Biomedical Devices

Abstract

A biomedical device is disclosed that is the polymerization product of a mixture comprising: (a) one or more difunctional isocyanates; (b) one or more polyalcohols; (c) one or more dihydroxy-terminated polysiloxane prepolymers; and (d) one or more polyoxazoline polyols having a weight average molecular weight of about 1000 Daltons or greater.

Description

[Technical Field]

[0001] Priority claims This application claims priority to U.S. Provisional Patent Application No. 63 / 161,002, entitled "Biomedical Devices," filed March 15, 2021, the contents of which are incorporated herein by reference in their entirety. [Background technology]

[0002] Biomedical devices, such as ophthalmic lenses, made from siloxy-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 an equilibrium state, while non-hydrogels do not absorb significant amounts of water. Regardless of their water content, both hydrogel and non-hydrogel siloxy and / or fluorinated contact lenses tend to be relatively hydrophobic and have non-wetting surfaces.

[0003] Hydrogels represent a desirable class of materials for many biomedical applications, including contact lenses and intraocular lenses. Hydrogels are hydrated crosslinked polymer systems that contain water in an equilibrium state. Silicone hydrogels are a well-known type of hydrogel, characterized by the inclusion of siloxy-containing materials. The advantage of silicone hydrogels over non-silicone hydrogels is that they typically have higher oxygen permeability due to the inclusion of siloxy-containing monomers. Most existing hydrogels are based on free radical polymerization of monomers containing crosslinkers, making these materials thermosetting polymers.

[0004] In the field of biomedical devices such as contact lenses, various physical and chemical properties, such as oxygen permeability, wettability, material strength and stability, are just a few of the factors that must be carefully balanced to provide a usable contact lens. For example, the cornea receives its oxygen supply from contact with the atmosphere, so good oxygen permeability is an important characteristic for certain contact lens materials. Wettability is also important in that if the lens is not sufficiently wettable, it will not remain lubricated and therefore will not be comfortable to wear on the eye. Therefore, an optimal contact lens will have at least both excellent oxygen permeability and excellent tear wettability. Summary of the Invention

[0005] According to an exemplary embodiment, the biomedical device is a polymerization product of a mixture comprising: (a) one or more difunctional isocyanates; (b) one or more polyalcohols; (c) one or more dihydroxy-terminated polysiloxane prepolymers; and (d) one or more polyoxazoline polyols having a weight average molecular weight of about 1000 Daltons or greater.

[0006] According to another exemplary embodiment, there is provided a method for making a biomedical device, the method comprising: (a) providing a mixture comprising: (i) one or more difunctional isocyanates; (ii) one or more polyalcohols; (iii) one or more dihydroxy-terminated polysiloxane prepolymers; and (iv) one or more polyoxazoline polyols having a weight average molecular weight of about 1000 Daltons or greater; (b) subjecting the mixture to polymerization conditions to provide a polymerized device; and (c) hydrating the polymerized device. DETAILED DESCRIPTION OF THE INVENTION

[0007] Various exemplary embodiments described herein are directed to biomedical devices derived from thermosetting or thermoplastic polyoxazoline-based silicone-containing polyurethane materials. The polyoxazoline-based silicone-containing polyurethane materials described herein in non-limiting exemplary embodiments are particularly suitable for use in the contact lens industry. Additionally, polyoxazoline-based silicone-containing polyurethane materials are thermoplastic or thermosetting materials that exhibit exemplary physical properties, particularly in terms of oxygen permeability and light transmission. Advantageously, the thermoplastic or thermosetting materials described herein are suitable for use in conventional molding equipment, thereby enabling high-throughput production of contact lenses.

[0008] Thermoplastic polyurethanes have minimal crosslinking, and any bonds within the polymer network are primarily through hydrogen bonding or other physical mechanisms. Due to the low level of crosslinking, thermoplastic polyurethanes are relatively flexible. The crosslinks in thermoplastic polyurethanes can be reversibly broken by increasing temperatures, such as during molding or extrusion. That is, thermoplastic materials soften when exposed to heat and return to their original state when cooled. Thermoset polyurethanes, on the other hand, are irreversibly fixed once cured. The crosslinks are irreversibly fixed and do not break even when exposed to heat. Therefore, thermoset polyurethanes, which typically have a high level of crosslinking, are relatively rigid. Therefore, as used herein, the term "thermoplastic" refers to a material that melts below its decomposition temperature. As used herein, the term "thermoset" refers to a material that melts above its decomposition temperature.

[0009] The biomedical devices disclosed herein are intended for direct contact with body tissues or fluids. As used herein, the term "biomedical device" refers to any article designed for use 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, prosthetic devices, and ophthalmic lens applications, where the lenses are intended for direct placement in or on the eye, such as intraocular devices and contact lenses. In an exemplary embodiment, the biomedical device is an ophthalmic device, particularly a contact lens, more particularly a contact lens made from a silicone hydrogel.

[0010] 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 care, drug delivery, diagnostic functions, or cosmetic enhancements or effects, or a combination of these properties. Useful ophthalmic devices include, but are not limited to, ophthalmic lenses, such as soft contact lenses (e.g., hydrogel soft lenses and non-hydrogel soft lenses), hard contact lenses (e.g., gas permeable hard lens materials), intraocular lenses, overlay lenses, intraocular inserts, and optical inserts. As will be understood by those skilled in the art, a lens is considered "soft" if it can fold back on itself without breaking.

[0011] In an exemplary embodiment, the ophthalmic device may be a high water content ophthalmic device. In an exemplary embodiment, the high water content ophthalmic device will have an equilibrium water content of at least about 65 weight percent. In another exemplary embodiment, the high water content ophthalmic device will have an equilibrium water content of at least about 70 weight percent. In another exemplary embodiment, the high water content ophthalmic device will have an equilibrium water content of at least about 75 weight percent.

[0012] In an exemplary, non-limiting embodiment, the biomedical devices disclosed herein are formed from the polymerization product of a mixture comprising: (a) one or more difunctional isocyanates; (b) one or more polyalcohols; (c) one or more dihydroxy-terminated polysiloxane prepolymers; and (d) one or more polyoxazoline polyols having a weight average molecular weight of about 1000 Daltons or greater.

[0013] Suitable one or more difunctional isocyanates include, for example, any aliphatic, alicyclic, or aromatic isocyanates. Suitable aromatic diisocyanates that can be used herein include, for example, toluene 2,4-diisocyanate (TDI), toluene 2,6-diisocyanate (TDI), 4,4'-methylenediphenyl diisocyanate (MDI), 2,4'-methylenediphenyl diisocyanate (MDI), polymeric methylenediphenyl diisocyanate (PMDI), p-phenylene diisocyanate (PPDI), m-phenylene diisocyanate (PDI), naphthalene 1,5-diisocyanate (NDI), naphthalene 2,4-diisocyanate (NDI), p-xylene diisocyanate (XDI), and homopolymers, copolymers, and blends thereof. Suitable aliphatic diisocyanates that may be used herein include, for example, isophorone diisocyanate (IPDI), 1,6-hexamethylene diisocyanate (HDI), 4,4'-dicyclohexylmethane diisocyanate ("HDI"). 12 Suitable polyfunctional isocyanates include HDI or H, meta-tetramethylxylene diisocyanate (TMXDI), trans-cyclohexane diisocyanate (CHDI), and homopolymers and copolymers and blends thereof. 12 This includes trimers, oligomers, or other derivatives of MDI. As used herein, the term "difunctional" means that the average functionality of the isocyanate composition and the polyhydroxy compound is about 2.

[0014] In an exemplary embodiment, the one or more difunctional isocyanates have the formula OCN-R 1 -NCO, wherein R 1 Straight or branched chain C3 to C 18 - alkylene, unsubstituted or substituted C6-C 10 -arylene, unsubstituted or substituted C7-C 18 -Aralkylene, unsubstituted or substituted C6-C 10 -Arylene-C1-C2-Alkylene-C6-C 10 -arylene, unsubstituted or substituted C3-C8-cycloalkylene, unsubstituted or substituted C3-C8-cycloalkylene-C1-C6-alkylene, unsubstituted or substituted C3-C8-cycloalkylene-C1-C6-alkylene-C3-C8-cycloalkylene, or unsubstituted or substituted C1-C6-alkylene-C3-C8-cyclo-alkylene-C1-C6-alkylene.

[0015] In exemplary embodiments, the one or more difunctional isocyanates may be present in the mixture in an amount ranging from about 20 to about 60 weight percent, based on the total weight of the mixture. In exemplary embodiments, the amount of the one or more difunctional isocyanates in the mixture may be in the range of about 30 to about 45 weight percent, based on the total weight of the mixture.

[0016] The mixture further comprises one or more polyalcohols. Suitable polyalcohols include, for example, linear or branched aliphatic or aromatic diols, triols, higher functional polyols having an average functionality greater than three, tertiary amine polyalcohols, alkoxylated polyalcohols, polyether polyalcohols, and mixtures thereof. In exemplary embodiments, the one or more polyalcohols may have, for example, from about 2 to about 1000 carbon atoms and from 2 to about 10 hydroxy groups. In other embodiments, the one or more polyalcohols may have up to about 1000 carbon atoms, or up to about 750 carbon atoms, or up to about 650 carbon atoms, or up to about 550 carbon atoms, or up to about 450 carbon atoms, or up to about 350 carbon atoms, or up to about 250 carbon atoms, or up to about 150 carbon atoms, or up to about 100 carbon atoms, or up to about 50 carbon atoms, and from 2 to about 10 hydroxy groups. In one embodiment, the one or more polyalcohols can have at least 2 carbon atoms, or at least about 5 carbon atoms, or at least about 10 carbon atoms, or at least about 15 carbon atoms, or at least about 20 carbon atoms, or at least about 25 carbon atoms, or at least about 30 carbon atoms, or at least about 40 carbon atoms, or at least about 50 carbon atoms, or at least about 100 carbon atoms, and from 2 to about 10 hydroxy groups. As one of ordinary skill in the art would readily understand, any of the foregoing lower limits can be combined with any of the upper limits.

[0017] In exemplary embodiments, the one or more polyalcohols can have, for example, about 1 to about 50 carbon atoms and 2 to 10 hydroxy groups. In exemplary embodiments, the one or more polyalcohols can have, for example, about 2 to about 50 carbon atoms and 2 to 10 hydroxy groups. When used as a chain extender, the one or more polyalcohols can have, for example, about 2 to about 20 carbon atoms, or about 2 to about 10 carbon atoms, or about 2 to about 5 carbon atoms, and 2 to 10 hydroxy groups, or 2 to 4 hydroxy groups.

[0018] Suitable diols include, for example, ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, trimethylene glycol, butylene glycol, neopentyl glycol, 2,2-dimethyl-1,3-propanediol, 1,6-hexanediol, 2-methyl-1,3-propanediol, 1,3-propaneglycol, 1,3-butanediol, 1,4-butanediol, 1,5-pentanediol, 3-hydroxy-2,2-dimethylpropyl-3-hydroxy-2,2-dimethylpropanoate (HPHP), 1,2-cyclohexanediol, 1,3-cyclohexanediol, 1,3-cyclohexanedimethanol, 1,4-cyclohexanedimethanol, resorcinol, hydroquinone, and poly(oxyalkylene) polyols derived from the condensation of ethylene oxide, propylene oxide, or combinations thereof. Mixtures of any diols are also contemplated. The polyalcohol component may also include triols, higher functionality polyols having an average functionality greater than three, or mixtures thereof.

[0019] Suitable triols and higher functionality polyalcohols include, for example, glycerol, diglycerol, trimethylolpropane, pentaerythritol, dipentaerythritol, sugars (e.g., sucrose, glucose, and fructose), sugar alcohols (e.g., sorbitol and mannitol), and combinations of any of the foregoing. For some embodiments, mixtures of diols, triols, and / or higher functionality polyalcohols are also contemplated.

[0020] Suitable tertiary amine polyalcohols include, for example, compounds having at least two hydroxyl groups and at least one tertiary amine group. In one embodiment, the tertiary amine polyalcohol may have, for example, about 2 to about 50 carbon atoms, or about 2 to about 20 carbon atoms, or about 2 to about 10 carbon atoms, or about 2 to about 5 carbon atoms, and 2 to 10 hydroxy groups, or 2 to 4 hydroxy groups. Representative examples of suitable tertiary amine polyalcohols include triethanolamine, N-methyldiethanolamine, N-ethyldiethanolamine, N-propyldiethanolamine, Nn-butyldiethanolamine, N-tert-butyldiethanolamine, N-bis(2-hydroxyethyl)octadecylamine, bis(2-hydroxyethyl)cocoalkylamine, bis(2-hydroxyethyl)oleylamine, ethoxylated (EO), propoxylated (PO), and mixed EO / PO tertiary amines, such as ethoxylated triethanolamine, and mixtures thereof.

[0021] Suitable alkoxylated polyalcohols may have, for example, about 2 to about 20 carbon atoms, or about 3 to about 20 carbon atoms, or about 4 to about 20 carbon atoms, or about 2 to about 10 carbon atoms, and 2 to 10 hydroxy groups, or 2 to 4 hydroxy groups. In one embodiment, the alkoxylated polyalcohol may have a number average molecular weight of 200 to 5,000 grams / mole. In one embodiment, a suitable alkoxylated polyalcohol may be polyoxyethylene glycol, i.e., "PEG," used to describe polyoxyethylene, followed by a number indicating the PEG moiety having the approximate molecular weight equivalent to that number. Representative examples of PEG for use herein include PEG 350, PEG 4000, PEG 6000, PEG 8000, and PEG 10000 (a PEG moiety having an approximate molecular weight of 10,000 daltons).

[0022] Representative examples of suitable alkoxylated polyalcohols include ethoxylated diols, ethoxylated triols, ethoxylated tetrols, ethoxylated pentaols, ethoxylated hexaols, propoxylated diols, propoxylated triols, propoxylated tetrols, propoxylated pentaols, propoxylated hexaols, butoxylated diols, butoxylated triols, butoxylated tetrols, butoxylated pentaols, butoxylated hexaols, etc. Representative examples of ethoxylated polyalcohols are ethoxylated glycerol, ethoxylated pentaerythritol, ethoxylated trimethylolpropane, ethoxylated glucosides, and ethoxylated glucose.

[0023] Suitable polyether polyalcohols include, for example, polyether polyalcohols containing one or more chains or polymeric moieties having one or more (-OR-) repeating units, where R is an alkylene or arylene group having from 2 to about 6 carbon atoms. The polyethers may be derived from block copolymers formed from different ratios of ethylene oxide (EO) and propylene oxide (PO) moieties. Such polyethers and their respective component segments may contain different attached hydrophobic and hydrophilic chemical functional groups moieties and segments.

[0024] A representative example of a suitable polyether polyalcohol is a poloxamer block copolymer. One particular type of poloxamer block copolymer is available under the trademark Pluronic® (BASF Wyandotte Corp., Wyandotte, Mich.). Poloxamers include Pluronics and reverse Pluronics. Pluronics generally have the formula (I): HO(C2H4O) a (C3H6O) b (C2H4O) a H (I) (wherein a is independently at least 1 and b is at least 1), and

[0025] Reverse Pluronics generally have the formula (II) HO(C3H6O) b (C2H4O) a (C3H6O) b H (II) The series is a series of BAB block copolymers, each composed of a poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) block represented by the formula: (where a is at least 1 and b is independently at least 1). The poly(ethylene oxide) (PEO) block is hydrophilic, while the poly(propylene oxide) (PPO) block is essentially hydrophobic. Each series of poloxamers has a different ratio of PEO to PPO, which ultimately determines the hydrophilic-lipophilic balance (HLB) of the material; i.e., the different HLB values ​​are based on different values ​​of a and b, where a represents the number of hydrophilic poly(ethylene oxide) units (PEO) present in the molecule and b represents the number of hydrophobic poly(propylene oxide) units (PPO) present in the molecule.

[0026] Another example of a suitable polyether polyalcohol may be a poloxamine block copolymer. The term block copolymer as used herein should be understood to mean a poloxamer and / or poloxamine having two or more blocks in the polymer backbone. While poloxamers and reverse poloxamers are considered to be bifunctional molecules (based on the terminal hydroxyl groups), poloxamines are in tetrafunctional form, i.e., these molecules are tetrafunctional block copolymers terminated with primary hydroxyl groups and linked by a central diamine. One particular type of poloxamine block copolymer is available under the trademark Tetronic (BASF). Poloxamines include Tetronics and reverse Tetronics. Poloxamines have the following formula (III): [ka] wherein a is independently at least 1 and b is independently at least 1.

[0027] The one or more polyalcohols described above can be present in the mixture in an amount ranging from about 10 to about 70 weight percent, based on the total weight of the mixture. In an exemplary embodiment, the amount of one or more polyalcohols in the mixture can range from about 12 to about 20 weight percent, based on the total weight of the mixture.

[0028] The mixture further comprises one or more hydroxy-terminated polysiloxane prepolymers. In an exemplary embodiment, the hydroxy-terminated polysiloxane prepolymer has the structure of formula (IV): [ka] wherein each R is independently a hydroxyl-containing reactive functional end group; 1 ~R 6 are independently hydrocarbyl groups, for example, linear or branched, substituted or unsubstituted C1-C 30Alkyl groups, substituted or unsubstituted C3-C 30 Cycloalkyl groups, substituted or unsubstituted C4-C 30 Cycloalkylalkyl groups, substituted or unsubstituted C3-C 30 Cycloalkenyl groups, substituted or unsubstituted C6-C 30 Aryl groups and substituted or unsubstituted C7-C 30 It is an arylalkyl group, L is independently a linking group, and x is 3 to 200.

[0029] A hydroxyl-containing reactive functional end group for use herein is a group containing at least one hydroxyl group. Representative examples of hydroxyl-containing reactive functional end groups for use herein include, by way of example, those of the following general formula -R 7 (OH), where R 7 are independently alkyl, aryl, and cycloalkyl groups, etc., as defined herein.

[0030] The linking groups L are independently straight-chain or branched, substituted or unsubstituted alkyl groups, substituted or unsubstituted cycloalkyl groups, substituted or unsubstituted aryl groups, substituted or unsubstituted ether or polyether groups, and substituted or unsubstituted ester groups.

[0031] Representative examples of alkyl groups for use herein include, by way of example, straight or branched alkyl chain groups containing carbon atoms and hydrogen atoms having from 1 to about 30 carbon atoms, or from 1 to about 12 carbon atoms, or from 1 to about 6 carbon atoms, relative to the remainder of the molecule, with or without unsaturation, such as methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl, methylene, ethylene, and the like.

[0032] 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.

[0033] Representative examples of cycloalkylalkyl groups for use herein include, by way of example, substituted or unsubstituted cyclic ring-containing groups containing from about 4 to about 30 carbon atoms, or from 3 to about 6 carbon atoms, directly attached to an alkyl group and then attached to the main structure of the monomer at any carbon from the alkyl group to produce a stable structure, such as cyclopropylmethyl, cyclobutylethyl, cyclopentylethyl, and the like, and the cyclic ring may optionally contain one or more heteroatoms, such as, for example, O and N.

[0034] Representative examples of cycloalkenyl groups for use herein include, by way of example, substituted or unsubstituted cyclic ring-containing groups containing from about 3 to about 30 carbon atoms, or from 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.

[0035] Representative examples of aryl groups for use herein include, by way of example, substituted or unsubstituted monocyclic or polycyclic aromatic groups containing from about 6 to about 30 carbon atoms, e.g., phenyl, naphthyl, tetrahydronaphthyl, indenyl, biphenyl, and the like, and optionally containing one or more heteroatoms such as, for example, O and N.

[0036] 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, —C2H4C6H5, etc., wherein the aryl group may optionally contain one or more heteroatoms, such as, for example, O and N.

[0037] Representative examples of ester groups for use herein include, by way of example, carboxylic acid esters having 1 to 20 carbon atoms.

[0038] 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 14 OR 15 ) t an ether group or a polyether group (wherein R 14 is a bond, a substituted or unsubstituted alkyl, cycloalkyl, or aryl group as defined herein, and R 15 is a substituted or unsubstituted alkyl, cycloalkyl, or aryl group as defined herein, and t is at least 1.

[0039] In an exemplary embodiment, the hydroxy-terminated polysiloxane prepolymer has the structure of formula (V): [ka] wherein each R, R 1 , R 2 , R 3 and R 4 The groups are independently H or hydrocarbyl groups, such as linear or branched, substituted or unsubstituted C1-C 12 represents an alkyl group, p is an integer of 0 to 40, for example, 1 to 10, q is an integer of 0 to 40, for example, 1 to 10, z is an integer of 2 to 50, for example, 2 to 10 or 2, u is an integer of 1 to 100, for example, 10 to 40, y is an integer of 0 to 40, for example, 1 to 10, w is an integer of 0 to 40, for example, 1 to 10, and v is an integer of 2 to 50, for example, 2 to 10, and each Q group independently represents a hydroxyl-containing reactive functional end group.

[0040] In an exemplary embodiment, at least one R 1 group represents a hydrocarbyl group, p represents an integer of 1 to 40, or at least one R 2 group represents a hydrocarbyl group, q represents an integer from 1 to 40, and at least one R 3 group represents a hydrocarbyl group, w represents an integer of 1 to 40, or at least one R 4 The group represents a hydrocarbyl group, and y represents an integer of 1 to 40.

[0041] In an exemplary embodiment, each R, R 1 , R 2 , R 3 and R 4 The groups independently represent H or an alkyl group such as a methyl, ethyl, or propyl group.

[0042] In an exemplary embodiment, at least one R 1 group and at least one R 4 The group represents a hydrocarbyl group, p represents an integer of 1 to 40, and y represents an integer of 1 to 40.

[0043] In an exemplary embodiment, at least one R 2 group and at least one R3 The group represents a hydrocarbyl group, q represents an integer of 1 to 40, and w represents an integer of 1 to 40.

[0044] In an exemplary embodiment, the silicone-containing compound is symmetrical, although asymmetrical structures with silicone compounds can also be used.

[0045] In an exemplary embodiment, 1 and / or R 4 represents a hydrocarbyl group, p and q each independently represent an integer of 1 to 5, and w and y each independently represent an integer of 1 to 10 or 5 to 10.

[0046] In an exemplary embodiment, 3 and / or R 4 represents a hydrocarbyl group, w and y each independently represent an integer of 1 to 5, and p and q each independently represent an integer of 1 to 10 or 5 to 10.

[0047] In an exemplary embodiment, Q is OH.

[0048] In another exemplary embodiment, the hydroxy-terminated polysiloxane prepolymer has the structure of formula (Va): [ka] wherein R1 and R4 are hydrocarbyl groups, such as linear or branched, substituted or unsubstituted C1-C 12 represents an alkyl group such as methyl, ethyl, or propyl; p represents an integer of 1 to 40, for example, 1 to 10; y represents an integer of 1 to 40, for example, 1 to 10; q represents an integer of 1 to 40, for example, 5 to 10; w represents an integer of 1 to 40, for example, 5 to 10; and Q, z, R, u, and v are as defined above.

[0049] In another exemplary embodiment, the hydroxy-terminated polysiloxane prepolymer has the structure of formula (Vb): [ka] where R 2 and R 3 is a hydrocarbyl group, for example, a linear or branched, substituted or unsubstituted C1-C 12 represents an alkyl group such as methyl, ethyl, or propyl; p represents an integer of 1 to 40, for example, 1 to 10; y represents an integer of 1 to 40, for example, 1 to 10; q represents an integer of 1 to 40, for example, 5 to 10; w represents an integer of 1 to 40, for example, 5 to 10; and Q, z, R, u, and v are as defined above.

[0050] In another exemplary embodiment, the hydroxy-terminated polysiloxane prepolymer has the structure of formula (Vc): [ka] where each R group is an alkyl group, such as methyl, ethyl, or propyl, and p, q, z, u, v, w, and y are as defined above. An example of a compound of formula (Vc) is Silsurf® 2510, available from Siltech Corporation, where each R group represents a methyl group, z is 25, p is 10, and y is 10.

[0051] In exemplary embodiments, the one or more hydroxy-terminated polysiloxane prepolymers may have a number average molecular weight of about 500 to about 5,000 daltons, as determined, for example, by size exclusion chromatography (i.e., gel permeation chromatography). In exemplary embodiments, the one or more hydroxy-terminated polysiloxane prepolymers may have a number average molecular weight of about 500 to about 3,500 daltons. In exemplary embodiments, the one or more hydroxy-terminated polysiloxane prepolymers may have a number average molecular weight of about 800 to about 3,000 daltons.

[0052] Methods for making one or more hydroxy-terminated polysiloxane prepolymers are well known and within the purview of those skilled in the art. Additionally, polysiloxane prepolymers are commercially available from sources such as, for example, Gelest, Silar, Shin-Etsu, Momentive, and Siltech.

[0053] The one or more hydroxy-terminated polysiloxane prepolymers may be present in the mixture in an amount ranging from about 3 to about 60 weight percent, based on the total weight of the mixture. In an exemplary embodiment, the amount of the one or more hydroxy-terminated polysiloxane prepolymers in the mixture may range from about 10 to about 50 weight percent, based on the total weight of the mixture.

[0054] The mixture further comprises one or more polyoxazoline polyols having a weight average molecular weight of about 1000 Daltons or greater, as determined, for example, by size exclusion chromatography (i.e., gel permeation chromatography). In exemplary embodiments, the one or more polyoxazoline polyols can have a weight average molecular weight of about 1000 Daltons or greater, and up to about 50,000,000 Daltons. In exemplary embodiments, the one or more polyoxazoline polyols may have a weight average molecular weight of about 1000 daltons or greater, or greater than 10,000 daltons, or greater than 25,000 daltons, or greater than 50,000 daltons, or greater than 100,000 daltons, or greater than 250,000 daltons, or greater than 500,000 daltons, or greater than 750,000 daltons, or greater than 1,000,000 daltons, or greater than 2,500,000 daltons, or greater than 5,000,000 daltons, or greater than 10,000,000 daltons, or greater than 25,000,000 daltons, up to about 50,000,000 daltons. In exemplary embodiments, the one or more polyoxazoline polyols may have a weight average molecular weight of less than about 50,000,000 daltons, or less than 25,000,000 daltons, or less than 10,000,000 daltons, or less than 5,000,000 daltons, or less than 2,500,000 daltons, or less than 1,000,000 daltons, or less than 750,000 daltons, or less than 500,000 daltons, or less than 250,000 daltons, or less than 100,000 daltons.

[0055] In exemplary embodiments, the one or more polyoxazoline polyols are difunctional, trifunctional, or tetrafunctional polyoxazoline polyols. In exemplary embodiments, a difunctional polyoxazoline polyol is a C1-C hydroxyl group-containing polyoxazoline polyol having two oxazoline-containing hydroxyl groups per alkyl molecule, the alkyl molecule optionally containing one or more ether and / or ester linkages. 12Alkyl polyoxazoline polyols, C6-C, with two oxazoline-containing hydroxyl groups per aromatic molecule 30 Aromatic polyoxazoline polyols and C3-C oxazoline-containing polyols with two hydroxyl groups per cycloalkyl molecule 20 In one embodiment, the aryl group is phenyl. For example, in one embodiment, one or more polyoxazoline polyols have the structure of formula (VI): [ka] wherein each R is a hydroxyl group, each R' is independently a hydrocarbyl group such as, for example, an alkyl group, a haloalkyl group, an alkene group, an alkyne group, a cycloalkyl group, a halocycloalkyl group, an aryl group, a haloaryl group, an aralkyl group, and a haloaralkyl group, Z is a divalent bond, and each of x and y is independently at least 1, for example, from 1 up to about 200. Representative Z bonds include C1-C aryl groups, including single bonds and optionally ether bonds. 12 Alkylene group, C6-C 30 Arylene group, C7-C 30 Alkarylene group and C3-C 20 Examples include cycloalkylene groups.

[0056] In another exemplary embodiment, the trifunctional polyoxazoline polyol is a C1-C oxazoline-containing alkyl polyol having three oxazoline-containing hydroxyl groups per alkyl molecule, the alkyl molecule optionally containing one or more of an ether linkage and / or an ester linkage. 12 In an exemplary embodiment, the alkyl polyoxazoline polyol is a C1-C 12The alkyl moiety may be a straight or branched alkyl chain molecule containing carbon and hydrogen atoms of 1 to 12 carbon atoms, or 1 to about 6 carbon atoms, relative to the remainder of the molecule, with or without unsaturation. The three oxazoline-containing hydroxyl groups may be the same or different and may be provided at any point of attachment to the alkyl moiety.

[0057] In another exemplary embodiment, the trifunctional polyoxazoline polyol is a C-C oxazoline-containing polyol having three oxazoline-containing hydroxyl groups per aromatic molecule. 30 In an exemplary embodiment, the aromatic polyoxazoline polyol is a C6-C 30 The aromatic may be a substituted or unsubstituted monocyclic or polycyclic aromatic group containing about 6 to about 30 carbon atoms, or 6 to 12 carbon atoms, such as phenyl, naphthyl, tetrahydronaphthyl, indenyl, biphenyl, etc., optionally containing one or more heteroatoms, such as O and N. The three oxazoline-containing hydroxyl groups may be the same or different and may be provided at any point of attachment to the aromatic molecule. In one embodiment, the aromatic molecule is phenyl.

[0058] In another exemplary embodiment, the trifunctional polyoxazoline polyol is a C3-C oxazoline-containing hydroxyl group-containing polyol having three oxazoline-containing hydroxyl groups per cycloalkyl molecule. 20 In an exemplary embodiment, the polyol is a cycloalkyl polyoxazoline polyol. 20The cycloalkyl molecule can be a substituted or unsubstituted non-aromatic monocyclic or polycyclic ring system of about 3 to about 20 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 O and N. The three oxazoline-containing hydroxyl groups can be the same or different and can be provided at any point of attachment to the cycloalkyl molecule.

[0059] In another exemplary embodiment, the tetrafunctional polyoxazoline polyol is a C1-C oxazoline-containing alkyl polyol having four oxazoline-containing hydroxyl groups per alkyl molecule, the alkyl molecule optionally containing one or more of an ether linkage and / or an ester linkage. 12 Alkyl polyoxazoline polyols, C6-C, with four oxazoline-containing hydroxyl groups per aromatic molecule 30 Aromatic polyoxazoline polyols and C3-C oxazoline-containing polyols with four hydroxyl groups per cycloalkyl molecule 20 In one embodiment, the aryl group is phenyl. 12 Alkyl molecules, C6-C 30 aromatic molecules, and C3~C 20 The cycloalkyl moiety can be any of those described above. In an exemplary embodiment, the four oxazoline-containing hydroxyl groups can be the same or different and can be provided at any point of attachment to the alkyl moiety, aromatic moiety, and cycloalkyl moiety.

[0060] One or more of the polyoxazoline polyols described above having a weight average molecular weight of about 1000 daltons or greater can be prepared by methods known in the art.

[0061] In one embodiment, the one or more polyoxazoline polyols are For example, bromine-containing initiator (A-2) (Br) a -Z (A-2) (wherein Z is a hydrocarbyl group and a is an integer of 2 to 4), to form a 2-substituted-2-oxazoline (A-1) [ka] The Z hydrocarbyl group of the bromo-containing initiator can be any C1-C 30 Alkyl groups, C6-C 30 Aromatic group, C3~C 20 Cycloalkyl, C1-C 20 Ester-containing groups, C1-C 20 It may be a polyether-containing group, etc. 30 Alkyl groups, C6-C 30 Aromatic group, C3~C 20 Cycloalkyl, C1-C 20 Ester-containing groups and C1-C 20 The polyether-containing group can be any of those described hereinabove. Suitable terminating agents other than water / sodium carbonate mixtures can be used, including, for example, glycolic acid, lactic acid, ethylene glycol, propylene glycol, and the like, in the presence of a base such as triazabicyclodecene.

[0062] In an exemplary embodiment, the one or more polyoxazoline polyols described above can be obtained by subjecting a 2-substituted-2-oxazoline (A-1) to a catalytic ring-opening polymerization process as shown below. [ka]

[0063] In another exemplary embodiment, the one or more polyoxazoline polyols described above can be obtained by subjecting a 2-substituted-2-oxazoline (A-1) to a catalytic ring-opening polymerization process as shown below. [ka]

[0064] Thus, suitable alkyl substituted oxazolines for use herein are of the formula: [ka] where R is an alkyl group of 1 to 12 carbon atoms. In an exemplary, non-limiting embodiment, the 2-alkyl substituted oxazoline for use herein is 2-isopropenyl-2-oxazoline. Thus, in an exemplary embodiment, the poly(2-alkyloxazoline) repeat unit as shown above in a catalytic ring-opening polymerization process is [ka]

[0065] where R is an alkyl group of 1 to 12 carbon atoms.

[0066] The one or more polyoxazoline polyols may be present in the mixture in an amount ranging from about 5 to about 65 weight percent, based on the total weight of the mixture. In an exemplary embodiment, the amount of one or more polyoxazoline polyols in the mixture may range from about 10 to about 45 weight percent, based on the total weight of the mixture.

[0067] In an exemplary embodiment, the mixture further contains a catalyst for carrying out the reaction to prepare the polymerization product. Suitable urethane catalysts include, for example, tin salts of carboxylic acids such as stannous octoate, stannous oleate, stannous acetate, and stannous laurate, dialkyltin dicarboxylates such as dibutyltin dilaurate and dibutyltin diacetate (which are known in the art as urethane catalysts and as tertiary amines), and tin mercaptides.

[0068] The amount of catalyst used is generally from about 0.005 to about 5 weight percent of the mixture being catalyzed, depending on the nature of the isocyanate.

[0069] The mixture may further contain other monomers. In an exemplary embodiment, the mixture may further include one or more antioxidants. Suitable antioxidants may be any of those commonly used in polyurethanes, such as BHA (butylated hydroxyanisole), BHT (butylated hydroxytoluene), and ascorbic acid. The one or more antioxidants may be used in an amount of about 0.01 to about 10 weight percent, or about 0.1 to about 5 weight percent, or about 0.2 to about 1 weight percent, based on the total weight of the mixture.

[0070] In another exemplary embodiment, the mixture may further comprise one or more end-functionalized surfactants. Suitable end-functionalized surfactants include, by way of example, poloxamers, such as the Pluronics and reverse Pluronics, and poloxamines, such as the Tetronics and reverse Tetronics described above.

[0071] Poloxamers and reverse poloxamers have terminal hydroxyl groups that can be end-functionalized. One example of an end-functionalized poloxamer is poloxamer dimethacrylate (e.g., Pluronic® F127 dimethacrylate), disclosed in U.S. Patent Application Publication No. 2003 / 0044468. Other examples include the glycidyl-terminated copolymers of polyethylene glycol and polypropylene glycol, disclosed in U.S. Patent No. 6,517,933.

[0072] The poloxamers and / or poloxamines can be functionalized to provide the desired reactivity at the ends of the molecules. The functionality can vary and is determined based on the intended use of the functionalized PEO- and PPO-containing block copolymers. That is, the PEO- and PPO-containing block copolymers are reacted to provide terminal functionality complementary to the intended device-forming mixture.

[0073] Representative examples of reaction sequences that can be used to end-functionalize PEO- and PPO-containing block copolymers are set forth below. [ka]

[0074] The reaction sequences described above are merely illustrative, but non-limiting examples of reactions that provide functionalized termini for PEO- and PPO-containing block copolymers. It should be understood that one skilled in the art could determine other reaction methods without undue experimentation. It should also be understood that any particular block copolymer molecule shown is only one chain length of a polydisperse population of the referenced material.

[0075] In one embodiment, the end-functionalized surfactant is selected from the group consisting of a poloxamer having at least one end functionalized, a reverse poloxamer having at least one end functionalized, a poloxamine having at least one end functionalized, a reverse poloxamine having at least one end functionalized, and mixtures thereof.

[0076] Generally, the end-functionalized surfactant will be present in the mixture in an amount ranging from about 0.01 to about 20 weight percent, or from about 1 to about 10 weight percent, or from about 3 to about 6 weight percent, based on the total weight of the mixture.

[0077] The mixture may further contain, if necessary, various additives such as one or more ultraviolet (UV) blocking agents, colorants, lubricating internal wetting agents, and reinforcing agents, as well as other components well known in the art, within the limits that do not impair the purpose and effects of the exemplary embodiments disclosed herein.

[0078] Exemplary embodiment biomedical devices, such as contact lenses or intraocular lenses, can be prepared by polymerizing the above-described mixture to form a product that can then be formed into the appropriate shape by lathing, injection molding, compression molding, cutting, etc. For example, in manufacturing contact lenses, the initial mixture may be polymerized in a tube to provide rod-shaped articles that are then cut into buttons. The buttons may then be lathed into contact lenses.

[0079] Alternatively, biomedical devices such as contact lenses may be cast directly from the mixture into a mold, e.g., a polypropylene mold, by, for example, spin casting and static casting. Spin casting is disclosed in U.S. Pat. Nos. 3,408,429 and 3,660,545, and static casting is disclosed in U.S. Pat. Nos. 4,113,224, 4,197,266, and 5,271,875. Spin casting involves filling a mold with the mixture to be polymerized and rotating the mold in a controlled manner while exposing the mixture to a radiation source, such as UV light. Static casting involves casting the mixture between two mold sections, one mold section shaped to form the anterior surface of the lens and the other mold section shaped to form the posterior surface of the lens, and curing the mixture while held within the mold assembly to form the lens. U.S. Patent No. 5,271,875 describes a static casting method that allows for the molding of a finished lens in a mold cavity defined by a posterior mold and an anterior mold. As an additional method, U.S. Patent No. 4,555,732 discloses a process in which an excess monomer mixture is cured by spin casting in a mold to form a molded article having a lens anterior surface and a relatively large thickness, and the posterior surface of the cured spin-cast article is subsequently lathed to provide a contact lens having the desired thickness and lens posterior surface.

[0080] The polymerization can be carried out in a reaction medium such as a solution or dispersion using a suitable solvent. Generally, the polymerization can be carried out for about 15 minutes to about 72 hours. If desired, the resulting polymerization product can be dried under high vacuum, for example, for about 5 to about 72 hours, or left in an aqueous solution before use.

[0081] Polymerization of the mixture preferably results in a polymer that, upon hydration, forms a hydrogel. When producing hydrogel lenses, the mixture may further include at least a diluent (e.g., a PEG-ether diluent) that ultimately displaces water when the polymerization product hydrates to form the hydrogel. The maximum amount of diluent that can be used will depend on the amount of swelling the diluent causes in the final polymer. Excessive swelling can cause or disrupt the copolymer when the diluent is replaced by water upon hydration. Generally, the water content of the hydrogel is as described hereinabove. The amount of diluent used should be less than about 50 weight percent, and in most cases, the diluent content is less than about 30 weight percent. However, for a particular polymer system, the practical limit will be determined by the solubility of the various monomers in the diluent. To produce an optically clear copolymer, it is important that no phase separation occurs between the comonomer and the diluent, or between the diluent and the final copolymer, which would result in visual opacity.

[0082] It may be desirable to remove residual diluent from the lens prior to the edge finishing operation, which can be accomplished by evaporation at or near ambient pressure or under high vacuum, if necessary. High temperatures can be used to reduce the time required to evaporate the diluent. The time, temperature, and pressure conditions for the solvent removal step will vary depending on factors such as the volatility of the diluent and the particular monomer components, as can be readily determined by one skilled in the art. If desired, the mixture used to make hydrogel lenses can further include crosslinkers and wetting agents known in the prior art for making hydrogel materials.

[0083] The biomedical devices, such as contact lenses, obtained herein may be subjected to optional machining operations. For example, other optional machining steps may include buffing or polishing the lens edges and / or surfaces. Generally, such machining processes may be performed before or after the product is released from the mold parts; for example, the lens is dry-released from the mold by using high-vacuum tweezers to lift the lens from the mold, after which the lens is transferred by mechanical tweezers to a second set of high-vacuum tweezers and placed against a rotating surface to smooth the surface or edges. The lens may then be flipped over to machine the other side of the lens.

[0084] The lenses may then be transferred to individual lens packages containing a buffered saline solution. The saline may be added to the package either before or after the lenses are transferred. Suitable package designs and materials are known in the art. The plastic package is peelably sealed with a film. Suitable sealing films are known in the art and include foils, polymer films, and mixtures thereof. The sealed package containing the lenses is then sterilized to ensure a sterile product.

[0085] As one skilled in the art would readily appreciate, other steps can be included in the above-described molding and packaging process, including, for example, coating the formed lenses, surface treating the lenses during formation (e.g., via mold transfer), inspecting the lenses, discarding defective lenses, cleaning mold halves, reusing mold halves, and the like, as well as combinations thereof.

[0086] The following examples are provided to enable one skilled in the art to practice the invention and are illustrative only and should not be construed as limiting the scope of the invention, which is defined by the claims.

[0087] Example 1 A polyoxazoline having a number average molecular weight of 400 Daltons and a weight average molecular weight of 1900 Daltons was prepared according to the following reaction scheme. [ka]

[0088] To a flame-dried, two-necked, 250 mL round-bottom flask equipped with a stopper, stir bar, and condenser was added via syringe 2-ethyl-2-oxazoline (25 mL), ethylene glycol bis(2-bromoprionate) (0.568 grams), and acetonitrile (55 mL). The flask was heated under N 2(g) The mixture was placed in an oil bath at 80°C and stirred overnight. The reaction was terminated by adding sodium bicarbonate (0.12 grams) and deionized (DI) water (0.2 mL) and stirred for 1 hour. The resulting polymer was precipitated into approximately 1500 mL of diethyl ether, filtered, and dried in a high vacuum oven.

[0089] Example 2 A polyoxazoline having a number average molecular weight of 5,000 daltons was prepared according to the following reaction scheme. [ka]

[0090] To a flame-dried, two-necked, 250 mL round-bottom flask equipped with a stopper, a stir bar, and a condenser, 2-ethyl-2-oxazoline (25 mL), α,α'-dibromo-p-xylene (0.45 grams), and acetonitrile (55 mL) were added via syringe. The flask was refrigerated under N 2(g) The mixture was placed in an oil bath at 80°C and stirred overnight. The reaction was terminated by adding sodium bicarbonate (0.12 grams) and DI water (0.2 mL) and stirred for 1 hour. The resulting polymer was precipitated into approximately 1500 mL of diethyl ether, filtered, and dried in a high vacuum oven.

[0091] Example 3 A polyoxazoline having a number average molecular weight of 700 Daltons and a weight average molecular weight of 7700 Daltons was prepared according to the following reaction scheme. [ka]

[0092] To a flame-dried, two-necked, 250 mL round-bottom flask equipped with a stopper, a stir bar, and a condenser, 2-ethyl-2-oxazoline (25 mL), 1,6-dibromohexane (0.26 mL), and acetonitrile (55 mL) were added via syringe. The flask was refrigerated under N 2(g) The mixture was placed in an oil bath at 80°C and stirred overnight. The reaction was terminated by adding sodium bicarbonate (0.12 grams) and DI water (0.2 mL) and stirred for 1 hour. The resulting polymer was precipitated into approximately 1500 mL of diethyl ether, filtered, and dried in a high vacuum oven.

[0093] Example 4 A polyoxazoline having a number average molecular weight of 800 Daltons and a weight average molecular weight of 14,400 Daltons was prepared according to the following reaction scheme. [ka]

[0094] To a flame-dried, two-necked, 250 mL round-bottom flask equipped with a stopper, stir bar, and condenser was added via syringe 2-ethyl-2-oxazoline (25 mL), 1,2,5,6-tetrakis(bromomethyl)benzene (0.77 grams), and acetonitrile (55 mL). The flask was refrigerated under N 2(g) The mixture was placed in an oil bath at 80°C and stirred overnight. The reaction was terminated by adding sodium bicarbonate (0.12 grams) and DI water (0.2 mL) and stirred for 1 hour. The resulting polymer was precipitated into approximately 1500 mL of diethyl ether, filtered, and dried in a high vacuum oven.

[0095] Example 5 A polyoxazoline having a number average molecular weight of 4,900 daltons and a weight average molecular weight of 9,135 daltons was prepared according to the following reaction scheme. [ka]

[0096] To a flame-dried, two-necked, 250 mL round-bottom flask was added 4,4'-bis(bromomethyl)biphenyl (0.54 g, 0.0016 mol) and 20 mL of anhydrous acetonitrile. Next, 2-ethyl-2-oxazoline (24.55 g, 0.2476 mol) was added via syringe. The flask was placed in a preheated oil bath at 80 °C for approximately 6 hours to form the polymer in ether, then cooled. Glycolic acid (2.20 g, 0.037 mol) and triethylamine (1.24 g, 0.012 mol) were added sequentially and placed in a preheated oil bath at 50 °C overnight. Additional solvent (approximately 5 mL) was added to keep the reaction stirring.

[0097] The mixture was cooled, diluted with dichloromethane (400 mL), and washed with saturated aqueous sodium bicarbonate (2 x 300 mL) and saturated aqueous sodium chloride (1 x 300 mL). The combined bicarbonate extracts were back-extracted with 1 x 400 mL of dichloromethane. The combined organics were dried over magnesium sulfate and evaporated. Dichloromethane (approximately 100 mL) was then added to the residue and precipitated in ether. The polymer was collected, dried, redissolved in dichloromethane, and precipitated in ether. The solid was filtered, rinsed, and dried at room temperature in a household high vacuum oven for several days. A white solid (18.60 g) (76%) was recovered.

[0098] Example 6 Preparation of polyoxazoline-based silicone-containing polyurethanes.

[0099] To a flame-dried, two-necked, 250 mL round-bottom flask equipped with a stopper, stir bar, addition funnel, and condenser, under nitrogen to maintain a dry environment, was added the polyoxazoline polymer from Example 2 (6.43 grams) and 1,2-dichloroethane (76 mL / 100 gram mixture). After the polymer was dissolved, Silsurf® 2510 (45.89 grams), triethylene glycol (13.14 grams), and dibutyltin dilaurate (0.05 grams) were added. The flask was placed in a heated oil bath (80°C) and stirred to combine the ingredients. Next, 4,4'-methylenebis(cyclohexyl isocyanate) (34.50 grams) was added via syringe. The reaction mixture was stirred under nitrogen for at least 2 hours while maintaining the temperature at 80°C. The reaction mixture was then cooled to room temperature and poured onto a treated glass plate to produce a thin film. The solvent was allowed to evaporate overnight in a hood.

[0100] For 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 formulation, and are disclosed herein, as if each and every such subcombination were individually and expressly disclosed herein.

[0101] It will be understood that various modifications can 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 implemented as the best mode for operating the embodiments disclosed herein, described above, are for illustrative purposes only. Those skilled in the art may implement other configurations and methods without departing from the scope and spirit of the present invention. Moreover, those skilled in the art will envision other modifications within the scope and spirit of the features and advantages added herein. One would assume that. The following is further disclosed in relation to the present invention. [1] a biomedical device that is the polymerization product of the mixture, (a) one or more difunctional isocyanates; (b) one or more polyalcohols; (c) one or more hydroxy-terminated polysiloxane prepolymers; and (d) one or more polyoxazoline polyols having a weight average molecular weight of about 1000 Daltons or greater. [2] 2. The biomedical device of claim 1, wherein the one or more difunctional isocyanates comprise an aliphatic isocyanate, a cycloaliphatic isocyanate, and an aromatic isocyanate. [3] The one or more difunctional isocyanates are of the formula OCN-R 1 -NCO, wherein R 1 But linear or branched chain C 3 ~C 18 - an alkylene group, unsubstituted or substituted C 6 ~C 10 -arylene group, unsubstituted or substituted C 7 ~C 18 -aralkylene group, C 6 ~C 10 -Arylene-C 1 ~C 2 -Alkylene-C 6 ~C 10 -arylene group, C 3 ~C 8 -cycloalkylene group, C 3 ~C 8 -Cycloalkylene-C 1 ~C 6 -Alkylene group, C 3 ~C 8 -Cycloalkylene-C 1 ~C 6 -Alkylene-C3 ~C 8 -cycloalkylene group, or C 1 ~C 6 -Alkylene-C 3 ~C 8 -cyclo-alkylene-C 1 ~C 6 The biomedical device according to [1], wherein the -alkylene group is an alkylene group. [4] The biomedical device according to any one of [1] to [3], wherein the one or more polyalcohols have from about 2 to about 50 carbon atoms and at least two hydroxy groups. [5] The biomedical device according to [1] to [3], wherein the one or more polyalcohols are selected from the group consisting of diols, triols, tertiary amine polyalcohols, alkoxylated polyalcohols, polyether polyalcohols, and mixtures thereof. [6] 8. The biomedical device of claim 7, wherein the diol is selected from the group consisting of ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, trimethylene glycol, butylene glycol, neopentyl glycol, 2,2-dimethyl-1,3-propanediol, 1,6-hexanediol, 2-methyl-1,3-propanediol, 1,3-propane glycol, 1,3-butanediol, 1,4-butanediol, 1,5-pentanediol, 3-hydroxy-2,2-dimethylpropyl-3-hydroxy-2,2-dimethylpropanoate, 1,2-cyclohexanediol, 1,3-cyclohexanediol, 1,3-cyclohexanedimethanol, 1,4-cyclohexanedimethanol, resorcinol, hydroquinone, poly(oxyalkylene) polyols derived from the condensation of ethylene oxide, propylene oxide, and mixtures thereof. [7] 6. The biomedical device of claim 5, wherein the triol is selected from the group consisting of glycerol, diglycerol, trimethylolpropane, pentaerythritol, dipentaerythritol, sucrose, glucose, fructose, sorbitol, mannitol, and mixtures thereof. [8] 10. The biomedical device of claim 9, wherein the tertiary amine polyalcohol is selected from the group consisting of triethanolamine, N-methyldiethanolamine, N-ethyldiethanolamine, N-propyldiethanolamine, Nn-butyldiethanolamine, N-tert-butyldiethanolamine, N-bis(2-hydroxyethyl)octadecylamine, bis(2-hydroxyethyl)cocoalkylamine, bis(2-hydroxyethyl)oleylamine, ethoxylated (EO), propoxylated (PO), and mixed EO / PO tertiary amines, and mixtures thereof. [9] 6. The biomedical device of claim 5, wherein the alkoxylated polyalcohol comprises one or more polyoxyethylene glycols.

[10] 5. The biomedical device of claim 5, wherein the polyether polyalcohol comprises a poloxamer block copolymer.

[11] 5. The biomedical device of claim 5, wherein the polyether polyalcohol comprises a poloxamine block copolymer.

[12] The one or more hydroxy-terminated polysiloxane prepolymers have the formula:

change

[13] The biomedical device according to any one of [1] to

[12] , wherein the one or more polyoxazoline polyols comprise one or more difunctional, trifunctional, and tetrafunctional polyoxazoline polyols.

[14] The one or more polyoxazoline polyols have the formula:

change

[15] 13. The biomedical device of claim 12, wherein the one or more bifunctional polyoxazoline polyols are one or more polyoxazoline polyols having two oxazoline-containing hydroxyl groups per molecule.

[16] one or more C difunctional polyoxazoline polyols having two oxazoline-containing hydroxyl groups per alkyl molecule, the alkyl molecules optionally containing one or more of an ether linkage and / or an ester linkage; 1 ~C 12 Alkyl polyoxazoline polyols, with two oxazoline-containing hydroxyl groups per aromatic molecule, C 6 ~C 30 Aromatic polyoxazoline polyols and C having two oxazoline-containing hydroxyl groups per cycloalkyl molecule. 3 ~C 20 The biomedical device according to

[13] , wherein the polyol is a cycloalkyl polyoxazoline polyol.

[17] 17. The biomedical device of claim 15 or 16, wherein each of the oxazoline-containing hydroxyl groups has 1 to about 200 repeating oxazoline units.

[18] The one or more bifunctional polyoxazoline polyols have two oxazoline-containing hydroxyl groups per aromatic molecule. 6 ~C 30 The biomedical device according to

[16] or

[17] , which is an aromatic polyoxazoline polyol, wherein the aromatic molecule is a phenyl group or a biphenyl group.

[19] 13. The biomedical device of claim 12, wherein the one or more trifunctional polyoxazoline polyols are one or more polyoxazoline polyols having three oxazoline-containing hydroxyl groups per molecule.

[20] one or more C trifunctional polyoxazoline polyols having three oxazoline-containing hydroxyl groups per alkyl molecule, the alkyl molecules optionally containing one or more of an ether linkage and / or an ester linkage; 1 ~C 12 Alkyl polyoxazoline polyols, containing one or more C alkyl groups, with three oxazoline-containing hydroxyl groups per aromatic molecule 6 ~C 30 an aromatic polyoxazoline polyol and one or more C cycloalkyl oxazoline-containing polyols having three oxazoline-containing hydroxyl groups per cycloalkyl molecule; 3 ~C 20 The biomedical device according to

[13] , wherein the polyol is a cycloalkyl polyoxazoline polyol.

[21] The biomedical device according to

[19] or

[20] , wherein each of the oxazoline-containing hydroxyl groups has 1 to about 200 repeating oxazoline units.

[22] The one or more trifunctional polyoxazoline polyols have three oxazoline-containing hydroxyl groups per aromatic molecule. 6 ~C 30 The biomedical device according to

[20] or

[21] , which is an aromatic polyoxazoline polyol, wherein the aromatic molecule is a phenyl group or a biphenyl group.

[23] 13. The biomedical device of claim 12, wherein the one or more tetrafunctional polyoxazoline polyols are one or more polyoxazoline polyols having four oxazoline-containing hydroxyl groups per molecule.

[24] one or more C tetrafunctional polyoxazoline polyols having four oxazoline-containing hydroxyl groups per alkyl molecule, the alkyl molecules optionally containing one or more of an ether linkage and / or an ester linkage; 1 ~C 12 Alkyl polyoxazoline polyols, with four oxazoline-containing hydroxyl groups per aromatic molecule, one or more C 6 ~C 30 an aromatic polyoxazoline polyol and one or more C cycloalkyl oxazoline-containing hydroxyl groups per cycloalkyl molecule; 3 ~C 20 The biomedical device according to

[13] , wherein the polyol is a cycloalkyl polyoxazoline polyol.

[25] 23. The biomedical device of claim 22, wherein each of the oxazoline-containing hydroxyl groups has 1 to about 200 repeating oxazoline units.

[26] The one or more tetrafunctional polyoxazoline polyols have four oxazoline-containing hydroxyl groups per aromatic molecule. 6 ~C 30 The biomedical device according to

[24] or

[25] , which is an aromatic polyoxazoline polyol, wherein the aromatic molecule is a phenyl group or a biphenyl group.

[27] The biomedical device according to any one of [1] to

[26] , wherein the one or more polyoxazoline polyols have a weight average molecular weight of at least about 1000 Daltons and up to about 50,000,000 Daltons.

[28] The biomedical device according to any one of [1] to

[27] , wherein the mixture further comprises a catalytic amount of one or more catalysts.

[29] The biomedical device according to any one of [1] to

[28] , wherein the mixture further comprises at least one silicone-containing monomer.

[30] The biomedical device according to any one of [1] to

[29] , which is a contact lens.

[31] The biomedical device according to any one of [1] to

[29] , which is a hydrogel contact lens.

[32] The biomedical device according to any one of [1] to

[29] , which is an intraocular lens.

[33] The biomedical device according to any one of [1] to

[32] , wherein the polymerization product is a thermosetting polymerization product.

[34] The mixture (a) about 20 to about 60 weight percent of the one or more difunctional isocyanates, based on the total weight of the mixture; (b) about 10 to about 70 weight percent of the one or more polyalcohols, based on the total weight of the mixture; (c) from about 3 to about 60 weight percent of said one or more hydroxy-terminated polysiloxane prepolymers, based on the total weight of said mixture; (d) about 5 to about 65 weight percent of the one or more polyoxazoline polyols having a weight average molecular weight of about 1000 daltons or more, based on the total weight of the mixture.

[35] The mixture (a) about 30 to about 45 weight percent of the one or more difunctional isocyanates, based on the total weight of the mixture; (b) about 12 to about 20 weight percent of said one or more polyalcohols, based on the total weight of said mixture; (c) about 10 to about 50 weight percent of the one or more hydroxy-terminated polysiloxane prepolymers, based on the total weight of the mixture; (d) about 10 to about 45 weight percent of the one or more polyoxazoline polyols having a weight average molecular weight of about 1,000 daltons or more, based on the total weight of the mixture.

[36] 1. A method of making a biomedical device, said method comprising: (a) providing a mixture comprising: (i) one or more difunctional isocyanates; (ii) one or more polyalcohols; (iii) one or more hydroxy-terminated polysiloxane prepolymers; and (iv) one or more polyoxazoline polyols having a weight average molecular weight of about 1000 Daltons or greater; (b) subjecting the mixture to polymerization conditions to provide a polymerized device; (c) hydrating the polymerized device.

[37]

[36] The method of

[36] , wherein the one or more difunctional isocyanates include aliphatic isocyanates, cycloaliphatic isocyanates, and aromatic isocyanates.

[38] The one or more difunctional isocyanates are of the formula OCN-R 1 -NCO, wherein R 1 But linear or branched chain C 3 ~C 18 - an alkylene group, unsubstituted or substituted C 6 ~C 10 -arylene group, unsubstituted or substituted C 7 ~C 18 -aralkylene group, C 6 ~C 10 -Arylene-C 1 ~C 2 -Alkylene-C 6 ~C 10 -arylene group, C 3 ~C 8 -cycloalkylene group, C 3 ~C 8 -Cycloalkylene-C 1 ~C 6 -Alkylene group, C 3 ~C 8 -Cycloalkylene-C 1 ~C 6 -Alkylene-C 3 ~C 8 -cycloalkylene group, or C 1 ~C 6 -Alkylene-C 3 ~C 8 -cyclo-alkylene-C 1 ~C 6 The method according to

[36] , wherein the -alkylene group is an -alkylene group.

[39] The method according to any one of

[36] to

[38] , wherein the one or more polyalcohols have about 2 to about 50 carbon atoms and at least two hydroxy groups.

[40] The method according to any one of

[36] to

[38] , wherein the one or more polyalcohols are selected from the group consisting of diols, triols, tertiary amine polyalcohols, alkoxylated polyalcohols, polyether polyalcohols, and mixtures thereof.

[41]

[40] The method according to

[41] , wherein the one or more alkoxylated polyalcohols comprise one or more polyoxyethylene glycols.

[42] 40. The method of claim 40, wherein the one or more polyether polyalcohols comprise one or more of a poloxamer block copolymer and a poloxamine block copolymer.

[43] The one or more hydroxy-terminated polysiloxane prepolymers have the formula:

change

[42] . The method according to

[36] to

[42] , wherein Q groups independently represent H or a hydrocarbyl group, p is an integer of 0 to 40, q is an integer of 0 to 40, z is an integer of 2 to 50, u is an integer of 1 to 100, y is an integer of 0 to 40, w is an integer of 0 to 40, and v is an integer of 2 to 50, and each Q group independently represents a hydroxyl-containing reactive functional end group.

[44] The method according to any one of

[36] to

[43] , wherein the one or more polyoxazoline polyols include one or more difunctional, trifunctional, and tetrafunctional polyoxazoline polyols.

[45] The one or more polyoxazoline polyols have the formula:

change

[46] The method according to any one of

[36] to

[45] , wherein the one or more polyoxazoline polyols have a weight average molecular weight of about 1000 daltons or more and up to about 50,000,000 daltons.

[47] The method according to any one of

[36] to

[46] , wherein the mixture further comprises a catalytic amount of one or more catalysts.

[48] The method according to any one of

[36] to

[47] , wherein the mixture further contains at least one silicone-containing monomer.

[49] The method according to any one of

[36] to

[48] , wherein the contact lens is a contact lens.

[50] The method according to any one of

[36] to

[48] , wherein the contact lens is a hydrogel contact lens.

[51] The method according to any one of

[36] to

[48] , wherein the intraocular lens is an intraocular lens.

[52] The method according to any one of

[36] to

[51] , wherein the polymerization product is a thermosetting polymerization product.

[53] The mixture (a) about 20 to about 60 weight percent of the one or more difunctional isocyanates, based on the total weight of the mixture; (b) about 10 to about 70 weight percent of the one or more polyalcohols, based on the total weight of the mixture; (c) from about 3 to about 60 weight percent of said one or more hydroxy-terminated polysiloxane prepolymers, based on the total weight of said mixture; (d) about 5 to about 65 weight percent of the one or more polyoxazoline polyols having a weight average molecular weight of about 1,000 daltons or more, based on the total weight of the mixture.

[54] The mixture (a) about 30 to about 45 weight percent of the one or more difunctional isocyanates, based on the total weight of the mixture; (b) about 12 to about 20 weight percent of said one or more polyalcohols, based on the total weight of said mixture; (c) about 10 to about 50 weight percent of the one or more hydroxy-terminated polysiloxane prepolymers, based on the total weight of the mixture; (d) about 10 to about 45 weight percent of the one or more polyoxazoline polyols having a weight average molecular weight of about 1,000 daltons or more, based on the total weight of the mixture.

Claims

1. a biomedical device that is the polymerization product of the mixture, (a) one or more difunctional isocyanates; (b) one or more polyalcohols; (c) one or more hydroxy-terminated polysiloxane prepolymers; and (d) one or more polyoxazoline polyols having a weight average molecular weight of 1000 Daltons or greater.

2. the one or more difunctional isocyanates include aliphatic isocyanates, cycloaliphatic isocyanates, and aromatic isocyanates; 10. The biomedical device of claim 1, wherein said one or more polyalcohols have from 2 to 50 carbon atoms and at least two hydroxy groups.

3. The one or more difunctional isocyanates are of the formula OCN-R １ —NCO, wherein R １ is a straight or branched chain C ３ ~C １８ - alkylene group, unsubstituted or substituted C ６ ~C １０ - an arylene group, unsubstituted or substituted C ７ ~C １８ -aralkylene group, C ６ ~C １０ -arylene-C １ ~C ２ -Alkylene-C ６ ~C １０ -arylene group, C ３ ~C ８ -cycloalkylene group, C ３ ~C ８ -cycloalkylene-C １ ~C ６ - alkylene group, C ３ ~C ８ -cycloalkylene-C １ ~C ６ -Alkylene-C ３ ~C ８ -cycloalkylene group, or C １ ~C ６ -Alkylene-C ３ ~C ８ -cyclo-alkylene-C １ ~C ６ - an alkylene group, 3. The biomedical device of claim 1 or 2, wherein the one or more polyalcohols are selected from the group consisting of diols, triols, tertiary amine polyalcohols, alkoxylated polyalcohols, polyether polyalcohols, and mixtures thereof.

4. The one or more hydroxy-terminated polysiloxane prepolymers have the formula: [Your Name] 4. The biomedical device of any one of claims 1 to 3, wherein each R 1 group independently represents an alkyl group, p is an integer from 0 to 40, q is an integer from 0 to 40, z is an integer from 2 to 50, u is an integer from 1 to 100, y is an integer from 0 to 40, w is an integer from 0 to 40, and v is an integer from 2 to 50.

5. 5. The biomedical device of any one of claims 1 to 4, wherein the one or more polyoxazoline polyols comprise one or more difunctional, trifunctional, and tetrafunctional polyoxazoline polyols.

6. The one or more polyoxazoline polyols have the formula: 【Chemical VI】 6. The biomedical device of any one of claims 1-5, wherein each R is a hydroxyl group, and each R' is independently an alkyl group, a haloalkyl group, an alkene group, an alkyne group, a cycloalkyl group, a halocycloalkyl group, an aryl group, a haloaryl group, an aralkyl group, and a haloaralkyl group; Z is a divalent bond; and each of x and y is independently at least 1.

7. The mixture (a) 20 to 60 weight percent of the one or more difunctional isocyanates, based on the total weight of the mixture; (b) 10 to 70 weight percent of said one or more polyalcohols, based on the total weight of said mixture; (c) 3 to 60 weight percent of said one or more hydroxy-terminated polysiloxane prepolymers, based on the total weight of said mixture; (d) 5 to 65 weight percent of the one or more polyoxazoline polyols having a weight average molecular weight of 1000 Daltons or greater, based on the total weight of the mixture.

8. The biomedical device of any one of claims 1 to 7, which is one of a contact lens or an intraocular lens.

9. The biomedical device of any one of claims 1 to 8, wherein the polymerization product is a thermosetting polymerization product.

10. 1. A method of making a biomedical device, said method comprising: (a) providing a mixture comprising: (i) one or more difunctional isocyanates; (ii) one or more polyalcohols; (iii) one or more hydroxy-terminated polysiloxane prepolymers; and (iv) one or more polyoxazoline polyols having a weight average molecular weight of 1000 Daltons or greater; (b) subjecting the mixture to polymerization conditions to provide a polymerized device; (c) hydrating the polymerized device.

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