WO1999018139A1 - Quatre composants copolymeres et lentilles oculaires fabriquees a l'aide de ces composants - Google Patents

Quatre composants copolymeres et lentilles oculaires fabriquees a l'aide de ces composants Download PDF

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Publication number
WO1999018139A1
WO1999018139A1 PCT/CN1998/000212 CN9800212W WO9918139A1 WO 1999018139 A1 WO1999018139 A1 WO 1999018139A1 CN 9800212 W CN9800212 W CN 9800212W WO 9918139 A1 WO9918139 A1 WO 9918139A1
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Prior art keywords
group
lower alkyl
copolymer according
hydrogen atom
alkyl group
Prior art date
Application number
PCT/CN1998/000212
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English (en)
French (fr)
Inventor
Fumian Li
Original Assignee
Santen Pharmaceutical Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Santen Pharmaceutical Co., Ltd. filed Critical Santen Pharmaceutical Co., Ltd.
Priority to KR1020007003780A priority Critical patent/KR20010030994A/ko
Priority to JP2000514945A priority patent/JP2001519445A/ja
Priority to CA002305747A priority patent/CA2305747A1/en
Priority to AU94276/98A priority patent/AU9427698A/en
Priority to EP98947275A priority patent/EP1026182A4/en
Priority to US09/509,445 priority patent/US6465588B1/en
Publication of WO1999018139A1 publication Critical patent/WO1999018139A1/zh
Priority to NO20001786A priority patent/NO20001786L/no

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    • 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
    • C08F220/20—Esters of polyhydric alcohols or phenols, e.g. 2-hydroxyethyl (meth)acrylate or glycerol mono-(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
    • 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
    • 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
    • C08F2/00—Processes of polymerisation
    • C08F2/44—Polymerisation in the presence of compounding ingredients, e.g. plasticisers, dyestuffs, fillers
    • 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
    • C08F220/04—Acids; Metal salts or ammonium salts thereof
    • C08F220/06—Acrylic acid; Methacrylic acid; Metal salts or ammonium salts thereof
    • 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
    • C08F220/12—Esters of monohydric alcohols or phenols
    • C08F220/14—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
    • C08F220/12—Esters of monohydric alcohols or phenols
    • C08F220/16—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms
    • C08F220/18—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms with acrylic or methacrylic acids
    • 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
    • C08F220/28—Esters containing oxygen in addition to the carboxy oxygen containing no aromatic rings in the alcohol moiety
    • C08F220/281—Esters containing oxygen in addition to the carboxy oxygen containing no aromatic rings in the alcohol moiety and containing only one oxygen, e.g. furfuryl (meth)acrylate or 2-methoxyethyl (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
    • C08F220/34—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (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
    • C08F220/52—Amides or imides
    • 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
    • C08F220/52—Amides or imides
    • C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
    • C08F220/58—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide containing oxygen in addition to the carbonamido oxygen, e.g. N-methylolacrylamide, N-(meth)acryloylmorpholine
    • 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
    • C08F220/52—Amides or imides
    • C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
    • C08F220/60—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide containing nitrogen in addition to the carbonamido nitrogen
    • 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
    • C08F220/52—Amides or imides
    • C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
    • C08F220/60—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide containing nitrogen in addition to the carbonamido nitrogen
    • C08F220/603—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide containing nitrogen in addition to the carbonamido nitrogen and containing oxygen in addition to the carbonamido oxygen and nitrogen
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
    • C08J3/242—Applying crosslinking or accelerating agent onto compounding ingredients such as fillers, reinforcements
    • 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
    • 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

Definitions

  • the present invention relates to a hydrophilic copolymer used for an ophthalmic lens such as an intraocular lens, a contact lens, and the like, in particular, a foldable intraocular lens (foldable IOL), that is, a hydrogel.
  • a foldable intraocular lens foldable IOL
  • the intraocular lens is used to replace the removed crystalline lens during cataract surgery. Since its first use in transplantation in 1949, various researches have been conducted on its material. With the tremendous changes in surgical methods and advances in surgical methods, the characteristics required by IOL have also changed. Recently, with the popularization of ultrasonic emulsification suction technology, turbid water crystals can be removed by cutting a small wound, so the characteristics required for the inserted IOL are gradually changing. For example, in order to achieve the purpose of inserting a wound from a young age, it is required to be able to be inserted in a folded form and then unfolded inside the ⁇ , which is also called a foldable IOL. In view of this, various studies have been conducted on IOL materials.
  • polymethyl methacrylate PMMA
  • polysiloxane acrylic resin
  • hydroxyethyl methacrylate is also used Copolymer of methyl ester and methyl methacrylate.
  • the following technologies have also been used in practical applications: hydroxybenzophenone or hydroxyphenylbenzotriazole ultraviolet absorbers have been added to prevent the effect of ultraviolet rays on the retina; To adapt to living body and prevent cell deposition, IOL surface is coated with polysaccharides such as heparin.
  • the polymer of the present invention contains an acrylic monomer having a pyrrolidone group as a component.
  • copolymers of vinylpyrrolidone and hydroxyethyl methacrylate and methyl methacrylate Japanese Patent Laid-Open No. 53-105250
  • methacryloyloxyethyl Copolymers of 2-Pyrrolidone and alkyl methacrylate and fluoroalkyl methacrylate Japanese Patent Application Laid-Open No. 5-150197
  • the research on these substances is mainly carried out for the purpose of applying to soft contact lenses, and not for the purpose of applying to IOLs.
  • the application possibility of the foldable IOL which is the main object of the present invention, is not involved at all.
  • the main object of the present invention is to provide an ophthalmic lens such as an intraocular lens or a contact lens. More specifically, the main purpose is to apply to a foldable IOL.
  • the refractive index must be considered when studying the foldable IOL material. , Surface strength, tensile strength, recovery speed, maintenance of transparency, etc. Examples include the following:
  • the refractive index is preferably in the range of 1.4-1.6.
  • the foldable IOL must be restored to its original shape within the crotch after insertion.
  • the speed of recovery varies depending on the habits and abilities of the person performing the operation, but in general, as the speed of recovery increases, mechanical damage to surrounding tissues will occur. On the other hand, as the recovery speed becomes slower, the operation time will be correspondingly longer, and the possibility of adverse effects on surrounding tissues increases. Therefore, the foldable IOL is required to have a proper recovery speed.
  • the present inventors have conducted research on materials that are more suitable for foldable IOL, and have found a particularly excellent material, which is a four-component copolymer containing an acrylic derivative having a pyrrolidone group.
  • the present invention relates to a novel polymer obtained by the following (a), (b), (c), (d) four-component copolymerization, a method for producing the same, and an ophthalmic lens using the polymer.
  • R 1 represents a hydrogen atom or a lower alkyl group
  • R 2 represents a lower alkylene group.
  • the alkylene group may be substituted by a hydroxyl group, or the alkylene chain may have an oxygen atom; the same applies hereinafter.
  • R 3 represents a hydrogen atom or a lower alkyl group
  • R 4 represents Or single bond
  • R 5 , R 6 , R 7 , R 8 respectively represent a hydrogen atom or a lower alkyl group
  • mn, p, and q represent integers from 1 to 4; the same applies hereinafter.
  • R 9 represents a hydrogen atom or a lower alkyl group
  • R 1G represents a lower alkyl group
  • R 11 represents a hydrogen atom or a lower alkyl group
  • R 12 represents a phenyl lower alkyl group, a naphthyl lower alkyl group, a pyrimidinyl group or a pyrimidinyl piperazinyl group, the phenyl lower alkyl group and a naphthyl lower alkyl group
  • the benzene ring and naphthalene ring may also be substituted with a lower alkyl group, a lower alkoxy group or an atom
  • X represents -O-, -NH- or a single bond; the same applies hereinafter.
  • copolymers are represented by constituent units, they are composed of the following constituent units represented by [I], [II], [III], and [IV], and the weight ratio of each unit is respectively, [] 40-80. [ II] 5-30, [III] 5-20, [IV] 5-30.
  • the preferred weight ratio of each constituent unit in the copolymer of the present invention is [I] 50 70, U 10-25, [III] 5-15 and [IV] 5-20.
  • the weight composition ratio refers to the ratio of the recorded numerical values after polymerization.
  • Lower alkyl refers to a straight chain or 1 to 6 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and hexyl.
  • Branched-chain alkyl groups; lower alkoxy groups are nail alkoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, hexyloxy and the like having 1 to 6 carbon atoms.
  • lower alkylene means -CH 2 _,-(CH 2 ) 2-,-[CH 2 ] 3 -,-CH (CH 3 ) 2 -,-(CH 2 ) 4-,-(CH 2 ) 6-and other straight or branched alkylene groups having 1 to 6 carbon atoms; halogen atoms refer to fluorine, chlorine, bromine, and the like.
  • R 1 is a hydrogen atom or a methyl group
  • R 2 is-(CH 2 ) 2 -or-(CH 2 ) 3-
  • R 3 is a hydrogen atom or a methyl group
  • R 4 is -OCH 2 -or-O CH 2 CH 2-
  • R 9 is a hydrogen atom or a methyl group
  • R 1G is a methyl group
  • R 11 is a hydrogen atom or a methyl group
  • R 12 is a benzyl group, a benzyl group or a pyrimidine Pyrazinyl.
  • the combination of the above-mentioned groups is still preferably a combination of the above-mentioned groups, especially R 1 is a methyl group, R 2 is-(CH 2 ) 2- , R 3 is a hydrogen atom, R 4 is -O CH 2 CH 2- , R 9 is a methyl group, R 1 () is a methyl group, R 11 is a hydrogen atom or a methyl group, and R 12 is a combination of a benzyl group, a phenethyl group, or a pyrimidinylpyrazinyl group.
  • the copolymer of the present invention preferably uses potassium persulfate, ammonium persulfate, benzophenone, methacryloxybenzophenone or N, N-dimethylaminoethyl methacrylate or a combination of these materials is used as
  • the polymerization initiator polymerizes the monomers (a), (b), (c), and (d).
  • azobisisobutyronitrile is most widely used, but it is difficult to obtain the physical strength of a foldable IOL material satisfying the object of the present invention by this method.
  • the present inventors conducted intensive research on a polymerization initiator, and found that potassium persulfate, ammonium persulfate, benzophenone, methylpropionyloxybenzophenone, or methylpropionic acid N, N -As a polymerization initiator, dimethylaminoethyl or a mixture thereof can be obtained as a copolymer satisfying the physical strength that a foldable IOL should have.
  • the molecular weight (viscosity average molecular weight) of the copolymer of the present invention is 10,000.
  • the above is good.
  • the molecular weight of the copolymer does not affect the characteristics of the copolymer. It is not an important factor, but it will involve the physical strength of the copolymer.
  • the molecular weight is less than 10,000, the molecular weight and the physical strength have a roughly linear proportional relationship, but if the molecular weight exceeds 10,000, the physical strength approaches the maximum value, and the improvement is not obvious. Therefore, a product with stable physical strength cannot be obtained below 10,000, and problems often occur as the physical strength of the foldable IOL, but there is no problem if the molecular weight reaches 10,000 or more.
  • the preferred molecular weight range of the copolymer is 1 to 100,000.
  • the molecular weight of the copolymer obtained from the following examples is falling within this range.
  • each constituent by appropriately selecting the ratio of each constituent, the refractive index, surface strength, tensile strength, recovery speed, moisture content, and the like can be set as necessary.
  • the main functions of each constituent are shown below.
  • the component [I] is a monomer widely used in polymers.
  • the monomer component is cheap and easily available and is an important component of the copolymer of the present invention. However, it does not play a very important role in the properties of the polymer. Increasing the ratio increases hydrophilicity, but has little effect on refractive index or recovery speed.
  • the component [II] is one of the characteristic components of the copolymer of the present invention, and an increase in the composition ratio is related to an increase in the refractive index and an increase in hydrophilicity.
  • Component [III] is a substance widely used in polymers, but the increase in its composition ratio is related to the improvement of resilience and the improvement of surface strength; but if it is too much, it leads to a decrease in refractive index and a decrease in hydrophilicity.
  • the component [IV] is one of the characteristic components of the copolymer of the present invention, and an increase in the composition ratio is related to an increase in the refractive index.
  • the preferred composition ratio is, for example, as described above. Using this preferred composition ratio, an excellent foldable IOL can be obtained.
  • the refractive index of the IOL is 1.4-1.6, and the recovery speed is neither too fast nor too slow, that is, 3 to 6 seconds.
  • the surface strength can fully withstand the operation of tweezers, that is, when it is actually inserted into the eye (when it is swollen), it is more than lOPsi, and it has excellent transparency.
  • the foldable IOL of the present invention can fully withstand the operation using tweezers or laser irradiation, eliminating the disadvantages of the acrylic-based foldable IOL, that is, the possibility of generating compression marks or scars during the insertion operation with tweezers, and eliminating the
  • the disadvantage of the silicone-based foldable IOL is that it cannot withstand the laser easily cracking the pits (Pit).
  • the recovery speed can be adjusted according to the habits of the operator as described above, and it can be set to about 3 to 6 seconds ⁇ 2 seconds.
  • the foldable IOL is hydrophobic and hydrophilic, and can be selected and used according to each purpose, but the copolymer of the present invention is hydrophilic.
  • the hydrophilic foldable IOL can be circulated and stored in a dry state. It can be swollen with purified water before use and inserted into the eye. It can also be stored in an aqueous state, that is, a wet state.
  • the degree of hydrophilicity can be estimated based on the water content, which will affect the biocompatibility and softness of the foldable IOL. In the case of the present invention, the water content can be selected by selecting the ratio of each component.
  • the preferred moisture content is 15-50%.
  • the copolymer of the present invention can also be cross-linked between molecules, and the physical strength and water absorption can be adjusted by cross-linking.
  • the cross-linking agent include an acrylate-based or acrylamide-based cross-linking agent, and specific examples thereof include ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, or N, N, -methylenebis ( Acrylamide), etc. If the amount of cross-linking agent used is too large, the polymer will harden and the recovery speed will be faster, but it will become brittle instead.
  • the amount of the crosslinking agent relative to the total weight of the monomers (with approximately equal weight of the copolymer) of 0.01 _ 2%, preferably
  • an ultraviolet absorber in the IOL, but the present invention may contain an ultraviolet absorber as a constituent component of the copolymer.
  • the type of the ultraviolet absorber for example, benzophenone-based or benzotriazole-based acrylic derivatives can be used.
  • the ultraviolet absorbent represented by the following structural formula is preferably used, and 4-methacryloyloxy-2-hydroxy group is particularly suitable for use. Benzophenone.
  • the technology of coating the surface of the IOL with polysaccharides has been frequently applied recently. Since the copolymer of the present invention has a free hydroxyl group at the terminal, it can form a copolymer with polysaccharides The valence bond does not cause the problem of peeling of the coating layer. In addition, the covalent bond is very easy to form, for example, it can be completed by only divinylsulfone treatment. Specific examples of the polysaccharides include heparin, hyaluronic acid and salts thereof (sodium salt, potassium salt, etc.).
  • the present invention relates to a flexible and flexible IOL material.
  • this kind of IOL is taken with tweezers, traces of tweezers often remain on the surface of the IOL, and it takes a period of time to recover the IOL.
  • the copolymer of the present invention has sufficient surface strength and excellent resilience, and can solve the above problems.
  • laser can also be used to treat posterior cataracts.
  • the original silicone IOL may crack and become cloudy, which may damage the transparency of the cut.
  • the copolymer of the present invention is less likely to have such white turbidity, can maintain transparency, and hardly causes denaturation of surrounding portions.
  • the copolymer of the present invention can be easily formed into a foldable IOL in a shape actually used. It can be formed by a known method.
  • the copolymer of the present invention is particularly suitable for foldable IOL, but its properties are also suitable for soft contact lenses.
  • HEMA 2-hydroxyethyl methacrylate
  • PyEA 2- (2-pyrrolidone-1-yl) ethyl acrylate
  • MMA methyl methacrylate
  • PEA 2-phenylethyl acrylate copolymer
  • the procedure for preparing rods is as follows: The above mixture is placed in a test tube made of hard glass, the remaining air is replaced with nitrogen, the tube is sealed, and the tube is heated at 40 ° C for 72 hours.
  • HPMA methacrylic acid 2-hydroxypropyl ester
  • NAPy 1-acryloyl-2 -pyrrolidone
  • PEA 2-phenylethyl acrylate
  • NMA 1-naphthyl methyl acrylate
  • NMMA 1-naphthyl methyl methacrylate
  • APMP N-acryloyl-N,-(2-pyrimidinyl) piperazine
  • Example 2 These copolymers and their flakes can also be prepared by the method of Example 2 described below.
  • Example 2
  • HEMA 2-hydroxyethyl methacrylate
  • PyEA 2- (2-pyrrolidone-1-yl) ethyl acrylate
  • MMA methyl methacrylate
  • PEA 2-phenylethyl acrylate
  • MAHBP 4-methacryloyloxy-2-hydroxybenzophenone
  • HEMA-PyEA-MMA-BzMA-MAHBP HEMA-PyEA-MMA-MPMP-MAHBP
  • HEMA-PyEA-MMA-PEA-MAPHBP HEM- PyEA- MMA-PEA- AEHBP
  • MAHBP 4-Methacryloyloxy-2-hydroxybenzophenone
  • MAPHBP 4-(2 -hydroxy-3 -methacryloyloxy) propoxy-2
  • AEHBP 4-(2 -acryloyloxy) ethoxy-2 -hydroxybenzophenone
  • HBMAT 2-[2 -hydroxy-3 -tert-butyl-5-(3 -methacryloyloxy) Propyl] 5-chloro-2H _ benzotriazole
  • Example 4 Synthesis of a crosslinked copolymer and a sheet or rod made of the copolymer
  • EGBMA radical polymerization Ethylene glycol propionate
  • EGDMA EGDMA
  • other cross-linking agents such as bismethacrylic acid esters such as diethylene glycol bismethylpropionate (DEGMA) or bisacrylamides such as N, N, -methylenebis (acrylamide) can be used.
  • the content of the cross-linking agent can also be selected as required.
  • Nos. 10 and 13 are uncrosslinked copolymers, and the others are copolymers crosslinked with ethylene glycol methacrylate (added by 0.1% by weight ratio for crosslinking).
  • the refractive index values shown in Table 1 are the results of measurement with an Abbe refractometer. "Dry” refers to the value obtained by directly measuring the prepared copolymer, and “wet” refers to the value obtained when the copolymer is swelled with water to reach equilibrium.
  • Moisture content, surface strength and tensile strength, and recovery speed of these copolymers have values in the required ranges.
  • the measurement method of each item is as follows.
  • Moisture content Put the copolymer cut into discs in water (room temperature, more than 2 days), After the water content is brought to an equilibrium state, the moisture attached to the surface is removed, and the weight is measured as
  • the sample was dehydrated at 60 ° C under reduced pressure for 48 hours, and the weight in a dry state was measured as W2.
  • Tensile speed The YQ-Z-7 measuring device was used to measure at a tensile speed of 12 cm / min.
  • the copolymer prepared in Example 1 or 3 was placed in an aqueous heparin solution (5%) for 24 hours, and then air-dried in the air for 1 hour. Then immerse it in a sodium carbonate buffer solution (pHll) containing divinyl sulfone (0.1%) at 40 ° € for 2 hours, and then wash it with phosphate buffer solution, and wash it thoroughly with water to make heparin and hydroxyl form a co-formation. Covalent state copolymer.
  • the same copolymer can be obtained by using sodium hyaluronate as a polysaccharide instead of heparin.
  • the present invention can provide novel copolymers particularly suitable for foldable IOL.

Description

四成分共聚物及由该共聚物形成的眼用透镜 发明所属技术领域
本发明涉及一种用于眼内透镜或隐形眼镜等的眼用透镜、 特 别是可折叠的眼内透镜（ foldable IOL ) 的亲水性共聚物， 也就 是水凝胶。
背景技术
眼内透镜（ IOL ) 用于在白内障手术时插入眼内以代替除去 的水晶体， 自 1949年首次用于移殖以来， 一直在进行着有关其材 料的各种研究。 随着手术方法的巨大变革以及手术方法的进步， IOL所要求的特性也发生了变化。 最近， 随着超声波乳化吸引技术 等的普及， 切开很小的创口即可除去混浊的水晶体等， 因此对于插 入的 IOL所要求的特性也在逐渐发生变化。 例如， 为了达到从小 的创口即可插入的目的， 就要求能够以折叠的形式插入， 然后在嚢 内展开的特性， 也就是所说的作为可折叠 IOL的特性。 鉴于此， 对于 IOL的材料也进行了各种研究。 作为 IOL的材料一直是广泛 使用聚甲基丙烯酸甲酯 （ PMMA ) 、 聚硅氧烷、 丙烯酸树脂等； 作为可折叠的 IOL材料使用聚硅氧烷或丙烯酸树脂， 最近也有使 用甲基丙烯酸羟乙基酯和甲基丙烯酸甲酯等的共聚物的。 另外， 除 了对这些材料的研究之外， 还在实际应用中采用了下列技术： 为防 止紫外线对视网膜的影响而加入了羟基二苯甲酮或羟苯基苯并三 唑紫外线吸收剂； 为提高生体适应性和防止细胞沉积而在 IOL表 面涂布肝素等多糖类。
本发明的聚合物的特征之一在于含有具有吡咯烷酮基的丙烯 酸单体作为一部分组成成分。 有关该种聚合物的报告例， 特别是有 关用于眼用透镜为目的使用的聚合物的报告例，例如有甲基丙烯酰 氧基乙基- 2 -吡咯烷酮和丙烯酸等形成的共聚物 （特开平 4 - 28705 )；由丙烯酸和吡咯烷酮与酰胺结合的单体形成的聚合物（特 开平 2 - 43208 )； 在聚氧化亚烷基骨架上带有吡咯烷酮基的聚合 物（特公平 2 - 8218 ) 等。 特别是作为三成分共聚物公开的不过 有下列几种， 乙烯基吡咯烷酮和甲基丙烯酸羟乙酯以及甲基丙烯酸 甲酯的共聚物（特开昭 53 - 105250 )； 甲基丙烯酰氧基乙基- 2 -吡咯烷酮和甲基丙烯酸烷基酯以及甲基丙烯酸氟代烷基酯的共 聚物（特开平 5 - 150197 ) 等。 而且有关这些物质的研究主要是 以应用于软性隐型形眼镜为目的进行的， 并不是以应用于 IOL为 目的， 特别是完全没有涉及作为本发明主要目的的可折叠 IOL的 应用可能性。
发明概述
本发明的主要目的是提供一种眼内透镜或隐形眼镜等的眼用 透镜， 更详细地说是以应用于可折叠的 IOL为主要目的， 但是在 研究可折叠 IOL材料时还必须考虑折射率、 表面强度、 拉伸强度、 复原速度、 透明性的维持等。 例如包括以下几方面：
( 1 )如果折射率过低， 则 IOL的厚度过度增大， 随之在周 边部分的色差（收差）变得过大， 因此必须要有合适的折射率。 具 体而言就是折射率最好在 1.4-1.6的范围内。
( 2 ) 因为要使用镊子进行插入可折叠 IOL的搡作， 所以要 有能耐受该操作的表面强度和拉伸强度。
( 3 ) 可折叠 IOL必须在插入后在嚢内恢复到原来的形状。 复原速度因实施手术人员的习惯和能力而异， 但一般而言， 随着复 原速度的加快， 会对周围组织产生机械伤害。 另一方面， 随着复原 速度的变慢， 手术时间会相应地变长， 给周围组织带来不良影响的 可能性加大。 因此要求可折叠 IOL具有适当的复原速度。
另外还必须要考虑容易成形。 基于上述要求的各种可折叠 IOL才可以实际应用， 有希望开发出更理想的材料。 例如， 市售的 聚硅氧烷类可折叠 IOL虽然能够满足折射率的要求， 但复原速度 过快； 丙埽酸类可折叠 IOL在用镊子进行插入操作时， 有造成压 迫痕迹和伤痕的可能， 都要求手术人员具有高精的技术。 另外， 聚 硅氧烷类可折叠 IOL不耐激光， 容易龟裂凹坑（ Pit ) , 而且还有 产生白浊的可能性。
进而， 为防止紫外线对视网膜的影响， 如果能够使其中含有 紫外线吸收剂则可以得到更好的材料，所以期待开发出一种具有上 述性质并且同时具有紫外线吸收效果的优良材料。
本发明人等为解决上述课题， 对更适合应用于可折叠 IOL的 材料进行了研究， 结果发现了一种特别优良的材料， 该材料是含有 具有吡咯烷酮基的丙烯酸衍生物的四成分共聚物。
发明详细说明
本发明涉及由下列 （ a ) 、 （ b ) 、 （ c ) 、 （ d ) 四成分 共聚得到的新的聚合物及其制造方法，以及使用该聚合物的眼用透 镜。
Figure imgf000005_0001
〔式中， R1表示氢原子或低级烷基， R2表示低级亚烷掌 基， 该亚烷基也可以被羟基取代， 或者该亚烷基链中也可以具有氧 原子； 下同。 〕
Figure imgf000005_0002
〔式中， R3表示氢原子或低级烷基， R4表示
Figure imgf000005_0003
或单键， R5、 R6、 R7、 R8分别表示氢原子或低级烷基, m n、 p和 q表示 1 - 4的整数； 下同。 〕
Figure imgf000006_0001
C-0— R
II
O
〔式中， R9表示氢原子或低级烷基， R1G表示低级烷基； 下 同。 〕
12
-X-R
Figure imgf000006_0002
〔式中， R11表示氢原子或低级烷基， R12表示苯基低级烷 基、 萘基低级烷基、 嘧啶基或嘧啶基哌嗪基， 该苯基低级烷基和萘 基低级烷基的苯环和萘环也可以被低级烷基、低级烷氧基或 原子 取代； X表示 - O -、 - NH -或单键； 下同。 〕
如果将这些共聚物以构成单元表示，则由下列 〔 I〕、 〔 II〕、 〔 III〕 和〔 IV〕表示的构成单元组成， 各单元的重量构成比分 别为， 〔 〕 40 - 80. 〔 II〕 5 - 30, 〔 III〕 5 - 20、 〔 IV〕 5一 30。
H2
]
Figure imgf000006_0003
本发明共聚物中各构成单元的优选重量构成比为， 〔 I〕 50 70、 U 10 - 25 , 〔 III〕 5 - 15、 〔 IV〕 5 - 20。
所说的重量构成比是指按记载的数值的比例混合经聚合后各 构成成分（单体）得到的共聚物中的构成单元的重量比。
以下对于上述规定的各基团进行详细说明， 低级烷基是指甲 基、 乙基、 丙基、 异丙基、 丁基、 异丁基、 己基等具有 1 - 6个碳 原子的直链或支链的烷基； 低级烷氧基是指甲氧基、 乙氧基、 丙氧 基、 异丙氧基、 丁氧基、 异丁氧基、 己氧基等具有 1 - 6个碳原子 的直链或支链的烷氧基； 低级亚烷基是指- CH2 _、 - ( CH2 ) 2 -、 - 〔 CH2〕 3 -、 - CH ( CH3 ) 2 -、 - （ CH2 ) 4 -、 - ( CH2 ) 6 -等具有 1 ― 6个碳原子的直链或支链的亚烷基； 卤原 子是指氟、 氯、 溴等。
上述各基团中特别优选的可例举： R1为氢原子或甲基； R2 为 - （ CH2 ) 2 -或- （ CH2 ) 3 -； R3为氢原子或甲基； R4为 - OCH2 -或- O CH2CH2 -； R9为氢原子或甲基； R1G为甲基； R11为氢原子或甲基； R12为苄基、 笨乙基或嘧啶基派嗪基。
上述各基团的组合还是优选组合上述各基困， 特别是 R1为甲 基、 R2为 - （ CH2 ) 2 -、 R3为氢原子、 R4为 - O CH2CH2 -、 R9为甲基、 R1()为甲基、 R11为氢原子或甲基、 R12为苄基、 苯乙 基或嘧啶基派嗪基的组合为好。
本发明的共聚物优选使用过硫酸钾、 过硫酸铵、 二苯甲酮、 甲基丙烯酰氧基二苯甲酮或甲基丙烯酸 N , N -二甲基氨基乙酯 或组合使用这些物质作为聚合引发剂使单体（ a )、 （ b )、 ( c ) 和（ d )聚合。 作为一般用于制造共聚物的聚合引发剂， 最广泛使 用的是偶氮二异丁腈，但该方法难以获得满足作为本发明目的产物 的可折叠 IOL材料的物理强度。 本发明人对于聚合引发剂进行了 深入的研究， 结果发现， 使用过硫酸钾、 过硫酸铵、 二苯甲酮、 甲 基丙浠酰氧基二苯甲酮或甲基丙类酸 N , N -二甲基氨基乙酯或 他们的混合物作为聚合引发剂， 可以得到满足作为可折叠 IOL的 材料所应当具有的物理强度的共聚物。
另外， 本发明的共聚物的分子量（粘度平均分子量） 以 1 万 以上为好。一般来说共聚物的分子量不会对共聚物的特性带来什么 影响， 并不是重要的因素， 但会涉及共聚物的物理强度。 在分子量 为 1万以下时分子量与物理强度大致呈直线的比例关系，但如果分 子量超过 1万， 则物理强度接近于达到最大值， 改进不明显。 因此 在 1万以下时不能得到物理强度稳定的产物，而且作为可折叠 IOL 的物理强度方面常发生问题，但如果分子量达到 1万以上则不会有 问题。 但是， 如果分子量过大则可折叠 IOL变脆， 这是所不希望 的， 所以共聚物的优选分子量范围为 1 - 10万， 由下述的实施例 得到的共聚物的分子量正落在该范围内。
利用本发明的构成， 通过适当选择各构成成分的比例， 可以 根据需要设定折射率、表面强度、拉伸强度、 复原速度、 含水率等。 各构成成分的主要作用如下所示。
成分〔 I〕是广泛用于聚合物的单体， 该单体成分廉价易得， 是本发明的共聚物的重要成分，但其自身对于聚合物的性质并不起 十分重要的作用， 其构成比例的增加会提高亲水性， 但对折射率或 复原速度几乎无影响。
成分〔 II〕是本发明的共聚物的特征成分之一， 其构成比例 的增加与折射率的增大和亲水性的增加有关。
成分〔 III〕是广泛用于聚合物的物质， 但其构成比例的增加 与复原性的提高和表面强度的提高有关；但如果过多则会导致折射 率的降低和亲水性的降低。
成分〔 IV〕是本发明的共聚物的特征成分之一， 其构成比例 的增加与折射率的增加有关。
通过更好地利用这些特性， 可以得到想要的可折叠 IOL。 优 选的成分比例如前所述， 利用该优选的成分比例， 可以得到一种优 良的可折叠 IOL , 该 IOL的折射率为 1.4-1.6， 复原速度即不过快 也不过慢， 即 3 - 6秒， 表面强度可以充分耐受镊子的操作， 也就 是在实际插入眼内时（膨润时） 为 lOPsi以上， 且透明性优良。 本发明的可折叠 IOL可以充分耐受使用镊子的操作或激光照 射， 消除了丙烯基系可折叠 IOL的缺点， 也就是说用镊子进行插 入操作时产生压迫痕迹或伤痕的可能性，并消除了聚硅氧烷类可折 叠 IOL的缺点，也就是不能耐受激光容易龟裂凹坑（ Pit )的问题。
另外， 也可以如上所述那样根据手术者的习惯来调整复原速 度， 可以将其设定为 3 - 6秒± 2秒左右。
可折叠 IOL有疏水性的和亲水性的， 可以依各自目的选择使 用， 但本发明的共聚物是亲水性的。 亲水性的可折叠 IOL可以在 干的状态下流通和保存， 在使用前用精制水使其膨润后插入眼内。 也可以在含水状态也就是湿状态下保存。亲水性的程度可以根据含 水率来推定， 对可折叠 IOL的生体物相容、 柔软性等会有影响。 在本发明的情况下， 可以通过选择各成分的比例来选择含水率。 优 选含水率为 15 - 50 % 。
本发明共聚物也可以分子间交联， 通过交联来调整物理强度 和吸水率。 交联剂例如可以举出丙烯酸酯类或丙烯酰胺类交联剂， 具体例如有双甲基丙烯酸乙二醇酯、 双甲基丙烯酸二乙二醇酯或 N , N，-亚甲基双（丙烯跣胺） 等， 如交联剂的使用量过多， 则 聚合物变硬， 复原速度变快， 但反而会变脆。 交联剂的使用量为相 对于单体的总重量（与共聚物重量大致相等） 的 0.01_2 % , 优选
0.05-1.5 % 。
为防止紫外线对视网膜的影响， 目前广泛使用的方法是使 IOL中含有紫外线吸收剂，但本发明可以含有紫外线吸收剂作为共 聚物的构成成分。紫外线吸收剂的种类例如可以使用二苯甲酮类或 苯并三唑类的丙烯酸衍生物，具体优选使用下列结构式表示的紫外 线吸收剂， 特别适合使用 4 -甲基丙烯酰氧基- 2 -羟基二苯甲 酮。
Figure imgf000009_0001
Figure imgf000010_0001
为达到提高生物相容性和防止细胞等的沉积的目的， 最近经 常应用将 IOL表面用多糖类包衣的技术， 本发明共聚物由于在末 端具有游离的羟基， 可以与多糖类形成共价键， 不会发生包覆层的 剥离问题。 此外， 该共价键非常容易形成， 例如只用二乙烯基砜处 理即可完成。 多糖类的具体例有肝素或透明质酸及其盐（钠盐、 钾 盐等） 。
本发明涉及具有可挠性的柔软的 IOL材料。 在用镊子夹取这 种 IOL时， 一般在 IOL表面常残留下镊子的痕迹， 到 IOL的复原 需要一段时间。 但本发明的共聚物表面强度充分， 且复原性优良， 可以解决上述问题。
另外还可以使用激光来治疗后发性白内障， 但是在装入 IOL 后又需要进行这种治疗时， 原有的聚硅氧烷类 IOL会发生龟裂白 浊， 有损割透明性的可能性， 另外也有引起周围部分稍稍变性的可 能性。 但是本发明的共聚物产生上述这种白浊的可能性小， 可以维 持透明性， 另外也几乎不引起周围部分的变性。
本发明的共聚物可以容易地成形为实际使用的形状的可折叠 IOL。 可以采用公知的方法成形。
本发明的共聚物特别适合于可折叠 IOL , 但其性质也适用于 软性隐性眼镜。
参考实施例 （单体的合成）
参考实施例 1
丙烯酸 2 - ( 2 -吡咯烷酮- 1 -基） 乙基酯（ PyEA ) 的 合成
在 1 - ( 2 -羟乙基） 一 1 —吡咯烷酮（ 50ml ) 和三乙胺 ( 85ml ) 的氯仿（ 150ml )溶液中， 边搅拌边在 2小时内滴加丙 烯酰氯（ 50ml ) 的氯仿（ 100ml )溶液。 将反应液在 4 °C下搅拌 20小时。 在 50 下搅拌 2小时。 冷却后过滤。 将滤液用 15 %碳 酸钠水溶液洗涤， 減压浓缩。 减压蒸馏得到的油状物， 为标题化合 物， 收率为 70 %。 b p : 1 12 - 11 3 °C 0. 5 Torr
NMR (ppm, TMS, CDClg) ： 6.14(m, 3H) ； 4.30(t, 2H); 3.60(m, 4 H) ； 2.20(m,4H)
I R (KBr, cm"1) :1735, 1676, 1639, 1361 与参考实施例 1同样得到以下化合物。
甲基丙烯酸 2 - ( 2 -吡咯烷酮- 1 -基） 乙基酯（ PyEMA ) b p ： 120 - 122 °C/0. 5 Torr
NMR (ppm,TMS，CDCl3) ： 6.10(s, IH); 5.59(s, 1H) ; 4.29(t, 2H)； 3.59(m,4H); 2.30(m,4H); 1.94(S,3H)
I R (KBr, cm"1) ： 1735, 1676, 1639, 1361 甲基丙烯酸 2 -吡咯烷酮- 1 -基酯（ PyMA )
b p ： 92 - 93°C/0. 5 Torr
NMR (ppm,TMS,CDCl3) ： 6.34-6.83 (m, 2H)； 6.06- 6.12(m, 1H), 5.37(m, 2H); 3.57-3.69(m, 2H)； 1.91-2.50(m, 4H)
I R (KBr, cm"1) ： 1708, 1639, 1415 甲基甲基丙烯酸 2 -吡咯烷酮- 1 -基酯（ PyMMA )
b p ： 95 - 96 °C/0. 5 Torr
NMR (ppm, TMS, CDClg) ·· 6.13- 6.16(s, 1H) ; 5.59-5.61(m, 1H), 5.41(s)2H)3.55(t,2H); 1.9- 2.43(ID, 4H)， 1.96(m, 3H)
I R (KBr, cm-1) ： 1716, 1636, 1420 参考实施例 2
N - ( 2 -吡咯烷酮- 1 -基甲基） 丙烯酰胺（ PyMAm ) 的合成
混合 1 -甲氧基甲基- 2 -吡咯烷酮 （ 65.6g ) 、 丙烯酰胺 ( 75.5g ) 、 甲苯磺酸（ 0.20g ) 和吩噻嗪（ 0.20g ) , 一边蒸馏 除去生成的甲醇， 一边将混合物在氮气环境下 150 °C下搅拌 1 小 时。 冷却残渣， 用丙酮重结晶， 得到标题化合物， 收率为 40 %。 m p ： 73 - 74 °C
NMR (ppm，TMS, CDC13) ： 7.31(m，lH); 6.19 - 6.31 (m, 2H) , 5.56-5.72 (m.lH), 4.75-4.81(d, 2H), 3.50 - 3.66 (t, 2H)， 1.91-2.44(m, 4H)
I R ( Br, cm"1) ： 3440, 1680, 1200-1600 与参考实施例 2同样操作， 得到以下各化合物。
N - ( 2 -吡咯烷酮- 1 -基甲基） 甲基丙烯酰胺（ PyMMAm ) m p ： 1 0 1 - 1 02 °C
NMR (ppm, TMS, CDC13) ： 6.70(s,lH); 5.69(s，lH)， 5.35(s, lH), 4.70-4.80 (d, 2H), 3.45-3.62(t, 2H), 1.95-2.45 (m, 7H) 参考实施例 3
1 -丙烯酰基- 2一吡咯烷酮（ NAPy ) 的合成
以 2 -吡咯烷酮和丙烯酰氯， 与参考实施例 1 同样操作， 得 到标题化合物， 收率为 70 %。
b p ： 85— 86 V/ 0. 5 Torr
NMR (ppm, TMS, CDC13) ： 7.31-7.65(m( IH) ; 6.56-6.59(m, IH) ; 5.74 -5.96(m, 1 H); 3.77-3.96(m, 2H) ; 2.52-2.73(m, 2H); 1.85-2.24(2m, 2H) I R (KBr, cm-1) :1737, 1679, 1408 与参考实施例 3同样操作， 得到以下化合物。
1 -甲基丙烯酰基- 2 -吡咯烷酮（ NMAPy )
b p ： 8 8 - 8 9 °C / 0 . 5 Torr
N M R (ppm, TMS, CDC13) ： 5. 28-5. 34 (s, 2H)； 3. 72-3. 90 (m, 2H) ; 2. 57- 2. 67 (m, 2 H)； 2. 00-2. 16 (m, 2H) ; 1. 97-1. 99 (s, 3H)
I R (Or, cm—1) ： 1745, 1676, 1403 实施例 （共聚物的合成及由该共聚物制成的片状物或棒状物） 实施例 1
制备由甲基丙烯酸- 2 -羟乙酯（ HEMA )、丙烯酸 2 - ( 2 -吡咯烷酮 - 1 -基）乙酯（ PyEA )、甲基丙烯酸甲酯 （ MMA ) 和丙烯酸 2 -苯基乙酯（ PEA )组成的共聚物（ HEMA-PyEA- MMA-PEA ) 以及由该共聚物制备片状物或棒状物。
混合 HEMA ( 7g ) 、 PyEA ( 2g ) 、 MMA ( 0.5g ) 、 PEA ( lg ) , 再加入过硫酸钾（ 0.2g ) 和水（ l.Og ) 混合， 将 得到的混合物保持在用隔板隔成 0.5mm或 0.1mm的间隔并用夹子 固定的 2片玻璃板（ 6cm X 5cm , 使用聚硅氧烷类密封化剂处理 过的） 之间， 在 60 °C下自由基聚合 22小时， 在 90 °C下处理 2小 时后完成聚合。 将得到的片状物从玻璃板上剥离， 浸入精制水中， 得到目标共聚物的片状物。另外， 2片玻璃板间的间隔可以根据需 要选择。
制备棒状物的操作如下： 将上述混合物装入硬质玻璃制试管 中， 用氮气置换残存的空气后， 封管， 于 40 °C下加热 72小时， 破 坏试管取出生成的棒状物。
与实施例 1 同样得到以下的共聚物和由共聚形成的片状物或 棒状物。
HEMA- PyEA- MA- PEA, HEMA-PyEA- MMA- PMA, HEMA- PyEA- MMA- PEMA, HEMA- PyEA- MMA- BzA, HEMA- PyEA- MMA- BzMA, HEMA-PyEA-MMA-BBzA, HEMA- PyEA- MMA- BBzMA, HEMA- PyEA- MMA- NMA, HEMA- PyEA-MMA- NMMA, HEMA-PyEA- MMA- APMP, HEMA-PyEA-MMA-MPMP, HEMA-PyEA-MMA-PMA, HEMA- PyEA- MMA- PMMA, HEMA-PyEMA-MMA-PEA, HEMA- PyMA- MMA- PEA, HEMA- PyMMA- MMA- PEA, HEMA-NAPy-M A-PEA, HEMA-PyMAm-MMA-PEA, HEMA- PyMMAm- MMA- PEA, HEA- PyEA- MMA- PEA, HPMA- PyEA- MMA-PEA, 上述略语表示如下的各化合物（下同） 。
HEMA: 甲基丙烯酸- 2 -羟乙酯
HEA: 丙烯酸- 2 -羟乙酯
HPMA: 甲基丙烯酸- 2 -羟丙酯
PyEA: 丙烯酸 2 - ( 2 -吡咯烷酮- 1 -基） 乙酯
PyEMA： 甲基丙烯酸 2 - ( 2 -吡咯烷酮- 1 -基） 乙酯
PyMA: 丙烯酸 2 -吡咯烷酮- 1 -基甲酯
PyMMA： 甲基丙烯酸 2 -吡咯烷酮- 1 -甲酯
NAPy： 1 -丙烯酰基- 2 -吡咯烷酮
PyMAm： N - ( 2 -吡咯烷酮 - 1 -甲基） 丙烯酰胺
PyMMAm： N - ( 2 -吡咯烷酮- 1 -甲基） 甲基丙烯酰胺
MA: 丙烯酸甲酯
MMA: 甲基丙烯酸甲酯
PMA: 丙烯酸笨基甲酯
PEA: 丙烯酸 2 -苯基乙酯
PEMA： 甲基丙烯酸 2 -苯基乙酯
BzA. 丙烯酸苄酯
BzMA: 甲基丙烯酸苄酯
BBzA： 丙烯酸 4 -溴苄酯
BBzMA： 甲基丙烯酸 4―溴苄酯
NMA: 丙烯酸 1 -萘基甲酯
NMMA: 甲基丙埽酸 1 -萘基甲酯 APMP： N 一丙烯酰基 - N， - ( 2 -嘧啶基 )哌嗪
MPMP： N -甲基丙烯跣基 - N， - （ 2 -嘧啶基）派嗪
PMA : N - ( 2 -嘧啶基） 丙烯酰胺
PMMA： N - ( 2 -嘧啶基） 甲基丙烯酰胺
这些共聚物及其片状物也可以使用下述实施例 2 的方法制 备。 实施例 2
利用光聚合合成共聚物 （ HEMA - PyEA - MMA - PEA ) 以及由该共聚物制成片状物
混合 HEMA ( 7g ) 、 PyEA ( 2g ) 、 MMA ( 0.5g ) 和 PEA ( lg ) , 再中入 0.2g的二苯甲酮（或 4 -甲基丙烯酰氧基二 苯甲酮）和 0.4g的甲基丙烯酸 N , N -二甲基氨基乙酯将得到的 混合物装入用隔板间隔成 0.5mm或 0.1mm并且用夹子固定的 2片 玻璃板（ 6cm X 5cm , 用聚硅氧烷类密封化剂处理过的）之间， 用 80W的水银灯紫外线照射 48小时使其发生光聚合。将得到的片 状物从玻璃板上剥离， 浸入精制水中除去未反应的单体， 得到目标 共聚物的片状物。 另外， 2 片玻璃板之间的间隔可以根据需要选 择。
实施例 3
除甲基丙烯酸- 2 -羟乙酯 （ HEMA )、 丙烯酸 2 - ( 2 - 吡咯烷酮- 1 -基）乙酯（ PyEA )、 甲基丙烯酸甲酯（ MMA )、 丙烯酸 2 -苯基乙酯（ PEA )之外， 还含有追加成分 4 -甲基丙 烯酰氧基- 2 -羟基二苯甲酮（ MAHBP ) 的共聚物 （ HEMA- PyEA-MMA-PEA-MAHBP ) 的合成及由该共聚物制成的片状物 或棒状物
混合 HEMA ( 7g ) 、 PyEA(2g)、 MMA ( 0.5g ) 、 PEA ( lg ) 和 MAHBP ( O.lg ) , 再加入过硫酸钾（ 0.2g ) 和水 ( 10g ) , 按与实施例 1同样的操作得到目标聚合物和由该共聚物 制成的片状物或棒状物。 与实施例 3同样操作， 得到以下各共聚物 及由这些共聚物制成的片状物或棒状物。
HEMA-PyEA-MMA-BzMA-MAHBP, HEMA-PyEA-MMA-MPMP-MAHBP,
HEMA-PyEA-MMA-PEA-MAPHBP, HEM- PyEA- MMA-PEA- AEHBP,
HEMA-PyEA-MMA-PEA-HBMAT, 上述略语表示以下各化合物 （下同） 。
MAHBP： 4 -甲基丙烯酰氧基- 2 -羟基二苯甲酮
MAPHBP： 4 - ( 2 -羟基- 3 -甲基丙烯酰氧基） 丙氧基- 2
-羟基二苯甲酮
AEHBP： 4 - ( 2 -丙烯酰氧基） 乙氧基- 2 -羟基二苯甲酮 HBMAT： 2 - 〔 2 -羟基- 3 -叔丁基 - 5 - ( 3 -甲基丙烯酰 氧基） 丙基〕 _ 5 -氯 - 2H _苯并三唑
实施例 4交联共聚物的合成及由该共聚物制成的片状物或棒状物 在实施例 1或 3的操作中， 在进行自由基聚合前的混合物中 加入 O.Olg的双甲基丙埽酸乙二醇酯（ EGBMA ) , 以下操作同实 施例 1 ,得到分子间交联的共聚物和由该共聚物制成的片状物或棒 状物。
可以使用其他的交联剂如双甲基丙埽酸二乙二醇酯 ( DEGMA )等双甲基丙烯酸酯或 N , N，-亚甲基双（丙烯酰胺） 等双丙烯酰胺来代替 EGDMA , 另外， 交联剂的含量也可以根据 需要选择。
由实施例 1或 4的方法制备的几例共聚物的物化性质如表 1 所示。 表 1
No. HEMA PyEA MMA PEA BzMA MPMP 折射率 (dry)折射率 (wet)
1 70 20 5 10 ― 一 1.52 1.47
2 70 20 5 5 ― ― 1.51 1.46
3 70 20 10 5 ― ― 1.51 1.46
4 70 20 5 ― 5 ― 1.52 1.46
5 67 19 5 一 10 ― 1.52 1.47
6 67 19 10 —— 5 ― 1.52 1.47
7 64 18 9 ― 9 一 1.52 1.46
8 64 18 9 ― ― 9 1.52 1.45
9 60 10 10 ― ― 20 1.53 1.46
1 0 60 10 10 ― ― 20 1.52 1.45
1 1 55 9 9 一 ― 27 1.53 1.46
1 2 50 20 10 ― ― 20 1.53 1.46
1 3 50 20 10 ― ― 20 1.53 1.46
注) No.lO及 13是未交联的共聚物，其他为用双甲基丙烯酸乙 二醇酯交联（按重量比加入 0。 1 %进行交联） 的共聚物。
表 1中示出的折射率值是用阿贝折射仪测定的结果。 " dry" 是指直接测定制成的共聚物所得到的数值， " wet"是指用水使共 聚物膨润并达到平衡状态时的测定得到的数值。
这些共聚物的含水率、 表面强度和拉伸强度、 复原速度都具 有要求范围内的数值。 各项的测定方法如下。
含水率：将切成圆片状的共聚物置于水中（室温， 2天以上）， 使含水量达到平衡状态后， 去除表面附着的水分， 测定其重量作为
W1 。
将试样在减压下 60 °C下脱水处理 48小时， 测定干燥状态的 重量， 作为 W2 。
计算（ W1 - W2 ) AV2的值， 算出含水率。
拉伸速度： 使用 YQ - Z - 7测定装置， 以 12cm/min的拉 伸速度进行测定。
复原速度： 将用水膨润达到平衡的共聚物切成 3.0 X 3.0cm 的大小， 用小镊子折叠后， 测定其直到恢复原样的时间。
实施例 5 利用多糖类对共聚物表面的修饰
将由实施例 1或 3制备的共聚物置于肝素水溶液（ 5 % ) 中 24小时后， 于空气中晾 1小时。 然后于含有二乙烯基砜（ 0.1 % ) 的碳酸钠緩冲 液中 （ pHll )于40 °€：下浸泡 2小时， 之后用磷酸 緩冲液洗涤， 用水充分洗涤， 制成肝素与羟基形成共价键状态的共 聚物。
使用透明质酸钠代替肝素作为多糖类， 也可以得到同样的共 聚物。
工业上的实用性
本发明可以提供特别适用于可折叠 IOL的新的共聚物。
其优点归纳如下：
( 1 ) 显示出从折叠状态迅速恢复的复原性。
( 2 ) 显示出理想的折射率。
( 3 )表面强度和拉伸强度优良。
( 4 ) 通过改变各单体的构成比例可以获得所要求的性质。
( 5 ) 即使用镊子操作， 也不会留下压迫痕迹或伤痕。
( 6 ) 可以保护视网膜免受紫外线的伤害。
( 7 ) 可以耐受激光处理。
( 8 ) 因为在分子内具有羟基和吡咯烷酮基， 所以可以在生 成共聚物后使之进行水和。
( 9 ) 因为可以容易地用多糖类修饰表面， 而且可以形成共 价键状态， 所以不会脱离。
( 10 ) 可以容易地进行分子间交联。

Claims

权 利 要 求
1. 由下式〔 I〕 、 〔 II〕 、 〔 III〕及〔 IV〕表示的构成单 元形成的共聚物， 各构成成分的重量构成比分别为： 〔 I〕 40 - 80、 〔 II〕 5 - 30、 〔 III〕 5 - 20、 〔 IV〕 5 - 30 ,
R1
I
H2C-C- [ I ]
CO
I
0
R2
I
OH 式中， R1表示氢原子或低级烷基； R2表示低级亚烷基，该亚烷基 也可以被羟基取代， 或该亚烷基链中也可以含有氧原子；
Figure imgf000020_0001
式中， R3表示氢原子或低级烷基； R4表示
R5 R6 R7 R8
I
— o CH- —— HN-(-CH ·)— +CH ^ ~ O -f-CH 4- m 、 ' π、 、 p 、 ' q 或单键； R5、 R6、 R7和 R8分别表示氢原子或低级烷基; m n、 q和 q表示 1 一 4的整数；
Figure imgf000020_0002
R10
式中， R9表示氢原子或低级烷基； R1()表示低级烷基;
Figure imgf000021_0001
式中， R11表示氢原子或低级烷基； R12表示苯基低级烷基、 萘基 低级烷基、 嘧啶基或嘧啶基派¾ xl嗪基， 该苯基低级烷基及萘基低级烷
2
基的苯环和萘环也可以被低级烷基、低级烷氧基或 ¾原子取代； X 表示 - O -、 - NH -或单键。
2. 如权利要求 1所述的共聚物， 其中各构成成分的重量构成比 为： 〔 I〕 50 - 70、 〔 II〕 10 - 25、 〔 III〕 5 - 15、 〔 IV〕 5 - 20。
3. 如权利要求 1所述的共聚物， 其分子量为 1万- 10万。
4. 如权利要求 1所述的共聚物， 其中 R1为氢原子或甲基， R2 为 - （ CH2 ) 2 -或- （ CH2 ) 3 -。
5. 如权利要求 1所述的共聚物， 其中 R3为氢原子或甲基， R4 为 - OCH2 -或- OCH2CH2 -。
6. 如权利要求 1所述的共聚物， 其中 R9为氢原子或甲基， R1G 为甲基。
7. 如权利要求 1所述的共聚物，其中 R11为氢原子或甲基， R12 为苄基、 苯乙基或嘧啶基哌嗪基。
8. 如权利要求 1所述的共聚物， 其中 R1为氢原子或甲基， R2 为 - （ CH2 ) 2 -或- （ CH2 ) 3 -， R3为氢原子或甲基， R4为 - OCH2或 - OCH2CH2 -， R9为氢原子或甲基， R1G为甲基， R11为氢原子或甲基， R12为苄基、 苯乙基或嘧啶基派嗪基。
9. 如权利要求 1所述的共聚物， 是用丙烯酸酯类或丙烯酰胺类 交联剂交联得到的。
10. 如权利要求 9所述的共聚物， 其中使用的交联剂是从双甲基 丙烯酸乙二醇酯、 双甲基丙烯酸二乙二醇酯或 N， N，-亚甲基双 (丙烯酰胺） 中选择的， 交联剂的量是共聚物构成成分总重量的
0.01-2 %。
11. 如权利要求 9所述的共聚物， 其中交联剂的量是共聚物构成 成分总重量的 0.05-1.5 %。
12. 如权利要求 1或 9所述的共聚物， 其中含有紫外线吸收剂。
13. 如权利要求 12所述的共聚物， 其中的紫外线吸收剂是二苯 甲酮类或苯并三唑类紫外线吸收剂。
14. 如权利要求 12所述的共聚物， 其中的紫外线吸收剂具有丙 烯基类残基， 并且是共聚物的 1个构成成分。
15. 如权利要求 12所述的共聚物， 其中的紫外线吸收剂是 2 - 羟基- 4 -甲基丙烯酰氧基二苯甲酮。
16. 如权利要求 1 、 9、 12中任一项所述的共聚物， 该共聚物 是用多糖类进行了表面加工。
17. 如权利要求 16所述的共聚物， 其中使用的多糖类是肝素或 透明质酸或其盐。
18. 如权利要求 16所述的共聚物， 其中所说的表面加工是通过 聚合物和多糖类型共价键来完成的。
19. 如权利要求 18所述的共聚物， 其中共价键的形成是使用二 乙烯基砜进行的。
20. 由权利要求 1 、 9 、 12或 16记载的共聚物成形的眼用透
21. 由权利要求 1、 2、 12或 16记载的共聚物成形的可折叠眼 内透镜。
22. 由权利要求 1、 9、 12或 16记载的共聚物成形的可折叠眼 内透镜， 该透镜具有下列特性：
( a )折射率 1.4-1.6 , ( b )从折叠状态恢复原状的复原速度为 3 - 6秒，
( c ) 膨润时的拉伸强度为 lOPsi以上。
23. 由下列 （ a )、 （ b )、 （ c )及（ d )共聚得到的共聚物， a ) ,
R1
I ^
H2C = c-C-0-R2— OH
II
o
式中， R1表示氢原子或低级烷基； R2表示低级亚烷基， 该 亚烷基也可以被羟基取代， 或者该亚烷基链中也可以含有氧原子；
Figure imgf000023_0001
式中， R3表示氢原子或低级烷基； R4表示
R5 R6 R7 R8
— O十 CH†"^ — HN- CH -n - CH )— 0-(-CH-)- 或单键； R5、 R6、 R7及 R8分别表示氢原子或低级烷基； m、 n、 p及 q表示 1 - 4的整数； c ) 9
R9
H2C=c-C-0— R10
I！
O
式中， R9表示氢原子或低级烷基； R1G表示低级烷基； d)
Figure imgf000023_0002
式中， R11表示氢原子或低级烷基； R12表示苯基低级烷基、 萘基低级烷基、 嘧啶基或嘧啶基哌溱基， 该笨基低级烷基及萘基低 级烷基的苯环和萘环也可以被低级烷基、 低级烷氧基或 ή原子取 代； X表示 - Ο -、 - ΝΗ -或单键。
24. 如权利要求 23所述的聚合物， 其分子量为 1万 - 10万。
25. 制备如权利要求 23所述的共聚物的方法， 该方法的特征在 于， 将权利要求 23规定的 （ a ) 、 （ b ) 、 （ c )及（ d ) 各成 分用过硫酸钾、 过硫酸铵、 二苯甲酮、 甲基丙烯酰氧基二笨甲酮或 甲基丙烯酸 N , N -二甲基氨基乙酯或他们的混合物作为聚合引 发剂进行共聚。
PCT/CN1998/000212 1997-10-07 1998-10-07 Quatre composants copolymeres et lentilles oculaires fabriquees a l'aide de ces composants WO1999018139A1 (fr)

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KR1020007003780A KR20010030994A (ko) 1997-10-07 1998-10-07 4성분 공중합체 및 이것으로 제조한 안구용 렌즈
JP2000514945A JP2001519445A (ja) 1997-10-07 1998-10-07 ４成分系共重合体及びその共重合体からなる眼用レンズ
CA002305747A CA2305747A1 (en) 1997-10-07 1998-10-07 Four component copolymer and the ocular lens made thereof
AU94276/98A AU9427698A (en) 1997-10-07 1998-10-07 Four component copolymer and the ocular lens made thereof
EP98947275A EP1026182A4 (en) 1997-10-07 1998-10-07 FOUR COPOLYMER COMPONENTS AND EYE LENSES MADE USING THESE COMPONENTS
US09/509,445 US6465588B1 (en) 1997-10-07 1998-11-07 Four component copolymers and the ocular lens made thereof
NO20001786A NO20001786L (no) 1997-10-07 2000-04-06 Firkomponent kopolymerer og den intraokulære linsen fremstilt herav

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CN97119353A CN1213671A (zh) 1997-10-07 1997-10-07 四成分共聚物及由该共聚物形成的眼用透镜

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6528602B1 (en) 1999-09-07 2003-03-04 Alcon Universal Ltd. Foldable ophthalmic and otorhinolaryngological device materials
US6851804B2 (en) * 2001-12-28 2005-02-08 Jagdish M. Jethmalani Readjustable optical elements

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5940345A (en) * 1997-12-12 1999-08-17 Cypress Semiconductor Corp. Combinational logic feedback circuit to ensure correct power-on-reset of a four-bit synchronous shift register
US7682669B1 (en) * 2001-07-30 2010-03-23 Advanced Cardiovascular Systems, Inc. Methods for covalently immobilizing anti-thrombogenic material into a coating on a medical device
US6852793B2 (en) * 2002-06-19 2005-02-08 Bausch & Lomb Incorporated Low water content, high refractive index, flexible, polymeric compositions
JP2007515972A (ja) * 2003-09-30 2007-06-21 ボーシュ アンド ローム インコーポレイティド Ｐｃｏとａｃｏを防ぐための眼内レンズ
US20050085908A1 (en) * 2003-10-20 2005-04-21 Chang Yu-An New ophthalmic lens materials with high refractive index and biocompatible surface
US9561309B2 (en) 2004-05-27 2017-02-07 Advanced Cardiovascular Systems, Inc. Antifouling heparin coatings
US8133274B2 (en) * 2004-06-18 2012-03-13 Medennium, Inc. Photochromic intraocular lenses and methods of making the same
US7446157B2 (en) 2004-12-07 2008-11-04 Key Medical Technologies, Inc. Nanohybrid polymers for ophthalmic applications
US7569073B2 (en) * 2004-12-29 2009-08-04 Bausch & Lomb Incorporated Small incision intraocular lens with anti-PCO feature
KR101484928B1 (ko) * 2006-06-01 2015-01-21 어드밴스드 비젼 사이언스, 인코포레이티드 반짝이는 부분이 없거나 감소된 안내 렌즈 및 이의 제조방법
WO2009015256A2 (en) * 2007-07-25 2009-01-29 Alcon, Inc. High refractive index ophthalmic device materials
FR2930731B1 (fr) * 2008-04-30 2014-06-27 Acrylian Materiau polymere acrylique, hydrophobe pour lentille intraoculaire
EP2501728B1 (en) * 2009-11-20 2015-01-07 Isp Investments Inc. Alkyl lactam ester polymers, and uses thereof
KR101242658B1 (ko) * 2010-10-11 2013-03-19 한국과학기술연구원 고굴절 친수성 안내 렌즈 및 그 제조방법
CN102558430B (zh) * 2011-12-26 2014-05-07 重庆科技学院 一种温敏性透明生物相容材料
US9389336B2 (en) * 2013-08-02 2016-07-12 Bausch & Lomb Incorporated Hydrogel monomer mix containing added water
FR3017800B1 (fr) 2014-02-27 2016-03-04 Acrylian Copolymere acrylique, hydrophobe, reticule, a base de 2-phenoxy-tetraethylene-glycol acrylate, pour lentilles intraoculaires
WO2016061457A1 (en) * 2014-10-17 2016-04-21 Key Medical Technologies, Inc. Polymers and methods for opthalmic applications
JP2019502776A (ja) * 2015-11-20 2019-01-31 アイエスピー インヴェストメンツ エルエルシー ラクタム部分を有する増殖性ポリマー
US10905636B2 (en) 2016-01-11 2021-02-02 Isp Investments Llc Block copolymers comprising repeating units derived from monomers comprising lactam and acryloyl moieties and hydrophobic monomers, compositions, and applications thereof
US20190382519A1 (en) * 2017-01-11 2019-12-19 Isp Investments Llc Cross-linked block copolymers comprising repeating units derived from monomers comprising lactam and acryloyl moieties, compositions, and applications thereof
WO2018132370A1 (en) * 2017-01-11 2018-07-19 Isp Investments Llc High molecular weight block copolymers comprising repeating units derived from monomers comprising lactam and acryloyl moieties and hydrophilic monomers, compositions, and applications thereof
CN115466349A (zh) * 2022-09-28 2022-12-13 长春工业大学 一种二苯甲酮衍生物防紫外线硅水凝胶隐形眼镜及其制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0580279A (ja) * 1991-09-24 1993-04-02 Seiko Epson Corp ソフトコンタクトレンズ
JPH09146052A (ja) * 1995-11-21 1997-06-06 Kuraray Co Ltd 含水性眼用レンズ材料
WO1997023523A1 (fr) * 1995-12-22 1997-07-03 Santen Pharmaceutical Co., Ltd. Nouveaux copolymeres constitues de trois composants et lentilles intraoculaires fabriquees a partir de ces copolymers
JPH09179073A (ja) * 1995-12-25 1997-07-11 Santen Pharmaceut Co Ltd ３成分系新規共重合体およびその共重合体からなる眼用レンズ

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4123407A (en) 1976-11-26 1978-10-31 American Optical Corporation Hydrophilic contact lens
ATE154049T1 (de) 1988-02-26 1997-06-15 Ciba Geigy Ag Benetzbares, biegsames, sauerstoffdurchlässiges, quellbares polymer mit polyoxyalkyleneinheiten in der hauptkette und kontaktlinse
CS270345B1 (en) 1988-06-08 1990-06-13 Vacik Jiri Hydrophilic transparent cross-linked copolymer and method of its production
JPH0428705A (ja) 1990-05-23 1992-01-31 Terumo Corp 医療用ヒドロゲル
JPH05150197A (ja) 1991-12-02 1993-06-18 Seiko Epson Corp ソフトコンタクトレンズ
US6132462A (en) * 1995-12-22 2000-10-17 Santen Pharmaceutical Co., Ltd. Copolymers formed from three components and intraocular lenses made thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0580279A (ja) * 1991-09-24 1993-04-02 Seiko Epson Corp ソフトコンタクトレンズ
JPH09146052A (ja) * 1995-11-21 1997-06-06 Kuraray Co Ltd 含水性眼用レンズ材料
WO1997023523A1 (fr) * 1995-12-22 1997-07-03 Santen Pharmaceutical Co., Ltd. Nouveaux copolymeres constitues de trois composants et lentilles intraoculaires fabriquees a partir de ces copolymers
JPH09179073A (ja) * 1995-12-25 1997-07-11 Santen Pharmaceut Co Ltd ３成分系新規共重合体およびその共重合体からなる眼用レンズ

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6528602B1 (en) 1999-09-07 2003-03-04 Alcon Universal Ltd. Foldable ophthalmic and otorhinolaryngological device materials
US6653422B2 (en) 1999-09-07 2003-11-25 Alcon Universal Ltd. Foldable ophthalmic and otorhinolaryngological device materials
US6851804B2 (en) * 2001-12-28 2005-02-08 Jagdish M. Jethmalani Readjustable optical elements

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NO20001786L (no) 2000-05-22
EP1026182A1 (en) 2000-08-09
JP2001519445A (ja) 2001-10-23
CN1274370A (zh) 2000-11-22
NO20001786D0 (no) 2000-04-06
KR20010030994A (ko) 2001-04-16
AU9427698A (en) 1999-04-27
US6465588B1 (en) 2002-10-15
EP1026182A4 (en) 2001-02-28
CA2305747A1 (en) 1999-04-15

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