WO2017019870A1 - Non-linear polysiloxane based multifunctional branched crosslinkers - Google Patents

Non-linear polysiloxane based multifunctional branched crosslinkers Download PDF

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WO2017019870A1
WO2017019870A1 PCT/US2016/044493 US2016044493W WO2017019870A1 WO 2017019870 A1 WO2017019870 A1 WO 2017019870A1 US 2016044493 W US2016044493 W US 2016044493W WO 2017019870 A1 WO2017019870 A1 WO 2017019870A1
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another embodiment
linear polysiloxane
diol
pdms
embodiment contemplates
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PCT/US2016/044493
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French (fr)
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Li Li
Ricky Wayne GALLAGHER
Scott Curtin
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Dsm Ip Assets B.V.
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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
    • C08G77/42—Block-or graft-polymers containing polysiloxane sequences
    • C08G77/458—Block-or graft-polymers containing polysiloxane sequences containing polyurethane sequences
    • 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
    • C08F290/08—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 side groups
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/08—Processes
    • C08G18/16—Catalysts
    • C08G18/22—Catalysts containing metal compounds
    • C08G18/24—Catalysts containing metal compounds of tin
    • C08G18/244—Catalysts containing metal compounds of tin tin salts of carboxylic acids
    • C08G18/246—Catalysts containing metal compounds of tin tin salts of carboxylic acids containing also tin-carbon bonds
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/2805—Compounds having only one group containing active hydrogen
    • C08G18/2815—Monohydroxy compounds
    • C08G18/283—Compounds containing ether groups, e.g. oxyalkylated monohydroxy compounds
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/30—Low-molecular-weight compounds
    • C08G18/32—Polyhydroxy compounds; Polyamines; Hydroxyamines
    • C08G18/3203—Polyhydroxy compounds
    • C08G18/3206—Polyhydroxy compounds aliphatic
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40—High-molecular-weight compounds
    • C08G18/48—Polyethers
    • C08G18/4833—Polyethers containing oxyethylene units
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
    • C08G18/72—Polyisocyanates or polyisothiocyanates
    • C08G18/74—Polyisocyanates or polyisothiocyanates cyclic
    • C08G18/75—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic
    • C08G18/751—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing only one cycloaliphatic ring
    • C08G18/752—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing only one cycloaliphatic ring containing at least one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group
    • C08G18/753—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing only one cycloaliphatic ring containing at least one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group containing one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group having a primary carbon atom next to the isocyanate or isothiocyanate group
    • C08G18/755—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing only one cycloaliphatic ring containing at least one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group containing one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group having a primary carbon atom next to the isocyanate or isothiocyanate group and at least one isocyanate or isothiocyanate group linked to a secondary carbon atom of the cycloaliphatic ring, e.g. isophorone diisocyanate
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L83/00—Compositions of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon only; Compositions of derivatives of such polymers
    • C08L83/04—Polysiloxanes
    • 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
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G2210/00—Compositions for preparing hydrogels
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
    • C08G77/04—Polysiloxanes
    • C08G77/14—Polysiloxanes containing silicon bound to oxygen-containing groups
    • C08G77/16—Polysiloxanes containing silicon bound to oxygen-containing groups to hydroxyl groups

Definitions

  • the invention is directed to polysiloxane based multi-functional crosslinkers, methods for their production, polymerizable compositions for forming silicone hydrogels, and ophthalmic devices.
  • ophthalmic devices such as contact lenses
  • many factors must be considered to optimize the physical, chemical and biological properties. Examples of these properties include oxygen permeability, modulus, wettability, lubricity, biocompatibility, and optical quality, to name just a few.
  • silicone based materials Due to their high oxygen permeability, silicone based materials have been used extensively over the last 10 years. However, silicone is a hydrophobic material, and for this reason silicone contact lenses tend to develop a relatively hydrophobic, non-wettable surface in contact with a hydrophobic lens mold during the manufacturing. Lipids and proteins have a high tendency to deposit on a hydrophobic surface and this may affect optical clarity. Likewise, adsorption of unwanted components from the ocular tear fluid on to the lens material during wear is one of the contributory factors for causing reduced comfort experienced by patients. In addition, bacterial infections can potentially occur if lens care regimens are not followed for use of the lenses. Various methods have been used to render the contact lens surface with sustained wettability and/or lubricity.
  • One of the common practices to increase the wettability is to add an internal wetting agent such as polyvinylpyrrolidone (PVP) or to alter the surface during plasma treatment, high energy irradiation, and by applying a topical coating to obtain an extremely hydrophilic surface.
  • PVP polyvinylpyrrolidone
  • Plasma treatment can be effective for silicone hydrogel contact lenses, but it is costly and time consuming to use this approach.
  • Topical coating can effectively alter the surface properties, but also introduces an additional step in manufacturing and is often complex in nature.
  • the oxygen permeability (Dk) is another important factor in contact lens design to maintain corneal health for contact lens wearers.
  • Holden and Mertz concluded that 24.1 Barrer/cm (Dk/t, t is the thickness of contact lens) was the oxygen transmissibility requirement for daily wear, and a minimum of 87 Barrer/cm is required for overnight wear to limit overnight edema to 4%. Further findings by Harvitt and Bonanno suggested that the minimum oxygen transmissibility required to avoid anoxia was 35 Barrer/cm for the open eye and 125 Barrer/cm for the closed eye.
  • Conventional hydrogels on the average have the Dk in the range of 8-40 Barrer depending on the water content. Physical properties such as oxygen flux (j), oxygen permeability (Dk), and oxygen
  • Oxygen flux can be defined as a volume of oxygen passing through a specified area of a contact lens over a set amount of time.
  • the physical units of oxygen flux can be described as microliters 0 2 (cm 2 sec).
  • Oxygen permeability can be defined as the amount of oxygen passing through a contact lens material over a set amount of time and pressure difference. Physical units of oxygen permeability can be described as 1
  • Oxygen transmissibility can be defined as the amount of oxygen passing through a contact lens of specified thickness over a set amount of time and pressure difference.
  • the physical units of oxygen transmissibility can be defined as 10 9 (cm ml 0 2 )/(ml sec mmHg).
  • Oxygen transmissibility relates to a lens type with a particular thickness.
  • Oxygen permeability is a material specific property that can be calculated from lens oxygen transmissibility.
  • Existing silicone hydrogel contact lenses have a modulus from between about 0.4 to about 1.5 MPa.
  • AIROPTIXTM Night & Day contact lens has a modulus of about 1.5 MPa (Dk is 140 Barrer)
  • the Pure VisionTM contact lens has a modulus of about 1.1 MPa (Dk is 99 Barrer)
  • the Air OptixTM has a modulus of about 1.0 MPa (Dk is 110 Barrer)
  • the PremiOTM contact lens has a modulus of about 0.9 (Dk is 129 Barrer)
  • the AcuvueTM advance contact lens has a modulus of about 0.4 MPa (Dk is 60 Barrer)
  • the Acuvue OasysTM contact lens has a modulus of about 0.72 MPa (Dk is 103 Barrer).
  • the increased modulus makes these materials easier to handle and more durable, but the initial comfort of the lens may be reduced and some patients notice greater lens awareness.
  • Lenses possessing a higher modulus necessitate a greater degree of precision in fitting than would otherwise be necessary for lenses having a low modulus.
  • a lens with a higher modulus is less likely to conform to the eye curvature.
  • Another significant problem with high modulus materials is several ocular complications that can arise as a result of mechanical irritation, particularly when worn in an extended wear modality.
  • a very low modulus can be a disadvantage as well when trying to achieve optimum vision, it also means that the lens material has poor handling characteristics and reduced durability.
  • non-linear polysiloxane based multifunctional branched crosslinker of structure is a non-linear polysiloxane based multifunctional branched crosslinker of structure:
  • (X) represents (X) friendship-S wherein the branching point S is derived from multifunctional alcohols or polyols, multifunctional amines or polyamines, or multifunctional thiols or polythiols, and which have a functionality m of 3 or greater and wherein m is equal to or greater than n; wherein X can be the same or different and is selected from the group consisting of formulae (S-I), (S-II), (S-III), (S-IV), or (S-V), wherein said formulae possess the following structures: -[I-PDMS]z-I-[[F-[I-PDMS]r]p-I- (S-I)
  • I is a unit derived from a diisocyanate
  • PDMS is a unit derived from a polydialkyl or polydiaryl or polyalkylaryl siloxane diol
  • F is a diol, diamine, or dithiol derived unit comprising at least one pendant oligomeric or polymeric group
  • p is an integer ranging from 1 to 50
  • r is an integer ranging from 1 to 50
  • z is an integer ranging from 1 to 50
  • at least three of the terminal diisocyanates I have been reacted with an ethylenically unsaturated monofunctional monomer, and wherein the total number average molecular weight is less than 100,000 Dalton and has a viscosity less than 1,000,000 mPa sec, and wherein there are substantially no remaining unreacted isocyanates in the branched crosslinker; or of structure: wherein the branching point T is derived from a multifunctional isocyanate with a functionality m of 3 or greater
  • I is a unit derived from a diisocyanate
  • PDMS is a unit derived from a polydialkyl or polydiaryl or polyalkylaryl siloxane diol
  • F is a diol, diamine, or dithiol derived unit comprising at least one pendant oligomeric or polymeric group
  • p is an integer ranging from 1 to 50
  • r is an integer ranging from 1 to 50
  • z is an integer ranging from 1 to 50, wherein at least three of the terminal hydroxyls have been reacted with the mono adduct of a diisocyanate and an ethylenically
  • non-linear polysiloxane based multifunctional branched crosslinkers methods for the production of the non-linear polysiloxane based multifunctional branched crosslinkers, polymerizable compositions comprising the non-linear polysiloxane based multifunctional branched crosslinkers, silicone hydrogel polymers formed by polymerizing polymerizable compositions comprising the non-linear polysiloxane based multifunctional branched crosslinkers, methods of manufacturing silicone hydrogel polymers formed from polymerizable compositions comprising the non-linear polysiloxane based multifunctional branched crosslinkers, and ophthalmic devices.
  • an “ophthalmic device”, as used herein, refers to a contact lens (hard or soft), an intraocular lens, a corneal inlay, corneal onlay, overlay lenses, ocular inserts, optical inserts, spectacle lenses, goggles, surgical glasses, other ophthalmic devices (e.g., stents, glaucoma shunt, or the like) used on or about the eye or ocular vicinity.
  • Contact Lens refers to a structure that can be placed on or within a wearer's eye. A contact lens can correct, improve, or alter a user's eyesight, but that need not be the case.
  • a contact lens can be of any appropriate material known in the art or later developed, and can be a soft lens, a hard lens, or a hybrid lens.
  • a “silicone hydrogel contact lens” refers to a contact lens comprising a silicone hydrogel material.
  • a "polymer” means a material formed by polymerizing/crosslinking one or more vinylic monomers, macromers, crosslinkers and/or prepolymers.
  • oligomer describes a compound intermediate between a monomer and a polymer, having a specified number of units between about five and a hundred, an oligomer consists of fewer monomer units than a polymer.
  • a “hydrogel” or “hydrogel material” refers to a water insoluble, crosslinked, three-dimensional networks of polymer chains plus water that fills the voids between polymer chains.
  • a “hydrogel” or “hydrogel material” can absorb at least 10 percent by weight of water when it is fully hydrated.
  • silicone hydrogel refers to a silicone-containing hydrogel obtained by copolymerization of a polymerizable composition comprising at least one silicone-containing vinylic monomer
  • Hydrophilic as used herein, describes a material or portion thereof that will more readily associate with water than with lipids.
  • Hydrophilic as used herein, describes a material or portion thereof that will more readily associate with lipids than with water.
  • a “pendant group” is generally a group of molecules arranged in linear or branched
  • a “monomer” refers to a compound that can be polymerized chemically, actinically or thermally.
  • a “modulus modifier” refers to a monomer, macromer, prepolymer, or crosslinker which improves the modulus, and/or tear strength of the resulting cured polymer such that it achieves an acceptable level of modulus and tear resistance in the resulting contact lens or ophthalmic device.
  • a “prepolymer” refers to a higher molecular weight oligomeric molecule that is typically the reaction product of a polyol, at least one linking moiety to that polyol, and at least one ethylenically unsaturated groups and can be polymerized actinically or thermally to form a polymer having a molecular weight larger than the starting prepolymer. This is sometimes alternately referred to as an "oligomer”. As used herein, "prepolymer” and “oligomer” are used interchangeably.
  • “Dry gas” means a gas that contains less than 0.01% humidity.
  • Inert gas means an essentially non-reactive gas, such as nitrogen or argon.
  • a "vinylic monomer”, as used herein, refers to a monomer that has at least one ethylenically unsaturated group and can be polymerized actinically or thermally.
  • actinically in reference to curing, crosslinking or polymerizing of a polymerizable composition, a prepolymer or a material means that the curing (e.g., crosslinked and/or polymerized) is performed by actinic irradiation, such as, for example, UV irradiation, ionizing radiation (e.g. gamma ray or X-ray irradiation), microwave irradiation, and the like.
  • actinic irradiation such as, for example, UV irradiation, ionizing radiation (e.g. gamma ray or X-ray irradiation), microwave irradiation, and the like.
  • a “crosslinker” refers to a compound having at least two ethylenically-unsaturated groups.
  • a “crosslinking agent” refers to a compound which belongs to a subclass of crosslinkers and comprises at least two ethylenically unsaturated groups and has a molecular weight of 700 Daltons or less.
  • a “multifunctional crosslinker” refers to a crosslinker that contain more than two ethylenically- unsaturated groups.
  • a “photoinitiator” refers to a chemical that initiates free radical crosslinking/polymerizing reaction by the use of light.
  • thermo initiator refers to a chemical that initiates radical crosslinking/polymerizing reaction by the use of heat energy.
  • Molecular weight of a polymeric material refers to the number-average molecular weight unless otherwise specifically noted or unless testing conditions indicate otherwise.
  • non-linear polysiloxane refers to a polysiloxane that contains at least one branching point in the siloxane main chain such that there are at least three polysiloxane arms contained within that siloxane main chain.
  • a "hydrophilic surface" in reference to a silicone hydrogel material or a contact lens means that the silicone hydrogel material or the contact lens has a surface hydrophilicity characterized by having an averaged water contact angle of about 100 degrees or less, preferably about 90 degrees or less, more preferably about 80 degrees or less, more preferably about 70 degrees or less.
  • An “contact angle” refers to a water contact angle (measured by Sessile Drop method), which is obtained by averaging measurements of at least 3 individual contact lenses.
  • “Fully hydrated” means the maximum amount of water retained in the cured polymer after the polymer has been rinsed thoroughly to remove unreacted components and, thereafter, soaked in a water bath.
  • a “viscosity” means a measurement of liquid flowability under force using the ASTM D1545 "Standard Test Method for Viscosity of Transparent Liquids by Bubble Time Method” and converting from stokes to mPa sec.
  • oxygen permeability in reference to a contact lens means an estimated intrinsic oxygen permeability Dk, which is corrected for the surface resistance to oxygen flux caused by the boundary layer effect as measured according to the procedures described in Example 1.
  • the intrinsic "oxygen permeability", Dk, of a material is the rate at which oxygen will pass through a material. Oxygen permeability is conventionally expressed in units of Barrer, where "Barrer” is defined as [(cm 3 oxygen)(mm)/(cm 2 )(sec)(mm Hg)] x 10 ⁇ 10 .
  • the "oxygen transmissibility", Dk/t, of a lens or material is the rate at which oxygen will pass through a specific lens or material with an average thickness of t [in units of mm] over the area being measured.
  • Oxygen transmissibility is conventionally expressed in units of Barrer/mm, where "Barrer/mm” is defined as [(cm 3 oxygen)/(cm 2 )(sec)(mm Hg)] x 10 ⁇ 9 .
  • branching point S is derived from multifunctional alcohols or polyols, multifunctional amines or polyamines, or multifunctional thiols or polythiols, and which have a functionality m of 3 or greater and wherein m is equal to or greater than n; wherein X can be the same or different and is selected from the group consisting of formulae (S-I), (S-II), (S-III), (S-IV), or (S-V), wherein said formulae possess the following structures:
  • I is a unit derived from a diisocyanate
  • PDMS is a unit derived from a polydialkyl or polydiaryl or polyalkylaryl siloxane diol
  • F is a diol, diamine, or dithiol derived unit comprising at least one pendant oligomeric or polymeric group
  • p is an integer ranging from 1 to 50
  • r is an integer ranging from 1 to 50
  • z is an integer ranging from 1 to 50
  • at least three of the terminal diisocyanates I have been reacted with an ethylenically unsaturated monofunctional monomer, and wherein the total number average molecular weight is less than 100,000 Dalton and has a viscosity less than 1,000,000 mPa sec, and wherein there are substantially no remaining unreacted isocyanates in the branched crosslinker;
  • I is a unit derived from a diisocyanate
  • PDMS is a unit derived from a polydialkyl or polydiaryl or polyalkylaryl siloxane diol
  • F is a diol, diamine, or dithiol derived unit comprising at least one pendant oligomeric or polymeric group
  • p is an integer ranging from 1 to 50
  • r is an integer ranging from 1 to 50
  • z is an integer ranging from 1 to 50, wherein at least three of the terminal hydroxyls have been reacted with the mono adduct of a diisocyanate and an ethylenically unsaturated monofunctional monomer, and wherein the total number average molecular weight is less than 100,000 Dalton and has a viscosity less than 1,000,000 mPa sec, and wherein there are substantially no remaining unreacted isocyanates in the branched cross
  • the pendant oligomeric or polymeric groups may be hydrophilic groups.
  • PDMS is a unit derived from an alkoxylated polydialkyl or polydiaryl or polyalkylaryl siloxane diol.
  • F is a diol derived unit.
  • the pendant hydrophilic oligomeric or polymeric groups may be polyethylene oxide (PEO) groups.
  • the pendant hydrophilic oligomeric or polymeric groups may be poly(2- oxazoline) groups.
  • the diol, diamine, or dithiol derived unit comprising at least one pendant oligomeric or polymeric group may have a Number average molecular weight Mn ranging from 300-5000 g/mol, as determined by Gel Permeation Chromatography using N, N-dimethylformamide (DMF) as the solvent at 53°C.
  • the backbone may contain units derived from polydimethylsiloxane diol and units derived from diisocyanate.
  • the diisocyanate units may be isophorone diisocyanate (IPDI).
  • the reactive double bond at a terminal end may be obtained by reacting hydroxyethylmethacrylate (HEMA).
  • HEMA hydroxyethylmethacrylate
  • the number average molecular weight of the total crosslinker may range from
  • non-linear polysiloxane based multifunctional branched crosslinker (hereinafter “non-linear multifunctional polysiloxane branched crosslinker”), comprises a double bond located at at least three terminal ends of the non-linear multifunctional polysiloxane branched crosslinker. Terminal ends are the ends of the polymeric chain of the non-linear multifunctional polysiloxane branched crosslinker.
  • the end groups can be the same or different.
  • the non-linear multifunctional polysiloxane branched crosslinker may be used as non-linear multifunctional polysiloxane branched crosslinkers in contact lens formulations and therefore the non-linear multifunctional polysiloxane branched crosslinker comprises reactive groups that can react with the other constituents of the contact lens formulation.
  • the end groups are reactive groups that contain at least one reactive double bond.
  • the double bond can, for example, be formed by an acryl or methacryl group and is formed on the ends of the polymeric chain by reaction of an isocyanate group with, for example, hydroxy acrylate, methacrylate or acrylamide.
  • HEMA hydroxyethyl methacrylate
  • a diol, diamine, or dithiol derived unit comprising at least one pendant hydrophilic oligomeric or polymeric group may separate the polysiloxane segments.
  • the diol, diamine, or dithiol derived unit may be derived from a diol or is the reaction product of a diol and contains a pendant oligomeric or polymeric group.
  • the hydroxyl groups of the diol may be reacted with the isocyanate units to form urethane bonds.
  • Suitable diols for use in the reaction may include a wide variety of diols comprising at least one pendant oligomeric or polymeric group.
  • the structure where the pendent group is attached to is typically referred to as "the backbone".
  • the diols used to provide the unit derived from a diol comprising at least one pendent oligomeric or polymeric group may for example have a butane diol, polycarbonate diol, hexane diol, or propane diol back bone, and the backbone comprises at least one pendent oligomeric or polymeric group.
  • a pendant group or a side group is generally a group of molecules arranged in linear or branched conformations and attached to the backbone polymer chain.
  • the pendant oligomeric or polymeric group in "F” unit is preferably a hydrophilic group.
  • the pendant oligomeric or polymeric group is a group that does not comprise any chemical moieties that may react with the diisocyanate used in the preparation of the non-linear multifunctional polysiloxane branched crosslinker under the reaction conditions applied in the synthesis of the crosslinker.
  • oligomeric or polymeric it is indicated that the pendant group comprises a unit that is repeated at least 2 times, but that may be repeated up to 75 times.
  • the pendant group may comprise the unit -(- C 2 H 4 -O-), from 2 up to and including 75 times. Other repeating units may also be present from 2-75 times.
  • the pendant oligomeric or polymeric group is a polyalkylene oxide.
  • the polyalkylene oxides may be linear or branched, cycloaliphatic, or aliphatic-cycloaliphatic, optionally containing one or more linkages of -S-, -C(O)-, or -NR-, wherein R is H or CI to C30 alkyl.
  • Examples of polyalkylene oxides are poly(ethylene glycol)(PEG), poly(propylene glycol), polyethylene oxide (PEO), poly(tetramethylene ether) glycol, and their monoalkyl-substituted derivatives.
  • the pendant oligomeric or polymeric groups comprise pendant oligomeric or polymeric oxyalkylene groups, such as poly(ethylene glycol) (PEG), poly(propylene glycol (PPG), and polyethylene oxide (PEO) comprising groups, copolymers thereof and their monoalkyl-substituted derivatives.
  • the pendant group comprises a polyethylene oxide (PEO) oligomer or polymer. More preferably, the pendant groups consists of a polyethylene oxide (PEO) oligomer or polymer.
  • poly(ethlyene glycol) refers to the same chemical component and these terms can be used in the prior art and this description when referring to the same component.
  • a diol comprising a pendant poly(ethylene glycol) group may be generally referred to as "PEG diol”.
  • PEG diol may include YmerTM N120, supplied by Perstorp or TegomerTM D 3404 supplied by Evonik, both commercial products comprise PEG(7)-2-ethylpropanel,3,diol.
  • the pendant oligomeric or polymeric groups comprise a polymethyl oxazoline or polyethyl oxazoline group, or a copolymer thereof.
  • a suitable diol comprising a polyethyl oxazoline group is shown in the figure below.
  • An amine diol used in synthesis of the diol comprising a pendant a polymethyl oxazoline or polyethyl oxazoline group, or a copolymer thereof may be any dihydroxy secondary amine bearing moiety that is aliphatic or cyclo aliphatic.
  • the pendant group comprising a polymethyl oxazoline or polyethyl oxazoline group, or a copolymer thereof preferably has a number average molecular weight ranging from 300 to 5000 g/mol. In an embodiment, the pendant group has a molecular weight of from 400 to 2500 g/mol.
  • the diol, diamine, or dithiol from which the unit comprising a pendant oligomeric or polymeric group has been derived preferably has a Mw ranging from 300-5000 g/mol, as determined by Gel Permeation Chromatography using ⁇ , ⁇ -dimethyl formamide (DMF) as the solvent at 80°C using polystyrene standards.
  • the backbone of the non-linear multifunctional polysiloxane branched crosslinker may contain polysiloxane units derived from polydimethylsiloxane diol and units derived from diisocyanate. In the present instance, the uses of diisocyanate units and results of using diisocyanate units to obtain a urethane bond are generally well understood.
  • the diisocyanate units can comprise aromatic or aliphatic
  • the diisocyanates may be selected from the group comprising alkyl diisocyanates, arylalkyl diisocyanates, cycloalkylalkyl diisocyanates, alkylaryl diisocyanates, cycloalkyl diisocyanates, aryl diisocyanates, cycloalkylaryl diisocyanates, and mixtures thereof.
  • diisocyanates are isophorone diisocyanate, hexane diisocyanate, 1 ,4- diisocyanatocyclohexane, lysine-diisocyanate, naphthalene diisocyanate, 4,4'-diphenylmethane diisocyanate, 2,2'-Methylenediphenyl diisocyanate, hexamethylene diisocyanate, 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, hexamethylene- 1 ,6-diisocyanate, tetramethylene-1 ,4-diisocyanate,
  • naphthalene- 1 ,5-diisocyanate naphthalene- 1 ,5-diisocyanate, xylylene diisocyanate, dicyclohexylmethane-4,4-diisocyanate, 1 ,4- benzene diisocyanate, 3,3'-diethoxy-4,4-diphenyl diisocyanate, m-phenylene diisocyanate, polymethylene polyphenyl diisocyanate, O-tolidine Diisocyanate, 2,4,6-triisopropyl-m-phenylene diisocyanate, 4- isocyanatocyclo-4 ' -isocyanate, and mixtures thereof.
  • IPDI isophrone diisocyanate
  • the backbone of the non-linear multifunctional polysiloxane branched crosslinker may contain polysiloxane units derived from a polydimethylsiloxane diol.
  • Polydimethylsiloxane (PDMS) is a siloxane unit according to the below formula:
  • Ri, R 2 , R3, R4, R5, and Rg may be the same or different and are selected from alkyl groups having 1 to 16 carbons or alkyloxy groups having 1 to 16 carbons, substituted and unsubstituted aromatic groups, and R7 and R8 are a bond or a divalent alkylene groups having 1 to 16 carbons or alkyleneoxy groups having 1 to 16 carbons and wherein p is an integer ranging from 1-25.
  • Ri, R2, R3, R4, R5, and Rg preferably are an alkyl group having from 1-4 carbons, most preferably they are methyl groups.
  • the preparation of the non-linear multifunctional polysiloxane branched crosslinker the siloxane unit originates form a diol siloxane compound.
  • a diol siloxane compound contains silicone which may be derived from the group comprising: linear or branched polysiloxane, polysiloxane substituted with alkyl, cycloalkyl or phenyl group, cage-like polysiloxane.
  • the number average molecular weight of the total non-linear multifunctional polysiloxane branched crosslinker is from 8,000 to 55,000 g/mol, preferably from 15,000 to 30,000 g/mol and more preferably from 17,000 to 27,000 g/mol as determined by Gel Permeation Chromatography using N,N- dimethyl formamide (DMF) as the solvent at 80°C and using polystyrene standards.
  • DMF N,N- dimethyl formamide
  • a diisocyanate may be reacted with a siloxane unit (preferably a polysiloxane diol) under an inert and/or dry gas at elevated temperature.
  • a siloxane unit preferably a polysiloxane diol
  • the maximum exothermic temperature is preferably less than 80°C to eliminate secondary reactions affecting the molecular weight and/or functionality of the resultant intermediate. More preferably the temperature is less than 75 °C.
  • the minimum temperature is generally 40°C, and the actual temperature is preferably about 55°C.
  • a catalyst may be included in the diisocyanate-siloxane mixture.
  • exemplary catalysts include organometallic compounds based on mercury, lead, tin (dibutyltin dilaurate), bismuth (bismuth octanoate), and zinc or tertiary amines such as triethylenediamine (TED A, also known as 1 ,4- diazabicyclo[2.2.2]octane or DABCO, an Air Products's trade mark), dimethylcyclohexylamine
  • DMCHA dimethylethanolamine
  • DMEA dimethylethanolamine
  • the amounts of a catalyst is in the range of 0.01-20 wt% of the total weight of the formulation.
  • One embodiment contemplates 0.01 - 1 wt%.
  • One embodiment contemplates 1-2 wt%.
  • Another embodiment contemplates 2-3 wt%.
  • Another embodiment contemplates 3-4 wt%.
  • Another embodiment contemplates 4-5 wt%.
  • Another embodiment contemplates 5-6 wt%.
  • Another embodiment contemplates 6-7 wt%.
  • Another embodiment contemplates 7-8 wt%.
  • Another embodiment contemplates 8-9 wt%.
  • Another embodiment contemplates 9-10 wt %.
  • Another embodiment contemplates 10-1 1 wt %.
  • diisocyanate-siloxane-diisocyanate mixture is reacted with one or more diols, diamines or dithiols comprising at least one pendant oligomeric or polymeric group, which pendent group typically comprises or is an oligomeric or polymeric polyalkylene oxides, mixtures thereof, copolymers thereof and/or their monoalkyl-substituted derivatives (for ease of use below, referred to as "diol with pendant group").
  • the diol, diamine, or dithiol with pendant group polymerizes with the diisocyanate-siloxane- diisocyanate intermediate under stirring, followed by addition of a catalyst to form a pre-polymer.
  • the maximum exothermic temperature is preferably less than 80°C. More preferably the temperature is less than 75°C.
  • the minimum temperature is generally 40°C, and the actual temperature is preferably about 55°C.
  • the pre-polymer is sparged with dry gas and reacted with and end-group forming compound, such as HEMA (hydroxyethyl methacrylate) and a catalyst.
  • end-group forming compound such as HEMA (hydroxyethyl methacrylate) and a catalyst.
  • the temperature for this reaction is at least 20°C and preferably 35°C and the maximum temperature is less than 50°C to eliminate auto
  • the amount of siloxane unit may range from 1-99% by weight of the total weight of the siloxane unit and the "diol with pendent group" in the composition.
  • Another embodiment contemplates 94-95 wt%. Another embodiment contemplates 95-96 wt%. Another embodiment contemplates 96-97 wt%. Another embodiment contemplates 97-98 wt%. Another embodiment contemplates 98-99 wt%.
  • the amount of "diol with pendent group” may range from 1-99% by weight of the total weight of siloxane unit and the "diol with pendent group” in the composition.
  • One embodiment contemplates 1-2 wt%. Another embodiment contemplates 2-3 wt%. Another embodiment contemplates 3-4 wt%. Another embodiment contemplates 4-5 wt%. Another embodiment contemplates 5-6 wt%. Another embodiment contemplates 6-7 wt%. Another embodiment contemplates 7-8 wt%. Another embodiment contemplates 8-9 wt%. Another embodiment contemplates 9-10 wt %. Another embodiment contemplates 10-11 wt %.
  • Another embodiment contemplates 91-92 wt%. Another embodiment contemplates 92- ⁇ 93 wt%. Another embodiment contemplates 93-94 wt%. Another embodiment contemplates 94. ⁇ 95 wt%. Another embodiment contemplates 95-96 wt%. Another embodiment contemplates 96- ⁇ 97 wt%. Another embodiment contemplates 97-98 wt%. Another embodiment contemplates 98- ⁇ 99 wt%.
  • urethane bonds are formed through (or derived from) a reaction of an -OH group and an isocyanate group.
  • a diol is reacted with a diisocyanate, resulting in a polymer comprising multiple urethane bonds.
  • the ratio of the diol versus the diisocyanate one can synthesize polyurethanes with either -OH groups at the two ends of the polyurethane polymer or isocyanate groups at the two ends of the polyurethane polymer.
  • the reaction may be carried out with a diol comprising at least one oligomeric or polymeric group or a siloxane diol with the desired diisocyanate.
  • non-linear polysiloxane based multifunctional branched crosslinker has the formula (X) n -S
  • multifunctional alcohols or polyols, multifunctional amines or polyamines, or multifunctional thiols or polythiols are added to the reaction mixture at any stage of the above reaction process.
  • triols and tetraol are glycerol, 1,2,6-Hexanetriol, l, l, l-Tris(hydroxymethyl)propane, pentane-l,2,3-triol, propane- 1, 1, 1-triol, cyclohexane- l,2,4-triol, cyclopropane-l,2,3-triol , benzenetriol, cyanuric acid, pentane- l, l,5,5-tetraol, hexane-l,2,5,6-tetraol, 1,2,4,5-tetrahydroxybenzene, butane- 1 ,2, 3,4-tetraol, [1, 1 '-biphenyl] -3 ,3 ',5 ,5 '-tetraol.
  • an isocyanate having a functionality of three or greater is added to the reaction mixture at any stage of the above reaction process.
  • triisocyanate and tetraisocyanate are methylidynetri-p-phenylene triisocyanate, undecane- 1 ,6, 1 1 -triyl triisocyanate, silicon tetraisocyanate.
  • a method of production of the non-linear polysiloxane based multi-functional cross-linker comprises the steps of: a. reacting a diisocyanate with one or more polysiloxane diols under an inert gas at elevated temperature in the presence of a catalyst to form an intermediate; b. reacting said intermediate with one or more diols comprising at least one pendant hydrophilic oligomeric or polymeric group, under a dry gas in the presence of a catalyst to form a polymer; c. reacting said polymer with a compound having at least one reactive double bond in the presence of a catalyst under a dry gas; and d.
  • a method of production of the non-linear polysiloxane based multi-functional cross-linker comprises the steps of: a. reacting a diisocyanate with one or more diols comprising at least one pendant hydrophilic oligomeric or polymeric group under an inert gas at elevated temperature in the presence of a catalyst to form an intermediate; b. reacting said intermediate with one or more polysiloxane diols, under a dry gas with stirring in the presence of a catalyst to form a polymer; c. reacting said polymer with a compound having at least one reactive double bond in the presence of a catalyst under a dry gas; and d.
  • glycerol, 1,2,6-Hexanetriol, or l, l, l-Tris(hydroxymethyl)propane is added to the reaction mixture at any stage of the above reaction process.
  • the amount of siloxane units is from 1 to 99% by weight of the total weight of the polysiloxane diol and the diol comprising at least one pendant oligomeric or polymeric group in the composition, and the amount of the diol comprising at least one pendant oligomeric or polymeric group is from 1 to 99% by weight of the total weight of the polysiloxane diol and the diol comprising at least one pendant oligomeric or polymeric group in the composition.
  • the non-linear polysiloxane based multifunctional branched crosslinkers may be used in polymerizable compositions to make ophthalmic devices, such as contact lenses.
  • ophthalmic devices such as contact lenses.
  • non-linear polysiloxane based multifunctional branched crosslinkers such as
  • polymerizable composition may comprise:
  • the hydrophilic monomers may be N,N- dimethylacrylamide (DMA), 2-hydroxyethylmethacrylate (HEMA), and mixtures thereof.
  • the polysiloxane vinylic monomers may be mono-methacryloxypropyl terminated polydimethylsiloxane, where the number average molecular weight of the silicone-containing monomer is from 600 to 800g/mol as determined by NMR.
  • the polymerizable composition may comprise isobornyl methacrylate.
  • the polymerizable composition to form a silicone hydrogel polymer can comprise at least one hydrophilic monomer, macromer, or prepolymer.
  • hydrophilic monomers, macromers, or prepolymers include N,N-dimethylacrylamide (DMA), 2-hydroxyethylmethacrylate (HEMA), N,N- dimethylmethacrylamide (DMMA), 2-acrylamidoglycolic acid, 3-acryloylamino-l-propanol, N- hydroxyethyl acrylamide, N-[tris(hydroxymethyl)methyl]-acrylamide, N-methyl-3-methylene-2- pyrrolidone, l-ethyl-3-methylene-2-pyrrolidone, l-methyl-5-methylene-2-pyrrolidone, l-ethyl-5- methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-n- propyl-3-
  • the polymerizable composition to form the silicone hydrogel polymer can comprise a polysiloxane vinylic monomer, macromer, or prepolymer. Examples includes those described in U.S. Pat Nos. 471 1943, 5070215, 5998498, 7071274, 71 12641 which are herein incorporated by reference in their entirety.
  • Polysiloxane vinylic monomers include without limitation: a silicon-containing vinyl carbonate monomer, a silicon-containing vinyl carbamate monomer, a monomethacryloxypropyl terminated polydimethylsiloxane monomer, a monomethacryloxypropyl terminated mono-n-butyl terminated polydimethyl siloxane monomer, and any combination thereof.
  • the polysiloxane vinylic monomers may be TRIS (3 -[tris(trimethylsilyloxy)silyl] -propyl methacrylate).
  • the polysiloxane vinylic monomers may be SIGMA methyl bis(trimethylsiloxy)silyl propyl glycerol methacrylate.
  • the polysiloxane vinylic monomers may be mono- methacryloxypropyl terminated polydimethylsiloxane, where the number average molecular weight of the silicone-containing monomer is ranging from 600 to 800g/mol as determined by NMR.
  • the polymerizable composition to form the silicone hydrogel polymer may comprise a modulus modifier.
  • modulus modifiers include without limitation: isobornyl methacrylate, isobornyl acrylate, dicyclopentandienyl acrylate, dicyclopentadienyl methacrylate, adamantanyl acrylate, adamantyanyl methacrylate, isopinocamphyl acrylate, isopinocamphyl methacrylate, and combination thereof.
  • the polymerizable composition to form the silicone hydrogel polymer may comprise a free radical initiator.
  • a free radical initiator can be either a photoinitiator or a thermal initiator. Suitable photoinitiators include, without limitation, benzoin methyl ether, diethoxyacetophenone, a
  • benzoylphosphine oxide 1, -hydroxy cyclohexyl phenyl ketone, Darocure® types of photoinitiators, and Irgacure® types of photoinitiators, preferably Darocure® 1 173, and Irgacure® 2959.
  • benzoylphosphine oxide initiators include 2,4,6-trimethylbenzoyldiphenylophosphine oxide (TPO); bis- (2,6-dichlorobenzoyl)-4-N-propylphenylphosphine oxide; and bis-(2,6-dichlorobenzoyl)-4-N- butylphenylphosphine oxide.
  • Reactive photoinitiators which can be incorporated, for example, into a prepolymer or can be used as a special monomer are also suitable.
  • reactive photoinitiators are those disclosed in EP 632 329, herein incorporated by reference in its entirety.
  • the polymerization can then be triggered off by actinic radiation, for example light, in particular UV light of a suitable wavelength.
  • actinic radiation for example light, in particular UV light of a suitable wavelength.
  • the spectral requirements can be controlled accordingly, if appropriate, by addition of suitable photosensitizers.
  • thermal initiators examples include, but are not limited to, 2,2'- azobis(2,4-dimethylpentanenitrile), 2,2'-azobis(2-methylpropanenitrile), 2,2'-azobis(2- methylbutanenitrile), peroxides such as benzoyl peroxide, and the like.
  • the thermal initiator is 2,2 '-azobis(isobutyronitrile) (AIBN) .
  • the polymerizable composition to form the silicone hydrogel polymer can comprise a solvent.
  • suitable solvents includes without limitation, water, alcohols (such as t-amyl alcohol, ethanol, 2-butanol, 1-propanol, 2-propanol, cyclohexanol etc.), tetrahydroiuran, ethyl acetate, dimethyl formamide, diethylene glycol methyl ether, acetone, methyl ethyl ketone, polyethylene glycols, methylene chloride, and mixtures thereof.
  • alcohols such as t-amyl alcohol, ethanol, 2-butanol, 1-propanol, 2-propanol, cyclohexanol etc.
  • tetrahydroiuran ethyl acetate
  • dimethyl formamide diethylene glycol methyl ether
  • acetone methyl ethyl ketone
  • polyethylene glycols methylene chloride, and mixtures thereof.
  • the polymerizable composition when activated in the presence of an ultraviolet source or under heat in the presence of one or more photoinitiators or thermal initiators, the polymerizable composition forms a crosslinked silicone hydrogel polymer.
  • a silicone hydrogel polymer is formed from the polymerizable composition.
  • the silicone hydrogel polymer have a relatively higher Dk and a relatively lower modulus compared to most existing silicone hydrogel contact lenses.
  • the present silicone hydrogel polymer may have a Dk of at least about 100 or at least 120 Barrer or at least about 130 Barrer or at least about 150 Barrer or at least about 200 or more Barrer, such as up to about 250 Barrer or about 300 Barrer or more, and the modulus of about 0.2 MPa or about 0.4 MPa to about 0.8 MPa or less than 1.0 MPa.
  • One example of a silicone hydrogel polymer has a Dk greater than about 100 Barrer and a modulus from about 0.3 MPa to less than about 0.8 MPa or less than 1.0 MPa.
  • the present silicone hydrogel polymer have a Dk of about 100 and a modulus of about 0.4 MPa. In other embodiments, the present silicone hydrogel polymer have a Dk of about 200 and a modulus of about 0.8 MPa. In yet another embodiment, the present silicone hydrogel polymer have a Dk of about 150 Barrer and a modulus of about 0.8 MPa.
  • the existing, commercially available Acuvue Advance contact lens has a modulus of about 0.4 MPa and a Dk of about 60.
  • the existing commercially available AIROPTIX Night & Day contact lens has a modulus of about 1.5 and a Dk of about 140.
  • a silicone hydrogel polymer formed from the polymerizable composition is transparent, and has when fully hydrated, an oxygen permeability of at least 100 Barrer, or a modulus from about 0.2 MPa to about 1.0 MPa, or any combination thereof.
  • the silicone hydrogel polymer is transparent and has a contact angle less than 120°, a modulus from about 0.2 MPa to about 1.0 MPa, and an oxygen permeability of more than about 100 Barrer.
  • the silicone hydrogel polymer is transparent and has a contact angle less than 1 10°, a modulus from about 0.2 MPa to about 0.8 MPa, and an oxygen permeability of more than about 1 10 Barrer. In certain embodiments, the silicone hydrogel polymer is transparent and has a contact angle less than 1 10° a modulus from about 0.2 MPa to about 0.5 MPa, and an oxygen permeability of more than about 1 10 Barrer.
  • a method of manufacturing a silicone hydrogel polymer comprises the steps of: i) introducing a lens formulation into a mold for making contact lenses, wherein the lens-forming formulation comprises
  • ophthalmic devices such as silicone hydrogel contact lenses, e.g., by cast-molding in molds of a lens formulation comprising at least a silicone containing monomer or polymer, at least one hydrophilic monomer or macromer, and other necessary components.
  • the hydrophilic component can be (in total or in part) the non-linear polysiloxane crosslinker.
  • the ophthalmic devices or contact lenses can be made with an ultraviolet or thermally curable formulation for use in a contact lens will frequently have a hydrophilic component which is
  • the hydrophilic components may be and typically are DMA (Dimethylacrylamide), HEMA, or NVP (N -vinyl Pyrrolidone).
  • the silicone component may account for approximately 20-70% by weight of the total composition.
  • the contact lens comprises at least 10 % silicone hydrogel and the present non-linear polysiloxane crosslinker.
  • the silicone component may include TRIS (3-[tris(trimethylsilyloxy)silyl]-propyl methacrylate), SIGMA methyl
  • an ophthalmic device such as a contact lens, is formed from the
  • An ophthalmic device or contact lens may consist of the present non-linear polysiloxane crosslinker.
  • the present non-linear polysiloxane crosslinker may be incorporated into an ophthalmic device or contact lens as a crosslinker by reacting them with hydrophilic and silicone components that make up the lens formulation, e.g. by reacting the non-linear polysiloxane crosslinker in one embodiment with DMA and TRIS or SIGMA to form a partially polymerized product. The partially polymerized product is then functionalized with one or more compounds having at least one reactive double bond.
  • lenses made with the present non-linear polysiloxane crosslinker include at least 10% by weight silicone hydrogel.
  • the number and molecular weight of diols The hydroxyl number of the diols is determined using ASTM D4274: Standard Test Methods for Testing Polyurethane Raw Materials: Determination of Hydroxyl Numbers of Polyols.
  • Isocyanate content in the polymer and prepolymers was determined by titration using ASTM D2572: Standard Test Methods for Isocyanate Groups in Urethane Materials or Prepolymers.
  • GPC Gel Permeation Chromatography
  • a post molding surface treatment is performed to enhance surface wettability and/or one or more other properties of the ophthalmic devices or contact lenses.
  • the intrinsic Dk value of a lens can be estimated based on a Dk value corrected for the surface resistance to oxygen flux caused by the boundary layer effect as follows.
  • the measurement used a stacking method of the material for correction of boundary layer effects.
  • Oxygen transmission rate J through the lens is measured by the coulometric method on a Mocon MH2/21 instrument (available from Mocon Inc) with Mocon Permeability System software.
  • the lens (or stack of lenses) are tested in a HPLC grade water cell at 34°C.
  • An air stream (from compressed air gas cylinder), having a known percentage of oxygen (e.g., 21%), is passed across one side of the lens at a rate of about 10 mL/min, while a nitrogen stream (from 98% compressed nitrogen/2% hydrogen gas cylinder) is passed on the opposite side of the lens at a rate of about 10 mL/min.
  • the pressure settings for nitrogen humidifier is 3.7 PSI to obtain about 88% relative humidity for nitrogen.
  • the stir motor's speed is set to 600 rpm, corresponding to an indicated setting of "6" on the control knob of motor controller.
  • the thickness (t) of the lens in the area being exposed for testing is determined by measuring about 10 locations with an Electronic Thickness Gauge Model ET-3 (available from Rehder Development Company), and averaging the measurements.
  • the residual oxygen resistance, Rr is equal to a.
  • the estimated intrinsic Dk is equal to 1/b.
  • Modulus is measured using Instron testing machine, Model No. 5566 (available from instron) with SOON load cell, and Bluehill software (version 2.1 1 , or equivalent). At least five specimens from the films are die cut using the ASTM D-1708 Microtensile die, polyethylene block and compression press. The Mitutoyo micrometer, Model No. 505-637-50 (available from Mitutoyo America Corporation) is used to measure the sample thickness. The distance between the grips on the Instron is adjusted to 0.9 inches by using the '"Fine Position" wheel and a ruler. The upper and lower ends of the specimen are inserted into the upper and lower grips and the grip jaws are closed. The pressure on the grips is 70 PSI. Run the test for modulus measurement.
  • the modulus is defined as the slope of the plot of tensile stress versus tensile strain from 0-10% strain (eq 1, 2 3 where F is the force applied to the sample, A is the cross-sectional area of the sample, L is the length of the sample and L 0 is the sample's original length).
  • F the force applied to the sample
  • A the cross-sectional area of the sample
  • L the length of the sample
  • L 0 the sample's original length
  • the tear strength is characterized on unmcked 90 °C angle specimens (type C) according to ASTM D624-00 "Standard Test Method for Tear Strength of Conventional Vulcanized Rubber and Thermoplastic Elastomers". All samples are tested using Instron testing machine, Model No. 5566 (available from Instron) with 500N load cell, and Bluehill software (version 2.11, or equivalent). The grip distance was set at 50.8 mm and samples were tested with a constant extension rate of 100 mm/min until failure. The Mitutoyo micrometer, Model No. 505-637-50 (available from Mitutoyo America Corporation) is used to measure the sample thickness.
  • the thickness of all samples is measured prior to testing in three locations near the site of tearing (at the apex, above and below the apex) and the three values are averaged to obtain the sample thickness.
  • the tear strength is calculated as the maximum force obtained during testing divided by the sample thickness (N/mm). The test is repeated for at least five test specimens and the measurements averaged.
  • Contact angle measurements are performed by the sessile drop method using rame-hart Model 590 Automated Goniometer with a DROPimage Advanced v 2.5 software (available from rame-hart instrument co.).
  • the contact lens is gently blotted with a piece of dry filter paper, it was then placed onto a Micro Slides (available from VWR, North American Cat. No. 48300-047) on the supporting stage of the Goniometer.
  • a PBS solution droplet (approximately 6-8 ⁇ ) is then dispensed on the central surface area of the lens.
  • Use DROPimage Advanced v 2.5 software to capture an image of the drop on the lens and through data analysis the contact angle at the liquid-solid interface is measured.
  • the process follows strict time schedule to avoid significant evaporation of the lens surface water as well as the liquid drop.
  • the time from the start of blotting to the completion of the measurement is closely controlled to be 1 minutes 35 seconds.
  • Hie lens was then returned to the PBS to soak for at least 10 mm before the process was repeated on at least two further occasions, giving a total of at least three measurement runs for each lens. The measurements are averaged.
  • the hydrated weight determination Prepare a piece of Whatman # 1 filter paper by folding it in half and adding PBS dropwise until it is barely moist. To ensure a consistent humidity level, add enough PBS as to leave the outer edge of the filter paper dry. The filter paper may be reused to blot lenses until the edge is no longer dry or three lenses have been blotted, whichever comes first. Using blunt-tipped tweezers, remove a single lens from the PBS storage solution, entraining a minimum amount of excess PBS on the surface. Place the lens flat on the filter paper, fold the paper over the lens, and tap firmly once. Unfold paper, move lens to a new location on the moistened paper, fold again, and blot a second time.
  • the dry weight determination Transfer blotted, weighed substrates and lenses to a 100°C oven for 16-18 hours or until their mass ceases to change. Lenses made of materials which degrade at that temperature may instead be dried in a vacuum oven at 60°C until constant mass. Remove from oven and transfer to ajar with active desiccant and allow to cool to room temperature, 1-2 hours. Record mass of dry lenses + weighing substrates to the nearest 0.1 mg.
  • the light transmission properties of a contact lens is measured using the procedure outlined in the IS/ISO 18369-3(2006): Ophthalmic Optics-Contact Lenses Part 3: Measurement Methods.
  • the measurement is performed using a Thermo Scientific Evolution 220UV-visible spectrophotometer (spectral bandwidth l-2nm) between the wavelengths of 400-75 Onm, which covers the entire visible spectrum.
  • the test is performed with the contact lens in a fully hydrated state whilst immersed in saline.
  • a special cuvette (5mm light path, 15 mm inner width) is helpful for positioning the contact lens perpendicular to the incident beam during the measurement and keeping the lens in a fixed position at the exact height that the incident beam passes through the cuvette.
  • the measurement is made inside the central optic zone of the contact lens.
  • Example 1 Synthesis of Ingredient 1
  • the amount of siloxane unit is 85% by weight of the total weight of the siloxane unit and PEG diol in the composition, and the amount of PEG diol is 15% by weight of the total weight of siloxane unit and PEG diol in the composition.
  • Triol used for synthesizing ingredient 1 is glycerol.
  • the heating/chiller connected to the 3 -neck, 1000ml, jacketed reactor was turned on to a set-point: 60- 65C. Both nitrogen gas and stirring were turned on. With reaction temperature at 51.4°C, 2 ⁇ 20 ⁇ 1 dibutyltin dilaurate (DBTDL) was added via micro-syringe. Heating mantle was turned off and reaction was allowed to exotherm (reaction high temp during exotherm 62.6°C). After exotherm was complete, and internal heat was at 58.5°C, heating mantle was turned on with set-point 53.5°C. Solution was allowed to react for 2hours.
  • DBTDL dibutyltin dilaurate
  • the number average molecular weight of Ingredient 1 is determined to be about 22000 Daltons based on conventional GPC using DMF at 53°C as the eluent and polystyrene as the standard (Table 1).
  • Table 1 The number average molecular weight of Ingredient 1 is determined to be about 22000 Daltons based on conventional GPC using DMF at 53°C as the eluent and polystyrene as the standard (Table 1).
  • the amount of siloxane unit is 75% by weight of the total weight of the siloxane unit and PEG diol in the composition, and the amount of PEG diol is 25% by weight of the total weight of siloxane unit and PEG diol in the composition.
  • Triol used for synthesizing ingredient la is glycerol.
  • Shinetsu 160AS-diol was added to (41.63g, 2.00mol) IPDI in a glass jar. Solution was removed from glove-box and fitted into a heating mantle (set-point: 81.0C) with overhead mechanical stirrer nitrogen inlet/outlet, and heating mantle was .
  • ingredient lb the amount of siloxane unit is 85% by weight of the total weight of the siloxane unit and PEG diol in the composition, and the amount of PEG diol is 15% by weight of the total weight of siloxane unit and PEG diol in the composition.
  • Triol used for synthesizing ingredient lb is 1,2,6- Hexanetriol.
  • Shinetsu 160AS-diol ,o bis(2- hydroxyethoxypropyl)-poiydimethylsiloxane, M.VV. ca 1000, from Shin-Etsu
  • Heating mantle was turned off and reaction was allowed to exotherm (reaction high temp during exotherm 62.6°C). After exotherm was complete, and internal heat was at 58.5°C, heating mantle was turned on with set-point 53.5°C. Solution was allowed to react for 2hours.
  • Example 4 Preparation of silicone hydrogel films with formulations containing ingredient 1 ingredient 1 is mixed with Methacrylate PDMS 600-800, ⁇ , M-dimethylacrylamide (DMA), 2- hydroxyethyl methacrylate (HEMA), lsobomyl methacrylate, Darocure 1173 with the formulation composition in Table 2.
  • DMA dimethylacrylamide
  • HEMA 2- hydroxyethyl methacrylate
  • lsobomyl methacrylate Darocure 1173
  • tins mixture t-amyl alcohol solvent was added (with weight of t-amyl alcohol to total weight before t-amyl alcohol ratio being 2:5).
  • the monomer mixture was placed in polypropylene lens molds or borosilicate glass molds and irradiated under UV light for about 5 rains.

Abstract

Disclosed is a non-linear polysiloxane based multifunctional branched crosslinker comprising pendent oligomeric or polymeric groups. Also disclosed are methods for forming the non-linear polysiloxane based multifunctional branched crosslinker, compositions comprising the non-linear polysiloxane based multifunctional branched crosslinker, silicone hydrogel polymers formed from the compositions, and articles comprising the silicone hydrogel polymers. The silicone hydrogel polymer may be used in ophthalmic devices.

Description

NON-LINEAR POLYSILOXANE BASED MULTIFUNCTIONAL BRANCHED CROSSLINKERS
Related Applications
This application claims priority to US Provisional Patent Applications 62/198352, 62/198346, and 62/198361, each of which has a filing date of July 29. 2015, and each of which is hereby incorporated by reference in their entirety.
Field
The invention is directed to polysiloxane based multi-functional crosslinkers, methods for their production, polymerizable compositions for forming silicone hydrogels, and ophthalmic devices.
Background
To design and select materials for ophthalmic devices, such as contact lenses, many factors must be considered to optimize the physical, chemical and biological properties. Examples of these properties include oxygen permeability, modulus, wettability, lubricity, biocompatibility, and optical quality, to name just a few.
While patient comfort has driven the market use of these lenses, the usefulness of these lenses depends on both the physical properties (including oxygen transport and lubricity of the lens) as well as the amount of protein and lipid deposition on the lenses during wear. Different technologies exist today to present a final lens that has the optical clarity and the desired lubricity, with controllable modulus and high oxygen permeability in the silicone hydrogel lenses.
Due to their high oxygen permeability, silicone based materials have been used extensively over the last 10 years. However, silicone is a hydrophobic material, and for this reason silicone contact lenses tend to develop a relatively hydrophobic, non-wettable surface in contact with a hydrophobic lens mold during the manufacturing. Lipids and proteins have a high tendency to deposit on a hydrophobic surface and this may affect optical clarity. Likewise, adsorption of unwanted components from the ocular tear fluid on to the lens material during wear is one of the contributory factors for causing reduced comfort experienced by patients. In addition, bacterial infections can potentially occur if lens care regimens are not followed for use of the lenses. Various methods have been used to render the contact lens surface with sustained wettability and/or lubricity. One of the common practices to increase the wettability is to add an internal wetting agent such as polyvinylpyrrolidone (PVP) or to alter the surface during plasma treatment, high energy irradiation, and by applying a topical coating to obtain an extremely hydrophilic surface. Plasma treatment can be effective for silicone hydrogel contact lenses, but it is costly and time consuming to use this approach. Topical coating can effectively alter the surface properties, but also introduces an additional step in manufacturing and is often complex in nature.
The oxygen permeability (Dk) is another important factor in contact lens design to maintain corneal health for contact lens wearers. Holden and Mertz concluded that 24.1 Barrer/cm (Dk/t, t is the thickness of contact lens) was the oxygen transmissibility requirement for daily wear, and a minimum of 87 Barrer/cm is required for overnight wear to limit overnight edema to 4%. Further findings by Harvitt and Bonanno suggested that the minimum oxygen transmissibility required to avoid anoxia was 35 Barrer/cm for the open eye and 125 Barrer/cm for the closed eye. Conventional hydrogels on the average have the Dk in the range of 8-40 Barrer depending on the water content. Physical properties such as oxygen flux (j), oxygen permeability (Dk), and oxygen
transmissibility (Dk/t) are used in referring to oxygen transporting properties of contact lenses. Oxygen flux can be defined as a volume of oxygen passing through a specified area of a contact lens over a set amount of time. The physical units of oxygen flux can be described as microliters 02 (cm2 sec). Oxygen permeability can be defined as the amount of oxygen passing through a contact lens material over a set amount of time and pressure difference. Physical units of oxygen permeability can be described as 1
Barrer or 10"11 (cm3 02 cm)/(cm3 sec mmHg). Oxygen transmissibility can be defined as the amount of oxygen passing through a contact lens of specified thickness over a set amount of time and pressure difference. The physical units of oxygen transmissibility can be defined as 10 9 (cm ml 02)/(ml sec mmHg). Oxygen transmissibility relates to a lens type with a particular thickness. Oxygen permeability is a material specific property that can be calculated from lens oxygen transmissibility.
In general, for most existing silicone hydrogel contact lenses, as the Dk increases, the modulus of the lens increases. Existing silicone hydrogel contact lenses have a modulus from between about 0.4 to about 1.5 MPa. For example, AIROPTIX™ Night & Day contact lens has a modulus of about 1.5 MPa (Dk is 140 Barrer), the Pure Vision™ contact lens has a modulus of about 1.1 MPa (Dk is 99 Barrer), the Air Optix™ has a modulus of about 1.0 MPa (Dk is 110 Barrer), the PremiO™ contact lens has a modulus of about 0.9 (Dk is 129 Barrer), the Acuvue™ advance contact lens has a modulus of about 0.4 MPa (Dk is 60 Barrer), and the Acuvue Oasys™ contact lens has a modulus of about 0.72 MPa (Dk is 103 Barrer).
The increased modulus makes these materials easier to handle and more durable, but the initial comfort of the lens may be reduced and some patients notice greater lens awareness. Lenses possessing a higher modulus necessitate a greater degree of precision in fitting than would otherwise be necessary for lenses having a low modulus. A lens with a higher modulus is less likely to conform to the eye curvature. Another significant problem with high modulus materials is several ocular complications that can arise as a result of mechanical irritation, particularly when worn in an extended wear modality. A very low modulus, however, can be a disadvantage as well when trying to achieve optimum vision, it also means that the lens material has poor handling characteristics and reduced durability.
Current trends in the materials science have seen introduction of only four lower modulus silicone hydrogel contact lenses while maintaining a high Dk with the use of novel polymer architecture. They are Biofinity™, Avaira™, Dailies Total 1™, and Ultra™ which show lower modulus (0.75, 0.5, 0.7, and 0.7MPa respectively) without as much compromise on the oxygen permeability (128, 100, 140, and 163 Barrer respectively).
There continues to be a need for new silicone hydrogel contact lenses which have advantageous combinations of properties such as transparency, relatively high levels of oxygen permeability, sustained wettability and/or lubricity, and ophthalmically acceptable modulus.
Summary
Disclosed herein is a non-linear polysiloxane based multifunctional branched crosslinker of structure:
(X)„-S wherein the branching point S is derived from multifunctional alcohols or polyols, multifunctional amines or polyamines, or multifunctional thiols or polythiols, and which have a functionality m of 3 or greater and wherein m is equal to or greater than n; wherein X can be the same or different and is selected from the group consisting of formulae (S-I), (S-II), (S-III), (S-IV), or (S-V), wherein said formulae possess the following structures: -[I-PDMS]z-I-[[F-[I-PDMS]r]p-I- (S-I)
-[I-F]z-I-[PDMS-[I-F]r]p-I- (S-II)
-I-[[F-[I-PDMS]r]p-I-F-I- (S-III)
-I-PDMS-[I-F]z-I-[PDMS-[I-F]r]p-I-PDMS-I- (S-IV) .(X)n-S-(X)n- (S-V)
wherein I is a unit derived from a diisocyanate, PDMS is a unit derived from a polydialkyl or polydiaryl or polyalkylaryl siloxane diol, F is a diol, diamine, or dithiol derived unit comprising at least one pendant oligomeric or polymeric group, wherein p is an integer ranging from 1 to 50, r is an integer ranging from 1 to 50, and z is an integer ranging from 1 to 50, wherein at least three of the terminal diisocyanates I have been reacted with an ethylenically unsaturated monofunctional monomer, and wherein the total number average molecular weight is less than 100,000 Dalton and has a viscosity less than 1,000,000 mPa sec, and wherein there are substantially no remaining unreacted isocyanates in the branched crosslinker; or of structure:
Figure imgf000005_0001
wherein the branching point T is derived from a multifunctional isocyanate with a functionality m of 3 or greater and wherein n = m; wherein X can be the same or different and is selected from the group consisting of formulae (T-I), (T-II), (T-III), (T-IV), or (T-V), wherein said formulae possess the following structures:
-[PDMS]z-I-[[F-[I-PDMS]r]p- (T-I)
-[[F-[I-PDMS]r]p-I-F- (T-II)
-[F]z-I-[PDMS-[I-F]r]p- (T-III) -PDMS-[I-F]z-I-[PDMS-[I-F]r]p-I-PDMS- (T-IV) -(X)n-T-(X)n- (T-V) wherein I is a unit derived from a diisocyanate, PDMS is a unit derived from a polydialkyl or polydiaryl or polyalkylaryl siloxane diol, F is a diol, diamine, or dithiol derived unit comprising at least one pendant oligomeric or polymeric group, wherein p is an integer ranging from 1 to 50, r is an integer ranging from 1 to 50, and z is an integer ranging from 1 to 50, wherein at least three of the terminal hydroxyls have been reacted with the mono adduct of a diisocyanate and an ethylenically unsaturated monofunctional monomer, and wherein the total number average molecular weight is less than 100,000 Dalton and has a viscosity less than 1,000,000 mPa sec, and wherein there are substantially no remaining unreacted isocyanates in the branched crosslinker. Further disclosed are methods for the production of the non-linear polysiloxane based multifunctional branched crosslinkers, polymerizable compositions comprising the non-linear polysiloxane based multifunctional branched crosslinkers, silicone hydrogel polymers formed by polymerizing polymerizable compositions comprising the non-linear polysiloxane based multifunctional branched crosslinkers, methods of manufacturing silicone hydrogel polymers formed from polymerizable compositions comprising the non-linear polysiloxane based multifunctional branched crosslinkers, and ophthalmic devices.
Detailed Description Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Generally, the nomenclature used herein and the laboratory procedures are well known and commonly employed in the art. Conventional methods are used for these procedures, such as those provided in the art and various general references. Where a term is provided in the singular, the inventors also contemplate the plural of that term. The nomenclature used herein and the laboratory procedures described below are those well- known and commonly employed in the art.
An "ophthalmic device", as used herein, refers to a contact lens (hard or soft), an intraocular lens, a corneal inlay, corneal onlay, overlay lenses, ocular inserts, optical inserts, spectacle lenses, goggles, surgical glasses, other ophthalmic devices (e.g., stents, glaucoma shunt, or the like) used on or about the eye or ocular vicinity. "Contact Lens" refers to a structure that can be placed on or within a wearer's eye. A contact lens can correct, improve, or alter a user's eyesight, but that need not be the case. A contact lens can be of any appropriate material known in the art or later developed, and can be a soft lens, a hard lens, or a hybrid lens. A "silicone hydrogel contact lens" refers to a contact lens comprising a silicone hydrogel material.
A "polymer" means a material formed by polymerizing/crosslinking one or more vinylic monomers, macromers, crosslinkers and/or prepolymers.
An "oligomer" describes a compound intermediate between a monomer and a polymer, having a specified number of units between about five and a hundred, an oligomer consists of fewer monomer units than a polymer.
A "hydrogel" or "hydrogel material" refers to a water insoluble, crosslinked, three-dimensional networks of polymer chains plus water that fills the voids between polymer chains. =A "hydrogel" or "hydrogel material" can absorb at least 10 percent by weight of water when it is fully hydrated.
A "silicone hydrogel" refers to a silicone-containing hydrogel obtained by copolymerization of a polymerizable composition comprising at least one silicone-containing vinylic monomer,
macromer,prepolymer or crosslinker .
"Hydrophilic" as used herein, describes a material or portion thereof that will more readily associate with water than with lipids.
"Hydrophobic" as used herein, describes a material or portion thereof that will more readily associate with lipids than with water.
A "pendant group" is generally a group of molecules arranged in linear or branched
conformations and attached to the backbone polymer chain.
A "monomer" refers to a compound that can be polymerized chemically, actinically or thermally.
A "modulus modifier" refers to a monomer, macromer, prepolymer, or crosslinker which improves the modulus, and/or tear strength of the resulting cured polymer such that it achieves an acceptable level of modulus and tear resistance in the resulting contact lens or ophthalmic device.
A "prepolymer" refers to a higher molecular weight oligomeric molecule that is typically the reaction product of a polyol, at least one linking moiety to that polyol, and at least one ethylenically unsaturated groups and can be polymerized actinically or thermally to form a polymer having a molecular weight larger than the starting prepolymer. This is sometimes alternately referred to as an "oligomer". As used herein, "prepolymer" and "oligomer" are used interchangeably.
"Dry gas" means a gas that contains less than 0.01% humidity.
"Inert gas" means an essentially non-reactive gas, such as nitrogen or argon.
A "vinylic monomer", as used herein, refers to a monomer that has at least one ethylenically unsaturated group and can be polymerized actinically or thermally.
As used herein, "actinically" in reference to curing, crosslinking or polymerizing of a polymerizable composition, a prepolymer or a material means that the curing (e.g., crosslinked and/or polymerized) is performed by actinic irradiation, such as, for example, UV irradiation, ionizing radiation (e.g. gamma ray or X-ray irradiation), microwave irradiation, and the like. Thermal curing or actinic curing methods are well-known to a person skilled in the art.
A "crosslinker" refers to a compound having at least two ethylenically-unsaturated groups. A "crosslinking agent" refers to a compound which belongs to a subclass of crosslinkers and comprises at least two ethylenically unsaturated groups and has a molecular weight of 700 Daltons or less. The term "olefinically unsaturated group" or "ethylenically unsaturated group" is employed herein in a broad sense and is intended to encompass any groups containing at least one >C=C< group. Exemplary ethylenically unsaturated groups include without limitation (meth)acryloyl, allyl, vinyl, styrenyl, or other C=C containing groups.
A "multifunctional crosslinker" refers to a crosslinker that contain more than two ethylenically- unsaturated groups.
A "photoinitiator" refers to a chemical that initiates free radical crosslinking/polymerizing reaction by the use of light.
A "thermal initiator" refers to a chemical that initiates radical crosslinking/polymerizing reaction by the use of heat energy.
"Molecular weight" of a polymeric material (including monomeric or macromeric materials), as used herein, refers to the number-average molecular weight unless otherwise specifically noted or unless testing conditions indicate otherwise. As used herein, the term "non-linear polysiloxane" refers to a polysiloxane that contains at least one branching point in the siloxane main chain such that there are at least three polysiloxane arms contained within that siloxane main chain.
A "hydrophilic surface" in reference to a silicone hydrogel material or a contact lens means that the silicone hydrogel material or the contact lens has a surface hydrophilicity characterized by having an averaged water contact angle of about 100 degrees or less, preferably about 90 degrees or less, more preferably about 80 degrees or less, more preferably about 70 degrees or less.
An "contact angle" refers to a water contact angle (measured by Sessile Drop method), which is obtained by averaging measurements of at least 3 individual contact lenses.
"Fully hydrated" means the maximum amount of water retained in the cured polymer after the polymer has been rinsed thoroughly to remove unreacted components and, thereafter, soaked in a water bath.
'Transparent" means greater than 85% transmission using the ISO 18369-3 entitled "ophthalmic optics - contact lenses - part 3, measurement methods", subsection 4.6 "determinations of the spectral and luminous transmittance".
A "viscosity" means a measurement of liquid flowability under force using the ASTM D1545 "Standard Test Method for Viscosity of Transparent Liquids by Bubble Time Method" and converting from stokes to mPa sec.
"Derived from" means "made from" through single or multiple chemical reaction steps.
The term "oxygen permeability" in reference to a contact lens means an estimated intrinsic oxygen permeability Dk, which is corrected for the surface resistance to oxygen flux caused by the boundary layer effect as measured according to the procedures described in Example 1. The intrinsic "oxygen permeability", Dk, of a material is the rate at which oxygen will pass through a material. Oxygen permeability is conventionally expressed in units of Barrer, where "Barrer" is defined as [(cm3 oxygen)(mm)/(cm2)(sec)(mm Hg)] x 10~10.
The "oxygen transmissibility", Dk/t, of a lens or material is the rate at which oxygen will pass through a specific lens or material with an average thickness of t [in units of mm] over the area being measured. Oxygen transmissibility is conventionally expressed in units of Barrer/mm, where "Barrer/mm" is defined as [(cm3 oxygen)/(cm2)(sec)(mm Hg)] x 10~9. According to a first aspect of the invention, there is disclosed a non-linear polysiloxane based multifunctional branched crosslinker of structure:
(X)„-S wherein the branching point S is derived from multifunctional alcohols or polyols, multifunctional amines or polyamines, or multifunctional thiols or polythiols, and which have a functionality m of 3 or greater and wherein m is equal to or greater than n; wherein X can be the same or different and is selected from the group consisting of formulae (S-I), (S-II), (S-III), (S-IV), or (S-V), wherein said formulae possess the following structures:
-[I-PDMS]z-I-[[F-[I-PDMS]r]p-I- (S-I)
-[I-F]z-I-[PDMS-[I-F]r]p-I- (S-II) -I-[[F-[I-PDMS]r]p-I-F-I- (S-III) -I-PDMS-[I-F]z-I-[PDMS-[I-F]r]p-I-PDMS-I- (S-IV) -(X)n-S-(X)n- (S-V)
wherein I is a unit derived from a diisocyanate, PDMS is a unit derived from a polydialkyl or polydiaryl or polyalkylaryl siloxane diol, F is a diol, diamine, or dithiol derived unit comprising at least one pendant oligomeric or polymeric group, wherein p is an integer ranging from 1 to 50, r is an integer ranging from 1 to 50, and z is an integer ranging from 1 to 50, wherein at least three of the terminal diisocyanates I have been reacted with an ethylenically unsaturated monofunctional monomer, and wherein the total number average molecular weight is less than 100,000 Dalton and has a viscosity less than 1,000,000 mPa sec, and wherein there are substantially no remaining unreacted isocyanates in the branched crosslinker;
or of structure:
(X)n-T wherein the branching point T is derived from a multifunctional isocyanate with a functionality m of 3 or greater and wherein n = m; wherein X can be the same or different and is selected from the group consisting of formulae (T-I), (T-II), (T-III), (T-IV), or (T-V), wherein said formulae possess the following structures:
-[PDMS]z-I-[[F-[I-PDMS]r]p- (T-I)
-[[F-[I-PDMS]r]p-I-F- (T-II)
-[F]z-I-[PDMS-[I-F]r]p- (T-III)
-PDMS-[I-F]z-I-[PDMS-[I-F]r]p-I-PDMS- (T-IV)
-(X)n-T-(X)n- (T-V) wherein I is a unit derived from a diisocyanate, PDMS is a unit derived from a polydialkyl or polydiaryl or polyalkylaryl siloxane diol, F is a diol, diamine, or dithiol derived unit comprising at least one pendant oligomeric or polymeric group, wherein p is an integer ranging from 1 to 50, r is an integer ranging from 1 to 50, and z is an integer ranging from 1 to 50, wherein at least three of the terminal hydroxyls have been reacted with the mono adduct of a diisocyanate and an ethylenically unsaturated monofunctional monomer, and wherein the total number average molecular weight is less than 100,000 Dalton and has a viscosity less than 1,000,000 mPa sec, and wherein there are substantially no remaining unreacted isocyanates in the branched crosslinker.
In an embodiment, the pendant oligomeric or polymeric groups may be hydrophilic groups.
In an embodiment, PDMS is a unit derived from an alkoxylated polydialkyl or polydiaryl or polyalkylaryl siloxane diol.
In an embodiment, F is a diol derived unit.
In an embodiment, the pendant hydrophilic oligomeric or polymeric groups may be polyethylene oxide (PEO) groups.
In an embodiment, the pendant hydrophilic oligomeric or polymeric groups may be poly(2- oxazoline) groups. In an embodiment, the diol, diamine, or dithiol derived unit comprising at least one pendant oligomeric or polymeric group may have a Number average molecular weight Mn ranging from 300-5000 g/mol, as determined by Gel Permeation Chromatography using N, N-dimethylformamide (DMF) as the solvent at 53°C. In an embodiment, the backbone may contain units derived from polydimethylsiloxane diol and units derived from diisocyanate.
In an embodiment, the diisocyanate units may be isophorone diisocyanate (IPDI).
In an embodiment, the reactive double bond at a terminal end may be obtained by reacting hydroxyethylmethacrylate (HEMA). In an embodiment, the number average molecular weight of the total crosslinker may range from
8000-55000g/mol as determined by Gel Permeation Chromatography using Ν,Ν-dimethyl formamide (DMF) as the solvent at 53°C.
The non-linear polysiloxane based multifunctional branched crosslinker (hereinafter "non-linear multifunctional polysiloxane branched crosslinker"), comprises a double bond located at at least three terminal ends of the non-linear multifunctional polysiloxane branched crosslinker. Terminal ends are the ends of the polymeric chain of the non-linear multifunctional polysiloxane branched crosslinker. The end groups can be the same or different. The non-linear multifunctional polysiloxane branched crosslinker may be used as non-linear multifunctional polysiloxane branched crosslinkers in contact lens formulations and therefore the non-linear multifunctional polysiloxane branched crosslinker comprises reactive groups that can react with the other constituents of the contact lens formulation. The end groups are reactive groups that contain at least one reactive double bond. The double bond can, for example, be formed by an acryl or methacryl group and is formed on the ends of the polymeric chain by reaction of an isocyanate group with, for example, hydroxy acrylate, methacrylate or acrylamide. Examples may include hydroxyl methyl methacrylate, hydroxyl ethyl acrylate, and hydroxy n-butyl acrylate. One exemplary end group forming compound is hydroxyethyl methacrylate (HEMA), shown below:
Figure imgf000012_0001
hydroxyethyl methacrylate (HEMA) In the non-linear multifunctional polysiloxane branched crosslinker, a diol, diamine, or dithiol derived unit comprising at least one pendant hydrophilic oligomeric or polymeric group may separate the polysiloxane segments. In an embodiment, the diol, diamine, or dithiol derived unit may be derived from a diol or is the reaction product of a diol and contains a pendant oligomeric or polymeric group. In the preparation of the non-linear multifunctional polysiloxane branched crosslinker, the hydroxyl groups of the diol may be reacted with the isocyanate units to form urethane bonds. Suitable diols for use in the reaction may include a wide variety of diols comprising at least one pendant oligomeric or polymeric group. The structure where the pendent group is attached to is typically referred to as "the backbone". The diols used to provide the unit derived from a diol comprising at least one pendent oligomeric or polymeric group may for example have a butane diol, polycarbonate diol, hexane diol, or propane diol back bone, and the backbone comprises at least one pendent oligomeric or polymeric group.
As known to one of skill in the art, a pendant group or a side group is generally a group of molecules arranged in linear or branched conformations and attached to the backbone polymer chain.
The pendant oligomeric or polymeric group in "F" unit is preferably a hydrophilic group. The pendant oligomeric or polymeric group is a group that does not comprise any chemical moieties that may react with the diisocyanate used in the preparation of the non-linear multifunctional polysiloxane branched crosslinker under the reaction conditions applied in the synthesis of the crosslinker. With "oligomeric or polymeric" it is indicated that the pendant group comprises a unit that is repeated at least 2 times, but that may be repeated up to 75 times. For example, the pendant group may comprise the unit -(- C2H4-O-), from 2 up to and including 75 times. Other repeating units may also be present from 2-75 times.
In an embodiment, the pendant oligomeric or polymeric group is a polyalkylene oxide. The polyalkylene oxides may be linear or branched, cycloaliphatic, or aliphatic-cycloaliphatic, optionally containing one or more linkages of -S-, -C(O)-, or -NR-, wherein R is H or CI to C30 alkyl. Examples of polyalkylene oxides are poly(ethylene glycol)(PEG), poly(propylene glycol), polyethylene oxide (PEO), poly(tetramethylene ether) glycol, and their monoalkyl-substituted derivatives.
In an embodiment, the pendant oligomeric or polymeric groups comprise pendant oligomeric or polymeric oxyalkylene groups, such as poly(ethylene glycol) (PEG), poly(propylene glycol (PPG), and polyethylene oxide (PEO) comprising groups, copolymers thereof and their monoalkyl-substituted derivatives. In an embodiment, the pendant group comprises a polyethylene oxide (PEO) oligomer or polymer. More preferably, the pendant groups consists of a polyethylene oxide (PEO) oligomer or polymer. The terms "poly(ethlyene glycol)", "poly(oxy ethylene)" and "polyethylene oxide" refer to the same chemical component and these terms can be used in the prior art and this description when referring to the same component. A diol comprising a pendant poly(ethylene glycol) group may be generally referred to as "PEG diol".
Examples of the "PEG diol" may include Ymer™ N120, supplied by Perstorp or Tegomer™ D 3404 supplied by Evonik, both commercial products comprise PEG(7)-2-ethylpropanel,3,diol.
Figure imgf000014_0001
PEG diol (Ymer N120, Tegomer D3404)
In an embodiment, the pendant oligomeric or polymeric groups comprise a polymethyl oxazoline or polyethyl oxazoline group, or a copolymer thereof. An example of a suitable diol comprising a polyethyl oxazoline group is shown in the figure below.
Figure imgf000014_0002
The synthesis of such diol is described in e.g. WO2009/058397, page 10 and figure 7. An amine diol used in synthesis of the diol comprising a pendant a polymethyl oxazoline or polyethyl oxazoline group, or a copolymer thereof may be any dihydroxy secondary amine bearing moiety that is aliphatic or cyclo aliphatic. In an embodiment, the pendant group comprising a polymethyl oxazoline or polyethyl oxazoline group, or a copolymer thereof , preferably has a number average molecular weight ranging from 300 to 5000 g/mol. In an embodiment, the pendant group has a molecular weight of from 400 to 2500 g/mol.
The diol, diamine, or dithiol from which the unit comprising a pendant oligomeric or polymeric group has been derived preferably has a Mw ranging from 300-5000 g/mol, as determined by Gel Permeation Chromatography using Ν,Ν-dimethyl formamide (DMF) as the solvent at 80°C using polystyrene standards. The backbone of the non-linear multifunctional polysiloxane branched crosslinker may contain polysiloxane units derived from polydimethylsiloxane diol and units derived from diisocyanate. In the present instance, the uses of diisocyanate units and results of using diisocyanate units to obtain a urethane bond are generally well understood. The diisocyanate units can comprise aromatic or aliphatic
diisocyanates. The diisocyanates may be selected from the group comprising alkyl diisocyanates, arylalkyl diisocyanates, cycloalkylalkyl diisocyanates, alkylaryl diisocyanates, cycloalkyl diisocyanates, aryl diisocyanates, cycloalkylaryl diisocyanates, and mixtures thereof.
Examples of diisocyanates are isophorone diisocyanate, hexane diisocyanate, 1 ,4- diisocyanatocyclohexane, lysine-diisocyanate, naphthalene diisocyanate, 4,4'-diphenylmethane diisocyanate, 2,2'-Methylenediphenyl diisocyanate, hexamethylene diisocyanate, 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, hexamethylene- 1 ,6-diisocyanate, tetramethylene-1 ,4-diisocyanate,
naphthalene- 1 ,5-diisocyanate, xylylene diisocyanate, dicyclohexylmethane-4,4-diisocyanate, 1 ,4- benzene diisocyanate, 3,3'-diethoxy-4,4-diphenyl diisocyanate, m-phenylene diisocyanate, polymethylene polyphenyl diisocyanate, O-tolidine Diisocyanate, 2,4,6-triisopropyl-m-phenylene diisocyanate, 4- isocyanatocyclo-4 ' -isocyanate, and mixtures thereof. Preferred are aliphatic diisocyanate units; more preferred are isophorone diisocyanate, 1 ,4-diisocyanatocyclohexane and mixtures thereof. As an example, the structure of isophrone diisocyanate (IPDI) is shown below:
Figure imgf000015_0001
isophorone diisocyanate (IPDI) The backbone of the non-linear multifunctional polysiloxane branched crosslinker may contain polysiloxane units derived from a polydimethylsiloxane diol. Polydimethylsiloxane (PDMS) is a siloxane unit according to the below formula:
-R8-SiRiR2-0-[-SiR3R4-0-]p-SiR5R6-R7- wherein Ri, R2, R3, R4, R5, and Rg may be the same or different and are selected from alkyl groups having 1 to 16 carbons or alkyloxy groups having 1 to 16 carbons, substituted and unsubstituted aromatic groups, and R7 and R8 are a bond or a divalent alkylene groups having 1 to 16 carbons or alkyleneoxy groups having 1 to 16 carbons and wherein p is an integer ranging from 1-25.
Ri, R2, R3, R4, R5, and Rg preferably are an alkyl group having from 1-4 carbons, most preferably they are methyl groups. In an embodiment, the preparation of the non-linear multifunctional polysiloxane branched crosslinker the siloxane unit originates form a diol siloxane compound. A diol siloxane compound contains silicone which may be derived from the group comprising: linear or branched polysiloxane, polysiloxane substituted with alkyl, cycloalkyl or phenyl group, cage-like polysiloxane. Specific examples of silicon containing compounds that may be used to make a diol siloxane compound include heptamethyltrisiloxane, tris(trimethylsiloxy)silane, tetramethyldisiloxane, hexamethyltrisiloxane, nonamethyltetrasiloxane, decamethylheptasiloxane, pentamethyldisiloxane, polydimethylsiloxane, 2- (trimethylsiloxy)-l,l,5,5-tetramethyltrisiloxane, l,3-tetrakis(trimethylsiloxy)disilane, 1,3- bis(trimethylsiloxy)-l,3-dimethyldisiloxane, phenyl substituted polydimethylsiloxane, alkyl substituted polydimethylsiloxane, cycloalkyl substituted polydimethylsiloxane, and polyhedral oligomeric silsesquioxane (POSS).
The number average molecular weight of the total non-linear multifunctional polysiloxane branched crosslinker is from 8,000 to 55,000 g/mol, preferably from 15,000 to 30,000 g/mol and more preferably from 17,000 to 27,000 g/mol as determined by Gel Permeation Chromatography using N,N- dimethyl formamide (DMF) as the solvent at 80°C and using polystyrene standards. To obtain the non-linear multifunctional polysiloxane branched crosslinker, a diisocyanate unit
(hereinafter "a diisocyanate") may be reacted with a siloxane unit (preferably a polysiloxane diol) under an inert and/or dry gas at elevated temperature. For instance, the maximum exothermic temperature is preferably less than 80°C to eliminate secondary reactions affecting the molecular weight and/or functionality of the resultant intermediate. More preferably the temperature is less than 75 °C. The minimum temperature is generally 40°C, and the actual temperature is preferably about 55°C.
A catalyst may be included in the diisocyanate-siloxane mixture. Exemplary catalysts include organometallic compounds based on mercury, lead, tin (dibutyltin dilaurate), bismuth (bismuth octanoate), and zinc or tertiary amines such as triethylenediamine (TED A, also known as 1 ,4- diazabicyclo[2.2.2]octane or DABCO, an Air Products's trade mark), dimethylcyclohexylamine
(DMCHA), and dimethylethanolamine (DMEA) or others known in the art may be added to the mixture. The amounts of a catalyst is in the range of 0.01-20 wt% of the total weight of the formulation. One embodiment contemplates 0.01 - 1 wt%. One embodiment contemplates 1-2 wt%. Another embodiment contemplates 2-3 wt%. Another embodiment contemplates 3-4 wt%. Another embodiment contemplates 4-5 wt%. Another embodiment contemplates 5-6 wt%. Another embodiment contemplates 6-7 wt%. Another embodiment contemplates 7-8 wt%. Another embodiment contemplates 8-9 wt%. Another embodiment contemplates 9-10 wt %. Another embodiment contemplates 10-1 1 wt %. Another embodiment contemplates l l-12 wt%. Another embodiment contemplates 12- 13 wt%. Another embodiment contemplates 13-14 wt%. Another embodiment contemplates 14- 15 wt%. Another embodiment contemplates 15-16 wt%. Another embodiment contemplates 16- 17 wt%. Another embodiment contemplates 17-18 wt%. Another embodiment contemplates 18- 19 wt%. Another embodiment contemplates 19-20 wt %.
Next the diisocyanate-siloxane-diisocyanate mixture is reacted with one or more diols, diamines or dithiols comprising at least one pendant oligomeric or polymeric group, which pendent group typically comprises or is an oligomeric or polymeric polyalkylene oxides, mixtures thereof, copolymers thereof and/or their monoalkyl-substituted derivatives (for ease of use below, referred to as "diol with pendant group"). The diol, diamine, or dithiol with pendant group polymerizes with the diisocyanate-siloxane- diisocyanate intermediate under stirring, followed by addition of a catalyst to form a pre-polymer. The maximum exothermic temperature is preferably less than 80°C. More preferably the temperature is less than 75°C. The minimum temperature is generally 40°C, and the actual temperature is preferably about 55°C.
The pre-polymer is sparged with dry gas and reacted with and end-group forming compound, such as HEMA (hydroxyethyl methacrylate) and a catalyst. The temperature for this reaction is at least 20°C and preferably 35°C and the maximum temperature is less than 50°C to eliminate auto
polymerization of the HEMA. In the non-linear multifunctional polysiloxane branched crosslinker the amount of siloxane unit may range from 1-99% by weight of the total weight of the siloxane unit and the "diol with pendent group" in the composition. One embodiment contemplates 1-2 wt%. Another embodiment contemplates 2-3 wt%. Another embodiment contemplates 3-4 wt%. Another embodiment contemplates 4-5 wt%. Another embodiment contemplates 5-6 wt%. Another embodiment contemplates 6-7 wt%. Another embodiment contemplates 7-8 wt%. Another embodiment contemplates 8-9 wt%. Another embodiment contemplates 9- 10 wt %. Another embodiment contemplates 10-1 1 wt %. Another embodiment contemplates 11- 12 wt%. Another embodiment contemplates 12-13 wt%. Another embodiment contemplates 13-14 wt%. Another embodiment contemplates 14-15 wt%. Another embodiment contemplates 15-16 wt%. Another embodiment contemplates 16-17 wt%. Another embodiment contemplates 17-18 wt%. Another embodiment contemplates 18-19 wt%. Another embodiment contemplates 19-20 wt %. Another embodiment contemplates 20-21 wt %. Another embodiment contemplates 21-22 wt%. Another embodiment contemplates 22-23 wt%. Another embodiment contemplates 23-24 wt%. Another embodiment contemplates 24-25 wt%. Another embodiment contemplates 25-26 wt%. Another embodiment contemplates 26-27 wt%. Another embodiment contemplates 27-28 wt%. Another embodiment contemplates 28-29 wt%. Another embodiment contemplates 29-30 wt %. Another embodiment contemplates 30-31 wt %. Another embodiment contemplates 31-32 wt%. Another embodiment contemplates 32-33 wt%. Another embodiment contemplates 33-34 wt%. Another embodiment contemplates 34-35 wt%. Another embodiment contemplates 35-36 wt%. Another embodiment contemplates 36-37 wt%. Another embodiment contemplates 37-38 wt%. Another embodiment contemplates 38-39 wt%. Another embodiment contemplates 39-40 wt %. Another embodiment contemplates 40-41 wt %. Another embodiment contemplates 41-42 wt%. Another embodiment contemplates 42-43 wt%. Another embodiment contemplates 43-44 wt%. Another embodiment contemplates 44-45 wt%. Another embodiment contemplates 45-46 wt%. Another embodiment contemplates 46-47 wt%. Another embodiment contemplates 47-48 wt%. Another embodiment contemplates 48-49 wt%. Another embodiment contemplates 49-50 wt %. Another embodiment contemplates 51-52 wt%. Another embodiment contemplates 52-53 wt%. Another embodiment contemplates 53-54 wt%. Another embodiment contemplates 54-55 wt%. Another embodiment contemplates 55-56 wt%. Another embodiment contemplates 56-57 wt%. Another embodiment contemplates 57-58 wt%. Another embodiment contemplates 58-59 wt%. Another embodiment contemplates 59-60 wt %. Another embodiment contemplates 60-61 wt %. Another embodiment contemplates 61-62 wt%. Another embodiment contemplates 62-63 wt%. Another embodiment contemplates 63-64 wt%. Another embodiment contemplates 64-65 wt%. Another embodiment contemplates 65-66 wt%. Another embodiment contemplates 66-67 wt%. Another embodiment contemplates 67-68 wt%. Another embodiment contemplates 68-69 wt%. Another embodiment contemplates 69-70 wt %. Another embodiment contemplates 70-71 wt %. Another embodiment contemplates 71-72 wt%. Another embodiment contemplates 72-73 wt%. Another embodiment contemplates 73-74 wt%. Another embodiment contemplates 74-75 wt%. Another embodiment contemplates 75-76 wt%. Another embodiment contemplates 76-77 wt%. Another embodiment contemplates 77-78 wt%. Another embodiment contemplates 78-79 wt%. Another embodiment contemplates 79-80 wt %. Another embodiment contemplates 80-81 wt %. Another embodiment contemplates 81-82 wt%. Another embodiment contemplates 82-83 wt%. Another embodiment contemplates 83-84 wt%. Another embodiment contemplates 84-85 wt%. Another embodiment contemplates 85-86 wt%. Another embodiment contemplates 86-87 wt%. Another embodiment contemplates 87-88 wt%. Another embodiment contemplates 88-89 wt%. Another embodiment contemplates 89-90 wt %. Another embodiment contemplates 90-91 wt %. Another embodiment contemplates 91-92 wt%. Another embodiment contemplates 92-93 wt%. Another embodiment contemplates 93-94 wt%. Another embodiment contemplates 94-95 wt%. Another embodiment contemplates 95-96 wt%. Another embodiment contemplates 96-97 wt%. Another embodiment contemplates 97-98 wt%. Another embodiment contemplates 98-99 wt%.
In the non-linear multifunctional polysiloxane branched crosslinker the amount of "diol with pendent group" may range from 1-99% by weight of the total weight of siloxane unit and the "diol with pendent group" in the composition. One embodiment contemplates 1-2 wt%. Another embodiment contemplates 2-3 wt%. Another embodiment contemplates 3-4 wt%. Another embodiment contemplates 4-5 wt%. Another embodiment contemplates 5-6 wt%. Another embodiment contemplates 6-7 wt%. Another embodiment contemplates 7-8 wt%. Another embodiment contemplates 8-9 wt%. Another embodiment contemplates 9-10 wt %. Another embodiment contemplates 10-11 wt %. Another embodiment contemplates l l-12 wt%. Another embodiment contemplates 12-13 wt%. Another embodiment contemplates 13-14 wt%. Another embodiment contemplates 14-15 wt%. Another embodiment contemplates 15-16 wt%. Another embodiment contemplates 16-17 wt%. Another embodiment contemplates 17-18 wt%. Another embodiment contemplates 18-19 wt%. Another embodiment contemplates 19-20 wt %. Another embodiment contemplates 20-21 wt %. Another embodiment contemplates 21-22 wt%. Another embodiment contemplates 22-23 wt%. Another embodiment contemplates 23-24 wt%. Another embodiment contemplates 24-25 wt%. Another embodiment contemplates 25-26 wt%. Another embodiment contemplates 26-27 wt%. Another embodiment contemplates 27-28 wt%. Another embodiment contemplates 28-29 wt%. Another embodiment contemplates 29-30 wt %. Another embodiment contemplates 30-31 wt %. Another embodiment contemplates 31-32 wt%. Another embodiment contemplates 32-33 wt%. Another embodiment contemplates 33-34 wt%. Another embodiment contemplates 34-35 wt%. Another embodiment contemplates 35-36 wt%. Another embodiment contemplates 36-37 wt%. Another embodiment contemplates 37-38 wt%. Another embodiment contemplates 38-39 wt%. Another embodiment contemplates 39-40 wt %. Another embodiment contemplates 40-41 wt %. Another embodiment contemplates 41-42 wt%. Another embodiment contemplates 42-43 wt%. Another embodiment contemplates 43-■44 wt%. Another embodiment contemplates 44-45 wt%. Another embodiment contemplates 45- ■46 wt%. Another embodiment contemplates 46-47 wt%. Another embodiment contemplates 47- ■48 wt%. Another embodiment contemplates 48-49 wt%. Another embodiment contemplates 49. ■50 wt %. Another embodiment contemplates 51-52 wt%. Another embodiment contemplates 52- ■53 wt%. Another embodiment contemplates 53-54 wt%. Another embodiment contemplates 54- ■55 wt%. Another embodiment contemplates 55-56 wt%. Another embodiment contemplates 56- ■57 wt%. Another embodiment contemplates 57-58 wt%. Another embodiment contemplates 58- ■59 wt%. Another embodiment contemplates 59-60 wt %. Another embodiment contemplates 60- ■61 wt %. Another embodiment contemplates 61-62 wt%. Another embodiment contemplates 62- ■63 wt%. Another embodiment contemplates 63-64 wt%. Another embodiment contemplates 64- ■65 wt%. Another embodiment contemplates 65-66 wt%. Another embodiment contemplates 66- ■67 wt%. Another embodiment contemplates 67-68 wt%. Another embodiment contemplates 68- ■69 wt%. Another embodiment contemplates 69-70 wt %. Another embodiment contemplates 70- ■71 wt %. Another embodiment contemplates 71-72 wt%. Another embodiment contemplates 72- ■73 wt%. Another embodiment contemplates 73-74 wt%. Another embodiment contemplates 74- ■75 wt%. Another embodiment contemplates 75-76 wt%. Another embodiment contemplates 76- ■77 wt%. Another embodiment contemplates 77-78 wt%. Another embodiment contemplates 78- ■79 wt%. Another embodiment contemplates 79-80 wt %. Another embodiment contemplates 80- ■81 wt %. Another embodiment contemplates 81-82 wt%. Another embodiment contemplates 82- ■83 wt%. Another embodiment contemplates 83-84 wt%. Another embodiment contemplates 84- ■85 wt%. Another embodiment contemplates 85-86 wt%. Another embodiment contemplates 86- ■87 wt%. Another embodiment contemplates 87-88 wt%. Another embodiment contemplates 88- ■89 wt%. Another embodiment contemplates 89-90 wt %. Another embodiment contemplates 90- ■91 wt %. Another embodiment contemplates 91-92 wt%. Another embodiment contemplates 92- ■93 wt%. Another embodiment contemplates 93-94 wt%. Another embodiment contemplates 94. ■95 wt%. Another embodiment contemplates 95-96 wt%. Another embodiment contemplates 96- ■97 wt%. Another embodiment contemplates 97-98 wt%. Another embodiment contemplates 98- ■99 wt%.
Overall the present methods include a polyurethane synthesis that permits reactant ratios and order of addition to be modified to control composition and molecular weight. As is well known, urethane bonds are formed through (or derived from) a reaction of an -OH group and an isocyanate group. During synthesis of polyurethanes, typically a diol is reacted with a diisocyanate, resulting in a polymer comprising multiple urethane bonds. By varying the ratio of the diol versus the diisocyanate, one can synthesize polyurethanes with either -OH groups at the two ends of the polyurethane polymer or isocyanate groups at the two ends of the polyurethane polymer. For the non-linear polysiloxane branched crosslinker the reaction may be carried out with a diol comprising at least one oligomeric or polymeric group or a siloxane diol with the desired diisocyanate.
In an embodiment, where the non-linear polysiloxane based multifunctional branched crosslinker has the formula (X)n-S, multifunctional alcohols or polyols, multifunctional amines or polyamines, or multifunctional thiols or polythiols, are added to the reaction mixture at any stage of the above reaction process. Examples of triols and tetraol are glycerol, 1,2,6-Hexanetriol, l, l, l-Tris(hydroxymethyl)propane, pentane-l,2,3-triol, propane- 1, 1, 1-triol, cyclohexane- l,2,4-triol, cyclopropane-l,2,3-triol , benzenetriol, cyanuric acid, pentane- l, l,5,5-tetraol, hexane-l,2,5,6-tetraol, 1,2,4,5-tetrahydroxybenzene, butane- 1 ,2, 3,4-tetraol, [1, 1 '-biphenyl] -3 ,3 ',5 ,5 '-tetraol.
In an embodiment where the non-linear polysiloxane based multifunctional branched crosslinker has the formula (X)n-T, an isocyanate having a functionality of three or greater is added to the reaction mixture at any stage of the above reaction process. Examples of triisocyanate and tetraisocyanate are methylidynetri-p-phenylene triisocyanate, undecane- 1 ,6, 1 1 -triyl triisocyanate, silicon tetraisocyanate.
As an example, the structures of glycerol, l, l, l-Tris(hydroxymethyl)propane, and undecane- 1,6, 1 1 -triyl triisocyanate are shown below:
Figure imgf000021_0001
Glycerol 1 , 1, 1 -Tris(hydroxymethyl)propane
Figure imgf000021_0002
undecane- 1,6, 1 1 -triyl triisocyanate It will be understood now that the reaction sequence described above can be altered by first reacting the diol comprising at least one oligomeric or polymeric group with the diisocyanate unit and chain extending the resultant prepolymer with the siloxane diol. This alters the end group composition. It is also possible to alter the component ratio so the remaining group is a hydroxyl group instead of an isocyanate group. This allows the formation of end groups using starting materials for the end groups comprising an isocyanate group in addition to a reactive double bond. For example isocyanatoethyl methacrylate (IEM) can then be incorporated as endgroup.
In an embodiment, a method of production of the non-linear polysiloxane based multi-functional cross-linker comprises the steps of: a. reacting a diisocyanate with one or more polysiloxane diols under an inert gas at elevated temperature in the presence of a catalyst to form an intermediate; b. reacting said intermediate with one or more diols comprising at least one pendant hydrophilic oligomeric or polymeric group, under a dry gas in the presence of a catalyst to form a polymer; c. reacting said polymer with a compound having at least one reactive double bond in the presence of a catalyst under a dry gas; and d. adding to the reaction mixture at any stage of the above reaction process an alcohol, amine, or thiol having a functionality of three or greater in the case that the non-linear polysiloxane based multifunctional branched crosslinker has the formula (X)n-S, or adding to the reaction mixture at any stage of the above reaction process an isocyanate having a functionality of three or greater in the case that the non-linear polysiloxane based multifunctional branched crosslinker has the formula (X)n-T.
In an embodiment, a method of production of the non-linear polysiloxane based multi-functional cross-linker comprises the steps of: a. reacting a diisocyanate with one or more diols comprising at least one pendant hydrophilic oligomeric or polymeric group under an inert gas at elevated temperature in the presence of a catalyst to form an intermediate; b. reacting said intermediate with one or more polysiloxane diols, under a dry gas with stirring in the presence of a catalyst to form a polymer; c. reacting said polymer with a compound having at least one reactive double bond in the presence of a catalyst under a dry gas; and d. adding to the reaction mixture at any stage of the above reaction process an alcohol having a functionality of three or greater in the case that the non-linear polysiloxane based multifunctional branched crosslinker has the formula (X)n-S, or adding to the reaction mixture at any stage of the above reaction process an isocyanate having a functionality of three or greater in the case that the non-linear polysiloxane based multifunctional branched crosslinker has the formula (X)n-T.
In an embodiment, glycerol, 1,2,6-Hexanetriol, or l, l, l-Tris(hydroxymethyl)propane is added to the reaction mixture at any stage of the above reaction process. In an embodiment, the amount of siloxane units is from 1 to 99% by weight of the total weight of the polysiloxane diol and the diol comprising at least one pendant oligomeric or polymeric group in the composition, and the amount of the diol comprising at least one pendant oligomeric or polymeric group is from 1 to 99% by weight of the total weight of the polysiloxane diol and the diol comprising at least one pendant oligomeric or polymeric group in the composition. The non-linear polysiloxane based multifunctional branched crosslinkers may be used in polymerizable compositions to make ophthalmic devices, such as contact lenses. In addition to comprising (a) the non-linear polysiloxane based multifunctional branched crosslinkers, such
polymerizable composition may comprise:
(b) free radical initiators; (c) optionally hydrophilic vinylic monomers, macromers or prepolymers;
(d) optionally polysiloxane vinylic monomers, macromers or prepolymers;
In an embodiment, in the polymerizable composition the hydrophilic monomers may be N,N- dimethylacrylamide (DMA), 2-hydroxyethylmethacrylate (HEMA), and mixtures thereof. In an embodiment, the polysiloxane vinylic monomers may be mono-methacryloxypropyl terminated polydimethylsiloxane, where the number average molecular weight of the silicone-containing monomer is from 600 to 800g/mol as determined by NMR. In an embodiment, the polymerizable composition may comprise isobornyl methacrylate.
The polymerizable composition to form a silicone hydrogel polymer can comprise at least one hydrophilic monomer, macromer, or prepolymer. Examples of hydrophilic monomers, macromers, or prepolymers include N,N-dimethylacrylamide (DMA), 2-hydroxyethylmethacrylate (HEMA), N,N- dimethylmethacrylamide (DMMA), 2-acrylamidoglycolic acid, 3-acryloylamino-l-propanol, N- hydroxyethyl acrylamide, N-[tris(hydroxymethyl)methyl]-acrylamide, N-methyl-3-methylene-2- pyrrolidone, l-ethyl-3-methylene-2-pyrrolidone, l-methyl-5-methylene-2-pyrrolidone, l-ethyl-5- methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-n- propyl-3-methylene-2-pyrrolidone, l-n-propyl-5-methylene-2-pyrrolidone, l-isopropyl-3-methylene-2- pyrrolidone, 1 -isopropyl-5 -methylene-2-pyrrolidone, 1 -n-butyl-3-methylene-2-pyrrolidone, 1 -tert-butyl-3 - methylene-2-pyrrolidone, 2-hydroxyethyl acrylate (HEA), hydroxypropyl acrylate, hydroxypropyl methacrylate (HPMA), trimethylammonium 2-hydroxy propylmethacrylate hydrochloride, aminopropyl methacrylate hydrochloride, dimethylaminoethyl methacrylate (DMAEMA), glycerol methacrylate (GMA), N-vinyl-2-pyrrolidone (NVP), allyl alcohol, vinylpyridine, a Ci-C4-alkoxy polyethylene glycol(meth)acrylate having a weight average molecular weight of up to 1500, methacrylic acid, N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, N-vinyl caprolactam, and mixtures thereof. The polymerizable composition to form the silicone hydrogel polymer, can comprise a polysiloxane vinylic monomer, macromer, or prepolymer. Examples includes those described in U.S. Pat Nos. 471 1943, 5070215, 5998498, 7071274, 71 12641 which are herein incorporated by reference in their entirety. Polysiloxane vinylic monomers include without limitation: a silicon-containing vinyl carbonate monomer, a silicon-containing vinyl carbamate monomer, a monomethacryloxypropyl terminated polydimethylsiloxane monomer, a monomethacryloxypropyl terminated mono-n-butyl terminated polydimethyl siloxane monomer, and any combination thereof. In certain embodiment, the polysiloxane vinylic monomers may be TRIS (3 -[tris(trimethylsilyloxy)silyl] -propyl methacrylate). In certain embodiments, the polysiloxane vinylic monomers may be SIGMA methyl bis(trimethylsiloxy)silyl propyl glycerol methacrylate. In certain embodiment, the polysiloxane vinylic monomers may be mono- methacryloxypropyl terminated polydimethylsiloxane, where the number average molecular weight of the silicone-containing monomer is ranging from 600 to 800g/mol as determined by NMR.
The polymerizable composition to form the silicone hydrogel polymer may comprise a modulus modifier. Examples of modulus modifiers include without limitation: isobornyl methacrylate, isobornyl acrylate, dicyclopentandienyl acrylate, dicyclopentadienyl methacrylate, adamantanyl acrylate, adamantyanyl methacrylate, isopinocamphyl acrylate, isopinocamphyl methacrylate, and combination thereof. The polymerizable composition to form the silicone hydrogel polymer may comprise a free radical initiator. A free radical initiator can be either a photoinitiator or a thermal initiator. Suitable photoinitiators include, without limitation, benzoin methyl ether, diethoxyacetophenone, a
benzoylphosphine oxide, 1 -hydroxy cyclohexyl phenyl ketone, Darocure® types of photoinitiators, and Irgacure® types of photoinitiators, preferably Darocure® 1 173, and Irgacure® 2959. Examples of benzoylphosphine oxide initiators include 2,4,6-trimethylbenzoyldiphenylophosphine oxide (TPO); bis- (2,6-dichlorobenzoyl)-4-N-propylphenylphosphine oxide; and bis-(2,6-dichlorobenzoyl)-4-N- butylphenylphosphine oxide. Reactive photoinitiators which can be incorporated, for example, into a prepolymer or can be used as a special monomer are also suitable. Examples of reactive photoinitiators are those disclosed in EP 632 329, herein incorporated by reference in its entirety. The polymerization can then be triggered off by actinic radiation, for example light, in particular UV light of a suitable wavelength. The spectral requirements can be controlled accordingly, if appropriate, by addition of suitable photosensitizers. Examples of suitable thermal initiators include, but are not limited to, 2,2'- azobis(2,4-dimethylpentanenitrile), 2,2'-azobis(2-methylpropanenitrile), 2,2'-azobis(2- methylbutanenitrile), peroxides such as benzoyl peroxide, and the like. Preferably, the thermal initiator is 2,2 '-azobis(isobutyronitrile) (AIBN) .
The polymerizable composition to form the silicone hydrogel polymer, can comprise a solvent. Example of suitable solvents includes without limitation, water, alcohols (such as t-amyl alcohol, ethanol, 2-butanol, 1-propanol, 2-propanol, cyclohexanol etc.), tetrahydroiuran, ethyl acetate, dimethyl formamide, diethylene glycol methyl ether, acetone, methyl ethyl ketone, polyethylene glycols, methylene chloride, and mixtures thereof.
Without being bound by any particular theory, it is believed that when the polymerizable composition are activated in the presence of an ultraviolet source or under heat in the presence of one or more photoinitiators or thermal initiators, the polymerizable composition forms a crosslinked silicone hydrogel polymer.
In an embodiment, a silicone hydrogel polymer is formed from the polymerizable composition.
Certain embodiments of the silicone hydrogel polymer have a relatively higher Dk and a relatively lower modulus compared to most existing silicone hydrogel contact lenses. For example, the present silicone hydrogel polymer may have a Dk of at least about 100 or at least 120 Barrer or at least about 130 Barrer or at least about 150 Barrer or at least about 200 or more Barrer, such as up to about 250 Barrer or about 300 Barrer or more, and the modulus of about 0.2 MPa or about 0.4 MPa to about 0.8 MPa or less than 1.0 MPa. One example of a silicone hydrogel polymer has a Dk greater than about 100 Barrer and a modulus from about 0.3 MPa to less than about 0.8 MPa or less than 1.0 MPa. In certain embodiments, the present silicone hydrogel polymer have a Dk of about 100 and a modulus of about 0.4 MPa. In other embodiments, the present silicone hydrogel polymer have a Dk of about 200 and a modulus of about 0.8 MPa. In yet another embodiment, the present silicone hydrogel polymer have a Dk of about 150 Barrer and a modulus of about 0.8 MPa. In comparison, the existing, commercially available Acuvue Advance contact lens has a modulus of about 0.4 MPa and a Dk of about 60. The existing commercially available AIROPTIX Night & Day contact lens has a modulus of about 1.5 and a Dk of about 140. Thus certain embodiments of the present silicone hydrogel polymer have a relatively greater Dk, and are relatively softer than existing silicone hydrogel contact lenses. In an embodiment, a silicone hydrogel polymer formed from the polymerizable composition is transparent, and has when fully hydrated, an oxygen permeability of at least 100 Barrer, or a modulus from about 0.2 MPa to about 1.0 MPa, or any combination thereof.
In certain embodiments, the silicone hydrogel polymer is transparent and has a contact angle less than 120°, a modulus from about 0.2 MPa to about 1.0 MPa, and an oxygen permeability of more than about 100 Barrer.
In certain embodiments, the silicone hydrogel polymer is transparent and has a contact angle less than 1 10°, a modulus from about 0.2 MPa to about 0.8 MPa, and an oxygen permeability of more than about 1 10 Barrer. In certain embodiments, the silicone hydrogel polymer is transparent and has a contact angle less than 1 10° a modulus from about 0.2 MPa to about 0.5 MPa, and an oxygen permeability of more than about 1 10 Barrer.
In an embodiment, a method of manufacturing a silicone hydrogel polymer comprises the steps of: i) introducing a lens formulation into a mold for making contact lenses, wherein the lens-forming formulation comprises
(a) a non-linear polysiloxane based multifunctional branched crosslinker as previously described;
(b) free radical initiator; (c) optionally hydrophilic vinylic monomers, macromers or prepolymers;
(d) optionally polysiloxane vinylic monomers, macromers or prepolymers; ii) polymerizing the lens formulation in the mold; iii) optionally, contacting the formed polymer with a washing liquid to remove extractable material from the polymer; and iv) optionally, hydrating the polymer.
A person skilled in the art may make ophthalmic devices, such as silicone hydrogel contact lenses, e.g., by cast-molding in molds of a lens formulation comprising at least a silicone containing monomer or polymer, at least one hydrophilic monomer or macromer, and other necessary components. In one embodiment, the hydrophilic component can be (in total or in part) the non-linear polysiloxane crosslinker. The ophthalmic devices or contact lenses can be made with an ultraviolet or thermally curable formulation for use in a contact lens will frequently have a hydrophilic component which is
approximately 30-80% by weight of the total weight of the composition. The hydrophilic components may be and typically are DMA (Dimethylacrylamide), HEMA, or NVP (N -vinyl Pyrrolidone). The silicone component may account for approximately 20-70% by weight of the total composition. When contact lenses are made using the present polymers, preferably the contact lens comprises at least 10 % silicone hydrogel and the present non-linear polysiloxane crosslinker. The silicone component may include TRIS (3-[tris(trimethylsilyloxy)silyl]-propyl methacrylate), SIGMA methyl
bis(trimethylsiloxy)silyl propyl glycerol methacrylate and/or polydimethlysiloxanes.
In an embodiment, an ophthalmic device, such as a contact lens, is formed from the
polymerizable composition. An ophthalmic device or contact lens may consist of the present non-linear polysiloxane crosslinker. On the other hand, the present non-linear polysiloxane crosslinker may be incorporated into an ophthalmic device or contact lens as a crosslinker by reacting them with hydrophilic and silicone components that make up the lens formulation, e.g. by reacting the non-linear polysiloxane crosslinker in one embodiment with DMA and TRIS or SIGMA to form a partially polymerized product. The partially polymerized product is then functionalized with one or more compounds having at least one reactive double bond. Preferably, lenses made with the present non-linear polysiloxane crosslinker include at least 10% by weight silicone hydrogel. The number and molecular weight of diols: The hydroxyl number of the diols is determined using ASTM D4274: Standard Test Methods for Testing Polyurethane Raw Materials: Determination of Hydroxyl Numbers of Polyols.
Isocyanate content in the polymer and prepolymers was determined by titration using ASTM D2572: Standard Test Methods for Isocyanate Groups in Urethane Materials or Prepolymers.
Molecular weights of polymer: The molecular weights for all polymer samples are determined using guidelines set in ASTM D5296: Standard Test Method for Molecular Weight Averages and Molecular Weight Distribution of Polystyrene by High Performance Size-Exclusion Chromatography. GPC weight average molecular weight (Mw) and GPC number average molecular weight (Mn) in g/mol and the polydispersity index (PDI=Mw/Mn) of the non-linear multifunctional polysiloxane branched crosslinker were determined by Gel Permeation Chromatography (GPC) using polystyrene standards and Ν,Ν-dimethylformamide (DMF) as the solvent at 53 °C.
In certain embodiments, a post molding surface treatment is performed to enhance surface wettability and/or one or more other properties of the ophthalmic devices or contact lenses. Although various embodiments of the invention have been described using specific terms, devices, and methods, such description is for illustrative purposes only. The words used are words of description rather than of limitation. It is to be understood that changes and variations may be made by those skilled in the art without departing from the spirit or scope of the present invention, which is set forth in the following claims. In addition, it should be understood that aspects of the various embodiments and preferred ranges may be interchanged either in whole or in part and/or be combined in any manners. Therefore, the spirit and scope of the appended claims should not be limited to the description of the preferred versions contained therein.
Examples The following test methods may be used in the Examples.
Oxvsen Permeability Measurements The intrinsic Dk value of a lens can be estimated based on a Dk value corrected for the surface resistance to oxygen flux caused by the boundary layer effect as follows. The measurement used a stacking method of the material for correction of boundary layer effects.
Oxygen transmission rate J through the lens is measured by the coulometric method on a Mocon MH2/21 instrument (available from Mocon Inc) with Mocon Permeability System software. The lens (or stack of lenses) are tested in a HPLC grade water cell at 34°C. An air stream (from compressed air gas cylinder), having a known percentage of oxygen (e.g., 21%), is passed across one side of the lens at a rate of about 10 mL/min, while a nitrogen stream (from 98% compressed nitrogen/2% hydrogen gas cylinder) is passed on the opposite side of the lens at a rate of about 10 mL/min. The pressure settings for nitrogen humidifier is 3.7 PSI to obtain about 88% relative humidity for nitrogen. The stir motor's speed is set to 600 rpm, corresponding to an indicated setting of "6" on the control knob of motor controller. The thickness (t) of the lens in the area being exposed for testing is determined by measuring about 10 locations with an Electronic Thickness Gauge Model ET-3 (available from Rehder Development Company), and averaging the measurements. The oxygen transmission rate J and thickness t of 1 lens, stack of 2 lenses, stack of 3 lenses are measured. Plot the resistance (ΔΡ/J) versus thickness t, and fit a curve of the form Y=a+bX, where Y=(AP/J), and X=t. The residual oxygen resistance, Rr is equal to a. The estimated intrinsic Dk is equal to 1/b. ΔΡ is partial pressure of oxygen and is obtained by calculation (assumptions: air pressure= latm, oxygen fraction in air = 0.2095), J is oxygen transmission rate, t is thickness. Modulus Measurements
Modulus is measured using Instron testing machine, Model No. 5566 (available from instron) with SOON load cell, and Bluehill software (version 2.1 1 , or equivalent). At least five specimens from the films are die cut using the ASTM D-1708 Microtensile die, polyethylene block and compression press. The Mitutoyo micrometer, Model No. 505-637-50 (available from Mitutoyo America Corporation) is used to measure the sample thickness. The distance between the grips on the Instron is adjusted to 0.9 inches by using the '"Fine Position" wheel and a ruler. The upper and lower ends of the specimen are inserted into the upper and lower grips and the grip jaws are closed. The pressure on the grips is 70 PSI. Run the test for modulus measurement. At the completion of the test, once the sample has broken and the crosshead has returned to gauge length, release the pressure on the grip and remove the sample. The modulus is defined as the slope of the plot of tensile stress versus tensile strain from 0-10% strain (eq 1, 2 3 where F is the force applied to the sample, A is the cross-sectional area of the sample, L is the length of the sample and L0 is the sample's original length). The test is repeated for at least five test specimens and averaging the measurements.
Modulus=stress/strain (eq 1)
Stress=F/A (eq 2) Strain=100% X (L-Lo)/L0 (eq3)
Tear Strength Measurements
The tear strength is characterized on unmcked 90 °C angle specimens (type C) according to ASTM D624-00 "Standard Test Method for Tear Strength of Conventional Vulcanized Rubber and Thermoplastic Elastomers". All samples are tested using Instron testing machine, Model No. 5566 (available from Instron) with 500N load cell, and Bluehill software (version 2.11, or equivalent). The grip distance was set at 50.8 mm and samples were tested with a constant extension rate of 100 mm/min until failure. The Mitutoyo micrometer, Model No. 505-637-50 (available from Mitutoyo America Corporation) is used to measure the sample thickness. The thickness of all samples is measured prior to testing in three locations near the site of tearing (at the apex, above and below the apex) and the three values are averaged to obtain the sample thickness. The tear strength is calculated as the maximum force obtained during testing divided by the sample thickness (N/mm). The test is repeated for at least five test specimens and the measurements averaged.
Contact Angle Measurements
Contact angle measurements are performed by the sessile drop method using rame-hart Model 590 Automated Goniometer with a DROPimage Advanced v 2.5 software (available from rame-hart instrument co.). The contact lens is gently blotted with a piece of dry filter paper, it was then placed onto a Micro Slides (available from VWR, North American Cat. No. 48300-047) on the supporting stage of the Goniometer. A PBS solution droplet (approximately 6-8 μί) is then dispensed on the central surface area of the lens. Use DROPimage Advanced v 2.5 software to capture an image of the drop on the lens and through data analysis the contact angle at the liquid-solid interface is measured. The process follows strict time schedule to avoid significant evaporation of the lens surface water as well as the liquid drop. The time from the start of blotting to the completion of the measurement is closely controlled to be 1 minutes 35 seconds. Hie lens was then returned to the PBS to soak for at least 10 mm before the process was repeated on at least two further occasions, giving a total of at least three measurement runs for each lens. The measurements are averaged.
Water Content Measurements
Water content is defined as: EWC = HydratedWe iSht - DryWeight ^
HydratedWe ight
The hydrated weight determination: Prepare a piece of Whatman # 1 filter paper by folding it in half and adding PBS dropwise until it is barely moist. To ensure a consistent humidity level, add enough PBS as to leave the outer edge of the filter paper dry. The filter paper may be reused to blot lenses until the edge is no longer dry or three lenses have been blotted, whichever comes first. Using blunt-tipped tweezers, remove a single lens from the PBS storage solution, entraining a minimum amount of excess PBS on the surface. Place the lens flat on the filter paper, fold the paper over the lens, and tap firmly once. Unfold paper, move lens to a new location on the moistened paper, fold again, and blot a second time. Move to a third location and blot a third time. Ensure tweezers are dry then transfer blotted lens to the weighing substrate and record combined mass of hydrated lens and substrate. Subtract the mass of the substrate to calculate the mass of the hydrated lens.
The dry weight determination: Transfer blotted, weighed substrates and lenses to a 100°C oven for 16-18 hours or until their mass ceases to change. Lenses made of materials which degrade at that temperature may instead be dried in a vacuum oven at 60°C until constant mass. Remove from oven and transfer to ajar with active desiccant and allow to cool to room temperature, 1-2 hours. Record mass of dry lenses + weighing substrates to the nearest 0.1 mg.
Light Transmission Measurements
The light transmission properties of a contact lens is measured using the procedure outlined in the IS/ISO 18369-3(2006): Ophthalmic Optics-Contact Lenses Part 3: Measurement Methods. The measurement is performed using a Thermo Scientific Evolution 220UV-visible spectrophotometer (spectral bandwidth l-2nm) between the wavelengths of 400-75 Onm, which covers the entire visible spectrum. The test is performed with the contact lens in a fully hydrated state whilst immersed in saline. A special cuvette (5mm light path, 15 mm inner width) is helpful for positioning the contact lens perpendicular to the incident beam during the measurement and keeping the lens in a fixed position at the exact height that the incident beam passes through the cuvette. The measurement is made inside the central optic zone of the contact lens.
Example 1 Synthesis of Ingredient 1 In ingredient 1 the amount of siloxane unit is 85% by weight of the total weight of the siloxane unit and PEG diol in the composition, and the amount of PEG diol is 15% by weight of the total weight of siloxane unit and PEG diol in the composition. Triol used for synthesizing ingredient 1 is glycerol.
In a nitrogen rich glove-box (126.85g, 1.38mol) Shinetsu 160AS-diol (a,oo-bis(2~hydroxyethoxypropyi)- polydimethylsiloxane, M.W. ca 1000, from Shin-Etsu) was added to a glass jar. In the same glove box, (42.34g, 1.95mol) isophorone diisocyanate IPDI was added to a separate glass jar. Both starting materials were removed from the glove-box and added to a 3 -neck, 1000ml, jacketed reactor. The 1000ml, 3 -neck jacketed reactor was fitted with a nitrogen inlet/outlet, thermocouple, and overhead mechanical stirrer. The heating/chiller connected to the 3 -neck, 1000ml, jacketed reactor was turned on to a set-point: 60- 65C. Both nitrogen gas and stirring were turned on. With reaction temperature at 51.4°C, 2Χ20μ1 dibutyltin dilaurate (DBTDL) was added via micro-syringe. Heating mantle was turned off and reaction was allowed to exotherm (reaction high temp during exotherm 62.6°C). After exotherm was complete, and internal heat was at 58.5°C, heating mantle was turned on with set-point 53.5°C. Solution was allowed to react for 2hours.
Weighed (22.40g, 0.21 lmol) Ymer N120 (mono-3,3-bis(hydroxymethyl)butyl- and mono- methoxy-terminated polyethylene glycol, M.W. ca 1000, from Perstorp Polyols, Inc.) into syringe and added to reaction. With reaction temperature at 50.2°C, 2Χ20μ1 DBTDL was added and solution was allowed to react 2 hours. After 2 hours (0.50g, 0.0054mol) glycerol and 2Χ20μ1 DBTDL was added via syringe. Again, solution was allowed to react with stirring for 2 hours. After 2 hours, the heater was turned down to 42.0°C. With internal temperature at 42.4°C, (7.9 lg 0.624mol) 2-hydroxyethyl methacryiate (HEMA)/(0.05g) butylated hydroxytoluene (BHT) and 2Χ20μ1 DBTDL was added. Solution was allowed to stir with heating set at 42.0°C overnight leading to formation of Ingredient 1.
The number average molecular weight of Ingredient 1 is determined to be about 22000 Daltons based on conventional GPC using DMF at 53°C as the eluent and polystyrene as the standard (Table 1). Table 1
Figure imgf000033_0001
:using DMF as solvent
Example 2 Synthesis of ingredient la
In ingredient la the amount of siloxane unit is 75% by weight of the total weight of the siloxane unit and PEG diol in the composition, and the amount of PEG diol is 25% by weight of the total weight of siloxane unit and PEG diol in the composition. Triol used for synthesizing ingredient la is glycerol. In a nitrogen rich glove-box (110.72g, 1.25mol) Shinetsu 160AS-diol was added to (41.63g, 2.00mol) IPDI in a glass jar. Solution was removed from glove-box and fitted into a heating mantle (set-point: 81.0C) with overhead mechanical stirrer nitrogen inlet/outlet, and heating mantle was . Both nitrogen gas and stirring were turned on. With reaction temperature at 55.5C, 2Χ20μ1 dibutyltin dilaurate(DBTDL) was added via micro-syringe. Heating mantle was turned off and reaction was allowed to exotherm (reaction high temp during exotherm 99.2C). After exotherm was complete, heating mantle was turned on with set-point 65.0C. Solution was allowed to react for 2 hours.
Weighed (37.36g, 0.3663mol) Ymer N120 into syringe and added to reaction. With reaction temperature at 57.7C, 2Χ20μ1 DBTDL was added and solution was allowed to react 2 hours. After 2hours (0.50g, 0.0109mol) glycerol and 2Χ20μ1 DBTDL was added via syringe. Again, solution was allowed to react with stirring for 2 hours. After 2 hours, (10.29g 0.8441mol) HEMA/(0.05g) BHT and 2Χ20μ1 DBTDL was added. Solution was allowed to stir with heating mantle set at 42.0C overnight leading to formation of Ingredient la. The number average molecular weight of Ingredient la is determined to be about 22503 Daltons based on conventional GPC using DMF at 53°C as the eluent and polystyrene as the standard.
Example 3 Synthesis of ingredient lb
In ingredient lb the amount of siloxane unit is 85% by weight of the total weight of the siloxane unit and PEG diol in the composition, and the amount of PEG diol is 15% by weight of the total weight of siloxane unit and PEG diol in the composition. Triol used for synthesizing ingredient lb is 1,2,6- Hexanetriol. In a nitrogen rich glove-box (126.85g, 1.38mol) Shinetsu 160AS-diol ( ,o bis(2- hydroxyethoxypropyl)-poiydimethylsiloxane, M.VV. ca 1000, from Shin-Etsu) was added to a glass jar. In the same glove box, (42.34g, 1.95mol) isophorone diisocyanate IPDI was added to a separate glass jar. Both starting materials were removed from the glove-box and added to a 3-neck, 1000ml, jacketed reactor. The 1000ml, 3-neck jacketed reactor was fitted with a nitrogen inlet/outlet, thermocouple, and overhead mechanical stirrer. The heating/chiller connected to the 3-neck, 1000ml, jacketed reactor was turned on to a set-point: 60-65C. Both nitrogen gas and stirring were turned on. With reaction temperature at 51.4°C, 2Χ20μ1 dibutyltin dilaurate (DBTDL) was added via micro-syringe. Heating mantle was turned off and reaction was allowed to exotherm (reaction high temp during exotherm 62.6°C). After exotherm was complete, and internal heat was at 58.5°C, heating mantle was turned on with set-point 53.5°C. Solution was allowed to react for 2hours.
Weighed (22.40g, 0.21 lmol) Ymer N120 (mono-3,3-bis(hydroxymethyl)butyl- and mono- methoxy-terminated polyethylene glycol, M.W. ca 1000, from Perstorp Polyols, Inc.) into syringe and added to reaction. With reaction temperature at 50.2°C, 2Χ20μ1 DBTDL was added and solution was allowed to react 2 hours. After 2hours (0.73g, 0.0054mol) 1,2,6-Hexanetriol and 2Χ20μ1 DBTDL was added via syringe. Again, solution was allowed to react with stirring for 2 hours. After 2 hours, the heater was turned down to 42.0°C. With internal temperature at 42.4°C, (7.9 lg 0.624mol) 2-hydroxyethyl methacrviate (HEMA)/(0.05g) butylated hydroxytoluene (BHT) and 2Χ20μ1 DBTDL was added. Solution was allowed to stir with heating set at 42.0°C overnight leading to formation of Ingredient lb. The number average molecular weight of Ingredient lb is determined to be about 18511 Daltons based on conventional GPC using DMF at 53°C as the eluent and polystyrene as the standard.
Example 4 Preparation of silicone hydrogel films with formulations containing ingredient 1 ingredient 1 is mixed with Methacrylate PDMS 600-800, ΊΜ, M-dimethylacrylamide (DMA), 2- hydroxyethyl methacrylate (HEMA), lsobomyl methacrylate, Darocure 1173 with the formulation composition in Table 2. To tins mixture, t-amyl alcohol solvent was added (with weight of t-amyl alcohol to total weight before t-amyl alcohol ratio being 2:5). The monomer mixture was placed in polypropylene lens molds or borosilicate glass molds and irradiated under UV light for about 5 rains. Films formed are removed from the molds and repeatedly extracted using IPA/water mixtures (1 :3, v/v) and hydrated in de- ionized (DI) water for a minimum of 4 hours. The films thus obtained show low modulus and high Dk. Evaluation of physical properties before and after autoclaving (100-120°C for a minimum of 1 hour) give results set forth in Table 3.
Table 2
Figure imgf000035_0001
before autoclaving # after autoclaving

Claims

CLAIMS What is claimed is:
1. A non-linear polysiloxane based multifunctional branched crosslinker of structure:
(X)„-S wherein the branching point S is derived from multifunctional alcohols or polyols, multifunctional amines or polyamines, or multifunctional thiols or polythiols, and which have a functionality m of 3 or greater and wherein m is equal to or greater than n; wherein X can be the same or different and is selected from the group consisting of formulae (S-I), (S-II), (S-III), (S-IV), or (S-V), wherein said formulae possess the following structures:
-[I-PDMS]z-I-[[F-[I-PDMS]r]p-I- (S-I)
-[I-F]z-I-[PDMS-[I-F]r]p-I- (S-II)
-I-[[F-[I-PDMS]r]p-I-F-I- (S-III)
-I-PDMS-[I-F]z-I-[PDMS-[I-F]r]p-I-PDMS-I- (S-IV)
-(X)n-S-(X)n- (S-V)
wherein I is a unit derived from a diisocyanate, PDMS is a unit derived from a polydialkyl or polydiaryl or polyalkylaryl siloxane diol, F is a diol, diamine, or dithiol derived unit comprising at least one pendant oligomeric or polymeric group, wherein p is an integer ranging from 1 to 50, r is an integer ranging from 1 to 50, and z is an integer ranging from 1 to 50, wherein at least three of the terminal diisocyanates I have been reacted with an ethylenically unsaturated monofunctional monomer, and wherein the total number average molecular weight is less than 100,000 Dalton and has a viscosity less than 1,000,000 mPa sec, and wherein there are substantially no remaining unreacted isocyanates in the branched crosslinker; or of structure:
Figure imgf000037_0001
wherein the branching point T is derived from a multifunctional isocyanate with a functionality m of 3 or greater and wherein n = m; wherein X can be the same or different and is selected from the group consisting of formulae (T-I), (T-II), (T-III), (T-IV), or (T-V), wherein said formulae possess the following structures:
-[PDMS]z-I-[[F-[I-PDMS]r]p- (T-I)
-[[F-[I-PDMS]r]p-I-F- (T-II)
-[F]z-I-[PDMS-[I-F]r]p- (T-III)
-PDMS-[I-F]z-I-[PDMS-[I-F]r]p-I-PDMS- (T-IV)
-(X)n-T-(X)n- (T-V) wherein I is a unit derived from a diisocyanate, PDMS is a unit derived from a polydialkyl or polydiaryl or polyalkylaryl siloxane diol, F is a diol, diamine, or dithiol derived unit comprising at least one pendant oligomeric or polymeric group, wherein p is an integer ranging from 1 to 50, r is an integer ranging from 1 to 50, and z is an integer ranging from 1 to 50, wherein at least three of the terminal hydroxyls have been reacted with the mono adduct of a diisocyanate and an ethylenically unsaturated monofunctional monomer, and wherein the total number average molecular weight is less than 100,000 Dalton and has a viscosity less than 1,000,000 mPa sec, and wherein there are substantially no remaining unreacted isocyanates in the branched crosslinker.
2. The non-linear polysiloxane based multifunctional branched crosslinker according to claim 1, wherein the pendant oligomeric or polymeric groups are hydrophilic groups.
3. The non-linear polysiloxane based multifunctional branched crosslinker according to claim 1 or 2, wherein the pendant hydrophilic oligomeric or polymeric groups are polyethylene oxide (PEO) groups.
4. The non-linear polysiloxane based multifunctional branched crosslinker according to claim 1 or 2, wherein the pendant hydrophilic oligomeric or polymeric groups are poly(2-oxazoline) groups.
5. The non-linear polysiloxane based multifunctional branched crosslinker according to any one of claim 1-4, wherein the diol, diamine, or dithiol derived unit comprising at least one pendant oligomeric or polymeric group has a Mn ranging from 300-5000 g/mol, as determined by Gel Permeation
Chromatography using N, N-dimethylformamide (DMF) as the solvent at 53 °C.
6. The non-linear polysiloxane based multifunctional branched crosslinker according to any one of claims 1-5, wherein the backbone contains units derived from polydimethylsiloxane diol and units derived from diisocyanate.
7. The non-linear polysiloxane based multifunctional branched crosslinker according to any one of claims 1-6, wherein the non-linear polysiloxane based multifunctional branched crosslinker comprises a double bond located at at least three terminal ends.
8. The non-linear polysiloxane based multifunctional branched crosslinker according to any one of claims 1-7, wherein a reactive double bond at a terminal end is formed from hydroxyethylmethacrylate (HEMA).
9. The non-linear polysiloxane based multifunctional branched crosslinker according to any one of claims 1-8, wherein the number average molecular weight of the crosslinker is from 8000 to 55000 g/mol as determined by Gel Permeation Chromatography using Ν,Ν-dimethyl formamide (DMF) as the solvent at 53°C.
10. The non-linear polysiloxane based multifunctional branched crosslinker according to any one of claim 1-9, wherein the diol, diamine, or dithiol derived unit comprising at least one pendant oligomeric or polymeric group has a Mn ranging from 400-2500 g/mol, as determined by Gel Permeation
Chromatography using N, N-dimethylformamide (DMF) as the solvent at 53 °C.
1 1. The non-linear polysiloxane based multifunctional branched crosslinker according to any one of claim 1-10, wherein the non-linear polysiloxane based multifunctional branched crosslinker has structure (X)„-S.
12. The non-linear polysiloxane based multifunctional branched crosslinker according to any one of claim 1-10, wherein the non-linear polysiloxane based multifunctional branched crosslinker has structure (X)„-T.
13. The non-linear polysiloxane based multifunctional branched crosslinker according to any one of claim 1-12, wherein F is a diol derived unit.
14. The non-linear polysiloxane based multifunctional branched crosslinker according to any one of claim 1-13, wherein PDMS is a unit derived from an alkoxylated polydialkyl or polydiaryl or polyalkylaryl siloxane diol.
15. A method for the production of the non-linear polysiloxane based multifunctional branched crosslinker according to any one of claims 1-14 comprising the steps of: a. reacting a diisocyanate with one or more polysiloxane diols under an inert gas at elevated temperature in the presence of a catalyst to form an intermediate; b. reacting said intermediate with one or more diols comprising at least one pendant hydrophilic oligomeric or polymeric group, under a dry gas in the presence of a catalyst to form a polymer; c. reacting said polymer with a compound having at least one reactive double bond in the presence of a catalyst under a dry gas; and d. adding to the reaction mixture at any stage of the above reaction process an alcohol, amine, or thiol having a functionality of three or greater in the case that the non-linear polysiloxane based multifunctional branched crosslinker has the formula (X)n-S, or adding to the reaction mixture at any stage of the above reaction process an isocyanate having a functionality of three or greater in the case that the non-linear polysiloxane based multifunctional branched crosslinker has the formula (X)n-T.
16. A method for the production of the non-linear polysiloxane based multifunctional branched crosslinker according to any one of claim 1-14, comprising the steps of: a. reacting a diisocyanate with one or more diols comprising at least one pendant hydrophilic oligomeric or polymeric group under an inert gas at elevated temperature in the presence of a catalyst to form an intermediate; b. reacting said intermediate with one or more polysiloxane diols, under a dry gas with stirring in the presence of a catalyst to form a polymer; c. reacting said polymer with a compound having at least one reactive double bond in the presence of a catalyst under a dry gas; and d. adding to the reaction mixture at any stage of the above reaction process an alcohol having a functionality of three or greater in the case that the non-linear polysiloxane based multifunctional branched crosslinker has the formula (X)n-S, or adding to the reaction mixture at any stage of the above reaction process an isocyanate having a functionality of three or greater in the case that the non-linear polysiloxane based multifunctional branched crosslinker has the formula (X)n-T.
17. The method for the production of the non-linear polysiloxane based multifunctional branched crosslinker according to claim 15 or 16, wherein glycerol, 1 ,2,6-Hexanetriol, or 1, 1, 1- Tris(hydroxymethyl)propane is added to the reaction mixture at any stage of the above reaction process.
18. The method of any one of claims 15-17, wherein the amount of siloxane units is from 1 to 99% by weight of the total weight of the polysiloxane diol and the diol comprising at least one pendant oligomeric or polymeric group in the composition, and wherein the amount of the diol comprising at least one pendant oligomeric or polymeric group is from 1 to 99% by weight of the total weight of the polysiloxane diol and the diol comprising at least one pendant oligomeric or polymeric group in the composition.
19. A polymerizable composition comprising:
(a) non-linear polysiloxane based multifunctional branched crosslinkers of any one of claims 1- 14;
(b) free radical initiators;
(c) optionally hydrophilic vinylic monomers, macromers or prepolymers;
(d) optionally polysiloxane vinylic monomers, macromers or prepolymers.
A polymerizable composition comprising:
(a) from 5-99.99 wt % based on the total weight of the polymerizable composition of the non-linear polysiloxane based multifunctional branched crosslinker of any one of claims 1-14;
(b) free radical initiators, in an amount of from 0.01 to 20 wt % based on the total weight of the polymerizable composition;
(c) optionally hydrophilic vinylic monomers, macromers or prepolymers, in an amount of from 0 to 95 wt % based on the total weight of the polymerizable composition;
(d) optionally polysiloxane vinylic monomers, macromers or prepolymers, in an amount of from 0 to 95 wt % based on the total weight of the polymerizable composition.
A polymerizable composition comprising:
(a) non-linear polysiloxane based multifunctional branched crosslinkers according to any claims 1-14; (b) 2-Hydroxy-2-methylpropiophenone as photoinitiator;
(c) hydrophilic monomers which are Ν,Ν-dimethylacrylamide (DMA) and 2- hydroxyethylmethacrylate (HEMA);
(d) mono-methacryloxypropyl terminated polydimethylsiloxane having a number average molecular weight of from 600 to 800 g/mol as determined by NMR.
22. The polymerizable composition according to claim 19 or 20, wherein the hydrophilic monomer is Ν,Ν-dimethylacrylamide (DMA), 2-hydroxyethylmethacrylate (HEMA), or a mixture thereof.
23. The polymerizable composition comprising according to claim 19 or 20, wherein the
polysiloxane vinylic monomers are mono-methacryloxypropyl terminated polydimethylsiloxane and the number average molecular weight of the silicone-containing vinylic monomer is from 600 to 800 g/mol as determined by NMR.
24. The polymerizable composition according to any one of claims 19-23, further comprising a modulus modifier.
25. The polymerizable composition according to claim 24, wherein the modulus modifier comprises isobornyl methacrylate.
26. A silicone hydrogel polymer formed by polymerizing the polymerizable composition of any one of claims 19-25.
27. The silicone hydrogel polymer according to claim 26, wherein the silicone hydrogel polymer is transparent, and when fully hydrated, has an oxygen permeability of at least 100 Barrer or a modulus from about 0.2 MPa to about 1.0 MPa.
28. The silicone hydrogel polymer according to claim 26, wherein the silicone hydrogel polymer is transparent, and when fully hydrated, has an oxygen permeability of at least 100 Barrer and a modulus from about 0.2 MPa to about 0.8 MPa.
29. The silicone hydrogel polymer according to any one of claims 26-28, wherein the silicone hydrogel polymer is transparent and has a contact angle less than 120°, a modulus from about 0.2 MPa to about 1.0 MPa, and an oxygen permeability of more than about 100 Barrer.
30. A silicone hydrogel polymer according to any one of claims 26-29, wherein the silicone hydrogel polymer is transparent and has a contact angle less than 120°, a modulus from about 0.2 MPa to about 0.8 MPa, and an oxygen permeability of more than about 1 10 Barrer.
31. A silicone hydrogel polymer according to any one of claims 26-30, wherein the silicone hydrogel polymer is transparent and has a contact angle less than 120°, a modulus from about 0.2 MPa to about 0.5 MPa, and an oxygen permeability of more than about 1 10 Barrer.
32. A method of manufacturing a silicone hydrogel polymer, comprising the steps of: i) introducing the polymerizable composition according to any one of claims 19-25 into a mold, ii) polymerizing the polymerizable composition in the mold.
33. The method according to claim 32, further comprising the step of: iii) contacting the formed polymer with a washing liquid to remove extractable material from the polymer.
34 The method according to claim 32 or 33, further comprising the step of: iv) hydrating the polymer; wherein said silicone hydrogel polymer is transparent, and has, when fully hydrated, an oxygen permeability of at least 100 Barrer, or a modulus from about 0.2 MPa to about 1 MPa, or any combination thereof.
35. An ophthalmic device comprising the silicone hydrogel polymer of any one of claims 26-31, wherein said ophthalmic device, when fully hydrated, has a modulus from about 0.2 to about 1 MPa, and an oxygen permeability of at least 100 Barrer.
36. The ophthalmic device according to claim 35, wherein the ophthalmic device is a pre-coated contact lens.
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