WO2006138213A1 - Ophthalmic and otorhinolaryngological device materials - Google Patents
Ophthalmic and otorhinolaryngological device materials Download PDFInfo
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- WO2006138213A1 WO2006138213A1 PCT/US2006/022808 US2006022808W WO2006138213A1 WO 2006138213 A1 WO2006138213 A1 WO 2006138213A1 US 2006022808 W US2006022808 W US 2006022808W WO 2006138213 A1 WO2006138213 A1 WO 2006138213A1
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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
- C08F220/12—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
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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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
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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
- C08F220/12—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
- C08F220/1808—C8-(meth)acrylate, e.g. isooctyl (meth)acrylate or 2-ethylhexyl (meth)acrylate
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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
- C08F222/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides, or nitriles thereof
- C08F222/10—Esters
- C08F222/1006—Esters of polyhydric alcohols or polyhydric phenols
-
- 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
- C08F265/00—Macromolecular compounds obtained by polymerising monomers on to polymers of unsaturated monocarboxylic acids or derivatives thereof as defined in group C08F20/00
- C08F265/04—Macromolecular compounds obtained by polymerising monomers on to polymers of unsaturated monocarboxylic acids or derivatives thereof as defined in group C08F20/00 on to polymers of esters
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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
- C08F290/00—Macromolecular compounds obtained by polymerising monomers on to polymers modified by introduction of aliphatic unsaturated end or side groups
- C08F290/02—Macromolecular compounds obtained by polymerising monomers on to polymers modified by introduction of aliphatic unsaturated end or side groups on to polymers modified by introduction of unsaturated end groups
- C08F290/04—Polymers provided for in subclasses C08C or C08F
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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
- C08F290/00—Macromolecular compounds obtained by polymerising monomers on to polymers modified by introduction of aliphatic unsaturated end or side groups
- C08F290/02—Macromolecular compounds obtained by polymerising monomers on to polymers modified by introduction of aliphatic unsaturated end or side groups on to polymers modified by introduction of unsaturated end groups
- C08F290/06—Polymers provided for in subclass C08G
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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
- C08F290/00—Macromolecular compounds obtained by polymerising monomers on to polymers modified by introduction of aliphatic unsaturated end or side groups
- C08F290/02—Macromolecular compounds obtained by polymerising monomers on to polymers modified by introduction of aliphatic unsaturated end or side groups on to polymers modified by introduction of unsaturated end groups
- C08F290/06—Polymers provided for in subclass C08G
- C08F290/061—Polyesters; Polycarbonates
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L51/00—Compositions of graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers
- C08L51/003—Compositions of graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers grafted on to macromolecular compounds obtained by reactions only involving unsaturated carbon-to-carbon bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/16—Materials or treatment for tissue regeneration for reconstruction of eye parts, e.g. intraocular lens, cornea
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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
- C08F222/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides, or nitriles thereof
- C08F222/10—Esters
- C08F222/1006—Esters of polyhydric alcohols or polyhydric phenols
- C08F222/102—Esters of polyhydric alcohols or polyhydric phenols of dialcohols, e.g. ethylene glycol di(meth)acrylate or 1,4-butanediol dimethacrylate
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L33/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- C08L33/04—Homopolymers or copolymers of esters
- C08L33/14—Homopolymers or copolymers of esters of esters containing halogen, nitrogen, sulfur, or oxygen atoms in addition to the carboxy oxygen
Definitions
- This invention is directed to improved ophthalmic and otorhinolaryngological device materials.
- this invention relates to soft, high refractive index acrylic device materials that have improved strength.
- hydrogels With the recent advances in small-incision cataract surgery, increased emphasis has been placed on developing soft, foldable materials suitable for use in artificial lenses. In general, these materials fall into one of three categories: hydrogels, silicones, and acrylics.
- hydrogel materials have a relatively low refractive index, making them less desirable than other materials because of the thicker lens optic necessary to achieve a given refractive power.
- Silicone materials generally have a higher refractive index than hydrogels, but tend to unfold explosively after being placed in the eye in a folded position. Explosive unfolding can potentially damage the corneal endothelium and/or rupture the natural lens capsule.
- Acrylic materials are desirable because they typically have a high refractive index and unfold more slowly or controllably than silicone materials.
- U.S. Patent No. 5,290,892 discloses high refractive index, acrylic materials suitable for use as an intraocular lens (“1OL") material. These acrylic materials contain, as principal components, two aryl acrylic monomers.
- the IOLs made of these acrylic materials can be rolled or folded for insertion through small incisions.
- U.S. Patent No. 5,331 ,073 also discloses soft acrylic IOL materials. These materials contain as principal components, two acrylic monomers which are defined by the properties of their respective homopolymers. The first monomer is defined as one in which its homopolymer has a refractive index of at least about 1.50. The second monomer is defined as one in which its homopolymer has a glass transition temperature less than about 22 0 C. These IOL materials also contain a cross-linking component. Additionally, these materials may optionally contain a fourth constituent, different from the first three constituents, which is derived from a hydrophilic monomer. These materials preferably have a total of less than about 15% by weight of a hydrophilic component.
- U.S. Patent No. 5,693,095 discloses foldable, high refractive index ophthalmic lens materials containing at least about 90 wt.% of only two principal components: one aryl acrylic hydrophobic monomer and one hydrophilic monomer.
- the aryl acrylic hydrophobic monomer has the formula
- Ar is any aromatic ring which can be unsubstituted or substituted with CH 3 , C 2 H 5 , n-C 3 H 7 , IsO-C 3 H 7 , OCH 3 , C 6 H 1 ⁇
- the lens materials described in the '095 Patent preferably have a glass- transition temperature ("T 9 ”) between about -20 and +25 °C.
- Flexible intraocular lenses may be folded and inserted through a small incision.
- a softer material may be deformed to a greater extent so that it can be inserted through an increasingly smaller incision.
- Soft acrylic or methacrylic materials typically do not have an appropriate combination of strength, flexibility and non-tacky surface properties to permit IOLs to be inserted through an incision as small as that required for silicone IOLs.
- the mechanical properties of silicone elastomers are improved by addition of an inorganic filler, typically surface treated silica. Surface treated silica improves the mechanical properties of soft acrylic rubbers, too, but reduces the optical clarity of the finished product.
- Alternative filler materials having a refractive index closer to soft acrylic rubber are needed.
- reinforcing fillers to soft polymers is known to improve tensile strength and tear resistance. Reinforcement stiffens the polymer and improves its toughness by restricting the local freedom of movement of polymer chains, and strengthens the structure by introducing a network of weak fix points.
- the reinforcing ability of a particular filler depends upon its characteristics (e.g. size and surface chemistry), the type of elastomer with which it is used, and the amount of filler present.
- Conventional fillers include carbon black and silicate fillers, where the particle size (for maximum surface area) and wettability (for strength of cohesion) are of primary importance. Covalent chemical bonding between the matrix and the filler is generally not required for effective reinforcement.
- Improved soft, foldable acrylic device materials which are particularly suited for use as lOLs, but which are also useful as other ophthalmic or otorhinolaryngological devices, such as contact lenses, keratoprostheses, corneal rings or inlays, otological ventilation tubes and nasal implants, have been discovered.
- These polymeric materials contain microphase-separated domains similar to that found in conventional block copolymers. The presence of the microphase-separated domains improves the strength and influences the surface properties of the polymeric materials without need for added filler.
- the properties of the materials of the present invention are different than statistical (random) copolymers with identical feed ratios.
- the device materials of the present invention are self-reinforced polymeric materials.
- the materials are copolymers comprising a) a monofunctional acrylate or methacrylate monomer [1], b) a difunctional
- the materials comprise a) a monofunctional acrylate or methacrylate monomer [1], b) a difunctional acrylate or methacrylate cross- linker [2], c) an acrylate or methacrylate terminated aromatic functional
- B O(CH 2 ) n , NH(CH 2 ) n , or NCH 3 (CH 2 ) n ;
- G H, C(E)(CH 3 )C(O)X(CH 2 )nH, C(E)(CH 3 )C(O)X(CH 2 CH 2 O) n CH 3 , or
- Free radical polymerization of these ingredients results in a cross- linked polymer network and, depending on the molecular weight of the macromonomer, phase-separated polyacrylate and polymethacrylate domains similar to that found in block copolymers.
- the phase-separated domains influence the strength and surface properties of the resulting material and produce a copolymer with different material properties than a statistical copolymer with identical feed ratio.
- Y C 6 Hs
- E CH 3
- Z and Z' (CH 2 ) 2
- p is such that the number average molecular weight (M n ) of macromer [3] is 5,000 - 50,000.
- Z' (CH 2 ) 2 ; and p is such than M n is 1 ,000 - 10,000.
- Monomers of formula [1] are known and can be made by known methods. See, for example, U.S. Patent Nos. 5,331 ,073 and 5,290,892. Many monomers of formula [1] are commercially available from a variety of sources.
- Monomers of formula [2] are known and can be made by known methods, and are commercially available.
- Preferred monomers of formula (2) include ethylene glycol dimethacrylate; diethylene glycol dimethacrylate; 1 ,6- hexanediol dimethacrylate; 1 ,4-butanediol dimethacrylate; poly(ethylene oxide)dimethacrylate (number average molecular weight 600 - 1000); and their corresponding acrylates.
- Macromers of formulas [3] and [4] are known. They are commercially available in some instances and can be made by known methods. Macromonomers of formula [3] and [4] can be made by covalently attaching a polymerizable group to a functional end group of a linear or branched acrylic or methacrylic polymer. For example, hydroxyl terminated poly(methyl methacrylate) may be synthesized by anionic polymerization of methyl methacrylate, then functionalized by termination with ethylene oxide to produce hydroxyl terminated poly(methyl methacrylate). The terminal hydroxyl groups are end-capped on one or both terminal chain ends with an acrylate or methacrylate functionality.
- end-caps are covalently attached via known methods, for example esterification with methacryloyl chloride or reaction with an isocyanate to form a carbamate linkage. See, generally, U.S. Patent Nos. 3,862,077 and 3,842,059, the entire contents of which are incorporated by reference.
- Macromers of formula [3] and [4] can also be prepared using atom transfer radical polymerization (ATRP) conditions.
- ATRP atom transfer radical polymerization
- a hydroxyl terminal initiator hydroxyethyl bromoisobutyrate
- copper(l) halide a solubilizing amine ligand.
- This can be used to initiate the polymerization of an acrylate or methacrylate monomer.
- the resulting hydroxyl terminated poly(acrylate) or poly(methacrylate) can then be reacted with methacryloyl chloride or isocyanatoethyl methacrylate. See, generally, U.S. Patent Nos. 5,852,129, 5,763,548, and 5,789,487.
- the flexibility of the copolymeric material of the present invention depends primarily on the glass transition temperature of the homopolymer formed from monomer [1].
- the concentration of monomer [1] is typically at least 35%, and preferably 65 - 85 wt%, of the total (monomer + macromer + cross-linker) concentration.
- the materials of the present invention have at least one macromer of [3] or [4], but could have macromers of [3] and [4].
- the total amount of macromers [3] and [4] depends on the glass transition temperature of the homopolymer formed from monomer [1] to ensure formation of a flexible polymeric material.
- the copolymeric materials of the present invention contain a total of at least 5 wt. % of macromers [3] and [4].
- the copolymeric device material of the present invention optionally contains one or more ingredients selected from the group consisting of a polymerizable UV absorber and a polymerizable colorant.
- the device material of the present invention contains no other ingredients besides the monomers of formulas [1] and [2], the macromers [3] and [4], and polymerizable UV absorbers and colorants.
- the device material of the present invention optionally contains reactive UV absorbers or reactive colorants.
- reactive UV absorbers are known.
- a preferred reactive UV absorber is 2-(2'-hydroxy-3'-methallyl-5'- methylphenyl)benzotriazole, commercially available as o-Methallyl Tinuvin P ("oMTP") from Polysciences, Inc., Warrington, Pennsylvania.
- UV absorbers are typically present in an amount from about 0.1 - 5 % (weight).
- Suitable reactive blue-light absorbing compounds include those described in U.S. Patent No. 5,470,932. Blue-light absorbers are typically present in an amount from about 0.01 - 0.5 % (weight).
- the device materials of the present invention preferably contain both a reactive UV absorber and a reactive colorant.
- the chosen ingredients [1], [2], and [3] and/or [4] are combined and polymerized using a radical initiator to initiate polymerization by the action of either heat or radiation.
- the device material is preferably polymerized in de-gassed polypropylene molds under nitrogen or in glass molds.
- Suitable polymerization initiators include thermal initiators and photoinitiators.
- Preferred thermal initiators include peroxy free-radical initiators, such as t-butyl (peroxy-2-ethyl)hexanoate and di-(tert-butylcyclohexyl) peroxydicarbonate (commercially available as Perkadox ® 16 from Akzo Chemicals Inc., Chicago, Illinois).
- preferred photoinitiators include benzoylphosphine oxide initiators, such as 2,4,6-trimethyl-benzoyldiphenyl-phosphine oxide, commercially available as Lucirin ® TPO from BASF Corporation (Charlotte, North Carolina). Initiators are typically present in an amount equal to about 5 % or less of the total formulation weight, and more preferably less than 2 % of the total formulation. As is customary for purposes of calculating component amounts, the initiator weight is not included in the formulation weight % calculation.
- the device materials of the present invention are used to make IOLs having an optic diameter of 5.5 or 6 mm that are designed to be compressed or stretched and inserted through surgical incision sizes of 2 mm or less.
- the device material preferably has a refractive index in the dry state of at least about 1.47, and more preferably at least about 1.50, as measured by an Abbe' refractometer at 589 nm (Na light source) and 25 0 C.
- Optics made from materials having a refractive index lower than 1.47 are necessarily thicker than optics of the same power which are made from materials having a higher refractive index.
- IOL optics made from materials with comparable mechanical properties and a refractive index lower than about 1.47 generally require relatively larger incisions for IOL implantation.
- the material morphology or phase structure will depend on the macromer concentration, molecular weight, it's miscibility in the copolymer network (which also depends on molecular weight), and the polymerization method.
- the microphase separated behavior can be observed by differential scanning calorimetry (DSC).
- DSC differential scanning calorimetry
- Microphase-separated materials will exhibit two glass-transition temperatures ("T 9 ").
- the continuous phase and non-continuous phase will each exhibit a separate T 9 .
- T 9 of the continuous phase will primarily determine the material's flexibility properties, and folding and unfolding characteristics, and is preferably less than about +25 0 C, and more preferably less than about 0 0 C.
- T 9 of the non-continuous phase has a lesser impact on the materials' flexibility than that of the continuous phase.
- T 9 is measured by differential scanning calorimetry at 10 °C/min., and is generally determined at the midpoint of the transition of the heat flux versus temperature curve.
- the device material preferably has an elongation of at least 150%, more preferably at 300%, and a Young's modulus of less than 6.0 MPa, more preferably less than 5.0 MPa. These properties indicate that a lens made from such material generally will fold easily and will not crack, tear or split when it is folded.
- Tensile properties of polymer samples are determined on dumbbell shaped tension test specimens with a 20 mm total length, length in the grip area of 4.88 mm, overall width of 2.49 mm, 0.833 mm width of the narrow section, a fillet radius of 8.83 mm, and a thickness of 0.9 mm.
- Tear resistance was measured on unnicked 90 0 C angle specimens (Die C) according to ASTM D624-91 "Standard Test Method for Tear Strength of Conventional Vulcanized Rubber and Thermoplastic Elastomers".
- the test specimens were 20 mm total length, 9.0 mm guage length and a thickness of 0.9 mm. Testing was performed on samples at standard laboratory conditions of 23 ⁇ 2 0 C using an lnstron Material Tester model 4400 with a 50 N load cell. The grip distance was 9.0 mm and the crosshead speed was 500 mm/minute and the sample was pulled to failure.
- the tear resistance (“Tear strength”) was calculated from the maximum force obtained during testing divided by the sample thickness.
- the IOLs constructed of the device materials of the present invention can be of any design capable of being stretched or compressed into a small cross section that can fit through a 2-mm incision.
- the IOLs can be of what is known as a one-piece or multi-piece design, and comprise optic and haptic components.
- the optic is that portion which serves as the lens and the haptics are attached to the optic and are like arms that hold the optic in its proper place in the eye.
- the optic and haptic(s) can be of the same or different material.
- a multi-piece lens is so called because the optic and the haptic(s) are made separately and then the haptics are attached to the optic.
- the optic and the haptics are formed out of one piece of material. Depending on the material, the haptics are then cut, or lathed, out of the material to produce the 1OL.
- the materials of the present invention are also suitable for use as other ophthalmic or otorhinolaryngological devices such as contact lenses, keratoprostheses, corneal inlays or rings, otological ventilation tubes and nasal implants.
- Example 1 Synthesis of hydroxyl terminated poly(2-phenylethyl methacrylate) All synthetic manipulations were performed in a N 2 -filled glove-box.
- the product was diluted with ethyl acetate and purified by column chromatography. The product was further purified by precipitation from acetone into a large excess of methanol at 0 0 C. The product was isolated by vacuum filtration and rinsed thoroughly with chilled methanol, then dried under vacuum at ambient temperature and resulted in 20.5920 g (67%) of a white solid. The molecular weight was determined by GPC in tetrahydrofuran (THF) against polystyrene standards.
- THF tetrahydrofuran
- the mixture was concentrated on a rotary evaporator and the crude polymer was chromatographed on silica gel column with dichloromethane mobile phase.
- the eluent was concentrated using a rotary evaporator and the polymer was isolated by precipitation into cold methanol.
- the product was isolated by vacuum filtration, rinsed thoroughly with methanol and dried under vacuum at ambient temperature to yield 15.8401 g (78%) of a white solid.
- the product was diluted with tetrahydrofuran and purified by column chromatography.
- the product was further purified by precipitation from dichloromethane into a large excess of methanol at -50 0 C.
- the product was isolated by cold vacuum filtration and rinsed thoroughly with chilled methanol, then dried under vacuum at ambient temperature and resulted in 4.761 g (67%) of a slightly yellow viscous liquid.
- the molecular weight was determined by GPC in THF against polystyrene standards.
- the methacryloyl chloride solution was added dropwise with stirring. Once the addition was complete, the ice bath was removed and the reaction was maintained at ambient temperature for 4 days under N 2 .
- the mixture was concentrated on a rotary evaporator and the crude polymer was chromatographed on a basic alumina column with dichloromethane mobile phase. The eluent was transferred to a separatory funnel and washed twice with 1 M HCI, twice with deionized H 2 O, then saturated NaCI.
- the organic phase was dried over anhydrous MgSO 4 , filtered, and the solvent was removed using a rotary evaporator to yield 2.9804 g (63%) of a colorless viscous liquid.
- a scintillation vial was charged with 0.6114 g (3.214 mmru, 30.45 wt%) of methacrylate terminated poly(2-phenylethyl methacrylate) (polyPEMA-MA), 1.3336 g (7.568 mmol, 66.42 wt%) of 2-phenylethyl acrylate (PEA), 0.0629 g (0.317 mmol, 3.13 wt%) of 1 ,4-butanediol diacrylate (BDDA), and 0.0247 g 0 (0.150 mmol) of 2-hydroxy-2-methyl-1-phenyl-propan-1-one (Darocur 1173).
- polyPEMA-MA methacrylate terminated poly(2-phenylethyl methacrylate)
- PEA 2-phenylethyl acrylate
- BDDA 1 ,4-butanediol diacrylate
- Darocur 1173 2-hydroxy-2-methyl-1-phenyl-prop
- the solution was mixed until the polyPEMA-MA dissolved then de-gassed with N 2 .
- the formulation was transferred to polypropylene molds and polymerized by exposure to UV light (-3.0 mW/cm 2 , 365 nm) for 30 min.
- the resulting polymer was extracted in acetone for 3 hr, rinsed with fresh acetone 5 and allowed to air dry.
- the extracted polymer was dried under vacuum at 60 0 C for at least 3 hr.
- the amount of extractables was determined gravimetrically. Representative properties are listed in Table 1.
- Example 7 Copolymerization of methacrylate terminated poly(2-phenylethyl 0 methacrylate) macromer (M n 18,470) with 2-phenylethyl acrylate and 1 ,4- butanediol diacrylate
- a scintillation vial was charged with 0.6114 g (3.214 mmru, 30.47 wt%) of polyPEMA-MA, 1.3259 g (7.525 mmol, 66.09 wt%) of PEA, 0.0690 g (0.348 mmol, 3.44 wt%) of BDDA, and 0.0227 g (0.138 mmol) of Darocur 1173.
- the solution was mixed to allow dissolution of polyPEMA-MA then de-gassed with N 2 .
- the formulation was transferred to polypropylene molds and polymerized by exposure to UV light (-3.0 mW/cm 2 , 365 nm) for 30 min.
- the resulting polymer was extracted in acetone for 3 hr, then rinsed with fresh acetone and allowed to air dry.
- the extracted polymer was dried under vacuum at 60 0 C for at least 3 hr.
- the amount of extractables was determined gravimetrically. Representative properties are listed in Table 1.
- Example 8 Copolymerization of methacrylate terminated poly(2-phenylethyl methacrylate) macromer (M n 24,624) with 2-phenylethyl acrylate and 1 ,4- butanediol diacrylate
- a scintillation vial was charged with 1.2218 g (6.422 mmru, 30.55 wt%) of polyPEMA-MA, 2.6495 g (15.04 mmol, 66.26 wt%) of PEA, 0.1276 g (0.644 mmol, 3.19 wt%) of BDDA, and 0.0407 g (0.248 mmol, 1.02 wt%) of Darocur 1173.
- the solution was mixed to allow dissolution of polyPEMA-MA then degassed with N 2 and filtered through a 1 -micron glass fiber filter.
- the formulation was transferred to polypropylene molds and polymerized by exposure to UV light (-3.0 mW/cm 2 , 365 nm) for 30 min.
- the resulting polymer was extracted in acetone for 3 hr, then rinsed with fresh acetone and allowed to air dry.
- the extracted polymer was dried under vacuum at 60 0 C for at least 3 hr.
- the amount of extractables was determined gravimetrically. Representative properties are listed in Table 1.
- Table 1 demonstrates that the addition of macromer (3) improves the strength properties of soft acrylic polymers allowing increased distortion without fracture.
- a 2-phenylethyl acrylate- poly(PEMA)MA graft copolymer (Ex. 6) has increased tensile strength and tear resistance as compared to a statistical copolymer of 2-phenylethyl acrylate and 2-phenylethyl methacrylate of identical monomer feed ratio (Ex. 5).
- Example 9 Copolymerization of 2-phenylethyl methacrylate, 2-phenylethyl acrylate and 1 ,4-butanediol diacrylate
- a scintillation vial was charged with 2.5011 g (13.15 mmol, 25.0 wt%) of PEMA, 7.4014 g (42.00 mmol, 74.0 wt%) of PEA, 0.1007 g (0.508 mmol, 1.00 wt%) of BDDA, and 0.1006 g (0.613 mmol) of Darocur 1173.
- the solution was mixed thoroughly then de-gassed with N 2 .
- the formulation was transferred to polypropylene molds and polymerized by exposure to UV light (-3.0 mW/cm 2 , 365 nm) for 30 min.
- the resulting polymer was extracted in acetone for 3 hr, rinsed with fresh acetone and allowed to air dry.
- the extracted polymer was dried under vacuum at 60 °C for at least 3 hr.
- the amount of extractables was determined gravimetrically. Representative properties are listed in Table 2.
- Example 10 Copolymerization of methacrylate terminated poly(2-phenylethyl methacrylate) macromer (M n 18,470) with 2-phenylethyl acrylate and 1 ,4- butanediol diacrylate
- a scintillation vial was charged with 0.5011 g (2.634 mmru, 24.85 wt%) of polyPEMA-MA, 1.4935 g (8.476 mmol, 74.07 wt%) of PEA, 0.0216 g (0.109 mmol, 1.07 wt%) of BDDA, and 0.0212 g (0.129 mmol) of Darocur 1173.
- the solution was mixed to allow dissolution of polyPEMA-MA then de-gassed with N2.
- the formulation was transferred to polypropylene molds and polymerized by exposure to UV light ( ⁇ 3.0 mW/cm 2 , 365 nm) for 30 min.
- the resulting polymer was extracted in acetone for 3 hr, then rinsed with fresh acetone and allowed to air dry.
- the extracted polymer was dried under vacuum at 60 0 C for at least 3 hr.
- the amount of extractables was determined gravimetrically. Representative properties are listed in Table 2.
- Example 11 Copolymerization of methacrylate terminated poly(2-phenylethyl methacrylate) macromer (M n 24,624) with 2-phenylethyl acrylate and 1 ,4- butanediol diacrylate
- a scintillation vial was charged with 1.0010 g (5.262 mmru, 24.96 wt%) of polyPEMA-MA, 2.9701 g (16.86 mmol, 74.06 wt%) of PEA, 0.0393 g (0.198 mmol, 0.98 wt%) of BDDA, and 0.0385 g (0.234 mmol, 0.96 wt%) of Darocur 1173.
- the solution was mixed to allow dissolution of polyPEMA-MA then degassed with N 2 and filtered through a 1 -micron glass fiber filter.
- the formulation was transferred to polypropylene molds and polymerized by exposure to UV light ( ⁇ 3.0 mW/cm 2 , 365 nm) for 30 min.
- the resulting polymer was extracted in acetone for 3 hr, then rinsed with fresh acetone and allowed to air dry.
- the extracted polymer was dried under vacuum at 60 0 C for at least 3 hr.
- the amount of extractables was determined gravimetrically. Representative properties are listed in Table 2.
- Example 12 Copolymerization of methacrylate terminated poly(2-phenylethyl methacrylate) macromer (M n 6,300) with 2-phenylethyl acrylate, 2-(2- methoxyethoxy)ethyl methacrylate and 1,4-butanediol diacrylate
- a 20-mL scintillation vial was charged with 0.8072 g of poly(2-phenylethyl methacrylate) macromer, 2.5693 g of 2-phenylethyl acrylate (PEA), 0.6131 g of 2-(2-methoxyethoxy)ethyl methacrylate (MEEMA), and 0.0410 g of 1 ,4- butanediol diacrylate (BDDA).
- PEA 2-phenylethyl acrylate
- MEEMA 2-(2-methoxyethoxy)ethyl methacrylate
- BDDA 0.0410 g of 1 ,4- butanediol
- the vial was closed and agitated to allow the macromonomer to dissolve.
- the monomer mixture was filtered through a 1.0- micron glass fiber membrane.
- the formulation was de-gassed by bubbling N 2 through the monomer mixture.
- Di(4-tert-butylcyclohexyl)peroxydicarbonate (Perkadox 16S) was added (0.0202 g) and the solution was mixed thoroughly.
- the monomer mixture was dispensed into vacuum de-gassed polypropylene molds under a N 2 atmosphere.
- the filled molds were placed in a 70 0 C mechanical convection for 1 hr, then post-cured at 110 0 C for 2 hrs.
- the product was removed from the polypropylene molds and residual monomer was removed by acetone extraction at room temperature.
- the product polymer was dried under vacuum at 60 0 C.
- the graft copolymers of the present invention also exhibit a reduced surface tackiness as compared to statistical copolymers of identical feed composition, and this improves the manufacturability and manipulation of lOLs.
Abstract
Description
Claims
Priority Applications (11)
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MX2007015856A MX2007015856A (en) | 2005-06-13 | 2006-06-12 | Ophthalmic and otorhinolaryngological device materials. |
AT06772916T ATE461948T1 (en) | 2005-06-13 | 2006-06-12 | MATERIALS FOR OPHTHALMIC AND OTORHINOLARYNGOLOGICAL DEVICES |
JP2008516977A JP5036068B2 (en) | 2005-06-13 | 2006-06-12 | Device materials for ophthalmology and otolaryngology |
EP06772916A EP1891127B1 (en) | 2005-06-13 | 2006-06-12 | Ophthalmic and otorhinolaryngological device materials |
DE602006013127T DE602006013127D1 (en) | 2005-06-13 | 2006-06-12 | MATERIALS FOR OPHTHALMIC AND OTORHINOLARYNGOLOGICAL DEVICES |
BRPI0611968A BRPI0611968B8 (en) | 2005-06-13 | 2006-06-12 | ophthalmic and otolaryngological devices, their material, and intraocular lens |
KR1020077030649A KR101283332B1 (en) | 2005-06-13 | 2006-06-12 | Ophthalmic and otorhinolaryngological device materials |
CN2006800208770A CN101193929B (en) | 2005-06-13 | 2006-06-12 | Ophthalmic and otorhinolaryngological device materials |
CA2609866A CA2609866C (en) | 2005-06-13 | 2006-06-12 | Ophthalmic and otorhinolaryngological device materials |
AU2006259605A AU2006259605B2 (en) | 2005-06-13 | 2006-06-12 | Ophthalmic and otorhinolaryngological device materials |
EGNA2007001267 EG24984A (en) | 2005-06-13 | 2007-11-20 | Ophthalmic and otorhinolaryngological device materials. |
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US69000005P | 2005-06-13 | 2005-06-13 | |
US60/690,000 | 2005-06-13 |
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US (1) | US7652076B2 (en) |
EP (1) | EP1891127B1 (en) |
JP (1) | JP5036068B2 (en) |
KR (1) | KR101283332B1 (en) |
CN (1) | CN101193929B (en) |
AT (1) | ATE461948T1 (en) |
AU (1) | AU2006259605B2 (en) |
BR (1) | BRPI0611968B8 (en) |
CA (1) | CA2609866C (en) |
DE (1) | DE602006013127D1 (en) |
EG (1) | EG24984A (en) |
ES (1) | ES2340520T3 (en) |
MX (1) | MX2007015856A (en) |
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Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009046045A1 (en) * | 2007-10-02 | 2009-04-09 | Alcon, Inc. | Ophthalmic and otorhinolaryngological device materials containing an alkyl ethoxylate |
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WO2009046055A1 (en) * | 2007-10-02 | 2009-04-09 | Alcon, Inc. | Ophthalmic and otorhinolaryngological device materials containing an alkylphenol ethoxylate |
WO2009046232A1 (en) | 2007-10-05 | 2009-04-09 | Alcon, Inc. | Ophthalmic and otorhinolaryngological device materials |
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6353069B1 (en) * | 1998-04-15 | 2002-03-05 | Alcon Manufacturing, Ltd. | High refractive index ophthalmic device materials |
WO2004007579A1 (en) * | 2002-07-16 | 2004-01-22 | Alcon, Inc. | Ophthalmic and otorhinolaryngological device materials |
US6872793B1 (en) * | 2003-08-07 | 2005-03-29 | Alcon, Inc. | Ophthalmic and otorhinolaryngological device materials |
Family Cites Families (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1096912A (en) | 1963-08-06 | 1967-12-29 | Ici Ltd | Synthetic polymers |
US4085168A (en) * | 1971-02-22 | 1978-04-18 | Cpc International Inc. | Chemically joined, phase separated self-cured hydrophilic thermoplastic graft copolymers and their preparation |
US3842059A (en) * | 1971-02-22 | 1974-10-15 | M Chiang | Acrylate and methacrylate terminated polystyrene macromolecular monomers having a substantially uniform molecular weight distribution |
US3862077A (en) * | 1971-02-22 | 1975-01-21 | Cpc International Inc | Stable latexes of a chemically joined, phase separated thermoplastic graft copolymer and method for preparing the same |
US5057366A (en) * | 1982-09-16 | 1991-10-15 | Minnesota Mining And Manufacturing Company | Acrylate copolymer pressure-sensitive adhesive coated sheet material |
US5290892A (en) * | 1990-11-07 | 1994-03-01 | Nestle S.A. | Flexible intraocular lenses made from high refractive index polymers |
US5192616A (en) * | 1990-11-15 | 1993-03-09 | Minnesota Mining And Manufacturing Company | Macromolecular monomers from living polymers |
US5331073A (en) * | 1992-11-09 | 1994-07-19 | Allergan, Inc. | Polymeric compositions and intraocular lenses made from same |
US6369164B1 (en) * | 1993-05-26 | 2002-04-09 | Dentsply G.M.B.H. | Polymerizable compounds and compositions |
US5470932A (en) * | 1993-10-18 | 1995-11-28 | Alcon Laboratories, Inc. | Polymerizable yellow dyes and their use in opthalmic lenses |
US5763548A (en) * | 1995-03-31 | 1998-06-09 | Carnegie-Mellon University | (Co)polymers and a novel polymerization process based on atom (or group) transfer radical polymerization |
DK0774983T3 (en) * | 1995-06-07 | 2003-03-03 | Alcon Lab Inc | Improved materials for high refractive index ophthalmic lenses |
US5789487A (en) * | 1996-07-10 | 1998-08-04 | Carnegie-Mellon University | Preparation of novel homo- and copolymers using atom transfer radical polymerization |
US5852129A (en) * | 1996-11-28 | 1998-12-22 | Kaneka Corporation | Method for producing hydroxyl-terminated (meth) acrylic polymer |
US5708094A (en) * | 1996-12-17 | 1998-01-13 | Bausch & Lomb Incorporated | Polybutadiene-based compositions for contact lenses |
US5951999A (en) * | 1997-02-21 | 1999-09-14 | Adhesives Research, Inc. | Transdermal pressure sensitive adhesive drug delivery system |
US6083856A (en) * | 1997-12-01 | 2000-07-04 | 3M Innovative Properties Company | Acrylate copolymeric fibers |
SE9803481D0 (en) * | 1998-10-13 | 1998-10-13 | Pharmacia & Upjohn Ab | Photocurable siloxane polymers |
US6450642B1 (en) * | 1999-01-12 | 2002-09-17 | California Institute Of Technology | Lenses capable of post-fabrication power modification |
US6787584B2 (en) * | 2000-08-11 | 2004-09-07 | Pentron Corporation | Dental/medical compositions comprising degradable polymers and methods of manufacture thereof |
US6723816B2 (en) | 2001-11-02 | 2004-04-20 | Bausch & Lomb Incorporated | High refractive index aromatic-based siloxane difunctional macromonomers |
US20030176521A1 (en) * | 2001-12-28 | 2003-09-18 | Calhoun Vision | Initiator and ultraviolet absorber for changing lens power by ultraviolet light |
-
2006
- 2006-06-12 WO PCT/US2006/022808 patent/WO2006138213A1/en active Application Filing
- 2006-06-12 CA CA2609866A patent/CA2609866C/en not_active Expired - Fee Related
- 2006-06-12 ES ES06772916T patent/ES2340520T3/en active Active
- 2006-06-12 KR KR1020077030649A patent/KR101283332B1/en active IP Right Grant
- 2006-06-12 CN CN2006800208770A patent/CN101193929B/en not_active Expired - Fee Related
- 2006-06-12 ZA ZA200710478A patent/ZA200710478B/en unknown
- 2006-06-12 RU RU2008101451/04A patent/RU2414481C2/en not_active IP Right Cessation
- 2006-06-12 DE DE602006013127T patent/DE602006013127D1/en active Active
- 2006-06-12 AU AU2006259605A patent/AU2006259605B2/en not_active Ceased
- 2006-06-12 US US11/451,097 patent/US7652076B2/en active Active
- 2006-06-12 AT AT06772916T patent/ATE461948T1/en not_active IP Right Cessation
- 2006-06-12 BR BRPI0611968A patent/BRPI0611968B8/en not_active IP Right Cessation
- 2006-06-12 EP EP06772916A patent/EP1891127B1/en active Active
- 2006-06-12 MX MX2007015856A patent/MX2007015856A/en active IP Right Grant
- 2006-06-12 JP JP2008516977A patent/JP5036068B2/en active Active
-
2007
- 2007-11-20 EG EGNA2007001267 patent/EG24984A/en active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6353069B1 (en) * | 1998-04-15 | 2002-03-05 | Alcon Manufacturing, Ltd. | High refractive index ophthalmic device materials |
WO2004007579A1 (en) * | 2002-07-16 | 2004-01-22 | Alcon, Inc. | Ophthalmic and otorhinolaryngological device materials |
US6872793B1 (en) * | 2003-08-07 | 2005-03-29 | Alcon, Inc. | Ophthalmic and otorhinolaryngological device materials |
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JP2013126583A (en) * | 2007-04-27 | 2013-06-27 | Yichieh Shiuey | Corneal implant, and method and system for placement of the corneal implant |
WO2009046055A1 (en) * | 2007-10-02 | 2009-04-09 | Alcon, Inc. | Ophthalmic and otorhinolaryngological device materials containing an alkylphenol ethoxylate |
WO2009046045A1 (en) * | 2007-10-02 | 2009-04-09 | Alcon, Inc. | Ophthalmic and otorhinolaryngological device materials containing an alkyl ethoxylate |
US8574292B2 (en) | 2007-10-02 | 2013-11-05 | Novartis Ag | Ophthalmic and otorhinolaryngological device materials containing an alkylphenol ethoxylate |
US8105378B2 (en) | 2007-10-02 | 2012-01-31 | Novartis Ag | Ophthalmic and otorhinolaryngological device materials containing an alkyl ethoxylate |
RU2468825C2 (en) * | 2007-10-03 | 2012-12-10 | Алькон, Инк. | Materials for ophthalmological and otorhinolaryngological apparatuses |
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RU2469743C2 (en) * | 2007-10-05 | 2012-12-20 | Алькон, Инк. | Materials for ophthalmological and otorhinolaryngologic devices |
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RU2467769C2 (en) * | 2007-10-05 | 2012-11-27 | Алькон, Инк. | Materials for ophthalmologic and otorhinolaryngologic devices |
US8728157B2 (en) | 2007-10-05 | 2014-05-20 | Novartis Ag | Ophthalmic and otorhinolaryngological device materials |
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ATE461948T1 (en) | 2010-04-15 |
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CN101193929A (en) | 2008-06-04 |
CN101193929B (en) | 2012-02-01 |
KR20080026564A (en) | 2008-03-25 |
KR101283332B1 (en) | 2013-07-15 |
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US7652076B2 (en) | 2010-01-26 |
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