Biomedical devices having surface coatings

Abstract

The biomedical device having a surface coating includes a bulk material having one or more biomedical device surface reactive functional groups and / or one or more biomedical device surface protection reactive functional groups, and a surface coating, wherein the surface coating is derived from a block copolymer including (a) monomer units derived from an ethylenically unsaturated-containing monomer having a ring-opening reactive functional group or a nucleolytic functional group complementary to the one or more biomedical device surface reactive functional groups and the one or more biomedical device surface protection reactive functional groups, and (b) monomer units derived from an ethylenically unsaturated-containing hydrophilic monomer.

Description

[Background technology]

[0001] Priority claims This application claims priority to U.S. Provisional Patent Application Serial No. 63 / 436,976, filed January 4, 2023, entitled "Biomedical Device Having a Surface Coating," the contents of which are incorporated herein by reference in their entirety.

[0002] Biomedical devices, such as ophthalmic lenses made from silicone-containing materials, have been investigated for several years. Such materials can generally be subdivided into two main types: hydrogels and non-hydrogels. Hydrogels can absorb and retain water in equilibrium, whereas non-hydrogels do not absorb significant amounts of water. Regardless of their water content, both hydrogel and non-hydrogel silicone medical devices tend to have a high affinity for lipids, are relatively hydrophobic, and have non-wettable surfaces. This issue is of particular concern with contact lenses.

[0003] Those skilled in the art have long recognized the need to modify the surfaces of biomedical devices, such as silicone contact lenses, to improve their compatibility with the eye. For example, increasing the hydrophilicity of the contact lens surface can improve the wettability of the contact lens. This is associated with improved wear comfort for the contact lens. Additionally, the lens surface can affect the susceptibility of the lens to deposition, particularly deposition of proteins and lipids from tears during lens wear. Accumulated deposits can cause eye discomfort or even irritation. For extended-wear lenses (i.e., lenses that are not removed daily before sleep), the surface is particularly important, as extended-wear lenses must be designed for high standards of comfort and biocompatibility over extended periods of time. Summary of the Invention

[0004] According to an exemplary embodiment, a biomedical device having a surface coating includes a bulk material having one or more biomedical device surface reactive functional groups and / or one or more biomedical device surface protection reactive functional groups, and a surface coating, wherein the surface coating is derived from a block copolymer including (a) monomer units derived from an ethylenically unsaturation-containing monomer having a ring-opening reactive functional group or a nucleolytic functional group complementary to the one or more biomedical device surface reactive functional groups and the one or more biomedical device surface protection reactive functional groups, and (b) monomer units derived from an ethylenically unsaturation-containing hydrophilic monomer.

[0005] According to another exemplary embodiment, a method for making a biomedical device having a surface coating comprises forming a surface coating on a biomedical device having one or more biomedical device surface reactive functional groups and / or one or more biomedical device surface protection reactive functional groups, wherein the surface coating is derived from a block copolymer comprising: (a) monomer units derived from an ethylenically unsaturation-containing monomer having a ring-opening reactive functional group or a nucleolytic functional group complementary to the one or more biomedical device surface reactive functional groups and the one or more biomedical device surface protection reactive functional groups; and (b) monomer units derived from an ethylenically unsaturation-containing hydrophilic monomer.

[0006] According to yet another exemplary embodiment, there is provided a use of a block copolymer for forming a surface coating on a surface of a biomedical device comprising a bulk material having one or more biomedical device surface reactive functional groups and / or one or more biomedical device surface protection reactive functional groups, the block copolymer comprising: (a) monomer units derived from an ethylenically unsaturation-containing monomer having a ring-opening reactive functional group or a nucleolytic functional group complementary to the one or more biomedical device surface reactive functional groups and the one or more biomedical device surface protection reactive functional groups; and (b) monomer units derived from an ethylenically unsaturation-containing hydrophilic monomer.

[0007] Exemplary embodiments are described in more detail below with reference to the accompanying drawings. [Brief explanation of the drawings]

[0008] [Figure 1] FIG. 1 shows the results of the coefficient of friction for Example 6 and Comparative Example 1.

[0009] [Figure 2A] FIG. 2A shows the XPS results for Examples 10 and 11 and Comparative Example 3. [Figure 2B] FIG. 2B shows the XPS results for Examples 10 and 11 and Comparative Example 3. DETAILED DESCRIPTION OF THE INVENTION

[0010] Various exemplary embodiments described herein include surface-modified biomedical devices. For example, increasing the hydrophilicity of a biomedical device, such as a contact lens surface, can improve the wettability of the contact lens, which is associated with improved wear comfort for the contact lens. Additionally, the lens surface can affect the susceptibility of the lens to deposition, particularly deposition of proteins and lipids from tear fluid during lens wear. Accumulated deposits can cause eye discomfort or even irritation. For extended-wear lenses (i.e., lenses worn daily without removing the lens before sleep), the surface is particularly important, as extended-wear lenses must be designed for high standards of comfort and biocompatibility over extended periods of time.

[0011] Therefore, it is desirable to provide improved biomedical devices having a highly wettable and / or lubricious surface coating thereon compared to untreated biomedical devices, such that the biomedical devices not only have improved wettability, but also typically have an optically clear hydrophilic surface coating to enable contact lenses to be used for extended periods in the human eye. Additionally, exemplary embodiments described herein provide biomedical devices having optically clear hydrophilic surface coatings that are fabricated in a simple and cost-effective manner.

[0012] Non-limiting exemplary embodiments disclosed herein relate to biomedical devices having a surface coating comprising a bulk material having one or more biomedical device surface reactive functional groups and / or one or more biomedical device surface protection reactive functional groups, and a surface coating, wherein the surface coating is derived from a block copolymer comprising monomer units derived from an ethylenically unsaturation-containing monomer having a reactive or denucleatable functionality complementary to the one or more biomedical device surface reactive functional groups and the one or more biomedical device surface protection reactive functional groups, and monomer units derived from an ethylenically unsaturation-containing hydrophilic monomer.

[0013] As used herein, a "biomedical device" is any article designed to be used in or on mammalian tissue or fluid, preferably human tissue or fluid. Representative examples of biomedical devices include, but are not limited to, artificial ureters, diaphragms, intrauterine contraceptive devices, heart valves, catheters, denture liners, prosthetics, and ophthalmic lens applications, where the lenses are intended for placement directly in or on the eye, such as, for example, intraocular devices and contact lenses. In an exemplary embodiment, the biomedical device is an ophthalmic device. In another exemplary embodiment, the biomedical device is a contact lens. In yet another exemplary embodiment, the biomedical device is a silicone hydrogel.

[0014] As used herein, the term "ophthalmic device" refers to a device that resides in and on the eye. These devices can provide optical correction, wound treatment, drug delivery, diagnostic functionality, or cosmetic enhancement or effect, or a combination of these properties. Suitable ophthalmic devices include ophthalmic lenses, such as soft contact lenses, e.g., soft hydrogel lenses; soft non-hydrogel lenses; hard contact lenses, e.g., rigid gas-permeable lens materials; intraocular lenses; overlay lenses; intraocular inserts; optical inserts; and the like. As will be understood by those skilled in the art, a lens is considered "soft" if it can be folded over itself without breaking.

[0015] The biomedical device whose surface is modified according to the non-limiting exemplary embodiments disclosed herein can be made of any material known in the art that can form the above-mentioned biomedical device. In one embodiment, the biomedical device includes a device formed from a material that is not itself hydrophilic. Such devices are formed from materials known in the art, including, for example, polysiloxanes, perfluoropolyethers, such as fluorinated poly(meth)acrylates or equivalent fluorinated polymers derived from other polymerizable carboxylic acids, polyalkyl(meth)acrylates or equivalent alkylester polymers derived from other polymerizable carboxylic acids, or fluorinated polyolefins such as fluorinated ethylene propylene polymers, or preferably tetrafluoroethylene in combination with a dioxole, such as perfluoro-2,2-dimethyl-1,3-dioxole. Representative examples of suitable bulk materials include, but are not limited to, Lotrafilcon A, Neofocon, Pasifocon, Telefocon, Silafocon, Fluorsilfocon, Paflufocon, Silafocon, Elastofilcon, Fluorofocon, or Teflon AF materials, such as Teflon AF 1600 or Teflon AF 2400, which are copolymers of about 63 to about 73 mol % perfluoro-2,2-dimethyl-1,3-dioxole and about 37 to about 27 mol % tetrafluoroethylene, or about 80 to about 90 mol % perfluoro-2,2-dimethyl-1,3-dioxole and about 20 to about 10 mol % tetrafluoroethylene.

[0016] In another embodiment, the biomedical device includes a device formed from a material that is itself hydrophilic, for example, because reactive groups such as carboxy, carbamoyl, sulfate, sulfonate, phosphate, amine, ammonium, or hydroxy groups are inherently present in the material and therefore present on the surface of a biomedical device fabricated therefrom. Such devices are formed from materials known in the art, including, by way of example, polyhydroxyethyl acrylate, hydroxyethyl methacrylate (HEMA), polyvinylpyrrolidone (PVP), polyacrylic acid, polymethacrylic acid, polyacrylamide, polydimethylacrylamide (DMA), polyvinyl alcohol, and the like, and copolymers thereof, for example, copolymers of two or more monomers selected from hydroxyethyl acrylate, hydroxyethyl methacrylate, N-vinylpyrrolidone, acrylic acid, methacrylic acid, acrylamide, dimethylacrylamide, vinyl alcohol, and the like. Representative examples of suitable bulk materials include, but are not limited to, Polymacon, Tefilcon, Methafilcon, Deltafilcon, Bufilcon, Phemfilcon, Ocufilcon, Focofilcon, Etafilcon, Hefilcon, Vifilcon, Tetrafilcon, Perfilcon, Droxifilcon, Dimefilcon, Isofilcon, Mafilcon, Nelfilcon, Atlafilcon, and the like.

[0017] In another embodiment, the ophthalmic device includes a device formed from a material that is an amphiphilic segmented copolymer containing at least one hydrophobic segment and at least one hydrophilic segment connected via a bond or bridging member.

[0018] The biocompatible materials herein are particularly useful for both soft and hard materials commonly used in ophthalmic lenses, including contact lenses.Generally, non-hydrogel materials are hydrophobic polymeric materials that do not contain water in their equilibrium state.Typical non-hydrogel materials include silicone acrylics, such as bulk silicone monomers (e.g., tris(trimethylsiloxy)silylpropyl methacrylate, commonly known as "tris" monomers), methacrylate end-capped poly(dimethylsiloxane) prepolymers, or silicones with fluoroalkyl side groups (polysiloxanes are also commonly known as silicone polymers).

[0019] Hydrogel materials, on the other hand, include hydrated crosslinked polymer systems that contain water in an equilibrium state. Hydrogel materials contain about 5% or more water by weight (e.g., up to about 80% by weight). In one embodiment, the hydrogel material includes a silicone hydrogel material. In another embodiment, the hydrogel material includes vinyl-functionalized polydimethylsiloxane copolymerized with hydrophilic monomers, and fluorinated methacrylate and methacrylate-functionalized fluorinated polyethylene oxide copolymerized with hydrophilic monomers. Representative examples of hydrogel materials suitable for use in the present invention include those disclosed in U.S. Patent Nos. 5,310,779, 5,387,662, 5,449,729, 5,512,205, 5,610,252, 5,616,757, 5,708,094, 5,710,302, 5,714,557, and 5,908,906, the contents of which are incorporated herein by reference.

[0020] In one embodiment, hydrogel materials for biomedical devices such as contact lenses can contain hydrophilic monomers, such as one or more unsaturated carboxylic acids, vinyl lactams, amides, polymerizable amines, vinyl carbonates, vinyl carbamates, oxazolone monomers, copolymers thereof, and mixtures thereof. Useful amides include acrylamides, such as N,N-dimethylacrylamide and N,N-dimethylmethacrylamide. Useful vinyl lactams include cyclic lactams such as N-vinyl-2-pyrrolidone. Examples of other hydrophilic monomers include hydrophilic prepolymers, such as poly(alkene glycols), functionalized with polymerizable groups. Examples of useful functionalized poly(alkene glycols) include poly(diethylene glycols) of various chain lengths containing monomethacrylate or dimethacrylate end caps. In some embodiments, the poly(alkene glycol) polymer contains at least two alkene glycol monomer units. Further examples include the hydrophilic vinyl carbonate or vinyl carbamate monomers disclosed in U.S. Patent No. 5,070,215 and the hydrophilic oxazolone monomers disclosed in U.S. Patent No. 4,910,277. Other suitable hydrophilic monomers will be apparent to those skilled in the art. In another embodiment, the hydrogel material can contain a siloxane-containing monomer and at least one of the aforementioned hydrophilic monomers and / or prepolymers.

[0021] In some embodiments, the hydrogel material may further comprise one or more hydrophobic monomers. Suitable hydrophobic monomers include, for example, substituted or unsubstituted C1-C6 20 Alkyl and C3-C 20 Cycloalkyl (meth)acrylates, such as (2-amino)ethyl methacrylate and methacrylic acid, substituted and unsubstituted aryl (meth)acrylates (wherein the aryl group contains 6 to 36 carbon atoms), (meth)acrylonitrile, styrene, lower alkyl styrenes, lower alkyl vinyl ethers, and C2 to C6 10This includes perfluoroalkyl (meth)acrylates and the corresponding partially fluorinated (meth)acrylates.

[0022] A wide variety of materials can be used herein, with silicone hydrogel contact lens materials being particularly preferred. Silicone hydrogels generally have a water content greater than about 5% by weight, more typically about 10 to about 80% by weight. Such materials are typically prepared by polymerizing a mixture containing at least one silicone-containing monomer and at least one hydrophilic monomer. Typically, the silicone-containing monomer or hydrophilic monomer functions as the crosslinker (a crosslinker is defined as a monomer having multiple polymerizable functional groups), or a separate crosslinker may be used. Silicone-containing monomers used to form silicone hydrogels are well known in the art, with numerous examples described in U.S. Patent Nos. 4,136,250, 4,153,641, 4,740,533, 5,034,461, 5,070,215, 5,260,000, 5,310,779, and 5,358,995.

[0023] In an exemplary embodiment, which can be combined with one or more of the preceding paragraphs, the one or more silicone-containing monomers can include one or more bulk silicon-containing monomers as a representative class of silicone-containing monomers. In an exemplary embodiment, an example of the one or more bulk silicon-containing monomers includes a bulk polysiloxanyl alkyl (meth)acrylic monomer represented by the structure of Formula I: [ka] X represents -O- or -NR-, R represents hydrogen or C1-C4 alkyl, and each R 1 independently represent hydrogen or methyl, and each R 2 independently represent a lower alkyl radical, a phenyl radical, or a group represented by [ka] Here, each R 2′ independently represent a lower alkyl or phenyl radical, and h is 1 to 10.

[0024] In an exemplary embodiment, the one or more bulk silicon-containing monomers include bulk polysiloxanyl alkylcarbamate monomers represented by the structure of Formula Ia: [ka] where X represents -NR-, R represents hydrogen or C1-C4 alkyl, and R 1 represents hydrogen or methyl, and each R 2 independently represent a lower alkyl radical, a phenyl radical, or a group represented by [ka] Here, each R 2’ independently represent a lower alkyl or phenyl radical, h is 1 to 10, etc.

[0025] Examples of bulk monomers include 3-methacryloyloxypropyltris(trimethyl-siloxy)silane or tris(trimethylsiloxy)silylpropyl methacrylate (sometimes referred to as Tris), and tris(trimethylsiloxy)silylpropyl vinylcarbamate (sometimes referred to as TRIS-VC), and the like, and mixtures thereof.

[0026] Such bulk monomers may be copolymerized with silicone macromonomers, which are poly(organosiloxanes) capped with unsaturated groups at two or more ends of the molecule. U.S. Patent No. 4,153,641 discloses various unsaturated groups, such as acryloxy or methacryloxy groups.

[0027] In an exemplary embodiment, which may be combined with one or more of the preceding paragraphs, the one or more silicone-containing monomers may include one or more silicone-containing vinyl carbonate or vinyl carbamate monomers, as a representative class of silicone-containing monomers. Suitable silicone-containing vinyl carbonate or vinyl carbamate monomers include, for example, 1,3-bis[4-vinyloxycarbonyloxy)but-1-yl]tetramethyldisiloxane, 3-(trimethylsilyl)propyl vinyl carbonate, 3-(vinyloxycarbonylthio)propyl-[tris(trimethylsiloxy)silane], 3-[tris(trimethylsiloxy)silyl]propyl vinyl carbamate, 3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate, 3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate, t-butyldimethylsiloxyethyl vinyl carbonate, trimethylsilylethyl vinyl carbonate, trimethylsilylmethyl vinyl carbonate, and the like, and mixtures thereof.

[0028] In an exemplary embodiment, which can be combined with one or more of the preceding paragraphs, the one or more silicone-containing monomers can include one or more polyurethane polysiloxane macromonomers (sometimes referred to as prepolymers), which, as a representative class of silicone-containing monomers, can have a hard-soft-hard block structure similar to conventional urethane elastomers. These may be end-capped with hydrophilic monomers such as HEMA. Examples of such silicone urethanes are disclosed in various publications, including Lai, Yu-Chin, "The Role of Bulky Polysiloxanylalkyl Methacryates in Polyurethane-Polysiloxane Hydrogels," Journal of Applied Polymer Science, Vol. 60, pp. 1193-1199 (1996). PCT Published Application No. WO 96 / 31792 discloses examples of such monomers, the disclosure of which is incorporated herein by reference in its entirety. Further examples of silicone urethane monomers are represented by Formulae II and III: E(*D*A*D*G) a *D*A*D*E' or (II) E(*D*G*D*A) a *D*A*D*E', or (III) where: D independently represents an alkyl diradical, alkylcycloalkyl diradical, cycloalkyl diradical, aryl diradical, or alkylaryl diradical having from 6 to about 30 carbon atoms; G independently represents an alkyl diradical, cycloalkyl diradical, alkylcycloalkyl diradical, aryl diradical, or alkylaryl diradical having from 1 to about 40 carbon atoms, which may contain ether, thio, or amine linkages in the backbone; * represents a urethane or ureido bond, a is at least 1, A independently represents a divalent polymer radical of formula IV, [ka] Here, each R S independently represent an alkyl or fluoro-substituted alkyl group having 1 to about 10 carbon atoms, which may contain an ether linkage between the carbon atoms; m' is at least 1; p is a number providing a moiety weight of about 400 to about 10,000; each of E and E′ independently represents a polymerizable unsaturated organic radical represented by formula V: [ka] R 3 is hydrogen or methyl, R 4 is hydrogen, an alkyl group having 1 to 6 carbon atoms, or -CO-YR 6 It is radical and Y is —O—, —S—, or —NH—; R 5 is a divalent alkylene radical having 1 to about 10 carbon atoms; R 6 is an alkyl radical having 1 to about 12 carbon atoms; X represents -CO- or -OCO-; Z represents -O- or -NH-; Ar represents an aromatic radical having from about 6 to about 30 carbon atoms; w is 0 to 6, x is 0 or 1, y is 0 or 1, and z is 0 or 1.

[0029] In some embodiments, the silicone-containing urethane monomer can be represented by Formula VI: [ka] where m is at least 1, preferably 3 or 4, a is at least 1, preferably 1, p is a number providing a part weight of from about 400 to about 10,000, preferably at least about 30, and R7 is the diradical of a diisocyanate after removal of an isocyanate group, such as the diradical of isophorone diisocyanate, and each E″ is a group represented by: [ka]

[0030] In another exemplary embodiment, the silicone hydrogel material comprises (in bulk, i.e., in the copolymerized monomer mixture) about 5 to about 50% by weight, preferably about 10 to about 25% by weight, of one or more silicone macromonomers; about 5 to about 75% by weight, preferably about 30 to about 60% by weight, of one or more polysiloxanylalkyl(meth)acrylic monomers; and about 10 to about 50% by weight, preferably about 20 to about 40% by weight, of a hydrophilic monomer. Generally, silicone macromonomers are poly(organosiloxanes) capped with unsaturated groups at two or more ends of the molecule. In addition to the end groups of the above structural formula, U.S. Pat. No. 4,153,641 discloses additional unsaturated groups, including acryloxy or methacryloxy. Fumarate-containing materials, such as those disclosed in U.S. Pat. Nos. 5,310,779, 5,449,729, and 5,512,205, are also useful substrates according to exemplary embodiments. The silane macromonomer may be a silicon-containing vinyl carbonate or vinyl carbamate, or a polyurethane-polysiloxane having one or more hard-soft-hard blocks and end-capped with a hydrophilic monomer.

[0031] In exemplary embodiments, as can be combined with one or more of the preceding paragraphs, the one or more silicone-containing monomers can include one or more fluorinated monomers as a representative class of silicone-containing monomers.Such monomers have been used in the formation of fluorosilicone hydrogels to reduce the accumulation of deposits on contact lenses made therefrom, as disclosed, for example, in U.S. Patent Nos. 4,954,587, 5,010,141 and 5,079,319.In addition, the use of silicone-containing monomers with certain fluorinated side groups, i.e., -(CF2)-H, has been found to improve the compatibility between hydrophilic monomer units and silicone-containing monomer units.See, for example, U.S. Patent Nos. 5,321,108 and 5,387,662.

[0032] The silicone materials described above are merely exemplary, and other materials for use as substrates that can benefit from being coated with the block copolymers disclosed herein and that are disclosed in various publications and are continually being developed for use in contact lenses and other medical devices can also be used. For example, the biomedical device can be formed from at least one cationic monomer, such as a cationic silicone-containing monomer or a cationic fluorinated silicone-containing monomer.

[0033] As those skilled in the art will readily appreciate, one or more biomedical device surface reactive functional groups of the biomedical devices disclosed herein may be inherently present on the surface of the biomedical device. However, if the biomedical device contains too few or no functional groups, the surface of the biomedical device can be modified by known techniques, such as plasma chemistry or conventional functionalization with groups such as -OH, -NH2, or -CO2H. For example, the surface of the biomedical device can be treated with plasma or corona discharge to introduce or increase the surface functional groups of the biomedical device. The type of gas introduced into the treatment chamber depends on the desired type of biomedical device surface functional group. For example, hydroxyl surface groups can be generated in a treatment chamber atmosphere containing water vapor or alcohol. Carboxyl surface groups can be generated in a treatment chamber atmosphere containing oxygen, air, or other oxygen-containing gases. Amino surface groups can be generated in a treatment chamber atmosphere containing ammonia or an amine source. Mercaptan surface groups can be generated in a treatment chamber atmosphere containing a sulfur-containing gas, such as an organic mercaptan or hydrogen sulfide. As one skilled in the art will readily appreciate, any combination of the aforementioned gases can be used in a treatment chamber to produce a combination of biomedical device surface functional groups on the surface of a biomedical device. Methods and apparatus for surface treatment by plasma discharge are disclosed, for example, in U.S. Patent Nos. 6,550,915 and 6,794,456, the contents of which are incorporated herein by reference.

[0034] Suitable biomedical device surface functional groups for the biomedical devices disclosed herein include a wide variety of groups familiar to those skilled in the art. Representative examples of such functional groups include, but are not limited to, groups replaceable with amino or hydroxy groups, such as hydroxy groups, tosylate groups, mesylate groups, triflate groups, nosyloxy groups, amino groups, carboxy groups, carbonyl groups, aldehyde groups, sulfonic acid groups, sulfonyl chloride groups, isocyanato groups, carboxyanhydride groups, lactone groups, azlactone groups, epoxy groups, and halo groups, groups capable of undergoing Michael addition-type reactions, and mixtures thereof. In one embodiment, the biomedical device surface functional groups of a biomedical device are amino and / or hydroxy groups.

[0035] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the biomedical devices disclosed herein can have one or more biomedical device surface-protecting reactive functional groups. The one or more biomedical device surface-protecting reactive functional groups can be attached to one or more monomers used to form the biomedical device. The one or more biomedical device surface-protecting functional groups on the monomers used to form the biomedical device are used when one or more groups on the monomers used to form the biomedical device are incompatible with the polymerization process, are incompatible with other monomers in the polymerization process, or when further functionalizing the biomedical device after polymerization.

[0036] These protected monomers must be deprotected before exposure to the block polymer in order to subsequently react with the ring-opening functional group of the coating block polymer. Deprotection of the monomers is accomplished by methods well known to those skilled in the art. In an exemplary embodiment, the deprotection of the BOC-protected amine is achieved by simple carbamate hydrolysis under acidic conditions, for example. For example, the starting material is dissolved in water or an organic solvent and then treated with typically used acids such as concentrated hydrochloric acid or trifluoroacetic acid (TFA). In another exemplary embodiment, the protected acid is hydrolyzed with a catalytic amount of acid or alkali under heating, for example. For example, the TMS group in 2-(trimethylsilyloxy)ethyl methacrylate is highly unstable to acid- or base-catalyzed solvolysis, attack by many nucleophiles, and hydrogenolysis.

[0037] In non-limiting exemplary embodiments, the one or more protected monomers can include, for example, protected HEMA, protected (2-amino)ethyl methacrylate, protected methacrylic acid, etc. These protected monomers are merely exemplary and should not be construed as limiting the protected monomers. All other protected monomers are contemplated herein. In exemplary embodiments, the following are representative examples of protected monomers: [ka]

[0038] The protected monomers are commercially available from suppliers such as Polysciences, Sigma-Aldrich, TCI, Florochem, Wako, and Sigma-Aldrich, or can be prepared according to methods known in the art. For example, the following protected monomers can be prepared according to Schemes I-X below. Scheme I [ka] Scheme II [ka] Scheme III [ka] Scheme IV [ka] Scheme V [ka] Scheme VI [ka] Scheme VII [ka] Scheme VIII [ka] Scheme IX [ka] Scheme X [ka]

[0039] According to non-limiting exemplary embodiments disclosed herein, a biomedical device having one or more biomedical device surface reactive functional groups and / or one or more biomedical device surface-protecting reactive functional groups is exposed to a block copolymer comprising (a) a monomer unit derived from an ethylenically unsaturated-containing monomer having a ring-opening reactive functional group complementary to the biomedical device surface reactive functional group, and (b) a monomer unit derived from an ethylenically unsaturated-containing hydrophilic monomer, wherein the ring-opening reactive functional group of the monomer unit derived from the ethylenically unsaturated-containing monomer having the ring-opening reactive functional group is covalently bonded to the surface of the biomedical device via the biomedical device surface reactive functional group. In exemplary embodiments, the block copolymer is a biomedical device surface coating-forming block copolymer. In exemplary embodiments, the block copolymer is a brush copolymer. As used herein, the term "polymer brush" should be understood to refer to a polymer brush containing polymer chains, one end of which is tethered, directly or indirectly, to a surface and the other end of which extends freely from the surface, somewhat similar to the bristles of a brush. In another exemplary embodiment, the block copolymer is a comb copolymer.

[0040] Representative examples of ethylenically unsaturated moieties of ethylenically unsaturated-containing monomers and ethylenically unsaturated-containing hydrophilic monomers having ring-opening reactive functional groups include, for example, (meth)acrylate-containing radicals, (meth)acrylamide-containing radicals, vinyl carbonate-containing radicals, vinyl carbamate-containing radicals, styrene-containing radicals, itaconic acid-containing radicals, vinyl-containing radicals, vinyloxy-containing radicals, fumaric acid-containing radicals, maleimide-containing radicals, vinyl sulfonyl radicals, etc. 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.

[0041] In one embodiment, the ethylenically unsaturated moiety is represented by the general formula: [ka] where R is hydrogen or an alkyl group having 1 to 6 carbon atoms, such as methyl, and each R ’ are independently hydrogen, an alkyl group having 1 to 6 carbon atoms, or -CO-YR ’’’ is a radical, Y is -O-, -S-, or -NH-, and R ’’’ R is an alkyl group having 1 to about 10 carbon atoms. ’’ is a linking group (e.g., a divalent alkyl radical having 1 to about 12 carbon atoms), B represents -O- or -NH-, Z represents -CO-, -OCO-, or -COO-, Ar represents an aromatic radical having 6 to about 30 carbon atoms, w is 0 to 6, a is 0 or 1, b is 0 or 1, and c is 0 or 1. The ethylenically unsaturation-containing moiety can be attached to the ethylenically unsaturation-containing monomer and the ethylenically unsaturation-containing hydrophilic monomer having a ring-opening reactive functional group as a pendant group, a terminal group, or both.

[0042] In an exemplary embodiment, the ethylenically unsaturated-containing monomer having a ring-opening reactive functional group complementary to the biomedical device surface reactive functional group includes an ethylenically unsaturated epoxy-containing monomer. Suitable ethylenically unsaturated epoxy-containing monomers include, for example, glycidyl-containing ethylenically unsaturated monomers such as glycidyl methacrylate, glycidyl acrylate, glycidyl vinyl carbonate, glycidyl vinyl carbamate, vinylcyclohexyl-1,2-epoxide, and the like.

[0043] In another exemplary embodiment, the ethylenically unsaturated-containing monomer having a ring-opening reactive functional group complementary to the biomedical device surface reactive functional group includes a ring-opening reactive monomer having an azlactone group represented by the formula: [ka] R 3 and R 4 are independently an alkyl group having 1 to 14 carbon atoms, a cycloalkyl group having 3 to about 14 carbon atoms, an aryl group having 5 to about 12 ring atoms, an arene group having 6 to about 26 carbon atoms, and 0 to 3 heteroatoms selected from S, N, and O, or R 3 and R 4 can, together with the carbon to which they are attached, form a carbocyclic ring containing 4 to 12 ring atoms, where n is an integer of 0 or 1. Such monomer units are disclosed, for example, in U.S. Pat. No. 5,177,165.

[0044] The ring structure of such reactive functional groups is susceptible to nucleophilic ring-opening reactions with complementary reactive functional groups on the surface of the substrate being treated. For example, the azlactone functional group may react with primary amines, hydroxyl radicals, etc., which may be present on the surface of the device, to form covalent bonds between the substrate and the hydrophilic reactive polymer at one or more locations along the polymer. Multiple attachments can form a series of polymer loops on the substrate, each loop containing a hydrophilic chain attached at both ends to the substrate.

[0045] The azlactone-functional monomer used to produce the block copolymer can be any monomer, prepolymer, or oligomer containing the azlactone functionality of the above formula in combination with a vinyl group on the unsaturated hydrocarbon to which the azlactone is attached. In one embodiment, the azlactone functionality is provided to the hydrophilic polymer by a 2-alkenyl azlactone monomer. 2-Alkenyl azlactone monomers are known compounds, and their synthesis is described, for example, in U.S. Pat. Nos. 4,304,705, 5,081,197, and 5,091,489, the contents of which are incorporated herein by reference. Suitable 2-alkenyl azlactones include 2-ethenyl-1,3-oxazolin-5-one, 2-ethenyl-4-methyl-1,3-oxazolin-5-one, 2-isopropenyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl-1,3-oxazolin-5-one, 2-ethenyl-4,4-dimethyl-1,3-oxazolin-5-one, 2-isopropenyl-4,-dimethyl-1,3-oxazolin-5-one, 2-ethenyl-4-methyl-ethyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl-4-butyl-1,3-oxazolin-5-one, 2-ethenyl-4,4-dibutyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl-4-dodecyl- including, but not limited to, 1,3-oxazolin-5-one, 2-isopropenyl-4,4-diphenyl-1,3-oxazolin-5-one, 2-isopropenyl-4,4-pentamethylene-1,3-oxazolin-5-one, 2-isopropenyl-4,4-tetramethylene-1,3-oxazolin-5-one, 2-ethenyl-4,4-diethyl-1,3-oxazolin-5-one, 2-ethenyl-4-methyl-4-nonyl-1,3-oxazolin-5-one, 2-isopropenyl-methyl-4-phenyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl-4-benzyl-1,3-oxazolin-5-one, and 2-ethenyl-4,4-pentamethylene-1,3-oxazolin-5-one.

[0046] In an exemplary embodiment, the azlactone monomer can be represented by the following general formula: [ka] R 1 and R 2 each independently represents a hydrogen atom or a lower alkyl group having 1 to 6 carbon atoms; R 3 and R 4 are independently an alkyl group having 1 to 6 carbon atoms or a cycloalkyl group having 5 or 6 carbon atoms. Specific examples include 2-isopropenyl-4,4-dimethyl-2-oxazolin-5-one (IPDMO), 2-vinyl-4,4-dimethyl-2-oxazolin-5-one (VDMO), spiro-4'-(2'-isopropenyl-2'-oxazolin-5-one)cyclohexane (IPCO), cyclohexane-spiro-4'-(2'-vinyl-2'-oxazol-5'-one) (VCO), and 2-(-1-propenyl)-4,4-dimethyl-oxazol-5-one (PDMO). These compounds and their preparation are known in the art; see, for example, U.S. Pat. No. 6,858,310, the contents of which are incorporated herein by reference.

[0047] In one exemplary embodiment, the ethylenically unsaturation-containing monomer with a ring-opening reactive functional group is a non-boronic acid-containing ethylenically unsaturation-containing monomer with a ring-opening reactive functional group.

[0048] The block copolymer further comprises a monomer unit derived from an ethylenically unsaturated hydrophilic monomer. Examples of the ethylenically unsaturated hydrophilic monomer include ethylenically unsaturated hydrophilic monomers containing acrylamide moieties such as N,N-dimethylacrylamide and N,N-dimethylmethacrylamide, acetamides such as N-vinyl-N-methylacetamide and N-vinylacetamide, formamides such as N-vinyl-N-methylformamide and N-vinylformamide, cyclic lactams such as N-vinyl-2-pyrrolidone, (meth)acrylated alcohols such as 2-hydroxyethyl methacrylate and 2-hydroxyethyl acrylate, ethylenically unsaturated polymerizable alkoxylated polymers, and mixtures thereof. Methacrylated sulfobetaine and methacrylated phosphocholine are also included in the present invention.

[0049] Suitable ethylenically unsaturated polymerizable alkoxylated polymers include, by way of example, polymerizable polyethylene glycols having, for example, number average molecular weights up to about 2000, e.g., those having CTFA designations such as PEG-200, PEG-400, PEG-600, PEG-1000, and mixtures thereof. Representative examples include, but are not limited to, (meth)acrylated poly(ethylene glycols) such as PEG-200 methacrylate, PEG-400 methacrylate, PEG-600 methacrylate, PEG-1000 methacrylate, and mixtures thereof.

[0050] In one exemplary embodiment, the ethylenically unsaturated containing hydrophilic monomer is a non-boronic acid containing ethylenically unsaturated hydrophilic monomer.

[0051] The block copolymers disclosed herein can be prepared using controlled radical polymerization techniques such as reversible addition-fragmentation chain transfer (RAFT) polymerization or atom transfer radical polymerization (ATRP) using chain transfer agents, which can produce block copolymers with well-defined molecular weight distributions and narrow polydispersities. RAFT polymerization is particularly preferred due to its compatibility with a variety of vinyl monomers.

[0052] In a non-limiting exemplary embodiment, RAFT agents suitable for the present invention may be based on thiocarbonylthio chemistry, which is well known to those skilled in the art. The thiocarbonylthio fragment may be derived from RAFT agents such as xanthate-, trithiocarbonate-, dithiocarbamate-, dithiobenzoate-, or dithioester-containing compounds, each of which contains a thiocarbonylthio group. One type of RAFT agent that can be used herein has the general formula: [ka] where x is 1 or 2 and Z is a substituted oxygen (e.g., xanthate (-OR)), substituted nitrogen (e.g., dithiocarbamate (-NRR)), substituted sulfur (e.g., trithiocarbonate (-SR)), dithiobenzoate, substituted or unsubstituted C1-C 20 Alkyl or C3-C 25 unsaturated, partially or fully saturated ring (e.g., dithioester (-R)) or carboxylic acid-containing group, and R is independently a linear or branched, substituted or unsubstituted C-C 30 Alkyl cyano groups, linear or branched, substituted or unsubstituted C1-C 30 Alkyl groups, substituted or unsubstituted C3-C 30 Cycloalkyl groups, substituted or unsubstituted C3-C 30 Cycloalkylalkyl groups, substituted or unsubstituted C3-C 30 Cycloalkenyl groups, substituted or unsubstituted C5-C 30 Aryl groups, substituted or unsubstituted C5-C 30 Arylalkyl groups, C1-C 20 Ester groups, ether or polyether-containing groups, alkyl or aryl amide groups, alkyl or aryl amine groups, substituted or unsubstituted C5-C 30 Heteroaryl groups, substituted or unsubstituted C3-C 30 Heterocyclic rings, substituted or unsubstituted C4-C 30Heterocycloalkyl groups, substituted or unsubstituted C6-C 30 heteroarylalkyl groups, and combinations thereof.

[0053] Representative examples of alkyl groups for use herein include, by way of example, straight or branched alkyl chain radicals containing carbon and hydrogen atoms having from 1 to about 30 carbon atoms, or from 1 to about 12 carbon atoms, with or without unsaturation relative to the remainder of the molecule, e.g., methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl, methylene, ethylene, and the like.

[0054] Representative examples of cycloalkyl groups for use herein include, by way of example, substituted or unsubstituted non-aromatic monocyclic or polycyclic ring systems of about 3 to about 30 carbon atoms, or 3 to about 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, perhydronaphthyl, adamantyl, and norbornyl groups, bridged cyclic or spiro bicyclic groups, such as spiro-(4,4)-non-2-yl, and the like, optionally containing one or more heteroatoms, such as, for example, O and N.

[0055] Representative examples of cycloalkylalkyl groups for use herein include, by way of example, substituted or unsubstituted cyclic ring-containing radicals containing from about 3 to about 30 carbon atoms, or from 3 to about 6 carbon atoms, directly bonded to an alkyl group and then attached to the main structure of the monomer at any carbon from the alkyl group to create a stable structure, e.g., cyclopropylmethyl, cyclobutylethyl, cyclopentylethyl, and the like, and the cyclic ring can optionally contain one or more heteroatoms, such as O and N.

[0056] Representative examples of cycloalkenyl groups for use herein include, by way of example, substituted or unsubstituted cyclic ring-containing radicals containing about 3 to about 30 carbon atoms, or 3 to about 6 carbon atoms, and having at least one carbon-carbon double bond, e.g., cyclopropenyl, cyclobutenyl, cyclopentenyl, and the like, wherein the cyclic ring can optionally contain one or more heteroatoms, such as, for example, O and N.

[0057] Representative examples of aryl groups for use herein include, by way of example, substituted or unsubstituted monocyclic or polycyclic aromatic radicals containing from about 5 to about 30 carbon atoms, or from 5 to about 8 carbon atoms, e.g., phenyl, naphthyl, tetrahydronaphthyl, indenyl, biphenyl, and the like, optionally containing one or more heteroatoms, such as, for example, O and N.

[0058] Representative examples of arylalkyl groups for use herein include, by way of example, a substituted or unsubstituted aryl group, as defined herein, directly bonded to an alkyl group, as defined herein, e.g., —CH2C6H5, —C2H5C6H5, etc., where the aryl group can optionally contain one or more heteroatoms, such as, for example, O and N.

[0059] Representative examples of ester groups for use herein include, by way of example, carboxylic acid esters having 1 to 20 carbon atoms, and the like.

[0060] Representative examples of ether- or polyether-containing groups for use herein include, by way of example, alkyl ethers, cycloalkyl ethers, cycloalkylalkyl ethers, cycloalkenyl ethers, aryl ethers, and arylalkyl ethers, where alkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, aryl, and arylalkyl groups are as defined herein. Exemplary ether- or polyether-containing groups include, by way of example, alkylene oxides, poly(alkylene oxides), such as ethylene oxide, propylene oxide, butylene oxide, poly(ethylene oxide), poly(ethylene glycol), poly(propylene oxide), poly(butylene oxide), and mixtures or copolymers thereof, alkylene oxides of the general formula -(R 2 OR 3 ) t an ether or polyether group (where R 2 is a bond, a substituted or unsubstituted alkyl, cycloalkyl, or aryl group as defined herein, and R 3 is a bond, a substituted or unsubstituted alkyl, cycloalkyl, or aryl group as defined herein, and t is at least 1, such as, for example, —CH2CH2OC6H5 and CH2—CH2—CH2—O—CH2—(CF2) z -H, and z is 1 to 6, -CH2CH2OC2H5, etc.

[0061] Representative examples of alkyl or arylamide groups as used herein include, for example, groups of the general formula -R 4 C(O)NR 5 R 6 where R 4 , R 5 and R 6 are independently C1-C 30 hydrocarbons, e.g., R 4 is an alkylene group, an arylene group, or a cycloalkylene group, and R 5 and R 6 can be alkyl, aryl, cycloalkyl, and the like, as defined herein.

[0062] Representative examples of alkyl or arylamine groups as used herein include, for example, groups of the general formula -R 7 NR 8 R 9 wherein R 7 is C2-C 30 alkylene, arylene, or cycloalkylene; R 8 and R 9 are independently C-C groups, such as alkyl, aryl, or cycloalkyl groups as defined herein. 30 It is a hydrocarbon.

[0063] Representative examples of heterocyclic ring groups for use herein include, by way of example, substituted or unsubstituted stable 3- to about 30-membered ring radicals containing carbon atoms and 1 to 5 heteroatoms (e.g., nitrogen, phosphorus, oxygen, sulfur, and mixtures thereof). Heterocyclic ring radicals suitable for use herein may be monocyclic, bicyclic, or tricyclic ring systems and may include fused, bridged, or spiro ring systems, and the nitrogen, phosphorus, carbon, oxygen, or sulfur atoms in the heterocyclic ring radical may be optionally oxidized to various oxidation states. Furthermore, the nitrogen atom may be optionally quaternized, and the ring radical may be partially or fully saturated (i.e., heteroaromatic or heteroaryl aromatic).

[0064] Representative examples of heteroaryl groups for use herein include, by way of example, substituted or unsubstituted heterocyclic ring radicals, as defined herein. The heteroaryl ring radical may be attached to the main structure at any heteroatom or carbon atom that results in the creation of a stable structure.

[0065] Representative examples of heteroarylalkyl groups for use herein include, by way of example, a substituted or unsubstituted heteroaryl ring radical, as defined herein, directly attached to an alkyl group, as defined herein. The heteroarylalkyl radical may be attached to the main structure at any carbon atom from the alkyl group that results in the creation of a stable structure.

[0066] Representative examples of heterocyclic groups for use herein include, by way of example, substituted or unsubstituted heterocyclic ring radicals, as defined herein. The heterocyclic ring group may be attached to the main structure at any heteroatom or carbon atom that results in the creation of a stable structure.

[0067] Representative examples of heterocycloalkyl groups for use herein include, by way of example, a substituted or unsubstituted heterocyclic ring radical, as defined herein, directly attached 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 that results in the creation of a stable structure.

[0068] The substituents in "substituted oxygen," "substituted nitrogen," "substituted sulfur," "substituted alkyl," "substituted alkylene," "substituted cycloalkyl," "substituted cycloalkylalkyl," "substituted cycloalkenyl," "substituted arylalkyl," "substituted aryl," "substituted heterocyclic ring," "substituted heteroaryl ring," "substituted heteroarylalkyl," "substituted heterocycloalkyl ring," "substituted cyclic ring" can 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, substituted heterocycloalkyl ring, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic ring, etc.

[0069] Representative examples of RAFT agents for use in the present invention include -cyano-4-(dodecylsulfanylthiocarbonyl)sulfanylpentanoic acid, S-cyanomethyl-5-dodecyltrithiocarbonate, S-(2-cyano-2-propyl)-S-dodecyltrithiocarbonate, 3-benzylsulfanylthiocarbonylsulfanylpropionic acid, cumyldithiobenzoate, 2-cyanoprop-2-yldithiobenzoate (i.e., cyanoisopropyldithiobenzoate), 4-thiobenzoylsulfanyl-4-cyanopentanoic acid (TCA), S,S'-bis(α,α'-dimethyl-α"-acetate),

[0033] Examples of suitable dodecyltrithiocarbonyl thiol compounds include, but are not limited to, 2-(dodecyltrithiocarbonyl)-trithiocarbonate (BATC), benzyldodecyltrithiocarbonate, ethyl-2-dodecyltrithiocarbonyl)propionate, S-sec propionic acid and O-ethyl xanthogenate, α-ethylxanthylphenylacetic acid, ethyl α-(o-ethylxanthyl)propionate, ethyl α-(ethylxanthyl)phenylacetate, ethyl 2-(dodecyltrithiocarbonyl)phenylacetate, ethyl 2-(dodecyltrithiocarbonyl)propionate, 2-(dodecylthiocarbonylthiol)propanoic acid, and the like, and mixtures thereof.

[0070] 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 agents can be prepared as illustrated in Schemes I-VII below. Scheme I [ka] Scheme II [ka] Scheme III [ka] Scheme IV [ka] Scheme V [ka]

[0071] The block copolymers disclosed herein can be obtained in a first step (a) by (1) mixing either an ethylenically unsaturated monomer or an ethylenically unsaturated hydrophilic monomer having a ring-opening reactive functional group with a RAFT agent, (2) adding a polymerization initiator, and (3) exposing the monomer / RAFT agent / initiator mixture to a heat source. Suitable initiators include, for example, free radical-generating polymerization initiators of the type represented by acetyl peroxide, lauroyl peroxide, decanoyl peroxide, coprylyl peroxide, benzoyl peroxide, tert-butyl peroxypivalate, sodium percarbonate, tert-butyl peroctoate, and azobis-isobutyronitrile (AIBN).

[0072] The reaction can be carried out at a temperature of about 15°C to about 120°C for a time of about 30 minutes to about 48 hours. If desired, the reaction can be carried out in the presence of a suitable solvent. Suitable solvents are, in principle, all solvents that dissolve the monomers used, such as 1,4-dioxane, hexanol, dimethylformamide, acetone, cyclohexanone, toluene, etc., and mixtures thereof.

[0073] In an exemplary embodiment, the ethylenically unsaturated monomer having a ring-opening reactive functionality, or the ethylenically unsaturated hydrophilic monomer, is used in an amount ranging from about 10 to about 50 wt % based on the total weight of the mixture. In an exemplary embodiment, the RAFT agent is used in an amount ranging from about 0.5 to about 3 wt % based on the total weight of the mixture. The level of initiator used varies within the range of 0.01 to 2 wt % of the monomer mixture. If desired, the above-described monomer mixture is heated while adding a free radical generator.

[0074] Next, in step (b), the product obtained in step (a) is mixed with the other of the ethylenically unsaturated monomer having a ring-opening reactive functional group or the ethylenically unsaturated hydrophilic monomer and an initiator, and exposed to a heat source until the desired block copolymer as described above is formed. In an exemplary embodiment, the other of the ethylenically unsaturated monomer having a ring-opening reactive functional group or the ethylenically unsaturated hydrophilic monomer is used in an amount ranging from about 10 to about 50 wt %, based on the total weight of the mixture. In an exemplary embodiment, the product obtained in step (a) is used in an amount ranging from about 1 to about 20 wt %, based on the total weight of the mixture.

[0075] A non-limiting schematic of a synthetic method for producing block copolymers using a RAFT agent is shown below in Scheme VI. Scheme VI [ka] Here, m is about 50 to about 300, n is 1 to about 30, and x is about 100 to about 1,000.

[0076] When the block copolymers disclosed herein are obtained by ATRP polymerization, the ethylenically unsaturated groups can be introduced by appropriately selecting an appropriate ATRP initiator or by substitution of terminal halogen atoms. ATRP groups suitable for the present invention include optional monofunctional or difunctional ATRP groups well known to those skilled in the art. A comprehensive review of the use of ATRP initiators or substitution of terminal halogen atoms using electrophilic, nucleophilic, or radical reactions to produce telechelic polymers is disclosed, for example, in Matyjaszewski, K., and Xia, J. Chem. Rev., 101, 2921-2990 (2001).

[0077] In one embodiment, useful ATRP groups include ethylenically unsaturated ATRP initiators, such as vinyl-functionalized ATRP initiators, such as prop-2-enyl-2′-bromoisobutyrate, vinyl chloroacetate, allyl chloroacetate, allyl bromide, etc. These initiators are used to polymerize either hydrophilic or hydrophobic monomers.

[0078] In another embodiment, useful ATRP groups include non-ethylenically unsaturated ATRP initiators that can be converted to ethylenically unsaturated initiators by the following process: Examples of such initiators include α-bromoisobutyric acid, hydroxyethyl 2-bromopropionate, glycidol 2-bromopropionate, t-butyl 2-bromopropionate, and 4-bromobenzyl bromide.

[0079] In an exemplary embodiment, the block copolymer is obtained by ATRP polymerization in a first step (a): (1) mixing either an ethylenically unsaturated monomer or an ethylenically unsaturated hydrophilic monomer having a ring-opening reactive functional group with an ATRP initiator and a suitable ATRP catalyst, such as copper(I) bromide, and placing the monomer / ATRP initiator / initiator mixture under a heat source. The reaction can be carried out at a temperature of about 15°C to about 120°C for a time period of about 30 minutes to about 48 hours. If desired, the reaction can be carried out in the presence of a suitable solvent. Suitable solvents are, in principle, any solvent that dissolves the monomers used, such as 1,4-dioxane, hexanol, dimethylformamide, acetone, cyclohexanone, toluene, etc., and mixtures thereof.

[0080] In an exemplary embodiment, the ethylenically unsaturated monomer or ethylenically unsaturated hydrophilic monomer having a ring-opening reactive functionality is used in an amount ranging from about 90% to about 99% by weight based on the total weight of the mixture. In an exemplary embodiment, the ATRP initiator is used in an amount ranging from about 0.5% to about 10% by weight based on the total weight of the mixture. The level of catalyst used varies from 0.01 to 2% by weight of the mixture of monomers.

[0081] Next, in step (b), the product obtained in step (a) is mixed with the other of the ethylenically unsaturated-containing monomer having a ring-opening reactive functional group or the ethylenically unsaturated-containing hydrophilic monomer and an initiator, and placed under a heat source as described above until the desired block copolymer is formed. In an exemplary embodiment, the other of the ethylenically unsaturated-containing monomer having a ring-opening reactive functional group or the ethylenically unsaturated-containing hydrophilic monomer is used in an amount ranging from about 90% to about 99% by weight based on the total weight of the mixture. In an exemplary embodiment, the product obtained in step (a) is used in an amount ranging from about 0.1% to about 10% by weight based on the total weight of the mixture.

[0082] The reaction can be carried out at a temperature of about 50° C. to about 150° C. for a time period of about 1 hour to about 48 hours. As mentioned above, the reaction can be carried out in the presence of a suitable solvent.

[0083] A non-limiting schematic of a synthetic method for producing block copolymers using an ATRP agent is shown below in Scheme VII. Scheme VII [ka] Here, m is about 50 to about 300, n is 1 to about 30, and x is about 100 to about 1,000.

[0084] As will be readily understood by those skilled in the art, a block copolymer contains a balance of monomer units derived from ethylenically unsaturated monomers having ring-opening reactive functional groups and monomer units derived from ethylenically unsaturated hydrophilic monomers. In a non-limiting exemplary embodiment, the number of monomer units in the block copolymer derived from ethylenically unsaturated monomers having ring-opening reactive functional groups can be from about 10 to about 60 units. In another non-limiting exemplary embodiment, the number of monomer units in the block copolymer derived from ethylenically unsaturated monomers having ring-opening reactive functional groups can be from about 15 to about 45 units. In another non-limiting exemplary embodiment, the number of monomer units in the block copolymer derived from ethylenically unsaturated monomers having ring-opening reactive functional groups can be from about 15 to about 30 units.

[0085] In a non-limiting exemplary embodiment, the number of monomer units in the block copolymer derived from the ethylenically unsaturated hydrophilic monomer can be from about 70 to about 250 units. In another non-limiting exemplary embodiment, the number of monomer units in the block copolymer derived from the ethylenically unsaturated hydrophilic monomer can be from about 100 to about 200 units. In another non-limiting exemplary embodiment, the number of monomer units in the block copolymer derived from the ethylenically unsaturated hydrophilic monomer can be from about 125 to about 175 units.

[0086] Any combination of the above ranges for the number of monomer units of the block copolymer derived from ethylenically unsaturation-containing monomers having ring-opening reactive functional groups and the number of monomer units of the block copolymer derived from ethylenically unsaturation-containing hydrophilic monomers is contemplated herein.

[0087] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, a biomedical device having one or more biomedical device surface reactive functional groups and / or one or more biomedical device surface protecting reactive functional groups is exposed to a block copolymer disclosed herein to form a surface coating on the biomedical device.

[0088] In a non-limiting exemplary embodiment, forming the surface coating can include diffusing the block copolymer into the biomedical device. For example, diffusing the block copolymer into the biomedical device can include at least (a) immersing the biomedical device in a swelling solution comprising one or more solvents and the block copolymer; and (b) removing the biomedical device from the swelling solution to provide the biomedical device comprising the block copolymer diffused within the biomedical device. In other words, diffusion of the block polymer within the biomedical device is achieved by swelling of the biomedical device, such that upon reversal of the swelling, the block copolymer diffuses and becomes entrapped within the biomedical device.

[0089] In an exemplary embodiment, step (a) above involves immersing the biomedical device in one or more solvent solutions and the block copolymer for a time sufficient to swell the biomedical device. Generally, the one or more solvent solutions can include, for example, solvents capable of swelling the biomedical device and solubilizing the block copolymer. In one embodiment, the one or more solvent solutions can include, for example, low-molecular-weight alcohol solvents, aliphatic hydrocarbon solvents, alicyclic hydrocarbon solvents, ketone solvents, nitrile solvents, amide-containing solvents, and mixtures thereof. Suitable low-molecular-weight alcohols include, for example, low-molecular-weight alcohols having about 1 to about 13 carbon atoms and / or a molecular weight of about 200 or less. Suitable low-molecular-weight alcohols can be selected from a variety of low-molecular-weight monohydric alcohols, each containing about 1 to about 13 carbon atoms. Suitable monohydric alcohols include, for example, methanol, ethanol, propanol, isopropyl alcohol, butanol, isobutyl alcohol, tert-butyl alcohol, hexanol, 2-ethylhexanol, dodecanol, and the like. Suitable aliphatic or alicyclic hydrocarbon solvents include, for example, pentane, hexane, heptane, cyclohexane, and the like.

[0090] Suitable ketone solvents include, for example, acetone, methyl ethyl ketone, diethyl ketone, methyl propyl ketone, methyl isopropyl ketone, ethyl propyl ketone, ethyl isopropyl ketone, dipropyl ketone, diisopropyl ketone, methyl butyl ketone, methyl isobutyl ketone, methyl sec-butyl ketone, methyl tert-butyl ketone, ethyl butyl ketone, ethyl isobutyl ketone, ethyl sec-butyl ketone, ethyl tert-butyl ketone, propyl butyl ketone, isopropyl butyl ketone, propyl isobutyl ketone, propyl sec-butyl ketone, propyl tert-butyl ketone, isopropyl isobutyl ketone, isopropyl sec-butyl ketone, isopropyl tert-butyl ketone, dibutyl ketone, diisobutyl ketone, di-sec-butyl ketone, di-tert-butyl ketone, butyl isobutyl ketone, butyl sec-butyl ketone, butyl tert-butyl ketone, isobutyl sec-butyl ketone, isobutyl tert-butyl ketone, sec-Butyl tert-butyl ketone, 5-heptanone, 5-methyl-2-hexanone (methyl isoamyl ketone), 4-methyl-2-hexanone, 3-methyl-2-hexanone, 3,4-dimethyl-2-pentanone, 3,3-dimethyl-2-pentanone, 4,4-dimethyl-2-pentanone, 3-octanone, 4-methyl-3-heptanone, 5-methyl-3-heptanone, 6-methyl-3-heptanone, 4,4-dimethyl-3-hexanone, 4,5-dimethyl-3-hexanone, 5,5-dimethyl Examples of ketone solvents include methyl-3-hexanone, 4-nonanone, 5-methyl-4-octanone, 6-methyl-4-octanone, 7-methyl-4-octanone, 5,5-dimethyl-4-neptanone, 5,6-dimethyl-4-heptanone, 6,6-dimethyl-4-heptanone, 2-undecanone, cyclopropanone, cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone, cyclooctanone, cyclononanone, cyclodecanone, cycloundecanone, cyclododecanone, and the like, and combinations thereof. In one embodiment, the ketone solvent is acetone.

[0091] Suitable nitrile solvents include, for example, saturated or unsaturated aliphatic, alicyclic, or aromatic compounds containing a nitrile group. Nitriles include compounds containing heteroatoms such as those selected from Groups 13, 14, 15, 16, and 17 of the Periodic Table of the Elements. Representative examples of nitriles useful in the present invention include acetonitrile, propionitrile, isopropionitrile, butyronitrile, isobutyronitrile, valeronitrile, isovaleronitrile, trimethylacetonitrile, hexanenitrile, heptanenitrile, heptyl cyanide, octyl cyanide, undecanenitrile, malononitrile, succinonitrile, glutaronitrile, adiponitrile, sebaconitrile, allyl cyanide, acrylonitrile, crotononitrile, methacrylonitrile, fumaronitrile, tetracyanoethylene, cyclopentanecarbonitrile, cyclohexanecarbonitrile, dichloroacetonitrile, fluoroacetonitrile, trichloroacetonitrile, benzonitrile, benzyl cyanide, 2-methylbenzyl cyanide, 2-chlorobenzonitrile, 3-chlorobenzonitrile, 4-chlorobenzonitrile, o-tolunitrile, m-tolunitrile, p-tolunitrile, and the like, and mixtures thereof. In one embodiment, the nitrile solvent is acetonitrile.

[0092] Suitable amide group-containing solvents include, for example, dimethylformamide, N-methylformanilide, N-formylpiperidine, N-formylmorpholine, dimethylacetamide, N-methylpyrrolidone, N,N-dimethylbenzamide, and mixtures thereof. In one embodiment, the amide group-containing solvent is N-methylpyrrolidone.

[0093] In one embodiment, the one or more solvent solutions may further comprise water in combination with any of the aforementioned solvents. For example, the one or more solvent solutions may be a mixture comprising about 25% to about 75% by weight of one or more solvent solutions and about 75% to about 25% by weight of water. In another embodiment, the mixture may comprise about 40% to about 60% by weight of one or more solvent solutions and about 60% to about 40% by weight of water.

[0094] The biomedical device is immersed in the one or more solvent solutions and the block copolymer for a time sufficient to swell the biomedical device. In one embodiment, the biomedical device is immersed in the one or more solvent solutions and the block copolymer for a time ranging from about 5 minutes to about 120 minutes. In one embodiment, the biomedical device is immersed in the one or more solvent solutions and the block copolymer for a time ranging from about 5 minutes to about 60 minutes. In one embodiment, the biomedical device is immersed in the one or more solvent solutions and the block copolymer for a time ranging from about 10 minutes to about 35 minutes.

[0095] As the biomedical device swells, the block copolymer diffuses into the swollen biomedical device. The biomedical device is then removed from the solvent solution to provide a biomedical device with the block copolymer diffused therein and forming a surface coating on the biomedical device. In step (b), the swollen biomedical device can be immersed in one or more solvent solutions containing the block copolymer to deswell the biomedical device and entrap the block copolymer within the biomedical device. Suitable solvent solutions include, for example, water and any of the aforementioned low molecular weight alcohol solvents, aliphatic hydrocarbon solvents, alicyclic hydrocarbon solvents, ketone solvents, nitrile solvents, ether solvents, and amide group-containing solvents.

[0096] After the biomedical device has been deswelled, it is removed and optionally further immersed in a series of aqueous solutions to further deswell the biomedical device. Generally, the biomedical device can be immersed in one or more aqueous solutions for a time period ranging from about 5 minutes to about 20 minutes.

[0097] The deswollen biomedical device is then sterilized. In one embodiment, the deswollen biomedical device is sterilized by immersing the deswollen biomedical device in borate buffered saline and then placing it under autoclave conditions for at least about 5 minutes, or at least about 20 minutes, or at least 24 hours, or up to about 72 hours. The sterilized biomedical device is then rinsed with water and placed in a package with borate buffered saline. The package is sealed, and the biomedical device is again placed under autoclave conditions.

[0098] Alternatively, the deswollen biomedical device can be placed in a container with a reservoir containing the deswollen ophthalmic device and a sterile packaging solution. Examples of containers include conventional blister packs for biomedical devices. The container contains the deswollen biomedical device immersed in the solution and is hermetically sealed, for example, by sealing a lid to the packaging over the container. For example, the lid seals around the reservoir. The solution and deswollen biomedical device are sterilized while sealed in the packaging. Examples of sterilization techniques include subjecting the solution and deswollen ophthalmic device to thermal energy, microwave irradiation, gamma irradiation, or ultraviolet irradiation. Specific examples include heating the solution and deswollen ophthalmic device sealed in the packaging to a temperature of at least 100°C, or at least 120°C, such as by autoclaving.

[0099] In another non-limiting exemplary embodiment, the step of forming a surface coating can include exposing a biomedical device having one or more biomedical device surface reactive functional groups and / or one or more biomedical device surface protection reactive functional groups to a block copolymer comprising (a) monomer units derived from an ethylenically unsaturation-containing monomer having a ring-opening reactive functional group or a nucleophilic functional group complementary to the one or more biomedical device surface reactive functional groups and the one or more biomedical device surface protection reactive functional groups, and (b) monomer units derived from an ethylenically unsaturation-containing hydrophilic monomer, such that the ring-opening reactive functional groups of the monomer units derived from the ethylenically unsaturation-containing monomer having the ring-opening reactive functional group of the block copolymer are adsorbed, entangled, or covalently bonded to the one or more biomedical device surface reactive functional groups and the one or more biomedical device surface protection reactive functional groups of the biomedical device. Entanglement between the block copolymer and the biomedical device is understood to mean a structure formed by intermolecular or intramolecular crosslinking points between polymer chains, where the polymer chains cannot move normally and are confined to a bulk matrix. Furthermore, absorption of block copolymers into the lenses of biomedical devices involves intermolecular forces brought about by electrostatic interactions, hydrogen bonding, and van der Waals forces.

[0100] In a non-limiting exemplary embodiment, the biomedical device can be released from the mold assembly and then contacted with an aqueous packaging solution containing a block copolymer disclosed herein. For example, the biomedical device can be transferred to an individual lens package containing a buffered saline solution containing at least a block copolymer disclosed herein and sterilized. In a non-limiting exemplary embodiment, the block copolymer disclosed herein is present in the aqueous packaging solution in an amount ranging from about 0.01 to about 3 wt %, based on the total weight of the aqueous packaging solution. In another non-limiting exemplary embodiment, the block copolymer disclosed herein is present in the aqueous packaging solution in an amount ranging from about 0.01 to about 1.5 wt %, based on the total weight of the aqueous packaging solution. In yet another non-limiting exemplary embodiment, the block copolymer disclosed herein is present in the aqueous packaging solution in an amount ranging from about 0.01 to about 1 wt %, based on the total weight of the aqueous packaging solution. In yet another non-limiting exemplary embodiment, the block copolymer disclosed herein is present in the aqueous packaging solution in an amount ranging from about 0.05 to about 0.5 wt %, based on the total weight of the aqueous packaging solution.

[0001] Suitable packaging designs and materials are known in the art. The plastic packaging is peelably sealed with a film. Suitable sealing films are known in the art and include foils, polymer 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, steam sterilization or autoclaving the sealed container at a temperature of about 120°C or higher.

[0101] The packaging solutions of exemplary embodiments are physiologically compatible. Specifically, the solutions must be "ophthalmically safe" for use with lenses, such as contact lenses, meaning that contact lenses treated with the solution are generally suitable and safe for direct placement on the eye without rinsing, i.e., the solution is safe and comfortable for daily contact with the eye by contact lenses wetted with the solution. An ophthalmically safe solution has a tonicity and pH that is compatible with the eye and contains materials, and amounts thereof, that are non-cytotoxic according to ISO standards and U.S. Food and Drug Administration (FDA) regulations.

[0102] The packaging solution must also be sterile, in that the absence of microbial contamination in the product prior to release must be statistically demonstrated to the extent necessary for such a product. Liquid media useful in the present invention are selected to have no substantial adverse effect on the lenses being treated or cured, and to enable or facilitate one or more treatments of the lenses. The liquid media is preferably aqueous. Particularly useful aqueous liquid media are those derived from saline, such as conventional saline or conventional buffered saline solutions.

[0103] The pH of the solution is maintained within the range of about 6 to about 9, preferably about 6.5 to about 7.8. As mentioned above, additional buffers such as boric acid, sodium borate, potassium citrate, sodium citrate, citric acid, sodium bicarbonate, various mixed phosphate buffers (including combinations of NaHPO, NaHPO, and KHPO), their hydrates, and mixtures thereof, can be optionally added. Generally, buffers are used in amounts of about 0.05 to about 2.5% by weight of the solution, preferably about 0.1 to about 1.5% by weight. However, in certain embodiments, tris(hydroxymethyl)aminomethane or a salt thereof serves as the sole buffer.

[0104] In one embodiment, the aqueous packaging solution may further comprise one or more buffering agents. Suitable buffering agents include, for example, phosphate buffers, borate buffers, citrate buffers, etc. Suitable phosphate buffers may be any known phosphate buffer. In one embodiment, the phosphate buffer includes one or more of sodium hydrogen phosphate, disodium hydrogen phosphate, potassium hydrogen phosphate, dipotassium hydrogen phosphate, and any suitable hydrates thereof, such as monohydrate and heptahydrate. Suitable borate buffers may be any known borate buffer. In one embodiment, the borate buffer includes one or more of boric acid and sodium borate. Suitable citrate buffers may be any known citrate buffer. In one embodiment, the citrate buffer includes one or more of citric acid and sodium citrate.

[0105] In one embodiment, the one or more buffering agents are present in the packaging solution in an amount ranging from about 0.001 to about 2.0 wt %, based on the total weight of the packaging solution. In one embodiment, the one or more buffering agents are present in the packaging solution in an amount ranging from about 0.001 to about 1 wt %, based on the total weight of the packaging solution.

[0106] Typically, aqueous packaging solutions are also adjusted with a tonicity agent to approximate the osmolality of normal tears, equivalent to a 0.9% sodium chloride solution or a 2.5% glycerol solution. The solution is made substantially isotonic with saline alone or in combination; otherwise, simply mixing with sterile water to make it hypotonic or hypertonic would cause the lens to lose its desired optical parameters. Accordingly, excess saline can produce a hypertonic solution that causes stinging and eye irritation.

[0107] Examples of suitable tonicity adjusting agents include, but are not limited to, sodium chloride, potassium chloride, dextrose, glycerin, calcium chloride, magnesium chloride, and the like, and mixtures thereof. These buffering agents are typically used individually in amounts ranging from about 0.01 to about 2.5% w / v, preferably from about 0.2 to about 1.5% w / v. Preferably, the tonicity adjusting agent is used in an amount that results in a final osmolality of at least about 200 mOsm / kg, or from about 200 to about 400 mOsm / kg, or from about 250 to about 350 mOsm / kg, or from about 280 to about 320 mOsm / kg.

[0108] If desired, one or more additional components may be included in the packaging solution. Such one or more additional components may be selected to impart or provide at least one beneficial or desired property to the packaging solution. Such additional components may be selected from components conventionally used in one or more ophthalmic device care compositions. Such additional components include, for example, cleaning agents, wetting agents, nutrients, sequestering agents, viscosity-increasing agents, contact lens conditioning agents, antioxidants, and the like, and mixtures thereof. Each of these additional components may be included in the packaging solution in an amount effective to impart or provide a beneficial or desired property to the packaging solution. For example, such additional components may be included in the packaging solution in an amount similar to the amount of such components used in other (e.g., conventional) contact lens care products.

[0109] Useful sequestering agents include, but are not limited to, for example, disodium ethylenediaminetetraacetic acid, alkali metal hexametaphosphate, citric acid, sodium citrate, and the like, and mixtures thereof.

[0110] Useful viscosity-enhancing agents include, but are not limited to, for example, hydroxyethyl cellulose, hydroxymethyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol, and the like, and mixtures thereof.

[0111] Useful antioxidants include, but are not limited to, for example, sodium metabisulfite, sodium thiosulfate, N-acetylcysteine, butylated hydroxyanisole, butylated hydroxytoluene, and the like, and mixtures thereof.

[0112] A method for packaging and storing biomedical devices, e.g., ophthalmic devices such as contact lenses, includes at least packaging the ophthalmic device immersed in an aqueous packaging solution containing the block copolymer disclosed herein and sterilizing the packaged solution. The method may include immersing the ophthalmic device in the aqueous packaging solution immediately after the manufacture of the contact lens and before delivery to the customer / wearer. Alternatively, packaging and storage in the solution of the present application may occur at an intermediate point after the manufacture and transportation of the lens in a dry state, but before delivery to the end customer (wearer), where the dry lens is hydrated by immersing the lens in the packaging solution. Thus, packaging for delivery to the customer may include a sealed container containing one or more unused contact lenses immersed in the aqueous packaging solution.

[0113] In one embodiment, the method disclosed herein is outlined in Scheme I below. Scheme I [ka] Here, n is about 10 to about 60, m is about 70 to about 250, and x is about 100 to about 1000.

[0114] After polymerization is complete, any formed non-covalently bound monomers, oligomers, or polymers can be removed, for example, by treatment with an appropriate solvent. The resulting surface-modified biomedical device can be used "as is." In other words, no additional surface treatment steps need to be performed to modify the resulting surface-modified biomedical device. As used herein, the phrase "without additional surface treatment steps" is understood to mean that the outer surface of the surface-modified biomedical device of the present invention is not subjected to any treatment to further modify its surface, for example, by oxidation treatment, plasma treatment, grafting treatment, coating treatment, etc. It should be understood, however, that the devices disclosed herein may be coated with coatings, such as coloring or other aesthetic enhancements.

[0115] The following examples are provided to enable one skilled in the art to practice the invention and are merely illustrative of the invention and should not be read as limiting the scope of the invention, which is defined by the claims.

[0116] Various block copolymers were prepared and coated onto contact lenses as described below and characterized using standard test procedures as follows.

[0117] Contact Angle: Captive bubble contact angle data were 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 in all experiments was measured using the pendant drop method. A surface tension value of 70-72 dynes / cm was expected for 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 sample. The advancing contact angle is defined as the angle measured in water as the bubble recedes from the lens surface (water advances across the surface). All captive bubble data were collected using a high-speed digital camera focused on the sample / bubble interface. Contact angles were calculated in digital frames just before the contact line traveled across the sample / bubble interface. The receding contact angle is defined as the angle measured in water when an air bubble is swollen across the sample surface (water is receding from the surface).

[0118] Sessile Drop Contact Angle: Data was collected using a Kruss DSA instrument. The lens was wiped with a Kimwipe to remove excess water from the lens surface, and then the lens was mounted in a spherical mount. During the test, the cuvette was empty and a syringe was lowered from above to dispense a drop of water onto the lens. Measurements were captured and recorded by software.

[0119] Coefficient of friction: The equipment used was a TA Discovery Hybrid controlled stress rheometer equipped with a dedicated ring tool with a surface roughness of approximately 50 nm. To eliminate the influence of water loss from the surface, a dedicated lens holder was designed for use in aqueous environments.

[0120] method

[0121] Vertical force F on the target NThe tool is lowered onto the lens surface until it reaches 0.05 N. The programmed experiment is designed to measure the static friction force, the low-speed kinetic friction force, and the high-speed kinetic friction force in three concise steps.

[0122] Step 1: Static Friction Coefficient - The friction tool torque is increased from 0 μN·m to 500 μN·m at 2 μN·m / s while monitoring the friction tool speed (v). When the torque applied to the friction tool exceeds the static friction force on the lens surface, the tool begins to rotate freely. The torque at which the disc begins to rotate, the radius of the disc, and the applied normal force are used to calculate the static friction coefficient.

[0123] Step 2: Coefficient of slow kinetic friction - The friction tool is rotated at a constant "slow" speed, the tangential force is recorded, and the coefficient of slow kinetic friction is calculated from the average value over a 90 second period.

[0124] Step 3: High-Speed ​​Kinetic Friction Coefficient - Increase the rotation of the friction tool for 30 seconds and again average the tangential forces to calculate the high-speed kinetic friction coefficient.

[0125] Sudan Black dyeing test

[0126] Step 1: Gently wipe the coated lens to remove excess water.

[0127] Step 2: The lens is placed in a 0.2% by weight solution of Sudan Black B in mineral oil and stirred for 10 minutes.

[0128] Step 3: Remove the lenses from the staining solution and rinse vigorously with water to remove excess stain and oil.

[0129] Step 4: Observe the lens for dirt; dirty areas indicate an incomplete hydrophobic surface or coating.

[0130] Example 1A A glycidyl methacrylate-poly(ethylene glycol) methacrylate block copolymer with 210 PEG moieties is prepared using the ATRP block synthesis method.

[0131] Glycidyl methacrylate (14.21 g, 0.100 mmol) was polymerized via ATRP using α-bromoisobutyric acid initiator (0.39 g, 2.00 mmol), 1,1,4,7,10,10-hexamethyltriethylenetetramine ligand (0.023 g, 0.10 mmol), and copper(I) bromide catalyst (0.0143 g, 0.1 mmol). The glycidyl methacrylate, initiator, and ligand were dissolved in 30 mL of acetonitrile and purged with nitrogen for 1 hour. The catalyst was added, and the solution was purged with N2 for 10 minutes. The solution was placed in a 45°C oil bath and stirred for 2.5 hours. The solution was precipitated into methanol, filtered, and dried under vacuum. Next, mPEG-methacrylate (500) (15 g, 30 mmol) was added to polyglycidyl methacrylate (0.161 g, 0.10 mmol) dissolved in a small amount of acetone and 30 mL of toluene. The solution was purged under nitrogen for 1 hour. The reaction vessel was sealed and placed in an oil bath at 60 °C for 8 hours. The reaction solution was concentrated and extracted three times with hexane. The residue was dissolved in acetone and passed through an aluminum oxide column. The polymer solution was precipitated with ethyl ether and dried overnight in a vacuum oven at 30 °C to remove the ether.

[0132] The reaction is generally as follows: [ka] Here, m is 210, n is 15, and x is 500.

[0133] Example 1B Preparation of glycidyl methacrylate-poly(ethylene glycol) methacrylate block copolymers with 106 PEG moieties using the ATRP block synthesis method.

[0134] Glycidyl methacrylate (14.21 g, 0.100 mmol) was polymerized via ATRP using α-bromoisobutyric acid initiator (0.39 g, 2.00 mmol), 1,1,4,7,10,10-hexamethyltriethylenetetramine ligand (0.023 g, 0.10 mmol), and copper(I) bromide catalyst (0.0143 g, 0.1 mmol). The glycidyl methacrylate, initiator, and ligand were dissolved in 30 mL of acetonitrile and purged with nitrogen for 1 hour. The catalyst was added, and the solution was purged with N2 for 10 minutes. The solution was placed in a 45°C oil bath and stirred for 2.5 hours. The solution was precipitated into methanol, filtered, and dried under vacuum. Next, mPEG-methacrylate (500) (7.50 g, 15 mmol) was added to polyglycidyl methacrylate (0.161 g, 0.10 mmol) dissolved in a small amount of acetone and 30 mL of toluene. The solution was purged under nitrogen for 1 hour. The reaction vessel was sealed and placed in a 60 °C oil bath for 8 hours. The reaction solution was concentrated and extracted three times with hexane. The residue was dissolved in acetone and passed through an aluminum oxide column. The polymer solution was precipitated with ethyl ether and dried overnight in a vacuum oven at 30 °C to remove the ether.

[0135] Example 2 Preparation of glycidyl methacrylate-poly(ethylene glycol) methacrylate block copolymers using RAFT block synthesis methodology.

[0136] A 50 mL air-free flask was charged with glycidyl methacrylate (9.63 g, 67.77 mmol), 2-cyanoprop-2-yldithiobenzoate (0.30 g, 1.36 mmol), recrystallized Vazo-64 (AIBN, 22.3 mg, 0.136 mmol), and acetonitrile (15 mL). The reaction vessel was equipped with a magnetic stirrer, and nitrogen was bubbled through the solution for 30 minutes to remove dissolved oxygen. The reaction flask was then heated to 60 °C and held for 12 hours. The reaction mixture was then slowly added to 200 mL of ethyl ether with thorough mechanical stirring. The polymer precipitated and was collected by vacuum filtration. The solid was placed in a vacuum oven at 30 °C overnight, and the ether was removed, yielding 4.50 g of polymer (macro-CTA for subsequent reactions). Next, 3.06 g (0.845 mmol) of the dried polymer was placed in a 250 mL air-free flask with 116 mL of toluene and 43 mL of acetonitrile. The polymer (macro-CTA) was dissolved using a magnetic stirrer. Vazo-64 (AIBN, 13.9 mg, 0.084 mmol) and mPEG-methacrylate (500) (84.50 g, 168.90 mmol) were added to the flask, and the flask was aerated for 30 minutes to remove dissolved oxygen. The reaction flask was then heated to 60 °C and held for an additional 12 hours. The reaction mixture was then slowly added to 500 mL of ethyl ether and thoroughly mechanically stirred. The block polymer precipitated and was collected by vacuum filtration. The solid was left overnight in a vacuum oven at 30 °C to remove the ether.

[0137] The reaction is generally as follows: [ka] Here, m is 200, n is 15, and x is 500.

[0138] Example 3 Glycidyl methacrylate-methacryloyloxyethyl phosphorylcholine methacrylate block copolymers are prepared using the ATRP block synthesis method.

[0139] Glycidyl methacrylate-methacryloyloxyethyl phosphorylcholine methacrylate block copolymer was prepared in a manner similar to that described in Examples 1A and 1B. Methacryloyloxyethyl phosphorylcholine methacrylate (8.86 g, 30 mmol) was added to polyglycidyl methacrylate (0.161 g, 0.10 mmol) along with 30 mL of ethanol, as prepared in Examples 1A and 1B. The solution was purged under nitrogen for 1 hour. The reaction vessel was sealed and placed in a 60°C oil bath for 8 hours. The reaction solution was concentrated and extracted three times with acetonitrile. The residue was dissolved in ethanol and passed through an aluminum oxide column. The polymer solution was precipitated into ethyl ether and dried overnight in a vacuum oven at 30°C to remove the ether.

[0140] Example 4 Preparation of glycidyl methacrylate-dimethylacrylamide block copolymers using RAFT block synthesis methodology.

[0141] A 50 mL air-free flask was charged with distilled N,N-dimethylacrylamide (DMA, 9.9 g, 0.1 mol), 4-cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanoic acid (0.081 g, 0.2 mmol), recrystallized Vazo-64 (AIBN, 6.0 mg, 0.36 mmol), and toluene (25 mL). The reaction vessel was equipped with a magnetic stirrer, and nitrogen was bubbled through the solution for 30 minutes to remove dissolved oxygen. The reaction flask was then heated to 60 °C and held for 12 hours. The reaction mixture was then slowly added to 200 mL of ethyl ether and thoroughly stirred mechanically. The polymer precipitated and was collected by vacuum filtration.

[0142] The solid was placed in a vacuum oven at 30 °C overnight to remove the ether, leaving 9.35 g of polymer (macro-CTA for the next reaction). The dried polymer was placed in a 50 ml air-free flask with 25 ml of toluene using a magnetic stirrer to completely dissolve the polymer (macro-CTA). Vazo-64 (AIBN, 6.0 mg, 0.36 mmol) and glycidyl methacrylate (GMA, 0.46 g, 3.2 mmol) were added to the flask, and the flask was bubbled through the solution for 30 minutes to remove dissolved oxygen. The reaction flask was then heated to 60 °C and held for an additional 12 hours. The reaction mixture was then slowly added to 200 ml of ethyl ether and thoroughly mechanically stirred. The block polymer precipitated and was collected by vacuum filtration. The solid was placed in a vacuum oven at 30 °C overnight to remove the ether.

[0143] Examples 5 to 8 and Comparative Example 1 In this example, Soflens Daily Disposal (SDD) contact lenses were used, which are composed primarily of poly 2-hydroxymethacrylate, poly n-vinylpyrrolidone, ethylene glycol dimethacrylate, and allyl methacrylate.

[0144] SDD contact lenses were coated with the block copolymer of Example 1a. Each lens was placed in a polypropylene blister package with the packaging solutions shown in Table 1 below, added in weight percent amounts based on the total weight of the solution. [Table 1]

[0145] The lenses were then steam sterilized in packaging solution.

[0146] To determine the success of the coating process, the contact angle, coefficient of friction, and fingertip lubricity were evaluated. The lenses were found to have significantly higher lubricity than the control lens (uncoated) of Comparative Example 1.

[0147] The contact angles of SDD contact lenses coated with each of the block copolymers of Examples 5, 7, and 8, and the uncoated lens of Comparative Example 1, were evaluated in the phosphate buffered packaging solution of Table 1. The results are shown in Table 2 below. [Table 2]

[0148] The coefficient of friction of the SDD contact lenses coated with the block copolymer of Example 6 and the uncoated lens of Comparative Example 1 was evaluated in the phosphate buffered packaging solution of Table 1. As shown in Figure 1, the low-speed dynamic friction coefficient (0.25 rad / s) decreased with the coating of the lenses.

[0149] Example 9 and Comparative Example 2 In this example, a representative SiHY contact lens was used, which is composed primarily of polyHEMA and polyDMA.

[0150] The SiHY contact lenses were coated with a block copolymer of 4. The lenses were placed in polypropylene blister packs with the packaging solutions shown in Table 3 below (the amount of packaging solution is given in weight percent, based on the total weight of the solution). [Table 3]

[0151] The lenses were then steam sterilized in packaging solution.

[0152] To determine the success of the coating process, Sudan Black staining, sessile drop contact angle, and fingertip lubricity were evaluated. It was confirmed that the lenses had higher lubricity than the uncoated SiHY contact lenses of Comparative Example 2.

[0153] The Sudan Black staining and sessile drop contact angle of SiHY lenses were evaluated before and after sterilization in the packaging solutions listed in Table 3. Because Sudan Black binds to hydrophobic surfaces, less blue staining of the coated lenses indicates a more hydrophilic surface. Observation of the SiHY lenses after application of Sudan Black stain revealed significantly less blue staining of the coated lenses after sterilization, indicating a more hydrophilic surface.

[0154] Additionally, applying a coating to the lens reduced the contact angle. The results of the sessile drop data based on contact angle measurements are shown in Table 4 below. [Table 4]

[0155] Examples 10 to 11 and Comparative Example 3 In this example, a Metaphilicon A contact lens was used. The contact lens is made of HEMA and methacrylic acid.

[0156] Metaphilicon A contact lenses were coated with the block copolymers of Examples 1A and 1B, which had different PEG lengths, and packaged in polypropylene blister packs as shown in Table 5 below. [Table 5]

[0157] The lenses were then steam sterilized in a packaging solution containing the block copolymer.

[0158] The samples were then washed in a water bath for 24 hours before XPS analysis. The results revealed a change in the chemical composition of the lens surface. As shown in Figure 2, the normalized spectrum showed a significant increase in CO bonds, indicating the presence of PEG on the surface.

[0159] According to one aspect of the present invention, a biomedical device having a surface coating comprises a bulk material having one or more biomedical device surface reactive functional groups and / or one or more biomedical device surface protection reactive functional groups, and a surface coating, wherein the surface coating is derived from a block copolymer comprising: (a) monomer units derived from an ethylenically unsaturation-containing monomer having a ring-opening reactive functional group or a nucleolytic functional group complementary to the one or more biomedical device surface reactive functional groups and the one or more biomedical device surface protection reactive functional groups; and (b) monomer units derived from an ethylenically unsaturation-containing hydrophilic monomer.

[0160] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the surface coating comprises a block copolymer dispersed in a bulk material.

[0161] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the surface coating comprises a block copolymer adsorbed, entangled, or covalently bonded to the surface of the biomedical device via one or more biomedical device surface reactive functional groups and / or one or more biomedical device surface protecting reactive functional groups.

[0162] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the one or more biomedical device surface reactive functional groups of the biomedical device are selected from the group consisting of hydroxy groups, tosylate groups, mesylate groups, triflate groups, nosyloxy groups, amino groups, carboxy groups, carbonyl groups, aldehyde groups, sulfonic acid groups, sulfonyl chloride groups, isocyanato groups, carboxyanhydride groups, lactone groups, azlactone groups, epoxy groups, groups capable of undergoing a Michael addition type reaction, and mixtures thereof.

[0163] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the one or more biomedical device surface reactive functional groups of the biomedical device are selected from the group consisting of hydroxy groups, amino groups, carboxy groups, and mixtures thereof, and the ring-opening reactive functional groups complementary to the one or more biomedical device surface reactive functional groups are selected from the group consisting of azlactone groups, epoxy groups, and mixtures thereof.

[0164] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the ethylenically unsaturated-containing monomer having a ring-opening reactive functional group contains 2 to about 18 carbon atoms substituted with a reactive group selected from the group consisting of an azlactone group, an epoxy group, and mixtures thereof, and the ethylenically unsaturated-containing hydrophilic monomer contains 2 to about 18 carbon atoms substituted with a reactive group selected from the group consisting of an amide group, a carboxyanhydride group, a carboxy group, a hydroxy group, and mixtures thereof.

[0165] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the ethylenically unsaturation-containing monomer having a ring-opening reactive functionality is selected from the following: [ka] where R 2 , R 3 , and R 4 are each independently hydrogen or C1-C4 alkyl, and (Alk**) is C2-C 12 It is alkylene.

[0166] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the ethylenically unsaturated-containing hydrophilic monomer is selected from the group consisting of acrylamide, formamide, cyclic lactam, (meth)acrylated alcohol, ethylenically unsaturated polymerizable alkoxylated polymer, methacrylated sulfobetaine, methacrylated phosphocholine, and mixtures thereof.

[0167] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the ethylenically unsaturation-containing monomer having a ring-opening reactive functionality is represented by the following structure: [ka] Here, n is 1 to about 30, and the monomer unit derived from an ethylenically unsaturated hydrophilic monomer is a monomer unit derived from an ethylenically unsaturated hydrophilic monomer selected from the group consisting of acrylamide, formamide, cyclic lactam, (meth)acrylated alcohol, ethylenically unsaturated polymerizable alkoxylated polymer, methacrylated sulfobetaine, methacrylated phosphocholine, and mixtures thereof.

[0168] In one or more additional non-limiting exemplary embodiments, which can be combined with one or more of the preceding paragraphs, the block copolymer comprises from about 10 to about 60 monomer units derived from an ethylenically unsaturated-containing monomer having a ring-opening reactive functional group and from about 70 to about 250 monomer units derived from an ethylenically unsaturated-containing hydrophilic monomer.

[0169] In one or more additional non-limiting exemplary embodiments, which can be combined with one or more of the preceding paragraphs, the block copolymer comprises from about 15 to about 45 monomer units derived from an ethylenically unsaturated-containing monomer having a ring-opening reactive functional group and from about 100 to about 200 monomer units derived from an ethylenically unsaturated-containing hydrophilic monomer.

[0170] In one or more additional non-limiting exemplary embodiments, which can be combined with one or more of the preceding paragraphs, the block copolymer includes monomer units derived from glycidyl methacrylate and monomer units derived from poly(alkylene glycol).

[0171] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the block copolymer is a brush block copolymer.

[0172] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the block copolymer is a comb block copolymer.

[0173] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the biomedical device is an ophthalmic lens.

[0174] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the ophthalmic lens is a contact lens or an intraocular lens.

[0175] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the biomedical device is a silicone contact lens or an intraocular device.

[0176] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the biomedical device is a silicone hydrogel continuous wear lens.

[0177] According to another aspect of the present invention, a method for making a biomedical device having a surface coating comprises forming a surface coating on a biomedical device having one or more biomedical device surface reactive functional groups and / or one or more biomedical device surface protection reactive functional groups, wherein the surface coating is derived from a block copolymer comprising: (a) monomer units derived from an ethylenically unsaturation-containing monomer having a ring-opening reactive functional group or a nucleolytic functional group complementary to the one or more biomedical device surface reactive functional groups and the one or more biomedical device surface protection reactive functional groups; and (b) monomer units derived from an ethylenically unsaturation-containing hydrophilic monomer.

[0178] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, forming the surface coating includes diffusing the block copolymer into the biomedical device.

[0179] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, diffusing the block copolymer into the biomedical device can include (a) immersing the biomedical device in a swelling solution comprising one or more solvents and the block copolymer; and (b) removing the biomedical device from the swelling solution to provide a biomedical device comprising the block copolymer diffused into the biomedical device.

[0180] In one or more additional non-limiting exemplary embodiments, which can be combined with one or more of the preceding paragraphs, forming the surface coating comprises exposing a biomedical device having one or more biomedical device surface reactive functional groups and / or one or more biomedical device surface protection reactive functional groups to a block copolymer comprising (a) monomer units derived from ethylenically unsaturation-containing monomers having ring-opening reactive functional groups complementary to the one or more biomedical device surface reactive functional groups, and (b) monomer units derived from ethylenically unsaturation-containing hydrophilic monomers, such that the ring-opening reactive functional groups of the monomer units derived from the ethylenically unsaturation-containing monomers having ring-opening reactive functional groups of the block copolymer adsorb, entangle, or covalently bond to the one or more biomedical device surface reactive functional groups and the one or more biomedical device surface protection reactive functional groups of the biomedical device.

[0181] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the one or more biomedical device surface reactive functional groups of the biomedical device are selected from the group consisting of hydroxy groups, tosylate groups, mesylate groups, triflate groups, nosyloxy groups, amino groups, carboxy groups, carbonyl groups, aldehyde groups, sulfonic acid groups, sulfonyl chloride groups, isocyanato groups, carboxyanhydride groups, lactone groups, azlactone groups, epoxy groups, groups capable of undergoing a Michael addition type reaction, and mixtures thereof.

[0182] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the one or more biomedical device surface reactive functional groups of the biomedical device are selected from the group consisting of hydroxy groups, amino groups, carboxy groups, and mixtures thereof, and the ring-opening reactive functional groups complementary to the one or more biomedical device surface reactive functional groups are selected from the group consisting of azlactone groups, epoxy groups, and mixtures thereof.

[0183] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the ethylenically unsaturated-containing monomer having a ring-opening reactive functional group contains 2 to about 18 carbon atoms substituted with a reactive group selected from the group consisting of an azlactone group, an epoxy group, and mixtures thereof, and the ethylenically unsaturated-containing hydrophilic monomer contains 2 to about 18 carbon atoms substituted with a reactive group selected from the group consisting of an amide group, a carboxyanhydride group, a carboxy group, a hydroxy group, and mixtures thereof.

[0184] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the ethylenically unsaturation-containing monomer having a ring-opening reactive functionality is selected from the following: [ka] R 2 , R 3 and R 4 are each independently hydrogen or C1-C4 alkyl, and (Alk**) is C2-C 12 It is alkylene.

[0185] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the ethylenically unsaturated-containing hydrophilic monomer is selected from the group consisting of acrylamide, formamide, cyclic lactam, (meth)acrylated alcohol, ethylenically unsaturated polymerizable alkoxylated polymer, methacrylated sulfobetaine, methacrylated phosphocholine, and mixtures thereof.

[0186] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the ethylenically unsaturation-containing monomer having a ring-opening reactive functionality is represented by the following structure: [ka] Here, n is 1 to about 30, and the monomer unit derived from an ethylenically unsaturated hydrophilic monomer is a monomer unit derived from an ethylenically unsaturated hydrophilic monomer selected from the group consisting of acrylamide, formamide, cyclic lactam, (meth)acrylated alcohol, ethylenically unsaturated polymerizable alkoxylated polymer, methacrylated sulfobetaine, methacrylated phosphocholine, and mixtures thereof.

[0187] In one or more additional non-limiting exemplary embodiments, which can be combined with one or more of the preceding paragraphs, the block copolymer comprises from about 10 to about 60 monomer units derived from an ethylenically unsaturated-containing monomer having a ring-opening reactive functional group and from about 70 to about 250 monomer units derived from an ethylenically unsaturated-containing hydrophilic monomer.

[0188] In one or more additional non-limiting exemplary embodiments, which can be combined with one or more of the preceding paragraphs, the block copolymer comprises from about 15 to about 45 monomer units derived from an ethylenically unsaturated-containing monomer having a ring-opening reactive functional group and from about 100 to about 200 monomer units derived from an ethylenically unsaturated-containing hydrophilic monomer.

[0189] In one or more additional non-limiting exemplary embodiments, which can be combined with one or more of the preceding paragraphs, the block copolymer includes monomer units derived from glycidyl methacrylate and monomer units derived from poly(alkylene glycol).

[0190] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the block copolymer is a brush block copolymer.

[0191] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the block copolymer is a comb block copolymer.

[0192] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the biomedical device is an ophthalmic lens.

[0193] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the ophthalmic lens is a contact lens or an intraocular lens.

[0194] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the biomedical device is a silicone contact lens or an intraocular device.

[0195] In one or more additional non-limiting exemplary embodiments, which may be combined with one or more of the preceding paragraphs, the biomedical device is a silicone hydrogel continuous wear lens.

[0196] For the sake of brevity, various features disclosed herein are described in the context of a single embodiment, but may also be provided separately or in any suitable subcombination.All combinations of 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 compositions of the present invention, and are disclosed herein, as if each and every such subcombination were individually and expressly disclosed herein.

[0197] It is 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 for 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. Moreover, those skilled in the art will envision other modifications within the scope and spirit of the additional features and advantages described herein.

Claims

1. 1. A biomedical device having a surface coating, comprising: a bulk material having one or more biomedical device surface reactive functional groups and / or one or more biomedical device surface protection reactive functional groups; and the surface coating, wherein the surface coating is derived from a block copolymer comprising: (a) monomer units derived from an ethylenically unsaturation-containing monomer having a ring-opening reactive functional group or a nucleolytic functional group complementary to the one or more biomedical device surface reactive functional groups and the one or more biomedical device surface protection reactive functional groups; and (b) monomer units derived from an ethylenically unsaturation-containing hydrophilic monomer.

2. 10. The biomedical device of claim 1, wherein said surface coating comprises said block copolymer dispersed in said bulk material.

3. 10. The biomedical device of claim 1, wherein said surface coating comprises said block copolymer adsorbed, entangled, or covalently bonded to the surface of said biomedical device via said one or more biomedical device surface reactive functional groups and / or said one or more biomedical device surface protecting reactive functional groups.

4. 4. The biomedical device of any one of claims 1 to 3, wherein said one or more biomedical device surface reactive functional groups of said biomedical device are selected from the group consisting of hydroxy groups, tosylate groups, mesylate groups, triflate groups, nosyloxy groups, amino groups, carboxy groups, carbonyl groups, aldehyde groups, sulfonic acid groups, sulfonyl chloride groups, isocyanato groups, carboxyanhydride groups, lactone groups, azlactone groups, epoxy groups, groups capable of undergoing a Michael addition type reaction, and mixtures thereof.

5. 4. The biomedical device of any one of claims 1 to 3, wherein the one or more biomedical device surface reactive functional groups of the biomedical device are selected from the group consisting of hydroxy groups, amino groups, carboxy groups, and mixtures thereof, and the ring-opening reactive functional groups complementary to the one or more biomedical device surface reactive functional groups are selected from the group consisting of azlactone groups, epoxy groups, and mixtures thereof.

6. 6. The biomedical device of any one of claims 1-5, wherein the ethylenically unsaturated-containing monomer having a ring-opening reactive functional group contains 2 to about 18 carbon atoms substituted with a reactive group selected from the group consisting of an azlactone group, an epoxy group, and mixtures thereof, and the ethylenically unsaturated-containing hydrophilic monomer contains 2 to about 18 carbon atoms substituted with a reactive group selected from the group consisting of an amide group, a carboxyanhydride group, a carboxy group, a hydroxy group, and mixtures thereof.

7. The ethylenically unsaturated monomer having a ring-opening reactive functional group is selected from the following: 【Chemistry 1】 R ２ , R ３ and R ４ are each independently hydrogen or C １ -C ４ alkyl, and (Alk**) is C ２ -C １２ The biomedical device of any one of claims 1 to 5, which is alkylene.

8. The ethylenically unsaturated monomer having a ring-opening reactive functional group is represented by the following structure: 【Chemistry 2】 6. The biomedical device of any one of claims 1 to 5, wherein n is from 1 to about 30, and the monomeric units derived from hydrophilic monomers containing ethylenic unsaturation are monomeric units derived from hydrophilic monomers containing ethylenic unsaturation selected from the group consisting of acrylamide, formamide, cyclic lactams, (meth)acrylated alcohols, ethylenically unsaturated polymerizable alkoxylated polymers, methacrylated sulfobetaines, methacrylated phosphocholines, and mixtures thereof.

9. 9. The biomedical device of any one of claims 1 to 8, wherein said ethylenically unsaturated containing hydrophilic monomer is selected from the group consisting of acrylamide, formamide, cyclic lactam, (meth)acrylated alcohol, ethylenically unsaturated polymerizable alkoxylated polymer, methacrylated sulfobetaine, methacrylated phosphocholine and mixtures thereof.

10. 10. The biomedical device of any one of claims 1-9, wherein said block copolymer comprises from about 10 to about 60 monomer units derived from ethylenically unsaturated-containing monomers having ring-opening reactive functional groups and from about 70 to about 250 monomer units derived from ethylenically unsaturated-containing hydrophilic monomers.

11. 10. The biomedical device of any one of claims 1-9, wherein said block copolymer comprises about 15 to about 45 monomer units derived from ethylenically unsaturated-containing monomers having ring-opening reactive functional groups and about 100 to about 200 monomer units derived from ethylenically unsaturated-containing hydrophilic monomers.

12. 10. The biomedical device of claim 1, wherein the block copolymer comprises monomer units derived from glycidyl methacrylate and monomer units derived from poly(alkylene glycol).

13. The biomedical device of any one of claims 1 to 12, wherein the block copolymer is a brush block copolymer.

14. The biomedical device of any one of claims 1 to 12, wherein the block copolymer is a comb block copolymer.

15. The biomedical device of claims 1 to 14, which is an ophthalmic lens.

16. 16. The biomedical device of claim 15, wherein the ophthalmic lens is a contact lens or an intraocular lens.

17. The biomedical device of any one of claims 1 to 14, which is a silicone contact lens or an intraocular device.

18. 15. The biomedical device of any one of claims 1 to 14, which is a silicone hydrogel continuous wear lens.

19. 1. A method for making a biomedical device having a surface coating, comprising forming a surface coating on a biomedical device having one or more biomedical device surface reactive functional groups and / or one or more biomedical device surface protection reactive functional groups, wherein the surface coating is derived from a block copolymer comprising: (a) monomer units derived from an ethylenically unsaturation-containing monomer having a ring-opening reactive functional group or a nucleolytic functional group complementary to the one or more biomedical device surface reactive functional groups and the one or more biomedical device surface protection reactive functional groups; and (b) monomer units derived from an ethylenically unsaturation-containing hydrophilic monomer.

20. 20. The method of claim 19, wherein forming the surface coating comprises diffusing the block copolymer into the biomedical device.

21. 21. The method of claim 20, wherein diffusing the block copolymer into the biomedical device comprises: (a) immersing the biomedical device in a swelling solution comprising one or more solvents and the block copolymer; and (b) removing the biomedical device from the swelling solution to provide a biomedical device comprising the block copolymer diffused into the biomedical device.

22. 20. The method of claim 19, wherein forming the surface coating comprises adsorbing, entangled, or covalently bonding the block copolymer to the surface of the biomedical device via the one or more biomedical device surface reactive functional groups and / or the one or more biomedical device surface protecting reactive functional groups.

23. 20. The method of claim 19, wherein forming the surface coating comprises exposing the biomedical device, having one or more biomedical device surface reactive functional groups and / or one or more biomedical device surface protection reactive functional groups, to a block copolymer comprising (a) monomer units derived from ethylenically unsaturation-containing monomers having ring-opening reactive functional groups complementary to the one or more biomedical device surface reactive functional groups, and (b) monomer units derived from ethylenically unsaturation-containing hydrophilic monomers, such that the ring-opening reactive functional groups of the monomer units derived from ethylenically unsaturation-containing monomers having ring-opening reactive functional groups of the block copolymer adsorb, entangle, or covalently bond to the one or more biomedical device surface reactive functional groups and the one or more biomedical device surface protection reactive functional groups of the biomedical device.

24. 24. The method of any one of claims 19-23, wherein the one or more biomedical device surface reactive functional groups of the biomedical device are selected from the group consisting of hydroxy groups, amino groups, carboxy groups, and mixtures thereof, and the ring-opening reactive functional groups complementary to the one or more biomedical device surface reactive functional groups are selected from the group consisting of azlactone groups, epoxy groups, and mixtures thereof.

25. 25. The method of any one of claims 19 to 24, wherein the block copolymer comprises from about 10 to about 60 monomer units derived from an ethylenically unsaturated-containing monomer having a ring-opening reactive functional group and from about 70 to about 250 monomer units derived from an ethylenically unsaturated-containing hydrophilic monomer.

26. The method of any one of claims 19 to 25, wherein the block copolymer comprises monomer units derived from glycidyl methacrylate and monomer units derived from poly(alkylene glycol).

27. 1. Use of a block copolymer for forming a surface coating on the surface of a biomedical device comprising a bulk material having one or more biomedical device surface reactive functional groups and / or one or more biomedical device surface protection reactive functional groups, wherein the block copolymer comprises: (a) monomer units derived from an ethylenically unsaturation-containing monomer having a ring-opening reactive functional group or a nucleolytic functional group complementary to the one or more biomedical device surface reactive functional groups and the one or more biomedical device surface protection reactive functional groups; and (b) monomer units derived from an ethylenically unsaturation-containing hydrophilic monomer.

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