EP0930357A1 - Kontaktlinsenreinigungslösungen - Google Patents

Kontaktlinsenreinigungslösungen Download PDF

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Publication number
EP0930357A1
EP0930357A1 EP97309921A EP97309921A EP0930357A1 EP 0930357 A1 EP0930357 A1 EP 0930357A1 EP 97309921 A EP97309921 A EP 97309921A EP 97309921 A EP97309921 A EP 97309921A EP 0930357 A1 EP0930357 A1 EP 0930357A1
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EP
European Patent Office
Prior art keywords
groups
group
alkyl
hydrogen
same
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EP97309921A
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English (en)
French (fr)
Inventor
Andrew Victor Graham Muir
Peter William Stratford
Stephen Alister Jones
Sean Leo Willis
Charles Bret Jessee
Johnathan William Bowers
Lee Rowan
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Abbott Vascular Devices Ltd
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Biocompatibles Ltd
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Application filed by Biocompatibles Ltd filed Critical Biocompatibles Ltd
Priority to EP97309921A priority Critical patent/EP0930357A1/de
Priority to AU14429/99A priority patent/AU1442999A/en
Priority to PCT/GB1998/003667 priority patent/WO1999029818A1/en
Publication of EP0930357A1 publication Critical patent/EP0930357A1/de
Withdrawn legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/16—Organic compounds
    • C11D3/37—Polymers
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/0005—Other compounding ingredients characterised by their effect
    • C11D3/0078—Compositions for cleaning contact lenses, spectacles or lenses

Definitions

  • the present invention relates to aqueous solutions for cleaning, soaking or storing contact lenses which contain a solution of a biocompatible polymer having pendant zwitterionic groups formed from monomers including zwitterionic groups and comonomers having hydrophobic groups which are fluoroalkyl or silyl groups.
  • a copolymer having hydrophobic pendant groups these were provided from a comonomer of the general formula Y 1 Q, in which Y 1 was an ethylenically unsaturated polymerisable group and Q was a straight or branched alkyl, alkoxy alkyl or (oligo-alkoxy) alkyl chain containing 6 to 12 carbon atoms, a fluoroalkyl group or a siloxane group.
  • a fluoroalkyl group could contain 2 to 23 carbon atoms whilst the siloxane group contained at least one dialkyl substituted silicon atom.
  • the polymer coatings of WO-A-93/01221 were intended to be stable, that is provide long term coatings which tended not to be removed in use.
  • the coating conferred biocompatibility on the underlying substrates, reducing protein adsorption and platelet activation.
  • Potential uses of the polymers were to coat implants, prostheses, membrane, catheters, contact lenses, intraocular lenses and extra corporeal circuitry.
  • the examples of polymers for coating hydrophobic surfaces, to produce coated articles to be used in an aqueous environment were all substantially-insoluble and were coated from solutions in an alcohol, a chlorinated solvent or a mixture thereof.
  • contact lenses formed from a cross linked polymer including residues derived from a zwitterionic monomer are described, as well as cleaning solutions containing a copolymer of the same zwitterionic monomer and suitable comonomers.
  • the zwitterionic monomer is 2-(methacryloyloxyethyl)-2'-(trimethylammoniumethyl) phosphate inner salt.
  • the comonomers used were n-butyl methacrylate, 2-hydroxyethyl methacrylate and styrene.
  • the contact lens treatment solutions in each case contain ethylene glycol in the solvent mixture.
  • JP-A-07-166154 contact lens cleaning solutions comprising a buffered solution containing or copolymers of 2((meth) acryloyloxyalkyl)-2'-(trialkylammoniumethyl) phosphate inner salt with comonomers, for instance butyl methacrylate are described.
  • the solutions contain no organic solvent.
  • a problem with the polymers described in WO-A-93/01221 and EP-A-0537932 is that they are dispersed in a non-aqueous solvent.
  • the presence of organic solvent in any solution for use with contact lenses is undesirable, since introduction of organic solvent into the eye must be avoided and removal of all traces from a cleaning or a soaking solution is hard.
  • the problem with the copolymers described in JP-A-07-166154 is that they bind inadequately to the surface of the contact lens and so provide very short term benefits.
  • copolymer which can be presented in the form of an aqueous solution, but which binds sufficiently strongly to the surface of a wide variety of contact lenses so that the polymer will remain coated on the surface during storage and after insertion of the lens back into the eye to provide long term biocompatibility, resistance to protein and lipid deposition.
  • a new composition according to the invention for cleaning, soaking or storing contact lenses or ocular implants or containers therefor or for use as an artificial tear or ophthal mic comfort drop is aqueous, substantially free of organic solvent and contains 0.01 to 5% by weight of a copolymer obtainable by copolymerising ethylenically unsaturated monomers including:
  • Preferred zwitterionic monomers are of general formula (III) or (IV) where R, A, B, K and X are as defined with reference to formula (I).
  • the group X may be a betaine monomer, for instance a sulpho-, carboxy- or phospho-betaine.
  • a betaine monomer has no overall charge and is preferably therefore a carboxy- or sulpho-betaine.
  • Such groups may be represented by the general formula -X 3 -R 24 -N + (R 25 ) 2 -R 26 -V in which X 3 is a valence bond, -O-, -S- or -NH-, preferably -O-;
  • the groups R 16 are the same. It is also preferable that at least one of the groups R 16 is methyl, and more preferable that the groups R 16 are both methyl.
  • d is 2 or 3, more preferably 3.
  • the monomer may be an amino acid type derivative in which the alpha carbon atom (to which an amine group and the carboxylic acid group are attached) is joined through a linker group to the group B of the monomer of the formula I.
  • groups may be represented by the general formula in which X 4 is a valence bond, -O-, -S- or -NH-, preferably -O-,
  • X is preferably of formula in which the moieties X 1 and X 2 , which are the same or different, are -O-, -S-, -NH- or a valence bond, preferably -O-, and W + is a group comprising an ammonium, phosphonium or sulphonium cationic group and a group linking the anionic and cationic moieties which is preferably a C 1-12 -alkylene group.
  • W contains as cationic group an ammonium group, more preferably a quaternary ammonium group.
  • the group W + may for example be a group of formula -W 1 -N + R 23 3 , -W 1 -P + R 23a 3 , -W 1 -S + R 23a 2 or -W 1 -Het + in which:
  • W 1 is a straight-chain alkylene group, most preferably 1,2-ethylene.
  • Preferred groups X of the formula VI are groups of formula VA.
  • the groups of formula (VA) are: where the groups R 12 are the same or different and each is hydrogen or C 1-4 alkyl, and e is from 1 to 4.
  • the groups R 12 are the same. It is also preferable that at least one of the groups R 12 is methyl, and more preferable that the groups R 12 are all methyl.
  • e is 2 or 3, more preferably 2.
  • X is a group of formula (VA)
  • B is a group of formula -(CR 13 2 )- or -(CR 13 2 ) 2 -, eg. -(CH 2 )- or -(CH 2 CH 2 )-.
  • ammonium phosphate estergroup VA may be replaced by a glycerol derivative of the formula VB, VC or VC defined below.
  • the groups of formula (VB) are: wherein the groups R 18 are the same or different and each is hydrogen or C 1-4 alkyl, R 18 - is hydrogen or, more preferably, a group -C(O)B 1 R 18b where R 18b is hydrogen or methyl, preferably methyl, B 1 is a valence bond or straight or branched alkylene, oxaalkylene or oligo-oxaalkalyene group, and f is from 1 to 4; and
  • the groups R 18 are the same. It is also preferable that at least one of the groups R 18 is methyl, and more preferable that the groups R 18 are all methyl.
  • f is 1 or 2, more preferably 2.
  • B 1 is:
  • Preferred groups B 1 include a valence bond and alkylene, oxaalkylene and oligo-oxaalkylene groups of up to 12 carbon atoms.
  • B and B 1 are the same.
  • B is a group of formula -[(CR 14 2 CR 14 2 ) c O b ]CR 14 2 CR 14 2 -, eg. -(CH 2 CH 2 O) c (CH 2 CH 2 )-.
  • the groups of formula (VC) are: wherein the groups R 19 are the same or different and each is hydrogen or C 1 -C 4 alkyl, R 19a is a hydrogen or, more preferably, a group -C(O)B 2 R 19b , R 19b is hydrogen or methyl, preferably methyl, B 2 is a valence bond or a straight or branched alkylene, oxaalkylene or oligo-oxaalkylene group, and g is from 1 to 4; and
  • the groups R 19 are the same. It is also preferable that at least one of the groups R 19 is methyl, and more preferable that the groups R 19 are all methyl.
  • g is 1 or 2, more preferably 2.
  • B 2 is:
  • Preferred groups B 2 include a valence bond and alkylene, oxalkylene and oligo-oxalkylene groups of up to 12 carbon atoms.
  • B and B 2 are the same.
  • B is a group of formula -[(CR 14 2 CR 14 2 ) b O] c CR 14 2 CR 14 2 -, eg. -(CH 2 CH 2 O) c CH 2 CH 2 -.
  • the groups of formula (VD) are: wherein the groups R 20 are the same or different and each is hydrogen or C 1-4 alkyl, R 20a is hydrogen or, more preferably, a group -C(O)B 3 R 20b where R 20b is hydrogen or methyl, preferably methyl, B 3 is a valence bond or a straight or branched - alkylene, oxaalkylene or oligo-oxaalkylene group, and h is from 1 to 4; and
  • the groups R 20 are the same. It is also preferable that at least one of the groups R 20 is methyl, and more preferable that the groups R 20 are all methyl.
  • h is 1 or 2, more preferably 2.
  • B 3 is:
  • Preferred groups B 3 include a valence bond and alkylene, oxaalkylene and oligo-oxaalkylene groups of up to 12 carbon atoms.
  • B and B 3 are the same.
  • B is a group of formula -[(CR 14 2 CR 14 2 ) b O] c CR 14 2 CR 14 2 -, eg. -(CH 2 CH 2 O) c CH 2 CH 2 -.
  • Monomers having group X of formula VA to D may be prepared using techniques described in WO-A-93/01221. The description of the methods of monomer synthesis of such monomers described in that document are incorporated herein by reference.
  • K may be a valence bond and B a group, K may be a group and B a valence bond, both K and B may be groups, or K and B may together be a valence bond.
  • B is a group where K is a valence bond.
  • K is a group then preferably p is from 1 to 6, more preferably 1,2 or 3 and most preferably p is 1.
  • K is a group -(CH 2 ) p NR 2 -, (CH 2 ) p NR 2 C(O)-, -(CH 2 ) p C(O)NR 2 , -(CH 2 ) p NR 2 C(O)O-, -(CH 2 ) p OC(O)NR 2 - or -(CH 2 ) p NR 2 C(O)NR 2 - then R 2 is preferably hydrogen, methyl or ethyl, more preferably hydrogen.
  • the vinyl group is para to the group -K-B-X.
  • the hydrophobic monomer is an acrylic type monomer. It is preferred in such monomers for the group R 14 to be hydrogen or more preferably, methyl, and for A 1 to be -O-.
  • Preferred groups B 4 are C 1-4 alkylene, preferably ethylene, a valence bond or a C 1-4 -alkylene sulphonamido group i.e. a group -(CR 13d 2 ) and N(R 29 )SO 2 - in which R 13d is hydrogen or C 1-4 -alkyl, and is 1 to 12, preferably 1 to 6, more preferably 2 and R 29 is hydrogen or C 1-4 -alkyl.
  • group R 3 which is a fluoroalkyl group has the formula -(CR 10 2 ) q (CR 11 2 ) p CR 11 3 wherein the groups (CR 10 2 ) are the same or different and in each group (CR 10 2 ) the groups R 10 are the same or different and are fluorine, hydrogen, or C 1-4 -alkyl or -fluoroalkyl and q is 1-23, the groups -(CR 11 2 )- are the same or different, and in each said group the groups R 11 are the same or different and each is hydrogen, fluorine, or C 1-4 -alkyl or fluoroalkyl and p is in the range 0 to 23, provided that at least one of the groups R 10 and/or one of the groups R 11 is fluorine or fluoroalkyl.
  • p is at least 2 and no more than 12.
  • a fluoroalkyl group R 3 contains at least 3 fluorine atoms.
  • R 10 are hydrogen or lower alkyl, most preferably hydrogen, and q is 1-4, most preferably 2.
  • hydrophobic fluoroalkyl group containing monomers has the formula IX where ad is 2 to 4, preferably 2, R 29' is hydrogen or C 1-4 alkyl, preferably methyl, ethyl, n-propyl or n-butyl, q ' is 0 to 6, and p ' is 1 to 9, preferably 2 to 6.
  • hydrophobic fluoroalkyl group containing monomers has the formula X where q'' is 2 to 4 and p'' is 1 to 9, preferably 2 to 8.
  • the groups R 7 are all hydrogen and n is 2 to 4.
  • the groups R 8 are preferably the same as one another.
  • the groups R 9 are preferably the same as one another and are preferably the same as the groups R 8 and group R 29 .
  • Groups R 8 , R 9 and R 29 are most preferably methyl.
  • the vinyl group is preferably parallel to the group K-R 3 .
  • the zwitterionic monomer and hydrophobic comonomer should be of the same type, for optimum copolymerisation properties.
  • the monomer of the formula I is an (alk) acrylate
  • the comonomer is also an (alk) acrylate.
  • the groups R and R 4 in the compounds III and II are the same, and are preferably hydrogen or methyl, most preferably methyl.
  • the groups A and A' are the same, and are most preferably -O-.
  • the polymers of the present invention may comprise residues of a diluent comonomer.
  • Such diluent comonomers may be of any known conventional radical polymerisable, preferably ethylenically unsaturated, type compatible with the other comonomer(s) and the zwitterionic monomer.
  • diluent comonomers include alkyl(alk)acrylate preferably containing 1 to 4 carbon atoms in the alkyl group of the ester moiety, such as methyl (alk)acrylate; a dialkylamino alkyl(alk)acrylate, preferably containing 1 to 4 carbon atoms in each alkyl moiety of the amine and 1 to 4 carbon atoms in the alkylene chain, e.g.
  • 2-(dimethylamino)ethyl (alk)acrylate 2-(dimethylamino)ethyl (alk)acrylate; an alkyl (alk)acrylamide preferably containing 1 to 4 carbon atoms in the alkyl group of the amide moiety; a hydroxyalkyl (alk)acrylate preferably containing from 1 to 4 carbon atoms in the hydroxyalkyl moiety, e.g.
  • a 2-hydroxyethyl (alk)acrylate or a vinyl monomer such as an N-vinyl lactam, preferably containing from 5 to 7 atoms in the lactam ring, for instance vinyl pyrrolidone; styrene or a styrene derivative which for example is substituted on the phenyl ring by one or more alkyl groups containing from 1 to 6, preferably 1 to 4, carbon atoms, and/or by one or more halogen, such as fluorine atoms, e.g. (pentafluorophenyl) styrene.
  • a vinyl monomer such as an N-vinyl lactam, preferably containing from 5 to 7 atoms in the lactam ring, for instance vinyl pyrrolidone
  • styrene or a styrene derivative which for example is substituted on the phenyl ring by one or more alkyl groups containing from 1 to 6, preferably 1
  • Suitable diluent comonomers include polyhydroxyl, for example sugar or glycerol, (alk)acrylates and (alk)acrylamides in which the alkyl group contains from 1 to 4 carbon atoms, e.g. sugar or glycerol acrylates, methacrylates, ethacrylates, acrylamides, methacrylamides and ethacrylamides.
  • Suitable sugars include glucose and sorbitol.
  • Particularly suitable diluent comonomers include methacryloyl glucose or sorbitol methacrylate.
  • diluents which may be mentioned specifically include polymerisable alkenes, preferably of 2-4 carbon atoms, eg. ethylene, dienes such as butadiene, alkylene anhydrides such as maleic anhydride and cyano-substituted alkylenes, such as acrylonitrile.
  • diluent comonomers are nonionic and are substantially inert. They may, in some cases, affect, for instance increase, the water solubility of the polymers by being relatively more hydrophilic than the combination of the zwitterionic monomer and the hydrophobic comonomer.
  • Preferred examples of diluent comonomer are hydroxy (including polyhydroxy) alkyl (alk) acrylate containing from 1 to 4 carbon atoms in the hydroxy alkyl moiety, especially 2-hydroxyalkyl (meth)acrylates and glyceryl monomethacrylate.
  • Any conventional technique may be used for polymerisation, typically thermal or photochemical polymerisation.
  • thermal polymerisation a temperature from 40 to 100°C, typically 50 to 80°C is used.
  • actinic radiation such as gamma, U.V., Visible or microwave radiation may be used.
  • U.V. radiation of wavelength 200 to 400 nm is used.
  • the polymerisation is generally performed in a reaction medium, which is for instance a solution or dispersion, using as a solvent for example acetonitrile, dimethyl formamide, chloroform, dichloromethane, ethyl acetate, dimethyl sulphoxide, dioxane, benzene, toluene, tetrahydrofuran, water or an alkanol containing from 1 to 4 carbon atoms, e.g. methanol, ethanol or propan-2-ol.
  • a mixture of any of the above solvents may be used.
  • the polymerisation may be carried out in the presence of one or more polymerisation initiators, such as benzoyl peroxide, 2,2'-azo-bis(2-methylpropionitrile) (AIBN), 4,4' Azobis (4-cyano-valeric acid (ACVA) or benzoin methyl ether.
  • polymerisation initiators such as benzoyl peroxide, 2,2'-azo-bis(2-methylpropionitrile) (AIBN), 4,4' Azobis (4-cyano-valeric acid (ACVA) or benzoin methyl ether.
  • Other polymerisation initiators which may be used are disclosed in "Polymer Handbook", 3rd edition, Ed. J. Brandrup and E.H. Immergut, pub. Wiley-Interscience, New York, 1989.
  • the copolymerisation is performed for 1 to 72 hours, preferably 8 to 48, for instance 16 to 24 hours, and under an inert atmosphere of for example nitrogen or argon.
  • the polymer is generally purified by dialysis, precipitation in a non-solvent (e.g. diethyl ether or acetone) or ultrafiltration.
  • the resulting polymer is generally dried under vacuum, e.g. for 5 to 72 hours and has a molecular weight from 10,000 to 10 million, preferably from 20,000 to 1 million.
  • the polymerisation usually involves monomers having the general formulae I and II. In some instances it may be possible to form a polymer having suitable derivatisable groups and reacting the polymer to introduce a group X or R 3 , as the case may be.
  • the ratio of zwitterionic monomer to hydrophobic monomer and the content of any diluent monomer should be suitable to confer upon the polymer water-solubility characteristics as well as binding characteristics onto the contact lens surface.
  • the amount of zwitterionic monomer is generally at least 20 mole % (based on the total moles of ethylenically unsaturated monomer) preferably at least 50% more preferably at least 75%, for instance up to 90% or even up to 95%.
  • the amount of hydrophobic monomer should be at least 1 mole %, more preferably at least 5 mole %, for instance 10 to 50 mole %.
  • the amount of diluent monomer should be up to 49 mole % based on the total moles of monomer, for instance in the range 5 to 40 mole %.
  • compositions of the invention have utilities which have in common the fact that the ingredients are acceptable for introduction into the eye, either by application directly into the eye or carried over with a lens or other intraocular device is introduced into the eye.
  • surfaces which the polymers of the compositions should adsorb are generally hydrophobic.
  • contact lenses especially gas permeable (soft silicone and fluorosilicone-based and hard type) contact lenses, contact lens cases and containers and the cornea, are all hydrophobic.
  • the hydrophobic group from the monomer of the formula II provides good adsorption properties to such substrates.
  • compositions of the invention should contain other ingredients suitable for contact lens cleaning, soaking or storage solutions or artificial tears/comfort drops.
  • Storage solutions mean solutions in a sealed sterilised package, in which the contact lenses are supplied to the consumer.
  • the composition generally contains 0.01 to 5%, preferably in the range 0.1 to 2.5%, for instance in the range 0.5 to 2% by weight of the polymer.
  • the concentration generally depends upon the use for which the solution is intended.
  • Cleaning solutions may have concentrations at the upper end of the range, for instance more than 1% by weight. Soaking solutions and storage solutions may have concentrations at the lower end of the range, for instance less than 2%, often less than 1% by weight.
  • Artificial tears and comfort drops may contain the polymer in an amount of at least 1% by weight, preferably at least 2% by weight, up to 10% preferably no
  • compositions are preferably buffered, for instance at physiological pH, around 7.2.
  • the compositions may contain surfactants especially non ionic surfactants, sequestrants (eg EDTA), preservatives e.g. quaternary ammonium disinfectants, pharmaceutically active ingredients, viscosity modifiers (for instance soluble cellulosic polymers or polyvinyl pyrrolidone wetting agents (for instance polyvinylalcohol or salts), etc.
  • surfactants especially non ionic surfactants, sequestrants (eg EDTA), preservatives e.g. quaternary ammonium disinfectants, pharmaceutically active ingredients, viscosity modifiers (for instance soluble cellulosic polymers or polyvinyl pyrrolidone wetting agents (for instance polyvinylalcohol or salts), etc.
  • surfactants especially non ionic surfactants, sequestrants (eg EDTA), preservatives e.g. qua
  • the present invention provides also a sealed package containing the novel composition, which is a storage composition, and a contact lens or an ocular implant.
  • the contact lens may be a hard (gas permeable) lens or a soft lens, for instance a hydrogel or a silicone based lens, for instance a daily wear lens, an extended wear lens or a disposable lens.
  • An ocular implant may be an intraocular lens, a glaucoma filtration implant or a drug delivery gel for laying on or in the eye.
  • the container generally contains the novel composition in amounts such that the composition is not all imbibed in the contact lens or implant.
  • a contact lens is treated by contacting it with the novel aqueous compositions.
  • the method may be for cleaning, rinsing or soaking a contact lens, for instance prior to insertion or reinsertion in the eye.
  • the polymer may be adsorbed or absorbed on or in the lens upon insertion in the eye.
  • the composition may alternatively be used as comfort drops for application directly into the eye (which may contain a contact lens, or not) to alleviate the symptoms of dry eye.
  • the polymers used in the compositions, products and methods of the invention whilst being water soluble, provide a coating on the surface of a lens or implant which appears to remain adhered over a substantial period of time, for instance after reinsertion of a treated lens into the eye.
  • the coating thus provides extended periods over which there is a reduction in protein deposition, this reduction being attributed to the presence of zwitterionic groups.
  • the coatings confer improved comfort on a lens immediately after insertion and for extended periods following insertion into the eye. The improved comfort is believed to be due to improved surface wettability, improved water retention at the surface of the lens, improved lubricity, as well as reduced protein deposition and lipid deposition as compared to the untreated lens.
  • the zwitterionic groups in the polymers may also contribute to the avoidance of adverse interactions with preservatives and/or surfactants.
  • the polymers are hydrolytically stable and can be subjected to sterilising in the aqueous compositions for instance by being subjected to elevated temperatures of at least 80°C preferably at least 100°C for periods of at least 10s., preferably at least 1 min.
  • compositions of the present invention may also be useful for rinsing contact lens storage containers and contact lens soaking containers, for instance for use by the contact lens wearer following removal of a daily wear or extended wear lens.
  • the polymers coat the surfaces of such containers, thereby reducing protein deposition as well as microbial adhesion which could otherwise lead to carrying of infective microorganisms into the eye and subsequent infection.
  • compositions may also be used to store intraocular lenses or other implants, or drug delivery gels prior to insertion in the eye
  • Test sheets representative of hard lens formulations were prepared from methyl methacrylate (MMA), tristrimethylsiloxy silylpropyl methacrylate (TRIS), a hydroxy analogue and a dimer form of TRIS used as a crosslinker, methacrylic acid (MAA), and trifluoroethyl methacrylate (TFEMA).
  • MMA methyl methacrylate
  • TRIS tristrimethylsiloxy silylpropyl methacrylate
  • MAA methacrylic acid
  • TFEMA trifluoroethyl methacrylate
  • the mixture of TRIS, its hydroxy-analogue and the dimer is commercially available from Vickers as Optomer 2417.
  • 2,2'-Azoisobutyronitrile (AIBN) was used as a free radical initiator.
  • the formulation of monomers and initiator were mixed, placed between two glass plates lined with PET sheet with a PTFE spacer and then placed in an oven at 60°C for 12 hours and at 100°C for 2 hours. The sheets were then removed from the moulds and washed in water for 2 hours. All sheets were then hydrated in water for at least 7 days. Two formulations were used, one without trifluoroethyl methacrylate (the silicone RGP material) and one containing trifluoro ethylmethacrylate (the fluorosilicone RGP material).
  • the effectiveness of the soluble polymer (synthesised as described below) at imparting wettability and hydrophilicity to the surface was assessed by Dynamic Contact Angle analysis as follows. A solution of the test polymer was prepared in water at 1% w/v. The surface tension of the solution was then measured using a Cahn Instruments DCA 312 with a flame-cleaned glass slide as the solid surface; assuming a contact angle of zero, the surface tension could then be calculated.
  • Dynamic contact angles (advancing and receding) of this solution on a sample of the hydrated test sheet were then measured over 7 immersion/emersion cycles using a Cahn instruments DCA312 with a stage speed of 100 ⁇ m/s.
  • Computer analysis of the force- displacement curve yields the average contact angle for each cycle.
  • a low advancing angle, and a low hysteresis (the difference between the advancing and receding contact angle in the same cycle) in indicative of good wettability of the polymer solution on the surface.
  • test solution was then changed to water and the dynamic contact angles measured for a further 7 cycles on the same test sheet.
  • a low advancing angle, and a low hysteresis is now indicative that the polymer is strongly adsorbed onto the surface and can therefore impart hydrophilicity to the surface.
  • the test solution was then changed for fresh water and the contact angles measured for a further 7 cycles. Again, low advancing angle, and a low hysteresis is indicative of good retention of the polymer on the surface.
  • the contact angle data for each sample is attached in graphical form; for simplicity, only the advancing angle is shown and compared for each sample to a homopolymer of HEMA-PC (described in Comparative Example 1). Both advancing and receding angles are shown for the styrene HEMA-PC comparative copolymer described in comparative Example 2.
  • the title copolymer was prepared according to the following procedure. 8.6g HEMA-PC and 1.38g HFIPMA were placed in a round bottom flask equipped with a reflux condenser and 120ml of ethanol added. 0.02g AIBN were added and the solution degassed with nitrogen for 20 minutes. Then temperature was then raised to 60°C and maintained at this temperature for 48 hours. The solution was then cooled and the solvent removed under reduced pressure. The polymer was redissolved in methanol/chloroform and precipitated into acetone before drying under vacuum.
  • the polymer in aqueous solution could be sterilised without any observable change in performance.
  • the title copolymer was prepared according to the following procedure. 19.9g HEMA-PC and 3.06g HFDMA were placed in a round bottom flask equipped with a reflux condenser and 200ml of trifluoro ethanol added. 0.089g azobis(cyanovaleric acid) were added and the solution degassed with nitrogen for 20 minutes. The temperature was then raised to 60°C and maintained at this temperature for 48 hours. The solution was then cooled and the solvent removed under reduced pressure. The polymer was redissolved in methanol/chloroform and precipitated into acetone before drying under vacuum.
  • the polymers in aqueous solution can be sterilised without any observable change in performance.
  • the title copolymer was prepared according to the following procedure 21.71g of HEMA-PC was placed in a round bottom flask and dissolved in 250ml ethanol. 3.58g trimethylsilymethyl methacrylate and 0.0135g AIBN were added and the solution degassed with nitrogen for 15 minutes. The solution was then stirred at 63°C for 36 hours and the solvent removed under removed pressure. The solid was dissolved in dichloromethane/methanol (70:30) and precipitated in acetone. The precipitation step was repeated and the polymer dried under vacuum at ambient temperature. The results of the DCA analysis on the silicone and fluorosilicone materials are shown below, in Figures 5 and 6, respectively, compared to HEMA-PC homopolymer using water as a control.
  • the polymer in aqueous solution could be sterilised without any change in performance.
  • the homopolymer was prepared in a similar manner to that described in Example 1 except that only HEMA-PC was used as the polymerisable monomer. This contact angle data is included in each graph showing the data for the three hydrophobically-modified polymers.
  • a copolymer of HEMA-PC and styrene was made using the technique described in Preparation Example 3 for contact lens treatment solutions as in EP-A-0537972. It was subjected to the contact angle test (applied from aqueous solution) as described above on the two membranes on which the polymers of the invention have been tested.
  • the advancing and receding contact angles ("ACA and "RCA", respectively) are shown in Figs 7a and 7b compared to water control ("con").
  • Hydrophobically modified copolymers of a phosphoryl choline-containing methacrylate according to the invention are strongly adsorbed onto a hydrophobic surface.
  • a copolymer synthesised according to the prior art but applied to the lens using the techniques in accordance with the present invention adsorbs to a lesser extent. It provides some change in contact angle at least before replacement of the test solution by water, but adsorption appears to be weaker. Unmodified PC homopolymer is easily removed from the surface.

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  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Wood Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
  • Detergent Compositions (AREA)
  • Materials For Medical Uses (AREA)
EP97309921A 1997-12-09 1997-12-09 Kontaktlinsenreinigungslösungen Withdrawn EP0930357A1 (de)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP97309921A EP0930357A1 (de) 1997-12-09 1997-12-09 Kontaktlinsenreinigungslösungen
AU14429/99A AU1442999A (en) 1997-12-09 1998-12-09 Contact lens cleaning solutions comprising a zwitterionic copolymer
PCT/GB1998/003667 WO1999029818A1 (en) 1997-12-09 1998-12-09 Contact lens cleaning solutions comprising a zwitterionic copolymer

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP97309921A EP0930357A1 (de) 1997-12-09 1997-12-09 Kontaktlinsenreinigungslösungen

Publications (1)

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EP0930357A1 true EP0930357A1 (de) 1999-07-21

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EP (1) EP0930357A1 (de)
AU (1) AU1442999A (de)
WO (1) WO1999029818A1 (de)

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US9486311B2 (en) 2013-02-14 2016-11-08 Shifamed Holdings, Llc Hydrophilic AIOL with bonding
US10195018B2 (en) 2013-03-21 2019-02-05 Shifamed Holdings, Llc Accommodating intraocular lens
US10350056B2 (en) 2016-12-23 2019-07-16 Shifamed Holdings, Llc Multi-piece accommodating intraocular lenses and methods for making and using same
US10548718B2 (en) 2013-03-21 2020-02-04 Shifamed Holdings, Llc Accommodating intraocular lens
US10736734B2 (en) 2014-08-26 2020-08-11 Shifamed Holdings, Llc Accommodating intraocular lens
US10987214B2 (en) 2017-05-30 2021-04-27 Shifamed Holdings, Llc Surface treatments for accommodating intraocular lenses and associated methods and devices
US11141263B2 (en) 2015-11-18 2021-10-12 Shifamed Holdings, Llc Multi-piece accommodating intraocular lens
US11266496B2 (en) 2017-06-07 2022-03-08 Shifamed Holdings, Llc Adjustable optical power intraocular lenses
US12167960B2 (en) 2016-12-23 2024-12-17 Shifamed Holdings, Llc Multi-piece accommodating intraocular lenses and methods for making and using same
US12376958B2 (en) 2015-11-18 2025-08-05 Shifamed Holdings, Llc Multi-piece accommodating intraocular lens
US12521232B2 (en) 2019-07-11 2026-01-13 Shifamed Holdings, Llc Accommodating intraocular lenses and associated methods

Families Citing this family (3)

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US20110097277A1 (en) 2005-08-25 2011-04-28 University Of Washington Particles coated with zwitterionic polymers
US20080314767A1 (en) * 2007-06-22 2008-12-25 Bausch & Lomb Incorporated Ophthalmic Solutions
US20090173643A1 (en) * 2008-01-09 2009-07-09 Yu-Chin Lai Packaging Solutions

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EP0537972A1 (de) * 1991-10-14 1993-04-21 Nof Corporation Behandlungslotion für Kontaktlinsen
JPH07166154A (ja) * 1993-12-10 1995-06-27 Nippon Oil & Fats Co Ltd コンタクトレンズ用溶液

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US4075131A (en) * 1976-09-17 1978-02-21 Minnesota Mining And Manufacturing Company Conditioning shampoo
EP0112592A2 (de) * 1982-12-23 1984-07-04 THE PROCTER & GAMBLE COMPANY Zwitterionische Polymere mit Fleckenentfernungs- und Anti-Wiederabsetz-Eeigenschaften, verwendbar in Detergenszusammensetzungen
WO1993001221A1 (en) * 1991-07-05 1993-01-21 Biocompatibles Limited Polymeric surface coatings
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JPH07166154A (ja) * 1993-12-10 1995-06-27 Nippon Oil & Fats Co Ltd コンタクトレンズ用溶液

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US11540916B2 (en) 2013-02-14 2023-01-03 Shifamed Holdings, Llc Accommodating intraocular lens
US9486311B2 (en) 2013-02-14 2016-11-08 Shifamed Holdings, Llc Hydrophilic AIOL with bonding
US10350057B2 (en) 2013-02-14 2019-07-16 Shifamed Holdings, Llc Hydrophilic AIOL with bonding
US10709549B2 (en) 2013-02-14 2020-07-14 Shifamed Holdings, Llc Hydrophilic AIOL with bonding
US10195018B2 (en) 2013-03-21 2019-02-05 Shifamed Holdings, Llc Accommodating intraocular lens
US10548718B2 (en) 2013-03-21 2020-02-04 Shifamed Holdings, Llc Accommodating intraocular lens
US11583390B2 (en) 2014-08-26 2023-02-21 Shifamed Holdings, Llc Accommodating intraocular lens
US10736734B2 (en) 2014-08-26 2020-08-11 Shifamed Holdings, Llc Accommodating intraocular lens
US12251303B2 (en) 2014-08-26 2025-03-18 Shifamed Holdings, Llc Accommodating intraocular lens
US11141263B2 (en) 2015-11-18 2021-10-12 Shifamed Holdings, Llc Multi-piece accommodating intraocular lens
US12376958B2 (en) 2015-11-18 2025-08-05 Shifamed Holdings, Llc Multi-piece accommodating intraocular lens
US12376957B2 (en) 2015-11-18 2025-08-05 Shifamed Holdings, Llc Multi-piece accommodating intraocular lens
US11065109B2 (en) 2016-12-23 2021-07-20 Shifamed Holdings, Llc Multi-piece accommodating intraocular lenses and methods for making and using same
US10350056B2 (en) 2016-12-23 2019-07-16 Shifamed Holdings, Llc Multi-piece accommodating intraocular lenses and methods for making and using same
US12167960B2 (en) 2016-12-23 2024-12-17 Shifamed Holdings, Llc Multi-piece accommodating intraocular lenses and methods for making and using same
US10987214B2 (en) 2017-05-30 2021-04-27 Shifamed Holdings, Llc Surface treatments for accommodating intraocular lenses and associated methods and devices
US11266496B2 (en) 2017-06-07 2022-03-08 Shifamed Holdings, Llc Adjustable optical power intraocular lenses
US12465483B2 (en) 2017-06-07 2025-11-11 Shifamed Holdings, Llc Adjustable optical power intraocular lenses
US12521232B2 (en) 2019-07-11 2026-01-13 Shifamed Holdings, Llc Accommodating intraocular lenses and associated methods

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WO1999029818A1 (en) 1999-06-17

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