WO2019228224A1 - 聚合物材料以及眼内透镜 - Google Patents

聚合物材料以及眼内透镜 Download PDF

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WO2019228224A1
WO2019228224A1 PCT/CN2019/087749 CN2019087749W WO2019228224A1 WO 2019228224 A1 WO2019228224 A1 WO 2019228224A1 CN 2019087749 W CN2019087749 W CN 2019087749W WO 2019228224 A1 WO2019228224 A1 WO 2019228224A1
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intraocular lens
monomer
meth
polymer material
acrylate
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PCT/CN2019/087749
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English (en)
French (fr)
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甲斐元虎
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上海富吉医疗器械有限公司
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Priority to CN201980036577.9A priority Critical patent/CN112204073B/zh
Priority to US15/734,039 priority patent/US12103992B2/en
Priority to EP19811260.9A priority patent/EP3805290B1/en
Publication of WO2019228224A1 publication Critical patent/WO2019228224A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L71/00—Compositions of polyethers obtained by reactions forming an ether link in the main chain; Compositions of derivatives of such polymers
    • C08L71/02—Polyalkylene oxides
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F20/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride, ester, amide, imide or nitrile thereof
    • C08F20/02—Monocarboxylic acids having less than ten carbon atoms, Derivatives thereof
    • C08F20/10—Esters
    • C08F20/26—Esters containing oxygen in addition to the carboxy oxygen
    • C08F20/30—Esters containing oxygen in addition to the carboxy oxygen containing aromatic rings in the alcohol moiety
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F20/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride, ester, amide, imide or nitrile thereof
    • C08F20/02—Monocarboxylic acids having less than ten carbon atoms, Derivatives thereof
    • C08F20/10—Esters
    • C08F20/12—Esters of monohydric alcohols or phenols
    • C08F20/14—Methyl esters, e.g. methyl (meth)acrylate
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
    • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
    • C08F220/10—Esters
    • C08F220/26—Esters containing oxygen in addition to the carboxy oxygen
    • C08F220/30—Esters containing oxygen in addition to the carboxy oxygen containing aromatic rings in the alcohol moiety
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
    • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
    • C08F220/10—Esters
    • C08F220/26—Esters containing oxygen in addition to the carboxy oxygen
    • C08F220/30—Esters containing oxygen in addition to the carboxy oxygen containing aromatic rings in the alcohol moiety
    • C08F220/301—Esters containing oxygen in addition to the carboxy oxygen containing aromatic rings in the alcohol moiety and one oxygen in the alcohol moiety
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F290/00—Macromolecular compounds obtained by polymerising monomers on to polymers modified by introduction of aliphatic unsaturated end or side groups
    • C08F290/02—Macromolecular compounds obtained by polymerising monomers on to polymers modified by introduction of aliphatic unsaturated end or side groups on to polymers modified by introduction of unsaturated end groups
    • C08F290/06—Polymers provided for in subclass C08G
    • C08F290/062—Polyethers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L33/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
    • C08L33/04—Homopolymers or copolymers of esters
    • C08L33/14—Homopolymers or copolymers of esters of esters containing halogen, nitrogen, sulfur, or oxygen atoms in addition to the carboxy oxygen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/14—Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
    • A61F2/16—Intraocular lenses
    • A61F2002/16965—Lens includes ultraviolet absorber
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/16—Materials or treatment for tissue regeneration for reconstruction of eye parts, e.g. intraocular lens, cornea

Definitions

  • the invention relates to polymer materials and intraocular lenses. More specifically, the present invention relates to a polymer material capable of producing an intraocular lens having a high refractive index, low adhesion on the lens surface, and suppressing the occurrence of flare and whitening, and an intraocular lens having the above characteristics.
  • an intraocular lens material In order to reduce the thickness of an intraocular lens, it is necessary to make such an intraocular lens material a high refractive index. In addition, in order to be inserted into the eye through a small incision, the intraocular lens can be rubbed or bent. For this reason, the material of the intraocular lens naturally needs to be soft, and also requires low adhesion, in order to prevent the surface of the optical portion from being adhered to reduce operability.
  • the intraocular lens material does not undergo the phenomenon of significant reduction in transparency due to hydration and condensation, which causes the transparency to decrease, that is, so-called glistening and sub-surfacenanoglistening. is crucial.
  • Patent Document 1 discloses a high refractive index acrylic material suitable as an intraocular lens material. The acrylic material is bendable and can be inserted into the eye from a small incision.
  • a polymer whose glass transition temperature is adjusted is obtained by selecting two or more kinds of monomers having different glass transition temperatures from the homopolymer formed, and changing the blending ratio of the monomers.
  • a homopolymer of an acrylate monomer has a lower glass transition temperature than a homopolymer of a methacrylate monomer. Therefore, in the intraocular lens material, an acrylate monomer is used at a higher blending amount.
  • the blending amount of the acrylate monomer increases, the adhesion of the surface of the intraocular lens material increases, and the surface of the optical portion becomes easier to adhere when rubbed or bent. Therefore, the operability of the intraocular lens is lowered, or the time taken for the intraocular lens to return to its original shape becomes longer, which is not preferable.
  • Patent Document 2 an attempt has been made to reduce the adhesiveness in a bendable acrylic material (for example, refer to Patent Document 2).
  • Patent Document 2 a fluorine-based monomer is used as one of the components to reduce the adhesion of the acrylic material.
  • Patent Document 3 a method of reducing the adhesion of the surface of the optical portion of the intraocular lens material by applying a plasma treatment to the surface has been proposed (for example, refer to Patent Document 3).
  • the refractive index of the obtained acrylic material is reduced by blending a fluorine-based monomer having a low refractive index.
  • a method based on surface modification as proposed in Patent Document 3 requires a large-scale device and complicates the process, so it is not preferable for mass production of intraocular lenses (intraocular lens materials). .
  • the adhesion is improved, the problem that the intraocular lens material is prone to sparkle and whitening after being inserted into the eye has not been solved.
  • Flashing and whitening are caused by the presence of trace amounts of water contained in the acrylic material.
  • the intraocular lens is in the aqueous humor in the eye, and absorbs the water from the aqueous humor and stabilizes it in a saturated water absorption state.
  • the temperature of the aqueous humor is easily affected by inflammation, body temperature, and even external environmental changes. If the temperature in the eye decreases, the water absorption of the intraocular lens decreases, and the water in the intraocular lens that has been absorbed becomes supersaturated. It is considered that because the supersaturated water has no escape space, an uneven portion in the three-dimensional network structure of the intraocular lens material undergoes phase separation, thereby causing flicker and whitening.
  • An intraocular lens using a bifunctional polyethylene glycol group-containing component (monomer and / or cross-linking agent) for the purpose of improving the flicker and whitening is disclosed (for example, refer to Patent Document 4).
  • a bifunctional polyethylene glycol group-containing component monomer and / or cross-linking agent
  • a lot of components containing polyethylene glycol groups are needed.
  • polyethylene glycol groups are the main factor that causes the refractive index of intraocular lenses to decrease, it is preferable to make polyethylene glycol groups The amount used is small.
  • an intraocular lens using a polyfunctional polyethylene glycol group-containing component is also disclosed (for example, refer to Patent Document 5).
  • Patent Document 1 Japanese Patent Application Laid-Open No. 4-292609
  • Patent Document 2 Japanese Unexamined Patent Publication No. 8-224295
  • Patent Document 3 US Patent No. 5,603,774
  • Patent Document 4 US Patent No. 6353069
  • Patent Document 5 Japanese Patent Publication No. 2015-512665
  • An object of the present invention is to provide a polymer material capable of producing an intraocular lens having a high refractive index, low adhesion on the lens surface, and suppressing the occurrence of flare and whitening.
  • Another object of the present invention is to provide a polymer material which can easily adjust its softness (glass transition temperature).
  • Another object of the present invention is to provide an intraocular lens having the above characteristics.
  • a macromonomer (A) represented by the following general formula (I) and at least one (methyl group having an aryl group) Polymerized from a monomer mixed solution of an acrylate monomer (B).
  • n are each independently 1 or 2
  • a, b, c, and d are each independently an integer of 4 or more
  • four Zs are each independently a substituent including a (meth) acryloyl group.
  • each of the Z is represented by the following formula (Z1), (Z2), or (Z3) ).
  • R 1 is a hydrogen atom or a methyl group.
  • R 2 is a hydrogen atom or a methyl group
  • m is an integer from 1 to 6
  • Y is a direct bond or an oxygen atom
  • D is a hydrogen atom, —C 6 H 5 , —CH 2 C 6 H 5 or —OC 6 H 5 .
  • An intraocular lens comprising the polymer material according to any one of (1) to (10) above.
  • the present invention it is possible to produce an intraocular lens having a high refractive index, low adhesion on the lens surface, and suppressing the occurrence of flare and whitening.
  • the glass transition temperature that is, flexibility
  • the intraocular lens polymer material
  • FIG. 1 is a model diagram briefly showing a polymer network formed when a macromonomer having a polyethylene glycol group in two branched chains is used.
  • FIG. 2 is a model diagram briefly illustrating a polymer network formed when a macromonomer having a polyethylene glycol group in four branch chains is used.
  • FIG. 3 is a photograph in the evaluation of flash and whitening.
  • FIG. 4 is a graph showing the relationship between the use amount of a macromonomer having a polyethylene glycol group in two branches and four branches and the glass transition temperature of an intraocular lens material (Examples 1 to 3 and Comparative Examples 1 to 6).
  • FIG. 5 is a graph showing the relationship between the amount of the macromonomer having a polyethylene glycol group in four branches and the glass transition temperature of the intraocular lens material (Examples 4 to 6).
  • the polymer material and the intraocular lens of the present invention will be described in detail.
  • a case where the polymer material of the present invention is used as an intraocular lens material will be described as a representative.
  • the monomer mixed liquid is preferably a monomer composition that can be used for producing an intraocular lens (intraocular lens material).
  • the monomer mixed liquid contains a macromonomer (A) and at least one (meth) acrylate monomer (B) having an aryl group.
  • the macromonomer (A) is a (meth) acrylate monomer having a polyethylene glycol group in four branches.
  • This macromonomer (A) has four polyethylene glycol groups and four (meth) acryloyl groups in one molecule as represented by the following general formula (I).
  • n are each independently 1 or 2
  • a, b, c, and d are each independently an integer of 4 or more
  • four Zs are each independently a substituent including a (meth) acryloyl group.
  • (meth) acryloyl means methacryloyl or acryl.
  • the macromonomer (A) as one of the components, it is possible to suppress the adhesion of the intraocular lens material, impart flexibility to the intraocular lens material, and suppress the occurrence of flicker and whitening.
  • the glass transition was adjusted by combining two or more (meth) acrylic acid ester monomers having different glass transition temperatures in the homopolymer to be composed and polymerizing them. Copolymer after temperature.
  • the glass transition temperature (flexibility) of the intraocular lens material can be adjusted only by appropriately changing the amount of the macromonomer (A) used.
  • the molecular weight of the macromonomer (A) is preferably about 1,000 to 3,000, and more preferably about 1400 to 2800.
  • the obtained intraocular lens material can be provided with softness and functions of suppressing flicker and whitening, and a homogeneous monomer mixed liquid can be obtained.
  • the molecular weight of the macromonomer (A) can be calculated from the saponification value of the macromonomer (A), and can also be expressed as a polystyrene-equivalent number by measurement by gel permeation chromatography (GPC). Average molecular weight.
  • Such a macromonomer (A) can be synthesized, for example, by the following steps.
  • the first route is a method for synthesizing a polyethylene glycol having four branches with a distributed number of repeating polyethylene glycol groups.
  • ethylene oxide is subjected to addition polymerization of pentaerythritol in the presence of a base catalyst.
  • the second path is a method of synthesizing a 4-branched polyethylene glycol having no distribution number of polyethylene glycol groups.
  • the number of repeats (average value) of the polyethylene glycol is 4 or more, a plurality of types having different repeat numbers are mixed.
  • the polyethylene glycol was purified by a chromatography column to obtain a polyethylene glycol having a uniform (single) repeat number (Compound 1).
  • TRT in the following route means a trityl group.
  • each Z may be a substituent including a (meth) acryloyl group, and may be a (meth) acryloyl group itself, or may include a (meth) acryloyl group and polyethylene glycol.
  • a group of a bonding group for example, an amide group (residue of a urethane group), a ketone group, or the like) bonded to the terminal of the alcohol.
  • a bonding group (such as an alkylene oxide group, an alkylene group, etc.) may be present between the (meth) acryloyl group and the bonding group.
  • each Z is preferably a substituent represented by the following formula (Z1), (Z2), or (Z3), and more preferably an acryl group.
  • R 1 is a hydrogen atom or a methyl group.
  • substituents can be easily and reliably introduced to the end of the 4-branched polyethylene glycol.
  • the four Zs may be different from each other, but are preferably the same.
  • the macromonomer (A) can be easily synthesized, and variation between batches can be reduced.
  • the macromonomer (A) can be represented by the following structural formulas A1, A2, A3, or A4.
  • polyethylene glycol group and “polyethylene glycol” refer to a structure in which the repeating number of ethylene oxide (in the general formula (I), each of a, b, c, and d) is 4 or more. .
  • the values of a, b, c, and d may have a distribution (ie, may be non-uniform), or may not have a distribution (ie, may be uniform).
  • the average value is an integer of 4 or more.
  • the fact that the values of a, b, c, and d do not have a distribution means that, for example, when the values of a, b, c, and d are 6, respectively, other values (for example, 5, 7, etc.) are not included.
  • a, b, c, and d are each preferably an integer of 4 to 14, and more preferably an integer of 6 to 12.
  • the total of a, b, c, and d is preferably an integer of 16 to 56, and more preferably an integer of 24 to 48.
  • a, b, c, and d By setting a, b, c, and d to a value greater than or equal to the above-mentioned lower limit values, it is possible to impart higher flexibility to the intraocular lens material, and to further suppress the occurrence of flicker and whitening.
  • a, b, c, and d by setting a, b, c, and d to a value that is equal to or less than the above upper limit, compatibility with other copolymerization components (other monomers) can be improved, and a more homogeneous monomer mixture can be obtained. liquid.
  • a, b , C, and d are preferably mutually approximated values.
  • the "average value” is applied to a case where the repeat number of the polyethylene glycol group in the macromonomer (A) is distributed.
  • the "average value” refers to a value obtained by performing a 1 H-NMR analysis on the macromonomer (A) and calculating a decimal point of the number of repetitions using a peak integral intensity ratio of an ethylene oxide unit. The first digit is rounded to get the value.
  • macromonomer means a monomer with a molecular weight of 900 or more.
  • the present inventors have conducted various investigations for the purpose of suppressing the adhesion of the intraocular lens material while providing flexibility, and also suppressing the occurrence of flicker and whitening.
  • the present inventors have found that although the detailed mechanism is not clear, the above-mentioned object can be achieved by using the macromonomer (A) in the range of 11 to 30% by mass. It has also been found that the softness (glass transition temperature) of an intraocular lens material can be adjusted only by appropriately changing the amount of use of the macromonomer (A). Then, based on these findings, the present inventors have completed the present invention.
  • a polyethylene glycol group is referred to as "PEG”
  • a macromonomer having a polyethylene glycol group is hereinafter also referred to as a "PEG-containing macromonomer”.
  • a macromonomer having a polyethylene glycol group in two branches hereinafter also referred to as a "2-branched PEG-containing macromonomer"
  • the obtained polymer is Cross-linking randomly results in a non-uniform structure.
  • dense portions and sparse portions are formed (see Fig. 1). Since water is phase-separated in the sparse part of the polymer network structure, it becomes easy to generate a flash and whitening.
  • the above tendency is also the same in the 3- and 8-chain PEG-containing macromonomers.
  • the difference in physical properties caused by the structure of the polymer is also applicable to the glass transition temperature of the polymer.
  • the crosslinking density of a polymer increases as the amount of the crosslinking agent used increases.
  • the degree of freedom of the mobility of the polymer chain is hindered, and the glass transition temperature of the polymer is increased.
  • the glass transition temperature of a homopolymer composed of two branched PEG-containing macromonomers is low.
  • the structure of the obtained polymer becomes uneven as described above. Therefore, the degree of freedom of the mobility of the polymer chain is hindered, and the glass transition temperature cannot be reduced significantly. This tendency is also found in PEG-containing macromonomers with 3 and 8 branches.
  • the 4-branched PEG-containing macromonomer since the 4-branched PEG-containing macromonomer easily forms a uniform network, the obtained polymer does not easily hinder the degree of freedom of the mobility of the polymer chain, and appears based on the flexibility of the polyethylene glycol group. Outstanding softness. Therefore, compared with a 2-branched PEG-containing macromonomer, the use of a 4-branched PEG-containing macromonomer can greatly reduce the glass transition temperature, and can also adjust the polymerization according to the amount used The glass transition temperature of the product.
  • the 4-branched PEG-containing macromonomer can reduce the glass transition temperature of the polymer in a smaller amount than the 2-branched PEG-containing macromonomer.
  • the polyethylene glycol group is the main cause of the decrease in the refractive index of the intraocular lens material, although it is preferably used in a small amount, its use can be reduced by using a 4-branched PEG-containing macromonomer. A reduction in the refractive index of the intraocular lens material is suppressed.
  • the use amount of the 4-branched PEG-containing macromonomer by reducing the use amount of the 4-branched PEG-containing macromonomer, the use amount of the (meth) acrylate monomer (B) described later can be increased, and as a result, the refractive index of the intraocular lens material can be increased.
  • the intraocular lens material of the present invention is different from conventional intraocular lens materials.
  • an acrylate monomer having an aryl group or reducing the amount of acrylate monomer having an aryl group it is possible to relatively increase the aryl group.
  • the amount of the methacrylic acid ester monomer can also suppress an increase in the adhesiveness of the obtained intraocular lens material.
  • the 4-branched PEG-containing macromonomer not only suppresses the adhesion of the lens material in the eye, but also provides flexibility, and also suppresses the occurrence of flicker and whitening. It also functions as a cross-linking agent component and exerts an effect of improving the mechanical strength of a polymer (intraocular lens material).
  • the amount (content) of the macromonomer (A) may be about 11 to 30% by mass, preferably about 12 to 25% by mass, and more preferably about 13 to 20% by mass.
  • the amount of the macromonomer (A) used is less than the above-mentioned lower limit value, the effect of suppressing the occurrence of flicker and whitening of the lens material in the eye cannot be sufficiently obtained.
  • the amount of the macromonomer (A) used exceeds the above-mentioned upper limit value, the refractive index of the intraocular lens material is extremely reduced.
  • the intraocular lens material becomes brittle.
  • the amount of the macromonomer (A) used is expressed in mol%, it is about 1.2 to 5 mol%, preferably about 1.2 to 4 mol%, and more preferably about 1.2 to 3 mol%.
  • mass% means that, based on the mass of the macromonomer (A), the mass of the (meth) acrylic acid ester monomer (B) described below, and having no aryl group as an optional component other than these two components, The value obtained by calculating the total amount (100%) of the mass of the (meth) acrylate monomer (C) and the crosslinkable monomer (D).
  • mol% also refers to the number of moles of the macromonomer (A), the number of moles of the (meth) acrylate monomer (B), the (meth) acrylate monomer (C), and the crosslinking The total value (100 mol%) of the number of moles of the monomer (D) was determined.
  • the (meth) acrylate monomer (B) is a monomer having an aryl group and a (meth) acryloyl group. This (meth) acrylate monomer (B) has the effect
  • the (meth) acrylate monomer (B) is preferably a monomer represented by the following general formula (II).
  • R 2 is a hydrogen atom or a methyl group
  • m is an integer of 1 to 6
  • Y is a direct bond or an oxygen atom
  • D is a hydrogen atom, -C 6 H 5 , -CH 2 C 6 H 5 or -OC 6 H 5 .
  • the (meth) acrylate monomer (B) include 2-phenylethyl (meth) acrylate, 3-phenylpropyl (meth) acrylate, and 4-benzene (meth) acrylate Butyl, 2-phenoxyethyl (meth) acrylate, 4-phenoxybutyl (meth) acrylate, 2- (4-phenylphenyl) ethyl (meth) acrylate, (formyl) 2- (3-phenylphenyl) ethyl acrylate, 2- (4-benzylphenyl) ethyl (meth) acrylate, 2- (4-phenylphenoxy) (meth) acrylate Ethyl ester, 2- (4-benzylphenoxy) ethyl (meth) acrylate, 3- (4-phenylphenoxy) propyl (meth) acrylate, 2- (4) (meth) acrylate -Phenoxyphenoxy) ethyl and the like. They
  • the (meth) acrylate monomer (B) is preferably selected from 2-phenoxyethyl methacrylate, 2-phenoxyethyl acrylate, 2-phenylethyl methacrylate, and acrylic acid 2 -At least one selected from phenylethyl ester, more preferably a combination of 2-phenoxyethyl methacrylate and 2-phenylethyl acrylate or 2-phenylethyl methacrylate and 2-benzene acrylate Of ethyl esters.
  • the glass transition temperature of the intraocular lens material can be further reduced.
  • the amount (content) of the (meth) acrylate monomer (B) is not particularly limited, but is preferably about 70 to 89% by mass, more preferably about 75 to 88% by mass, and still more preferably 77 to 87% by mass about.
  • the refractive index of the intraocular lens material can be sufficiently increased, and a decrease in the flexibility of the intraocular lens material can be suppressed.
  • the amount of the (meth) acrylate monomer (B) used is expressed in mol%, it is preferably 85 to 98.8 mol%, more preferably 87 to 98.8 mol%, and even more preferably 90 to 98.8 mol%. .
  • the monomer mixed liquid may contain other monomers (C) to (F) and the like other than the macromonomer (A) and the (meth) acrylate monomer (B).
  • the (meth) acrylate monomer (C) is a monomer which does not have an aryl group but has a (meth) acryloyl group.
  • This (meth) acrylate monomer (C) is one of the auxiliary monomers mixed in the monomer mixed liquid for the purpose of adjusting the flexibility and / or water absorption of the intraocular lens material.
  • the (meth) acrylate monomer (C) is preferably a monomer represented by the following general formula (III).
  • R 3 is a hydrogen atom or a methyl group, p is an integer of 0 to 4, Y is a direct bond or an oxygen atom, and R 4 is a hydrogen atom, a linear or branched C 1 to C 8 alkyl group Alternatively, it may be a linear or branched C 1 to C 8 alkyl group which may be substituted with a fluorine atom.
  • (meth) acrylate monomer (C) examples include 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, and 4-hydroxybutyl (meth) acrylate.
  • Esters methyl (meth) acrylate, ethyl (meth) acrylate, n-propyl (meth) acrylate, isopropyl (meth) acrylate, isobutyl (meth) acrylate, (meth) acrylic acid N-butyl ester, tert-butyl (meth) acrylate, isoamyl (meth) acrylate, hexyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, 2-formyl (meth) acrylate Ethoxyethyl, 2-ethoxyethyl (meth) acrylate, 2,2,2-trifluoroethyl (meth) acrylate, 2,2,3,3-
  • the crosslinkable monomer (D) is a type of auxiliary monomer incorporated in the monomer mixed liquid for the purpose of adjusting the mechanical strength of the intraocular lens material.
  • crosslinkable monomer (D) examples include ethylene glycol di (meth) acrylate, diethylene glycol di (meth) acrylate, and triethylene glycol di (meth) acrylic acid.
  • Ester tetraethylene glycol di (meth) acrylate, 1,3-propanediol di (meth) acrylate, 2,3-propanediol di (meth) acrylate, 1,4-butanediol di (meth) acrylate Base) acrylate, 1,6-hexanediol di (meth) acrylate, 1,9-nonanediol di (meth) acrylate, neopentyl glycol di (meth) acrylate, glycerol bis ( (Meth) acrylate, 3-methyl-1,5-pentanediol diacrylate, 2-hydroxy-3-acryloyloxypropyl (meth) acrylate, polyethylene glycol di (meth) Acry
  • the total amount (content) of the (meth) acrylate monomer (C) and the crosslinkable monomer (D) is preferably less than 10% by mass, more preferably about 0.1 to 9% by mass, and still more preferably 0.2 to 8 About mass%.
  • the used amount of the (meth) acrylate monomer (B) can be maintained relatively high, and as a result, the refractive index of the intraocular lens material can be prevented from being lowered.
  • the total amount of the (meth) acrylate monomer (C) and the crosslinkable monomer (D) is expressed in mol%, it is preferably less than 13 mol%, and more preferably 0.02 to 11 mol%. It is preferably about 0.04 to 8 mol%.
  • the polymerizable monomer (E) has a structure capable of absorbing ultraviolet rays, and is blended in the monomer mixed solution for the purpose of imparting ultraviolet absorbing ability to an intraocular lens (intraocular lens material).
  • polymerizable monomer (E) examples include 5-chloro-2- [2-hydroxy-5- ( ⁇ -methacryloxyethylcarbamoyloxyethyl)] benzene, for example.
  • -2H-benzotriazole 2- [2-hydroxy-5- ( ⁇ -methacryloxyethylcarbamoyloxyethyl)] phenyl-2H-benzotriazole
  • the polymerizable monomer (F) has, for example, a yellow structure capable of absorbing blue light, and is blended in the monomer mixture for the purpose of coloring the intraocular lens.
  • an azo-based, pyrazolone-based, or cyanine-based yellow colorant can be used as the polymerizable monomer (F).
  • Specific examples include, for example, Japanese Patent Laid-Open No. 10-195324, Japanese Patent Laid-Open No. 2000-290256, Japanese Patent Laid-Open No. 2003-119226, Japanese Patent No. 2008-520811, and Japanese Patent No. 2008-520352.
  • the used amount (content) of the polymerizable monomer (E) is preferably 5% by mass or less with respect to the total amount (100% by mass) of the mass of the monomers (A) to (D), and more preferably 0.1 to 3% by mass. about.
  • the used amount (content) of the polymerizable monomer (F) is preferably 1% by mass or less with respect to the total amount (100% by mass) of the mass of the monomers (A) to (D), and more preferably 0.01 to 0.5. About mass%.
  • any of a thermal polymerization initiator and a photopolymerization initiator can be used.
  • thermal polymerization initiator examples include bis (3,5,5-trimethylhexanoyl) peroxide, dilauroyl peroxide, benzoyl peroxide, and 2-ethyl peroxide.
  • Peroxide such as tert-hexyl hexanoate, 1,1,3,3-tetramethylbutyl peroxy-2-ethylhexanoate, tert-butyl peroxy-2-ethylhexanoate; 2,2 '-Azobis (2,4-dimethylvaleronitrile), 2,2'-azobis (isobutyronitrile), 2,2'-azobis (2-methylpropionate), 2,2'-azobis (2-methylbutyronitrile), 1,1'-azobis (1-cyclohexanecarboxylic acid methyl ester), 1,1'-azobis (cyclohexane-1 -Carbonitrile) and the like.
  • photopolymerization initiator examples include benzoin methyl ether, 1-hydroxycyclohexylphenyl ketone, 2,2-dimethoxy-2-phenylacetophenone, and 2-hydroxy-2-dimethylformaldehyde.
  • the amount (content) of the polymerization initiator (G) is appropriately selected depending on the polymerization temperature, the irradiation wavelength of light, and the irradiation intensity, etc., but is preferably a total amount (100% by mass) relative to the mass of the monomers (A) to (D). ) Is about 0.1 to 1% by mass.
  • the monomer mixture is poured into an injection mold for producing an intraocular lens corresponding to the shape of the intraocular lens to be produced, and then polymerized.
  • This injection mold is a combination mold in which a curved recess is formed, and is made of a material such as a metal material or a resin material.
  • the polymer (intraocular lens material or intraocular lens) of the monomer mixed liquid has a good peelability and is excellent in solvent resistance and heat resistance.
  • a resin injection mold can be easily formed into a shape required for a desired lens design, and is therefore preferred.
  • the resin material is preferably selected from materials having low mold shrinkage, good transferability from a surface of a metal material, and excellent dimensional accuracy and solvent resistance. Particularly, polypropylene is preferred as the resin material in terms of being inexpensive and easily available.
  • the resin material is not limited to polypropylene.
  • polyethylene polyethylene terephthalate, polymethylpentene, polysulfone, polyphenylene sulfide, cyclic olefin copolymer, and ethylene may be used.
  • -Vinyl alcohol copolymers and the like are examples of polypropylene.
  • an injection mold immediately after molding can be used.
  • an injection mold that has been stored for about 10 to 72 hours can also be used.
  • the pressure on the mold surface can be sufficiently reduced to remove substances that affect the polymerization reaction, such as moisture and oxygen.
  • an inert gas such as nitrogen or argon
  • the monomer can be removed.
  • the mixed liquid is poured into an injection mold.
  • the monomer mixture liquid when injecting the monomer mixture liquid, may be previously bubbled with an inert gas such as nitrogen or argon, thereby removing the oxygen dissolved in the monomer mixture liquid and using it. It is used after removing dissolved oxygen.
  • an inert gas such as nitrogen or argon
  • Examples of the polymerization method include a thermal polymerization method in which a thermal polymerization initiator is mixed in a monomer mixed solution and heated; or a photopolymerization initiator is mixed in a monomer mixed solution, and then photopolymerized by irradiation with ultraviolet rays or visible light. law.
  • the temperature is increased stepwise or continuously within a temperature range of about 20 to 130 ° C. and the heating is performed for about 5 to 48 hours, or the injection mold is heated. It can be arranged in a polymerization device set to a predetermined temperature (100 to 120 ° C) in advance and then heated for about 1 to 24 hours.
  • the atmosphere during the thermal polymerization may be an atmospheric atmosphere, but an inert gas atmosphere such as a nitrogen atmosphere or an argon atmosphere is preferred.
  • an inert gas atmosphere such as a nitrogen atmosphere or an argon atmosphere.
  • the pressure in the polymerization apparatus is preferably 2 kgf / cm 2 (0.196 MPa) or less.
  • the wavelength of the light to be irradiated is appropriately selected according to the characteristics of the photopolymerization initiator to be blended, and is not particularly limited.
  • the lamp used for light irradiation for example, a lamp having a strong peak at a wavelength of 200 to 280 nm and a wavelength of 350 nm, a lamp having an enhanced wavelength at a wavelength of 350 to 400 nm, and A lamp whose wavelength is centered to increase the wavelength in the 400 to 425 nm range, a lamp to increase the wavelength in the 400 to 450 nm range, and the like.
  • the value of the light irradiation intensity varies depending on the area of the light receiving portion of the device for measuring the irradiation intensity, but it is preferably about 5 to 100 mW / cm 2 , for example.
  • the irradiation time (polymerization time) of light is appropriately set according to the irradiation intensity of light, it is not particularly limited.
  • the light irradiation intensity is about 5 to 100 mW / cm 2
  • the light irradiation time is preferably set to about 5 to 60 minutes.
  • light may be irradiated in a polymerization device which is set to a predetermined temperature (about 40 to 80 ° C.) in advance. This can increase the polymerization rate of the monomers and reduce the amount of unreacted monomers.
  • the atmosphere during photopolymerization may be an atmospheric atmosphere, but may also be an inert gas atmosphere such as a nitrogen atmosphere or an argon atmosphere.
  • the photopolymerization in the above atmosphere can further increase the polymerization rate of the monomer.
  • the intraocular lens material is removed from the injection mold, or the intraocular lens material is not removed from the injection mold (that is, the intraocular lens material is stored in the injection mold), and the This intraocular lens material is processed into a desired shape by cutting and grinding (for example, the shape of the intraocular lens itself, and the shape of the optical portion of the intraocular lens).
  • the monomer mixture may be polymerized in an appropriate mold or container to produce a rod-shaped, block-shaped, or plate-shaped intraocular lens material, and then the intraocular lens material may be formed at a low temperature. It is processed into a desired shape by cutting and grinding.
  • the intraocular lens material can be taken out from the injection mold, and can be directly used as the intraocular lens itself or the optical part (lens body) of the intraocular lens without cutting or grinding.
  • a support part for supporting an optical part may be manufactured separately from an optical part, and a support part may be attached to an optical part as an intraocular lens.
  • the support portion may be formed integrally with the optical portion at the same time.
  • Examples of a constituent material of the support portion include polypropylene and polymethyl methacrylate (PMMA).
  • the intraocular lens of the present invention is composed of a predetermined shape of the intraocular lens material itself, or a processed product having the intraocular lens material.
  • the intraocular lens may be subjected to a process of reheating.
  • This reheating process is performed by arranging the intraocular lens in a device preset to a certain temperature (about 100 to 125 ° C.) and reheating for about 5 to 72 hours.
  • the atmosphere in the device at this time may be an atmospheric pressure atmosphere or an atmosphere (decompressed atmosphere) after being decompressed using a vacuum pump or the like.
  • the surface of the optical portion of the intraocular lens may be subjected to a low-temperature plasma treatment, an atmospheric pressure plasma treatment, or a cleaning treatment using ultraviolet rays or the like. According to the above-mentioned treatment, the cleanliness of the surface of the optical portion of the intraocular lens and the cell adhesion can be improved.
  • the value of the refractive index in a saturated water absorption state is preferably about 1.51 to 1.57, and more preferably It is about 1.52 to 1.57, and more preferably about 1.525 to 1.57.
  • the water absorption of the intraocular lens material is preferably about 0.7 to 4.5% by mass, more preferably about 0.8 to 3% by mass, and even more preferably about 0.9 to 2% by mass at 23 ° C.
  • the intraocular lens material is used as an intraocular lens that can be bent at room temperature, it is preferable to have a glass transition temperature lower than a normal human body temperature (about 37 ° C).
  • the lower limit value of the glass transition temperature of the intraocular lens material is preferably about 0 ° C, more preferably about 3 ° C, even more preferably about 5 ° C, particularly preferably about 7 ° C, and most preferably about 10 ° C.
  • the upper limit value of the glass transition temperature is preferably about 20 ° C, more preferably about 18 ° C, still more preferably about 17 ° C, still more preferably about 15 ° C, and particularly preferably about 12 ° C.
  • the glass transition temperature of the intraocular lens material is preferably about 10 to 15 ° C. from the viewpoint of being an intraocular lens material having a moderate shape resilience.
  • the intraocular lens material as described above is more resistant to flare and whitening than conventional intraocular lens materials.
  • the flash and whitening were evaluated according to the following procedures.
  • a lens-shaped or flat-plate-shaped sample was immersed in a physiological saline solution at 45 ° C. for more than 24 hours.
  • the immersed sample was left to stand for 2 hours under an environment set at 23 ° C. Then, the appearance (transparency) of this sample is observed with a microscope ("VHX-5000", manufactured by Keyence Corporation) at a magnification of 20 times or more.
  • flash means a state in which several to several tens of water particles having a particle diameter of 1 to 10 ⁇ m are generated in the intraocular lens material, but the transparency of the intraocular lens material does not substantially decrease.
  • whitening refers to a state in which the surface of the lens material of the eye looks hazy and whitened due to the aggregation of a large number of minute water particles having an average particle diameter of 100 nm.
  • the evaluation of flicker and whitening is based on a temperature change in the eye that occurs when an intraocular lens is actually inserted into a human eye, or a living environment after the intraocular lens is inserted into the eye.
  • the temperature change is performed.
  • the polymer material and the intraocular lens of the present invention may add other optional components to the configuration of the above-described embodiment, or may be replaced with optional components that perform the same function.
  • the polymer material of the present invention can also be used for making ophthalmic medical devices such as corneal inlays and corneal rings, as well as otolaryngology such as otolaryngological ventilation tubes and nasal implants.
  • ophthalmic medical devices such as corneal inlays and corneal rings
  • otolaryngology such as otolaryngological ventilation tubes and nasal implants.
  • Various medical devices such as medical devices.
  • Ph-A 1.770 g (44.25 mass%, 53.22 mol%)
  • Norbloc7966 0.060 g (1.5% by mass based on the total amount of Po-MA, Ph-A, and 4-ArmPEG34)
  • AIBN 0.012 g (0.3% by mass based on the total amount of Po-MA, Ph-A, and 4-ArmPEG34)
  • this monomer mixed solution is poured into a cell for producing an intraocular lens material.
  • This tank is composed of two polypropylene plates cut into a size of 7.5 cm in length and 5.0 cm in width, and a polytetrafluoroethylene liner sheet sandwiched between the two plates and having a predetermined distance. .
  • the cell filled with the monomer mixture was placed in a polymerization device, and the temperature was raised from 20 ° C to 50 ° C over 30 minutes, and the temperature was maintained at 50 ° C for 8 hours, and then further heated to 120 ° C over 6 hours, and maintained at 120 ° C After 2 hours of temperature, it was finally cooled to 40 ° C over 4 hours. Thereby, the monomers contained in the monomer mixed liquid are polymerized.
  • the atmosphere in the polymerization apparatus was a nitrogen atmosphere, and the pressure in the apparatus was 0.2 kgf / cm 2 (0.0196 MPa).
  • the obtained intraocular lens material was placed in a dryer set in advance at 120 ° C., and subjected to a heat treatment for 8 hours. Thereby, unreacted monomer is removed from the intraocular lens material.
  • the thickness of the obtained flat intraocular lens was in the range of 0.6 to 0.7 mm.
  • An intraocular lens material was produced in the same manner as in Example 1 except that a monomer mixed liquid having the composition shown in Table 1 was prepared.
  • An intraocular lens material was produced in the same manner as in Example 1 except that a monomer mixed liquid having the composition shown in Table 2 was prepared.
  • An intraocular lens material was produced in the same manner as in Example 1 except that a monomer mixed solution having the composition shown in Table 3 was prepared.
  • An intraocular lens material was produced in the same manner as in Example 1 except that a monomer mixed liquid having the composition shown in Table 1 was prepared.
  • An intraocular lens material was produced in the same manner as in Example 1 except that a monomer mixed solution having the composition shown in Table 3 was prepared.
  • the intraocular lens materials obtained in each of the examples and comparative examples were measured for refractive index, water absorption, and glass transition temperature, and evaluated for adhesion and flash and whitening.
  • an intraocular lens material cut into a rectangular shape with a width of 10 mm and a length of 15 mm was used as a test piece.
  • an intraocular lens material punched into a disc shape using a biopsy hole of ⁇ 5 mm was used as a test piece.
  • an intraocular lens material punched out to a size equivalent to the optical portion (lens body) of the intraocular lens using a biopsy hole of ⁇ 6 mm was used as a test piece.
  • the test piece was immersed in physiological saline at 25 ° C. for 72 hours, and became saturated with water.
  • the refractive index of e-rays (546.1 nm) at 25 ° C. of this test piece was measured using a refractive index meter (“DR-M2” manufactured by Atago Corporation).
  • the weight (Ww) of the test piece after reaching a saturated water absorption state at 23 ° C. and the weight (Wd) of the test piece after drying at 60 ° C. for 4 hours (vacuity: 266.6 Pa) using a reduced-pressure vacuum dryer were measured.
  • the water absorption was calculated by the following formula.
  • test piece was held in a folded state with tweezers for 1 minute. Then, the state of the test piece released from the forceps was observed with the naked eye, and evaluation was performed according to the following evaluation criteria.
  • test piece was immersed in 45 ° C physiological saline for 48 hours, and then left to stand for 2 hours in an environment set at 23 ° C. Then, the appearance (transparency) of the test piece in physiological saline was observed with a microscope ("VHX-5000", manufactured by Keyence Corporation) at a magnification of 50 times, and evaluated according to the following evaluation criteria.
  • the glass transition temperature (Tg) of the test piece (dry state) was measured using a differential scanning calorimeter as follows. First, the test piece was temporarily heated to a temperature above the glass transition temperature, and after a given thermal history was given, it was cooled to -20 ° C at 10 ° C / min, and then heated again from -20 ° C to 50 ° C at 10 ° C / min. The data obtained uses the midpoint of the transition region of the heat flux curve as the glass transition temperature.
  • the unit of the used amount of each component is expressed by mass%.
  • the amounts of the (E) component, (F) component, and (G) component are respectively based on the total amount of the (A) component, (B) component, (C) component, and (D) component (100 mass). %).
  • "*" is expressed as a ratio with respect to the total number of moles of the (A) component, (B) component, (C) component, and (D) component.
  • the refractive indices of the intraocular lens materials obtained in Examples 1 to 3 were 1.548, 1.543, and 1.535, respectively, and did not show adhesiveness, nor did they cause flicker and whitening.
  • the intraocular lens materials obtained in Comparative Example 1 and Comparative Example 2 in which the amount of use of the 4-branched PEG-containing macromonomer (A) was 10% by mass or less produced surface haze. To whiten. In addition, as indicated by an arrow in FIG. 3, the presence of numerous water particles was also confirmed. Similarly, although the intraocular lens material obtained in Comparative Example 3 had transparency, as shown by an arrow in FIG. 3, a flicker was confirmed in which the presence of numerous water particles was confirmed.
  • FIG. 4 the usage amount (mol%) of 4-ArmPEG34 (Examples 1 to 3 and Comparative Examples 1 to 3) and PEG-1000A (Comparative Examples 4 to 6) is plotted on the horizontal axis, and the eyes are shown.
  • the glass transition temperature of the inner lens material is plotted on the vertical axis.
  • the ratio of reduction in glass transition temperature of the intraocular lens material using 4-ArmPEG34 is larger than the intraocular lens material using PEG-1000A. It is thought that this is because 4-ArmPEG34 is easier to form a uniform network than PEG-1000A, and it is not easy to hinder the degree of freedom of the mobility of the polymer chain. As a result, the flexibility of the polyethylene glycol group is significantly reflected.
  • 4-ArmPEG34 can reduce the glass transition temperature of the intraocular lens material with a smaller amount of use, the amount of (meth) acrylate monomer (B) having an aryl group can be increased, and as a result, it can provide Intraocular lens material with high refractive index.
  • the unit of the used amount of each component is expressed by mass%.
  • the amounts of the (E) component, (F) component, and (G) component are respectively based on the total amount of the (A) component, (B) component, (C) component, and (D) component (100 mass). %).
  • "*" is expressed as a ratio with respect to the total number of moles of the (A) component, (B) component, (C) component, and (D) component.
  • the intraocular lens materials obtained in Examples 4 to 6 were colored yellow.
  • the intraocular lens materials obtained in Examples 4 to 6 did not exhibit adhesiveness, nor did they cause flicker and whitening.
  • FIG. 5 shows a graph in which the amount (mol%) of 4-ArmPEG34 (Examples 4 to 6) is plotted on the horizontal axis and the glass transition temperature of the intraocular lens material is plotted on the vertical axis.
  • the unit of the used amount of each component is expressed by mass%.
  • the amounts of the (E) component, (F) component, and (G) component are respectively based on the total amount of the (A) component, (B) component, (C) component, and (D) component (100 mass). %).
  • "*" is expressed as a ratio with respect to the total number of moles of the (A) component, (B) component, (C) component, and (D) component.
  • the intraocular lens material obtained in Comparative Example 7 exhibited adhesiveness, and the surface of the optical portion was bonded.
  • the intraocular lens material obtained in Comparative Example 7 had a haze-like whitening on its surface.
  • a monomer represented by the above-mentioned (A2) to (A4), a repeating number (a, b, c, d) of a polyethylene glycol group of 8 or 9 and a total of a, b, c, and d of 34 is used.
  • an intraocular lens material was produced as a 4-branched PEG-containing macromonomer (A) in the same manner as in Examples 1 to 13, results showing the same tendency as in Examples 1 to 13 were obtained.

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Abstract

一种聚合物材料，其能够制作折射率高、透镜表面的粘合性低且抑制闪光以及白化的产生的眼内透镜。此外，提供具有上述特性的眼内透镜。所述聚合物材料优选能够用于制作眼内透镜，其将含有11～30质量％的以下述通式(I)表示的大分子单体(A)和至少一种具有芳基的(甲基)丙烯酸酯单体(B)的单体混合液聚合而成。[式（I）中，4个n分别独立地为1或者2，a、b、c以及d分别独立地为4以上的整数，4个Z分别独立地为包含(甲基)丙烯酰基的取代基。]

Description

聚合物材料以及眼内透镜 技术领域
本发明涉及聚合物材料以及眼内透镜。更详细而言，本发明涉及能够制作折射率高、透镜表面的粘合性低且抑制闪光及白化的产生的眼内透镜的聚合物材料、以及具有上述特性的眼内透镜。
背景技术
随着小切口白内障手术的进步，为了作为眼内透镜使用而对具有柔软性且可弯折的眼内透镜材料的开发备受重视。
想要能够减薄眼内透镜的厚度，需要使这样的眼内透镜材料为高折射率。此外，为了通过小切口而插入眼内，而使眼内透镜能够被搓揉或弯折。为此，眼内透镜的材料自然需要是柔软的，并且还需要较低的粘合性，以避免光学部表面贴合而降低操作性。
进而，在向眼内插入后，眼内透镜材料不会发生由于水合以及凝聚使水分点状地显现而使其透明性显著降低的现象、即所谓的闪光(glistening)以及白化(sub-surfacenanoglistening)是至关重要的。
作为眼内透镜材料，公知有高折射率且柔软的丙烯酸材料(例如参照专利文献1)。在专利文献1中，公开了适合作为眼内透镜材料的高折射率丙烯酸材料。该丙烯酸材料可弯折，能够从小切口插入至眼内。
在此，为了提高眼内透镜材料的柔软性，降低其玻璃化转变温度是有效的。通常而言，通过从所构成的均聚物其玻璃化转变温度不同的单体中，选择两种以上并变更它们的掺混比而进行聚合，从而得到调节了玻璃化转变温度的聚合物。
例如，与甲基丙烯酸酯单体的均聚物相比，丙烯酸酯单体的均聚物具有较低的玻璃化转变温度。因此，在眼内透镜材料中，以较高的掺混量使用丙烯酸酯单体。
但是，随着丙烯酸酯单体的掺混量变多，眼内透镜材料的表面的粘合性增大，在搓揉或弯折时光学部表面变得容易贴合。因此，眼内透镜的操作性降低，或者眼内透镜复原到原本的形状为止的时间变长，不作优选。
此外，还进行为了在可弯折的丙烯酸材料中降低粘合性的尝试(例如 参照专利文献2)。在专利文献2中，将氟系单体作为成分之一使用，从而降低丙烯酸材料的粘合性。此外，还提出有通过对表面施行等离子体处理，从而降低眼内透镜材料的光学部表面的粘合性的方法(例如参照专利文献3)。
但是，在专利文献2中，通过掺混折射率低的氟系单体，从而使得到的丙烯酸材料(眼内透镜材料)的折射率降低。此外，如在专利文献3中所提出的那样的基于表面改性的方法，由于需要大规模的装置，工序变得复杂，所以对于眼内透镜(眼内透镜材料)的大量生产而言不作优选。此外，即便改善了粘合性，也并未解决在插入眼内后眼内透镜材料容易产生闪光以及白化的问题点。
闪光以及白化是由丙烯酸材料中所包含的微量的水的存在引起的。眼内透镜在眼内处于房水中，吸收来自房水中的水而稳定在饱和吸水状态下。房水的温度容易受到炎症、体温甚至外部环境变化的影响。若眼内的温度降低，则眼内透镜的吸水率降低，已经被吸取的眼内透镜中的水变得过饱和。认为由于该变得过饱和的水没有了逃逸空间而在眼内透镜材料的三维网络结构中的不均一部分进行相分离，由此引起闪光以及白化。
公开有以改善该闪光以及白化作为目的而使用了含双官能性的聚乙二醇基的成分(单体以及/或者交联剂)的眼内透镜(例如参照专利文献4)。在此，为了改善闪光以及白化，需要较多含聚乙二醇基的成分，但是由于聚乙二醇基是导致眼内透镜的折射率降低的主要因素，所以优选使聚乙二醇基的使用量是少量的。
但是，在专利文献4中被公开的含双官能性的聚乙二醇基的成分中，如果不使用较多的量，则不能改善闪光以及白化。
此外，还公开有使用了含多官能性的聚乙二醇基的成分的眼内透镜(例如参照专利文献5)。
但是，以专利文献5所公开的含多官能性的聚乙二醇基的成分的使用量，并不能够充分得到对闪光以及白化的改善效果。
并且，若含多官能性的聚乙二醇基的成分的使用量过少，则得到的眼内透镜材料的玻璃化转变温度显示出变高的倾向，即显示出柔软性降低的倾向。但是，在专利文献5中，关于含多官能性的聚乙二醇基的成分的使用量与眼内透镜的柔软性的关系未做任何探讨。
现有技术文献
专利文献
专利文献1：日本特开平4-292609号公报
专利文献2：日本特开平8-224295号公报
专利文献3：美国专利第5603774号说明书
专利文献4：美国专利第6353069号说明书
专利文献5：日本特表2015-512665号公报
发明内容
发明要解决的技术问题
本发明的目的在于提供一种聚合物材料，其能够制作折射率高、透镜表面的粘合性低且抑制闪光以及白化的产生的眼内透镜。
此外，本发明的其他目的还在于提供一种聚合物材料，其能够非常容易地调节其柔软性(玻璃化转变温度)。
进而，本发明的其他目的还在于提供一种具有上述特性的眼内透镜。
用于解决上述技术问题的方案
上述目的通过下述的(1)～(13)的本发明而实现。
(1)一种聚合物材料，其特征在于，其是将含有11～30质量％的以下述通式(I)表示的大分子单体(A)和至少一种具有芳基的(甲基)丙烯酸酯单体(B)的单体混合液聚合而成的。
【化学式1】
Figure PCTCN2019087749-appb-000001
[式中，4个n分别独立地为1或者2，a、b、c以及d分别独立地为4以上的整数，4个Z分别独立地为包含(甲基)丙烯酰基的取代基。]
(2)如上述(1)所记载的聚合物材料，其特征在于，在所述通式 (I)中，所述a、b、c以及d分别独立地为4～14的整数，并且所述a、b、c以及d的合计为16～56的整数。
(3)如上述(1)或者(2)所记载的聚合物材料，其特征在于，在所述通式(I)中，各个所述Z以下述式(Z1)、(Z2)或者(Z3)表示。
【化学式2】
Figure PCTCN2019087749-appb-000002
[各个式中，R 1为氢原子或者甲基。]
(4)如上述(1)～(3)中任一项所记载的聚合物材料，其特征在于，在所述通式(I)中，所述4个Z是相同的。
(5)如上述(4)所记载的聚合物材料，其特征在于，在所述通式(I)中，所述4个Z均为丙烯酰基。
(6)如上述(1)～(5)中任一项所记载的聚合物材料，其特征在于，所述(甲基)丙烯酸酯单体(B)以下述通式(II)表示。
【化学式3】
Figure PCTCN2019087749-appb-000003
[式中，R 2为氢原子或者甲基，m为1～6的整数，Y为直接键或者氧原子，D为氢原子、—C 6H 5、—CH 2C 6H 5或者—OC 6H 5。]
(7)如上述(1)～(6)中任一项所记载的聚合物材料，其特征在于，所述单体混合液含有70～89质量％的所述(甲基)丙烯酸酯单体(B)。
(8)如上述(1)～(7)中任一项所记载的聚合物材料，其特征在于，所述单体混合液还含有具有紫外线吸收性的聚合性单体。
(9)如上述(1)～(8)中任一项所记载的聚合物材料，其特征在于，所述单体混合液还含有具有着色性的聚合性单体。
(10)如上述(1)～(9)中任一项所记载的聚合物材料，其特征在于，所述单体混合液还含有选自不具有芳基的(甲基)丙烯酸酯单体以及交联性单体中的至少一种的辅助单体。
(11)如上述(1)～(10)中任一项所记载的聚合物材料，其特征在于，该聚合物材料是眼内透镜材料。
(12)一种眼内透镜，其特征在于，其具有上述(11)所记载的眼内透镜材料的加工物。
(13)一种眼内透镜，其特征在于，其包含上述(1)～(10)中任一项所记载的聚合物材料。
发明效果
根据本发明，能够制作折射率高、透镜表面的粘合性低并且抑制闪光以及白化的产生的眼内透镜。此外，根据本发明，仅通过变更大分子单体(A)的使用量(掺混量)，就能够容易地调节眼内透镜(聚合物材料)的玻璃化转变温度(即柔软性)。
附图说明
图1是简易地示出在使用了在2个支链中具有聚乙二醇基的大分子单体的情况下形成的高分子网络的模型图。
图2是简易地示出在使用了在4个支链中具有聚乙二醇基的大分子单体的情况下形成的高分子网络的模型图。
图3是闪光、白化的评价中的照片。
图4是示出了在2个支链以及4个支链中具有聚乙二醇基的大分子单体的使用量与眼内透镜材料的玻璃化转变温度的关系的图表(实施例1～3以及比较例1～6)。
图5是示出了在4个支链中具有聚乙二醇基的大分子单体的使用量与眼内透镜材料的玻璃化转变温度的关系的图表(实施例4～6)。
具体实施方式
以下对本发明的聚合物材料以及眼内透镜详细地进行说明。另外， 在下文中，以将本发明的聚合物材料用作眼内透镜材料的情况作为代表而进行说明。
<单体混合液>
单体混合液优选为能够用于制作眼内透镜(眼内透镜材料)的单体组合物。该单体混合液含有大分子单体(A)和至少一种具有芳基的(甲基)丙烯酸酯单体(B)。
《大分子单体(A)》
大分子单体(A)是在4个支链中具有聚乙二醇基的(甲基)丙烯酸酯单体。该大分子单体(A)如下述通式(I)所表示的那样在1个分子中具有4个聚乙二醇基和4个(甲基)丙烯酰基。
【化学式4】
Figure PCTCN2019087749-appb-000004
[式中，4个n分别独立地为1或者2，a、b、c以及d分别独立地为4以上的整数，4个Z分别独立地为包含(甲基)丙烯酰基的取代基。]
在此，在本说明书中，“(甲基)丙烯酰基”是指甲基丙烯酰基或丙烯酰基。
通过将该大分子单体(A)作为成分之一使用，从而既能抑制眼内透镜材料的粘合性，又能对眼内透镜材料赋予柔软性，还能抑制闪光以及白化的产生。
以往，通过将所构成的均聚物其玻璃化转换温度不同的2种以上的(甲基)丙烯酸酯单体进行组合，变更它们的掺混量并使其聚合，从而得到了调节玻璃化转变温度后的共聚物。与此相对，在本发明中，仅通过适当变更大分子单体(A)的使用量，就能够调节眼内透镜材料的玻璃化转变温度(柔软性)。
大分子单体(A)的分子量优选为1000～3000左右，更优选为1400～ 2800左右。通过使用具有上述分子量的大分子单体(A)，能够对所得的眼内透镜材料赋予柔软性和抑制闪光以及白化的功能，并且还能够得到均质的单体混合液。
大分子单体(A)的分子量除了能够由大分子单体(A)的皂化值来计算以外，还能够通过基于凝胶渗透色谱法(GPC)的测定而表示为以聚苯乙烯换算的数均分子量。
这样的大分子单体(A)例如能够按以下的步骤进行合成。
[1]首先，合成作为起始材料的4支链的聚乙二醇。
在该4支链的聚乙二醇的合成中，例如能够使用以下两种路径。
第1个路径是合成聚乙二醇基的重复数具有分布的4支链的聚乙二醇的方法。在该方法中，在碱催化剂的存在下，使环氧乙烷对季戊四醇进行加成聚合。
【化学式5】
Figure PCTCN2019087749-appb-000005
第二个路径是合成聚乙二醇基的重复数不具有分布的4支链的聚乙二醇的方法。
通常，聚乙二醇在其重复数(平均值)为4以上的情况下混合存在重复数不同的多种。
因此，首先通过色谱柱对聚乙二醇进行纯化，得到重复数均一(单一)的聚乙二醇(化合物1)。
接着，得到用三苯甲基氯保护聚乙二醇的一端的化合物2后，使四溴季戊四醇与另一端反应，得到末端被保护的4支链的聚乙二醇(化合物3)。
最后，通过脱保护，得到4支链的聚乙二醇。
另外，下述路径中的“TRT”表示三苯甲基。
【化学式6】
Figure PCTCN2019087749-appb-000006
[2]接着，通过将取代基引入至得到的4支链的聚乙二醇的末端，从而得到大分子单体(A)。
在引入作为取代基的(甲基)丙烯酸酯基的情况下，在脱卤化氢催化剂的共存下，使甲基丙烯酰氯或丙烯酰氯与4支链的聚乙二醇反应。
【化学式7】
Figure PCTCN2019087749-appb-000007
此外，在引入包含(甲基)丙烯酰基和氨基甲酸酯基的残基的取代基的情况下，在锡系氨基甲酸酯化催化剂或非锡系氨基甲酸酯化催化剂的共存下，使例如2-异氰酸酯乙基(甲基)丙烯酸酯、2-(2-异氰酸酯乙氧基)乙基(甲基)丙烯酸酯等与4支链的聚乙二醇反应。
在通式(I)中，各Z只要是包含(甲基)丙烯酰基的取代基即可，可以是(甲基)丙烯酰基本身，也可以是包含(甲基)丙烯酰基和与聚乙二醇的末端键合的键合基团(例如酰胺基(氨基甲酸酯基的残基)、 酮基等)的基团。
在后者的情况下，也可以在(甲基)丙烯酰基与键合基团之间存在键合基团(例如亚烷基氧基(alkylene oxide group)、亚烷基等)。
其中，各Z优选为以下述式(Z1)、(Z2)或(Z3)表示的取代基，更优选为丙烯酰基。
【化学式8】
Figure PCTCN2019087749-appb-000008
(各式中，R 1为氢原子或者甲基。)
这些取代基能够容易且可靠地引入至4支链的聚乙二醇的末端。特别地，通过使用向末端引入了作为取代基的丙烯酰基的4支链的聚乙二醇，从而能够降低眼内透镜材料的玻璃化转变温度。
此外，在通式(I)中，4个Z可以相互不同，但优选为相同。通过使4个Z为相同的取代基(特别是丙烯酰基)，能够容易地进行大分子单体(A)的合成，并且能够减少批次间的偏差。
具体而言，大分子单体(A)能够以下述结构式A1、A2、A3或者A4表示。
【化学式9】
Figure PCTCN2019087749-appb-000009
在本说明书中，“聚乙二醇基”以及“聚乙二醇”是指环氧乙烷的重复数(通式(I)中，a、b、c、d各自)为4以上的结构。
此外，在通式(I)中，a、b、c以及d的值可以分别具有分布(即，可以是不均一的)，也可以不具有分布(即，可以是均一的)。a、b、c以及d的值分别具有分布的情况下，其平均值为4以上的整数。另外，a、b、c以及d的值不具有分布是指例如在a、b、c以及d的值分别为6时不包含其他的值(例如5、7等)。
a、b、c以及d分别优选为4～14的整数，更优选为6～12的整数。此外，a、b、c以及d的合计优选为16～56的整数，更优选为24～48的整数。
通过使a、b、c以及d分别为上述下限值以上的值，能够赋予眼内透镜材料更高的柔软性，并且能够更好地抑制闪光以及白化的产生。另 一方面，通过使a、b、c以及d分别为上述上限值以下的值，能够提高与其他共聚成分(其他的单体)的相容性，从而能够得到更加均质的单体混合液。
特别地，从使单体混合液中所包含的单体聚合而得到的聚合物的结构均一的观点出发，优选为使4个分支的支链的长度尽可能地均一，相应地，a、b、c以及d优选为相互近似的值。
在本说明书中，“平均值”应用于大分子单体(A)中的聚乙二醇基的重复数存在分布的情况。具体而言，该“平均值”是指以下值：对大分子单体(A)进行 1H-NMR分析，将使用环氧乙烷单元的峰积分强度比而计算出的重复数的小数点后第一位四舍五入，从而得到的值。
此外，在本说明书中，“大分子单体”是指分子量为900以上的单体。
本发明人以既抑制眼内透镜材料的粘合性、又赋予柔软性、还抑制闪光以及白化的产生为目的，进行了各种探讨。其结果使本发明人发现：虽然详细的机制尚未明确，但通过在11～30质量％的范围内使用大分子单体(A)，能够达成上述目的。此外还发现：仅通过适当变更该大分子单体(A)的使用量，就能够调节眼内透镜材料的柔软性(玻璃化转变温度)。然后，基于这些见解，本发明人完成了本发明。
在此，在1个分子中具有聚乙二醇基和(甲基)丙烯酸酯基的大分子单体中，存在具有以以下的通式表示的各种结构的化合物。另外，式中，将聚乙二醇基记作“PEG”，在下文中，还将具有聚乙二醇基的大分子单体记载为“含PEG的大分子单体”。
作为含PEG的大分子单体的代表性结构，存在2支链型、3支链型、4支链型以及8支链型。
【化学式10】
Figure PCTCN2019087749-appb-000010
例如，在使用了在2个支链中具有聚乙二醇基的大分子单体(以下也称为“2支链的含PEG的大分子单体”)的情况下，得到的聚合物由于随机地交联所以变为不均一的结构，在聚合物的网络结构中，形成有致密的部分和稀疏的部分(参照图1)。由于水在该聚合物的网络结构中的稀疏的部分相分离，所以变得容易产生闪光以及白化。上述倾向在3支链以及8支链的含PEG的大分子单体中也是同样的。
另一方面，在使用了在4支链中具有聚乙二醇基的大分子单体(以下也称为“4支链的含PEG的大分子单体”)的情况下，容易形成交联点间距离的偏差较小且均一的网络(参照图2)。如此，推断聚合物的网络结构的均一性的提高有助于抑制闪光以及白化的产生。
由该聚合物的结构造成的物性的差异也同样适用于聚合物的玻璃化转变温度。通常，聚合物的交联密度随着交联剂的使用量变多而变高。其结果为：阻碍了聚合物链运动性的自由度，使聚合物的玻璃化转变温度变高。
在此，由于聚乙二醇基是柔软性高的结构，所以由2支链的含PEG的大分子单体所构成的均聚物的玻璃化转变温度较低。但是，即便使用2支链的含PEG的大分子单体，得到的聚合物的结构也如上所述地变得不均一。因此，阻碍了聚合物链运动性的自由度，不能够大幅地降低玻璃化转变温度。在3支链以及8支链的含PEG的大分子单体中同样具有该倾向。
另一方面，4支链的含PEG的大分子单体由于容易形成均一的网络，所以得到的聚合物不易阻碍该聚合物链运动性的自由度，基于聚乙二醇基的柔软性而显现出显著的柔软性。因此，与使用2支链的含PEG的大分子单体相比，通过使用4支链的含PEG的大分子单体，能够大幅地降低玻璃化转变温度，并且还能够根据其使用量调节聚合物的玻璃化转变温度。
如此，4支链的含PEG的大分子单体能够以比2支链的含PEG的大分子单体更少的使用量来降低聚合物的玻璃化转变温度。但是，由于聚乙二醇基是导致眼内透镜材料的折射率降低的主要原因，所以虽然优选其使用量为少量，但是通过使用4支链的含PEG的大分子单体，能够减少其使用量而抑制眼内透镜材料的折射率的降低。此外，通过减少4支链的含PEG的大分子单体的使用量，能够提高后述的(甲基)丙烯酸酯单体(B)的使用量，结果能够提高眼内透镜材料的折射率。
进而，以往，通过提高作为眼内透镜材料的成分的、具有芳基的丙烯酸酯单体的使用量，从而赋予了聚合物柔软性。在该情况下，由于使用丙烯酸酯单体，因此导致眼内透镜材料的粘合性增大。与此相对，在本发明中，通过使用4支链的含PEG的大分子单体，能够大幅地降低眼内透镜材料的玻璃化转变温度(柔软性)。因此，本发明的眼内透镜材料与以往的眼内透镜材料不同，通过不使用具有芳基的丙烯酸酯单体或者减少具有芳基的丙烯酸酯单体的使用量，能够相对地提高具有芳基的甲基丙烯酸酯单体的量，其结果还能够抑制所得到的眼内透镜材料的粘合性的增大。
另外，4支链的含PEG的大分子单体(大分子单体(A))不仅有既抑制眼内透镜材料的粘合性、又赋予柔软性、还抑制闪光以及白化的产生的效果，而且还作为交联剂成分发挥作用，发挥提高聚合物(眼内透镜材料)的机械强度的效果。
该大分子单体(A)的使用量(含量)只要为11～30质量％左右即可，优选为12～25质量％左右，更优选为13～20质量％左右。
若大分子单体(A)的使用量不足上述下限值，则不能够充分地得到抑制眼内透镜材料的闪光以及白化的产生的效果。另一方面，若大分子单体(A)的使用量超过上述上限值，则眼内透镜材料的折射率极度地降低。此外，由于交联点变多，而使眼内透镜材料变脆。
另外，在大分子单体(A)的使用量用摩尔％表示的情况下，为1.2～5摩尔％左右，优选为1.2～4摩尔％左右，更优选为1.2～3摩尔％左右。
另外，“质量％”是指根据大分子单体(A)的质量、后述的(甲基)丙烯酸酯单体(B)的质量、这两种成分以外的作为任意成分的不具有芳基的(甲基)丙烯酸酯单体(C)以及交联性单体(D)的质量的合计量(100％)求得的值。
同样地，“摩尔％”也是指根据大分子单体(A)的摩尔数、(甲基)丙烯酸酯单体(B)的摩尔数、(甲基)丙烯酸酯单体(C)以及交联性单体(D)的摩尔数的合计量(100摩尔％)求得的值。
《(甲基)丙烯酸酯单体(B)》
(甲基)丙烯酸酯单体(B)是具有芳基和(甲基)丙烯酰基的单体。该(甲基)丙烯酸酯单体(B)具有提高所得到的眼内透镜材料的折射率的作用。
(甲基)丙烯酸酯单体(B)优选为以下述通式(II)表示的单体。
【化学式11】
Figure PCTCN2019087749-appb-000011
[式中，R 2为氢原子或者甲基，m为1～6的整数，Y为直接键或者氧原子，D为氢原子、-C 6H 5、-CH 2C 6H 5或者-OC 6H 5。]
作为(甲基)丙烯酸酯单体(B)的具体例，能够列举(甲基)丙烯酸2-苯基乙酯、(甲基)丙烯酸3-苯基丙酯、(甲基)丙烯酸4-苯基丁酯、(甲基)丙烯酸2-苯氧基乙酯、(甲基)丙烯酸4-苯氧基丁酯、(甲基)丙烯酸2-(4-苯基苯基)乙酯、(甲基)丙烯酸2-(3-苯基苯基)乙酯、(甲基)丙烯酸2-(4-苄基苯基)乙酯、(甲基)丙烯酸2-(4-苯基苯氧基)乙酯、(甲基)丙烯酸2-(4-苄基苯氧基)乙酯、(甲基)丙烯酸3-(4-苯基苯氧基)丙酯、(甲基)丙烯酸2-(4-苯氧基苯氧基)乙酯等。它们可以单独使用一种，也可以将两种以上并用。
其中，作为(甲基)丙烯酸酯单体(B)，优选为从甲基丙烯酸2-苯氧基乙酯、丙烯酸2-苯氧基乙酯、甲基丙烯酸2-苯基乙酯以及丙烯酸2-苯基乙酯中选择的至少一种，更优选为甲基丙烯酸2-苯氧基乙酯与丙烯酸2-苯基乙酯的组合或者甲基丙烯酸2-苯基乙酯与丙烯酸2-苯基乙 酯的组合。通过使用上述(甲基)丙烯酸酯单体(B)，能够进一步降低眼内透镜材料的玻璃化转变温度。
(甲基)丙烯酸酯单体(B)的使用量(含量)没有特别地限制，但优选为70～89质量％左右，更优选为75～88质量％左右，进一步优选为77～87质量％左右。
通过使(甲基)丙烯酸酯单体(B)的使用量在上述范围，能够充分地提高眼内透镜材料的折射率，并且能够抑制眼内透镜材料的柔软性降低。
另外，在(甲基)丙烯酸酯单体(B)的使用量以摩尔％表示的情况下，优选为85～98.8摩尔％，更优选为87～98.8摩尔％，进一步优选为90～98.8摩尔％。
单体混合液还可以含有除大分子单体(A)以及(甲基)丙烯酸酯单体(B)以外的其他单体(C)～(F)等。
《(甲基)丙烯酸酯单体(C)》
(甲基)丙烯酸酯单体(C)为不具有芳基但具有(甲基)丙烯酰基的单体。该(甲基)丙烯酸酯单体(C)是以调节眼内透镜材料的柔软性以及/或者吸水率为目的而掺混在单体混合液中的辅助单体的一种。
(甲基)丙烯酸酯单体(C)优选为以下述通式(Ⅲ)表示的单体。
【化学式12】
Figure PCTCN2019087749-appb-000012
[式中，R 3为氢原子或者甲基，p为0～4的整数，Y为直接键或者氧原子，R 4为氢原子、直链状或者支链状的C 1～C 8烷基或者可以被氟原子取代的直链状或支链状的C 1～C 8烷基。](甲基)丙烯酸异丙酯
作为(甲基)丙烯酸酯单体(C)的具体例，例如能够列举(甲基)丙烯酸2-羟基乙酯、(甲基)丙烯酸2-羟基丙酯、(甲基)丙烯酸4-羟基丁酯、(甲基)丙烯酸甲酯、(甲基)丙烯酸乙酯、(甲基)丙烯酸正丙酯、(甲基)丙烯酸异丙酯、(甲基)丙烯酸异丁酯、(甲基)丙烯酸正丁酯、(甲基)丙烯酸叔丁酯、(甲基)丙烯酸异戊酯、(甲基)丙烯酸己酯、(甲基)丙烯酸2-乙基己酯、(甲基)丙烯酸2-甲氧基乙酯、(甲基)丙烯酸2-乙氧基乙酯、(甲基)丙烯酸2,2,2-三氟乙 酯、(甲基)丙烯酸2,2,3,3-四氟丙酯、(甲基)丙烯酸2,2,3,3,3-五氟丙酯、(甲基)丙烯酸1,1,1,3,3,3-六氟异丙酯、(甲基)丙烯酸八氟戊酯等。它们可以单独使用一种，也可以将两种以上并用。
《交联性单体(D)》
交联性单体(D)是以调节眼内透镜材料的机械强度为目的而掺混在单体混合液中的辅助单体的一种。
作为该交联性单体(D)的具体例，例如能够列举乙二醇二(甲基)丙烯酸酯、二乙二醇二(甲基)丙烯酸酯、三乙二醇二(甲基)丙烯酸酯、四乙二醇二(甲基)丙烯酸酯、1,3-丙二醇二(甲基)丙烯酸酯、2,3-丙二醇二(甲基)丙烯酸酯、1,4-丁二醇二(甲基)丙烯酸酯、1,6-己二醇二(甲基)丙烯酸酯、1,9-壬二醇二(甲基)丙烯酸酯、新戊二醇二(甲基)丙烯酸酯、甘油二(甲基)丙烯酸酯、3-甲基-1,5-戊二醇二丙烯酸酯、2-羟基-3-丙烯酰氧基丙基(甲基)丙烯酸酯、聚乙二醇二(甲基)丙烯酸酯等。它们可以单独使用一种，也可以将两种以上并用。
(甲基)丙烯酸酯单体(C)以及交联性单体(D)的合计使用量(含量)优选为不足10质量％，更优选为0.1～9质量％左右，进一步优选为0.2～8质量％左右。
通过使这些单体的合计使用量在上述范围，能够较高地维持(甲基)丙烯酸酯单体(B)的使用量，结果能够防止眼内透镜材料的折射率降低。
另外，在(甲基)丙烯酸酯单体(C)以及交联性单体(D)的合计使用量以摩尔％表示的情况下，优选为不足13摩尔％，更优选为0.02～11摩尔％左右，进一步优选为0.04～8摩尔％左右。
《具有紫外线吸收性的聚合性单体(E)、具有着色性的聚合性单体(F)》
聚合性单体(E)具有能够吸收紫外线的结构，并且以赋予眼内透镜(眼内透镜材料)紫外线吸收能力为目的而掺混在单体混合液中。
作为该聚合型单体(E)的具体例，例如能够列举5-氯-2-[2-羟基-5-(β-甲基丙烯酰氧基乙基氨基甲酰氧基乙基)]苯基-2H-苯并三唑、2-[2-羟基-5-(β-甲基丙烯酰氧基乙基氨基甲酰氧基乙基)]苯基-2H-苯并三唑、5-氯-2-[2-羟基-4-(对乙烯基苄氧基-2-羟丙基氧基)]苯基-2H-苯并三唑、4-甲基丙烯酰氧基-2-羟基二苯甲酮、2-(2’-羟基-3’-叔丁基-5’-甲基苯基)-5-(2’-甲基丙烯酰氧基乙基)苯并三唑、2- (2’-羟基-5’-甲基丙烯酰氧基乙基苯基)-2H-苯并三唑、2-(2’-羟基-3’-甲基烯丙基-5’-甲基苯基)苯并三唑、2-(2-羟基-3-(甲基丙烯酰氧基氨基甲基)-5-叔辛基苯基)-2H-苯并三唑、2-(2’-羟基-3’-叔丁基-5’-甲基苯基)-5-(2’-甲基丙烯酰氧基乙基)苯并三唑、2-[3’-叔丁基-2’-羟基-5’-(3”-甲基丙烯酰氧基丙基)苯基]-5-甲氧基苯并三唑等。它们可以单独使用一种，也可以将两种以上并用。
聚合性单体(F)例如具有呈现能够吸收蓝色光的黄色的结构，以对眼内透镜进行着色为目的而掺混在单体混合液中。
该聚合性单体(F)能够使用偶氮系、吡唑酮系、花青系的黄色着色剂。作为具体例，例如能够列举日本特开平10-195324号公报、日本特开2000-290256号公报、日本特开2003-119226号公报、日本特表2008-520811号公报、日本特表2008-520352号公报、日本特表2012-532244号公报等中记载的黄色着色剂。将这些公报中记载的全部事项引用至本说明书中。
聚合性单体(E)的使用量(含量)相对于上述单体(A)～(D)的质量的合计量(100质量％)优选为5质量％以下，更优选为0.1～3质量％左右。
此外，聚合性单体(F)的使用量(含量)相对于上述单体(A)～(D)的质量的合计量(100质量％)优选为1质量％以下，更优选为0.01～0.5质量％左右。
将如上所述的大分子单体(A)、(甲基)丙烯酸酯单体(B)、根据需要的单体(C)～(F)以及聚合引发剂(G)混合并充分搅拌，从而得到均质的单体混合液。
《聚合引发剂(G)》
聚合引发剂(G)能够使用热聚合引发剂以及光聚合引发剂中的任一种。
作为热聚合引发剂，例如能够列举：如二(3,5,5-三甲基己酰基)过氧化物、二月桂酰基过氧化物、苯甲酰过氧化物、过氧化-2-乙基己酸叔己酯、过氧化-2-乙基己酸1,1,3,3-四甲基丁酯、过氧化-2-乙基己酸叔丁酯那样的过氧化物；2,2’-偶氮双(2,4-二甲基戊腈)、2,2’-偶氮双(异丁腈)、2,2’-偶氮双(2-甲基丙酸甲酯)、2,2’-偶氮双(2-甲基丁腈)、1,1’-偶氮双(1-环己烷甲酸甲酯)、1,1’-偶氮双(环 己烷-1-甲腈)等。
作为光聚合引发剂，例如能够列举苯偶姻甲基醚、1-羟基环己基苯基酮、2,2-二甲氧基-2-苯基苯乙酮、2-羟基-2-二甲氧基-1-苯基丙烷-1-酮、苯基双(2,4,6-三甲基苯甲酰基)氧化膦、2,4,6-三甲基苯甲酰基-二苯基-氧化膦等。
聚合引发剂(G)的使用量(含量)根据聚合温度、光的照射波长以及照射强度等适当选择，但优选为相对于单体(A)～(D)的质量的合计量(100质量％)为0.1～1质量％左右。
<眼内透镜>
将单体混合液注入到具有与应制作的眼内透镜的形状相对应的眼内透镜制作用的注塑模内，之后进行聚合。
该注塑模是形成有弯曲凹部的组合模，由金属材料、树脂材料这样的材质构成。但是，优选为单体混合液的聚合物(眼内透镜材料或眼内透镜)的剥离性良好且耐溶剂性、耐热性优异的材质。树脂制的注塑模能够容易地形成为期望的透镜设计所需要的形状，因此优选。
树脂材料优选从成形收缩性低、从金属材料的表面转印的转印性良好、尺寸精度以及耐溶剂性优异的材料中选择。特别是从廉价、能够容易获得等方面出发，优选聚丙烯作为树脂材料。
但是，作为树脂材料，并不限于聚丙烯，例如也可以使用聚乙烯、聚对苯二甲酸乙二醇酯、聚甲基戊烯、聚砜、聚苯硫醚、环状烯烃共聚物、乙烯-乙烯醇共聚物等。
在注入单体混合液时，可以使用刚成形后的注塑模，为了使弯曲凹部的形状(曲率)稳定，也可以使用保管10～72小时左右后的注塑模。
此外，还可以在使用注塑模之前，充分减压而除去模具表面的水分、氧这样的对聚合反应造成影响的物质，进而在用氮气、氩气这样的惰性气体进行吹扫后，将单体混合液注入注塑模中。
进而，在注入单体混合液时，还可以预先用氮气、氩气这样的惰性气体对单体混合液进行鼓泡，由此除去溶解于单体混合液中的氧后进行使用，也可以不除去溶解氧而进行使用。
作为聚合方法，能够列举：在单体混合液中掺混热聚合引发剂进行加热的热聚合法；或者在单体混合液中掺混光聚合引发剂，再照射紫外线或可见光线等的光聚合法。
在应用热聚合法的情况下，只要在将注塑模配置于聚合装置内后，阶段性或者连续地在20～130℃左右的温度范围内进行升温并加热5～48小时左右、或者将注塑模配置在预先设定为一定温度(100～120℃)左右的聚合装置内再加热1～24小时左右即可。
进行热聚合时的气氛可以为大气气氛，但优选为氮气气氛、氩气气氛这样的惰性气体气氛。通过在上述气氛中进行热聚合，能够提高单体的聚合率而降低未反应单体的量。在该情况下，聚合装置内的压力优选为2kgf/cm 2(0.196MPa)以下。
在应用光聚合法的情况下，照射的光的波长根据掺混的光聚合引发剂的特性适当选择，因此没有特别地限制。
另外，作为光的照射所采用的灯的具体例，例如能够列举在200～280nm区域的波长以及350nm的波长具有较强峰的灯、增强了350～400nm区域的波长的灯、以420nm区域的波长为中心而增强了400～425nm区域的波长的灯、增强了400～450nm区域的波长的灯等。
光的照射强度的值会因测定照射强度的机器的受光部面积不同而不同，但优选为例如5～100mW/cm 2左右。
由于光的照射时间(聚合时间)根据光的照射强度适当设定，因此没有特别地限制。例如，在光的照射强度为5～100mW/cm 2左右的情况下，优选将光的照射时间设定为5～60分钟左右。
此外，在进行光聚合时，也可以在预先设定为一定温度(40～80℃左右)的聚合装置内照射光。由此，能够提高单体的聚合率而降低未反应单体的量。
进行光聚合时的气氛可以为大气气氛，但也可以为氮气气氛、氩气气氛这样的惰性气体气氛。通过在上述气氛中进行光聚合，能够进一步提高单体的聚合率。
在单体混合液聚合后，从注塑模取出眼内透镜材料后，或者不从注塑模取出眼内透镜材料(即，将眼内透镜材料收纳在注塑模内的状态下)而在低温下对该眼内透镜材料进行切削、研磨，由此加工成期望的形状(例如眼内透镜本身的形状、眼内透镜的光学部的形状)。
在其他方法中，也可以在适当的模具或容器中进行单体混合液的聚合，制作棒状、块状、板状这样的规定形状的眼内透镜材料后，在低温下对该眼内透镜材料进行切削、研磨，由此加工成期望的形状。
另外，也可以从注塑模取出眼内透镜材料，不进行切削、研磨，而直接作为眼内透镜本身或眼内透镜的光学部(透镜主体)使用。
此外，在制作了光学部的情况下，也可以在与光学部分开制作用于支承光学部的支承部后，将支承部安装在光学部上而作为眼内透镜。另外，支承部也可以与光学部同时一体地成形。
作为支承部的构成材料，例如能够列举聚丙烯、聚甲基丙烯酸甲酯(PMMA)等。
如上所述，本发明的眼内透镜由规定形状的眼内透镜材料本身所构成、或者具有眼内透镜材料的加工物。
也可以在得到眼内透镜后，对眼内透镜(光学部)实施基于再加热的处理。由此，能够除去残留在眼内透镜中的微量的未反应单体等。该基于再加热的处理是通过将眼内透镜配置在预先设定为一定温度(100～125℃左右)的装置内、再加热5～72小时左右来进行的。此时的装置内的气氛既可以是大气压气氛，也可以是使用真空泵等减压后的气氛(减压气氛)。
另外，也可以通过进行除了基于再加热的处理以外的、将眼内透镜浸渍在乙醇、异丙醇、丙酮这样的有机溶剂中的处理，从而除去残留在眼内透镜中的微量的未反应单体等。
此外，也可以对眼内透镜的光学部表面实施低温等离子体处理、大气压等离子体处理、使用紫外线等的清洗处理。根据上述处理，能够提高眼内透镜的光学部表面的清洁性、细胞粘附性。
当使用e射线(546.1nm)在25℃下用阿贝折射率计测定如此得到的眼内透镜材料的折射率时，在饱和吸水状态下的折射率的值优选为1.51～1.57左右，更优选为1.52～1.57左右，进一步优选为1.525～1.57左右。
此外，眼内透镜材料的吸水率在23℃下优选为0.7～4.5质量％左右，更优选为0.8～3质量％左右，进一步优选为0.9～2质量％左右。
进而，眼内透镜材料被用作在室温下能够弯折的眼内透镜，因此优选具有比通常的人类的体温(约37℃)低的玻璃化转变温度。具体而言，眼内透镜材料的玻璃化转变温度的下限值优选为0℃左右，更优选为3℃左右，进一步优选为5℃左右，特别优选为7℃左右，最优选为10℃左右。另一方面，玻璃化转变温度的上限值优选为20℃左右，更优选为 18℃左右，更加优选为17℃左右，进一步优选为15℃左右，特别优选为12℃左右。从成为具有适度的形状复原性的眼内透镜材料的观点出发，眼内透镜材料的玻璃化转变温度优选为10～15℃左右。
如上所述的眼内透镜材料相比于以往的眼内透镜材料对于闪光以及白化的耐性更高。在此，按照以下的步骤对闪光以及白化进行评价。
首先，将透镜形状或者平板形状的试样在45℃的生理盐水中浸渍24小时以上。接着，在设定为23℃的环境下，将浸渍后的试样静置2小时。然后，使用例如显微镜(株式会社基恩士制，“VHX-5000”)以20倍以上的倍率对该试样的外观(透明性)进行观察。
在本说明书中，“闪光”是指在眼内透镜材料中产生几个～几十个的具有1～10μm的粒径的水粒子但实质上并未发生眼内透镜材料的透明性降低的状态。另一方面，“白化”是指由于具有平均粒径100nm的微小的水粒子大量聚集而使眼内透镜材料的表面看起来雾状地白色化的状态。
另外，闪光以及白化的评价基于认为是在实际上将眼内透镜插入到人的眼内的眼科手术时产生的眼内的温度变化、或者将眼内透镜插入到眼内后的生活环境下的温度变化来进行。
认为由于该在体内的温度变化而在眼内透镜材料上产生闪光以及白化。通常而言，在吸水率低的眼内透镜材料的情况下，温度越高，则吸水率越高。因此，可以说在更宽范围的温度变化(45℃～23℃)下对闪光以及白化的评价是在更严酷的条件下实施的。根据本发明的眼内透镜材料，即便在上述严酷的条件下，也未能确认到产生闪光以及白化。
以上对本发明的聚合物材料以及眼内透镜进行了说明，但是本发明并不限于上述的实施方式的构成。
例如，本发明的聚合物材料以及眼内透镜可以在上述的实施方式的构成中追加其他任意的成分，也可以置换成发挥同样功能的任意成分。
另外，除了眼内透镜之外，本发明的聚合物材料还能够用于制作角膜镶嵌、角膜环那样的眼科用医疗器件、以及耳鼻科用换气管、鼻用植入体那样的耳鼻喉科用医疗器件等的各种医疗器件。
实施例
以下利用实施例更详细地对本发明进行说明，但本发明并不限于这些实施例。
1.使用成分
示出在以下的实施例以及比较例中所使用的化合物的名称与缩写。
(A)4支链的含PEG的大分子单体
·4-ArmPEG34:
以上述式(A1)表示、聚乙二醇基的重复数(a、b、c以及d各自)为8或者9且a、b、c以及d的合计为34的单体[分子量：1846]
·4-ArmPEG40:
以上述式(A1)表示、聚乙二醇基的重复数(a、b、c以及d全部)为10且a、b、c以及d的合计为40的单体[分子量：2112]
(B)具有芳基的(甲基)丙烯酸酯单体
·Po-MA：
甲基丙烯酸2-苯氧基乙酯[分子量：206]
·Po-A:
丙烯酸2-苯氧基乙酯[分子量：192]
·Ph-MA:
甲基丙烯酸2-苯基乙酯[分子量：190]
·Ph-A:
丙烯酸2-苯基乙酯[分子量：176]
(C)不具有芳基的(甲基)丙烯酸酯单体
·n-BuMA：甲基丙烯酸正丁酯[分子量：142]
(D)交联性单体
·PEG-1000A：
以下述式(D1)表示的聚乙二醇二丙烯酸酯[分子量：1097]
【化学式13】
Figure PCTCN2019087749-appb-000013
·TEGDMA:
四乙二醇二甲基丙烯酸酯[分子量：330]
(E)具有紫外线吸收性的聚合性单体
·Norbloc7966：
2-(2’-羟基-5’-甲基丙烯酰氧基乙基苯基)-2H-苯并三唑[分子量：266]
(F)具有着色性的聚合性单体
·BL01：
4-(苯基偶氮)苯基-2-甲基丙烯酸酯[分子量：226]
(G)聚合引发剂
·AIBN：
2,2’-偶氮双(异丁腈)[分子量：164]
2.眼内透镜材料的制作
(实施例1)
首先分别按以下的量向容量10mL的玻璃瓶中投入Po-MA、Ph-A、4-ArmPEG34、Norbloc7966以及AIBN，在室温下搅拌约20小时。由此，制备单体混合液。
·Po-MA：1.770g(44.25质量％、45.47摩尔％)
·Ph-A：1.770g(44.25质量％、53.22摩尔％)
·4-ArmPEG34：0.460g(11.5质量％、1.32摩尔％)
·Norbloc7966：0.060g(相对于Po-MA、Ph-A以及4-ArmPEG34的合计量为1.5质量％)
·AIBN：0.012g(相对于Po-MA、Ph-A以及4-ArmPEG34的合计量为0.3质量％)
接着，将该单体混合液注入到用于制作眼内透镜材料的池(cell)中。该池是具备切割成纵7.5cm、横5.0cm的大小的2张聚丙烯制的板材和夹持在这2张板材之间且规定了间隔距离的聚四氟乙烯制的衬垫片的构成。
然后，将注入了单体混合液的池配置于聚合装置内，用30分钟从20℃升温至50℃，维持50℃的温度8小时后，进一步用6小时升温至120℃，维持120℃的温度2小时后，最后用4小时冷却至40℃。由此，使单体混合液中所包含的单体聚合。另外，聚合装置内的气氛为氮气气氛，装置内的压力为0.2kgf/cm 2(0.0196MPa)。
接着，将得到的眼内透镜材料配置于预先设定成120℃的干燥器内，实施8小时加热处理。由此，从眼内透镜材料中除去未反应单体。另外，得到的平板形状的眼内透镜的厚度为0.6～0.7mm的范围。
(实施例2、3)
除了制备表1所示的组成的单体混合液以外，与所述实施例1同样地制作了眼内透镜材料。
(实施例4～6)
除了制备表2所示的组成的单体混合液以外，与所述实施例1同样地制作了眼内透镜材料。
(实施例7～13)
除了制备表3所示的组成的单体混合液以外，与所述实施例1同样地制作了眼内透镜材料。
(比较例1～6)
除了制备表1所示的组成的单体混合液以外，与所述实施例1同样地制作了眼内透镜材料。
(比较例7)
除了制备表3所示的组成的单体混合液以外，与所述实施例1同样地制作了眼内透镜材料。
3.测定以及评价
对于在各实施例以及各比较例中得到的眼内透镜材料，进行了折射率、吸水率以及玻璃化转变温度的测定、粘合性以及闪光、白化的评价。
在折射率的测定中，将切割成宽度10mm、长度15mm的长方形形状的眼内透镜材料作为试验片。
此外，在玻璃化转变温度的测定中，将使用φ5mm的活检穿孔而冲切成圆盘形状的眼内透镜材料作为试验片。
进而，在其他的测定以及评价中，将使用φ6mm的活检穿孔而冲切成相当于眼内透镜的光学部(透镜主体)的大小的眼内透镜材料作为试验片。
3-1.折射率的测定
将试验片在25℃的生理盐水中浸渍72小时，成为饱和吸水状态。使用折射率计(株式会社爱宕制、“DR-M2”)测定了该试验片在25℃下的e射线(546.1nm)的折射率。
3-2.吸水率的测定
测定在23℃下达到饱和吸水状态后的试验片的重量(Ww)与使用减压真空干燥器在60℃下干燥4小时(真空度：266.6Pa)后的试验片的 重量(Wd)，通过下述式计算出吸水率。
式：吸水率(质量％)＝{(Ww-Wd)/Wd}×100
3-3.粘合性的评价
在用镊子将试验片以对折的状态夹持1分钟。然后，通过肉眼观察从镊子解脱后的试验片的状态，按以下的评价基准进行评价。
<评价基准>
G(Good)：对折后的试验片未贴合而迅速地复原到原来的形状。
B(Bad)：对折后的试验片贴合而直至开始复原到原来的形状需要耗费时间。
3-4.闪光、白化的评价
将试验片在45℃的生理盐水中浸渍48小时，接着在设定为23℃的环境下静置2小时。然后，使用显微镜(株式会社基恩士制，“VHX-5000”)在50倍的倍率下对在生理盐水中的试验片的外观(透明性)进行观察，并按以下的评价基准进行评价。
<评价基准>
G(Good)：试验片透明性优异，并且也未确认到在内部存在水粒子。
B(Bad)：试验片发生白浊(白化)或者虽然透明但在内部确认到水粒子(闪光)。
3-5.玻璃化转变温度的测定
使用差示扫描热量测定装置如下所述地对试验片(干燥状态)的玻璃化转变温度(Tg)进行测定。首先，使试验片暂时升温至玻璃化转变温度以上，在赋予了一定的热历程后，以10℃/分钟冷却至-20℃，再次以10℃/分钟从-20℃升温至50℃，使用所得到的数据将热通量曲线的转化区域的中间点作为玻璃化转变温度。
将得到的结果示于以下的表1～表3以及图3～图5中。
【表1】
Figure PCTCN2019087749-appb-000014
表中，用质量％表示各成分的使用量的单位。另外，(E)成分、(F)成分以及(G)成分的使用量分别以相对于(A)成分、(B)成分、(C)成分以及(D)成分的质量的合计量(100质量％)的比例来表示。
此外，“*”以相对于(A)成分、(B)成分、(C)成分以及(D)成分的摩尔数的合计量的比例来表示。
如表1以及图3所述，在实施例1～3中得到的眼内透镜材料的折射率分别为1.548、1.543以及1.535，并且未显示出粘合性，也未产生闪光以及白化。
与此相对，在使4支链的含PEG的大分子单体(A)的使用量为10质量％以下的比较例1以及比较例2中得到的眼内透镜材料均产生了其表面雾状地白色化的白化。此外，如图3中的箭头所示，还确认到无数的水粒子的存在。同样地，在比较例3中得到的眼内透镜材料虽然具有透明性，但是如图3中的箭头所示，产生了确认到存在无数水粒子的闪光。
此外，在使用2支链的含PEG的大分子单体代替4支链的含PEG的大分子单体(A)的比较例4～6中得到的眼内透镜材料中，2支链的含PEG的大分子单体(PEG-1000A)的使用量与4支链的含PEG的大分子单体(A)(4-ArmPEG34)的使用量为大致相同的摩尔％。但是，在比较例4以及5中得到的眼内透镜材料中，产生了其表面雾状地白色化的白化。此外，如图3中的箭头所示，也确认到无数的水粒子的存在。同样地，在比较例6中得到的眼内透镜材料虽然具有透明性，但是如图3中的箭头所示，产生了确认到存在无数水粒子的闪光。
在此，1分子4-ArmPEG34中存在34个亚乙基氧基(-CH 2CH 2O-)。由于该亚乙基氧基的分子量为44，因此计算出在1分子4-ArmPEG34中聚乙二醇基所占的比例为81.04％(∵44×34÷1846×100＝81.04％)。
同样地，在1分子PEG-1000A中存在22个亚乙基氧基，所以计算出在1分子PEG-1000A中聚乙二醇基所占的比例为88.24％(∵44×22÷1097×100＝88.24％)。
如此，对于在眼内透镜材料中聚乙二醇基所占的比例而言，尽管PEG-1000A比4-ArmPEG34高，但在比较例4～6中得到的眼内透镜材料中，产生了闪光以及白化。这表明大分子单体的4支链的结构有助于抑制闪光以及白化的产生。
在图4中，示出将4-ArmPEG34(实施例1～3、比较例1～3)以及PEG-1000A(比较例4～6)的使用量(摩尔％)标绘在横轴、将眼内透镜材料的玻璃化转变温度标绘在纵轴的图表。
从图4可知，4-ArmPEG34的使用量与眼内透镜材料的玻璃化转变温 度间的关系显示了良好的线性。从该结果可知，仅通过对4-ArmPEG34的使用量进行各种变更，就可以使眼内透镜材料的玻璃化转变温度发生变化。
此外，对于玻璃化转变温度降低的比例而言，使用了4-ArmPEG34的眼内透镜材料比使用了PEG-1000A的眼内透镜材料大。认为这是由于：4-ArmPEG34容易形成比PEG-1000A均一的网络，不易阻碍聚合物链运动性的自由度，结果显著地反映出聚乙二醇基的柔软性。
因此，由于4-ArmPEG34能够以较少的使用量使眼内透镜材料的玻璃化转变温度降低，所以能够增多具有芳基的(甲基)丙烯酸酯单体(B)的使用量，结果能够提供折射率高的眼内透镜材料。
【表2】
Figure PCTCN2019087749-appb-000015
表中，用质量％表示各成分的使用量的单位。另外，(E)成分、(F)成分以及(G)成分的使用量分别以相对于(A)成分、(B)成分、(C)成分以及(D)成分的质量的合计量(100质量％)的比例来表示。
此外，“*”以相对于(A)成分、(B)成分、(C)成分以及(D)成分的摩尔数的合计量的比例来表示。
通过使用BL01作为聚合性单体(F)，从而将在实施例4～6中得到的眼内透镜材料着色为黄色。此外，如表2所示，在实施例4～6中得到的眼内透镜材料未显示出粘合性，也未产生闪光以及白化。
在图5中，示出将4-ArmPEG34(实施例4～6)的使用量(摩尔％)标绘在横轴、将眼内透镜材料的玻璃化转变温度标绘在纵轴的图表。
从图5可知，4-ArmPEG34的使用量与眼内透镜材料的玻璃化转变温度间的关系显示了良好的线性，并且确认到4-ArmPEG34的使用量与眼内透镜材料的玻璃化转变温度间的相关性。
【表3】
Figure PCTCN2019087749-appb-000016
表中，用质量％表示各成分的使用量的单位。另外，(E)成分、(F)成分以及(G)成分的使用量分别以相对于(A)成分、(B)成分、(C)成分以及(D)成分的质量的合计量(100质量％)的比例来表示。
此外，“*”以相对于(A)成分、(B)成分、(C)成分以及(D)成分的摩尔数的合计量的比例来表示。
如表3所示，在实施例7～13中得到的眼内透镜材料均未显示出粘合性，也未产生闪光以及白化。
与此相对地，在比较例7中得到的眼内透镜材料显示出粘合性，光学部表面贴合。此外，在比较例7中得到的眼内透镜材料在其表面产生了雾状地白色化的白化。
此外，使用以上述(A2)～(A4)表示、聚乙二醇基的重复数(a、b、c、d)为8或者9且a、b、c以及d的合计为34的单体作为4支链的含PEG的大分子单体(A)，与实施例1～13同样地制作眼内透镜材料时，得到了显示出与所述实施例1～13同样的倾向的结果。
进而，使用如上所述的芳基的种类不同的(甲基)丙烯酸酯单体(B)，与实施例1～13同样地制作眼内透镜材料时，得到了显示出与所述实施例1～13同样的倾向的结果。

Claims (13)

  1. 一种聚合物材料，其特征在于，其是将含有11～30质量％的以下述通式(I)表示的大分子单体(A)和至少一种具有芳基的(甲基)丙烯酸酯单体(B)的单体混合液聚合而成的，
    Figure PCTCN2019087749-appb-100001
    式中，4个n分别独立地为1或者2，a、b、c以及d分别独立地为4以上的整数，4个Z分别独立地为包含(甲基)丙烯酰基的取代基。
  2. 如权利要求1所述聚合物材料，其特征在于，
    在所述通式(I)中，所述a、b、c以及d分别独立地为4～14的整数，并且所述a、b、c以及d的和为16～56的整数。
  3. 如权利要求1或者2所述的聚合物材料，其特征在于，在所述通式(I)中，各个所述Z以下述式(Z1)、(Z2)或者(Z3)表示，
    Figure PCTCN2019087749-appb-100002
    各个式中，R 1为氢原子或者甲基。
  4. 如权利要求1～3中任一项所述的聚合物材料，其特征在于，在所述通式(I)中，所述4个Z是相同的。
  5. 如权利要求4所述的聚合物材料，其特征在于，在所述通式(I)中，所述4个Z均为丙烯酰基。
  6. 如权利要求1～5中任一项所述的聚合物材料，其特征在于，所述(甲基)丙烯酸酯单体(B)以下述通式(II)表示，
    Figure PCTCN2019087749-appb-100003
    式中，R 2为氢原子或者甲基，m为1～6的整数，Y为直接键或者氧原子，D为氢原子、—C 6H 5、—CH 2C 6H 5或者—OC 6H 5。
  7. 如权利要求1～6中任一项所述的聚合物材料，其特征在于，所述单体混合液含有70～89质量％的所述(甲基)丙烯酸酯单体(B)。
  8. 如权利要求1～7中任一项所述的聚合物材料，其特征在于，所述单体混合液还含有具有紫外线吸收性的聚合性单体。
  9. 如权利要求1～8中任一项所述的聚合物材料，其特征在于，所述单体混合液还含有具有着色性的聚合性单体。
  10. 如权利要求1～9中任一项所述的聚合物材料，其特征在于，所述单体混合液还含有选自不具有芳基的(甲基)丙烯酸酯单体以及交联性单体中的至少一种的辅助单体。
  11. 如权利要求1～10中任一项所述的聚合物材料，其特征在于，该聚合物材料是眼内透镜材料。
  12. 一种眼内透镜，其特征在于，其具有权利要求11所述的眼内透镜材料的加工物。
  13. 一种眼内透镜，其特征在于，其包含权利要求1～10中任一项所述的聚合物材料。
PCT/CN2019/087749 2018-06-01 2019-05-21 聚合物材料以及眼内透镜 WO2019228224A1 (zh)

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