Ophthalmic Devices

Abstract

The ophthalmic device is the polymerization product of a monomer mixture that includes (a) one or more cationic initiators that include one or more polymerizable groups, and (b) one or more alkyl-substituted oxazolines.

Description

[Technical field]

[0001] Claiming priority This application claims priority to U.S. Provisional Patent Application No. 63 / 313,413, entitled "Ophthalmic Device," filed February 24, 2022, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] Ophthalmic devices such as contact lenses are made from a variety of polymeric materials, including rigid gas permeable materials, soft elastomeric materials, and soft hydrogel materials. Many of the contact lenses sold today are made from soft hydrogel materials. Hydrogels are crosslinked polymer systems that absorb and retain water, typically 10 to 80 percent by weight. Hydrogel lenses are commonly prepared by polymerizing a lens-forming monomer mixture. In the case of silicone hydrogel lenses, silicone-containing monomers are copolymerized with hydrophilic monomers. Summary of the Invention

[0003] According to an exemplary embodiment, an ophthalmic device that is a polymerization product of a monomer mixture comprising: (a) one or more cationic initiators containing one or more polymerizable groups; (b) one or more alkyl-substituted oxazolines.

[0004] According to another exemplary embodiment, a method for making an ophthalmic device includes: (a) Below, (i) one or more cationic initiators containing one or more polymerizable groups, and (ii) one or more alkyl-substituted oxazolines; providing an ophthalmic device-forming monomer mixture comprising: (b) subjecting the ophthalmic device-forming monomer mixture to polymerization conditions to provide a polymerized ophthalmic device; (c) hydrating the polymerized ophthalmic device. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0005] Various exemplary embodiments described herein are directed to ophthalmic devices. In the field of ophthalmic devices, various physical and chemical properties, such as oxygen permeability, wettability, material strength, and stability, are just some of the factors that must be carefully balanced to provide a usable ophthalmic device, such as a contact lens. For example, oxygen permeability is an important feature for certain contact lens materials, since the cornea receives its oxygen supply from contact with the atmosphere. Wettability is also important in that if the lens is not sufficiently wetted, it will not remain lubricated and therefore will not be comfortable to wear on the eye. Therefore, an optimal contact lens will have at least both excellent oxygen permeability and excellent tear wettability.

[0006] Those skilled in the art have long recognized the need to modify the surface of contact lenses to make them compatible with the eye. It is known that increasing the hydrophilicity of the lens surface improves the wettability of contact lenses. This is associated with increased wearing comfort of contact lenses. Additionally, the lens surface can affect the susceptibility of the lens to deposition, in particular the deposition of proteins and lipids resulting from tear fluid during lens wear. Accumulated deposits can cause eye discomfort or even irritation. In the case of extended wear lenses (i.e. lenses that are used without removing the lens every day before sleep), the surface is particularly important, as extended wear lenses must be designed for high standards of comfort and biocompatibility over time.

[0007] The ophthalmic devices described herein advantageously provide increased lubricity, anti-fouling properties, and water content, thus providing improved comfort. The ophthalmic devices described herein are intended to be in direct contact with body tissues or fluids. As used herein, the term "ophthalmic device" refers to a device that resides in and on the eye. These lenses can provide optical correction, wound treatment, drug delivery, diagnostic functions, or cosmetic enhancement or effects, or a combination of these properties. Useful ophthalmic devices include, but are not limited to, ophthalmic lenses, such as soft contact lenses, e.g., soft hydrogel soft lenses, soft non-hydrogel soft lenses, hard contact lenses, e.g., hard gas-permeable hard lens materials, intraocular lenses, overlay lenses, intraocular inserts, optical inserts, etc. As will be understood by those skilled in the art, a lens is considered to be "soft" if it can fold back on itself without breaking.

[0008] As used herein, the term "(meth)" refers to an optional methyl substituent. Thus, for example, a term such as "(meth)acrylate" refers to either methacrylate or acrylate, and "(meth)acrylamide" refers to either methacrylamide or acrylamide.

[0009] In an exemplary embodiment, the ophthalmic devices described herein will have an equilibrium water content of at least about 20 percent by weight. In another exemplary embodiment, the ophthalmic devices described herein will have an equilibrium water content of at least about 30 percent by weight. In another exemplary embodiment, the ophthalmic devices described herein will have an equilibrium water content of about 20 percent to about 90 percent by weight. In another exemplary embodiment, the ophthalmic devices described herein will have an equilibrium water content of about 50 percent to about 90 percent by weight.

[0010] In a non-limiting exemplary embodiment, the ophthalmic devices described herein are the polymerization product of a monomer mixture comprising: (a) one or more cationic initiators comprising one or more polymerizable groups; and (b) one or more alkyl-substituted oxazolines.

[0011] In an exemplary embodiment, cationic initiators comprising one or more polymerizable groups for use herein include, for example, sulfonate cationic initiators comprising one or more polymerizable groups. For example, suitable sulfonate cationic initiators include substituted or unsubstituted hydrocarbon radical-containing sulfonate cationic initiators comprising one or more polymerizable groups, such as substituted or unsubstituted alkyl-containing and aryl-containing sulfonate cationic initiators comprising one or more polymerizable groups, fluorinated substituted or unsubstituted alkyl-containing and aryl-containing sulfonate cationic initiators comprising one or more polymerizable groups, and the like. Representative examples of such sulfonate cationic initiators include tosylates, nosylates, mesylates, triflates, and the like, each of which comprises one or more polymerizable groups. In a non-limiting exemplary embodiment, suitable one or more polymerizable groups include, for example, (meth)acrylate end groups, vinyl end groups, acrylamide end groups, and the like.

[0012] In an exemplary embodiment, the polymerizable group is a methacrylate-containing reactive end group. A suitable methacrylate-containing reactive end group has the structure [ka] (In the formula, R * is a linking group or a bond) Suitable linking groups include, for example, heteroatoms such as O, independently linear or branched, substituted or unsubstituted C1-C6 alkyl groups, substituted or unsubstituted C3-C6 alkyl groups, and the like. 12 Cycloalkyl groups, substituted or unsubstituted C4-C 12 Cycloalkyl groups, substituted or unsubstituted C3-C 12 Cycloalkenyl groups, substituted or unsubstituted C6-C 12Aryl groups, substituted or unsubstituted C7-C 12 Included are any divalent hydrocarbon radicals or moieties, such as arylalkyl groups, and substituted or unsubstituted ether-containing groups.

[0013] Generally, one or more cationic initiators including one or more polymerizable groups can be obtained by reacting a cationic initiator precursor monomer with a monomer having a first reactive functional group for reacting with the cationic initiator precursor and a second reactive functional group that is one or more polymerizable groups. For example, in an exemplary embodiment, suitable cationic initiator precursor monomers include, for example, monomers of the formula R-SO2-X, where R is independently a linear or branched, substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C3-C6 alkyl group, a substituted or unsubstituted C4-C6 alkyl group, a substituted or unsubstituted C5-C6 alkyl group, a substituted or unsubstituted C6-C7 alkyl group, a substituted or unsubstituted C7-C8 alkyl group, a substituted or unsubstituted C8-C9 alkyl group, a substituted or unsubstituted C9-C10 alkyl group, a substituted or unsubstituted C10-C12 ... 12 Cycloalkyl groups, substituted or unsubstituted C4-C 12 Cycloalkyl groups, substituted or unsubstituted C6-C 12 Aryl groups, and substituted or unsubstituted C7-C 12 and X is a hydrocarbon radical or moiety such as an arylalkyl group, and X is a halogen such as chlorine, fluorine, bromine, etc. In an exemplary embodiment, suitable monomers having a first reactive functional group for reaction with a cationic initiator precursor and a second reactive functional group that is one or more polymerizable groups include, for example, hydroxyl-containing (meth)acrylates, such as 2-hydroxyethyl methacrylate.

[0014] In an exemplary embodiment, the reaction is carried out at a temperature ranging from about -20°C to about 100°C for a period ranging from about 30 minutes to about 16 hours. In an exemplary embodiment, the cationic initiator precursor monomer is added to the reaction mixture in an amount ranging from about 0.5 to about 50% by weight, based on the total weight of the mixture. In an exemplary embodiment, a monomer having a first reactive functional group for reacting with the cationic initiator precursor monomer and a second reactive functional group that is one or more polymerizable groups is added to the reaction mixture in an amount ranging from about 0.5 to about 80% by weight, based on the total weight of the mixture.

[0015] In one embodiment, a representative synthetic scheme for obtaining a cationic initiator containing one or more polymerizable groups is shown below. [ka]

[0016] In an exemplary embodiment, one or more cationic initiators comprising one or more polymerizable groups are reacted with an alkyl-substituted oxazoline in a cationic ring-opening polymerization of the alkyl-substituted oxazoline to provide a brush polymer network comprising poly(2-alkyloxazoline) repeat units in the polymer backbone. Suitable alkyl-substituted oxazolines for use herein have the formula: [ka] wherein R is an alkyl group of 1 to 12 carbon atoms. In a non-limiting exemplary embodiment, the 2-alkyl substituted oxazoline for use herein is 2-isopropenyl-2-oxazoline.

[0017] In an exemplary embodiment, the poly(2-alkyloxazoline) repeat unit is represented as follows: [ka] wherein R is an alkyl group of 1 to 12 carbon atoms. In an exemplary embodiment, the brush polymer network comprises about 3 to about 150 repeat units of poly(2-alkyloxazoline) in the polymer backbone. In another exemplary embodiment, the brush polymer network comprises about 10 to about 100 repeat units of poly(2-alkyloxazoline) in the polymer backbone. The brush polymer network can be formed through a combination of different mechanisms. For example, one mechanism involves grafting of polyoxazoline from an incorporated cationic initiator in the polymer chain. In another example, a mechanism involves grafting through a polyoxazoline formed from an unincorporated cationic initiator.

[0018] Generally, a "polymer brush" contains a polymer chain, one end of which is directly or indirectly tethered to a surface and another end of which extends freely from the surface, somewhat similar to the bristles of a brush. The brush polymer network described herein has one or more repeat units of a poly(2-alkyloxazoline) repeat unit that is bonded to one or more polymerizable groups of a cationic initiator and forms a hydrophilic surface of an ophthalmic device. As used herein, the terms "bonded," "bonding," or terms of similar import refer to various chemical interactions, such as electrostatic, ionic, complexation, hydrogen bonding, or other interactions between one or more cationic initiators containing one or more polymerizable groups and alkyl-substituted oxazolines.

[0019] In an exemplary embodiment, the monomer mixture can contain from about 0.1% to about 30% by weight of one or more cationic initiators, based on the total weight of the monomer mixture, and from about 10% to about 80% by weight of one or more alkyl-substituted oxazolines, based on the total weight of the monomer mixture. In an exemplary embodiment, the monomer mixture can contain from about 0.1% to about 10% by weight of one or more cationic initiators, based on the total weight of the monomer mixture, and from about 20% to about 50% by weight of one or more alkyl-substituted oxazolines, based on the total weight of the monomer mixture.

[0020] In a non-limiting exemplary embodiment, the monomer mixture described herein may further contain one or more crosslinkers. Suitable crosslinkers include, for example, crosslinkers having a number average molecular weight of about 100 to about 20,000 Da, as determined, for example, by intrinsic viscosity measurement. In a non-limiting exemplary embodiment, suitable crosslinkers include crosslinkers containing at least two ethylenically unsaturated reactive end groups. In one exemplary embodiment, suitable crosslinkers containing at least two ethylenically unsaturated reactive end groups include, for example, one or more alkane polyol di(meth)acrylate-containing crosslinkers, such as one or more alkylene glycol di(meth)acrylate crosslinkers. Representative examples of one or more alkylene glycol di(meth)acrylate crosslinkers include tetraethylene glycol di(meth)acrylate, ethylene glycol di(meth)acrylate, butylene glycol di(meth)acrylate, and the like.

[0021] In one exemplary embodiment, suitable crosslinkers containing at least two ethylenically unsaturated reactive end groups include one or more end-functionalized poloxamers. In an exemplary embodiment, the one or more end-functionalized poloxamers include one or more poloxamer di(meth)acrylates. Representative examples of suitable poloxamers are end-functionalized poloxamer block copolymers. One particular class of poloxamer block copolymers are those available under the trademark Pluronic (BASF Wyandotte Corp., Wyandotte, Mich.). Poloxamers include Pluronics and reverse Pluronics. Pluronics are generally represented by the formula I HO(C2H4O) a (C3H6O) b (C2H4O) a H (I) (wherein a is independently at least 1 and b is at least 1). A series of ABA block copolymers consisting of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) blocks represented by the formula:

[0022] Reverse Pluronics are generally represented by the formula II HO(C3H6O) b (C2H4O) a (C3H6O) b H (II) (wherein a is at least 1 and b is independently at least 1). The series of BAB block copolymers are composed of poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) blocks represented by the formula: The poly(ethylene oxide) (PEO) blocks are hydrophilic in nature, whereas the poly(propylene oxide) (PPO) blocks are hydrophobic in nature. Each series of poloxamers has a different ratio of PEO to PPO that ultimately determines the hydrophilic-lipophilic balance (HLB) of the material, i.e., the different HLB values ​​are based on different values ​​of a and b, where a represents the number of hydrophilic poly(ethylene oxide) units (PEO) present in the molecule, and b represents the number of hydrophobic poly(propylene oxide) units (PPO) present in the molecule. In one embodiment, the poloxamers will have an HLB in the range of about 5 to about 24. In another embodiment, the poloxamers will have an HLB in the range of about 1 to about 5.

[0023] Poloxamers and reverse poloxamers have terminal hydroxyl groups that are end-functionalized to provide crosslinkers containing at least two ethylenically unsaturated reactive end groups, such as poloxamer di(meth)acrylate. One example of an end-functionalized poloxamer is poloxamer dimethacrylate (e.g., Pluronic® F127 dimethacrylate) disclosed in U.S. Patent Application Publication No. 2003 / 0044468 and U.S. Patent No. 9,309,357, the contents of which are incorporated herein by reference, as discussed herein. Other examples include glycidyl-terminated copolymers of polyethylene glycol and polypropylene glycol disclosed in U.S. Patent No. 6,517,933, the contents of which are incorporated herein by reference.

[0024] Poloxamers are functionalized to provide desired reactivity at the ends of the molecule. The functionality can vary and is determined based on the intended use of the functionalized PEO- and PPO-containing block copolymers. That is, the PEO- and PPO-containing block copolymers are reacted to provide terminal functionality that is complementary to the intended device-forming monomer mixture. As used herein, the term block copolymer is understood to mean a poloxamer with two or more blocks in the polymer backbone(s).

[0025] In another embodiment, suitable crosslinkers include, for example, ethylenically unsaturated polymerizable alkoxylated polymers. In an exemplary embodiment, the ethylenically unsaturated polymerizable alkoxylated polymer has, for example, a number average molecular weight of up to about 1000, for example, from about 200 to about 1000. Suitable ethylenically unsaturated polymerizable alkoxylated polymers include, for example, polymerizable polyethylene glycols having a molecular weight of up to about 1000, for example, those having CTFA names such as PEG-200, PEG-400, PEG-600, PEG-1000, and mixtures thereof. Representative examples include PEG-200 dimethacrylate, PEG-400 dimethacrylate, PEG-600 dimethacrylate, PEG-1000 dimethacrylate, and the like, and mixtures thereof.

[0026] In an exemplary embodiment, the monomer mix can contain from about 0.5% to about 50% by weight of one or more crosslinking agents, based on the total weight of the monomer mix. In an exemplary embodiment, the monomer mix can contain from about 0.5% to about 30% by weight of one or more crosslinking agents, based on the total weight of the monomer mix.

[0027] In a non-limiting exemplary embodiment, the monomer mixture described herein may further contain one or more hydrophilic monomers. Suitable hydrophilic monomers include, for example, amides, vinyl lactams, poly(alkyleneoxy)(meth)acrylates, hydrophilic vinyl carbonates, hydrophilic vinyl carbamates, hydrophilic oxazolones, and poly(alkene glycols) functionalized with polymerizable groups, and mixtures thereof. Representative examples of amides include alkylacrylamides in which the alkyl group has 1 to 6 carbon atoms. Suitable alkylacrylamides include, for example, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N,N-diethylacrylamide, N,N-diethylmethacrylamide, N,N-diisopropylacrylamide, N,N-diisopropylmethacrylamide, and mixtures thereof. Representative examples of vinyl lactams include cyclic lactams such as N-vinyl-2-pyrrolidone, N-vinylcaprolactam, N-vinyl-2-piperidone, and mixtures thereof. Representative examples of functionalized poly(alkene glycols) include poly(diethylene glycols) of various chain lengths containing monomethacrylate or dimethacrylate end caps. In one embodiment, the poly(alkene glycol) polymer contains at least two alkene glycol monomer units. Further examples are the hydrophilic vinyl carbonate or vinyl carbamate monomers disclosed in U.S. Pat. No. 5,070,215 and the hydrophilic oxazolone monomers 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 aforementioned hydrophilic monomers can also be used in the monomer mixtures herein.

[0028] As those skilled in the art will readily appreciate, the growth of polyoxazoline repeat units is based at least in part on the formation of cations (i.e., oxazolinium ions) and the reaction between cationic and oxazoline monomers. Thus, living cations are necessary throughout the polymerization process. Cations are known to typically react with nucleophiles (e.g., -OH, -NH2, -COOH, water, etc.). Therefore, it is desirable to select hydrophilic monomers that do not contain one or more of the aforementioned nucleophiles. Thus, in an exemplary embodiment, the one or more hydrophilic monomers include one or more of the above acrylamides and cyclic lactams that do not have their nucleophile moieties, and thus are considered equivalent to cationic polymerization.

[0029] In an exemplary embodiment, the monomer mixture can contain from about 5% to about 90% by weight of one or more hydrophilic monomers, based on the total weight of the monomer mixture. In an exemplary embodiment, the monomer mixture can contain from about 10% to about 80% by weight of one or more hydrophilic monomers, based on the total weight of the monomer mixture.

[0030] In a non-limiting exemplary embodiment, the monomer mixture described herein may further contain one or more protected hydrophilic monomers. Suitable hydrophilic monomers that need to be protected for use in the monomer mixture described herein include unsaturated carboxylic acids, (meth)acrylic-substituted alcohols, (meth)acrylic-substituted amino compounds, and the like. Representative examples of unsaturated carboxylic acids include methacrylic acid, acrylic acid, and the like, and mixtures thereof. Representative examples of (meth)acrylic-substituted alcohols include 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, glyceryl methacrylate, and the like, and mixtures thereof. Representative examples of (meth)acrylic-substituted amino compounds include (2-amino)ethyl methacrylate, and the like.

[0031] Suitable protecting groups include, for example, t-butyloxycarbonyl (also known as BOC), vinyloxycarbonyl, trimethylsilyl, triethylsilyl, methoxymethyl, tetrahydropyranyl, tetrahydrofuranyl, t-butyl (for carboxylic acid hydrophilic monomers), and toluenesulfonyl (for carboxylic acid hydrophilic monomers).

[0032] Representative examples of protected hydrophilic monomers for use herein are shown below. [ka]

[0033] The protected hydrophilic monomers are commercially available from sources such as, for example, Sigma-Aldrich, BOC Sciences, and TCI AMERICA, or can be prepared by methods within the purview of one skilled in the art. Representative examples of various synthetic routes for making the aforementioned protected hydrophilic monomers are as follows: [ka] [ka]

[0034] In an exemplary embodiment, the monomer mixture can contain from about 0% to about 80% by weight of one or more protected hydrophilic monomers, based on the total weight of the monomer mixture. In an exemplary embodiment, the monomer mixture can contain from about 0% to about 60% by weight of one or more protected hydrophilic monomers, based on the total weight of the monomer mixture. In an exemplary embodiment, the monomer mixture can contain from about 0.1% to about 80% by weight of one or more protected hydrophilic monomers, based on the total weight of the monomer mixture. In an exemplary embodiment, the monomer mixture can contain from about 0.1% to about 60% by weight of one or more protected hydrophilic monomers, based on the total weight of the monomer mixture.

[0035] In another exemplary embodiment, the monomer mixture further comprises one or more ultraviolet (UV) blocking agents. In one exemplary embodiment, suitable UV blocking agents include, for example, one or more compounds of the following formula: [ka] (2-propenoic acid, 2-methyl, 2-(4-benzoyl 3-hydroxyphenoxy)-1-[(4-benzoyl 3-hydroxyphenoxy)methyl ester), [ka] These compounds are merely exemplary and are not intended to be limiting. Any known or later developed UV blocking agent is contemplated for use herein.

[0036] Although not required, the monomer mixtures described herein may optionally have one or more toughening agents added prior to polymerization, preferably in an amount less than about 80 weight percent, such as from about 20 to about 60 weight percent. Non-limiting examples of suitable toughening agents are described in U.S. Patent Nos. 4,327,203, 4,355,147, and 5,270,418, each of which is incorporated herein by reference in its entirety. Specific examples of such toughening agents include, but are not intended to be limiting, cycloalkyl acrylates and methacrylates, such as tert-butyl cyclohexyl methacrylate and isopropyl cyclopentyl acrylate.

[0037] The monomer mixture to be polymerized may further contain various additives such as antioxidants, colorants, UV absorbers, lubricants, internal wetting agents, reinforcing agents, and other components well known in the art, if necessary, within the limits not impairing the purpose and effect of the exemplary embodiments described herein.

[0038] Ophthalmic devices described herein, e.g., contact lenses or intraocular lenses, can be prepared by polymerizing the monomer mixture described above to form a product that can then be formed into the appropriate shape, e.g., by lathing, injection molding, compression molding, cutting, etc. For example, in manufacturing contact lenses, the initial mixture may be polymerized in a tube to provide rod-like articles that are then cut into buttons. The buttons may then be lathed into contact lenses.

[0039] Polymerization may be promoted by exposing a monomer mixture of one or more cationic initiators containing one or more polymerizable groups and alkyl-substituted oxazolines, optionally together with one or more crosslinkers and / or one or more hydrophilic monomers and / or protected hydrophilic monomers, to heat and / or radiation, such as ultraviolet light, visible light, or high-energy radiation. A polymerization initiator may be included in the mixture to promote the polymerization step. Representative examples of free radical thermal polymerization initiators include organic peroxides, such as acetyl peroxide, lauroyl peroxide, decanoyl peroxide, stearoyl peroxide, benzoyl peroxide, tertiary butyl peroxypivalate, peroxydicarbonates, and the like, and azo compounds, such as 2,2'-azobisisobutyronitrile (AIBN), 1,1'-azobis(cyclohexanecarbonitrile), 4,4'-azobis(4-cyanovaleric acid), and the like. Representative UV initiators are known in the art and include benzoin methyl ether, benzoin ethyl ether, Darocure® 1173, 1164, 2273, 1116, 2959, 3331 (EM Industries), and Irgacure® 651 and 184 (Ciba-Geigy), 2,2' azobis(2-methylpropionitrile) (VAZO 64), etc. Generally, initiators will be used in the monomer mixture at a concentration of about 0.01 to about 5 weight percent of the total mixture.

[0040] The polymerization is generally carried out in a reaction medium such as a solvent or dispersion using a solvent such as water or an alkanol containing 1 to 4 carbon atoms such as methanol, ethanol, or propan-2-ol. Alternatively, mixtures of any of the above solvents may be used.

[0041] Generally, the polymerization can be carried out under an inert atmosphere of, for example, nitrogen or argon, for about 15 minutes to about 72 hours. If desired, the resulting polymerization product can be dried under vacuum, for example, for about 5 to about 72 hours, or left in an aqueous solution before use.

[0042] In an exemplary embodiment, an exemplary synthetic scheme using duel free radical and cationic polymerization processes to obtain the polymerization products described herein is shown below. [ka] Here, a is about 10 to about 100, b is 1 to about 250, c is 0 to about 100, x is 1 to 100, y is 1 to about 100, z is 0 to about 500, R1 is -H or -CH3, and R2 is C1 to C6.

[0043] In another exemplary embodiment, an exemplary synthetic scheme using duel free radical and cationic polymerization processes to obtain the polymerization products described herein is shown below. [ka] Here, a is about 10 to about 100, b is about 1 to about 250, c is 0 to about 150, x is about 1 to about 100, y is about 1 to about 100, z is 0 to about 50, R1 is -H or -CH3, and R2 is C1 to C6.

[0044] Ophthalmic devices such as contact lenses may be poured directly from the mixture into a mold, e.g., a polypropylene mold, by, for example, spin casting and static casting. Spin casting is disclosed in U.S. Pat. Nos. 3,408,429 and 3,660,545, and static casting is disclosed in U.S. Pat. Nos. 4,113,224, 4,197,266, and 5,271,875. Spin casting involves filling a mold with the mixture to be polymerized and rotating the mold in a controlled manner while exposing the mixture to a radiation source, such as UV light. Static casting involves filling the mixture between two mold parts, one mold part shaped to form the anterior surface of the lens and the other mold part shaped to form the posterior surface of the lens, and curing the mixture while held in the mold assembly to form a lens, e.g., by free radical polymerization of the mixture as discussed above. No. 5,271,875 describes a static casting method that allows for the molding of a finished lens in a mold cavity defined by a posterior mold and an anterior mold.As an additional method, U.S. Pat. No. 4,555,732 discloses a process in which an excess of a monomer mixture is cured by spin casting in a mold to form a molded article having an anterior lens surface and a relatively large thickness, and the posterior surface of the cured spin cast article is then lathed to provide a contact lens having a desired thickness and posterior lens surface.

[0045] Polymerization of the mixture results in a polymer that, when hydrated, preferably forms a hydrogel. When producing hydrogel lenses, the mixture may further include at least one diluent that is ultimately replaced by water when the polymerization product is hydrated to form a hydrogel. Typically, the water content of the hydrogel is greater than about 5 weight percent, more typically about 10 to about 80 weight percent. The amount of diluent used should be less than about 50 weight percent, and in most cases the diluent content is less than about 30 weight percent. However, for a particular polymer system, the practical limit will be determined by the solubility of the various monomers in the diluent. 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 would result in visual opacity.

[0046] Additionally, the maximum amount of diluent that can be used will be determined by the amount of swelling that the diluent causes to the final polymer. Excessive swelling can cause or disintegrate the copolymer when the diluent is replaced by water upon hydration. Suitable diluents include, but are not limited to, ethylene glycol, glycerin, liquid poly(ethylene glycol), alcohol, alcohol / water mixtures, ethylene oxide / propylene oxide block copolymers, low molecular weight linear poly(2-hydroxyethyl methacrylate), glycol esters of lactic acid, formamides, ketones, dialkyl sulfoxides, butyl carbitol, and the like, and mixtures thereof.

[0047] It may be desirable to remove residual diluent from the lens, if necessary, prior to the edge finishing operation, which can be accomplished by evaporation at or near ambient pressure, or under vacuum. High temperatures can be used to reduce the time required to evaporate the diluent. The time, temperature, and pressure conditions for the solvent removal step will vary depending on factors such as the volatility of the diluent and the particular monomeric components, as can be readily determined by one of ordinary skill in the art. If desired, the mixture used to make the hydrogel lenses may further include crosslinkers and wetting agents known in the prior art for making hydrogel materials.

[0048] In the case of intraocular lenses, the monomer mixture to be polymerized may further include a monomer to increase the refractive index of the resulting copolymer. Examples of such monomers are aromatic (meth)acrylates, such as phenyl (meth)acrylate, 2-phenylethyl (meth)acrylate, 2-phenoxyethyl methacrylate, and benzyl (meth)acrylate.

[0049] The ophthalmic devices, such as contact lenses, obtained herein may be subjected to optional machining operations. For example, other optional machining steps may include buffing or polishing the lens edges and / or surfaces. Generally, such machining processes may be performed before or after the product is released from the mold parts, for example, the lens is dry demolded from the mold by lifting the lens from the mold with vacuum tweezers, after which the lens is transferred by mechanical tweezers to a second set of vacuum tweezers and placed against a rotating surface to smooth the surface or edges. The lens may then be flipped over to machine the other side of the lens.

[0050] The lenses may then be transferred to individual lens packages containing a buffered saline solution. Saline may be added to the package either before or after transfer of the lenses. Suitable package designs and materials are known in the art. The plastic package is peelably 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 lenses is then sterilized to ensure a sterile product. Suitable sterilization means and conditions are known in the art and include, for example, autoclaving.

[0051] As one of ordinary skill in the art would readily appreciate, other steps can be included in the above-described molding and packaging process, including, for example, coating the formed lenses, surface treating the lenses during formation (e.g., via mold transfer), inspecting the lenses, discarding defective lenses, cleaning mold halves, and reusing mold halves, as well as combinations thereof.

[0052] The following examples are provided to enable one of ordinary skill in the art to practice the invention and are merely illustrative and should not be read as limiting the scope of the invention as defined by the claims.

[0053] In the examples, the following abbreviations are used:

[0054] DMA: N,N-dimethylacetamide.

[0055] HEMA: 2-hydroxyethyl methacrylate.

[0056] AIBN: 2,2'-azobisisobutyronitrile.

[0057] Dimethacrylate-PEG: A compound with a number average molecular weight of 550 Da as determined by intrinsic viscosity measurements.

[0058] SA Monomer: 2-[3-(2H-benzotriazol-2-yl)-4-hydroxyphenyl]ethyl methacrylate used as a UV class I blocker.

[0059] As discussed below, various polymerization products were formed and characterized by standard test procedures as follows.

[0060] Moisture content: Two sets of six hydrated lenses or films are blotted dry on a piece of filter paper to remove excess water and the samples are weighed (wet weight). The samples are then placed in a jar containing desiccant and heated in a microwave oven for 10 minutes. The samples are then allowed to stand for 30 minutes to equilibrate to room temperature and reweighed (dry weight). The moisture content is calculated from the wet and dry weights.

[0061] Contact angle: Captive bubble contact angle data was collected on a First Ten Angstroms FTA-1000 prop Shape Instrument. All samples were rinsed in HPLC grade water prior to analysis to remove components of the packaging solution from the sample surface. Prior to data collection, the surface tension of the water used for all experiments was measured using the pendant drop method. Surface tension values ​​of 70-72 dynes / cm were expected for the water to be deemed suitable for use. All lens samples were placed on a curved sample holder and submerged in a quartz cell filled with HPLC grade water. Advancing and receding captive bubble contact angles were collected for each specimen. The advancing contact angle is defined as the angle measured in water as the bubble is receding from the lens surface (water is advancing across the surface). All captive bubble data was collected using a high speed digital camera focused on the sample / bubble interface. Contact angles were calculated in digital frames just prior to the contact line movement across the sample / bubble interface. The receding contact angle is defined as the angle measured in water when an air bubble is swelling across the sample surface (the water is receding from the surface).

[0062] The film samples were immersed in borate buffered saline and the elastic modulus (g / mm) was measured according to ASTM 1708 using an Instron (Model 4502) instrument. 2 ) was measured, the approximate size of the film sample was 22 mm gauge length and 4.75 mm width, the sample further had ends forming a dog bone shape to accommodate gripping of the sample by the clamps of the Instron instrument, and was 100±50 microns thick.

[0063] Gel Fraction: Gel Fraction %=weight of purified dry lens / weight of unpurified dry lens*100%. Gel Fraction % indicates the approximate number of monomer conversions in the curing process and is used to track the completion of curing.

[0064] Example 1

[0065] Synthesis of HEMA-tosylate. A 100 mL flask equipped with a stir bar was dried under vacuum using a heat gun. (Hydroxyethyl)methacrylate (4.0 g, 31 mmol, 1 equiv.), triethylamine (3.5 g, 34 mmol, 1.1 equiv.), and anhydrous dichloromethane (20 mL) were injected into the flask using a syringe. The flask was placed in an ice bath and cooled to 0 °C. 4-Toluenesulfonyl chloride (6.2 g, 32.5 mmol, 1.05 equiv.) was then slowly injected into the solution using a syringe. After injection, the solution was allowed to warm to room temperature and stirred overnight. The solution was concentrated in a rotary evaporator, and the concentrated crude was then purified by flash chromatography on silica gel using eluents (ethyl acetate / hexane = 1 / 9 to ethyl acetate / hexane = 3 / 7) to give HEMA-tosylate as a clear liquid (3.7 g, 42%). 1 H NMR(400MHz,CDCl3)δ ppm 1.77-1.93(m,3H)2.36-2.49(m,3H)4.17-4.26(m,2H)4.26-4.37(m,2H) 5.47-5.62(m,1H)5.97-6.09(m,1H)7.28-7.40(m,2H)7.71-7.87(m,2H).

[0066] Examples 2 to 10 A monomer mixture was made by mixing the following components listed in Table 1 in the amounts by weight: [Table 1]

[0067] The resulting monomer mixture was cast into a contact lens by introducing the monomer mixture into a polypropylene mold assembly. The mold assembly and monomer mixture were then purged with N2 for 3 hours at 25°C, heated to 63°C for 20 minutes, heated to 93°C for 30 minutes, heated to 110°C for 1 hour, and then cooled to 55°C for 1 hour to form a contact lens. The resulting contact lens was removed from the mold assembly, extracted with deionized water, and placed in a boronization buffer before being autoclaved.

[0068] Examples 11 to 17 A monomer mixture was made by mixing the following components in the amounts by weight listed in Table 2. [Table 2]

[0069] The resulting monomer mixture was cast into a contact lens by introducing the monomer mixture into a polypropylene mold assembly. The mold assembly and monomer mixture were then cured to form a contact lens by heating the mixture at 65° C. for 30 minutes and at 100° C. for an additional 4.5 hours. The resulting contact lens was removed from the mold assembly, extracted with deionized water, and placed in a boronization buffer solution before being autoclaved.

[0070] For the sake of brevity, various features disclosed herein are described in the context of a single embodiment, but may be provided separately or in any suitable subcombination.All combinations of the embodiments are specifically encompassed by the exemplary embodiments disclosed herein, as if each and every combination were individually and expressly disclosed.In addition, all subcombinations listed in the embodiments describing such variables are also specifically encompassed by the formulations of the present invention, and are disclosed herein, as if each and every subcombination were individually and expressly disclosed herein.

[0071] It will be understood that various modifications can be made to the non-limiting exemplary embodiments disclosed herein. Thus, the above description should not be construed as limiting, but only as an exemplification of preferred embodiments. For example, the functions described above and implemented as the best mode for operating the non-limiting exemplary embodiments are for illustrative purposes only. Other configurations and methods can be implemented by those skilled in the art without departing from the scope and spirit of the present specification. Moreover, those skilled in the art will envision other modifications within the scope and spirit of the features and advantages added herein.

Claims

1. 1. An ophthalmic device that is the polymerization product of a monomer mixture, the monomer mixture comprising: (a) one or more sulfonate cationic initiators and one or more cationic initiators comprising one or more polymerizable groups; (b) one or more alkyl-substituted oxazolines.

2. The ophthalmic device of claim 1, wherein the one or more cationic initiators include one or more of a substituted or unsubstituted alkyl- and aryl-containing sulfonate cationic initiator containing one or more polymerizable groups, and a fluorinated substituted or unsubstituted alkyl- and aryl-containing sulfonate cationic initiator containing one or more polymerizable groups.

3. 10. The ophthalmic device of claim 1, wherein the one or more cationic initiators comprise one or more sulfonate cationic initiators selected from the group consisting of tosylates, nosylates, mesylates, and triflates, each containing one or more polymerizable groups.

4. The one or more cationic initiators are selected from the group consisting of a hydroxyl-containing (meth)acrylate and a compound of the formula R—SO ２ 10. The ophthalmic device of claim 1, comprising the reaction product of a compound of formula -X, where R is a hydrocarbon radical or moiety and X is a halogen.

5. The ophthalmic device of claim 1 , wherein the one or more cationic initiators comprising one or more polymerizable groups are 2-(tosyloxy)ethyl methacrylate.

6. The polymerization product has the following formula: 【Chemistry 1】 wherein R is an alkyl group of 1 to 12 carbon atoms.

6. The ophthalmic device of claim 1, comprising a brush polymer network comprising poly(2-alkyloxazoline) repeat units in a polymer backbone represented by:

7. The ophthalmic device of claim 6, wherein the brush polymer network comprises from about 3 to about 150 repeat units of the poly(2-alkyloxazoline) in the polymer backbone.

8. The ophthalmic device of any one of claims 1 to 5, wherein the monomer mixture further comprises one or more crosslinkers selected from an ethylenically unsaturated polymerizable alkoxylated polymer, or an end-functionalized poloxamer.

9. 6. The ophthalmic device of claim 1, wherein the monomer mixture further comprises one or more hydrophilic monomers, protected hydrophilic monomers selected from the group consisting of protected (meth)acrylic acids and protected hydroxyl-containing (meth)acrylates, and an ultraviolet light blocking agent.

10. 1. A method for making an ophthalmic device, comprising: (a) providing an ophthalmic device-forming monomer mixture comprising: (i) one or more sulfonate cationic initiators and one or more cationic initiators comprising one or more polymerizable groups, and (ii) one or more alkyl-substituted oxazolines; (b) subjecting the mixture to polymerization conditions to provide a polymerized ophthalmic device; (c) hydrating the polymerized ophthalmic device.

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