Modifier for ophthalmic devices

Abstract

Provided is a modifier that is for an ophthalmological device and that is capable of imparting high wettability and lubricity to silicone hydrogel, or more specifically, a modifier that is for an ophthalmological device and that is capable of exhibiting the effect with a small contained amount. In addition, the present invention provides: a silicone hydrogel that is obtained by curing a silicone hydrogel composition containing the modifier for an ophthalmological device; and an ophthalmological device using the silicone hydrogel.　According to the present invention, it was found that a water-soluble silicone-containing water-soluble copolymer obtained by copolymerization of a phosphorylcholine group-containing monomer and a specific silicone monomer is capable of imparting high wettability and lubricity to silicone hydrogel with a small contained amount.

Description

[Technical Field]

[0001] This invention relates to contact lenses, intraocular lenses, artificial This invention relates to a modifier for ophthalmic devices, such as corneas, that contains a silicone-containing water-soluble copolymer and is optimally incorporated into the manufacturing of such devices. This application claims priority to Japanese Patent Application No. 2020-199789, as incorporated herein by reference. [Background technology]

[0002] Silicone hydrogel contact lenses have significantly higher oxygen permeability compared to conventional contact lenses, resulting in increased oxygen supply to the cornea and reduced strain on eye tissue. Silicone hydrogel contact lenses are becoming the mainstream type of contact lens prescribed in recent years and are expected to become even more widespread in the future. On the other hand, silicone hydrogel lenses have a low water content and high hydrophobicity, which makes them prone to repelling tears and accumulating lipid deposits. Furthermore, in recent years, it has been reported that friction between the eyelid conjunctival margin and the eye surface during blinking can cause shedding and degeneration of epithelial cells in the superficial layer of the eyelid conjunctiva (Non-Patent Literature 1, Non-Patent Literature 2). As a result, there is a need to impart both hydrophilicity and lubricity to silicone hydrogel lenses. Therefore, various methods are being considered to improve the hydrophilicity and lubricity of the surface of silicone hydrogel lenses. For example, plasma treatment of lenses is widely incorporated into the production process of contact lenses. Plasma treatment has the advantage of imparting relatively high hydrophilicity and durability, but it has the disadvantages of not being able to impart slipperiness and requiring large-scale capital investment. As a method that does not require large-scale capital investment, it is widely practiced to manufacture lenses using hydrophilic monomers. In particular, when 2-methacryloyloxyethyl phosphorylcholine (hereinafter sometimes abbreviated as "MPC"), which has an amphoteric structure, is used, it is known that lenses can be obtained with high hydrophilicity and lubricity.

[0003] Patent Document 1 describes a silicone hydrogel lens obtained from a specific composition that may contain MPC. However, while Patent Document 1 shows improvement in the hydrophilicity of the lens surface by measuring the water breakup time, it does not consider the slipperiness in the sense of reducing friction on the lens surface, and there is room for improvement.

[0004] Patent Document 2 discloses that a silicone hydrogel lens with good lubricity can be obtained by using MPC and certain other monomers in a specific composition ratio. However, in order to obtain good lubricity, it is necessary to add 5% by weight or more of MPC, and to obtain the highest lubricity, it is necessary to add about 20% by weight. In order to make such a high concentration of MPC compatible with a highly hydrophobic silicone component, certain constraints are placed on the lens monomer composition. Therefore, there was a need to develop technology that could be applied to a wider range of lens compositions. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] Japanese Patent Publication No. 2014-89477 [Patent Document 2] International Publication No. 2020 / 054711 [Non-patent literature]

[0006] [Non-Patent Document 1] DRKorb et al.,2002,CLAO J.,28,211-126 [Non-Patent Document 2] DRKorb et al.,2005,Eye&Contact Lens,31,2-8 [Overview of the project] [Problems that the invention aims to solve]

[0007] The object of the present invention is to provide an ophthalmic device modifier that can impart high wettability and slipperiness to silicone hydrogels, more specifically, an ophthalmic device modifier that can exhibit its effects even in small amounts. Furthermore, the invention aims to provide a silicone hydrogel obtained by curing a silicone hydrogel composition containing the ophthalmic device modifier, and an ophthalmic device using the silicone hydrogel. [Means for solving the problem]

[0008] In view of the above problems, the inventors conducted diligent studies and, to their surprise, discovered that a water-soluble silicone-containing copolymer, obtained by copolymerizing a phosphorylcholine group-containing monomer with a specific silicone monomer, can impart high wettability and slipperiness to silicone hydrogels with only a small amount of content, thus completing the present invention. In other words, the present invention is as follows:

[0009] 1. A copolymer comprising a constituent unit based on a hydrophilic monomer a represented by the following formula (1), and a constituent unit based on a silicone monomer b represented by the following formula (2) or formula (3), wherein the copolymer does not dissolve at 1.0% (w / v) in water at 20°C, but dissolves at 0.1% (w / v) or more in boiling water, and is a modifier for ophthalmic devices. [ka] (In formula (1), R 1 represents a hydrogen atom or a methyl group, L 1 R represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group. 2 ~R 4 Each of these independently represents a hydrocarbon group with 1 to 3 carbon atoms. [ka] (In formula (2), X 1represents a (meth)acryloyloxy group, 3-(2-hydroxyethyloxycarbonyl)-2-methylenepropanoyloxy group, 3-(2-hydroxyethyloxycarbonyl)-3-butenoyloxy group or 3-(2-hydroxyethyloxycarbonyl)-2-propenoyloxy group, and L 2 represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxy group, and R 5 ~R 13 each independently represents a methyl group or an ethyl group, and n1 represents 0 or 1.) [Chemical formula] (In formula (3), R 14 represents a hydrogen atom or a methyl group, and L 3 represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxy group, n2 represents an integer of 4 to 20, and R 15 ~R 17 each independently represents an alkyl group having 1 to 8 carbon atoms.) 2. The modifier for ophthalmic devices according to item 1 above, wherein the copolymer further contains a structural unit based on a thermally reactive monomer or a photo-reactive monomer c. 3. The structural unit based on the hydrophilic monomer a represented by the formula (1) is 2-methacryloyloxyethyl phosphorylcholine, and the structural unit based on the silicone monomer b represented by the formula (2) or formula (3) is tris(trimethylsiloxy)silylpropyl methacrylate, polydimethylsiloxane monomethacrylate, 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate or 3-(3-(methylbis(trimethylsiloxy)silyl)propyl)glycerol-1-methacrylate, and the structural unit based on the thermally reactive monomer or the photo-reactive monomer c is glycidyl methacrylate, methacryloyloxybenzophenone or 4-(4-azidobenzoyloxymethyl)vinylbenzene. The modifier for ophthalmic devices according to item 2 above. 4. Constituent units based on the hydrophilic monomer a represented by formula (1), constituent units based on the silicone monomer b represented by formula (2) or formula (3), and / or heat The combination of constituent units based on reactive monomers or photoreactive monomers c is selected from any one of the following, as described in item 2 above, for the ophthalmic device modifier. 1) 2-Methacryloyloxyethyl phosphorylcholine and tris(trimethylsiloxy)silylpropyl methacrylate 2) 2-Methacryloyloxyethyl phosphorylcholine and polydimethylsiloxane monomethacrylate 3) 2-Methacryloyloxyethyl phosphorylcholine and 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate 4) 2-Methacryloyloxyethyl phosphorylcholine, tris(trimethylsiloxy)silylpropyl methacrylate and glycidyl methacrylate 5) 2-Methacryloyloxyethyl phosphorylcholine, polydimethylsiloxane monomethacrylate, and glycidyl methacrylate 6) 2-Methacryloyloxyethyl phosphorylcholine, tris(trimethylsiloxy)silylpropyl methacrylate, and methacryloyloxybenzophenone 7) 2-Methacryloyloxyethyl phosphorylcholine, polydimethylsiloxane monomethacrylate, and methacryloyloxybenzophenone 8) 2-methacryloyloxyethyl phosphorylcholine, 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate and 4-(4-azidobenzoyloxymethyl)vinylbenzene, and 9) 2-Methacryloyloxyethyl phosphorylcholine, 3-(3-(methylbis(trimethylsiloxy)silyl)propyl)glycerol-1-methacrylate and methacryloyloxybenzophenone 5. A silicone hydrogel composition comprising the copolymer and base composition described in item 1 or 2 above, A silicone hydrogel composition comprising 0.05 to 2 parts by mass of the copolymer per 100 parts by mass of the base composition. 6. A silicone hydrogel obtained by curing the silicone hydrogel composition described in item 5 above. 7. An ophthalmic device using the silicone hydrogel described in item 6 above. 8. An ophthalmic device described in item 7 above, which is a soft contact lens. 9. A method for producing a silicone hydrogel, comprising the step of curing a silicone hydrogel composition containing a copolymer. Herein, the copolymer is a copolymer containing a constituent unit based on a hydrophilic monomer a represented by the following formula (1), and a constituent unit based on a silicone monomer b represented by the following formula (2) or formula (3), wherein the copolymer does not dissolve in water at 20°C at a concentration of 1.0% (w / v), but dissolves in boiling water at a concentration of 0.1% (w / v) or more, and is a method for producing such a copolymer. [ka] (In formula (1), R 1 represents a hydrogen atom or a methyl group, L 1 R represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group. 2 ~R 4 Each of these independently represents a hydrocarbon group with 1 to 3 carbon atoms. [ka] (In formula (2), X 1 L represents a (meth)acryloyloxy group, a 3-(2-hydroxyethyloxycarbonyl)-2-methylenepropanoyloxy group, a 3-(2-hydroxyethyloxycarbonyl)-3-butenoyloxy group, or a 3-(2-hydroxyethyloxycarbonyl)-2-propenoyloxy group. 2 R represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group. 5 ~R 13Each of these independently represents either a methyl group or an ethyl group, and n1 represents either 0 or 1. [ka] (In formula (3), R 14 represents a hydrogen atom or a methyl group, L 3 n represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group, n2 represents an integer from 4 to 20, and R 15 ~R 17 Each of these independently represents an alkyl group with 1 to 8 carbon atoms. 10. The method for producing a silicone hydrogel according to paragraph 9, wherein the amount of the copolymer in the silicone hydrogel composition is 0.1 to 1 part by mass. 11. The method for producing a silicone hydrogel according to paragraph 9, wherein the silicone hydrogel composition further comprises a base composition, and the copolymer is present in an amount of 0.05 to 2 parts by mass per 100 parts by mass of the base composition. 12. A method for producing a silicone hydrogel according to paragraph 9, wherein the constituent unit based on the hydrophilic monomer a represented by formula (1) is 2-methacryloyloxyethyl phosphorylcholine, the constituent unit based on the silicone monomer b represented by formula (2) or formula (3) is tris(trimethylsiloxy)silylpropyl methacrylate, polydimethylsiloxane monomethacrylate, 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate or 3-(3-(methylbis(trimethylsiloxy)silyl)propyl)glycerol-1-methacrylate), and the constituent unit based on the thermally reactive monomer or photoreactive monomer c is glycidyl methacrylate, methacryloyloxybenzophenone or 4-(4-azidobenzoyloxymethyl)vinylbenzene. 13. Constituent units based on the hydrophilic monomer a represented by formula (1), constituent units based on the silicone monomer b represented by formula (2) or formula (3), and / or heatA method for producing a silicone hydrogel as described in paragraph 9, wherein the combination of constituent units based on a reactive monomer or a photoreactive monomer c is selected from any one of the following: 1) 2-Methacryloyloxyethyl phosphorylcholine and tris(trimethylsiloxy)silylpropyl methacrylate 2) 2-Methacryloyloxyethyl phosphorylcholine and polydimethylsiloxane monomethacrylate 3) 2-Methacryloyloxyethyl phosphorylcholine and 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate 4) 2-Methacryloyloxyethyl phosphorylcholine, tris(trimethylsiloxy)silylpropyl methacrylate and glycidyl methacrylate 5) 2-Methacryloyloxyethyl phosphorylcholine, polydimethylsiloxane monomethacrylate, and glycidyl methacrylate 6) 2-Methacryloyloxyethyl phosphorylcholine, tris(trimethylsiloxy)silylpropyl methacrylate, and methacryloyloxybenzophenone 7) 2-Methacryloyloxyethyl phosphorylcholine, polydimethylsiloxane monomethacrylate, and methacryloyloxybenzophenone 8) 2-methacryloyloxyethyl phosphorylcholine, 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate and 4-(4-azidobenzoyloxymethyl)vinylbenzene, and 9) 2-Methacryloyloxyethyl phosphorylcholine, 3-(3-(methylbis(trimethylsiloxy)silyl)propyl)glycerol-1-methacrylate and methacryloyloxybenzophenone 14. Use of a copolymer containing a constituent unit based on a hydrophilic monomer a represented by the following formula (1), and a constituent unit based on a silicone monomer b represented by the following formula (2) or formula (3), which does not dissolve in water at 20°C at a concentration of 1.0% (w / v), but dissolves in boiling water at a concentration of 0.1% (w / v) or more, as a modifier for ophthalmic devices. [ka] (In formula (1), R 1 represents a hydrogen atom or a methyl group, L 1 R represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group. 2 ~R 4 Each of these independently represents a hydrocarbon group with 1 to 3 carbon atoms. [ka] (In formula (2), X 1 L represents a (meth)acryloyloxy group, a 3-(2-hydroxyethyloxycarbonyl)-2-methylenepropanoyloxy group, a 3-(2-hydroxyethyloxycarbonyl)-3-butenoyloxy group, or a 3-(2-hydroxyethyloxycarbonyl)-2-propenoyloxy group. 2 R represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group. 5 ~R 13 Each of these independently represents either a methyl group or an ethyl group, and n1 represents either 0 or 1. [ka] (In formula (3), R 14 represents a hydrogen atom or a methyl group, L 3 n represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group, n2 represents an integer from 4 to 20, and R 15 ~R 17 Each of these independently represents an alkyl group with 1 to 8 carbon atoms. 15. Use as a modifier for ophthalmic devices as described in paragraph 14 above, wherein the constituent unit based on the hydrophilic monomer a represented by formula (1) is 2-methacryloyloxyethyl phosphorylcholine, the constituent unit based on the silicone monomer b represented by formula (2) or formula (3) is tris(trimethylsiloxy)silylpropyl methacrylate, polydimethylsiloxane monomethacrylate, 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate or 3-(3-(methylbis(trimethylsiloxy)silyl)propyl)glycerol-1-methacrylate), and the constituent unit based on the thermally reactive monomer or photoreactive monomer c is glycidyl methacrylate, methacryloyloxybenzophenone or 4-(4-azidobenzoyloxymethyl)vinylbenzene. 16. Constituent units based on the hydrophilic monomer a represented by formula (1), constituent units based on the silicone monomer b represented by formula (2) or formula (3), and / or heat A combination of constituent units based on reactive monomers or photoreactive monomers c is selected from any one of the following for use in the manufacture of ophthalmic device modifiers as described in paragraph 14 above. 1) 2-Methacryloyloxyethyl phosphorylcholine and tris(trimethylsiloxy)silylpropyl methacrylate 2) 2-Methacryloyloxyethyl phosphorylcholine and polydimethylsiloxane monomethacrylate 3) 2-Methacryloyloxyethyl phosphorylcholine and 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate 4) 2-Methacryloyloxyethyl phosphorylcholine, tris(trimethylsiloxy)silylpropyl methacrylate and glycidyl methacrylate 5) 2-Methacryloyloxyethyl phosphorylcholine, polydimethylsiloxane monomethacrylate, and glycidyl methacrylate 6) 2-Methacryloyloxyethyl phosphorylcholine, tris(trimethylsiloxy)silylpropyl methacrylate, and methacryloyloxybenzophenone 7) 2-Methacryloyloxyethyl phosphorylcholine, polydimethylsiloxane monomethacrylate, and methacryloyloxybenzophenone 8) 2-methacryloyloxyethyl phosphorylcholine, 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate and 4-(4-azidobenzoyloxymethyl)vinylbenzene, and 9) 2-Methacryloyloxyethyl phosphorylcholine, 3-(3-(methylbis(trimethylsiloxy)silyl)propyl)glycerol-1-methacrylate and methacryloyloxybenzophenone [Effects of the Invention]

[0010] By using the ophthalmic device modifier of the present invention, high wettability and slipperiness can be imparted to silicone hydrogels. [Modes for carrying out the invention]

[0011] The present invention will be described in more detail below. In this specification, "(meth)acrylic acid" means "acrylic acid or methacrylic acid," and the same applies to other similar terms. Furthermore, when preferred numerical ranges (e.g., ranges for content or weight-average molecular weight) are described in steps in this specification, each lower limit and upper limit can be combined independently. For example, in the description "preferably 10 to 100, more preferably 20 to 90", the "preferred lower limit: 10" and the "more preferred upper limit: 90" can be combined to arrive at "10 to 90".

[0012] One form of the copolymer (hereinafter sometimes referred to as "the copolymer of the present invention") contained in the ophthalmic device modifier or silicone hydrogel composition of the present invention is a copolymer obtained by copolymerizing a hydrophilic monomer a represented by the following formula (1) and a silicone monomer b represented by the following formula (2) or formula (3) (a copolymer containing a constituent unit based on the hydrophilic monomer a represented by the following formula (1) and a constituent unit based on the silicone monomer b represented by the following formula (2) or formula (3)), which does not dissolve in water at 20°C at a concentration of 1.0% (w / v) but dissolves in boiling water at a concentration of 0.1% (w / v) or more.

[0013] [ka] (In formula (1), R 1 represents a hydrogen atom or a methyl group, L 1 R represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group. 2 ~R 4 Each of these independently represents a hydrocarbon group with 1 to 3 carbon atoms.

[0014] [ka] (In formula (2), X 1 L represents a (meth)acryloyloxy group, a 3-(2-hydroxyethyloxycarbonyl)-2-methylenepropanoyloxy group, a 3-(2-hydroxyethyloxycarbonyl)-3-butenoyloxy group, or a 3-(2-hydroxyethyloxycarbonyl)-2-propenoyloxy group. 2 R represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group. 5 ~R 13 Each of these independently represents either a methyl group or an ethyl group. n1 represents either 0 or 1.

[0015] [ka] (In formula (3), R 14 L represents a hydrogen atom or a methyl group. 3 n² represents an organic group having 2 to 6 carbon atoms, which may optionally contain one ether bond and / or one hydroxyl group. n² represents an integer between 4 and 20. 15 ~R 17 Each of these independently represents an alkyl group with 1 to 8 carbon atoms.

[0016] [Hydrophilic monomer a] R of the hydrophilic monomer a represented by formula (1) 1 The symbol represents either a hydrogen atom or a methyl group, but a methyl group is preferred from the viewpoint of raw material availability. Also L 1 represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group, but from the viewpoint of raw material availability, -C2H4-, -C2H4-O-C2H4-, and -C2H5- are preferred, and -C2H5- is particularly preferred. Here, an organic group is a group composed of elements such as C, Si, N, P, O, and S, and may be a polymer having repeating units. Furthermore, its structure may include groups such as ketone groups, ester groups, ether groups, hydroxyl groups, amide groups, thioether groups, and isocyanurate groups. Also R 2 ~R 4 Each of these independently represents a hydrocarbon group having 1 to 3 carbon atoms, but from the viewpoint of raw material availability, it is preferable to use methyl groups for all of them. Therefore, specific examples of hydrophilic monomer a include 2-methacryloyloxyethyl phosphorylcholine and the like. The monomer a used in this invention may be a single monomer or a combination of multiple monomers.

[0017] [Silicone monomer b] X of silicone monomer b when represented by formula (2) 1This represents one of the polymerizable functional groups: (meth)acryloyloxy group, 3-(2-hydroxyethyloxycarbonyl)-2-methylenepropanoyloxy group, 3-(2-hydroxyethyloxycarbonyl)-3-butenoyloxy group, or 3-(2-hydroxyethyloxycarbonyl)-2-propenoyloxy group. Of these, the methacryloyloxy group is preferred from the viewpoint of raw material availability, and the 3-(2-hydroxyethyloxycarbonyl)-2-methylenepropanoyloxy group is preferred from the viewpoint of compatibility with hydrophilic monomers. Also L 2 The symbol represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group, but -n-C3H6- is preferred from the viewpoint of raw material availability. Also R 5 ~R 13 Each of these independently represents either a methyl group or an ethyl group, but from the viewpoint of raw material availability, it is preferable to have all of them be methyl groups. Furthermore, n1 represents either 0 or 1, but from the viewpoint of improving compatibility with the silicone hydrogel composition, it is preferable to set it to 1. Therefore, specific examples of monomer b represented by formula (2) include tris(trimethylsiloxy)silylpropyl methacrylate and 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate.

[0018] R of silicone monomer b when represented by formula (3) 14 The symbol represents either a hydrogen atom or a methyl group, but a methyl group is preferred from the viewpoint of storage stability of the resulting copolymer. Also L 3 represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group. Furthermore, n² represents an integer between 4 and 20. Typically, n² has a distribution, and in that case, it is preferable that its mean value is within the range of 4 to 20. Also, R 15 ~R17 Each of these independently represents an alkyl group having 1 to 8 carbon atoms. Therefore, specific examples of monomer b represented by formula (3) include polydimethylsiloxane monomethacrylate and monomethacryloyloxypropyl modified polydimethylsiloxane.

[0019] The monomer b used in this invention may be a single monomer or a combination of multiple monomers. Furthermore, either the monomer represented by formula (2) or the monomer represented by formula (3) may be used alone, or both may be used in combination. From the viewpoint of compatibility with silicone hydrogel monomer formulations (silicone hydrogel compositions), it is preferable to use the monomer represented by formula (2) alone.

[0020] [Ratio of monomer a to monomer b] The ratio of monomer a to monomer b is preferably monomer a:monomer b = 2:1 to 300:1 (mass ratio), more preferably 5:1 to 50:1, and even more preferably 7:1 to 25:1. By setting the ratio within this range, the mixture is preferably compatible with the silicone hydrogel composition, and the effect of imparting wettability and slipperiness to the silicone hydrogel obtained by curing the silicone hydrogel composition is enhanced. Furthermore, the amount of monomer b can be 0.3 to 50 parts by mass, preferably 2 to 20 parts by mass, and more preferably 4 to 14 parts by mass, relative to 100 parts by mass of monomer a. Furthermore, the combined ratio of monomers a and b to all monomers used in preparing the copolymer of the present invention is preferably 50 to 100 mol%, and more preferably 90 to 100 mol%, because this allows the effects of the present invention to be favorably expressed.

[0021] [Thermally reactive monomer or photoreactive monomer c] Another form of the copolymer of the present invention is a copolymer obtained by copolymerizing monomers a and b with a further thermoreactive monomer or photoreactive monomer c (a copolymer containing constituent units based on hydrophilic monomer a, constituent units based on silicone monomer b, and constituent units based on thermoreactive monomer or photoreactive monomer c), which does not dissolve in water at 20°C at a concentration of 1.0% (w / v), but dissolves in boiling water at a concentration of 0.1% (w / v) or more. The thermally reactive monomer or photoreactive monomer c of the present invention refers to a monomer having a functional group that can impart reactivity to a copolymer obtained by copolymerizing monomer c, such that heating or light irradiation can induce reactivity that allows the copolymer to form carbon-carbon covalent bonds with coexisting organic matter. When the method for preparing the silicone hydrogel using the copolymer of the present invention is by thermal polymerization, monomer c is preferably a thermoreactive monomer induced by heating. When the method for preparing the silicone hydrogel is by photopolymerization, a photoreactive monomer induced by light irradiation is preferred. Specific examples of monomer c whose reactivity is induced by heating include glycidyl (meth)acrylate and the like. Specific examples of monomer c whose reactivity is induced by light irradiation include 4-(meth)acryloyloxybenzophenone and (azidobenzoyloxymethyl)vinylbenzene. In line with the spirit of the present invention, it is also possible to introduce polymerizable functional groups such as (meth)acrylic groups and vinyl groups by polymer reaction after the synthesis of the copolymer by utilizing the reactivity of monomer c described above. The monomer c used in this invention may be a single monomer or a combination of multiple monomers. The ratio of monomer c to all monomers used in preparing the copolymer of the present invention is preferably 0 to 50 mol%, and more preferably 0 to 10 mol%, because this allows the effects of the present invention to be favorably expressed.

[0022] [Other monomers d] The copolymers obtained by copolymerizing monomers a and b, and copolymers obtained by copolymerizing monomers a, b, and c of the present invention may also be copolymerized with another monomer d, to the extent that the effects of the present invention are not impaired. Monomer d can be arbitrarily selected from monomers copolymerizable with monomers a, b, and c. Examples of such monomers that are preferred include (meth)acrylic acid and its derivatives, (meth)acrylamide and its derivatives, and vinyl compounds. Preferred derivatives of (meth)acrylic acid include, for example, alkyl (meth)acrylates such as methyl (meth)acrylate and ethyl (meth)acrylate, and hydroxyalkyl (meth)acrylates such as hydroxyethyl (meth)acrylate and hydroxypropyl (meth)acrylate. Examples of preferred (meth)acrylamide derivatives include dimethyl(meth)acrylamide and hydroxyethyl(meth)acrylamide. Examples of preferred vinyl compounds include hydroxyalkyl vinyl ethers such as hydroxyethyl vinyl ether and hydroxybutyl vinyl ether, oligoethylene glycol monovinyl ethers such as diethylene glycol monovinyl ether, and pyrrolidone derivatives such as N-vinylpyrrolidone. Monomer d may be a single monomer or a combination of multiple monomers. When preparing the copolymer of the present invention, the ratio of monomer d to all monomers used is preferably 0 to 10 mol%, because this is necessary for the effects of the present invention to be favorably exhibited.

[0023] [Manufacturing of copolymers] For obtaining the copolymer of the present invention, known polymerization methods such as solution polymerization, bulk polymerization, emulsion polymerization, and suspension polymerization can be used. For example, a method such as radical polymerization can be employed in which monomers a and b, and optionally monomers c and d, are polymerized in a solvent in the presence of a polymerization initiator. Any commonly used initiator can be used as the initiator for polymerization reactions. For example, in radical polymerization, aliphatic azo compounds, organic peroxides, persulfates, etc., can be used. Examples of these polymerization initiators include 2,2'-azobis(isobutyronitrile), 2,2'-azobis(2,4-dimethylvaleronitrile), benzoyl peroxide, lauroyl peroxide, diisopropyl peroxydicarbonate, t-butylperoxy-2-ethylhexanoate, t-butylperoxypivalate, t-butylperoxydiisobutyrate, potassium persulfate, ammonium persulfate, etc. Two or more of these polymerization initiators may be used in combination. In addition, redox-type radical accelerators may be used with polymerization initiators. The polymerization temperature is preferably 30 to 80°C, and more preferably 40 to 70°C. The polymerization time is also preferably 2 to 72 hours, as this allows the polymerization reaction to proceed smoothly. Furthermore, a solvent may be used to facilitate the polymerization reaction. Examples of such solvents include water, alcohols such as methanol, ethanol, and propanol, benzene, toluene, dimethylformamide, tetrahydrofuran, dioxane, chloroform, or mixtures thereof.

[0024] [Molecular weight of copolymer] The weight-average molecular weight of the copolymer of the present invention is preferably 20,000 to 2,000,000, more preferably 50,000 to 1,600,000, even more preferably 100,000 to 1,000,000, and particularly preferably 200,000 to 500,000. By setting the weight-average molecular weight within this range, it is possible to make the copolymer easily compatible with silicone hydrogel monomer formulations (silicone hydrogel compositions) and to preferably impart wettability and slipperiness to the silicone hydrogel. The weight-average molecular weight of the copolymer of the present invention can be determined in terms of polyethylene glycol by the measurement method described in the examples of this application.

[0025] [Water solubility of copolymers] The copolymer of the present invention does not dissolve in water at 20°C at a concentration of 1.0% (w / v), but dissolves in boiling water at a concentration of 0.1% (w / v) or more. If the substance has high water solubility, dissolving at 1.0% (w / v) or more in 20°C water, there is a high possibility that its compatibility with silicone hydrogel monomer formulations containing highly hydrophobic silicone components will be impaired. Conversely, if the substance has low water solubility, dissolving at 0.1% (w / v) or less in boiling water, there is a high possibility that its effect in imparting wettability to silicone hydrogels will be impaired.

[0026] The water solubility of the copolymer of the present invention can be easily evaluated by, for example, the following procedure. (1) Weigh an appropriate amount of copolymer into a heat-resistant container that can be tightly sealed. Examples of such containers include glass vacuum vials. (2) Add pure water to the container to adjust it to the specified concentration. For example, to prepare a 5.0% (w / v) solution, add 10 mL of pure water to 0.5 g of copolymer. (3) Stir under 20°C conditions and visually confirm solubility. (4) Boil under normal pressure for 30 minutes, then stir and allow to return to room temperature before visually checking for solubility. (Solubility in boiling water) Alternatively, autoclaving at 121°C for 20 minutes may be used instead of boiling. In this context, "dissolution" refers to a state in which, under visual inspection, all of the added copolymer is uniformly mixed with water, and no insoluble matter, turbidity, or stagnation is visible. The water solubility of the copolymer of the present invention is positively correlated with the ratio of monomer a / monomer b (mass ratio) of the copolymer, and negatively correlated with the weight-average molecular weight of the copolymer. Therefore, the water solubility index (WSI) can be defined as shown in equation (4) below.

number

[0027] [Silicone hydrogel composition] The present invention also applies to the following silicone hydrogel compositions. A copolymer containing a constituent unit based on a hydrophilic monomer a represented by the following formula (1), and a constituent unit based on a silicone monomer b represented by the following formula (2) or formula (3), or A copolymer comprising a constituent unit based on a hydrophilic monomer a represented by the following formula (1), a constituent unit based on a silicone monomer b represented by the following formula (2) or formula (3), and a constituent unit based on a thermally reactive monomer or a photoreactive monomer c, Here, we have copolymers that do not dissolve at 1.0% (w / v) in water at 20°C, but dissolve at 0.1% (w / v) or more in boiling water, and A silicone hydrogel composition comprising a base composition, The copolymer is contained in a silicone hydrogel composition comprising 0.05 to 2 parts by mass per 100 parts by mass of the base composition. [ka] (In formula (1), R 1 represents a hydrogen atom or a methyl group, L 1 R represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group. 2 ~R 4 Each of these independently represents a hydrocarbon group with 1 to 3 carbon atoms. [ka] (In formula (2), X 1 L represents a (meth)acryloyloxy group, a 3-(2-hydroxyethyloxycarbonyl)-2-methylenepropanoyloxy group, a 3-(2-hydroxyethyloxycarbonyl)-3-butenoyloxy group, or a 3-(2-hydroxyethyloxycarbonyl)-2-propenoyloxy group. 2R represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group. 5 ~R 13 Each of these independently represents either a methyl group or an ethyl group, and n1 represents either 0 or 1. [ka] (In formula (3), R 14 represents a hydrogen atom or a methyl group, L 3 n represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group, n2 represents an integer from 4 to 20, and R 15 ~R 17 Each of these independently represents an alkyl group with 1 to 8 carbon atoms.

[0028] [Silicone hydrogel] Another embodiment of the present invention is a silicone hydrogel obtained by curing a monomer composition (silicone hydrogel composition) containing 0.05 to 2 parts by mass of the copolymer of the present invention per 100 parts by mass of a base composition. The amount of the copolymer of the present invention in the silicone hydrogel composition is more preferably 0.1 to 1 part by mass. This allows for good compatibility with the silicone hydrogel composition and more preferably imparts wettability and slipperiness to the silicone hydrogel. Considering the above preferred ranges, it is expected that the proportion of monomer a in 100 parts by weight of the silicone hydrogel composition of the present invention will preferably be at most 2 parts by mass. In other words, by incorporating a significantly smaller amount of MPC-type hydrophilic monomer than in the prior art, it is possible to preferably impart wettability and slipperiness to the silicone hydrogel.

[0029] In this specification, the base composition refers to a mixture of monomers, reaction initiators, and other components added as needed for preparing a silicone hydrogel. The base composition preferably contains 15 parts by weight or more of an alcohol such as propanol and a hydroxyl group-containing monomer such as hydroxyethyl (meth)acrylate. This is because it enhances the compatibility of the copolymer of the present invention. Examples of compounds included in the base composition include, but are not limited to, propanol, hexanol, hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, N-vinylpyrrolidone, methyl (meth)acrylate, tetraethylene glycol di(meth)acrylate, triethylene glycol divinyl ether, (meth)acrylic acid, aminoethyl (meth)acrylate, 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate, polydimethylsiloxane mono(meth)acrylate, etc.

[0030] The preparation of silicone hydrogel compositions and the preparation of silicone hydrogels using them can be carried out using known methods such as those disclosed in International Publication WO2020 / 054711, etc. The process of curing the silicone hydrogel composition is preferably carried out by heating (thermal polymerization) or light irradiation (photopolymerization).

[0031] [A method for producing a silicone hydrogel, comprising a step of curing a silicone hydrogel composition containing the copolymer of the present invention] The present invention also includes the following methods for producing silicone hydrogels. A method for producing a silicone hydrogel, comprising the step of curing a silicone hydrogel composition containing the copolymer of the present invention. The copolymer is a copolymer containing a constituent unit based on a hydrophilic monomer a represented by the following formula (1), and a constituent unit based on a silicone monomer b represented by the following formula (2) or formula (3), wherein it does not dissolve at 1.0% (w / v) in water at 20°C, but dissolves at 0.1% (w / v) or more in boiling water. [ka] (In formula (1), R1 represents a hydrogen atom or a methyl group, L 1 R represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group. 2 ~R 4 Each of these independently represents a hydrocarbon group with 1 to 3 carbon atoms. [ka] (In formula (2), X 1 L represents a (meth)acryloyloxy group, a 3-(2-hydroxyethyloxycarbonyl)-2-methylenepropanoyloxy group, a 3-(2-hydroxyethyloxycarbonyl)-3-butenoyloxy group, or a 3-(2-hydroxyethyloxycarbonyl)-2-propenoyloxy group. 2 R represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group. 5 ~R 13 Each of these independently represents either a methyl group or an ethyl group, and n1 represents either 0 or 1. [ka] (In formula (3), R 14 represents a hydrogen atom or a methyl group, L 3 n represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group, n2 represents an integer from 4 to 20, and R 15 ~R 17 Each of these independently represents an alkyl group with 1 to 8 carbon atoms. Furthermore, the amount of the copolymer in the silicone hydrogel composition is preferably 0.1 to 1 part by mass. Preferably, the silicone hydrogel composition further comprises a base composition, and the copolymer is present in an amount of 0.05 to 2 parts by mass per 100 parts by mass of the base composition.

[0032] [Use of the copolymer of the present invention as a modifier for ophthalmic devices] The present invention also includes the use of the following copolymer of the present invention in the production of a modifier for ophthalmic devices. A copolymer containing a structural unit based on a hydrophilic monomer a represented by the following formula (1) and a structural unit based on a silicone monomer b represented by the following formula (2) or formula (3), which is not soluble in water at 20 °C at 1.0% (w / v) but is soluble in boiling water at 0.1% (w / v) or more, for use in the production of a modifier for ophthalmic devices.

Chemical formula

Chemical formula

Chemical formula

[0033] The copolymer of the present invention comprises a constituent unit based on a hydrophilic monomer a represented by formula (1), a constituent unit based on a silicone monomer b represented by formula (2) or formula (3), heat Examples of combinations of constituent units based on reactive monomers or photoreactive monomers c, and / or constituent units based on other monomers d, are shown in Table 1 below. Furthermore, those skilled in the art can obtain copolymers containing various constituent units by appropriately changing the composition of each constituent unit listed in Table 1. [Examples]

[0034] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0035] [Synthesis of copolymers] For the synthesis of copolymers used in the examples, 14 copolymers shown in Table 1, i.e., copolymers 1-1 to 3-6 which are within the scope of the present invention, were synthesized.

[0036] [Synthesis Example 1-1] 22.5 g of 2-methacryloyloxyethyl phosphorylcholine (hereinafter referred to as MPC) and 1.0 g of tris(trimethylsiloxy)silylpropyl methacrylate (hereinafter referred to as TRIS) (monomer composition molar ratio: MPC / TRIS = 97 / 3) were weighed into a polymerization glass flask, and 35.3 g of ethanol, the polymerization solvent, was added to dissolve them. After thoroughly purging the reaction vessel with nitrogen, 12 mg of 2,2'-azobis(2,4-dimethylvaleronitrile) (hereinafter referred to as ADVN) was added as a polymerization initiator, and the polymerization reaction was carried out by slowly raising the temperature to 60°C and maintaining it at 60°C overnight. The polymer was precipitated by dropping the resulting reaction solution into a large excess of acetone. The precipitate was filtered off, washed with acetone, and then vacuum dried to obtain copolymer 1-1, a white solid. The weight-average molecular weight of the obtained copolymer 1-1 was determined to be 356,000 in terms of polyethylene glycol by gel filtration chromatography (GPC).

[0037] [Synthesis Example 1-2] 21.2 g of MPC and 2.3 g of TRIS (monomer composition molar ratio: MPC / TRIS = 93 / 7) were weighed into a glass flask for polymerization, and 35.3 g of n-propanol (hereinafter referred to as NPA), the polymerization solvent, was added and dissolved. After thoroughly purging the reaction vessel with nitrogen, 12 mg of ADVN was added as a polymerization initiator, and polymerization and recovery were carried out in the same manner as in Synthesis Example 1-1 to obtain copolymer 1-2, a white solid. The weight-average molecular weight of the obtained copolymer 1-2 was determined to be 288,000 in terms of polyethylene glycol by GPC measurement.

[0038] [Synthesis Examples 1-3] 19.5 g of MPC and 4.0 g of TRIS (monomer molar ratio: MPC / TRIS = 87.5 / 12.5) were weighed into a glass flask for polymerization, and 35.3 g of NPA, the polymerization solvent, was added to dissolve them. After thoroughly purging the reaction vessel with nitrogen, 8 mg of ADVN was added as a polymerization initiator, and polymerization and recovery were carried out in the same manner as in Synthesis Example 1-1 to obtain copolymer 1-3, a white solid. The weight-average molecular weight of the obtained copolymers 1-3 was determined to be 411,000 in terms of polyethylene glycol by GPC measurement.

[0039] [Synthesis Examples 1-4] 23.1 g of MPC and 0.5 g of polydimethylsiloxane monomethacrylate (manufactured by Shin-Etsu Chemical Co., Ltd., hereinafter referred to as PDMSMA) (monomer composition molar ratio: MPC / PDMSMA = 99.4 / 0.6, calculated assuming a number-average molecular weight of PDMSMA of 1,000) were weighed into a glass flask for polymerization, and 94.1 g of NPA, the polymerization solvent, was added to dissolve them. After thoroughly purging the reaction vessel with nitrogen, 6 mg of ADVN was added as a polymerization initiator, and then polymerization and recovery were carried out in the same manner as in Synthesis Example 1-1 to obtain copolymer 1-4, a white solid. The weight-average molecular weight of the obtained copolymers 1-4 was determined to be 364,000 in terms of polyethylene glycol by GPC measurement.

[0040] [Synthesis Examples 1-5] 23.1 g of MPC and 0.5 g of PDMSMA (monomer molar ratio: MPC / PDMSMA = 99.4 / 0.6) were weighed into a glass flask for polymerization, and 35.3 g of NPA, the polymerization solvent, was added to dissolve them. After thoroughly purging the reaction vessel with nitrogen, 8 mg of 2,2'-azobis(isobutyronitrile) (hereinafter referred to as AIBN) was added as a polymerization initiator, and polymerization and recovery were carried out in the same manner as in Synthesis Example 1-1 to obtain copolymer 1-5, a white solid. The weight-average molecular weight of the obtained copolymers 1-5 was determined to be 1,550,000 in terms of polyethylene glycol by GPC measurement.

[0041] [Synthesis Examples 1-6] 21.4 g of MPC, 2.6 g of 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioete (hereinafter referred to as ETS), and 1.0 g of hydroxyethylacrylamide (hereinafter referred to as HEAA) (monomer composition molar ratio: MPC / ETS / HEAA = 84 / 6 / 10) were weighed into a glass flask for polymerization, and 100.0 g of NPA, the polymerization solvent, was added to dissolve them. After thoroughly purging the reaction vessel with nitrogen, 6 mg of ADVN was added as a polymerization initiator, and then polymerization and recovery were carried out in the same manner as in Synthesis Example 1-1 to obtain copolymer 1-6, a white solid. The weight-average molecular weight of the obtained copolymers 1-6 was determined to be 301,000 in terms of polyethylene glycol by GPC measurement. [Synthesis Example 2-1] 19.0 g of MPC, 2.1 g of TRIS, and 1.1 g of glycidyl methacrylate (hereinafter referred to as GMA) (monomer composition molar ratio: MPC / TRIS / GMA = 84 / 6 / 10) were weighed into a glass flask for polymerization, and 88.9 g of NPA, the polymerization solvent, was added to dissolve them. After thoroughly purging the reaction vessel with nitrogen, 55 mg of ADVN was added as a polymerization initiator, and then polymerization and recovery were carried out in the same manner as in Synthesis Example 1-1 to obtain copolymer 2-1, a white solid. The weight-average molecular weight of the obtained copolymer 2-1 was determined to be 72,000 in terms of polyethylene glycol by GPC measurement.

[0042] [Synthesis Example 2-2] 20.7 g of MPC, 0.4 g of PDMSMA, and 1.1 g of GMA (monomer molar ratio: MPC / PDMSMA / GMA = 89.5 / 0.5 / 10) were weighed into a glass flask for polymerization, and 88.9 g of NPA, the polymerization solvent, was added to dissolve them. After thoroughly purging the reaction vessel with nitrogen, 55 mg of ADVN was added as a polymerization initiator, and polymerization and recovery were carried out in the same manner as in Synthesis Example 1-1 to obtain copolymer 2-2, a white solid. The weight-average molecular weight of the obtained copolymer 2-2 was determined to be 150,000 in terms of polyethylene glycol by GPC measurement.

[0043] [Synthesis Example 3-1] 18.4 g of MPC, 1.9 g of TRIS, and 2.0 g of 4-methacryloyloxybenzophenone (hereinafter referred to as MBP) (monomer composition molar ratio: MPC / TRIS / MBP = 84 / 6 / 10) were weighed into a glass flask for polymerization, and 88.9 g of NPA, the polymerization solvent, was added to dissolve them. After thoroughly purging the reaction vessel with nitrogen, 55 mg of ADVN was added as a polymerization initiator, and then polymerization and recovery were carried out in the same manner as in Synthesis Example 1-1 to obtain copolymer 3-1, a white solid. The weight-average molecular weight of the obtained copolymer 3-1 was determined to be 72,000 in terms of polyethylene glycol by GPC measurement.

[0044] [Synthesis Example 3-2] 16.0 g of MPC, 3.3 g of TRIS, and 1.8 g of MBP (monomer molar ratio: MPC / TRIS / MBP = 79 / 11 / 10) were weighed into a polymerization glass flask, and 84.2 g of NPA, the polymerization solvent, was added to dissolve them. After thoroughly purging the reaction vessel with nitrogen, 52 mg of ADVN was added as a polymerization initiator, and then polymerization and recovery were carried out in the same manner as in Synthesis Example 1-1 to obtain copolymer 3-2, a white solid. The weight-average molecular weight of the obtained copolymer 3-2 was determined to be 21,000 in terms of polyethylene glycol by GPC measurement.

[0045] [Synthesis Example 3-3] 21.0 g of MPC, 0.4 g of PDMSMA, and 2.1 g of MBP (monomer molar ratio: MPC / PDMSMA / MBP = 89.5 / 0.5 / 10) were weighed into a glass flask for polymerization, and 94.1 g of NPA, the polymerization solvent, was added to dissolve them. After thoroughly purging the reaction vessel with nitrogen, 59 mg of ADVN was added as a polymerization initiator, and polymerization and recovery were carried out in the same manner as in Synthesis Example 1-1 to obtain copolymer 3-3, a white solid. The weight-average molecular weight of the obtained copolymer 3-3 was determined to be 105,000 in terms of polyethylene glycol by GPC measurement.

[0046] [Synthesis Example 3-4] 21.0 g of MPC, 0.4 g of PDMSMA, and 2.1 g of MBP (monomer molar ratio: MPC / PDMSMA / MBP = 89.5 / 0.5 / 10) were weighed into a glass flask for polymerization, and 35.3 g of NPA, the polymerization solvent, was added to dissolve them. After thoroughly purging the reaction vessel with nitrogen, 6 mg of ADVN was added as a polymerization initiator, and then polymerization and recovery were carried out in the same manner as in Synthesis Example 1-1 to obtain copolymer 3-4, a white solid. The weight-average molecular weight of the obtained copolymer 3-4 was determined to be 951,000 in terms of polyethylene glycol by GPC measurement.

[0047] [Synthesis Example 3-5] 20.2 g of MPC, 2.5 g of ETS, and 2.3 g of 4-(4-azidobenzoyloxymethyl)vinylbenzene (hereinafter referred to as AzSt) (monomer composition molar ratio: MPC / ETS / AzSt = 84 / 6 / 10) were weighed into a glass flask for polymerization, and 100.0 g of NPA, the polymerization solvent, was added to dissolve them. After thoroughly purging the reaction vessel with nitrogen, 62 mg of ADVN was added as a polymerization initiator, and then polymerization and recovery were carried out in the same manner as in Synthesis Example 1-1 to obtain copolymer 3-5, a white solid. The weight-average molecular weight of the obtained copolymer 3-5 was determined to be 70,000 in terms of polyethylene glycol by GPC measurement.

[0048] [Synthesis Example 3-6] 18.4 g of MPC, 1.9 g of 3-(3-(methylbis(trimethylsiloxy)silyl)propyl)glycerol-1-methacrylate (hereinafter referred to as SiGMA), and 2.0 g of MBP (monomer composition molar ratio: MPC / SiGMA / MBP = 84 / 6 / 10) were weighed into a glass flask for polymerization, and 88.9 g of NPA, the polymerization solvent, was added to dissolve them. After thoroughly purging the reaction vessel with nitrogen, 55 mg of ADVN was added as a polymerization initiator, and then polymerization and recovery were carried out in the same manner as in Synthesis Example 1-1 to obtain copolymer 3-6, a white solid. The weight-average molecular weight of the obtained copolymer 3-6 was determined to be 74,000 in terms of polyethylene glycol by GPC measurement.

[0049] [GPC measurement] GPC measurements of each copolymer from synthesis examples 1-1 to 3-6 above were performed under the following conditions. GPC System: EcoSEC System (manufactured by Tosoh Corporation) Columns: Shodex OHpak SB-802.5HQ (manufactured by Showa Denko Corporation) and SB-806HQ (manufactured by Showa Denko Corporation) connected in series. Developing solvent: 20 mM sodium phosphate buffer (pH 7.4) Detector: Differential refractive index detector Molecular weight standard: EasiVial PEG / PEO (manufactured by Agilent Technologies) Flow rate: 0.5mL / min Column temperature: 40℃ Sample: Dilute the obtained copolymer with the developing solvent to a final concentration of 0.1% by weight. Injection volume: 100μL

[0050] [Determination of water solubility] The water solubility of each copolymer described in Synthesis Examples 1-1 to 3-6 was determined by the following procedure. (1) Each copolymer was weighed into a 30cc glass vial in an appropriate amount to achieve the following predetermined concentration. (2) 10 mL of deionized water was added. (3) The mixture was stirred under 20°C conditions, and its solubility in water at 20°C was visually confirmed. (4) After autoclaving at 121°C for 20 minutes, the mixture was stirred and allowed to return to room temperature, and its solubility in boiling water was visually confirmed. (5) The above steps (1) to (4) were performed for concentrations of 0.1% (w / v), 0.5% (w / v), 1.0% (w / v), and 5.0% (w / v). (6) For both 20°C water and boiling water, the highest concentration among the four concentrations listed above in which dissolution was confirmed was recorded. However, if a substance did not dissolve even at 0.1% (w / v), it was recorded as "×".

[0051] Table 1 shows the water solubility and weight-average molecular weight of each copolymer obtained in Synthesis Examples 1-1 to 3-6.

[0052] [Table 1]

[0053] *1 MPC: 2-methacryloyloxyethyl phosphorylcholine TRIS: Tris(trimethylsiloxy)silylpropyl methacrylate PDMSMA: Polydimethylsiloxane monomethacrylate ETS: 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate HEAA: Hydroxyethylacrylamide GMA: Glycidyl methacrylate MBP: Methacryloyloxybenzophenone AzSt: 4-(4-azidobenzoyloxymethyl)vinylbenzene SiGMA:3-(3-(methylbis(trimethylsiloxy)silyl)propyl)glycerol-1-methacrylate ―: Does not contain the corresponding monomer. *2 For water at 20°C and boiling water (above 100°C), the maximum concentration at which each copolymer dissolved is recorded (unit: %(w / v). However, if a copolymer did not dissolve at a concentration of 0.1%(w / v), it is marked with "×").

[0054] Copolymers 1-1 to 3-6 do not dissolve at 1.0% (w / v) in water at 20°C, but it was confirmed that they dissolve at 0.1% (w / v) or more in boiling water.

[0055] [Preparation of Silicone Hydrogel Composition] The effects of the copolymer of the present invention were verified by preparing a silicone hydrogel and performing the evaluation described below. The silicone hydrogels used in the examples and comparative examples were prepared in the following manner.

[0056] [Preparation of monomer composition] A monomer composition was prepared by mixing predetermined amounts of each copolymer prepared in each of the above synthesis examples with the lens monomers of the common composition heat 1-3 and light 1-2 shown in Table 2. After weighing and mixing the copolymers prepared in each synthesis example (see Table 3), NPA, and hydroxyethyl methacrylate (hereinafter referred to as HEMA) in predetermined amounts, N-vinylpyrrolidone (hereinafter referred to as NVP), methyl methacrylate (hereinafter referred to as MMA) in Photo 1 and Photo 2, tetraethylene glycol dimethacrylate (hereinafter referred to as TEGDMA), triethylene glycol divinyl ether (hereinafter referred to as TEGDV), methacrylic acid (hereinafter referred to as MA) in Heat 2, and aminoethyl methacrylate in Heat 3. The reaction was prepared by adding a predetermined amount of methacrylate (hereinafter referred to as AeMA) and mixing again, then adding ETS and mixing again, then adding PDMSMA and mixing again, and finally adding the reaction initiator AIBN in heat 1-3, the reaction initiator 2-hydroxy-2-methyl-1-phenylpropanone (hereinafter referred to as O-1173) in light 1, and the reaction initiator bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide (hereinafter referred to as O-819) in light 2.

[0057] [Table 2]

[0058] NPA:n-propanol HEMA: Hydroxyethyl methacrylate NVP: N-vinylpyrrolidone MMA: Methyl methacrylate TEGDMA: Tetraethylene glycol dimethacrylate TEGDV: Triethylene glycol divinyl ether MA: Methacrylic acid AeMA: Aminoethyl methacrylate (11 wt% aqueous solution) ETS: 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate PDMSMA: Polydimethylsiloxane monomethacrylate AIBN: 2,2'-Azobis(isobutyronitrile) O-1173: 2-Hydroxy-2-methyl-1-phenylpropanone O-819: Bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide

[0059] [Preparation of silicone hydrogel by thermosetting] In order to mold Heat 1, Heat 2, and Heat 3 (see Table 2), which are the above monomer compositions, into a disc shape as a model of a contact lens, they were injected into a polypropylene mold with an inner dimension of φ1.1 cm × 0.1 mm and left standing in an oven. After replacing the inside of the oven with nitrogen, the temperature was slowly raised to 80°C and kept at 80°C for 12 hours to perform thermosetting and obtain a cured product. This cured product was taken out of the mold and immersed in 40 g of iso-propanol (hereinafter referred to as IPA) for 4 hours per sheet of the cured product, and then immersed in 50 g of ion-exchanged water for 4 hours for purification to extract and remove unreacted substances and the like. Next, the above cured product was taken out and immersed in the physiological saline (hereinafter referred to as PBS) described in ISO-18369-3 for 4 hours, and then autoclaved and sterilized while immersed in fresh PBS to obtain a silicone hydrogel.

[0060] [Preparation of silicone hydrogel by photocuring] In order to mold Light 1 and Light 2 (see Table 2), which are the above monomer compositions, into a disc shape as a model of a contact lens, they were injected into a polypropylene mold with an inner dimension of φ1.1 cm × 0.1 mm and left standing in a light irradiation machine. Light with a wavelength of 365 nm or 405 nm and an illuminance of 1.5 mW / cm 2 was irradiated for 20 minutes to perform photocuring and obtain a cured product. Thereafter, similar to the case of thermosetting, the cured product was taken out, purified, and sterilized to obtain a silicone hydrogel.

[0061] [Compatibility of monomer composition] The prepared monomer composition was put into a transparent glass container, and the compatibility of the monomer composition was visually evaluated according to the following criteria. ++: Uniform and transparent +: Slight turbidity and scattering ×: Turbidity, sedimentation

[0062] [Evaluation of silicone hydrogels] The following evaluations were performed on the prepared silicone hydrogel.

[0063] [Transparency] The transparency of the prepared silicone hydrogel was visually determined according to the following criteria. ++:Transparent +: slightly cloudy ×: Milky white

[0064] [shape] The shape of the prepared silicone hydrogel was determined visually according to the following criteria. ++: No distortion detected +: Slight distortion observed ×: Distortion and hardening defects were observed.

[0065] [Wettability] The surface wettability of the prepared silicone hydrogel was evaluated using the following procedure. (1) The prepared silicone hydrogel immersed in PBS was removed into the air using tweezers. (2) The surface of the silicone hydrogel was visually observed, and the time [seconds] (BUT) from the time of removal until the water film on the surface began to break down was measured. In other words, the longer the BUT, the higher the surface wettability was evaluated. (3) The following criteria were used for the determination. +++:30 seconds≦BUT ++:10 seconds≦BUT<30 seconds +:5 seconds≦BUT<10 seconds ×: BUT < 5 seconds

[0066] [Slippery] The surface slipperiness of the prepared silicone hydrogel was evaluated using the following procedure. (1) I pinched the silicone hydrogel lens between my thumb and middle finger. (2) Based on sensory evaluation, Polymacon was assigned a score of 2 for slipperiness and Omafilcon A was assigned a score of 8, with a total score from 0 to 10. In other words, a higher score indicates higher slipperiness. (3) The following criteria were used for the determination. +++:8 points~10 points ++:5 points~7 points +:3~4 points ×: 0~2 points

[0067] [Examples 1-1 to 1-5] The silicone hydrogels obtained when monomer b is one of the copolymers 1-1 to 1-3 represented by formula (2) were added to the silicone hydrogel composition were evaluated. For the common composition, heat 1 was used, and curing was performed by thermosetting. [Examples 1-6 to 1-7] The silicone hydrogels obtained when each of copolymers 1-4 to 1-5 was added to a silicone hydrogel composition were evaluated. For the common composition, heat 1 was used, and curing was performed by thermosetting. [Examples 1-8] The silicone hydrogels obtained when copolymers 1-6 were added to a silicone hydrogel composition were evaluated. A common composition was used, and curing was performed by thermal curing. [Examples 2-1 to 2-4] Using the copolymer, common composition, and curing method described in Table 3, the resulting silicone hydrogel was evaluated in the same manner as in Example 1. [Examples 3-1 to 3-8] Using the copolymers and common compositions listed in Table 3, the resulting silicone hydrogels were evaluated in the same manner as in Example 1. Curing was performed at a wavelength of 365 nm and an illuminance of 1.5 mW / cm². 2 This was carried out by irradiating with ultraviolet light. [Examples 3-9] Using the copolymers and common compositions listed in Table 3, the resulting silicone hydrogels were evaluated in the same manner as in Example 1. Curing was performed at a wavelength of 405 nm and an illuminance of 1.5 mW / cm². 2 This was carried out by irradiating with purple light. The preparation of the silicone hydrogel performed using the above procedure, and its evaluation results, are shown in Table 3.

[0068] [Table 3-1]

[0069] [Table 3-2]

[0070] [Table 3-3]

[0071] *1 MPC: 2-methacryloyloxyethyl phosphorylcholine TRIS: Tris(trimethylsiloxy)silylpropyl methacrylate PDMSMA: Polydimethylsiloxane monomethacrylate ETS: 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate HEAA: Hydroxyethylacrylamide GMA: Glycidyl methacrylate MBP: 4-methacryloyloxybenzophenone AzSt: (Azidobenzoyloxymethyl)vinylbenzene SiGMA:3-(3-(methylbis(trimethylsiloxy)silyl)propyl)glycerol-1-methacrylate *2 Under the conditions of 20℃ 1% (w / v) and boiling water 0.1% (w / v), the substances found to be water-soluble were: ++ Those that were not approved - I added it.

[0072] [Comparative Examples 1-1~2-3] As a control test that did not use the copolymer of the present invention, seven types of silicone hydrogels shown in Table 4 were prepared in the same manner as in the examples and evaluated in the same manner as in the examples.

[0073] [Table 4]

[0074] MPC: 2-methacryloyloxyethyl phosphorylcholine

[0075] The results in Tables 3 and 4 show that the silicone hydrogels of Examples 1-1 to 3-9 exhibited excellent compatibility, transparency, and shape, as well as high wettability and slipperiness simultaneously. In contrast, Comparative Examples 1-1 to 2-3, lacking the copolymer of the present invention, exhibited low wettability and / or slipperiness. Comparative Examples 1-2 and 2-2 also exhibited low wettability and slipperiness even when MPC was used as a monomer instead of the copolymer of the present invention. From the above examples and comparative examples, it is clear that the wettability and slipperiness of silicone hydrogels can be suitably improved by using the ophthalmic device modifier of the present invention. [Industrial applicability]

[0076] Using a silicone hydrogel obtained by curing a silicone hydrogel composition containing the ophthalmic device modifier of the present invention, contact lenses, intraocular lenses, artificial We can provide ophthalmic devices, such as those for the cornea.

Claims

1. A modifier for ophthalmic devices comprising a copolymer containing a constituent unit based on a hydrophilic monomer a represented by the following formula (1), and a constituent unit based on a silicone monomer b represented by the following formula (2) or formula (3), Here, the copolymer does not dissolve in water at 20°C at a concentration of 1.0% (w / v), but dissolves in boiling water at a concentration of 0.1% (w / v) or more and 5.0% (w / v) or less, and the water solubility index WSI of the copolymer, as defined by the following formula (4), is between 20 and 700. Modifier for ophthalmic devices. 【number】 (In formula (1), R １ L represents a hydrogen atom or a methyl group. １ R represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group. ２ ~R ４ Each of these independently represents a hydrocarbon group with 1 to 3 carbon atoms. 【number】 (In formula (2), X １ represents a (meth)acryloyloxy group, a 3-(2-hydroxyethyloxycarbonyl)-2-methylenepropanoyloxy group, a 3-(2-hydroxyethyloxycarbonyl)-3-butenoyloxy group or a 3-(2-hydroxyethyloxycarbonyl)-2-propenoyloxy group, L ２ represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxy group, R ５ to R １３ each independently represent a methyl group or an ethyl group, and n １ represents 0 or 1.) 【number】 (In formula (3), R １４ L represents a hydrogen atom or a methyl group. ３ represents an organic group having 2 to 6 carbon atoms, where the organic group may optionally contain one ether bond and / or one hydroxyl group, n ２ R represents integers from 4 to 20. １５ ~R １７ Each of these independently represents an alkyl group having 1 to 8 carbon atoms. [Math 1]

2. The ophthalmic device modifier according to claim 1, wherein the mass ratio of monomer a to monomer b is 5:1 to 50:

1.

3. The modifier for ophthalmic devices according to claim 1, wherein the weight-average molecular weight of the copolymer is 50,000 to 1,600,000.

4. The ophthalmic device modifier according to claim 1, wherein the copolymer further contains a constituent unit based on a heat-reactive monomer or a photoreactive monomer c.

5. The ophthalmic device modifier according to claim 4, wherein the constituent unit based on the hydrophilic monomer a represented by formula (1) is 2-methacryloyloxyethyl phosphorylcholine, the constituent unit based on the silicone monomer b represented by formula (2) or formula (3) is tris(trimethylsiloxy)silylpropyl methacrylate, polydimethylsiloxane monomethacrylate, 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate or 3-(3-(methylbis(trimethylsiloxy)silyl)propyl)glycerol-1-methacrylate), and the constituent unit based on the thermally reactive monomer or photoreactive monomer c is glycidyl methacrylate, methacryloyloxybenzophenone or 4-(4-azidobenzoyloxymethyl)vinylbenzene.

6. The modifier for ophthalmic devices according to claim 4, wherein the combination of a constituent unit based on a hydrophilic monomer a represented by formula (1), a constituent unit based on a silicone monomer b represented by formula (2) or formula (3), and / or a constituent unit based on a thermally reactive monomer or a photoreactive monomer c is selected from any one of the following. 1) 2-Methacryloyloxyethyl phosphorylcholine and tris(trimethylsiloxy)silylpropyl methacrylate 2) 2-Methacryloyloxyethyl phosphorylcholine and polydimethylsiloxane monomethacrylate 3) 2-methacryloyloxyethyl phosphorylcholine and 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate 4) 2-Methacryloyloxyethyl phosphorylcholine, tris(trimethylsiloxy)silylpropyl methacrylate and glycidyl methacrylate 5) 2-Methacryloyloxyethyl phosphorylcholine, polydimethylsiloxane monomethacrylate, and glycidyl methacrylate 6) 2-Methacryloyloxyethyl phosphorylcholine, tris(trimethylsiloxy)silylpropyl methacrylate, and methacryloyloxybenzophenone 7) 2-Methacryloyloxyethyl phosphorylcholine, polydimethylsiloxane monomethacrylate, and methacryloyloxybenzophenone 8) 2-methacryloyloxyethyl phosphorylcholine, 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate and 4-(4-azidobenzoyloxymethyl)vinylbenzene 9) 2-Methacryloyloxyethyl phosphorylcholine, 3-(3-(methylbis(trimethylsiloxy)silyl)propyl)glycerol-1-methacrylate and methacryloyloxybenzophenone

7. A silicone hydrogel composition comprising the copolymer and base composition according to claim 1 or 4, A silicone hydrogel composition comprising 0.05 to 2 parts by mass of the copolymer per 100 parts by mass of the base composition.

8. A silicone hydrogel obtained by curing the silicone hydrogel composition described in claim 7.

9. An ophthalmic device using the silicone hydrogel described in claim 8.

10. The ophthalmic device according to claim 9, which is a soft contact lens.

11. A modifier for ophthalmic devices comprising a copolymer containing a constituent unit based on a hydrophilic monomer a, a constituent unit based on a silicone monomer b, and a constituent unit based on a thermally reactive monomer or a photoreactive monomer c, Here, the copolymer does not dissolve in water at 20°C at a concentration of 1.0% (w / v), but dissolves in boiling water at a concentration of 0.1% (w / v) or more and 5.0% (w / v) or less, and the constituent unit based on the hydrophilic monomer a is 2-methacryloyloxyethyl phosphorylcholine, the constituent unit based on the silicone monomer b is tris(trimethylsiloxy)silylpropyl methacrylate, polydimethylsiloxane monomethacrylate, 4-(2-hydroxyethyl)-2-methylene-1-(tris(trimethylsiloxy)silylpropyl)butane-1,4-dioate, or 3-(3-(methylbis(trimethylsiloxy)silyl)propyl)glycerol-1-methacrylate), and the constituent unit based on the heat-reactive monomer or photoreactive monomer c is glycidyl methacrylate, methacryloyloxybenzophenone, or 4-(4-azidobenzoyloxymethyl)vinylbenzene. Modifier for ophthalmic devices.

Images