[go: up one dir, main page]

WO2024203572A1 - Copolymère et solution de traitement de lentille de contact - Google Patents

Copolymère et solution de traitement de lentille de contact Download PDF

Info

Publication number
WO2024203572A1
WO2024203572A1 PCT/JP2024/010658 JP2024010658W WO2024203572A1 WO 2024203572 A1 WO2024203572 A1 WO 2024203572A1 JP 2024010658 W JP2024010658 W JP 2024010658W WO 2024203572 A1 WO2024203572 A1 WO 2024203572A1
Authority
WO
WIPO (PCT)
Prior art keywords
copolymer
formula
contact lens
carbon atoms
group
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.)
Pending
Application number
PCT/JP2024/010658
Other languages
English (en)
Japanese (ja)
Inventor
俊祐 尾▲崎▼
規郎 岩切
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
NOF Corp
Original Assignee
NOF Corp
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.)
Filing date
Publication date
Application filed by NOF Corp filed Critical NOF Corp
Publication of WO2024203572A1 publication Critical patent/WO2024203572A1/fr
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
    • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
    • C08F220/10—Esters
    • C08F220/34—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K3/00—Materials not provided for elsewhere

Definitions

  • the present invention relates to a copolymer and a treatment solution for contact lenses.
  • Surface treatment agents have been widely proposed that can impart surface hydrophilicity, biocompatibility, antithrombogenicity, etc. due to phosphorylcholine groups by treating the surfaces of various materials with phosphorylcholine group-containing copolymers.
  • Applications include hydrophilization treatment to hydrophobic substrates, antifouling treatment of industrial filter surfaces, and surface treatment to suppress the adsorption of proteins and cells to medical polymer materials. In particular, they have been used in soft contact lenses in recent years.
  • the comfort of wearing soft contact lenses is closely related to the hydrophilicity and lubricity of the lens surface, and maintaining these properties for a long period of time leads to sustained comfort when worn all day.
  • Patent Document 1 discloses a technique in which soft contact lenses are subjected to plasma treatment and hydrophilized with zwitterionic groups.
  • Patent Document 2 discloses a technique in which a soft contact lens containing reactive groups is chemically reacted with and bonded to a hydrophilic polymer having reactive groups, thereby hydrophilizing the surface of the soft contact lens. These techniques involve treating the soft contact lens itself to impart hydrophilicity to the surface, and because the treatment process is complicated, they require highly controlled manufacturing equipment tailored to the treatment technology, which can be economically disadvantageous.
  • Patent Documents 3, 4, and 5 which incorporate polyethylene glycol or a cellulose-based polymer into a treatment solution for soft contact lenses to impart and enhance hydrophilicity to the surface of soft contact lenses and improve wearing comfort.
  • phosphorylcholine group-containing polymers have a structure similar to phospholipids derived from biological membranes, and are known to have excellent properties such as being very hydrophilic and having high moisturizing properties.
  • Patent Document 6 discloses a technology that improves the wearing comfort by adding a copolymer of a phosphorylcholine group-containing monomer and butyl methacrylate to a treatment solution for soft contact lenses.
  • the present invention aims to provide a copolymer that can easily impart hydrophilicity and lubricity to the surface of a soft contact lens and maintain these properties for a long period of time, and a contact lens treatment solution using the copolymer.
  • the present invention comprises the following [1] to [4].
  • R 1 and R 2 each independently represent a hydrogen atom or a methyl group.
  • X represents O or NR 3 , where R 3 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.
  • R 4 O represents an oxyalkylene group having 2 to 4 carbon atoms, R 4 O contains at least two kinds of oxyalkylene groups having different carbon numbers, and the addition form thereof may be either block or random, and p represents the average number of moles of oxyalkylene groups added, which is a number from 4 to 100.
  • [2] The copolymer according to [1], wherein the copolymer has a constitutional unit represented by the following formula (C) or (D), and the sum of the molar ratios nC and nD of the constitutional units represented by the following formula ( C ) or (D) relative to the entire copolymer is more than 0 mol% and 50 mol% or less.
  • R 5 is H or a methylene group
  • R 6 is an alkyl group having 1 to 5 carbon atoms, or when R 5 is a methylene group, an alkylene group having 1 to 5 carbon atoms, the end of which is bonded to R 5 to form a cyclic structure.
  • R 7 is a hydrogen atom or a methyl group
  • Y is O or NR 10
  • R 10 is H or an alkyl group having 1 to 4 carbon atoms
  • E 1 is a structure represented by formula (E)
  • E 1 is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a structure represented by formula (E).
  • R 8 is H or an alkyl group having 1 to 4 carbon atoms
  • R 9 is a hydrogen atom or an alkyl group having 1 to 18 carbon atoms.
  • the copolymer of the present invention can impart excellent hydrophilicity and lubricity to the surface of soft contact lenses, and these properties are sustainable. Therefore, the copolymer of the present invention is suitable as a treatment solution for soft contact lenses.
  • FIG. 1 is a drawing for explaining wb and wf in a chromatogram (vertical axis: refractive index intensity, horizontal axis: retention time).
  • (meth)acrylate means “acrylate or methacrylate,” and the same applies to other similar terms.
  • an alkyl group may be either linear or branched.
  • all day refers to the period from when contact lenses are first worn to when they are finished being worn in one day, and is assumed to be 8 to 16 hours of continuous wear.
  • Long periods refers to the time contact lenses are worn throughout the day.
  • compositions containing the copolymer of the present invention include compositions that are applied directly to the eye, and compositions used to treat devices worn on the eye, such as contact lenses, and can be specified as follows. Specific examples include contact lens treatment solutions. Further, specific product forms of the contact lens treatment solution of the present invention include contact lens packing solutions (contact lens shipping solutions), contact lens storage solutions, contact lens cleaning solutions, contact lens cleaning and storage solutions, contact lens disinfectants, contact lens wearing agents, etc.
  • shipping solution for soft contact lenses refers to a solution that is sealed in a packaging container such as a blister package together with soft contact lenses when the soft contact lenses are distributed. Since soft contact lenses are generally used in a state where they are swollen with an aqueous solution, the lenses are sealed in a packaging container in a state where they are swollen with an aqueous solution when shipped from the factory so that they can be used immediately.
  • the copolymer (P) of the present invention contains constitutional units represented by the following formulas (A) and (B), the molar ratio nA of the constitutional units represented by the following formula (A) to the whole copolymer (P) is 10 to 80 mol %, the molar ratio nB of the constitutional units represented by the following formula (B) to the whole copolymer (P) is 20 to 90 mol %, and the weight average molecular weight is 10,000 to 2,000,000.
  • R 1 and R 2 each independently represent a hydrogen atom or a methyl group.
  • X in formula (A) is O or NR 3 , where R 3 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.
  • R 4 O in formula (B) represents an oxyalkylene group having 2 to 4 carbon atoms, R 4 O contains at least two kinds of oxyalkylene groups having different carbon numbers, and the addition form thereof may be either block or random, and p represents the average number of moles of oxyalkylene groups added and is a number from 4 to 100.
  • the copolymer (P) used in the present invention has a constitutional unit represented by general formula (A).
  • the constitutional unit is obtained by polymerizing a monomer having a phosphorylcholine structure represented by the following general formula (a) (hereinafter, also referred to as a "PC monomer").
  • PC monomer a monomer having a phosphorylcholine structure represented by the following general formula (a)
  • hydrophilicity can be imparted to the soft contact lens.
  • R 1 represents a hydrogen atom or a methyl group
  • X represents O or NR 3
  • R 3 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.
  • the PC monomer is preferably 2-((meth)acryloyloxy)ethyl 2-(trimethylammonio)ethyl phosphate, and more preferably 2-(methacryloyloxy)ethyl 2-(trimethylammonio)ethyl phosphate (hereinafter also referred to as "2-methacryloyloxyethyl phosphorylcholine”) represented by the following formula (a').
  • the content of the structural unit represented by formula (A) in the copolymer (P) (molar ratio n A ) is 10-80 mol%, preferably 15-75 mol%, more preferably 25-65 mol%, and even more preferably 30-55%. If the molar ratio n A is less than 10 mol%, the effect of improving the hydrophilicity of the soft contact lens surface cannot be expected, and if the molar ratio n A is more than 80 mol%, the content of the structural unit represented by formula (B) is reduced, the adsorption force of the copolymer (P) to the soft contact lens surface is reduced, and the durability of the good wearing feeling is insufficient.
  • the effect of improving the hydrophilicity and lubricity of the soft contact lens surface can be further enhanced by adjusting the ratio of the structural unit represented by formula (A) and the structural unit represented by formula (B).
  • the copolymer (P) used in the present invention has a constitutional unit represented by the following formula (B).
  • the constitutional unit is obtained by polymerizing a monomer represented by the following general formula (b), that is, a monomer having a polyalkylene glycol structure (hereinafter also referred to as "PAG monomer").
  • PAG monomer a monomer having a polyalkylene glycol structure
  • the copolymer (P) may also contain multiple structural units represented by the following (B) having different values of p.
  • R2 represents a hydrogen atom or a methyl group
  • R4O represents an oxyalkylene group having 2 to 4 carbon atoms
  • R4O includes at least two types of oxyalkylene groups having different numbers of carbon atoms.
  • Formula (b) is, for example, a polyalkylene glycol mono(meth)acrylate containing at least two of oxyalkylene groups selected from oxyethylene groups (-CH 2 CH 2 O-), oxypropylene groups (-CH(CH 3 )CH 2 O-, -CH 2 CH(CH 3 )O-), and oxybutylene groups (-CH(CH 2 CH 3 )CH 2 O-, -CH 2 CH(CH 2 CH 3 )O-, -CH(CH 3 )CH(CH 3 )O-), in which the addition form of R 4 O may be either block or random, and p represents the average number of moles of oxyalkylene groups added, p being a number from 4 to 100.
  • oxyalkylene groups selected from oxyethylene groups (-CH 2 CH 2 O-), oxypropylene groups (-CH(CH 3 )CH 2 O-, -CH 2 CH(CH 3 )O-), and oxybutylene groups (-CH(CH 2 CH 3
  • the oxyalkylene groups in formulae (B) and (b) preferably have a form consisting of an oxyethylene group and an oxypropylene group, an oxyethylene group and an oxybutylene group, an oxypropylene group and an oxybutylene group, or an oxypropylene group, an oxyethylene group and an oxybutylene group, and more preferably have a form consisting of an oxyethylene group and an oxypropylene group.
  • the molar ratio of oxyethylene groups to the number of moles of all oxyalkylene groups added is 0-90%, preferably 40-90%, and more preferably 60-80%.
  • the molar ratio of oxypropylene groups added is 0-70%, more preferably 10-50%, and the molar ratio of oxybutylene groups added is 0-70%, more preferably 0-30%.
  • the molar ratio of oxyethylene groups added is more than 90%, the ratios of oxypropylene groups and oxybutylene groups are relatively reduced, and the adsorptive force to the contact lens surface is reduced.
  • the oxypropylene groups and oxybutylene groups exceed 70%, the cohesive force between the copolymers (P) becomes excessive, and the transparency of the resulting contact lens treatment solution and the contact lens after treatment is deteriorated.
  • the monomer represented by formula (b) is a monomer having a ratio wb/wf of wb to wf calculated from a chromatogram (vertical axis: refractive index intensity, horizontal axis: retention time) obtained by gel permeation chromatography ( GPC) measurement using a differential refractometer , which satisfies the following formula (1): 1.10 ⁇ w b /w f ⁇ 2.50 (1) (In formula (1), when the retention time at the maximum peak height (h) in the peak of the chromatogram is th and two retention times at 1/10 (h 1/10 ) of the maximum peak height are tf and tb (where tf ⁇ tb ), wf represents the difference between th and tf ( th - tf ), and wb represents the difference between tb and th ( tb - th )) is preferably satisfied (see FIG. 1).
  • the wb / wf of the monomer (b) is smaller than 1.10, the molecular weight distribution of the monomer (b) may be biased toward the high molecular weight side, the concentration of the polymerizable functional group may be reduced, and the polymerizability of the monomer (b) may be reduced.
  • the wb / wf is preferably 1.20 or more, and more preferably 1.30 or more.
  • the adsorptivity of the copolymer (P) to the surface of a soft contact lens may decrease.
  • wb / wf is 2.00 or less, more preferably 1.80 or less.
  • the chromatogram for calculating w b /w f (vertical axis: refractive index intensity, horizontal axis: retention time) was obtained by using an EcoSEC GPC calculation program, with a gel permeation chromatography (GPC) system equipped with an HLC-8320GPC (registered trademark), a guard column equipped with a SHODEXKF-G, and three SHODEXKF804L columns in series, a column temperature of 40° C., tetrahydrofuran as a developing solvent flowing at a flow rate of 1 mL/min, and 0.1 mL of a 0.1 wt % tetrahydrofuran solution of polyalkylene glycol mono(meth)acrylate injected.
  • GPC gel permeation chromatography
  • the content (molar ratio n B ) of the structural unit represented by formula (B) in copolymer (P) is 20 to 90 mol %, preferably 25 to 85 mol %, more preferably 35 to 75 mol %, and even more preferably 45 to 70 mol %.
  • copolymer (P) used in the present invention has a monomer represented by formula (B) as a structural unit, the adsorptive power of copolymer (P) to the surface of a soft contact lens can be improved, and the durability of the wearing comfort can be improved.
  • the content of the structural unit represented by formula (B) is preferably greater than the content of the structural unit represented by formula (A) (molar ratio nA ). This further enhances the effect of improving the hydrophilicity and lubricity of the soft contact lens surface.
  • the ratio of the molar ratio nA to the molar ratio nB ( nB / nA ) is preferably 0.5 to 7.0, and more preferably 1.0 to 3.0.
  • p is 4 to 100, preferably 5 to 70, and more preferably 7 to 40. If p is less than 4, the adhesive force of the copolymer (P) to the surface of a soft contact lens decreases, and if it is greater than 100, the cohesive force between the copolymers (P) becomes strong, and the transparency of the resulting contact lens treatment solution and the contact lens after treatment deteriorates.
  • the above formula (b) can be produced by adding ethylene oxide, propylene oxide, or butylene oxide (preferably propylene oxide or ethylene oxide) to a starting material (e.g., 2-hydroxypropyl methacrylate) in the presence of a composite metal cyanide complex catalyst (hereinafter sometimes referred to as "DMC catalyst").
  • a composite metal cyanide complex catalyst hereinafter sometimes referred to as "DMC catalyst”
  • the starting material and the DMC catalyst are added to a reaction vessel, and at least two of ethylene oxide, propylene oxide, and butylene oxide (hereinafter collectively referred to as "alkylene oxides having 2 to 4 carbon atoms") are added continuously or intermittently under stirring in an inert gas atmosphere to carry out addition polymerization.
  • the alkylene oxides having 2 to 4 carbon atoms may be added under pressure or at atmospheric pressure.
  • the reaction temperature for adding an alkylene oxide having 2 to 4 carbon atoms to the starting material is preferably 50°C to 120°C, and more preferably 70°C to 90°C. If the reaction temperature is lower than 50°C, the reaction rate is very slow, and if it is higher than 120°C, problems such as polymerization of the polymerizable groups in the starting material and discoloration occur.
  • a known DMC catalyst can be used in the present invention, for example, the DMC catalyst described in JP-A-2022-130139.
  • a particularly preferred DMC catalyst is Zn(II) 3 [Co(III)(CN) 6 ] 2 (H 2 O) 4 (tert-butyl alcohol) 2 .
  • the amount of the DMC catalyst used is not particularly limited, but is preferably 0.0001 to 0.1 parts by mass, and more preferably 0.001 to 0.05 parts by mass, per 100 parts by mass of the monomer represented by formula (b).
  • the DMC catalyst may be added to the reaction system all at once at the beginning, or may be added in portions one by one. After the polymerization reaction is completed, the DMC catalyst is removed.
  • the catalyst can be removed by known methods such as filtration, centrifugation, or treatment with a synthetic adsorbent.
  • hydroquinone (HQ), hydroquinone monomethyl ether (MQ), 2,6-di-tert-butylhydroxytoluene (BHT), di-tert-butylhydroxyanisole (BHA), ⁇ -tocopherol, ⁇ -tocopherol, ⁇ -tocopherol, etc. may be added to the reaction system as a polymerization inhibitor.
  • the polymerization inhibitor is preferably MQ and/or BHT, more preferably BHT.
  • the amount of polymerization inhibitor added is preferably 0.001 to 0.3 parts by mass per 100 parts by mass of the total of the starting material (e.g., 2-hydroxypropyl methacrylate) and the alkylene oxide having 2 to 4 carbon atoms. If the amount added is less than 0.001 part by mass, the function of the polymerization inhibitor becomes insufficient, and gelation may occur during the addition of the alkylene oxide having 2 to 4 carbon atoms. If the amount added is more than 0.3 parts by mass, the purity of the resulting compound of formula (1b') may be low.
  • the copolymer (P) used in the present invention may contain a structural unit represented by the following formula (C) or (D).
  • the structural unit is obtained by polymerizing a monomer represented by the following general formula (c) or (d), respectively.
  • R 5 is H or a methylene group
  • R 6 is an alkyl group having 1 to 5 carbon atoms, or when R 5 is a methylene group, R 6 is an alkylene group having 1 to 5 carbon atoms that is bonded to R 5 to form a cyclic structure.
  • R 7 is a hydrogen atom or a methyl group
  • Y is O or NR 10
  • R 10 is H or an alkyl group having 1 to 4 carbon atoms
  • E 1 is a structure represented by formula (E)
  • E 1 is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a structure represented by formula (E).
  • R 8 is H or an alkyl group having 1 to 4 carbon atoms
  • R 9 is a hydrogen atom or an alkyl group having 1 to 18 carbon atoms.
  • Examples of the monomer represented by formula (c) include N-vinylpyrrolidone, N-vinylcaprolactam, N-vinylformamide, N-vinylacetamide, and N-methyl-N-vinylacetamide.
  • Examples of the monomer represented by formula (d) include N-methyl(meth)acrylamide, N-ethyl(meth)acrylamide, N-propyl(meth)acrylamide, N-isopropyl(meth)acrylamide, N-butyl(meth)acrylamide, N-tert-butyl(meth)acrylamide, N,N-dimethyl(meth)acrylamide, N,N-diethyl(meth)acrylamide, 2-(acetylamino)ethyl(meth)acrylate, 2-(stearamido)ethyl(meth)acrylate, and 2-palmitamidoethyl(meth)acrylate.
  • copolymer (P) contains structural units represented by formula (C) and formula (D), the total content of the structural unit represented by formula (C) (molar ratio n C ) and the content of the structural unit represented by formula (D) (molar ratio n D ) in copolymer (P) is preferably more than 0 mol and not more than 50 mol%, and more preferably 10 to 50 mol%.
  • the monomer in which E 1 in the formula (d) is the formula (E) is, for example, as described in JP 2017-160380 A, which can be synthesized by an esterification reaction between an alcohol having an amide structure at its terminal and (meth)acrylic acid or (meth)acrylic acid chloride.
  • Copolymer (P) may contain polymerizable monomers other than the PC monomer, PAG monomer, and the structural units represented by (c) or (d) within a range that does not impair the effects of the present invention.
  • the blending ratio of these monomers may be appropriately selected within a range that does not affect the effects of the present invention, but it is preferable that the copolymer (P) is composed only of the PC monomer and PAG monomer.
  • the other monomers may be, for example, polymerizable monomers selected from linear or branched alkyl (meth)acrylates, cyclic alkyl (meth)acrylates, aromatic group-containing (meth)acrylates, styrene-based monomers, vinyl ether monomers, vinyl ester monomers, hydroxyl group-containing (meth)acrylates, carboxyl group-containing monomers, and sulfonyl group-containing monomers.
  • polymerizable monomers selected from linear or branched alkyl (meth)acrylates, cyclic alkyl (meth)acrylates, aromatic group-containing (meth)acrylates, styrene-based monomers, vinyl ether monomers, vinyl ester monomers, hydroxyl group-containing (meth)acrylates, carboxyl group-containing monomers, and sulfonyl group-containing monomers.
  • linear or branched alkyl (meth)acrylate examples include methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, butyl (meth)acrylate, ethylhexyl (meth)acrylate, lauryl (meth)acrylate, stearyl (meth)acrylate, ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, and triethylene glycol di(meth)acrylate.
  • cyclic alkyl (meth)acrylates examples include cyclohexyl (meth)acrylate.
  • aromatic group-containing (meth)acrylates include benzyl (meth)acrylate and phenoxyethyl (meth)acrylate.
  • styrene monomer examples include styrene, methylstyrene, and chlorostyrene.
  • vinyl ether monomer include methyl vinyl ether, propyl vinyl ether, butyl vinyl ether, triethylene glycol divinyl ether, and ethylene glycol monovinyl ether.
  • vinyl ester monomers include vinyl acetate and vinyl propionate.
  • hydrophilic hydroxyl group-containing (meth)acrylates examples include hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, hydroxybutyl (meth)acrylate, and glycerol (meth)acrylate.
  • carboxyl group-containing monomer and the sulfonyl group-containing monomer include (meth)acrylic acid, styrenesulfonic acid, and (meth)acryloyloxyphosphonic acid.
  • the weight average molecular weight of the copolymer (P) is 10,000 to 2,000,000, preferably 20,000 or more, more preferably 30,000 or more, even more preferably 40,000 or more, and preferably 1,000,000 or less, more preferably 500,000 or less, and even more preferably 300,000 or less.
  • weight-average molecular weight is less than 10,000, the adhesive force to the soft contact lens surface will decrease, and the effect of the copolymer (P) on the soft contact lens surface may not be sustained. If the weight-average molecular weight is more than 2,000,000, the viscosity may increase, making handling difficult.
  • the weight average molecular weight of the copolymer (P) is the value measured by gel permeation chromatography (GPC).
  • the copolymer (P) can be prepared by copolymerizing the above-mentioned monomers. It is usually a random copolymer, but may be an alternating copolymer or a block copolymer in which the monomers are regularly arranged, or may have a graft structure in part.
  • a mixture of the monomers can be subjected to radical polymerization in the presence of a radical polymerization initiator under an inert gas atmosphere such as nitrogen, carbon dioxide, argon, or helium to obtain a copolymer (P).
  • a radical polymerization initiator under an inert gas atmosphere such as nitrogen, carbon dioxide, argon, or helium to obtain a copolymer (P).
  • the radical polymerization method can be carried out by known methods such as bulk polymerization, suspension polymerization, emulsion polymerization, and solution polymerization. Of the radical polymerization methods, solution polymerization is preferred from the viewpoint of purification, etc.
  • the copolymer (P) can be purified by general purification methods such as reprecipitation, dialysis, and ultrafiltration.
  • radical polymerization initiator examples include an azo-based radical polymerization initiator, an organic peroxide, and a persulfate.
  • examples of the azo radical polymerization initiator include 2,2'-azobis(2-methylpropionamidine) dihydrochloride (V-50), 2,2'-azobis(2-diaminopropyl) dihydrochloride, 2,2'-azobis(2-(5-methyl-2-imidazolin-2-yl)propane) dihydrochloride, 4,4'-azobis(4-cyanovaleric acid), 2,2'-azobisisobutyronitrile dihydrate, 2,2'-azobis(2,4-dimethylvaleronitrile), and 2,2'-azobisisobutyronitrile (AIBN).
  • V-50 2,2'-azobis(2-methylpropionamidine) dihydrochloride
  • 2,2'-azobis(2-diaminopropyl) dihydrochloride 2,2'-azobis(2-(5
  • organic peroxides examples include t-butyl peroxyneodecanate (Perbutyl (registered trademark) ND), benzoyl peroxide, diisopropyl peroxydicarbonate, t-butyl peroxy-2-ethylhexanoate, t-butyl peroxypivalate, t-butyl peroxyisobutyrate, lauroyl peroxide, t-butyl peroxydecanoate, and succinic acid peroxide (succinyl peroxide).
  • persulfate oxides include ammonium persulfate, potassium persulfate, and sodium persulfate.
  • radical polymerization initiators can be used alone or in combination of two or more.
  • the amount of the polymerization initiator used is usually 0.001 to 10 parts by mass, preferably 0.02 to 5.0 parts by mass, and more preferably 0.03 to 3.0 parts by mass, based on 100 parts by mass of the total of the monomers.
  • the polymerization reaction of the copolymer (P) can be carried out in the presence of a solvent.
  • the solvent is not particularly limited as long as it dissolves each monomer composition and is not reactive itself, and examples of the solvent include water, alcohol solvents, ketone solvents, ester solvents, linear or cyclic ether solvents, and nitrogen-containing solvents.
  • the alcohol solvent include methanol, ethanol, n-propanol, and isopropanol.
  • the ketone solvent include acetone, methyl ethyl ketone, and diethyl ketone.
  • An example of the ester solvent is ethyl acetate.
  • linear or cyclic ether solvents examples include ethyl cellosolve and tetrahydrofuran.
  • nitrogen-containing solvents include acetonitrile, nitromethane, and N-methylpyrrolidone.
  • a mixed solvent of water and an alcohol is preferred.
  • the soft contact lens treatment solution of the present invention has a concentration of copolymer (P) of 0.001 w/v % or more, preferably 0.01 w/v % or more, more preferably 0.05 w/v % or more, and 5.0 w/v % or less, preferably 2.0 w/v % or less, more preferably 1.0 w/v % or less.
  • the concentration of the copolymer (P) is less than 0.001 w/v%, the amount of the copolymer (P) added is so small that sufficient hydrophilicity and lubricity and their durability cannot be obtained, whereas if the concentration exceeds 5.0 w/v%, the sterile filtration performed during production may become difficult.
  • w/v % refers to the mass of a certain component in 100 mL of solution, expressed in grams (g).
  • the treatment solution of the present invention contains 1.0 w/v % copolymer (P)” means that 100 mL of solution contains 1.0 g of copolymer (P).
  • the solvent used in the treatment solution of the present invention may be water, ethanol, n-propanol, isopropanol, glycerol, alcohol such as propylene glycol, or a mixture of these. Water or a mixture of water and alcohol is preferred, and water is more preferred.
  • the water used in the contact lens treatment solution of the present invention can be water that is normally used in the manufacture of pharmaceuticals and medical devices. Specifically, ion-exchanged water, purified water, sterilized purified water, distilled water, and water for injection can be used.
  • the contact lens treatment solution of the present invention may contain other ingredients, such as vitamins, amino acids, sugars, thickening agents, cooling agents, inorganic salts, salts of organic acids, acids, bases, antioxidants, stabilizers, preservatives, etc., as necessary.
  • vitamins include sodium flavin adenine dinucleotide, cyanocobalamin, retinol acetate, retinol palmitate, pyridoxine hydrochloride, panthenol, sodium pantothenate, calcium pantothenate, and the like.
  • the amino acids include aspartic acid or a salt thereof, and aminoethylsulfonic acid.
  • sugars include glucose, mannitol, sorbitol, xylitol, and trehalose.
  • thickening agents include hydroxypropylmethylcellulose and hydroxyethylcellulose.
  • cooling agent include menthol and camphor.
  • inorganic salts include sodium chloride, potassium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate, anhydrous sodium dihydrogen phosphate, potassium dihydrogen phosphate, and dipotassium hydrogen phosphate.
  • the salts of organic acids include sodium citrate and the like. Examples of the acid include phosphoric acid, citric acid, sulfuric acid, acetic acid, hydrochloric acid, and boric acid.
  • Examples of the base include potassium hydroxide, sodium hydroxide, borax, trishydroxymethylaminomethane, monoethanolamine, and the like.
  • Examples of the antioxidant include tocopherol acetate and dibutylhydroxytoluene.
  • examples of stabilizers include sodium edetate, glycine, and taurine.
  • Examples of preservatives include benzalkonium chloride, chlorhexidine gluconate, potassium sorbate, methylparaben, ethylparaben, propylparaben, isopropylparaben, butylparaben, isobutylparaben, polyhexanide hydrochloride, and sulfamexazole.
  • the pH of the contact lens treatment solution of the present invention is preferably 3.0 to 8.0, more preferably 3.5 to 7.8, even more preferably 4.0 to 7.6, and still more preferably 4.5 to 7.5.
  • the pH of the contact lens treatment solution refers to a value measured in accordance with the 18th Edition of the Japanese Pharmacopoeia, General Test Method 2.54 pH Measurement Method.
  • the osmotic pressure of the contact lens treatment solution of the present invention is preferably 200 to 400 mOsm, more preferably 225 to 375 mOsm, even more preferably 230 to 350 mOsm, and even more preferably 240 to 340 mOsm.
  • the osmotic pressure ratio is preferably 0.7 to 1.4, more preferably 0.7 to 1.3, and even more preferably 0.8 to 1.2.
  • the osmotic pressure of the contact lens treatment solution refers to a value measured in accordance with the 18th Edition of the Japanese Pharmacopoeia, General Test Method 2.47 Osmotic Pressure Measurement Method (Osmolarity Measurement Method), and the osmotic pressure ratio refers to a value obtained by dividing the obtained osmotic pressure value by the osmotic pressure value (286 mOsm) of 0.9 mass % physiological saline solution.
  • the soft contact lens treatment solution of the present invention can be produced by a general method for producing a contact lens solution. For example, it can be produced by mixing and stirring the polymer (P), a solvent and other components as necessary.
  • the obtained soft contact lens treatment solution may be subjected to a procedure such as sterilization filtration as necessary.
  • the reaction mixture was filtered to remove the precipitate, and the filtrate was washed with water, a saturated aqueous solution of sodium bicarbonate, and a saturated aqueous solution of sodium chloride in that order, and then dried with sodium sulfate.
  • the mixture was concentrated under reduced pressure with a rotary evaporator to obtain an oily product.
  • the mixture was further purified by silica gel chromatography using hexane and ethyl acetate as eluents, and the example compound 2-(acetylamino)ethyl methacrylate was obtained.
  • the structure was confirmed by 1 H NMR.
  • 2-(acetylamino)ethyl methacrylate (MAEM) was synthesized according to the procedure described in JP-A-2017-160380.
  • MPC 2-methacryloyloxyethyl phosphorylcholine (product of NOF Corporation)
  • MAEM 2-(acetylamino)ethyl methacrylate (synthesized in Synthesis Example 1-3)
  • NVP N-vinylpyrrolidone (product of Fujifilm Wako Pure Chemical Industries, Ltd.) Table 1 summarizes the corresponding formulas of the compounds used.
  • PB-ND Perbutyl (registered trademark) ND
  • Lens A One Day Fine UV Plus, a soft contact lens (a product of Seed Co., Ltd.)
  • Lens B AQUAFORCE UV, a soft contact lens (a product of Aimi Co., Ltd.)
  • a physiological saline solution was prepared with reference to the literature (ISO 18369-3:2017, Ophthalmic Optics-Contact Lenses Part 3: Measurement Methods.). 8.3 g of sodium chloride, 5.993 g of sodium hydrogen phosphate dodecahydrate, and 0.528 g of sodium dihydrogen phosphate dihydrate were weighed out, dissolved in water to make 1000 mL, and filtered to make physiological saline solution.
  • Example 2-1> The solution of copolymer 1 was dissolved in a predetermined amount of physiological saline to prepare a 5 wt % polymer solution as shown in Table 2 below. Furthermore, 2 g of the polymer solution was mixed with 98 g of physiological saline to prepare a contact lens treatment solution as shown in Table 2 below. Test contact lenses treated with this contact lens treatment solution were evaluated for hydrophilicity, lubricity and durability. The evaluation results are shown in Table 2 below.
  • Examples 2-2 to 2-9 The hydrophilicity, lubricity and durability of test contact lenses treated with contact lens treatment solutions prepared according to the same procedure as in Example 1 were evaluated, except that the polymers shown in Tables 2 and 3 were used. The evaluation results are shown in Tables 2 and 3.
  • the surface hydrophilicity of the soft contact lenses was evaluated according to the following procedure: Surface hydrophilicity evaluation assuming the start of wearing the soft contact lenses (1) 10 mL of physiological saline was added to a 15 mL conical tube, and five test contact lenses removed from the blister pack were immersed in the solution, and the lenses were shaken at room temperature for 6 hours at a rotation speed of 50 rpm using a roller mixer. (2) The test contact lenses were taken out and each was placed in a 10 mL glass vial containing 5 mL of the prepared soft contact lens treatment solution. (3) The container was sterilized at 121°C for 20 minutes. (4) The test contact lens was removed from the glass vial, and the time (BUT) until the water film on the lens surface disappeared was measured with a stopwatch and evaluated according to the following criteria.
  • test contact lens taken out of the glass vial was immersed in the saline solution, followed by shaking at 80 rpm at 37° C. for 4 hours using a shaker.
  • the test contact lenses were removed from the 12-well plate, and the time (BUT) until the water film on the lens surface disappeared was measured with a stopwatch and evaluated according to the following criteria.
  • the evaluation assuming the end of wearing takes into account the actual tear volume and blink rate throughout the day, and estimates the condition of the contact lenses after wearing them all day (12 hours of continuous wear).
  • the evaluation criteria are as follows: 4 points: 20 seconds or more 3 points: 15 seconds or more 2 points: 10 seconds or more but less than 15 seconds 1 point: 5 seconds or more but less than 10 seconds 0 point: Less than 5 seconds
  • the lubricity evaluation of the contact lenses was carried out according to the following procedure: Lubricity evaluation assuming the start of wearing soft contact lenses (1) 10 mL of physiological saline was added to a 15 mL conical tube, and five test contact lenses removed from a blister pack were immersed in the solution, and the solution was shaken at room temperature for 6 hours at a rotation speed of 50 rpm using a roller mixer. (2) The test contact lenses were taken out and each was placed in a 10 mL glass vial containing 5 mL of the prepared soft contact lens treatment solution. (3) The container was sterilized at 121°C for 20 minutes.
  • test contact lens was removed from the glass vial, and the friction coefficient in physiological saline was measured using a nanotribometer NTR3 (probe material: polypropylene, load: 2 mN, movement distance: 1.00 mm, speed: 0.1 mm/s), and the results were evaluated according to the following criteria.
  • Lubricity evaluation assuming the end of wearing soft contact lenses (1) 10 mL of physiological saline was added to a 15 mL conical tube, and five test contact lenses removed from their blister packs were immersed in the solution, followed by shaking at room temperature for 6 hours at a rotation speed of 50 rpm using a roller mixer. (2) The test contact lenses were taken out and each was placed in a 10 mL glass vial containing 5 mL of the prepared soft contact lens treatment solution. (3) The container was sterilized at 121°C for 20 minutes. (4) 2 mL of physiological saline was added to one well of a 12-well plate, and one test contact lens taken out of the glass vial was immersed in the saline solution, followed by shaking at 80 rpm at 37° C.
  • test contact lenses were removed from the 12-well plate, and the friction coefficient was measured using a nanotribometer NTR3 (probe material: polypropylene, load: 2 mN, movement distance: 1.00 mm, speed: 0.1 mm/s) and evaluated according to the following criteria.
  • the evaluation assuming the end of wearing takes into account the actual tear volume and blink rate throughout the day, and estimates the condition of the contact lenses after wearing them all day (12 hours of continuous wear).
  • the evaluation criteria are as follows: 4 points: less than 0.30 3 points: 0.30 or more, less than 0.5 2 points: 0.50 or more, less than 1.0 1 point: 1.0 or more, less than 1.5 0 point: 1.5 or more
  • ⁇ Sustainability evaluation> the durability was evaluated based on the evaluation results of hydrophilicity and lubricity and was evaluated according to the following criteria.
  • the scores for the assumed time at the start and end of wearing were reduced by 2 points in either evaluation.
  • the scores for the assumed time at the start and end of wearing were reduced by 2 points in both evaluations, or the scores for the assumed time at the start and end of wearing were reduced by 3 points or more in either evaluation.
  • the contact lens treatment solutions of Examples 2-2, 2-4, 2-5, and 2-9 were able to impart excellent hydrophilicity and excellent lubricity to the surface of soft contact lenses at the start and end of wear, and the persistence of these properties was also very good. That is, the contact lens treatment solutions of Examples 2-2, 2-4, 2-5, and 2-9 were able to impart an excellent wearing sensation to soft contact lenses for a long period of time due to their excellent hydrophilicity and lubricity and the persistence of these properties.
  • the contact lens treatment solutions of Examples 2-7 and 2-8 were able to impart good hydrophilicity and good lubricity to the surface of soft contact lenses at the start and end of wear, and the persistence of these properties was also very good.
  • the contact lens treatment solutions of Examples 2-7 and 2-8 were able to impart good wearing comfort to soft contact lenses for long periods of time due to their good hydrophilicity and good lubricity and the persistence of these properties.
  • the contact lens treatment solutions of Examples 2-1, 2-3, and 2-6 were able to impart good hydrophilicity and good lubricity to the surface of soft contact lenses at the start and end of wear, and the persistence of these properties was also good. That is, the contact lens treatment solutions of Examples 2-1, 2-3, and 2-6 were able to impart good wearing comfort to soft contact lenses for long periods of time due to their good hydrophilicity and lubricity and the persistence of these properties.
  • the contact lens treatment solution of Comparative Example 1-1 had good hydrophilicity at the start of use compared to the other Examples, but was significantly inferior in durability.
  • the contact lens treatment solution of Comparative Example 1-2 had good hydrophilicity as expected at the start of wearing, but did not have sufficient lubricity and was not comfortable to wear.
  • the contact lens treatment solution of Comparative Example 1-3 had good hydrophilicity as expected at the start of use, but did not have sufficient lubricity, and the durability and wearing comfort were also insufficient.
  • the contact lens treatment solution of Comparative Example 1-4 had good hydrophilicity as expected at the start of wearing, but did not have sufficient lubricity and was extremely poor in durability.
  • the contact lens treatment solution of Comparative Example 1-5 provided a good wearing sensation as expected at the beginning of use, but was significantly inferior in durability.
  • the soft contact lens treatment solution of the present invention By using the soft contact lens treatment solution of the present invention on soft contact lenses, it is possible to impart excellent wearing comfort to the soft contact lenses all day (for a long period of time).

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
  • Polyethers (AREA)

Abstract

L'invention propose un copolymère qui peut facilement conférer des propriétés hydrophiles et des propriétés de lubrification à la surface de lentilles de contact souples, et une longue durée de vie supérieure auxdites propriétés. Le copolymère présente des unités constitutives représentées par les formules (A) et (B). Un rapport molaire nA de l'unité constitutive représentée par la formule (A) par rapport à la totalité du copolymère (P) est de 10 à 80 % en moles, un rapport molaire nB de l'unité constitutive représentée par la formule (B) par rapport à la totalité du copolymère (P) est de 20 à 90 % en moles, et le poids moléculaire moyen en poids du copolymère est de 10 000 à 2 000 000. [Dans la formule (A) et la formule (B), R1 et R2 représentent chacun indépendamment un atome d'hydrogène ou un groupe méthyle.] X dans la formule (A) correspond à O ou NR3, R3 étant un atome d'hydrogène ou un groupe alkyle ayant un nombre d'atomes de carbone de 1 à 4. R4O dans la formule (B) représente un groupe oxyalkylène ayant un nombre d'atomes de carbone de 2 à 4, R4O comprenant au moins deux types de groupes oxyalkylène ayant différents nombres d'atomes de carbone, une forme supplémentaire de ceux-ci peut être sous forme de bloc ou aléatoire, et p représente le nombre moyen de moles des groupes oxyalkylène ajoutés et est un nombre de 4 à 100.]
PCT/JP2024/010658 2023-03-29 2024-03-19 Copolymère et solution de traitement de lentille de contact Pending WO2024203572A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2023-053617 2023-03-29
JP2023053617 2023-03-29

Publications (1)

Publication Number Publication Date
WO2024203572A1 true WO2024203572A1 (fr) 2024-10-03

Family

ID=92904776

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2024/010658 Pending WO2024203572A1 (fr) 2023-03-29 2024-03-19 Copolymère et solution de traitement de lentille de contact

Country Status (2)

Country Link
TW (1) TW202438545A (fr)
WO (1) WO2024203572A1 (fr)

Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005008607A (ja) * 2003-06-23 2005-01-13 National Institute Of Advanced Industrial & Technology インスリン分泌促進ならびにエンドセリン−１産生抑制物質
CN102796224A (zh) * 2012-08-01 2012-11-28 刘丽平 多功能仿生聚合物及其制备方法和应用
CN103193927A (zh) * 2013-04-27 2013-07-10 南京构友生物材料有限公司 可键合的血液友好聚合物及其制法与用途
JP2013228383A (ja) * 2012-03-27 2013-11-07 Sumitomo Bakelite Co Ltd 検出キットおよび検査方法
WO2014192731A1 (fr) * 2013-05-27 2014-12-04 Jsr株式会社 Agent de traitement de surface pour une surface configurée à partir d'un matériau inorganique, outil et dispositif présentant une surface modifiée, et procédé de fabrication de l'outil et du dispositif
WO2017018425A1 (fr) * 2015-07-27 2017-02-02 Jsr株式会社 Procédé de production de dispositif médical, et dispositif médical
WO2017022815A1 (fr) * 2015-08-04 2017-02-09 Jsr株式会社 Composition polymère, article, dispositif médical, procédé de production d'article, et procédé de production d'amas cellulaire
JP2018070716A (ja) * 2016-10-27 2018-05-10 住友ベークライト株式会社 共重合体、生体分子捕捉用の生理活性物質固定化ポリマー、コーティング組成物、および物品
JP2018178072A (ja) * 2017-04-13 2018-11-15 株式会社日本触媒 生体適合性医療用材料
JP2019026825A (ja) * 2017-08-03 2019-02-21 住友ベークライト株式会社 共重合体、コーティング組成物、及び物品
JP2021509738A (ja) * 2018-01-30 2021-04-01 アルコン インク． その上に潤滑性コーティングを有するコンタクトレンズ
JP2022535605A (ja) * 2019-06-28 2022-08-09 アルコン インク． 眼用組成物

Patent Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005008607A (ja) * 2003-06-23 2005-01-13 National Institute Of Advanced Industrial & Technology インスリン分泌促進ならびにエンドセリン−１産生抑制物質
JP2013228383A (ja) * 2012-03-27 2013-11-07 Sumitomo Bakelite Co Ltd 検出キットおよび検査方法
CN102796224A (zh) * 2012-08-01 2012-11-28 刘丽平 多功能仿生聚合物及其制备方法和应用
CN103193927A (zh) * 2013-04-27 2013-07-10 南京构友生物材料有限公司 可键合的血液友好聚合物及其制法与用途
WO2014173299A1 (fr) * 2013-04-27 2014-10-30 南京构友生物材料有限公司 Polymère hémocompatible pouvant être collé, et son procédé de préparation et son utilisation
WO2014192731A1 (fr) * 2013-05-27 2014-12-04 Jsr株式会社 Agent de traitement de surface pour une surface configurée à partir d'un matériau inorganique, outil et dispositif présentant une surface modifiée, et procédé de fabrication de l'outil et du dispositif
WO2017018425A1 (fr) * 2015-07-27 2017-02-02 Jsr株式会社 Procédé de production de dispositif médical, et dispositif médical
WO2017022815A1 (fr) * 2015-08-04 2017-02-09 Jsr株式会社 Composition polymère, article, dispositif médical, procédé de production d'article, et procédé de production d'amas cellulaire
JP2018070716A (ja) * 2016-10-27 2018-05-10 住友ベークライト株式会社 共重合体、生体分子捕捉用の生理活性物質固定化ポリマー、コーティング組成物、および物品
JP2018178072A (ja) * 2017-04-13 2018-11-15 株式会社日本触媒 生体適合性医療用材料
JP2019026825A (ja) * 2017-08-03 2019-02-21 住友ベークライト株式会社 共重合体、コーティング組成物、及び物品
JP2021509738A (ja) * 2018-01-30 2021-04-01 アルコン インク． その上に潤滑性コーティングを有するコンタクトレンズ
JP2022535605A (ja) * 2019-06-28 2022-08-09 アルコン インク． 眼用組成物

Also Published As

Publication number Publication date
TW202438545A (zh) 2024-10-01

Similar Documents

Publication Publication Date Title
JP5707843B2 (ja) コンタクトレンズ用ケア製剤及びパッケージング溶液
EP2821841B1 (fr) Préparation de nettoyage et solution de conditionnement de lentille de contact
JP7228119B2 (ja) ソフトコンタクトレンズ用処理液
US20030186825A1 (en) Contact lens wetting solution
JP5609525B2 (ja) コンタクトレンズ用ケア製剤及びパッケージング溶液
US9295747B2 (en) Contact lens care preparation and packaging solution
EP0580435B1 (fr) Diester monomère, son polymère, lentille de contact souple contenant de l'eau et une solution pour préparer des lentilles de contact
JP7567803B2 (ja) ソフトコンタクトレンズ表面を処理する方法
WO2024203572A1 (fr) Copolymère et solution de traitement de lentille de contact
US20250206863A1 (en) Copolymer and contact lens treatment solution
JP6944124B2 (ja) 眼科用剤
JP7415306B2 (ja) 眼用レンズ用組成物
WO2023074596A1 (fr) Fluide de traitement pour lentille de contact souple
JP2019060917A (ja) ソフトコンタクトレンズ保存用溶液
JP2019219620A (ja) コンタクトレンズ用溶液
JP2022151117A (ja) コンタクトレンズ用保存液
CN117561473A (zh) 软性隐形眼镜用溶液
JP7099077B2 (ja) コンタクトレンズ用溶液
WO2025206088A1 (fr) Copolymère et composition oculaire dans lequel celui-ci est utilisé
TW202540326A (zh) 共聚物及使用其的眼用組成物
JP2019101278A (ja) コンタクトレンズ用処理液
JP2019060916A (ja) ソフトコンタクトレンズ保存用溶液

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24779697

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE