Soft contact lenses are based upon hydrogels. Many users find soft contact lenses comfortable enough to wear all day. There are two main classes of soft contact lens materials, conventional soft contact lenses which are formed from hydrogels containing no silicone, and silicone hydrogels.
Silicone hydrogels are water-swollen polymer networks that have high oxygen permeability. These lenses provide a good level of comfort to many lens wearers, but there are some users who experience discomfort and excessive ocular deposits leading to reduced visual acuity when using these lenses, in particular during extended periods of wear such as for several days in a row, for example, up to about 30 days. Such discomfort and deposits have been attributed to the hydrophobic character of the surfaces of lenses, and the interaction of those surfaces with the protein, lipids and mucin and the hydrophilic surface of the eye.
Silicone hydrogels have typically been prepared by polymerizing mixtures containing at least one silicone-containing monomer or macromer and at least one hydrophilic monomer. This class of lens material is desirable because it reduces the corneal edema and hyper-vasculature associated with conventional hydrogel lenses. Such materials, however, can be difficult to produce because the silicone components and the hydrophilic components are incompatible.
Silicone hydrogels are synthesized from reactive monomer mixtures composed of hydrophilic monomers, silicone monomers, initiators, crosslinking agents, diluents, and other ingredients for specific effects or properties, such as dyes, ultraviolet blockers, and wetting agents. These complex mixtures must be homogeneous and chemically stable. In some cases, the order of addition and mixing conditions are of paramount importance. Macromers or macromonomers have been employed to make graft copolymer segments within the silicone hydrogel to impart or enhance certain physical and mechanical properties. In addition, high molecular weight crosslinking agents or multi-functional prepolymers have also been used for the same reasons.
However, as the number of components increases, the chances of forming homogeneous and stable reactive monomer mixtures decrease which in turn make the formation of contact lenses unpredictable or unreproducible. Even if the reactive monomer mixture is reasonably homogeneous and stable, upon polymerization, the resulting silicone hydrogel may not exhibit the properties, such as transparency and low modulus, for use as a soft contact lens. As a result, there is a need in the art for developing reactive components that compatibilize the other components in the reactive monomer mixture as well as to create durable interphases between the various domains in the resulting silicone hydrogel, thereby resulting in unique physical, mechanical, and biological properties.
Group transfer polymerization (GTP) is a living anionic polymerization process for (meth)acrylate monomers, using trimethylsilyl ketene acetals as initiators and nucleophilic anions as catalysts (see U.S. Pat. Nos. 4,414,372; 4,417,034; 4,508,880; 4,524,196; and 4,581,428). GTP has shown the capability of making a wide range of polymers and block copolymers with good control over molecular weight and its distribution. However, GTP does not work with monomers with active hydrogen atoms such as 2-hydroxyethyl methacrylate or methacrylic acid, and preparing high molecular weight polymers is sometimes problematic because of backbiting reactions or other chain termination events (see J. American Chem. Society 1983, 105, 5706-5707; Macromolecules 1987, 20, 1473-1488; and Adv. Poly Sci. 2004, 167, 1-34).
GTP has been used to prepare linear, branched, block, and star macromers or prepolymers. Prepolymers were synthesized by using 2-trimethylsiloxyethyl methacrylate in the GTP polymerization, followed by deprotection with aqueous acidic methanol and acylation of the pendent hydroxyl groups with an acylating agent such as isopropenyl α,α-dimethylbenzyl isocyanate (TMI). These prepolymers have been incorporated as compatibilizing components in reactive monomer mixtures from which contact lenses are manufactured (see U.S. Pat. Nos. 4,659,782, 4,659,783, 4,771,116, 5,244,981, 5,314,960, 5,331,067, and 5,371,147). U.S. Pat. No. 6,367,929 discloses a tri-block prepolymer and its use in the fabrication of contact lenses. This tri-block prepolymer was prepared by the sequential addition of reactive monomer mixtures, resulting in a tri-block polymer with end blocks consisting of random copolymers of 2-hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA) and a middle block consisting of a random terpolymer of HEMA, mono-n-butyl terminated monomethacryloxypropyl terminated polydimethylsiloxane (mPDMS), and 3-methacryloxypropyl tris(trimethylsiloxy)silane (TRIS), followed by a acylation step using isopropenyl α,α-dimethylbenzyl isocyanate (TMI). Contact lenses were made from reactive monomer mixtures comprising this tri-block prepolymer, dimethyl acrylamide (DMA), polyvinylpyrrolidone (PVP), TRIS, and mPDMS. Evaluations of contact lenses made from such reactive monomer mixtures were inconsistent, perhaps because the reaction conditions for deprotecting the 2-trimethylsiloxyethyl methacrylate repeating units in the tri-block copolymer may have also hydrolyzed some of the TRIS repeating units, and the degree of such hydrolysis may have varied from batch to batch. As a result, GTP has shown to lack reproducible methods of making certain tri-block copolymers, especially those from silyl-protected monomers and other silicone-containing monomers.
Alternatively, there are several living radical polymerization (LRP) or controlled radical polymerization (CRP) techniques that may avoid or minimize some of the side reactions associated with the GTP of (meth)acrylates and thereby enable the reproducible synthesis of tri-block prepolymers. These methods include nitroxide mediated LRPs (see Chem. Rev. 2001, 101, 3661-3688); metal catalyzed LRPs (see Chem. Rev. 2001, 101, 3689-3745 and Chem. Rev. 2009, 109, 4963-5050); atom transfer radical polymerizations (ATRP) (see Chem. Rev. 2001, 101, 2921-2990); reversible addition fragmentation chain transfer (RAFT) polymerizations (see Acc. Chem. Res. 2008, 9, 1133-1142); and organotellurium mediated living free radical polymerizations (TERP) (see Chem. Rev. 2009, 109, 5051-5068) (see U.S. Pat. Nos. 7,276,569; 7,291,690; 7,615,601; and 7,662,899).
TERPs are versatile and relatively insensitive to the types of monomer used and functional groups present. In particular, monomers with active hydrogen atoms may be used in contrast to GTP. Typically, the monomers of interest along with an organotellurium chain transfer agent are mixed with or without a thermal free radical initiator or a photoinitiator under common polymerization conditions to produce a polymer with good molecular weight control (see JACS 2002, 124, 13666-13667 and JACS 2003, 125, 8720-8721). Block copolymers are made by sequential addition of monomer mixtures or by photo-induced radical coupling reactions (see J. Poly. Sci. Pt. A Polym. Chem. 2006, 44, 1-12 and JACS 2012, 134, 5536-5539). Polymers made by TERP have an organotellurium end group that may be reduced, for example, by using 2,2,6,6-tetramethylpiperine 1-oxyl (TEMPO), to create a vinylidene end group, which is also polymerizable, thereby transforming the polymer into a macromer or macromonomer (see Reactive & Functional Polymers 2009, 69, 416-423).
Polydimethylsiloxane (PDMS) copolymers have been studied (see Chem. Rev. 2010, 110, 1233-1277). PDMS block copolymers with HEMA have been prepared by various macroinitiator methods (see Polymer J. 2012, 44, 1087-1097). mPDMS graft copolymers using mPDMS macromers have also been described (see Macromolecules 2002, 35, 5953-5962 and Macromolecules 2003, 36, 4772-4778). Such graft copolymers are not suitable as prepolymers because of the lack of any polymerizable groups.
There is a need in the art for extended wear contact lenses, requiring extended wear silicone hydrogels that exhibit enhanced permeability of tear film components. There is also a need to provide silicone-containing prepolymers that are compatible with the reactive monomer mixtures used in the fabrication of silicone contact lenses.