Hydrogel for absorbing blue light

Abstract

To provide a hydrogel applicable to ophthalmic lenses capable of effectively absorbing blue light without using a yellow colorant even when the content of a monomer capable of absorbing light in a blue light wavelength range is low.SOLUTION: The above object is achieved by a blue light-absorbing hydrogel containing a residue originating from a polymerizable blue light absorbent represented by the following general formula (I): U-L-Py ...(I), where U represents a blue light absorbing moiety having a tert-butyl group, L represents a hydrophilic non-polyalkylene glycol linker consisting of at least four carbon atoms, and Py represents an ethylenically unsaturated polymerizable moiety.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a hydrogel for absorbing blue light, which can be used for absorbing blue light.

Background Art

[0002] In recent years, as light that has an adverse effect on eye tissues, not only ultraviolet rays from natural light but also blue light contained in large amounts in LED displays such as personal computers and smartphones and LED lighting has attracted attention. Therefore, ophthalmic lenses for absorbing blue light containing a material for absorbing blue light have been developed so far (see, for example, Patent Documents 1 to 4).

[0003] In ophthalmic lenses for absorbing blue light, blending a yellow colorant, which is a protective color for blue light, is used as an effective method. However, the ophthalmic lenses obtained by this method are colored yellow. On the other hand, among ophthalmic lenses, in contact lenses, contaminants such as proteins contained in tears are deposited during wearing and the lenses turn yellow. Therefore, contact lenses colored yellow by a colorant will remind a third party of contact lenses on which contaminants are deposited, and they cannot be said to have a good appearance.

[0004] In addition, the wavelength range of blue light, 380 nm to 500 nm, also overlaps with the visible light range. Therefore, the use of a large amount of yellow colorant to improve the blue light absorption ability may have an adverse effect on the optical properties of contact lenses.

[0005] On the other hand, compounds that absorb ultraviolet rays instead of blue light are known. In addition, the application of such ultraviolet absorbers to ophthalmic lenses has been attempted. For example, a hydrogel synthesized using a monomer composed of an ultraviolet absorbing site, a linker, and an ethylenically unsaturated polymerizable site is known (see, for example, Patent Document 5).

Prior Art Documents

Patent Documents

[0006] [Patent Document 1] Japanese Translation of PCT International Publication No. 2019-510265 [Patent Document 2] Japanese Translation of PCT International Publication No. 2019-504619 [Patent Document 3] Japanese Translation of PCT International Publication No. 2017-503905 [Patent Document 4] Japanese Translation of PCT International Publication No. 2015-528048 [Patent Document 5] International Publication WO2020 / 118361 [Summary of the Invention] [Problems to be Solved by the Invention]

[0007] By using the hydrogel described in Patent Document 5, it is possible to provide a hydrogel having effective ultraviolet absorption ability while maintaining acceptable properties of the hydrogel material. However, the wavelength range of ultraviolet light is 380 nm or less, which is different from the wavelength range of blue light, 380 nm to 500 nm. And the hydrogel described in Patent Document 5 effectively absorbs ultraviolet light but does not effectively absorb blue light.

[0008] In addition, monomers having ultraviolet absorption ability such as HMB-Cys-MA described in Patent Document 5 have low affinity for water. Therefore, when a large amount of such monomers are blended, it is impossible to obtain an ophthalmic lens having desired hydrophilicity, and there is a problem that the applicable range is limited and the versatility is lacking.

[0009] Therefore, an object of the present invention is to provide a hydrogel applicable to an ophthalmic lens that can efficiently absorb blue light with a small amount of monomers that can absorb the wavelength range of blue light without using a yellow colorant. [Means for Solving the Problems]

[0010] In order to solve the above problems, the present inventors attempted to synthesize a compound having a blue light absorption effect applicable to a hydrogel. Among them, when a hydrogel was prepared using the compound described in Patent Document 5, some had a blue light absorption effect while others did not. Then, through further intensive studies and repeated trials and errors, surprisingly, it was found that a hydrogel prepared using a compound having a blue light absorption site with a tert-butyl group exhibited excellent blue light absorption effect. Based on such findings, the present inventors succeeded in creating a blue light absorbing hydrogel as a solution to the problems of the present invention. The present invention was completed based on such findings and successful examples.

[0011] That is, according to the present invention, the following aspects are provided: [1] A blue light absorbing hydrogel containing a residue derived from a polymerizable blue light absorber represented by the following general formula (I). U-L-Py (I) (In the formula, U is a blue light absorption site having a tert-butyl group, L is a hydrophilic non-polyalkylene glycol linker consisting of at least 4 carbon atoms, Py is an ethylenically unsaturated polymerizable site.) [2] The blue light absorbing hydrogel according to [1], wherein the blue light absorption site (U) having a tert-butyl group has a structure represented by the following general formula (II). [Chemical formula] (II) (In the formula, R 2 represents a tert-butyl group, R 3 is selected from a hydrogen atom, a halogen atom, and -CF 3 , R 4 represents a bonding point to the linker (L).) [3] The linker (L) is a linker derived from an amino acid, and the hydrogel according to [1] or [2]. [4] The ethylenically unsaturated polymerizable site (Py) contains a polymerizable functional group selected from the group consisting of allyl, vinyl, acryloyl, methacryloyl, and styrenyl, and the hydrogel according to any one of [1] to [3]. [5] A blue light-absorbing hydrogel containing a residue derived from tBu-HBA-Lys-MA represented by the following formula (1).

Chemical formula

Chemical formula

Advantages of the Invention

[0012] According to the present invention, by preparing a hydrogel using a polymerizable blue light absorber having a blue light-absorbing site having a tert-butyl group, a blue light-absorbing hydrogel can be prepared while flexibly setting the range of the amount of use of the polymerizable blue light absorber.

[0013] Further, according to the present invention, since it is not necessary to use a yellow colorant, the resulting hydrogel can be made to have reduced influence on optical properties without being colored yellow.

[0014] Thus, according to the present invention, it is possible to obtain a highly versatile blue light-absorbing hydrogel capable of setting various properties, and such a hydrogel is expected to be applied to ophthalmic lenses such as contact lenses. BRIEF DESCRIPTION OF THE DRAWINGS

[0015]

Figure 1

[0016] Hereinafter, the details of each aspect of the present invention will be described. However, the present invention is not limited only by the matters in this section, and can take various aspects as long as the object of the present invention is achieved.

[0017] Each term in this specification is used in the meaning usually used by those skilled in the art in the industry dealing with ophthalmic lenses such as contact lenses, unless otherwise specified, and should not be construed as having an unduly limiting meaning. Also, the speculations and theories made in this specification are based on the knowledge and experience of the present inventors so far, and thus the present invention is not restricted only by such speculations and theories.

[0018] "Content" is synonymous with "concentration" and means the ratio of the amount of a component to the total amount of the solution. However, the total content of the components shall not exceed 100%. In this specification, unless otherwise specified, the unit of content means "mass% (w / w%)". Note that when using a commercially available product, the content of the component is preferably the amount of the component contained in the commercially available product, but it may also be the amount of the commercially available product itself. The term "and / or" means any one of the plurality of listed related items, or any combination or all combinations of two or more of them.

[0019] The present invention generally relates to a hydrogel for absorbing blue light applicable to an ophthalmic lens used on or in the eye. The hydrogel of one embodiment of the present invention has an effective blue light absorption effect while maintaining acceptable properties of the hydrogel material.

[0020] An ophthalmic lens of one embodiment of the present invention is an ophthalmic device intended to be placed on or in the eye of a subject. Examples of the ophthalmic lens include a contact lens, an intraocular lens, and the like.

[0021] According to one aspect of the present invention, general formula (I): U-L-Py (I) A hydrogel containing a residue derived from a polymerizable blue light absorber represented by the formula is provided. In general formula (I), U is a blue light absorbing site having a tert-butyl group; L is a hydrophilic non-polyalkylene glycol linker composed of at least 4 carbon atoms; and Py is an ethylenically unsaturated polymerizable site.

[0022] In order to be a hydrogel exhibiting advantageous properties for application to an ophthalmic lens, a monomer mixture containing a polymerizable blue light absorber represented by the general formula (I) is polymerized. The hydrogel containing residues derived from the polymerizable blue light absorber surprisingly and advantageously exhibits properties such as good water content and transparency, and excellent blue light absorption. In the polymerizable blue light absorber, the forms of the blue light absorbing site (U) having a tert-butyl group and the linker (L) are considered to play characteristic roles in achieving such properties.

[0023] The hydrogel is based on a polymer (polymer) of monomers containing a hydrophilic monomer. The hydrogel swells with an aqueous liquid such as water or a solution containing water in the polymer matrix and retains the aqueous liquid. The hydrogel may include an interpenetrating network of a plurality of polymers such as a hydrophilic polymer and a silicone polymer constituting the silicone hydrogel.

[0024] The network polymer component of the hydrogel is also referred to as a "hydrogel polymer". A polymer (macromolecule) is formed by polymerization of monomers (monomers), and the structural units derived from each monomer in the polymer are also referred to as residues and sites (moieties).

[0025] The hydrogel polymer can be prepared by polymerizing an effective amount of a polymerizable blue light absorber represented by the general formula (I) with at least one comonomer. As a result, the polymerizable blue light absorber of the general formula (I) is covalently incorporated as a residue in the polymer together with at least one comonomer. By incorporating the comonomer and the polymerizable blue light absorber of the general formula (I) as residues in the hydrogel polymer, it becomes possible to prepare a hydrogel having an effective blue light absorption effect.

[0026] The hydrogel polymer contains residues derived from a polymerizable blue light absorber of general formula (I). The polymerizable blue light absorber of formula (I) may be used alone or in combination with other polymerizable blue light absorbers to impart a blue light absorbing effect to the ophthalmic lens.

[0027] The polymerizable blue light absorber of general formula (I) contains a blue light absorbing site (U) having a tert-butyl group. The blue light absorbing site can absorb blue light and impart a blue light absorbing effect to the hydrogel of one aspect of the present invention. Typically, blue light is present at wavelengths of 380 nm to 500 nm, preferably 380 nm to 420 nm.

[0028] The blue light absorbing site (U) is selected from the group consisting of, for example, benzotriazole, benzophenone, triazine, avobenzone, benzylidene, azobenzene, salicylate, anthranilate, chloroaniline, cyanodiphenyl, benzimidazole, oxanilide, phenylbenzothiazole and benzothiazole, preferably selected from benzotriazole and benzophenone. That is, the blue light absorbing site (U) is preferably a benzotriazole site or a benzophenone site. The benzotriazole site is preferably a hydroxyphenylbenzotriazole site.

[0029] The blue light absorbing site (U) has a tert-butyl group. By having a tert-butyl group in the blue light absorbing site (U), an excellent blue light absorbing effect is exhibited.

[0030] The blue light absorbing site (U) having a tert-butyl group is preferably a hydroxyphenylbenzotriazole moiety represented by general formula (II).

[0031]

Chemical formula

[0032] In general formula (II), R 2represents a tert-butyl group, and R 3 is selected from a hydrogen atom, a halogen atom, and -CF 3 , and R 4 represents a bonding point to a hydrophilic non-polyalkylene glycol linker (L). Examples of the halogen atom of R 3 include, but are not limited to, bromo, chloro, fluoro, iodo, etc.

[0033] The hydrophilic non-polyalkylene glycol linker (L) linked to the blue light absorbing site of the general formula (II) can be selected from any one of the linkers described below. When the linker (L) is derived from an amino acid, the terminal of the blue light absorbing site forms a covalent bond with the amino group or carboxyl group of the linker (L). Therefore, when the linker (L) is derived from an amino acid, R 4 in the blue light absorbing site is preferably a carboxyl group or an amino group which may have an alkylene group of C 1 to C 4 .

[0034] The polymerizable blue light absorber of the general formula (I) can be represented as in the following general formula (IIa) following the blue light absorbing site of the general formula (II).

[0035]

Chemical formula

[0036] In the general formula (IIa), R 2 represents a tert-butyl group; R 3 is selected from a hydrogen atom, a halogen atom, and -CF 3 ; L is a hydrophilic non-polyalkylene glycol linker consisting of at least 4 carbon atoms; and Py is an ethylenically unsaturated polymerizable site.

[0037] The polymerizable blue light absorber of general formula (I) is a monomer having a structure in which a blue light absorbing site having a tert-butyl group and an ethylenically unsaturated polymerizable site are bonded via a hydrophilic non-polyalkylene glycol linker (L) consisting of at least 4 carbon atoms.

[0038] The fact that the linker (L) in general formula (I) is a "non-polyalkylene glycol linker" means that it does not contain a part derived from or composed of polyalkylene glycol (such as polyethylene glycol and polypropylene glycol including C 2 ~C 4 For example, the non-polyalkylene glycol linker does not contain a part having a structure of -(C 2 H 4 O)n-, -(CH(CH 3 )CH 2 O)n-, or -(CH 2 CH(CH 3 )O)n- (n is an integer in the range of 2 to 10).

[0039] The hydrophilic non-polyalkylene glycol linker (L) is disposed between the blue light absorbing site (U) and the ethylenically unsaturated polymerizable site (Py), and is covalently bonded to the blue light absorbing site and the ethylenically unsaturated polymerizable site, respectively.

[0040] The linker (L) in the polymerizable blue light absorber of general formula (I) is characterized by being hydrophilic. The presence of the hydrophilic linker can assist in improving the affinity of the polymerizable blue light absorber and the polymer material containing the polymerizable blue light absorber in an aqueous environment. For example, although commonly used ultraviolet absorbers are hydrophobic, introducing a hydrophilic non-polyalkylene glycol linker into the molecule can also impart hydrophilicity to the resulting hydrogel. Therefore, even when an ultraviolet absorber is incorporated into the hydrogel, it is possible to suppress significant changes in the properties of the hydrogel, such as optical properties and water content. In addition, the hydrophilicity of the polymerizable ultraviolet absorber also acts to improve the affinity with other components for forming the hydrogel.

[0041] The hydrophilicity of the non-polyalkylene glycol linker can be determined by evaluating the solubility of the polymerizable blue light absorber containing the non-polyalkylene glycol linker in an aqueous liquid such as water or a solution containing water (e.g., an aqueous monomer solution). For example, it has been confirmed that the polymerizable blue light absorber of general formula (I) can dissolve a larger amount in an aqueous liquid compared to commercially available ultraviolet absorbers such as 2-[3-(2H)-benzotriazol-2-yl)-4-hydroxyphenyl]ethyl methacrylate (HMB) and 2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate (which do not have a hydrophilic linker and are generally considered hydrophobic). The fact that a larger amount of the ultraviolet absorber of formula (I) can be dissolved in the aqueous liquid indicates that the linker portion of the ultraviolet absorber is hydrophilic and also means that it can affect the hydrophilicity of the molecule.

[0042] The hydrophilic non-polyalkylene glycol linker (L) contains at least 4, preferably at least 5, at least 6, or at least 7 carbon atoms. By having the linker (L) contain at least 4 carbon atoms, it is considered that harmful interference between the linker and the blue light absorbing site is minimized. It has been confirmed that by having the linker contain at least 4 carbon atoms, the blue light absorbing action of the blue light absorbing site is made excellent.

[0043] Since the hydrophilic non-polyalkylene glycol linker (L) contains at least 4 carbon atoms while imparting hydrophilicity, it is preferable that the charged portion is derived from an amino acid, and more preferably it is cysteine, aspartic acid, glutamic acid, and lysine.

[0044] The polymerizable blue light absorber of general formula (I) contains an ethylenically unsaturated polymerizable site (Py) in addition to the blue light absorbing site (U) and the hydrophilic non-polyalkylene glycol linker (L). The ethylenically unsaturated polymerizable site acts such that under appropriate polymerization conditions, the polymerizable blue light absorber and other monomers form a polymer by covalent bonding. The polymerization conditions are not particularly limited, and examples include free radical polymerization.

[0045] The ethylenically unsaturated polymerizable site can be selected from any site suitable for undergoing a reaction via free radical polymerization. For this purpose, the ethylenically unsaturated polymerizable site (Py) preferably contains a polymerizable functional group selected from the group consisting of allyl, vinyl, acryloyl, methacryloyl, and styrenyl.

[0046] When the ethylenically unsaturated polymerizable site (Py) is a polymerizable acryloyl group, it can be an acrylate group or an acrylamide group. Similarly, when it is a polymerizable methacryloyl group, it can be a methacrylate group or a methacrylamide group.

[0047] The polymerizable blue light absorber represented by the general formula (I) is not particularly limited as long as it consists of a blue light absorption site (U) having the above-mentioned tert-butyl group, a hydrophilic non-polyalkylene glycol linker (L) composed of at least 4 carbon atoms, and an ethylenically unsaturated polymerizable site (Py). A non-limiting specific example of the polymerizable blue light absorber is tBu-HBA-Lys-MA represented by the formula (1).

[0048]

Chemical formula

[0049] In the compound of the formula (1), the blue light absorption site having a tert-butyl group is derived from tBu-HBA (3-(3-(2H-Benzo[d][1,2,3]triazol-2-yl)-5-(tert-butyl)-4-hydroxyphenyl)propanoic acid); the hydrophilic non-polyalkylene glycol linker (L) composed of at least 4 carbon atoms is derived from lysine; and the ethylenically unsaturated polymerizable site (Py) is derived from maleic acid. That is, the compound of the formula (1) has a structure in which tBu-HBA, Lys, and MA are covalently bonded.

[0050] The polymerizable blue light absorber of the general formula (I) can be synthesized according to the method described in Patent Document 5. For example, according to the method described in the item "Synthesis of polymerisable UV absorber with hydroxyphenyl-benzotriazole moiety and an alternative anionic linker:HBA-Lys-MA" in "EXAMPLES" described in Patent Document 5, by using tBu-HBA (3-(3-(2H-Benzo[d][1,2,3]triazol-2-yl)-5-(tert-butyl)-4-hydroxyphenyl)propanoic acid) instead of HBA, tBu-HBA-Lys-MA of the formula (1) can be synthesized.

[0051] In the hydrogel of one embodiment of the present invention, the polymerizable blue light absorber of the general formula (I) is incorporated into the polymer component of the hydrogel by a covalent bond. Thereby, it is possible to prevent the polymerizable blue light absorber from eluting from the hydrogel material. When the polymerizable blue light absorber elutes, problems such as toxicity may occur or the loss of the blue light absorption effect may be impaired. Therefore, improving the stability is important when applying the hydrogel to an ophthalmic lens, particularly an implantable ophthalmic lens such as an intraocular lens (IOL).

[0052] In the blue light-absorbing hydrogel of one embodiment of the present invention, one selected from the group consisting of the polymerizable blue light absorbers of the general formula (I) can be used alone or in combination of two or more. The preferable blending amount of the polymerizable blue light absorber of the general formula (I) in the blue light-absorbing hydrogel of one embodiment of the present invention is not particularly limited. For example, in order for the hydrogel to have transparency and a blue light absorption effect, it is preferably 0.01% by weight to 10% by weight, more preferably 0.1% by weight to 7% by weight, based on the total amount of the monomer components constituting the hydrogel. When the blending amount of the polymerizable blue light absorber of the general formula (I) is less than 0.01% by weight, it becomes difficult to exhibit the absorbability of blue light in the obtained hydrogel. When the blending amount of the polymerizable blue light absorber of the general formula (I) exceeds 10% by weight, cloudiness and a decrease in strength are likely to occur in the obtained hydrogel, which is not preferable.

[0053] The hydrogel of one embodiment of the present invention is preferably a copolymer of a polymerizable blue light absorber of the general formula (I) and an ethylenically unsaturated monomer copolymerizable with the polymerizable blue light absorber. That is, for the hydrogel of one embodiment of the present invention, the hydrogel polymer is composed of a residue derived from the polymerizable blue light absorber of the general formula (I) and a residue derived from the ethylenically unsaturated monomer. Examples of such ethylenically unsaturated monomers include, but are not limited to: (a) Acryloyl and methacryloyl monomers such as acrylic acid, methacrylic acid, acrylamide, and methacrylamide, and derivatives of their esters and amides; (b) Silicone-substituted acrylate or methacrylate; (c) Fluorinated acrylate or methacrylate; and (d) Vinyl or vinylidene compounds such as vinyl pyrrolidone, vinyl silane, vinyl sulfone, vinyl alcohol or ester.

[0054] Hereinafter, specific examples of ethylenically unsaturated monomers copolymerizable with the polymerizable blue light absorber of the general formula (I) will be listed according to their characteristics and / or functions.

[0055] Also, the polymerizable blue light absorber of the general formula (I) and a benzotriazole-based ultraviolet absorber may be used in combination. By using these in combination, the absorbability of blue light can be further improved. Specific examples of the benzotriazole-based ultraviolet absorber include 2-(2'-hydroxy-5'-methylphenyl)benzotriazole, 2-(2'-hydroxy-5'-tert-butylphenyl)benzotriazole, 2-(2'-hydroxy-3'-tert-butyl-5'-methylphenyl)-5-chlorobenzotriazole, 2-(2'-hydroxy-3',5'-di-tert-aminophenyl)-5-chlorobenzotriazole, 2-(2'-hydroxy-3',5'-di-tert-butylphenyl)-5-chlorobenzotriazole, 2-(2'-hydroxy-5'-methacryloxyphenyl)-2H-benzotriazole, etc., but are not limited thereto. Among these, in the present invention, 2-(2'-hydroxy-5'-methacryloxyphenyl)-2H-benzotriazole having a copolymerizable functional group in the molecule is preferably used. In the blue light absorbing hydrogel of the present invention, the blending amount of the benzotriazole-based ultraviolet absorber is not particularly limited. For example, from the viewpoint of compatibility with the polymerizable blue light absorber of the general formula (I), it is preferably 0.1% by weight to 5% by weight, more preferably 0.1% by weight to 3% by weight.

[0056] In the blue light-absorbing hydrogel according to one aspect of the present invention, it is preferable to use a hydrophilic monomer as a monomer copolymerizable with the polymerizable blue light absorber of the general formula (I). The hydrophilic monomer has a portion contributing to hydrophilicity and a polymerizable functional group, and is not particularly limited as long as it is usually used as a hydrogel material, particularly an ophthalmic lens material such as a contact lens. For example, (meth)acrylic monomers such as N,N-dimethylacrylamide, 2-hydroxyethyl methacrylate, (meth)acrylic acid, polyethylene glycol monomethacrylate, and glycerol methacrylate; vinyl monomers such as N-vinylpyrrolidone, N-vinyl-N-methylacetamide, N-vinyl-N-ethylacetamide, N-vinyl-N-ethylformamide, and N-vinylformamide. These can be used alone or in combination of two or more. The blending amount of the hydrophilic monomer is not particularly limited. For example, in order to impart a preferable water content rate to the obtained hydrogel, it is preferably 85% by weight to 99.9% by weight, more preferably 90% by weight to 99.5% by weight, based on the total amount of the monomer components constituting the hydrogel. By controlling the types and blending amounts of the polymerizable blue light absorber of the general formula (I) and the hydrophilic monomer, it becomes possible to obtain a hydrogel having desired flexibility and water content rate.

[0057] In the blue light-absorbing hydrogel according to one aspect of the present invention, a hydrophobic monomer can be used as a constituent component for the purpose of imparting strength, shape stability, and flexibility to the obtained hydrogel ophthalmic lens. The hydrophobic monomer does not have a portion contributing to hydrophilicity, or even if it has such a portion, it has hydrophobicity as a whole molecule to such an extent, and has a polymerizable functional group, and is not particularly limited as long as it is usually used as a hydrogel material, particularly an ophthalmic lens material such as a contact lens. For example, linear, branched, or cyclic alkyl (meth)acrylates such as methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, i-propyl (meth)acrylate, n-butyl (meth)acrylate, i-butyl (meth)acrylate, t-butyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, cyclohexyl (meth)acrylate, methoxydiethylene glycol (meth)acrylate, ethoxydiethylene glycol (meth)acrylate, phenyl (meth)acrylate, phenoxyethyl (meth)acrylate, benzyl (meth)acrylate, isobornyl (meth)acrylate, etc. can be mentioned. The hydrophobic monomer can be appropriately blended alone or in combination of two or more according to the desired physical properties. The blending amount of the hydrophobic monomer is not particularly limited and may be appropriately set according to the desired physical properties. For example, it is preferably 0 wt% to 30 wt%, more preferably 0 wt% to 20 wt% with respect to the total amount of the monomer components constituting the hydrogel. When the blending amount of the hydrophobic monomer exceeds 30 wt%, the strength, shape stability, flexibility, etc. of the obtained hydrogel polymer may decrease.

[0058] In the blue light-absorbing hydrogel according to one aspect of the present invention, a crosslinkable monomer can be used as a constituent component for the purpose of imparting heat resistance and mechanical properties to the obtained hydrogel. The crosslinkable monomer is not particularly limited as long as it has at least two polymerizable functional groups and is usually used as a hydrogel material, particularly an ophthalmic lens material such as a contact lens. For example, (meth)acrylate-based crosslinkable compounds such as ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, propylene glycol di(meth)acrylate, dipropylene glycol di(meth)acrylate, trimethylolpropane tri(meth)acrylate, and pentaerythritol tri(meth)acrylate; vinyl-based crosslinkable compounds such as allyl methacrylate, diallyl maleate, diallyl fumarate, diallyl succinate, diallyl phthalate, triallyl cyanurate, triallyl isocyanurate, diethylene glycol bisallyl carbonate, triallyl phosphate, triallyl trimellitate, diallyl ether, N,N-diallyl melamine, and divinylbenzene can be mentioned. The crosslinkable monomer can be appropriately blended alone or in combination of two or more according to the desired physical properties. The blending amount of the crosslinkable monomer is not particularly limited and may be appropriately set according to the properties to be imparted to the hydrogel. For example, it is preferably 0.01% by weight to 10% by weight, more preferably 0.05% by weight to 3% by weight, based on the total amount of the monomer components constituting the hydrogel. If the blending amount of the crosslinkable monomer exceeds 10% by weight, the flexibility of the obtained hydrogel may decrease.

[0059] The blue light-absorbing hydrogel according to one aspect of the present invention can be produced by combining steps known to those skilled in the art, and its production method is not particularly limited. As a non-limiting production method of the blue light-absorbing hydrogel according to one aspect of the present invention, for example, a method including the following steps can be mentioned: After weighing in a blue light absorber of general formula (I) as a constituent, a hydrophilic monomer, and, if desired, other monomers such as a hydrophobic monomer and a crosslinkable monomer, a polymerization initiator is added and stirred and dissolved to obtain a monomer mixture; a step of putting the obtained monomer mixture into a desired mold and obtaining a copolymer by copolymerization reaction; a step of cooling the copolymer and peeling it from the mold, cutting and polishing it as necessary, and then hydrating and swelling the formed copolymer to obtain a hydrogel.

[0060] The polymerization initiator is not particularly limited, and examples thereof include a thermal polymerization initiator and a photopolymerization initiator. Specifically, peroxide-based polymerization initiators such as lauroyl peroxide, cumene hydroperoxide, and benzoyl peroxide, which are general radical polymerization initiators; azo-based polymerization initiators such as azobisdimethylvaleronitrile and azobisisobutyronitrile (AIBN) can be used alone or in combination of two or more. The addition amount of the polymerization initiator is not particularly limited as long as it is a sufficient amount to promote the copolymerization reaction of the monomers. For example, 10 ppm to 7,000 ppm is preferable based on the total amount of the monomer components constituting the hydrogel.

[0061] The step of obtaining the copolymer can be carried out by putting the monomer mixture into a mold such as metal, glass, or plastic, sealing it, and heating it stepwise or continuously in the range of 25°C to 120°C in a constant temperature bath or the like to complete the polymerization in 5 hours to 120 hours. Ultraviolet rays, electron beams, gamma rays, etc. may be used to induce radical polymerization. Also, solution polymerization may be applied by adding water or an organic solvent to the monomer mixture.

[0062] The step of obtaining the hydrogel is to cool the mold to room temperature after the polymerization is completed, then peel the polymer from the mold, cut and polish it as necessary, and then hydrate and swell it to obtain a hydrogel. Examples of the liquid (swelling liquid) to be used include water, physiological saline, and isotonic buffer solutions. The swelling liquid is heated to 60°C to 100°C and immersed for a certain period of time to make it in a swollen state. Also, it is preferable to remove the unreacted monomers contained in the polymer during the swelling treatment.

[0063] The hydrogel of one aspect of the present invention can contain about 40% (w / w) to about 80% (w / w) of a polymer. That is, the polymer (solid) component can form about 40% by weight to about 80% by weight of the hydrogel. The remainder of the hydrogel is typically formed from a liquid component (e.g., water) that hydrates the polymer component of the hydrogel. For example, a HEMA hydrogel can contain about 42% by weight of a solid component, and the remainder is a liquid component such as water.

[0064] If necessary, other additives or components known in the art can be included in the monomer mixture. Such additives or other components can include, for example, diluents, stabilizers, dyes, pigments, antibacterial compounds, release agents, and the like.

[0065] A hydrogel having a polymer component formed using a polymerizable blue light absorber of general formula (I) can have hydrophilic and optical properties suitable for the production of ophthalmic lenses such as contact lenses and intraocular lenses. The properties of the hydrogel are also imparted to the ophthalmic lenses manufactured using the hydrogel material. Since the hydrogel has a blue light absorbing effect, contact lenses and intraocular lenses formed using the hydrogel also have a blue light absorbing effect.

[0066] As a finding obtained by the present inventors, it has been found that the properties of the hydrogel beneficial for the application of ophthalmic lenses such as water content, optical transparency, and color do not change unacceptably as a result of the presence of the polymerizable blue light absorber of general formula (I) in the hydrogel polymer. That is, the hydrogel of one aspect of the present invention, for example, a hydrogel formed using tBu-HBA-Lys-MA of formula (1), is comparable to a base hydrogel having a polymer component that does not contain tBu-HBA-Lys-MA in terms of water content, optical transparency, and color when the area, diameter, and thickness are the same, and is at least within an acceptable range of variation.

[0067] When applied as an ophthalmic lens, the hydrogel of one embodiment of the present invention preferably has a thickness of 50 μm to 150 μm. The hydrogel of one embodiment of the present invention is obtained by subjecting a monomer mixture containing 1.0 to 2.0 parts by mass of the polymerizable blue light absorber of the general formula (I) to a copolymerization reaction with respect to 100 parts by mass of the total amount of the monomer components constituting the hydrogel. When the thickness of the central portion is 90 μm, the visual transmittance is 99% or more, and the absorption rate of blue light having a wavelength of 380 nm to 420 nm is 8% or more, preferably 10% or more, and / or the absorption rate of blue light having a wavelength of 380 nm to 500 nm may be 4% or more, preferably 5% or more. The visual transmittance and the blue light absorption rate are measured by the method described in the examples below.

[0068] According to another aspect of the present invention, there is provided an ophthalmic lens composed of the hydrogel of one embodiment of the present invention having the above thickness. The ophthalmic lens of one embodiment of the present invention preferably does not show a yellow appearance when placed on white paper. Further, the ophthalmic lens of one embodiment of the present invention preferably has a water content of 10% (w / w) or more, and more preferably 20% (w / w) to 70% (w / w).

[0069] The ophthalmic lens of one embodiment of the present invention can be a contact lens. The contact lens is a hydrophilic lens and can be a soft contact lens or a hard contact lens (i.e., rigid gas permeable (RGP)) depending on the monomer or combination of monomers that copolymerize with the polymerizable blue light absorber of the general formula (I).

[0070] The contact lens may include a lens for correcting visual impairment, a so-called "bandage lens" used for treating eye disorders, and a cosmetic lens used for purposes such as changing the apparent eye color. Also, as one embodiment of the present invention, it can also be an intraocular lens (IOL).

[0071] Hereinafter, the present invention will be described in more detail with reference to the embodiments of the present invention. However, the present invention is not limited to these embodiments, and the present invention can take various forms as long as the problems of the present invention can be solved.

Examples

[0072] Example 1. Evaluation of the blue light absorption effect of 2-(2-hydroxyphenyl)benzotriazole derivatives (1) A monomer mixed solution containing tBu-HBA-Lys-MA, HMB-Cys-MA, HBE-Glu-MA, and HBA-Lys-MA, which are 2-(2-hydroxyphenyl)benzotriazole derivatives, as constituent components was prepared, and the blue light absorption effect of the monomer mixed solution was evaluated.

[0073] (Evaluation method) [Ultraviolet-visible transmission spectrum] Using an ultraviolet-visible spectrophotometer ("UV-3150"; Shimadzu Corporation), the ultraviolet-visible transmission spectrum (wavelength range: 300 nm - 500 nm, interval: 1 nm) of the monomer mixed solution was measured.

[0074] (Synthesis of tBu-HBA-Lys-MA) According to the method described in the item "Synthesis of polymerisable UV absorber with hydroxyphenyl-benzotriazole moiety and an alternative anionic linker: HBA-Lys-MA" in "EXAMPLES" in International Publication WO2020 / 118361 (International Application Number: PCT / AU2019 / 051356; Patent Document 5), tBu-HBA (3-(3-(2H-Benzo[d][1,2,3]triazol-2-yl)-5-(tert-butyl)-4-hydroxyphenyl)propanoic acid) shown in the following formula (A) was used instead of HBA to synthesize tBu-HBA-Lys-MA of the following formula (1).

[0075]

Chemical formula

[0076]

Chem.

[0077] (Synthesis of (2-(2-hydroxyphenyl)benzotriazole derivatives)) According to the method described in International Publication WO2020 / 118361, HMB-Cys-MA, HBE-Glu-MA, and HBA-Lys-MA of the following formulas (2) to (4) were synthesized.

[0078]

Chem.

[0079]

Chem.

[0080]

Chem.

[0081] (Preparation of monomer solution containing (2-(2-hydroxyphenyl)benzotriazole derivatives)) To HEMA, which is a base monomer, 0.2 mM of tBu-HBA-Lys-MA (0.01% by mass), HMB-Cys-MA (0.01% by mass), HBE-Glu-MA (0.008% by mass), or HBA-Lys-MA (0.009% by mass) was added, and the mixture was stirred for about 1 hour while thoroughly purging with nitrogen.

[0082] (Evaluation results) The results of measuring the ultraviolet-visible transmission spectra of each monomer mixed solution are shown in Fig. 1.

[0083] As shown in Fig. 1, the monomer mixed solution containing tBu-HBA-Lys-MA had a lower light transmittance in the wavelength range of 380 nm to 500 nm corresponding to blue light compared to the monomer mixed solution containing HMB-Cys-MA, HBE-Glu-MA, or HBA-Lys-MA.

[0084] In particular, when comparing the blue light absorption rates (= 100 - [light transmittance]) in the short wavelength side of 380 nm to 420 nm, which has strong energy among blue lights, the monomer solutions containing HMB-Cys-MA, HBE-Glu-MA, or HBA-Lys-MA were 5.2% to 8.8%, while the monomer solution containing tBu-HBA-Lys-MA was 19.8%, and a difference of more than twice was observed between them.

[0085] From the above results, among 2-(2-hydroxyphenyl)benzotriazole derivatives, it was found that tBu-HBA-Lys-MA has an excellent blue light absorption effect. Also, from this, it was suggested that the linker (Lys) in tBu-HBA-Lys-MA has little effect on the blue light absorption effect of tBu-HBA-Lys-MA.

[0086] Example 2. Evaluation of the blue light absorption effect of the hydrogel having tBu-HBA-Lys-MA As a copolymer component, a hydrogel containing tBu-HBA-Lys-MA residues and / or HMB residues, which are 2-(2-hydroxyphenyl)benzotriazole derivatives, was prepared, and the transparency and blue light absorption effect of the hydrogel were evaluated.

[0087] (Evaluation method) [Visual transmittance] Using an ultraviolet-visible spectrophotometer ("V-750"; manufactured by JASCO Corporation), the light transmittance (%) (wavelength range: 380 nm - 780 nm; interval: 5 nm) of at least three hydrogels was measured, and based on the test method of ISO18369-3, the visual transmittance (%) was calculated from the measured light transmittance at each wavelength.

[0088] [Blue light absorption rate] Using an ultraviolet-visible spectrophotometer (“V-750”; manufactured by JASCO Corporation), the light transmittance (%) of at least three hydrogels was measured (wavelength range: 380 nm - 500 nm, 380 nm - 420 nm; interval: 5 nm), and the light absorption rate was calculated from the measured values (= 100 - [light transmittance]), and further, the average value of the obtained light absorption rates was calculated to obtain the blue light absorption rate (%).

[0089] [Thickness correction of visual transmittance and blue light absorption rate] Taking into account the influence of the thickness of the hydrogel, based on the thickness of 0.09 mm, which is common for the central part as a contact lens, the correction was made and evaluated according to the following calculation formula (X).

[0090] [Equation] Light transmittance at the measurement wavelength; %T Central thickness of the hydrogel; t Light transmittance after thickness correction; %Tc

[0091] (Synthesis of tBu-HBA-Lys-MA / HMB-containing hydrogel) To 100 parts by mass of a base monomer mixture (96.5% by mass of 2-hydroxyethyl methacrylate (HEMA), 3.3% by mass of methyl methacrylate (MMA), 0.2% by mass of ethylene glycol dimethacrylate (EGDMA)), tBu-HBA-Lys-MA and / or 2-(2'-hydroxy-5'-methacryloxyphenyl)-2H-benzotriazole (HMB) in the proportions shown in Table 1 and 0.2 parts by mass of azobisisobutyronitrile (AIBN), which is a polymerization initiator, were added, and the mixture was stirred for about 1 hour while thoroughly purging with nitrogen.

[0092] The obtained monomer mixture was put into a mold for contact lenses and then subjected to a copolymerization reaction in which the temperature was raised from 50 °C to 100 °C over 25 hours. After the reaction, the mold was cooled to room temperature, and the copolymer in the mold was taken out. The obtained copolymer was subjected to a hydration swelling treatment by immersing it in distilled water at about 80 °C for about 4 hours to obtain a colorless and transparent hydrogel.

[0093] (Evaluation results) Table 1 shows the results of measuring the visual transmittance, blue light absorption rate, and central thickness of each hydrogel.

[0094] As shown in Table 1, the hydrogel having the tBu-HBA-Lys-MA moiety ensured good transparency, had a blue light absorption effect, and, surprisingly, this blue light absorption effect increased in a tBu-HBA-Lys-MA amount-dependent manner.

[0095] Also, the blue light absorption effect of the hydrogel having the tBu-HBA-Lys-MA moiety was not significantly affected by the coexisting HMB moiety.

[0096] [Table 1]

[0097] From the above results, it was found that the hydrogel having the tBu-HBA-Lys-MA residue has transparency and a blue light absorption effect, and is useful as a contact lens or the like that reduces the influence on eye tissues by blue light (blue light).

[0098] Example 3. Evaluation of the blue light absorption effect of 2-(2-hydroxyphenyl)benzotriazole derivatives (2) Similar to tBu-HBA-Lys-MA, a monomer mixed solution containing tBu-HBA-PEGMA, which has a tBu-HBA moiety in the molecule and is a 2-(2-hydroxyphenyl)benzotriazole derivative, as a constituent component was prepared, and the blue light absorption effect of the monomer mixed solution was evaluated.

[0099] (Synthesis of tBu-HBA-PEGMA) According to the method described in International Publication WO2020 / 118361, tBu-HBA-PEGMA of the following formula (5) was synthesized. Further, purification by silica gel column chromatography was performed on the obtained tBu-HBA-PEGMA, and tBu-HBA-PEGMA having different PEG chain lengths (n is 3 to 6) 3, tBu-HBA-PEGMA 4 , tBu-HBA-PEGMA 5 and tBu-HBA-PEGMA 6 were fractionated and isolated.

[0100] [Chemical formula] (5)

[0101] (Preparation of monomer mixed solution containing tBu-HBA-PEGMA) Instead of tBu-HBA-Lys-MA, etc., tBu-HBA-PEGMA 3 , tBu-HBA-PEGMA 4 , tBu-HBA-PEGMA 5 and tBu-HBA-PEGMA 6 A monomer mixed solution was prepared in the same manner as in Example 1, except that tBu-HBA-PEGMA was used.

[0102] (Evaluation results) In the same manner as in Example 1, the ultraviolet-visible transmission spectra of monomer mixed solutions containing tBu-HBA-Lys-MA, tBu-HBA-PEGMA 3 , tBu-HBA-PEGMA 4 , tBu-HBA-PEGMA 5 or tBu-HBA-PEGMA 6 were measured.

[0103] From the measured spectra, when the blue light absorption rates in the wavelength range of 380 nm to 420 nm were compared, no significant difference was found between the monomer mixed solution containing tBu-HBA-Lys-MA (19.8%) and the monomer mixed solution containing tBu-HBA-PEGMA (17.1% - 20.6%).

[0104] On the one hand, as described in International Publication WO2020 / 118361, the hydrogel having a tBu-HBA-PEGMA moiety was opaque and unsuitable as a contact lens. Similarly, as described in International Publication WO2020 / 118361, when HMB having an HBA and a polymerizable group in the molecule and no linker was used, the resulting hydrogel was also opaque and unsuitable as a contact lens.

[0105] From the above results, by using a 2-(2-hydroxyphenyl)benzotriazole derivative having an ultraviolet absorption site with a tBu group, a non-PEG linker, and a polymerizable site as a blue light-absorbing monomer, the resulting hydrogel has transparency and a blue light-absorbing effect, and it was found to be useful as a contact lens or the like that reduces the influence on eye tissues by blue light (blue light).

Industrial Applicability

[0106] According to the present invention, through industrial production and commercial provision, it is possible to suppress or block blue light emitted from LED displays and LED lighting such as computer displays, smartphones, and video game consoles, thereby preventing adverse effects on human tissues such as eye tissues by blue light, and thus contributing to the health and well-being of living organisms.

Claims

1. An ophthalmic lens selected from the group consisting of a contact lens and an intraocular lens, comprising a hydrogel for blue light absorption containing a residue derived from a polymerizable blue light absorber represented by the following general formula (I). U-L-Py (I) (In the formula, U is a blue light absorbing site having a tert-butyl group, L is a hydrophilic non-polyalkylene glycol linker consisting of at least 4 carbon atoms, and Py is an ethylenically unsaturated polymerizable site.)

2. The ophthalmic lens according to claim 1, wherein the blue light absorbing site (U) having the tert-butyl group has a structure represented by the following general formula (II). 【Chemical 1】 (II) (In the formula, R ２ represents a tert-butyl group, R ３ is selected from a hydrogen atom, a halogen atom, and -CF ３ and R ４ represents a binding point to the linker (L).)

3. The ophthalmic lens according to claim 1 or 2, wherein the linker (L) is a linker derived from an amino acid.

4. The ophthalmic lens according to any one of claims 1 to 3, wherein the ethylenically unsaturated polymerizable site (Py) contains a polymerizable functional group selected from the group consisting of allyl, vinyl, acryloyl, methacryloyl and styrenyl.

5. An ophthalmic lens selected from the group consisting of a contact lens and an intraocular lens, comprising a hydrogel for blue light absorption containing a residue derived from tBu-HBA-Lys-MA represented by the following formula (1). [Chemical Formula 2] （１）

6. The hydrogel contains, per 100 parts by mass of the hydrogel, 0.01 part by mass to 10 parts by mass of a residue derived from the polymerizable blue light absorber represented by the general formula (I) or a residue derived from tBu-HBA-Lys-MA represented by the formula (1). The ophthalmic lens according to any one of claims 1 to 5.

7. The ophthalmic lens according to any one of claims 1 to 6, wherein the blue light absorption rate at 380 nm to 500 nm is 5% or more.

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