to 85 mol%, based on the total amount of the copolymer.
  • the molecular weight of the polymer used as the component (A) varies depending on the type of monomer, etc., and is limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.
  • the weight average molecular weight is 5,000 to 2,000,000, preferably 40,000 to 1,200,000, more preferably 100,000 to 1,000,000, and particularly preferably 400,000 to 800,000.
  • the weight average molecular weight is measured by GPC analysis.
  • Monomer (I) and monomer (II) are known compounds or known methods from known compounds (for example, JP-A-58-154591, JP-A-60-184093, polymer articles) Vol.35, 423-427, 1978, published by the Society of Polymer Science, Japan).
  • the polymer used as the component (A) can be obtained by polymerizing the monomer (I) and, if necessary, other monomers according to a known method in the field of polymer chemistry. Specifically, the polymerization reaction is carried out in the presence of a polymerization initiator in an appropriate solvent such as water, methanol, ethanol, propanol, t-butanol, benzene, toluene, dimethylformamide, tetrahydrofuran, chloroform, or a mixed solvent thereof. The polymerization may be performed for a certain period of time under appropriate temperature conditions.
  • MPC homopolymer or the copolymer of MPC and monomer (II) may be referred to as MPC polymer.
  • the polymer used as the component (A) can be a commercially available product, and as the commercially available component (A), the Lipidure series (trade name: “LIPIDURE-PMB (BG ) ”,“ LIPIDURE-PMB (Ph10) ”,“ LIPIDURE-PMB ”,“ LIPIDURE-HM ”,“ LIPIDURE-HM-500 ”).
  • the Lipidure series trade name: “LIPIDURE-PMB (BG ) ”,“ LIPIDURE-PMB (Ph10) ”,“ LIPIDURE-PMB ”,“ LIPIDURE-HM ”,“ LIPIDURE-HM-500 ”).
  • the blending ratio of the component (A) is set within the range of 0.001 to 2 w / v% of the total amount of the component (A) with respect to the total amount of the ophthalmic composition-1.
  • it is more preferably 0.005 to 2 w / v%, still more preferably 0.01 to 2 w / v%, still more preferably 0.01 to 1 w / v%, particularly preferably. Examples are 0.01 to 0.5 w / v%.
  • the blending ratio of the component (A) exemplified here is also suitable from the viewpoint of suppressing menthol adsorption to SHCL or suppressing adhesion of corneal epithelial cells to nonionic SHCL.
  • the ophthalmic composition-1 of the present invention contains menthol (hereinafter sometimes simply referred to as the component (B-1)) at a rate of 0.001 to 0.02 w / v%. .
  • menthol hereinafter sometimes simply referred to as the component (B-1)
  • the components (A) and (B-1) in combination at a specific ratio, it is possible to synergistically enhance and exhibit the histamine release inhibitory action.
  • the combined use of the component (A) and the component (B-1) is also effective in obtaining an effect of inhibiting menthol adsorption on SHCL and an effect of inhibiting cell adhesion on nonionic SHCL.
  • the menthol used as the component (B-1) is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable, and may be any of d-form, l-form or dl-form. Good.
  • an essential oil containing menthol may be used as the component (B-1). Examples of such essential oils include cool mint oil, peppermint oil, and peppermint oil.
  • the blending ratio of the component (B-1) is in the range of 0.001 to 0.02 w / v% of the total amount of the component (B-1) with respect to the total amount of the ophthalmic composition-1. However, it is preferably 0.001 to 0.015 w / v%, more preferably 0.001 to 0.01 w / v% from the viewpoint of further enhancing the histamine release inhibitory action.
  • the blending ratio of the component (B-1) exemplified here is also effective for suppressing adsorption of menthol to SHCL or suppressing adhesion of corneal epithelial cells to nonionic SHCL.
  • when using the essential oil containing menthol as said (B-1) component it sets so that the menthol content in the essential oil mix
  • the ratio of the component (B-1) to the component (A) is not particularly limited as long as the blending ratio described above is satisfied, but it further enhances the histamine release inhibitory action. From the viewpoint, the ratio that the total amount of component (B-1) is 0.02 to 20000 parts by weight, preferably 0.2 to 2000 parts by weight, more preferably 0.2 to 200 parts by weight per 100 parts by weight of the total amount of component (A) is satisfied. It is desirable to do.
  • the blending ratio of the component (B-1) exemplified here is effective in suppressing adsorption of menthol to SHCL or suppressing adhesion of corneal epithelial cells to nonionic SHCL, but nonionic SHCL From the standpoint of further enhancing the adhesion-suppressing action of corneal epithelial cells, the total amount of component (B-1) is preferably 0.4 to 100 parts by weight per 100 parts by weight of component (A).
  • blended is set so that the said ratio may be satisfy
  • the ophthalmic composition-1 of the present invention preferably further contains a buffering agent in addition to the components (A) and (B-1).
  • the buffering agent that can be incorporated into the ophthalmic composition-1 of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.
  • buffers include borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, tris buffer, epsilon-aminocaproic acid, aspartic acid, aspartate and the like. These buffering agents may be used in combination.
  • Preferred buffering agents are borate buffer, phosphate buffer, carbonate buffer, and citrate buffer, and particularly preferred buffers are borate buffer and phosphate buffer.
  • boric acid buffer examples include borates such as alkali metal borate and alkaline earth metal borate.
  • phosphate buffer examples include phosphates such as alkali metal phosphates and alkaline earth metal phosphates.
  • carbonate buffer examples include carbonates such as alkali metal carbonates and alkaline earth metal carbonates.
  • citrate buffer examples include alkali metal citrate and alkaline earth metal citrate. Moreover, you may use the borate or the hydrate of a phosphate as a borate buffer or a phosphate buffer.
  • boric acid or a salt thereof sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.
  • phosphoric acid or a salt thereof diisodium hydrogen phosphate, dihydrogen phosphate) Sodium, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate), carbonic acid or a salt thereof (sodium hydrogen carbonate, sodium carbonate, ammonium carbonate, potassium carbonate, Calcium carbonate, potassium hydrogen carbonate, magnesium carbonate, etc.), citric acid or a salt thereof (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.), acetic acid or a salt thereof (ammonium acetate) , Potassium acetate, calcium acetate, sodium acetate, etc.), asparagus Examples thereof include formic acid or a salt thereof (sodium as
  • buffering agents may be used alone or in any combination of two or more.
  • boric acid buffering agents are preferably used from the viewpoint of further enhancing the effects of the present invention.
  • boric acid buffering agents boric acid and / or borax are particularly preferable, and an embodiment in which boric acid and borax are used in combination is most preferable.
  • the blending ratio of the buffering agent varies depending on the type of buffering agent used, the type and amount of other blending components, and should be specified uniformly.
  • the total amount of the buffer is 0.01 to 10 w / v%, preferably 0.1 to 5 w / v%, more preferably 0.5 to 2 w with respect to the total amount of ophthalmic composition-1.
  • a ratio of / v% is exemplified.
  • the total amount of borate buffer is 0.1 to 5 w / v%, preferably 0.1 to 3 w / v with respect to the total amount of ophthalmic composition-1.
  • examples are v%, more preferably 0.2 to 2 w / v%, particularly preferably 0.5 to 2 w / v%.
  • the ophthalmic composition-1 of the present invention preferably further contains a surfactant.
  • the surfactant that can be blended in the ophthalmic composition-1 of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable, and is nonionic surfactant. Any of an agent, an amphoteric surfactant, an anionic surfactant, and a cationic surfactant may be used.
  • POE sorbitan fatty acid esters such as monostearic acid POE (20) sorbitan (polysorbate 60), tristearic acid POE (20) sorbitan (polysorbate 65), monooleic acid POE (20) sorbitan (polysorbate 80); POE / POP block copolymers such as poloxamer 235, poloxamer 188, poloxamer 403, poloxamer 237 and poloxamer 124; POE cured castor oil such as POE (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60); POE ( 9) POE alkyl ethers such as lauryl ether; POE-POP alkyl ethers such as POE (20) POP (4) cetyl ether POE (10) POE alkylphenyl ethers such as nonylphenyl ether.
  • POE cured castor oil such as POE (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil
  • POE polyoxyethylene
  • POP polyoxypropylene
  • the numbers in parentheses indicate the number of moles added.
  • amphoteric surfactants that can be incorporated into the ophthalmic composition-1 of the present invention include alkyldiaminoethylglycine.
  • Specific examples of the cationic surfactant that can be blended in the ophthalmic composition-1 of the present invention include benzalkonium chloride and benzethonium chloride.
  • these surfactants may be used alone or in combination of two or more.
  • nonionic surfactants are preferred, and particularly preferred surfactants include POE (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60), poloxamer 407, monooleic acid.
  • the blending ratio of the surfactant can be appropriately set according to the kind of surfactant, the kind and amount of other blending components, and the like.
  • the total amount of the surfactant is 0.001 to 1.0 w / v%, preferably 0.005 to 0.5 w / v with respect to the total amount of the ophthalmic composition-1. %, More preferably 0.01 to 0.3 w / v%.
  • the ophthalmic composition-1 of the present invention preferably further contains an isotonic agent.
  • the isotonic agent that can be incorporated into the ophthalmic composition-1 of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.
  • Specific examples of such isotonic agents include, for example, sodium bisulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, potassium acetate, sodium acetate, sodium bicarbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate , Glycerin, propylene glycol and the like. These isotonic agents may be used alone or in any combination of two or more.
  • the blending ratio of the isotonic agent varies depending on the type of tonicity agent used and cannot be uniformly defined.
  • the total amount of tonicity agent is 0.01 to 10 w / v%, preferably 0.05 to 5 w / v%, more preferably 0.1 to 2 w /% with respect to the total amount of ophthalmic composition-1.
  • the ratio of v% is exemplified.
  • the pH of the ophthalmic composition-1 of the present invention is not particularly limited as long as it is within a pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable range.
  • An example of the pH of the ophthalmic composition-1 of the present invention is in the range of 4.0 to 9.5, preferably 5.0 to 8.5, and more preferably 5.5 to 8.0.
  • the osmotic pressure of the ophthalmic composition-1 of the present invention is not particularly limited as long as it is within a range acceptable for a living body.
  • An example of the osmotic pressure ratio of the ophthalmic composition-1 of the present invention is preferably in the range of 0.7 to 5.0, more preferably 0.9 to 3.0, particularly preferably 1.0 to 2.0. Can be mentioned.
  • the osmotic pressure can be adjusted by a method known in the art using inorganic salts, polyhydric alcohols, sugar alcohols, saccharides and the like.
  • the osmotic pressure ratio is the ratio of the osmotic pressure of the sample to the osmotic pressure of 0.9w / v% sodium chloride aqueous solution based on the 15th revised Japanese Pharmacopoeia. Measure with reference to.
  • the standard solution for osmotic pressure ratio measurement is sodium chloride (Japanese Pharmacopoeia standard reagent) dried at 500-650 ° C for 40-50 minutes, then allowed to cool in a desiccator (silica gel), accurately weigh 0.900 g and purify. Dissolve in water to prepare exactly 100 mL, or use a commercially available standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution).
  • the ophthalmic composition-1 of the present invention can contain a proper amount of various active ingredients (pharmacologically active ingredients, physiologically active ingredients, etc.) in combination with the above ingredients.
  • composition-1 of the present invention various components and additives are appropriately selected in accordance with conventional methods depending on the use and form as long as they do not impair the effects of the invention. The above can be used in combination.
  • the ophthalmic composition-1 of the present invention is prepared by adding a desired amount of the above-mentioned components (A) and (B-1) and, if necessary, other blending components to a desired concentration.
  • a desired concentration for example, in the case of eye drops, contact lens mounting solution, eye wash or contact lens care agent, the above components are dissolved or suspended in purified water, adjusted to a predetermined pH and osmotic pressure, and sterilized by filtration sterilization or the like.
  • highly hydrophobic components such as menthol (terpenoids)
  • components that have a solubilizing action such as surfactants in advance, it may be dissolved or suspended by adding purified water. Good.
  • the ophthalmic composition-1 of the present invention is not particularly limited as long as it can be used in the ophthalmic field, and examples thereof include a liquid form and an ointment form. Among these, liquid is preferable.
  • water that is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable may be used as an aqueous carrier. Examples include distilled water, normal water, purified water, sterilized purified water, water for injection, distilled water for injection, and the like. These definitions are based on the 15th revision Japanese Pharmacopoeia.
  • the ophthalmic composition-1 of the present invention comprises eye drops (however, eye drops include eye drops that can be applied while wearing contact lenses), eye ointments, eye wash (however, eye lenses are contact lenses) Including eye wash that can be washed while wearing), contact lens mounting fluid, contact lens care agent (contact lens disinfectant, contact lens preservative, contact lens cleaner, contact lens cleaner, etc.) ) Etc.
  • eye drops, eye washes, and contact lens mounting liquids, in particular eye drops are suitable formulation forms of the ophthalmic composition-1 of the present invention.
  • the term “contact lens” includes all contact lenses including hard contact lenses, oxygen-permeable hard contact lenses, soft contact lenses, and silicone hydrogel lenses.
  • menthol is significantly more easily adsorbed by SHCL than conventional soft contact lenses not containing a silicone material.
  • the ophthalmic composition-1 of the present invention by using the components (A) and (B-1) together, adsorption of menthol to SHCL can be suppressed, and SHCL is used with high safety. It is possible to do.
  • an example of a suitable formulation form of the ophthalmic composition-1 of the present invention is an eye drop that can be instilled during SHCL wearing (SHCL eye drop).
  • an example of a suitable formulation form of the ophthalmic composition-1 of the present invention is an eye drop that can be instilled during ionic SHCL wearing (an eye drop for ionic SHCL).
  • an eye drop for ionic SHCL when it only displays as SHCL, both ionic and nonionic SHCL are included.
  • ionic SHCL refers to SHCL with an ionic component content of 1 mol% or more in the SHCL material in accordance with US FDA (US Food and Drug Administration) standards
  • nonionic SHCL refers to US FDA (US According to Food and Drug Administration)
  • the ophthalmic composition-1 of the present invention can synergistically suppress corneal cell adhesion with high nonionic SHCL.
  • nonionic SHCL with high safety, and the above-mentioned problems peculiar to nonionic SHCL can be solved.
  • the ophthalmic composition-1 of the present invention when the ophthalmic composition-1 of the present invention is supplied as an eye drop that can be instilled while wearing nonionic SHCL (an eye drop for nonionic SHCL), the histamine release inhibitory effect and the terpenoid to SHCL In addition to the effect of suppressing adsorption of corneal cells, it can also have an effect of suppressing adhesion of corneal cells to nonionic SHCL.
  • an example of a suitable formulation form of the ophthalmic composition-1 of the present invention is an eye drop that can be instilled while wearing a non-ionic SHCL (non-ionic SHCL eye drop).
  • nonionic SHCL As an example of a suitable application target for exhibiting the corneal epithelial cell adhesion inhibitory effect using the ophthalmic composition-1 of the present invention, among nonionic SHCL, mention may be made of nonionic SHCL having a water content of 35% or less. it can. Since SHCL contains a hydrogel material, it contains at least more than 0% moisture.
  • the moisture content of SHCL indicates the ratio of water in SHCL, and is specifically determined by the following formula.
  • Moisture content (%) (weight of hydrated water / weight of hydrated SHCL) x 100 Such moisture content can be measured by a gravimetric method according to the description of ISO18369-4: 2006.
  • the ophthalmic composition-1 of the present invention is an eye drop that can be instilled while wearing a contact lens (eye drop for contact lens), an eye wash that can be washed while wearing a contact lens (eye wash for contact lens), and an eye drop for SHCL , Ionic SHCL eye drops, or non-ionic SHCL eye drops, it may be applied directly to the eye wearing each lens, or applied to the eye before each lens is attached. May be.
  • the ophthalmic composition-1 of the present invention can exert a histamine release inhibitory action by the synergistic action of the components (A) and (B-1), it is antiallergic (for pollen, etc.), itching is suppressed, and contact lenses are not used. Can be used for purposes such as pleasure suppression.
  • the ophthalmic composition-1 of the present invention is effective for preventing or treating dry eye and dry eyes based on the component (A), and is also useful for improving dry eye and dry eyes.
  • the container for storing the ophthalmic composition-1 of the present invention may be made of glass or plastic.
  • the constituent material of the plastic container is not particularly limited.
  • the copolymer is mainly composed of any one of ethylene-2,6-naphthalate units, arylate units, ethylene terephthalate units, propylene units, ethylene units, and imide units, and other polyester units and imide units. Examples of the copolymer include.
  • Ophthalmic composition-2 The ophthalmic composition-2 of the present invention is an ophthalmic composition used for SHCL.
  • the ophthalmic composition-2 of the present invention is a polymer in which the monomer represented by the general formula (I) is polymerized with another monomer that can be copolymerized alone or copolymerized (hereinafter simply referred to as “component (A)”) Is also included.
  • component (A) used in ophthalmic composition-2 of the present invention and preferred examples of component (A) are the same as component (A) used in ophthalmic composition-1. .
  • the content of the component (A) is not particularly limited, but from the viewpoint of further enhancing the action of inhibiting the adsorption of terpenoids to SHCL, the total amount of the ophthalmic composition-2
  • the total amount of component (A) is 0.0001 to 5 w / v%, preferably 0.001 to 2 w / v%, more preferably 0.01 to 1 w / v%, still more preferably 0.01 to 0.5 w / v%, and particularly preferably 0.02 to 0.5% w / v.
  • component (A) When the content ratio of component (A) satisfies the above range, it is effective to more effectively suppress the adhesion of corneal epithelial cells to nonionic SHCL, but particularly when it is 0.05 to 0.25 w / v%. It becomes possible to remarkably enhance the adhesion-suppressing effect of corneal epithelial cells on nonionic SHCL.
  • the ophthalmic composition-2 of the present invention contains a terpenoid (hereinafter sometimes referred to as the component (B-2)) in addition to the component (A).
  • a terpenoid hereinafter sometimes referred to as the component (B-2)
  • component (B-2) a terpenoid
  • Such combined use of component (A) and component (B-2) is also effective in obtaining an effect of inhibiting cell adhesion to nonionic SHCL.
  • the terpenoid used as the component (B-2) is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.
  • Specific examples of such terpenoids include menthol, menthone, camphor, borneol, geraniol, cineol, citronellol, carvone, anethole, eugenol, limonene, linalool, linalyl acetate, and derivatives thereof. These compounds may be d-form, l-form or dl-form.
  • an essential oil containing the above compound may be used as a terpenoid.
  • terpenoids examples include eucalyptus oil, bergamot oil, peppermint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, and rose oil. These terpenoids may be used alone or in any combination of two or more.
  • menthol, camphor, borneol and the like Preferred essential oils containing these include cool mint oil, peppermint oil, peppermint oil, camphor oil and the like. More preferably, menthol and camphor (d-camphor, dl-camphor, etc.) are mentioned, and more preferably, menthols such as l-menthol, d-menthol and dl-menthol or derivatives thereof are included, and these are contained. Examples of essential oils include cool mint oil, peppermint oil, and peppermint oil. Particularly preferred is l-menthol.
  • the content ratio of the component (B-2) is not particularly limited, but from the viewpoint of further enhancing the action of inhibiting the adsorption of terpenoids to SHCL, the total amount of the ophthalmic composition-2 is used.
  • the total amount of component (B-2) is 0.0001 to 1 w / v%, preferably 0.001 to 0.08 w / v%, more preferably 0.001 to 0.05 w / v%, and particularly preferably 0.001 to 0.02 w / v%. Is mentioned.
  • the content ratio of the component (B-2) satisfies the above range, it is effective in further effectively suppressing adhesion of corneal epithelial cells to nonionic SHCL.
  • the essential oil containing a terpenoid as said (B-2) component it sets so that the total amount of terpenoid content in the essential oil mix
  • the ratio of the component (B-2) to the component (A) is not particularly limited as long as the content ratio described above is satisfied, but the action of inhibiting adsorption of terpenoids to SHCL
  • the total amount of component (B-2) is 0.0002 to 50,000 parts by weight, preferably 0.02 to 500 parts by weight, more preferably 0.2 to 500 parts by weight, per 100 parts by weight of component (A). It is desirable to satisfy this ratio.
  • the total amount of (A) ingredient per 100 parts by weight of (B-2) ingredient is desirable that the ratio is such that the total amount is 0.2 to 5000 parts by weight, preferably 0.2 to 2000 parts by weight, and more preferably 0.4 to 100 parts by weight.
  • (B -2) Menthol is used as the component, and the content of component (A) is 0.001 to 2 w / v%, preferably 0.005 to 2 w / v%, more preferably 0.01 to the total amount of ophthalmic composition-2.
  • component (B-2) is 0.001 to 0.02 w / v%, preferably 0.001 It is desirable to satisfy ⁇ 0.015 w / v%, more preferably 0.001 to 0.01 w / v%.
  • the above (A) and (B- 2) The ratio of the component (A) to the component (B-2) is 100% by weight of the total amount of the component (A), and the total amount of the component (B-2) is 0.02 to 20000 wt. Part, preferably 0.2 to 2000 parts by weight, more preferably 0.2 to 200 parts by weight.
  • the ophthalmic composition-2 of the present invention preferably further contains a buffer in addition to the components (A) and (B-2).
  • the kind of the buffer used in the ophthalmic composition-2 of the present invention, a suitable example of the buffer, and the content of the buffer are the same as those of the buffer used in the ophthalmic composition-1. It is.
  • the ophthalmic composition-2 of the present invention further contains a surfactant.
  • a surfactant used in the ophthalmic composition-2 of the present invention, a preferable example of the surfactant, and the content ratio of the surfactant, the surfactant used in the ophthalmic composition-1 It is the same as the case of.
  • the ophthalmic composition-2 of the present invention preferably further contains an isotonic agent.
  • the type of tonicity agent used in the ophthalmic composition-2 of the present invention, a suitable example of the tonicity agent, and the content ratio of the tonicity agent are used in the ophthalmic composition-1. The same as in the case of the tonicity agent.
  • the pH and osmotic pressure of the ophthalmic composition-2 of the present invention are the same as those of the ophthalmic composition-1.
  • the ophthalmic composition-2 of the present invention can contain active ingredients (pharmacologically active ingredients, physiologically active ingredients, etc.) and other various ingredients and additives.
  • the ophthalmic composition-2 of the present invention is prepared by adding a desired amount of the above-mentioned components (A) and (B-2), and other components as necessary to a desired concentration.
  • the dosage form of the ophthalmic composition-2 of the present invention is the same as that of the ophthalmic composition-1.
  • the ophthalmic composition-2 of the present invention is used as an ophthalmic composition for SHCL, and specific examples of the formulation include eye drops that can be instilled while wearing SHCL (eye drops for SHCL), eyewash while wearing SHCL. Possible eyewashes (SHCL eyewashes), SHCL mounting solutions, SHCL care agents (including SHCL disinfectants, SHCL preservatives, SHCL cleaners, SHCL cleaners, etc.) and the like.
  • SHCL eyewashes Possible eyewashes (SHCL eyewashes), SHCL mounting solutions, SHCL care agents (including SHCL disinfectants, SHCL preservatives, SHCL cleaners, SHCL cleaners, etc.) and the like.
  • SHCL care agents including SHCL disinfectants, SHCL preservatives, SHCL cleaners, SHCL cleaners, etc.
  • it may be directly applied to the eye wearing SHCL, or may be applied to the eye before wearing SHCL.
  • the eye drops for SHCL are preferable, and the eye drops for SHCL are particularly suitable for the ophthalmic composition-2 of the present invention.
  • ionic SHCL is more easily adsorbed by terpenoids than nonionic SHCL, and a higher level of terpenoid adsorption suppression effect is required, but according to the ophthalmic composition-2 of the present invention. Moreover, adsorption of terpenoids to ionic SHCL can also be effectively suppressed.
  • an ophthalmic composition for ionic SHCL more preferably an eye drop for ionic SHCL, an eye wash for ionic SHCL, An ionic SHCL cleaning agent, an ionic SHCL mounting solution, particularly preferably an ionic SHCL eye drop.
  • nonionic SHCL among soft contact lenses, easily adheres to corneal epithelial cells. Therefore, an ophthalmic composition applied to nonionic SHCL is required to have an action of suppressing adhesion of corneal epithelial cells to nonionic SHCL.
  • the ophthalmic composition-2 of the present invention the combined use of the components (A) and (B-2) can synergistically suppress corneal cell adhesion with high nonionic SHCL. It is possible to wear nonionic SHCL with high safety.
  • an ophthalmic composition for nonionic SHCL more preferably an eye drop for nonionic SHCL, an eyewash for nonionic SHCL
  • Nonionic SHCL cleaning agents for nonionic SHCL
  • nonionic SHCL mounting solutions particularly preferably nonionic SHCL eye drops.
  • the water content of the nonionic SHCL to be applied is not particularly limited, but at least more than 0% And 35% or less.
  • the method for measuring the water content of the nonionic SHCL to be used the method described in the column of the “ophthalmic composition-1” is used.
  • the ophthalmic composition-2 of the present invention is effective for the prevention or treatment of dry eye based on the above component (A), and is also useful for improving dry eye.
  • the ophthalmic composition-2 of the present invention is in an aspect capable of exhibiting an excellent histamine release inhibitory action, it is used for applications such as antiallergy (for pollen, etc.), itching, and discomfort when wearing contact lenses. it can.
  • the container for storing the ophthalmic composition-2 of the present invention is the same as the case of the ophthalmic composition-1.
  • the ophthalmic composition has a histamine release inhibitory action that is synergistically enhanced by combining the components (A) and (B-1) at a specific content ratio. Can be made.
  • the present invention from yet another point of view, in an ophthalmic composition, (A) a polymer obtained by polymerizing a monomer represented by the general formula (I), either alone or with another copolymerizable monomer, 0.001 to 2 w / v % And (B-1) menthol 0.001 to 0.02 w / v% in combination, a method for imparting a histamine inhibitory action to an ophthalmic composition is provided.
  • the types and content ratios and ratios of the components (A) and (B-1) to be used, the types and content ratios of other components, the formulation form of the ophthalmic composition, and the container for storing the ophthalmic composition are the same as in “1. Ophthalmic composition-1”.
  • the present invention from yet another point of view, (A) a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, and (B-2) a terpenoid.
  • a method for suppressing adsorption of terpenoids to SHCL which comprises contacting an ophthalmic composition containing SHCL with SHCL.
  • the present invention also includes (B-2) a terpenoid in an ophthalmic composition, together with a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization.
  • Method for inhibiting adhesion of corneal epithelial cells to nonionic SHCL method for imparting corneal epithelial cell adhesion inhibiting action to nonionic SHCL to ophthalmic composition
  • combining components (A) and (B-2) can be used to synergistically suppress adhesion of corneal epithelial cells to nonionic SHCL.
  • the present invention from yet another point of view, (A) a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, and (B-2) a terpenoid.
  • a method for suppressing adhesion of corneal epithelial cells to nonionic SHCL which comprises bringing the ophthalmic composition contained therein into contact with nonionic SHCL.
  • the present invention also includes (B-2) a terpenoid in an ophthalmic composition, together with a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization.
  • the types and content ratios of the components (A) and (B-2) to be used the types and content ratios of other components to be blended, the types of nonionic SHCL to be applied, etc. This is the same as “2. Ophthalmic composition-2”.
  • Test Example 1 Histamine release inhibitory effect test 1 ⁇ 10 5 of a rat basophil cell line (RBL-2H3) suspended in DMEM medium (Invitrogen) supplemented with 10% by volume fetal calf serum (Invitrogen) A 96-well microtiter plate (Corning) was seeded at a density of cells / cm 2 and cultured at 37 ° C. under 5% CO 2 for 24 hours.
  • PIPES buffer is Hanks balanced salt (manufactured by Invitrogen) supplemented with 20 mM PIPES (Piperazine-1,4-bis (2-ethanesulfonic acid; manufactured by Sigma)) and 0.1 w / v bovine serum albumin (manufactured by Sigma).
  • composition CaCl 2 1.26 mM, MgCl 2 ⁇ 6H 2 O 0.493 mM, MgSO 4 ⁇ 7H 2 O 0.407 mM, KCl 5.33 mM, KH 2 PO 4 0.441 mM, NaHCO 3 4.17 mM, NaCl 137.93 mM, Na 2 HPO 4 0.338 mM) was used. Thereafter, 2 ⁇ l of 1 mM A23187 (reagent: Sigma) was added to each well and further incubated for 20 minutes at 37 ° C. under 5% CO 2 . The supernatant of each well was collected, and the histamine concentration was quantified using an ELISA kit (Oxford Biochemical Research).
  • a PIPES buffer solution that does not dissolve the test substance was added in an amount of 0.2 ml per well and tested in the same manner as above, and a blank was tested in the same manner as the control except that A23187 was not added.
  • the histamine concentration was quantified. Using the histamine concentration of each obtained sample, the histamine release inhibition rate (%) was calculated according to the following calculation formula.
  • Histamine release inhibition rate (%) ⁇ 1-(histamine concentration of each sample-blank histamine concentration) / (control histamine concentration-blank histamine concentration) ⁇ x 100
  • Reference Test Example 1 Histamine release inhibitory effect test
  • pyridoxine hydrochloride and MPC polymer which are known to have a histamine release inhibitory action
  • pyridoxine hydrochloride at concentrations shown in Table 5 as test substances and Using MPC polymer the histamine release inhibition rate was determined in the same manner as in Test Example 1 above.
  • Test Example 2 Inhibition test of adsorption of terpenoid to SHCL The following experiment was conducted using two types of SHCL shown in Table 6 to evaluate the adsorption property of terpenoid to SHCL. In addition, all SHCL used for this test is a commercial item.
  • SHCL Two types of SHCL shown in Table 6 were immersed in 5 mL of physiological saline solution for 72 hours (lens pretreatment). Moreover, the prescription liquid was created according to Table 7, and each prescription liquid was filled into 6 mL capacity
  • Reference Test Example 2 Evaluation of Adhesion of Corneal Epithelial Cells of Various Soft Contact Lenses The following experiment was conducted using five types of soft contact lenses shown in Table 8 to evaluate the adhesion of corneal epithelial cells on the surface of the soft contact lens. .
  • the soft contact lenses used in this test are all commercially available products.
  • Each soft contact lens was immersed one by one in a 24-well microplate containing 900 ⁇ L of growth medium (DMEM medium containing 10% fetal bovine serum) so that the convex surface was on the top.
  • growth medium DMEM medium containing 10% fetal bovine serum
  • Each well was seeded with 100 ⁇ L each of a cell suspension (1 ⁇ 10 5 cell / ml) of a rabbit corneal epithelial cell line SIRC (ATCC number: CCL-60) prepared using a growth medium, and incubated at 37 ° C., 5 ° C. After culturing for 48 hours under% CO 2 conditions, the number of viable cells adhered to the soft contact lens was counted.
  • control group cells were cultured on the bottom of the microplate without immersing any lens, and the number of viable cells in the wells was counted (control group).
  • control group Cell Counting Kit (manufactured by Dojindo Laboratories) was used for the measurement of the number of viable cells.
  • ratio of the number of viable cells adhering to the surface of each soft contact lens ratio of the number of viable cells to the control group;%) was calculated with respect to the total number of viable cells contained in the wells of the control group.
  • the lenses A and B which are nonionic SHCL
  • the lens C which is an ionic silicone hydrogel contact lens
  • the lens D or E which is a nonsilicone hydrogel contact lens. It was confirmed that there was remarkable corneal epithelial cell adhesion.
  • cell adhesion was hardly confirmed in the lenses C, D, and E, but corneal epithelial cells were present on the entire surfaces of the lenses A and B. It was confirmed that they were adhered. From the above results, it was confirmed that nonionic SHCL has significantly higher adhesion of corneal epithelial cells than other types of lenses, and wearing nonionic SHCL has adverse effects such as damage to the corneal surface. It became clear that it could be given.
  • Test Example 3 Adhesion Inhibition Test of Corneal Epithelial Cells to Nonionic SHCL The following experiment was performed using the lens B shown in Table 8 above, and the corneal epithelial cell adhesion to the nonionic SHCL surface was evaluated. Specifically, it was evaluated by the following method. Using the growth medium (DMEM medium containing 10% fetal bovine serum), the formulation solutions (Examples 3-1 to 3-4 and Comparative Examples 3-1 to 3-7) having the compositions shown in Tables 9 and 10 were aseptically prepared. It was prepared. 1000 ⁇ L of each formulation solution was placed in a 24-well microplate, and SHCL was immersed therein with the convex surface up.
  • DMEM medium containing 10% fetal bovine serum the formulation solutions having the compositions shown in Tables 9 and 10 were aseptically prepared. It was prepared. 1000 ⁇ L of each formulation solution was placed in a 24-well microplate, and SHCL was immersed therein with the convex surface up.
  • the blank used was treated in the same manner as above except that SHCL and cells were not added.
  • the formulation liquids of Examples 3-1 to 3-4 containing both the MPC polymer and the terpenoid contained Comparative Example 3-1 containing only one of the MPC polymer and the terpenoid. It was confirmed that a higher inhibition rate of corneal epithelial cell adhesion was obtained compared to the case of the prescription liquids of ⁇ 3-7. This demonstrates that by using an ophthalmic composition containing an MPC polymer and a terpenoid, adverse effects such as damage to the corneal surface caused by nonionic SHCL can be suppressed.
  • Reference test example 3 Adhesion inhibition test of corneal epithelial cells to nonionic SHCL
  • the test solution having the composition shown in Table 11
  • the cell adhesion inhibition rate was determined in the same manner as in Test Example 3 above.
  • the ophthalmic composition formulation of Formulation Example 1 above was prepared according to a conventional method, and 15 mL of a 15 mL capacity PET container was filled to prepare eye drops and SHCL eye drops.
  • the ophthalmic composition formulation of Formulation Example 2 above was prepared according to a conventional method, and 10 mL of a 10 mL PET container was filled with 10 mL of eye drops, contact lens mounting solution, SHCL eye drop, and SHCL contact lens mounting solution. did. Moreover, it replaced with said container and 500 mL capacity

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Abstract

La présente invention concerne : une composition ophtalmique selon une nouvelle préparation non conventionnelle, qui a une action d'inhibition de la libération de l'histamine ; et une composition ophtalmique pour une lentille de contact à base d'hydrogel de silicone, qui est capable de supprimer l'adsorption de terpénoïde à une lentille de contact à base d'hydrogel de silicone. Spécifiquement, la composition ophtalmique est préparée en utilisant (A) de 0,001 à 2 % p/v d'un polymère qui a un groupe phosphorylcholine analogue dans une chaîne latérale en combinaison avec (B-1) 0,001 à 0,02 % p/v de menthol. La composition ophtalmique pour une lentille de contact à base d'hydrogel de silicone est préparée en utilisant (A) un polymère qui a un groupe phosphorylcholine analogue dans une chaîne latérale en combinaison avec (B-2) un terpénoïde.
PCT/JP2010/067153 2009-09-30 2010-09-30 Composition ophtalmique Ceased WO2011040572A1 (fr)

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HK12112234.7A HK1171380B (en) 2009-09-30 2010-09-30 Ophthalmic composition
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JP6462201B2 (ja) * 2012-06-14 2019-01-30 ロート製薬株式会社 水性眼科組成物
KR102293485B1 (ko) 2013-08-30 2021-08-24 니치유 가부시키가이샤 점안제
JP2017132764A (ja) * 2016-01-27 2017-08-03 ロート製薬株式会社 シリコーンハイドロゲルカラーコンタクトレンズ用眼科組成物
JP2018052887A (ja) * 2016-09-29 2018-04-05 小林製薬株式会社 水性製剤
TWI607768B (zh) * 2017-03-31 2017-12-11 晶碩光學股份有限公司 隱形眼鏡用組成物及隱形眼鏡的保養方法
CN108690740A (zh) * 2017-04-12 2018-10-23 晶硕光学股份有限公司 隐形眼镜用组合物及隐形眼镜的保养方法
TWI651095B (zh) * 2017-10-18 2019-02-21 晶碩光學股份有限公司 具有抗敏舒緩效果的眼用產品
JP2019101120A (ja) * 2017-11-29 2019-06-24 日油株式会社 コンタクトレンズ用溶液
TWI671086B (zh) * 2018-05-25 2019-09-11 晶碩光學股份有限公司 眼科產品及其眼科組成物
WO2019232717A1 (fr) * 2018-06-06 2019-12-12 晶硕光学股份有限公司 Produit ophtalmique et composition ophtalmique associée
CN110564519A (zh) * 2018-06-06 2019-12-13 晶硕光学股份有限公司 眼科产品及其眼科组合物
WO2020184479A1 (fr) * 2019-03-08 2020-09-17 ロート製薬株式会社 Composition ophtalmique à sensation d'irritation inhibée
JP6687781B1 (ja) * 2019-03-08 2020-04-28 ロート製薬株式会社 刺激感が抑制された眼科組成物
KR20210072720A (ko) * 2019-12-09 2021-06-17 니치유 가부시키가이샤 소프트 콘택트렌즈용 화분 흡착 억제제 및 화분 단백 흡착 억제제
WO2021193491A1 (fr) * 2020-03-26 2021-09-30 日油株式会社 Inhibiteur d'adsorption pour particules fines inorganiques à utiliser dans des lentilles de contact souples
KR102479119B1 (ko) * 2020-10-07 2022-12-19 주식회사 휴메디솔 생체적합성 mpc 고분자 기반의 콘택트렌즈 다기능 용액 및 이의 제조방법
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