WO2017061550A1 - 非含水性眼用レンズの製造方法及び非含水性眼用レンズ - Google Patents
非含水性眼用レンズの製造方法及び非含水性眼用レンズ Download PDFInfo
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- WO2017061550A1 WO2017061550A1 PCT/JP2016/079810 JP2016079810W WO2017061550A1 WO 2017061550 A1 WO2017061550 A1 WO 2017061550A1 JP 2016079810 W JP2016079810 W JP 2016079810W WO 2017061550 A1 WO2017061550 A1 WO 2017061550A1
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- ophthalmic lens
- hydrophilic
- monomer
- lens
- hydrous
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- G—PHYSICS
- G02—OPTICS
- G02C—SPECTACLES; SUNGLASSES OR GOGGLES INSOFAR AS THEY HAVE THE SAME FEATURES AS SPECTACLES; CONTACT LENSES
- G02C7/00—Optical parts
- G02C7/02—Lenses; Lens systems ; Methods of designing lenses
- G02C7/04—Contact lenses for the eyes
- G02C7/049—Contact lenses having special fitting or structural features achieved by special materials or material structures
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- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B1/00—Optical elements characterised by the material of which they are made; Optical coatings for optical elements
- G02B1/04—Optical elements characterised by the material of which they are made; Optical coatings for optical elements made of organic materials, e.g. plastics
- G02B1/041—Lenses
- G02B1/043—Contact lenses
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- G—PHYSICS
- G02—OPTICS
- G02C—SPECTACLES; SUNGLASSES OR GOGGLES INSOFAR AS THEY HAVE THE SAME FEATURES AS SPECTACLES; CONTACT LENSES
- G02C7/00—Optical parts
- G02C7/02—Lenses; Lens systems ; Methods of designing lenses
- G02C7/04—Contact lenses for the eyes
-
- G—PHYSICS
- G02—OPTICS
- G02C—SPECTACLES; SUNGLASSES OR GOGGLES INSOFAR AS THEY HAVE THE SAME FEATURES AS SPECTACLES; CONTACT LENSES
- G02C7/00—Optical parts
- G02C7/02—Lenses; Lens systems ; Methods of designing lenses
- G02C7/024—Methods of designing ophthalmic lenses
Definitions
- the present invention relates to a method for producing a non-hydrophilic ophthalmic lens having a hydrophilized lens surface and a non-hydrophilic ophthalmic lens having a hydrophilized lens surface obtained by the production method.
- the eye is an organ that should be kept transparent.
- the eye is supplied with oxygen to keep the eye cells healthy.
- the supply of oxygen to the eye cells cannot be performed via blood, but is performed directly from the atmosphere via the cornea.
- oxygen supply to the cornea is significantly hindered.
- wearing a contact lens for a long period of time causes an oxygen-deficient state of the cornea and causes eye diseases such as hyperemia, corneal edema, and vascular infiltration. Therefore, oxygen permeability, which is one of the physical properties of the contact lens, affects the amount of oxygen supplied to the eye cells, so particular attention should be paid to the physical properties of the contact lens.
- Hard contact lenses (RGP) and non-hydrous soft contact lenses have high oxygen permeability due to the silicone component as a constituent component.
- these contact lenses have a problem of low lubricity due to the high lipophilicity and water repellency of the silicone component, and oils and proteins are likely to adhere. If oil or protein adheres to the contact lens due to this problem, problems such as foreign object feeling and poor visibility may occur when the lens is worn. Accordingly, various surface modification methods for contact lenses having a silicone component as a constituent component for the purpose of preventing the adhesion of oil and proteins and improving the water wettability of the surface have been studied.
- Patent Document 1 the entire description of which is incorporated herein by reference
- radical treatment is performed on the surface of the treated ophthalmic lens by performing plasma treatment on the ophthalmic lens substrate.
- a method of modifying the graft polymer on the surface of the ophthalmic lens by generating the polymer and then immersing the ophthalmic lens in a monomer solution to perform polymerization is disclosed.
- Patent Document 2 discloses a method for hydrophilizing a device surface by alternately laminating an acidic polymer and a basic polymer on the surface of a soft resin device. Is disclosed.
- Patent Document 3 uses an atom transfer radical polymerization (ATRP) method or a reversible addition-fragmentation chain transfer (RAFT) polymerization method in advance.
- a polymer surface modifying agent having a functional group at the terminal is prepared, and the surface modifying agent is covalently bonded to the functional group on the surface of the ophthalmic lens to immobilize the surface modifying agent on the lens surface.
- a method for modifying the surface of a lens is disclosed.
- Patent Documents 1 to 3 have various problems.
- the method of Patent Document 1 has a problem that the ophthalmic lens base material may be denatured and yellowed by performing plasma treatment on the ophthalmic lens base material.
- radicals generated by plasma treatment tend to be deactivated, it is difficult to modify the lens surface with a polymer other than a homopolymer composed of a single component or a random copolymer composed of a certain composition. There is a problem of lacking.
- Patent Document 2 has a problem that unless three or more laminated films are formed, the film structure is unstable and it is difficult to obtain a sufficient surface modification effect.
- a laminated film is formed by alternately laminating an acidic polymer and a basic polymer, the laminated film is easily decomposed by neutralizing the charge of the polymer due to the influence of the surrounding environment such as pH and salt strength. .
- the ophthalmic lens obtained by the method of Patent Document 2 has a problem that the film structure becomes unstable depending on the care product used for storage and washing.
- Patent Document 3 requires a prior preparation such as purification and separation of a polymer compound that serves as a surface modifier, which complicates the surface modification process and further binds a polymer chain to a lens substrate. It is a graft-to-reaction. Therefore, the method of Patent Document 3 has a problem that the reaction between the lens surface and the surface modifier is easily hindered by the bulkiness of the surface modifier, and it is difficult to form a graft polymer that satisfies the water wettability on the lens surface. There is.
- Patent Documents 1 to 3 can cause damage to the ophthalmic lens base material due to the surface modification treatment of the ophthalmic lens base material, lack of variety of surface modification treatment, and surface modification treatment.
- satisfactory hydrophilization cannot be achieved, the surface modification part is brittle, and the surface modification treatment process is complicated.
- As a method for obtaining a optic eye lens it is a method lacking practicality and industrial productivity.
- the lens surface of a non-hydrous ophthalmic lens having a silicone compound as a constituent component is imparted with a desired water wettability and stability to the surrounding environment by a simple method, thereby making the lens surface hydrophilic. It is an object of the present invention to provide a method for producing a sexualized non-hydrous ophthalmic lens.
- ATRP atom transfer radical polymerization method
- the termination reaction is suppressed by the equilibrium with active species that are largely biased toward dormant species, so that it is possible to obtain a polymer with a narrow molecular weight distribution.
- the terminal of the polymer obtained by ATRP is a dormant species, even if the polymer has once stopped the growth reaction, the growth reaction proceeds again when the reaction condition is satisfied again. From this characteristic, the block copolymer can be obtained relatively easily by recovering the polymer obtained after polymerizing the first monomer and then polymerizing the second monomer.
- the present inventors have introduced a halogenated alkyl group-containing component as an ATRP dormant initiator into an ophthalmic lens base material, and then brought the ophthalmic lens base material into contact with a hydrophilic monomer and a metal complex. While the hydrophilic monomer is polymerized from the surface of the lens base material, the so-called graft from method prevents steric hindrance to the reaction between the ophthalmic lens surface and the hydrophilic monomer, while preventing the ophthalmic lens surface. In addition, sufficient water wettability and stain resistance are imparted, and a block copolymer that has been difficult with conventional graft polymerization methods can be introduced to form various hydrophilic surfaces according to the purpose. I thought.
- the ophthalmic lens base material is a non-hydrous ophthalmic lens base material
- the graft polymerization reaction solvent is water.
- the ophthalmic lens base material is immersed in an aqueous solution containing two or more different hydrophilic monomers, and each hydrophilic monomer is polymerized in order to form a block copolymer or a random copolymer having a different composition. Succeeded in producing a non-hydrous ophthalmic lens on the lens surface.
- the present invention has been completed based on these successful examples.
- a hydrophilic polymer having a terminal halogenated by bringing a non-hydrous ophthalmic lens having a halogenated alkyl group into contact with an aqueous solution containing a hydrophilic monomer and a metal complex.
- a method for producing a non-hydrous ophthalmic lens having a hydrophilic polymer having a terminal halogenated on the lens surface comprising a step of obtaining a non-hydrous ophthalmic lens having a lens surface on the lens surface.
- the hydrophilic polymer is a hydrophilic homopolymer, a hydrophilic block copolymer, or a hydrophilic random copolymer.
- the non-hydrous ophthalmic lens having a halogenated alkyl group includes a polymer of monomer components including a halogenated alkyl monomer and a hydrophobic monomer. It is a lens.
- the halogenated alkyl monomer is a halogenated alkyl monomer containing a 2-haloisobutyl group and a polymerizable functional group.
- the halogenated alkyl monomer is 2- (2-bromoisobutyloxy) ethyl (meth) acrylate.
- the metal complex is a metal complex composed of a copper ion and a ligand.
- the aqueous solution further contains a reducing agent.
- the reducing agent is at least one selected from the group consisting of di (ethylhexane) tin, L-ascorbic acid, sodium L-ascorbate, glucose and hydrazine. It is a reducing agent.
- a terminal is halogenated by contacting a non-hydrous ophthalmic lens having an alkyl halide group with an aqueous solution containing two or more kinds of hydrophilic monomers and metal complexes.
- a method for producing a non-hydrous ophthalmic lens having a terminally halogenated hydrophilic random copolymer on the lens surface comprising the step of obtaining a non-hydrous ophthalmic lens having the hydrophilic random copolymer on the lens surface.
- a non-hydrous ophthalmic lens having a halogenated alkyl group is brought into contact with a first aqueous solution containing a first hydrophilic monomer and a metal complex, whereby a terminal is halogenated.
- a hydrophilic block copolymer comprising a second hydrophilic polymer having a terminal halogenated and a first hydrophilic polymer by contacting with a second aqueous solution containing the second hydrophilic monomer and the metal complex.
- a method for producing a non-hydrous ophthalmic lens having a hydrophilic block copolymer having a terminal halogenated on the lens surface comprising a step of obtaining a non-hydrous ophthalmic lens having a surface is provided. It is.
- a non-hydrous ophthalmic lens having a hydrophilic polymer having a halogenated terminal on the lens surface and having a contact angle of less than 90 °.
- the hydrophilic polymer is a hydrophilic homopolymer, a hydrophilic block copolymer, or a hydrophilic random copolymer.
- the non-hydrous ophthalmic lens of one embodiment of the present invention includes a copolymer of a halogenated alkyl monomer and a hydrophobic monomer.
- a mechanical treatment such as plasma irradiation is indispensable for forming a radical that is a starting point of graft polymerization.
- a mechanical treatment such as plasma irradiation is indispensable for forming a radical that is a starting point of graft polymerization.
- the polymer formed on the surface of the ophthalmic lens is chemically bonded, it is stable regardless of the surrounding environment such as pH and salt concentration, and is semi-permanent. Water wettability can be provided to the ophthalmic lens surface.
- the manufacturing method of one embodiment of the present invention can be achieved as a simple process of immersing the ophthalmic lens base material in an aqueous solution under normal temperature conditions, so that complicated process control can be omitted, which is economically advantageous. Therefore, it is suitable for manufacturing disposable ophthalmic lenses that require production quantities.
- the hydrophilic polymer formed on the lens surface of the ophthalmic lens obtained by the manufacturing method of one embodiment of the present invention or the ophthalmic lens of one embodiment of the present invention is not limited to a homopolymer, and may be a block copolymer or a random copolymer. It can be varied depending on the type of hydrophilic monomer used.
- the lens surface can be kept clean, and the adhesion of lipids and proteins to the lens surface and the increase in friction are suppressed even during long-time wearing. Therefore, it is possible to provide an ophthalmic lens that can suppress a decrease in wearing feeling and an eye damage caused by them.
- FIG. 1A is a graph showing a change in infrared spectrum with respect to an immersion time in an ATRP reaction solution for Examples 12-1 to 8 described in Examples. “0 min” represents Reference Example 1.
- FIG. 1B is a diagram showing the change in the infrared spectroscopic spectrum with respect to the immersion time in the ATRP reaction solution for Example 12-5 (30 minutes) and Example 12-7 (60 minutes) described in the Examples. is there. “0 min” represents Reference Example 1.
- FIG. 2A is a graph showing the change in the infrared spectrum with respect to the immersion time in the ATRP reaction solution for Examples 13-1 to 13-4 described in Examples. “0 min” represents Reference Example 1.
- FIG. 1B is a diagram showing the change in the infrared spectroscopic spectrum with respect to the immersion time in the ATRP reaction solution for Example 12-5 (30 minutes) and Example 12-7 (60 minutes) described in the Examples. is there. “0 min” represents Reference Example 1.
- FIG. 2A is a graph showing the change in the infrared spectrum with
- FIG. 2B is a diagram showing the change in the infrared spectrum with respect to the immersion time in the ATRP reaction solution for Example 13-2 (20 min) and Example 13-4 (45 min) described in the examples.
- “0 min” represents Reference Example 1.
- FIG. 3 is a graph showing the change in the infrared spectrum with respect to the immersion time in the ATRP reaction solution for Examples 14-1 and 14-2 described in the Examples.
- “MAAc30min” represents Example 13-3.
- FIG. 4 is a diagram showing a change in water contact angle with respect to the immersion time of the ATRP reaction solution described in the examples.
- FIG. 5 is a diagram showing an infrared spectrum of Comparative Example 1 described in the examples.
- a first aspect of the present invention is a method for producing a non-hydrous ophthalmic lens having a hydrophilic polymer having a halogenated terminal on the lens surface.
- a non-hydrophilic ophthalmic lens having a halogenated alkyl group is brought into contact with an aqueous solution containing a hydrophilic monomer and a metal complex to thereby form a hydrophilic polymer having a terminal halogenated. It includes at least a step of obtaining a non-hydrous ophthalmic lens on the lens surface.
- halogenated alkyl group in the present specification is not particularly limited as long as at least a part of the alkyl group is a halogenated functional group.
- X—R—, X 2 —R—, X—R— It can be expressed as a structural formula such as CO—, X—R—CO—O— (wherein R represents a substituted or unsubstituted alkylene group).
- a hydrophilic polymer having a terminal end halogenated is directly bonded to the lens surface by a covalent bond, and a terminal end halogenated hydrophilic polymer is obtained.
- a non-hydrous ophthalmic lens having a lens surface is produced.
- a hydrophilic surface on which a hydrophilic polymer having a terminal halogenated is formed is stable regardless of the surrounding environment such as pH and salt concentration, and can maintain semi-permanent water wettability.
- the hydrophilic polymer is an arbitrary block copolymer or random copolymer formed using two or more kinds of hydrophilic monomers in addition to the hydrophilic homopolymer formed using one kind of hydrophilic monomer. Therefore, the non-hydrous ophthalmic lens having a hydrophilic surface obtained by the manufacturing method of one embodiment of the present invention can be manufactured with a surface design according to the purpose.
- CL represents an ophthalmic lens substrate
- S represents —O—CO—R— (wherein R represents a substituted or unsubstituted alkylene group having 2 to 4 carbon atoms); M represents a metal ion; Z represents an integer of 1 to 3; L represents a ligand; M represents a monomer; and n represents an integer of 2 or more.)
- the monomer is a hydrophilic monomer
- the hydrophilic polymer is formed on the surface of the ophthalmic lens substrate by graft polymerization, the lens surface is rendered hydrophilic.
- a silicone component is included as a component of the ophthalmic lens, the compatibility between the silicone component and the hydrophilic polymer is poor, and if both coexist in the lens, white turbidity and deformation due to phase separation may occur.
- a non-hydrous ophthalmic lens base material made of a polymer of monomer components containing an alkyl halide monomer, a silicone monomer, a hydrophobic monomer, and the like is used for the ophthalmic lens base,
- an aqueous solution containing a metal complex and a hydrophilic monomer By immersing the non-hydrous ophthalmic lens base material in an aqueous solution containing a metal complex and a hydrophilic monomer, the aqueous solution enters the inside of the lens base material by bringing them into contact with each other (hereinafter also referred to as ATRP reaction).
- the metal complex and the hydrophilic monomer can be supplied to the surface of the lens base material, and as a result, the ATRP is mainly advanced on the surface of the lens base material, and the halogenated hydrophilic polymer is formed. It is possible to produce a non-hydrous ophthalmic lens on the lens surface.
- the phase separation between the ophthalmic lens base material and the formed hydrophilic polymer can be reduced, and hydrophilicity can be achieved without causing alteration of the ophthalmic lens base material.
- Surface modification can be achieved.
- the type of the hydrophilic monomer; the type of the aqueous solution containing the hydrophilic monomer and the metal complex; the number of ATRP reactions is not particularly limited. , Hydrophilic homopolymers, hydrophilic block copolymers, hydrophilic random copolymers and combinations thereof.
- a non-hydrous ophthalmic lens obtained by graft polymerization of the first hydrophilic monomer on the lens surface in an aqueous solution containing a second hydrophilic monomer and a metal complex different from the first hydrophilic monomer, A graft polymer chain of the second hydrophilic monomer is formed by extending to the graft polymer chain of the first hydrophilic monomer, and as a result, a hydrophilic block copolymer comprising two types of graft polymer chains is provided on the lens surface. It becomes possible to manufacture a non-hydrous ophthalmic lens.
- a graft copolymer having a plurality of different building blocks can be obtained by selecting the hydrophilic monomer, and various types can be selected depending on the purpose.
- Various lens surface designs are possible.
- a non-hydrous ophthalmic lens having a halogenated alkyl group which is an ophthalmic lens substrate, is used.
- a method for preparing a non-hydrous ophthalmic lens having a halogenated alkyl group is not particularly limited.
- monomers such as silicone monomers, hydrophobic monomers, and polymerizable halogenated alkyl agents (halogenated alkyl monomers) as constituent components
- a polymerization initiator is prepared by preparing a solution containing at least the components and optionally adding a polymerization initiator such as bis (2,4,6-trimethylbenzoyl) -phenylphosphine oxide or azobisisobutyronitrile.
- the solution can be obtained by subjecting the solution to heat or light to polymerize and cure.
- the term “monomer” is used as a term that is paired with the term “polymer” and refers to a molecule having a polymerizable functional group such as —C ⁇ C— group.
- polymer means a polymer composed of a polymer obtained by polymerizing monomers.
- the silicone monomer is not particularly limited as long as it is a monomer having a repeating unit of a siloxane bond as a silicone and having a polymerizable functional group.
- Specific examples of the silicone monomer include methacryloxypropylbis (trimethylsiloxy) methylsilane, ⁇ , ⁇ -dimethacryloxypropylpolydimethylsiloxane, ⁇ -methacryloxy- ⁇ -butylpolydimethylsiloxane, methacryloxypropyltris (trimethylsiloxy) silane (Tristrimethylsiloxypropyl methacrylate) and the like.
- the silicone monomer can be blended as one or a combination of two or more of the above specific examples so that an ophthalmic lens having a desired oxygen permeability can be obtained.
- the method for obtaining the silicone monomer and the blending amount thereof are not particularly limited.
- a commercially available monomer may be 25 to 65 wt% based on the total amount of the monomer components blended as a constituent component of the ophthalmic lens base material. Can be used at 35 to 55 wt%.
- the hydrophobic monomer is not particularly limited as long as it is a monomer having a hydrophobic group such as fluorine or hydrocarbon and a polymerizable functional group.
- Specific examples of the hydrophobic monomer include methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, i-propyl (meth) acrylate, n-butyl (meth) acrylate, and i-butyl (meth) acrylate.
- T-butyl (meth) acrylate pentyl (meth) acrylate, trimethylcyclohexyl (meth) acrylate, t-butylcyclohexyl (meth) acrylate, hexyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, cyclohexyl (meth) acrylate , Heptyl (meth) acrylate, octyl (meth) acrylate, nonyl (meth) acrylate, decyl (meth) acrylate, dodecyl (meth) acrylate, lauryl (meth) acrylate, tridecyl (medium ) Acrylate, tetradecyl (meth) acrylate, methoxydiethylene glycol (meth) acrylate, ethoxydiethylene glycol (meth) acrylate, ethylene glycol di (meth) acrylate,
- the hydrophobic monomer may be blended as one or a combination of two or more of the above specific examples so that an ophthalmic lens having desired physical properties can be obtained.
- a hard non-hydrated ophthalmic lens (so-called hard contact lens) is prepared by using a monomer having a low glass transition temperature point as a hydrophobic monomer, and conversely, a soft, non-hydrated product using a monomer having a high glass transition temperature point.
- sexual ophthalmic lenses can be prepared.
- Hydrophobic monomers are not particularly limited in terms of the method of obtaining them and the blending amount.
- a commercially available monomer is 30 to 70 wt% based on the total amount of monomer components blended as a constituent component of the ophthalmic lens substrate.
- 40 to 60 wt% can be used.
- the blending ratio of the silicone monomer and the hydrophobic monomer is not particularly limited.
- the blending ratio of hydrophobic monomer: silicone monomer can be 70 to 30:29 to 69, and preferably 60 to 50:39 to 49.
- a dormant species that is the starting point of ATRP can be introduced into the lens surface.
- the halogenated alkyl monomer is not particularly limited as long as it is a compound having a halogenated alkyl group such as a 2-haloisobutyryl group and a polymerizable functional group.
- R 1 , R 2 and R 3 each represent an independent hydrogen group or methyl group; Z represents an O, COO or CONH group; Y represents (CH 2 ) nO (where n is an integer) X represents a halogen group such as a chlorine group or a bromine group.
- Non-limiting specific examples of the compound of the general formula (1) include, for example, the following formula (2) (2)
- 2- (2-bromoisobutyryloxy) ethyl methacrylate represented by: 2- (2-bromoisobutyryloxy) ethyl acrylate, 2- (2-bromopropionyloxy) ethyl methacrylate
- Examples include, but are not limited to, 2- (2-bromopropionyloxy) ethyl acrylate.
- the blending amount of the halogenated alkyl monomer is not particularly limited. For example, although it varies depending on the type, 0.01 to 10 wt% with respect to the total amount of the monomer components blended as a constituent component of the ophthalmic lens substrate. And preferably 0.05 to 5 wt%, more preferably 0.1 to 3.0 wt%.
- the halogenated alkyl monomer is generally a water-absorbing compound, and the density of the graft polymer formed on the lens surface may vary depending on the blending amount of the halogenated alkyl monomer.
- the ophthalmic lens base material retains water content, and by absorbing water, the hydrophilic monomer or metal is transferred to the halogenated alkyl group inside the lens.
- phase separation may occur between the ophthalmic lens and the graft polymer, and the white turbidity or shape change of the lens may occur.
- the blending amount of the halogenated alkyl monomer is too small, the density of the graft polymer is insufficient, so that the hydrophobic ophthalmic lens surface cannot be sufficiently coated, and sufficient hydrophilicity is obtained. It may not be possible.
- a monomer component used as a component of a non-hydrous ophthalmic lens that is an ophthalmic lens base material in addition to a silicone monomer, a hydrophobic monomer, and an alkyl halide monomer, other monomer components may be blended. .
- the blending amount of the other monomer component is not particularly limited.
- the blending amount of the hydrophilic monomer is that of the monomer component blended as a constituent component of the ophthalmic lens substrate. It is 10 wt% or less with respect to the total amount, preferably 6 wt% or less.
- the method for producing a non-hydrous ophthalmic lens that becomes an ophthalmic lens substrate is not particularly limited, and can be produced by a known method.
- a non-hydrous ophthalmic lens can be obtained by a mold production method, cutting, or the like. .
- the obtained non-hydrous ophthalmic lens can remove unreacted components through, for example, immersion in an organic solvent. In this way, a non-hydrous ophthalmic lens having a halogenated alkyl group serving as a reaction starting point is prepared.
- the method for preparing the aqueous solution containing the hydrophilic monomer and the metal complex used in the above step is not particularly limited.
- the hydrophilic monomer, the metal salt and the ligand are weighed and then dissolved in a predetermined amount of pure water.
- an aqueous solution containing a hydrophilic monomer and a metal complex (hereinafter also referred to as ATRP reaction solution) can be prepared.
- ATRP reaction solution an aqueous solution containing a hydrophilic monomer and a metal complex
- the metal complex those already converted into metal complexes by metal ions and ligands may be used, and metal salts, metal ions and ligands as raw materials thereof may be added individually and used.
- the hydrophilic monomer is a monomer component that is a raw material for the graft polymer.
- the metal ion and the ligand form a metal complex and play a role of extracting a halogen element from the alkyl halide in the non-hydrous ophthalmic lens in the ATRP reaction.
- the ATRP reaction solution when metal ions are oxidized by oxygen supplied from an aqueous solution or from the air interface, the halogen abstraction reaction by the metal complex does not proceed, and the initiation radical may not be generated. Therefore, it is preferable that oxygen is removed from the ATRP reaction solution.
- the method for removing oxygen from the ATRP reaction liquid is not particularly limited, and examples thereof include bubbling with an inert gas, vacuum degassing, and addition of a reducing agent, and these can be used alone or in combination.
- ARGET ATRP method ATRP performed by adding a reducing agent.
- the ARGET ATRP method can suppress the deactivation of metal ions due to oxidation, compared to the classic ATRP method, which is a method that does not add a reducing agent. In this method, it is possible to easily remove the metal ions and to reduce the coloring of the polymer by the metal ions.
- the hydrophilic monomer used in the ATRP reaction solution has one or more polymerizable functional groups such as (meth) acrylic group, (meth) acrylamide group, and vinyl group in the molecule, and has high water solubility as a molecule. If there is no particular limitation. Specific examples include acrylic acid, methacrylic acid, 2-dimethylaminomethyl acrylate, glycidyl (meth) acrylate, glycerol mono (meth) acrylate, 2-methacryloyloxyethyl phosphorylcholine, glycerol di (meth) acrylate, hydroxyethyl (methacrylate).
- polymerizable functional groups such as (meth) acrylic group, (meth) acrylamide group, and vinyl group in the molecule, and has high water solubility as a molecule. If there is no particular limitation. Specific examples include acrylic acid, methacrylic acid, 2-dimethylaminomethyl acrylate, glycidyl (meth)
- the hydrophilic monomer may be any of nonionic, anionic, cationic and zwitterionic.
- the blending amount of the hydrophilic monomer used in the ATRP reaction liquid is not particularly limited. For example, it is preferably 1 to 10 wt% with respect to the solvent of the aqueous solution, that is, the mass of water.
- the amount of the hydrophilic monomer is excessive, the non-hydrous ophthalmic lens immersed in the ATRP reaction solution is swollen by the monomer, and the graft polymerization proceeds from the starting point inside the lens, so that the lens becomes clouded or deformed. there is a possibility.
- the blending amount of the hydrophilic monomer is too small, graft polymerization is difficult to proceed, and there is a possibility that a sufficient surface modification effect cannot be obtained in the non-hydrous ophthalmic lens after treatment.
- the ATRP reaction liquid may contain other components in addition to the hydrophilic monomer and the metal complex.
- a crosslinking agent may be added to the ATRP reaction solution.
- the crosslinking agent is not particularly limited as long as it has a polymerizable functional group such as two or more (meth) acrylic groups, (meth) acrylamide groups, and vinyl groups in the molecule, and has high water solubility as a molecule.
- a polymerizable functional group such as two or more (meth) acrylic groups, (meth) acrylamide groups, and vinyl groups in the molecule, and has high water solubility as a molecule.
- Specific examples include N, N′-methylenebisacrylamide, ethylene glycol di (meth) acrylate, polyethylene glycol di (meth) acrylate, trimethylolpropane tri (meth) acrylate, pentaerythritol tri (meth) acrylate, and tripentaerythritol.
- (Meth) acrylate, (meth) acryl group-terminated dendrimer, tris (meth) acryloyloxyethyl phosphate, and the like can be used, and one or a combination of two or more of these can be used.
- the blending amount of the crosslinking agent is not particularly limited, but for example, 0 to 20 wt% is preferable with respect to the total mass of the hydrophilic monomer blended in the aqueous solution. When the blending amount of the crosslinking agent exceeds 20 wt%, the graft polymer becomes rigid, and there is a possibility that a foreign body sensation is induced to the wearer when the finally obtained ophthalmic lens is worn.
- the metal complex to be blended in the ATRP reaction liquid and the metal ion and ligand constituting the metal complex are not particularly limited.
- a radical is extracted from a halogenated alkyl group such as a 2-haloisobutyl group as a reaction starting point.
- Any metal complex or the like may be used as long as it produces an equilibrium with the dormant species and has the effect of suppressing the radical termination reaction.
- metal ions to be blended in the ATRP reaction liquid include ions of metal elements such as copper, titanium, iron, cobalt, nickel, molybdenum, and ruthenium. Copper ions are preferable from the viewpoint of reaction rate and cost.
- the metal ion is usually in the form of a metal salt and is added when preparing the ATRP reaction solution. Although it does not specifically limit as a metal salt, For example, when a metal ion is a copper ion, copper chloride (I), copper (II) chloride, copper bromide (I), copper bromide (II), copper iodide (I) etc. are mentioned.
- Metal ions bind to ligands in ATRP solution to form metal complexes.
- the metal complex has a strong color depending on the metal ion and causes the coloring of the graft polymer, which may affect the appearance and light transmittance of the lens.
- the color development of the metal complex is roughly proportional to the concentration of metal ions.
- the metal complex is easily oxidized, and a large amount of metal salt is blended to promote the graft polymerization reaction. It is supposed to be 1,000 to 10,000 ppm.
- the ARGET ATRP method it is possible to reduce the blending amount of the metal salt due to the effect of the reducing agent blended in the ATRP reaction solution. Therefore, in the manufacturing method of one embodiment of the present invention, it is preferable to add a reducing agent to the ATRP reaction solution. Thereby, it is preferable that the compounding quantity of the metal salt in an ATRP reaction liquid shall be 1,000 ppm or less.
- the compounding amount of the metal salt in the ATRP reaction liquid can be appropriately set depending on the type of the metal salt, the compounding amount of the hydrophilic monomer, and the like, and is not particularly limited.
- the metal salt is a copper salt It is 10 to 2,000 ppm, preferably 50 to 1,000 ppm, and more preferably 50 to 500 ppm.
- the metal salt forms a metal complex by coexisting a predetermined ligand, and extracts a halogen from the halogenated alkyl group to generate an initiation radical.
- the initiating radical and the growing radical are in an equilibrium between the active species and the dormant species, and the termination reaction is greatly suppressed.
- a ligand is not specifically limited, For example, it can select suitably with the kind of metal ion used for complex formation. When copper ions are used as metal ions, nitrogen-containing ligands are useful for complex formation.
- the rate of initiation radical generation and the equilibrium constant between the dormant and the active species change, and the ratio between the active species and the dormant species changes.
- the rate of graft polymerization can vary.
- the ligand include 2,2'-dipyridyl, 4,4'-dimethyl-2,2'-dipyridyl, 4,4'-ditertiary butyl-2,2'-dipyridyl, 4,4 ' -Dinonyl-2,2'-dipyridyl, N-butyl-2-pyridylmethanimine, N-octyl-2-pyridylmethanimine, N-dodecyl-N- (2-pyridylmethylene) amine, N-octadecyl-N- (2-pyridylmethylene) amine, N, N, N ′, N ′′, N ′′ -pentamethyldiethylenetriamine, tris (2-pyridylmethyl) amine, 1,1,4,7,10,10-hexamethyl Triethylenetetramine, tris [2- (dimethylamino) ethyl] amine, 1,4,8,11-t
- the blending amount of the ligand is not particularly limited, but for example, the blending amount is preferably 1 to 10 mole times the coordinated metal ion.
- the active species cannot be formed enough to cause the reaction to proceed stably, and thus the reaction may not proceed easily.
- a method for preparing an ATRP reaction liquid containing at least a metal complex composed of a hydrophilic monomer and a metal salt and a ligand is not particularly limited.
- the hydrophilic monomer, the metal salt and the ligand are sufficiently added to water.
- the method include mixing and stirring to dissolve each component to obtain an aqueous solution, and then removing unnecessary oxygen in the aqueous solution by bubbling an inert gas or vacuum degassing.
- a reducing agent can be blended with the above components in the ATRP reaction solution.
- the reducing agent acts on metal ions oxidized by oxygen or radicals, and reduces the valence to which the growth radicals and dormant species can form, thereby suppressing the deactivation of the reaction system.
- Specific examples of the reducing agent include di (ethylhexane) tin, L-ascorbic acid, sodium L-ascorbate, glucose, hydrazine, and the like, and one or a combination of two or more thereof can be used. .
- oxygen may be redissolved in the ATRP reaction solution.
- the amount of the reducing agent in the ATRP reaction solution is preferably 0.01 wt% or more with respect to the mass of water used in the aqueous solution, taking into account the amount of oxygen to be redissolved, 0.1 wt% or more It is more preferable that If the blending amount is less than 0.01 wt%, metal ions may oxidize due to a shortage of reducing agent, and the ATRP reaction may not occur.
- graft polymerization by ATRP is performed on the lens surface of a non-hydrous ophthalmic lens that is an ophthalmic lens substrate.
- a non-water-absorptive ocular lens CL-O-CO-R -X
- a ATRP reaction hydrophilic monomer M
- the metal complexes Mt z / L
- the method for bringing the non-hydrous ophthalmic lens having a halogenated alkyl group into contact with an aqueous solution containing a hydrophilic monomer and a metal complex is not particularly limited, and the terminal of the non-hydrous ophthalmic lens and the aqueous solution is halogenated. Any method can be used as long as the non-hydrous ophthalmic lens having the hydrophilic polymer formed on the lens surface can be obtained.
- the ATRP reaction is a reversible reaction, an active species and a dormant species are repeatedly generated, and when the active species are generated, a hydrophilic polymer that is a graft polymer chain is formed. Since the hydrophilic polymer obtained by the ATRP reaction is a dormant species in which the terminal end is halogenated, a growing radical can be generated by contact with the metal complex again. Therefore, by subjecting a non-hydrous ophthalmic lens having a hydrophilic polymer to the lens surface by ATRP reaction to another ATRP reaction liquid, another newly generated hydrophilic polymer from the halogenated terminating end of the hydrophilic polymer is newly generated. It is possible to grow a graft polymer.
- the number of ATRP reactions is not particularly limited, and can be set as appropriate depending on the number of contact between the non-hydrated ophthalmic lens and the ATRP reaction solution.
- a homopolymer, a random copolymer, a block copolymer, or a plurality of non-hydrous ophthalmic lenses depending on the type of hydrophilic monomer to be blended with the ATRP reaction solution and the number of times of contact with the ATRP reaction solution. It is possible to form copolymers having different structures on the lens surface of a non-hydrous ophthalmic lens.
- a non-hydrous ophthalmic lens having a halogenated alkyl group is used as one kind of hydrophilic polymer.
- the following general formula (3) is obtained by immersing once in an ATRP reaction solution containing a functional monomer.
- R 1 represents a hydrogen group or a methyl group
- R 2 represents a functional group imparting hydrophilicity to the molecule
- 1 represents an integer of 1 or more
- X represents a chlorine group or a bromine group
- Mt represents a metal ion.
- a non-hydrous ophthalmic lens having a halogenated alkyl group is The following general formula (4) is obtained by immersing once in an ATRP reaction liquid containing at least one kind of hydrophilic monomer.
- R 1, R 3 and R n each independently represent a hydrogen group or a methyl group
- R 2, R 4 and R m each independently represents a functional group which imparts hydrophilicity to the molecule
- N each independently represents an integer of 1 or more
- X represents a chlorine group or bromine group
- Mt represents a metal ion
- L represents a ligand
- Z represents an integer of 1 to 3; Indicates a non-hydrous ophthalmic lens substrate.
- the non-hydrous ophthalmic lens having a hydrophilic random copolymer having a terminal halogenated on the lens surface is obtained as the polymerization reaction proceeds.
- a block copolymer is formed as a graft polymer to be formed on the surface of an ophthalmic lens
- a non-hydrous ophthalmic lens having a halogenated alkyl group is used as the first method.
- the following general formula (5) is obtained by sequentially immersing in the ATRP reaction liquid containing the hydrophilic monomer and the ATRP reaction liquid containing the second hydrophilic monomer different from the first hydrophilic monomer.
- R 1 , R 3 , R n each independently represents a hydrogen group or a methyl group
- R 2 , R 4 , R m each independently represents a functional group that imparts hydrophilicity to the molecule
- N each independently represents an integer of 1 or more
- X represents a chlorine group or bromine group
- Mt represents a metal ion
- L represents a ligand
- Z represents each independently an integer of 1 to 3
- CL represents a non-hydrous ophthalmic lens substrate.
- the number of polymerization reactions is not limited, the desired number of ATRP reaction solutions are prepared, and the non-hydrous ophthalmic lens having a halogenated alkyl group is sequentially immersed in each ATRP reaction solution. A block copolymer with corresponding block units is formed.
- a hydrophilic monomer is added.
- Two or more kinds of the prepared ATRP reaction liquids are prepared according to the type of the hydrophilic monomer, and the non-hydrous ophthalmic lens having a halogenated alkyl group is sequentially immersed in each ATRP reaction liquid, whereby the following general formula (6) (6) (R 1 , R 3 , R 5 , R n each independently represents a hydrogen group or a methyl group; R 2 , R 4 , R 6 , R m are each independently a functional group that imparts hydrophilicity to the molecule.
- L, m and n each independently represents an integer of 1 or more; X represents a chlorine group or bromine group; Mt represents a metal ion; L represents a ligand; Z represents 1 to 3 CL represents a non-hydrous ophthalmic lens substrate.)
- a non-hydrous ophthalmic lens having a hydrophilic block copolymer and / or a hydrophilic random block copolymer having a halogenated terminal on the lens surface is obtained as shown in FIG. Since the number of polymerization reactions is not limited, the desired number of ATRP reaction solutions are prepared, and the non-hydrous ophthalmic lens having a halogenated alkyl group is sequentially immersed in each ATRP reaction solution. Corresponding block unit and random unit copolymers are formed.
- the conditions of the ATRP reaction (graft polymerization reaction) in the production method of one embodiment of the present invention are particularly limited as long as a non-hydrous ophthalmic lens having a hydrophilic polymer having a halogenated terminal as a product is obtained.
- it can be set as appropriate depending on the type and amount of components involved in the ATRP reaction, such as halogenated alkyl groups, hydrophilic monomers, metal complexes, etc.
- the reaction is carried out at 0 to 30 ° C., preferably at room temperature in the atmosphere.
- the reaction can be performed under conditions where the time is 10 to 120 minutes, preferably 10 to 60 minutes.
- the reaction time is shorter than 10 minutes, the graft polymerization reaction occurs, but the desired wettability may not be imparted to the lens surface of the non-hydrous ophthalmic lens. Even if the reaction time is excessive, there is no particular problem. However, in some cases, excessive graft polymer is formed on the lens surface, and undesirable water content is imparted. White turbidity may occur.
- the process termination condition in the production method of one embodiment of the present invention is not particularly limited as long as a non-hydrous ophthalmic lens having a hydrophilic polymer having a halogenated terminal on the lens surface is obtained.
- the halogen at the end of the hydrophilic polymer on the lens surface of the non-hydrous ophthalmic lens is not extracted to the metal complex.
- the reaction may be stopped.
- the reaction stop state can be achieved, for example, by oxidation of metal ions or removal of metal ions.
- the oxidation of the metal ions can be performed, for example, by immersing the non-hydrated ophthalmic lens in which the reaction is completed in an aqueous solution in which dissolved oxygen that has not been degassed is observed. Metal ions in the vicinity of the lens surface are oxidized by oxygen in the aqueous solution, and a metal complex cannot be formed, so that the catalytic effect is impaired.
- the removal of metal ions can be performed, for example, by immersing and washing the non-hydrated ophthalmic lens that has been reacted in a solution containing a chelating agent such as ethylenediaminetetraacetic acid (EDTA).
- EDTA ethylenediaminetetraacetic acid
- a non-hydrous ophthalmic lens in which desired wettability and contamination resistance are imparted to the lens surface can be obtained. Further, according to the production method of one embodiment of the present invention, it is possible to introduce a block copolymer, which has been difficult with the conventional graft polymerization method, onto the lens surface. It is possible to produce a non-hydrous ophthalmic lens having
- the second aspect of the present invention is a non-hydrous ophthalmic lens having a hydrophilic polymer having a halogenated terminal on the lens surface and a contact angle of less than 90 °.
- the hydrophilic polymer on the lens surface may be a hydrophilic homopolymer, a hydrophilic block copolymer, or a hydrophilic random copolymer.
- the non-hydrous ophthalmic lens of one embodiment of the present invention preferably contains a copolymer of monomer components including an alkyl halide monomer and a hydrophobic monomer as an ophthalmic lens base material.
- the non-hydrated ophthalmic lens of one embodiment of the present invention can be used as an ophthalmic lens that is used directly or indirectly on the eye, such as a hard contact lens, a soft contact lens, and a disposable contact lens.
- the non-water-containing ophthalmic lens of one embodiment of the present invention has a lens surface contact angle of less than 90 ° and excellent wettability, and excellent slipperiness, contamination resistance, and resistance to the external environment shown in the examples.
- it contains a silicone component and has excellent oxygen permeability, it can withstand long-term wearing and is very convenient for the wearer.
- non-hydrous soft ophthalmic lens substrate 4 As shown in Table 1, a non-hydrous soft ophthalmic lens substrate 4 was obtained by the same operation as the ophthalmic lenses 1 and 2 except that BIMA was not included as a constituent component.
- Non-Hydrophilic Hard Eye Lens Base Material 5 As shown in Table 2, a non-hydrous hard ophthalmic lens base material 5 was obtained by the same operation as the ophthalmic lens 3 except that BIMA was not included as a constituent component.
- ATRP reaction solution Each component was weighed according to Table 3, and the mixture obtained by stirring for 30 minutes was uniformly mixed at room temperature using a magnetic stirrer. The obtained uniform mixed solution was subjected to argon bubbling for 15 minutes to obtain ATRP reaction solutions A to F, G (1), G (2), H (1), H (2) and I.
- the wettability of the ophthalmic lens was evaluated by the water contact angle.
- the contact angle is measured by placing the ophthalmic lens on the female lens of the ophthalmic lens mold, removing excess water, dropping 1 mg of pure water onto the apex of the ophthalmic lens, and measuring the contact angle. It was.
- the evaluation criteria were as follows. ⁇ : Contact angle is less than 90 ° ⁇ : Contact angle is 90 ° or more
- the ophthalmic lens resistant to the external environment was immersed in a 5 wt% sodium chloride aqueous solution and sterilized by high-pressure steam at 121 ° C. and 2 atm. Thereafter, the ophthalmic lens was taken out and thoroughly washed with pure water, and then evaluated for wettability and slipperiness.
- each ATRP reaction solution was immersed at room temperature for 30 minutes.
- the ophthalmic lens substrate was immersed in G (1) or H (1) at room temperature for 30 minutes, then washed with a 0.5 wt% EDTA aqueous solution, and then with pure water. After washing, the ophthalmic lens substrate was immersed in G (2) or H (2) for 30 minutes at room temperature.
- the ophthalmic lens substrate was taken out from the ATRP reaction solution, washed with a 0.5 wt% EDTA aqueous solution, and then washed with pure water, whereby the non-hydrous soft ophthalmic lenses of Examples 1 to 11 and the non-aqueous hydrous lens were used.
- a hard ophthalmic lens was obtained.
- the non-hydrous soft ophthalmic lens substrate 1 was used as an ophthalmic lens without being immersed in the ATRP reaction solution.
- the obtained non-hydrous soft ophthalmic lens was transferred to a sealed container together with physiological saline, and autoclaved at 121 ° C. for 20 minutes. Further, the obtained non-hydrous hard ophthalmic lens was subjected to an evaluation test without performing high-pressure steam sterilization.
- Comparative Examples 1 to 4 (Comparative Example 1) Surface modification of soft ophthalmic lens not containing BIMA The non-hydrous soft eye lens substrate 4 was treated in the same manner as in Example 1 except that the non-hydrous soft ophthalmic lens substrate 4 was used. A soft ophthalmic lens was obtained.
- Comparative Example 2 Surface modification of a hard ophthalmic lens not containing BIMA
- the non-hydrous hard water of Comparative Example 2 was treated by the same operation as in Example 11 except that the non-hydrous hard ophthalmic lens base material 5 was used. A hard ophthalmic lens was obtained.
- a non-hydrous hard ophthalmic lens substrate 5 is a plasma chamber (capacity 45L, electrode surface area 400cm 2 , electrode substrate distance 15cm). ), The chamber was decompressed to 1.0 Barr, and then discharged at a power density of 0.15 W / cm 2 for 30 minutes. After the treatment was completed, it was immersed in a 10 mL aqueous solution in which 0.5 g of acrylamide and 0.01 g of ferrous ammonium sulfate were dissolved, and left at 35 ° C. for 1 hour. Thereafter, unreacted components were removed with distilled water to obtain a non-hydrous hard ophthalmic lens of Comparative Example 3 modified with a graft polymer starting from a radical generated by plasma irradiation.
- a non-hydrous soft ophthalmic lens base material 4 is made of a polyacrylic acid 1.0 wt% aqueous solution, a polyallylamine 1.0 wt% aqueous solution, and polyacrylic acid 1.0 wt%. It was sequentially immersed in an aqueous solution and washed with pure water. As a result, a non-hydrous soft ophthalmic lens of Comparative Example 4 coated with polyacrylic acid-polyallylamine-polyacrylic acid was obtained.
- the surfaces of the ophthalmic lenses of Examples 1 to 11 prepared from a lens substrate made of a polymer obtained by polymerizing a monomer component containing a polymerizable alkyl halide agent were immersed in an ATRP reaction solution.
- a graft polymer with a hydrophilic monomer contained in By introducing a graft polymer with a hydrophilic monomer contained in, the wettability, slipperiness and stain resistance were superior to the surface of the lens substrate used.
- the effect of surface modification was not obtained for the ophthalmic lenses of Comparative Examples 1 and 2.
- the ophthalmic lens of Comparative Example 3 although slipperiness was observed, the residual oil was confirmed in the stain resistance test, and the stain resistance was low.
- the ophthalmic lens of Comparative Example 4 was found to have poor wettability and easy slipperiness and low durability against changes in the external environment according to the external environment resistance test.
- the ophthalmic lens of Comparative Example 1 could not confirm the elongation of the graft polymer from the infrared spectrum measurement.
- the extension of the graft polymer could not be confirmed from the infrared spectrum measurement.
- the ophthalmic lenses of the examples were treated with an ATRP reaction solution on the lens surface using a lens substrate made of a polymer obtained by polymerizing a monomer component containing a polymerizable halogenated alkyl agent.
- a graft polymer with a hydrophilic monomer By having a graft polymer with a hydrophilic monomer, the lens surface has wettability and slipperiness compared to those having no graft polymer on the lens surface or those modified by other methods. It was excellent in resistance and stain resistance.
- the fact that an ophthalmic lens having a graft polymer on the lens surface was actually produced was verified by infrared absorption spectrum measurement.
- a non-hydrous ophthalmic lens having a hydrophilic polymer having an alkyl halide at the terminal on the lens surface and a non-hydrous ophthalmic lens manufacturing method that stably achieves desired hydrophilicity on the lens surface.
- the ophthalmic lens obtained by the manufacturing method is oxygen permeable but has reduced lipophilicity and water repellency on the lens surface, so that it can be worn for a long time for ophthalmic lens wearers. It can be used as an eye lens and contributes to human health and welfare.
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Abstract
Description
本発明の第1の態様は、末端がハロゲン化された親水性ポリマーをレンズ表面に有する非含水性眼用レンズの製造方法である。本発明の一態様の製造方法は、ハロゲン化アルキル基を有する非含水性眼用レンズと、親水性モノマー及び金属錯体を含む水溶液とを接触させることにより、末端がハロゲン化された親水性ポリマーをレンズ表面に有する非含水性眼用レンズを得る工程を少なくとも含む。本明細書における「ハロゲン化アルキル基」は、アルキル基の少なくとも一部がハロゲン化された官能基であれば特に限定されず、例えば、X-R-、X2-R-、X-R-CO-、X-R-CO-O-などの構造式として表わすことができる(ただし、Rは置換又は非置換のアルキレン基を示す)。
(式中、CLは眼用レンズ基材を示し;Sは-O-CO-R-を示し(ただし、Rは炭素数が2~4の置換又は非置換のアルキレン基を示す);Xはハロゲン基を示し;Mtは金属イオンを示し;Zは1~3の整数を示し;Lは配位子を示し;Mはモノマーを示し;nは2以上の整数を示す。)
ハロゲン化アルキル基(-O-CO-R-X)を有する非含水性眼用レンズ(CL-O-CO-R-X)と、親水性モノマー(M)及び金属錯体(Mtz/L)を含む水溶液とを接触させることにより、末端がハロゲン化された親水性ポリマーをレンズ表面に有する非含水性眼用レンズ(CL-O-CO-R-Mn-X)を得る工程
(式中、R1、R2及びR3はそれぞれ独立した水素基又はメチル基を示し;ZはO、COO又はCONH基を示し;Yは(CH2)nOを示し(ただし、nは整数を示す);Xは塩素基や臭素基などのハロゲン基を示す。)
で表わされる化合物が挙げられる。
で表わされる2-(2-ブロモイソブチリルオキシ)エチルメタクリレートが挙げられ、この他にも2-(2-ブロモイソブチリルオキシ)エチルアクリレート、2-(2-ブロモプロピオニルオキシ)エチルメタクリレート、2-(2-ブロモプロピオニルオキシ)エチルアクリレートなどが挙げられるが、これらに限定されない。これらは、例えば、市販品として入手することができ、さらにマティヤスゼウスキーらの文献(Krzyusztof Matyjaszewski et al.,Macromolecules,1997,30,5192-5194、該文献の全記載はここに開示として援用される)に記載の方法に従って、2-ヒドロキシアルキル(メタ)アクリレートと2-ブロモイソブチリルブロミドや2-ブロモプロピオニルブロミドなどの酸ハロゲン化物との反応により製造され得る。また、該反応を応用して、酸ハロゲン化物として2-クロロプロピオニルクロリドなどを用いれば、臭素以外のハロゲン元素を有する一般式(1)で示される基本骨格を有する化合物が得られ得る。
(R1は水素基又はメチル基を示し;R2は分子に親水性を付与する官能基を示し;lは1以上の整数を示し;Xは塩素基又は臭素基を示し;Mtは金属イオンを示し;Lは配位子を示し;Zは1~3の整数を示し;CLは非含水性眼用レンズ基材を示す。)
に示されるとおりの重合反応が進行し、末端がハロゲン化された親水性ポリマーをレンズ表面に有する非含水性眼用レンズが得られる。
(R1、R3、Rnはそれぞれ独立して水素基又はメチル基を示し;R2、R4、Rmはそれぞれ独立して分子に親水性を付与する官能基を示し;l、m、nはそれぞれ独立して1以上の整数を示し;Xは塩素基又は臭素基を示し;Mtは金属イオンを示し;Lは配位子を示し;Zは1~3の整数を示し;CLは非含水性眼用レンズ基材を示す。)
に示されるとおりの重合反応が進行し、末端がハロゲン化された親水性ランダムコポリマーをレンズ表面に有する非含水性眼用レンズが得られる。
(R1、R3、Rnはそれぞれ独立して水素基又はメチル基を示し;R2、R4、Rmはそれぞれ独立して分子に親水性を付与する官能基を示し;l、m、nはそれぞれ独立して1以上の整数を示し;Xは塩素基又は臭素基を示し;Mtは金属イオンを示し;Lは配位子を示し;Zはそれぞれ独立して1~3の整数を示し;CLは非含水性眼用レンズ基材を示す。)
に示されるとおりの重合反応が進行し、末端がハロゲン化された親水性ブロックコポリマーをレンズ表面に有する非含水性眼用レンズが得られる。重合反応には回数に限定がないことから、所望の回数分のATRP反応液を調製し、ハロゲン化アルキル基を有する非含水性眼用レンズを各ATRP反応液へ順次浸漬すれば、その回数に応じたブロック単位を有するブロックコポリマーが形成される。
(R1、R3、R5、Rnはそれぞれ独立して水素基又はメチル基を示し;R2、R4、R6、Rmはそれぞれ独立して分子に親水性を付与する官能基を示し;l、m、nはそれぞれ独立して1以上の整数を示し;Xは塩素基又は臭素基を示し;Mtは金属イオンを示し;Lは配位子を示し;Zは1~3の整数を示し;CLは非含水性眼用レンズ基材を示す。)
に示されるとおりの重合反応が進行し、末端がハロゲン化された親水性ブロックコポリマー及び/又は親水性ランダムブロックコポリマーをレンズ表面に有する非含水性眼用レンズが得られる。重合反応には回数に限定がないことから、所望の回数分のATRP反応液を調製し、ハロゲン化アルキル基を有する非含水性眼用レンズを各ATRP反応液へ順次浸漬すれば、その回数に応じたブロック単位及びランダム単位のコポリマーが形成される。
各成分を表1に示した量(g)で秤量した後、30分間撹拌し、室温で均一に混合することで調合液を調製した。得られた調合液を眼用レンズ形状のポリプロピレン製鋳型の雌型に入れ、対応する雄型で型を閉じた。次いで、閉じた型を波長405nmのLED光源にて、1.00mW/cm2の照度で1時間照射し、重合を完了した。雄型と雌型とを分離し、付着した重合体を鋳型から剥離した後、60℃のイソプロピルアルコールに1時間浸漬した。この浸漬操作は、液を交換して2度繰り返し行い、重合体から余剰の成分を取り除いた。その後、90℃のオーブンに一晩静置し、重合体中からイソプロピルアルコールを除去することで非含水性軟質眼用レンズ基材1及び2を得た。
各成分を表2に示した量(g)で秤量した後、30分間撹拌し、室温で均一に混合することで調合液を調製した。得られた調合液を円柱状のポリプロピレン製鋳型に入れ、開口部を封止した。次いで、型を室温から90℃まで段階的に加温し、重合を完了した。得られた棒状重合体を型から取り出し、切削及び研磨を行い、非含水性硬質眼用レンズ基材3を得た。
表1に示すように、構成成分にBIMAを有さない以外は、眼用レンズ1及び2と同一の操作により、非含水性軟質眼用レンズ基材4を得た。
表2に示すように、構成成分にBIMAを有さない以外は、眼用レンズ3と同一の操作により非含水性硬質眼用レンズ基材5を得た。
各成分を表3に従い秤量し、30分間撹拌して得た混合液を、マグネットスターラーを用いて室温で均一に混合した。得られた均一混合液にアルゴンバブリングを15分間行うことによって、ATRP反応液A~F、G(1)、G(2)、H(1)、H(2)及びIを得た。
Fm-7725:α,ω-ジメタクリロキシプロピルポリ(ジメチルシロキサン)
LA:ラウリルアクリレート
V-3F:3,3,3-トリフルオロエチルアクリレート
BIMA:2-(2-ブロモイソブチリルオキシ)エチルメタクリレート
IC819:ビス(2,4,6-トリメチルベンゾイル)-フェニルフォスフィンオキシド
Tris:メタクリル酸トリストリメチルシロキシプロピル
MMA:メタクリル酸メチル
MAA:メタクリル酸
ED:エチレングリコールジメタクリレート
後述する眼用レンズを下記の評価基準に従い評価した。
眼用レンズの湿潤性について、水接触角により評価した。接触角の測定は、眼用レンズを眼用レンズ型の雌型上に配置し、余剰の水分を取り除いた後、純水1mgを眼用レンズ頂点部に滴下し接触角を測定することで行った。評価基準は、以下の通りとした。
○:接触角が90°未満
×:接触角が90°以上
得られた眼用レンズの易滑性について、触指確認による評価を行った。評価基準は、以下のとおりとした。
○:潤滑性の高い表面である。
△:滑りやすい表面である。
×:粘着感、摩擦感を感じる。
スダンブラックB(Aldrich)の0.5wt%トコフェロール溶液を調製し、眼用レンズを当該溶液に5分間浸漬させた。浸漬後の眼用レンズについて、温水を用いて余剰の染液をすすぎ落とした後、乾燥させた。乾燥後の眼用レンズの染色度合いを目視で評価した。評価基準は以下のとおりとした。
○:染色、油分の残存が確認されない。
△:染色は確認されないが、油分の残存が確認される。
×:染色、油分の残存がはっきりわかる。
眼用レンズを5wt%塩化ナトリウム水溶液に浸漬し、121℃、2気圧で高圧蒸気滅菌した。その後、眼用レンズを取り出し、純水で十分に洗浄した後、湿潤性及び易滑性の評価を行った。
ATRP反応液への浸漬時間の違いが及ぼす眼用レンズ表面の親水性化への影響を赤外スペクトル及び水接触角の測定結果から評価した。
非含水性軟質眼用レンズ基材1及び2並びに非含水性硬質眼用レンズ基材3を用いて、表4に従い、各ATRP反応液に常温で30分間浸漬した。なお、ATRP反応液G及びHについては、眼用レンズ基材をG(1)又はH(1)に常温で30分間浸漬した後、次いで0.5wt%EDTA水溶液で洗浄し、次いで純水で洗浄した後、眼用レンズ基材をG(2)又はH(2)に常温で30分間浸漬した。その後、ATRP反応液から眼用レンズ基材を取り出し、0.5wt%EDTA水溶液で洗浄し、次いで純水で洗浄することにより、実施例1~11の非含水性軟質眼用レンズ及び非含水性硬質眼用レンズを得た。また、参考例1については、非含水性軟質眼用レンズ基材1をATRP反応液に浸漬させることなく、そのまま眼用レンズとして用いた。得られた非含水性軟質眼用レンズは、生理食塩水とともに密閉容器に移載し、121℃、20分間で高圧蒸気滅菌を行った。また、得られた非含水性硬質眼用レンズは、高圧蒸気滅菌を行わずに、評価試験に供した。
表5に従い、浸漬時間を変更していること以外は実施例1~11と同様にして、実施例12-1~8、実施例13-1~4及び実施例14-1~2の非含水性軟質眼用レンズを得た。なお、実施例13-1~4については、ATRP反応液G(1)への浸漬後のATRP反応液G(2)への浸漬は実施していない。実施例14-1~2については、ATRP反応液G(1)への浸漬時間を30分間とし、ATRP反応液G(2)への浸漬時間を10分間又は30分間とした。
(比較例1)BIMAを含有しない軟質眼用レンズの表面修飾
非含水性軟質眼用レンズ基材4を用いた以外は、実施例1と同一の操作により処理して、比較例1の非含水性軟質眼用レンズを得た。
非含水性硬質眼用レンズ基材5を用いた以外は、実施例11と同一の操作により処理して、比較例2の非含水性硬質眼用レンズを得た。
非含水性硬質眼用レンズ基材5をプラズマチャンバー(容量45L、電極表面積400cm2、電極基盤間距離15cm)に設置し、チャンバー内を1.0Barrに減圧した後、電力密度0.15W/cm2で30分間放電した。処理が完了した後、アクリルアミド0.5gと硫酸第一鉄アンモニウム0.01gとを溶解させた10mLの水溶液に浸漬し、35℃で1時間静置した。その後、蒸留水により未反応成分を取り除き、プラズマ照射により発生したラジカルを開始点としたグラフトポリマーにより修飾された比較例3の非含水性硬質眼用レンズを得た。
非含水性軟質眼用レンズ基材4をポリアクリル酸1.0wt%水溶液、ポリアリルアミン1.0wt%水溶液、ポリアクリル酸1.0wt%水溶液に順次浸漬し、純水で洗浄を行った。これにより、ポリアクリル酸-ポリアリルアミン-ポリアクリル酸がコーティングされた比較例4の非含水性軟質眼用レンズを得た。
上記6に記載の眼用レンズの評価(5)に基づいて、実施例12~14及び比較例1の眼用レンズ表面の親水性化について、赤外スペクトル及び水接触角を測定した結果を図1~5及び表5に示す。
Claims (11)
- ハロゲン化アルキル基を有する非含水性眼用レンズと、親水性モノマー及び金属錯体を含む水溶液とを接触させることにより、末端がハロゲン化された親水性ポリマーをレンズ表面に有する非含水性眼用レンズを得る工程
を含む、末端がハロゲン化された親水性ポリマーをレンズ表面に有する非含水性眼用レンズの製造方法。 - 前記親水性ポリマーが、親水性ホモポリマー、親水性ブロックコポリマー又は親水性ランダムコポリマーである、請求項1に記載の製造方法。
- 前記ハロゲン化アルキル基を有する非含水性眼用レンズが、ハロゲン化アルキルモノマー及び疎水性モノマーの共重合体を含む非含水性眼用レンズである、請求項1に記載の製造方法。
- 前記ハロゲン化アルキル基を有する非含水性眼用レンズが、2-ハロイソブチル基及び重合性官能基を含むハロゲン化アルキルモノマー及び疎水性モノマーの共重合体を含む非含水性眼用レンズである、請求項1に記載の製造方法。
- 前記ハロゲン化アルキル基を有する非含水性眼用レンズが、2-(2-ブロモイソブチルオキシ)エチル(メタ)アクリレート及び疎水性モノマーの共重合体を含む非含水性眼用レンズである、請求項1に記載の製造方法。
- 前記金属錯体が、銅イオン及び配位子からなる金属錯体である、請求項1に記載の製造方法。
- 前記水溶液が、さらに還元剤を含む、請求項1に記載の製造方法。
- 前記水溶液が、さらにジ(エチルヘキサン)スズ、L-アスコルビン酸、L-アスコルビン酸ナトリウム、グルコース及びヒドラジンからなる群から選択される少なくとも1種の還元剤を含む、請求項1に記載の製造方法。
- 末端がハロゲン化された親水性ポリマーをレンズ表面に有し、かつ、接触角が90°未満である、非含水性眼用レンズ。
- 前記親水性ポリマーが、親水性ホモポリマー、親水性ブロックコポリマー又は親水性ランダムコポリマーである、請求項9に記載の非含水性眼用レンズ。
- 非含水性眼用レンズが、ハロゲン化アルキルモノマー及び疎水性モノマーの共重合体を含む、請求項9に記載の非含水性眼用レンズ。
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CN201680057804.2A CN108139608B (zh) | 2015-10-07 | 2016-10-06 | 非含水性眼用镜片的制造方法和非含水性眼用镜片 |
CA2999980A CA2999980A1 (en) | 2015-10-07 | 2016-10-06 | Production method of unhydrated ophthalmic lens and unhydrated ophthalmic lens |
US15/764,812 US10642069B2 (en) | 2015-10-07 | 2016-10-06 | Production method of unhydrated ophthalmic lens and unhydrated ophthalmic lens |
EP16853702.5A EP3361307B1 (en) | 2015-10-07 | 2016-10-06 | Process for producing a non hydrated ocular lens |
JP2017544224A JP6740235B2 (ja) | 2015-10-07 | 2016-10-06 | 非含水性眼用レンズの製造方法及び非含水性眼用レンズ |
SG11201802066WA SG11201802066WA (en) | 2015-10-07 | 2016-10-06 | Production method of unhydrated ophthalmic lens and unhydrated ophthalmic lens |
HK18110600.1A HK1251302A1 (zh) | 2015-10-07 | 2018-08-17 | 非含水性眼用鏡片的製造方法和非含水性眼用鏡片 |
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US20090171024A1 (en) | 2005-12-21 | 2009-07-02 | Carnegie Mellon University | Preparation of block copolymers |
EP1892080A1 (en) * | 2006-08-25 | 2008-02-27 | Sauflon CL Limited | Method of coating a contact lens |
US20080179770A1 (en) * | 2007-01-31 | 2008-07-31 | Rooney Thomas R | Free form ophthalmic lens mold |
EP2453940A2 (en) * | 2009-07-13 | 2012-05-23 | Yissum Research Development Company of The Hebrew University of Jerusalem | Intraluminal polymeric devices for the treatment of aneurysms |
JP5872465B2 (ja) * | 2009-07-15 | 2016-03-01 | テクニカル ユニバーシティ オブ デンマーク | 表面開始原子移動ラジカル重合により合成されるメトキシエチルアクリレート単位を含むポリマーコーティング |
JP2013057932A (ja) | 2011-08-17 | 2013-03-28 | Toray Ind Inc | 軟質樹脂デバイス |
EP3988992A1 (en) * | 2013-11-15 | 2022-04-27 | Tangible Science, Inc. | Contact lens with a hydrophilic layer |
US10466235B2 (en) | 2014-03-05 | 2019-11-05 | Jsr Corporation | Solid support, ligand-bound solid support, detection or separation method for target substance, solid support production method, and ligand-bound solid support production method |
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JPH01133022A (ja) * | 1987-09-03 | 1989-05-25 | Bayer Ag | 光学接触物体 |
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CN108139608B (zh) | 2020-11-17 |
EP3361307A4 (en) | 2019-05-22 |
JPWO2017061550A1 (ja) | 2018-07-26 |
JP6740235B2 (ja) | 2020-08-12 |
US10642069B2 (en) | 2020-05-05 |
EP3361307A1 (en) | 2018-08-15 |
EP3361307B1 (en) | 2020-10-21 |
CA2999980A1 (en) | 2017-04-13 |
HK1251302A1 (zh) | 2019-01-25 |
US20180275426A1 (en) | 2018-09-27 |
CN108139608A (zh) | 2018-06-08 |
SG11201802066WA (en) | 2018-04-27 |
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