# Patent

## Title
Silicone-containing polymeric materials with hydrolyzable groups

## Abstract

The invention provides a silicone hydrogel contact lens including a hydrolyzable units. The hydrolyzable units can be converted by hydrolysis into a hydrophilic units which is capable of imparting the silicone hydrogel contact lens a hydrophilic surface without post-curing surface treatment. The invention also provides an actinically crosslinkable prepolymer including hydrolyzable units and use of the prepolymer of the invention. In addition, the invention provides a method for making wettable silicone hydrogel contact lens without posterior surface treatments other than hydrolysis.

## Background
This application is a divisional application of application Ser. No. 12/499,117, filed Jul. 8, 2009 now U.S. Pat. No. 8,079,703, which claims the benefit under 35 USC §119 (e) of U.S. provisional application No. 61/135,474 filed on Jul. 21, 2008, incorporated herein by reference in its entirety.


TECHNICAL FIELD OF THE INVENTION
The present invention is related to a class of silicone-containing prepolymers and uses thereof and to silicone hydrogel contact lenses made from prepolymers of the invention and from a lens formulation containing a monomer with a hydrolyzable silicone-containing group.
BACKGROUND
In recent years, soft silicone hydrogel contact lenses become popular because of their high oxygen permeability and comfort. “Soft” contact lenses can conform closely to the shape of the eye, so oxygen cannot easily circumvent the lens. Soft contact lenses must allow oxygen from the surrounding air (i.e., oxygen) to reach the cornea because the cornea does not receive oxygen from the blood supply like other tissue. If sufficient oxygen does not reach the cornea, corneal swelling occurs. Extended periods of oxygen deprivation cause the undesirable growth of blood vessels in the cornea. By having high oxygen permeability, a silicone hydrogel contact lens allows sufficient oxygen to permeate through the lens to the cornea and to have minimal adverse effects on corneal health.
However, all commercially available silicone hydrogel contact lenses are produced according to a conventional cast molding technique involving use of disposable plastic molds and a mixture of monomers and/or macromers. There are several disadvantages with such conventional cast-molding technique. For example, a traditional cast-molding manufacturing process must include lens extraction in which unpolymerized monomers must be removed from the lenses by using an organic solvent. Such lens extraction increases the production cost and decreases the production efficiency. In addition, disposable plastic molds inherently have unavoidable dimensional variations, because, during injection-molding of plastic molds, fluctuations in the dimensions of molds can occur as a result of fluctuations in the production process (temperatures, pressures, material properties), and also because the resultant molds may undergo non-uniform shrinkage after the injection molding. These dimensional changes in the mold may lead to fluctuations in the parameters of contact lenses to be produced (peak refractive index, diameter, basic curve, central thickness etc.) and to a low fidelity in duplicating complex lens design.
The above described disadvantages encountered in a conventional cast-molding technique can be overcome by using the so-called Lightstream TechnologyTM (CIBA Vision), which involves (1) a lens-forming composition being substantially free of monomers and comprising a substantially purified prepolymer with ethylenically-unsaturated groups, (2) reusable molds produced in high precision, and (3) curing under a spatial limitation of actinic radiation (e.g., UV), as described in U.S. Pat. Nos. 5,508,317, 5,583,463, 5,789,464, and 5,849,810. Lenses can be produced at relatively lower cost according to the Lightstream TechnologyTM to have high consistency and high fidelity to the original lens design.
In order to fully utilize the Lightstream TechnologyTM to make silicone hydrogel contact lenses, there is still a need for new actinically-crosslinkable prepolymers suitable for making silicone hydrogel contact lenses with desired bulk and surface properties according to the Lightstream TechnologyTM.
SUMMARY OF THE INVENTION
The present invention, in one aspect, provides an actinically crosslinkable prepolymer. The prepolymer of the invention is obtained by: (a) copolymerizing an actinically polymerizable composition to obtain an intermediary copolymer with first functional groups, wherein the actinically polymerizable composition comprises (1) at least one vinylic monomer including a hydrolyzable silicone-containing group, (2) at least one hydrophilic vinylic monomer, (3) at least one siloxane-containing monomer having one ethylenically unsaturated group, at least one siloxane-containing macromer having one ethylenically unsaturated group, at least one siloxane-containing monomer having two or more ethylenically unsaturated groups, at least one siloxane-containing macromer having two or more ethylenically unsaturated groups, or a combination of two or more thereof, and (4) optionally a chain transfer agent, provided that at least one of components (2)-(4) further comprises at least one first functional group; and (b) reacting an organic compound with the copolymerization product to form the crosslinkable prepolymer having actinically crosslinkable groups, wherein the organic compound comprises an actinically crosslinkable group and a second functional group, wherein the second functional group of the organic compound reacts with one of the first functional groups of the intermediary copolymer.
In another aspect, the invention provides a soft contact lens. The soft contact lens of the invention comprises: a silicone hydrogel material that is obtained by curing a lens-forming material in a mold and comprises first and/or second hydrolyzable silicone-containing groups, wherein the lens-forming material comprises at least one actinically crosslinkable monomer having one first hydrolyzable silicone-containing group and/or at least one actinically crosslinkable prepolymer having multiple second hydrolyzable silicone-containing groups, wherein the first and second hydrolyzable silicone-containing groups are capable of being cleaved from the silicone hydrogel material by means of hydrolysis so as to provide the soft contact lens with a water contact angle of about 90 degrees or less without post-curing surface treatment.
In a further aspect, the invention provides a method for producing soft contact lenses. The method comprises the steps of: providing a mold for making a soft contact lens, wherein the mold has a first mold half with a first molding surface defining the anterior surface of a contact lens and a second mold half with a second molding surface defining the posterior surface of the contact lens, wherein said first and second mold halves are configured to receive each other such that a cavity is formed between said first and second molding surfaces; introducing a lens-forming material into the cavity, wherein the lens-forming material wherein the lens-forming material comprises at least one actinically crosslinkable monomer having one first hydrolyzable silicone-containing group and/or one actinically crosslinkable prepolymer having multiple second hydrolyzable silicone-containing groups; curing the lens-forming material to form a soft contact lens composed of a silicone hydrogel material including first and/or second hydrolyzable silicone-containing groups; and subjecting the soft contact lens to hydrolysis, whereby during hydrolysis the first and second hydrolyzable silicone-containing groups are cleaved from the silicone hydrogel material so as to provide the soft contact lens with a water contact angle of about 90 degrees or less without post-curing surface treatment.


DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION
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 onlay, 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 “hydrogel” or “hydrogel material” refers to a polymeric material which 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 monomer or at least one silicone-containing macromer or at least one crosslinkable silicone-containing prepolymer.
“Hydrophilic,” as used herein, describes a material or portion thereof that will more readily associate with water than with lipids.
A “monomer” means a low molecular weight compound that can be polymerized. Low molecular weight typically means average molecular weights less than 700 Daltons.
An “actinically-polymerizable monomer” refers to a monomer which can be polymerized actinically. In accordance with the invention, an actinically-polymerizable monomer can be a vinylic monomer or a compound comprising two thiol groups. A compound with two thiol groups can participate in thiol-ene step-growth radical polymerization with a monomer with vinyl group to form a polymer. Step-growth radical polymerization can be used in making contact lenses, as described in a commonly-owned copending US patent application No. 60/869,812 filed Dec. 13, 2006 (entitled “PRODUCTION OF OPHTHALMIC DEVICES BASED ON PHOTO-INDUCED STEP GROWTH POLYMERIZATION”, herein incorporated in reference in its entirety.
A “siloxane-containing monomer” refers to a monomer containing a divalent radical of




in which R1 and R2 are independently a monovalent C1-C10 alkyl, C1-C10 ether, C1-C10 fluoroalkyl, C1-C10 fluoroether or C6-C18 aryl radical, which may comprise hydroxy group, primary, secondary, or tertiary amine group, carboxy group, or carboxylic acid; n is an integer of 4 or higher.

A “vinylic monomer”, as used herein, refers to a monomer that has an ethylenically unsaturated group and can be polymerized actinically or thermally.
The term “olefinically unsaturated group” or “ethylenticaly unsaturated group” is employed herein in a broad sense and is intended to encompass any groups containing a >C═C< group. Exemplary ethylenically unsaturated groups include without limitation acryloyl, methacryloyl, allyl, vinyl, styrenyl, or other C═C containing groups.
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, ionized 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.
The term “fluid” as used herein indicates that a material is capable of flowing like a liquid.
A “hydrophilic monomer” refers to a monomer which can be polymerized to form a polymer that is water-soluble or can absorb at least 10 percent by weight of water.
A “hydrophobic monomer”, as used herein, refers to a vinylic monomer which is polymerized to form a polymer that is insoluble in water and can absorb less than 10 percent by weight water.
A “macromer” refers to a medium and high molecular weight compound which can be polymerized and/or crosslinked. Medium and high molecular weight typically means average molecular weights greater than 700 Daltons.
An “actinically-polymerizable macromer” refers to a macromer which can be polymerized actinically. In accordance with the invention, an actinically-polymerizable macromer can be a macromer with one or more ethylenically unsaturated groups or with two or more thiol groups, which can participate in either free radical chain growth polymerization or thiol-ene step-growth radical polymerization. Preferably, a macromer contains ethylenically unsaturated groups and can be polymerized actinically or thermally.
A “prepolymer” refers to a starting polymer which contains multiple actinically crosslinkable groups and can be cured (e.g., crosslinked) actinically to obtain a crosslinked polymer having a molecular weight much higher than the starting polymer.
“Actinically crosslinkable groups” refers to ethylenically unsaturated groups or thiol groups.
A “silicone-containing prepolymer” refers to a prepolymer which contains silicone and can be crosslinked actinically to obtain a crosslinked polymer having a molecular weight much higher than the starting polymer.
“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.
“Polymer” means a material formed by polymerizing one or more monomers.
As used herein, the term “ethylenically functionalize” in reference to a copolymer or a compound is intended to describe that one or more actinically crosslinkable groups have been covalently attached to a copolymer or compound through the pendant or terminal functional groups of the copolymer or the compound according to a coupling process.
As used herein, the term “multiple” refers to at least two, preferably at least three.
The term “dangling hydrophilic polymer chains” in reference to a prepolymer is intended to describe that the prepolymer comprises hydrophilic polymer chains which each are anchored to the main chain of the prepolymer through one single covalent linkage (preferably at one of the ends of the hydrophilic polymer chain).
A “photoinitiator” refers to a chemical that initiates radical crosslinking/polymerizing reaction by the use of light. Suitable photoinitiators include, without limitation, benzoin methyl ether, diethoxyacetophenone, a benzoylphosphine oxide, 1-hydroxycyclohexyl phenyl ketone, Darocure® types, and Irgacure® types, preferably Darocure® 1173, and Irgacure® 2959.
A “thermal initiator” refers to a chemical that initiates radical crosslinking/polymerizing reaction by the use of heat energy. 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).
A “spatial limitation of actinic radiation” refers to an act or process in which energy radiation in the form of rays is directed by, for example, a mask or screen or combinations thereof, to impinge, in a spatially restricted manner, onto an area having a well defined peripheral boundary. For example, a spatial limitation of UV radiation can be achieved by using a mask or screen that has a transparent or open region (unmasked region) surrounded by a UV impermeable region (masked region), as schematically illustrated in FIGS. 1-9 of U.S. Pat. No. 6,627,124 (herein incorporated by reference in its entirety). The unmasked region has a well defined peripheral boundary with the unmasked region. The energy used for the crosslinking is radiation energy, especially UV radiation, gamma radiation, electron radiation or thermal radiation, the radiation energy preferably being in the form of a substantially parallel beam in order on the one hand to achieve good restriction and on the other hand efficient use of the energy.
“Visibility tinting” in reference to a lens means dying (or coloring) of a lens to enable the user to easily locate a lens in a clear solution within a lens storage, disinfecting or cleaning container. It is well known in the art that a dye and/or a pigment can be used in visibility tinting a lens.
“Dye” means a substance that is soluble in a solvent and that is used to impart color. Dyes are typically translucent and absorb but do not scatter light. Any suitable biocompatible dye can be used in the present invention.
A “Pigment” means a powdered substance that is suspended in a liquid in which it is insoluble. A pigment can be a fluorescent pigment, phosphorescent pigment, pearlescent pigment, or conventional pigment. While any suitable pigment may be employed, it is presently preferred that the pigment be heat resistant, non-toxic and insoluble in aqueous solutions.
“Surface modification”, as used herein, means that an article has been treated in a surface treatment process (or a surface modification process) prior to or posterior to the formation of the article, in which (1) a coating is applied to the surface of the article, (2) chemical species are adsorbed onto the surface of the article, (3) the chemical nature (e.g., electrostatic charge) of chemical groups on the surface of the article are altered, or (4) the surface properties of the article are otherwise modified. Exemplary surface treatment processes include, but are not limited to, plasma processes in which an ionized gas is applied to the surface of an article (see, for example, U.S. Pat. Nos. 4,312,575 and 4,632,844 herein incorporated by reference in its entirety); a surface treatment by energy other than plasma (e.g., a static electrical charge, irradiation, or other energy source); chemical treatments; the grafting of hydrophilic monomers or macromers onto the surface of an article; mold-transfer coating process disclosed in U.S. Pat. No. 6,719,929 (herein incorporated by reference in its entirety); the incorporation of wetting agents into a lens formulation for making contact lenses (i.e., surface treatment prior to polymerization) proposed in U.S. Pat. Nos. 4,045,547, 4,042,552, 5,198,477, 5,219,965, 6,367,929 and 6,822,016, 7,279,507 (herein incorporated by references in their entireties); reinforced mold-transfer coating disclosed in PCT Patent Application Publication No. WO2007/146137 (herein incorporated by reference in its entirety); and layer-by-layer coating (“LbL coating”) obtained according to methods described in U.S. Pat. No. 6,451,871, 6,719,929, 6,793,973, 6,811,805, 6,896,926 (herein incorporated by references in their entireties).
Exemplary plasma gases and processing conditions are described in U.S. Pat. Nos. 4,312,575 and 4,632,844. The plasma gas is preferably a mixture of lower alkanes and nitrogen, oxygen or an inert gas.
“LbL coating”, as used herein, refers to a coating that is not covalently attached to a contact lens or a mold half and is obtained through a layer-by-layer (“LbL”) deposition of polyionic (or charged) and/or non-charged materials on the lens or mold half. An LbL coating can be composed of one or more layers.
As used herein, a “polyionic material” refers to a polymeric material that has a plurality of charged groups or ionizable groups, such as polyelectrolytes, p- and n-type doped conducting polymers. Polyionic materials include both polycationic (having positive charges) and polyanionic (having negative charges) materials.
Formation of an LbL coating on a contact lens or mold half may be accomplished in a number of ways, for example, as described in U.S. Pat. Nos. 6,451,871, 6,719,929, 6,793,973, 6,811,805, 6,896,926 (herein incorporated by references in their entirety).
“Post-curing surface treatment”, in reference to a silicone hydrogel material or a soft contact lens, means a surface treatment process, other than hydrolysis, that is performed after the formation (curing) of the hydrogel material or the soft contact lens in a mold.
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 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, more preferably about 60 degrees or less.
An “average contact angle” refers to a water contact angle (advancing angle measured by Wilhelmy Plate method), which is obtained by averaging measurements of at least 3 individual contact lenses.
An “antimicrobial agent”, as used herein, refers to a chemical that is capable of decreasing or eliminating or inhibiting the growth of microorganisms such as that term is known in the art.
“Antimicrobial metals” are metals whose ions have an antimicrobial effect and which are biocompatible. Preferred antimicrobial metals include Ag, Au, Pt, Pd, Ir, Sn, Cu, Sb, Bi and Zn, with Ag being most preferred.
“Antimicrobial metal-containing nanoparticles” refer to particles having a size of less than 1 micrometer and containing at least one antimicrobial metal present in one or more of its oxidation states.
“Antimicrobial metal nanoparticles” refer to particles which is made essentially of an antimicrobial metal and have a size of less than 1 micrometer. The antimicrobial metal in the antimicrobial metal nanoparticles can be present in one or more of its oxidation states. For example, silver-containing nanoparticles can contain silver in one or more of its oxidation states, such as Ag0, Ag1+, and Ag2+.
“Stabilized antimicrobial metal nanoparticles” refer to antimicrobial metal nanoparticles which are stabilized by a stabilizer during their preparation. Stabilized antimicrobial metal nano-particles can be either positively charged or negatively charged or neutral, largely depending on a material (or so-called stabilizer) which is present in a solution for preparing the nano-particles and can stabilize the resultant nano-particles. A stabilizer can be any known suitable material. Exemplary stabilizers include, without limitation, positively charged polyionic materials, negatively charged polyionic materials, polymers, surfactants, salicylic acid, alcohols and the like.
The “oxygen transmissibility” of a lens, as used herein, is the rate at which oxygen will pass through a specific ophthalmic lens. Oxygen transmissibility, Dk/t, is conventionally expressed in units of barrers/mm, where t is the average thickness of the material [in units of mm] over the area being measured and “barrer/mm” is defined as:

[(cm3 oxygen)/(cm2)(sec)(mm Hg)]×10−9 

The intrinsic “oxygen permeability”, Dk, of a lens material does not depend on lens thickness. Intrinsic oxygen permeability is the rate at which oxygen will pass through a material. Oxygen permeability is conventionally expressed in units of barrers, where “barrer” is defined as:

[(cm3 oxygen)(mm)/(cm2)(sec)(mm Hg)]×10−10 

These are the units commonly used in the art. Thus, in order to be consistent with the use in the art, the unit “barrer” will have the meanings as defined above. For example, a lens having a Dk of 90 barrers (“oxygen permeability barrers”) and a thickness of 90 microns (0.090 mm) would have a Dk/t of 100 barrers/mm (oxygen transmissibility barrers/mm). In accordance with the invention, a high oxygen permeability in reference to a material or a contact lens characterized by apparent oxygen permeability of at least 40 barrers or larger measured with a sample (film or lens) of 100 microns in thickness according to a coulometric method described in Examples.

The “ion permeability” through a lens correlates with both the lonoflux Diffusion Coefficient and the lonoton Ion Permeability Coefficient.
The lonoflux Diffusion Coefficient, D, is determined by applying Fick's law as follows:

D=−n′/(A×dc/dx)

where

    
    
        n′=rate of ion transport [mol/min]
        A=area of lens exposed [mm2]
        D=lonoflux Diffusion Coefficient [mm2/min]
        dc=concentration difference [mol/L]
        dx=thickness of lens [mm]
    
    


The lonoton Ion Permeability Coefficient, P, is then determined in accordance with the following equation:

ln(1−2C(t)/C(0))=−2APt/Vd 

where:

    
    
        C(t)=concentration of sodium ions at time t in the receiving cell
        C(0)=initial concentration of sodium ions in donor cell
        A=membrane area, i.e., lens area exposed to cells
        V=volume of cell compartment (3.0 ml)
        d=average lens thickness in the area exposed
        P=permeability coefficient
    
    


An lonoflux Diffusion Coefficient, D, of greater than about 1.5×10−6 mm2/min is preferred, while greater than about 2.6×10−6 mm2/min is more preferred and greater than about 6.4×10−6 mm2/min is most preferred.
It is known that on-eye movement of the lens is required to ensure good tear exchange, and ultimately, to ensure good corneal health. Ion permeability is one of the predictors of on-eye movement, because the permeability of ions is believed to be directly proportional to the permeability of water.
The invention is directed to use of monomers having hydrolyzable silicone containing group to prepare silicone containing prepolymers or silicone hydrogel materials. This invention is partly based on the discovery that addition of TRIS-acrylate (TRIS represents tris(methylsiloxy) group) to a polymerizable composition for preparing silicone containing prepolymer can yield a prepolymer which is much more water processable. However, addition of TRIS also reduces both oxygen permeability and ion permeability of a silicone hydrogel material derived from the resultant prepolymer. It is believed that by incorporating a cleavable (hydrolyzable) TRIS-like monomer into the synthesis of prepolymer, one can make the resultant prepolymer more processable, such as, for example, ultrafiltration in water and can prepare a lens formulation from the resultant prepolymers using water or water/organic solvent mixture. After curing the lens formulation in a mold for making contact lenses, the resultant lens then can be exposed to some stimulus to cleave off the TRIS group and leave a hydrophilic group behind. The stimulus to cleave off the TRIS group could be heat (prior to or during the autoclave step), light (either the curing light itself or an additional light exposure at another wavelength lysing off the TRIS group), and/or some chemicals.
The invention is also partly based on the discovery that a silicone hydrogel contact lens, which is obtained from a lens formulation containing one or more monomer having a hydrolyzable trimethylsilyl groups, can be rendered by hydrolysis to have a hydrophilic surface (i.e., an averaged water contact angle of 90 degrees or less). It is believed that trimethylsilyl groups have great tendency to migrate to lens surface because of their low energy. If a polymer system contains more than one component, the component that, when localized at the interface will result in a minimum interfacial energy will, if possible, migrate to the surface. Trimethylsilyl groups are such components. The hydrophobic trimethylsilyl groups on or near the lens can be cleaved in the hydration process to leave behind a hydrophilic group after hydrolysis, thereby changing the surface property of the lens from hydrophobic to hydrophilic. This can be a cost effective process for making silicone hydrogel contact lenses having a hydrophilic surface.
The present invention, in one aspect, provides an actinically crosslinkable prepolymer. The prepolymer of the invention is obtained by: (a) copolymerizing an actinically polymerizable composition to obtain an intermediary copolymer with first functional groups, wherein the actinically polymerizable composition comprises (1) at least one vinylic monomer including a hydrolyzable silicone-containing group, (2) at least one hydrophilic vinylic monomer, (3) at least one siloxane-containing monomer having one ethylenically unsaturated group, at least one siloxane-containing macromer having one ethylenically unsaturated group, at least one siloxane-containing monomer having two or more ethylenically unsaturated groups, at least one siloxane-containing macromer having two or more ethylenically unsaturated groups, or a combination of two or more thereof, and (4) optionally a chain transfer agent, provided that at least one of components (2)-(4) further comprises at least one first functional group; and (b) reacting an organic compound with the copolymerization product to form the crosslinkable prepolymer having actinically crosslinkable groups, wherein the organic compound comprises an actinically crosslinkable group and a second functional group, wherein the second functional group of the organic compound reacts with one of the first functional groups of the intermediary copolymer to form a covalent linkage.
A prepolymer of the invention comprises multiple actinically crosslinkable groups selected from the group consisting of ethylenically unsaturated groups and thiol groups.
Where crosslinking of a prepolymer of the invention is based on the mechanism of free radical chain-growth polymerization, the prepolymer comprises preferably at least three ethylenically unsaturated groups.
Where crosslinking of a prepolymer of the invention is based on the mechanism of thiol-ene step-growth radical polymerization, the actinically crosslinkable groups of the prepolymer preferably comprises at least three thiol groups or at least three ene-containing groups. An “ene-containing group” is intended to describe a mono-valent or divalent radical that contains a carbon-carbon double which is not directly linked to a carbonyl group (—CO—), nitrogen atom, or oxygen atom, is preferably defined by any one of formula (I)-(III)




in which R1 is hydrogen, or C1-C10 alkyl; R2 and R3 independent of each other are hydrogen, C1-C10 alkene divalent radical, C1-C10 alkyl, or —(R18)a—(X1)b—R19 in which R18 is C1-C10 alkene divalent radical, X1 is an ether linkage (—O—), a urethane linkage (—N), a urea linkage, an ester linkage, an amid linkage, or carbonyl, R19 is hydrogen, a single bond, amino group, carboxylic group, hydroxyl group, carbonyl group, C1-C12 aminoalkyl group, C1-C18 alkylaminoalkyl group, C1-C18 carboxyalkyl group, C1-C18 hydroxyalkyl group, C1-C18 alkylalkoxy group, C1-C12 aminoalkoxy group, C1-C18 alkylaminoalkoxy group, C1-C18 carboxyalkoxy group, or C1-C18 hydroxyalkoxy group, a and b independent of each other is zero or 1, provided that only one of R2 and R3 is a divalent radical; R4-R9, independent of each other, are hydrogen, C1-C10 alkene divalent radical, C1-C10 alkyl, or —(R18)a—(X1)b—R19, optionally R4 and R9 are linked through an alkene divalent radical to form a cyclic ring, provided that at least one of R4-R9 are divalent radicals; n and m independent of each other are integer number from 0 to 9, provided that the sum of n and m is an integer number from 2 to 9; R10-R17, independent of each other, are hydrogen, C1-C10 alkene divalent radical, C1-C10 alkyl, or —(R18)a—(X1)b—R19, p is an integer number from 1 to 3, provided that only one or two of R10-R17 are divalent radicals.

Where the prepolymer comprises multiple ene-containing groups, these groups undergo thiol-ene step-growth radical polymerization in the presence of thiol groups which can be provided by a step-growth-crosslinking agent having two or more thiol groups. Similarly, where the prepolymer comprises multiple thiol groups, these groups undergo thiol-ene step-growth radical polymerization in the presence of ene-containing groups which can be provided by a step-growth-crosslinking agent having two or more ene-containing groups.
In accordance with the invention, a vinylic monomer including a hydrolyzable silicone-containing group can be a vinylic monomer having a tris(trimethylsiloxy) group linked to the remaining part of the monomer via a urea linkage or having a trimethylsilyl group covalently linked to an oxygen or nitrogen atom of the vinylic monomer. Both tris(trimethylsiloxy) group and trimethylsilyl group are hydrophobic. Hydrolysis of urea linkage can cleave the tris(trimethylsiloxy) group and leave a hydrophilic group behind. Similarly, hydrolysis of the bond between the trimethylsilyl group and the oxygen or nitrogen atom will cleave away the trimethylsilyl group and leave a hydrophilic group behind.
A vinylic monomer having a hydrolyzable trimethylsilyl group covalently linked to an oxygen or nitrogen atom of the vinylic monomer is defined by formula (1)




in which 1R is H or —CH3, -L- is —O— or





2R is trimethylsilyl group (—Si(CH3)3) or a C4-C25 alkyl which is substituted by at least one trimethylsilyloxy, trimethylsilylamino group or trimethylsilyl-C1-C7 alkylamino group, 3R is H or C1-C8 alkyl group.

Examples of preferred monomers of formula (1) include without limitation N-trimethylsilylmethacrylamide, N-trimethylsilylacrylamide, trimethylsilylacrylate, trimethylsilylmethacrylate, 2,3-di-trimethylsilyloxyacrylate, 2,3-di-trimethylsilyloxymethacrylate, 5,6-di-trimethylsilyloxyhexylacrylate, and 5,6-di-trimethylsilyloxyhexylmethacrylate.
A vinylic monomer having a hydrolyzable tris(methylsiloxy)alkyl group covalently linked to the remaining part of the monomer via a urea linkage is defined by formula (2)




in which 1R is H or —CH3, -L- is —O— or





3R is H or C1-C8 alkyl group, 4R is C1-C12 unsubstituted alkylene (divalent radical) or substituted alkylene in which one or more hydrogens are substituted by C1-C3 alkoxy groups, hydroxy groups, amino groups, thiol groups, and/or carboxyl groups, 5R is C1-C7 alkylene group.

A vinylic monomer of formula (2) can be prepared based on the known reaction between an isocyanate group and amino group to form an urea linkage. For example, an isocyanate-containing acrylate (or methacrylate) reacts with aminoalkyl-tris(trimethylsiloxy) silane can form a vinylic monomer of formula (2). Alternatively, an isocyanatoalkyl-tris(trimethylsiloxy) silane can react with an amino-containing acrylate, methacrylate, acrylamide, or methacrylamide to form a vinylic monomer of formula (2). Examples of isocyanatoalkylacrylate and isocyanatoalkylacrylate include without limitation isocyanatomethylacrylate, isocyanatoethylacrylate, isocyanatopropylacrylate, isocyanatoisopropylacrylate, isocyanatobutylacrylate, isocyanatopentylacrylate, isocyanatohexylylacrylate, isocyanatoheptylacrylate, isocyanatomethylmethacrylate, isocyanatoethylmethacrylate, isocyanatopropylmethacrylate, isocyanatoisopropylmethacrylate, isocyanatobutylmethacrylate, isocyanatopentylmethacrylate, isocyanatohexylmethacrylate, and isocyanatoheptylmethacrylate. Examples of aminoalkyl-tris(trimethylsiloxy) silane include without limitation aminoethyl-tris(trimethylsiloxy) silane, aminopropyl-tris(trimethylsiloxy) silane, aminobutyl-tris(trimethylsiloxy) silane, aminopentyl-tris(trimethylsiloxy) silane, aminohexyl-tris(trimethylsiloxy) silane, and aminoheptyl-tris(trimethylsiloxy) silane.
Nearly any hydrophilic vinylic monomer can be used in the actinically polymerizable composition for preparing the intermediary copolymer with pendant or terminal functional groups. Suitable hydrophilic vinylic monomers are, without this being an exhaustive list, hydroxyl-substituted C1-C8 alkylacrylates and methacrylates, acrylamide, methacrylamide, C1-C8 alkylacrylamides, C1-C8 alkylmethacrylamides, ethoxylated acrylates, ethoxylated methacrylates, hydroxyl-substituted C1-C8 alkylacrylamides, hydroxyl-substituted C1-C8 alkylmethacrylamides, hydroxyl-substituted lower alkyl vinyl ethers, sodium vinylsulfonate, sodium styrenesulfonate, 2-acrylamido-2-methylpropanesulfonic acid, N-vinylpyrrole, N-vinyl-2-pyrrolidone, 2-vinyloxazoline, 2-vinyl4,4′-dialkyloxazolin-5-one, 2- and 4-vinylpyridine, vinylically unsaturated carboxylic acids having a total of 3 to 5 carbon atoms, amino(lower alkyl)—(where the term “amino” also includes quaternary ammonium), mono(lower alkylamino)(lower alkyl) and di(lower alkylamino)(lower alkyl)acrylates and methacrylates, allyl alcohol, N-vinyl alkylamide, N-vinyl-N-alkylamide, and the like.
Among the preferred hydrophilic vinylic monomers are N,N-dimethylacrylamide (DMA), 2-hydroxyethylmethacrylate (HEMA), 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), dimethylaminoethylmethacrylamide, acrylamide, methacrylamide, allyl alcohol, vinylpyridine, N-(1,1dimethyl-3-oxobutyl)acrylamide, acrylic acid, a C1-C4-alkoxy polyethylene glycol (meth)acrylate having a weight average molecular weight of from 200 to 1500, methacrylic acid, N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, and N-vinyl caprolactam.
Any known suitable siloxane-containing monomers or macromers with one or more ethylenically unsaturated groups can be used in the actinically polymerizable composition for preparing the intermediary copolymer with pendant or terminal functional groups. Preferred examples of such monomers or macromers are monomethacrylated or monoacrylated polydimethylsiloxanes of various molecular weight (e.g., mono-3-methacryloxypropyl terminated, mono-butyl terminated polydimethylsiloxane or mono-(3-methacryloxy-2-hydroxypropyloxy)propyl terminated, mono-butyl terminated polydimethylsiloxane); dimethacrylated or diacrylated polydimethylsiloxanes of various molecular weight; vinyl terminated polydimethylsiloxanes; vinyl terminated polydimethylsiloxanes of various molecular weight; methacrylamide-terminated polydimethylsiloxanes; acrylamide-terminated polydimethylsiloxanes; acrylate-terminated polydimethylsiloxanes; methacrylate-terminated polydimethylsiloxanes; bis-3-methacryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane; N,N,N′,N′-tetrakis(3-methacryloxy-2-hydroxypropyl)-alpha,omega-bis-3-aminopropyl-polydimethylsiloxane; polysiloxanylalkyl (meth)acrylic monomers; siloxane-containing macromer selected from the group consisting of Macromer A, Macromer B, Macromer C, and Macromer D described in U.S. Pat. No. 5,760,100 (herein incorporated by reference in its entirety); the reaction products of glycidyl methacrylate with amino-functional polydimethylsiloxanes; hydroxyl-functionalized siloxane-containing monomers or macromers; siloxane-containing macromers disclosed in U.S. Pat. No. 6,762,264 (here incorporated by reference in its entirety). Di and triblock macromers consisting of polydimethylsiloxane and polyakyleneoxides could also be of utility. For example one might use methacrylate end capped polyethyleneoxide-block-polydimethylsiloxane-block-polyethyleneoxide to enhance oxygen permeability. Suitable monofunctional hydroxyl-functionalized siloxane-containing monomers and suitable multifunctional hydroxyl-functionalized siloxane-containing monomers are commercially available from Gelest, Inc, Morrisville, Pa.
Preferably, an intermediary copolymer of the invention comprises: from about 15% to about 80% by weight, preferably from about 25% to about 70%, of siloxane units derived from one or more siloxane-containing monomers and/or one or more siloxane-containing macromers; from about 10% to about 80%, preferably from about 15% to 60% by weight, of hydrophilic units derived from one or more hydrophilic monomers and/or one or more hydrophilic macromers; from about 1% to about 30%, preferably from about 5% to about 25% of silicone-containing units derived from one or more silicone-containing vinylic monomers; and about 2% to about 30%, preferably from about 4% to about 20% by weight, of hydrolyzable units derived from at least one vinylic monomer including a hydrolyzable silicone-containing group.
The functional chain transfer agent is used to control the molecular weight of the resulting copolymer and to provide functionality for subsequent addition of a thiol group, an ene-containing group, a cinnamic acid moiety, a dialkylmaleimide group. The chain transfer agent may comprise one or more thiol groups, for example two or most preferably one thiol group. Suitable chain transfer agents include organic primary thiols or mercaptans having a further functional group such as, for example, hydroxy, amino, carboxy or a suitable derivative thereof. The chain transfer agent may be present in the polymerizable composition for making an intermediary copolymer in an amount of, for example, from about 0.5 to about 5%, preferably from about 1% to about 4%, and in particular from about 1.5% to about 3.5% by weight, relative to the combined weight of all of polymerizable components.
In accordance with the invention, the actinically polymerizable composition can comprise one or more hydrophobic vinylic monomer. Nearly any hydrophobic vinylic monomer can be used in the actinically polymerizable composition for preparing the intermediary copolymer with pendant or terminal functional groups. Suitable hydrophobic vinylic monomers include, without limitation, C1-C18-alkylacrylates and -methacrylates, C3-C18 alkylacrylamides and -methacrylamides, acrylonitrile, methacrylonitrile, vinyl-C1-C18-alkanoates, C2-C18-alkenes, C2-C18-halo-alkenes, styrene, C1-C6-alkylstyrene, vinylalkylethers in which the alkyl moiety has 1 to 6 carbon atoms, C2-C10-perfluoralkyl-acrylates and -methacrylates or correspondingly partially fluorinated acrylates and methacrylates, C3-C12-perfluoralkyl-ethyl-thiocarbonylaminoethyl-acrylates and -methacrylates, acryloxy and methacryloxy-alkylsiloxanes, N-vinylcarbazole, C1-C12-alkylesters of maleic acid, fumaric acid, itaconic acid, mesaconic acid and the like. Preference is given e.g. to C1-C4-alkylesters of vinylically unsaturated carboxylic acids with 3 to 5 carbon atoms or vinylesters of carboxylic acids with up to 5 carbon atoms.
Examples of preferred hydrophobic vinylic monomers include methylacrylate, ethyl-acrylate, propylacrylate, isopropylacrylate, cyclohexylacrylate, 2-ethylhexylacrylate, methylmethacrylate, ethyl methacrylate, propyl methacrylate, vinyl acetate, vinyl propionate, vinyl butyrate, vinyl valerate, styrene, chloroprene, vinyl chloride, vinylidene chloride, acrylonitrile, 1-butene, butadiene, methacrylonitrile, vinyl toluene, vinyl ethyl ether, perfluorohexylethyl-thio-carbonyl-aminoethyl-methacrylate, isobornyl methacrylate, trifluoroethyl methacrylate, hexafluoro-isopropyl methacrylate, hexafluorobutyl methacrylate, tris-trimethylsilyloxy-silyl-propyl methacrylate, 3-methacryloxypropyl-pentamethyl-disiloxane and bis(methacryloxypropyl)-tetramethyl-disiloxane.
Any know suitable vinylic monomer containing at least one functional group can be used in the actinically polymerizable composition for preparing the intermediary copolymer with pendant or terminal functional groups. Preferred examples of such vinylic monomers includes methacrylic acid (MAA), acrylic acid, glycidylmethacrylate, glycidylacrylate, HEMA, HEA, methacrylic anhydride, N-hydroxymethylacrylamide (NHMA), 2-bromoethylmethacrylate, and vinylbenzylchoride.
It should be understood that a vinylic monomer can be used both as a hydrophilic vinylic monomer and as a functionalizing vinylic monomer in the actinically polymerizable composition for preparing the silicone-containing polymer with pendant or terminal functional groups. Preferably, the hydrophilic vinylic monomer is devoid of functional groups (e.g., DMA, NVP).
The actinically polymerizable composition for preparing an intermediary copolymer can also comprise a hydrophilic polymer having one sole ethylenically unsaturated group.
In a preferred embodiment, the intermediary copolymer is obtained by copolymerization of an actinically polymerizable composition comprising (1) at least one vinylic monomer including a hydrolyzable silicone-containing group, (2) at least one hydrophilic vinylic monomer, (3) at least one siloxane-containing monomer having one ethylenically unsaturated group, at least one siloxane-containing macromer having one ethylenically unsaturated group, at least one siloxane-containing monomer having two or more ethylenically unsaturated groups, at least one siloxane-containing macromer having two or more ethylenically unsaturated groups, or a combination of two or more thereof, (4) optionally a chain transfer agent, and (5) at least one monoethylenically functionalized hydrophilic polymer (i.e., with one sole ethylenically unsaturated group), provided that at least one of components (2)-(4) further comprises at least one first functional group.
In another preferred embodiment, the intermediary copolymer with pendant or terminal functional groups is obtained by copolymerization of a composition comprising (1) at least one vinylic monomer including a hydrolyzable silicone-containing group, (2) at least one hydrophilic vinylic monomer, (3) at least one siloxane-containing monomer having one ethylenically unsaturated group, at least one siloxane-containing macromer having one ethylenically unsaturated group, at least one siloxane-containing monomer having two or more ethylenically unsaturated groups, at least one siloxane-containing macromer having two or more ethylenically unsaturated groups, or a combination of two or more thereof, (4) optionally a chain transfer agent, (5) at least one monoethylenically functionalized hydrophilic polymer (i.e., with one sole ethylenically unsaturated group), and (6) at least one di- or multi-ethylenically functionalized hydrophilic polymer, provided that at least one of components (2)-(4) further comprises at least one first functional group.
In accordance with the invention, the mono-, di- or multi-ethylenically functionalized hydrophilic polymers can be prepared by covalently attaching one or more ethylenically unsaturated groups to the functional groups (e.g., amine, hydroxyl, carboxyl, isocyanate, epoxy groups) of a mono-, di- or multi-functionalized hydrophilic precursor polymer or copolymers (i.e., with one or more functional groups). Any vinylic monomer having a hydroxy, amino, carboxyl, epoxy, acid-chloride, isocyanate group, which is coreactive with isocyanate, amine, hydroxyl, carboxy, or epoxy groups of a polymer or copolymer in the absence or presence of a coupling agent (such as, e.g., EDC, diisocyanate, or diacid chloride), can be used in ethylenically functionalizing the precursor polymer or copolymer. Examples of such vinylic monomers include, without limitation, for reacting with terminal hydroxy groups, 2-isocyanatoethyl methacrylate, methacrylic anhydride, 3-isopropenyl-alpha, alpha-dimethylbenzyl isocyanate, acryloyl chloride, or methacryloyl chloride, glycidyl methacrylate; for reacting with terminal amine groups, 2-isocyanatoethyl methacrylate, 3-isopropenyl-alpha, alpha-dimethylbenzyl isocyanate, methacrylic anhydride, acrylic acid, methacrylic acid, acryloyl chloride, or methacryloyl chloride; for reacting with terminal carboxy groups in the presence of EDC, vinylamine, 2-aminoethyl methacrylate or 3-aminopropyl methacrylamide. The above list is not exhaustive but illustrative. A person skilled in the art will know how to select a vinylic monomer with a functional group to functionalize ethylenically hydrophilic precursor polymers or copolymers.
Examples of mono-, di- or multi-ethylenically functionalized hydrophilic polymers includes without limitation hydrophilic polymers or copolymers having one terminal acryloyl




methacryloyl





or vinyl group; hydrophilic polymers or copolymers with two terminal acryloyl, methacryloyl, or vinyl groups; and hydrophilic polymers or copolymers with multiple (i.e., 3 or more) acryloyl, methacryloyl, or vinyl groups. The hydrophilic polymers or copolymers are preferably selected from the group consisting of: PEGs; PEG/PPG block copolymers; polyalkylacrylamides; poyalkylmethacrylamides; polyvinylpyrrolidones; copolymers of N-vinylpyrrolidone with dialkylaminoalkylacrylate (e.g., dimethylaminoethylacrylate), dialkylaminoalkylmethacrylate (e.g., dimethylaminoethylmethacrylate), N,N-dialkylacrylamide, N,N-dialkylmethacrylamide, vinylacetate, or mixture thereof; polyvinylalcohols (derived from polyvinylacetates); copoymers of vinylacetate with dialkylaminoalkylacrylate (e.g., dimethylaminoethylacrylate), dialkylaminoalkylmethacrylate (e.g., dimethylaminoethylmethacrylate), N,N-dialkylacrylamide, N,N-dialkylmethacrylamide, vinylacetate, or mixture thereof.

Mono-ethylenically functionalized PEGs or block PEG/PPG copolymers and di-ethylenically functionalized PEGs or block PEG/PPG copolymers either are commercially available or can be prepared by covalently attaching acryloyl, methacryloyl or vinyl groups to monofunctional group terminated PEGs or block copolymers of ethylene oxide and propylene oxide and difunctional group terminated PEGs or block copolymers of ethylene oxide and propylene oxide.
A “monoethylenically functionalized” polymer or copolymer means that the polymer or copolymer has one single ethylencially unsaturated group. A “diethylenically functionalized” polyer or copolymer means that the polymer or copolymer has only two ethylencially unsaturated groups.
Mono- or di-ethylenically functionalized polyalkylacrylamides, poyalkylmethacrylamides, polyvinylpyrrolidones; copolymers of N-vinylpyrrolidone with one or more vinylic monomers, polyvinylalcohols (derived from polyvinylacetates), or copoymers of vinylacetate with one or more vinylic monomers can be prepared from their corresponding mono-functional group terminated precursor polymers or copolymers described above.
Where mono- or di-functional group terminated hydrophilic precursor polymers or copolymers are polyvinyl alcohols or polyvinylalcohol copolymers, the terminal functional groups preferably are amine or carboxyl groups. In general, isocyanate groups would first react with amine groups even in the presence of hydroxyl groups. Also, amine groups or carboxyl groups will participate in EDC mediated coupling reaction whereas hydroxyl groups will not.
In accordance with the invention, multiethylencially functionalized hydrophilic polymers are derived from hydrophilic precursor polymers or copolymers containing multiple pendant and/or terminal functional groups (e.g., —NH2, —COOH, —OH). Examples of such hydrophilic precursor copolymers are the copolymers of N-vinylpyrrolidone, N,N-dialkylacrylamide, N,N-dialkylmethacrylamide, dialkylaminoalkylmethacrylate, or dialkylaminoalkylacrylate with at least one functional group-containing vinylic monomer selected from the group consisting of vinylacetate, acrylic acid, methacrylic acid, hydroxylalkylacrylate, hydroxymethacylate, aminoalkyacrylate, and aminoalkymethacrylate. The percentage of units derived from functional group-containing vinylic monomer is preferably less than about 15%, more preferably less than about 10%, even more preferably less than about 5% by weight.
In accordance with the invention, the monoethylenically functionalized hydrophilic polymer has a molecular weight of from about 500 to about 20,000, preferably from about 1000 to about 10,000, more preferably from about 2000 to about 6000 Daltons.
It is understood that a mixture of one or more monoethylenically functionalized hydrophilic polymers and one or more diethylenically functionalized hydrophilic polymers can be advantageously used in preparing the intermediary copolymer, the precursor of a prepolymer of the invention.
The actinically polymerizable composition for preparing an intermediary copolymer can be a melt, a solventless liquid in which all necessary components are blended together preferably in the presence of one or more blending vinylic monomers, or a solution in which all necessary component is dissolved in an organic solvent, or mixture of two or more organic solvents, as known to a person skilled in the art.
Example of organic solvents includes without limitation tetrahydrofuran, tripropylene glycol methyl ether, dipropylene glycol methyl ether, ethylene glycol n-butyl ether, diethylene glycol n-butyl ether, diethylene glycol methyl ether, ethylene glycol phenyl ether, propylene glycol methyl ether, propylene glycol methyl ether acetate, dipropylene glycol methyl ether acetate, propylene glycol n-propyl ether, dipropylene glycol n-propyl ether, tripropylene glycol n-butyl ether, propylene glycol n-butyl ether, dipropylene glycol n-butyl ether, tripropylene glycol n-butyl ether, propylene glycol phenyl ether dipropylene glycol dimetyl ether, polyethylene glycols, polypropylene glycols, ethyl acetate, butyl acetate, amyl acetate, methyl lactate, ethyl lactate, i-propyl lactate, methylene chloride, 2-butanol, 2-propanol, menthol, cyclohexanol, cyclopentanol and exonorborneol, 2-pentanol, 3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2-heptanol, 2-octanol, 2-nonanol, 2-decanol, 3-octanol, norborneol, tert-butanol, tert-amyl, alcohol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol, 3-methyl-3-pentanol, 1-methylcyclohexanol, 2-methyl-2-hexanol, 3,7-dimethyl-3-octanol, 1-chloro-2-methyl-2-propanol, 2-methyl-2-heptanol, 2-methyl-2-octanol, 2-2-methyl-2-nonanol, 2-methyl-2-decanol, 3-methyl-3-hexanol, 3-methyl-3-heptanol, 4-methyl-4-heptanol, 3-methyl-3-octanol, 4-methyl-4-octanol, 3-methyl-3-nonanol, 4-methyl-4-nonanol, 3-methyl-3-octanol, 3-ethyl-3-hexanol, 3-methyl-3-heptanol, 4-ethyl-4-heptanol, 4-propyl-4-heptanol, 4-isopropyl-4-heptanol, 2,4-dimethyl-2-pentanol, 1-methylcyclopentanol, 1-ethylcyclopentanol, 1-ethylcyclopentanol, 3-hydroxy-3-methyl-1-butene, 4-hydroxy-4-methyl-1-cyclopentanol, 2-phenyl-2-propanol, 2-methoxy-2-methyl-2-propanol 2,3,4-trimethyl-3-pentanol, 3,7-dimethyl-3-octanol, 2-phenyl-2-butanol, 2-methyl-1-phenyl-2-propanol and 3-ethyl-3-pentanol, 1-ethoxy-2-propanol, 1-methyl-2-propanol, t-amyl alcohol, isopropanol, 1-methyl-2-pyrrolidone, N,N-dimethylpropionamide, dimethyl formamide, dimethyl acetamide, dimethyl propionamide, N-methyl pyrrolidinone, and mixtures thereof.
The one or more blending vinylic monomers are in an amount sufficient to dissolve both hydrophilic and hydrophobic components of the actinically polymerizable composition. A “blending vinylic monomer” refers to a vinylic monomer which can function both as a solvent to dissolve both hydrophilic and hydrophobic components of an actinically polymerizable composition and as one of polymerizable components to be polymerized to form a silicone hydrogel material. Preferably, the blending vinylic monomer is present in the actinically polymerizable composition in an amount of from about 5% to about 30% by weight.
Any suitable vinylic monomers, capable of dissolving both hydrophilic and hydrophobic components of a polymerizable composition of the invention to form a solution, can be used in the invention. Preferred examples of blending vinylic monomers include, without limitation, aromatic vinylic monomers, cycloalkyl-containing vinylic monomers. Those preferred blending monomers can increase the predominant glass transition temperature of a silicone hydrogel material prepared by curing a polymerizable composition containing those preferred blending monomer.
Examples of preferred aromatic vinylic monomers include styrene, 2,4,6-trimethylstyrene (TMS), t-butyl styrene (TBS), 2,3,4,5,6-pentafluorostyrene, benzylmethacrylate, divinylbenzene, and 2-vinylnaphthalene. Of these monomers, a styrene-containing monomer is preferred. A styrene-containing monomer is defined herein to be a monomer that contains a vinyl group bonded directly to a phenyl group in which the phenyl group can be substituted by other than a fused ring, e.g., as above with one to three C1-C6 alkyl groups. Styrene itself [H2C═CH—C6H5] is a particularly preferred styrene-containing monomer.
A cycloalkyl-containing vinylic monomer is defined herein to be a vinylic monomer containing a cycloalkyl which can be substituted by up to three C1-C6 alkyl groups. Preferred cycloalkyl-containing vinylic monomers include, without limitation, acrylates and methacrylates each comprising a cyclopentyl or cyclohexyl or cycloheptyl, which can be substituted by up to 3 C1-C6 alkyl groups. Examples of preferred cycloalkyl-containing vinylic monomers include isobornylmethacrylate, isobornylacrylate, cyclohexylmethacrylate, cyclohexylacrylate, and the like.
The copolymerization of a polymerizable composition for preparing an intermediary copolymer may be induced photochemically or preferably thermally. Suitable thermal polymerization initiators are known to the skilled artisan and comprise, for example peroxides, hydroperoxides, azo-bis(alkyl- or cycloalkylnitriles), persulfates, percarbonates or mixtures thereof. Examples are benzoylperoxide, tert.-butyl peroxide, di-tert.-butyl-diperoxyphthalate, tert.-butyl hydroperoxide, azo-bis(isobutyronitrile) (AIBN), 1,1-azodiisobutyramidine, 1,1′-azo-bis (1-cyclohexanecarbonitrile), 2,2′-azo-bis(2,4-dimethylvaleronitrile) and the like. The polymerization is carried out conveniently in an above-mentioned solvent at elevated temperature, for example at a temperature of from 25 to 100° C. and preferably 40 to 80° C. The reaction time may vary within wide limits, but is conveniently, for example, from 1 to 24 hours or preferably from 2 to 12 hours. It is advantageous to previously degas the components and solvents used in the polymerization reaction and to carry out said copolymerization reaction under an inert atmosphere, for example under a nitrogen or argon atmosphere. Copolymerization can yield optical clear well-defined copolymers which may be worked up in conventional manner using for example extraction, precipitation, ultrafiltration and the like techniques.
In accordance with the invention, ethylenically functionalizing of the intermediary copolymer can be carried out by covalently attaching ethylenically unsaturated groups to the functional groups (e.g., amine, hydroxyl, carboxyl, isocyanate, epoxy groups) of the intermediary copolymer. Any vinylic monomer having a hydroxy, amino, carboxyl, epoxy, acid-chloride, isocyanate group, which is coreactive with isocyanate, amine, hydroxyl, carboxyl, or epoxy groups of an intermediary copolymer in the absence or presence of a coupling agent (such as, e.g., EDC, diisocyanate, or diacid chloride), can be used in ethylenically functionalizing the intermediary copolymer. Examples of such vinylic monomers include, without limitation, for reacting with terminal hydroxy groups, 2-isocyanatoethyl methacrylate, methacrylic anhydride, 3-isopropenyl-alpha, alpha-dimethylbenzyl isocyanate, acryloyl chloride, or methacryloyl chloride, glycidyl methacrylate; for reacting with terminal amine groups, 2-isocyanatoethyl methacrylate, 3-isopropenyl-alpha, alpha-dimethylbenzyl isocyanate, methacrylic anhydride, acrylic acid, methacrylic acid, acryloyl chloride, or methacryloyl chloride; for reacting with terminal carboxy groups in the presence of EDC, vinylamine, 2-aminoethyl methacrylate or 3-aminopropyl methacrylamide. The above list is not exhaustive but illustrative. A person skilled in the art will know how to select a vinylic monomer with a functional group to functionalize ethylenically intermediary copolymers, provided that the first and second functional groups are not selected to form urea linkages.
Preferably, the functional groups of the intermediary copolymer are selected from the group consisting of hydroxyl groups (—OH), primary amino groups (—NH2), secondary amino groups (—NHR), carboxyl groups (—COOH), epoxy groups, aldehyde groups (—CHO), amide groups (—CONH2), acid halide groups (—COX, X═Cl, Br, or I), isothiocyanate groups, isocyanate groups, halide groups (—X, X═Cl, Br, or I), acid anhydride groups, and combinations thereof.
A prepolymer of the invention is capable of forming, preferably in the absence of any hydrophilic vinylic monomer, a silicone hydrogel or contact lens, which has a high oxygen permeability (characterized by an apparent oxygen permeability of at least 40 barrers, preferably at least about 60 barrers, even more preferably at least 80 barrers) and a hydrophilic surface (characterized by having an averaged water contact angle of less than about 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, even more preferably about 60 degrees or less). The silicone hydrogel material or contact lens preferably has a high ion permeability (characterized by an lonoflux Diffusion Coefficient, D, of greater than about 1.5×10−6 mm2/min, preferably greater than about 2.6×10−6 mm2/min, more preferably greater than about 6.4×10−6 mm2/min). The silicone hydrogel material or contact lens preferably has an elastic modulus of about 2.0 MPa or less, preferably about 1.5 MPa or less, more preferably about 1.2 or less, even more preferably from about 0.4 MPa to about 1.0 MPa. The silicone hydrogel material or contact lens preferably has a water content of preferably from about 18% to about 55%, more preferably from about 20% to about 38% by weight when fully hydrated. The water content of a silicone hydrogel contact lens can be measured according to Bulk Technique as disclosed in U.S. Pat. No. 5,849,811.
Preferably, the prepolymers used in the invention are previously purified in a manner known per se, for example by precipitation with organic solvents, such as acetone, filtration and washing, extraction in a suitable solvent, dialysis or ultrafiltration, ultrafiltration being especially preferred. By means of that purification process the prepolymers can be obtained in extremely pure form, for example in the form of concentrated solutions that are free, or at least substantially free, from reaction products, such as salts, and from starting materials, such as, for example, non-polymeric constituents. The preferred purification process for the prepolymers used in the process according to the invention, ultrafiltration, can be carried out in a manner known per se. It is possible for the ultrafiltration to be carried out repeatedly, for example from two to ten times. Alternatively, the ultrafiltration can be carried out continuously until the selected degree of purity is attained. The selected degree of purity can in principle be as high as desired. A suitable measure for the degree of purity is, for example, the concentration of dissolved salts obtained as by-products, which can be determined simply in known manner. Thus, after polymerization, the device will not require subsequent purification such as, for example, costly and complicated extraction of unpolymerized matrix-forming material. Furthermore, crosslinking of the prepolymer can take place absent a solvent or in aqueous solution so that a subsequent solvent exchange or the hydration step is not necessary.
In another aspect, the invention provides a soft contact lens. The soft contact lens of the invention comprises: a silicone hydrogel material that is obtained by curing a lens-forming material in a mold and comprises first and/or second hydrolyzable silicone-containing groups, wherein the lens-forming material comprises at least one actinically crosslinkable monomer having one first hydrolyzable silicone-containing group and/or at least one actinically crosslinkable prepolymer having multiple second hydrolyzable silicone-containing groups, wherein the first and second hydrolyzable silicone-containing groups are capable of being cleaved from the silicone hydrogel material by means of hydrolysis so as to provide the soft contact lens with a water contact angle of about 90 degrees or less without post-curing surface treatment.
The silicone hydrogel material can comprise polymeric units derived from a vinylic monomer of formula (1) or (2) described above.
Various embodiments of an actinically crosslinkable prepolymer having multiple hydrolyzable silicone-containing groups described above can be used in the aspect of the invention.
A lens-forming material can be any polymerizable composition which can be cured (i.e., polymerized and/or crosslinked) thermally or actinically in a mold to obtain a contact lens. Lens-forming materials are well known to a person skilled in the art. In accordance with the invention, a lens-forming material can be prepared from any lens formulations for making soft contact lenses by adding at least one actinically crosslinkable monomer having one first hydrolyzable silicone-containing group and/or at least one actinically crosslinkable prepolymer having multiple second hydrolyzable silicone-containing groups. Exemplary lens formulations include without limitation the formulations of lotrafilcon A, lotrafilcon B, etafilcon A, genfilcon A, lenefilcon A, polymacon, acquafilcon A, balafilcon, senofilcon A, and the like. Preferably, a silicone hydrogel lens-forming material used in the present invention comprises a silicone-containing macromer or prepolymer.
In accordance with the present invention, a silicone hydrogel lens-forming material can also comprise at least one member selected from the group consisting of a hydrophilic monomer, a siloxane-containing monomer having one ethylenically unsaturated group, a siloxane-containing macromer having one ethylenically unsaturated group, a siloxane-containing monomer having two or more ethylenically unsaturated groups, a siloxane-containing macromer having two or more ethylenically unsaturated groups, a silicone-containing prepolymer, a hydrophobic monomer, a hydrophilic polymer having one sole ethylenically unsaturated group, a di- or multi-ethylenically functionalized hydrophilic polymer, di-ethylenically functionalized hydrophilic polymer, a multi-ethylenically functionalized hydrophilic polymer, and combination of two or more thereof. Various embodiments described above of these components can be used in this aspect of the invention.
Examples of silicone-containing prepolymers include without limitation those disclosed in US Patent Application Publication Nos. 2001/0037001 A1, US 2005/0237483 A1 and 2008/0015315 A1, U.S. Pat. No. 6,039,913, co-pending U.S. patent application Ser. Nos. 12/001,562, 12/001,521, 60/896,326, and 60/896,325, which are incorporated herein by references in their entireties. Preferably, the prepolymers used in the invention are previously purified in a manner known per se, for example by precipitation with organic solvents, such as acetone, filtration and washing, extraction in a suitable solvent, dialysis or ultrafiltration, ultrafiltration being especially preferred. By means of that purification process the prepolymers can be obtained in extremely pure form, for example in the form of concentrated aqueous solutions that are free, or at least substantially free, from reaction products, such as salts, and from starting materials, such as, for example, non-polymeric constituents. The preferred purification process for the prepolymers used in the process according to the invention, ultrafiltration, can be carried out in a manner known per se. It is possible for the ultrafiltration to be carried out repeatedly, for example from two to ten times. Alternatively, the ultrafiltration can be carried out continuously until the selected degree of purity is attained. The selected degree of purity can in principle be as high as desired. A suitable measure for the degree of purity is, for example, the concentration of dissolved salts obtained as by-products, which can be determined simply in known manner.
It must be understood that a lens-forming material can also comprise various components, such as, for example, polymerization initiators (e.g., photoinitiator or thermal initiator), a visibility tinting agent (e.g., dyes, pigments, or mixtures thereof), UV-blocking (absorbing) agent, photosensitizers, inhibitors, antimicrobial agents (e.g., preferably silver nanoparticles or stabilized silver nanoparticles), bioactive agent, leachable lubricants, fillers, and the like, as known to a person skilled in the art.
Cross-linking agents may be used to improve structural integrity and mechanical strength. Examples of cross-linking agents include without limitation allyl(meth)acrylate, lower alkylene glycol di(meth)acrylate, poly lower alkylene glycol di(meth)acrylate, lower alkylene di(meth)acrylate, divinyl ether, divinyl sulfone, di- or trivinylbenzene, trimethylolpropane tri(meth)acrylate, pentaerythritol tetra(meth)acrylate, bisphenol A di(meth)acrylate, methylenebis(meth)acrylamide, triallyl phthalate or diallyl phthalate. A preferred cross-linking agent is ethylene glycol dimethacrylate (EGDMA).
The amount of a cross-linking agent used is expressed in the weight content with respect to the total polymer and is preferably in the range from 0.05 to 5%, and more preferably in the range from 0.1 to 2%.
Initiators, for example, selected from materials well known for such use in the polymerization art, may be included in the lens-forming material in order to promote, and/or increase the rate of, the polymerization reaction. An initiator is a chemical agent capable of initiating polymerization reactions. The initiator can be a photoinitiator or a thermal initiator.
A photoinitiator can initiate free radical polymerization and/or crosslinking by the use of light. Suitable photoinitiators are benzoin methyl ether, diethoxyacetophenone, a benzoylphosphine oxide, 1-hydroxycyclohexyl phenyl ketone and Darocur and Irgacur types, preferably Darocur 1173® and Darocur 2959®. Examples of benzoylphosphine initiators include 2,4,6-trimethylbenzoyldiphenylophosphine oxide; 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 macromer 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 azobisisobutyronite (AIBN).
Examples of preferred pigments include any colorant permitted in medical devices and approved by the FDA, such as D&C Blue No. 6, D&C Green No. 6, D&C Violet No. 2, carbazole violet, certain copper complexes, certain chromium oxides, various iron oxides, phthalocyanine green, phthalocyanine blue, titanium dioxides, etc. See Marmiom DM Handbook of U.S. Colorants for a list of colorants that may be used with the present invention. A more preferred embodiment of a pigment include (C.I. is the color index no.), without limitation, for a blue color, phthalocyanine blue (pigment blue 15:3, C.I. 74160), cobalt blue (pigment blue 36, C.I. 77343), Toner cyan BG (Clariant), Permajet blue B2G (Clariant); for a green color, phthalocyanine green (Pigment green 7, C.I. 74260) and chromium sesquioxide; for yellow, red, brown and black colors, various iron oxides; PR122, PY154, for violet, carbazole violet; for black, Monolith black C-K (CIBA Specialty Chemicals).
The bioactive agent incorporated in the polymeric matrix is any compound that can prevent a malady in the eye or reduce the symptoms of an eye malady. The bioactive agent can be a drug, an amino acid (e.g., taurine, glycine, etc.), a polypeptide, a protein, a nucleic acid, or any combination thereof. Examples of drugs useful herein include, but are not limited to, rebamipide, ketotifen, olaptidine, cromoglycolate, cyclosporine, nedocromil, levocabastine, lodoxamide, ketotifen, or the pharmaceutically acceptable salt or ester thereof. Other examples of bioactive agents include 2-pyrrolidone-5-carboxylic acid (PCA), alpha hydroxyl acids (e.g., glycolic, lactic, malic, tartaric, mandelic and citric acids and salts thereof, etc.), linoleic and gamma linoleic acids, and vitamins (e.g., B5, A, B6, etc.).
Any hydrophilic polymers or copolymers without any ethylenically unsaturated groups can be used as leachable lubricants. Preferred examples of non-crossllinkable hydrophilic polymers include, but are not limited to, polyvinyl alcohols (PVAs), polyamides, polyimides, polylactone, a homopolymer of a vinyl lactam, a copolymer of at least one vinyl lactam in the presence or in the absence of one or more vinylic comonomers, a homopolymer of acrylamide or methacrylamide, a copolymer of acrylamide or methacrylamide with one or more hydrophilic vinylic monomers, polyethylene oxide (i.e., polyethylene glycol (PEG)), a polyoxyethylene derivative, poly-N—N-dimethylacrylamide, polyacrylic acid, poly 2 ethyl oxazoline, heparin polysaccharides, polysaccharides, and mixtures thereof.
The molecular weight of the non-crosslinkable hydrophilic polymer is preferably from about 20,000 to about 1,500,000 daltons, more preferably from about 50,000 to 1,200,000 daltons, even more preferably from 100,000 to 1,000,000 daltons.
In accordance with the invention, a lens-forming material is a composition which can be a solution or a melt at a temperature from about 20° C. to about 85° C. Preferably, a lens-forming material is a solution of all desirable components in water, or an organic solvent, or a mixture of water and one or more organic solvents.
A solution of all desirable components can be prepared by dissolving them in any suitable solvent known to a person skilled in the art. Various embodiments described above of organic solvents can be used in this aspect of the invention.
In accordance with the invention, the lens-forming material can be introduced (dispensed) into a cavity formed by a mold according to any known methods.
Lens molds for making contact lenses are well known to a person skilled in the art and, for example, are employed in cast molding or spin casting. For example, a mold (for cast molding) generally comprises at least two mold sections (or portions) or mold halves, i.e. first and second mold halves. The first mold half defines a first molding (or optical) surface and the second mold half defines a second molding (or optical) surface. The first and second mold halves are configured to receive each other such that a lens forming cavity is formed between the first molding surface and the second molding surface. The molding surface of a mold half is the cavity-forming surface of the mold and in direct contact with lens-forming material.
Methods of manufacturing mold sections for cast-molding a contact lens are generally well known to those of ordinary skill in the art. The process of the present invention is not limited to any particular method of forming a mold. In fact, any method of forming a mold can be used in the present invention. The first and second mold halves can be formed through various techniques, such as injection molding or lathing. Examples of suitable processes for forming the mold halves are disclosed in U.S. Pat. No. 4,444,711 to Schad; U.S. Pat. No. 4,460,534 to Boehm et al.; U.S. Pat. No. 5,843,346 to Morrill; and U.S. Pat. No. 5,894,002 to Boneberger et al., which are also incorporated herein by reference.
Virtually all materials known in the art for making molds can be used to make molds for preparing ocular lenses. For example, polymeric materials, such as polyethylene, polypropylene, polystyrene, PMMA, cyclic olefin copolymers (e.g., Topas® COO from Ticona GmbH of Frankfurt, Germany and Summit, N.J.; Zeonex® and Zeonor® from Zeon Chemicals LP, Louisville, Ky.), or the like can be used. Other materials that allow UV light transmission could be used, such as quartz, glass, CaF2, and sapphire.
In a preferred embodiment, when the polymerizable components in the lens-forming material is composed essentially of prepolymers, reusable molds can be used. Examples of reusable molds made of quartz or glass are those disclosed in U.S. Pat. No. 6,627,124, which is incorporated by reference in their entireties. In this aspect, the lens-forming material is poured into a mold consisting of two mold halves, the two mold halves not touching each other but having a thin gap of annular design arranged between them. The gap is connected to the mold cavity, so that excess lens-forming material can flow into the gap. Instead of polypropylene molds that can be used only once, it is possible for reusable quartz, glass, sapphire molds to be used, since, following the production of a lens, these molds can be cleaned rapidly and effectively to remove unreacted materials and other residues, using water or a suitable solvent, and can be dried with air. Reusable molds can also be made of a cyclic olefin copolymer, such as for example, Topas® COC grade 8007-S10 (clear amorphous copolymer of ethylene and norbornene) from Ticona GmbH of Frankfurt, Germany and Summit, N.J., Zeonex® and Zeonor® from Zeon Chemicals LP, Louisville, Ky. Because of the reusability of the mold halves, a relatively high outlay can be expended at the time of their production in order to obtain molds of extremely high precision and reproducibility. Since the mold halves do not touch each other in the region of the lens to be produced, i.e. the cavity or actual mold faces, damage as a result of contact is ruled out. This ensures a high service life of the molds, which, in particular, also ensures high reproducibility of the contact lenses to be produced and high fidelity to the lens design.
After the lens-forming material is dispensed into the mold, it is polymerized to produce a contact lens. Crosslinking may be initiated in the mold e.g. by means of actinic radiation, such as UV irradiation, ionizing radiation (e.g., gamma or X-ray irradiation). Where prepolymers of the invention are the polymerizable components in the lens-forming material, the mold containing the lens-forming material can be exposed to a spatial limitation of actinic radiation to crosslink the prepolymers.
The crosslinking according to the invention may be effected in a very short time, e.g. in ≦60 minutes, advantageously in ≦20 minutes, preferably in ≦10 minutes, most preferably in ≦5 minutes, particularly preferably in 1 to 60 seconds and most particularly in 1 to 30 seconds.
The contact lenses according to the invention can be produced from one or more radiation-curable prepolymers of the invention in a very simple and efficient way compared with the prior art. This is based on many factors. On the one hand, the starting materials may be acquired or produced inexpensively. Secondly, there is the advantage that the prepolymers are surprisingly stable, so that they may undergo a high degree of purification. There is no practical need for subsequent purification, such as in particular complicated extraction of unpolymerized constituents after curing lenses. Furthermore, the new polymerization method can be used to produce contact lenses with desirable mechanical and physical properties. Finally, photo-polymerization is effected within a short period, so that from this point of view also the production process for the contact lenses according to the invention may be set up in an extremely economic way.
Opening of the mold so that the molded article can be removed from the mold may take place in a manner known per se.
If the molded contact lens is produced solvent-free from an already purified prepolymer according to the invention, then after removal of the molded lens, it is not normally necessary to follow up with purification steps such as extraction. This is because the prepolymers employed do not contain any undesired constituents of low molecular weight; consequently, the crosslinked product is also free or substantially free from such constituents and subsequent extraction can be dispensed with. Accordingly, the contact lens can be directly transformed in the usual way, by hydration, into a ready-to-use contact lens. Appropriate embodiments of hydration are known to the person skilled in the art, whereby ready-to-use contact lenses with very varied water content may be obtained. The contact lens is expanded, for example, in water, in an aqueous salt solution, especially an aqueous salt solution having an osmolarity of about 200 to 450 milli-osmole in 1000 ml (unit: mOsm/ml), preferably about 250 to 350 mOsm/l and especially about 300 mOsm/l, or in a mixture of water or an aqueous salt solution with a physiologically compatible polar organic solvent, e.g. glycerol. Preference is given to expansions of the article in water or in aqueous salt solutions.
If the molded contact lens is produced from a solvent solution of an already purified prepolymer according to the invention, it is not necessary to carry out subsequent extraction, but instead of hydration process to replace the solvent.
Hydrolysis of the hydrolyzable groups in the silicone hydrogel contact lens can be carried out according to any methods known to a person skilled in the art. Preferably, hydrolysis is carried out in-situ, i.e., directly in a sealed package containing the lens. Generally, contact lenses are packed in the primary package in an ophthalmically compatible storage solution and then is sterilized (e.g. in an autoclave at about 120° C. for a desired period of time) in the sealed primary package. Hydrolyzable polymer is preferably converted into hydrophilic polymer in the primary package during autoclave.
An “ophthalmically compatible solution” is characterized by at least having a pH in the range of from 6.0 to 8.0 and an osmolarity from 250 to 400 mOsmol/kg.
A “primary package” as used herein, refers to a package directly comprising the ophthalmic lens as to be used by the ophthalmic lens user. A typical primary package may be a blister package (as for example disclosed in EP-A-0680895 or EP-A-0233581, herein incorporated by references in their entireties) comprising a shell or base portion sealed with a laminated foil or cover. A primary package usually contains one contact lens in a small amount of an ophthalmically compatible solution (as for example a saline buffer solution with or without other comfort additives, e.g., surfactants, PVP, PVA, cellulose, polyethyleneglycol, etc.).
The molded contact lenses can further subject to further processes, such as, for example, surface treatment, sterilization, and the like.
A contact lens of the invention has an oxygen permeability of preferably at least about 40 barrers, more preferably at least about 60 barrers, even more preferably at least about 80 barrers. In accordance with the invention, an oxygen permeability is an apparent (directly measured when testing a sample with a thickness of about 100 microns) oxygen permeability according to procedures described in Examples.
A contact lens of the invention has an elastic modulus of about 2.0 MPa or less, preferably about 1.5 MPa or less, more preferably about 1.2 or less, even more preferably from about 0.4 MPa to about 1.0 MPa.
A contact lens of the invention further has an lonoflux Diffusion Coefficient, D, of, preferably at least about 1.5×10−6 mm2/min, more preferably at least about 2.6×10−6 mm2/min, even more preferably at least about 6.4×10−6 mm2/min.
A contact lens of the invention further has a water content of preferably from about 15% to about 55%, more preferably from about 20% to about 38% by weight when fully hydrated. The water content of a silicone hydrogel contact lens can be measured according to Bulk Technique as disclosed in U.S. Pat. No. 5,849,811.
A contact lens of the invention has a surface hydrophilicity characterized by having an averaged water contact angle of about 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, more preferably about 60 degrees or less.
In a further aspect, the invention provides a method for producing soft contact lenses. The method comprises the steps of: providing a mold for making a soft contact lens, wherein the mold has a first mold half with a first molding surface defining the anterior surface of a contact lens and a second mold half with a second molding surface defining the posterior surface of the contact lens, wherein said first and second mold halves are configured to receive each other such that a cavity is formed between said first and second molding surfaces; introducing a lens-forming material into the cavity, wherein the lens-forming material wherein the lens-forming material comprises at least one actinically crosslinkable monomer having one first hydrolyzable silicone-containing group and/or one actinically crosslinkable prepolymer having multiple second hydrolyzable silicone-containing groups; curing the lens-forming material to form a soft contact lens composed of a silicone hydrogel material including first and/or second hydrolyzable silicone-containing groups; and subjecting the soft contact lens to hydrolysis, whereby during hydrolysis the first and second hydrolyzable silicone-containing groups are cleaved from the silicone hydrogel material so as to provide the soft contact lens with a water contact angle of about 90 degrees or less without post-curing surface treatment.
All of the various embodiments of the prepolymer, lens-forming material, molds, and contact lens described above can be used in this aspect of the invention.
The previous disclosure will enable one having ordinary skill in the art to practice the invention. In order to better enable the reader to understand specific embodiments and the advantages thereof, reference to the following non-limiting examples is suggested. However, the following examples should not be read to limit the scope of the invention.
Example 1
Surface Hydrophilicity (Wetability) Tests
Water contact angle on a contact lens is a general measure of the surface hydrophilicity (or wetability) of the contact lens. In particular, a low water contact angle corresponds to more hydrophilic surface. Average contact angles (advancing) of contact lenses are measured using Wilhelmy Plate method.
Oxygen Permeability Measurements.
The oxygen permeability of a lens and oxygen transmissibility of a lens material is determined according to a technique similar to the one described in U.S. Pat. No. 5,760,100 and in an article by Winterton et al., (The Cornea: Transactions of the World Congress on the Cornea 111, H. D. Cavanagh Ed., Raven Press: New York 1988, pp 273-280), both of which are herein incorporated by reference in their entireties. Oxygen fluxes (J) are measured at 34° C. in a wet cell (i.e., gas streams are maintained at about 100% relative humidity) using a Dk1000 instrument (available from Applied Design and Development Co., Norcross, Ga.), or similar analytical instrument. An air stream, having a known percentage of oxygen (e.g., 21%), is passed across one side of the lens at a rate of about 10 to 20 cm3/min., while a nitrogen stream is passed on the opposite side of the lens at a rate of about 10 to 20 cm3/min. A sample is equilibrated in a test media (i.e., saline or distilled water) at the prescribed test temperature for at least 30 minutes prior to measurement but not more than 45 minutes. Any test media used as the overlayer is equilibrated at the prescribed test temperature for at least 30 minutes prior to measurement but not more than 45 minutes. The stir motor's speed is set to 1200±50 rpm, corresponding to an indicated setting of 400±15 on the stepper motor controller. The barometric pressure surrounding the system, Pmeasured, is measured. The thickness (t) of the lens in the area being exposed for testing is determined by measuring about 10 locations with a Mitotoya micrometer VL-50, or similar instrument, and averaging the measurements. The oxygen concentration in the nitrogen stream (i.e., oxygen which diffuses through the lens) is measured using the DK1000 instrument. The apparent oxygen permeability of the lens material, Dkapp, is determined from the following formula:

Dkapp=Jt/(Poxygen)

where

    
    
        J=oxygen flux [microliters O2/cm2-minute]
        Poxygen=(Pmeasured−Pwater vapor)=(% O2 in air stream) [mm Hg]=partial pressure of oxygen in the air stream
        Pmeasured=barometric pressure (mm Hg)
        Pwater vapor=0 mm Hg at 34° C. (in a dry cell) (mm Hg)
        Pwater vapor=40 mm Hg at 34° C. (in a wet cell) (mm Hg)
        t=average thickness of the lens over the exposed test area (mm)

where Dkapp is expressed in units of barrers. The oxygen transmissibility (Dk/t) of the material may be calculated by dividing the oxygen permeability (Dkapp) by the average thickness (t) of the lens.

    
    


Ion Permeability Measurements.
The ion permeability of a lens is measured according to procedures described in U.S. Pat. No. 5,760,100 (herein incorporated by reference in its entirety. The values of ion permeability reported in the following examples are relative ionoflux diffusion coefficients (D/Dref) in reference to a lens material, Alsacon, as reference material. Alsacon has an ionoflux diffusion coefficient of 0.314×10−3 mm2/minute.

## Claims

1. An actinically crosslinkable prepolymer, being obtained by:
(a) copolymerizing an actinically polymerizable composition to obtain an intermediary copolymer with first functional groups, wherein the actinically polymerizable composition comprises
(1) at least one vinylic monomer including a hydrolyzable silicone-containing group and being represented by formula (1) or (2),







in which 1R is H or —CH3, -L- is —O— or







2R is trimethylsilyl group (—Si(CH3)3) or a C4-C25 alkyl which is substituted by at least one trimethylsilyloxy, trimethylsilylamino group or trimethylsilyl-C1-C7 alkylamino group, 3R is H or C1-C8 alkyl group,





in which 1R is H or —CH3, -L- is —O— or







3R is H or C1-C8 alkyl group, 4R is C1-C12 unsubstituted alkylene (divalent radical) or substituted alkylene in which one or more hydrogens are substituted by C1-C3 alkoxy groups, hydroxy groups, amino groups, thiol groups, and/or carboxyl groups, 5R is C1-C7 alkylene group,

(2) at least one hydrophilic vinylic monomer,
(3) at least one siloxane-containing monomer having one ethylenically unsaturated group, at least one siloxane-containing macromer having one ethylenically unsaturated group, at least one siloxane-containing monomer having two or more ethylenically unsaturated groups, at least one siloxane-containing macromer having two or more ethylenically unsaturated groups, or a combination of two or more thereof, and
(4) optionally a chain transfer agent,
provided that at least one of components (2)-(4) further comprises at least one first functional group; and

(b) reacting an organic compound with the copolymerization product to form the crosslinkable prepolymer having actinically crosslinkable groups, wherein the organic compound comprises an actinically crosslinkable group and a second functional group, wherein the second functional group of the organic compound reacts with one of the first functional groups of the intermediary copolymer.

2. The prepolymer of claim 1, wherein the at least one vinylic monomer including a hydrolyzable silicone-containing group is a vinylic monomer of formula (1).

3. The prepolymer of claim 1, wherein the at least one vinylic monomer including a hydrolyzable silicone-containing group a vinylic monomer of formula (2).

4. The prepolymer of claim 1, wherein the hydrophilic vinylic monomer is selected from the group consisting of N,N-dimethylacrylamide (DMA), 2-hydroxyethylmethacrylate (HEMA), 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), dimethylaminoethylmethacrylamide, acrylamide, methacrylamide, allyl alcohol, vinylpyridine, N-(1,1-dimethyl-3-oxobutyl)acrylamide, acrylic acid, a C1-C4-alkoxy polyethylene glycol (meth)acrylate having a weight average molecular weight of from 200 to 1500, methacrylic acid, N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, N-vinyl caprolactam, and combinations thereof.

5. The prepolymer of claim 1, wherein the prepolymer comprises dangling polymeric chains derived from one or more hydrophilic polymers each having one sole ethylenically unsaturated group, wherein the one or more hydrophilic polymers each having one sole ethylenically unsaturated group are selected from the group consisting of polyethyleneglycol, polyethylene glycol/polypropylene glycol block copolymer, polyalkylacrylamide, poyalkylmethacrylamide, polyvinylpyrrolidone, a copolymer of N-vinylpyrrolidone with dialkylaminoalkylacrylate, a copolymer of N-vinylpyrrolidone with dialkylaminoalkylmethacrylate, a copolymer of N-vinylpyrrolidone with N,N-dialkylacrylamide, a copolymer of N-vinylpyrrolidone with N,N-dialkylmethacrylamide, a copolymer of N-vinylpyrrolidone with vinylacetate, polyvinylalcohol, a copolymer of vinylacetate with dialkylaminoalkylacrylate, a copolymer of vinylacetate with dialkylaminoalkylmethacrylate, a copolymer of vinylacetate with N,N-dialkylacrylamide, a copolymer of vinylacetate with N,N-dialkylmethacrylamide, and combination thereof.

6. The prepolymer of claim 2, wherein the hydrophilic vinylic monomer is selected from the group consisting of N,N-dimethylacrylamide (DMA), 2-hydroxyethylmethacrylate (HEMA), 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), dimethylaminoethylmethacrylamide, acrylamide, methacrylamide, allyl alcohol, vinylpyridine, N-(1,1-dimethyl-3-oxobutyl)acrylamide, acrylic acid, a C1-C4-alkoxy polyethylene glycol (meth)acrylate having a weight average molecular weight of from 200 to 1500, methacrylic acid, N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, N-vinyl caprolactam, and combinations thereof.

7. The prepolymer of claim 3, wherein the hydrophilic vinylic monomer is selected from the group consisting of N,N-dimethylacrylamide (DMA), 2-hydroxyethylmethacrylate (HEMA), 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), dimethylaminoethylmethacrylamide, acrylamide, methacrylamide, alkyl alcohol, vinylpyridine, N-(1,1-dimethyl-3-oxobutyl)acrylamide, acrylic acid, a C1-C4-alkoxy polyethylene glycol (meth)acrylate having a weight average molecular weight of from 200 to 1500, methacrylic acid, N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, N-vinyl caprolactam, and combinations thereof.

8. The prepolymer of claim 2, wherein the prepolymer comprises dangling polymeric chains derived from one or more hydrophilic polymers each having one sole ethylenically unsaturated group, wherein the one or more hydrophilic polymers each having one sole ethylenically unsaturated group are selected from the group consisting of polyethyleneglycol, polyethylene glycol/polypropylene glycol block copolymer, polyalkylacrylamide, poyalkylmethacrylamide, polyvinylpyrrolidone, a copolymer of N-vinylpyrrolidone with dialkylaminoalkylacrylate, a copolymer of N-vinylpyrrolidone with dialkylaminoalkylmethacrylate, a copolymer of N-vinylpyrrolidone with N,N-dialkylacrylamide, a copolymer of N-vinylpyrrolidone with N,N-dialkylmethacrylamide, a copolymer of N-vinylpyrrolidone with vinylacetate, polyvinylalcohol, a copolymer of vinylacetate with dialkylaminoalkylacrylate, a copolymer of vinylacetate with dialkylaminoalkylmethacrylate, a copolymer of vinylacetate with N,N-dialkylacrylamide, a copolymer of vinylacetate with N,N-dialkylmethacrylamide, and combination thereof.

9. The prepolymer of claim 3, wherein the prepolymer comprises dangling polymeric chains derived from one or more hydrophilic polymers each having one sole ethylenically unsaturated group, wherein the one or more hydrophilic polymers each having one sole ethylenically unsaturated group are selected from the group consisting of polyethyleneglycol, polyethylene glycol/polypropylene glycol block copolymer, polyalkylacrylamide, poyalkylmethacrylamide, polyvinylpyrrolidone, a copolymer of N-vinylpyrrolidone with dialkylaminoalkylacrylate, a copolymer of N-vinylpyrrolidone with dialkylaminoalkylmethacrylate, a copolymer of N-vinylpyrrolidone with N,N-dialkylacrylamide, a copolymer of N-vinylpyrrolidone with N,N-dialkylmethacrylamide, a copolymer of N-vinylpyrrolidone with vinylacetate, polyvinylalcohol, a copolymer of vinylacetate with dialkylaminoalkylacrylate, a copolymer of vinylacetate with dialkylaminoalkylmethacrylate, a copolymer of vinylacetate with N,N-dialkylacrylamide, a copolymer of vinylacetate with N,N-dialkylmethacrylamide, and combination thereof.

10. The prepolymer of claim 6, wherein the prepolymer comprises dangling polymeric chains derived from one or more hydrophilic polymers each having one sole ethylenically unsaturated group, wherein the one or more hydrophilic polymers each having one sole ethylenically unsaturated group are selected from the group consisting of polyethyleneglycol, polyethylene glycol/polypropylene glycol block copolymer, polyalkylacrylamide, poyalkylmethacrylamide, polyvinylpyrrolidone, a copolymer of N-vinylpyrrolidone with dialkylaminoalkylacrylate, a copolymer of N-vinylpyrrolidone with dialkylaminoalkylmethacrylate, a copolymer of N-vinylpyrrolidone with N,N-dialkylacrylamide, a copolymer of N-vinylpyrrolidone with N,N-dialkylmethacrylamide, a copolymer of N-vinylpyrrolidone with vinylacetate, polyvinylalcohol, a copolymer of vinylacetate with dialkylaminoalkylacrylate, a copolymer of vinylacetate with dialkylaminoalkylmethacrylate, a copolymer of vinylacetate with N,N-dialkylacrylamide, a copolymer of vinylacetate with N,N-dialkylmethacrylamide, and combination thereof.

11. The prepolymer of claim 7, wherein the prepolymer comprises dangling polymeric chains derived from one or more hydrophilic polymers each having one sole ethylenically unsaturated group, wherein the one or more hydrophilic polymers each having one sole ethylenically unsaturated group are selected from the group consisting of polyethyleneglycol, polyethylene glycol/polypropylene glycol block copolymer, polyalkylacrylamide, poyalkylmethacrylamide, polyvinylpyrrolidone, a copolymer of N-vinylpyrrolidone with dialkylaminoalkylacrylate, a copolymer of N-vinylpyrrolidone with dialkylaminoalkylmethacrylate, a copolymer of N-vinylpyrrolidone with N,N-dialkylacrylamide, a copolymer of N-vinylpyrrolidone with N,N-dialkylmethacrylamide, a copolymer of N-vinylpyrrolidone with vinylacetate, polyvinylalcohol, a copolymer of vinylacetate with dialkylaminoalkylacrylate, a copolymer of vinylacetate with dialkylaminoalkylmethacrylate, a copolymer of vinylacetate with N,N-dialkylacrylamide, a copolymer of vinylacetate with N,N-dialkylmethacrylamide, and combination thereof.

12. The prepolymer of claim 1, wherein the first functional groups of the intermediary copolymer are selected from the group consisting of hydroxyl groups, primary amino groups, secondary amino groups, carboxyl groups, epoxy groups, acid halide groups (—COX, X═Cl, Br, or I), isocyanate groups, and combinations thereof, wherein the organic compound is a vinylic monomer having a hydroxy, amino, carboxyl, epoxy, acid-chloride, isocyanate group which is coreactive with one of the first functional groups of the intermediary copolymer in the absence or presence of a coupling agent.

13. The prepolymer of claim 1, wherein the intermediary copolymer comprises: from about 15% to about 80% by weight of siloxane units derived from one or more siloxane-containing monomers and/or one or more siloxane-containing macromers; from about 10% to about 80% of hydrophilic units derived from one or more hydrophilic monomers and/or one or more hydrophilic macromers; from about 1% to about 30% of silicone-containing units derived from one or more silicone-containing vinylic monomers; and about 2% to about 30% by weight of hydrolyzable units derived from at least one vinylic monomer including a hydrolyzable silicone-containing group.