CN112930487B

CN112930487B - Ophthalmic device

Info

Publication number: CN112930487B
Application number: CN201880096494.4A
Authority: CN
Inventors: I·M·努涅斯; L·寇拉德; D·J·霍克; R·B·斯特芬; D·M·阿蒙; J·M·亨特; A·马克
Original assignee: Bausch and Lomb Inc
Current assignee: Bausch and Lomb Inc
Filing date: 2018-08-10
Publication date: 2024-07-02
Anticipated expiration: 2038-08-10

Abstract

An ophthalmic device is disclosed that is the polymerization product of a monomer mixture comprising: (a) A major amount of one or more non-silicone containing hydrophilic monomers; (b) A crosslinker mixture comprising (i) one or more first crosslinkers containing at least two ethylenically unsaturated reactive end groups, wherein the at least two ethylenically unsaturated reactive end groups are (meth) acrylate-containing reactive end groups, and (ii) one or more second crosslinkers containing at least two ethylenically unsaturated reactive end groups, wherein at least one of the ethylenically unsaturated reactive end groups is a non- (meth) acrylate-reactive end group, and (c) one or more hydrophilic polymers or copolymers comprising one or more hydrophilic units and a thiocarbonylthio fragment of a reversible addition fragmentation chain transfer ("RAFT") agent, wherein the ophthalmic device has an equilibrium water content of at least about 45% by weight.

Description

Ophthalmic device

Technical Field

The present invention relates generally to ophthalmic devices, such as contact lenses.

Background

Ophthalmic devices (e.g., contact lenses) are made from a variety of polymeric materials including rigid gas permeable materials, soft elastic materials, and soft hydrogel materials. Most contact lenses sold today are made of soft hydrogel materials. Hydrogels are crosslinked polymer systems that absorb and retain water, typically 10 to 80% by weight and specifically 20 to 70% by weight. Hydrogel lenses are typically prepared by polymerizing a lens-forming monomer mixture comprising at least one hydrophilic monomer, such as 2-hydroxyethyl methacrylate, N-dimethylacrylamide, N-vinyl-2-pyrrolidone, glycerol methacrylate, and methacrylic acid. In the case of silicone hydrogel lenses, the silicone-containing monomer is copolymerized with a hydrophilic monomer. Both hydrogel and non-hydrogel siloxy and/or fluorinated contact lenses tend to have relatively hydrophobic, non-wettable surfaces regardless of their water content.

In the field of ophthalmic devices (e.g., contact lenses), various physical and chemical properties (e.g., oxygen permeability, wettability, material strength, and stability) are just a few factors that must be carefully balanced in order to provide a useful contact lens. For example, oxygen permeability is an important property of certain contact lens materials because the cornea receives its oxygen supply by contact with the atmosphere. Wettability is also important because if the lens is not sufficiently wet, it cannot remain lubricated and therefore cannot be comfortably worn on the eye. Thus, an optimal contact lens will have at least both excellent oxygen permeability and excellent tear wettability.

Increasing the hydrophilicity of a contact lens surface is known to improve the wettability of the contact lens. This in turn is associated with an increase in the wearing comfort of the lens. Furthermore, the surface of the lens can affect the overall sensitivity of the lens to protein and lipid deposition from tear fluid during lens wear. Accumulated deposits can cause eye discomfort, or even inflammation. In the case of extended wear lenses, i.e. lenses that do not need to be removed for use every day before sleeping, the surface is particularly important as extended wear lenses must be designed to have high standards of comfort and biocompatibility over extended periods of time. Thus, new formulations are still desired, which make it possible to obtain improved surface quality.

Accordingly, it would be desirable to provide improved ophthalmic devices (e.g., contact lenses) that exhibit suitable physical and chemical properties (e.g., oxygen permeability, lubricity, and wettability) for prolonged contact with the body while also being biocompatible. It would also be desirable to provide improved ophthalmic devices that are easy to manufacture in a simple, cost-effective manner.

Disclosure of Invention

According to one embodiment of the present invention, there is provided an ophthalmic device that is a polymerization product of a monomer mixture comprising: (a) A major amount of one or more non-silicone containing hydrophilic monomers; (b) A crosslinker mixture comprising (i) one or more first crosslinkers containing at least two ethylenically unsaturated reactive end groups, wherein the at least two ethylenically unsaturated reactive end groups are (meth) acrylate-containing reactive end groups, and (ii) one or more second crosslinkers containing at least two ethylenically unsaturated reactive end groups, wherein at least one of the ethylenically unsaturated reactive end groups is a non- (meth) acrylate-reactive end group, and (c) one or more hydrophilic polymers or copolymers comprising one or more hydrophilic units and a thiocarbonylthio fragment of a reversible addition fragmentation chain transfer ("RAFT") agent, wherein the ophthalmic device has an equilibrium water content of at least about 45% by weight.

According to a second embodiment of the present invention, there is provided a method of making an ophthalmic device, the method comprising (a) providing a monomer mixture comprising: (i) A major amount of one or more non-silicone containing hydrophilic monomers; (ii) A crosslinker mixture comprising (1) one or more first crosslinkers containing at least two ethylenically unsaturated reactive end groups, wherein the at least two ethylenically unsaturated reactive end groups are (meth) acrylate-containing reactive end groups, and (2) one or more second crosslinkers containing at least two ethylenically unsaturated reactive end groups, wherein at least one of the ethylenically unsaturated reactive end groups is a non- (meth) acrylate-reactive end group, and (iii) one or more hydrophilic polymers or copolymers comprising one or more hydrophilic units and thiocarbonylthio fragments of a RAFT agent; (b) Subjecting the monomer mixture to polymerization conditions to provide a polymerization device, and (c) hydrating the polymerization device, wherein the ophthalmic device has an equilibrium water content of at least about 45 wt%.

The ophthalmic devices of the present invention advantageously exhibit suitable physical and chemical properties (e.g., oxygen permeability, lubricity, and wettability) for prolonged contact with the body by: polymerizing a monomer mixture comprising: (a) A major amount of one or more first non-silicone containing hydrophilic monomers; (b) One or more first crosslinking agents containing at least two ethylenically unsaturated reactive end groups, wherein the at least two ethylenically unsaturated reactive end groups are (meth) acrylate-containing reactive end groups, and (ii) one or more second crosslinking agents containing at least two ethylenically unsaturated reactive end groups, wherein at least one of the ethylenically unsaturated reactive end groups is a non- (meth) acrylate-reactive end group, and (c) one or more hydrophilic polymers or copolymers, thiocarbonylthio fragments comprising one or more hydrophilic units and a RAFT agent, wherein the ophthalmic device has an equilibrium water content of at least about 45 wt%. Furthermore, the ophthalmic devices of the present invention advantageously exhibit improved dimensional stability, lower extractability, and improved tear resistance and modulus.

Detailed Description

The illustrative embodiments described herein are directed to ophthalmic devices. While the illustrative embodiments are applicable to a variety of ophthalmic devices, one particular illustrative embodiment is particularly useful and advantageous for contact lenses. The terms "ophthalmic device" and "lens" as used herein refer to devices that reside in or on the eye. These devices may provide optical correction, wound care, drug delivery, diagnostic function or cosmetic enhancement, or any combination of these properties. Representative examples of such devices include, but are not limited to, soft contact lenses, such as soft hydrogel lenses, soft non-hydrogel lenses, and the like, intraocular lenses, overlay lenses, ocular inserts, optical inserts, bandaged lenses, therapeutic lenses, and the like. As understood by those skilled in the art, a lens is considered "soft" if it can fold back upon itself without breaking. Ophthalmic devices (e.g., contact lenses of the illustrative embodiments) can be spherical, toric, bifocal, can contain cosmetic colors, opaque cosmetic patterns, combinations thereof, and the like.

In one illustrative embodiment, the ophthalmic device will have an equilibrium water content of at least about 45% by weight. In another illustrative embodiment, the ophthalmic device will have an equilibrium water content of at least about 50% by weight. In another illustrative embodiment, the ophthalmic device will have an equilibrium water content of at least about 60% by weight. In another illustrative embodiment, the ophthalmic device will have an equilibrium water content of about 50% to about 65% by weight. In another illustrative embodiment, the ophthalmic device will have an equilibrium water content of about 55% to about 65% by weight. In one illustrative embodiment, the ophthalmic device will have a trapped bubble contact angle of about 30 ° to about 70 °.

Generally, ophthalmic devices are the polymerization product of a monomer mixture comprising: (a) A major amount of one or more first non-silicone containing hydrophilic monomers; (b) A crosslinker mixture comprising (i) one or more first crosslinkers containing at least two ethylenically unsaturated reactive end groups, wherein the at least two ethylenically unsaturated reactive end groups are (meth) acrylate-containing reactive end groups, and (ii) one or more second crosslinkers containing at least two ethylenically unsaturated reactive end groups, wherein at least one of the ethylenically unsaturated reactive end groups is a non- (meth) acrylate-reactive end group, and (c) one or more hydrophilic polymers or copolymers comprising one or more hydrophilic units and thiocarbonylthio fragments of a RAFT agent, wherein the ophthalmic device has an equilibrium water content of at least about 45 wt%. As will be readily appreciated by those skilled in the art, the crosslinker mixture comprises one or more first crosslinkers comprising at least two ethylenically unsaturated reactive end groups, wherein the at least two ethylenically unsaturated reactive end groups are (meth) acrylate-containing reactive end groups; and one or more second cross-linking agents containing at least two ethylenically unsaturated reactive end groups, wherein at least one of the ethylenically unsaturated reactive end groups is a non- (meth) acrylate reactive end group and the one or more hydrophilic polymers or copolymers comprise one or more hydrophilic units and thiocarbonylthio fragments of a RAFT agent, the cross-linking agent mixture being mutually exclusive of the one or more hydrophilic polymers or copolymers. In one illustrative embodiment, the monomer mixture contains a non-silicone containing monomer.

The term "(methyl)" as used herein means an optional methyl substituent. Thus, terms such as "(meth) acrylate" refer to either methacrylate or acrylate, and "(meth) acrylamide" refers to either methacrylamide or acrylamide.

Suitable non-silicone containing hydrophilic monomers include amides, cyclic lactams, hydroxyl-containing (meth) acrylates, poly (alkylene glycols) functionalized with polymerizable groups, and the like, and mixtures thereof. Representative examples of amides include alkylamides such as N, N-dimethylacrylamide, N-dimethylmethacrylamide, and the like, and mixtures thereof. Representative examples of cyclic lactams include N-vinyl-2-pyrrolidone, N-vinyl caprolactam, N-vinyl-2-piperidone, and the like, and mixtures thereof. Representative examples of hydroxyl group-containing (meth) acrylates include 2-hydroxyethyl methacrylate (HEMA), glycerol methacrylate, and the like, and mixtures thereof. Representative examples of functionalized poly (alkylene glycols) include poly (diethylene glycol) of different chain lengths containing monomethacrylate or dimethacrylate end caps. In one embodiment, the poly (alkylene glycol) polymer comprises at least two alkylene glycol monomer units. Further examples are hydrophilic vinyl carbonate or vinyl carbamate monomers as disclosed in U.S. Pat. No. 5,070,215, and hydrophilic oxazolone monomers as disclosed in U.S. Pat. No. 4,910,277. Other suitable hydrophilic monomers will be apparent to those skilled in the art. Mixtures of the foregoing non-silicone containing hydrophilic monomers may also be used in the monomer mixtures herein.

In one illustrative embodiment, the monomer mixture will include a major amount of one or more first non-silicone-containing hydrophilic monomers that are one or more hydroxyl-containing (meth) acrylates. In another illustrative embodiment, the monomer mixture will include a major amount of one or more first non-silicone containing hydrophilic monomers that are 2-hydroxyethyl methacrylate.

Generally, the one or more non-silicone-containing hydrophilic monomers are present in the monomer mixture in a major amount (e.g., an amount of at least about 70 wt%, or an amount of at least about 70 wt% up to about 95 wt%, or an amount of at least about 80 wt% up to about 95 wt%, based on the total weight of the monomer mixture).

The monomer mixture further comprises a crosslinker mixture comprising (i) one or more first crosslinkers containing at least two ethylenically unsaturated reactive end groups, wherein the ethylenically unsaturated reactive end groups are (meth) acrylate-containing reactive end groups; and (ii) one or more second crosslinking agents containing at least two ethylenically unsaturated reactive end groups, wherein at least one of the ethylenically unsaturated reactive end groups is a non- (meth) acrylate reactive end group. In one illustrative embodiment, useful one or more first crosslinkers containing at least two ethylenically unsaturated reactive end groups include one or more di, tri, or tetra (meth) acrylate-containing crosslinkers where the ethylenically unsaturated reactive end groups are (meth) acrylate-containing reactive end groups.

In one illustrative embodiment, useful one or more di-, tri-, or tetra (meth) acrylate-containing crosslinkers include alkane polyol di-, tri-, or tetra (meth) acrylate-containing crosslinkers, such as one or more alkylene glycol di (meth) acrylate crosslinkers, one or more alkylene glycol tri (meth) acrylate crosslinkers, one or more alkylene glycol tetra (meth) acrylate crosslinkers, one or more alkylene glycol di (meth) acrylate crosslinkers, alkylene glycol tri (meth) acrylate crosslinkers, alkylene glycol tetra (meth) acrylate crosslinkers, agents, one or more alkanetriol di (meth) acrylate crosslinkers, alkanetriol tri (meth) acrylate crosslinkers, alkanetriol tetra (meth) acrylate crosslinkers, agents, one or more alkanetetrol di (meth) acrylate crosslinkers, alkanetetrol tri (meth) acrylate crosslinkers, alkanetetrol tetra (meth) acrylate crosslinkers, and the like, and mixtures thereof.

In one embodiment, the one or more alkylene glycol di (meth) acrylate cross-linking agents include tetraethylene glycol dimethacrylate, ethylene glycol di (meth) acrylate having up to about 10 ethylene glycol repeating units, butylene glycol di (meth) acrylate, and the like. In one embodiment, the one or more alkylene glycol di (meth) acrylate cross-linking agents include butylene glycol di (meth) acrylate cross-linking agents, hexylene glycol di (meth) acrylate, and the like. In one embodiment, the one or more alkanetriol tri (meth) acrylate crosslinker is a trimethylolpropane trimethacrylate crosslinker. In one embodiment, the one or more alkyl tetra (meth) acrylate cross-linking agents are pentaerythritol tetramethyl acrylate cross-linking agents.

In one illustrative embodiment, useful one or more second crosslinking agents containing at least two ethylenically unsaturated reactive end groups include one or more di-, tri-, or tetra-urethane-containing crosslinking agents, one or more di-, tri-, or tetra-carbonate-containing crosslinking agents, one or more isocyanurate-containing crosslinking agents, and the like, and mixtures thereof, wherein at least one of the ethylenically unsaturated reactive end groups is a non- (meth) acrylate reactive end group.

Representative examples of the one or more di-, tri-, or tetra-urethane-containing crosslinkers include one or more di (N-vinyl urethane-containing crosslinkers, one or more di (N-allyl urethane-containing crosslinkers, one or more di (O-vinyl urethane-containing crosslinkers, one or more di (O-allyl urethane-containing crosslinkers, one or more tri (N-vinyl urethane-containing crosslinkers, one or more tri (N-allyl urethane) -containing crosslinkers, one or more tri (O-vinyl urethane) -containing crosslinkers, one or more tri (O-allyl urethane) -containing crosslinkers, one or more tetra (N-vinyl urethane) -containing crosslinkers, one or more tetra (N-allyl urethane) -containing crosslinkers, one or more tetra (O-allyl urethane) -containing crosslinkers, and the like, and mixtures thereof.

Representative examples of the one or more di-, tri-, or tetra-carbonate-containing crosslinking agents include di (O-vinyl carbonate) -containing crosslinking agents, di (O-allyl carbonate) -containing crosslinking agents, tri (O-vinyl carbonate) -containing crosslinking agents, tri (O-allyl carbonate) -containing crosslinking agents, tetra (O-vinyl carbonate) -containing crosslinking agents, tetra (O-allyl carbonate) -containing crosslinking agents, and the like, and mixtures thereof.

Representative examples of the one or more isocyanurate-containing crosslinkers include one or more diallyl isocyanurate, triallyl isocyanurate, divinyl isocyanurate, trivinyl isocyanurate, and the like, as well as mixtures thereof.

In one embodiment, the one or more dicarbamate-containing crosslinkers include bis (N-vinyl carbamate) having the structure:

wherein x is 0 to 10.

In one embodiment, the one or more dicarbamate-containing crosslinkers include bis (O-vinyl carbamate) having the structure:

wherein x is 0 to 10.

In one embodiment, the one or more dicarbamate-containing crosslinkers include diethylene glycol bis (N-vinyl carbamate), diethylene glycol bis (O-allyl carbamate), and the like, and mixtures thereof.

In one embodiment, the one or more second crosslinking agents are selected from the group consisting of diethylene glycol bis (N-vinyl carbamate), diethylene glycol bis (N-allyl carbamate), diethylene glycol bis (O-vinyl carbamate), diethylene glycol bis (O-allyl carbamate), and mixtures thereof, 1, 4-butanediol bis (N-vinyl carbamate), ethylene glycol bis (O-vinyl carbonate), diethylene glycol bis (O-vinyl carbonate), 1, 4-butanediol bis (O-vinyl carbonate), and mixtures thereof.

In one embodiment, the one or more second crosslinking agents containing at least two ethylenically unsaturated reactive end groups include at least one reactive end group containing allyl groups and at least one reactive end group containing (meth) acrylate esters. In one embodiment, the one or more second crosslinking agents include allyl methacrylate.

Generally, the one or more first and/or second crosslinking agents are present in the monomer mixture in an amount to form an ophthalmic device. In one embodiment, the one or more first crosslinking agents are present in the monomer mixture in an amount of about 0.1 wt.% to about 2.0 wt.% based on the total weight of the monomer mixture, and the second crosslinking agent is present in the monomer mixture in an amount of about 0.05 wt.% to about 2.0 wt.% based on the total weight of the monomer mixture.

The monomer mixture further comprises one or more hydrophilic polymers or copolymers comprising one or more hydrophilic units and thiocarbonylthio fragments of a RAFT agent. The term "hydrophilic polymer or copolymer" as used herein is understood to mean a hydrophilic polymer or copolymer containing polar or charged functional groups that render it water soluble. Hydrophilic polymers or copolymers comprising one or more hydrophilic units and thiocarbonylthio fragments of a RAFT agent are prepared by RAFT polymerization, i.e. monomers are polymerized by RAFT mechanism to form hydrophilic polymers or copolymers (e.g. block or random copolymers), wherein the molecular weight of each of the blocks or the whole polymer can be precisely controlled. RAFT polymerization is thus a free radical polymerization technique capable of preparing polymers with a well-defined molecular architecture and low dispersibility.

RAFT agents suitable for use herein are based on thiocarbonylthio chemistry well known to those of ordinary skill in the art. The RAFT agent may be, for example, a xanthate-containing compound, a trithiocarbonate-containing compound, a dithiocarbamate-containing compound, or a dithioester-containing compound, each of which contains thiocarbonylthio. One class of RAFT agents useful herein has the general formula:

Wherein Z is a substituted oxygen (e.g., xanthate (-O-R)), a substituted nitrogen (e.g., dithiocarbamate (-NRR)), a substituted sulfur (e.g., trithiocarbonate (-S-R)), a substituted or unsubstituted C ₁-C₂₀ alkyl or C ₃-C₂₅ unsaturated or partially or fully saturated ring (e.g., dithioester (-R)), or a carboxylic acid-containing group; and R is independently a linear or branched substituted or unsubstituted C ₁-C₃₀ alkyl, substituted or unsubstituted C ₃-C₃₀ cycloalkyl, substituted or unsubstituted C ₃-C₃₀ cycloalkylalkyl, substituted or unsubstituted C ₃-C₃₀ cycloalkenyl, substituted or unsubstituted C ₅-C₃₀ aryl, substituted or unsubstituted C ₅-C₃₀ arylalkyl, C ₁-C₂₀ ester group; ether or polyether containing groups; alkyl or aryl amide groups; alkyl or arylamine groups; a substituted or unsubstituted C ₅-C₃₀ heteroaryl; a substituted or unsubstituted C ₃-C₃₀ heterocycle; a substituted or unsubstituted C ₄-C₃₀ heterocycloalkyl; a substituted or unsubstituted C ₆-C₃₀ heteroarylalkyl group; and combinations thereof.

Representative examples of alkyl groups for use herein include, by way of example, saturated or unsaturated, straight or branched alkyl chain radicals containing from 1 to about 30 carbon atoms, and preferably from 1 to about 12 carbon atoms, and hydrogen atoms, relative to the remainder of the molecule, such as methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl, methylene, ethylene, and the like.

Representative examples of cycloalkyl groups for use herein include, by way of example, a substituted or unsubstituted, non-aromatic, mono-or polycyclic ring system of from about 3 to about 30 carbon atoms, and preferably from 3 to about 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, perhydronaphthyl, adamantyl and norbornyl, bridged or spiro-bicyclic groups (e.g., spiro- (4, 4) -non-2-yl), and the like, optionally containing one or more heteroatoms (e.g., O and N), and the like.

Representative examples of cycloalkylalkyl groups for use herein include, for example, a substituted or unsubstituted cyclic ring-containing radical containing from about 3 to about 30 carbon atoms, and preferably from 3 to about 6 carbon atoms, directly attached to the alkyl group, then attached to the main structure of the monomer at any carbon of the alkyl group, thereby yielding a stable structure, such as cyclopropylmethyl, cyclobutylethyl, cyclopentylethyl, and the like, wherein the cyclic ring may optionally contain one or more heteroatoms (e.g., O and N), and the like.

Representative examples of cycloalkenyl groups for use herein include, by way of example, a substituted or unsubstituted cyclic ring-containing radical containing from about 3 to about 30 carbon atoms, and preferably 3 to about 6 carbon atoms, and having at least one carbon-carbon double bond, such as cyclopropenyl, cyclobutenyl, cyclopentenyl, and the like, wherein the cyclic ring may optionally contain one or more heteroatoms (e.g., O and N), and the like.

Representative examples of aryl groups for use herein include, by way of example, a substituted or unsubstituted monoaromatic or polyaromatic radical containing from about 5 to about 30 carbon atoms, such as phenyl, naphthyl, tetrahydronaphthyl, indenyl, biphenyl, and the like, optionally containing one or more heteroatoms (e.g., O and N), and the like.

Representative examples of arylalkyl groups for use herein include, by way of example, a substituted or unsubstituted aryl group as defined herein, e.g., -CH ₂C₆H₅、-C₂H₅C₆H₅, and the like, directly bonded to an alkyl group as defined herein, wherein the aryl group may optionally contain one or more heteroatoms (e.g., O and N), and the like.

Representative examples of ester groups for use herein include, by way of example, carboxylic acid esters having from 1 to 20 carbon atoms and the like.

Representative examples of ether-containing or polyether groups for use herein include, by way of example, alkyl ethers, cycloalkyl ethers, cycloalkylalkyl ethers, cycloalkenyl ethers, aryl ethers, arylalkyl ethers, wherein alkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, aryl, and arylalkyl are as defined herein. For example, exemplary ether-or polyether-containing groups include alkylene oxides, poly (alkylene oxides) (e.g., ethylene oxide, propylene oxide, butylene oxide, poly (ethylene oxide), poly (ethylene glycol), poly (propylene oxide), poly (butylene oxide), and mixtures or copolymers thereof), ether or polyether groups of the formula- (R ²OR³)_t), wherein R ² is a bond, a substituted or unsubstituted alkyl, cycloalkyl, or aryl group as defined herein, and R ³ is a substituted or unsubstituted alkyl, cycloalkyl, or aryl group as defined herein, and t is at least 1, e.g., -CH ₂CH₂OC₆H₅ and CH ₂-CH₂-CH₂-O-CH₂-(CF₂)_z -H (where z is 1 to 6), -CH ₂CH₂OC₂H₅, and the like.

Representative examples of alkyl or aryl amide groups for use herein include, for example, amides of the general formula-R ⁴C(O)NR⁵R⁶ wherein R ⁴、R⁵ and R ⁶ are independently C ₁-C₃₀ hydrocarbons, e.g., R ⁴ can be alkylene, arylene, cycloalkylene, and R ⁵ and R ⁶ can be alkyl, aryl, cycloalkyl, and the like, as defined herein.

Representative examples of alkyl or arylamino groups for use herein include, for example, an amine of the general formula-R ⁷NR⁸R⁹ wherein R ⁷ is C ₂-C₃₀ alkylene, arylene, or cycloalkylene, and R ⁸ and R ⁹ are independently C ₁-C₃₀ hydrocarbons, such as alkyl, aryl, or cycloalkyl as defined herein.

Representative examples of heterocyclic ring groups for use herein include, by way of example, a substituted or unsubstituted stable 3 to about 30 membered ring radical containing carbon atoms and 1 to 5 heteroatoms such as nitrogen, phosphorus, oxygen, sulfur and mixtures thereof. Suitable heterocyclic ring radicals for use herein may be a monocyclic, bicyclic or tricyclic ring system, which may include fused, bridged or spiro ring systems, and the nitrogen, phosphorus, carbon, oxygen or sulfur atoms in the heterocyclic ring radical may optionally be oxidized to various oxidation states. In addition, the nitrogen atom may optionally be quaternized; and the ring radicals may be partially or fully saturated (i.e., heteroaromatic or heteroaryl aromatic). Examples of such heterocyclic ring radicals include, but are not limited to, azetidinyl, acridinyl, benzodioxolyl, benzodioxanyl, benzofuranyl, carbazolyl, cinnolinyl, dioxapenyl, indolizinyl, naphthyridinyl, perhydroazepinyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pyridinyl, pteridinyl, purinyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrazolyl, imidazolyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, azepinyl, pyrrolyl, 4-piperidonyl, pyrrolidinyl, pyrazinyl, pyrimidinyl, pyridazinyl oxazolyl, oxazolinyl, oxazolidinyl, triazolyl, indanyl, isoxazolyl, morpholinyl, thiazolyl, thiazolinyl, thiazolidinyl, isothiazolyl, quinuclidinyl, isothiazolidinyl, indolyl, isoindolyl, indolinyl, isoindolinyl, octahydroindolyl, octahydroisoindolyl, quinolinyl, isoquinolinyl, decahydroisoquinolinyl, benzimidazolyl, thiadiazolyl, benzopyranyl, benzothiazolyl, benzoxazolyl, furanyl, tetrahydrofuranyl, tetrahydropyranyl, thienyl, benzothienyl, thiomorpholinyl sulfoxide, thiomorpholinyl sulfone, dioxaphosphorinanyl, oxadiazolyl, chromanyl, isochromanyl, and the like, and mixtures thereof.

Representative examples of heteroaryl groups for use herein include, by way of example, a substituted or unsubstituted heterocyclic ring radical as defined herein. The heteroaryl ring radical may be attached to the main structure at any heteroatom or carbon atom that results in a stable structure.

Representative examples of heteroarylalkyl groups for use herein include, by way of example, a substituted or unsubstituted heteroaryl ring radical as defined herein directly bonded to an alkyl group as defined herein. The heteroarylalkyl radical may be attached to the main structure at any carbon atom of the alkyl group, thereby creating a stable structure.

Representative examples of heterocyclic groups for use herein include, by way of example, a substituted or unsubstituted heterocyclic ring radical as defined herein. The heterocyclic ring radical may be attached to the main structure at any heteroatom or carbon atom that results in a stable structure.

Representative examples of heterocycloalkyl groups for use herein include, by way of example, a substituted or unsubstituted heterocyclic ring radical as defined herein directly bonded to an alkyl group as defined herein. The heterocycloalkyl radical may be attached to the main structure at any carbon atom in the alkyl group, resulting in a stable structure.

The substituents in the 'substituted oxygen', 'substituted nitrogen', 'substituted sulfur', 'substituted alkyl', 'substituted alkylene', 'substituted cycloalkyl', 'substituted cycloalkylalkyl', 'substituted cycloalkenyl', 'substituted arylalkyl', 'substituted aryl', 'substituted heterocyclo-ring', 'substituted heteroaryl-ring', 'substituted heteroarylalkyl', 'substituted heterocyclo-ring', 'substituted heterocycloalkyl-ring', 'substituted cyclic ring' may be the same or different and include one or more substituents such as hydrogen, hydroxy, halogen, carboxyl, cyano, nitro, oxo (=o), thio (=s), substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and the like.

Representative examples of carboxylic acid-containing groups for use herein include, for example, a carboxylic acid group attached to the remainder of the molecule through a linker, e.g., a group of the formula-R ¹¹ C (O) OH, wherein R ¹¹ is a bond, a substituted or unsubstituted alkylene, a substituted or unsubstituted cycloalkylene, a substituted or unsubstituted cycloalkylalkylene, a substituted or unsubstituted arylene, or a substituted or unsubstituted arylalkylene, e.g., -CH (Ar) (C (O) OH), -C (CH ₃) (C (O) OH), and the like, wherein the carboxylic acid group may be attached to a substituent or directly to an alkylene, cycloalkylene, arylene, or arylalkylene group.

Representative examples of RAFT agents for use herein include, but are not limited to, benzyldodecyltrithiocarbonate, ethyl-2-dodecyltrithiocarbonyl) propionate, O-ethylxanthate of S-sec propionate, α -ethylxanthylphenylacetic acid, ethylα - (orthoethylxanthenyl) propionate, ethylα - (ethylxanthenyl) phenylacetate, ethyl 2- (dodecyltrithiocarbonyl) propionate, 2- (dodecylthiocarbonylthiol) propionic acid, and the like, and mixtures thereof.

Representative examples of RAFT agents for use herein include carboxylic acid trithiocarbonates as described below:

Benzyl trithiocarbonate as described below:

Xanthates of the formula:

wherein x is from 0 to 23,

Wherein x is from 0 to 23,

The cyano RAFT reagent is as follows:

The dithiobenzoate is as follows:

The organic chemistry used to form the RAFT agent is not particularly limited and is within the purview of one skilled in the art. The following working examples also provide guidance. For example, RAFT reagents may be prepared as illustrated in schemes I-V below.

Scheme I

Scheme II

Scheme IV

Scheme V

In addition to the thiocarbonylthio fragment of the RAFT agent, the hydrophilic polymers or copolymers described herein contain one or more hydrophilic units. Generally, the hydrophilic unit is derived from at least one hydrophilic monomer. Suitable hydrophilic monomers include, for example, acrylamides, such as N, N-dimethylacrylamide, and the like; acetamides such as N-vinyl-N-methylacetamide, N-vinylacetamide, and the like; formamide, such as N-vinyl-N-methylformamide, N-vinylformamide, etc.; cyclic lactams such as N-vinyl-2-pyrrolidone and the like; (meth) acrylic alcohols such as 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, and the like; (meth) acrylated poly (ethylene glycol) and the like; ethylenically unsaturated carboxylic acids, such as methacrylic acid, acrylic acid, and the like, and mixtures thereof.

In one embodiment, the hydrophilic polymer or copolymer containing thiocarbonylthio fragments of a RAFT agent can further comprise one or more hydrophilic units derived from an ethylenically unsaturated polymerizable monomer having ring-opening reactive functionality. Such monomers may include one or more ring-opening reactive groups, such as azlactone, epoxy, anhydride, and the like. Suitable polymerizable monomers having ring-opening reactive functionalities include, but are not limited to, glycidyl Methacrylate (GMA), maleic anhydride, itaconic anhydride, and the like, and mixtures thereof. The units derived from ethylenically unsaturated polymerizable monomers having ring-opening reactive functionalities may be copolymerized with hydrophilic comonomers to form hydrophilic units in the resulting hydrophilic polymer. Non-limiting examples of comonomers that can be used to copolymerize with the ring-opening reactive functionality of the monomer to form the hydrophilic polymer or copolymer used to prepare the ophthalmic device according to the present invention include those described above, preferably dimethylacrylamide, hydroxyethyl methacrylate (HEMA), and/or N-vinyl pyrrolidone. Alternatively, units derived from ethylenically unsaturated polymerizable hydrophilic monomers having ring-opening reactive functionalities may undergo a ring-opening reaction (e.g., by hydrolysis with water) and form hydrophilic units in the resulting hydrophilic polymer.

In one embodiment, the hydrophilic polymer or copolymer containing thiocarbonylthio fragments of a RAFT agent can further comprise units derived from an ethylenically unsaturated polymerizable alkoxylated polymer. Suitable ethylenically unsaturated polymerizable alkoxylated polymers include, for example, polymerizable polyethylene glycols having a number average molecular weight of up to, for example, about 2000, such as those having CTFA names PEG-200, PEG-400, PEG-600, PEG-1000, and mixtures thereof. Representative examples include PEG-200 methacrylate, PEG-400 methacrylate, PEG-600 methacrylate, PEG-1000 methacrylate, and the like, and mixtures thereof.

In one embodiment, the size of the units derived from the ethylenically unsaturated polymerizable alkoxylated polymer may vary widely, for example the number of units may range from 0 mole% to about 20 mole% of the total number of units in the polymerization product or from 1 mole% to about 10 mole% of the total number of units in the polymerization product.

The resulting hydrophilic polymers or copolymers may be in the form of homopolymers, block copolymers and random copolymers. In one illustrative embodiment, the one or more hydrophilic polymers or copolymers will have a number average molecular weight of at least about 30 kilodaltons (kDa), such as a number average molecular weight of about 30kDa to about 125 kDa. In one illustrative embodiment, the one or more hydrophilic polymers or copolymers will have a number average molecular weight of at least about 45kDa, such as a number average molecular weight of about 45kDa to about 100 kDa. In one illustrative embodiment, the one or more hydrophilic polymers or copolymers will have a number average molecular weight of at least about 60kDa, such as a number average molecular weight of about 60kDa to about 80 kDa. In general, the number average molecular weight of the one or more hydrophilic polymers or copolymers may be determined by Size Exclusion Chromatography (SEC) (also known as Gel Permeation Chromatography (GPC).

Methods for preparing hydrophilic polymers or copolymers containing thiocarbonylthio fragments of RAFT agents as described above are within the purview of one skilled in the art. Representative schemes for preparing hydrophilic polymers are described below in schemes VI-VIII:

scheme VI

Wherein a is from about 10 to about 2700.

Scheme VII

Wherein x is from about 15 to about 3000 and y is from about 1 to about 250.

Scheme VIII

Wherein x is from about 12 to about 3000 and y is from about 1 to about 250.

Generally, the one or more hydrophilic polymers or copolymers comprising hydrophilic units and thiocarbonylthio fragments of a RAFT agent are present in the monomer mixture in an amount of from about 0.5 wt% to about 20 wt% based on the total weight of the monomer mixture. In one embodiment, the one or more hydrophilic polymers or copolymers comprising hydrophilic units and thiocarbonylthio fragments of a RAFT agent are present in the monomer mixture in an amount of about 0.5 wt.% to about 8.5 wt.%, based on the total weight of the monomer mixture.

The monomer mixture may further comprise one or more hydrophobic monomers. Suitable hydrophobic monomers include ethylenically unsaturated hydrophobic monomers such as (meth) acrylate-containing hydrophobic monomers, N-alkyl (meth) acrylamide-containing hydrophobic monomers, alkyl vinyl carbonate-containing hydrophobic monomers, alkyl vinyl carbamate-containing hydrophobic monomers, fluoroalkyl (meth) acrylate-containing hydrophobic monomers, N-fluoroalkyl (meth) acrylamide-containing hydrophobic monomers, N-fluoroalkyl vinyl carbonate-containing hydrophobic monomers, N-fluoroalkyl vinyl carbamate-containing hydrophobic monomers, silicone (meth) acrylate-containing hydrophobic monomers, (meth) acrylamide-containing hydrophobic monomers, vinyl carbonate-containing hydrophobic monomers, vinyl carbamate-containing hydrophobic monomers, styrene-containing hydrophobic monomers, polyoxypropylene (meth) acrylate-containing hydrophobic monomers, and the like, and mixtures thereof.

In one illustrative embodiment, wherein the one or more hydrophobic monomers are represented by the structure of formula I:

wherein R ¹ is methyl or hydrogen; r ² is-O-or-NH-; r ³ and R ⁴ are independently selected from the group consisting of-CH ₂ -; -a divalent radical of the group consisting of CHOH-and-CHR ⁶ -; r ⁵ and R ⁶ are independently branched C ₃-C₈ alkyl; r ⁷ is hydrogen or-OH; n is an integer of at least 1, and m and p are independently 0 or an integer of at least 1, provided that the sum of m, p and n is 2, 3,4 or 5.

Representative examples of one or more hydrophobic monomers (b) represented by the structure of formula I include, but are not limited to, 4-tert-butyl-2-hydroxycyclohexyl methacrylate (TBE); 4-tert-butyl-2-hydroxycyclopentyl methacrylate; 4-tert-butyl-2-hydroxycyclohexyl methacrylamide (TBA); 6-isopentyl-3-hydroxycyclohexyl methacrylate; 2-isohexyl-5-hydroxycyclopentyl methacrylamide, 4-tert-butylcyclohexyl methacrylate, isobornyl methacrylate, adamantyl methacrylate, n-butyl methacrylate, n-hexyl methacrylate, lauryl methacrylate, benzyl methacrylate, and the like. In one embodiment, the one or more hydrophobic monomers (b) include compounds of formula I wherein R ³ is-CH ₂ -, m is 1 or 2, p is 0, and the sum of m and n is 3 or 4.

The one or more hydrophobic monomers will typically be present in the monomer mixture in an amount of from about 0.5% to about 25% by weight or from about 1% to about 10% by weight, based on the total weight of the monomer mixture.

In another illustrative embodiment, the monomer mixture further includes one or more Ultraviolet (UV) blocking agents. In one embodiment, useful ultraviolet blockers include one or more compounds of the formula:

(2-acrylic acid, 2-methyl, 2- (4-benzoyl-3-hydroxyphenoxy) -1- [ (4-benzoyl-3-hydroxyphenoxy) methyl ester),

The monomer mixture may further contain various additives such as antioxidants, colorants, wetting agents, toughening agents, and the like, as well as other components known in the art, as necessary and within the limits not detrimental to the objects and effects of the present invention.

In one embodiment, suitable humectants can be glycerin, propylene glycol, mono-or disaccharides, polyethylene glycol, ethoxylated glucose, and combinations thereof. In one embodiment, a suitable wetting agent may be a polymer containing carboxylic acid functionality, such as a polymer containing PAA. Specific coating wetting agents include P (vinylpyrrolidone (VP) -co-Acrylic Acid (AA)), P (methyl vinyl ether-alternating-maleic acid), P (acrylic acid-graft-ethylene oxide), P (acrylic acid-co-methacrylic acid), P (acrylamide-co-AA), P (AA-co-maleic acid), P (butadiene-maleic acid) and P (N-vinylpyrrolidone-co-vinyl acetate), polyvinyl alcohol.

The ophthalmic devices (e.g., contact lenses or intraocular lenses) of the illustrative embodiments may be prepared by: the aforementioned monomer mixture is polymerized to form a product, which can then be formed into a suitable shape by, for example, turning, injection molding, compression molding, cutting, and the like. For example, in the production of contact lenses, the initial mixture may be polymerized in a tube to provide a rod-shaped article, which is then cut into buttons. The button can then be turned into a contact lens.

Alternatively, ophthalmic devices (e.g., contact lenses) can be cast directly in a mold (e.g., polypropylene mold) from the mixture, for example, by spin casting and static casting methods. Spin casting methods are disclosed in U.S. Pat. nos. 3,408,429 and 3,660,545, and static casting methods are disclosed in U.S. Pat. nos. 4,113,224, 4,197,266 and 5,271,875. The spin casting method includes loading a mixture to be polymerized into a mold and rotating the mold in a controlled manner while exposing the mixture to a radiation source (e.g., ultraviolet light). The static casting method includes loading a monomer mixture between two mold sections, one mold section being shaped to form a front lens surface and the other mold section being shaped to form a rear lens surface, and curing the mixture while remaining in the mold assembly to form a lens, such as by free radical polymerization of the mixture. Examples of free radical reaction techniques for curing the lens material include thermal radiation, infrared radiation, electron beam radiation, gamma radiation, ultraviolet (UV) radiation, and the like; or a combination of these techniques may be used. U.S. Pat. No. 5,271,875 describes a static cast molding method that allows molding of a finished lens in a mold cavity defined by a posterior mold and an anterior mold. As another method, U.S. patent No. 4,555,732 discloses a process in which an excess monomer mixture is cured by spin casting in a mold to form a shaped article having an anterior lens surface and a relatively large thickness, and then the rear surface of the cured spin-cast article is turned to provide a contact lens having the desired thickness and rear lens surface.

Polymerization may be promoted by exposing the mixture to heat and/or radiation (e.g., ultraviolet light, visible light, or high energy radiation). A polymerization initiator may be included in the mixture to facilitate the polymerization step. Representative examples of the radical thermal polymerization initiator include organic peroxides such as acetyl peroxide, lauroyl peroxide, decanoyl peroxide, stearoyl peroxide, benzoyl peroxide, t-butyl peroxypivalate, peroxydicarbonate, and the like. Representative ultraviolet initiators are those known in the art and include benzoin methyl ether, benzoin ethyl ether, darone 1173. 1164, 2273, 1116, 2959, 3331 (EM Industries) and gorgeous good (R.E.)651 And 184 (Ciba-Geigy), 2' azobis (2-methylpropanenitrile) (VAZO 64), etc. Generally, the initiator will be employed in the monomer mixture at a concentration of from about 0.01% to about 5% by weight of the total mixture.

The polymerization is generally carried out in a reaction medium, for example using a solution or dispersion of a solvent, for example water or an alkanol containing 1 to 4 carbon atoms (for example methanol, ethanol or propan-2-ol). Alternatively, a mixture of any of the above solvents may be used.

In general, the polymerization may be conducted under an inert atmosphere such as nitrogen or argon for about 15 minutes to about 72 hours. If desired, the resulting polymerization product may be dried under vacuum, for example, from about 5 to about 72 hours or left in aqueous solution prior to use.

Polymerization of the mixture will produce a polymer that, when hydrated, preferably forms a hydrogel. When producing hydrogel lenses, the mixture may further include at least one diluent that is eventually replaced with water when the polymerization product hydrates to form a hydrogel. Generally, the water content of the hydrogel is as described above, i.e., at least about 45% by weight or at least about 50% by weight. The amount of diluent should be less than about 50% by weight and in most cases the diluent content will be less than about 30% by weight. However, in certain polymer systems, the practical limit will be determined by the solubility of the various monomers in the diluent. In order to produce an optically clear copolymer, it is important that no phase separation occurs between the comonomer and the diluent, or between the diluent and the final copolymer, which leads to visual opacity.

Furthermore, the maximum amount of diluent that can be used will depend on the amount of diluent that results in swelling of the final polymer. Excessive swelling will or may result in collapse of the copolymer when the diluent is replaced by water upon hydration. Suitable diluents include, but are not limited to, ethylene glycol; glycerol; liquid poly (ethylene glycol); an alcohol; an alcohol/water mixture; ethylene oxide/propylene oxide block copolymers; low molecular weight linear poly (2-hydroxyethyl methacrylate); glycol esters of lactic acid; formamide; a ketone; dialkyl sulfoxides; butyl carbitol; borates of polyols, such as borates of glycerol and the like, and mixtures thereof.

If desired, it may be desirable to remove residual diluent from the lens prior to the edge finishing operation, which may be accomplished by evaporation at or near ambient pressure or under vacuum. High temperatures can be used to shorten the time required to evaporate the diluent. The time, temperature and pressure conditions of the solvent removal step will vary depending on factors such as the volatility of the diluent and the particular monomer component, which can be readily determined by one skilled in the art. The mixture used to produce the hydrogel lenses may further include cross-linking and wetting agents known in the art for making hydrogel materials, if desired.

In the case of intraocular lenses, the monomer mixture to be polymerized may further include monomers for increasing the refractive index of the resulting polymerized product. Examples of such monomers include aromatic (meth) acrylates such as phenyl (meth) acrylate, 2-phenethyl (meth) acrylate, 2-phenoxyethyl methacrylate, and benzyl (meth) acrylate.

The ophthalmic devices (e.g., contact lenses) obtained herein may be subjected to optional processing operations. For example, optional processing steps may include polishing or buffing the lens edge and/or surface. In general, such processing may be performed before or after release of the product from the mold parts, such as by lifting the lens from the mold using vacuum tweezers, dry releasing the lens from the mold, and then transferring the lens to a second set of vacuum tweezers by mechanical tweezers and placing against a rotating surface to smooth the surface or edge. The lens may then be flipped over in order to process the other side of the lens.

The lenses may then be transferred to individual lens packages containing buffered saline solution. The saline solution may be added to the package either before or after transferring the lens. Suitable package designs and materials are known in the art. The plastic packaging is releasably sealed with a film. Suitable sealing films are known in the art and include foils, polymeric films, and mixtures thereof. The sealed package containing the lens is then sterilized to ensure sterility of the product. Suitable sterilization methods and conditions are known in the art and include, for example, autoclaving.

Other steps may be included in the molding and packaging process described above, as will be readily appreciated by those skilled in the art. Such other steps may include, for example, coating the formed lens, surface treating the lens during formation (e.g., via mold transfer), inspecting the lens, discarding defective lenses, cleaning mold halves, reusing mold halves, and the like, as well as combinations thereof.

The following examples are presented to enable one skilled in the art to practice the invention and are merely illustrative. These examples should not be construed as limiting the scope of the invention as defined in the claims.

Various polymerization products were formed as described below and characterized by standard test procedures, such as:

Water%: two sets of six hydrated lenses or membranes were blotted dry on one piece of filter paper to remove excess water and the samples were weighed (wet weight). The sample was then placed in a microwave oven in a jar containing a desiccant for 10 minutes. The sample was then allowed to stand for 30 minutes to equilibrate to room temperature and re-weighed (dry weight). The percentage of water is calculated on the basis of wet and dry weight.

Contact angle: the captured bubble contact angle data was collected on the first 10 angstrom FTA-1000 post shape instrument. All samples were rinsed in HPLC grade water to remove components of the packaging solution from the sample surface prior to analysis. The surface tension of all experimental waters was measured using the pendant drop method prior to collecting the data. For water to be suitable for use, a surface tension value of 70-72 dynes/cm is desirable. All lens samples were placed on a curved sample holder and immersed in a quartz cell filled with HPLC grade water. The advancing and receding capture bubble contact angles for each sample were collected. The advancing contact angle is defined as the angle measured in water as the bubble retracts from the lens surface (water advances across the surface). All captured bubble data was collected using a high-speed digital camera focused on the sample/bubble interface. Just before the contact line moves across the sample/bubble interface, the contact angle is calculated at the digital frame. The receding contact angle is defined as the angle measured in water as a bubble expands across the surface of a sample (water recedes from the surface).

Modulus (g/mm ²) and elongation were measured according to ASTM 1708 using an Instron (model 4502) instrument, in which a film sample was immersed in borate buffered saline; suitable dimensions for the film sample are a gauge length of 22mm and a width of 4.75mm, wherein the sample further has ends forming a dog bone shape to accommodate holding the sample with a clamp of an instron instrument and a thickness of 100±50 microns.

Tensile strength (g/mm ²) was measured according to ASTM test method D1708 a.

Tear strength was measured according to ASTM D-1938 under the same physical conditions as tensile modulus.

Sagittal depth (SAG) was measured on a dell electronic comparator.

According to a typical method, refractive Index (RI) is measured on a hydrated sample using a refractometer.

In examples, the following abbreviations are used.

DMA: n, N-dimethylacrylamide

HEMA: 2-hydroxyethyl methacrylate

NVP: n-vinyl-2-pyrrolidone

AMA: allyl methacrylate

EGDMA: ethylene glycol dimethacrylate

Vazo ^TM 64,64: azobis-isobutyronitrile (AIBN)

Brilliant-good solids 819 (photoinitiator): a compound having the structure:

CIX-4: a compound having the structure:

SA monomer: a compound having the structure:

PDMA-C2-RAFT: a polymer having a number average molecular weight of 79.6kDa and having the following structure:

Where x is 1 and n is 735.

PDMA-C12-RAFT: a polymer having a number average molecular weight of 62.6kDa and having the following structure:

where x is 11 and n is 662.

PDMA-C18-RAFT: a polymer having a number average molecular weight of 65.4kDa and having the following structure:

Where x is 17 and n is 655.

PVP-RAFT: a polymer having a number average molecular weight of 53.1kDa and having the following structure:

Wherein x is 1 and n is 476.

PDMA-co-mPEGMA 400: a polymer having a number average molecular weight of 60kDa and having the following structure:

tetraethylene glycol dimethacrylate (TEGDMA): a compound having the structure:

Trimethylolpropane trimethacrylate (TMPTMA): a compound having the structure:

1, 4-butanediol dimethacrylate (1, 4-DBDDMA): a compound having the structure:

Examples 1 to 5

The monomer mixture was prepared by mixing the following components listed in table 1 below in amounts by weight.

TABLE 1

Formulation of	Example 1	Example 2	Example 3	Example 4	Example 5
						HEMA	57.67	57.67	57.67	57.67	57.67
NVP	27.66	27.66	27.66	27.66	27.66
						EGDMA	0.10	0.22	0.50	0.75	1.00
CIX-4	0.26	0.26	0.26	0.26	0.26
						Glycerol	14.20	14.20	14.20	14.20	14.20
AIBN	0.50	0.50	0.50	0.50	0.50
						PDMA-RAFT-C12	8.58	8.58	8.58	8.58	8.58
SA monomer	2.34	2.34	2.34	2.34	2.34
						Color of	0.01	0.01	0.01	0.01	0.01

						Properties of (C)
Modulus (g/mm ²)	29	32	44	54	65
						Tensile Strength (g/mm ²)	38	45	48	40	49
Elongation percent (%)	223	211	157	98	97
						Moisture content (%)	59.87	59.06	57.41	55.82	55.82
Advancing contact angle	60	67	54	47	46
						Diameter (mm)	14.42	14.36	14.16	14.03	13.92
Sagging (mm)	3.93	3.89	3.84	3.67	3.74

The resulting monomer mixture is cast into a contact lens by introducing the monomer mixture into a polypropylene mold assembly. The mold assembly and monomer mixture was then heat cured for about 3.0 hours to form a contact lens. The resulting contact lens is released from the mold assembly.

Examples 6 to 10

The monomer mixture was prepared by mixing the following components listed in table 2 below in amounts by weight.

TABLE 2

Examples 11 to 15

The monomer mixture was prepared by mixing the following components listed in table 3 below in amounts by weight.

TABLE 3 Table 3

Formulation of	Example 11	Example 12	Example 13	Example 14	Example 15
						HEMA	57.67	57.67	57.67	57.67	57.67
NVP	27.66	27.66	27.66	27.66	27.66
						EGDMA	0.10	0.22	0.50	0.75	1.00
CIX-4	0.26	0.26	0.26	0.26	0.26
						Glycerol	14.20	14.20	14.20	14.20	14.20
AIBN	0.50	0.50	0.50	0.50	0.50
						PDMA-RAFT	8.58	8.58	8.58	8.58	8.58
SA monomer	2.34	2.34	2.34	2.34	2.34
						Color of	0.01	0.01	0.01	0.01	0.01

						Properties of (C)
Modulus (g/mm ²)	26	31	43	58	67
						Tensile Strength (g/mm ²)	65	64	29	62	63
Elongation percent (%)	331	280	88	73	108
						Moisture content (%)	59.93	59.29	57.47	56.25	55.14
Advancing contact angle	46	55	40	37	36
						Diameter (mm)	14.26	14.38	14.19	14.09	13.98
Sagging (mm)	3.91	3.91	3.86	3.80	3.76

Examples 16 to 19

The monomer mixture was prepared by mixing the following components listed in table 4 below in amounts by weight.

TABLE 4 Table 4

Formulation of	Example 16	Example 17	Example 18	Example 19
					HEMA	57.67	57.67	57.67	57.67
NVP	27.66	27.66	27.66	27.66
					EGDMA	0.22	0.50	0.75	1.00
CIX-4	0.26	0.26	0.26	0.26
					Glycerol	14.20	14.20	14.20	14.20
AIBN	0.50	0.50	0.50	0.50
					PVP-RAFT	8.58	8.58	8.58	8.58
SA monomer	2.34	2.34	2.34	2.34
					Color of	0.01	0.01	0.01	0.01

					Properties of (C)
Modulus (g/mm ²)	30	42	51	63
					Tensile Strength (g/mm ²)	43	49	45	50
Elongation percent (%)	234	175	128	107
					Moisture content (%)	57.15	55.88	54.24	53.51
Advancing contact angle	41	47	52	49
					Diameter (mm)	13.74	13.68	13.64	13.51
Sagging (mm)	3.71)	3.63	3.61	3.59

Examples 20 to 24

The monomer mixture was prepared by mixing the following components listed in table 5 below in amounts by weight.

TABLE 5

Examples 25 to 29

The monomer mixture was prepared by mixing the following components listed in table 6 below in amounts by weight.

TABLE 6

Examples 30 to 34

The monomer mixture was prepared by mixing the following components listed in table 7 below in amounts by weight.

TABLE 7

Examples 35 to 40

The monomer mixture was prepared by mixing the following components listed in table 8 below in amounts by weight.

TABLE 8

Examples 41 to 47

The monomer mixture was prepared by mixing the following components listed in table 9 below in amounts by weight.

TABLE 9

Formulation of	Example 41	Example 42	EXAMPLE 43	EXAMPLE 44	Example 46	Example 47
							HEMA	57.67	57.67	57.67	57.67	57.67	57.67
NVP	27.66	27.66	27.66	27.66	27.66	27.66
							EGDMA	0.75	0.75	0.75	0.75	0.75	0.75
CIX-4	0.26	0.26	0.26	0.26	0.26	0.26
							Glycerol	14.20	14.20	14.20	14.20	14.20	14.20
AIBN	0.50	0.50	0.50	0.50	0.50	0.50
							PDMA-co-mPEGMA 400,400	5.00	3.50	2.00	1.00	0.50	8.58
SA monomer	2.34	2.34	2.34	2.34	2.34	2.34
							Color of	0.01	0.01	0.01	0.01	0.01	0.01

							Properties of (C)
Modulus (g/mm ²)	53	56	57	52	60	49
							Tensile Strength (g/mm ²)	29	47	52	37	51	43
Elongation percent (%)	64	99	111	80	106	113
							Moisture content (%)	54.31	53.37	52.24	51.64	51.89	55.73
Advancing contact angle	42	56	63	68	69	39

Examples 48 to 53

The monomer mixture was prepared by mixing the following components listed in table 10 below in amounts by weight.

Table 10

Formulation of	EXAMPLE 48	Example 49	Example 50	Example 51	Example 52	Example 53
							HEMA	57.67	57.67	57.67	57.67	57.67	57.67
NVP	27.66	27.66	27.66	27.66	27.66	27.66
							EGDMA	1.00	1.00	1.00	1.00	1.00	1.00
CIX-4	0.26	0.26	0.26	0.26	0.26	0.26
							Glycerol	14.20	14.20	14.20	14.20	14.20	14.20
AIBN	0.50	0.50	0.50	0.50	0.50	0.50
							PDMA-co-mPEG 400MA	5.00	3.50	2.00	1.00	0.50	8.58
SA monomer	2.34	2.34	2.34	2.34	2.34	2.34
							Color of	0.01	0.01	0.01	0.01	0.01	0.01

							Properties of (C)
Modulus (g/mm ²)	63	53	69	71	74	74
							Tensile Strength (g/mm ²)	46	24	45	53	42	49
Elongation percent (%)	96	75	88	100	74	87
							Moisture content (%)	55.63	54.27	52.93	51.80	51.13	50.73
Advancing contact angle	38	41	39	51	45	43

Examples 54 to 58

The monomer mixture was prepared by mixing the following components listed in table 11 below in amounts by weight.

TABLE 11

Examples 59 to 64

The monomer mixture was prepared by mixing the following components listed in table 12 below in amounts by weight.

Table 12

The resulting monomer mixture is cast into a contact lens by introducing the monomer mixture into a polypropylene mold assembly. The mold assembly and monomer mixture were then blue light cured at 5mW/cm ² for about 25 minutes to form a contact lens. The resulting contact lens is released from the mold assembly. As shown in table 12, when using a blue-light curing monomer mixture, additional EGDMA is required to form the lens.

It should be understood that various modifications may be made to the embodiments disclosed herein. Therefore, the above description should not be construed as limiting, but merely as exemplifications of preferred embodiments. For example, the functions described above and implemented as the best mode of operating the invention are for illustrative purposes only. Other arrangements and methods may be implemented by those skilled in the art without departing from the scope and spirit of the invention. Further, other modifications will occur to those skilled in the art within the scope and spirit of the appended features and advantages.

Claims

1. An ophthalmic device that is a polymerization product of a monomer mixture comprising:

(a) At least 70 weight percent of one or more non-silicone containing hydrophilic monomers, wherein the weight percent is based on the total weight of the monomer mixture;

(b) A crosslinker mixture comprising (i) 0.1-2.0 wt% of one or more first crosslinkers containing at least two ethylenically unsaturated reactive end groups, wherein the at least two ethylenically unsaturated reactive end groups are (meth) acrylate-containing reactive end groups, and (ii) 0.05-2.0 wt% of one or more second crosslinkers containing at least two ethylenically unsaturated reactive end groups, wherein at least one of the ethylenically unsaturated reactive end groups is a non- (meth) acrylate reactive end group, based on the total weight of the monomer mixture; and

(C) One or more hydrophilic polymers or copolymers comprising one or more hydrophilic units and a thiocarbonylthio fragment of a reversible addition fragmentation chain transfer reagent;

Wherein the ophthalmic device has an equilibrium water content of at least 50 wt% and a trapped bubble contact angle of 30 ° to 70 °.

2. The ophthalmic device of claim 1, wherein the one or more non-silicone containing hydrophilic monomers are selected from the group consisting of amides, cyclic lactams, hydroxyl-containing (meth) acrylates, poly (alkylene glycols) functionalized with polymerizable groups, and mixtures thereof.

3. The ophthalmic device of claim 2, wherein the amide is selected from the group consisting of N, N-dimethylacrylamide, and mixtures thereof.

4. The ophthalmic device of claim 2, wherein the cyclic lactam is selected from the group consisting of N-vinyl-2-pyrrolidone, N-vinyl caprolactam, N-vinyl-2-piperidone, and mixtures thereof.

5. The ophthalmic device of claim 1, wherein the one or more non-silicone containing hydrophilic monomers are selected from the group consisting of N, N-dimethylacrylamide, N-dimethylmethacrylamide, N-vinyl-2-pyrrolidone, N-vinylcaprolactam, N-vinyl-2-piperidone, 2-hydroxyethyl methacrylate, N- (2-hydroxyethyl) methacrylamide, glycerol methacrylate, N-methacryloylglycine, (2-hydroxy-3-methacryloylpropyl) -4-methoxyphenyl ether, and mixtures thereof.

6. The ophthalmic device of claim 1, wherein the one or more first crosslinking agents containing at least two ethylenically unsaturated reactive end groups are selected from the group consisting of alkylene glycol-containing di (meth) acrylate crosslinking agents, alkylene glycol-containing tri (meth) acrylate crosslinking agents, alkylene glycol-containing tetra (meth) acrylate crosslinking agents, and mixtures thereof.

7. The ophthalmic device of claim 6, wherein the alkylene glycol di (meth) acrylate crosslinker is ethylene glycol di (meth) acrylate having up to 10 ethylene glycol units.

8. The ophthalmic device of claim 1, wherein the one or more second crosslinking agents containing at least two ethylenically unsaturated reactive end groups are selected from the group consisting of a di (N-vinyl carbamate) -containing crosslinking agent, a di (N-allyl carbamate) -containing crosslinking agent, a di (O-vinyl carbamate) -containing crosslinking agent, a di (O-allyl carbamate) -containing crosslinking agent, a di (O-vinyl carbonate) -containing crosslinking agent, a di (O-allyl carbonate) -containing crosslinking agent, a tri (N-vinyl carbamate) -containing crosslinking agent, a tri (N-allyl carbamate) -containing crosslinking agent, a tri (O-vinyl carbamate) -containing crosslinking agent, a tri (O-allyl carbamate) -containing crosslinking agent, a tri (O-vinyl carbonate) -containing crosslinking agent, a tetra (O-allyl carbonate) -containing crosslinking agent, a tetra (N-allyl carbamate) -containing crosslinking agent, a tetra (O-vinyl carbamate) -containing crosslinking agent, a tetra (O-allyl carbonate) -containing crosslinking agent, a tetra (O-vinyl carbonate) -containing crosslinking agent, and mixtures thereof.

9. The ophthalmic device of claim 1, wherein the one or more second crosslinking agents containing at least two ethylenically unsaturated reactive end groups are selected from the group consisting of diethylene glycol bis (N-vinyl carbamate), diethylene glycol bis (N-allyl carbamate), diethylene glycol bis (O-vinyl carbamate), diethylene glycol bis (O-allyl carbamate), 1, 4-butanediol bis (N-vinyl carbamate), ethylene glycol bis (O-vinyl carbonate), diethylene glycol bis (O-vinyl carbonate), 1, 4-butanediol bis (O-vinyl carbonate), allyl methacrylate, and mixtures thereof.

10. The ophthalmic device of claim 1, wherein the thiocarbonylthio fragment of the hydrophilic polymer or copolymer is a reversible addition fragmentation chain transfer reagent comprising a dithioester group, xanthate group, dithiocarbamate group, or trithiocarbonate group.

11. The ophthalmic device of claim 1, wherein the one or more hydrophilic units of the one or more hydrophilic polymers or copolymers are derived from one or more hydrophilic monomers selected from the group consisting of unsaturated carboxylic acids, acrylamides, cyclic lactams, poly (alkylene oxide) (meth) acrylates, hydroxyl-containing- (meth) acrylates, hydrophilic ethylene carbonate, hydrophilic ethylene carbamate monomers, hydrophilic oxazolone monomers, and mixtures thereof.

12. The ophthalmic device of claim 1, wherein the one or more hydrophilic polymers or copolymers have a number average molecular weight of at least 30 kDa.

13. The ophthalmic device of claim 1, wherein the one or more hydrophilic polymers or copolymers have a number average molecular weight of at least 45 kDa.

14. The ophthalmic device of claim 1, wherein the one or more hydrophilic polymers or copolymers have a number average molecular weight of at least 60 kDa.

15. The ophthalmic device of claim 1, wherein the one or more hydrophilic polymers or copolymers further comprise units derived from an ethylenically unsaturated polymerizable alkoxylated polymer selected from the group consisting of: PEG-200 methacrylate, PEG-400 methacrylate, PEG-600 methacrylate, PEG-1000 methacrylate, and mixtures thereof.

16. The ophthalmic device of claim 1, wherein the monomer mixture further comprises an ultraviolet blocker.

17. The ophthalmic device of claim 1, wherein the ophthalmic device is a contact lens.

18. The ophthalmic device of claim 1, wherein the ophthalmic device is a hydrogel.

19. The ophthalmic device of claim 1, wherein the monomer mixture is free of silicone-containing monomers.

20. A method of making an ophthalmic device, comprising:

(a) Providing a monomer mixture comprising (i) at least 70 weight percent of one or more non-silicone containing hydrophilic monomers, based on the total weight of the monomer mixture; (ii) A crosslinker mixture comprising, based on the total weight of the monomer mixture, (1) 0.1-2 weight percent of one or more first crosslinkers containing at least two ethylenically unsaturated reactive end groups, wherein the at least two ethylenically unsaturated reactive end groups are (meth) acrylate-containing reactive end groups, and (2) 0.05-2 weight percent of one or more second crosslinkers containing at least two ethylenically unsaturated reactive end groups, wherein at least one of the reactive end groups is a non- (meth) acrylate reactive end group; and (iii) one or more hydrophilic polymers or copolymers comprising one or more hydrophilic units and a thiocarbonylthio fragment of a reversible addition fragmentation chain transfer reagent;

(b) Subjecting the monomer mixture to polymerization conditions to provide a polymerization apparatus; and

(C) Hydrating the polymerization device;

21. The method of claim 20, wherein the one or more non-silicone containing hydrophilic monomers are selected from the group consisting of amides, cyclic lactams, hydroxyl-containing (meth) acrylates, poly (alkylene glycols) functionalized with polymerizable groups, and mixtures thereof.

22. The method of claim 20, wherein the one or more first crosslinkers containing at least two ethylenically unsaturated reactive end groups are selected from the group consisting of alkylene glycol-containing di (meth) acrylate crosslinkers, alkylene glycol-containing tri (meth) acrylate crosslinkers, alkylene glycol-containing tetra (meth) acrylate crosslinkers, and mixtures thereof.

23. The method of claim 20, wherein the one or more second cross-linking agents containing at least two ethylenically unsaturated reactive end groups are selected from the group consisting of a di (N-vinyl carbamate) -containing cross-linking agent, a di (N-allyl carbamate) -containing cross-linking agent, a di (O-vinyl carbamate) -containing cross-linking agent, a di (O-allyl carbamate) -containing cross-linking agent, a di (O-vinyl carbonate) -containing cross-linking agent, a di (O-allyl carbonate) -containing cross-linking agent, a tri (N-vinyl carbamate) -containing cross-linking agent, a tri (N-allyl carbamate) -containing cross-linking agent, a tri (O-vinyl carbonate) -containing cross-linking agent, a tri (O-allyl carbonate) -containing cross-linking agent, a tetra (N-vinyl carbamate) -containing cross-linking agent, a tetra (N-allyl carbamate) -containing cross-linking agent, a tetra (O-allyl carbonate) -containing cross-linking agent, a tetra (O-vinyl carbonate-containing cross-linking agent, a tetra (O-allyl carbonate) -containing cross-linking agent, and mixtures thereof.

24. The method of claim 20, wherein the thiocarbonylthio fragment of the hydrophilic polymer or copolymer is a reversible addition fragmentation chain transfer reagent comprising a dithioester group, xanthate group, dithiocarbamate group, or trithiocarbonate group.

25. The method of claim 20, wherein the monomer mixture further comprises an ultraviolet blocker.

26. The method of claim 20, wherein the ophthalmic device is a contact lens or a hydrogel.

27. The method of claim 22, wherein the monomer mixture is free of silicone-containing monomers.