Classifications

• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
  • C08F20/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride, ester, amide, imide or nitrile thereof
  • C08F20/02—Monocarboxylic acids having less than ten carbon atoms, Derivatives thereof
  • C08F20/10—Esters
  • C08F20/26—Esters containing oxygen in addition to the carboxy oxygen
  • C08F20/30—Esters containing oxygen in addition to the carboxy oxygen containing aromatic rings in the alcohol moiety
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/14—Macromolecular materials
  • A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • 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
• • 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

Definitions

• the present invention relates " to a polymerisable composition, a polymer formed from the polymerisable composition, and ophthalmic lenses and ophthalmic lens blanks formed from the polymer.
• IOLs intraocular lenses
• a typical procedure involves fragmenting the patient's cataractous lens by ultrasonic vibration, aspirating the fragmented lens pieces from the patient's eye through an incision in the eye, and then inserting an IOL into the eye through the same incision.
• foldable IOLs In order to reduce surgical trauma, it is advantageous to minimise the size of the incision. For this reason, foldable IOLs have been developed which can be shaped into a small package for insertion through the incision and which unfold into a final shape after being located in the eye.
• a significant class of foldable IOLs are formed from flexible polymers which are capable of unfolding at the temperature of the eye (i.e., about 37 °C) into an appropriate lens shape.
• Hydrophobic acrylic-based polymers have been used for forming flexible IOLs of this type, e.g., as disclosed by US-5674960, US-5922821 and WO 96/40303. Such polymers are rollable and foldable, and have relatively high refractive indices (which enables IOLs to be made thinner without sacrificing optical refractory power) . Conventionally, IOLs formed of these polymers are produced in a one-step moulding process which gives the IOL its final lens shape. The glass transition temperatures, T g , for the polymers are generally lower than 20°C so that the IOLs can be folded at room temperature.
• the present invention is at least partly based on the recognition that conventional hydrophobic acrylic-based polymers are not particularly suited to alternative processes, such as machining, for providing the final lens shape.
• An object of the present invention is to improve the machinability of polymers for use in flexible IOLs.
• a first aspect of the present invention provides a polymerisable composition comprising one or more monomers having the formula:
• -X is -H or -CH 3 ;
• -Y is -H or a Ci to Cio alkyl group, and is preferably -H or -CH 3 ;
• alkyl refers to a monovalent moiety obtained by removing a hydrogen atom from a carbon atom of a hydrocarbon compound having from 1 to 10 carbon atoms, which may be aliphatic or alicyclic, or a combination thereof, and which may be saturated, partially unsaturated, or fully unsaturated.
• aryl as used herein, pertains to a monovalent moiety obtained by removing a hydrogen atom from an aromatic ring atom of an aromatic compound.
• aromatic refers to compounds and/or groups which have one ring, or two or more rings (e.g., fused), wherein at least one of said ring(s) is aromatic.
• polymer IOLs formed from such a composition can be sufficiently flexible to fold or roll the IOLs to a small size for surgical insertion.
• the physical properties of the polymers can be such that the polymers are machinable at temperatures of 20 °C or higher, and/or at high speeds (which is desirable from the point of using conventional ophthalmic lens machine tooling, e.g., of the type used to machine contact lenses) . Machining with such tooling would be difficult to perform on conventional low T g polymers .
• the -CH 2 -CHY-0- group or groups of the monomer side chain play a significant part in providing the advantageous physical properties of the polymers.
• the amount of the above monomers in the composition may be at least 20% by weight of the composition, preferably at least 50% and more preferably at least 70%.
• the composition may further comprise one or more second monomers for forming a copolymer with the first monomer, the second monomers having an acrylate or methacrylate group.
• the second monomers may be methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate, hexyl acrylate, cyclohexyl acrylate, methoxymethyl acrylate, ethoxyethyl acrylate, methoxyethyl acrylate, ethoxymethyl acrylate, phenylether acrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate, butyl methacrylate, hexyl methacrylate, cyclohexyl methacrylate, methoxymethyl methacrylate, ethoxyethyl methacrylate, methoxyethyl methacrylate, ethoxymethyl methacrylate, and phenylether me
• the composition may further comprise one or more hydrophilic third monomers for forming a copolymer with the first monomer and optionally the second monomer.
• the third monomers may be 2 ⁇ hydroxyethyl methacrylate, hydroxypropyl methacrylate, N-vinyl pyrolidone, methacrylic acid, acrylic acid, acrylamide, methacrylamide, N,N-dimethyl acrylamide, hydroxyethyl acrylate and hydroxypropyl acrylate.
• the amount of the third monomers in the composition is less than 50% by weight of the composition, more preferably less than 25% by weight and desirably less than 15% by weight.
• the composition may further comprise one or more crosslinking fourth monomers having a plurality of ethylenically unsaturated groups.
• the fourth monomers may be ethylene glycol dimethylacrylate, diethylene glycol dimethylacrylate, allyl methacrylate, 1, 3-propanediol dimethacrylate, di-allyl maleate, 1, 6-hexanediol dimethacrylate, 1, 4-butanediol dimethacrylate and 1, 4-butanediol diacrylate.
• the amount of the fourth monomers in the composition is at least 0.1% by weight of the composition, more preferably at least 0.5% and desirably at least 1% or 4%.
• the optional addition of the second, third and/or fourth monomers to the composition can be useful for adjusting the physical or optical properties of the polymer formed from the composition.
• the composition may further comprise conventional compounds, including but not limited to a thermally- or light-activated polymerisation initiator (preferably in an amount of up to 5% by weight of the composition) , a UV-light absorber (preferably in an amount of up to 5% by weight of the composition) , or a blue-light absorber (preferably in an amount of up to 0.5% by weight of the composition), or a combination thereof.
• Another aspect of the present invention provides a polymer formed from the polymerisable composition of the previous aspect.
• the polymer has a T g (as measured by dynamic mechanical thermal analysis, DMTA) in the range of 0 to 50 °C, preferably 0 to 35°C (more preferably in the range 5 to 30°C) or 10 to 40°C.
• T g as measured by dynamic mechanical thermal analysis, DMTA
• the polymer has an elongation at 20°C of at least 50% (e.g., from 50% to 250%), and more preferably of at least 75% (e.g., from 75% to 150%).
• the polymer may have a refractive index (e.g., as measured by an Abbe refractometer) at 20 °C of at least 1.49.
• a refractive index e.g., as measured by an Abbe refractometer
• machining the blank to form an ophthalmic lens (b) machining the blank to form an ophthalmic lens.
• a finished IOL can be machined using milling and lathe cutting processes familiar to those skilled in the art.
• This has the advantage that a mould is not required to form a finished IOL, such moulds being relatively expensive articles and each mould in any event being capable of producing an IOL of only one geometry (and hence one focussing power) .
• the finished lens shape be formed by moulding (i.e., without a machining step) if desired.
• the physical properties of the polymer which we believe are due in large part to the first monomer but may be modified by the second, third and fourth monomers, facilitate the machining of the ophthalmic lens according to this aspect of the invention.
• the monomer poly (propylene glycol) 6 monobenzoate monomethacrylate (code named DP237) is formable by the following method.
• the reaction is conveniently carried out in tetrahydrofuran (THF) .
• THF tetrahydrofuran
• the alkoxide functionalities are removed by the addition of a solvent capable of abstracting a proton.
• Methacrylic acid is converted to its acid chloride by the addition of thionyl chloride using standard reflux conditions. Any excess thionyl chloride is easily removed by distillation.
• the acid chloride is then reacted with the product of the first reaction. Since the alcohol is losing a proton, the primary alcohol is much more reactive than the secondary alcohol site and, as such, the product is a hydroxy terminated methacrylate. At this point, the product is isolated and any impurities, such as hydroxypropyl methacrylate, are removed.
• the aromatic portion of the molecule is added by the Schotten-Baumann technique.
• the benzoyl acid is converted to its acid chloride, again by reaction with thionyl chloride followed by purification by distillation.
• the acid chloride is then added in portions to the hydroxy compound, this time in dichloromethane, in the presence of pyridine .
• the mixture is shaken vigorously, since the aromatic acid chlorides are not as reactive as the aliphatic derivatives.
• the pyridine is present to neutralise the hydrogen chloride that would otherwise be liberated.
• the resulting product is washed with water, since the dichloromethane is immiscible with water, and the pH is noted. Any acid that is present is removed by treatment with aqueous ammonia solution.
• Other derivatives can be produced using different acid chloride derivatives in the final reaction.
• MMA is methyl methacrylate
• HEMA is 2-hydroxyethyl methacrylate
• DAM is di-allyl maleate (a crosslinking agent)
• AIBN is azo iso butyronitrile (a thermally-activated polymerisation initiator) .
• compositions were thoroughly mixed and poured into a circularly cylindrical mould which was then evacuated and sealed.
• the compositions were polymerised at 60°C for 18 hours to form cylindrical blanks which were then removed from the moulds.
• Each blank had a diameter of 12.5 mm and a length of 7 mm.
• the values of the refractive index at 20°C, the Shore D hardness at 20°C and the T g was measured (the refractive index were measured by an Abbe refractometer, and the T g by dynamic mechanical thermal analysis) .
• the measured values are given in the table above.
• each blank was machined to a bi-convex shape (diameter 6 mm, central thickness 0.75 mm) corresponding to the central optic portion of a finished IOL.
• IOL central optic portions were rolled at 35°C, and inserted into narrow tubes of approximately 3 mm internal diameter.
• the rolled up lenses and tubes were then placed in an environmental cabinet at 35°C for a period of time to simulate the conditions in a human eye. When the lenses and tubes had had sufficient time to reach equilibrium with these conditions, the lenses were removed from the tubes. In each case the IOL portion spontaneously unrolled and assumed its original bi-convex shape in less than one minute. This demonstrates that the IOL portions were not damaged by rolling and storage, and suggests that they are suitable for use in cataractous lens replacement surgery.

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• 2001
  • 2001-03-26 GB GBGB0107540.7A patent/GB0107540D0/en not_active Ceased
• 2002
  • 2002-03-25 WO PCT/GB2002/001460 patent/WO2002077044A2/en not_active Application Discontinuation
  • 2002-03-25 GB GB0207013A patent/GB2375114A/en not_active Withdrawn
  • 2002-03-25 EP EP02708503A patent/EP1381636A2/de not_active Withdrawn
  • 2002-03-25 AU AU2002242865A patent/AU2002242865A1/en not_active Abandoned

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